Guillaume Passot

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

BackgroundIn 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 Nu2009+u2009patients 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/designGASTRICHIP 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 (5xa0years). 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 registrationEudraCT 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

PurposeThe 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).MethodsA 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.ResultsTwelve procedures (9.7xa0%) resulted in pCRs, defined as no residual cancer cells in all specimens, 25 (20.2xa0%) resulted in major responses (1 to 49xa0% residual cancer cells), and 87 (70.1xa0%) resulted in minor or no responses (>50xa0% residual cancer cells). The cumulative 5-year survival rates were 75 and 57xa0% for patients with pCR and major responses, respectively. Using multivariate analysis, pathological response was the only independent predictor of survival (Pxa0=xa00.01; major response: hazard ratio [HR]xa0=xa04.91; minor response: HRxa0=xa013.46). No significant predictor of pathological response was identified.ConclusionsPathological 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.

Bevacizumab Doubles the Early Postoperative Complication Rate after Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Carcinomatosis of Colorectal Origin

AbstractBackgroundnPatients with stage IV colorectal cancer and peritoneal carcinomatosis are increasingly treated with curative intent and perioperative systemic chemotherapy combined with targeted therapy. The aim of this study was to analyze the potential impact of bevacizumab on early morbidity after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis of colorectal origin.nMethodsnFrom 2004 to 2010, in three referral centers, 182 patients with colorectal carcinomatosis were treated with complete cytoreduction followed by HIPEC after either preoperative systemic chemotherapy alone or in combination with bevacizumab. Because there was no control on treatment allocation, propensity score methods were used to control for this bias.ResultsThe median time from discontinuation of bevacizumab to HIPEC was 7xa0weeks (range 6–10xa0weeks). Major morbidity was greater in the bevacizumab group (34 vs. 19xa0%, pxa0=xa00.020). Nine patients died postoperatively, 5 (6.2xa0%) in the bevacizumab group (nxa0=xa080) and 4 (3.9xa0%) in the group treated with chemotherapy alone (nxa0=xa0102) (pxa0=xa00.130). The rate of digestive fistulas was greater in the bevacizumab group, although not statistically significant (18 vs. 10xa0%, pxa0=xa00.300). The effect of bevacizumab on major morbidity (including death) was found to be statistically significant (odds ratio 2.28, 95xa0% confidence interval 1.05–4.95) (pxa0=xa00.04).ConclusionsAdministration of bevacizumab before surgery with complete cytoreduction followed by HIPEC for colorectal carcinomatosis is associated with twofold increased morbidity. The oncologic benefit of bevacizumab before HIPEC remains to be evaluated.

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

To review our 25‐year experience with hyperthermic intra‐peritoneal chemotherapy (HIPEC).

Pseudomyxoma Peritonei: Role of 18F-FDG PET in preoperative evaluation of pathological grade and potential for complete cytoreduction

INTRODUCTIONnFor pseudomyxoma peritonei (PMP), survival depends on pathological grade and completeness of cytoreductive surgery. The aim of the study was to assess the ability of preoperative 18F-FDG PET to determine these 2 prognosis indicators.nnnMATERIAL AND METHODSnIn this prospective single centre study, all patients presenting with PMP were included. They underwent a preoperative 18F-FDG PET with a double radiological evaluation and an explorative laparotomy with the objective of optimal cytoreduction followed by a hyperthermic intra-operative intraperitoneal chemotherapy (HIPEC). Patients with non resectable disease underwent debulking surgery without HIPEC. The Completeness of Cytoreduction was assessed by CC score.nnnRESULTSnThirty-four patients were included. PET scanning was positive for 19 patients with grade II (hybrid form) or III (Peritoneal Mucinous Carcinomatosis) and for 2 patients with grade I (disseminated peritoneal adenomucinosis), and negative for 3 patients with grade II - III and for 10 patients with grade I. PET scanning was positive for 6 patients with CC score 2 - 3 and for 16 patients with CC score 0, and negative for 2 patients with CC score 2 - 3 and for 10 patients with CC score 0. The 18F-FDG PET interpretation distinguished 2 patients groups (grade I and grade II - III) with a sensitivity of 90% and a specificity of 77%. Moreover, probability of complete cytoreduction when PET was negative was over 80%.nnnCONCLUSIONnPreoperative 18F-FDG PET may predict pathological grade and completeness of cytoreduction which are the two main prognostic factors in patients with PMP.

