Publications by authors named "Fabrice Muscari"

76 Publications

Are gastric metastases of renal cell carcinoma really rare? A case report and systematic review of the literature.

Int J Surg Case Rep 2021 Apr 6;82:105867. Epub 2021 Apr 6.

Department of Digestive Surgery, Toulouse University Hospital, 31059, Toulouse, France.

Introduction: Renal cell carcinoma (RCC) represents above 3 % of all cancers. At diagnosis, above 25 % of patients with RCC present an advanced disease. Gastric metastasis of RCC is associated with poor outcome. We report the case of a patient treated for a gastric metastasis of RCC and we conducted a systematic review of the literature to report all published cases of RCC patients with gastric metastasis.

Case Presentation: In December 2010, a 61-year-old man was treated by open partial nephrectomy for a localized right clear cell RCC. In September 2018, a metachronous gastric metastasis was found on CT scan. The lesion was located on the lesser curvature of the stomach, measuring 4.5 cm long axis. No other secondary lesions were identified. A laparoscopic wedge resection, converted to laparotomy was performed. Two years later, in September 2020, a CT scan was performed, revealing a 17 mm adenopathy behind the hepatic hilum and a surgical management was performed, including a lymph node dissection of the hepatic hilum and the hepatic artery. Actually, he remains healthy.

Clinical Discussion And Conclusion: Our systematic review suggests that solitary gastric metastasis of RCC are scarce. In comparison of patients with multiple metastatic sites, the median survival of patients with solitary gastric metastasis is longer.
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http://dx.doi.org/10.1016/j.ijscr.2021.105867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055614PMC
April 2021

Author response to: Prevention of biliary fistula after partial hepatectomy by transcystic biliary drainage: randomized clinical trial.

Br J Surg 2021 03;108(2):e91

Department of Digestive Surgery and Liver Transplantation, Toulouse University Hospital, Toulouse, France.

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http://dx.doi.org/10.1093/bjs/znaa100DOI Listing
March 2021

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

Management of anastomotic biliary stricture after liver transplantation and impact on survival.

HPB (Oxford) 2020 Dec 26. Epub 2020 Dec 26.

The Digestive Surgery and Liver Transplantation Department, Toulouse University Hospital, Toulouse, France. Electronic address:

Background: Anastomotic biliary strictures (AS) is the main surgical complication after liver transplantation. The aims of this study are to investigate the risk factors of AS, its management and its impact on overall survival and survival of the graft.

Methods: All patients who had received a liver transplantation with duct-to-duct anastomosis at Toulouse University Hospital between 2010 and 2016 were included.

Results: Of 225 included patients, 56 (24.9%) presented with AS. The median time to discovery of AS was 83 days and 69.6% of the AS appeared within 6 months. Transplantation in critically ill patients, with a liver score >800 points, was an independent predictive factor of survival (P = 0.003). The first-line treatment was endoscopic (87.5%), with a success rate of 79.6% and a median of 4 procedures per patient in 12 months. In cases of failure of endoscopic therapy, percutaneous treatment had a high failure rate (50%). AS had no impact in terms of overall survival or in terms of graft survival.

Conclusion: AS do not have any repercussions on patient or graft survival, requiring long endoscopic treatment with multiple procedures. In the event of failure of this first-line endoscopic treatment, it seems preferable to turn directly towards surgical repair.
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http://dx.doi.org/10.1016/j.hpb.2020.12.008DOI Listing
December 2020

Improving Provision of Preanesthetic Information Through Use of the Digital Conversational Agent "MyAnesth": Prospective Observational Trial.

J Med Internet Res 2020 12 4;22(12):e20455. Epub 2020 Dec 4.

Département d'Anesthésie-Réanimation, Hopital Pierre-Paul Riquet, CHU Purpan, Toulouse, France.

Background: Due to time limitations, the preanesthetic consultation (PAC) is not the best time for patients to integrate information specific to their perioperative care pathway.

Objective: The main objectives of this study were to evaluate the effectiveness of a digital companion on patients' knowledge of anesthesia and their satisfaction after real-life implementation.

Methods: We conducted a prospective, monocentric, comparative study using a before-and-after design. In phase 1, a 9-item self-reported anesthesia knowledge test (Delphi method) was administered to patients before and after their PAC (control group: PAC group). In phase 2, the study was repeated immediately after the implementation of a digital conversational agent, MyAnesth (@+PAC group). Patients' satisfaction and their representations for anesthesia were also assessed using a Likert scale and the Abric method of hierarchized evocation.

Results: A total of 600 tests were distributed; 205 patients and 98 patients were included in the PAC group and @+PAC group, respectively. Demographic characteristics and mean scores on the 9-point preinformation test (PAC group: 4.2 points, 95% CI 3.9-4.4; @+PAC: 4.3 points, 95% CI 4-4.7; P=.37) were similar in the two groups. The mean score after receiving information was better in the @+PAC group than in the PAC group (6.1 points, 95% CI 5.8-6.4 points versus 5.2 points, 95% CI 5.0-5.4 points, respectively; P<.001), with an added value of 0.7 points (95% CI 0.3-1.1; P<.001). Among the respondents in the @+PAC group, 82% found the information to be clear and appropriate, and 74% found it easily accessible. Before receiving information, the central core of patients' representations for anesthesia was focused on the fear of being put to sleep and thereafter on caregiver skills and comfort.

Conclusions: The implementation of our digital conversational agent in addition to the PAC improved patients' knowledge about their perioperative care pathway. This innovative audiovisual support seemed clear, adapted, easily accessible, and reassuring. Future studies should focus on adapting both the content and delivery of a digital conversational agent for the PAC in order to maximize its benefit to patients.
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http://dx.doi.org/10.2196/20455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748965PMC
December 2020

Preoperative alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC): is this 50-year biomarker still up-to-date?

Transl Gastroenterol Hepatol 2020 5;5:46. Epub 2020 Oct 5.

Department of Digestive Surgery and Transplantation, Toulouse University Hospital, Toulouse, France.

