Jean Robert Delpero

Portal Vein Ligation as an Efficient Method of Increasing the Future Liver Remnant Volume in the Surgical Treatment of Colorectal Metastases

OBJECTIVE To compare the volumetric increase of segments 2 and 3, segment 4, and the caudate lobe after portal vein ligation (PVL) and portal vein embolization (PVE). The small size of the remnant liver and chemotherapy-induced liver injury increase the risk of postoperative hepatic insufficiency after major hepatic resection for colorectal liver metastases. Portal vein ligation has been suggested to be less effective than embolization in inducing hypertrophy of the remnant liver. DESIGN, SETTING, AND PATIENTS We retrospectively reviewed 48 patients with colorectal liver metastases who underwent PVL (n = 17) or PVE (n = 31) at the Istituto per la Ricerca e la Cura del Cancro or the Institut Paoli-Calmette from March 1, 2000, through August 31, 2006. MAIN OUTCOME MEASURES To compare the volume increase of segments 2 and 3, segment 4, and of the caudate lobe in patients who have undergone PVL or PVE in preparation for a major hepatic resection. RESULTS There were no deaths related to PVE or PVL. Portal vein ligation was associated with resection of synchronous colorectal cancer in 16 patients. Resection of a liver metastasis in the remnant liver was performed in 11 patients. The median estimated baseline volume of segments 2 and 3 was 17.7% in the PVL group and 17.5% in the PVE group (P = .72). After PVL or PVE, it increased to 26.9% and 24.7%, respectively (P = .95), for volumetric increases of 43.1% and 53.4%, respectively (P = .39). The volumetric increases of segment 4 and the caudate lobe were similar. CONCLUSION Portal vein ligation is as effective as PVE in inducing hypertrophy of the remnant liver volume.

Resection of the Inferior Vena Cava for Neoplasms With or Without Prosthetic Replacement: A 14-Patient Series

ObjectiveTo review the outcome of resection of the suprarenal or infrarenal inferior vena cava (IVC) and possible indications for prosthetic replacement. Summary Background DataInvolvement of the IVC has long been considered a limiting factor for curative surgery for advanced tumors because the surgical risks are high and the long-term prognosis is poor. Prosthetic replacement of the IVC is controversial. MethodsThe authors retrospectively reviewed a 7-year series of 14 patients who underwent en bloc resection including a circumferential segment of the IVC. The tumor was malignant in 12 patients and benign in 2. The resected segment of the IVC was located above the kidneys in eight patients and below in six. Resection was performed without extracorporeal circulation in all patients. ResultsIn all but one patient, IVC resection was associated with multivisceral resection, including extended nephrectomy (n = 8), major hepatic resection (n = 3), digestive resection (n = 3), and infrarenal aortic replacement (n = 2). Prosthetic replacement of the IVC was performed in eight patients cases and was more common after resection of a suprarenal (6/8) than an infrarenal segment of the IVC (2/6). One patient died of multiorgan failure. Major complications occurred in 29% of patients. Symptomatic complications of prosthetic replacement occurred in one patient (acute postoperative thrombosis, successfully treated by surgical disobstruction). Graft-related infection was not observed. Marked symptoms of venous obstruction developed in three of the six patients who did not undergo venous replacement. In patients undergoing surgery for malignant disease, the estimated median survival was 37 months and the actuarial survival rate was 67% at 1 year. ConclusionMultivisceral resection including a segment of IVC is justified to achieve complete extirpation in selected patients with extensive abdominal tumors. Prosthetic replacement of the IVC may be required, particularly in cases of suprarenal resection. It is a safe procedure with a low complication rate and good functional results.

Pancreatic fistula after a pancreaticoduodenectomy for ductal adenocarcinoma and its association with morbidity: a multicentre study of the French Surgical Association

BACKGROUNDS A pancreatic fistula (PF) is the most relevant complication after a pancreaticoduodenectomy (PD). This retrospective multicentric study attempts to elucidate the risk factors and complications of a PF in a large cohort of patients undergoing a PD for ductal adenocarcinoma. METHODS Using a survey tool, clinical data of 1325 patients undergoing a PD for ductal adenocarcinoma at 37 institutions, between January 2004 and December 2009, were collected. Peri-operative risk factors associated with PF and its association with morbidity and mortality were assessed. Morbidity and PF were graded according to the ISGPF (International Study group for pancreatic fistula) definition and the Dindo-Clavien classification. RESULTS Overall PF, mortality, morbidity and relaparotomy rates were 14.3%, 3.8%, 54.4% and 11.7%, respectively. PF occurred more frequently after a pancreaticojejunostomy (PJ) compared with a pancreaticogastrostomy (PG) (16.8% vs. 10.4%; P = 0.0012). Independent risk factors for PF by multivariate analysis were absence of pre-operative diabetes (P = 0.0014), PJ reconstruction (P = 0.0035), soft pancreatic parenchyma (P < 0.0001) and low-volume centre (P = 0.0286). Clinically relevant PF (grade B and C) and severe complications (Dindo-Clavien grade IIIB, IV, V) were significantly more frequent after PJ than PG (71.6% vs. 28.3%; P = 0.030 and 24.8% vs. 19.1%; P = 0.015, respectively). Overall mortality and relaparotomy rates were similar after PG and PJ. CONCLUSIONS A soft pancreatic parenchyma, the absence of pre-operative diabetes, PJ and low-volume centre are independent risk factors for PF after PD for ductal adenocarcinoma. A significantly higher incidence and clinical severity of PF are associated with PJ.

