Microbiota in mesenteric adipose tissue from Crohn’s disease promote colitis in mice

Background Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat is a pathologic characteristic of Crohn’s disease (CD). The reserve of creeping fat in surgery is associated with poor prognosis of CD patients, but the mechanism remains unknown. Methods Mesenteric microbiome, metabolome, and host transcriptome were characterized using a cohort of 48 patients with CD and 16 non-CD controls. Multidimensional data including 16S ribosomal RNA gene sequencing (16S rRNA), host RNA sequencing, and metabolome were integrated to reveal network interaction. Mesenteric resident bacteria were isolated from mAT and functionally investigated both in the dextran sulfate sodium (DSS) model and in the Il10 gene-deficient (Il10−/−) mouse colitis model to validate their pro-inflammatory roles. Results Mesenteric microbiota contributed to aberrant metabolites production and transcripts in mATs from patients with CD. The presence of mAT resident microbiota was associated with the development of CD. Achromobacter pulmonis (A. pulmonis) isolated from CD mAT could translocate to mAT and exacerbate both DSS-induced and Il10 gene-deficient (Il10−/−) spontaneous colitis in mice. The levels of A. pulmonis in both mAT and mucous layer from CD patients were higher compared to those from the non-CD group. Conclusions This study suggests that the mesenteric microbiota from patients with CD sculpt a detrimental microenvironment and promote intestinal inflammation.

Microbiota in Mesenteric Adipose Tissue From Crohn’s Disease Promote Colitis in Mice

Background: Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat is a pathologic characteristic of Crohn’s disease (CD). The reserve of creeping fat in surgery is associated with poor prognosis of CD patients, but the mechanism remains unknown.Methods: Mesenteric microbiome, metabolome and host transcriptome were characterized using a cohort of 48 patients with CD and 16 non-CD controls. Multidimensional data including 16S ribosomal RNA gene sequencing (16S rRNA), host RNA sequencing and metabolome were integrated to reveal network interaction. Mesenteric resident bacteria were isolated from mAT and functionally investigated both in dextran sulfate sodium (DSS) model and Il10 gene deficient (Il10-/-) mouse colitis model to validate their pro-inflammatory roles. Results: Mesenteric microbiota contributed to aberrant metabolites production and transcripts in mATs from patients with CD. Presence of mAT resident microbiota was associated with the development of CD. Achromobacter pulmonis (A. pulmonis) isolated from CD mAT could translocate to mAT and exacerbate both DSS-induced and Il10 gene deficient (Il10-/-) spontaneous colitis in mice. The levels of A. pulmonis both in mAT and mucous layer from CD patients were higher compared to those from non-CD group. Conclusions: This study suggests that the mesenteric microbiota from patients with CD sculpt a detrimental microenvironment and promote intestinal inflammation.

COLORECTAL CANCER AND LYMPH NODE COUNT: IS THE NUMBER RECOMMENDED FOR STAGING RETRIEVED?

Background Colorectal cancer (CRC) ranks as the third most commonly diagnosed cancer in males and the second in females. According to the TNM staging system, status of the draining lymph nodes is a key pathologic characteristic. Inadequate lymph node harvesting may result in under treatment of patients. The purpose of the present study was to evaluate the factors that influence the number of lymph nodes retrieved in colorectal cancer specimens. Methods Sixty five patients with histologically proven colorectal adenocarcinoma over a period of 18 months were included. All patients underwent surgical resection for their disease. All significant patient, tumour and treatment variables were assessed for their impact on the average total number of lymph node harvested. Further, the efficacy of the GEWF solution (glacial acetic acid, ethanol, distilled water, formaldehyde) in lymph node retrieval was also assessed. Results In this study, 43 men and 22 women with a median age of 61 years were included. The median total number of lymph nodes examined was 17. 87.6% had adequate (≥ 12) lymph nodes examined, and 12.4% had <12 nodes examined. The number of lymph nodes were found to be higher and statistically significant in under 60-year-old group (p=0.001), tumours of size > 5cm (p=0.002), tumours of the ascending colon (p=0.025) and cases operated on by super specialist surgeons (p=0.017).Factors such as gender (p=0.23),BMI (p=0.22),tumour differentiation (p=0.348) and T staging (p=0.026) had no statistically significant association with lymph node harvest. Mean LN count was significantly higher (p = 0.0001) regrossing by a senior pathologist. However a statistically significant increase in LN harvest was not seen (p=0.159) when specimens were further subjected to GEWF treatment. Conclusions This study indicates that several modifiable factors impact LN retrieval and hence gives scope for improvement. Refinement of surgical and pathological care is suggested especially in challenging cases like rectal cancer and elderly patients.