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http://dx.doi.org/10.21037/tgh.2019.12.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530322PMC
October 2020

Does Fungal Biliary Contamination after Preoperative Biliary Drainage Increase Postoperative Complications after Pancreaticoduodenectomy?

Cancers (Basel) 2020 Sep 30;12(10). Epub 2020 Sep 30.

Department of Digestive Surgery, Rouen University Hospital, 1 rue de Germont, F-76031 Rouen, CEDEX, France.

(1) Background: preoperative biliary drainage before pancreaticoduodenectomy (PD) is associated with bacterial biliary contamination (>85%) and a significant increase in global and infectious complications. In view of the lack of published data, the aim of our study was to investigate the impact of fungal biliary contamination after biliary drainage on the complication rate after PD. (2) Methods: a multicentric retrospective study that included 224 patients who underwent PD after biliary drainage with intraoperative biliary culture. (3) Results: the global rate of positive intraoperative biliary sample was 92%. Respectively, the global rate of biliary bacterial contamination and the rate of fungal contamination were 75% and 25%, making it possible to identify two subgroups: bacterial contamination only (B+, = 154), and bacterial and fungal contamination (BF+, = 52). An extended duration of preoperative drainage (62 vs. 49 days; = 0.08) increased the risk of fungal contamination. The overall and infectious complication rates were not different between the two groups. In the event of postoperative infectious or surgical complications, the infectious samples taken did not reveal more fungal infections in the BF+ group. (4) Conclusions: fungal biliary contamination, although frequent, does not seem to increase the rate of global and infectious complications after PD, preceded by preoperative biliary drainage.
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http://dx.doi.org/10.3390/cancers12102814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599947PMC
September 2020

Blended learning of radiology improves medical students' performance, satisfaction, and engagement.

Insights Imaging 2020 Apr 28;11(1):61. Epub 2020 Apr 28.

Service de Radiologie, CHU Toulouse-Rangueil, 1 avenue du Professeur Jean Poulhès, TSA 50032, 31059, Toulouse, Cedex 9, France.

Purpose: To evaluate the impact of blended learning using a combination of educational resources (flipped classroom and short videos) on medical students' (MSs) for radiology learning.

Material And Methods: A cohort of 353 MSs from 2015 to 2018 was prospectively evaluated. MSs were assigned to four groups (high, high-intermediate, low-intermediate, and low achievers) based on their results to a 20-MCQs performance evaluation referred to as the pretest. MSs had then free access to a self-paced course totalizing 61 videos based on abdominal imaging over a period of 3 months. Performance was evaluated using the change between posttest (the same 20 MCQs as pretest) and pretest results. Satisfaction was measured using a satisfaction survey with directed and spontaneous feedbacks. Engagement was graded according to audience retention and attendance on a web content management system.

Results: Performance change between pre and posttest was significantly different between the four categories (ANOVA, P = 10): low pretest achievers demonstrated the highest improvement (mean ± SD, + 11.3 ± 22.8 points) while high pretest achievers showed a decrease in their posttest score (mean ± SD, - 3.6 ± 19 points). Directed feedback collected from 73.3% of participants showed a 99% of overall satisfaction. Spontaneous feedback showed that the concept of "pleasure in learning" was the most cited advantage, followed by "flexibility." Engagement increased over years and the number of views increased of 2.47-fold in 2 years.

Conclusion: Learning formats including new pedagogical concepts as blended learning, and current technologies allow improvement in medical student's performance, satisfaction, and engagement.
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http://dx.doi.org/10.1186/s13244-020-00865-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188751PMC
April 2020

Peritoneal Carcinomatosis Risk and Long-Term Survival Following Hepatectomy for Spontaneous Hepatocellular Carcinoma Rupture: Results of a Multicenter French Study (FRENCH-AFC).

Ann Surg Oncol 2020 Sep 13;27(9):3383-3392. Epub 2020 Apr 13.

Department of Digestive Surgery, Hôpital Charles Nicolle, Rouen University Hospital, Rouen Cedex, France.

Background: Spontaneous rupture of hepatocellular carcinoma (HCC) remains a life-threatening complication, with a reported mortality rate of between 16 and 30% and an incidence rate of approximately 3% in Europe. Survival data and risk factors after ruptured HCC are lacking, especially for peritoneal metastasis (PM).

Objectives: The aims of this study were to evaluate the pattern of recurrence and mortality after hepatectomy for ruptured HCC, and to focus on PM.

Methods: We retrospectively reviewed the files of patients admitted to 14 French surgical centers for spontaneous rupture of HCC between May 2000 and May 2012.

Results: Overall, 135 patients were included in this study. The median disease-free survival and overall survival (OS) rates were 16.1 (11.0-21.1) and 28.7 (26.0-31.5) months, respectively, and the median follow-up period was 29 months. At last follow-up, recurrences were observed in 65.1% of patients (n = 88). The overall rate of PM following ruptured HCC was 12% (n = 16). Surgical management of PM was performed for six patients, with a median OS of 36.6 months. An α-fetoprotein level > 30 ng/mL (p = 0.0009), tumor size at rupture > 70 mm (p = 0.0009), and vascular involvement (p < 0.0001) were found to be independently associated with an increased likelihood of recurrence. No risk factor for PM was observed.

Conclusion: This large-cohort French study confirmed that 12% of patients had PM after ruptured HCC. A curative approach may be an option for highly selected patients with exclusive PD because of the survival benefit it could provide.
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http://dx.doi.org/10.1245/s10434-020-08442-5DOI Listing
September 2020

A New Score to Predict the Resectability of Pancreatic Adenocarcinoma: The BACAP Score.

Cancers (Basel) 2020 Mar 25;12(4). Epub 2020 Mar 25.

The Digestive Surgery and Liver Transplantation Department, Toulouse University Hospital, 31400 Toulouse, France.

