An Unusual Presentation of Synchronous Breast Cancer and Skin Malignancy in a Patient with Lynch Syndrome: A Case Report and Review of the Literature.

BACKGROUND: Lynch syndrome is an autosomal dominant condition that leads to an increased risk of many neoplasms. In the United Kingdom, NICE recommends that patients with colorectal and endometrial cancer should be tested for Lynch syndrome. There is conflicting evidence in the literature on the link between breast cancer and Lynch syndrome. CASE PRESENTATION: A 54-year-old woman presented with a lump in her right breast with a background of locally advanced colorectal cancer and Lynch syndrome due to a MLH1 gene mutation. A core biopsy showed a grade 3, invasive, triple-negative NST carcinoma. The tumour was triple-negative with patchy positivity for CK14 and CK5/6. Simultaneously, a cystic skin lesion in the contralateral breast was noted, which comprised lesional cells with a proliferation of clear cells and bland basaloid cells. The lesion had evidence of sebaceous differentiation with AR, podoplanin and p63 positivity. MSH1 and PMS2 deficiency was found in the breast and skin lesions. CONCLUSIONS: In Lynch syndrome, it is vital to be aware of the increased risk of various types of cancer. This case adds to the body of evidence of the spectrum of malignancies that can be encountered in patients with Lynch syndrome.

Pathologic Lymph Node Regression After Neoadjuvant Chemotherapy Predicts Recurrence and Survival in Esophageal Adenocarcinoma: A Multicenter Study in the United Kingdom.

PURPOSE: There is limited evidence regarding the prognostic effects of pathologic lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma. METHODS: Multicenter cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centers in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS)-LNRS 1, complete response; 2, <10% residual tumor; 3, 10%-50% residual tumor; 4, >50% residual tumor; and 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike information criterion and Harrell C-index. RESULTS: In total, 17,930 LNs from 763 patients were examined. LN response classified as complete LN response (LNRS 1 ≥1 LN, no residual tumor in any LN; n = 62, 8.1%), partial LN response (LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n = 155, 20.3%), poor/no LN response (LNRS 4-5; n = 303, 39.7%), or LN negative (no tumor/regression; n = 243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN response (hazard ratio [HR], 0.35; 95% CI, 0.22 to 0.56), partial LN response (HR, 0.72; 95% CI, 0.57 to 0.93) or negative LNs (HR, 0.32; 95% CI, 0.25 to 0.42) compared with those with poor/no LN response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%). CONCLUSION: Pathologic LN regression after neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathologic TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathologic reporting of esophagectomy specimens.

Where Are We Now with Liver Transplantation in Neuroendocrine Neoplasms? The Place of Liver Transplantation for Grades 1 and 2 Well-Differentiated Unresectable Liver Metastatic Neuroendocrine Tumours.

PURPOSE OF REVIEW: This review outlines the role of liver transplantation in selected patients with unresectable neuroendocrine tumour liver metastases. It discusses the international consensus on eligibility criteria and outlines the efforts taking place in the UK and Ireland to develop effective national liver transplant programmes for neuroendocrine tumour patients. RECENT FINDINGS: In the early history of liver transplantation, indications included cancer metastases to the liver as well as primaries of liver origin. Often, liver transplantation was a salvage procedure. The early results were disappointing, including in patients with neuroendocrine tumours. These data discouraged the widespread adoption of liver transplantation for neuroendocrine tumour liver metastases (NET LM). A few centres persisted in performing liver transplantation for patients with NET LM and in determining parameters predictive of good outcomes. Their work has provided evidence for benefit of liver transplantation in a selected group of patients with NET LM. Liver transplantation for NET LM is now accepted as a valid indication by many professional bodies, including the European Neuroendocrine Tumour Society (ENETS) and the United Network for Organ Sharing (UNOS). It is nevertheless rarely utilised. The UK and the Republic of Ireland are commencing a pilot programme of liver transplantation in selected patients. This programme will help develop the expertise and infrastructure to make liver transplantation for NET LM a routine procedure.

The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy.

