Publications by authors named "Emmanuel Buc"

48 Publications

Study Protocol of the PreFiPS Study: Prevention of Postoperative Pancreatic Fistula by Somatostatin Compared With Octreotide, a Prospective Randomized Controlled Trial.

Front Med (Lausanne) 2020 15;7:488. Epub 2021 Jan 15.

Department of Digestive, Hepatobiliary and Endocrine Surgery, Paris Descartes University, Cochin Hospital, Paris, France.

Pancreatic fistula (PF), i. e., a failure of the pancreatic anastomosis or closure of the remnant pancreas after distal pancreatectomy, is one of the most feared complications after pancreatic surgery. PF is also one of the most common complications after pancreatic surgery, occurring in about 30% of patients. Prevention of a PF is still a major challenge for surgeons, and various technical and pharmacological interventions have been investigated, with conflicting results. Pancreatic exocrine secretion has been proposed as one of the mechanisms by which PF occurs. Pharmacological prevention using somatostatin or its analogs to inhibit pancreatic exocrine secretion has shown promising results. We can hypothesize that continuous intravenous infusion of somatostatin-14, the natural peptide hormone, associated with 10-50 times stronger affinity with all somatostatin receptor compared with somatostatin analogs, will be associated with an improved PF prevention. A French comparative randomized open multicentric study comparing somatostatin vs. octreotide in adult patients undergoing pancreaticoduodenectomy (PD) or distal pancreatectomy with or without splenectomy. Patients with neoadjuvant radiation therapy and/or neoadjuvant chemotherapy within 4 weeks before surgery are excluded from the study. The main objective of this study is to compare 90-day grade B or C postoperative PF as defined by the last ISGPF (International Study Group on Pancreatic Fistula) classification between patients who receive perioperative somatostatin and octreotide. In addition, we analyze overall length of stay, readmission rate, cost-effectiveness, and postoperative quality of life after pancreatic surgery in patients undergoing PD. The PreFiPS study aims to evaluate somatostatin vs. octreotide for the prevention of postoperative PF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2020.00488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844059PMC
January 2021

A case series study of augmented reality in laparoscopic liver resection with a deformable preoperative model.

Surg Endosc 2020 12 20;34(12):5642-5648. Epub 2020 Jul 20.

UMR6602, Endoscopy and Computer Vision Group, Faculté de Médecine, Institut Pascal, Bâtiment 3C, 28 place Henri Dunant, 63000, Clermont-Ferrand, France.

Background: Previous work in augmented reality (AR) guidance in monocular laparoscopic hepatectomy requires the surgeon to manually overlay a rigid preoperative model onto a laparoscopy image. This may be fairly inaccurate because of significant liver deformation. We have proposed a technique which overlays a deformable preoperative model semi-automatically onto a laparoscopic image using a new software called Hepataug. The aim of this study is to show the feasibility of Hepataug to perform AR with a deformable model in laparoscopic hepatectomy.

Methods: We ran Hepataug during the procedures, as well as the usual means of laparoscopic ultrasonography (LUS) and visual inspection of the preoperative CT or MRI. The primary objective was to assess the feasibility of Hepataug, in terms of minimal disruption of the surgical workflow. The secondary objective was to assess the potential benefit of Hepataug, by subjective comparison with LUS.

Results: From July 2017 to March 2019, 17 consecutive patients were included in this study. AR was feasible in all procedures, with good correlation with LUS. However, for 2 patients, LUS did not reveal the location of the tumors. Hepataug gave a prediction of the tumor locations, which was confirmed and refined by careful inspection of the preoperative CT or MRI.

Conclusion: Hepataug showed a minimal disruption of the surgical workflow and can thus be feasibly used in real hepatectomy procedures. Thanks to its new mechanism of semi-automatic deformable alignment, Hepataug also showed a good agreement with LUS and visual CT or MRI inspection in subsurface tumor localization. Importantly, Hepataug yields reproducible results. It is easy to use and could be deployed in any existing operating room. Nevertheless, comparative prospective studies are needed to study its efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-020-07815-xDOI Listing
December 2020

Pancreaticoduodenectomy following endoscopic ultrasound-guided choledochoduodenostomy with electrocautery-enhanced lumen-apposing stents an ACHBT - SFED study.

HPB (Oxford) 2021 Jan 6;23(1):154-160. Epub 2020 Jul 6.

Service de Gastroentérologie, Hopital Privé Jean Mermoz, Ramsay Générale de Santé, Lyon, France.

Background: After ERCP failure or if ERCP is declined for preoperative biliary drainage before pancreaticoduodenectomy, endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) with electrocautery-enhanced lumen-apposing stents (ECE-LAMS) might be needed. The aim of the present study was to assess the technical feasibility and short-term outcomes of pancreaticoduodenectomy (PD) following endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) with electrocautery-enhanced lumen-apposing stents (ECE-LAMS).

Methods: A retrospective study of all EUS-CDS procedures with ECE-LAMS followed by PD performed in France since the availability of the device in 2016.

Results: 21 patients underwent PD in 9 departments of surgery following EUS-CDS with ECE-LAMS. The median bilirubin level at endoscopic procedure was 292 μmol/L. A 6 mm diameter stent was used in 20 cases. No complications occurred during the procedure. During the waiting time, 1 patient had an acute pancreatitis post ERCP and 3 patients developed cholangitis, treated by either an additional percutaneous biliary drainage, or an endoscopic procedure to extract a bezoar occluding the stent, or antibiotics, respectively. PD with a curative intent was performed in all cases. Overall, postoperative mortality was nil and postoperative morbidity occurred in 17 patients (81%), including 3 with severe complications (14%). No patient developed postoperative biliary fistula. In the 21 patients followed at least 6 months, no biliary complications occurred, and no tumor recurrence developed on the hepaticojejunostomy/hepatic pedicle.

Conclusion: Pancreaticoduodenectomy following EUS-CDS with ECE-LAMS is technically feasible with acceptable short-term postoperative outcome, including healing of biliary anastomosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hpb.2020.06.001DOI Listing
January 2021

Combining Visual Cues with Interactions for 3D-2D Registration in Liver Laparoscopy.

Ann Biomed Eng 2020 Jun 28;48(6):1712-1727. Epub 2020 Feb 28.

EnCoV, Institut Pascal, UMR 6602 CNRS/Université Clermont-Auvergne, Clermont-Ferrand, France.