Surgery remains the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). Therefore, a predictive score for resectability on diagnosis is needed. A total of 814 patients were included between 2014 and 2017 from 15 centers included in the BACAP (the national Anatomo-Clinical Database on Pancreatic Adenocarcinoma) prospective cohort. Three groups were defined: resectable (Res), locally advanced (LA), and metastatic (Met). Variables were analyzed and a predictive score was devised. Of the 814 patients included, 703 could be evaluated: 164 Res, 266 LA, and 273 Met. The median ages of the patients were 69, 71, and 69, respectively. The median survival times were 21, 15, and nine months, respectively. Six criteria were significantly associated with a lower probability of resectability in multivariate analysis: venous/arterial thrombosis ( = 0.017), performance status 1 ( = 0.032) or ≥ 2 ( = 0.010), pain ( = 0.003), weight loss ≥ 8% ( = 0.019), topography of the tumor (body/tail) ( = 0.005), and maximal tumor size 20-33 mm ( < 0.013) or >33 mm ( < 0.001). The BACAP score was devised using these criteria (http://jdlp.fr/resectability/) with an accuracy of 81.17% and an area under the receive operating characteristic (ROC) curve of 0.82 (95% confidence interval (CI): 0.78; 0.86). The presence of pejorative criteria or a BACAP score < 50% indicates that further investigations and even neoadjuvant treatment might be warranted. Trial registration: NCT02818829.
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http://dx.doi.org/10.3390/cancers12040783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226323PMC
March 2020

Identification of risk factors for morbidity and mortality after Hartmann's reversal surgery - a retrospective study from two French centers.

Sci Rep 2020 02 27;10(1):3643. Epub 2020 Feb 27.

Service de chirurgie digestive, endocrinienne et générale, CHU de Limoges, Avenue Martin Luther King, Limoges Cedex, 87042, France.

Hartmann's reversal procedures are often fraught with complications or failure to recover. This being a fact, it is often difficult to select patients with the optimal indications for a reversal. The post-recovery morbidity and mortality rates in the literature are heterogeneous between 0.8 and 44%. The identification of predictive risk factors of failure of such interventions would therefore be very useful to help the practitioner in his approach. Given these elements, it was important to us to analyze the practice of two French university hospitals in order to highlight such risk factors and to allow surgeons to select the best therapeutic strategy. We performed a bicentric observational retrospective study between 2010 and 2015 that studied the characteristics of patients who had undergone Hartmann surgery and were subsequently reestablished. The aim of the study was to identify factors influencing morbidity and postoperative mortality of Hartmann's reversal. Primary outcome was complications within the first 90 postoperative days. 240 patients were studied of which 60.4% were men. The mean age was 69.48 years. The median time to reversal was 8 months. 79.17% of patients were operated as emergency cases where the indication was a diverticular complication (39.17%). Seventy patients (29.2%) underwent a reversal and approximately 43% of these had complications within the first 90 postoperative days. The mean age of these seventy patients was 61.3 years old and 65.7% were males. None of them benefited from a reversal in the first three months. We identified some risk factors for morbidity such as pre-operative low albuminemia (p = 0.005) and moderate renal impairment (p = 0.019). However, chronic corticosteroid use (p = 0.004), moderate renal insufficiency (p = 0.014) and coronary artery disease (p = 0.014) seem to favour the development of anastomotic fistula, which is itself, a risk factor for mortality (p = 0.007). Our study highlights an important rate of complications including significant anastomotic fistula after Hartmann's reversal. Precarious nutritional status and cardiovascular comorbidities should clearly lead us to reconsider the surgical indication for continuity restoration.
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http://dx.doi.org/10.1038/s41598-020-60481-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046632PMC
February 2020

Outcomes of solid organ transplant recipients with invasive aspergillosis and other mold infections.

Transpl Infect Dis 2020 Feb 6;22(1):e13200. Epub 2019 Nov 6.

Département de Néphrologie et Transplantation d'organes, Hôpital Rangueil, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Objectives: To characterize the clinical presentation and outcomes of invasive mold infections (IMI) in solid organ transplant (SOT) recipients.

Methods: Inclusion of all SOT recipients with IMI diagnosed between 2008 and 2016 at a referral center for SOT. Univariable analyses identified factors associated with death at one year, and logistic regression models retained independent predictors.

Results: Of the 1739 patients that received a SOT during this period, 68 developed IMI (invasive aspergillosis [IA] in 58). Cumulative incidence of IMI at 1 year ranged from 1.2% to 18.8% (kidney and heart transplantation, respectively). At baseline, compared with other IMI, the need for vasoactive drugs was more frequent in patients with IA. During follow-up, 35 patients (51%) were admitted to the ICU and required mechanical ventilation (n = 27), vasoactive drugs (n = 31), or renal replacement therapy (n = 31). The need for vasoactive drugs (OR 7.34; P = .003) and a positive direct examination (OR 10.1; P = .004) were independently associated with the risk of death at 1 year in patients with IA (n = 33; 57%) CONCLUSIONS: Characteristics of IMI at presentation varied according to the underlying transplanted organ and the mold species. Following IA, one-year mortality may be predicted by the need for hemodynamic support and initial fungal load.
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http://dx.doi.org/10.1111/tid.13200DOI Listing
February 2020

One-Year Postoperative Mortality in MEN1 Patients Operated on Gastric and Duodenopancreatic Neuroendocrine Tumors: An AFCE and GTE Cohort Study.

World J Surg 2019 11;43(11):2856-2864

Department of Digestive and Endocrine Surgery, Dijon University Hospital, Dijon, France.

Importance: In MEN1 patients with gastric and duodenopancreatic neuroendocrine tumors (GPD-NET), surgery aims to control secretions or to prevent metastatic spread, but after GPD-NET resection, postoperative mortality may be related to the surgery itself or to other associated MEN1 lesions with their own uncontrolled secretions or metastatic behavior.

Objective: To analyze the causes of death within 1 year following a GPD-NET resection in MEN1 patients.

