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26 Jan 2022 at 01:34
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Bibliography on: Invasive Ductal Carcinoma


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RJR: Recommended Bibliography 26 Jan 2022 at 01:34 Created: 

Invasive Ductal Carcinoma

Invasive ductal carcinoma (IDC), also known as infiltrating ductal carcinoma, is cancer that began growing in a milk duct and has invaded the fibrous or fatty tissue of the breast outside of the duct. IDC is the most common form of breast cancer, representing 80 percent of all breast cancer diagnoses.

Created with PubMed® Query: ("invasive ductal carcinoma" OR IDC) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2022-01-20

Kwon D, Ko BK, Jung SP, et al (2022)

Survival analysis in patients with invasive lobular cancer and invasive ductal cancer according to hormone receptor expression status in the Korean population.

PloS one, 17(1):e0262709 pii:PONE-D-21-17221.

BACKGROUND: We compared the clinicopathological characteristics and survival outcomes of invasive lobular carcinoma (ILC) cases with those of invasive ductal carcinoma (IDC) cases in various hormone receptor expression subgroups.

METHODS: We compared clinicopathological characteristics, overall survival (OS), and breast cancer-specific survival (BCSS) between patients with IDC (n = 95,486) and ILC (n = 3,023). In addition, we analyzed the effects of different hormone receptor expression subgroups on survival.

RESULTS: The ILC group had more instances of advanced stage and hormonal receptor positivity than did the IDC group (p < 0.001), but the IDC group had higher histological grade and nuclear grade, as well as higher frequency of human epidermal growth factor receptor 2 and Ki67 expression than did the ILC group (p < 0.001). The OS and BCSS were not significantly different between the IDC and ILC groups. The 5-year OS of the IDC group was 88.8%, while that of the ILC group was 90.6% (p = 0.113). The 5-year BCSS of the IDC group was 94.8%, while that of the ILC group was 95.0% (p = 0.552). When analyzing each hormone receptor expression subgroup, there were no significant differences in survival between the IDC and ILC groups. However, the estrogen receptor (ER) negative/progesterone receptor (PR) negative subgroup showed differences in survival between the IDC and ILC groups. Moreover, the hazard ratio of ILC in the ER negative/PR negative subgroup was 1.345 (95% confidence interval: 1.012-1.788; p = 0.041).

CONCLUSIONS: Hormone receptor expression should be considered when determining prognosis and treatment regimen for IDC and ILC. Researchers should further study the ER negative/PR negative population to identify treatment and prognostic models that will facilitate the development of individualized therapy for these patients, which is needed for good outcomes.

RevDate: 2022-01-20

Zhang J, Wang G, Ren J, et al (2022)

Multiparametric MRI-based radiomics nomogram for preoperative prediction of lymphovascular invasion and clinical outcomes in patients with breast invasive ductal carcinoma.

European radiology [Epub ahead of print].

OBJECTIVE: To develop a multiparametric MRI-based radiomics nomogram for predicting lymphovascular invasion (LVI) status and clinical outcomes in patients with breast invasive ductal carcinoma (IDC).

METHODS: A total of 160 patients with pathologically confirmed breast IDC (training cohort: n = 112; validation cohort: n = 48) who underwent preoperative breast MRI were included. Imaging features were extracted from T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC) maps, and contrast-enhanced T1-weighted imaging (cT1WI) sequences. A four-step procedure was applied for feature selection and radiomics signature building. Univariate and multivariate logistic regression analyses were conducted to identify the features associated with LVI, which were then incorporated into the radiomics nomogram. The performance of the nomogram was evaluated by its discrimination, calibration, and clinical usefulness. Kaplan-Meier survival curves based on the two radiomics models were used to estimate disease-free survival (DFS).

RESULTS: The fusion radiomics signature of the T2WI, cT1WI, and ADC maps achieved a better predictive efficacy for LVI than either of them alone. The proposed radiomics nomogram, incorporating the fusion radiomics signature and MRI-reported peritumoral edema, showed satisfactory capabilities of calibration and discrimination in both training and validation datasets, with AUCs of 0.919 (95% CI: 0.871-0.967) and 0.863 (95% CI: 0.726-0.999), respectively. The radiomics signature and nomogram-defined high-risk groups had a shorter DFS than those in the low-risk groups (both p < 0.05). Higher Rad-scores were independently associated with a worse DFS in the whole cohort (p < 0.05).

CONCLUSIONS: The proposed nomogram, incorporating multiparametric MRI-based radiomics signature and MRI-reported peritumoral edema, achieved a satisfactory preoperative prediction of LVI and clinical outcomes in IDC patients.

KEY POINTS: • The fusion radiomics signature of the T2WI, cT1WI, and ADC maps achieved a better predictive efficacy for LVI than either of them alone. • The proposed nomogram achieved a favorable prediction of LVI in IDC patients with AUCs of 0.919 and 0.863 in the training and validation datasets, respectively. • The radiomics model could classify patients into high- and low-risk groups with significant differences in DFS.

RevDate: 2022-01-20

Jiang M, Lei S, Zhang J, et al (2022)

Multimodal Imaging of Target Detection Algorithm under Artificial Intelligence in the Diagnosis of Early Breast Cancer.

Journal of healthcare engineering, 2022:9322937.

This study aimed to analyze the diagnostic value of multimodal images based on artificial intelligence target detection algorithms for early breast cancer, so as to provide help for clinical imaging examinations of breast cancer. This article combined residual block with inception block, constructed a new target detection algorithm to detect breast lumps, used deep convolutional neural network and ultrasound imaging in diagnosing benign and malignant breast lumps, took breast density grading with mammography, compared the convolutional neural network (CNN) algorithm with the proposed algorithm, and then applied the proposed algorithm to the diagnosis of 120 female patients with breast lumps. According to the results, accuracy rates of breast lump detection (94.76%), benign and malignant breast lumps diagnosis (98.22%), and breast grading (93.65%) with the algorithm applied in this study were significantly higher than those (75.67%, 87.23%, and 79.54%) with CNN algorithm, and the difference was statistically significant (P < 0.05); among 62 patients with malignant breast lumps of the 120 patients with breast lumps, 37 were patients with invasive ductal carcinoma, 8 with lobular carcinoma in situ, 16 with intraductal carcinoma, and 4 with mucinous carcinoma; among the remaining 58 patients with benign breast lumps, 28 were patients with fibrocystic breast disease, 17 with intraductal papilloma, 4 with breast hyperplasia, and 9 with adenopathy; the differences in shape, growth direction, edge, and internal echo of multimodal ultrasound imaging of patients with benign and malignant breast lumps had statistical significance (P < 0.05); the malignant constituent ratios of patients with breast density grades I to IV were 0%, 7.10%, 80.40%, and 100%, respectively. In short, the multimodal imaging diagnosis under the algorithm in this article was superior to CNN algorithm in all aspects; according to the judgment on benign and malignant breast lumps and breast density with multimodal imaging features, the higher the breast density, the higher the probability of breast cancer.

RevDate: 2022-01-20

Adachi K, Kubota H, Suzuki S, et al (2021)

[Hereditary Breast and Ovarian Cancer(HBOC)in a Young Adult-A Case Report].

Gan to kagaku ryoho. Cancer & chemotherapy, 48(13):1843-1845.

We report a case of hereditary breast and ovarian cancer(HBOC)in a young adult. A 31-year-old woman consulted at our hospital for a lump on her left breast. Ultrasonography revealed an irregular-shaped mass. A core needle biopsy was performed, and the pathological diagnosis was invasive ductal carcinoma. There were multiple enlarged lymph nodes in the axilla and internal mammary areas but no evidence of metastasis. She underwent mastectomy and axially dissection. The pathological findings from the surgically resected specimens showed scirrhous carcinoma positive for ER and PgR and negative for HER2/neu protein expression. The tumor size was 16 mm, and 3 axillary lymph node metastases were seen. We identified the pathological stage as T1cN3bM0, stage ⅢC. She received chemotherapy, radiotherapy, and endocrine therapy after surgery. At present, 1 year after surgery, the patient is alive without recurrence. With a low age of onset and a family history of ovarian cancer, she was diagnosed with HBOC as a result of breast cancer susceptibility gene(BRCA)genetic testing. In addition to the recommended surveillance, prophylactic surgery will be performed in the future.

RevDate: 2022-01-20

Yanai A, Nishino M, Kojima S, et al (2021)

[A Case of Breast Cancer in the Elderly Localized in the Nipple].

Gan to kagaku ryoho. Cancer & chemotherapy, 48(13):1801-1803.

An 89-year-old woman presented to our clinic with a complaint of a wound in the left nipple. The pathological diagnosis via skin biopsy revealed adenocarcinoma. A physical examination, mammography, ultrasonography, and CT scan revealed a mass in the left nipple. However, a definite diagnosis could not be established by skin biopsy. Left breast-conserving surgery and sentinel lymph node biopsy were performed for diagnosis and treatment. Histological examination revealed a scirrhous type invasive ductal carcinoma in the left nipple and areola with skin invasion and lymph node metastasis. Radiation and hormone therapy were used as adjuvant therapy. She is alive with no local recurrence for 5 months post surgery. Since ductal carcinoma of the nipple is uncommon, we present this case report along with a review of the relevant literature.

RevDate: 2022-01-20

Kawai H, Imamura Y, Kondoh A, et al (2021)

[A Case of Intraductal Apocrine Carcinoma of the Breast].

Gan to kagaku ryoho. Cancer & chemotherapy, 48(13):1643-1645.

A female in her 60s who complained of nipple discharge in her left breast for 1 year. A soft mass ill-defined margin in the border of AB area was observed. Mammography showed a focal asymmetric density. Ultrasonography disclosed an irregular heterogenous low echoic lesion in the AB area of her left breast. MRI image showed an enhanced lesion in the inner area. The pathological diagnosis by core needle biopsy was non-invasive ductal carcinoma with apocrine metaplasia. Mastectomy with sentinel lymph node biopsy of the left breast was performed. Post operative histopathological examination revealed intraductal apocrine carcinoma without lymph node metastasis. Estrogen and progesterone receptors were negative. Three years after operation without any adjuvant treatment, she has no recurrence of lesion.

RevDate: 2022-01-20

Terakawa H, Ogaito T, Okamoto K, et al (2021)

[Stage Ⅳ HER2-Positive Breast Cancer That Showed Complete Response for Over One Year after Discontinuation of Anti-HER2 Therapy-A Case Report].

Gan to kagaku ryoho. Cancer & chemotherapy, 48(13):1559-1560.

A 75-year-old woman with a left breast mass on breast cancer screening was referred to our hospital for detailed evaluation. Further examination revealed left breast cancer with metastases to the left axilla, left parasternal region, left supraclavicular fossa, mediastinum, and left hilar lymph nodes, as well as multiple lung metastases. Histopathological evaluation of a needle biopsy specimen revealed invasive ductal carcinoma(scirrhous type), and she was diagnosed with Stage Ⅳ human epidermal growth factor receptor 2(HER2)-positive breast cancer. Following diagnosis, treatment was initiated with trastuzumab, pertuzumab, and docetaxel; however, she developed hypersensitivity to docetaxel and received only trastuzumab and pertuzumab after the second course. We observed a complete response after 3 courses, and treatment was discontinued after 13 courses. She underwent regular evaluation after treatment discontinuation, and a complete response was maintained for 1 year and 6 months. We conclude that combination therapy comprising trastuzumab and pertuzumab was effective for Stage Ⅳ HER2-positive breast cancer and that a complete response could be maintained even after treatment discontinuation.

RevDate: 2022-01-19

Satoh E, Yatabe Y, Uehira D, et al (2021)

[A Case of Pyloric Stenosis Due to Gastric Metastasis of Breast Cancer].

Gan to kagaku ryoho. Cancer & chemotherapy, 48(13):2103-2105.

We report a case of left advanced breast cancer(T4N1M0, Stage ⅢA)in a 67-year-old woman. In August 2010, her breast cancer(triple-negative invasive ductal carcinoma)was resected(mastectomy plus axillary lymph node dissection) with adjuvant chemotherapy(TC)and irradiation to her chest wall. In July 2018, she experienced recurrent vomiting. Gastrointestinal endoscopy(GS)revealed type Ⅳ advanced gastric cancer-like appearance with pyloric stenosis. Pathological findings confirmed hormone-positive gastric metastasis of breast cancer. Systemic chemo-endocrine therapy(EC and anastrozole) was performed, following which her symptoms improved. In May 2019, recurrent vomiting appeared again. Thereafter, systemic chemo-endocrine therapy(paclitaxel plus bevacizumab and fulvestrant)was initiated, and her symptoms showed improvement. In November 2020, she showed obstructive jaundice due to malignant biliary stenosis. She was treated using endoscopic biliary stenting, but died 2 months later. Gastric metastasis is reported rarely in 4% of all breast cancers, and GS should be recommended in cases of recurrent abdominal complaints.

RevDate: 2022-01-19

Goto W, Nagamori M, Yamakoshi Y, et al (2021)

[A Case of Adenoid Cystic Carcinoma of the Breast].

Gan to kagaku ryoho. Cancer & chemotherapy, 48(13):2033-2035.

Primary adenoid cystic carcinoma(ACC)of the breast is a rare type of breast cancer. A 53-year-old woman with a right breast mass was examined at our institute. Ultrasonography showed 12.5×10.3×8.4 mm sized an ill-defined hypoechoic mass at zone C of the right breast. Pathological examination of core needle biopsy revealed atypical cells with solid and cribriform growth pattern. Computed tomography did not reveal lymph node metastases or distant metastases. The preoperative diagnosis was Stage ⅠA(cT1cN0M0, ER/PgR/HER2=-/-/1+)invasive ductal carcinoma or ACC. Surgery consisted of breast-conserving surgery and sentinel node biopsy. Pathological examination of the excised specimen revealed a so- called adenoid cystic pattern, so the final diagnosis was Stage ⅠA(pT1cN0M0, ER/PgR/HER2=-/-/1+)ACC. After 1 year of observation without adjuvant treatment, there has been no recurrence.

RevDate: 2022-01-19

Nakanishi K, Goto W, Ishihara A, et al (2021)

[A Case of Synchronous Double Cancer including Borderline Resectable Pancreatic Body Cancer and Breast Carcinoma with Osseous/Cartilaginous Differentiation Treated with Neoadjuvant Chemotherapy and Radical Resection].

Gan to kagaku ryoho. Cancer & chemotherapy, 48(13):2005-2007.

A 78-year-old woman with a left breast cancer was examined at our institute. Ultrasonography showed 48 mm sized mass at zone C of the left breast, and left axillary lymph node swelling. Pathological examination of core needle biopsy revealed invasive ductal carcinoma and lymph node metastasis. In addition, contrast computed tomography showed 30 mm sized an hypovascular mass at pancreatic body involved the portal vein. Endoscopic ultrasound guided fine needle aspiration biopsy of the pancreas revealed adenocarcinoma. The diagnosis was synchronous double cancer including borderline resectable pancreatic body cancer and left breast cancer, and she received neoadjuvant chemotherapy consisting of gemcitabine and nab-paclitaxel. The effect of neoadjuvant chemotherapy was judged to be stable disease for breast cancer, partial response for pancreatic cancer. Then, she underwent pancreatosplenectomy with portal vein and gastroduodenal artery resection and reconstruction, left mastectomy and axillary lymph node dissection. Pathologic examination of the excised specimen revealed the diagnosis of breast cancer with osseous/cartilaginous differentiation and pancreatic moderately differentiated adenocarcinoma. She was treated with fluorouracil, epirubicin, and cyclophosphamide as adjuvant therapy, and there has been no recurrence.

RevDate: 2022-01-19

Otake H, Takizawa K, Nagaro H, et al (2021)

[A Case of Long-Term Survival after Resection of Pancreatic Ductal Adenocarcinoma with Para-Aortic Lymph Node Metastasis].

Gan to kagaku ryoho. Cancer & chemotherapy, 48(13):2002-2004.

The patient was a 64-year-old man with diagnosis of pancreatic head cancer. Initially, abdominal CT showed pancreatic head tumor with bile duct invasion and no distant metastases including para-aortic lymph nodes(PALN). Although, subtotal stomach-preserving pancreatoduodenectomy(SSPPD)and PALN sampling was performed, intraoperative frozen section examination revealed PALN metastasis. He had chronic kidney disease and was unsuitable for standard chemotherapy, SSPPD and PALN dissection was performed instead of standard chemotherapy. Histopathological examination of the resected specimens revealed invasive ductal carcinoma in the pancreatic head region and 11 nodes out of the 17 dissected PALN. Adjuvant chemotherapy with S-1 was performed. 22 months after surgery, intraabdominal lymph nodes metastasis and lung metastasis was found. 24 months after surgery, palliative radiation therapy at a dose of 40 Gy was performed. Systemic chemotherapy with gemcitabine alone was performed, but he was dead 67 months after the initial therapy.

RevDate: 2022-01-19

Tojo K, Abe S, Tachibana K, et al (2021)

[A Case Report of Uterine Metastasis Four Years after Breast Surgery for Breast Cancer].

Gan to kagaku ryoho. Cancer & chemotherapy, 48(13):1885-1888.

We report a case of uterine metastasis of the breast cancer. The patient was diagnosed with invasive ductal carcinoma of the breast and underwent partial right mastectomy and sentinel lymph node biopsy. Tamoxifen was administered as adjuvant endocrine therapy. Four years after the surgery, she had irregular genital bleeding, and was referred to our hospital for cytological diagnosis of uterine cancer. Postoperative pathological diagnosis showed uterine metastasis of breast cancer, and it was decided to treat the recurrence of breast cancer with aromatase inhibitors and CDK4/6 inhibitors, a molecular targeted therapy. The patient has been progression-free for 5 months.

RevDate: 2022-01-18

Imhoff R, Zimmer F, Klein O, et al (2022)

Conspiracy mentality and political orientation across 26 countries.

Nature human behaviour [Epub ahead of print].

People differ in their general tendency to endorse conspiracy theories (that is, conspiracy mentality). Previous research yielded inconsistent findings on the relationship between conspiracy mentality and political orientation, showing a greater conspiracy mentality either among the political right (a linear relation) or amongst both the left and right extremes (a curvilinear relation). We revisited this relationship across two studies spanning 26 countries (combined N = 104,253) and found overall evidence for both linear and quadratic relations, albeit small and heterogeneous across countries. We also observed stronger support for conspiracy mentality among voters of opposition parties (that is, those deprived of political control). Nonetheless, the quadratic effect of political orientation remained significant when adjusting for political control deprivation. We conclude that conspiracy mentality is associated with extreme left- and especially extreme right-wing beliefs, and that this non-linear relation may be strengthened by, but is not reducible to, deprivation of political control.

RevDate: 2022-01-17

Das Majumdar SK, Das DK, Barik S, et al (2021)

Evaluation of Clinicopathological and Prognostic Factors of Male Breast Cancer: A Single-Centre Experience.

Cureus, 13(12):e20298.

Male breast cancer (MBC) is a rare malignancy with an overall incidence of less than 1%. The epidemiological data of MBC is very limited owing to its rarity, particularly data from India. Hence, it is important to study different aspects of this rare malignancy. This paper reports a single-center experience from India that evaluated the clinicopathological behavior of MBC, their management, and outcomes. This was a retrospective review, which included 18 patients managed between 2013 to 2021. Seventeen out of the 18 patients were aged ≥50 years; the median age was 60 years. Left sides were affected more than right (left: 11, right: seven), and the most commonly affected quadrant was central (n=15/17, 88.2%). The most common (n=14) surgery was modified radical mastectomy (MRM), and the invasive ductal carcinoma was the most common (n=14) histological finding. Most cases were estrogen-receptor (ER) and progesterone-receptor-positive (n=15/18, 83.3%). The present study, though with a small sample size, adds valuable information to the literature about this rare occurrence in men.