Augmented Reality (AR) in monocular liver laparoscopy requires one to register a preoperative 3D liver model to a laparoscopy image. This is a difficult problem because the preoperative shape may significantly differ from the unknown intraoperative shape and the liver is only partially visible in the laparoscopy image. Previous approaches are either manual, using a rigid model, or automatic, using visual cues and a biomechanical model. We propose a new approach called the hybrid approach combining the best of both worlds. The visual cues allow us to capture the machine perception while user interaction allows us to take advantage of the surgeon's prior knowledge and spatial understanding of the patient anatomy. The registration accuracy and repeatability were evaluated on phantom, animal ex vivo and patient data respectively. The proposed registration outperforms the state of the art methods both in terms of accuracy and repeatability. An average registration error below the 1 cm oncologic margin advised in the literature for tumour resection in laparoscopy hepatectomy was obtained.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10439-020-02479-zDOI Listing
June 2020

Combined biembolization induces higher hypertrophy than portal vein embolization before major liver resection.

HPB (Oxford) 2020 02 31;22(2):298-305. Epub 2019 Aug 31.

Department of Vascular Radiology, Hôpital Gabriel Montpied, CHU Clermont-Ferrand, Place Henri Dunant, 63000 Clermont-Ferrand, France; UMR Auvergne CNRS 6284, Clermont-Ferrand Faculty of Medicine, 28 Place Henri Dunant, 63000 Clermont-Ferrand, France.

Background: Combined preoperative portal and hepatic vein embolization (biembolization, BE) has been recently described and may further enhance preoperative FLR growth. The objective of this study was to compare the efficacy of combined preoperative biembolization and portal vein embolization (PVE).

Methods: This study was performed between 2010 and 2017. From 2010 to 2014, patients only underwent preoperative PVE. After 2014, BE was proposed as an alternative to PVE. Liver volumetry was assessed by a CT-scan before BE or PVE and then three weeks later.

Results: During the study period, 72 patients underwent radiological procedures that included 41 PVE (PVE group) and 31 BE (BE group). The time elapsing between the procedure and surgery was similar (p = 0.760). The mean percentage of FLR ratio hypertrophy in the PVE group was 31.9% (±34), but reached 51.2% (±42) in the BE group (p = 0.018) and this difference remained significant under multivariate analysis that included age, gender, body mass index, diabetes mellitus, cirrhosis and NASH. The kinetic growth rates were 19% (±17%) and 8% (±13%) in the BE and PVE groups, respectively (p = 0.026).

Conclusion: This study shows that BE induces higher hypertrophy than portal vein embolization before major liver resection with no more morbidity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hpb.2019.08.005DOI Listing
February 2020

Pancreaticoduodenectomy with right gastric vessels preservation: impact on intraoperative and postoperative outcomes.

ANZ J Surg 2019 04 29;89(4):E147-E152. Epub 2018 Nov 29.

Department of Surgery, Léon Bérard Cancer Center, Lyon, France.

Background: Sympathetic denervation of the antropyloric area combined with relative devascularization from division of the right gastric vessels (RGV) during pancreaticoduodenectomy (PD) could predispose to delayed gastric emptying (DGE). Therefore, some authors advocated for RGV preservation (RGVP), where feasibility and utility for the prevention of post-operative DGE have never been investigated.

Methods: From 2011 to 2014, patients who underwent classic Whipple PD (CWPD, n = 34), standard pylorus-preserving PD (PPPD, n = 44) or PPPD with RGVP (n = 22) were retrospectively analysed.

Results: RGVP was not possible in 12% of the cases because of an intraoperative injury of the RGV. There was no difference between CWPD, standard PPPD and PPPD with RGVP in terms of intraoperative blood loss, operative time, number of lymph node harvested and resection margins. Post-operative morbidity and mortality were comparable between the three groups, including rate (27%, 34% and 32%, P = 0.77) and severity of DGE, delay in removing nasogastric tube and use of prokinetics. Hospital stay was similar in all the compared groups.

Conclusion: This is the first study comparing post-operative outcomes after PPPD with RGVP, standard PPPD and CWPD. Although feasible and safe, RGVP during PPPD appeared to offer no obvious clinical benefit in terms of preventing post-operative complications, especially DGE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ans.14956DOI Listing
April 2019

Preoperative liver registration for augmented monocular laparoscopy using backward-forward biomechanical simulation.

Int J Comput Assist Radiol Surg 2018 Oct 9;13(10):1629-1640. Epub 2018 Aug 9.

EnCoV, IP, UMR 6602 CNRS, Universitè Clermont Auvergne, SIGMA, Aubière, France.

Purpose: Augmented reality for monocular laparoscopy from a preoperative volume such as CT is achieved in two steps. The first step is to segment the organ in the preoperative volume and reconstruct its 3D model. The second step is to register the preoperative 3D model to an initial intraoperative laparoscopy image. To date, there does not exist an automatic initial registration method to solve the second step for the liver in the de facto operating room conditions of monocular laparoscopy. Existing methods attempt to solve for both deformation and pose simultaneously, leading to nonconvex problems with no optimal solution algorithms.

Methods: We propose in contrast to break the problem down into two parts, solving for (i) deformation and (ii) pose. Part (i) simulates biomechanical deformations from the preoperative to the intraoperative state to predict the liver's unknown intraoperative shape by modeling gravity, the abdominopelvic cavity's pressure and boundary conditions. Part (ii) rigidly registers the simulated shape to the laparoscopy image using contour cues.

Results: Our formulation leads to a well-posed problem, contrary to existing methods. This is because it exploits strong environment priors to complement the weak laparoscopic visual cues.

Conclusion: Quantitative results with in silico and phantom experiments and qualitative results with laparosurgery images for two patients show that our method outperforms the state-of-the-art in accuracy and registration time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11548-018-1842-3DOI Listing
October 2018

Specificities of Human Hepatocellular Carcinoma Developed on Non-Alcoholic Fatty Liver Disease in Absence of Cirrhosis Revealed by Tissue Extracts ¹H-NMR Spectroscopy.

Metabolites 2017 Sep 22;7(4). Epub 2017 Sep 22.

INRA, Human Nutrition Unit, CRNH Auvergne, Clermont Auvergne University, F-63000 Clermont-Ferrand, France.

