A surgically induced hypoxic environment causes changes in the metastatic behaviour of tumours in vitro.

The use of laparoscopic techniques for curative resections of malignant tumours has been under scrutiny. The potential benefits to the patient in the form of earlier recovery and less immune paresis are countered by the reports of increased tumour recurrence. The biological sequelae of the hypoxic laparoscopic environment on tumour cells is unknown. Components of the metastatic cascade were evaluated under in vitro laparoscopic conditions using a human colonic adenocarcinoma cell line (SW1222). Exposure to the laparoscopic gases carbon dioxide and helium for 4 h, comparable to the duration of a laparoscopic colorectal resection, had no effect on cell viability. A cellular hypoxic insult was demonstrated by the induction of hypoxia inducible factor 1alpha (HIF-1alpha). Exposure also resulted in significant reduction in homotypic adhesion as well as to a variety of extracellular matrix components. These effects were recoverable under re-oxygenation. The changes were reflected at the molecular level by significant down regulation of adhesion molecules known to be involved in tumour progression (E-cadherin, CD44 and beta1 sub-unit). Modulation of adherence has significant implications for laparoscopic oncological surgery, demonstrating that tumours become potentially more friable and easier to disseminate in surgeons who are less experienced or where instrumentation is sub-optimal.

Laparoscopic environmental changes during surgery enhance the invasive potential of tumours.

OBJECTIVE: The use of laparoscopic techniques in resection of malignant tumours has been proposed to offer potential benefit to the patient in the form of earlier recovery and less immune paresis; however, reported tumour seeding, both peritoneal and at port site, has put this approach into question. The biological effects of the introduction of carbon dioxide or helium to form a pneumoperitoneum on tumour invasion and dissemination are unknown. METHODS: A human colonic adenocarcinoma cell line (SW1222) was exposed to in vitro laparoscopic environment of either carbon dioxide or helium for 4 h, mimicking the duration of a laparoscopic colorectal resection. Alteration in production of matrix metalloproteinase (MMP)-2, MMP-9 and urokinase-type plasminogen activator (uPA) due to exposure to a laparoscopic environment was determined by zymography and correlated to invasive capacity by a standard Matrigel-based invasion assay. Incorporation of specific gelatinase inhibitors or antibodies directed at the uPA receptor was utilized to determine the relative importance of proteases. RESULTS: Exposure to the laparoscopic environment significantly enhanced production of the proteases MMP-2, MMP-9 and uPA. A concomitant enhancement of invasive capacity was also observed, being blocked by specific protease inhibitors. Changes in both protease production and aggression were observable for at least 24 h following the removal of the operative environment, indicating the possible long-term effects of the initial insult. CONCLUSION: Exposure to the laparoscopic environment enhances the invasive capacity of colonic adenocarcinomas via a well-defined protease-determined pathway. It therefore appears likely that tumour cells released into the operative field can be made increasingly aggressive by a laparoscopic operative environment and can thus contribute to disease dissemination.

Laparoscopic surgery for colon cancer.

Acceptance of laparoscopy for the management of oncological disease has been slow due to the increased complexity of the technique, requirement of technological advances, and fears for the oncological safety of the approach. Laparoscopic oncological surgery has a role in the management of oncological patients at all stages of disease. Good evidence exists for the laparoscopic approach being a viable option for colon cancer patients. Current large multicenter trials will report the true outcomes of laparoscopic colon cancer surgery and how it compares with open surgery. This article examines some of the parameters by which laparoscopic colectomy will be judged.

Laparoscopy for malignancy: current status.

The acceptance of laparoscopy for the management of oncologic disease has been slow because of initial fears regarding the effect of this new approach on the interaction between the patient and the tumor. Since the initial attempts at laparoscopic resection, experience and technology have improved in parallel, facilitating improvements in this area. Laparoscopic oncologic surgery has a role in the management of oncologic patients at all stages of disease. Good evidence exists that laparoscopy has become an invaluable staging tool in many upper gastrointestinal cancers as well as lymphomas. The specter of port-site recurrence has loomed over the use of a laparoscopic approach for curative resections. However, it is clear from many reported trials that the initial prevalence of port-site metastases was more a technical issue rather than a problem with laparoscopy. Current large, multicenter trials will report the true outcomes of laparoscopic colon cancer surgery and its comparison with open surgery. It does appear that laparoscopic cancer surgery is feasible, safe, and oncologically sound. We fully believe that laparoscopic cancer surgery will play an increasingly major role in the management of gastrointestinal malignancies.

Laparoscopic staging of pancreatic tumors induces increased invasive capacity in vitro.

