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.

Is treatment in certified cancer centers related to better survival in patients with pancreatic cancer? Evidence from a large German cohort study.

BACKGROUND: Treatment of cancer patients in certified cancer centers, that meet specific quality standards in term of structures and procedures of medical care, is a national treatment goal in Germany. However, convincing evidence that treatment in certified cancer centers is associated with better outcomes in patients with pancreatic cancer is still missing. METHODS: We used patient-specific information (demographic characteristics, diagnoses, treatments) from German statutory health insurance data covering the period 2009-2017 and hospital characteristics from the German Standardized Quality Reports. We investigated differences in survival between patients treated in hospitals with and without pancreatic cancer center certification by the German Cancer Society (GCS) using the Kaplan-Meier estimator and Cox regression with shared frailty. RESULTS: The final sample included 45,318 patients with pancreatic cancer treated in 1,051 hospitals (96 GCS-certified, 955 not GCS-certified). 5,426 (12.0%) of the patients were treated in GCS-certified pancreatic cancer centers. Patients treated in certified and non-certified hospitals had similar distributions of age, sex, and comorbidities. Median survival was 8.0 months in GCS-certified pancreatic cancer centers and 4.4 months in non-certified hospitals. Cox regression adjusting for multiple patient and hospital characteristics yielded a significantly lower hazard of long-term, all-cause mortality in patients treated in GCS-certified pancreatic centers (Hazard ratio = 0.89; 95%-CI = 0.85-0.93). This result remained robust in multiple sensitivity analyses, including stratified estimations for subgroups of patients and hospitals. CONCLUSION: This robust observational evidence suggests that patients with pancreatic cancer benefit from treatment in a certified cancer center in terms of survival. Therefore, the certification of hospitals appears to be a powerful strategy to improve patient outcomes in pancreatic cancer care. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04334239 ).

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.

Decision-Making Analysis for Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer: A Survey by the Executive Committee of the Peritoneal Surface Oncology Group International (PSOGI).

OBJECTIVES: To assess the individual treatment strategies among international experts in peritoneal carcinosis, specifically their decision-making in the process of patient selection for hyperthermic intraperitoneal chemotherapy (HIPEC) in women suffering from ovarian cancer, to identify relevant decision-making criteria, and to quantify the level of consensus for or against HIPEC. METHODS: The members of the executive committee of the Peritoneal Surface Oncology Group International (PSOGI) were asked to describe the clinical conditions under which they would recommend HIPEC in patients with ovarian cancer and to describe any disease or patient characteristics relevant to their decision. All answers were then merged and converted into decision trees. The decision trees were then analyzed by applying the objective consensus methodology. RESULTS: Nine experts in surgical oncology provided information on their multidisciplinary treatment strategy including HIPEC for patients with advanced ovarian cancer. Three of the total of 12 experts did not perform HIPEC. Five criteria relevant to the decision on whether HIPEC is performed were applied. In patients with resectable disease, a peritoneal cancer index (PCI) <21, and epithelial ovarian cancer without distant metastasis, consent was received by 75% to perform HIPEC for women suffering from recurrent disease. Furthermore, in the primary disease setting, consent was received by 67% to perform HIPEC according to the same criteria. DISCUSSION AND CONCLUSION: Among surgical oncology experts in peritoneal surface malignancy and HIPEC, HIPEC plays an important role in primary and recurrent ovarian cancer, and the PCI is the most important criterion in this decision.

Preventive HIPEC in combination with perioperative FLOT versus FLOT alone for resectable diffuse type gastric and gastroesophageal junction type II/III adenocarcinoma - the phase III "PREVENT"- (FLOT9) trial of the AIO /CAOGI /ACO.

