Reduction of anastomotic failure in laparoscopic colorectal surgery using antitraction sutures.

BACKGROUND: Anastomotic leakage is a major complication in colorectal surgery. This study investigates a new method for reducing anastomotic failure using antitraction sutures. METHODS: In 2007, the authors began routine placement of three sutures at every one-third of the circular end-to-end anastomosis to reduce traction. Before the start of the new protocol, 76 patients received laparoscopic colorectal left sided surgery, 21 (28%) of whom received a defunctioning stoma. After the start of the new protocol, 77 patients received laparoscopic colorectal surgery, 6 (8%) of whom received a defunctioning stoma. RESULTS: Placement of a defunctioning stoma was significantly reduced (n = 21 vs. 6; P = 0.01). Only one patient (1%) in the sutured group experienced anastomotic leakage compared with six patients in the control group (P = 0.025). Other anastomosis-related complications during the follow-up period, including anastomotic stenosis and intraabdominal abscess, occurred more frequently in the control group, although the difference did not reach significance. CONCLUSION: The use of antitraction sutures to support the anastomosis seems to reduce the occurrence of anastomotic leakage in laparoscopic left colorectal surgery. A prospective randomized trial is necessary to prove the decreasing effect of antitraction sutures on anastomotic leakage as well as the major decreasing effect on the necessity of placement of defunctioning stomas.

Decrease of CD117 expression as possible prognostic marker for recurrence in the resected specimen after imatinib treatment in patients with initially unresectable gastrointestinal stromal tumors: a clinicopathological analysis.

Gastrointestinal stromal tumors (GIST) are the most common malignant mesenchymal tumors of the gastrointestinal tract. The principal treatment modality for primary GIST is surgery whereas for metastatic GIST, imatinib has an established role. In patients with locally advanced and metastatic GIST, the role of surgery in the imatinib era is still unclear. Fifteen patients with locally advanced (n=9) and/or metastatic GIST (n=6) were treated with imatinib followed by resection. Detailed histopathological examination was performed before and after treatment with imatinib, which was given for a median of 11 months before surgery. Ten patients showed a radiographic partial response, four patients had stable disease, and one patient progressed. At the time of surgery, the median tumor diameter was 6.5 cm. In all the nine patients with locally advanced GIST, a R0 resection could be performed. Histopathological examination showed imatinib effects in all tumors, including the case with progressive disease. All patients with locally advanced disease (n=9) were alive after a median follow-up of 40 months (range: 18-59), of which seven patients were free of disease. Four of the six patients treated for metastatic GIST died of disease after 30, 45, 50, and 74 months of follow-up. Remarkably, in five of six patients in whom CD117 expression was diminished or lost in the resection specimen, disease recurrence was observed. In patients with retained CD117 expression, one of the nine patients had recurrent disease. In conclusion, preoperative imatinib treatment in patients with locally advanced GIST resulted in a decrease of tumor load in most patients, enabling complete surgical resection. For patients with metastatic GIST, the role of surgery remains less clear. Loss or decrease of CD117 expression in the resected specimen after imatinib treatment may be associated with disease recurrence.

Increased tumor growth after high pressure pneumoperitoneum with helium and air.

BACKGROUND: Tumor growth appears proportional to the pressure of carbon dioxide insufflation during laparoscopic surgery. Air and helium are alternative insufflation gases. The objective of this study is to assess tumor growth after air and helium insufflation at different pressures. METHOD: Ninety-six WAG rats were allocated to either air or helium. In both arms, rats were randomly exposed to a one hour gasless procedure, or to 4 mm Hg, 10 mm Hg, or 16 mm Hg insufflation. At the start of the procedure, 500,000 CC531 tumor cells were injected intraperitoneally. After three weeks, intraperitoneal tumor growth was assessed. RESULTS: Higher insufflation pressures were associated with greater tumor growth. No difference of tumor growth between air and helium insufflation was found. CONCLUSION: In this experimental model, insufflation pressure appeared to have a greater impact on tumor growth than the type of gas. Further studies are necessary but it seems prudent to recommend employment of lower insufflation pressures in laparoscopic oncologic surgery.

Irrigation of port sites: prevention of port site metastases?

