Prehabilitation before major abdominal surgery: Evaluation of the impact of a perioperative clinical pathway, a pilot study.

BACKGROUND & OBJECTIVE: Major abdominal surgery morbidity can reach 50%. Prehabilitation has shown promising results in decreasing complications. However, it is unknown if prehabilitation can have a positive effect specifically after major abdominal surgery. The goal of this study was to evaluate the feasibility and safety of a prehabilitation program before major abdominal surgery. METHODS: All patients evaluated for major abdominal surgery between February and April 2018 were eligible. A 4-week trimodal prehabilitation program combining physical therapy, nutritional support and psychological preparation was set up. RESULTS: Among 106 patients evaluated for major abdominal surgery during the study period, 60 were included in the prehabilitation program. No cardiovascular events occurred during prehabilitation. The 6-min walking distance increased significantly (+45 m, increase of 9.3%, p = 0.008) after prehabilitation (and before the operation). Anxiety, depression, and several quality of life (QoL) items improved. Postoperative 90-day mortality and morbidity were 3.4% and 48%, respectively. Median hospital length of stay, and intensive care unit length of stay were 14 and 6 days, respectively. For 19 patients readmitted, the treatment was medical, radiological, or surgical, for 11, 5, and 3 patients, respectively. CONCLUSIONS: Prehabilitation before major abdominal surgery is feasible, safe, and improve patients' functional reserves, QoL, and psychological status.

Enteral versus parenteral nutrition in the conservative treatment of upper gastrointestinal fistula after surgery: a multicenter, randomized, parallel-group, open-label, phase III study (NUTRILEAK study).

BACKGROUND: Postoperative upper gastrointestinal fistula (PUGIF) is a devastating complication, leading to high mortality (reaching up to 80%), increased length of hospital stay, reduced health-related quality of life and increased health costs. Nutritional support is a key component of therapy in such cases, which is related to the high prevalence of malnutrition. In the prophylactic setting, enteral nutrition (EN) is associated with a shorter hospital stay, a lower incidence of severe infectious complications, lower severity of complications and decreased cost compared to total parenteral nutrition (TPN) following major upper gastrointestinal (GI) surgery. There is little evidence available for the curative setting after fistula occurrence. We hypothesize that EN increases the 30-day fistula closure rate in PUGIF, allowing better health-related quality of life without increasing the morbidity or mortality. METHODS/DESIGN: The NUTRILEAK trial is a multicenter, randomized, parallel-group, open-label phase III trial to assess the efficacy of EN (the experimental group) compared with TPN (the control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after esophagogastric resection including bariatric surgery, duodenojejunal resection or pancreatic resection with digestive tract violation) in terms of the 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month postrandomization fistula closure rate, time of first fistula closure (in days), the medical- and surgical treatment-related complication rate at 6 months after randomization, the fistula-related complication rate at 6 months after randomization, the type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days after randomization), 30-day and 6-month postrandomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 postrandomization, the mean length of hospital stay, the patient's health-related quality of life (by self-assessment questionnaire), oral feeding time and direct costs of treatment. A total of 321 patients will be enrolled. DISCUSSION: The two nutritional supports are already used in daily practice, but most surgeons are reluctant to use the enteral route in case of PUGIF. This study will be the first randomized trial testing the role of EN versus TPN in PUGIF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03742752. Registered on 14 November 2018.

An update of peritonectomy procedures used in cytoreductive surgery for peritoneal malignancy.

Background: Complete cytoreduction is acknowledged to be an effective way to achieve macroscopic tumor clearance for a variety of tumors confined to the peritoneal cavity. Recent trials have shown that surgery respecting anatomical planes results in excellent outcomes and even the chance of cure for some from what was once thought to be life-limiting disease. Objective: To describe peritonectomy procedures in the current era. Method: A thorough and systematic method for cytoreductive surgery aimed at complete surgical resection of peritoneal metastases (PMs) was described. Results: The general principles of cytoreductive surgery were set out including preoperative preparation, patient positioning and incision. Strategies for assessing disease extent and planning surgical steps were outlined and established peritonectomy procedures such as Glisson's capsulectomy, omentectomy, left and right diaphragmatic peritonectomy, lesser omentectomy, stripping of the omental bursa, and pelvic peritonectomy were described. Novel techniques such as anterior pancreatic peritonectomy, small bowel mesenteric peritonectomy and cardiophrenic lymph node dissection were explained, and illustrated with accompanying video. Conclusion: Peritoneal metastases present a challenge to the surgeon which calls for a unique skill set if optimal outcomes are to be achieved. Attempts to standardize the surgical techniques described will allow further refinement as new technological advances occur.

Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer With Peritoneal Metastases (CYTO-CHIP study): A Propensity Score Analysis.

PURPOSE: Gastric cancer (GC) with peritoneal metastases (PMs) is a poor prognostic evolution. Cytoreductive surgery (CRS) yields promising results, but the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial. Here we aimed to compare outcomes between CRS-HIPEC versus CRS alone (CRSa) among patients with PMs from GC. PATIENTS AND METHODS: From prospective databases, we identified 277 patients with PMs from GC who were treated with complete CRS with curative intent (no residual nodules > 2.5 mm) at 19 French centers from 1989 to 2014. Of these patients, 180 underwent CRS-HIPEC and 97 CRSa. Tumor burden was assessed using the peritoneal cancer index. A Cox proportional hazards regression model with inverse probability of treatment weighting (IPTW) based on propensity score was used to assess the effect of HIPEC and account for confounding factors. RESULTS: After IPTW adjustment, the groups were similar, except that median peritoneal cancer index remained higher in the CRS-HIPEC group (6 v 2; P = .003). CRS-HIPEC improved overall survival (OS) in both crude and IPTW models. Upon IPTW analysis, in CRS-HIPEC and CRSa groups, median OS was 18.8 versus 12.1 months, 3- and 5-year OS rates were 26.21% and 19.87% versus 10.82% and 6.43% (adjusted hazard ratio, 0.60; 95% CI, 0.42 to 0.86; P = .005), and 3- and 5-year recurrence-free survival rates were 20.40% and 17.05% versus 5.87% and 3.76% (P = .001), respectively; the groups did not differ regarding 90-day mortality (7.4% v 10.1%, respectively; P = .820) or major complication rate (53.7% v 55.3%, respectively; P = .496). CONCLUSION: Compared with CRSa, CRS-HIPEC improved OS and recurrence-free survival, without additional morbidity or mortality. When complete CRS is possible, CRS-HIPEC may be considered a valuable therapy for strictly selected patients with limited PMs from GC.

Ninety-day post-operative morbidity and mortality using the National Cancer Institute's common terminology criteria for adverse events better describe post-operative outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The post-operative morbidity and mortality after CRS-HIPEC has been widely evaluated. However, there is a major discrepancy between rates reported due to different metrics and time of analysis used. OBJECTIVE: To evaluate the legitimacy of 90-day morbidity and mortality based on the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0 classification as criteria of quality for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: A prospective database of all patients undergoing CRS-HIPEC for peritoneal carcinomatosis between 2004 and 2015 was queried for 90-day morbidity and mortality and survival. RESULTS: Among 881 patients, the 90-day major complication rate based on NCI-CTCAE classification and Clavien-Dindo's classification were 51% (n = 447 patients) and 25% (n = 222 patients), respectively. Among patients who presented with a 90-day complication based on the NCI-CTCAE classification, 50% (n = 225 patients) presented a medical complication not reported by Clavien-Dindo's classification. After surgery, 24 patients (2.7%) died of post-operative complications, for only 10 (42%) of them the death occurred within 30-day after surgery. Occurrence of major complication based on either NCI-CTCAE classification, Clavien-Dindo's classification or the medical complication not reported by Clavien-Dindo's classification all negatively impacts the overall survival. CONCLUSION: Among commonly reported morbidity's classification, 90-day morbidity based on NCI-CTCAE classification represents a legitimate metric of CRS-HIPEC quality. Post-operative morbidity after CRS-HIPEC should be reported using 90-day NCI-CTCAE classification.

A Perioperative Clinical Pathway Can Dramatically Reduce Failure-to-rescue Rates After Cytoreductive Surgery for Peritoneal Carcinomatosis: A Retrospective Study of 666 Consecutive Cytoreductions.

