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Following the introduction of total mesorectal excision (TME) in the curative treatment of rectal cancer, the role of neoadjuvant therapy has evolved. By improving the surgical technique the local recurrence rate could be reduced by TME surgery alone to below 8 %. Even if local control was further improved by additional preoperative irradiation this did not lead to a general survival benefit. Guidelines advocate that all patients in UICC stage II and III should be pretreated; however, the stage-based indications for neoadjuvant therapy have limitations. This is mainly attributable to the facts that patients with T3 tumors comprise a very heterogeneous prognostic group and preoperative lymph node diagnostics lack accuracy. In contrast, in recent years the circumferential resection margin (CRM) has become an important prognostic parameter. Patients with tumors that are very close to or infiltrate the pelvic fascia (positive CRM) have a higher rate of local recurrence and poorer survival. With high-resolution pelvic magnetic resonance imaging (MRI) examination in patients with rectal cancer, the preoperative CRM can be determined with a high sensitivity and specificity. Improved T staging and better prediction of the resection margins by pelvic MRI potentially facilitate the selection of patients for study-based treatment strategies omitting neoadjuvant radiotherapy. [ABSTRACT FROM AUTHOR]

Perioperative complications following surgical procedures of the lower gastrointestinal tract still represent a relevant problem. The perioperative morbidity may negatively affect short and long-term outcomes of treatment of individual patients. The additional diagnostics and treatment required also lead to additional costs that burden the healthcare system. Ideally, complications should be avoided by preventive measures. In the event of a complication, early detection is essential for appropriate treatment. Surgical site infections (SSI) have been described as the most common complication in the postoperative period and may occur in up to 30 % of cases. Through various perioperative measures up to 40-60 % of SSI are preventable. Depending on the location, the reported anastomotic leakage rate ranges from 1 % to 23 %. The therapeutic strategy ranges from conservative measures through interventional methods up to surgical revision. An early postoperative burst abdomen occurs in about 3 % of cases. A midline closure with small stitches and small suture distances (suture length to wound length ratio of 4) seems to be superior to large stitches with long distance intervals. A rare but potentially fatal complication is bleeding. The identification of patients with relevant risk factors is of great importance. This article summarizes the prevention, recognition and treatment of perioperative complications after surgery of the lower gastrointestinal tract. [ABSTRACT FROM AUTHOR]

The treatment of rectal cancer has evolved significantly in recent decades. Both modern radiotherapy treatment concepts and surgical techniques have been able to improve oncological as well as functional outcomes for rectal cancer patients. Large-scale, multicenter, randomized trials have been able to demonstrate the benefits of neoadjuvant treatment over adjuvant radiotherapy. In addition, local tumor control is improved by neoadjuvant irradiation. Conversely, patients receiving a total mesorectal excision showed no survival advantage following irradiation vs. only surgically resected patients. In addition, radiation therapy is associated with a certain morbidity and mortality. This paper summarizes the available evidence regarding postoperative morbidity, mortality, and long-term chronic effects of neoadjuvant radiotherapy. [ABSTRACT FROM AUTHOR]

Herpes simplex virus-1 (HSV-1) replication in cancer cells leads to their destruction (viral oncolysis) and has been under investigation as an experimental cancer therapy in clinical trials as single agents, and as combinations with chemotherapy. Cellular responses to chemotherapy modulate viral replication, but these interactions are poorly understood. To investigate the effect of chemotherapy on HSV-1 oncolysis, viral replication in cells exposed to 5-fluorouracil (5-FU), irinotecan (CPT-11), methotrexate (MTX) or a cytokine (tumor necrosis factor-α (TNF-α)) was examined. Exposure of colon and pancreatic cancer cells to 5-FU, CPT-11 or MTX in vitro significantly antagonizes both HSV-1 replication and lytic oncolysis. Nuclear factor-κB (NF-κB) activation is required for efficient viral replication, and experimental inhibition of this response with an IκBα dominant-negative repressor significantly antagonizes HSV-1 replication. Nonetheless, cells exposed to 5-FU, CPT-11, TNF-α or HSV-1 activate NF-κB. Cells exposed to MTX do not activate NF-κB, suggesting a possible role for NF-κB inhibition in the decreased viral replication observed following exposure to MTX. The role of eukaryotic initiation factor 2α (eIF-2α) dephosphorylation was examined; HSV-1-mediated eIF-2α dephosphorylation proceeds normally in HT29 cells exposed to 5-FU, CPT-11 or MTX. This report demonstrates that cellular responses to chemotherapeutic agents provide an unfavorable environment for HSV-1-mediated oncolysis, and these observations are relevant to the design of both preclinical and clinical studies of HSV-1 oncolysis. [ABSTRACT FROM AUTHOR]

hrR3 is an oncolytic herpes simplex virus 1 (HSV-1) mutant that replicates preferentially in tumors compared with normal tissues. Portal venous administration of hrR3 in mice bearing diffuse colorectal carcinoma liver metastases significantly reduces tumor burden and prolongs animal survival. In this study, we compared survival benefit and biodistribution of hrR3 following intravenous (i.v.) administration versus intraperitoneal (i.p.) administration in immunocompetent mice bearing colon carcinoma peritoneal metastases. Mice bearing peritoneal metastases received 1 × 108 plaque-forming units hrR3 or mock-infected media every other day for three doses and were randomized to have the viruses administered by either an i.p. or i.v. route. Biodistribution was assessed by PCR amplification of HSV-1-specific sequences from tumor and normal tissues including the small bowel, liver, spleen, kidney, lung, heart and brain. LD50 for i.p. administration was compared with the LD50 for i.v. administration. In subsequent experiments, animals were monitored for survival. The frequency of HSV-1 detection in peritoneal tumors was similar in mice randomized to either i.p. or i.v. administration. However, i.p. administration resulted in a more restricted systemic biodistribution, with a reduced frequency of virus detected in the kidney, lung and heart. The LD50 associated with i.p. administration was higher than that with i.v. administration. Tumor burden was more effectively reduced with i.p. compared with i.v. administration. Median survival following i.p. administration was approximately twice that observed with i.v. administration. I.p. administration of an HSV-1 oncolytic mutant is associated with a more restricted biodistribution, less toxicity and greater efficacy against peritoneal metastases compared with i.v. administration.Cancer Gene Therapy (2009) 16, 291–297; doi:10.1038/cgt.2008.83; published online 7 November 2008 [ABSTRACT FROM AUTHOR]