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.

Effect of Hyperthermic Intraperitoneal Chemotherapy on Cytoreductive Surgery in Gastric Cancer With Synchronous Peritoneal Metastases: The Phase III GASTRIPEC-I Trial.

PURPOSE: In patients with peritoneal metastasis (PM) from gastric cancer (GC), chemotherapy is the treatment of choice. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are still being debated. This randomized, controlled, open-label, multicenter phase III trial (EudraCT 2006-006088-22; ClinicalTrials.gov identifier: NCT02158988) explored the impact on overall survival (OS) of HIPEC after CRS. PATIENTS AND METHODS: Adult patients with GC and histologically proven PM were randomly assigned (1:1) to perioperative chemotherapy and CRS alone (CRS-A) or CRS plus HIPEC (CRS + H). HIPEC comprised mitomycin C 15 mg/m2 and cisplatin 75 mg/m2 in 5 L of saline perfused for 60 minutes at 42°C. The primary end point was OS; secondary endpoints included progression-free survival (PFS), other distant metastasis-free survival (MFS), and safety. Analyses followed the intention-to-treat principle. RESULTS: Between March 2014 and June 2018, 105 patients were randomly assigned (53 patients to CRS-A and 52 patients to CRS + H). The trial stopped prematurely because of slow recruitment. In 55 patients, treatment stopped before CRS mainly due to disease progression/death. Median OS was the same for both groups (CRS + H, 14.9 [97.2% CI, 8.7 to 17.7] months v CRS-A, 14.9 [97.2% CI, 7.0 to 19.4] months; P = .1647). The PFS was 3.5 months (95% CI, 3.0 to 7.0) in the CRS-A group and 7.1 months (95% CI, 3.7 to 10.5; P = .047) in the CRS + H group. The CRS + H group showed better MFS (10.2 months [95% CI, 7.7 to 14.7] v CRS-A, 9.2 months [95% CI, 6.8 to 11.5]; P = .0286). The incidence of grade ≥3 adverse events (AEs) was similar between groups (CRS-A, 38.1% v CRS + H, 43.6%; P = .79). CONCLUSION: This study showed no OS difference between CRS + H and CRS-A. PFS and MFS were significantly better in the CRS + H group, which needs further exploration. HIPEC did not increase AEs.

Prolonged hyperthermic intraperitoneal chemotherapy duration with 90 minutes cisplatin might increase overall survival in gastric cancer patients with peritoneal metastases.

BACKGROUND: Advanced gastric cancer with synchronous peritoneal metastases (GC-PM) is associated with a poor prognosis. Although cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a promising approach, only a limited number of Western studies exist. AIM: To investigate the clinicopathological outcomes of patients who underwent CRS-HIPEC for GC-PM. METHODS: A retrospective analysis of patients with GC-PM was conducted. All patients were seen at the Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg, Germany between January 2011 and July 2021 and underwent CRS-HIPEC. Preoperative laboratory results, the use of neoadjuvant trastuzumab, and the details of CRS-HIPEC, including peritoneal carcinomatosis index, completeness of cytoreduction, and surgical procedures were recorded. Disease-specific (DSS), and overall survival (OS) of patients were calculated. RESULTS: A total of 73 patients were included in the study. Patients treated with neoadjuvant trastuzumab (n = 5) showed longer DSS (P = 0.0482). Higher white blood cell counts (DSS: P = 0.0433) and carcinoembryonic antigen levels (OS and DSS: P < 0.01), and lower hemoglobin (OS and DSS: P < 0.05) and serum total protein (OS: P = 0.0368) levels were associated with shorter survival. Longer HIPEC duration was associated with more advantageous median survival times [60-min (n = 59): 12.86 mo; 90-min (n = 14): 27.30 mo], but without statistical difference. To obtain additional data from this observation, further separation of the study population was performed. First, propensity score-matched patient pairs (n = 14 in each group) were created. Statistically different DSS was found between patient pairs (hazard ratio = 0.2843; 95% confidence interval: 0.1119-0.7222; P = 0.0082). Second, those patients who were treated with trastuzumab and/or had human epidermal growth factor receptor 2 positivity (median survival: 12.68 mo vs 24.02 mo), or had to undergo the procedure before 2016 (median survival: 12.68 mo vs 27.30 mo; P = 0.0493) were removed from the original study population. CONCLUSION: Based on our experience, CRS-HIPEC is a safe and secure method to improve the survival of advanced GC-PM patients. Prolonged HIPEC duration may serve as a good therapy for these patients.