RevDate: 2022-01-16

Kim MY, Suh YJ, YY An (2022)

Comparison of Abbreviated Breast MRI vs Digital Breast Tomosynthesis for Breast Cancer Detection among Women with a History of Breast Cancer.

Academic radiology pii:S1076-6332(21)00574-2 [Epub ahead of print].

RATIONALE AND OBJECTIVES: To compare the diagnostic performance of abbreviated breast MRI (AB-MRI) and digital breast tomosynthesis (DBT) in women with a personal history (PH) of breast cancer as a postoperative screening tool.

MATERIALS AND METHODS: A total of 471 patients who completed both DBT and AB-MRI examinations were included in this study (median age, 54.5 years). The detected cancer characteristics were analyzed. The cancer detection rate (CDR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) were calculated by receiver operating characteristic (ROC) curve analysis.

RESULTS: Eleven malignancies were diagnosed, and most of the detected cancers were stage I (7 of 11, 63.6%). Eight were invasive ductal carcinomas (IDC), and 3 were ductal carcinoma in situ (DCIS). Of the 11 recurrences, 6 malignancies were detected by DBT, and 11 were detected by AB-MRI. AB-MRI detected all 8 IDC and 3 DCIS lesions, and DBT detected 6 of 8 IDC lesions. The CDRs for DBT and AB-MRI screenings were 12.7 and 23.4 per 1,000 women, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of DBT versus AB-MRI were 54.6% versus 100%, 97.6% versus 96.5%, 35.3% versus 40.7%, 98.9% versus 100%, and 96.6% versus 96.6%, respectively. AB-MRI showed a higher AUC value (0.983) than DBT (0.761) (p = 0.0049).

CONCLUSION: AB-MRI showed an improved CDR, especially for invasive cancer. The diagnostic performance of AB-MRI was superior to that of DBT with high sensitivity and PPV without sacrificing specificity in women with a PH of breast cancer.

RevDate: 2022-01-14

Taitelbaum-Swead R, Icht M, BM Ben-David (2022)

More Than Words: the Relative Roles of Prosody and Semantics in the Perception of Emotions in Spoken Language by Postlingual Cochlear Implant Users.

Ear and hearing pii:00003446-900000000-98364 [Epub ahead of print].

OBJECTIVES: The processing of emotional speech calls for the perception and integration of semantic and prosodic cues. Although cochlear implants allow for significant auditory improvements, they are limited in the transmission of spectro-temporal fine-structure information that may not support the processing of voice pitch cues. The goal of the current study is to compare the performance of postlingual cochlear implant (CI) users and a matched control group on perception, selective attention, and integration of emotional semantics and prosody.

DESIGN: Fifteen CI users and 15 normal hearing (NH) peers (age range, 18-65 years) 1istened to spoken sentences composed of different combinations of four discrete emotions (anger, happiness, sadness, and neutrality) presented in prosodic and semantic channels-T-RES: Test for Rating Emotions in Speech. In three separate tasks, listeners were asked to attend to the sentence as a whole, thus integrating both speech channels (integration), or to focus on one channel only (rating of target emotion) and ignore the other (selective attention). Their task was to rate how much they agreed that the sentence conveyed each of the predefined emotions. In addition, all participants performed standard tests of speech perception.

RESULTS: When asked to focus on one channel, semantics or prosody, both groups rated emotions similarly with comparable levels of selective attention. When the task was called for channel integration, group differences were found. CI users appeared to use semantic emotional information more than did their NH peers. CI users assigned higher ratings than did their NH peers to sentences that did not present the target emotion, indicating some degree of confusion. In addition, for CI users, individual differences in speech comprehension over the phone and identification of intonation were significantly related to emotional semantic and prosodic ratings, respectively.

CONCLUSIONS: CI users and NH controls did not differ in perception of prosodic and semantic emotions and in auditory selective attention. However, when the task called for integration of prosody and semantics, CI users overused the semantic information (as compared with NH). We suggest that as CI users adopt diverse cue weighting strategies with device experience, their weighting of prosody and semantics differs from those used by NH. Finally, CI users may benefit from rehabilitation strategies that strengthen perception of prosodic information to better understand emotional speech.

RevDate: 2022-01-14

Hussain M, Abbott M, Zargham R, et al (2022)

Evolution of an invasive ductal carcinoma to a small cell carcinoma of the breast: A case report.

Medicine, 101(2):e28433.

RATIONALE: Small cell carcinoma (SCC) is a rare subtype of breast cancer and presents a complex diagnostic and treatment challenge, due to paucity of data. To the best of our knowledge, most cases of breast SCC reported in the literature describe a de novo breast primary. Our case is unique as it describes the evolution of an invasive ductal carcinoma after treatment into a SCC of the breast.

We report a case of a 53-year-old female, lifelong non-smoker, who initially presented with breast mass noted on self examination. Breast and axillary lymph node biopsy demonstrated a hormone receptor positive invasive ductal carcinoma with a metastatic T3 lesion.

INTERVENTION: She was treated with first-line palbociclib/letrozole with initial clinical response, and at progression was switched to capecitabine with no response. Repeat biopsy of the axillary lesion showed evolution of the tumor into a triple negative breast cancer. She was then treated with third-line paclitaxel and radiation therapy with good initial response. She eventually had further disease progression and presented with a new mediastinal lymphadenopathy causing SVC syndrome. Biopsy of this showed a small cell variant of breast neuroendocrine carcinoma. Due to the evolution of histology in this case, a retrospective review of her initial breast specimen as well as the second biopsy from the axilla was conducted which confirmed that the mediastinal lymphadenopathy was metastatic from the original breast tumor.

OUTCOMES AND LESSONS: We speculate that the initial treatment allowed a minority of treatment-resistant neuroendocrine cells to grow and become the dominant face of the tumor. Our patient had an excellent response to carboplatin/etoposide and consolidative locoregional radiotherapy but presented with an early intracranial recurrence. This is a similar pattern of metastases as seen in lung SCC and highlights a potential role for prophylactic cranial irradiation in breast SCC. Further studies are needed to better understand the biology and treatment of breast SCC which continues to present a challenge for clinicians.

RevDate: 2022-01-14

Makower D, Qin J, Lin J, et al (2022)

The 21-gene recurrence score in early non-ductal breast cancer: a National Cancer Database analysis.

NPJ breast cancer, 8(1):4.

The 21-gene recurrence score (RS) is prognostic for recurrence and predictive of chemotherapy benefit in early estrogen receptor-positive (ER +) HER2-negative (HER2-) breast cancer (BCA). We evaluated clinicopathologic characteristics, RS and chemotherapy benefit in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and carcinomas of mixed histologies (ductal + lobular (DLC), ductal + other (DOC), lobular + other (LOC)). Women diagnosed between 1/1/2010 and 1/1/2014 with ER + HER2- BCA, measuring <5 cm, with 0-3 involved axillary nodes, surgery as first treatment, and available RS, were identified from the NCDB. Associations between categorical variables were examined using chi-square test. Cox proportional hazards model was used to examine overall survival (OS) differences among histology subtypes. IDC was associated with smaller size, high grade, and RS > 26. ILC was associated with larger size, and least likely to be high grade (p < 0.0001). Lobular histology was associated with lower incidence of RS > 26. IDC patients (pts) were more likely to receive chemotherapy than pts with other histologies (p < 0.0001). OS for IDC, ILC and DOC were similar. DLC was associated with improved OS (HR 0.82, p = 0.02). Adjuvant chemotherapy was associated with improved OS in IDC (HR = 0.76, p < 0.0001) but not in ILC (HR = 0.99, p = 0.93), DLC (HR = 1.04, p = 0.86), DOC (HR = 0.87, p = 0.71), or LOC (HR = 2.91, p = 0.10). Lobular and mixed BCA histologies have distinct clinicopathologic features compared with IDC, and are less likely to have high RS. OS is similar for IDC and ILC. Although chemotherapy benefit was seen only in IDC, benefit for ILC with RS > 26 cannot be excluded.

RevDate: 2022-01-13

Kawaguchi Y, Kuba S, Morita M, et al (2022)

A Case of Bilateral Inflammatory Breast Cancer that Developed Two Years after Treatment for Triple-negative Breast Cancer1.

Internal medicine (Tokyo, Japan) [Epub ahead of print].

A 66-year-old woman underwent partial mastectomy and a sentinel lymph node biopsy for left breast cancer; the pathological diagnosis was invasive ductal carcinoma (pT1aN0, pStage I, triple-negative subtype). Postoperative radiotherapy was performed. Two years later, she developed redness and induration at both breasts. The diagnosis was bilateral inflammatory breast cancer. After four cycles of dose-dense epirubicin and cyclophosphamide followed by 12 weekly paclitaxel cycles, bilateral total mastectomy and axillary lymph node dissection were performed. At the one-year follow-up after undergoing operation and radiotherapy, she remained alive without recurrence. Dose-dense treatment regimens may help patients achieve complete resection without short-term recurrence.

RevDate: 2022-01-12

Mishra S, Kim ES, Sharma PK, et al (2020)

Tailored Biofunctionalized Biosensor for the Label-Free Sensing of Prostate-Specific Antigen.

ACS applied bio materials, 3(11):7821-7830.

The increase in the demand and popularity of smart biosensors has brought a novel and innovative concept to develop a diverse range of semen mutual biomarker (i.e., prostate-specific antigen, PSA)-based biodevices for our daily life applications. Using a versatile strategy, here we have developed a next-generation miniaturized capacitive biomarker-based sensor, which facilitates a direct, rapid quantitation and ultrafast detection of prostate-specific antigen (PSA) selectively. To fabricate an affordable PSA biosensor, an interdigitated capacitor (IDC) was functionalized and to detect PSA at concentrations varying from 0.1 to 10 μL/mL, with a response time of 3 s. Moreover, the PSA biosensor showed a high level of selectivity due to the successful probing of the capacitive response-generated biomolecular interactions using external stimuli at the bioelectrode. The resulting IDC-based PSA biosensors are capable of excellent reproducibility and reusability, which are required for real-time biosensing of any targeted biomolecules where low-concentration detection is a key for point-of-care, on-site sensing applications. We anticipate that this research could open exciting opportunities for PSA detection at a low concentration level.

RevDate: 2022-01-11

Gault N, Sallah K, Régent A, et al (2021)

[Analysis of off-label prescriptions of medicines in hospital in adult patients and feasibility study of their detection using CIM-10 coding].

Therapie pii:S0040-5957(21)00210-9 [Epub ahead of print].

Analysis of off-label prescriptions of medicines in hospital in adult patients and study of feasibility of their detection by use of international disease classification, 10th version (IDC-10 codes).

CONTEXT: In order to improve the appropriate use of medicines, a method of detection of off label prescriptions, especially in hospitalised patients, should be available.

STUDY OBJECTIVES: Evaluate the performance of the detection of off-label prescriptions in hospitalised patients by use of IDC-10 codes.

METHODS: Data prescriptions (excluding those directly taken in charge by the national health care system), clinical history and biological results were extracted from Assistance publique des Hôpitaux de Paris (AP-HP) data-warehouse for 108 in-hospital adults patients' journeys. An adjudication committee established the classification reference for the appropriate or off label drug prescriptions status after analysis of medical information for each patient. IDC-10 codification that is performed after every hospitalisation was crossed with those IDC-10 codes that were to be expected corresponding to the marketing authorisation labelling (section 4.1 of specifications of product characteristics [SPC]). Results of IDC-10 coding were compared to the reference for off label use identification.

RESULTS: Out of the 1131 analysed prescriptions, 44 (3.9%) were classified as off label by the adjudication committee. Sensitivity of detection by IDC-10 coding was 87 (95% CI [0.73-0.96]) to 92% (95% CI [0.79-0.98]) and specificity 25 (95% CI [0.22-0.27]) to 41% (95% CI [0.38-0.44]) according to the number of characters of ICD-10 that could be used.

CONCLUSIONS: Incidence of in-hospital off label use of drugs (restricted to within drug related groups prescriptions) appeared relatively low (3.9%). Its semi-automatic detection by IDC-10 coding appears feasible with a good sensitivity but a low specificity. Such method could be further assessed as a first step detection focusing on one pharmacological class or on one pathologic condition.

RevDate: 2022-01-11

Rachamim L, Mualem-Taylor H, Rachamim O, et al (2021)

Acute and Long-Term Effects of an Internet-Based, Self-Help Comprehensive Behavioral Intervention for Children and Teens with Tic Disorders with Comorbid Attention Deficit Hyperactivity Disorder, or Obsessive Compulsive Disorder: A Reanalysis of Data from a Randomized Controlled Trial.

Journal of clinical medicine, 11(1): pii:jcm11010045.

Attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD) and tic disorders (TD) commonly co-occur. In addition, specific inattention difficulties and poor impulse control are related to TD in the absence of comorbid ADHD. In this study we reanalyzed data from a recently completed study comparing internet-delivered, self-help comprehensive behavioral intervention for tics (ICBIT) with a waiting-list control group. The current study describes the effects of an (ICBIT) in children and adolescents with TD with and without comorbid diagnoses of ADHD or OCD at post intervention and over three- and six-month follow-up periods. Thirty-eight 7 to 18-year-olds completed the ICBIT. Of these, 16 were diagnosed with comorbid ADHD and 11 were diagnosed with OCD. A significant improvement in tic measures was found in all groups. Both the TD + ADHD and the TD - ADHD groups were similar in the magnitude of tic reduction from baseline to post-treatment, and at the three and six-month follow-up assessments. However, the TD + OCD group benefitted less from intervention than the TD-OCD group. There were meaningful reductions in parental reports of inattention, as well as hyperactive and impulsive symptoms at post intervention and over the 6-month follow-up period. Thus, ICBIT can be effectively delivered in the presence of comorbid ADHD or OCD symptomatology and may reduce symptoms of inattention and impulsivity. Larger studies of ICBIT in children and teens with TD and comorbid ADHD and OCD are needed to optimize responses to ICBIT.

RevDate: 2022-01-11

Greulich F, Bielefeld KA, Scheundel R, et al (2021)

Enhancer RNA Expression in Response to Glucocorticoid Treatment in Murine Macrophages.

Cells, 11(1): pii:cells11010028.

Glucocorticoids are potent anti-inflammatory drugs; however, their molecular mode of action remains complex and elusive. They bind to the glucocorticoid receptor (GR), a nuclear receptor that controls gene expression in almost all tissues in a cell type-specific manner. While GR's transcriptional targets mediate beneficial reactions in immune cells, they also harbor the potential of adverse metabolic effects in other cell types such as hepatocytes. Here, we have profiled nascent transcription upon glucocorticoid stimulation in LPS-activated primary murine macrophages using 4sU-seq. We compared our results to publicly available nascent transcriptomics data from murine liver and bioinformatically identified non-coding RNAs transcribed from intergenic GR binding sites in a tissue-specific fashion. These tissue-specific enhancer RNAs (eRNAs) correlate with target gene expression, reflecting cell type-specific glucocorticoid responses. We further associate GR-mediated eRNA expression with changes in H3K27 acetylation and BRD4 recruitment in inflammatory macrophages upon glucocorticoid treatment. In summary, we propose a common mechanism by which GR-bound enhancers regulate target gene expression by changes in histone acetylation, BRD4 recruitment and eRNA expression. We argue that local eRNAs are potential therapeutic targets downstream of GR signaling which may modulate glucocorticoid response in a cell type-specific way.

RevDate: 2022-01-11

Geppert J, Walth AA, Terrón Expósito R, et al (2021)

Aging Aggravates Cachexia in Tumor-Bearing Mice.

Cancers, 14(1): pii:cancers14010090.

BACKGROUND: Cancer is primarily a disease of high age in humans, yet most mouse studies on cancer cachexia are conducted using young adolescent mice. Given that metabolism and muscle function change with age, we hypothesized that aging may affect cachexia progression in mouse models.

METHODS: We compare tumor and cachexia development in young and old mice of three different strains (C57BL/6J, C57BL/6N, BALB/c) and with two different tumor cell lines (Lewis Lung Cancer, Colon26). Tumor size, body and organ weights, fiber cross-sectional area, circulating cachexia biomarkers, and molecular markers of muscle atrophy and adipose tissue wasting are shown. We correlate inflammatory markers and body weight dependent on age in patients with cancer.

RESULTS: We note fundamental differences between mouse strains. Aging aggravates weight loss in LLC-injected C57BL/6J mice, drives it in C57BL/6N mice, and does not influence weight loss in C26-injected BALB/c mice. Glucose tolerance is unchanged in cachectic young and old mice. The stress marker GDF15 is elevated in cachectic BALB/c mice independent of age and increased in old C57BL/6N and J mice. Inflammatory markers correlate significantly with weight loss only in young mice and patients.

CONCLUSIONS: Aging affects cachexia development and progression in mice in a strain-dependent manner and influences the inflammatory profile in both mice and patients. Age is an important factor to consider for future cachexia studies.

RevDate: 2022-01-10

Mikulincer M, PR Shaver (2021)

An attachment perspective on loss and grief.

Current opinion in psychology, 45:101283 pii:S2352-250X(21)00227-X [Epub ahead of print].

Attachment theory provides a useful framework for understanding emotional reactions to separation and loss and the process of adapting to these painful events. In this article, we review adult attachment studies that have examined emotional reactions and adjustment to separation and loss in romantic and marital relationships. We begin with a brief account of attachment theory. Next, we review studies examining the emotional consequences of losing a relationship partner and the coping responses that can help a person adjust to this loss. Throughout the article, we also summarize research documenting attachment-related individual differences in responses to separation and loss. (99 words).

RevDate: 2022-01-10

Pereira C, Martis M, D'Souza R, et al (2021)

Correlation of Clinicopathological Features of Breast Cancer with Molecular Subtypes Taking Ki-67 into Consideration: Single Institution Experience Over 5 Years.

Current health sciences journal, 47(3):348-352.

BACKGROUND: Molecular classification of breast cancer is commonly done to determine response to therapy and cancer prognosis. Aim of the study was to compare prevalence of molecular subtypes of breast cancer in our institute using immunohistochemistry, including Ki-67, and correlate it with clinical and pathological prognostic factors.

RESULTS: 300 cases of invasive breast cancer were included in the study. Average age at time of diagnosis was 44 years and average size of tumor was 3.4cms. Invasive ductal carcinoma was the most common histological type (75.3%). The most common molecular subtype was triple negative (34.3%) followed by Luminal B (33.4%), luminal A (17%) and Her-2 positive (15.3%). Large size and poorly differentiated tumors were predominantly triple negative tumors while lymph node metastasis was most commonly seen in Her-2 positive tumors.

CONCLUSION: Molecular subtype of breast carcinoma should routinely be done for all cases of carcinoma breast as it allows to identify aggressive tumors and target therapy accordingly.

RevDate: 2022-01-09

Aftab F, Ahmed S, Ali SM, et al (2022)

Cohort Profile: The Alliance for Maternal and Newborn Health Improvement (AMANHI) biobanking study.

International journal of epidemiology, 50(6):1780-1781i.

RevDate: 2022-01-09

Kotschi S, Jung A, Willemsen N, et al (2022)

NFE2L1-mediated proteasome function protects from ferroptosis.

Molecular metabolism pii:S2212-8778(22)00005-9 [Epub ahead of print].