Design: An observational study collecting data from the Groupe d'étude des Tumeurs Endocrines (GTE) database. The analysis considered the time between surgery and death (early deaths [<1 month after surgery] versus delayed deaths [beyond 1 month after surgery]) and the period (before 1990 vs after 1990). Causes of death were classified as related to GDP surgery, related to surgery for other MEN1 lesions or not related to MEN1 causes.

Setting: GTE database which includes 1220 MEN1 patients and 441 GPD-NET resections.

Participants: Four hundred and forty-one GPD-NET resections.

Main Outcome Measures: The primary end point was postoperative mortality within 1 year after surgery.

Results: Twenty-four patients met the inclusion criteria (2%). Median age at death was 50.5 years. Sixteen deaths occurred in the 30-day postoperative period (76%). Among the 8 delayed deaths, 3 occurred as a result of medical complications between 30 and 90 postoperative days. After 1990, mean age at death increased from 48 to 58 years (p = 0.09), deaths related to uncontrolled acid secretion disappeared (p < 0.001) and deaths related to associated MEN1 lesions increased from 8 to 54% (p = 0.16).

Conclusion: Surgery and uncontrolled secretions remain the two main causes of death in MEN1 patients operated for a GPD-NET tumor. Improving the prognosis of these patients requires a strict evaluation of the secretory syndrome and MEN1 aggressiveness before GDP surgery.
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http://dx.doi.org/10.1007/s00268-019-05107-7DOI Listing
November 2019

Liquid Biopsy Approach for Pancreatic Ductal Adenocarcinoma.

Cancers (Basel) 2019 Jun 19;11(6). Epub 2019 Jun 19.

Université Fédérale Toulouse Midi-Pyrénées, Université Toulouse III Paul Sabatier, INSERM, CRCT, 31330 Toulouse, France.

Pancreatic cancer is a public health problem because of its increasing incidence, the absence of early diagnostic tools, and its aggressiveness. Despite recent progress in chemotherapy, the 5-year survival rate remains below 5%. Liquid biopsies are of particular interest from a clinical point of view because they are non-invasive biomarkers released by primary tumours and metastases, remotely reflecting disease burden. Pilot studies have been conducted in pancreatic cancer patients evaluating the detection of circulating tumour cells, cell-free circulating tumour DNA, exosomes, and tumour-educated platelets. There is heterogeneity between the methods used to isolate circulating tumour elements as well as the targets used for their identification. Performances for the diagnosis of pancreatic cancer vary depending of the technique but also the stage of the disease: 30-50% of resectable tumours are positive and 50-100% are positive in locally advanced and/or metastatic cases. A significant prognostic value is demonstrated in 50-70% of clinical studies, irrespective of the type of liquid biopsy. Large prospective studies of homogeneous cohorts of patients are lacking. One way to improve diagnostic and prognostic performances would be to use a combined technological approach for the detection of circulating tumour cells, exosomes, and DNA.
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http://dx.doi.org/10.3390/cancers11060852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627808PMC
June 2019

Predictive factors of histological response of colorectal liver metastases after neoadjuvant chemotherapy.

World J Gastrointest Oncol 2019 Apr;11(4):295-309

Department of Digestive Surgery and Liver Transplantation, Toulouse-Rangueil University Hospital, Toulouse 31059, France.

Background: Colorectal cancer is the third most common cancer in men and the second most common in women worldwide. Almost a third of the patients has or will develop liver metastases. Neoadjuvant chemotherapy (NAC) has recently become nearly systematic prior to surgery of colorectal livers metastases (CRLMs). The response to NAC is evaluated by radiological imaging according to morphological criteria. More recently, the response to NAC has been evaluated based on histological criteria of the resected specimen. The most often used score is the tumor regression grade (TRG), which considers the necrosis, fibrosis, and number of viable tumor cells.

Aim: To analyze the predictive factors of the histological response, according to the TRG, on CRLM surgery performed after NAC.

Methods: From January 2006 to December 2013, 150 patients who had underwent surgery for CRLMs after NAC were included. The patients were separated into two groups based on their histological response, according to Rubbia-Brandt TRG. Based on their TRG, each patient was either assigned to the responder (R) group (TRG 1, 2, and 3) or to the non-responder (NR) group (TRG 4 and 5). All of the histology slides were re-evaluated in a blind manner by the same specialized pathologist. Univariate and multivariate analyses were performed.

Results: Seventy-four patients were classified as responders and 76 as non-responders. The postoperative mortality rate was 0.7%, with a complication rate of 38%. Multivariate analysis identified five predictive factors of histological response. Three were predictive of non-response: More than seven NAC sessions, the absence of a radiological response after NAC, and a repeat hepatectomy ( < 0.005). Two were predictive of a good response: A rectal origin of the primary tumor and a liver-first strategy ( < 0.005). The overall survival was 57% at 3 yr and 36% at 5 yr. The disease-free survival rates were 14% at 3 yr and 11% at 5 yr. The factors contributing to a poor prognosis for disease-free survival were: No histological response after NAC, largest metastasis > 3 cm, more than three preoperative metastases, R1 resection, and the use of a targeted therapy with NAC ( < 0.005).

Conclusion: A non-radiological response and a number of NAC sessions > 7 are the two most pertinent predictive factors of non-histological response (TRG 4 or 5).
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http://dx.doi.org/10.4251/wjgo.v11.i4.295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475675PMC
April 2019

Caval replacement with parietal peritoneum tube graft for septic thrombophlebitis after hepatectomy: A case report.

World J Hepatol 2019 Jan;11(1):133-137

Digestive Surgery, Toulouse University Hospital, Toulouse 31400, France.

Background: Caval vein thrombosis after hepatectomy is rare, although it increases mortality and morbidity. The evolution of this thrombosis into a septic thrombophlebitis responsible for persistent septicaemia after a hepatectomy has not been reported to date in the literature. We here report the management of a 54-year-old woman operated for a peripheral cholangiocarcinoma who developed a suppurated thrombophlebitis of the vena cava following a hepatectomy.