There is a rising incidence of non-alcoholic fatty liver disease (NAFLD) as well as of the frequency of Hepato-Cellular Carcinoma (HCC) associated with NAFLD To seek for putative metabolic pathways specific of the NAFLD etiology, we performed comparative metabolomics between HCC associated with NAFLD and HCC associated with cirrhosis. The study included 28 pairs of HCC tissue versus distant Non-Tumoral Tissue (NTT) collected from patients undergoing hepatectomy. HCC was associated with cirrhosis ( = 9), normal liver ( = 6) and NAFLD ( = 13). Metabolomics was performed using 1H-NMR Spectroscopy on tissue extracts and combined to multivariate statistical analysis. In HCC compared to NTT, statistical models showed high levels of lactate and phosphocholine, and low level of glucose. Shared and Unique Structures (SUS) plots were performed to remove the impact of underlying disease on the metabolic profile of HCC. HCC-cirrhosis was characterized by high levels of β-hydroxybutyrate, tyrosine, phenylalanine and histidine whereas HCC-NAFLD was characterized by high levels of glutamine/glutamate. In addition, the overexpression glutamine/glutamate on HCC-NAFLD was confirmed by both Glutamine Synthetase (GS) immuno-staining and NMR-spectroscopy glutamine quantification. This study provides evidence of metabolic specificities of HCC associated with non-cirrhotic NAFLD versus HCC associated with cirrhosis. These alterations could suggest activation of glutamine synthetase pathway in HCC-NAFLD and mitochondrial dysfunction in HCC-cirrhosis, that may be part of specific carcinogenic processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/metabo7040049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746729PMC
September 2017

A Normal Preoperative Lipase Serum Level Is an Easy and Objective Risk Factor of Pancreatic Fistula After Pancreaticoduodenectomy.

Pancreas 2017 10;46(9):1133-1140

From the *Department of Digestive and Hepatobiliary Surgery, Estaing University Hospital; †UMR 1071 INSERM/Université Clermont-Auvergne; ‡Department of Radiology, Gabriel Montpied University Hospital; §Biostatistics, Délégation à la Recherche Clinique et à l'Innovation, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France; and ∥Department of Surgical Oncology, Léon Bérard Cancer Center, Lyon, France.

Objectives: The evaluation of the risk of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy is crucial to optimize perioperative strategies. Many risk factors of POPF have been identified and were included in scores. Performances of these scores have to be improved because of the use of subjective and/or intraoperative factors. We tried to identify new risk factors of POPF that could improve the performance of validated scores.

Methods: We analyzed data from a prospective database of 191 consecutive patients who underwent a pancreaticoduodenectomy. Recorded data included a comprehensive inventory of pre-, intra- and postoperative clinical, biological and radiological data.

Results: The rate of POPF was significantly increased in patients with a normal preoperative lipase serum level (LSL) (29.8% vs 6.8%; P = 0.001). After multivariate analysis, a normal preoperative LSL was a strong independent risk factor of both POPF (odds ratio, 7.06; P = 0.001) and clinically relevant POPF (odds ratio, 3.11; P = 0.036). The addition of the normality of the preoperative LSL to the Fistula Risk Score significantly improved its performance (P < 0.001).

Conclusions: A normal preoperative LSL was a strong, easy, and objective preoperative risk factor of POPF. Its addition to the Fistula Risk Score improved its performance and allows a more accurate evaluation of the risk of POPF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000000905DOI Listing
October 2017

Preliminary trial of augmented reality performed on a laparoscopic left hepatectomy.

Surg Endosc 2018 01 8;32(1):514-515. Epub 2017 Aug 8.

UMR Auvergne CNRS 6284, Faculty of Medicine from Clermont-Ferrand, 28 Place Henri Dunant, 63000, Clermont-Ferrand, France.

Background: Laparoscopic liver surgery is seldom performed, mainly because of the risk of hepatic vein bleeding or incomplete resection of the tumour. This risk may be reduced by means of an augmented reality guidance system (ARGS), which have the potential to aid one in finding the position of intrahepatic tumours and hepatic veins and thus in facilitating the oncological resection and in limiting the risk of operative bleeding.

Methods: We report the case of an 81-year-old man who was diagnosed with a hepatocellular carcinoma after an intraabdominal bleeding. The preoperative CT scan did not show metastases. We describe our preferred approach for laparoscopic left hepatectomy with initial control of the left hepatic vein and preliminary results of our novel ARGS achieved postoperatively. In our ARGS, a 3D virtual anatomical model is created from the abdominal CT scan and manually registered to selected laparoscopic images. For this patient, the virtual model was composed of the segmented left liver, right liver, tumour and median hepatic vein.

Results: The patient's operating time was summed up to 205 min where a blood loss of 300 cc was recorded. The postoperative course was simple. Histopathological analysis revealed the presence of a hepatocellular carcinoma with free margins. Our results of intrahepatic visualization suggest that ARGS can be beneficial in detecting the tumour, transection plane and medial hepatic vein prior to parenchymal transection, where it does not work due to the substantial changes to the liver's shape.

Conclusions: As of today, we have performed eight similar left hepatectomies, with good results. Our ARGS has shown promising results and should now be attempted intraoperatively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-017-5733-4DOI Listing
January 2018

Portal blood pressure and hypoxemia: The 2 main mechanisms of liver regeneration?

Surgery 2017 12 20;162(6):1347-1348. Epub 2017 Jun 20.

Department of Digestive and Hepatobiliary Surgery, Estaing hospital, CHU Clermont-Ferrand, 1 Place Lucie et Raymond Aubrac, Clermont-Ferrand, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2017.04.019DOI Listing
December 2017

Does intraoperative closed-suction drainage influence the rate of pancreatic fistula after pancreaticoduodenectomy?

BMC Surg 2017 May 16;17(1):58. Epub 2017 May 16.

Department of Digestive and Hepatobiliary Surgery, Estaing University Hospital, 1, place Lucie et Raymond Aubrac, 63000, Clermont-Ferrand, France.

Background: Although drainage of pancreatic anastomoses after pancreaticoduodenectomy (PD) is still debated, it remains recommended, especially in patients with a high risk of post-operative pancreatic fistula (POPF). Modalities of drainage of pancreatic anastomoses, especially the use of passive (PAD) or closed-suction (CSD) drains, and their impact on surgical outcomes, have been poorly studied. The aim was to compare CSD versus PAD on surgical outcomes after PD.

Methods: Retrospective analysis of 197 consecutive patients who underwent a standardized PD at two tertiary centers between March 2012 and April 2015. Patients with PAD (n = 132) or CSD (n = 65) were compared.