OBJECTIVE: Ferroptosis continues to emerge as a novel modality of cell death with important therapeutic implications for a variety of diseases, most notably cancer and degenerative diseases. While susceptibility, initiation, and execution of ferroptosis have been linked to reprogramming of cellular lipid metabolism, imbalances in iron-redox homeostasis, and aberrant mitochondrial respiration, the detailed mechanisms of ferroptosis are still insufficiently well understood.

METHODS AND RESULTS: Here we show that diminished proteasome function is a new mechanistic feature of ferroptosis. The transcription factor nuclear factor erythroid-2, like-1 (NFE2L1) protects from ferroptosis by sustaining proteasomal activity. In cellular systems, loss of NFE2L1 reduced cellular viability after the induction of both chemically and genetically induced ferroptosis, which was linked to the regulation of proteasomal activity under these conditions. Importantly, this was reproduced in a Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) patient-derived cell line carrying mutated glutathione peroxidase-4 (GPX4), a critical regulator of ferroptosis. Also, reduced proteasomal activity was associated with ferroptosis in Gpx4-deficient mice. In a mouse model for genetic Nfe2l1 deficiency, we observed brown adipose tissue (BAT) involution, hyperubiquitination of ferroptosis regulators, including the GPX4 pathway, and other hallmarks of ferroptosis.

CONCLUSION: Our data highlight the relevance of the NFE2L1-proteasome pathway in ferroptosis. Manipulation of NFE2L1 activity might enhance ferroptosis-inducing cancer therapies as well as protect from aberrant ferroptosis in neurodegeneration, general metabolism, and beyond.

RevDate: 2022-01-07

Jeong S, TH Kim (2022)

Diffusion-weighted imaging of breast invasive lobular carcinoma: comparison with invasive carcinoma of no special type using a histogram analysis.

Quantitative imaging in medicine and surgery, 12(1):95-105.

Background: To investigate the imaging findings and visibility of breast invasive lobular carcinoma (ILC) on diffusion-weighted imaging (DWI) and compare quantitative apparent diffusion coefficient (ADC) metrics of ILC and invasive carcinoma of no special type (NST) using a histogram analysis.

Methods: We performed an observational retrospective study of 629 consecutive women with pathologically proven ILC and invasive ductal carcinoma of NST, who underwent 3-T MRI including DWI, between January 2017 and August 2020.

Results: After propensity score matching, 71 women were allocated to each group. On DWI, 9 (12.7%) lesions of ILC and 4 (5.6%) invasive carcinomas of the NST were not visualized. For the tumor visibility on DWI, tumor size, tumor ADC value, and background diffusion grade were significantly associated with the visibility score in both groups (all P<0.05), whereas the mean background ADC value was not significant (P>0.05). The mean ADC (1.226×10-3 vs. 1.052×10-3 mm2/s, P<0.001), median ADC (1.222×10-3 vs. 1.051×10-3 mm2/s, P=0.002), maximum ADC (1.758×10-3 vs. 1.504×10-3 mm2/s, P<0.001), minimum ADC (0.717×10-3 vs. 0.649×10-3 mm2/s, P=0.003), 90th percentile ADC (1.506×10-3 vs. 1.292×10-3 mm2/s, P<0.001) and 10th percentile ADC (0.956×10-3 vs. 0.818×10-3 mm2/s, P=0.008) were higher in ILC than in invasive carcinoma of NST. Additionally, the ADC difference value of the ILC was higher than that of invasive carcinoma of NST (1.04×10-3 vs. 0.855×10-3 mm2/s, P=0.027).

Conclusions: On DWI, the visibility of ILC was lower compared to invasive carcinoma of NST. ILC showed higher quantitative ADC values and higher ADC difference values.

RevDate: 2022-01-06

Rasmussen M, Reddy M, Nolan R, et al (2022)

RNA profiles reveal signatures of future health and disease in pregnancy.

Nature [Epub ahead of print].

Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden1. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method2. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia.

RevDate: 2022-01-05

McLean-Holden AC, Rooper LM, Lubin DJ, et al (2022)

Frankly Invasive Carcinoma Ex-intraductal Carcinoma: Expanding on an Emerging and Perplexing Concept in Salivary Gland Tumor Pathology.

Head and neck pathology [Epub ahead of print].

Intraductal carcinoma (IDC) of the salivary glands is an uncommon and enigmatic tumor, our understanding of which is rapidly evolving. Recent studies have demonstrated multiple IDC subtypes and consistent gene fusions, most frequently involving RET. Because IDC is a ductal proliferation surrounded by flattened myoepithelial cells, it was previously presumed to be analogous to breast ductal carcinoma in situ, but recent evidence has shown that the myoepithelial cells of fusion-positive IDC harbor the same genetic alterations of the ductal cells and are therefore neoplastic. In addition, there are rare reports of fusion-positive IDC with overt areas of irregular invasion lacking myoepithelial cells, but this phenomenon is not well documented or understood. This study aims to better characterize these frankly invasive carcinoma ex-IDC. All cases of frankly invasive carcinoma ex-IDC were obtained from the authors' files. Inclusion criteria included a component of concurrent or antecedent IDC and/or a fusion known to be associated with IDC. Immunohistochemistry (S100, SOX10, mammaglobin, androgen receptor, p63, p40) and molecular analysis (targeted RNA sequencing or large panel DNA next generation sequencing) was performed. Clinical follow-up was obtained from medical records. Ten cases of frankly invasive carcinoma ex-IDC were identified. The tumors occurred in 8 men and 2 women ranging from 33 to 82 years (mean, 66.3). All but one case arose in the parotid gland. In 4 cases, the IDC component was intercalated duct type. It was mixed apocrine/intercalated duct in two, and in the remaining 4 cases, no residual IDC was identified. The frankly invasive carcinomas were remarkably heterogeneous, ranging from minimally to widely invasive beyond the confines of the IDC, low-grade to high-grade, with morphologies that varied from duct-forming to those having clear cell or sarcomatoid features, to frankly apocrine. The original diagnoses for these cases were (adeno) carcinoma, not otherwise specified (n = 6), salivary duct carcinoma (n = 3), and secretory carcinoma (n = 1). All cases harbored fusions: NCOA4::RET (n = 6), TRIM33::RET (n = 2), TRIM27::RET (n = 1), and STRN::ALK (n = 1). Clinically, one tumor recurred locally, cervical lymph node metastases occurred in five patients, and distant metastasis later developed in four of these patients. Our findings highlight striking diversity in frankly invasive carcinomas that arise from fusion-positive IDC, a tumor which may serve as a precursor neoplasm like pleomorphic adenoma. These carcinomas vary in their extent of invasion, grade, histologic appearances, and clinical behavior. Importantly, in contrast to pure IDC, which is believed to be indolent, many frankly invasive cases were aggressive. Because RET and ALK fusions are targetable, it is important to recognize the broad spectrum of frankly invasive carcinomas that can arise from IDC, particularly because some cases are completely overrun or recur without any recognizable IDC component. These results suggest fusion analysis may be of clinical benefit on any salivary gland (adeno) carcinoma, not otherwise specified or salivary duct carcinoma.

RevDate: 2022-01-05

Betlloch-Mas I, Soriano-García T, Boira I, et al (2021)

Cutaneous Metastases of Solid Tumors: Demographic, Clinical, and Survival Characteristics.

Cureus, 13(11):e19970.

BACKGROUND: Cutaneous metastasis (CM), while uncommon, is usually an indicator of poor prognosis. With cancer patients living longer, the incidence of CM has increased, which justifies its analysis.

OBJECTIVES: The objective of this study was to carry out a descriptive study of CM diagnosed for 18 years in a dermatology department of a tertiary care hospital and to assess the epidemiological, clinical, and histological variables that condition them, as well as data on their survival and prognosis.

METHODS: We performed a descriptive study of cases of CM diagnosed over 18 years in the dermatology department of a tertiary referral hospital analyzing the following variables: patient age and sex, site of primary neoplasm, pathochronology, survival time, histological findings, immunohistochemical markers, the anatomical area affected, the clinical appearance of the metastasis, therapeutic plan, and existence of metastases in other regions. We checked normal distribution using the Kolmogorov-Smirnov test and then compared the quantitative variables using the Student's t-test (unpaired samples), Mann-Whitney test (non-normal distribution), analysis of variance (ANOVA; for more than two groups), and categorical variables using the chi-square or Fisher's exact test.

RESULTS: We included 37 cases (20 men and 17 women), of whom 32 had died. The mean age was 62 ± 15 years. CM detection was defined early in 8% of cases, synchronous in 32%, and metachronous in 60%. The most frequent primary tumor sites were lungs (24%), breasts (21%), and bladders (11%). Most metastases were solitary. The most frequent locations for CM were the scalp, trunk, armpits, and groin. Most lesions had a nodular presentation (81%). Squamous cell carcinoma and adenocarcinoma showed the same frequency in lung cancer CM. Breast cancer leading to CM was the most common invasive ductal carcinoma. The most aggressive cases, with the worst survival, originated in lung neoplasms. Therapeutic management for most patients involved surgery in combination with other procedures. The only difference detected between the lung and breast cancer CM was the predominance of lung tumors in men (89%) and breast tumors in women compared with metastases from other sites; breast cancer CM manifested more frequently as plaques and less frequently as nodules (p < 0.05) and was less frequently associated with multisystemic metastasis. In lung cancer CM, time from tumor diagnosis to CM occurrence was shorter (p < 0.01) and multisystemic metastasis was more frequent than in CM of other tumors.

CONCLUSIONS: CM tends to affect patients aged above 60 years and arises predominantly from lung cancer in men and breast cancer in women. The most typical locations are the chest and scalp, and the appearance is usually nodular. Survival after CM detection is low, particularly in lung cancer CM.

RevDate: 2022-01-04

Remmers S, Nieboer D, Rijstenberg LL, et al (2022)

Updating the Rotterdam Prostate Cancer Risk Calculator with Invasive Cribriform and/or Intraductal Carcinoma for Men with a Prior Negative Biopsy.

European urology open science, 36:19-22.

The Rotterdam Prostate Cancer Risk Calculator (RPCRC) is a well-validated tool for upfront risk stratification to reduce the number of prostate biopsies and magnetic resonance imaging scans among both biopsy-naïve and previously biopsied men. The presence of invasive cribriform and/or intraductal carcinoma (CR/IDC) identifies men with aggressive grade group (GG) 2 tumors. This finding was recently incorporated in the RPCRC for biopsy-naïve men to predict the probability of no PCa, indolent PCa (GG 1 disease and GG 2 disease without CR/IDC), and clinically significant PCa (csPCa: GG 2 disease with CR/IDC and higher). The aim of the current study was to update the RPCRC for men with a previous negative biopsy with the presence of CR/IDC. A total of 2215 men were eligible for analyses, of whom 1776 (80%) were not diagnosed with PCa, 358 (16%) were diagnosed with indolent PCa, and 81 (4%) were diagnosed with csPCa according to the original 2014 Gleason grading. The optimism-corrected area under the curve was 0.69 for any PCa and 0.77 for csPCa. With a threshold of 10% for indolent PCa or 1% for csPCa, 20% of all prostate biopsies could be avoided and 2% of all csPCa cases would be missed. Our results support upfront risk stratification with the updated RPCRC.

Patient summary: Risk stratification for men without a prior diagnosis of prostate cancer can reduce the number of prostate biopsies and magnetic resonance imaging scans carried out in this patient population. Our study shows that it is possible to update the Rotterdam Prostate Cancer Risk Calculator for men with a previous negative biopsy with the presence of invasive cribriform and/or intraductal carcinoma.

RevDate: 2022-01-04

Constantin A, Alexandru C, Korte J, et al (2021)

Distributing participation in design: Addressing challenges of a global pandemic.

International journal of child-computer interaction, 28:100255.

Participatory Design (PD) - whose inclusive benefits are broadly recognised in design - can be very challenging, especially when involving children. The recent COVID-19 pandemic has given rise to further barriers to PD with such groups. One key barrier is the advent of social distancing and government-imposed social restrictions due to the additional risks posed for e.g. children and families vulnerable to COVID-19. This disrupts traditional in-person PD (which involves close socio-emotional and often physical collaboration between participants and researchers). However, alongside such barriers, we have identified opportunities for new and augmented approaches to PD across distributed geographies, backgrounds, ages and abilities. We examine Distributed Participatory Design (DPD) as a solution for overcoming these new barriers, during and after COVID-19. We offer new ways to think about DPD, and unpick some of its ambiguities. We do this through an examination of the results from an online Interaction Design and Children (IDC) 2020 workshop. The workshop included 24 researchers with experience in PD, in a range of forms, in the context of children. Initially designed to take place in-person and to include a design session with children in a school in London, the workshop was adjusted to an online format in response to the COVID-19 pandemic. Despite the adverse circumstances, we discovered that the unexpected change of the workshop style from in-person to online was an opportunity and an impetus for us to address the new PD challenges of the global pandemic. In this article we contribute seven themes which were revealed during our IDC workshop, providing guidance on important areas for consideration when planning and conducting PD in the context of a global pandemic. With a focus on the term 'distributed', we offer insights on how DPD can be applied and explored in these circumstances with child participants. We conclude with a number of lessons learned, highlighting the opportunities and challenges DPD offers to enable continued co-design during a global pandemic. In particular, DPD provides greater access for some populations to be involved in PD, but technical and social challenges must be addressed.

RevDate: 2022-01-04

Rafiq MT, Hamid MSA, E Hafiz (2021)

Short-Term Effects of Strengthening Exercises of the Lower Limb Rehabilitation Protocol on Pain, Stiffness, Physical Function, and Body Mass Index among Knee Osteoarthritis Participants Who Were Overweight or Obese: A Clinical Trial.

TheScientificWorldJournal, 2021:6672274.

Background: Osteoarthritis (OA) of the knee is defined as a progressive disease of the synovial joints and is characterized by wear and tear of the cartilage and underlying bone. This study aimed to determine the short-term effects of the lower limb rehabilitation protocol (LLRP) on pain, stiffness, physical function, and body mass index (BMI) among knee OA participants who were overweight or obese. Methodology. A single-blinded randomized controlled trial of one-month duration was conducted at Rehmatul-Lil-Alameen Postgraduate Institute, Lahore, Pakistan. Fifty overweight or obese participants with knee OA were randomly divided into two groups by a computer-generated number. Participants in the rehabilitation protocol group (RPG) were provided with leaflets explaining the strengthening exercises of the LLRP and instruction of daily care (IDC), while the participants in the control group (CG) were provided with leaflets explaining the IDC only for a duration of four weeks. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness, and physical function. The secondary outcome measures were BMI, exercise adherence, and patients' satisfaction assessed by using the numeric rating scale ranging from 0 to 10. The paired-sample t-test was used to analyze the differences within groups from baseline to posttest evaluations. The analysis of variance 2 × 2 factor was used to analyze the differences in BMI, knee pain, stiffness, and physical function between the groups.

Results: Participants in the RPG and CG reported a statistically significant reduction in knee pain and stiffness (p ≤ 0.05) within the group. The reduction in the scores of knee pain was higher in participants in the RPG than that in participants in the CG (p=0.001). Additionally, participants in the RPG reported greater satisfaction (p=0.001) and higher self-reported exercise adherence (p=0.010) and coordinator-reported exercise adherence (p=0.046) than the participants in the CG.

Conclusion: Short-term effects of the LLRP appear to reduce knee pain and stiffness only, but not physical function and BMI.

RevDate: 2022-01-04
CmpDate: 2022-01-04

Salih MM, Higgo AA, EM Eed (2022)

Prognostic Significance of p16 Protein Expression in Breast Cancer.

In vivo (Athens, Greece), 36(1):336-340.

BACKGROUND/AIM: Breast cancer is the most common cancer in Sudan. The p16 protein plays a vital role in the regulation of the cell cycle.

PATIENTS AND METHODS: This study analysed the protein expression of p16 in 202 paraffin blocks from Sudanese women with breast cancer using immunohistochemistry.

RESULTS: This study included 168 (83.2%), 16 (7.9%), and 18 (8.9%) patients with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. There were 95 cases (47.0%) with grade III, 70 cases (34.6%) with grade II, and 23 cases (11.4%) with grade I breast cancer. The hormone receptor status was available for 119 of the cases, and 31 (15.3%), 25 (12.4%), and 63 (31.2%) cases were positive for oestrogen, progesterone, and HER2 receptors, respectively.

CONCLUSION: p16 protein expression was associated with high histologic grade, lymph node metastasis, and poor prognosis. p16 protein expression may potentially be used as a prognostic marker.

RevDate: 2021-12-30

Abbasi A, Rahimi S, Mahmoudzadeh L, et al (2021)

High grade breast ductal carcinomas have high density of tumor-associated macrophages.

Experimental oncology, 43(4):328-330.

BACKGROUND: The role of tumor-associated macrophages (TAMs) is double-natured and still controversial. Depending on different settings, macrophages may suppress or promote tumor growth. TAM density may be one of the predictive factors of treatment outcome in cancer patients.

AIM: To evaluate the density of tumor-associated macrophages in breast cancer and its relationship with various histopathologic findings.

MATERIALS AND METHODS: 55 patients with invasive ductal carcinoma of breast who underwent mastectomy were enrolled. Sections of tumor samples were stained and the density of CD68+ cells was evaluated.

RESULTS: There was an association between estrogen receptor (ER) expression and CD68 density (p = 0.010) as the higher densities of CD68 were seen in ER negative tumors. Moreover, there was a significant relationship between histological grade and CD68 density (p = 0.006).

CONCLUSION: The higher TAM density is associated with higher tumor grade and negative ER expression in breast cancer tissues. These findings revealed that inflammation could have an important role in malignancies.

RevDate: 2021-12-29

Mikoshi A, Miyai K, Hamabe F, et al (2021)

MRI-detectability and histological factors of prostate cancer including intraductal carcinoma and cribriform pattern.

The Prostate [Epub ahead of print].

BACKGROUND: Histopathological characteristics affecting the detectability of clinically significant prostate cancer (csPCa) on magnetic resonance imaging (MRI) remain unclear. This study aimed to compare the histopathology between MRI-detectable and MRI-undetectable cancers, emphasizing intraductal carcinoma of the prostate (IDC-P) and predominant Gleason pattern 4 subtype.

METHODS: This single-center retrospective study enrolled 153 consecutive patients with 191 lesions who underwent preoperative multiparametric MRI and subsequent radical prostatectomy. MRI/histopathological findings and area fractions of histological components (cancer cells, stroma, and luminal spaces) of MRI-detectable and MRI-undetectable cancers were compared. Data were analyzed using Fisher's exact, independent t, or Mann-Whitney U tests.

RESULTS: Overall, 148 (77%) and 43 (23%) cancers were MRI-detectable and MRI-undetectable, respectively. MRI-detectable cancers were significantly larger than MRI-undetectable cancers (p = 0.03). The percentage of lesions in Grade Group 3 or higher was significantly higher among MRI-detectable cancers than among MRI-undetectable cancers (p = 0.02). MRI detectability of csPCa was associated with increases in relative area fractions of cancer cells (p < 0.001) and decreases in those of stroma (p < 0.001) and luminal spaces (p < 0.001) in prostate cancer (PCa) than the percentage of Gleason pattern 4 (p = 0.09). The percentage of lesions containing IDC-P was similar for MRI-detectable and MRI-undetectable cancers (40% vs. 33%; p = 0.48). The distribution of cribriform gland subtypes was not significantly different between MRI-detectable and MRI-undetectable Gleason pattern 4 subtype cancers (p > 0.99). Contrarily, the ratio of fused gland subtype was significantly higher in MRI-detectable than in MRI-undetectable cancers (p = 0.03). Furthermore, the ratio of poorly-formed gland subtype was significantly higher in MRI-undetectable than in MRI-detectable cancers (p = 0.01).