Prolonged Survival in Peritoneal Metastatic Appendiceal Carcinoma Patients Treated With Combined Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Primary treatment for peritoneal dissemination of appendiceal cancer is the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The endpoints were overall survival and evaluation of prognostic factors. METHODS: Clinicopathological and treatment-related factors were obtained from a prospective database. A total of 84 patients, 55 (65%) primary and 29 (35%) recurrent malignant appendiceal carcinomas with synchronous and metachronous peritoneal metastases, underwent multimodal treatment between 2011 and 2021. The endpoints of the study were overall survival and evaluation of prognostic factors. RESULTS: The median follow-up was 4.8 y; the mean age was 54.5 y (range 25-77), with a sex distribution of 69% female and 31% male. The mean peritoneal cancer index was 11.3. The proportion of mucinous, intestinal-type, signet ring cell, and goblet cell carcinoma was 56%, 23%, 11%, and 10%, respectively. The 5-y survival rate of the whole cohort was 56.7%. In primary and recurrent diseases, the overall median survival was 8.4 and 4.9 y. Significantly improved survival was detected after complete cytoreduction resection (hazard ratio [HR] for CCR-2 versus CCR-0: 9.388, 95% confidence interval [CI] 3.026-29.124, P = 0.001) and initial local operation with undelayed admission to the center (HR 0.262, 95% CI 0.089-0.773; P = 0.015). The five independent factors in Kaplan-Meier analysis and univariable Cox regression analysis associated with significant adverse survival were cancer antigen (CA) 19-9 over 37 IU/mL, signet ring cell and intestinal-type histology, positive nodal status, grading, and peritoneal cancer index >20. Neoadjuvant chemotherapy administration did not impact survival (HR 1.220, 95% CI 0.612-2.432, P = 0.571). CONCLUSIONS: With multimodal treatment, prolonged survival is attainable in stage IV primary and recurrent appendiceal carcinoma with peritoneal dissemination. Direct referral to specialized centers after confirmation of peritoneal metastasis is recommended because prompt definitive treatment may significantly improve survival.

Rare Histologies and Infrequent Indications for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

AIM: This single-centre study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with rare histologies and uncommon tumour origins. PATIENTS AND METHODS: Prospectively collected data from the data registry of a single institution was retrospectively investigated. We present a series of selected patients who underwent CRS and HIPEC between 2011 and 2021 for peritoneal metastases arising from infrequent tumour entities. RESULTS: The study included 76 patients. From the wide range of histologies, seven groups were formed: Cancer of unknown primary, uncommon ovarian cancer types, other gynaecological tumours (endosalpingiosis, endometrial and cervical cancer), small bowel carcinoma, recurrent peritoneal mesothelioma, desmoplastic small round-cell tumour, and other rare malignancies. The median peritoneal cancer index was 8. Fifty-five patients with primary and 22 patients with recurrent disease were examined. Complete macroscopic tumour resection was achieved in 84% of cases. The median survival was 68.53 months considering the entire cohort, whilst the longest survival rate was registered in the group with rare ovarian cancer, and the shortest in the group of patients with small round-cell tumour, at 112.3 and 11.4 months, respectively (small round-cell tumour versus rare ovarian cancer, hazard ratio=15.6817; 95% confidence interval=2.6585-92.5030; p=0.0024). CONCLUSION: Based on the encouraging results in some test groups, especially in rare ovarian cancer, CUP, small bowel cancer and recurrent mesothelioma, multicenter prospective studies examining such rare tumour histologies are needed to reach a higher number of cases and, thus, explore the impact of multimodal therapy on these patients.

Ten-year single-center experience with treatment of primary diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

PURPOSE: This single-center study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM). METHODS: Prospectively collected data from a single institution data registry was retrospectively investigated. Eighty-four patients with primary malignant peritoneal mesothelioma underwent CRS and HIPEC with cisplatin and doxorubicin either for 60 min or 90 min of duration from 2011 to 2021. The primary endpoint was overall survival. The secondary endpoint was the evaluation of prognostic factors for overall survival. The tertiary endpoint was to assess the effect of neoadjuvant chemotherapy on survival. RESULTS: The median follow-up was 5.0 years (95%-CI 4.6-5.5). The median age was 59.2 years (IQR: 47-66). Eighty-two patients (97.6%) had epithelioid tumors. The median peritoneal cancer index was 18.0 (IQR: 13-27). Sixty-six patients (78.6%) had complete or near-complete cytoreduction (CCR 0 or CCR 1). Seventy patients (83.3%) received HIPEC for 60 min and 14 patients (16.7%) received it for 90 min. Twenty-two patients (26.2%) had grade 3 to 4 complications. Acute kidney injury (AKI) stage I-III occurred in 30 (35.7%) patients. Three patients (3.6%) died perioperatively. The overall median survival was 38.4 months (95%-CI 23.6-54.3), and the 5-year survival rate was 42%. Survival was independently associated with age, female gender, and thrombocytosis. Preoperative chemotherapy did not emerge as an adverse prognostic factor. CONCLUSION: In well-selected patients with DMPM, prolonged survival is achievable with CRS and HIPEC in specialized centers.