INTRODUCTION: Laparoscopy and laparoscopic ultrasound have a well-defined role in staging patients with pancreatic malignancy. The effect of the hypoxic pneumoperitoneum induction on tumor biology is unknown. The authors investigated whether an in vitro pneumoperitoneum augments the invasive capacity of pancreatic tumors and elucidate a mechanism by which this may occur. METHODS: A pancreatic (PSN-1) adenocarcinoma cell line was exposed to an in vitro pneumoperitoneum (carbon dioxide (CO2) or helium) for a maximum of 2 h or left in normal growth conditions (control). Cells were nonenzymatically harvested and placed in invasion assays. These were performed over 72 h using Matrigel coated 8-mm Transwell filters and analyzed using MTS colorimetric assay. Gelatin zymography was employed to assess the level of matrix metalloproteases (MMP) 2 and 9 (gelatinase A and B) secretion. Expression of tissue inhibitor of metalloproteases 1 (TIMP-1) was assessed using ELISA (Biotrak). Inhibition of invasion assays was performed using a specific gelatinase inhibitor (MMPI; Calbiochem). RESULTS: The invasive capacity of pancreatic tumour cells is augmented versus control in both helium (p <0.05) and CO2 (p <0.001) groups. Concomitant significant upregulation of the gelatinase activity was demonstrated with both insufflants (p <0.05; 0.001, respectively). Enhanced invasion was attenuated by the addition of a specific gelatinase inhibitor (p <0.05). CONCLUSIONS: These results indicate the invasive capacity of pancreatic tumor cells is augmented by laparoscopic staging in vitro. This is in part mediated by increased gelatinase activity and may be attenuated by the addition of specific inhibitors.

Pneumoperitoneum augmented tumor invasiveness is abolished by matrix metalloproteinase blockade.

BACKGROUND: Certain surgical strategies, including Helium (He) and carbon dioxide (CO2) insufflation in laparoscopy, have been shown to induce a hypoxic environment. This may have a significant effect on the invasive capacity of tumor cells and may be a factor in the incidence of port-site metastases seen in patients following laparoscopic resection for malignancy. METHODS: A colon adenocarcinoma cell line (SW1222) was exposed to an in vitro pneumoperitoneum of CO2 or He at 3 mmHg or left in normal growth conditions (control). After a 4-hour exposure to an in vitro pneumoperitoneum, the ability of the cells to invade through 8.0-microm Transwell filters coated with Matrigel was analyzed by colorimetric MTS assay and by direct staining of the filters. The effect of the addition of a known blocker of matrix metalloproteinases (MMPs), 1,10-phenanthroline (1,10-P), was investigated. RESULTS: Cells exposed to an in vitro pneumoperitoneum demonstrate significantly increased invasive capacity compared to the control set, without loss of viability (He vs control, p <0.001; CO2 vs control, p <0.001). This augmented capacity is abolished by the addition of 1,10-P (p <0.01). CONCLUSION: Exposure of a colonic adenocarcinoma cell line to either a CO2 or He pneumoperitoneum causes an increase in tumor cell invasiveness, which is abolished by the presence of a known inhibitor of MMPs. This suggests that MMPs have an important role in the metastatic potential of tumors exposed to a hypoxic operative environment.

Laparoscopic herniorrhaphy: initial experience in 126 patients.

The initial experience in laparoscopic transabdominal preperitoneal mesh (TAPP) repairs is reviewed. In this study, consecutive TAPP repairs were performed in 126 patients. There were no intraoperative complications, and only 1 procedure had to be converted to open surgery. Forty-six patients had direct inguinal hernias, 56 had indirect inguinal hernias, and 24 had both, of which 21 were recurrent. Fifty-one hernias were right sided, 46 were left sided, and 29 were bilaterals. The male/female ratio was 116:10, and the mean age of the patients was 49.8 (range 17-76). Minor complications included parasthesia over the distribution of the lateral cutaneous nerve of the thigh in 2 patients, hydrocoeles in 2 patients, hematomata in 6 patients, and testicular pain in 4 patients, all of which resolved on conservative management. Incomplete bowel obstruction has been the only major postoperative complication to date, where an area of bowel herniated between two staples in the peritoneum. This was further complicated by an aspiration pneumonia and death of the patient. The mean hospital stay was 1.2 days (range 1-3), and the mean return to unrestricted activity was 8 days (range 3-12). There have been 2 true recurrences to date. One patient had a tender swelling after the repair, which was thought to be a recurrent strangulated hernia. On investigation, it was found to be a hematoma. The mean follow-up has been 7 months (range 1-18). Although early results of the TAPP repair are encouraging, we have had 1 significant complication that may have been avoided if an endoscopic extraperitoneal approach was employed.