Gastric-type adenocarcinoma of the cervix: Clinical outcomes and genomic drivers.

OBJECTIVES: Gastric-type endocervical adenocarcinoma (GEA) is a rare form of cervical cancer not associated with human papilloma virus (HPV) infection. We summarize our experience with GEA at a large cancer center. METHODS: Clinical and demographic information on all patients diagnosed with GEA between June 1, 2002 and July 1, 2019 was obtained retrospectively from clinical charts. Kaplan-Meier survival analysis was performed to describe progression-free survival (PFS) and overall survival (OS). Tumors from a subset of patients underwent next generation sequencing (NGS) analysis. RESULTS: A total of 70 women with GEA were identified, including 43 who received initial treatment at our institution: of these 4 (9%) underwent surgery alone, 15 (35%) underwent surgery followed by adjuvant therapy, 10 (23%) were treated with definitive concurrent chemoradiation (CCRT), 7 (16%) with chemotherapy alone, and 3 (7%) with neoadjuvant CCRT and hysterectomy with or without chemotherapy. One-third (n = 14) of patients experienced disease progression, of whom 86% (n = 12) had prior CCRT. The median PFS and OS for patients with stage I GEA were 107 months (95% CI 14.8-199.2 months) and 111 months (95% CI 17-205.1 months) respectively, compared to 17 months (95% CI 5.6-28.4 months) and 33 months (95% CI 28.2-37.8 months) for patients with stages II-IV, respectively. On NGS, 4 patients (14%) had ERBB2 alterations, including 2 patients who received trastuzumab. CONCLUSIONS: GEA is an aggressive form of cervical cancer with poor PFS and OS when diagnosed at stage II or later. Further investigation is needed to identify the optimal management approach for this rare subtype.

Molecular analysis of encapsulated papillary carcinoma of the breast with and without invasion.

Encapsulated papillary carcinomas (EPCs) of the breast are a unique variant of papillary carcinoma confined to a cystic space with absent or attenuated myoepithelial cell layer. Although staged as an in situ lesion, it can be associated with invasive ductal carcinoma (IDC). We sought to compare the genomic characteristics of pure EPC and EPC with associated invasive carcinoma (EPCi) at the genomic level. All cases of EPCi harbored recurrent hotspot mutations in PIK3CA. PIK3CA, KMT2A, and CREBBP deleterious somatic events were found across both tumor groups, irrespective of invasion status. At the whole transcriptomic level, EPCi cases displayed remarkably similar mRNA profiles when compared to EPC. When EPCi cases were compared with their corresponding IDC, despite significant overlap, we identified differential gene expression in 39 genes with enrichment of multiple pathways including extracellular matrix regulation, cell adhesion, and collagen fibril organization. Despite morphologic, genotypic, and transcriptomic overlap between pure EPC and EPCi, the latter tumors are likely advanced lesions with PIK3CA activating mutations and enrichment of stromal-related genes implicated in the switch to IDC.

The genomic landscape of carcinomas with mucinous differentiation.

Mucinous carcinomas can arise in any organ with epithelial cells that produce mucus. While mucinous tumors from different organs are histologically similar, it remains to be elucidated whether they share molecular alterations. Here we analyzed a total of 902 patients across six cancer types by comparing mucinous and non-mucinous samples, integrating text mining of pathology reports, gene expression, methylation, mutational and copy-number profiling. We found that, in addition to genes involved in mucin processing and secretion, MUC2 up-regulation is a multi-cancer biomarker of mucinous histology and is regulated by DNA methylation in colorectal, breast and stomach cancer. The majority of carcinomas with mucinous differentiation had fewer DNA copy-number alterations than non-mucinous tumors. The tumor mutational burden was lower in breast and lung with mucinous differentiation compared to their non-mucinous counterparts. We found several differences in the frequency of oncogenic gene and pathway alterations between mucinous and non-mucinous carcinomas, including a lower frequency of p53 pathway alterations in colorectal and lung cancer, and a lower frequency of PI-3-Kinase/Akt pathway alterations in breast and stomach cancer with mucinous differentiation. This study shows that carcinomas with mucinous differentiation originating from different organs share transcriptomic and genomic similarities. These results might pave the way for a more biologically relevant taxonomy for these rare cancers.

Computer-assisted Diagnosis of Breast Cancer by Cell Network Matrix Extraction and Multilayer Perceptron Analysis.

OBJECTIVE: Diagnosis of breast cancer is based on identification of various morphologic features by histopathologic examination of the specimen. Ancillary immunohistochemical and molecular analyses provide additional information that is prognostic and guides therapy. Because of subjectivity in this approach, we sought to develop a computer model which could assist in differentiating normal or benign tissue from malignant breast carcinoma. METHODS: Cases of benign sclerosing adenosis (20) and high-grade invasive ductal carcinomas (20) of breast were retrieved and re-examined. Five images of the diagnostic areas from each case were captured (400x). Each image was divided into quadrants and saved as 1-megapixel each. These 800 images were then binarized and segmented using the watershed method. The cell graphs were extracted to identify the matrix of adjacent cells and the network properties were determined for each image. The local network features were fed into a PAM model and global network features were fed into a multilayer perceptrons (MLP) to distinguish between benign and malignant samples. These characteristics were evaluated by training the models on 40% (320) of the randomly assigned images followed by real-time testing of the remaining 60% (480) images. In addition, normal breast tissue from five cases was retrieved and forty (40) images were captured to further test the model. RESULTS: Both local and global network feature models had high area under the curve (AUC) (0.63 and 0.99 respectively), with their adjusted Rand indices (ARI) being 0.61 and 0.87, respectively. Pooling the pseudoprobabilities of the two neural networks greatly increased the accuracy of the model with predictions of the combined model at image level being 100% accurate with AUC of 1. CONCLUSION: This study shows that using a combination of cell-graph extraction and a deep learning algorithm computers can accurately distinguish between benign and malignant breast lesions.