Selection Criteria for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy With Special Emphasis on Laparoscopy as an Efficient Tool.

BACKGROUND/AIM: The aim of the study was to assess diagnostic tools implemented in selecting candidates for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with special emphasis on diagnostic laparoscopy. PATIENTS AND METHODS: A total of 229 patients underwent laparoscopy between January 2011 and December 2015 with peritoneal carcinomatosis and were analyzed retrospectively to study the role of laparoscopy in selecting patients for CRS and HIPEC. RESULTS: After initial laparoscopy, 101 (44%) of patients underwent CRS and HIPEC with 128 (56%) being aborted. The most prevalent overall exclusion criterion was extensive small bowel disease with a prevalence of 107 (47%) patients. The rate of complete cytoreduction (CCR0 and CCR1) in patients who were deemed initially operable during laparoscopy was 96%. The most prevalent primary tumor site was the stomach with a prevalence of 36,7%. The overall median peritoneal cancer index (PCI) score of the excluded patients were 16.8 and 4.6 in the CRS and HIPEC group. Port-site metastasis was 3.1% and bowel perforation rate 3.0%. CONCLUSION: Laparoscopy is a proper selection tool in patients with peritoneal metastases for multimodal treatment. Sensitivity for detecting non-resectable patients is high and the morbidity and mortality low.

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.

[Recent Developments in the Regional Treatment of Peritoneal and Pleural Tumours (incl. HIPEC and HITOC)]. / Aktuelle Entwicklungen in der regionalen Behandlung von peritonealen und pleuralen Tumoren (inkl. HIPEC und HITOC).

The multimodal treatment of limited peritoneal metastases may improve prognosis in selected patients (pseudomyxoma peritonei, malignant peritoneal mesothelioma, colorectal, gastric and ovarian cancer) provided complete cytoreduction can be performed. Additive intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is often performed. If the treatment is undertaken in experienced (and certified) centres, associated mortality is low. Intrapleural hyperthermic chemoperfusion (HITOC) can be performed in patients with pleural malignancies, mainly for malignant pleural mesothelioma or metastases from a thymoma. In single patients, pleural metastases from gastrointestinal malignancies might be an indication. Both therapies (HIPEC and HITOC) are complex and their exact role has to be defined within further prospective randomised trials.

Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A multi-institutional experience.

BACKGROUND AND OBJECTIVES: The aims of this multi-institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival. METHODS: Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases. RESULTS: The study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high-grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence-free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5-year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 ( P = 0.02) and lymph node positivity ( P = 0.04), and from iCRS, PCI > 10 ( P = 0.03 for PCI 11-20; P < 0.001 for PCI > 20), high-grade complications ( P = 0.012), and incomplete cytoreduction ( P < 0.001). CONCLUSION: iCRS can provide long-term survival benefits to highly selected colorectal peritoneal carcinomatosis patients with comparable mortality and morbidity rates to the initial CRS procedure. Careful patient selection is necessary to improve overall outcomes.

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.

Metastatic Colorectal Cancer to the Peritoneum: Current Treatment Options.

OPINION STATEMENT: Peritoneal metastases (PM) are common in advanced-stage colorectal cancer (CRC) patients representing the second most common metastatic site of CRC. In the past, this clinical situation was treated with palliative intent. The introduction of new chemotherapeutic and targeted biologic agents has improved the prognosis of patients with metastatic colorectal cancer. However, the inclusion of treatment options such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as inherent components of a multidisciplinary treatment was evolving for the management of these patients. Notably, the surgical approach of CRS/HIPEC has been effective offering a prolonged survival with curative intent in patients with colorectal PM. This article reviews and highlights the recent evidence of CRS and HIPEC as well as current research going on in this form of locoregional treatment in the setting of peritoneal metastases of colorectal cancer.