Results: There was no significant difference in terms of 30-day overall and severe post-operative morbidity, post-operative hemorrhage, post-operative intra-abdominal fluid collections, 90-day post-operative mortality and mean length of hospital stay. The rate of POPF was significantly increased in the CSD group (47.7% vs. 32.6%; p = 0.04). CSD was associated with an increase of grade A POPF (21.5% vs. 8.3%; p = 0.03), while clinically relevant POPF were not impacted. In patients with grade A POPF, the rate of undrained intra-abdominal fluid collections was increased in the PAD group (46.1% vs. 21.4%; p = 0.18). After multivariate analysis, CSD was an independent factor associated with an increased rate of POPF (OR = 2.43; p = 0.012).

Conclusions: There was no strongly relevant difference in terms of surgical outcomes between PAD or CSD of pancreatic anastomoses after PD, but CSD may help to decrease the rate of undrained post-operative intra-abdominal collections in some patients. Further randomized, multi-institutional studies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12893-017-0257-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434540PMC
May 2017

An original technique of venous autoplasty after duodenopancreatectomy for tumors involving the infrarenal inferior vena cava.

J Surg Case Rep 2017 Feb 8;2017(2):rjx011. Epub 2017 Feb 8.

1Department of Digestive and Hepatobiliary Surgery, Liver Transplantation, Estaing University Hospital, Clermont-Ferrand 63000, France.

Tumor involvement of the inferior vena cava (IVC) by hepatobiliary, pancreatic or duodenal malignancies can compromise adequate resection. However, radical resection with negative histological margins remains the only chance of cure. Various techniques are used for venous reconstruction, using a prosthetic graft interposition in most of the cases. However, in case of associated digestive resections, such as pancreaticoduodenectomy, postoperative complications can be responsible for prosthesis infection and related vascular complications. In this setting, the use of biological material for venous reconstruction appears to be preferable. We present an original, easy and useful technique of a venous autoplasty after pancreaticoduodenectomy for tumors involving the anterior wall of the infrarenal IVC, using a patch from the posterior wall of the IVC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jscr/rjx011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400417PMC
February 2017

Combined Preoperative Portal and Hepatic Vein Embolization (Biembolization) to Improve Liver Regeneration Before Major Liver Resection: A Preliminary Report.

World J Surg 2017 07;41(7):1848-1856

Department of Digestive and Hepatobiliary Surgery, Estaing Hospital, CHU Clermont-Ferrand, 1 Place Lucie et Raymond Aubrac, 63003, Clermont-Ferrand, France.

Background: Insufficient volume of the future liver remnant (FLR) is a major cause of non-resectable disease in patients presenting with primary or metastatic liver tumours. The objective of this study was to evaluate the safety and efficacy of the combined preoperative portal and hepatic vein embolization (biembolization) before extended right liver resections.

Methods: This retrospective study was performed in a tertiary centre between 2014 and 2015. Combined right portal and hepatic vein embolization (biembolization) was proposed, as an alternative to ALPPS procedure, for all patients with primary or metastatic liver tumour, before right extended hepatectomy. CT scan liver volumetry was assessed before biembolization, three weeks after biembolization and one week after surgery.

Results: Seven patients underwent biembolization. All patients had right portal vein embolization (PVE) combined with right hepatic vein embolization (HVE, n = 4), median HVE (n = 2) and right + median HVE (n = 1). Three patients had preoperative liver disease and two received preoperative chemotherapy. No biembolization procedure-related complications occurred. The mean FLR regeneration rate was 52.6% (range: 18.2-187.9) after the biembolization. One patient with gallbladder carcinoma was not operated because of peritoneal carcinomatosis diagnosed after the biembolization. The remnant six patients did not develop postoperative liver failure.

Conclusions: Biembolization seems to induce safe, reproducible and effective FLR growth before extended right hepatectomy, in patients with primary or metastatic liver tumour.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-017-4016-5DOI Listing
July 2017

Early Enteral Versus Total Parenteral Nutrition in Patients Undergoing Pancreaticoduodenectomy: A Randomized Multicenter Controlled Trial (Nutri-DPC).

Ann Surg 2016 Nov;264(5):731-737

*Department of Hepato-Biliary and Pancreatic Surgery, Edouard Herriot Hospital, HCL, UCBL1, Lyon, France†Department of Digestive and General Surgery, Hôpital C. Huriez CHRU, Lille, France‡Department of Digestive Surgery, Hôpital Cochin - St-Vincent de Paul, Paris, France§Department of Digestive Surgery, CHU Timone, Marseille, France¶Department of Digestive Surgery, CHU Dupuytren, Limoges, France||Department of Digestive Surgery and Liver Transplantation, Hôpital de la Croix Rousse, Lyon, France**Pole Information Médicale Evaluation Recherche, HCL, Lyon, France††Department of Hepato-Biliary and Pancreatic Surgery, APHP, Hôpital Beaujon, Clichy, France‡‡Department of Digestive Surgery, APHP, Hôpital Lariboisières, Paris, France§§Department of Digestive Pathology, Surgery Unit, CHU Clermont Ferrand Hôtel Dieu NHE, Clermont Ferrand, France.

Objectives: The aim of this study was to compare nasojejunal early enteral nutrition (NJEEN) with total parenteral nutrition (TPN), after pancreaticoduodenectomy (PD), in terms of postoperative complications.

Background: Current nutritional guidelines recommend the use of enteral over parenteral nutrition in patients undergoing gastrointestinal surgery. However, the NJEEN remains controversial in patients undergoing PD.

Methods: Multicenter, randomized, controlled trial was conducted between 2011 and 2014. Nine centers in France analyzed 204 patients undergoing PD to NJEEN (n = 103) or TPN (n = 101). Primary outcome was the rate of postoperative complications according to Clavien-Dindo classification. Successful NJEEN was defined as insertion of a nasojejunal feeding tube, delivering at least 50% of nutritional needs on PoD 5, and no TPN for more than consecutive 48 hours.