BACKGROUND: The main reason for treatment failure after curative surgical resection of gastric cancer is intra-abdominal spread, with 40-50% peritoneal seeding as primary localization of recurrence. Peritoneal relapse is seen in 60-70% of tumors of diffuse type, compared to only 20-30% of intestinal type. Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) is an increasingly used therapy method for patients with peritoneal metastases. The preventive use of HIPEC could represent an elegant approach for patients (pts) before macroscopic peritoneal seeding, since pts. with operable disease are fit and may have potential risk of microscopic involvement, thus having a theoretical chance of cure with HIPEC even without the need for cytoreduction. No results from a PCRT from the Western hemisphere have yet been published. METHODS: This is a multicenter, randomized, controlled, open-label study including a total of 200 pts. with localized and locally advanced diffuse or mixed type (Laurens's classification) adenocarcinoma of the stomach and Type II/III GEJ. All enrolled pts. will have received 3-6 pre-operative cycles of biweekly FLOT (Docetaxel 50 mg/m2; Oxaliplatin 85 mg/m2; Leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2wk). Pts will be randomized 1:1 to receive surgery only and postoperative FLOT (control arm) or surgery + intraoperative HIPEC (cisplatin 75 mg/m2 solution administered at a temperature of 42 °C for 90 min) and postoperative FLOT (experimental arm). Surgery is carried out as gastrectomy or transhiatal extended gastrectomy. Primary endpoint is PFS/DFS, major secondary endpoints are OS, rate of pts. with peritoneal relapse at 2 and 3 years, perioperative morbidity/mortality and quality of life. The trial starts with a safety run-in phase. After 20 pts. had curatively intended resection in Arm B, an interim safety analysis is performed. Recruitment has already started and first patient in was on January 18th, 2021. DISCUSSION: If the PREVENT concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, pts. with gastric cancer and no peritoneal involvement will not be treated with HIPEC during surgery. TRIAL REGISTRATION: The study is registered on June 25th, 2020 under ClinicalTrials.gov Identifier: NCT04447352 ; EudraCT: 2017-003832-35 .

Neoadjuvant chemotherapy with gemcitabine plus cisplatin followed by radical liver resection versus immediate radical liver resection alone with or without adjuvant chemotherapy in incidentally detected gallbladder carcinoma after simple cholecystectomy or in front of radical resection of BTC (ICC/ECC) - a phase III study of the German registry of incidental gallbladder carcinoma platform (GR)- the AIO/ CALGP/ ACO- GAIN-trial.

BACKGROUND: Currently, complete surgical resection represents the only potentially curative treatment option for Biliary Tract Cancer (BTC) including Gallbladder Cancer (GBC). Even after curative resection, 5-year OS is only 20-40%. Gallbladder carcinoma is relatively rare, but still the fifth most common neoplasm of the digestive tract and even the most frequent cancer of the biliary system. Gallbladder carcinoma is suspected preoperatively in only 30% of all pts., while the majority of cases are discovered incidentally by the pathologist after cholecystectomy for a benign indication. For improving curative rates in BTC and GBC, early systemic therapy combined with radical resection seems to be a promising approach. The earliest moment to apply chemotherapy would be in front of radical surgery. The encouraging results of neoadjuvant/perioperative concepts in other malignancies provide an additional rationale to use this treatment in the early phase of GBC management and even ICC/ECC. Especially because data regarding pure adjuvant chemotherapy in BTC's are conflicting. METHODS: This is a multicenter, randomized, controlled, open-label phase III study including pts. with incidentally discovered GBCs after simple cholecystectomy in front of radical liver resection and pts. with resectable/ borderline resectable cholangiocarcinomas (ICC/ ECC) scheduled to receive perioperative chemotherapy (Gemcitabine + Cisplatin 3 cycles pre- and post-surgery) or surgery alone followed by a therapy of investigator's choice. Primary endpoint is OS; secondary endpoints are PFS, R0-resection rate, toxicity, perioperative morbidity, mortality and QoL. A total of N = 333 patients with GBC or BTC will be included. Recruitment has started in August 2019. DISCUSSION: The current proposed phase III GAIN study investigates whether induction chemotherapy followed by radical resection in ICC/ECC and re-resection in IGBC (and - if possible - postoperative chemotherapy) prolongs overall survival compared to radical surgery alone for incidental gallbladder carcinoma and primary resectable or borderline resectable cholangiocarcinoma. Utilizing a neoadjuvant approach including a second radical surgery will help to raise awareness for the necessity of radical surgery, especially second radical completion surgery in IGBC and improve the adherence to the guidelines. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03673072 from 17.09.2018. EudraCT number: 2017-004444-38 from 02.11.2017.

Peritoneal metastasis in gastric cancer: results from the German database.

