Iatrogenic superior mesenteric vein injury: the perils of high ligation.

PURPOSE: The purpose of this review is to highlight the perils and pitfalls associated with high vascular ligation during right colectomies for adenocarcinoma and to identify the various mechanisms of injury to the superior mesenteric vein (SMV) and its tributaries. METHODS: This is a retrospective chart review of 304 right colectomies (159 open and 145 laparoscopic) performed over a period of 10 years (1 June 2006-31 May 2016) for right-sided colonic adenocarcinoma in an academic medical center. RESULTS: During a 10-year study period, we encountered five cases in which significant damage to the SMV and its tributaries occurred. This accounts for a total of 1.6 % of all right colectomies performed for colonic adenocarcinoma. CONCLUSIONS: Iatrogenic superior mesenteric vein injury is a rare, severe, and underreported complication of both open and laparoscopic right colectomy for colonic adenocarcinoma. We identified several mechanisms of injury such as anatomic misperception, excessive traction and pulling on the venous system, extensive tumor involvement of the mesentery, and uncontrolled suturing attempts at hemostasis. We believe that increased awareness of this complication with profound understanding of vascular anatomy and the different mechanisms of injury will allow surgeons to avoid this often devastating complication.

The use of molecular markers as a method to predict the response to neoadjuvant therapy for advanced stage rectal adenocarcinoma.

AIM: The response to combined neoadjuvant therapy for advanced stage rectal adenocarcinoma is predictive of outcome. In addition to both clinical and pathological features, the expression of a variety of molecules may provide another method of identifying tumour responsiveness to pre-operative therapy. The aim of this study was to evaluate several markers in the apoptotic pathway as well as expression of Cox-2 and vascular endothelial growth factor (VEGF) to determine their ability to predict response to neoadjuvant therapy. METHOD: In total, 152 patients with advanced rectal adenocarcinoma were treated with neoadjuvant therapy followed by resection. Paraffin-embedded sections obtained before and after therapy were assessed by immunohistochemical staining for Cox-2, VEGF, p53, p21, p27, Bax, BCL-2 and apoptosis protease-activating factor 1 (APAF-1). These stains were correlated with tumour regression grade, complete pathological response and T-downstaging of the surgical specimen. Clinical and pathological data were also collected. Data were analysed using the χ2 and Spearman's correlation tests. RESULTS: Pathological complete response was seen in 24.5% of patients. Amongst the apoptosis-associated markers, only APAF-1 expression was found to be significantly associated with tumour regression grade (P<0.001), complete pathological response (P<0.031) and T-downstaging (P<0.004). On multivariate analysis, APAF-1 expression was found to be independently associated with good tumour regression grade. In contrast, overexpression of Cox-2 and VEGF in pretreatment biopsies was related to less tumour regression (P<0.003) and less likelihood of T-downstaging (P<0.03). CONCLUSION: Immunohistochemical evaluation of initial biopsy specimens of rectal cancer with APAF-1, Cox-2 and VEGF may predict tumour response to neoadjuvant therapy in patients with advanced rectal adenocarcinoma. Those with an expected limited response may be considered for other investigational neoadjuvant protocols.

Herpes simplex virus delivery to orthotopic rectal carcinoma results in an efficient and selective antitumor effect.

Cancer of the rectum poses a complex therapeutic challenge because of its proximity to adjacent organs and anal sphincters. The addition of radiotherapy before surgical resection has been shown to confer good survival rates while preserving sphincter function. Nevertheless, radiation is associated with significant side effects. On the basis of our previous work showing that herpes simplex virus type-1 (HSV-1) preferentially infects human colon cancer, we set out to examine the oncolytic effect of HSV-1 on orthotopic rectal tumors in mice. Two vectors were compared for oncolytic activity, HSV-1(Gbeta) with wild-type replication and an attenuated HSV-1 vector (HSV-G47Delta). Intratumoral injection of HSV-1(Gbeta) and HSV-G47Delta resulted in a significant reduction or disappearance of the tumors and increased survival of mice. Although the use of HSV-1(Gbeta) was associated with systemic toxicity, HSV-G47Delta appears to possess a selective oncolytic activity. Moreover, infection with HSV-G47Delta resulted in the activation of the double-stranded RNA-dependent protein kinase (PKR) pathway. A significant improvement in viral replication and the antitumor effect was observed when the PKR inhibitor 2-aminopurine was coadministered with HSV-G47Delta to the tumor. In conclusion, the efficacy of local delivery of HSV-G47Delta combined with a specific chemical inhibitor of antiviral activity points to a novel therapeutic modality for rectal cancer and other solid tumors.