Case Summary: This patient was operated by left lobectomy extended to segment V with bile duct resection and Roux-en-Y hepaticojejunostomy. After the surgery, she developed , and bacteraemias, as well as fungemia. A computed tomography scan revealed a bilioma which was percutaneously drained. Despite adequate antibiotic therapy, the patient's condition remained septic. A diagnosis of septic thrombophlebitis of the vena cava was made on post-operative day 25. The patient was then operated again for a surgical thrombectomy and complete caval reconstruction with a parietal peritoneum tube graft. Use of the peritoneum as a vascular graft is an inexpensive technique, it is readily and rapidly available, and it allows caval replacement in a septic area. Septic thrombophlebitis of the vena cava after hepatectomy has not been described previously and it warrants being added to the spectrum of potential complications of this procedure.

Conclusion: Septic thrombophlebitis of the vena cava was successfully treated with antibiotic and anticoagulation treatments, prompt surgical thrombectomy and caval reconstruction.
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http://dx.doi.org/10.4254/wjh.v11.i1.133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354118PMC
January 2019

Evaluation of postoperative ascites after somatostatin infusion following hepatectomy for hepatocellular carcinoma by laparotomy: a multicenter randomized double-blind controlled trial (SOMAPROTECT).

BMC Cancer 2018 Aug 23;18(1):844. Epub 2018 Aug 23.

Department of General Surgery and Liver Transplantation, Hospices Civils de Lyon, Croix-Rousse University Hospital, 103, Grande Rue de la Croix-Rousse, 69317, Lyon Cedex 04, France.

Background: The majority of patients undergoing hepatectomy for hepatocellular carcinoma (HCC) suffer from underlying liver disease and are exposed to the risk of postoperative ascites, which is favored by an imbalance between portal venous inflow and a diminished hepatic volume. Finding a reversible, non-invasive method for modulating the portal inflow would be of interest as it could be used temporarily during the early postoperative course. Somatostatin, a well-known drug already used in several indications, may limit the risk of postoperative ascites and liver failure by decreasing portal pressure after hepatectomy for HCC in patients with underlying liver disease. We aimed to evaluate the impact of somatostatin postoperative infusion on the incidence of ascites following hepatectomy by laparotomy for HCC in patients with underlying liver disease.

Methods/design: The SOMAPROTECT study is a multicenter randomized double-blind placebo controlled phase III trial comparing two arms of patients with underlying liver disease undergoing hepatectomy for HCC by open approach. All patients will have primary abdominal drainage before closure. Patients in the experimental arm will receive a postoperative intravenous infusion of somatostatin during 6 days. Patients in the control group will receive a placebo infusion for the same duration. The primary endpoint will be the presence or absence of postoperative ascites occurring during the 90-day postoperative course, defined as ≥500 ml/24 h of fluid in the drains during at least 3 days or any ascites requiring an invasive procedure comprising percutaneous puncture or drainage. Secondary endpoints will be duration and total volume of ascites, postoperative 90-day mortality and morbidity, liver failure, acute renal failure, length of stay in intensive care unit and hospital stay. The total number of patients to be enrolled was calculated to be 152.

Discussion: Postoperative ascites remains a major issue after hepatectomy for HCC as it is associated with increased morbidity, liver and renal failure, the need for specific treatments and prolonged hospital stay. This study represents the first randomized controlled trial to assess the benefits of somatostatin on the risk of postoperative ascites after surgery for HCC.

Trial Registration: NCT02799212 (ClinicalTrials.gov identifier). Registered prior to conducting the research on 9 June 2016.
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http://dx.doi.org/10.1186/s12885-018-4667-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108122PMC
August 2018

High tacrolimus intra-patient variability is associated with graft rejection, and donor-specific antibodies occurrence after liver transplantation.

World J Gastroenterol 2018 Apr;24(16):1795-1802

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse 31000, France.

Aim: To investigate the role of tacrolimus intra-patient variability (IPV) in adult liver-transplant recipients.

Methods: We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and analyzed its effect on the occurrence of graft rejection and donor-specific antibodies (DSAs), as well as graft survival during the first 2 years posttransplantation. Between 02/08 and 06/2015, 116 patients that received tacrolimus plus mycophenolate mofetil (with or without steroids) were included.

Results: Twenty-two patients (18.5%) experienced at least one acute-rejection episode (BPAR). Predictive factors for a BPAR were a tacrolimus IPV of > 35% [OR = 3.07 95%CI (1.14-8.24), = 0.03] or > 40% [OR = 4.16 (1.38-12.50), = 0.01), and a tacrolimus trough level of < 5 ng/mL [OR=3.68 (1.3-10.4), =0.014]. Thirteen patients (11.2%) developed at least one DSA during the follow-up. Tacrolimus IPV [coded as a continuous variable: OR = 1.1, 95%CI (1.0-1.12), = 0.006] of > 35% [OR = 4.83, 95%CI (1.39-16.72), = 0.01] and > 40% [OR = 9.73, 95%CI (2.65-35.76), = 0.001] were identified as predictors to detect DSAs. IPV did not impact on patient- or graft-survival rates during the follow-up.

Conclusion: Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a DSA after liver transplantation.
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http://dx.doi.org/10.3748/wjg.v24.i16.1795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922997PMC
April 2018

Transjugular intrahepatic portosystemic shunt placement before abdominal intervention in cirrhotic patients with portal hypertension: lessons from a pilot study.

Eur J Gastroenterol Hepatol 2018 Jan;30(1):21-26

Department of Hepatology and Gastroenterology.

Background: Abdominal interventions are usually contraindicated in patients with cirrhosis and portal hypertension because of increased morbidity and mortality. Decreasing portal pressure with transjugular intrahepatic portosystemic shunt (TIPS) may improve patient outcomes. We report our experience with patients treated by neoadjuvant TIPS to identify those who would most benefit from this two-step procedure.

Patients And Methods: All patients treated by dedicated neoadjuvant TIPS between 2005 and March 2013 in two tertiary referral hospitals were included. The primary endpoint was the rate of failure, defined by the inability to proceed to the planned intervention after TIPS placement or persistent liver decompensation 3 months after intervention. The secondary endpoints were the rate of complications, parameters associated with failure, and 1-year survival.