Side-branch intraductal papillary mucinous neoplasms of the pancreatic head/uncinate: resection or enucleation?

INTRODUCTION Side-branch intraductal papillary mucinous neoplasms (IPMN) of the pancreatic head/uncinate are an increasingly common indication for pancreaticoduodenectomy (PD). However, enucleation (EN) may be an alternative to PD in selected patients to improve outcomes and preserve pancreatic parenchyma. AIM To determine peri-operative outcomes in patients with side-branch IPMN of the pancreatic head/uncinate undergoing EN or PD compared with a cohort of patients with pancreatic adenocarcinoma (PA) undergoing PD. METHODS Retrospective review of a prospectively collected, combined, academic institutional series from 2005 to 2008. Of 107 pancreatic head/uncinate IPMN, enucleation was performed in 7 (IPMN EN) and PD was performed in 100 (IPMN PD) with 17 of these radiographically amenable to EN (IPMN PD(en) ). During the same time period, 281 patients underwent PD for PA (Control PD). RESULTS Operative time was shorter (p<0.05) and blood loss (p<0.05) was less in the IPMN EN group compared with all other groups. Peri-operative mortality and morbidity of all IPMN groups (IPMN EN, IPMN PD(en) ) were similar to the Control PD group. Overall pancreatic fistulae rate in the IPMN EN group was higher than in the IPMN PD(en) and Control PD groups; however, the rate of grade C pancreatic fistulae was the same in all groups. CONCLUSIONS Pancreaticoduodenectomy for side-branch IPMNs can be performed safely. Compared with PD, enucleation for IPMN has less blood loss, shorter operative time and similar morbidity, mortality, hospital length of stay (LOS) and readmission rate. Enucleation should be considered more frequently as an option for patients with unifocal side-branch IPMN.

Pancreatic endocrine tumors: a large single-center experience.

Objectives: Pancreatic endocrine tumors (PETs) are infrequent, which makes large experiences unlikely. Our aim was to describe a large single-center experience with PETs and the use of endoscopic ultrasound (EUS) and a cancer staging system (TNM). Methods: This study involves a retrospective analysis of 86 patients (44 men; age, 58 ± 14 years) who underwent EUS-fine needle aspiration (EUS-FNA). Immunohistochemistry was used. Lesions were classified as recommended by TNM classification. Results: Typical EUS features were well-demarcated, hypoechoic, solid, homogeneous lesions. Ninety percent had the diagnosis obtained by EUS-FNA. Twelve PETs (14%) were functioning, 8 (9.3%) were cystic, and 14 (16%) were 10 mm or smaller. Nonfunctional PETs and larger lesions were more advanced. The TNM stage was I in 24, II in 10, III in 18, and IV in 34 patients. Sixteen patients (27%) died, and 30 patients (52%) had progression/recurrence during the follow-up (34 ± 27 months). TNM stage and surgery with curative intent were related to progression. The overall 5-year survival was 60%. The mean survival time was 94 ± 12 months for stage I, 52 ± 12 months for stage III, and 54 ± 7 months for stage IV (P = 0.06). Conclusions: Nonfunctional PETs were more common and advanced. The EUS-FNA has a high accuracy for diagnosing PETs. Progression and poorer survival were associated with TNM stage.

Sonic Hedgehog and Gli1 Expression Predict Outcome in Resected Pancreatic Adenocarcinoma

Purpose: Aberrant activation of the hedgehog (Hh) pathway is implicated in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis. We investigated the prognostic and predictive value of four Hh signaling proteins and of the tumor stromal density. Experimental Design: Using tissue microarray and immunohistochemistry, the expression of Shh, Gli1, SMO, and PTCH1 was assessed in 567 patients from three independent cohorts who underwent surgical resection for PDAC. In 82 patients, the tumor stromal index (SI) was calculated, and its association with overall survival (OS) and disease-free survival (DFS) was investigated. Results: Shh and Gli1 protein abundance were independent prognostic factors in resected PDACs; low expressors for those proteins experiencing a better OS and DFS. The combination of Shh and Gli1 levels was the most significant predictor for OS and defined 3 clinically relevant subgroups of patients with different prognosis (Gli1 and Shh low; HR set at 1 vs. 3.08 for Shh or Gli1 high vs. 5.69 for Shh and Gli1 high; P < 0.001). The two validating cohorts recapitulated the findings of the training cohort. After further stratification by lymph node status, the prognostic significance of combined Shh and Gli1 was maintained. The tumor SI was correlated with Shh levels and was significantly associated with OS (P = 0.023). Conclusions: Shh and Gli1 are prognostic biomarkers for patients with resected PDAC. Clin Cancer Res; 21(5); 1215–24. ©2014 AACR.

