Susan J. Neuhaus

Surgical management of primary and recurrent retroperitoneal liposarcoma.

Surgery plays a dominant role in the initial and subsequent treatment of retroperitoneal liposarcoma (RPLS). This study was a review of outcomes of patients treated at the Royal Marsden Hospital.

Tumor implantation following laparoscopy using different insufflation gases

AbstractBackground: Laparoscopic manipulation of malignancies is associated with an increased incidence of metastasis to port sites in experimental models. This study investigated the effect of different insufflation gases on the implantation of a tumor cell suspension following laparoscopic surgery in an established small animal model. Methods: Forty Dark Agouti rats underwent laparoscopy and the introduction into the peritoneal cavity of a tumor cell suspension. The insufflating gas used for each procedure was one of the following gases (10 rats in each group): carbon dioxide (CO2), nitrous oxide (N2O), helium, and air. The rats were killed 7 days after surgery, and the peritoneal cavity and port sites were examined for the presence of tumor. Results: Although no significant differences were seen between air, CO2, and N2O insufflation groups, tumor involvement of peritoneal surfaces was less likely following helium insufflation. Conclusion: The results of this study suggest that tumor metastasis to port sites following laparoscopic surgery may be influenced by the choice of insufflation gas. In this study, helium was associated with reduced tumor growth.

Pneumoperitoneum and peritoneal surface changes: a review

BackgroundRecent evidence suggests that the use of carbon dioxide to create a pneumoperitoneum during laparoscopy can lead to adverse structural, metabolic, and immune derangements within the peritoneal cavity, and that these can be dependent on the specific insufflation gas used. These changes include structural alterations in the mesothelial lining, pH disturbances, and alterations in peritoneal macrophage responsiveness. This contrasts with an apparent systemic benefit associated with laparoscopic, as compared with open, surgery.MethodsRecently published clinical and experimental studies related to the effect of pneumoperitoneum on the peritoneal surface are reviewed, and their relevance is discussed.ResultsStructural changes in the peritoneal mesothelial surface layer such as widening of the intercellular junctions can be demonstrated with electron microscopy. Acidification of the peritoneum in response to carbon dioxide insufflation occurs not only at the peritoneal surface, but also in the underlying connective tissue, resulting in disturbances in the electrical surface charge and the release of various immune mediators such as endotoxin. Pneumoperitoneum also affects the local peritoneal immune environment resulting in alterations in cytokine production and phagocytic function, as well as diminished antitumor cell cytotoxicity.ConclusionsUltrastructural, metabolic, and immune alterations are observed at the peritoneal surface in response to a pneumoperitoneum. Experimental evidence suggests that these changes are carbon dioxide–specific effects. The consequences of these alterations to the local peritoneal environment are not well understood, but they may facilitate tumor implantation within the peritoneal cavity and adversely affect the ability to clear intraperitoneal infections. Further investigation into this area is warranted.

Helium and other alternative insufflation gases for laparoscopy

Background: Carbon dioxide (CO2) is currently the insufflation gas of choice for laparoscopy. It fulfills most of the requirements for an ideal insufflation gas, being colorless, noninflammable, and rapidly excreted from the circulation. However, its use is associated with adverse cardiorespiratory effects, especially in patients with preexisting cardiorespiratory compromise.Methods: The descriptive review of relevant literature, moreover, has been proposed that it increases the incidence of port site (wound) metastases from abdominal cancers when used during oncological surgery. In addition, it may cause postoperative pain due to peritoneal irritation, and its use is associated with physiological and immunological impairment. Hence, there is scope for the investigation of alternative insufflation gases. Other possibilities include gasless laparoscopy, helium, nitrous oxide, (N2O), and argon. Helium insufflation has been used extensively in animal models but only to a limited extent in humans. In experimental studies, it has been shown to produce fewer changes in cardiorespiratory and intraperitoneal immunological status than CO2 insufflation, and its use is associated with less spread of tumors to port sites in a variety of small animal tumor models. However, helium also has the potential for some adverse effects. Helium pneumothorax probably resolves more slowly than CO2 pneumothorax, and helium gas embolism is tolerated poorly in animal models. The clinical significance of these potential problems has yet to be determined.Conclusions: Although the use of alternative gases appears to be promising, further evaluation is needed within both clinical and laboratory settings before their routine clinical use can be supported.