Immune checkpoint blockade has recently proven effective in subsets of patients with esophageal adenocarcinoma (EAC) but little is known regarding the EAC immune microenvironment. We determined the single cell transcriptional profile of EAC in 8 patients who were treatment-naive (n = 4) or had received neoadjuvant chemotherapy (n = 4). Analysis of 52,387 cells revealed 10 major cell subsets of tumor, immune and stromal cells. Prior to chemotherapy tumors were heavy infiltrated by T regulatory cells and exhausted effector T cells whilst plasmacytoid dendritic cells were markedly expanded. Two dominant cancer-associated fibroblast populations were also observed whilst endothelial populations were suppressed. Pathological remission following chemotherapy associated with broad reversal of immune abnormalities together with fibroblast transition and an increase in endothelial cells whilst a chemoresistant epithelial stem cell population correlated with poor response. These findings reveal features that underlie and limit the response to current immunotherapy and identify a range of novel opportunities for targeted therapy.

Impact of neoadjuvant chemotherapy on nodal regression and survival in oesophageal adenocarcinoma.

BACKGROUND: The prognostic value of lymph node regression (LNR) following neoadjuvant chemotherapy (nCT) for oesophageal and gastro-oeosphageal adenocarcinoma remains unclear. This study aimed to characterise the long-term survival outcomes of LNR in patients having resectional surgery after nCT. METHODS: This study included patients undergoing oesophagectomy or extended total gastrectomy for oesophageal and junctional tumours (Siewert types 1,2,3) at the Queen Elizabeth Hospital Birmingham from 2012 to 2018. Lymph nodes retrieved at surgery were examined for evidence of a response to chemotherapy. Patients were classified as lymph node-negative (either negative nodes with no evidence of previous tumour involvement or negative with evidence of complete regression) or positive with either partial or no response. RESULTS: This study identified 183 patients who received nCT, of which 71% (130/183) had positive lymph nodes. Of these 130 patients, 44% (57/130) had a lymph node response and 56% (73/130) did not. The remaining 53 patients (29.0%) had negative lymph nodes with no evidence of tumour. Lymph node responders had a significant survival benefit compared to patients without lymph node response, but shorter than those with negative lymph nodes (median: 27 vs 18 vs NR months, p < 0·001). On multivariable analysis, lymph node responders had an improved overall (Hazard ratio (HR): 0.86, 95% CI: 0.80-0.92, p < 0.001) and recurrence-free (HR: 0.90, 95% CI: 0.82-0.98, p = 0.030) survival. CONCLUSION: Lymph node regression is an important prognostic factor, warranting closer evaluation over primary tumour response to help with planning further adjuvant therapy in these patients.

Survival and Nutritional Status of Male and Female Heart Transplant Patients Based on the Nutritional Risk Index.

Malnutrition among heart-transplant patients may affect survival. The aim was to investigate the survival and nutrition status among male and female heart transplant patients who underwent transplantation, before and 1 year after surgery based on the nutritional risk index (NRI). The medical records of ninety heart-transplant patients (2009-2014) from the King Faisal Specialist Hospital, Riyadh, were reviewed. The assessment included demographic data, anthropometric measurements, and NRI calculation. Moreover, postoperative data included the length of stay and survival. Paired t-test and survival analysis by Kaplan-Meier (KM) curves were used. A total of 90 patients (males 77.78%) were included. The prevalence of malnutrition in the preoperative phase by NRI was 60% (7.78% as severe; 40% as moderate, and 12.22% mild NRI scores). After 1 year, body mass index (BMI) and NRI increased significantly (p < 0.001). Furthermore, NRI was significantly different between men and women (p < 0.01), while KM survival curves were insignificantly different (p = 0.67). Recipients with postoperative moderate or severe nutritional risk (NRI < 97.5) had significantly shorter survival in the first-year post-transplantation (HR = 0.82; 95% CI, 0.75-0.89; p < 0.001). Our findings indicate that the NRI after 1 year of transplant correlated significantly with mortality. Besides, there was no significant gender difference regarding survival; however, malnutrition and low survival were more prominent among women.

High glucose load and endotoxemia among overweight and obese Arab women with and without diabetes: An observational study.

