Vadim Gushchin

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: A consensus statement

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin : a consensus statement

Prospective Morbidity and Mortality Assessment of Cytoreductive Surgery Plus Perioperative Intraperitoneal Chemotherapy To Treat Peritoneal Dissemination of Appendiceal Mucinous Malignancy

BackgroundAppendiceal mucinous neoplasms present, in most patients, with peritoneal dissemination at the time of initial diagnosis. Patients may have a borderline tumor showing disseminated peritoneal adenomucinosis or an aggressive malignancy identified as peritoneal mucinous adenocarcinoma. Patients with these diagnoses were treated by cytoreductive surgery and perioperative intraperitoneal chemotherapy.MethodsA database was established in 1998 that prospectively evaluated the morbidity and mortality of this group of patients. By using common toxicity grading criteria, 8 categories were scored on a grade of I to V. Grade IV indicated that the adverse event required urgent and definitive intervention: often a return to the operating room or to the surgical intensive care unit. Grade V indicated that the adverse events resulted in the patient’s death. Adverse events were tabulated for each cytoreduction performed in these appendiceal malignancy patients.ResultsThere were 356 procedures in patients taken to the operating room who received cytoreductive surgery with peritonectomy procedures plus heated intraoperative intraperitoneal chemotherapy. Only patients who had this combined treatment at our institution were included in the analysis. The total 30-day or in-hospital mortality was 2.0%. Nineteen percent of procedures were accompanied by at least one grade IV adverse event, and 11.1% of patients returned to the operating room. The most common category of grade IV complications was hematological (28%), followed by gastrointestinal (26%).ConclusionsThe mortality of 2.0% and the overall grade IV morbidity of 19% in these patients may be acceptable in light of modern standards for the management of gastrointestinal cancer.

Complete Cytoreduction Offers Longterm Survival in Patients with Peritoneal Carcinomatosis from Appendiceal Tumors of Unfavorable Histology

BACKGROUND Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a rapidly evolving treatment for metastatic appendiceal neoplasms. The aim of this study was to show the effect of complete cytoreduction (CC) on survival in patients undergoing CRS and HIPEC for high-grade appendiceal neoplasm. STUDY DESIGN A retrospective study of a prospective database of 56 patients (from 1999 to 2007) with appendiceal neoplasms treated with CRS and HIPEC was carried out. Histology of the disease, CC score, and peritoneal cancer index (PCI) score were assessed independently and collectively for each group of patients. Survival analysis was performed using the Cox proportional hazard model. RESULTS Three-year overall survival was 60%. The median peritoneal cancer index score was 25 or higher. Survival analysis by tumor histology was 80% for patients with low-grade tumors and 52% for patients with high-grade tumors (p = 0.024). Survival by completeness of cytoreduction was 78% for patients with a low CC score (0 to 1) and 28% in patients with a high CC score (2 to 3; p = 0.01). There was no statistically significant difference in survival between the low-grade and high-grade tumors when a complete cytoreduction was performed in both groups of patients: 80% versus 68% (p = 0.69). CONCLUSIONS CRS and HIPEC is an effective treatment for patients with disseminated appendiceal tumors. High-grade tumors also benefit from this approach and should not be excluded from CRS and HIPEC. Every effort should be made to achieve a complete cytoreduction regardless of the tumor histology.

Neoplasms of the Appendix: Current Treatment Guidelines

The purpose of this article is to update the medical community on the current management of patients with appendiceal neoplasms. The authors discuss clinical evidence of medical and surgical treatment with emphasis on presentation, diagnosis, pathology, and surgical technique. Current available clinical evidence on the use of systemic chemotherapy is included. The authors describe in detail management of peritoneal carcinomatosis arising from tumors of the appendix with cytoreductive surgery and hyperthermic intraperitoneal therapy as standard of care.

Clinical utility of elevated tumor markers in patients with disseminated appendiceal malignancies treated by cytoreductive surgery and HIPEC.

