Heated IntraPEritoneal Chemotherapy (HIPEC) for Patients With Recurrent Ovarian Cancer A Systematic Literature Review

BackgroundDespite advances in surgical oncology, most patients with primary ovarian cancer develop a recurrence that is associated with a poor prognosis. The aim of this review was to establish the impact of Heated IntraPEritoneal Chemotherapy (HIPEC) in the overall survival of patients with recurrent ovarian cancer.MethodsA search of PubMed/MEDLINE databases was performed in February 2015 using the terms “recurrent ovarian cancer,” “cytoreductive surgery/cytoreduction,” and “heated/hyperthermic intraperitoneal chemotherapy.” Only English articles with available abstracts assessing the impact of HIPEC in patients with recurrent ovarian cancer were examined. The primary outcome measure was overall survival, whereas secondary outcomes included disease-free survival and HIPEC-related morbidity.ResultsSixteen studies with 1168 patients were analyzed. Most studies were Level IV, with 4 studies graded as Level III and 1 Level II. Cisplatin was the main chemotherapeutic agent used, but variations were observed in the actual technique, temperature of perfusate, and duration of treatment. In patients undergoing cytoreductive surgery and HIPEC, the overall survival ranged between 26.7 and 35 months, with disease-free survival varying between 8.5 and 48 months. Heated IntraPEritoneal Chemotherapy seems to confer survival benefits to patients with recurrent disease, with a randomized controlled study reporting that the overall survival is doubled when cytoreductive surgery is compared with cytoreductive surgery and chemotherapy (13. 4 vs 26.7 months). Heated IntraPEritoneal Chemotherapy–related morbidity ranged between 13.6% and 100%, but it was mainly minor and not significantly different from that experienced by patients who only underwent cytoreduction.ConclusionsCytoreductive surgery and HIPEC seem to be associated with promising results in patients with recurrent ovarian cancer. Large international prospective studies are required to further quantify the true efficacy of HIPEC and identify the optimal treatment protocol for a maximum survival benefit.</jats:sec

Resection of the liver for colorectal carcinoma metastases - A multi-institutional study of long-term survivors

In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primarycarcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized. © 1988 American Society of Colon and Rectal Surgeons

Eradication of intractable malignant ascites by abdominocentesis, reinfusion of concentrated ascites, and adoptive immunotherapy with dendritic cells and activated killer cells in a patient with recurrent lung cancer: a case report

<p>Abstract</p> <p>Introduction</p> <p>Malignant ascites is often a sign of a terminal stage in several malignant diseases. To control ascites, drainage and intra-abdominal chemotherapy are often used in those patients but eradication of ascites is difficult and prognosis is poor.</p> <p>Case presentation</p> <p>A 55-year-old woman was admitted to our hospital on 26 January 2007 with dyspnea, abdominal distention and oliguria. Abdominocentesis revealed peritoneal carcinomatosis resulting from abdominal recurrence from lung cancer. To alleviate the dyspnea and abdominal distention, we drained the ascites aseptically and infused them intravenously back into the patient after removal of tumor cells by centrifugation, and then concentration by apheresis. After the drainage of ascites, we intraperitoneally infused activated killer cells and dendritic cells from the patient's tumor-draining lymph nodes, together with 4.5 × 10⁵U interleukin-2 in 50 ml saline by 2.1 ml/hour infuser balloon.</p> <p>Drastic decreases in the tumor cell count and in ascite retention were observed after several courses of ascites drainage, intravenous infusion and intraperitoneal immunotherapy. The plasma protein level was maintained during the treatment notwithstanding the repeated drainage of ascites. Cell surface marker analysis, cytotoxic activities against autologous tumor cells and interferon-gamma examination of ascites suggested the possibility that these effects were mediated by immunological responses of activated killer cells and dendritic cells infused intraperitoneally.</p> <p>Conclusion</p> <p>Combination of local administration of immune cells and infusion of concentrated cell free ascites may be applicable for patients afflicted with refractory ascites.</p

Small bowel involvement is a prognostic factor in colorectal carcinomatosis treated with complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy

<p>Abstract</p> <p>Background</p> <p>Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment for patients with peritoneal carcinomatosis (PC). Our objective was to identify new prognostic factors in patients with PC from colorectal cancer treated with this procedure.</p> <p>Methods</p> <p>All patients with PC from colorectal cancer treated by HIPEC from January 2000 to December 2007 were prospectively included. The tumor extension was assessed by the Peritoneal Cancer Index (PCI) and the residual disease was recorded using the completeness cytoreductive score (CCs). All clinical and treatment data were computed in univariate and multivariable analyses using survival as primary end point.</p> <p>Results</p> <p>We carried out 51 complete procedures in 49 consecutive patients. The mean PCI was 10. The allocation of CCs was: CC-0 = 37, CC-1 = 14. The five-year overall and progression-free survival rate were 40% and 20%, respectively. Several prognostic factors for survival were identified by univariate analysis: PCI < 9 (<it>P </it>< 0.001), CC-0 vs. CC-1 (<it>P </it>< 0.01) and involvement of area 4 (<it>P </it>= 0.06), area 5 (<it>P </it>= 0.031), area 7 (<it>P </it>= 0.014), area 8 (<it>P </it>= 0.022), area 10 (<it>P </it>< 0.0001), and area 11 (<it>P </it>= 0.02). Only the involvement of the distal jejunum (area 10) was significant in the multivariable analysis (<it>P </it>= 0.027).</p> <p>Conclusions</p> <p>We demonstrated that the involvement of area 10 (distal jejunum of the PCI score) was an independent factor associated with poor prognosis.</p

Drug Sensitivity Testing in Cytoreductive Surgery and Intraperitoneal Chemotherapy of Pseudomyxoma Peritonei

BACKGROUND: Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) is an established therapy for pseudomyxoma peritonei (PMP). However, the role of IPC is unclear. By ex vivo assessment of PMP tumor cell sensitivity to cytotoxic drugs, we investigated the basis for IPC drug selection and the role of IPC in the management of PMP. METHODS: Tumor cells were prepared by collagenase digestion of tumor tissue from 133 PMP patients planned for CRS and IPC. Tumor cell sensitivity to oxaliplatin, 5FU, mitomycin C, doxorubicin, irinotecan, and cisplatin was assessed in a 72-h cell-viability assay. Drug sensitivity was correlated to progression-free survival (PFS) and overall survival (OS). RESULTS: Samples from 92 patients were analyzed successfully. Drug sensitivity varied considerably between samples. Peritoneal mucinous carcinomatosis (PMCA), compared with PMCA intermediate or disseminated peritoneal adenomucinosis, was slightly more resistant to platinum and 5FU and tumor cells from patients previously treated with chemotherapy were generally less sensitive than those from untreated patients. Multivariate analysis showed patient performance status and completeness of CRS to be prognostic for OS. Among patients with complete CRS (n = 61), PFS tended to be associated with sensitivity to mitomycin C and cisplatin (p ≈ 0.06). At the highest drug concentration tested, the hazard ratio for disease relapse increased stepwise with drug resistance for all drugs. CONCLUSIONS: Ex vivo assessment of drug sensitivity in PMP provides prognostic information. The results suggest a role for IPC as therapeutic adjunct to CRS and for individualization of IPC by pretreatment assessment of drug sensitivity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1245/s10434-015-4675-0) contains supplementary material, which is available to authorized users

Histological response of peritoneal carcinomatosis after hyperthermic intraperitoneal chemoperfusion (HIPEC) in experimental investigations

BACKGROUND: In selected patients with peritoneal carcinomatosis from colorectal cancer prognosis can be improved by hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery. The aim of this study was to evaluate the tumor response of peritoneal carcinomatosis in tumor-bearing rats treated with HIPEC. METHODS: CC531 colon carcinoma (2,5 × 10(6 )cells), implanted intraperitoneally in Wag/Rija rats, was treated by hyperthermic intraperitoneal chemotherapy. After 10 days of tumor growth the animals were randomized into five groups of six animals each: group I: control (n = 6), group II: sham operated animals (n = 6), group III: hyperthermic intraperitoneal perfusion (HIP) without cytostatic drugs, group IV: HIPEC with mitomycin C in a concentration of 15 mg/m(2 )(n = 6), group V: mitomycin C i.p. alone in a concentration of 10 mg/m(2 )(n = 6). After 10 days the extent of tumor spread and histological outcome were analysed by autopsy. RESULTS: All control animals developed extensive intraperitoneal tumor growth. Histological tumor load was significantly reduced in group III and group V and was lowest in group IV. In group II tumor load was significantly higher than in group I. Implanted metastases were significantly decreased in group IV compared with group I and group II. CONCLUSION: These findings indicate that HIPEC is an effective treatment for peritoneal carcinomatosis in this animal model. HIPEC reduced macroscopic and microscopic intraperitoneal tumor spread