OBJECTIVE: To determine whether a perioperative, standardized clinical pathway could impact the failure-to-rescue rate after cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) in a tertiary center. SUMMARY OF BACKGROUND DATA: Morbidity and mortality remain significant after CRS for PC. Clinical pathways have been associated with better outcomes after surgery. The failure-to-rescue rate is a useful metric for evaluating quality in surgery. MATERIALS AND METHODS: This study included 666 patients that received CRS for PC between 2009 and 2014. Starting in 2012, a standardized perioperative clinical pathway was introduced, which focused on patient selection, nutrition, renal protection, pain management, prevention, and early detection of complications. Complications were evaluated with the National Cancer Institute's Common Terminology Criteria for Adverse Events. We used multivariate analyses to evaluate clinicopathological and perioperative factors for associations with major complications and failure-to-rescue. Complication rates were compared before and after the clinical pathway implementation. RESULTS: Major complications occurred in 341 patients (51%), leading to 15 deaths. The complication rate was similar before and after clinical pathway introduction (54.75% vs 48.9%, respectively; P = 0.138). Only prolonged surgery (longer than 240 mins) was independently associated with major complications. The failure-to-rescue rate was 4.4% for the entire period, but it significantly decreased after introducing the clinical pathway (9.02% vs 1.02%; P < 0.001). On multivariate analysis, only renal complications were associated with the failure-to-rescue. CONCLUSION: Morbidity after CRS remains significant, but standardized management facilitated a reduction in the failure-to-rescue rate and improved the quality of care. Specific effort should be dedicated to preventing postoperative renal failure.

Digital Glissonectomy: A Safe Perihepatic Peritonectomy.

BACKGROUND: Complete cytoreductive surgery (CRS), combining organ resection and peritonectomy, is the only treatment that could offer cure for patients with peritoneal carcinomatosis. Initially, when the Glisson's capsule was involved without deep liver parenchyma invasion, either electroevaporation or Glisson's capsule resection was proposed. The objective of this study is to present and evaluate the safety of this standardized digital glissonectomy. METHODS: Since 2009, the peritonectomy of the Glisson's capsule, or digital glissonectomy, has been standardized at our institution. RESULTS: Among 655 patients who underwent a complete CRS between 2009 and 2014, 91 (14 %) glissonectomies were performed. Pseudomyxoma peritonei was the primary indication, and a glissonectomy was more frequently performed for patients with high peritoneal cancer index. The morbidity and mortality of CRS were not increased after glissonectomy (p = 0.069 and 0.949, respectively). CONCLUSIONS: Digital glissonectomy is feasible and safe, when proposed for superficial deposits on Glisson's capsule.

Is Extended Lymphadenectomy Needed for Elderly Patients With Gastric Adenocarcinoma?

BACKGROUND: Extensive surgery is associated with greater mortality for elderly patients. For gastric adenocarcinoma (GA), it is unclear whether the benefit of an extended lymphadenectomy in this population outweighs the associated risks. This study aimed to determine the impact of lymphadenectomy on postoperative outcomes and survival for the elderly. OBJECTIVE: To determine the impact of lymphadenectomy on postoperative outcomes and survival for elderly. METHODS: From a cohort of 19 centers, patients who underwent resection of GA with curative intent between 1997 and 2010 were included in this study. Lymphadenectomy was defined according to the total number of lymph nodes in the surgical specimen (limited, <15; intermediate, 15-25; extended, >25). Postoperative outcomes and survival were compared between elderly (≥75 years) and younger patients and regarding the extent of lymphadenectomy for the elderly. RESULTS: Of 1348 patients, 386 were elderly. The elderly presented with a higher American Society of Anesthesiologist (ASA) score (ASA 3-4: 45 vs. 16.5 %; p < 0.001) as well as greater postoperative morbidity (45 vs. 37 %; p = 0.009) and mortality (8 vs. 2.5 %; p < 0.001) despite less aggressive treatment including less neoadjuvant chemotherapy (5 vs. 20 %; p < 0.001) and adjuvant chemotherapy (7 vs. 44 %; p < 0.001), fewer total gastrectomies (41.5 vs. 60 %; p < 0.001), and less extended lymphadenectomy (38 vs. 48.5 %; p < 0.001). Among the elderly patients, limited lymphadenectomy (n = 116), intermediate lymphadenectomy (n = 125), and extended lymphadenectomy (n = 145) were comparable with respect to tumor stage, perioperative treatment, morbidity, and mortality. For the elderly patients, overall survival (OS) was 30.8 months, and disease-specific survival (DSS) was 63.9 months. The extent of the lymphadenectomy did not have an impact on OS or DSS for the elderly patients. CONCLUSION: The expected benefit in terms of long-term survival did not justify an extended lymphadenectomy for elderly patients.