CONCLUSIONS: MRI detectability of csPCa is strongly associated with the relative area fractions of cancer cells, stroma, and luminal spaces in PCa rather than conventional histopathological parameters. Neither the presence nor the percentage of IDC-P affected MRI detectability.

RevDate: 2021-12-29

Azhar M, Hamdani SAM, Iftikhar J, et al (2021)

An Unusual Occurrence of Uterine Metastases in a Case of Invasive Ductal Breast Carcinoma.

Cureus, 13(11):e19820.

Breast cancer is the most frequent cancer in women and has a high proclivity for metastasizing, yet it seldom affects gynaecological organs. We present a case of invasive ductal carcinoma of the breast that metastasized to the uterus following initial curative treatment. Our patient was taking tamoxifen, which can induce endometrial hyperplasia and make diagnosis more complicated.

RevDate: 2021-12-25

Adachi Y, Katsuki T, Sasaguri T, et al (2021)

Invasive cribriform carcinoma of the breast detected incidentally on computed tomography: A case report.

Clinical case reports, 9(12):e05214.

Invasive cribriform carcinoma is a rare type of invasive breast carcinoma, and a few cases have been reported. Its features are a cribriform pattern resembling the histological structures of cribriform ductal carcinoma in situ and an excellent prognosis. However, the extent of progress for intraductal extension must be carefully evaluated.

RevDate: 2021-12-24

Mthembu JG, M Bhuiyan (2021)

Profile of molecular subtyping of breast cancer and clinicopathological features in Mankweng Hospital breast oncology clinic, Limpopo Province, South Africa.

South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 111(11b):1132-1135.

BACKGROUND: Breast cancer is recognised as a heterogeneous disorder, comprising a number of subcategories of several cellular compositions, molecular alterations as well as clinical behaviour. Across the world, research has been able to show that the most common molecular subtype is luminal A, followed by triple negative and human epidermal receptor 2 (HER2)-positive (non-luminal) subtype. However, another study found that the most common molecular subtype was HER2/neu amplification, suggesting that subtypes case frequencies differ in different people.

OBJECTIVES: To determine the case frequency of molecular subtypes of breast cancers and the associated clinicopathological features in women from Limpopo Province, South Africa.

METHOD: We performed a retrospective, cross-sectional descriptive study from July 2021 - June 2021 at Mankweng Hospital breast oncology clinic. The inclusion criterion was all women with histologically confirmed breast cancer.

RESULT: We identified 222 women who met the inclusion criteria, and the age range (median) was 25 - 91 (54.8) years. The majority of the women came from the Vhembe district (28%; n=62), followed by Capricorn district (26%; n=59), Mopani district (17%; n=38), Sekhukhune district (16%; n=35), and Waterberg district (13%; n=28). Histology revealed that the most common type was invasive ductal carcinoma (no special type; 91.44%; n=203), followed by invasive mucinous carcinoma (4%; n=9). The most predominant molecular subtype was luminal B (48.19%; n=107), followed by luminal A (22.97%; n=51), triple negative (17.12%; n=38) and 11.75% (n=26) overexpressed HER2. More than one-third of the cancers were HER2-positive (40.54%; n=90), and 59.46% (n=132) were HER2-negative. The majority of patients presented with late-stage cancer (62.16%; n=138), and the rest presented with early-stage (I and II) disease (37.84%; n=84).

CONCLUSION: The majority of our patients had luminal subtypes and hormonal receptor-positive breast cancers, which should be associated with very good clinical outcomes. However, the majority of patients presented late with advanced-stage disease and high Ki-67 expression. Therefore, research is required to help us understand why in our context patients present late with advanced-stage disease.

RevDate: 2021-12-24

Mavhungu R, Bhuiyan M, F Ooko (2021)

Profile of patients seen at Pietersburg and Mankweng breast cancer clinics in Limpopo.

South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 111(11b):1129-1131.

BACKGROUND: Breast cancer is the most common cancer diagnosed among women worldwide. It is the most prevalent cancer and leading cause of death among South African (SA) women. The increasing incidence of breast cancer is a major health concern. Until now, the distribution of breast cancer demography, stage at first presentation, and histological characterisation have not been studied in Limpopo Province, SA.

OBJECTIVES: To record the demographic profile of breast cancer patients, to report the stage at the time of presentation and to characterise the pattern of malignant disease in Limpopo, SA.

METHODS: We conducted a retrospective descriptive review of the records of patients managed at Pietersburg Hospital oncology and Mankweng Hospital breast cancer clinics during the period 1 March 2015 - 28 February 2017. Stata was used to analyse data.

RESULTS: A total of 248 patients with a mean age of 55 years were included for analysis, 7 males (3%) and 241 females (97%). Capricorn and Vhembe districts constituted 32% and 27% respectively. The majority (69%) of patients were diagnosed with disease stage III or IV. The most common histological type was invasive ductal cell carcinoma (IDC) (87%).

CONCLUSIONS: More than one-third of patients were younger than 50 years. The majority (69%) had an advanced breast cancer (stage III or IV). We recommend provision of mammography services in regional hospitals.

RevDate: 2021-12-24

Zhang J, Sum SY, Hsu JG, et al (2021)

Adjuvant Whole Breast Radiotherapy Improve Survival in Women with Heart Failure with Reduced Ejection Fraction Receiving Breast-Conserving Surgery.

Journal of personalized medicine, 11(12): pii:jpm11121358.

BACKGROUND: to date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF).

PATIENTS AND METHODS: we included 294 women with left-breast IDC at clinical stages IA-IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs).

RESULTS: in the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.60; 95% confidence interval [CI]: 0.44-0.94) was a significant independent prognostic factor for all-cause death (p = 0.0424), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.33 (0.24-0.71; p = 0.0017) and 0.37 (0.22-0.63; p = 0.0004), respectively, compared with the non-adjuvant WBRT group.

CONCLUSION: Adjuvant WBRT was associated with a decrease in all-cause death, LRR, and DM in women with left IDC and HFrEF compared with non-adjuvant WBRT.

RevDate: 2021-12-24

Diop MK, Albadine R, Kougioumoutzakis A, et al (2021)

Identification of Morphologic Criteria Associated with Biochemical Recurrence in Intraductal Carcinoma of the Prostate.

Cancers, 13(24): pii:cancers13246243.

Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer strongly associated with an increased risk of biochemical recurrence (BCR). However, approximately 40% of men with IDC-P remain BCR-free five years after radical prostatectomy. In this retrospective multicenter study, we aimed to identify histologic criteria associated with BCR for IDC-P lesions. A total of 108 first-line radical prostatectomy specimens were reviewed. In our test cohort (n = 39), presence of larger duct size (>573 µm in diameter), cells with irregular nuclear contours (CINC) (≥5 CINC in two distinct high-power fields), high mitotic score (>1.81 mitoses/mm2), blood vessels, and comedonecrosis were associated with early BCR (<18 months) (p < 0.05). In our validation cohort (n = 69), the presence of CINC or blood vessels was independently associated with an increased risk of BCR (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.09-4.96, p = 0.029). When combining the criteria, the presence of any CINC, blood vessels, high mitotic score, or comedonecrosis showed a stronger association with BCR (HR 2.74, 95% CI 1.21-6.19, p = 0.015). Our results suggest that IDC-P can be classified as low versus high-risk of BCR. The defined morphologic criteria can be easily assessed and should be integrated for clinical application following validation in larger cohorts.

RevDate: 2021-12-23

Tan CMP, Kaliya-Perumal AK, Ho GWK, et al (2021)

Postoperative Urinary Retention Following Thoracolumbosacral Spinal Fusion: Prevalence, Risk Factors, and Outcomes.

Cureus, 13(11):e19724.

Objective Postoperative urinary retention (POUR) is an often-underestimated common complication following spine surgery, and it is essential to avoid its untoward long-term consequences. Besides, a dilemma exists regarding the appropriate timing for the postoperative removal of indwelling catheter (IDC). Hence, we aim to describe the prevalence, risk factors, and outcomes of POUR and also come up with recommendations for the removal of IDC. Methods Electronic records of patients who underwent elective thoracolumbosacral spinal fusion surgery from January 2017 to December 2019 were retrospectively reviewed. Excluded were those who underwent fusion for indications such as trauma, cauda equina syndrome, infection, and malignancy. Both surgery-related and patient-related risk factors were tabulated, and their association with the likely development of POUR was assessed by univariate and multivariate analysis. Results One hundred sixty-eight patients (median age=64.1 years; 58.9% female) were included, with the incidence of POUR being 7.8%. Our findings suggest surgery-related factors, both intra- and postoperative, including operating time (p=0.008), anesthetic time (p=0.005), number of fusion levels (p<0.001), mobilization status prior to trial off catheter (TOC; p=0.021), and TOC timing (p=0.029) may have an association with POUR. In addition, patient-related factors, including the use of beta-blockers (p=0.020) and pre-operative mobility status (p<0.001), may also be associated with the likely development of POUR. Conclusion POUR seems to be a frequent complication following thoracolumbosacral spinal fusion surgery, which was found to have an association with some surgery-related and patient-related factors. While most of these factors are non-modifiable, certain modifiable risk factors provide the surgeon an opportunity to prevent POUR. Considering these factors, we recommend appropriate and timely mobilization of the patient prior to removal of IDC, which is to be performed preferably in the daytime.

RevDate: 2021-12-23

Tarrab R, Sabouni R, Jarad L, et al (2021)

Metachronous breast cancer in a male with previous history of liposarcoma: A case report from Syria.

Annals of medicine and surgery (2012), 72:103151.

Introduction: Multiple primary cancers (MPC) are defined as the occurrence of two or more non-related cancers. The acquiring of male breast cancer (MBC) as secondary cancer in a sequence of MPC is extremely rare. Only one case of breast cancer following liposarcoma (LP) was previously reported in a female patient. We report the first case of MBC following LP.

Case presentation: A non-smoker male patient with a history of a well-differentiated liposarcoma was treated surgically and with radiotherapy 14 years ago with no signs of recurrence. The patient presented with a left breast mass; The excisional biopsy showed poorly differentiated grade III invasive ductal carcinoma. The patient underwent a mastectomy with axillary node resection and the final diagnosis was invasive ductal carcinoma stage IIA [T:2, N:0, M:0]. The tumor markers reported; Positive Estrogen Receptor (ER+), negative Progesterone Receptor (PR-), and negative Human Epidermal Receptor (HER-). He received eight sessions of chemotherapy with Docetaxel and 16 fractions of radiotherapy. The follow-up showed no signs of recurrence.

Discussion: Despite the rarity of diagnosis MBC as a second primary. Studies have found a relation between different types of breast cancer in male patients, and further, a relation was also found between MBC and lymphoma. While no studies that link MBC and LP were previously reported.

Conclusion: We found that acquiring a treated LP would not affect the MBC prognosis or its response to treatment, yet further studies are needed to confirm this outcome.

RevDate: 2021-12-22

Abel MK, Shui AM, Melisko M, et al (2021)

The incidence of discordant clinical and genomic risk in patients with invasive lobular or ductal carcinoma of the breast: a National Cancer Database Study.

NPJ breast cancer, 7(1):156.

When molecular testing classifies breast tumors as low risk but clinical risk is high, the optimal management strategy is unknown. One group of patients who may be more likely to have such discordant risk are those with invasive lobular carcinoma of the breast. We sought to examine whether patients with invasive lobular carcinoma are more likely to have clinical high/genomic low-risk tumors compared to those with invasive ductal carcinoma, and to evaluate the impact on receipt of chemotherapy and overall survival. We conducted a cohort study using the National Cancer Database from 2010-2016. Patients with hormone receptor positive, HER2 negative, stage I-III breast cancer who underwent 70-gene signature testing were included. We evaluated the proportion of patients with discordant clinical and genomic risk by histology using Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models with and without propensity score matching. A total of 7399 patients (1497 with invasive lobular carcinoma [20.2%]) were identified. Patients with invasive lobular carcinoma were significantly more likely to fall into a discordant risk category compared to those with invasive ductal carcinoma (46.8% versus 37.1%, p < 0.001), especially in the clinical high/genomic low risk subgroup (35.6% versus 19.2%, p < 0.001). In unadjusted analysis of the clinical high/genomic low-risk cohort who received chemotherapy, invasive ductal carcinoma patients had significantly improved overall survival compared to those with invasive lobular carcinoma (p = 0.02). These findings suggest that current tools for stratifying clinical and genomic risk could be improved for those with invasive lobular carcinoma to better tailor treatment selection.

RevDate: 2021-12-21

Gebretsadik A, Bogale N, DG Negera (2021)

Epidemiological Trends of Breast Cancer in Southern Ethiopia: A Seven-Year Retrospective Review.

Cancer control : journal of the Moffitt Cancer Center, 28:10732748211055262.

INTRODUCTION: African women are affected by cancer at an early age of their productivity. However, the exact prevalence and incidence of cancer, including breast cancer is not known in most sub-Saharan African countries, including Ethiopia because of lack of well-established cancer registry. This study aims to assess the epidemiology of breast cancer at Hawassa University Comprehensive Specialized Hospital (HUCSH), the biggest referral hospital with cancer treatment center serving the southern part of the country.

METHODS: Retrospective review of charts of all patients with a diagnosis of breast cancer between 2013 and 2019 at HUCSH was conducted. A standardized questionnaire was used to collect relevant data that include sociodemographic, symptoms, type of diagnosis, treatment, and outcomes. Data were entered using epidata version 3.1 and analyzed using MS Excel and SPSS version 20.

RESULTS: Five hundred fifty-nine (18.6%) breast cancer cases were retrieved in 7 years between 2013 and 2019. Of this, 548 (98%) were women. The median ages of the patents were 38 years. Invasive ductal carcinoma was the leading 309 (55.3%) histologic type followed by 185 (33.1%) lobular carcinoma. One hundred seventy-seven (31.7%) were moderately differentiated and 155 (27.7%) were poorly differentiated. Three hundred seventy-two (66.5%) were advanced breast cancer (Stages III and IV). Trends of breast cancer showed the case load is continuously increasing except with a slight reduction of cases in between 2015 and 2016. The majority were advanced breast cancer occurring at an early age by the time diagnosis made. Invasive ductal carcinomas were the predominant one. The trend also showed a continuous increment of cancer case load. Therefore, cancer registration center establishment, community awareness creation, and intensive early detection strategy are mandatory.

RevDate: 2021-12-20

Worthmann A, A Bartelt (2021)

MALDI MSI for a fresh view on atherosclerotic plaque lipids.

RevDate: 2021-12-20

Zhang L, Cheng M, Chen Y, et al (2021)

Visualization positioning-guided biopsy of suspicious breast microcalcifications: a retrospective cohort study.

Annals of translational medicine, 9(21):1620.

Background: At present, most histological evaluations of microcalcifications without a mass are performed using X-ray guided hook wire localization or vacuum-assisted stereotactic biopsy (VASB), but there are still several limitations to these techniques. Therefore, we designed a visualization positioning technique based on three directions of mammography to accurately locate suspected microcalcifications to guide the biopsy.

Methods: We retrospectively analyzed consecutive patients with suspicious microcalcifications who underwent visualization positioning-guided biopsy (VPB) from June 1, 2016, to June 1, 2021. The visualization positioning technique was performed using an electronic ruler to measure the vertical distance from the microcalcification core to the vertical lines on mammography.

Results: A total of 133 patients (median age 46 years; range, 22-87 years) who underwent VPB were included in our study. Among the 133 cases of microcalcifications based on pathological results, 104 were benign, 14 were high risk, and 15 were malignant. In 124 (93.2%) patients, microcalcification was confirmed during the first round of VPB specimen analysis. Only 6 (4.5%) and 3 (2.3%) patients underwent second and third extended resections, respectively, as the resected specimens did not contain microcalcifications. Four patients (3.0%) with malignant biopsy results underwent a subsequent operation. Two patients with DCIS underwent mastectomy and sentinel lymph node biopsy because of diffuse calcification. One patient had no residual cancer, and the other was upgraded to invasive ductal carcinoma (IDC). Two patients with IDC underwent breast-conserving surgery and mastectomy with sentinel lymph node biopsy.

Conclusions: VPB can be used to evaluate breast microcalcifications when a mass is not present, making it an effective diagnostic technique.

RevDate: 2021-12-20

Yu Y, Wang R, Deng J, et al (2021)

Invasive micropapillary carcinoma of mixed breast cancer metastasizing to the cervical region and thyroid: report of a rare case.

Gland surgery, 10(11):3141-3146.

While the incidence of metastatic breast cancer tumors in the thyroid gland is extremely rare, invasive micropapillary carcinoma (IMPC) of the breast metastasizing to the thyroid gland is even rarer. There are no known reported cases in which both invasive ductal carcinoma-no special type (IDC-NST) and IMPC existed in the breast tissue and where only the latter metastasized into the thyroid gland. This report details the case of a 59-year-old Chinese woman who was first diagnosed with grade 2 IDC-NST of the breast with involvement of 6 axillary lymph nodes in 2015. However, 5 years later, blood tests revealed increased tumor markers. Imaging revealed multiple solid nodules in both sides of the thyroid gland. Total thyroidectomy and bilateral cervical lymph node dissection were performed; the findings showed both IDC-NST and IMPC in the lymph nodes, but only the latter in the thyroid gland. Immunohistochemically, these tumor cells were positive for estrogen receptor (ER), progesterone receptor (PR), GATA binding protein 3 (GATA3), and mammaglobin, but negative for thyroglobulin (TG) and thyroid transcription factor-1 (TTF-1). Ultimately, the patient was diagnosed as having mixed breast cancer with metastatic IMPC in the thyroid gland, and chemotherapy was continued. Apart from the possibility of IDC-NST in breast tissue metastasizing to the thyroid, metastasis of IMPC of the breast must also be taken into consideration, especially when the patient has a history of breast cancer and thyroid nodules. Accurate diagnosis of metastatic breast carcinoma is vital for precise treatment and can improve the prognosis of patients.

RevDate: 2021-12-20

Rana MK, Rana APS, U Khera (2021)

Expression of p53 and p16 in Carcinoma Breast Tissue: Depicts Prognostic Significance or Coincidence.

Cureus, 13(11):e19395.

Breast cancer remains the most common malignancy among the Indian female population. The p16 and p53 genes are frequently mutated in breast cancer. Therefore, we aimed to evaluate the prognostic significance of p16 and p53 overexpression in breast cancer and their correlation with various traditional prognostic parameters. Total of 100 confirmed cases of breast cancers were selected. Patients who underwent chemotherapy treatment were excluded from the study. Estrogen receptor (ER), progesterone receptor (PR), and Her2neu immunohistochemistry were performed. The p16 and p53 immunohistochemistry was performed on all cases and association with various clinicopathologic parameters was determined. The mean age of carcinoma breast was 53.3+11.6 with age ranging from 28 to 82 years. On histopathological examination, 93% of cases were of invasive ductal cell carcinoma (IDC) with majority of grade I (43%). Only 14% of cases showed positive p53 expression and 19% of cases showed positive p16 expression. P16 was seen in a very significant correlation with p53 expression in all breast carcinoma cases (<0.002). p53 expression showed a positively significant (<0.05) correlation with age and grade III. The p16 expression was seen significantly correlated with low mitotic activity index (MAI) only. The p53 over-expression was seen in worse prognostic factors such as high tumor grade, Her2neu and triple-negative expression suggested its potential role in pathogenesis of carcinoma breast. In addition, high expression of p16 seen in low mitotic count and Her2neu expression also emphasized the role of this biomarker and recommends further molecular-based research.