BACKGROUND: Patients with peritoneal metastases of gastric cancer have a poor prognosis with a median survival of 7 months. A benefit of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) could be shown in several selected patient cohorts but remains controversial. The aim of this study was, to reflect the results of a national German HIPEC registry initiated by the German Society of General and Visceral Surgery (DGAV). METHODS: The DGAV HIPEC registry StuDoQ|Peritoneum documents patients with peritoneal malignancy contributed from 52 hospitals. All consecutive documented patients from 2011 until 2016 (n = 3078) were treated with CRS and HIPEC and were analysed. A total of 315 (10%) suffered from gastric cancer and were analysed. RESULTS: A complete data set of 235 patients was available for this study, including 113 male (48.1%) and 122 female (51.9%) patients with a median age of 53.4 years (SD ± 11.9). The median PCI was 8.0 (range 1-30). A complete cytoreduction was achieved in 121 patients (71.6%). Postoperative complications (Clavien-Dindo grades 3-4) occurred in 40 patients (17%). The median overall survival (OS) time was 13 months. The 5-year survival rate was 6%. According to the PCI from 0-6 (n = 74); 7-15 (n = 70) and 16-39 (n = 24) the median OS differs significantly (18 months vs. 12 months vs. 5 months; p = 0.002). CONCLUSIONS: CRS and HIPEC in selected patients with gastric cancer and peritoneal spread can improve survival when they are treated in centers. An accurate staging and patient selection are of major importance to achieve long-term survival.

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.

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.

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.

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.

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.

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.

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.

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.

Prognostic significance of Sugarbaker's peritoneal cancer index for the operability of ovarian carcinoma.

INTRODUCTION: This study aimed to investigate Sugarbaker's peritoneal cancer index (PCI) as a prognostic indicator for the resectability of ovarian carcinoma (OC), as depicted in the study using the completeness of cytoreduction score (CCS).Currently, the intraoperative assessment of operability in OC surgery is primarily a subjective measurement that is dependent on the surgeon. METHODS: The retrospective data from 98 patients with OC International Federation of Gynecology and Obstetrics (FIGO) III to IV who had received surgery between January 2010 and December 2011 were analyzed. The PCI and the CCS were determined retrospectively using surgical reports, histological findings, and intraoperative photographic documentation. Receiver operating characteristic curves and ordinal regression were applied to evaluate the predictability of CCS using the PCI. RESULTS: Of 98 patients, 80 (81.6%) were staged FIGO III and 18 (18.4%) FIGO IV. A statistically significant correlation was demonstrated between the PCI and CCS (P < 0.01). A receiver operating characteristic curve with an area under the curve of 0.839 demonstrated the high precision in discrimination with which the PCI could predict the CCS. Using ordinal regression, it was possible to estimate the probabilities of achieving CCS 0, CCS 1, CCS 2, or CCS 3 for a given PCI (pseudo R(2) according to Cox and Snell 0.428, Nagelkerke 0.476, and McFadden 0.244). CONCLUSIONS: The PCI more precisely defined the heterogeneous group of patients with OC FIGO III. The PCI provided objectivity and reproducibility, and it seems to be a possible prognostic indicator for OC resectability.

Oxaliplatin-based versus irinotecan-based hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis from appendiceal and colorectal cancer: a retrospective analysis.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provide an effective treatment option for selected patients with colorectal peritoneal metastasis with encouraging survival results. Many different drug combinations and HIPEC regimens including bidirectional, i.e. synchronous intravenous and intraperitoneal, drug application have been used. However, there is still no standardization of the HIPEC regimen. METHODS: Between 05/2007 and 04/2010 190 patients underwent CRS and HIPEC at the University Hospital Regensburg. Thirty-two patients with peritoneal metastasis arising from colorectal or appendiceal cancer underwent complete macroscopic cytoreduction (CC-0/1) and bidirectional HIPEC and completed at least 3-year follow-up. Twenty patients received oxaliplatin-based (OX) and twelve patients received irinotecan-based HIPEC (IRI). Group-specific perioperative morbidity and 3-year survival has been determined. RESULTS: The grade 3/4 morbidity rate according to CTCAE v4 was 35.0% in the OX group vs. 33.3% in the IRI group (p = 1.000). There was no perioperative mortality in both groups. Median survival was 26.8 months (95% CI 15.7-33.1 months) in the IRI group and has not yet been reached in the OX group during a median follow-up of 39.4 months. Three-year survival rates were 65.0% in the OX group vs. 41.7% in the IRI group (p = 0.295). CONCLUSIONS: The morbidity and toxicity rates of bidirectional irinotecan-based and oxaliplatin-based HIPEC are comparable. Nevertheless, in the absence of contraindications oxaliplatin-based HIPEC might be preferred due to the positive trend regarding 3-year and median survival.