Quality of life after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: A prospective study of 216 patients

INTRODUCTIONnCytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have demonstrated promising results in the treatment of peritoneal carcinomatosis (PC). The purpose of this study was to assess the impact of this combined procedure on quality of life (QoL).nnnMATERIALS AND METHODSnA prospective single centre study of 216 consecutive patients treated with CRS and HIPEC was conducted using the Gastro-Intestinal Quality of Life Index questionnaire (GIQLI), completed preoperatively and at 1, 3, 6 and 12 months.nnnRESULTSnQuestionnaire compliance was 81%, 90%, 89%, 89% and 74% at baseline, 1, 3, 6 and 12 months respectively. QoL was significantly decreased up to 6 months and returned to baseline at 12 months. In multivariate analysis, factors decreasing QoL were origin of PC at 3 months, presence of stoma at 6 months and length of surgery over 270 min and disease recurrence at 12 months.nnnCONCLUSIONSnDespite morbidity associated with CRS and HIPEC, QoL returned to baseline at one year after surgery. This treatment strategy should be considered for the treatment of peritoneal carcinomatosis.

Reply to: lack of prognostic significance of conventional peritoneal cytology in colorectal and gastric cancers: results of EVOCAPE 2 multicentre prospective study.

Abstract Aim In digestive cancers, the prognostic significance of intraperitoneal free cancer cells remains unclear (IPCC). The main objective of this study was to assess the prognostic significance of IPCC in colorectal and gastric adenocarcinoma. The secondary objectives were to evaluate the predictive significance of IPCC for the development of peritoneal carcinomatosis (PC) and to evaluate the prevalence of synchronous PC and IPCC. Methods This was a prospective multicentre study. All patients undergoing surgery for a digestive tract cancer had peritoneal cytology taken. Patients with gastric and colorectal cancer with no residual tumour after surgery and no evidence of PC were followed-up for 2 years. The primary end point was overall survival. Results Between 2002 and 2007, 1364 patients were enrolled and 956 were followed-up over 2 years. Prevalence of IPCC was 5.7% in colon cancer, 0.6% in rectal cancer and 19.5% in gastric cancer. The overall 2-year survival rate for patients with IPCC was 34.7% versus 86.8% for patients with negative cytology ( p Conclusion The presence of IPCC was not an independent prognostic and didnt add any additional prognostic information to the usual prognostic factors related to the tumour (pTNM and differentiation). Moreover the presence of IPCC detected with this method didnt appear to predict development of PC. Peritoneal cytology using conventional staining doesnt seem to be a useful tool for the staging of colorectal and gastric cancers.

Postoperative outcomes of laparoscopic vs open cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of peritoneal surface malignancies

BACKGROUNDnCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the only curative treatment for many peritoneal surface malignancies. The purpose of this study was to evaluate feasibility and safety of CRS combined with HIPEC by laparoscopy for patients with limited peritoneal disease and to compare postoperative outcomes with those for an open procedure.nnnMETHODSnBetween January 2011 and November 2012, all patients with low-grade pseudomyxoma peritonei (PMP) or multicystic mesothelioma (MM) and limited peritoneal disease (Peritoneal Cancer Index [PCI] less than 10) underwent CRS and HIPEC by a laparoscopic approach. The study cohort was matched with a historical cohort of patients with the same characteristics (completeness of cytoreduction, HIPEC agent, PCIxa0±xa011 and agexa0±xa020 years) treated with CRS and HIPEC by laparotomy.nnnRESULTSnEight patients (five low-grade PMP and three MM) treated by a laparoscopic approach were compared to eight patients treated by laparotomy. All patients underwent complete cytoreductive surgery with HIPEC, and no conversion to laparotomy was needed. The median surgical length was 210xa0min (150-300) vs 240 (210-360), with a median hospital stay of 12 days (9-18) vs 19 (13-33). One patient had a postoperative complication (intraperitoneal haematoma treated by radiological drainage) vs four in the laparotomy group.nnnCONCLUSIONnLaparoscopic CRS combined with HIPEC is feasible and safe for curative treatment of strictly selected patients with peritoneal surface malignancy and might reduce postoperative complications and length of hospital stay.

