Role of gut microbiota-immunity axis in patients undergoing surgery for colorectal cancer:Focus on short and long-term outcomes

Human body is colonized by a huge amount of microorganisms mostly located in the gastrointestinal tract.These dynamic communities,the environment and their metabolites constitute the microbiota.Growing data suggests a causal role of a dysbiotic microbiota in several pathologies,such as metabolic and neurological disorders,immunity dysregulations and cancer,especially the well-studied colorectal cancer development.However,many were preclinical studies and a complete knowledge of the pathogenetic mechanisms in humans is still absent.The gut microbiota can exert direct or indirect effects in different phases of colorectal cancer genesis.For example,Fusobacterium nucleatum promotes cancer through cellular proliferation and some strains of Escherichia coli and Bacteroides fragilis produce genotoxins.However,dysbiosis may also cause a proinflammatory state and the stimulation of a Th17 response with IL-17 and IL-22 secretion that have a pro-oncogenic activity,as demonstrated for Fusobacterium nucleatum.Microbiota has a crucial role in several stages of postoperative course;dysbiosis in fact seems related with surgical site infections and Enterococcus faecalis(and other collagenase-producers microbes)are suggested as a cause of anastomotic leak.Consequently,unbalanced presence of some species,together with altered immune response may also have a prognostic role.Microbiota has also a substantial role in effectiveness of chemotherapy,chemoresistance and in the related side effects.In other words,a complete knowledge of the fine pathological mechanisms of gut microbiota may provide a wide range of new diagnostic tools other than therapeutic targets in the light of tailored medicine.

Multiple Detector-Row CT in Gastric Cancer Staging: Prospective Study

The aim of this study was to evaluate the accuracy of multiple detector computed tomography (MDCT) in the preoperative staging of gastric cancer, prospectively comparing CT findings with pathological findings at surgery, in a single-center study. A total of 19 consecutive patients with primary cancer recruited between March and July 2014 were submitted to preoperative MDCT staging according to a standard protocol. All diagnostic procedures were performed by dedicated radiologists who were unaware of the final pathological results. Subsequently, 16 patients underwent surgical treatment and 15 were finally included in the study. The primary tumor was detected at CT in all 15 cases. CT results for T staging were in agreement with pathological findings in 12 of 15 cases, with overall accuracy of 80%. Stage-specific sensibility was high for advanced stages (sensibility for T1, T3, and T4 resulted 60%, 85.7%, and 100%, respectively), while earlier stages showed higher specificity (specificity for T1, T3, and T4 resulted 100%, 75%, and 91.7%, respectively). Overall N staging accuracy was 86.7%, with 13 of 15 patients correctly staged. Stage-specific sensibility was 75% for N0 and 100% for N3, while specificity was 100% for N0 and lower for advanced stages. Accuracy for peritoneal involvement was 100%. Our findings show a good performance of the diagnostic protocol performed with MDCT tested in this study.

Evaluation of prognostic factors and clinicopathological patterns of recurrence after curative surgery for colorectal cancer

