Peritoneal Metastatic Gastric Cancer: Local Treatment Options and Recommendations.

Peritoneal metastasis is a common finding in patients with advanced gastric cancer. Beyond systemic chemotherapy, additive local treatments such as cytoreductive surgery and intraperitoneal chemotherapy are considered an inherent part of different multimodal treatment concepts for selected patients with peritoneal metastatic gastric cancer. This review article discusses the role of cytoreductive surgery (CRS) and intraperitoneal chemotherapy, including HIPEC, NIPS, and PIPAC, as additive therapeutic options with curative and palliative intent.

Re-operations for early postoperative complications after CRS and HIPEC: indication, timing, procedure, and outcome.

PURPOSE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have become standard of care for many peritoneal malignancies in selected patients. Nevertheless, this aggressive treatment strategy is associated with significant major morbidity. The aim of the present study is to analyze the re-operation rate and clinical outcome following CRS and HIPEC. PATIENTS AND METHODS: In the present study, prospectively documented data of 474 consecutive patients treated with CRS and HIPEC between February 2011 and December 2015 in a high-volume certified reference center for peritoneal malignancies in Germany have been retrospectively analyzed. RESULTS: The re-operation rate was 14.5%. The most frequent reasons for revisional surgery were fascial dehiscence, intraabdominal hemorrhage, and anastomotic leak. Most complications occurred between postoperative day 7 and 9. However, postoperative bleeding was more common within the first 5 days after surgery. The overall in-hospital mortality rate was 2.1% for all patients and 10% after revisional surgery. CONCLUSIONS: CRS and HIPEC are associated with an acceptable re-operation rate and low mortality rate. Most frequently, re-operations are performed on 7-9 days after initial surgery due to fascial dehiscence, pancreatitis, or anastomotic leak. Postoperative bleedings are more common within the first 5 days after surgery.

Morbidity and Mortality Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Data from the DGAV StuDoQ Registry with 2149 Consecutive Patients.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are performed for well-selected patients with peritoneal surface malignancies. This combined treatment is potentially associated with an increased rate of complications. OBJECTIVE: The aim of this paper was to analyze the morbidity and mortality of CRS and HIPEC in the German national registry. METHODS: We present a retrospective analysis of 2149 consecutive patients from 52 hospitals. The data were prospectively documented in the DGAV StuDoQ Registry between February 2011 and December 2016. RESULTS: Almost two-thirds of all patients had a colorectal malignancy; therefore, the most frequently performed resections were colectomies (54%) and rectal resections (30%). Only 36.2% of all patients had no anastomosis, and fewer than 20% of all patients were older than 70 years of age (16.4%). Enteric fistula and anastomotic leaks occurred in 10.5% of all cases. The reoperation rate was 14.6% (95% confidence interval [CI] 11.51-18.1). Major grade 3 and 4 complications (Clavien-Dindo classification) occurred in 19.3% of all patients, half of which were due to surgical complications. The overall 30-day postoperative hospital mortality was 2.3% (95% CI 1.02-3.85). Multivariate analysis showed an increased risk for morbidity associated with pancreatic resections (odds ratio [OR] 2.4), rectal resection (OR 1.5), or at least one anastomosis (OR 1.35), and mortality with reoperation (OR 8.7) or age > 70 years (OR 3.35). CONCLUSIONS: CRS and HIPEC are associated with acceptable morbidity and low mortality. These results show that CRS and HIPEC can be safely performed nationwide when close mentoring by experienced centers is provided.