Results: Postoperative complications occurred in 77.5% [95% confidence interval (95% CI) 68.1-85.1] patients in the NJEEN group versus 64.4% (95% CI 54.2-73.6) in TPN group (P = 0.040). NJEEN was associated with higher frequency of postoperative pancreatic fistula (POPF) (48.1% vs 27.7%, P = 0.012) and higher severity (grade B/C 29.4% vs 13.9%; P = 0.007). There was no significant difference in the incidence of post-pancreatectomy hemorrhage, delayed gastric emptying, infectious complications, the grade of postoperative complications, and the length of postoperative stay. A successful NJEEN was achieved in 63% patients. In TPN group, average energy intake was significantly higher (P < 0.001) and patients had an earlier recovery of oral feeding (P = 0.0009).

Conclusions: In patients undergoing PD, NJEEN was associated with an increased overall postoperative complications rate. The frequency and the severity of POPF were also significantly increased after NJEEN. In terms of safety and feasibility, NJEEN should not be recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000001896DOI Listing
November 2016

Complete agenesis of the coeliac artery: the first documented case.

ANZ J Surg 2018 07 15;88(7-8):E627-E628. Epub 2016 Apr 15.

Department of Digestive and Hepatobiliary Surgery, CHU Estaing, Clermont-Ferrand, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ans.13587DOI Listing
July 2018

Non-lethal Right Liver Atrophy After TIPS Occlusion in A Cirrhotic Patient: Introducing The Hepatic Biembolization.

J Gastrointest Surg 2016 09 25;20(9):1671-2. Epub 2016 Mar 25.

Department of Digestive and Hepatobiliary Surgery, Estaing Hospital, CHU Clermont-Ferrand, 1 Place Lucie et Raymond Aubrac, 63003, Clermont-Ferrand, France.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is the standard procedure in the treatment of refractory ascites and variceal bleeding in the setting of portal hypertension. Secondary obstruction of the shunt is a classic but potentially lethal complication.

Methods: We present here the case of a cirrhotic patient that underwent a TIPS for refractory ascites, with early complete thrombosis without lethal complication.

Results: Obstruction of the TIPS led to thrombosis of both the right hepatic and the right portal veins with progressive total atrophy of the right liver and marked hypertrophy of the left liver. Despite initial poor liver function, biological hepatic markers improved slowly until complete recovery.

Conclusion: Hence, we suggest the concept of combined right portal and hepatic vein embolization as a new procedure to induce partial liver hypertrophy before major liver resection, even in cirrhotic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11605-016-3133-zDOI Listing
September 2016

Pancreaticobiliary maljunction and choledochal cysts: from embryogenesis to therapeutics aspects.

Surg Radiol Anat 2016 Nov 22;38(9):1053-1060. Epub 2016 Mar 22.

Department of Hepatobiliary Surgery, Estaing Hospital, CHU Clermont-Ferrand, 1 Place Lucie et Raymond Aubrac, 63003, Clermont-Ferrand, France.

Pancreaticobiliary maljunction (PBM) and choledochal cysts (CC) are rare and little-known diseases. Several definitions have been proposed for the PBM, but the most widely accepted is an excessive length of the common pancreaticobiliary duct due to the abnormal convergence of the pancreatic and biliary ducts out of the duodenal wall. This anomaly, thought to develop during embryogenesis, is associated with a loss of regulation of the Oddi's sphincter leading to a pancreaticobiliary or biliopancreatic backflow. This reflux could be responsible, or associated with cystic dilatation of the bile ducts and biliary tract cancers, to various biliary or pancreatic events such as cholangitis or pancreatitis. For the diagnosis of PBM, magnetic resonance cholangiopancreatography has now become the gold standard as a noninvasive imaging tool. However, the main risk of PBM is the development of bile duct cancer, most often on a distended area. PBM without CC increase the occurrence of gallbladder cancer and require a preventive cholecystectomy. Surgical treatment of PBM with concomitant CC is more complex and depends on localization of the dilatation(s) as reported in the Todani's classification. This review describes the pathogenesis, embryogenesis, clinical features, investigation and management of PBM and CC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00276-016-1669-yDOI Listing
November 2016

Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study.

PLoS One 2016 9;11(2):e0148739. Epub 2016 Feb 9.

CHU Clermont-Ferrand, Délégation à la Recherche Clinique et à l'Innovation, F-63003, Clermont-Ferrand, France.

Background: Adjuvant chemotherapy for colorectal cancer is mainly based on the combination of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4). The pharmacological target of oxaliplatin remains intracellular and therefore dependent on its entry into cells. The intracellular distribution of oxaliplatin is mediated by organic cation transporters 1, 2 and 3 (OCT1, 2 and 3), copper transporter 1 (CTR1) and ATPase Cu2+ transporting beta polypeptide (ATP7B) and may modulate the efficacy of oxaliplatin-based chemotherapy. The aim of this study was to perform a retrospective study to assess the relation between the expression of oxaliplatin transporters in colorectal cancer before chemotherapy and the response to FOLFOX-4 adjuvant chemotherapy in responder and non-responder patients.

Methods: This retrospective study was conducted at a single center (University Hospital of Clermont-Ferrand, France). The target population was patients with resectable colorectal cancer operated between 2006 and 2013. Inclusion criteria were defined for the responder patients as no cancer recurrence 3 years after the end of chemotherapy, and for the non-responder patients as cancer recurrence within 1 year. Other inclusion criteria were stages IIb-IV cancers, first-line adjuvant FOLFOX-4 chemotherapy, and the availability of resected primary tumor samples. Exclusion criteria were preoperative chemotherapy and/or radiotherapy, a targeted therapy, other anticancer drugs, cancer recurrence between the first and the third year after the end of chemotherapy and follow-up < 3 years. Immunostaining of oxaliplatin transporters (OCT1, 2, 3, CTR1 and ATP7B) and Ki-67 was assessed in tumor samples.

Results: Retrospectively, 31 patients have been selected according to inclusion and exclusion criteria (15 responders and 16 non-responders). Before FOLFOX-4 regimen, OCT3 expression was significantly lower in responder patients compared to non-responders (p<0.001). According to multivariate analysis, OCT3 remains an independent criterion for adjuvant FOLFOX chemotherapy response (p = 0.039). No significant relation is reported between chemotherapy response and the expression of OCT1 (p = 0.49), OCT2 (p = 0.09), CTR1 (p = 0.45), ATP7B (p = 0.94) and Ki-67 (p = 0.34) in tumors.

Conclusions: High expression of OCT3 could be an independent factor related to resistance to FOLFOX-4 chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148739PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747515PMC
July 2016

Gut microbiota imbalance and colorectal cancer.