What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: A 25-year experience with 1,125 procedures.

OBJECTIVE: To review our 25-year experience with hyperthermic intra-peritoneal chemotherapy (HIPEC). BACKGROUND: Combining cytoreductive surgery (CRS) and HIPEC as local treatments for peritoneal carcinomatosis (PC) was proposed 25 years ago. METHODS: A prospective database of all patients undergoing HIPEC for PC since 1989 was searched for clinicopathological data, 90-day morbidity and mortality, and survival. RESULTS: Among 1,125 HIPEC procedures, PC origin was colorectal (342; 30%), ovarian (271; 24%), pseudomyxoma peritonei (189; 17%), gastric (127; 11%), malignant mesothelioma (84; 8%), or other (112; 10%). Between 2004-2009 (n = 321) and 2010-2015 (n = 560), the median peritoneal cancer index decreased (11 vs. 8; P < 0.001), fewer patients underwent incomplete cytoreduction (CC2-3: 4% vs. 0.5%; P < 0.001), and more were included in randomized trials (5% vs. 16%; P < 0.001). Postoperative morbidity (52% vs. 50%, P = 0.672) was not different, but mortality significantly decreased (5% vs. 2%; P = 0.030). Median overall-survival was 42 months, and improved significantly for each 5-year period except for 2006-2010 vs. 2011-2015 (P = 0.097). The 10-year survival without recurrence was 53%, 14%, 4%, 10%, and 9% for pseudomyxoma, mesothelioma, ovarian, colorectal, and gastric PC, respectively. CONCLUSION: This study demonstrated that CRS and HIPEC provide long-term survival irrespective of PC origin, and survival improves with experience. J. Surg. Oncol. 2016;113:796-803. © 2016 Wiley Periodicals, Inc.

Splenectomy Increases Postoperative Complications Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is increasingly performed on patients with peritoneal carcinomatosis of various origins. Splenectomy often is required in these patients to achieve complete tumor removal. Although splenectomy has been associated with increased morbidity in many major abdominal surgeries, its effect in patients undergoing CRS + HIPEC is unknown. The purpose of this study was to evaluate the impact of splenectomy during CRS + HIPEC on postoperative outcomes. METHODS: We retrospectively identified 39 patients who underwent CRS + HIPEC with splenectomy during a 3-year study period from a prospective database. We compared them to case controls (CRS + HIPEC without splenectomy) that were matched for the complexity of the procedure. We evaluated the complication rate and outcomes of patients in each group. RESULTS: During the study period, splenectomy was performed in 32 % of patients undergoing CRS + HIPEC procedure. Patients in the splenectomy group experienced more grade 3-4 complications than patients in the control group (59 vs. 35.9 %, p = 0.041) as well as more pulmonary complications (41 vs. 7.7 %, p = 0.0006). Multivariate analysis identified splenectomy as the only predictor of overall major complications (odds ratio = 2.57, 95 % confidence interval = 1.03-6.40). Mortality was similar in both groups. CONCLUSIONS: Splenectomy increases major complication rate in patients undergoing CRS + HIPEC and efforts should be made to preserve the spleen during the surgery.

Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin Increases the Risk of Postoperative Hemorrhagic Complications: Analysis of Predictive Factors.