Isolated Limb Perfusion With Melphalan and Tumor Necrosis Factor α for Advanced Melanoma and Soft-Tissue Sarcoma

BackgroundIsolated limb perfusion (ILP) with melphalan is used in the treatment of advanced in-transit melanoma but has no real efficacy for irresectable soft tissue sarcomas arising in the extremities. The addition of tumor necrosis factor (TNF)-α may increase response rates for bulky melanoma and for sarcoma, but the potential for major systemic toxicity has limited its use.MethodsBetween October 2000 and April 2004, 49 ILPs were performed with melphalan and TNF-α. All procedures were performed with continuous leakage monitoring and regional hyperthermia.ResultsForty-nine ILPs were performed for melanoma (n = 30), sarcoma (n = 16), or other tumors (n = 3). The most common indications were widespread in-transit disease for melanoma (n = 29) and irresectable primary disease for sarcoma (n = 9). Complete and partial responses for melanoma were 40% and 37%, and for sarcoma they were 20% and 33%. At a median follow-up of 14 months, 66% of melanoma patients who responded had not experienced local progression, compared with only 37% of sarcoma patients. Progression-free survival was significantly less for patients with sarcoma than melanoma (P = .0476). Four of 16 patients with sarcoma subsequently required amputation for progressive disease.ConclusionsILP with melphalan and TNF-α is a valuable treatment for advanced in-transit melanoma. Significant response rates were also seen in irresectable sarcoma, although the duration of response was limited.

Influence of cytotoxic agents on intraperitoneal tumor implantation after laparoscopy

PURPOSE: Recent experimental studies suggest that laparoscopic surgery for abdominal malignancy may be associated with increased tumor implantation. This study investigated the influence of cytotoxic agents (administered intraperitoneally or intramuscularly) on implantation of a tumor cell suspension after laparoscopic surgery in an experimental model. METHODS: Thirty-three Dark Agouti rats underwent laparoscopy with CO2 insufflation and instillation of a tumor cell suspension into the abdominal cavity. Rats were randomly allocated to one of the following study groups (9 rats in the control group, 6 rats in all other groups): 1) control (no intraperitoneal instillation); 2) intraperitoneal normal saline (0.9 percent); 3) intraperitoneal povidoneiodine (Betadine® to normal saline 1:10 dilution); 4) intraperitoneal methotrexate (2 doses of 0.125 mg/kg body weight in normal saline administered 24 hours apart); 5) intramuscular injection of 2 doses of 0.125 mg/kg body weight administered 24 hours apart (no intraperitoneal agent). Rats were killed 7 days after the procedure, and the peritoneal cavity and port sites were examined for the presence of tumor. RESULTS: A significant reduction in tumor implantation and port-site metastases was observed in all treatment groups (povidone-iodine and intramuscular and intraperitoneal methotrexate). CONCLUSIONS: This study suggests that tumor implantation after laparoscopic surgery and port-site metastases might be prevented by the intraperitoneal or systemic administration of cytotoxic agents. Further studies are needed to determine whether these findings can be applied to clinical practice.

Influence of gases on intraperitoneal immunity during laparoscopy in tumor-bearing rats.