World J Gastroenterol 2016 Jan;22(2):501-18

Johan Gagnière, Jennifer Raisch, Julie Veziant, Nicolas Barnich, Richard Bonnet, Emmanuel Buc, Marie-Agnès Bringer, Denis Pezet, Mathilde Bonnet, Clermont Université, UMR 1071 Inserm/Université d'Auvergne, 63000 Clermont-Ferrand, France.

The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v22.i2.501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716055PMC
January 2016

High Resectability Rate of Initially Unresectable Colorectal Liver Metastases After UGT1A1-Adapted High-Dose Irinotecan Combined with LV5FU2 and Cetuximab: A Multicenter Phase II Study (ERBIFORT).

Ann Surg Oncol 2016 07 6;23(7):2161-6. Epub 2016 Jan 6.

Leon Berard Center, Lyon, France.

Background: The purpose of this study was to assess the efficacy and tolerance of induction chemotherapy combining LV5FU2 with increased doses of irinotecan adapted to UGT1A1 genotyping and cetuximab in untreated potentially resectable liver metastases of colorectal cancer.

Methods: Twenty-six patients, PS 0-1, with class II hepatic metastases received chemotherapy combining irinotecan 260 mg/m(2) on day 1 for UGT1A1 6/6 and 6/7 genotypes and 220 mg/m(2) for UGT1A1 7/7 genotypes, with leucovorin on day 1, 5FU 400 mg/m(2) bolus on day 1 and continuous 5FU infusion for 46 h, and cetuximab on day 1 (day 1 = day 14). Primary prevention with lenograstim (day 5-9) was given to UGT1A1 6/7 and 7/7 genotypes. The primary endpoint was the response rate (RECIST1.1), and the secondary endpoints were tolerance (NCI-CTC criteria) and R0 resection rate.

Results: The average number of cycles per patient was 6 (±1.9). The UGT1A1 genotype was 6/6 in 34.6 %, 6/7 in 53.9 %, and 7/7 in 11.5 % of patients. At 6 cycles, 18 patients (69.2 %) presented a partial response, 5 patients (19.2 %) had stable disease, 2 patients (7.7 %) died independently of chemotherapy, and 1 patient (3.9 %) refused the treatment after 3 cycles. Four patients received 2 more cycles and the cumulative response rate at 8 cycles was 76.9 % (20/26). There was no progression. Among assessable patients (n = 23), the overall response rate was 82.6 % and 21 patients (80.7 %) had a metastasis resection. The most frequent grade 3-4 toxicities were neutropenia (31 %), diarrhea (20.8 %), and anorexia (16.4 %). There were no deaths due to toxicity.

Conclusions: High-dose FOLFIRI combined with cetuximab yielded high response rates and enabled complete resection of class II hepatic metastases in most patients. It seemed to be well-tolerated among healthy selected patients thanks to irinotecan dose adaptation according to UGT1A1 pharmacogenomics status. This intensified chemotherapy regimen needs to be confirmed in a randomized, phase III study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-015-5072-4DOI Listing
July 2016

Previous radiation for prostate neoplasm alters surgical and oncologic outcomes after rectal cancer surgery.

J Surg Oncol 2015 Dec 29;112(8):802-8. Epub 2015 Oct 29.

Department of Digestive Surgery, Estaing University Hospital, Clermont-Ferrand, France.

Background: Previous radiation for prostate cancer (PC) contra-indicates neoadjuvant chemoradiotherapy for rectal cancer (RC) because of risk of cumulative radiation dose toxicity. Postoperative outcomes after proctectomy have not been well studied in these patients who did not receive optimal treatment.

Methods: Eighty-four consecutive male patients underwent surgery for stage II-III mid or low RC between 2002 and 2011. Patients who previously received radiation for PC (n = 8) and patients who had not previously undergone radiation for PC but who received neoadjuvant chemoradiotherapy for RC (n = 64) were retrospectively compared.

Results: Previous radiation for PC was an independent factor that significantly increased intraoperative (25% vs. 1.6%, P = 0.002) and postoperative morbidities (62.5% vs. 28.1%, P = 0.028), anastomotic leakage (62.5% vs. 12.5%, P < 0.001) and definitive stoma rates (25% vs. 17.4%, P = 0.022). It significantly altered median overall survival (32.0 vs. 130.6 months, P = 0.05) and local recurrence-free survival rates (14.0 months vs. "median not reached," P = 0.016).

Conclusions: This is the first report of altered survival rates after proctectomy in patients who had previously received radiation for PC. Postoperative morbidity and definitive defunctioning stoma rates were significantly increased in these patients with poor prognoses. Therapeutic strategies should thus be individualized. Large, multicenter cohort studies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.24075DOI Listing
December 2015

Endoscopic ultrasound-guided biliary drainage after failed ERCP: cumulative experience of 101 procedures at a single center.

Endoscopy 2015 Sep 11;47(9):794-801. Epub 2015 May 11.

Department of Digestive and Hepatobiliary Diseases, CHU Estaing Clermont-Ferrand, Clermont-Ferrand, France.

Background And Study Aim: Endoscopic ultrasound (EUS)-guided biliary access is an alternative to percutaneous access after failed endoscopic retrograde cholangiopancreatography (ERCP). This report presents 7 years' cumulative experience of EUS-guided biliary drainage for obstructive jaundice in patients with failed ERCP.

Patients And Methods: Between February 2006 and February 2013, 101 patients (malignant = 98, benign = 3) with previous failed ERCP underwent an EUS intra- or extrahepatic approach with transluminal stenting or an EUS-guided rendezvous procedure with transpapillary stent placement. A single endoscopist performed all procedures.

Results: A total of 71 patients underwent the intrahepatic approach (66 hepatogastrostomies and 5 EUS-guided rendezvous), and 30 underwent the extrahepatic approach (26 choledochoduodenostomies, 1 choledochojejunostomy, 1 choledochoantrostomy, and 2 EUS-guided cholangiographies). Technical and clinical success rates were 98.0 % and 92.1 %, respectively. There was no difference in efficacy between hepatogastrostomies and choledochoduodenostomies (94 % vs. 90 %; P = 0.69) or in major complications (10.6 % vs. 6.7 %; P = 1). Adverse events occurred in 12 patients (11.9 %): 10 in the hepatogastrostomy group (2 limited pneumoperitoneum, 1 hepatic hematoma, 5 bile leakage, 2 sepsis), and 2 in the choledochoduodenostomy group (1 arteriobiliary fistula and 1 sepsis). There were six procedure-related deaths, five among the first 50 patients and one among the last 51 patients. Hepatogastrostomy vs. choledochoduodenostomy, plastic vs. metal stenting, stent-in-stent vs. 1 stent, nasobiliary drain, or postoperative octreotide infusion were not prognostic of bile leakage.

