Short-term outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy used as treatment of colo-rectal carcinomatosis: a multicentric study.

The aim of this study is to assess the morbidity and mortality related to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colo-rectal carcinomatosis. A retrospective multi-institutional study from seven Italian Centers was performed. One hundred and seventy-two patients, submitted to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) to treat carcinomatosis of colorectal origin, were recorded. Postoperative morbidity was evaluated in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Post-operative mortality was evaluated as patients' death within 60 days from surgical procedures. Predictors of morbidity were evaluated with univariate and multivariate analyses. Post-operative morbidity occurred in 83 patients (48.3%): grades 1-2 in 29 cases (16.9%), and grades 3-4 in 54 (31.4%). Mortality occurred in four cases (2.3%). Number of anastomoses (OR 1.45; 95% CI 1.05-2.00; p = 0.024), number of blood transfusions (OR 1.31; 95% CI 1.11-1.54; p = 0.001) and chemotherapy regimen [Oxaliplatin (OX): OR 2.87; 95% CI 1.22-6.75; p = 0.015] remained, in multivariate analysis, in a statistically significant correlation with overall morbidity. The only variable that was proven to have statistically significant correlation with 3-4 morbidity was the number of blood transfusions (OR 1.25; 95% CI 1.07-1.46; p = 0.005). Morbidity and mortality do not preclude the use of CRS plus HIPEC in the treatment of peritoneal carcinomatosis of colorectal origin.

Short-term outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: preliminary analysis of a multicentre study.

AIM: To assess the incidence of morbidity and mortality of Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy. PATIENTS AND METHODS: A retrospective multicentric study was performed. Six hundred and eighty-three patients were recorded. Predictors of morbidity and mortality were evaluated with univariate and multivariate analysis. RESULTS: In univariate analysis, older age, Eastern Cooperative Oncology Group score, a greater value of Peritoneal Cancer Index (PCI) and sub-optimal cytoreduction were correlated with higher mortality, while older age, presence of ascites, ovarian origin of carcinomatosis, closed technique, a greater value of PCI, longer operative time and sub-optimal cytoreduction were predictors of higher morbidity. In multivariate analysis, older age and a greater value of PCI were correlated with higher mortality; older age, ovarian origin of tumor, presence of ascites, closed technique and longer operative time were predictors of higher morbidity. CONCLUSION: Careful patient selection has to be performed to improve clinical outcomes.

Treatment of peritoneal carcinomatosis from colonic cancer by cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC). Experience of ten years.

INTRODUCTION: Peritoneal carcinomatosis (PC) is one of the routes of dissemination of abdominal neoplasms and is generally considered a lethal disease, with a poor prognosis by conventional chemotherapeutic treatments. While systemic chemotherapy has little impact on the treatment of peritoneal disease, some centers have reported encouraging results with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). This approach is based on surgical cytoreduction of the primary tumour, peritonectomy (stripping of implants on the peritoneal surface) and HIPEC. The rationale of this treatment, after macroscopic disease removal, is to obtain an elevated and persistent drug concentration in the peritoneal cavity, with limited systemic effects. Many studies have reported encouraging results on overall survival (OS) and the disease-free interval in patients affected by PC. PATIENTS AND METHODS: From October 1997 to November 2008, 411 operations for PC were performed in our institution; in 232 cases, cytoreduction plus HIPEC was carried out. Out of 72 operations for colonic cancer: 40 cytoreductions plus HIPEC, 12 cytoreductions+ EPIC (early postoperative intraperitoneal chemotherapy) and 16 debulking or explorative laparoscopies/laparotomies were performed. For the present study, the 40 patients who had undergone cytoreduction plus HIPEC for PC of colorectal cancer (CRC) were considered. RESULTS: The complication rate was 55% (22/40) and mortality rate 2.5% (1/40). The specific features of both groups were considered for the survival curves and complication rates, with special reference to the peritoneal carcinomatosis index (PCI; range 0, absence of disease to 39) and completeness of cytoreduction score (CCR; 0, no residual tumor, to CCR 3, residual nodules greater than 25 mm). In Group A, patients operated on prior to 2002, the median survival time was 16.7 months compared to 24.6 months for Group B, those operated on after 2002. The poor survival of Group A seemed to be related to higher PCI and CCR scores. CONCLUSION: Correct patient selection based on a maximum PCI of 16, associated with complete cytoreduction (CCR-0), produced encouraging results in our experience. To improve this encouraging survival outcome, it is very important to unify the surgical experience of expertise centres. Our results also suggest the need for an integrated approach to this condition to identify the correct aspect of the surgical domain and results that may be influencing the prognosis and the evolution of this patients.

