Showing papers by "Philippe Bachellier published in 2019"

Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis

Abstract: Background: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. Methods: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III–IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. Results: We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n ¼ 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] ¼ 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI ¼ 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patientlevel survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI ¼ 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI ¼ 14.5 to 21.5 months). Pooled event rates for grade III–IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI ¼ 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI ¼ 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI ¼ 8.1 to 14.2). No deaths were attributed to FOLFIRINOX. Conclusions: This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.

Early 18 F-FDOPA PET/CT imaging after carbidopa premedication as a valuable diagnostic option in patients with insulinoma

Abstract: Data on the diagnostic value of 18F-FDOPA PET/CT in patients with insulinoma are limited and are focused on small patient populations explored using different PET/CT protocols and the inconsistent use of carbidopa premedication. The aim of this study was to improve the current knowledge about the diagnostic value of 18F-FDOPA PET/CT combined with oral carbidopa premedication and early pancreatic imaging for tumour localization in patients with insulinoma-related hyperinsulinaemic hypoglycaemia (HH). The relationships among 18F-FDOPA quantitative uptake parameters, insulin secretion and tumour pathological features were also investigated. Of 34 patients with suspicion of insulinoma-related HH examined by dual time-point carbidopa-assisted 18F-FDOPA PET/CT, 24 with histologically proven insulinoma were retrospectively included. One patient underwent two PET/CT examinations for relapsing insulinoma after surgical excision. Thus, 25 preoperative 18F-FDOPA PET/CT studies were finally retained and analysed. All studies were performed under carbidopa premedication (200 mg orally, 1–2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after 18F-FDOPA injection) over the upper abdomen and a delayed whole-body acquisition starting 20–30 min later. The cytological and/or histopathological diagnosis of insulinoma was the diagnostic standard of truth. 18F-FDOPA PET/CT localized insulinoma in 21 of the 25 studies, leading to a primary lesion detection rate of 84%. Four lesions (19%) were detected only on early acquisitions. The false-negative tumour detection rates were, respectively, 22% and 12.5% in patients receiving and not receiving treatment for hypoglycaemic symptoms at the time of PET/CT. In benign insulinomas, the early maximum standardized uptake value (SUVmax) was significantly higher than the delayed SUVmax. Compared to the 21 benign lesions, four malignant insulinomas showed significantly higher 18F-FDOPA uptake. Lesion size, fasting-end insulin and C-peptide levels correlated with tumour 18F-FDOPA uptake, dopaminergic tumour volume and metabolic burden. The present study showed that 18F-FDOPA PET/CT combined with carbidopa premedication and early pancreatic acquisitions is a valuable diagnostic option in patients with insulinoma when GLP1R-based imaging is not available. The results also provide new insights into the relationships between tumour secretion and imaging phenotype in insulinomas.

Improved Survival in Liver Transplant Patients Receiving Prolonged-release Tacrolimus-based Immunosuppression in the European Liver Transplant Registry (ELTR): An Extension Study.

Abstract: Background.We compared, through the European Liver Transplant Registry, long-term liver transplantation outcomes with prolonged-release tacrolimus (PR-T) versus immediate-release tacrolimus (IR-T)–based immunosuppression. This retrospective analysis comprises up to 8-year data collected between 2008

Macrovascular venous invasion of pancreatic neuroendocrine tumours: impact on surgical outcomes and survival.

Abstract: Background This study evaluates the impact of macrovascular venous invasion (MVI) on surgical and survival outcomes of pancreatic neuroendocrine tumours (PNETs). Methods We retrospectively reviewed data of 125 patients operated for PNETs. Operative, pathological,and survival outcomes were compared between PNETs with and without MVI. Results Macrovascular venous invasion was detected in 25 of 125 PNETs (20%) presenting as tumour thrombi (n = 12) or venous wall invasion (n = 13). MVI was associated with larger tumours, a higher rate of lymph node involvement, less differentiated tumours, and a higher rate of perineural invasion. Resection of PNETS with MVI more often necessitated combined hepatic, venous and multivisceral resections, had a higher rate of intraoperative blood transfusion (p = 0.04) but similar morbidity (44% vs. 42%) and mortality (0 vs. 1%) as PNETs without MVI. PNETs with MVI had a lower median overall survival rate (60 vs. 149 months; p = 0.03). Multivariate analysis revealed that PNETs of the pancreatic head, synchronous liver metastases and higher tumour grade were prognostic factors for overall survival. Conclusions MVI is found in more advanced PNETs. Resection of PNETs with MVI is characterized by increased transfusion rate and reduced overall survival.