RevDate: 2021-12-20

Szepsenwol O, Simpson JA, Griskevicius V, et al (2021)

The effects of childhood unpredictability and harshness on emotional control and relationship quality: A life history perspective.

Development and psychopathology pii:S0954579421001371 [Epub ahead of print].

Being able to control oneself in emotionally upsetting situations is essential for good relationship functioning. According to life history theory, childhood exposure to harshness and unpredictability should forecast diminished emotional control and lower relationship quality. We examined this in three studies. In Studies 1 and 2, greater childhood unpredictability (frequent financial, residential, and familial changes), but not harshness (low SES), was associated with lower emotional control in adolescents (N = 1041) and adults (N = 327). These effects were stronger during the participants' reproductive years. Moreover, in Study 2, greater childhood unpredictability was indirectly associated with lower relationship quality through lower emotional control. In study 3, we leveraged the Minnesota Longitudinal Study of Risk and Adaptation (N = 160). Greater early-life unpredictability (ages 0-4) prospectively predicted lower relationship quality at age 32 via lower emotional control at the same age. This relation was serially mediated by less supportive observed early maternal care (ages 1.5-3.5) and insecure attachment representations (ages 19 and 26). Early unpredictability also predicted greater observed emotional distress during conflict interactions with romantic partners (ages 19-36). These findings point to the role of emotional control in mediating the effects of unpredictable childhood environments on relationship functioning in adulthood.

RevDate: 2021-12-17

Avci O, Tacar SY, Seber ES, et al (2021)

Breast cancer in young and very young women; Is age related to outcome?.

Journal of cancer research and therapeutics, 17(6):1322-1327.

Background: Breast cancer in young women is associated with aggressive biology. We analyzed histopathological and clinical properties of breast cancer patients diagnosed at ≤40 years of age.

Methods: Breast cancer patients who were admitted between 2015 and 2019 were included. Baseline characteristics of the patients with treatment-related outcomes were assessed. The study group was divided into two subgroups; <35 years old as "very young" and ≥35 years old as "young."

Results: The data of 137 patients (60 patients <35 years) were reviewed. The mean age was 34.7 years. The mean follow-up duration was 44.45 ± 26.39 months, and the mean disease-free survival was 36.17 ± 21.97 months. 11.4% of the patients were diagnosed with Stage 4 disease. Pathologic subtype was invasive ductal carcinoma in 86% of patients. 16.8% of the patients were luminal A, 38.7% luminal B, 30.5% were human epidermal growth factor receptor-2-positive type, and 15.3% were triple-negative. Only 5 (3.3%) patients had given birth after chemotherapy. During the follow-up period of early-staged diagnosed patients, metastatic disease occurred in 24.6%. The rate of distant metastasis development was statistically higher in the very young group (31% vs. 11%; P = 0.004). Thirteen patients (10.7%) died due to disease progression. Thirty-seven percent of the patients had a positive family history for either breast or ovarian cancer.

Conclusions: Very young breast cancer patients seem to have a more aggressive disease course. The low rate of childbearing in this young patient population is conspicuous. An interdisciplinary approach for the management of this special patient population should be taken into consideration.

RevDate: 2021-12-20
CmpDate: 2021-12-20

Cai W, Zhuang Y, Chen J, et al (2021)

[Effect of postmastectomy radiotherapy on survival outcomes of patients with metaplastic breast cancer].

Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 41(11):1733-1740.

OBJECTIVE: To evaluate the effect of postmastectomy radiotherapy (PMRT) on the overall survival (OS) and breast cancer-specific survival (BCSS) of patients with metaplastic breast cancer (MpBC) in comparison with those of patients with invasive ductal breast carcinoma (IDC).

METHODS: We selected the patients with pathologically confirmed MpBC and IDC who either received PMRT or not from the archived cases (from January, 1998 to December, 2016) in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. In total, 31 982 patients were selected, including 308 patients with MpBC and PMRT, 629 with MpBC and PMRT, and 31 045 with IDC and PMRT. All the included patients were above 18 years of age without distant metastases or a second primary cancer and underwent radical surgery. Baseline characteristics of the patients were compared among the 3 subgroups, and multivariate Cox regression and Kaplan-Meier analyses were performed for analyzing the prognostic factors of MpBC, OS, and BCSS.

RESULTS: The majority (81.2%) of patients with MpBC were older than 50 years, had pathological grade III (68%), and were negative for ER (75.9%) and PR (79.8%) and in stage T2-3 (71.3%) and N0-1 (85.6%). Multivariate Cox regression analysis showed that age, T stage, N stage, PMRT, and chemotherapy were significantly associated with the prognosis of patients with MpBC (P < 0.05), while pathological grade, ER status, or PR status did not significantly affect the prognosis (P>0.05). Kaplan-Meier analysis showed that the patients with MpBC and PMRT had better OS (HR=1.394, 95% CI: 1.125-1.727; P < 0.05) and BCSS (HR=1.390, 95% CI: 1.074-1.800; P < 0.05) than those with MpBC who did not receive PMRT; but after PMRT, the patients with MpBC had worse OS (HR=1.626, 95%CI: 1.386-1.908; P < 0.001) and BCSS (HR=1.710, 95% CI: 1.418-2.062; P < 0.001) as compared with those with IDC.

CONCLUSION: MpBC has unique clinicopathological features. In patients with MpBC, age, T stage, N stage, radiotherapy and chemotherapy are all the prognostic factors affecting the survival outcomes, and PMRT can improve the OS and BCSS of the patients.

RevDate: 2021-12-13

Kopf S, Kumar V, Kender Z, et al (2021)

Diabetic Pneumopathy-A New Diabetes-Associated Complication: Mechanisms, Consequences and Treatment Considerations.

Frontiers in endocrinology, 12:765201.

Patients with diabetes are over-represented among the total cases reported with "idiopathic" pulmonary fibrosis (IPF). This raises the question, whether this is an association only or whether diabetes itself can cause pulmonary fibrosis. Recent studies in mouse models of type 1 and type 2 diabetes demonstrated that diabetes causes pulmonary fibrosis. Both types of diabetes trigger a cascade, starting with increased DNA damage, an impaired DNA repair, and leading to persistent DNA damage signaling. This response, in turn, induces senescence, a senescence-associated-secretory phenotype (SASP), marked by the release of pro-inflammatory cytokines and growth factors, finally resulting in fibrosis. Restoring DNA repair drives fibrosis into remission, thus proving causality. These data can be translated clinically to patients with type 2 diabetes, characterized by long-term diabetes and albuminuria. Hence there are several arguments, to substitute the term "idiopathic" pulmonary fibrosis (IPF) in patients with diabetes (and exclusion of other causes of lung diseases) by the term "diabetes-induced pulmonary fibrosis" (DiPF). However, future studies are required to establish this term and to study whether patients with diabetes respond to the established therapies similar to non-diabetic patients.

RevDate: 2021-12-13

Somerville LAL, List RP, Compton MH, et al (2021)

Real-World Outcomes in Cystic Fibrosis Telemedicine Clinical Care in a Time of a Global Pandemic.

Chest pii:S0012-3692(21)04444-5 [Epub ahead of print].

BACKGROUND: During the COVID-19 pandemic, the University of Virginia adult cystic fibrosis (CF) center transitioned from in-person clinical encounters to a model that included interdisciplinary telemedicine. The pandemic presented an unprecedented opportunity to assess the impact of the interdisciplinary telemedicine model on clinical CF outcomes.

RESEARCH QUESTION: What are the clinical outcomes of a care model that includes interdisciplinary telemedicine (IDC-TM) compared to in-person clinical care for persons with cystic fibrosis during the COVID-19 pandemic?

STUDY DESIGN AND METHODS: Adults with CF were included. Pre-pandemic year (PPY) was defined as March 17, 2019 through March 16, 2020 and pandemic year (PY) as March 17, 2020 through March 16, 2021. Subjects were enrolled starting in PY. Pre-pandemic data were gathered retrospectively. Telemedicine visits were defined as clinical encounters via secured video communication. Hybrid visits were in-person evaluations by physician, with in-clinic video communication by other team members. In-person visits were encounters with in-person providers only. All encounters included pre-visit screening. Outcomes were lung function, BMI, exacerbations, and antibiotic use. %FEV1, exacerbations, and antibiotic use were adjusted for the effect of elexacaftor/ tezacaftor/ ivacaftor (ETI).

RESULTS: 124 subjects participated. 110 subjects were analyzed (mean age 35, range 18-69). 95% had access to telemedicine (n=105). Telemedicine visits accounted for 64% of encounters (n=260), hybrid visits with telemedicine support 28% (n=114), and in-person visits 7% (n=30). There was no difference in lung function or exacerbation rate during PY. BMI increased from 25 to 26 (t100 = -4.72, P < 0.001). Antibiotic use decreased from 316 episodes to 124 (z = 8.81, P < 0.0001).

INTERPRETATION: This CF care model which includes IDC-TM successfully monitored lung function and BMI, identified exacerbations, and followed guidelines-based care during the pandemic. A significant decrease in antibiotic use suggests social mitigation strategies were protective.

RevDate: 2021-12-11

Mohr H, Foscarini A, Steiger K, et al (2021)

Imaging pheochromocytoma in small animals: preclinical models to improve diagnosis and treatment.

EJNMMI research, 11(1):121.

Pheochromocytomas (PCCs) and paragangliomas (PGLs), together referred to as PPGLs, are rare chromaffin cell-derived tumors. They require timely diagnosis as this is the only way to achieve a cure through surgery and because of the potentially serious cardiovascular complications and sometimes life-threatening comorbidities that can occur if left untreated. The biochemical diagnosis of PPGLs has improved over the last decades, and the knowledge of the underlying genetics has dramatically increased. In addition to conventional anatomical imaging by CT and MRI for PPGL detection, new functional imaging modalities have emerged as very useful for patient surveillance and stratification for therapy. The availability of validated and predictive animal models of cancer is essential for translating molecular, imaging and therapy response findings from the bench to the bedside. This is especially true for rare tumors, such as PPGLs, for which access to large cohorts of patients is limited. There are few animal models of PPGLs that have been instrumental in refining imaging modalities for early tumor detection, as well as in identifying and evaluating novel imaging tracers holding promise for the detection and/or treatment of human PPGLs. The in vivo PPGL models mainly include xenografts/allografts generated by engrafting rat or mouse cell lines, as no representative human cell line is available. In addition, there is a model of endogenous PCCs (i.e., MENX rats) that was characterized in our laboratory. In this review, we will summarize the contribution that various representative models of PPGL have given to the visualization of these tumors in vivo and we present an example of a tracer first evaluated in MENX rats, and then translated to the detection of these tumors in human patients. In addition, we will illustrate briefly the potential of ex vivo biological imaging of intact adrenal glands in MENX rats.

RevDate: 2021-12-10

Moriano JA, Molero F, Laguía A, et al (2021)

Security Providing Leadership: A Job Resource to Prevent Employees' Burnout.

International journal of environmental research and public health, 18(23): pii:ijerph182312551.

Leadership styles in work contexts play a role in employees' well-being, contributing to better health or, on the contrary, being a source of stress. In this study we propose that security providing leadership may be considered as a resource to prevent employees' job burnout. First, we examine the relationship between employees' perception of their leader's degree of security in providing leadership and the employees' degree of job-related burnout. Second, the underlying processes by which leaders as security providers exert their influence on burnout are analyzed with a focus on the mediating role of two variables: an organizational climate oriented to psychological safety and organizational dehumanization. A total of 655 Spanish employees (53.7% women) completed a paper-and-pencil self-report questionnaire. To recruit participants, we employed an exponential non-discriminative snowball sampling. Results, using Partial Least Squares Structural Equation Modeling (PLS-SEM) to test hypotheses, show that security providing leadership was related negatively to burnout. Furthermore, psychological safety climate and organizational dehumanization mediated the relationship between security providing leadership and burnout. These findings support the attachment approach to leadership and open new avenues for creating better organizational environments. Security-providing leaders, by supporting employees and treating them in a personalized way, can enhance the psychological safety climate and prevent organizational dehumanization and consequent job burnout.

RevDate: 2021-12-10

Kang M, Lee H, Byeon SJ, et al (2021)

Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate.

International journal of molecular sciences, 22(23): pii:ijms222313125.

Intraductal carcinoma of the prostate (IDC-P) is a rare and unique form of aggressive prostate carcinoma, which is characterized by an expansile proliferation of malignant prostatic epithelial cells within prostatic ducts or acini and the preservation of basal cell layers around the involved glands. The vast majority of IDC-P tumors result from adjacent high-grade invasive cancer via the retrograde spreading of tumor cells into normal prostatic ducts or acini. A subset of IDC-P tumors is rarely derived from the de novo intraductal proliferation of premalignant cells. The presence of IDC-P in biopsy or surgical specimens is significantly associated with aggressive pathologic features, such as high Gleason grade, large tumor volume, and advanced tumor stage, and with poor clinical courses, including earlier biochemical recurrence, distant metastasis, and worse survival outcomes. These architectural and behavioral features of IDC-P may be driven by specific molecular properties. Notably, IDC-P possesses distinct genomic profiles, including higher rates of TMPRSS2-ERG gene fusions and PTEN loss, increased percentage of genomic instability, and higher prevalence of germline BRCA2 mutations. Considering that IDC-P tumors are usually resistant to conventional therapies for prostate cancer, further studies should be performed to develop optimal therapeutic strategies based on distinct genomic features, such as treatment with immune checkpoint blockades or poly (adenosine diphosphate-ribose) polymerase inhibitors for patients harboring increased genomic instability or BRCA2 mutations, as well as genetic counseling with genetic testing. Patient-derived xenografts and tumor organoid models can be the promising in vitro platforms for investigating the molecular features of IDC-P tumor.

RevDate: 2021-12-10

Betz IR, Qaiyumi SJ, Goeritzer M, et al (2021)

Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation.

International journal of molecular sciences, 22(23): pii:ijms222312695.

Palmitoleic acid (C16:1n7) has been identified as a regulator of physiological cardiac hypertrophy. In the present study, we aimed to investigate the molecular pathways involved in C16:1n7 responses in primary murine cardiomyocytes (PCM) and a mouse model of isoproterenol (ISO)-induced cardiac damage. PCMs were stimulated with C16:1n7 or a vehicle. Afterwards, RNA sequencing was performed using an Illumina HiSeq sequencer. Confirmatory analysis was performed in PCMs and HL-1 cardiomyocytes. For an in vivo study, 129 sv mice were orally treated with a vehicle or C16:1n7 for 22 days. After 5 days of pre-treatment, the mice were injected with ISO (25 mg/kg/d s. c.) for 4 consecutive days. Cardiac phenotyping was performed using echocardiography. In total, 129 genes were differentially expressed in PCMs stimulated with C16:1n7, including Angiopoietin-like factor 4 (Angptl4) and Pyruvate Dehydrogenase Kinase 4 (Pdk4). Both Angptl4 and Pdk4 are proxisome proliferator-activated receptor α/δ (PPARα/δ) target genes. Our in vivo results indicated cardioprotective and anti-fibrotic effects of C16:1n7 application in mice. This was associated with the C16:1n7-dependent regulation of the cardiac PPAR-specific signaling pathways. In conclusion, our experiments demonstrated that C16:1n7 might have protective effects on cardiac fibrosis and inflammation. Our study may help to develop future lipid-based therapies for catecholamine-induced cardiac damage.

RevDate: 2021-12-09

Sidhanth C, Bindhya S, Shabna A, et al (2021)

LASP-1 interacts with ErbB2 in ovarian cancer cells.

The Biochemical journal pii:230419 [Epub ahead of print].

LASP-1 was identified as a protein following mass spectrometric analysis of phosphoproteins consequent to signaling by ErbB2 in SKOV-3 cells. It has been previously identified as an oncogene and is located on chromosomal arm 17q 0.76Mb centromeric to ErbB2. It is expressed in serous ovarian cancer cell lines as a 40kDa protein. In SKOV-3 cells, it was phosphorylated and was inhibited by Lapatinib and CP7274714. LASP-1 co-immunoprecipitated with ErbB2 in SKOV-3 cells, suggesting a direct interaction. This interaction and phosphorylation were independent of the kinase activity of ErbB2. Moreover, the binding of LASP-1 to ErbB2 was independent of the tyrosine phosphorylation of LASP-1. LASP-1 was neither expressed on the surface epithelium of the normal ovary nor in the fallopian tube. It was expressed in 28% of ovarian tumours (n=101) that did not significantly correlate with other clinical factors. In tumours from patients with invasive ductal carcinoma of the breast who had ErbB2 amplification (3+), LASP-1 was expressed in 3/20 (p <0.001). Analysis of the expression of an independent dataset of ovarian and breast tumors from TCGA showed the significant co-occurrence of ErbB2 and LASP-1 (p<0.01). These results suggest that LASP-1 and ErbB2 interaction could be important in the pathogenesis of ovarian cancer.

RevDate: 2021-12-11

Dudgeon SN, Wen S, Hanna MG, et al (2021)

A Pathologist-Annotated Dataset for Validating Artificial Intelligence: A Project Description and Pilot Study.

Journal of pathology informatics, 12:45.

Purpose: Validating artificial intelligence algorithms for clinical use in medical images is a challenging endeavor due to a lack of standard reference data (ground truth). This topic typically occupies a small portion of the discussion in research papers since most of the efforts are focused on developing novel algorithms. In this work, we present a collaboration to create a validation dataset of pathologist annotations for algorithms that process whole slide images. We focus on data collection and evaluation of algorithm performance in the context of estimating the density of stromal tumor-infiltrating lymphocytes (sTILs) in breast cancer.

Methods: We digitized 64 glass slides of hematoxylin- and eosin-stained invasive ductal carcinoma core biopsies prepared at a single clinical site. A collaborating pathologist selected 10 regions of interest (ROIs) per slide for evaluation. We created training materials and workflows to crowdsource pathologist image annotations on two modes: an optical microscope and two digital platforms. The microscope platform allows the same ROIs to be evaluated in both modes. The workflows collect the ROI type, a decision on whether the ROI is appropriate for estimating the density of sTILs, and if appropriate, the sTIL density value for that ROI.

Results: In total, 19 pathologists made 1645 ROI evaluations during a data collection event and the following 2 weeks. The pilot study yielded an abundant number of cases with nominal sTIL infiltration. Furthermore, we found that the sTIL densities are correlated within a case, and there is notable pathologist variability. Consequently, we outline plans to improve our ROI and case sampling methods. We also outline statistical methods to account for ROI correlations within a case and pathologist variability when validating an algorithm.

Conclusion: We have built workflows for efficient data collection and tested them in a pilot study. As we prepare for pivotal studies, we will investigate methods to use the dataset as an external validation tool for algorithms. We will also consider what it will take for the dataset to be fit for a regulatory purpose: study size, patient population, and pathologist training and qualifications. To this end, we will elicit feedback from the Food and Drug Administration via the Medical Device Development Tool program and from the broader digital pathology and AI community. Ultimately, we intend to share the dataset, statistical methods, and lessons learned.

RevDate: 2021-12-11

Athamnah M, Rabai NA, Shkoukani ZW, et al (2021)

Nipple-Sparing Mastectomy: Initial Experience Evaluating Patients Satisfaction and Oncological Safety in a Tertiary Care Centre in Jordan.

Cureus, 13(11):e19238.