Management of pseudomyxoma peritonei by cytoreduction+HIPEC (hyperthermic intraperitoneal chemotherapy): results analysis of a twelve-year experience.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare peritoneal carcinomatosis, characterized by a slowly progressive disease process with a large amount of mucus containing occasional epithelial cells. PMP is histologically classified into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA) and an intermediate or discordant feature group (ID). Recent studies have shown that most cases of PMP originate from ruptured appendiceal tumors with progressive dissemination in the peritoneal cavity of mucin-producing epithelial cells. Encouraging results in the treatment of PMP have been reported by surgical cytoreduction of the primitive cancer, peritonectomy (stripping of implants on the peritoneal surface) and intraperitoneal hyperthermic chemoperfusion (HIPEC). In recent trials, this combined approach has been proposed as the standard treatment for PMP. PATIENTS AND METHODS: In this study, the results of twelve years single-institution experience on 60 consecutive patients affected by PMP, treated by cytoreductive surgery and the original semi-closed HIPEC technique are reported with special reference to overall survival (OS) and progression-free survival (PFS). RESULTS: The postoperative morbidity rate was 45% (27 patients); surgical morbidity was observed in 19 patients and medical complications in 9 cases. No postoperative deaths were observed. The survival data, 53 patients were analized (the last 7 were considered only for the complications rate, postoperative mortality and cancer features, not for OS or PFS because they were too recent for evaluation). At the final follow-up of the 53 patients, five and ten years OS were respectively 94% and 84.6% . DFS was 80% and 70% at five and ten years respectively. The follow-up data indicated that the survival probability may be good in patients with hystological type appendicular adenoma optimally cytoreduced (CCR-0). Interestingly if preoperative chemotherapy was performed represented a negative prognostic factor with statistically significant impact both on OS and DFS. CONCLUSION: As in other similar studies, cytoreductive surgery plus HIPEC, even when combined with an aggressive surgical procedure, is associated with an acceptable risk of postoperative complications and mortality. This combined treatment results in DFS and OS rates that are not described in the literature for surgery associated with systemic chemotherapy and, in our opinion, may be considered the gold standard treatment for this rare tumor.

Cytoreduction and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis from pseudomyxoma peritonei.

AIM: To investigate the most important aspects of hyperthermic intraperitoneal chemotherapy (HIPEC) that has been accepted as the standard treatment for pseudomyxoma peritonei (PMP), with special regard to morbidity, overall survival (OS) and disease free survival (DFS) over 10 years. METHODS: Fifty-three patients affected by PMP underwent cytoreduction (CCR) and HIPEC with a "semi-closed" abdomen technique in our institution. The peritonectomy procedure and completeness of CCR were classified according to Sugarbaker criteria. Preoperative evaluation always included thoracic and abdominal CT scan to stage peritoneal disease and exclude distant metastases. Fifty-one patients in our series were treated with a protocol based on administration of cisplatinum 100 mg/m(2) plus mitomycin C 16 mg/m(2), at a temperature of 41.5 degrees centigrade for 60 min. Anastomoses were always performed at the end of HIPEC. The mean duration of surgery was 12 h including HIPEC. Continuous monitoring of hepatic and renal functions and hydroelectrolytic balance was performed in the postoperative period. RESULTS: Twenty-four patients presented with postoperative complications: surgical morbidity was observed in 16 patients and 6 patients were re-operated. All complications were successfully treated and no postoperative deaths were observed. Risk factors for postoperative morbidity were considered to be gender, age, body surface, duration of surgery, Peritoneal Cancer Index (PCI) and tumor residual value (CC score). No statistically significant correlation was found during the multivariate analysis: only the CC score was statistically significant. The OS in our experience was 81.8%, with a DFS of 80% at 5 years and of 70% at 10 years. CONCLUSION: In our experience, even if HIPEC combined with cytoreductive surgery involves a high risk of morbidity, postoperative complications can be resolved favorably in most cases with correct patient selection and adequate postoperative care, thus minimizing mortality. The association of CCR and HIPEC can be considered as the standard treatment for PMP. The OS and DFS results confirm the validity of this combined approach for the treatment of this rare neoplasm. The impact of preoperative chemotherapy on OS, in our opinion, is due to a major aggressiveness of tumors in treated patients.

Treatment of peritoneal carcinomatosis by cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion (IHCP): postoperative outcome and risk factors for morbidity.

BACKGROUND: Cytoreductive surgery with limited or extended peritonectomy associated with intraperitoneal hyperthermic chemoperfusion (IHCP) has been proposed for treatment of peritoneal carcinomatosis (PC) from abdominal neoplasms. METHODS: Fifty-nine patients with PC from abdominal neoplasms underwent 61 treatments using this technique from January 2000 to August 2005. Surgical debulking, completed by partial or total peritonectomy, was performed in most cases. In 16 patients with positive peritoneal cytology without macroscopic peritoneal disease, IHCP was performed in order to prevent peritoneal recurrence. IHCP was carried out throughout the abdominopelvic cavity for 60 minutes using a closed abdomen technique. Intra-abdominal temperature ranged between 41 degrees C and 43 degrees C; mitomycin C (25 mg/mq) and cisplatin (100 mg/mq) were the anticancer drugs generally used, and they were administered with a flow rate of 700-800 ml/minute. RESULTS: Mean hospital stay was 13 +/- 7 (range 7-49) days. Postoperative complications occurred in 27 patients (44.3%); of these, major morbidity was observed in 17 (27.9%). The most frequent complications were wound infection (9 cases), grade 2 or greater hematological toxicity (5 cases), intestinal fistula (5 cases), and pleural effusion requiring drainage (5 cases). Reoperation was necessary in 5 patients (8.2%). One patient with multiorgan failure died in the postoperative period (mortality rate: 1.6%). Multivariate analysis of several variables identified completeness of cancer resection (CCR-2/3 vs. CCR-0/1, relative risk: 9.27) and age (relative risk: 1.06 per year) as independent predictors of postoperative morbidity. Preliminary follow-up data indicate that survival probability may be high in patients with ovarian or colorectal cancer and low in patients with gastric cancer. CONCLUSIONS: IHCP combined with cytoreductive surgery involves a high risk of morbidity, but postoperative complications could be resolved favorably in most cases with correct patient selection and adequate postoperative care. Tumor residual and advanced age significantly increase the risk of morbidity after this procedure.