Use of bioresorbable membranes to reduce abdominal and perihepatic adhesions in 2-stage hepatectomy of liver metastases from colorectal cancer: results of a prospective, randomized controlled phase II trial.

Objective:To assess by prospective randomized controlled trial the feasibility and efficacy of using a bioresorbable hyaluronic acid/carboxymethylcellulose membrane (HA membrane) to prevent abdominal and perihepatic adhesions in metastatic colorectal cancer patients requiring 2-stage hepatectomy. Background:Two-stage hepatectomy offers the possibility of long-term survival to selected patients whose liver metastases cannot be removed in a single procedure. However, the second operation is made more difficult by adhesions arising from the first. HA membrane reduces adhesions in gynecologic and abdominal surgery but this is the first trial in hepatectomy. Methods:Fifty-four candidates for 2-stage hepatectomy were randomized at the end of the first procedure to implantation of HA membrane (n = 41) or standard management (n = 13). Thirty patients from the membrane arm and 11 well-matched controls underwent the planned second hepatectomy. Results:Positioning of the HA membranes was feasible in all but one patient and did not increase complications associated with the first hepatectomy. At second hepatectomy, patients in the HA membrane arm required 33% less time than controls to achieve complete liver mobilization (median: 50 vs 75 minutes; primary endpoint). The risk of extensive adhesions was reduced in the HA membrane group (31% had grade 3–4 adhesions vs 55% in controls), as was adhesion severity (17% thick and hypervascular adhesions vs 46%). The proportion of patients with complications at second hepatectomy was higher in the control group (55% vs 23% in the HA membrane group, P = 0.07). Conclusion:Use of 4 HA membranes at the end of first hepatectomy reduced the extent and severity of adhesions and facilitated the second hepatectomy in patients with liver metastases who required a 2-stage hepatectomy. A larger study to confirm these findings is warranted. (NCT01262417)

Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials) ☆

BACKGROUND Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. METHODS Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). RESULTS For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. CONCLUSION The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.

Colorectal function preservation in posterior and total supralevator exenteration for gynecologic malignancies: an 89-patient series

OBJECTIVE The objective of this study was to analyze our experience with colorectal function preservation at the time of pelvic exenteration. METHODS Between January 1980 and December 2001, 201 pelvic exenterations for gynecologic malignancies were performed in our hospital. Ninety-eight were supralevator exenterations and 89 were selected for this study because low colorectal anastomosis (LCRA) was performed. There were locally advanced or recurrent cancers including 50 cervical, 28 ovarian, 11 endometrial, and 3 vaginal malignancies and 5 pelvic sarcomas. RESULTS Thirty-nine patients (44%) had a history of previous irradiation. There were were 50 posterior and 39 total exenterations. A diverting stomy and/or pelvic filling were performed respectively in 44 (49.4%) and 26 (29%) cases. The postoperative mortality rate was 4.5% (4/89). Seventeen patients experienced a colorectal anastomotic fistula (AF). AF occurred significantly more frequently in irradiated patients (14/17 = 82%). The mortality rate related to AF was 6% (1/17). Ultimately the functional colorectal anastomosis rate was 71.9%, respectively 61.5 and 80% in irradiated and nonirradiated patients. CONCLUSIONS Colorectal function preservation in supralevator exenteration for gynecologic malignancies can be achieved safely in a majority of patients. In irradiated patients a systematically diverting stomy may result in a low mortality rate.

Bevacizumab-Related Surgical Site Complication Despite Primary Tumor Resection in Colorectal Cancer Patients

BackgroundCombining conventional systemic chemotherapy with the angiogenesis inhibitor bevacizumab is now recommended as a first treatment for metastatic colorectal neoplasms. The risk for short-term postoperative complications related to bevacizumab has been assessed. Late postoperative complications related to bevacizumab have also been suggested by preliminary reports.MethodsWe reviewed a cohort of 142 patients with previous surgery for primary colonic or rectal tumor and without evidence of local recurrence, receiving bevacizumab for metastatic disease.ResultsFour patients experienced a late surgical site complication related to bevacizumab. Common features were rectal location, low anastomosis, and preoperative irradiation. Combining these three factors, the risk of a bevacizumab-related complication was 4 in 27 (14.8%); if previous history of postoperative leakage was reported, the risk was raised to 2 in 4. No complications occurred in colonic location or the non-irradiated patients. The mechanism of these complications could be ischemic lesion in post-irradiated tissues involving anastomoses.ConclusionWe conclude that angiogenesis inhibitors should be carefully considered for patients having low colorectal anastomosis and previous irradiation.