Abstract. Laparoscopy has been associated with metastases to abdominal wall wounds. In addition, many recent experimental studies suggest that laparoscopy is associated with increased tumor dissemination. It is possible that immune or metabolic disturbances due to the use of a pneumoperitoneum could contribute to this problem. To investigate this possibility, we studied the effect of two insufflation gases and gasless laparoscopy on in vivo peritoneal macrophage function and intraperitoneal pH in an experimental model. A carcinoma was implanted into the flank of 32 experimental rats that underwent laparoscopic surgery in one of four treatment groups: anesthesia alone, gasless laparoscopy, helium insufflation, and CO2 insufflation. Intraperitoneal pH was monitored during surgery, and peritoneal macrophage function was determined 3 days after surgery by harvesting peritoneal macrophages and then examining their ability to produce tumour necrosis factor-α (TNF-α). CO2 insufflation was associated with a consistent fall in intraperitoneal pH and a significant reduction in TNFα production. These findings did not occur in the other study groups. The results of this study demonstrate that CO2 insufflation results in depressed intraperitoneal macrophage activity. It is possible that it is mediated by pH changes. In addition, it could be a contributing factor to the development of port-site metastases. Further studies are needed to determine whether the factors identified act during clinical surgery.

Metabolic and immunologic consequences of laparoscopy with helium or carbon dioxide insufflation: a randomized clinical study.

Background: Previous studies using animal models have demonstrated that carbon dioxide (CO2) pneumoperitoneum during laparoscopy is associated with adverse physiological, metabolic, immunological and oncological effects, and many of these problems can be avoided by the use of helium insufflation. The present study was performed in patients to compare the effect of helium and CO2 insufflation on intraperitoneal markers of immunological and metabolic function.

Treatment and outcome of radiation-induced soft-tissue sarcomas at a specialist institution.

BACKGROUND Radiation-induced sarcoma (RIS) is a rare late complication of therapeutic irradiation with a reputation for aggressive pathology and poor outcome. METHODS We retrospectively reviewed histopathological features, surgery and outcome in 67 patients with RIS treated between 1990 and 2005 at a single tertiary referral center. RESULTS Previous breast cancer was the most common indication for radiotherapy. The median interval from irradiation to development of RIS of was 11 years (3-36 years). Median tumour size was 7 cm with 56% classified as high grade, 31% intermediate grade and 13% low grade. The commonest histology was leiomyosarcoma. The only relationship for histology with site was for angiosarcoma (n=9), all of which developed on the chest wall/breast after irradiation for breast cancer. Of 67 patients, 34 underwent potentially curative surgery, and microscopically clear margins were achieved in 75% of cases. Pedicled or free tissue transfer was required in 12 patients and abdominal or chest wall mesh reconstructions were required in 8 patients. No patient received adjuvant radiotherapy but 7 received adjuvant/neoadjuvant chemotherapy. Median follow up is 53 months. Median sarcoma specific survival was 54 months (2- & 5-year survival: 75% & 45%). The local relapse rate was 65%. Negative histopathological margins were a significant predictor of sarcoma specific survival (HR 3.0 95% CI 1.1-8.6 p=0.04). Grade and size of tumour approached, but did not attain significance. CONCLUSION RIS is a biologically aggressive tumour with high rates of local relapse despite aggressive attempts at curative surgery.

The effect of immune enhancement and suppression on the development of laparoscopic port site metastases.

AbstractBackground: Recent clinical case reports and experimental studies have suggested that laparoscopic cancer surgery is associated with an increased risk of tumor spread to abdominal wall wounds. While the etiology of this problem was initially believed to be related to mechanical contamination of wounds, it is now recognized that there are other contributory factors, including disturbed immune function within the peritoneal cavity. To investigate this question further, we evaluated the effect of immune modulation within an established laparoscopic cancer model. Methods: Eighteen immune-competent syngeneic rats underwent modulation of their immune system, followed 18 h later by laparoscopy with the introduction of a suspension of adenocarcinoma cells into the peritoneal cavity. Rats were randomly allocated to receive either systemic cyclosporin (immune suppresser), intraperitoneal endotoxin (immune enhancer), or no agent (controls). Seven days later, all rats were killed and their peritoneal cavity was inspected for tumor implantation and port site metastases. Results: Cyclosporin did not influence the study outcome, but tumor growth (p= 0.008) and port site metastases (p < 0.0001) were less common following the administration of intraperitoneal endotoxin. Conclusion: The results of this study suggest that the immune system plays a role in the genesis of port site metastases. A preventive role for endotoxin in patients undergoing laparoscopic cancer surgery, however, remains speculative.