BACKGROUND: Treatment of peritoneal carcinomatosis (PC) using cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended as curative treatment for selected patients. Modalities of HIPEC remain heterogeneous and HIPEC using oxaliplatin (HIPEC-Ox) appears to increase the risk of postoperative hemorrhagic complications (HCs). OBJECTIVE: The aim of this study was to assess the risk of HCs after CRS combined with HIPEC-Ox versus other drugs, and to determine predictive factors for HCs after HIPEC-Ox. METHODS: Data from 701 patients included in the National French Registry who were treated with CRS and HIPEC at 24 centers between 1998 and 2007 were used to evaluate the incidence of HCs following HIPEC with or without oxaliplatin. Overall, 771 patients treated with HIPEC-Ox at five French specialty centers were then analyzed to determine factors associated with the occurrence of HCs. RESULTS: The overall incidence of HCs was 9.8 %. When used with HIPEC, oxaliplatin significantly and independently increased the rate of HCs (15.7 vs. 2.6 % for other drugs; p = 0.004, odds ratio 32.4). Among the 771 patients who underwent HIPEC-Ox, HCs occurred in 14.3 % of patients. The only independent risk factor for HCs was an extended PC with a Peritoneal Cancer Index (PCI) >12 (p = 0.040). CONCLUSION: HIPEC-Ox increases the risk of HCs compared with HIPEC with other drugs. The potential oncologic benefit of oxaliplatin and the risk of HCs should be considered in patients with PC who have a high PCI, as well as in at-risk patients.

Definition of giant ventral hernias: Development of standardization through a practice survey.

BACKGROUND: Giant ventral hernias represent a real handicap for patients and constitute a challenge for surgeons. European Hernia Society classification defines all ventral hernia over 10 cm in the same group. However, this group represents different clinical entities with numerous therapeutic possibilities, and no standardized recommendation has been made. The objective of our work was to define consensual criteria that define giant ventral hernias requiring specific management and determine management modalities. METHODS: A national survey consisting of 21 questions was proposed through a secure, anonymous internet interface and on a voluntary basis to all surgeons practising in France involved in care of patients affected by giant ventral hernias. RESULTS: For more than 68% of respondents, loss of domain and a hernia volume greater than 30% of abdominal volume were mandatory to define giant ventral hernias. Pre-operative screening should include abdominal CT scan, functional respiratory exploration, and a cardiology consultation for 98%, 71% and 50% of the respondents respectively. Respiratory and cutaneous preparations were systematically proposed before surgery by 91% and 56% of respondents. Regarding surgical techniques, none has gained the support of the majority of respondents. However, 71% of respondents use a non-resorbable mesh in retro muscular position for more than 70% of their patients treated for giant ventral hernias. CONCLUSION: Giant ventral hernias could be defined as ventral hernia larger than 10 cm with loss of domain. A specific management is advocated.

Survival outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from gastric cancer: a systematic review.

Background: The current treatment of choice for peritoneal carcinomatosis from gastric cancer is systemic chemotherapy. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a new aggressive form of loco-regional treatment that is currently being used in pseudomyxoma peritoneii, peritoneal mesothelioma and peritoneal carcinomatosis from colorectal cancer. It is still under investigation for its use in gastric cancer. Methods: The literature between 1970 and 2016 was surveyed systematically through a review of published studies on the treatment outcomes of CRS and HIPEC for peritoneal carcinomatosis from gastric cancer. Results: Seventeen studies were included in this review. The median survival for all patients ranged from 6.6 to 15.8 months. The 5-years overall survival ranged from 6 to 31%. For patients with complete cytoreduction, the median survival was 11.2 to 43.4 months and the 5-years overall survival was 13 % to 23%. Important prognostic factors were found to be a low peritoneal carcarcinomatosis index (PCI) score and the completeness of cytoreduction. Conclusion: The current evidence suggests that CRS and HIPEC has a role to play in the treatment of peritoneal carcinomatosis from gastric cancer. Long term survival has been shown for a select group of patients. However, further studies are needed to validate these results.

Impact of neoadjuvant chemoradiotherapy on postoperative outcomes after esophageal cancer resection: results of a European multicenter study.