Safety of rectum anastomosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND AND OBJECTIVES: In highly selected patients with peritoneal carcinomatosis, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can be an aggressive but worthwhile treatment regimen. Resection of the rectosigmoid is frequently performed with CRS. The aim of the study was to assess the safety of the rectal anastomosis in this setting. METHODS: Between 2005 and 2016, 436 patients underwent CRS/HIPEC. Clinical data were analyzed with respect to the morbidity associated with a rectum resection. RESULTS: In 436 patients, 174 rectum resections (40%) were performed with CRS, including 149 anterior resections of the rectosigmoid, 23 low anterior rectum resections, and 2 abdominoperineal rectum excisions. A total of 141 rectum anastomoses were performed; 33 patients received a permanent ostomy, and 48 patients received a protective ileostomy. After changing the operation technique of the rectum anastomosis, the number of protective ileostomies decreased from 65% to 20%. The overall postoperative morbidity was 31%. Rectal anastomotic leakages were seen in only 5% of cases. CONCLUSIONS: Anastomotic leakages of the rectum are rarely seen after CRS/HIPEC. HIPEC performed immediately after surgery seems to have no negative effect on the rectum anastomosis. Performing rectum anastomoses after CRS/ HIPEC appears to be a safe procedure.

Benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with isolated peritoneal metastases from colorectal cancer.

BACKGROUND: Ever since Sugarbaker has established the cytoreductive surgery (CRS) in combination with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), there is a chance of cure for selected patients with peritoneal metastases from colorectal cancer. Objective of this study was to investigate the benefit of CRS and HIPEC compared to other therapy options in patients with isolated synchronous and metachronous peritoneal metastases of colorectal origin in terms of long-term overall survival. METHODS: A retrospective population-based cohort study, including 370 patients diagnosed with isolated synchronous and metachronous peritoneal metastases of colorectal origin, was carried out. Therefore, data were acquired from the cancer registry at the Regensburg Tumor Center in Bavaria, Germany. Patients' overall survival (OAS) according to their therapy received was analyzed by means of Kaplan-Meier method and multivariable Cox regression. RESULTS: Overall median survival was 41.6 months for patients treated with CRS and HIPEC, compared with surgery and chemotherapy (24.0 months, log-rank p = 0.015), chemotherapy only (14.1 months, p < 0.001), surgery only (11.4 months, p < 0.001), and best supportive care (7.9 months, p < 0.001). This benefit persisted after adjustment for further risk factors in multivariable analysis. CONCLUSION: The effect of CRS and HIPEC stands out significantly in comparison to all other therapies. The multimodality approach should be a regular option for patients with isolated peritoneal metastases.

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.

Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases From a Small Bowel Adenocarcinoma: Multi-Institutional Experience.

BACKGROUND: The multi-institutional registry in this study evaluated the outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases (PM) from small bowel adenocarcinoma (SBA). METHODS: A multi-institutional data registry including 152 patients with PM from SBA was established. The primary end point was overall survival (OS) after CRS plus HIPEC. RESULTS: Between 1989 and 2016, 152 patients from 21 institutions received a treatment of CRS plus HIPEC. The median follow-up period was 20 months (range 1-100 months). Of the 152 patients, 70 (46.1%) were women with a median age of 54 years. The median peritoneal cancer index (PCI) was 10 (mean 12; range 1-33). Completeness of cytoreduction (CCR) 0 or 1 was achieved for 134 patients (88.2%). After CRS and HIPEC, the median OS was 32 months (range 1-100 months), with survival rates of 83.2% at 1 year, 46.4% at 3 years, and 30.8% at 5 years. The median disease-free survival after CCR 0/1 was 14 months (range 1-100 months). The treatment-related mortality rate was 2%, and 29 patients (19.1%) experienced grades 3 or 4 operative complications. The period between detection of PM and CRS plus HIPEC was 6 months or less (P = 0.008), and multivariate analysis identified absence of lymph node metastasis (P = 0.037), well-differentiated tumor (P = 0.028), and PCI of 15 or lower (P = 0.003) as independently associated with improved OS. CONCLUSION: The combined treatment strategy of CRS plus HIPEC achieved prolonged survival for selected patients who had PM from SBA with acceptable morbidity and mortality.

Laparoscopy as a useful selection tool for patients with prior surgery and peritoneal metastases suitable for multimodality treatment strategies.