Temporary Right Portocaval Shunt During Piggyback Liver Transplantation.

Abstract: During piggyback liver transplantation (LT), a temporary end-to-side portocaval anastomosis (PCA) facilitates native total hepatectomy while maintaining hemodynamic stability. Some argue that PCA, performed on the main portal trunk (PT), might shorten the main portal vein and could cause technical difficulties during LT. We describe a temporary PCA performed on the right portal vein (R-PCA). The technique entails complete dissection of the main portal trunk up its right and left branches. After having ligated the left portal vein, the right is anastomosed end-to-side to the anterior face of the inferior vena cava. Taken down of R-PCA, before graft-recipient portal vein anastomosis, is achieved by stapling or suturing. An R-PCA has been performed in 14 over 15 planned procedures at our unit. In one case, because of intraoperative difficulties the PCA was performed on the PT. A temporary R-PCA represents a feasible alternative method of portal decompression during LT. Its use can be implemented into the technical armamentarium of transplant surgeons.

Metabolomics of Small Intestine Neuroendocrine Tumors and Related Hepatic Metastases.

Abstract: To assess the metabolomic fingerprint of small intestine neuroendocrine tumors (SI-NETs) and related hepatic metastases, and to investigate the influence of the hepatic environment on SI-NETs metabolome. Ninety-four tissue samples, including 46 SI-NETs, 18 hepatic NET metastases and 30 normal SI and liver samples, were analyzed using 1H-magic angle spinning (HRMAS) NMR nuclear magnetic resonance (NMR) spectroscopy. Twenty-seven metabolites were identified and quantified. Differences between primary NETs vs. normal SI and primary NETs vs. hepatic metastases, were assessed. Network analysis was performed according to several clinical and pathological features. Succinate, glutathion, taurine, myoinositol and glycerophosphocholine characterized NETs. Normal SI specimens showed higher levels of alanine, creatine, ethanolamine and aspartate. PLS-DA revealed a continuum-like distribution among normal SI, G1-SI-NETs and G2-SI-NETs. The G2-SI-NET distribution was closer and clearly separated from normal SI tissue. Lower concentration of glucose, serine and glycine, and increased levels of choline-containing compounds, taurine, lactate and alanine, were found in SI-NETs with more aggressive tumors. Higher abundance of acetate, succinate, choline, phosphocholine, taurine, lactate and aspartate discriminated liver metastases from normal hepatic parenchyma. Higher levels of alanine, ethanolamine, glycerophosphocholine and glucose was found in hepatic metastases than in primary SI-NETs. The present work gives for the first time a snapshot of the metabolomic characteristics of SI-NETs, suggesting the existence of complex metabolic reality, maybe characteristic of different tumor evolution.

Metabolomic profiling highlights the metabolic bases of acute-on-chronic and post-hepatectomy liver failure.

Abstract: Background Posthepatectomy liver failure (PHLF) is the main limitation to extending liver resection but its pathophysiology is not yet fully understood. The aim of the study was to describe the metabolic adaptations that occur with PHLF. Methods A retrospective study of 82 patients using nuclear magnetic resonance metabolomics to identify and quantify intra-hepatic metabolites was performed. The metabolite levels were compared using metabolic network analysis ADEMA between fatal PHLF (FLF) and non fatal PHLF and according to PHLF/ACLF grading. Results Metabolomic profiles were significantly different between patients presenting FLF and non FLF or grade 3 ACLF versus Conclusion Clinical andbiological severity of ACLF and PHLF correlate with specific metabolic adaptations. Metabolomics can predict fatal liver failure after hepatectomy and underline significant differences in the metabolic patterns of ACLF and PHLF.