OBJECTIVES: To assess the impact of neoadjuvant chemoradiotherapy (NCRT) on anastomotic leakage (AL) and other postoperative outcomes after esophageal cancer (EC) resection. BACKGROUND: Conflicting data have emerged from randomized studies regarding the impact of NCRT on AL. METHODS: Among 2944 consecutive patients operated on for EC between 2000 and 2010 in 30 European centers, patients treated by NCRT after surgery (n=593) were compared with those treated by primary surgery (n=1487). Multivariable analyses and propensity score matching were used to compensate for the differences in some baseline characteristics. RESULTS: Patients in the NCRT group were younger, with a higher prevalence of male sex, malnutrition, advanced tumor stage, squamous cell carcinoma, and surgery after 2005 when compared with the primary surgery group. Postoperative AL rates were 8.8% versus 10.6% (P=0.220), and 90-day postoperative mortality and morbidity rates were 9.3% versus 7.2% (P=0.110) and 33.4% versus 32.1% (P=0.564), respectively. Pulmonary complication rates did not differ between groups (24.6% vs 22.5%; P=0.291), whereas chylothorax (2.5% vs 1.2%; P=0.020), cardiovascular complications (8.6% vs 0.1%; P=0.037), and thromboembolic events (8.6% vs 6.0%; P=0.037) were higher in the NCRT group. After propensity score matching, AL rates were 8.8% versus 11.3% (P=0.228), with more chylothorax (2.5% vs 0.7%; P=0.030) and trend toward more cardiovascular and thromboembolic events in the NCRT group (P=0.069). Predictors of AL were high American Society of Anesthesiologists scores, supracarinal tumoral location, and cervical anastomosis, but not NCRT. CONCLUSIONS: Neoadjuvant chemoradiotherapy does not have an impact on the AL rate after EC resection (NCT 01927016).

GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study.

BACKGROUND: In Europe, gastric cancer remains diagnosed at advanced stage (serosal and/or lymph node involvement). Despite curative management combining perioperative systemic chemotherapy and gastrectomy with D1-D2 lymph node dissection, 5-year survival rates of T3 and/or N + patients remain under 30%. More than 50% of recurrences are peritoneal and/or locoregional. The use of adjuvant hyperthermic intraperitoneal chemotherapy that eliminates free cancer cells that can be released into peritoneal cavity during the gastrectomy and prevents peritoneal carcinomatosis recurrences, was extensively evaluated by several randomized trials conducted in Asia. Two meta-analysis reported that adjuvant hyperthermic intraperitoneal chemotherapy significantly reduces the peritoneal recurrences and significantly improves the overall survival. As it was previously done for the evaluation of the extension of lymph node dissection, it seems very important to validate on European or caucasian patients the results observed in trials performed in Asia. METHODS/DESIGN: GASTRICHIP is a prospective, open, randomized multicenter phase III clinical study with two arms that aims to evaluate the effects of hyperthermic intraperitoneal chemotherapy with oxaliplatin on patients with gastric cancer involving the serosa and/or lymph node involvement and/or with positive cytology at peritoneal washing, treated with perioperative systemic chemotherapy and D1-D2 curative gastrectomy. Peroperatively, at the end of curative surgery, patients will be randomized after preoperatively written consent has been given for participation. Primary endpoint will be overall survival from the date of surgery to the date of death or to the end of follow-up (5 years). Secondary endpoint will be 3- and 5-year recurrence-free survival, site of recurrence, morbidity, and quality of life. An ancillary study will compare the incidence of positive peritoneal cytology pre- and post-gastrectomy in two arms of the study, and assess its impact on 5-year survival. The number of patients to be randomized was calculated to be 306. TRIAL REGISTRATION: EudraCT number: 2012-005748-12, ClinicalTrials.gov identifier: NCT01882933.

Pathological response to neoadjuvant chemotherapy: a new prognosis tool for the curative management of peritoneal colorectal carcinomatosis.