Conclusion: EUS-guided biliary drainage is an efficient technique, but is associated with significant morbidity that seems to decrease with the learning curve. It should be performed in tertiary care centers in selected patients. Prospective randomized studies are needed to compare EUS-guided biliary drainage with percutaneous transhepatic cholangiography drainage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0034-1391988DOI Listing
September 2015

Resection of pancreatic ductal adenocarcinoma with synchronous distant metastasis: is it worthwhile?

World J Surg Oncol 2014 Nov 18;12:347. Epub 2014 Nov 18.

Department of Digestive and HPB Surgery, CHU Estaing - 1, Place Lucie et Raymond Aubrac, 63003 Clermont-Ferrand, France.

Background: The purpose of this study is to report prolonged survival in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) managed by chemotherapy and surgery.

Methods: Between January 2009 and August 2013, 284 patients with metastatic PDAC were managed in our oncologic department. Among them, three (1%) with a single metastasis (liver in two cases and interaorticaval in one case) underwent one- or two-stage surgical resection of the metastasis and the main tumor. Perioperative data were recorded retrospectively, including disease-free and overall survival.

Results: The three patients had chemotherapy (FOLFOX or FOLFIRINOX regimen) with objective response or stable disease prior to surgery. Median time between chemotherapy and surgery was 9 (8 to 15) months. Resection consisted in pancreaticoduodenectomy in the three cases. None of the patients had grade III/IV postoperative complications, and median hospital stay was 12 (12 to 22) days. All the patients had postoperative chemotherapy. Only one patient experienced recurrence 11 months after surgery and died after 32.5 months. The two other patients were alive with no recurrence 26.3 and 24.7 months after initial treatment.

Conclusion: Radical resection of PDAC with single distant metastases can offer prolonged survival with low morbidity after accurate selection by neoadjuvant chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1477-7819-12-347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289271PMC
November 2014

Colon cancer-associated B2 Escherichia coli colonize gut mucosa and promote cell proliferation.

World J Gastroenterol 2014 Jun;20(21):6560-72

Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.

Aim: To provide further insight into the characterization of mucosa-associated Escherichia coli (E. coli) isolated from the colonic mucosa of cancer patients.

Methods: Phylogroups and the presence of cyclomodulin-encoding genes of mucosa-associated E. coli from colon cancer and diverticulosis specimens were determined by PCR. Adhesion and invasion experiments were performed with I-407 intestinal epithelial cells using gentamicin protection assay. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) expression in T84 intestinal epithelial cells was measured by enzyme-linked immunosorbent assay and by Western Blot. Gut colonization, inflammation and pro-carcinogenic potential were assessed in a chronic infection model using CEABAC10 transgenic mice. Cell proliferation was analyzed by real-time mRNA quantification of PCNA and immunohistochemistry staining of Ki67.

Results: Analysis of mucosa-associated E. coli from colon cancer and diverticulosis specimens showed that whatever the origin of the E. coli strains, 86% of cyclomodulin-positive E. coli belonged to B2 phylogroup and most harbored polyketide synthase (pks) island, which encodes colibactin, and/or cytotoxic necrotizing factor (cnf) genes. In vitro assays using I-407 intestinal epithelial cells revealed that mucosa-associated B2 E. coli strains were poorly adherent and invasive. However, mucosa-associated B2 E. coli similarly to Crohn's disease-associated E. coli are able to induce CEACAM6 expression in T84 intestinal epithelial cells. In addition, in vivo experiments using a chronic infection model of CEACAM6 expressing mice showed that B2 E. coli strain 11G5 isolated from colon cancer is able to highly persist in the gut, and to induce colon inflammation, epithelial damages and cell proliferation.

Conclusion: In conclusion, these data bring new insights into the ability of E. coli isolated from patients with colon cancer to establish persistent colonization, exacerbate inflammation and trigger carcinogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v20.i21.6560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047342PMC
June 2014

Giant mucinous cystic adenoma with pancreatic atrophy mimicking dorsal agenesis of the pancreas.

World J Gastrointest Surg 2014 Mar;6(3):42-6

Johan Gagnière, Aurélien Dupré, Denis Pezet, Emmanuel Buc, Department of Digestive and Hepatobiliary Surgery, Centre Hospitalier Universitaire Estaing, 63003 Clermont-Ferrand, France.

Mucinous cystic adenoma (MCA) of the pancreas is a rare benign cystic tumor with ovarian-like stroma and lack of communication with the pancreatic ductal system. The ovarian tissue is incorporated from the left gonad within the dorsal pancreas during embryogenesis. Consequently, congenital dorsal agenesis of the pancreas (DAP) cannot be associated with MCA. We report the case of a giant MCA associated with atrophy of the dorsal pancreas mimicking complete DAP. Pancreato-magnetic resonance imaging failed to identify the dorsal pancreas but the absence of diabetes mellitus and compression of the splenic vein with major tributaries rectified the diagnosis of secondary atrophy of the distal pancreas. Unusual proximal location of the cyst in the pancreas may have induced chronic obstruction of both the dorsal pancreatic duct and the splenic vein, with secondary atrophy of the distal pancreas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4240/wjgs.v6.i3.42DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964414PMC
March 2014

Bacterial genotoxin colibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype.

Gut 2014 Dec 21;63(12):1932-42. Epub 2014 Mar 21.

Clermont Université, UMR 1071 Inserm/Université d'Auvergne, Clermont-Ferrand, France INRA, USC 2018, Clermont-Ferrand, France Service de Bactériologie, Centre Hospitalier Universitaire, Clermont-Ferrand, France.

Background: Escherichia coli strains harbouring the pks island (pks+ E. coli) are often seen in human colorectal tumours and have a carcinogenic effect independent of inflammation in an AOM/IL-10(-/-) (azoxymethane/interleukin) mouse model.

Objective: To investigate the mechanism sustaining pks+ E. coli-induced carcinogenesis.