Limited role of carbidopa-assisted 18F-FDOPA PET/CT in patients with sporadic non-functional gastroduodenal neuroendocrine neoplasms

Abstract: To evaluate 18F-fluorodihydroxyphenylalanine (18F-FDOPA) positron emission tomography/computed tomography (PET/CT) after carbidopa premedication to localize sporadic, well-differentiated, nonfunctioning gastroduodenal neuroendocrine neoplasms (NENs). Ten patients undergoing staging carbidopa-assisted 18F-FDOPA PET/CT before endoscopic or surgical resection of gastroduodenal NENs were retrospectively selected. Preoperative imaging work up also included CT, magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy (SRS) single-photon emission computed tomography/computed tomography (SPECT/CT) in ten, six, and eight patients, respectively. Histopathological diagnosis of primary NEN was the diagnostic standard of truth. Metastatic spread was defined as the presence of histologically proven nodal, visceral, and/or bone metastases. Tumors were located in the duodenal bulb in five patients, in descending duodenum in three, and in the gastric fundus in two. Three patients presented with both lymph nodes and distant metastases, and two with exclusive lymphatic spread. CT and MRI detected primary tumor in one out of ten and three out of six patients, respectively. SRS failed to detect intestinal NEN in all cases. 18F-FDOPA PET/CT detected four primary NENs (one gastric and three duodenal tumors) and was false negative in six patients. NENs missed by 18F-FDOPA PET/CT were smaller than 10 mm in two cases and measured about 30 mm in three patients. The remaining tumor was detected only on blind endoscopic biopsy. Among patients who underwent both 18F-FDOPA PET/CT and SRS, three presented discordant results for primary tumor detection (PET/CT positive/SRS negative) and five showed concordant negative studies. 18F-FDOPA PET/CT correctly identified all three patients with both nodal and visceral metastatic disease and failed to detect lymph node metastases in both N+ M0 patients. 18F-FDOPA PET/CT is not sufficiently accurate for localization of primary well-differentiated nonfunctioning sporadic gastroduodenal NENs. 18F-FDOPA PET/CT’s value for the assessment of visceral and lymph node metastases needs to be clarified in multicenter trials including a larger number of patients.

Dépenses en dispositifs médicaux stériles dans certains actes de chirurgie hépatobiliaire et digestive : que resterait-il du Groupe Homogène de Séjour ?

Abstract: Resume Objectif Les dernieres innovations en termes de dispositifs medicaux et les procedures associees impactent le budget des etablissements de sante. L’objectif de ce travail a ete d’evaluer le cout des dispositifs medicaux utilises lors de differentes interventions chirurgicales au regard des recettes percues issues de la cotation du sejour patient. Methode Une analyse prospective des dispositifs medicaux utilises au bloc operatoire a ete realisee pour differents types d’interventions chirurgicales programmees. Pendant cinq semaines, les references des dispositifs medicaux steriles a usage unique utilises au cours des interventions ont ete colligees. Resultats Les depenses en dispositifs medicaux utilises pendant l’acte de chirurgie representaient 5,7 % de la valorisation du sejour pour une cure de hernie inguinale, 12 % pour une cholecystectomie, 9,35 % pour une colectomie, 14,5 % pour une hepatectomie et 7 % pour une pancreatectomie, tout indice de severite confondu. Les correlations les plus importantes existaient entre la duree de l’acte et le niveau de severite du patient et entre la duree du temps operatoire et les depenses en consommables. Conclusion Les pistes d’optimisation des couts s’orientent vers les equivalences de certaines gammes de dispositifs medicaux, les achats regroupes via des groupements nationaux et vers de potentielles diminutions de temps operatoires liees a l’utilisation de nouveaux dispositifs medicaux de technologie innovante.