BACKGROUND Appendiceal malignancies with peritoneal spread have been successfully treated with Cytoreductive Surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study is to clarify the utility of common tumor markers in selecting patients for the combined treatment. METHODS Data on 56 patients with appendiceal neoplasms treated with CRS and HIPEC were prospectively collected. Chi square test was used to analyze a link between common tumor markers and completeness of cytoreduction score (CC score) and preoperative peritoneal cancer index score (PCI score). Cox proportional hazard model was used to perform survival analysis. RESULTS Forty-two patients were alive after 3 years of follow-up. Hazard ratio of disease related death was 5.6 (95% CI, 1.8-17.2) among patients with high CC score as compared to those with low CC score. Number of abnormal tumor markers (0 vs 1/2/3) correlated with PCI score 16.2 vs 32.5 (p < 0.001) but not with completeness of cytoreduction or survival. The 3-year survival rates in patients with normal vs abnormal CA 125 levels were 83% vs 52%(p = 0.003). CONCLUSIONS Multiple abnormal tumor markers were not useful as an exclusion criterion for patients undergoing CRS. Elevation in CA 125 was an important indicator of survival in these patients. Complete cytoreduction was crucial for long-term survival.

Repeated cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from appendiceal cancer: Analysis of survival outcomes

BACKGROUND Cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC) is the procedure of choice in patients with peritoneal dissemination from appendiceal cancer. Although recurrence rates are 26%-44% after first CRS/HIPEC, the role of repeated CRS/HIPEC has not been well defined. We hypothesize that patients undergoing multiple CRS/HIPECs have meaningful long term survival. METHODS A retrospective study of a prospective database of 294 patients with peritoneal carcinomatosis (PC) was conducted, of these 162 had PC of appendiceal origin. Twenty-six of these patients underwent 56 CRS/HIPEC. Survival and outcomes was analyzed. RESULTS The percentage of patients with pre-surgical PCI scores ≥ 20 for the first, second, and third CRS/HIPEC was 65, 65, and 25%, respectively. Complete cytoreduction (CC 0-1) at first, second, and, third surgeries was 96, 65 and 75%, respectively. The mean operating time was 10.1 h. There was no 30-day peri-operative mortality. Following the first, second, and third CRS/HIPEC 27, 42, and 50% experienced grade III complications, respectively. Mean follow up was 51, 28, and 16 months from the first, second, and third CRS/HIPEC, respectively. Overall survival rate for the first CRS/HIPEC was 100, 83, 54, and 46% at years 1, 3, 5 and 10, respectively; from the second CRS/HIPEC 91, 53, and 34% at 1, 3, and 5 years, respectively; and from the third CRS/HIPEC was 75% at one year. CONCLUSION Repeat CRS/HIPEC can lead to meaningful long term survival rates in patients with appendiceal peritoneal carcinomatosis with morbidity and mortality similar to those of the initial CRS/HIPEC.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of recurrent high-grade uterine sarcoma with peritoneal dissemination

OBJECTIVE Peritoneal sarcomatosis from primary uterine sarcoma (US) is a rare condition. Conventional therapeutic modalities have failed to improve survival and outcomes among patients with high-grade US with extrapelvic spread. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown improved outcomes for peritoneal carcinomatosis from other epithelial primaries with similar clinical presentation. We report our experience applying this treatment in 3 patients with recurrent high-grade US with peritoneal dissemination. STUDY DESIGN This retrospective review of a prospective database of 378 patients with peritoneal dissemination of cancer treated with CRS/HIPEC identified 3 patients with recurrent high-grade US. Follow-up for disease progression was carried out by physical examination and computed tomography scan of the chest, abdomen, and pelvis. RESULTS Two leiomyosarcomas and 1 adenosarcoma with sarcomatous overgrowth were identified. Two of the 3 had failed standard treatment with surgery and systemic chemotherapy before CRS/HIPEC was performed. Follow-up ranged from 34 to 140 months. All 3 patients are alive, 2 with no evidence of disease (NED), and 1 alive with disease. Adramycin/cisplatin was used for HIPEC in 1 case (140 months with NED), whereas melphalan was used in the other 2 cases (53 months alive with disease, 34 months with NED). Two patients underwent 1 CRS/HIPEC, whereas 1 required 3 CRS/HIPEC due to disease recurrence. CONCLUSION CRS/HIPEC shows promise as a treatment modality for the management of selected patients with recurrent high-grade US with peritoneal dissemination. Further studies are warranted.