Method: Underlying cell processes were investigated in vitro and in vivo (xenograft model) using intestinal epithelial cells infected by pks+ E. coli or by an isogenic mutant defective for pks (pks- E. coli). The results were supported by data obtained from an AOM/DSS (azoxymethane/dextran sodium sulphate) colon cancer mouse model and from human colon cancer biopsy specimens colonised by pks+ E. coli or pks- E. coli.

Results: Colibactin-producing E. coli enhanced tumour growth in both xenograft and AOM/DSS models. Growth was sustained by cellular senescence (a direct consequence of small ubiquitin-like modifier (SUMO)-conjugated p53 accumulation), which was accompanied by the production of hepatocyte growth factor (HGF). The underlying mechanisms involve microRNA-20a-5p, which targets SENP1, a key protein regulating p53 deSUMOylation. These results are consistent with the expression of SENP1, microRNA-20a-5p, HGF and phosphorylation of HGF receptor found in human and mouse colon cancers colonised by pks+ E. coli.

Conclusion: These data reveal a new paradigm for carcinogenesis, in which colibactin-induced senescence has an important role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gutjnl-2013-305257DOI Listing
December 2014

Colonization of the human gut by E. coli and colorectal cancer risk.

Clin Cancer Res 2014 Feb 13;20(4):859-67. Epub 2013 Dec 13.

Authors' Affiliations: Clermont Université, UMR 1071Inserm/Université d'Auvergne; Institut National de la Recherche Agronomique (INRA), USC-2018; and Centre Hospitalier Universitaire, Clermont-Ferrand, France.

Purpose: The intestinal microbiota is potentially involved in the development of colorectal carcinoma via various mechanisms. Escherichia coli are commensal bacteria of the human gut microbiota, but some pathogenic strains have acquired the ability to induce chronic inflammation and/or produce toxins, such as cyclomodulin, which could participate in the carcinogenesis process. Here, we analyzed the E. coli population associated with mucosa of patients with colon cancer in relation to clinicopathologic characteristics. We assessed carcinogenic properties of a colon cancer-associated E. coli strain in multiple intestinal neoplasia (Min) mice.

Experimental Design: Mucosa-associated or internalized E. coli were quantified and characterized from tumors and mucosa of patients with colon cancer and the healthy mucosa of diverticulosis controls. Min mice were inoculated with a colon cancer-associated E. coli strain (11G5). The number of colonic polyps was evaluated at 7 weeks after infection.

Results: An increased level of mucosa-associated and internalized E. coli was observed in the tumors compared with normal tissue. A relationship between poor prognostic factors for colon cancer (tumor-node-metastasis stage) and colonization of mucosa by E. coli was observed. Pathogenic cyclomodulin-positive E. coli strains were more prevalent on mucosa of patients with stages III/IV than those with stage I colon cancer. Proliferative index and E. coli colonization level of the mucosa distant from the tumor significantly correlated. Min mice infected with the E. coli strain 11G5 displayed a marked increase in the number of visible colonic polyps compared with controls.

Conclusion: These findings support that pathogenic E. coli could be a cofactor in pathogenesis of colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-13-1343DOI Listing
February 2014

Massive hepatic necrosis with toxic liver syndrome following portal vein ligation.

World J Gastroenterol 2013 May;19(18):2826-9

Department of Digestive and Hepatobiliary Surgery, CHU Estaing, 1 Place Lucie et Raymond Aubrac, 63003 Clermont-Ferrand, France.

Right portal vein ligation (PVL) is a safe and widespread procedure to induce controlateral liver hypertrophy for the treatment of bilobar colorectal liver metastases. We report a case of a 60-year-old man treated by both right PVL and ligation of the glissonian branches of segment 4 for colorectal liver metastases surrounding the right and median hepatic veins. After surgery, the patient developed massive hepatic necrosis with secondary pulmonary and renal insufficiency requiring transfer to the intensive care unit. This so-called toxic liver syndrome finally regressed after hemofiltration and positive oxygen therapy. Diagnosis of acute congestion of the ligated lobe was suspected. The mechanism suspected was an increase in arterial inflow secondary to portal vein ligation concomitant with a decrease in venous outflow due to liver metastases encircling the right and median hepatic vein. This is the first documented case of toxic liver syndrome in a non-cirrhotic patient with favorable issue, and a rare complication of PVL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v19.i18.2826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653158PMC
May 2013

High prevalence of mucosa-associated E. coli producing cyclomodulin and genotoxin in colon cancer.

PLoS One 2013 14;8(2):e56964. Epub 2013 Feb 14.

UMR 1071 Inserm/Université d'Auvergne, Clermont Université, Clermont-Ferrand, France.

Some Escherichia coli strains produce toxins designated cyclomodulins (CMs) which interfere with the eukaryotic cell cycle of host cells, suggesting a possible link between these bacteria and cancers. There are relatively few data available concerning the colonization of colon tumors by cyclomodulin- and genotoxic-producing E. coli. We did a qualitative and phylogenetic analysis of mucosa-associated E. coli harboring cyclomodulin-encoding genes from 38 patients with colorectal cancer (CRC) and 31 with diverticulosis. The functionality of these genes was investigated on cell cultures and the genotoxic activity of strains devoid of known CM-encoding gene was investigated. Results showed a higher prevalence of B2 phylogroup E. coli harboring the colibatin-producing genes in biopsies of patients with CRC (55.3%) than in those of patients with diverticulosis (19.3%), (p<0.01). Likewise, a higher prevalence of B2 E. coli harboring the CNF1-encoding genes in biopsies of patients with CRC (39.5%) than in those of patients with diverticulosis (12.9%), (p = 0.01). Functional analysis revealed that the majority of these genes were functional. Analysis of the ability of E. coli to adhere to intestinal epithelial cells Int-407 indicated that highly adherent E. coli strains mostly belonged to A and D phylogroups, whatever the origin of the strains (CRC or diverticulosis), and that most E. coli strains belonging to B2 phylogroup displayed very low levels of adhesion. In addition, 27.6% (n = 21/76) E. coli strains devoid of known cyclomodulin-encoding genes induced DNA damage in vitro, as assessed by the comet assay. In contrast to cyclomodulin-producing E. coli, these strains mainly belonged to A or D E. coli phylogroups, and exhibited a non significant difference in the distribution of CRC and diverticulosis specimens (22% versus 32.5%, p = 0.91). In conclusion, cyclomodulin-producing E. coli belonging mostly to B2 phylogroup colonize the colonic mucosa of patients with CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056964PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572998PMC
August 2013