Dietary intake influences gut microbiota activity. Nevertheless, there is a lack of evidence available that illustrates the acute effects of high glucose meal on metabolic endotoxemia. The present study assessed the acute impact of high glucose meal on endotoxemia and other clinical parameters in Saudi females with varying degrees of glycemia.The subjects were 64 consenting pre-menopausal women, grouped into 3: control [n = 14 lean, non-T2DM, BMI = 22.2 ±â€Š2.2 kg/m]; overweight [n = 16, non-T2DM, BMI = 28.5 ±â€Š1.5 kg/m] and T2DM [n = 34, BMI = 35.2 ±â€Š7.7 kg/m]. After an overnight fast, all subjects were given a standardized high-glucose (75 g) meal. Anthropometrics were taken and blood samples were withdrawn at baseline and postprandial (0, 2 and 4-hours), serum glucose, endotoxin and lipid profile were quantified.At baseline, total cholesterol, LDL-cholesterol, triglycerides and serum glucose levels were significantly higher (P values <.01) whereas significantly lower HDL-cholesterol levels (P < .01) were observed in T2DM subjects compared to other groups. Baseline endotoxin levels were highest in the overweight group (3.2 ±â€Š1.1 mmol/L) as compared to control (2.0 ±â€Š0.5 mmol/L) and T2DM (2.7 ±â€Š1.2 mmol/L) (P = .046). HDL-cholesterol, LDL-cholesterol and triglycerides, significantly decreased in the T2DM group after 2 hours (P values <.05), whereas unremarkable changes observed in other groups. Lastly, endotoxin levels significantly increased only in the overweight group (3.2 ±â€Š1.1 vs 4.2 ±â€Š1.4 mmol/L; P < .05), 4 hours postprandial.High glucose meal elevates endotoxemia only among overweight subjects and impairs dysbiosis.

Unusual Presentation of Mammary Calciphylaxis in a Patient on Long-Standing Renal Dialysis.

INTRODUCTION: Calciphylaxis is a condition which involves ectopic deposition of calcium in arterioles of various organ systems. Here, we present a rare case of mammographic calcifications in a patient on long-standing renal dialysis. CASE: This is a 57-year-old female who presented to breast clinic with unilateral severe pain and lumpiness of her breast. On mammography, calcifications were identified which were associated with focal lesions on ultrasound. An image-guided core biopsy showed numerous foci of histological calcification within a large area of fat necrosis. The location within arterioles was confirmed by CD31 immunohistochemistry. The diagnosis of fat necrosis with benign calcifications due to mammary calciphylaxis was made. CONCLUSION: The hallmark of calciphylaxis is the deposition of calcium within small- to medium-sized vessel walls. This leads to ischaemia and necrosis of tissue. In the breast, only a few cases were reported in which patients presented with a necrotic lesion resembling carcinoma. These are reviewed in this report.

Effect of Housing System and Rosemary and Cinnamon Essential Oils on Layers Performance, Egg Quality, Haematological Traits, Blood Chemistry, Immunity, and Antioxidant.