Introduction Nipple-sparing mastectomy (NSM), a procedure involving careful dissection of the breast tissue whilst keeping the nipple-areola complex (NAC) intact, is now increasingly practiced amongst surgeons in the treatment of certain situations of breast cancer. Given the importance of breasts to the female body image, this type of conservative breast surgery takes into account patient satisfaction and overall cosmesis, whilst ensuring appropriate oncological safety. Methods and results Four nipple-sparing mastectomy procedures were performed in our tertiary care centre, Princess Basma Teaching Hospital, in Jordan between June and September 2019. Indications for these procedures included invasive ductal carcinoma, malignant phyllodes, and high-grade ductal carcinoma in-situ. Patients were carefully assessed prior to surgical intervention using radiological imaging, ensuring a distance from NAC of >2 cm in all cases. Procedures were performed successfully with minimal intraoperative and no post-operative complications. Follow-up was carried out at 24 months, with no cases of local or distant post-operative recurrence, and patient satisfaction was qualitatively measured with the use of a BREAST-Q questionnaire. The questionnaire demonstrated improved overall physical well-being and satisfaction with an average overall post-operative physical well-being of 97%. Conclusion Following nipple-sparing mastectomy and immediate submuscular reconstruction with silicone implants,patients demonstrated high levels of satisfaction and quality of life (QoL) as measured by BREAST-Q survey. Two years of follow-up confirmed high patient satisfaction with increased scores from the preoperative baseline level.

RevDate: 2021-12-11

Adrada BE, Karbasian N, Huang M, et al (2021)

Imaging Surveillance of the Reconstructed Breast in a Subset of Patients May Aid in Early Detection of Breast Cancer Recurrence.

Journal of clinical imaging science, 11:58.

Objectives: The purpose of this study is to determine the biological markers more frequently associated with recurrence in the reconstructed breast, to evaluate the detection method, and to correlate recurrent breast cancers with the detection method.

Material and Methods: An institutional review board-approved retrospective study was conducted at a single institution on 131 patients treated with mastectomy for primary breast cancer followed by breast reconstruction between 2005 and 2012. Imaging features were correlated with clinical and pathologic findings.

Results: Of the 131 patients who met our inclusion criteria, 40 patients presented with breast cancer recurrence. The most common histopathologic type of primary breast cancer was invasive ductal carcinoma in 82.5% (33/40) of patients. Triple-negative breast cancer was the most common biological marker with 42.1% (16/38) of cases. Clinically, 70% (28/40) of the recurrences presented as palpable abnormalities. Of nine patients who underwent mammography, a mass was seen in eight patients. Of the 35 patients who underwent ultrasound evaluation, an irregular mass was found in 48.6% (17/35) of patients. Nine patients with recurrent breast cancer underwent breast MRI, and MRI showed an irregular enhancing mass in four patients, an oval mass in four patients, and skin and trabecular thickening in one patient. About 55% of patients with recurrent breast cancer were found to have distant metastases.

Conclusion: Patients at higher risk for locoregional recurrence may benefit from imaging surveillance in order to detect early local recurrences.

RevDate: 2021-12-07

Aldulaijan FA, Alsahwan AG, Alsulaiman MHA, et al (2021)

Histiocytoid variant of invasive lobular breast carcinoma. A case report and literature review.

Annals of medicine and surgery (2012), 72:103091.

Introduction: Histiocytoid breast carcinoma (HBC) is a variant of invasive lobular carcinoma. The occurrence of HBC is rare and the natural history and clinical course of HBC is still not well known due to limited numbers of reported cases. In reality, many tumors have been misdiagnosed and reported as benign lesions.

Case presentation: A 66-year-old- postmenopausal women, who has previous personal history of right breast invasive ductal carcinoma, for which she underwent right breast wide local excision with negative sentinel lymph node biopsy and received adjuvant radiotherapy and hormonal therapy. Two years later, a new left breast suspicious lesion was detected by Imaging. Breast Ultrasound showed left breast hypo-echoic area at 12-1 o'clock with irregular spiculated lesion 3 cm away from the nipple with posterior acoustic shadowing measuring 1 × 0.7 × 0.7 cm and mild tissue distortion with thicken cortical left Axillary lymph node. Mammography of both breasts confirmed the left breast lesion at 12o'clock with necrosis and irregular margins measuring 1.1 × 1.0 cm. MRI breasts showed, left breast heterogeneously enhancing mass at 12 o'clock with no other suspicious mass in the left or right breast. Ultrasound guided left breast biopsy of the suspicious lesion seen at 12-1 o'clock which confirmed the diagnosis of invasive lobular carcinoma, histiocytoid variant She underwent wire guided left breast wide local excision with left sentinel lymph node and axillary clearance. Final histopathology showed invasive lobular carcinoma, histiocytoid variant.

Clinical discussion: The recognition of histiocytoid breast carcinoma is often a challenge, particularly when histiocytoid tumor cells occur in a metastatic site before the primary diagnosis of breast cancer. An awareness of histological features are needed to make the accurate diagnosis.

Conclusion: Findings that support the correct diagnosis include identifying tumor cells with more cytological atypia, the presence of cytoplasmic vacuoles and secretions. Moreover, coexistence with invasive lobular carcinoma and/or lobular neoplasia and the use of immunohistochemistry to confirm their epithelial nature. clinico-radiological correlation is essential, as any discordance should trigger further diagnostic determination.

RevDate: 2021-12-07

Teixeira PC, Ducret A, Langen H, et al (2021)

Impairment of Multiple Mitochondrial Energy Metabolism Pathways in the Heart of Chagas Disease Cardiomyopathy Patients.

Frontiers in immunology, 12:755782.

Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients' myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.

RevDate: 2021-12-05

O'Connor DJ, Davey MG, Barkley LR, et al (2021)

Differences in sensitivity to neoadjuvant chemotherapy among invasive lobular and ductal carcinoma of the breast and implications on surgery-A systematic review and meta-analysis.

Breast (Edinburgh, Scotland), 61:1-10 pii:S0960-9776(21)00999-1 [Epub ahead of print].

Meta-analysis of >87,000 patients demonstrates that patients with invasive lobular carcinoma of the breast are far less likely to achieve pCR of the breast or axilla compared to their ductal counterparts, receive less BCS and more frequently return positive margins.

BACKGROUND: Neoadjuvant chemotherapy (NACT) facilitates tumour downstaging, increases breast conserving surgery (BCS) and assesses tumour chemosensitivity. Despite clinicopathological differences in Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC), decision making surrounding the use NACT does not take account of histological differences.

AIM: To determine the impact NACT on pathological complete response (pCR), breast conserving surgery (BCS), margin status and axillary pCR in ILC and IDC.

METHODS: A systematic review was performed in accordance with the PRISMA guidelines. Studies reporting outcomes among ILC and IDCs following NACT were identified. Dichotomous variables were pooled as odds ratios (ORs) with 95% confidence intervals_(CI) using the Mantel-Haenszel method. P-values <0.05 were statistically significant.

RESULTS: 40 studies including 87,303 (7596 ILC [8.7%]and 79,708 IDC [91.3%]) patients were available for analysis. Mean age at diagnosis was 54.9 vs. 50.9 years for ILC and IDC, respectively. IDCs were significantly more likely to achieve pCR (22.1% v 7.4%, OR: 3.03 [95% CI 2.5-3.68] p < 0.00001), axillary pCR (23.6% vs. 13.4%, OR: 2.01 [95% CI 1.77-2.28] p < 0.00001) and receive BCS (45.7% vs. 33.3%, OR 2.14 [95% CI 1.87-2.45] p < 0.00001) versus ILCs. ILCs were significantly more likely to have positive margins at the time of surgery (36% vs 13.5%, OR 4.84 [95% CI 2.88-8.15] p < 0.00001).

CONCLUSION: This is the largest study comparing the impact of NACT among ILC and IDC with respect to pCR and BCS. ILC has different outcomes to IDC following NACT and incorporate it into treatment decisions and future clinical guidelines.

RevDate: 2021-12-06

Di Lena É, Hopkins B, Wong SM, et al (2021)

Delays in operative management of early-stage, estrogen receptor-positive breast cancer during the COVID-19 pandemic: A multi-institutional matched historical cohort study.

Surgery [Epub ahead of print].

BACKGROUND: During the COVID-19 pandemic, guidelines recommended that breast cancer centers delay estrogen receptor-positive breast cancer surgeries with neoadjuvant endocrine therapy. We aimed to evaluate pathologic upstaging of breast cancer patients affected by these guidelines.

METHODS: Female patients with stage I/II breast cancer receiving neoadjuvant endocrine therapy were prospectively identified and were matched to a historical cohort of stage I/II estrogen receptor-positive breast cancer patients treated with upfront surgery ≤35 days. Primary outcomes were pathologic T and N upstaging versus clinical staging.

RESULTS: After matching, 28 neoadjuvant endocrine therapy and 48 control patients remained. Median age in each group was 65 (P = .68). Most patients (78.6% and 79.2%) had invasive ductal carcinoma with a clinical tumor size of 0.9 cm vs 1.7 cm (P = .056). Time to surgery was 68 days in the neoadjuvant endocrine therapy group and 26.5 days in the control (P < .001). A total of 23 neoadjuvant endocrine therapy patients (82.1%) had the same or lower pT-stage compared with 31 (64.5%) control patients (P = .115). Only 3 (10.7%) neoadjuvant endocrine therapy patients had increased pN-stage vs 14 (29.2%) control patients (P = .063).

CONCLUSION: Despite 2.5-times longer delays, patients with early-stage estrogen receptor-positive breast cancer receiving neoadjuvant endocrine therapy did not experience pathologic upstaging during the COVID-19 pandemic. These findings may support the use of neoadjuvant endocrine therapy in similar patients if delays to surgery are projected.

RevDate: 2021-12-04

Sanilevici M, Reuveni O, Lev-Ari S, et al (2021)

Mindfulness-Based Stress Reduction Increases Mental Wellbeing and Emotion Regulation During the First Wave of the COVID-19 Pandemic: A Synchronous Online Intervention Study.

Frontiers in psychology, 12:720965.

The COVID-19 pandemic imposed extreme living conditions of social distancing, which triggered negative mental health problems and created challenges in seeking mental health support. Mindfulness-based interventions (MBIs) have been found to enhance wellbeing and mental health by reducing stress and anxiety and improving emotion regulation. Preliminary evidence suggests that online, synchronous MBIs may produce beneficial effects similar to face-to-face programs. However, the effectiveness of such online-MBIs to support mental health in highly stressful times, such as a global pandemic, requires further study. To this end, we investigated the effect of an online 8-week Mindfulness-Based Stress Reduction (MBSR) program on aspects of mental health during the first wave of the COVID-19 pandemic. Participants (N=92) who expressed interest in discounted online-MBSR programs were recruited for the study. The division into experimental and control groups was based on actual enrollment to the courses. Those who enrolled in a program were assigned to the experimental condition and those who decided not to enroll served as controls. Participants were assessed pre-intervention, post-intervention, and 1-month post-intervention for levels of mindfulness, perceived stress, anxiety, emotion regulation, and intolerance of uncertainty. Differences between the groups were tested using the general linear mixed effects model (GLMM) and Individual Growth Curve Models (IGCM) in intent to treat analysis. The findings indicated that, relative to the control group, MBSR improved mindfulness abilities (p <0.001), decreased anxiety (p <0.001), and stress (p <0.001) and increased emotion regulation (p <0.001). These effects were found to persist 1 month after the end of the program, despite the increased governmental public-health restrictions due to COVID-19 at that time. The ability to tolerate uncertainty, a central characteristic of the pandemic, was not found to be affected by the program. A mediation analysis revealed that the effect of the intervention on mental health improvement was partially mediated by the improvement in emotion regulation. Overall, the findings provide positive evidence for the feasibility of an online-MBSR program to support the mental health of individuals from the general population through the mediation of emotion regulation in challenging times, such as a global pandemic.

RevDate: 2021-12-02

Highton PJ, March DS, Churchward DR, et al (2021)

Intradialytic cycling does not exacerbate microparticles or circulating markers of systemic inflammation in haemodialysis patients.

European journal of applied physiology [Epub ahead of print].

PURPOSE: Patients receiving haemodialysis (HD) display elevated circulating microparticle (MP) concentration, tissue factor (TF) expression and markers of systemic inflammation, though regular intradialytic cycling (IDC) may have a therapeutic effect. This study investigated the impact of regular, moderate-intensity IDC on circulating MPs and inflammatory markers in unit-based HD patients.

METHODS: Patients were cluster-randomised to intervention (n = 20, age: 51.4 ± 18.1 years, body mass: 77.6 ± 18.3 kg, mean ± SD) or no-exercise control (n = 20, 56.8 ± 14.0 years, 80.5 ± 26.5 kg). Intervention participants completed 30 min of moderate intensity (rating of perceived exertion [RPE] of 12-14) IDC, thrice weekly for 6 months. Pre-dialysis venous blood samples were obtained at 0, 3 and 6 months. Circulating MP phenotypes, cytokines, chemokine and MP TF expression were quantified using flow cytometry and cytometric bead array assays.

RESULTS: Despite high exercise compliance (82%), no IDC-dependent effects were observed for any MP, cytokine or chemokine measure (p ≥ 0.051, ηρ2 ≤ 0.399) other than TNF-α (p = 0.001, ηρ2 = 0.186), though no significance was revealed upon post hoc analysis.

CONCLUSION: Six months of regular, moderate-intensity IDC had no effect on MPs, cytokines or chemokines. This suggests that the exercise did not exacerbate thrombotic or inflammatory status, though further functional assays are required to confirm this.

TRIAL REGISTRATION: ISRCTN1129707, prospectively registered on 05/03/2015.

RevDate: 2021-12-03

Husain S, Isa M, R Almarzooq (2021)

A Rare Metastatic Site of Invasive Lobular Breast Carcinoma: A Case Report.

Case reports in surgery, 2021:9922296.

Here, we report a case of a 42-year-old female patient with left lobular breast cancer-gastric metastasis (initially misdiagnosed five years ago as an invasive ductal carcinoma) presenting with dyspepsia, weight loss, and persistent vomiting lasting for four weeks. Upper GI endoscopy revealed evidence of linitis plastica, and histological and immunocytochemical analyses of the biopsy confirmed gastric metastasis secondary to invasive lobular breast carcinoma.

RevDate: 2021-12-01

Khanam R, Fleischer TC, Boghossian NS, et al (2021)

Performance of a validated spontaneous preterm delivery predictor in South Asian and Sub-Saharan African women: a nested case control study.

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians [Epub ahead of print].

OBJECTIVES: To address the disproportionate burden of preterm birth (PTB) in low- and middle-income countries, this study aimed to (1) verify the performance of the United States-validated spontaneous PTB (sPTB) predictor, comprised of the IBP4/SHBG protein ratio, in subjects from Bangladesh, Pakistan and Tanzania enrolled in the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, and (2) discover biomarkers that improve performance of IBP4/SHBG in the AMANHI cohort.

STUDY DESIGN: The performance of the IBP4/SHBG biomarker was first evaluated in a nested case control validation study, then utilized in a follow-on discovery study performed on the same samples. Levels of serum proteins were measured by targeted mass spectrometry. Differences between the AMANHI and U.S. cohorts were adjusted using body mass index (BMI) and gestational age (GA) at blood draw as covariates. Prediction of sPTB < 37 weeks and < 34 weeks was assessed by area under the receiver operator curve (AUC). In the discovery phase, an artificial intelligence method selected additional protein biomarkers complementary to IBP4/SHBG in the AMANHI cohort.

RESULTS: The IBP4/SHBG biomarker significantly predicted sPTB < 37 weeks (n = 88 vs. 171 terms ≥ 37 weeks) after adjusting for BMI and GA at blood draw (AUC= 0.64, 95% CI: 0.57-0.71, p < .001). Performance was similar for sPTB < 34 weeks (n = 17 vs. 184 ≥ 34 weeks): AUC = 0.66, 95% CI: 0.51-0.82, p = .012. The discovery phase of the study showed that the addition of endoglin, prolactin, and tetranectin to the above model resulted in the prediction of sPTB < 37 with an AUC= 0.72 (95% CI: 0.66-0.79, p-value < .001) and prediction of sPTB < 34 with an AUC of 0.78 (95% CI: 0.67-0.90, p < .001).

CONCLUSION: A protein biomarker pair developed in the U.S. may have broader application in diverse non-U.S. populations.

RevDate: 2021-12-08

Kamal AM, Pal UM, Kumar A, et al (2021)

Toward the development of portable light emitting diode-based polarization spectroscopy tools for breast cancer diagnosis.

Journal of biophotonics [Epub ahead of print].

A robust, affordable and portable light emitting diode-based diagnostic tools (POLS-NIRDx) using a polarization-sensitive (linear as well as circular polarization) technique were designed and developed to quantify the degree of linear polarization (DOLP), degree of circular polarization (DOCP). The study was performed on malignant (invasive ductal carcinoma) and adjacent normal ex-vivo biopsy tissues excised from N = 10 patients at the operating wavelengths of 850 and 940 nm. The average DOLP and DOCP values were lower for malignant than adjacent normal while operating at 850 and 940 nm. The highest accuracy was observed for DOLP (100%) and DOCP (80%) while operating at 850 nm, which reduced (80% for DOLP and 65% for DOCP) at 940 nm. This pilot study can be utilized as a differentiating factor to delineate malignant tissues from adjacent normal tissues.

RevDate: 2021-11-30

Erener S, Ellis CE, Ramzy A, et al (2021)

Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice.

Cell reports. Medicine, 2(11):100434.

miRNAs have crucial functions in many biological processes and are candidate biomarkers of disease. Here, we show that miR-216a is a conserved, pancreas-specific miRNA with important roles in pancreatic islet and acinar cells. Deletion of miR-216a in mice leads to a reduction in islet size, β-cell mass, and insulin levels. Single-cell RNA sequencing reveals a subpopulation of β-cells with upregulated acinar cell markers under a high-fat diet. miR-216a is induced by TGF-β signaling, and inhibition of miR-216a increases apoptosis and decreases cell proliferation in pancreatic cells. Deletion of miR-216a in the pancreatic cancer-prone mouse line Kras G12D ;Ptf1a CreER reduces the propensity of pancreatic cancer precursor lesions. Notably, circulating miR-216a levels are elevated in both mice and humans with pancreatic cancer. Collectively, our study gives insights into how β-cell mass and acinar cell growth are modulated by a pancreas-specific miRNA and also suggests miR-216a as a potential biomarker for diagnosis of pancreatic diseases.

RevDate: 2021-11-30

Beltran-Bless A, Murshed M, Zakikhani M, et al (2021)

Histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients.

Bone reports, 15:101145.

Background: Despite widespread use of repeated doses of potent bone-targeting agents (BTA) in oncology patients, relatively little is known about their in vivo effects on bone homeostasis, bone quality, and bone architecture. Traditionally bone quality has been assessed using a trans-iliac bone biopsy with a 7 mm "Bordier" core needle. We examined the feasibility of using a 2 mm "Jamshidi™" core needle as a more practical and less invasive technique.

Methods: Patients with metastatic breast cancer on BTAs were divided according to the extent of bone metastases. They were given 2 courses of tetracycline labeling and then underwent a posterior trans-iliac trephine biopsy and bone marrow aspirate. Samples were analyzed for the extent of tumor invasion and parameters of bone turnover and bone formation by histomorphometry.