BACKGROUND: Complete macroscopic cytoreduction in patients with peritoneal carcinomatosis (PC) is the basic requirement for long-term survival. Diagnostic laparoscopy (DL) can be difficult and of limited clinical value secondary to postoperative or tumor-induced adhesions. The aim of this study was to evaluate the role of DL in patients with prior surgery and PC. METHODS: The database of the surgical department of the University Medical Center of Regensburg was reviewed (9/2010-10/2014) selecting for DL in patients with PC. The operative report had a standardized format allowing for the determination of the extent of the intra-abdominal visible area and the extent of tumor on the surface of the small intestine. For the classification we used our own developed score. RESULTS: DL was performed in 102 patients. The complete abdominal cavity was evaluable in 48%. At least two quadrants and the largest part of the small intestine could be assessed in 70%. 37% of the patients had massive tumor manifestation on the small intestine or its mesentery. PCI (Peritoneal Cancer Index) could not be calculated in 71% of the patients due to incomplete visualization of the abdominal cavity and/or multiple tumor manifestations on the small intestine. 54% of patients were classified as non-resectable and 85% who seemed suitable for cytoreductive surgery underwent a CCR-0 resection and HIPEC. CONCLUSIONS: In spite of prior surgery and PC, DL is frequently possible and a useful tool to define the extent of tumor spread. Lots of patients can be prevented from needless open laparotomy. The extent of tumor involvement of the small intestine seems to be more relevant than calculation of the PCI to determine the potential for complete resection. Therefore, in the presence of adhesions, inspection of the complete abdominal cavity does not offer added clinical benefit and further adhesiolysis can be avoided.

"En bloc" caudate lobe and inferior vena cava resection following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal and liver metastasis of colorectal cancer.

There are diverse protocols to manage patients with recurrent disease after primary cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis. We describe a case of metachronous liver metastasis after CRS and HIPEC for colorectal cancer, successfully treated with a selective metastectomy and partial graft of the inferior vena cava. A 35-year-old female presented with a large tumour in the cecum and consequent colonic stenosis. After an emergency right colectomy, the patient received adjuvant chemotherapy. One year later she was diagnosed with peritoneal carcinomatosis, and it was decided to carry out a CRS/HIPEC. After 2 years of total remission, an isolated metachronous liver metastasis was detected by magnetic resonance imaging surveillance. The patient underwent a third procedure including a caudate lobe and partial inferior vena cava resection with a prosthetic graft interposition, achieving an R0 situation. The postoperative course was uneventful and the patient was discharged on postoperative day 17 after the liver resection. At 18-mo follow-up after the liver resection the patient remained free of recurrence. In selected patients, the option of re-operation due to recurrent disease should be discussed. Even liver resection of a metachronous metastasis and an extended vascular resection are acceptable after CRS/HIPEC and can be considered as a potential treatment option to remove all macroscopic lesions.

Is the Combination of Distal Pancreatectomy and Cytoreductive Surgery With HIPEC Reasonable?: Results of an International Multicenter Study.

OBJECTIVE: To report the morbidity and risk factors for overall complications and for pancreatic fistula (PF) after distal pancreatic resection (DP) during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). SUMMARY BACKGROUND DATA: The safety of DP in patients with peritoneal surface malignancies treated by CRS and HIPEC has been debated. The risk of PF and its impact on surgical outcomes are not well defined. METHODS: Between 2001 and 2012, 118 patients with peritoneal surface malignancy undergoing CRS/HIPEC required DP at 7 oncological surgical centers. The incidence, clinical impact, and risk factors of PF were analyzed. RESULTS: The indications for DP were tumoral invasion of the pancreatic gland with (n = 24; 20%) or without splenic extension (n = 76; 64%), invasion of the pancreatic capsule (n = 10; 9%), or iatrogenic lesions during CRS (n = 8; 7%). The rate of 90 days postoperative mortality was 7.6%, and the rate of severe morbidity (Clavien-Dindo ≥III) was 44%. Pancreatic fistula was observed in 39 cases (33%), with the majority grade B (48.7%) or C (28.2%). In multivariate analysis, the risk factors for PF were a peritoneal cancer index more than 20 (risk ratio: 3.01; P = 0.022) and an operative time more than 550 min (risk ratio: 2.74; P = 0.038). The occurrence of PF was not associated with a higher risk of 90-day mortality (5.1% vs 8.8%, not significant). CONCLUSIONS: With regard to reported morbi-mortality rates, DP associated with CRS/HIPEC may be a reasonable procedure in highly selected patients when done in high-volume centers. Therefore, distal pancreatic involvement should not be considered as a definitive contraindication for CRS/HIPEC in patients with resectable peritoneal surface disease.