Obesity is a strong risk factor for cancer progression, posing obesity-related cancer as one of the leading causes of death. Nevertheless, the molecular mechanisms that endow cancer cells with metastatic properties in patients affected by obesity remain unexplored.Here, we show that IL-6 and HGF, secreted by tumor neighboring visceral adipose stromal cells (V-ASCs), expand the metastatic colorectal (CR) cancer cell compartment (CD44v6 + ), which in turn secretes neurotrophins such as NGF and NT-3, and recruits adipose stem cells within tumor mass. Visceral adipose-derived factors promote vasculogenesis and the onset of metastatic dissemination by activation of STAT3, which inhibits miR-200a and enhances ZEB2 expression, effectively reprogramming CRC cells into a highly metastatic phenotype. Notably, obesity-associated tumor microenvironment provokes a transition in the transcriptomic expression profile of cells derived from the epithelial consensus molecular subtype (CMS2) CRC patients towards a mesenchymal subtype (CMS4). STAT3 pathway inhibition reduces ZEB2 expression and abrogates the metastatic growth sustained by adipose-released proteins. Together, our data suggest that targeting adipose factors in colorectal cancer patients with obesity may represent a therapeutic strategy for preventing metastatic disease.

The aim of the paper was to establish if the 12 lymph nodes recommended by tumor-node-metastasis (TNM) system are sufficient for a correct staging of rectal cancer. For this purpose, we first compared the mean number of lymph nodes recovered in the same surgical specimen at the routine sampling and at a resampling performed by a second expert gastrointestinal pathologist. The study was performed on 50 cases of pT2N0 and pT3N0 rectal cancers, with a minimum number of 12 lymph nodes recovered at first sampling, histologically negative for metastases. Resampling retrieved a variable number (1 to 24) of nodes missed at first sampling. The final pN0 status was maintained in pT2 patients, whereas in 18.7% of pT3 patients, metastatic lymph nodes were detected if the mean number of lymph nodes increased from 17.8 to 26.8 after the second sampling. Interestingly, all pN1 patients had only a single metastatic lymph node measuring less than 4.9 mm. As we have shown that most (five out of six) missed metastatic lymph nodes were detected in specimens in which a maximum number of 19 lymph nodes had been originally recovered, we strongly suggest a resampling of pT3N0 rectal specimens if less than 20 lymph nodes have been recovered.

Rectal gastrointestinal stromal tumors (GISTs) are uncommon, and the role of local excision versus a more extensive resection after the advent of effective targeted chemotherapy with imatinib is not known. Our aim is to present two cases of large anorectal GIST treated with local excision through a new anterolateral trans-sphincteric approach followed by adjuvant therapy with imatinib. Two patients (both males, 68 and 63 years old) presented at our institution with anorectal GIST in the period October-November 2010. Their medical records, pathology results, and imaging studies were retrospectively reviewed. Both patients presented with an anterior perianal mass. Imaging studies were characteristic of GIST originating in the lower rectum, circumscribed by a pseudocapsule, and protruding into the ischiorectal fossa. Both patients underwent local excision via an anterolateral trans-sphincteric approach. Both tumors were removed intact, with microscopically negative margins. The maximum tumor diameter was 8 and 9 cm, and the diagnosis of GIST was confirmed by positive CD117 and CD34 staining in both cases. Both tumors had a high (>5/50HPF) mitotic index. The patients had an uneventful postoperative course and were discharged on days 5 and 6. Both patients were started on imatinib 400 mg bid postoperatively. Postoperative magnetic resonance imaging and positron emission tomography computed tomography were carried out at 12 months and did not reveal any signs of recurrence. The patients are currently disease-free at 24 and 23 months of follow-up. In selected cases, complete excision of rectal GIST with negative margins is feasible via a trans-sphincteric approach. With the use of adjuvant therapy, which is currently advocated in all high-risk cases, it is possible that local excision with its reduced morbidity may become a viable alternative, especially in patients who would otherwise require abdominoperineal excision such as the two presented here. Prospective studies with longer follow-up are needed to confirm adequate oncologic results.

Between June, 1984 and December, 1985, a total of 41 patients were enrolled in a prospective controlled randomized trial comparing prophylactic sclerotherapy and medical treatment for the prevention of the first esophageal variceal bleeding. All patients had nonalcoholic liver cirrhosis, fourth degree varices, and no past history of gastrointestinal bleeding. The patients were randomly assigned to the control group (20 patients) or to the sclerotherapy group (21 patients); most of the patients belonged to Child's classes A and B. After a mean follow-up of 16.8 months, there were 3 variceal bleeding episodes and a 10% mortality rate in the control group whereas neither hemorrhage nor death was observed in the sclerotherapy group. In the latter group, severe complications occurred in 9.5% of the patients; the rate of recurrence after eradication of esophageal varices was 40%. Although there were no statistically significant results, the favorable trend toward a lower bleeding risk and better survival observed in the treated patients suggests that a longer trial in a larger population of cirrhotic patients with a longer follow-up should be considered.

a b s t r a c tEndometriosis within a perineal scar after a Miles' procedure has not been previously reported in literature. We report a case of a 35-year-old-female who was treated 10 years before at the same institution for a low rectal cancer that presents with two discrete subcutaneous bulges within her perineal wound. Since the patient was asymptomatic and the complete work up for recurrent disease showed no evidence of malignancy, first line therapy was conservative. After two pregnancies and a caesarean section, the patient presented at our observation with enlarged and tender perineal nodules. The patient was treated with a wide excision of the perineal scar en-bloc with the nodules. Final pathology report was consistent with scar endometriosis.