Results: Twenty-eight consecutive patients were included, with a mean age of 61.2±6.6 years, mean Child-Pugh score of 6.6±1.5, and mean model for end-stage liver disease score of 10.4±3.3. Procedures were digestive (43%) or liver (25%) resections, abdominal wall surgery (21%), or interventional gastrointestinal endoscopies (11%). The scheduled procedure was performed in 24 (86%) patients within a median of 25 days after TIPS. Procedure failures occurred in six (21%) patients: four did not undergo surgery and two experienced persistent liver decompensation. Seven (25%) patients had postoperative complications, mainly local. Viral origin of cirrhosis, history of encephalopathy, and hepatic surgery were found to be associated with failure. One-year survival in the whole cohort was 70%.

Conclusion: In selected patients, extrahepatic surgery or interventional endoscopies can be safely performed after portal hypertension has been controlled by TIPS.
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http://dx.doi.org/10.1097/MEG.0000000000000990DOI Listing
January 2018

Rescue associating liver partition and portal vein ligation for staged hepatectomy after portal embolization: Our experience and literature review.

World J Clin Oncol 2017 Aug;8(4):351-359

Charlotte Maulat, Antoine Philis, Bérénice Charriere, Bertrand Suc, Fabrice Muscari, Department of Visceral Surgery, Toulouse-Rangueil University Hospital, 31059 Toulouse Cedex 9, France.

Aim: To report a single-center experience in rescue associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), after failure of previous portal embolization. We also performed a literature review.

Methods: Between January 2014 and December 2015, every patient who underwent a rescue ALPPS procedure in Toulouse Rangueil University Hospital, France, was included. Every patient included had a project of major hepatectomy and a previous portal vein embolization (PVE) with insufficient future liver remnant to body weight ratio after the procedure. The ALPPS procedure was performed in two steps (ALPPS-1 and ALPPS-2), separated by an interval phase. ALPPS-2 was done within 7 to 9 d after ALPPS-1. To estimate the FLR, a computed tomography scan examination was performed 3 to 6 wk after the PVE procedure and 6 to 8 d after ALPPS-1. A transcystic stent was placed during ALPPS-1 and remained opened during the interval phase, in order to avoid biliary complications. Postoperative liver failure was defined using the 50-50 criteria. Postoperative complications were assessed according to the Dindo-Clavien Classification.

Results: From January 2014 to December 2015, 7 patients underwent a rescue ALPPS procedure. Median FLR before PVE, ALPPS-1 and ALPPS-2 were respectively 263 cc (221-380), 450 cc (372-506), and 660 cc (575-776). Median FLR/BWR before PVE, ALPPS-1 and ALPPS-2 were respectively 0.4% (0.3-0.5), 0.6% (0.5-0.8), and 1% (0.8-1.2). Median volume growth of FLR was 69% (18-92) after PVE, and 45% (36-82) after ALPPS-1. The combination of PVE and ALPPS induced a growth of median initial FLR of +408 cc (254-513), leading to an increase of +149% (68-199). After ALPPS-2, 4 patients had stage I-II complications. Three patients had more severe complications (one stage III, one stage IV and one death due to bowel perforation). Two patients suffered from postoperative liver failure according to the 50/50 criteria. None of our patients developed any biliary complication during the ALPPS procedure.

Conclusion: Rescue ALPPS may be an alternative after unsuccessful PVE and could allow previously unresectable patients to reach surgery. Biliary drainage seems to reduce biliary complications.
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http://dx.doi.org/10.5306/wjco.v8.i4.351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554879PMC
August 2017

Bleeding Recurrence and Mortality Following Interventional Management of Spontaneous HCC Rupture: Results of a Multicenter European Study.

World J Surg 2018 01;42(1):225-232

Department of General Surgery and Liver Transplantation, APHM, Hôpital de la Conception, Marseille University Hospital, Marseille, France.

Background: The incidence of spontaneous rupture of hepatocellular carcinoma (HCC) is low in Europe, at less than 3%. HCC rupture remains a life-threatening complication, with mortality reported between 16 and 30%. The risk of bleeding recurrence has never been clearly evaluated in such clinical situation. The objectives of this study were to evaluate the current risk of mortality related to HCC rupture and to focus on the risk of bleeding recurrence following interventional management.

Methods: All patients admitted to 14 French-Italian surgical centers for spontaneous rupture of HCC between May 2000 and May 2012 were retrospectively included. Clinical data, imaging features, relevant laboratory data, treatment strategies, and prognoses were analyzed.

Results: Overall, 58 of the 138 included patients (42%) had cirrhosis. Thirty-five patients (25%) presented with hemorrhagic shock, and 19% with organ(s) dysfunction. Bleeding control was obtained by interventional hemostasis, emergency liver resection, and conservative medical management in 86 (62%), 24 (18%), and 21 (15%) patients, respectively. Best supportive care was chosen for 7 (5%) patients. The mortality rate following rupture was 24%. The bleeding recurrence rate was 22% with related mortality of 52%. In multivariate analysis, a bilirubin level >17 micromol/L (HR 3.768; p = 0.006), bleeding recurrence (HR 5.400; p < 0.0001), and ICU admission after initial management (HR 8.199; p < 0.0001) were associated with in-hospital mortality.

Conclusion: This European, multicenter, large-cohort study confirmed that the prognosis of ruptured HCC is poor with an overall mortality rate of 24%, despite important advances in endovascular techniques. Overall, the rate of bleeding recurrence was more than 20%, with a related high risk of mortality.
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http://dx.doi.org/10.1007/s00268-017-4163-8DOI Listing
January 2018

Management of liver cancer. The Surgeon's point of view.

Rep Pract Oncol Radiother 2017 Mar-Apr;22(2):176-180. Epub 2017 Mar 23.

Department of Digestive Surgery and Liver Transplantation, Rangueil Hospital, 1, Avenue du Pr Jean Poulhès TSA 50032, 31059 Toulouse Cedex, France.