PURPOSE: The primary objective of this study was to determine the incidence rate of pathological complete responses (pCRs) following neoadjuvant systemic chemotherapy for the treatment of peritoneal carcinomatosis (PC) of colorectal origin. The secondary objective was to evaluate whether pathological response assessments predict survival of patients treated with curative intent by complete cytoreductive surgery (CRS). METHODS: A retrospective review was performed of 115 patients who underwent preoperative irinotecan- or oxaliplatin-based chemotherapy, followed by 124 procedures of complete CRS alone or combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The pathological response was defined as the mean percentage of cancer cells remaining within all specimens. Univariate and multivariate analyses were performed to identify predictors of survival and pathological response outcome. RESULTS: Twelve procedures (9.7 %) resulted in pCRs, defined as no residual cancer cells in all specimens, 25 (20.2 %) resulted in major responses (1 to 49 % residual cancer cells), and 87 (70.1 %) resulted in minor or no responses (>50 % residual cancer cells). The cumulative 5-year survival rates were 75 and 57 % for patients with pCR and major responses, respectively. Using multivariate analysis, pathological response was the only independent predictor of survival (P = 0.01; major response: hazard ratio [HR] = 4.91; minor response: HR = 13.46). No significant predictor of pathological response was identified. CONCLUSIONS: Pathological complete response can be achieved with preoperative systemic chemotherapy for patients with PC of colorectal origin. The degree of pathological response can be assessed and represented as a new outcome for prognosis following treatment with curative intent.

Progression following neoadjuvant systemic chemotherapy may not be a contraindication to a curative approach for colorectal carcinomatosis.

OBJECTIVE: The objective of this retrospective study was to evaluate the influence of neoadjuvant systemic chemotherapy on patients with colorectal carcinomatosis before a curative procedure. BACKGROUND: Peritoneal carcinomatosis (PC) from colorectal cancer may be treated with a curative intent by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The role of perioperative systemic chemotherapy for this particular metastatic disease remains unclear. METHODS: One hundred twenty patients with PC from colorectal cancer were consecutively treated by 131 procedures combining CRS with HIPEC. The response to neoadjuvant systemic chemotherapy was assessed on data from previous explorative surgery and/or radiological imaging. RESULTS: Ninety patients (75%) were treated with neoadjuvant systemic chemotherapy in whom 32 (36%) were considered to have responded, 19 (21%) had stable disease, and 19 (21%) developed diseases progression. Response could not be evaluated in 20 patients (22%). On univariate analysis, the use of neoadjuvant systemic chemotherapy had a significant positive prognostic influence (P = 0.042). On multivariate analysis, the completeness of CRS and the use of adjuvant systemic chemotherapy were the only significant prognostic factors (P < 0.001 and P = 0.049, respectively). Response to neoadjuvant systemic chemotherapy had no significant prognostic impact with median survival of 31.4 months in patients showing disease progression. CONCLUSIONS: In patients with PC from colorectal cancer without extraperitoneal metastases, failure of neoadjuvant systemic chemotherapy should not constitute an absolute contraindication to a curative procedure combining CRS and HIPEC.

Iterative procedures combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal recurrence: postoperative and long-term results.

OBJECTIVE: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the best treatment of several peritoneal surface malignancies. Isolated peritoneal recurrence may be treated by iterative procedures. The aim of this study was to evaluate immediate postoperative and long-term results after iterative CRS-HIPEC. METHODS: From 1990 to 2010, 30 patients with isolated peritoneal recurrence underwent iterative procedures combining CRS-HIPEC. RESULTS: Origins of peritoneal carcinomatosis were ovarian, colorectal, pseudomyxoma peritonei, peritoneal mesothelioma, gastric cancer, cholangiocarcinoma, leiomyosarcoma, and primary peritoneal serous carcinoma. Median recurrence-free survival (RFS) was 16.2 months from the first procedure. After the second procedure, one (3.3%) postoperative death occurred. Severe morbidity following the second procedure was 40% versus 30% after the first procedure (P = 0.37). At most recent follow up, 11 patients were disease-free, 10 were alive with recurrence, and 9 were dead with recurrence. Five-year overall survival after initial CRS with HIPEC was 65%, and overall median survival from diagnosis was 140 months. CONCLUSION: Iterative procedures combining CRS-HIPEC are feasible and allow long-term survival but may result in significant morbidity and mortality. Patients must be carefully selected, based on the following criteria: Origin of carcinomatosis, magnitude of first procedure, length of RFS, physiological age, co-morbidity, and possibility of complete cytoreduction.