Extensive surgical history prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is associated with poor survival outcomes in patients with peritoneal mucinous carcinomatosis of appendiceal origin

BACKGROUND Patients with PMCA commonly undergo surgery before CRS/HIPEC. We evaluated the role of extensive surgical treatment before CRS/HIPEC in terms of overall survival (OS). METHODS 105 patients with PMCA who underwent a CRS/HIPEC procedure were identified from a prospective database. Patients were divided into two groups based on Prior Surgery Score (PSS): PSS ≤ 1 limited surgery group (LSG), PSS >1 extensive surgery group (ESG). Survival of lymph node (LN) negative and positive patients was analyzed separately. RESULTS 40 patients were in LSG and 65 in ESG. Mean time from diagnosis to CRS/HIPEC was 6 and 17 months for LSG and ESG, respectively (p = 0.004). Groups were well balanced in peritoneal cancer index, complete cytoreduction rate, and LN status. One, 3, and 5-year OS among LN negative patients was 95, 83, and 75% for the LSG (n = 22) group and 87, 55, and 32% for the ESG (n = 35), group respectively (p = 0.026). One, 3, and 5-year OS among LN positive patients was 69, 50, and 17% for the LSG (n = 18) group and 80, 21, and 14% for the ESG (n = 30), group respectively (p = 0.613). For all patients 1, 3, and 5-year OS was 84, 65, and 54% for the LSG (n = 40) group and 86, 43, and 26% for the ESG (n = 65) group, respectively (p = 0.029). CONCLUSION Extensive surgical treatment before CRS/HIPEC is associated with delay of CRS/HIPEC and poorer OS overall, especially among LN negative patients. We recommend early referral of PMCA patients to a peritoneal surface malignancy center.

The role of VEGFR-2 expression in outcomes and survival of patients with peritoneal carcinomatosis from appendiceal cancer

BACKGROUND Vascular endothelial growth factor (VEGF) is a prognostic factor and target treatment for metastatic colorectal and ovarian cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival on peritoneal carcinomatosis (PC) from appendiceal cancer. We hypothesize that tumoral high expression of VEGF receptor 2 (VEGFR-2) is a negative prognostic factor for survival in patients with PC from appendiceal cancer. METHODS A retrospective study of a prospective database revealed 89 patients with PC from appendiceal cancer who underwent 127 CRS/HIPECs. Surgical specimens from 59 patients were tested to identify high vs. low VEGFR-2 expression. Patient outcomes and survival were analyzed. RESULTS There were 26 males and 33 females. Mean age was 51 years. Forty-seven VEGFR-2 high expressers and 15 low expressers were identified. Mean follow-up of high and low expressers was 25.1 and 26.6 months, respectively (p = 0.806). At follow-up, 33 (70%) high expressers were alive and 14 (30%) deceased, while 11 (92%) low expressers were alive and 1 (8%) deceased. Recurrence, use of bevacizumab, CC score, PCI, and LN status showed no differences between high and low expressers. OS for high expressers was 90.5%, 59.8%, and 47.1% at 1-, 3-, and 5-years, respectively, while OS for low expressers remained stable at 91.7% at 1-, 3-, and 5-years (p = 0.133). CONCLUSION There is a trend towards better outcomes and survival in patients with PC from appendiceal cancer who have low expression of VEGFR-2 compared to high expression. More studies are encouraged to confirm this trend.

Erratum: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: A consensus statement (Annals of Surgical Oncology 14 (128-133)DOI: 10.1245/s10434-006-9185-7)

J. Esquivel, R. Sticca, P. Sugarbaker, E. Levine, T. D. Yan, R. Alexander, D. Baratti, D. Bartlett, R. Barone, P. Barrios, S. Bieligk, P. Bretcha-Boix, C. K. Chang, F. Chu, Q. Chu, S. Daniel, E. deBree, M. Deraco, L. Dominguez-Parra, D. Elias, R. Flynn, J. Foster, A. Garofalo, F. N. Gilly, O. Glehen, A. Gomez-Portilla, L. Gonzalez-Bayon, S. Gonzalez-Moreno, M. Goodman, V. Gushchin, N. Hanna, J. Hartmann, L. Harrison, R. Hoefer, J. Kane, D. Kecmanovic, S. Kelley, J. Kuhn, J. LaMont, J. Lange, B. Li, B. Loggie, H. Mahteme, G. Mann, R. Martin, R. A. Misih, B. Moran, D. Morris, L. Onate-Ocana, N. Petrelli, G. Philippe, J. Pingpank, A. Pitroff, P. Piso, M. Quinones, L. Riley, L. Rutstein, S. Saha, S. Alrawi, A. Sardi, S. Schneebaum, P. Shen, D. Shibata, J. Spellman, A. Stojadinovic, J. Stewart, J. Torres-Melero, T. Tuttle, V. Verwaal, J. Villar, N. Wilkinson, R. Younan, H. Zeh, F. Zoetmulder, and G. Sebbag