Perioperative Systemic Chemotherapy, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: Results of the Prospective Multicenter Phase 2 COMBATAC Trial.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as parts of an interdisciplinary treatment concept including systemic chemotherapy can improve survival of selected patients with peritoneal metastatic colorectal cancer (pmCRC). Nevertheless, the sequence of the therapeutic options is still a matter of debate. Thus, the COMBATAC (COMBined Anticancer Treatment of Advanced Colorectal cancer) trial was conducted to evaluate a combined treatment regimen consisting of preoperative systemic polychemotherapy + cetuximab followed by CRS + HIPEC and postoperative systemic polychemotherapy + cetuximab. PATIENTS AND METHODS: The COMBATAC trial is a prospective, multicenter, open-label, single-arm, single-stage phase 2 trial. Twenty-six patients with synchronous or metachronous colorectal or appendiceal peritoneal carcinomatosis were included. Enrollment was terminated prematurely by the sponsor because of slow recruitment. Progression-free survival as primary end point and overall survival were estimated by the Kaplan-Meier method. Also evaluated were morbidity according to Common Terminology Criteria for Adverse Events v4.0 and feasibility of the combined treatment concept. RESULTS: Median progression-free survival for the intention-to-treat population (n = 25) was 14.9 months. Median overall survival was not reached during the study duration. Ninety-two adverse events were documented in 16 patients, including 14 serious adverse events in 9 patients. The overall morbidity rate was 64%, and the grade 3/4 morbidity rate was 44%. Of all grade 3/4 morbidity events, 36.4% were related to systemic chemotherapy and 22.7% to surgery, whereas 40.9% were not directly related. There was no treatment-related mortality. CONCLUSION: The results of the COMBATAC trial show that the multimodal treatment concept consisting of perioperative systemic chemotherapy and CRS + HIPEC is safe and feasible. Progression-free survival in selected patients with colorectal or appendiceal peritoneal metastasis might be improved.

Treatment-related morbidity and toxicity of CRS and oxaliplatin-based HIPEC compared to a mitomycin and doxorubicin-based HIPEC protocol in patients with peritoneal carcinomatosis: a matched-pair analysis.

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provide a promising therapeutic option for selected patients with peritoneal carcinomatosis. The use of intraperitoneal oxaliplatin seems to further improve the efficacy of the combined treatment concept. Nevertheless, additional toxicity might be expected. PATIENTS AND METHODS: Between 03/2004 and 08/2010 307 patients underwent CRS and HIPEC at the University Medical Center Regensburg. Forty of these patients received oxaliplatin-based HIPEC. A matched-pair analysis was performed to compare IP oxaliplatin to our former standard HIPEC protocol with mitomycin C (MMC) and doxorubicin. RESULTS: The mean operating time in the OX and the MMC group was 315 and 313 min, respectively. Median hospital stay was 15.5 days in the OX group and 17 days in the MMC group. The grade 3/4 morbidity rate according to CTCAEv3.0 was 42.5% versus 37.5% (P = 0.648). Perioperative mortality was 2.5% versus 0%. CONCLUSION: Our data suggest that the use of IP oxaliplatin in the context of CRS and HIPEC does not significantly increase perioperative morbidity and/or mortality rates. Nevertheless, randomized controlled trials are required to determine the optimal intraperitoneal chemotherapeutic regimen regarding toxicity, postoperative complications, and oncological outcome.

Current status and future directions in gastric cancer with peritoneal dissemination.

Peritoneal carcinomatosis arising from gastric cancer is mostly associated with poor prognosis. Despite the improvement of survival with modern polychemotherapy, the results are still unsatisfactory. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy might provide an additional therapeutic option for highly selected patients with gastric cancer and peritoneal metastasis leading to improved prognosis. Considering the increased rate of perioperative morbidity and the crucial prognostic role of complete macroscopic cytoreduction, adequate preoperative diagnostics and patient selection are strongly recommended. Further prospective randomized trials are needed to determine the roles of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as part of an interdisciplinary treatment concept.

Hepatobiliary procedures in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The long-term prognosis of patients with peritoneal malignancies has greatly improved since the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Nevertheless, CRS can be associated with high postoperative morbidity. In this retrospective study, we analyzed the influence of hepatobiliary surgery as part of CRS on postoperative short-term patient outcome. METHODS: Between 2005 and 2008, a total of 63 (25%) of 252 patients with peritoneal surface malignancies undergoing CRS and HIPEC required hepatobiliary surgery. Liver resection was performed in 22, resection of Glisson capsule in 39, and bile duct resection in 2 patients. The mean age of the study population was 49.3 years. Thirty-four patients (54%) were women. RESULTS: Complete macroscopic cytoreduction (CC-0/1) was reached in 59 patients (93.7%). The median hospital stay was 18 days. Twenty-two patients developed minor complications (35%), such as moderate fever, pain, or secondary wound healing. In 21 patients (33%), severe complications occurred, most commonly pancreatitis and abdominal abscess. Three patients (4.8%) developed a biliary leakage. Of these, 2 had to be reoperated. CONCLUSIONS: In our experience, hepatobiliary procedures have to be performed in up to one-third of patients and are associated with a low rate of specific complications, such as biliary leakages.