During the last twenty years, a huge progress has been achieved in the treatment of liver cancer and recent strategies include interventional radiology, chemotherapy regimens and surgery. Meanwhile, Stereotactic Body Radiation Therapy (SRBT) has developed in the treatment of all organs with millimetre accuracy, very few side effects and a high control rate. So, SRBT has become a therapeutic weapon in his own right in liver tumour treatment. Many publications have reported encouraging results in colorectal liver metastasis, hepatocellular carcinoma on cirrhosis and peripheric cholangiocarcinoma. It is important that radiation therapists involve systematic multidisciplinary "liver tumour" meetings to discuss therapeutic indications and initiate treatments quickly.
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http://dx.doi.org/10.1016/j.rpor.2017.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411896PMC
March 2017

Short-term outcomes of laparoscopic vs. open liver resection for hepatocellular adenoma: a multicenter propensity score adjustment analysis by the AFC-HCA-2013 study group.

Surg Endosc 2017 10 9;31(10):4136-4144. Epub 2017 Mar 9.

Department of Digestive, Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor University Hospital, Paris Est University, APHP, 51 Avenue du Maréchal de Lattre de Tassigny, 94010, Creteil, France.

Background: Patients with hepatocellular adenomas are, in selected cases, candidates for liver resection, which can be approached via laparoscopy or laparotomy. The present study aimed to investigate the effects of the surgical approach on the postoperative morbidities of both minor and major liver resections.

Methods: In this multi-institutional study, all patients who underwent open or laparoscopic hepatectomies for hepatocellular adenomas between 1989 and 2013 in 27 European centers were retrospectively reviewed. A multiple imputation model was constructed to manage missing variables. Comparisons of both the overall rate and the types of complications between open and laparoscopic hepatectomy were performed after propensity score adjustment (via the standardized mortality ratio weighting method) on the factors that influenced the choice of the surgical approach.

Results: The laparoscopic approach was selected in 208 (38%) of the 533 included patients. There were 194 (93%) women. The median age was 38.9 years. After the application of multiple imputation, 208 patients who underwent laparoscopic operations were compared with 216 patients who underwent laparotomic operations. After adjustment, there were 20 (9.6%) major liver resections in the laparoscopy group and 17 (7.9%) in the open group. The conversion rate was 6.3%. The two surgical approaches exhibited similar postoperative morbidity rates and severities. Laparoscopic resection was associated with significantly less blood loss (93 vs. 196 ml, p < 0.001), a less frequent need for pedicle clamping (21 vs. 40%, p = 0.002), a reduced need for transfusion (8 vs. 24 red blood cells units, p < 0.001), and a shorter hospital stay (5 vs. 7 days, p < 0.001). The mortality was nil.

Conclusions: Laparoscopy can achieve short-term outcomes similar to those of open surgery for hepatocellular adenomas and has the additional benefits of a reduced blood loss, need for transfusion, and a shorter hospital stay.
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http://dx.doi.org/10.1007/s00464-017-5466-4DOI Listing
October 2017

Prediction of hepatocellular carcinoma recurrence after liver transplantation: Comparison of four explant-based prognostic models.

Liver Int 2017 05 24;37(5):717-726. Epub 2017 Mar 24.

Service d'hépatologie, Hôpital Henri Mondor, Créteil, France.

Aim: Discordance between pre-LT imaging and explanted liver findings have been reported after liver transplantation (LT) for hepatocellular carcinoma (HCC), suggesting the need of reassessing the risk of HCC recurrence post-LT. Our aims were to compare pre-LT imaging and explants features and to test the performances of four explant-based predictive models of recurrence in an external cohort.

Methods: Staging according to pre-LT imaging and explant features were compared. Four explants-based models were retrospectively tested in a cohort of 372 patients transplanted for HCC in 19 French centres between 2003 and 2005. Accuracies of the scores were compared.

Results: Pre-LT imaging underestimated tumour burden in 83 (22.7%) patients according to Milan criteria. The highest AUCs for prediction of 5-years recurrence were observed in the "Up to seven" (0.7915 [95% CI: 0.7339-0.849]) and Decaens models (0.747 [95% CI: 0.6877-0.806]), with two levels of risk: low (10%) and high (>50%). Chan and Iwatsuki models identified 3 and 4 levels of risk, but had lower AUCs (0.68 and 0.70) respectively. Accuracy of the "Up to seven" model was superior to the Decaens model (P=.034), which was superior to the Chan model (P=.0041) but not to the Iwatsuki model (P=.17).

Conclusion: Pre-LT imaging underestimates tumour burden, and prediction of recurrence should be reassessed after LT. The explant-based "Up to seven" and Decaens models provided the best accuracy for prediction of 5-year recurrence, identifying only two levels of risk. New models are needed to further refine the prediction of recurrence after LT.
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http://dx.doi.org/10.1111/liv.13388DOI Listing
May 2017

Endoscopic ultrasound-guided fine-needle aspiration plus KRAS and GNAS mutation in malignant intraductal papillary mucinous neoplasm of the pancreas.

Endosc Int Open 2016 Dec 10;4(12):E1228-E1235. Epub 2016 Nov 10.