Emerging Role of Chinese Herbal Medicines in the Treatment of Pancreatic Fibrosis

Pancreatic fibrosis is the main pathologic characteristic in chronic pancreatitis (CP), a common disease that arises from surgery. Pancreatitis is caused by various etiologies, but the mechanism of fibrosis is not completely understood. Existing clinical approaches mainly focus on mitigating the symptoms and therefore do not cure the phenomena. In recent years, there has been a heightened interest in the use of Chinese herbal medicine (CHMs) in the prevention and cure of CP as expressed by increasing numbers of clinical and experimental research. Despite early cell culture and animal models, CHMs are able to interact with plenty of molecular targets involved in the pathogenesis of pancreatic fibrosis mostly via the TGF-[Formula: see text]/Smads pathway; however, integrated and up-to-date communication in this domain is unavailable. This review focuses on the research progress of CHMs against pancreatic fibrosis due to CP in vitro and in vivo and summarizes the potential mechanisms. We also outlined the toxicology of some CHMs for fibrosis treatment in order to provide a fuller understanding of drug safety. This review may provide reference for further innovative drug research and the future development of treatments for CP with pancreatic fibrosis.

Tumor infiltrative pattern predicts sites of recurrence after curative gastrectomy for gastric cancer.

38 Background: In East Asia, the tumor infiltrative pattern (INF) has been routinely evaluated by hematoxylin and eosin-stained sections as a pathologic characteristic of surgically resected specimens. Methods: The infiltrative pattern of gastric cancer (GC) has been histopathologically classified as INFa (expansive growth), INFb (intermediate type) and INFc (infiltrative growth) according to the Japanese Classification of Gastric Carcinoma. The prognostic value and characteristics of the disease recurrence pattern for each INF type were assessed in 785 patients with various stages of GC and also in 243 patients with stages 2 and 3 GC. Results: Comparison of the overall survival experienced by patients independently of stage showed that INF was significantly associated with prognosis. Specifically, peritoneal metastasis was present in 91 % of stage 4 patients in the INFc group, whereas hepatic metastasis was present in 39 % of stage 4 patients in the INFa and INFb group. After curative gastrectomy of patients with stages 2 or 3 GC, INF was not significantly associated with survival. The prevalence of peritoneal recurrence was significantly higher in the INFc group than in the INFa and INFb group, whereas the prevalence of hepatic recurrence was significantly higher in the INFa and INFb group than in the INFc group. Multivariate analysis identified INFc as an independent risk factor for peritoneal recurrence after curative gastrectomy. The association of the INF type with the incidence of peritoneal recurrence was observed with all disease stages regardless whether the patient was given adjuvant chemotherapy or not. Conclusions: Evaluation of the INF type shows promise for its role as a predictor of postoperative recurrence sites in patients with GC.

A novel pathology-based preoperative risk score to predict distant and locoregional residual disease and survival for incidentally discovered gallbladder cancer: A 10-institution study from the US Extrahepatic Biliary Malignancy Consortium.

202 Background: T-stage alone is currently used to guide treatment for incidentally discovered gallbladder cancer. We aimed to develop a more robust predictive model for discovering distant or locoregional residual disease at the time of re-resection. Methods: All patients with incidentally discovered gallbladder cancer who underwent re-resection at 10 institutions from 2000-2015 were included. We utilized routine pathology data from initial cholecystectomy to create a gallbladder cancer predictive risk score (GBRS) for finding distant or locoregional residual disease at re-resection and predicting overall survival (OS). Results: Of 449pts with gallbladder cancer, 262 (58%) were incidentally discovered and underwent attempted re-resection. Advanced T-stage, grade, and lymphovascular (LVI) and perineural (PNI) invasion were all associated with increased rates of distant and locoregional residual disease, and decreased OS. Each pathologic characteristic was assigned a value (T1a: 0, T1b: 1, T2: 2, T3/4: 3; well diff: 1, mod diff: 2, poor diff: 3; LVI neg: 1, LVI pos: 2; PNI neg: 1, PNI pos: 2), which were added for a total GBRS score ranging from 3-10. The scores were then separated into 3 risk groups (Low: 3-4; Intermediate: 5-7; High: 8-10). Each progressive GBRS group was associated with an increased risk of finding distant and isolated locoregional residual disease at the time of re-resection, and was associated with reduced median OS (Table). Conclusions: By accounting for pathologic variations within each T-stage, this novel predictive risk-score redistributes T1b, T2, and T3 disease across separate risk-groups and more accurately identifies patients with incidentally discovered gallbladder cancer at risk for distant and locoregional residual disease, and decreased long-term survival. This score may help to better optimize treatment strategy for patients with incidentally discovered gallbladder cancer. [Table: see text]