Time-Series Analysis of Laboratory Values in the Context of Long-Term Hospitalized Patient Mortality.

OBJECTIVES: Long-term hospitalized patients have a higher risk of adverse outcomes and mortality rate. These patients often rapidly deteriorate, leading to death. We aim to evaluate end-of-life laboratory values time trends among deceased long-term inpatients. METHODS: Time-stamped laboratory data for adult inpatients who had died in the hospital were extracted. The data were normalized and time-series analysis was performed. The patients were also clustered based on the laboratory result trends. RESULTS: Laboratory results from 257 patients were evaluated. Significant time trends were observed: serum urea nitrogen, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and potassium increased while platelets and albumin decreased. Most patients showed significant shifts in at least four major laboratory indices within the last week of life. CONCLUSIONS: In the last week of life in chronically hospitalized patients, an alteration of the physiologic state of the patient occurs that manifests as subtle changes in metabolite levels compared with the patient's baseline.

Stability of Values for the Activities of Critical Enzymes Assayed in Serum Frozen for Prolonged Time Periods.

OBJECTIVES: Our medical center laboratory receives frozen clinical chemistry samples from outlying hospitals for which assays for critical enzyme activities are requested. Our objective is to determine the effects of freezing (-20°C) on these enzyme activities in samples over a one month period. METHODS: Enzyme activities for ALP, AST, ALT, CK and LD for 30 patient's sera were stored at-20°C and were assayed on a Beckman-Coulter AU5800 analyzer at 0, 15 and 30 days after collection. Statistical tests were performed to determine if the values were statistically the same or different. RESULTS: F-tests for all five enzyme levels showed no statistically significant differences (p>>0.05); linear regression analysis showed high correlation of results (r>0.99 for all correlations) with some bias for ALT. CONCLUSIONS: We conclude that the activities of these enzymes are stable, except possibly ALT, when stored frozen at -20°C over the 15- and 30-day storage periods.

A comparison of the quality of life of the patients undergoing hemodialysis versus peritoneal dialysis and its correlation to the quality of dialysis.

Over the years, there has been a steady increase in the number of patients requiring dialysis. However, no consensus exists between choosing either hemodialysis (HD) or peritoneal dialysis (PD) as the preferred method of dialysis for patients. In this study, we have compared the quality of life of the patients undergoing either HD or PD. This cross-sectional study was performed in the dialysis center of the Noor and Saint Ali Asghar University Hospital in Isfahan, Iran in 2012. Forty-six patients who underwent PD (28 males and 18 females) and 46 similar patients undergoing HD (26 males and 20 females) were compared. A standardized Persian version of the short form-36 (SF-36) tool was used to assess the quality of life and to assess the quality of dialysis weekly Kt/V in patients undergoing PD and single random Kt/V sampling in HD patients were assessed. Patients undergoing PD reported higher scores in physical functioning. The lowest scores in both groups were reported in mental health section. In physical functioning section, physical role functioning section and overall score of the SF-36 tool, PD patients reported significantly higher scores compared to the HD patients (P <0.05). There was no significant difference between the qualities of the dialysis in the two patient groups. Aspects of quality of life such as physical functioning, physical role functioning, bodily pain, general health perceptions, and overall score were significantly different between the two groups. If these results are substantiated by subsequent longitudinal studies, then the choice of dialysis could be better guided in patients by the quality of life issues.

Effects of 8 weeks of military training on lower extremity and lower back clinical findings of young Iranian male recruits: A prospective case series.

BACKGROUND: In this prospective case series we have assessed the clinical effects of 8 weeks military training on the lower extremity of the recruits. MATERIALS AND METHODS: Military recruits who met the eligibility criteria and gave informed consent were entered into the study. They were asked to fill out a self-reporting pain and functionality questionnaire before and after their training. They were also examined by a physician before and after their military training. The questionnaire and examination were concentrated on three blocs: lower back, knee, and foot. RESULTS: Three-hundred and seventy-three study subjects were evaluated. The study showed that there is a significant difference in reporting lower back pain after the training compared to the rate of complaints prior to the training (P < 0.001), knee pain, and foot pain also increased significantly (P < 0.1 and P < 0.0001, respectively) The difference was most prominent in foot complaints. Physical examination also showed significant increase in lower extremity findings following the training (P < 0.05). CONCLUSION: Our study shows that there is a need for a new approach to military training of male recruits in Iran in order to minimize the adverse health effects.