BACKGROUND Colorectal cancer is a common tumor with a quite high-related mortality.Despite the used curative treatments,patients will develop cancer recurrence in up to 50%of the cases and/or other primary neoplasms.Although most of the recurrences are discovered within 3 years from the first treatment,a small percentage is found after 5 years.The early detection of recurrence is crucial to allow further therapies improving patients’survival.Several follow-up programs have been developed but the optimal one is far from being established.AIM To evaluation of potential prognostic factors for timing and patterns of recurrence in order to plan tailored follow-up programs.METHODS Perioperative and long-term data of all consecutive patients surgically treated with curative intent,from January 2006 to June 2009,for colorectal adenocarcinoma,were retrospectively reviewed to find potential prognostic factors associated with:(1)Recurrence incidence;(2)Incidence of an early(within 3 years from surgery)or late recurrence;and(3)Different sites of recurrence.In addition,the incidence of other primary neoplasms has been evaluated in a cohort of patients with a minimum potential follow-up of 10 years.RESULTS Our study included 234 patients.The median follow-up period has been 119±46.2 mo.The recurrence rate has been 25.6%.Patients with a higher chance to develop recurrence had also the following characteristics:Higher levels of preoperative glycemia and carcinoembryonic antigen,highest anaesthesiologists Score score,occlusion,received a complex operation performed with an open technique,after a longer hospital stay,and showed advanced tumors.The independent prognostic factors for recurrence were the hospital stay,N stage 2,and M stage 1(multivariate analysis).Younger ages were significantly associated with an early recurrence onset.Patients that received intermediate colectomies or segmental resections,having an N stage 2 or American Joint Committee on Cancer stage 3 tumors were also associated with a higher risk of liver recurrence,while metastatic diseases at diagnosis were linked with local recurrence.Neoadjuvant treatments showed lung recurrence.Finally,bigger tumors and higher lymph node ratio were associated with peritoneal recurrence(marginally significant).Thirty patients developed a second malignancy during the follow-up time.CONCLUSION Several prognostic factors should be considered for tailored follow-up programs,eventually,beyond 5 years from the first treatment.

Complications Following Surgery for Gastric Cancer: Analysis of Prospectively Collected Data

Background and Aims: The complication rate after surgery for gastric cancer varies according to the particular definition of morbidity, so it’s necessary to report them using a standardized method, the Clavien-Dindo system. The purpose of this study was to prospectively analyze all post-gastrectomy complications in patients with gastric adenocarcinoma according to the severity grade using Clavien-Dindo system, in order to identify risk factors for postoperative complications and their prognostic significance on survival. Methods: This study is based on data from 90 consecutive patients who underwent gastrectomy for gastric neoplasia between January 2010 and February 2014 at the same unit. 15 patients were excluded (benign tumors, GISTs, missing data). Complications were categorized according to the Clavien-Dindo classification (uncomplicated patients vs patients classified ≥Grade I). The following risk factors were studied: age, BMI, sex, operation method, extent of resection, duration of surgery, transfusions, TNM staging, and lymph node ratio. Multivariate logistic regression was used to evaluate the association between risk factors and presence of complications. To assess the effect on overall survival, after selection of covariates using backward elimination, the Cox proportional hazard model was applied. Results: Among these patients, 49 (65.3%) developed complications, stratified as follows: Grade I, 6 (8%);Grade II, 24 (32%);Grade III, 6 (8%);Grade IV, 13 (17.3%). The laparoscopic technique (OR = 0.050;95% CI = 0.005 - 0.550, p = 0.0143) and no transfusions (OR = 0.219;95% CI = 0.058 - 0.827, p = 0.0251) were found to reduce the incidence of postoperative complications in the multivariate analysis. With regard to the survival analysis, lymph node ratio, malnutrition, extended resection and presence of complications were significant predictors of reduced survival in the multivariate analysis. Conclusions: Some variables can predict the risk of postoperative complications, the occurrence of which is a predictor of reduced probability of survival. In this respect it’s essential to reduce complications.

A New Early Gastric Cancer after Subtotal Gastric Resection for Early Cancer: Case Report and Review of the Literature

Although the prognosis of early gastric cancer (EGC) is considered to be satisfactory, some patients experience tumor relapse after curative surgery. Both pathogenesis and risk factors of recurrence remain unclear. We describe a case report of a 49-year-old male who underwent subtotal gastric resection D2A for angular gastric cancer. Histological examination revealed gastric adenocarcinoma with low grade of differentiation and colloid areas, intramucosal, and absence of neoplastic proliferation in the surgical margins, in omental stroma and in the six examined lymph nodes (pT1, pN0). 11 years later, the same patient underwent D2 total gastrectomy for gastric cancer in the remnant stomach. New histological examination revealed again gastric adenocarcinoma, intramucosal, medium degree of differentiation, no documentable neoplastic proliferation within the limits of surgical resection, in the thirty-three examined lymph nodes and in the omentum (pT1, pN0).