Housing system and nutrition are non-genetic factors that can improve the well-being of animals to obtain higher quality products. A better understanding of how different housing systems and essential oils can influence the performance of layers is very important at the research and commercial levels. The current study aimed to investigate the effects of a housing system and dietary supplementation of rosemary and cinnamon essential oils on layers' performance and egg quality. A factorial arrangement (2 × 3) was performed include two housing systems (floor and cage) and three different types of essential oils (0, 300 mg/kg diet of rosemary and 300 mg/kg diet of cinnamon essential oils) to study their effects on the productive performance, egg quality, immunity, oxidative stress and haematology of ISA brown laying hens during the production stages (from 28 to 76 weeks of age). Birds were randomly divided into two groups each comprising of 1500 birds; the first group was moved from the litter to reared laying cages while the second group was floor reared. Each group was randomly divided into three groups, the first was considered as a control group, the second treated with rosemary essential oil, and the third with cinnamon essential oil. The differences in egg production and weight, egg quality, feed intake and conversion, blood picture and chemistry, immunity, and antioxidant parameters between the different housing systems (floor and cage) were not significant at (p < 0.05 or 0.01). On the other hand, the egg production and weight, Haugh unit, feed intake and conversion, blood cholesterol, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), urea, Ca, P, immunity, and antioxidant parameters were significantly (p < 0.05 or 0.01) better in rosemary and cinnamon groups than in the control group. Furthermore, the results of dietary supplementation with rosemary and cinnamon were very close. Regarding egg production and weight, there were no significant differences due to the interactions. The differences in egg mass among the interactions were also not significant except at 68-76 weeks, where the cage × cinnamon group was the highest. Under the floor rearing system, birds that were fed a diet supplemented with or without essential oils (EOs) consumed more feed than those raised under the cage system. Regarding feed conversion rate (FCR), the differences among the interactions were not significant except at 44-52, 52-60 and 68-76 weeks, where the cage × cinnamon group was the lowest. Excluding glutathione peroxidase (GPx) activity (p < 0.001), all immunity and antioxidant indices were not statistically different as a consequence of the interaction among EOs and housing systems. Additionally, the highest levels of phosphorus were observed for layers fed diets enriched with cinnamon oil with the cage or floor system. In conclusion, the data suggested that supplementation of rosemary and cinnamon essential oils in laying hen diet showed significantly positive effects on hen performance and egg production. Cholesterol, liver and kidney functions, immunity, and antioxidant parameters improved with rosemary and cinnamon supplementation when compared to the control. Additionally, the different housing systems did not result in any positive or negative impact on these traits.

Retrospective study on mixed neuroendocrine non-neuroendocrine neoplasms from five European centres.

BACKGROUND: Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare diagnosis, mainly encountered in the gastro-entero-pancreatic tract. There is limited knowledge of its epidemiology, prognosis and biology, and the best management for affected patients is still to be defined. AIM: To investigate clinical-pathological characteristics, treatment modalities and survival outcomes of a retrospective cohort of patients with a diagnosis of MiNEN. METHODS: Consecutive patients with a histologically proven diagnosis of MiNEN were identified at 5 European centres. Patient data were retrospectively collected from medical records. Pathological samples were reviewed to ascertain compliance with the 2017 World Health Organisation definition of MiNEN. Tumour responses to systemic treatment were assessed according to the Response Evaluation Criteria in Solid Tumours 1.1. Kaplan-Meier analysis was applied to estimate survival outcomes. Associations between clinical-pathological characteristics and survival outcomes were explored using Log-rank test for equality of survivors functions (univariate) and Cox-regression analysis (multivariable). RESULTS: Sixty-nine consecutive patients identified; Median age at diagnosis: 64 years. Males: 63.8%. Localised disease (curable): 53.6%. Commonest sites of origin: colon-rectum (43.5%) and oesophagus/oesophagogastric junction (15.9%). The neuroendocrine component was; predominant in 58.6%, poorly differentiated in 86.3%, and large cell in 81.25%, of cases analysed. Most distant metastases analysed (73.4%) were occupied only by a poorly differentiated neuroendocrine component. Ninety-four percent of patients with localised disease underwent curative surgery; 53% also received perioperative treatment, most often in line with protocols for adenocarcinomas from the same sites of origin. Chemotherapy was offered to most patients (68.1%) with advanced disease, and followed protocols for pure neuroendocrine carcinomas or adenocarcinomas in equal proportion. In localised cases, median recurrence free survival (RFS); 14.0 mo (95%CI: 9.2-24.4), and median overall survival (OS): 28.6 mo (95%CI: 18.3-41.1). On univariate analysis, receipt of perioperative treatment (vs surgery alone) did not improve RFS (P = 0.375), or OS (P = 0.240). In advanced cases, median progression free survival (PFS); 5.6 mo (95%CI: 4.4-7.4), and median OS; 9.0 mo (95%CI: 5.2-13.4). On univariate analysis, receipt of palliative active treatment (vs best supportive care) prolonged PFS and OS (both, P < 0.001). CONCLUSION: MiNEN is most commonly driven by a poorly differentiated neuroendocrine component, and has poor prognosis. Advances in its biological understanding are needed to identify effective treatments and improve patient outcomes.