INTRODUCTION: Port site metastases can occur when free viable tumor cells implant at trocar wounds. Irrigation of port sites with cytotoxic agents has been suggested to prevent port site metastases. The objective of this study is to assess whether tumor growth at port sites can be reduced by irrigation of these port sites. METHODS: WAG rats were insufflated with CO(2) for 20 minutes and 5 x 10(5) CC531 tumor cells were injected intraperitoneally. Port sites were irrigated after completion of the pneumoperitoneum with povidone-iodine, a mixture of taurolidine and heparin, or sodium chloride. Controls did not undergo any irrigation of port sites. In experiment 1, all 16 rats had all 4 irrigation modalities. In experiment 2, four groups of 20 rats had one type of irrigation on two trocar wounds. Tumor growth was evaluated 4 weeks after the procedure. RESULTS: No difference in tumor growth at trocar wounds was found between any type of irrigation and controls in both experiments. CONCLUSION: In this experimental model, no beneficial or adverse effects of irrigation of port sites could be shown.

Anti-tumor effect and increased survival after treatment with [177Lu-DOTA0,Tyr3]octreotate in a rat liver micrometastases model.

Peptide receptor scintigraphy with [(111)In-DTPA(0)]octreotide (a stabilized radiolabeled somatostatin (SS) analogue, OctreoScan) is widely used for the visualization and staging of somatostatin receptor-positive tumors. The application of likewise somatostatin analogues as vehicle for the deliverance of radionuclides to somatostatin receptor-positive targets are now in use for peptide receptor-targeted radionuclide therapy (PRRT). Currently preclinical and clinical investigation are ongoing trying to find the optimal combination of radionuclide and ligand. The anti-tumoral effects of such combinations, like [90Y-DOTA degrees, Tyr(3)]octreotide and [(177)Lu-DOTA degrees, Tyr(3)]octreotate, on SSR-positive solid tumors have been reported. In this study we present the anti-tumor effects of (177)Lu-DOTA-tate on: a) a single SSR-positive cell model and b) on a SSR-positive tumor in a rat liver micrometastatic model, mimicking disseminated disease. (177)Lu-DOTA-tate showed anti-tumoral effects in both cases and significant survival in the PRRT-treated rats. (177)Lu-DOTA-tate is a very promising new treatment modality for SSR-positive tumors, including disseminated disease.

Somatostatin receptor gene therapy combined with targeted therapy with radiolabeled octreotide: a new treatment for liver metastases.

OBJECTIVE: To evaluate the effect of peptide receptor radionuclide therapy (PRRT) on somatostatin receptor (SSR)-transfected colon carcinoma cells in a rat liver metastases model. SUMMARY BACKGROUND DATA: Previously the authors have shown highly effective therapy with PRRT of SSR-positive tumors. This treatment is SSR-mediated; successful treatment is seen only in SSR-positive tumors, with no effect in SSR-negative tumors. As many tumors lack this receptor, the idea arose to transfect SSR-negative tumor cells with an SSR gene to apply PRRT on these SSR-transfected tumor cells. METHODS: CC531 colon carcinoma cells (SSR-negative) were transfected in vitro with an SSR (subtype 2) gene (CC2B). Liver metastases were produced after intraportal injection of these tumor cells in rats. On day 7, animals were treated with 185 or 370 MBq [177 Lu-DOTA0, Tyr3 ]octreotate. After 21 days rats were killed and liver metastases were counted. RESULTS: Treatment with 370 MBq [177 Lu-DOTA0, Tyr3 ]octreotate showed a significant antitumor response in rats with CC2B liver metastases (SSR-positive) in comparison with controls. No significant antitumor effect was seen in PRRT-treated rats with CC531 liver metastases (SSR-negative). Also, a dose-dependent tumor response was seen in rats with CC2B liver metastases treated with 185 MBq [ 177Lu-DOTA0, Tyr3 ]octreotate compared with controls. In addition, rats with mixed liver metastases treated with 185 MBq [177 Lu-DOTA0, Tyr3 ]octreotate had significantly fewer metastases compared with controls. CONCLUSIONS: The authors showed an impressive antitumor effect of SSR (subtype 2)-transfected colon carcinoma cells with PRRT in a rat liver metastasis model. Moreover, rats with mixed liver metastases had significantly fewer liver metastases compared with control rats, which may be due to a radiologic bystander effect of [177 Lu-DOTA0, Tyr3 ]octreotate. This phenomenon is beneficial in the concept of in vivo gene therapy.