The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named ‘Immunoscore’ has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune). © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Purpose: To determine whether the tumor immune infiltrate, as recently evaluated with the Immunoscore methodology, could be a useful prognostic marker in patients with rectal cancers.Experimental design: The influence of the immune infiltrate on patient's outcome was investigated in patients with or without preoperative chemoradiation therapy (pCRT). The density of total (CD3 þ ) and cytotoxic (CD8 þ ) T lymphocytes was evaluated by immunohistochemistry and quantified by a dedicated image analysis software in surgical specimens of patients with rectal cancer (n ¼ 111) who did not receive pCRT and in tumor biopsies performed before pCRT from additional 55 patients. The results were correlated with tumor recurrence, patient's survival, and response to pCRT.Results: The densities of CD3 þ and CD8 þ lymphocytes and the associated Immunoscore (from I0 to I4)were significantly correlated with differences in disease-free and overall survival (HR, 1.81 and 1.72, respectively; all P < 0.005). Cox multivariate analysis supports the advantage of the Immunoscore compared with the tumor-node-metastasis (TNM) staging in predicting recurrence and survival (all P < 0.001). Lymph node ratio added information in a prognostic model (all P < 0.05). In addition, high infiltration of CD3 þ and CD8 þ lymphocytes in tumor biopsies was associated with downstaging of the tumor after pCRT (CD3 þ cells; Fisher exact test P ¼ 0.01). Conclusions:The Immunoscore could be a useful prognostic marker in patients with rectal cancer treated by primary surgery. The determination of the immune infiltrate in biopsies before treatment could be a valuable information for the prediction of response to pCRT.

Purpose: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (IS B) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy ("Watchand-Wait"). Experimental Design: Biopsies from two independent cohorts (n 1 ¼ 131, n 2 ¼ 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3 þ and CD8 þ T cells and quantified by digital pathology to determine IS B. The expression of immune-related genes post-nT was investigated (n ¼ 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The IS B prognostic performance was further assessed in a multicentric cohort (n ¼ 73 patients) treated by Watch-and-Wait. Results: IS B positively correlated with the degree of histologic response (P < 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P ¼ 0.006). IS B high identified patients at lower risk of relapse or death compared with IS B low [HR, 0.21; 95% confidence interval (CI), 0.06-0.78; P ¼ 0.009]. Prognostic performance of IS B for DFS was confirmed in a validation cohort. IS B was an independent parameter, more informative than pre-(P < 0.001) and post-nT (P < 0.05) imaging to predict DFS. IS B combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the "Watch-and-Wait" cohort (n ¼ 73), no relapse was observed in patients with IS B high (23.3%). Conclusions: IS B predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.

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Between 1980 and 1993, 18 patients underwent formal laparotomy after laparostomy and healing of the peritoneal cavity by granulation. The majority (12 patients) were men and the median age was 47 (range 22-67) years. Intraabdominal infection following surgery for Crohn's disease (four patients) and necrotizing pancreatitis (six) was the most common primary condition requiring laparostomy. A total of 23 reconstructive operations were carried out on the 18 patients a median of 6 (range 1-18) months after laparostomy. The indication for surgery was for closure and/or resection of an enteric fistula in 13 patients. The site of the fistula included three gastric, two duodenal, 11 small bowel and seven colonic. A further four patients required operation for closure or refashioning of a stoma. Five patients subsequently required a second laparotomy: two for elective restoration of bowel continuity, two for recurrent fistula and one for an acute abdomen. After reconstructive surgery following laparostomy 16 patients were discharged home alive and well, one requiring home parenteral nutrition for short bowel syndrome. In contrast, the two oldest patients in the series died from multiple organ failure immediately after initial reconstructive surgery. Both had pre-existing medical problems and in neither was there evidence of further intra-abdominal infection after reconstruction.

BackgroundNew and fully validated tests need to be brought into clinical practice to improve the estimation of recurrence risk in patients with colon cancer. The aim of this study was to assess the analytical performances of the Immunoscore (IS) and show its contribution to prognosis prediction.MethodsImmunohistochemical staining of CD3+ and CD8+ T cells on adjacent sections of colon cancer tissues were quantified in the core of the tumor and its invasive margin with dedicated IS modules integrated into digital pathology software. Staining intensity across samples collected between 1989 and 2016 (n=595) was measured. The accuracy of the IS workflow was established by comparing optical and automatic counts. Analytical precision of the IS was evaluated within individual tumor block on distant sections and between eligible blocks. The IS interlaboratory reproducibility (n=100) and overall assay precision were assessed (n=3). Contribution of the IS to prediction of recurrence based on clinical and molecular parameters was determined (n=538).ResultsOptical and automatic counts for CD3+ or CD8+ were strongly correlated (r=0.94, p<0.001 and r=0.92, p<0.001, respectively). CD3 and CD8 staining intensities were not altered by the age of the tumor block over a period of 30 years. Neither the position of tested tissue sections within a tumor block nor the selection of the tissue blocks affected the IS. Reproducibility of the IS was not affected by multiple variables (eg, antibody lots, DAB revelation kits, immunohistochemistry automates and operators). Interassay repeatability of the IS was 100% and interlaboratory reproducibility between two testing centers was 93%. Finally, in a case series of patients with stage II–III colon cancer, the relative proportion of variance for time to recurrence was greatest for the IS (53% of prognostic variability) in a model that included IS, T-stage, microsatellite instability status and total number of lymph nodes.ConclusionIS is a robust and validated clinical assay leveraging immune scoring to predict recurrence risk of patient with localized colon cancer. The strong and independent prognostic value of IS should pave the way for it use in clinical practice.

BS apparently has positive effects on kidney function and tends to normalize GFR across different categories of renal impairment (hyperfiltration and CKD patients).

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