GRECCAR 8: impact on survival of the primary tumor resection in rectal cancer with unresectable synchronous metastasis: a randomized multicentre study

BackgroundA majority of patients with rectal cancer and metastasis are not eligible to curative treatment because of an extensive and unresectable metastatic disease. Primary tumor resection is still debated in this situation. Rectal surgery treats or prevents the symptoms and avoids the risk of acute complications related to the primary tumor. Several studies on colorectal cancers seem to show interesting results in terms of survival in favor to the resection of the primary tumor. To date, no randomized trial or even a prospective study has assessed the impact of primary tumor resection on overall survival in patients with colorectal cancer with unresectable metastasis. All published studies were retrospective and included colon and rectal cancers. Rectal cancer is associated with specific problems related to the rectal surgery. Surgery is more complex, and may be source of more morbidity and postoperative functional dysfunctions (stoma, digestive, sexual, urinary) than colic surgery. On the other hand, symptoms related to the progression of rectal tumor are often very disabling: pain, rectal syndrome.Methods/DesignGRECCAR 8 is a multicentre randomized open-label controlled trial aimed to evaluate the impact on survival of the primary tumor resection in rectal cancer with unresectable synchronous metastasis. Patients must undergo upfront systemic chemotherapy for at least 4 courses before inclusion. Patients with progressive metastatic disease during upfront chemotherapy will be excluded from the study. Patients will be randomly assigned in a 1:1 ratio to Arm A: primary tumor resection followed by systemic chemotherapy versus Arm B: systemic chemotherapy alone. Primary endpoint will be overall survival measured from the date of randomization to the date of death or to the end of follow-up (2xa0years). Secondary endpoints will include progression-free survival, quality of life, toxicity of chemotherapy, response of the primary tumor and metastatic disease to chemotherapy, postoperative morbidity and mortality, rate of patient not eligible for postoperative chemotherapy (arm A), primary tumor related complications and rate of emergency surgery (arm B). The number of patients needed is 290.Trial registrationClinicalTrial.gov: NCT02314182

Acute Cholecystitis-Optimal Timing for Early Cholecystectomy: a French Nationwide Study.

BackgroundThe recommended treatment for acute calculous cholecystitis combines antibiotics and cholecystectomy. To reduce morbidity and mortality, guidelines recommend early cholecystectomy. However, the optimal timing for surgery on first admission remains controversial. This study aims to determine the best timing for cholecystectomy in patients presenting with acute calculous cholecystitis.Study DesignThe French national health-care database was analyzed to identify all patients undergoing cholecystectomy for acute cholecystitis during the same hospital stay between January 2010 and December 2013. Data regarding patients, procedures, and hospitals characteristics were collected. The relationship between surgery’s timing and clinical outcome was evaluated by multiple logistic regressions.ResultsOverall, 42,452 patients from 507 hospitals were included in the study. Postoperative complications requiring invasive treatment occurred in 961 patients (2.3xa0%), and the mortality rate was 1.1xa0%. Adverse postoperative outcomes—intensive care admission, reoperation, and postoperative sepsis—were significantly lower when surgery was performed between days 1 and 3 (3–3.3, 0.5–0.6, and 3.8–4.1xa0%, respectively) when compared to surgery performed on the day of admission (5.6, 1.2, and 5.2xa0%, pu2009<u20090.001) or from day 5 onward (4.5, 1, and 6.5xa0%, respectively; pu2009<u20090.001). Mortality was also significantly lower in patients undergoing cholecystectomy between days 1 and 3 after admission (0.8–1xa0%) when compared to patients operated on the day of admission or after day 3 (1.4xa0% on day 0, 1.2xa0% on day 4, and 1.9xa0% from day 5: all pu2009<u20090.001).ConclusionFor patients with acute calculous cholecystitis, all efforts should be made to perform cholecystectomy within 3xa0days after hospital admission in order to decrease morbidity and mortality.