Results: Twelve patients were accrued, 1 had no bone metastases, 3 had limited bone metastases (LSM) (<3 lesions) and 7 had extensive bone metastases (ESM) (>3 lesions). Most of the primary tumors were estrogen receptor (ER)/progesterone receptor (PR) positive. The procedure was well tolerated. The sample quality was sufficient to analyze bone trabecular structure and bone turnover by histomorphometry in 11 out of 12 patients. There was a good correlation between imaging data and morphometric analysis of tumor invasion. Patients with no evidence or minimal bone metastases had no evidence of tumor invasion. Most had suppressed bone turnover and no detectable bone formation when treated with BTA. In contrast, 6 out of 7 patients with extensive bone invasion by imaging and evidence of tumor cells in the marrow had intense osteoclastic activity as measured by the number of osteoclasts. Of these 7 patients with ESM, 6 were treated with BTA with 5 showing resistance to BTA as demonstrated by the high number of osteoclasts present. 3 of these 6 patients had active bone formation. Based on osteoblast activity and bone formation, 3 out of 6 patients with ESM responded to BTA compared to all 3 with LSM. Compared to untreated patients, all patients treated with BTA showed a trend towards suppression of bone formation, as measured by tetracycline labelling. There was also a trend towards a significant difference between ESM and LSM treated with BTA, highly suggestive of resistance although limited by the small sample size.

Discussion: Our results indicate that trans-iliac bone biopsy using a 2 mm trephine shows excellent correlation between imaging assessment of tumor invasion and tumor burden by morphometric analysis of bone tissues. In addition, our approach provides additional mechanistic information on therapeutic response to BTA supporting the current clinical understanding that the majority of patients with extensive bone involvement eventually fail to suppress bone turnover (Petrut B, et al. 2008). This suggests that antiresorptive therapies become less effective as disease progresses.

RevDate: 2021-11-27

Price J (2021)

12-year review of MRI-detected breast cancers. How often was a diagnosis of malignancy established using targeted ultrasound and standard 14-gauge core biopsy?.

Journal of medical imaging and radiation oncology [Epub ahead of print].

INTRODUCTION: This retrospective study aimed to determine the percentage of MRI-detected breast cancers diagnosed using targeted ultrasound and standard 14-gauge (14g) biopsy in the setting of an Australian breast MRI service. This is of clinical relevance because malignancies not identifiable on mammography or by ultrasound may then require more invasive, technically demanding and costly MRI-guided interventional procedures, usually by large-core vacuum-assisted biopsy (VAB) or hook-wire localisation with open surgical biopsy.

METHODS: On review of the 12-year period 2006-2018, we identified 67 new breast cancer events in 64 women where the diagnosis was made on the basis of the MRI scan findings either alone (n = 60) or in combination with a concurrent mammogram (n = 7), with no recorded clinical abnormality. The percentage in which malignancy was confirmed on histopathology using targeted ultrasound in combination with 14g biopsy was determined versus other biopsy methods, for both invasive cancer and in situ disease.

RESULTS: Ultrasound-guided 14g biopsy was successful in establishing the presence of malignancy in 42/46 (91%) of events with a final diagnosis of invasive cancer, with 2 more proven by MRI-guided interventional procedures (1 VAB and 1 hook-wire) and 1 by open surgical biopsy. In the final case, a 5 mm focus on MRI with no sonographic correlate at the initial presentation was only identified and biopsied by ultrasound at 12-month follow-up. For events with a final diagnosis of DCIS/pLCIS (pleomorphic LCIS, n = 2), US-guided 14g biopsy was successful in 10/21 (48%), while 4/7 events with corresponding mammographic microcalcifications were proven by x-ray stereotactic interventions. A further 5 events had MRI-guided interventions (3 VAB and 2 hook-wires) and 1 an open surgical biopsy to confirm malignancy. In the final case (a woman with a 30 × 20 mm focal area of non-mass enhancement with corresponding microcalcifications consistent with DCIS), a pathologic diagnosis was not made until the patient presented 5 years later with invasive disease. There were also 3 instances of upgrades to invasion on final surgical pathology, one from pLCIS to microinvasion and 2 others from DCIS to IDC. Among the DCIS/pLCIS events, semi-random 14g core biopsy (sampling at the expected location of the MRI abnormality without a specific sonographic correlate) proved to be successful in 3 women.

CONCLUSION: Ultrasound-guided 14g core biopsy established a malignant diagnosis in 91% of invasive cancers and in 48% of DCIS/pLCIS cases. This relatively non-invasive, technically easy to perform and low-cost biopsy procedure can be used immediately when targeted ultrasound shows a correlate for a suspicious MRI scan finding. Careful imaging-pathologic correlation is required after 14g biopsy, and a discordant result will usually prompt recourse to an MRI-guided VAB or hook-wire localisation.

RevDate: 2021-11-29

Keller CR, Hu Y, Ruud KF, et al (2021)

Human Breast Extracellular Matrix Microstructures and Protein Hydrogel 3D Cultures of Mammary Epithelial Cells.

Cancers, 13(22):.

Tissue extracellular matrix (ECM) is a structurally and compositionally unique microenvironment within which native cells can perform their natural biological activities. Cells grown on artificial substrata differ biologically and phenotypically from those grown within their native tissue microenvironment. Studies examining human tissue ECM structures and the biology of human tissue cells in their corresponding tissue ECM are lacking. Such investigations will improve our understanding about human pathophysiological conditions for better clinical care. We report here human normal breast tissue and invasive ductal carcinoma tissue ECM structural features. For the first time, a hydrogel was successfully fabricated using whole protein extracts of human normal breast ECM. Using immunofluorescence staining of type I collagen (Col I) and machine learning of its fibrous patterns in the polymerized human breast ECM hydrogel, we have defined the microstructural characteristics of the hydrogel and compared the microstructures with those of other native ECM hydrogels. Importantly, the ECM hydrogel supported 3D growth and cell-ECM interaction of both normal and cancerous mammary epithelial cells. This work represents further advancement toward full reconstitution of the human breast tissue microenvironment, an accomplishment that will accelerate the use of human pathophysiological tissue-derived matrices for individualized biomedical research and therapeutic development.

RevDate: 2021-11-29

Liu PF, Shu CW, Yang HC, et al (2021)

Combined Evaluation of MAP1LC3B and SQSTM1 for Biological and Clinical Significance in Ductal Carcinoma of Breast Cancer.

Biomedicines, 9(11):.

Breast cancer is the leading cause of cancer death in women worldwide. The microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1 (SQSTM1) are two major markers for autophagy. Increased protein levels of MAP1LC3B and SQSTM1 are considered to be causes of autophagy inhibition or activation in various types of cancers. However, the roles of MAP1LC3B and SQSTM1 in breast cancer are still not clear. Using a tissue microarray from 274 breast invasive ductal carcinoma (IDC) patients, we found that tumor tissues showed higher protein levels of MAP1LC3B and cytoplasmic SQSTM1 in comparison to those in adjacent normal tissues. Moreover, high levels of MAP1LC3B were associated with better survival, including disease-specific survival and disease-free survival (DFS) in IDC patients. Furthermore, high co-expression of MAP1LC3B and SQSTM1 was significantly associated with better DFS in IDC patients. Astonishingly, the autophagy inhibitor accumulated the protein levels of MAP1LC3B/SQSTM1 and enhanced the cytotoxic effects of cisplatin and paclitaxel in MCF7 and BT474 breast cancer cell lines, implying that autophagy inhibition might result in poor prognosis and chemosensitivity in IDC. Taken together, high co-expression of MAP1LC3B and SQSTM1 might serve as a potential diagnostic and prognostic biomarker for IDC patients.

RevDate: 2021-11-26

Kulali F, G Guner (2021)

Outcomes in Sonographically Categorized Complex Cystic Breast Lesions.

Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine [Epub ahead of print].

OBJECTIVES: To investigate outcomes of patients with complex cystic breast lesions and to determine malignancy rates for each sonographic category.

MATERIAL AND METHODS: A total of 124 women with a mean age of 45 were enrolled in this retrospective study. Complex cysts were classified into four categories according to sonographic findings (thick septa/wall, intramural nodule, solid/cystic ratio) by two radiologists. Size, margin, short-to-long axis ratio, and vascularity were also noted. The relationship between sonographic features and histopathological/follow-up results was evaluated.

RESULTS: Of 124 complex cysts, 11 were malignant and 113 were benign. There were 31 with thick septa/wall (category 1), 14 with intramural nodule (category 2), 60 with solid/cystic ratio < 1 (category 3), and 19 with solid/cystic ratio > 1 (category 4). Among 11 malignant tumors, six intraductal papillary carcinomas and three invasive ductal carcinomas were in category 3, whereas one invasive ductal carcinoma was in category 1 and one was in category 4. Most of malignant lesions (9/11, 82%) were in category 3. Most of benign lesions (96/113, 85%) were fibroadenomatoid/fibrocystic changes. The presence of vascularity (96%), irregular margin (94%), and short-to-long axis ratio ≥ 1 (94%) had higher accuracy rates for diagnosis of malignancy.

CONCLUSION: The malignancy rate was 8.8% in our study. Besides internal morphological features, other sonographic features should be considered in the evaluation of complex cystic breast lesions. Due to substantial risk of malignancy and the overlapping sonographic features of benign and malignant lesions, tissue sampling of all complex cysts should be performed.

RevDate: 2021-11-26

Rafiq MT, Hamid MSA, Hafiz E, et al (2021)

The role of rehabilitation exercises on weight, functional strength and exercise adherence in knee osteoarthritis patients.

Current rheumatology reviews pii:CRR-EPUB-116779 [Epub ahead of print].

INTRODUCTION: Knee osteoarthritis (OA) is a weight-bearing joint disease and is more common in overweight and obese persons. The objective of this study was to determine the role of rehabilitation exercises (REs) of lower limbs on weight, functional strength, and exercise adherence in overweight and obese knee OA patients.

MATERIALS AND METHOD: The patients were recruited from the Urban community of Lahore, Pakistan. The patients were divided into the rehabilitation group (RG) and control group (CG). The patients in the RG performed the REs of lower limbs and followed the instructions of daily care (IDC), while the patients in the CG only followed the IDC for 12 weeks. Outcome measures were assessed at pre-test before grouping and post-test after 12-weeks of interventions. The measures included: weight, functional strength, and exercise adherence. The Paired Samples t-test (for the normally distributed data) and the Wilcoxon Signed Ranked Test (for the data that was not normally distributed) were used to analyze the differences within groups from pre to post-test measurements. The analysis of variance 2 × 2 factors and the Mann-Whitney U-test were used to analyze the difference of weight and functional strength respectively between the groups.

RESULTS: The patients in the RG reported a statistically significant weight reduction (p < 0.001) and improvement in the functional strength (p < 0.001) within the group. Similarly, the patients in the CG also reported a significant improvement in the scores of functional strength (p = 0.004) within the group. The improvement in the scores of functional strength was greater in the patients of RG than the CG (p < 0.001. Similarly, the patients in the RG reported a statistically significant reduction in weight than the CG (p < 0.001).

CONCLUSION: The REs could improve weight, functional strength and exercise adherence.

RevDate: 2021-11-27

Eto R, Nakamura R, Yamamoto N, et al (2022)

Synchronous early-stage breast cancer and axillary follicular lymphoma diagnosed by core needle biopsy: A case report.

Molecular and clinical oncology, 16(1):3.

Synchronous double cancers are an infrequent finding. The focus of this study was a case of diagnosed synchronous double breast cancer (BC) and axillary (Ax) follicular lymphoma (FL). The patient was a 73-year-old woman who had been visiting her local doctor for follow-up of a fibroadenoma of the left breast, and was referred to our hospital after being diagnosed with invasive ductal carcinoma (IDC) of the left breast. Ultrasonography (US) revealed enlarged Ax lymph nodes (LNs) and US-guided core needle biopsy (CNB) was performed. CNB revealed no metastasis of IDC; however, a diagnosis of FL was made. Therefore, the patient was diagnosed with synchronous double BC and Ax FL and underwent partial surgical resection of the BC and close monitoring of the FL. To the best of our knowledge, this is the first case of malignant lymphoma diagnosed by CNB of Ax LNs during preoperative BC screening. CNB allows for a shorter waiting time for the examination, and it is considered to be minimally invasive, cost-effective and non-inferior to surgical resection in terms of specimen volume. Therefore, active preoperative evaluation of Ax LNs using US-guided CNB may contribute to BC staging, and may also help diagnose synchronous cancers.

RevDate: 2021-11-27

Gnanamuttupulle M, Henke O, Ntundu SH, et al (2021)

Clinicopathological characteristics of breast cancer patients from Northern Tanzania: common aspects of late stage presentation and triple negative breast cancer.

Ecancermedicalscience, 15:1282.

Purpose: Breast cancer (BC) is the second most common cancer among Tanzanian women. Oestrogen (ER), progesterone and human epidermal growth factor receptor 2 play major roles in prognosis and treatment but data for Tanzania are sparse. This study aimed to determine these patterns and histological types, tumour grading and staging of BC patients in northern Tanzania for a better understanding of BC in the Sub-Saharan African (SSA) setting.

Methods: A cross-sectional study recorded newly diagnosed BC cases at Kilimanjaro Christian Medical Centre between October 2018 and March 2019. Receptor status, histological types and grade, clinical stage and socio-demographic were recorded and descriptive and bivariate analyses performed.

Results: 116 patients were enrolled. Median age was 53 years, 71.6% were ≥45 years. The commonest molecular subtype was triple negative breast cancer (TNBC) (n = 33; 28.4%). One hundred and two (87.9%) patients had invasive ductal carcinoma (IDC), poorly differentiated tumours (60; 51.7%) and clinical stage III disease (62; 53.0%). ER negative tumours were associated with poorly differentiated histological grade (relative risk (RR): 1.34 (0.87-2.07)), tumour size > 5 cm (RR: 1.67 (0.33-8.35)) and IDC (RR: 3.35 (0.56-20.23)). Clinical stages III & IV (odds ratio (OR): 1.64 (0.63-4.24)) were associated with hormone receptor (HR) negative tumours and metastasis (OR: 1.60 (0.68-3.74)) with TNBC. 18% of the patients reported about first-degree relatives with BC.

Conclusions: Most patients presented in advanced stages and TNBC in their menopause. HR negative tumours were associated with poor histological differentiation and IDC. The high percentage of positive family history of BC and the differences in receptor patterns compared to other parts of the world should urge further genetic research on BC in SSA.

RevDate: 2021-12-11

Della Torre S, Benedusi V, Pepe G, et al (2021)

Dietary essential amino acids restore liver metabolism in ovariectomized mice via hepatic estrogen receptor α.

Nature communications, 12(1):6883.

In female mammals, the cessation of ovarian functions is associated with significant metabolic alterations, weight gain, and increased susceptibility to a number of pathologies associated with ageing. The molecular mechanisms triggering these systemic events are unknown because most tissues are responsive to lowered circulating sex steroids. As it has been demonstrated that isoform alpha of the estrogen receptor (ERα) may be activated by both estrogens and amino acids, we test the metabolic effects of a diet enriched in specific amino acids in ovariectomized (OVX) mice. This diet is able to block the OVX-induced weight gain and fat deposition in the liver. The use of liver-specific ERα KO mice demonstrates that the hepatic ERα, through the control of liver lipid metabolism, has a key role in the systemic response to OVX. The study suggests that the liver ERα might be a valuable target for dietary treatments for the post-menopause.

RevDate: 2021-11-26

Salih AM, Hammood ZD, Kakamad FH, et al (2021)

Paget's disease of the breast in male with underlying invasive ductal carcinoma: A case report with review of literature.

Annals of medicine and surgery (2012), 72:103035.

Introduction: Paget's disease of the breast is a rare cutaneous eczema-like condition that occurs in the nipple-areolar complex of the breast. The current study aims to report a rare case of Paget's disease of the breast associated with invasive ductal carcinoma in a male breast.

Case report: A 54-year-old male presented with ulceration of the left nipple-areolar complex that has been progressing over the last 6 months. On examination; there was a palpable axillary lymph node. On ultrasound, a small hypoechoic heterogenous mass was seen beneath the areola (8*4 mm) with surrounding vascularity, and a few axillary lymph nodes with normal morphology and cortical thickness. The mammography revealed some points of calcification arranged in clusters. The patient underwent left side mastectomy and sentinel lymph node biopsy. The result of histopathological examination showed left side unifocal invasive ductal carcinoma.

Discussion: There are two main theories that explain the histogenesis of Paget's disease of the breast with and without underlying malignancy: epidermotropic theory, which suggests an epidermal infiltration of the nipple with Paget cells, and transformative theory, which proposes a malignant transformation of normal glandular cells of the epidermis.

Conclusion: The clinical presentation of Paget's disease of the breast is characteristic and should always warn the surgeon of the possibility of underlying malignancy.

RevDate: 2021-11-24

Mizukoshi K, Fujii M, Yamauchi Y, et al (2021)

A rare case of malignant biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma.

Clinical journal of gastroenterology [Epub ahead of print].

A 50-year-old woman was referred to our hospital for elevated hepatobiliary enzymes. She had a medical history of mastectomy for left breast invasive ductal carcinoma about 10 years ago, and no apparent recurrence had been observed. Contrast-enhanced computed tomography (CT) revealed soft-tissue shadows surrounding the portal vein, celiac artery, and other vessels. The lesions involved the hilar bile duct, and the upstream bile ducts were dilated. Endoscopic retrograde cholangiography showed an obstruction in the hilar bile duct, and biopsies were taken at the site of biliary stenosis. H&E staining showed that cells with strong nuclear atypia and prominent chromatin staining infiltrated in the stroma. Immunohistochemical analysis revealed that the cells were positive for CK7, GATA3 and weakly positive for CK20. Based on these results, we made the diagnosis of biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma. Biliary inside stents were placed across the biliary stricture, and she received chemotherapy plus endocrine therapy for breast cancer. So far, the partial response has been maintained for 1 year since the diagnosis of retroperitoneal metastasis. Although retroperitoneal metastasis from breast cancer, especially breast invasive ductal carcinoma, is extremely rare, it could be a differential diagnosis for biliary stenosis.

RevDate: 2021-11-23

Verbrugge SAJ, Alhusen JA, Kempin S, et al (2021)

Genes controlling skeletal muscle glucose uptake and their regulation by endurance and resistance exercise.

Journal of cellular biochemistry [Epub ahead of print].

Exercise improves the insulin sensitivity of glucose uptake in skeletal muscle. Due to that, exercise has become a cornerstone treatment for type 2 diabetes mellitus (T2DM). The mechanisms by which exercise improves skeletal muscle insulin sensitivity are, however, incompletely understood. We conducted a systematic review to identify all genes whose gain or loss of function alters skeletal muscle glucose uptake. We subsequently cross-referenced these genes with recently generated data sets on exercise-induced gene expression and signaling. Our search revealed 176 muscle glucose-uptake genes, meaning that their genetic manipulation altered glucose uptake in skeletal muscle. Notably, exercise regulates the expression or phosphorylation of more than 50% of the glucose-uptake genes or their protein products. This included many genes that previously have not been associated with exercise-induced insulin sensitivity. Interestingly, endurance and resistance exercise triggered some common but mostly unique changes in expression and phosphorylation of glucose-uptake genes or their protein products. Collectively, our work provides a resource of potentially new molecular effectors that play a role in the incompletely understood regulation of muscle insulin sensitivity by exercise.

RevDate: 2021-11-23

Feresin RG, Johnson SA, Elam ML, et al (2021)

Effects of strawberries on bone biomarkers in pre- and stage 1-hypertensive postmenopausal women: a secondary analysis.

Food & function [Epub ahead of print].