Results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal cancer.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provide a promising additional treatment option for selected patients with peritoneal carcinomatosis arising from colorectal cancer. Due to the aggressive surgery the concept is associated with a significant morbidity rate. Thus, the operative risk has to be evaluated against the background of the expected improvement of the oncological outcome.

Quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with high morbidity. The Quality of Life (QoL) assessment in this patient group with a limited life expectancy and high recurrence rate is important. Published data show an impairment of postoperative Quality of Life at 3 months postoperatively with an improvement over 6-12 months at levels higher than the baseline. Standardized instruments QoL have to be included in clinical trials assessing the efficacy of CRS and HIPEC.

Patient selection for a curative approach to carcinomatosis.

There is an increasing evidence showing that in selected patients with peritoneal carcinomatosis cytoreductive surgery and hyperthermic intraperitoneal chemotherapy may improve survival. Adequate patient selection is crucial to obtain a complete macroscopic cytoreduction, a leading predictor of patient outcome. However, selection is a very difficult process and is associated with a significant learning curve. Many selection criteria have to be assessed in each patient: performance status, comorbiditites, response to previous chemotherapies, histology grading, and presence of extra-abdominal or liver metastases, small bowel involvement, and tumor volume assessed by the peritoneal cancer index. All these factors have to be discussed interdisciplinary and with the patient to create an individualized treatment strategy. It is difficult to decide the relative importance of each selection criteria. However, completeness of cytoreduction, tumor volume, and histology grading are most important in many multivariate analysis independent prognostic factors. For appropriate selected patients with peritoneal carcinomatosis arising from appendiceal and colon cancer, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy should be considered standard of care.

Safety of gastric resections during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery (CRS) including gastric resection combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve the prognosis of selected patients with peritoneal surface malignancies. Perioperative morbidity of this aggressive treatment strategy is high; however, overall mortality can be low in specialized centers. The aim of this study was to assess the safety of gastric resections with anastomosis during CRS and HIPEC. METHODS: Between 2005 and 2008, 204 patients underwent CRS and HIPEC at our tertiary referral centre. Of these, 37 procedures (male/female 24/13, median age 55 years) included gastric resections. The clinical data of all patients were introduced into a database and analyzed with respect to the morbidity associated with the gastric resections. RESULTS: Of all patients included, 16 had pseudomyxoma peritonei, 11 gastric carcinoma, 4 ovarian carcinoma, 3 malignant peritoneal mesothelioma, and 3 colon carcinoma. Twenty-seven patients had previous surgery (n = 22) and/or systemic chemotherapy (n = 18). Fifteen total gastrectomies, 3 subtotal gastrectomies, 12 distal gastrectomies, and 7 gastric wedge resections were performed during CRS. The overall postoperative morbidity was 45%; main surgical complications were pancreatitis (n = 6), abdominal abscess (n = 4), bile leakage (n = 2), and digestive fistula (leakage of ileorectostomy and small bowel perforation) (n = 2). However, no complications occurred at the site of the esophageal anastomosis (n = 15), gastric anastomosis (n = 15) or gastric suture (n = 7). No patient died postoperatively during the hospitalization period. CONCLUSIONS: CRS in combination with HIPEC is associated with high postoperative morbidity; however, anastomosis following total or subtotal gastrectomy is safe in experienced centers. No leakages related to gastric resections occurred in this high-risk patient group.

Peritoneal carcinomatosis: patients selection, perioperative complications and quality of life related to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Peritoneal tumor dissemination arising from colorectal cancer, appendiceal cancer, gastric cancer, gynecologic malignancies or peritoneal mesothelioma is a common sign of advanced tumor stage or disease recurrence and mostly associated with poor prognosis. METHODS AND RESULTS: In the present review article preoperative workup, surgical technique, postoperative morbidity and mortality rates, oncological outcome and quality of life after CRS and HIPEC are reported regarding the different tumor entities. CONCLUSION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provide a promising combined treatment strategy for selected patients with peritoneal carcinomatosis that can improve patient survival and quality of life. The extent of intraperitoneal tumor dissemination and the completeness of cytoreduction are the leading predictors of postoperative patient outcome. Thus, consistent preoperative diagnostics and patient selection are crucial to obtain a complete macroscopic cytoreduction (CCR-0/1).