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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-022-01666-x

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

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 &lt; 0·001). On multivariable analysis, lymph node responders had an improved overall (Hazard ratio (HR): 0.86, 95% CI: 0.80-0.92, p &lt; 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.</p

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

Serum trace elements in obese Egyptian children: a case–control study

BACKGROUND: To date, only a few studies on child obesity concerned Trace Elements (TE). TE is involved in the pathogenesis of obesity and obesity related diseases. We tried to assess trace elements status [zinc (Zn), copper (Cu), selenium (Se), iron (Fe), and chromium (Cr)] in obese Egyptian children and their relationships with serum leptin and metabolic risk factors of obesity. METHODS: This was a case–control study performed with 80 obese children (BMI ≥ 95(th)centile for age and gender) and 80 healthy non-obese children with comparable age and gender as the control group. For all subjects, serum Zn, Cu, Se, Fe, ferritin and Cr as well as biochemical parameters including lipid profile, serum glucose and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed. Levels of serum leptin were measured by (enzyme-linked immunosorbent assay [ELISA] method), and serum insulin was measured by an electrochemiluminesce immunoassay. RESULTS: Compared to the control group, serum Zn, Se, and Fe levels were significantly lower (all P < 0.01) and serum Cu level was significantly higher (P < 0.01) in the obese children. Meanwhile, no significant differences were observed in serum ferritin or Cr levels (P > 0.05). A significant negative correlation was found between serum leptin and zinc levels in the obese children (r = −0.746; P < 0.01). Further, serum Zn showed significant negative correlations with total cholesterol TC levels (P < 0.05) and were positively correlated with high density lipoprotein- cholesterol HDL-C levels (P < 0.01) in the obese children. In addition, serum Se levels showed significant positive correlations with HOMA-IR values in the obese children (P < 0.01). CONCLUSION: The obese children may be at a greater risk of developing imbalance (mainly deficiency) of trace elements which may be playing an important role in the pathogenesis of obesity and related metabolic risk factors

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&rsquo; performance and egg quality. A factorial arrangement (2 &times; 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 &lt; 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 &lt; 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&ndash;76 weeks, where the cage &times; 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&ndash;52, 52&ndash;60 and 68&ndash;76 weeks, where the cage &times; cinnamon group was the lowest. Excluding glutathione peroxidase (GPx) activity (p &lt; 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

Impact of neuroendocrine morphology on cancer outcomes and stage at diagnosis: a UK nationwide cohort study 2013-2015.

BACKGROUND The diagnosis of neuroendocrine neoplasms (NENs) is often delayed. This first UK population-based epidemiological study of NENs compares outcomes with non-NENs to identify any inequalities. METHODS Age-standardised incidence rate (ASR), 1-year overall survival, hazard ratios and standardised mortality rates (SMRs) were calculated for all malignant NENs diagnosed 2013-2015 from UK national Public Health records. Comparison with non-NENs assessed 1-year overall survival (1YS) and association between diagnosis at stage IV and morphology. RESULTS A total of 15,222 NENs were identified, with an ASR (2013-2015 combined) of 8.6 per 100,000 (95% CI 8.5-8.7); 4.6 per 100 000 (95% CI, 4.5-4.7) for gastro-entero-pancreatic (GEP) NENs. The 1YS was 75% (95% CI, 73.9-75.4) varying significantly by sex. Site and morphology were prognostic. NENs (predominantly small cell carcinomas) in the oesophagus, bladder, prostate, and female reproductive organs had a poorer outcome and were three times more likely to be diagnosed at stage IV than non-NENs. CONCLUSION Advanced stage at diagnosis with significantly poorer outcomes of some NENs compared with non-NENs at the same anatomical site, highlight the need for improved access to specialist services and targeted service improvement

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 ( surgery alone) did not improve RFS ( = 0.375), or OS ( = 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 ( best supportive care) prolonged PFS and OS (both, < 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