Postmenopausal women experience an increase in bone remodeling with the rate of bone resorption superseding the rate of bone formation. This results in a net bone loss with a subsequent increased risk for osteoporosis and fractures. High blood pressure (BP) has been associated with loss of bone mineral density and increased propensity to fractures. Strawberries are rich in polyphenols, which have been shown to have anti-hypertensive and bone-protective properties. Thus, we examined whether daily intake of strawberries would positively affect biomarkers of bone metabolism in postmenopausal women with pre- and stage 1-hypertension. Participants (age: 59 ± 6 years; body mass index: 31.5 ± 4.1 kg m-2; systolic BP: 140 ± 13 mmHg) were randomly assigned to consume (1) 50 g of freeze-dried strawberry powder (FDSP), (2) 25 g FDSP + 25 g of placebo powder, or (3) 50 g placebo powder for eight weeks. Results indicate a significant time-by-treatment interaction (P = 0.04) for serum insulin-like growth factor (IGF)-1, a hormone that plays a major role in bone formation. Serum concentrations of bone-specific alkaline phosphatase, a marker of bone formation, and tartrate-resistant acid phosphatase-5b, a specific marker of bone resorption, were not affected by FDSP compared to placebo. Although not statistically significant, after eight weeks, osteocalcin increased in the 50 g FDSP group with a large effect size (d = 0.6) when compared to the placebo-control group. Adiponectin increased by 5% and 6% in the 25 g and 50 g FDSP groups, respectively, while it declined in the placebo-control group by 25% (P = 0.03 for time-by-treatment interaction). Our findings suggest that consumption of 25 g FDSP increases IGF-1 in postmenopausal women with pre- and stage 1-hypertension. However, further studies are needed to assert the effectiveness of a strawberry intervention for bone health.

RevDate: 2021-11-23

Lee AY, Pant A, Pojchanun K, et al (2021)

Three-Dimensional Printing of Food Foams Stabilized by Hydrocolloids for Hydration in Dysphagia.

International journal of bioprinting, 7(4):393.

Three-dimensional food printing offers the possibility of modifying the structural design, nutrition, and texture of food, which may be used for consumers with special dietary requirements such as dysphagic patients. One of the food matrices that can be used for liquid delivery to dysphagic patients is food foams. Foams are widely used in different food products to adjust food density, rheological properties, and texture. Foams allow the food to stay in the mouth for sufficient time to provide hydration while minimizing the danger of choking. Our work studies the foam properties and printability of both egg white foams and eggless foams with a strong focus on their foaming properties, rheological properties, printability, and suitability for dysphagic patients. Food hydrocolloid, xanthan gum (XG), is added to improve foam stability and rheological properties so that the inks are printable. Rheological and syneresis properties of the pre-printed foam inks are examined. The texture profile and microstructure properties are studied post-printing. International dysphagia diet standardization initiative tests are carried out to assess the inks' potential for dysphagic diets. Inks with XG performed better with minimal water seepage, better foam stability, and excellent printability. This suggests that hydrocolloids lead to more stable food foams that are suitable for 3DFP and safe for hydration delivery to dysphagic patients.

RevDate: 2021-11-22

Fernández S, Saguy T, Gaviria E, et al (2021)

The Role of Witnesses in Humiliation: Why Does the Presence of an Audience Facilitate Humiliation Among Victims of Devaluation?.

Personality & social psychology bulletin [Epub ahead of print].

We examined the role that witnesses play in triggering humiliation. We hypothesized that witnesses trigger humiliation because they intensify the two core appraisals underlying humiliation: unfairness and internalization of a devaluation of the self. However, we further propose that witnesses are not a defining characteristic of humiliating situations. Results of a preliminary study using an event-recall method confirmed that witnesses were as characteristic of humiliating episodes as of those that elicited shame or anger. In Experiments 1 and 2, we manipulated the presence (vs. absence) of witnesses when a professor devalued participants and the hostile tone of this devaluation. As hypothesized, in both experiments, witnesses indirectly increased humiliation via the appraisal of unfairness. Results of Experiment 2 revealed that the presence of witnesses also interacted with hostility, enhancing humiliation. As expected, this moderating effect occurred via the other key appraisal of humiliation (i.e., internalization).

RevDate: 2021-12-06

Mampel A, Sottile ML, Denita-Juárez SP, et al (2021)

Double heterozygous pathogenic variants in the BRCA1 and BRCA2 genes in a patient with bilateral metachronous breast cancer.

Double heterozygosity pathogenic variants in BRCA1 and BRCA2 genes are a very rare finding, particularly in non-Ashkenazi individuals. We described the first case of double heterozygosity variants in a non-Ashkenazi Argentinean woman with metachronous bilateral breast cancer. The proband is a 65-year-old female diagnosed with invasive ductal carcinoma in the left breast at 45 years old and invasive carcinoma in the right breast at 65 years old. She underwent a multi-gene panel testing indicating the presence of two concurrent heterozygous germline deleterious variants NM_007300.4(BRCA1):c.4201C>T (p.Gln1401Ter), and NM_000059.3(BRCA2):c.5146_5149del (p.Tyr1716fs). . The patient's son (40 years-old) was found to have the inherited pathogenic variant in BRCA2 gene. There are few reports of double heterozygosity variants in BRCA1 and BRCA2 genes in Latin America. The two pathogenic variants identified in our patient have not been described together so far.

RevDate: 2021-11-22

Chi MS, Ko HL, Chen CC, et al (2021)

Single institute experience of intraoperative radiation therapy in early-stage breast cancer.

Medicine, 100(46):e27842.

ABSTRACT: Intraoperative radiation therapy (IORT) is an alternative to whole breast irradiation in selected early-stage breast cancer patients. In this single institute analysis, we report the preliminary results of IORT given by Axxent Electronic Brachytherapy (eBT) system.Patients treated with lumpectomy and eBT within a minimum follow-up period of 12 months were analyzed. Eligible criteria include being over the age of 45, having unifocal invasive ductal carcinoma (IDC) or ductal carcinoma in situ <3 cm in diameter, not exhibiting lymph node involvement on preoperative images, and negative sentinel lymph node biopsy. The eBT was given by preloaded radiation plans to deliver a single fraction of 20 Gray (Gy) right after lumpectomy.From January 2016 to April 2019, a total of 103 patients were collected. There were 78 patients with IDC and 25 with ductal carcinoma in situ. At a mean follow-up time of 31.1 months (range, 14.5-54.0 months), the local control rate was 98.1%. Two IDC patients had tumor recurrences (1 local and 1 regional failure). Post-IORT radiotherapy was given to 4 patients. There were no cancer related deaths, no distant metastases, and treatment side effects greater than grade 3 documented.We report the largest single institute analysis using the eBT system in Taiwan. The low recurrence and complication rates at a 31.1 month follow-up time support the use of the eBT system in selected early-stage breast cancer patients.

RevDate: 2021-11-19

Zhang J, Ling Y, Wang T, et al (2021)

Analysis of sentinel lymph node biopsy and non-sentinel lymph node metastasis in invasive ductal and invasive lobular breast cancer: a nationwide cross-sectional study (CSBrS-001).

Annals of translational medicine, 9(20):1588.

Background: Information regarding the implementation of sentinel lymph node biopsy (SLNB) in invasive lobular carcinoma (ILC) is scarce, and whether ILC patients with 1-2 positive sentinel lymph nodes (SLNs) can be omitted from axillary lymph node dissection (ALND) remains controversial. This study aimed to compare involvement of SLNs and non-SLNs between patients with invasive ductal carcinoma (IDC) and ILC.

Methods: We retrospectively collected the clinical and pathological data of invasive breast cancer patients from 37 medical centers in China from January 2018 to December 2018. The number of resected SLNs, positive rate of SLNs, and non-SLNs metastasis were compared between patients with IDC and ILC.

Results: A total of 6,922 patients were included, comprising 6,650 with IDC (96.1%) and 272 with ILC (3.9%). No difference was observed in the number of resected SLNs between patients with IDC and ILC (IDC: 4.0±1.9 vs. ILC: 3.9±1.6, P=0.352). The positive rate of SLNs was significantly higher in patients with IDC than that in patients with ILC (19.3% in IDC vs. 12.9% in ILC, P=0.008). The difference in positive rate of SLNs between IDC and ILC was mainly attributed to macro-metastasis. For patients with positive SLNs who received ALND, and those with 1-2 positive SLNs, the metastatic rate of non-SLNs in the ILC group was higher than that in the IDC group (for patients with positive SLNs: 50.0% in ILC vs. 39.9% in IDC, P=0.317; for patients with 1-2 positive SLNs: 45.4% in ILC vs. 34.8% in IDC, P=0.366), but the differences were not statistically significant.

Conclusions: Patients with ILC had similar number of resected SLNs and lower positive rate of SLNs compared to those with IDC. In participants with 1-2 positive SLNs, the ILC group had an increased tendency for non-SLNs metastasis compared with the IDC group. Surgeons may need to be more cautious about omitting ALND for ILC patients with 1-2 positive SLNs.

RevDate: 2021-12-04

Sebag SC, Zhang Z, Qian Q, et al (2021)

ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue.

Cell reports, 37(7):110003.

Brown adipose tissue (BAT) thermogenic activity is tightly regulated by cellular redox status, but the underlying molecular mechanisms are incompletely understood. Protein S-nitrosylation, the nitric-oxide-mediated cysteine thiol protein modification, plays important roles in cellular redox regulation. Here we show that diet-induced obesity (DIO) and acute cold exposure elevate BAT protein S-nitrosylation, including UCP1. This thermogenic-induced nitric oxide bioactivity is regulated by S-nitrosoglutathione reductase (GSNOR; alcohol dehydrogenase 5 [ADH5]), a denitrosylase that balances the intracellular nitroso-redox status. Loss of ADH5 in BAT impairs cold-induced UCP1-dependent thermogenesis and worsens obesity-associated metabolic dysfunction. Mechanistically, we demonstrate that Adh5 expression is induced by the transcription factor heat shock factor 1 (HSF1), and administration of an HSF1 activator to BAT of DIO mice increases Adh5 expression and significantly improves UCP1-mediated respiration. Together, these data indicate that ADH5 controls BAT nitroso-redox homeostasis to regulate adipose thermogenesis, which may be therapeutically targeted to improve metabolic health.

RevDate: 2021-11-19
CmpDate: 2021-11-17

Kostoglou A, Vlastos D, Bakalis A, et al (2021)

Breast cancer-associated opsoclonus-myoclonus syndrome: a case report.

World journal of surgical oncology, 19(1):328.

BACKGROUND: Paraneoplastic neurological syndromes constitute rare neurological complications of malignant disease, manifesting in <1% of patients with cancer. Opsoclonus-myoclonus syndrome (OMS) presents with chaotic ocular saccades (opsoclonus), spontaneous muscular jerking (myoclonus) that may be accompanied by ataxia, strabismus, aphasia, or mutism. Its paraneoplastic variant in the adult is most commonly associated with small-cell lung cancer, followed by breast cancer. Importantly, neurological symptoms usually precede the diagnosis of breast cancer and tend to recure after its treatment.

CASE PRESENTATION: A 43-year-old premenopausal Caucasian woman with a medical history of hypertension was admitted following an episode of focal seizure. This progressed to generalised tonic-clonic seizures and she was subsequently loaded with phenytoin, valproate, and levetiracetam. Initial workup included whole body CT scan, viral and autoimmune serology. The CT scan revealed an enhancing right axillary lymph node, which in combination with Anti-Ri antibody positivity raised the spectre of paraneoplastic OMS. MRI of the head revealed subtle nonspecific white matter signal change within the centrum semiovale without any mass lesions, while MRI of the spine was unremarkable. An uncomplicated right mastectomy and axillary lymph node clearance was performed: histopathology revealed a 9-mm, grade 2, oestrogen receptor-positive, progesterone receptor-negative (ER8, PR0), Her2-negative invasive ductal carcinoma, and 4/6 positive lymph nodes (T1b N2 M0). Two months later, she was readmitted with vertigo, diplopia, facial weakness, and ataxia, setting the diagnosis anti-Ri syndrome recurrence. MDT recommended mammogram and ultrasound of the left breast, which were normal. Subsequently, four months after initial discharge, she suffered another neurological recurrence; due to concomitant abdominal pain, PET-CT was performed demonstrating a hypermetabolic right ovarian focus. Bilateral salpingo-oophorectomy was performed as per gynaecology MDT and final histology showed normal tubes and ovaries. She has remained on remission since then, with a negative annual mammogram follow-up.

CONCLUSIONS: In conclusion, we report a case of OMS associated with breast cancer anti-Ri onconeural antibody. Its manifestations preceded the diagnosis of malignancy and it persisted after cancer treatment, underlining the importance for high clinical suspicion in cases of classical paraneoplastic neurological syndromes as well as the need for long-term clinical follow-up.

RevDate: 2021-11-30

Jeong JS, Cho KJ, Kim D, et al (2021)

Genomic alteration in rare subtype of sarcomatoid salivary duct carcinoma.

Pathology, research and practice, 228:153678.

AIMS: Salivary duct carcinoma (SDC) is an aggressive salivary gland neoplasm with a poor prognosis. Morphologically, it has many variants including sarcomatoid SDC. We evaluated the morphological features, immunohistochemistry profile, and genomic alteration of the rare variant, sarcomatoid SDC.

METHODS AND RESULTS: We evaluated the clinicopathological and molecular pathology for rare variant of sarcomatoid SDC. Among 102 SDC patients, three had sarcomatoid SDC. Review of clinicopathological features and immunohistochemistry and targeted exome sequencing was performed according to carcinomatous and sarcomatoid areas, respectively. The tumors were present in two submandibular glands and one parotid gland. In one case, a SDC arose in carcinoma ex pleomorphic adenoma. All consisted of a conventional invasive ductal carcinoma area and sarcomatoid features including spindle cells and multinucleated giant cells. AR and epithelial membrane antigen (EMA) were positive in both carcinoma and sarcomatoid areas. Cytokeratin AE1/AE3 were negative in all sarcomatoid areas. Targeted exome sequencing revealed multiple heterogeneous alterations including PIK3CA and TP53. Genomic alterations were nearly identical between typical carcinoma and sarcomatoid areas.

CONCLUSIONS: Clinicopathological features of sarcomatoid SDCs were not different from typical SDC, and genomic alteration according to subtypes was also similar to that of the conventional type. Androgen receptor (AR) expression is helpful in the diagnosis of SDC. The findings indicate that EMA and AR are useful in diagnosing sarcomatoid SDC when the tumor is composed of predominantly sarcomatoid components.

RevDate: 2021-11-23

O'Donnell AJ, Greischar MA, SE Reece (2021)

Mistimed malaria parasites re-synchronize with host feeding-fasting rhythms by shortening the duration of intra-erythrocytic development.

Parasite immunology [Epub ahead of print].

AIMS: Malaria parasites exhibit daily rhythms in the intra-erythrocytic development cycle (IDC) that underpins asexual replication in the blood. The IDC schedule is aligned with the timing of host feeding-fasting rhythms. When the IDC schedule is perturbed to become mismatched to host rhythms, it readily reschedules but it is not known how.

METHODS: We intensively follow four groups of infections that have different temporal alignments between host rhythms and the IDC schedule for 10 days, before and after the peak in asexual densities. We compare how the duration, synchrony and timing of the IDC differs between parasites in control infections and those forced to reschedule by 12 hours and ask whether the density of parasites affects the rescheduling process.

RESULTS AND CONCLUSIONS: Our experiments reveal parasites shorten the IDC duration by 2-3 hours to become realigned to host feeding-fasting rhythms with 5-6 days, in a density-independent manner. Furthermore, parasites are able to reschedule without significant fitness costs for them or their hosts. Understanding the extent of, and limits on, plasticity in the IDC schedule may reveal targets for novel interventions, such as drugs to disrupt IDC regulation and preventing IDC dormancy conferring tolerance to existing drugs.

RevDate: 2021-11-17

Gogia B, Shanina E, Fang X, et al (2021)

Case Report: Amphiphysin Antibody-Associated Stiff-Limb Syndrome and Myelopathy: An Unusual Presentation of Breast Cancer in an Elderly Woman.

Frontiers in neurology, 12:735895.

Background: Paraneoplastic stiff-limb syndrome (SLS) is a rare manifestation of underlying malignancy and could have distinctive features different from the classic stiff-person syndrome (SPS). Case Description: We present a case of anti-amphiphysin antibody (Ab)-associated paraneoplastic SLS, in an 83-year-old woman with invasive ductal carcinoma of the breast. She presented with stiffness, painful spasms of the distal legs, and asymmetrical fixed posturing of the foot. There are coexisting long-tract disturbance and lower-extremity weakness. Treatment with diazepam provided symptomatic relief while plasma exchange (PLEX) did not lead to significant clinical improvement. The patient was bedridden within 3 months and passed away within 6 months from symptom onset. Conclusion: This case highlights the importance of recognition of uncommon presentation of SPS and its oncological significance. This entity requires a high degree of suspicion for initiation of the proper workup. The rapid identification and treatment of the underlying tumor might offer the best chance for recovery.

RevDate: 2021-11-18

Tzelepi V, Grypari IM, Logotheti S, et al (2021)

Contemporary Grading of Prostate Cancer: The Impact of Grading Criteria and the Significance of the Amount of Intraductal Carcinoma.

Cancers, 13(21):.

(1) Background: Prognostic grade group (PGG) is an important prognostic parameter in prostate cancer that guides therapeutic decisions. The cribriform pattern and intraductal carcinoma (IDC) are two histological patterns, that have additional prognostic significance. However, discrepancies exist regarding the handling of IDC according to the guidelines published by two international genitourinary pathology societies. Furthermore, whether, in addition to its presence, the amount of IDC is also of importance has not been studied before. Lastly, the handling of tertiary patterns has also been a matter of debate in the literature. (2) Methods: A total of 129 prostatectomy cases were retrieved and a detailed histopathologic analysis was performed. (3) Results: Two cases (1.6%) upgraded their PGG, when IDC was incorporated in the grading system. The presence and the amount of IDC, as well as the presence of cribriform carcinoma were associated with adverse pathologic characteristics. Interestingly, in six cases (4.7%) there was a difference in PGG when using the different guidelines regarding the handling of tertiary patterns. In total, 6.2% of the cases would be assigned a different grade depending on the guidelines followed. (4) Conclusions: These findings highlight a potential area of confusion among pathologists and clinicians and underscore the need for a consensus grading system.

RevDate: 2021-11-18

Kanavati F, M Tsuneki (2021)

Breast Invasive Ductal Carcinoma Classification on Whole Slide Images with Weakly-Supervised and Transfer Learning.

Cancers, 13(21):.

Invasive ductal carcinoma (IDC) is the most common form of breast cancer. For the non-operative diagnosis of breast carcinoma, core needle biopsy has been widely used in recent years for the evaluation of histopathological features, as it can provide a definitive diagnosis between IDC and benign lesion (e.g., fibroadenoma), and it is cost effective. Due to its widespread use, it could potentially benefit from the use of AI-based tools to aid pathologists in their pathological diagnosis workflows. In this paper, we trained invasive ductal carcinoma (IDC) whole slide image (WSI) classification models using transfer learning and weakly-supervised learning. We evaluated the models on a core needle biopsy (n = 522) test set as well as three surgical test sets (n = 1129) obtaining ROC AUCs in the range of 0.95-0.98. The promising results demonstrate the potential of applying such models as diagnostic aid tools for pathologists in clinical practice.


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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Cancer is the generic name for more than 100 diseases in which cells begin to grow and divide in an uncontrolled manner. Usually, when cells get too old or damaged, they die and new cells take their place. Cancer begins when genetic changes impair this orderly process so that some cells start to grow uncontrollably. The Emperor of All Maladies is a "biography" of cancer — from its first documented appearances thousands of years ago through the epic battles in the twentieth century to cure, control, and conquer it to a radical new understanding of its essence. This is a must read book for anyone with an interest in cancer. R. Robbins

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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RJR Picks from Around the Web (updated 11 MAY 2018 )