Department of Gastroenterology and INSERM UMR 1037, CHU Toulouse Rangueil, University of Toulouse, Toulouse, France; INSERM UMR 1037, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France.

and mutations are common in intraductal papillary mucinous neoplasia of the pancreas (IPMN). The aims of this study were to assess the role of pre-therapeutic cytopathology combined with and mutation assays within cystic fluid sampled by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to predict malignancy of IPMN. We prospectively included 37 IPMN patients with clinical and/or imaging predictors of malignancy (men: 24; mean age: 69.5 years). Cytopathology (performed on cystic fluid and/or IPMN nodules), (Exon 2, codon 12) and (Exon 8, codon 201) mutations assays (using TaqMan allelic discrimination) were performed on EUS-FNA material. The final diagnosis was obtained from IPMN resections (n = 18); surgical biopsies, EUS-FNA analyses, and follow-up (n = 19): 10 and 27 IPMN were benign and malignant, respectively. Sensitivity, specificity, positive and negative predictive values, and accuracy of cytopathology alone to diagnose IPMN malignancy were 55 %, 100 %, 100 %, 45 %, and 66 %, respectively. When mutation analysis was combined with cytopathology these values were 92 %, 50 %, 83 %, 71 %, and 81 %, respectively. assays did not improve the performances of cytopathology alone or those of cytopathology plus a assay. In patients with a likelihood of malignant IPMN at pre-therapeutic investigation, testing for mutations in cystic fluid sampling by EUS-FNA improved the results of cytopathology for the diagnosis of malignancy whereas mutation assay did not.
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http://dx.doi.org/10.1055/s-0042-117216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161125PMC
December 2016

Outcomes of patients with hepatocellular carcinoma are determined in multidisciplinary team meetings.

J Surg Oncol 2017 Mar 4;115(3):330-336. Epub 2016 Nov 4.

Service de chirurgie digestive et hépatobiliaire, Centre Hospitalier Universitaire Rangueil, Université Paul Sabatier III, Toulouse, France.

Background And Objectives: To analyze overall survival (OS) rates for the three curative treatments of hepatocellular carcinoma (HCC) on an intention-to-treat (ITT) basis.

Methods: Cohort study based on data from a multidisciplinary team meeting (MDT) dedicated to HCC. From 2006 to 2013, we included every patient with newly diagnosed HCC, for whom curative treatment (liver transplantation (LT), radiofrequency ablation (RFA), surgical resection (SR)) was decided upon.

Results: We included 387 consecutive patients. LT was decided in 136 cases, RFA in 131 cases, SR in 120 cases. Sixty-six percent of patients received the planned treatment. Five-year OS on an ITT basis were: 35% for the LT-group, 32% for the RFA-group, 34% for the SR-group (P = 0.77). In multivariate analyses, the main negative prognostic factors were not following the MDT decision (HR: 0.39, CI95% [0.27-0.54], P < 0.001), elevated alpha-fetoprotein level (HR: 0.63, CI95% [0.45-0.87], P = 0.005), being outside the Milan criteria (HR: 0.45, CI95% [0.31-0.65], P < 0.001). When curative treatment was performed, per-protocol 5-year OS were 64% for LT, 34% for RFA, 40% for SR.

Conclusion: On an ITT basis, OS was similar whatever the type of curative treatment chosen in MDT. Negative prognostic factors were not following the MDT decision, elevated alpha-fetoprotein, being outside the Milan criteria. J. Surg. Oncol. 2017;115:330-336. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jso.24500DOI Listing
March 2017

Histological long-term outcomes from acute antibody-mediated rejection following ABO-compatible liver transplantation.

J Gastroenterol Hepatol 2017 Apr;32(4):887-893

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.

Background And Aim: Acute antibody-mediated rejection (aAMR) is an unusual complication after orthotopic ABO-compatible liver transplantation. To date, the clinical and histological long-term outcomes after aAMR are not well known.

Method: Herein, we describe nine cases of aAMR that occurred in our liver-transplant center between 2008 and 2016, with an initial and reevaluation liver biopsy available for reexamination.

Results: Two patients presented with aAMR at 10.5 (10, 11) days post-transplantation, caused by preformed donor-specific antibodies. Seven other recipients developed de novo donor-specific antibodies and aAMR at 11.2 (3-24) months post-transplantation. Eight of the nine patients received a B-cell targeting agent (rituximab, with or without plasma exchange), associated with polyclonal antibodies (three patients) or intravenous immunoglobulins (three patients). At the last follow up (i.e. 21 [4-90] months post-aAMR), seven patients were alive, including two patients with normal liver tests. Grafts' survival was 66%. A liver biopsy performed at 11.5 (5-48.5) months after the first biopsy showed no significant improvement in aAMR score (from 2 ± 1.3 to 1.6 ± 1.5, P = 0.6), a significant improvement in chronic AMR score (from 37 ± 9 to 25 ± 8, P = 0.003) and an increase in the Metavir score (1.2 ± 0.6 to 2.1 ± 0.9, P = 0.03).

Conclusion: In this study, a B-cell-depleting agent seemed to improve the prognosis of aAMR in selected cases, but several patients kept active lesions antibody-mediated rejection.
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http://dx.doi.org/10.1111/jgh.13613DOI Listing
April 2017

Outcomes of Rehepatectomy for Colorectal Liver Metastases: A Contemporary Multi-Institutional Analysis from the French Surgical Association Database.

Ann Surg Oncol 2016 12 29;23(Suppl 5):894-903. Epub 2016 Aug 29.

Institut Hospitalo-Universitaire (IHU), Institute for Minimally Hybrid Invasive Image-Guided Surgery, Université de Strasbourg, Strasbourg, France.

Background: Recurrence remains frequent after curative-intent hepatectomy for colorectal liver metastases (CRLM). We sought to define short- and long-term outcomes, and identify prehepatectomy factors associated with survival, following rehepatectomy (RH) for recurrence.

Methods: We conducted a multi-institutional cohort study of hepatectomy for CRLM over 2006-2013. Second-stage resections were excluded. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS) assessed using Kaplan-Meier methods. Secondary outcomes included 30-day overall morbidity and mortality, and survival from recurrence. Outcomes of RH and initial hepatectomy (IH) were compared.

Results: Of 2771 hepatectomies included in the study, 447 were RH. Median operative time, 30-day morbidity, mortality, and median length of stay did not differ for RH and IH. Five-year OS did not statistically differ, i.e. 56.5 % from RH and 67.6 % from IH [adjusted hazard ratio (HR) 0.9, 95 % confidence interval (CI) 0.5-1.7], and 5-year RFS was inferior after RH (18.5 vs. 28.8 %; adjusted HR 1.3, 95 % CI 1.0-1.7). In patients who eventually recurred, 5-year survival from the time of recurrence did not differ whether it was after RH (46.5 %) or after IH (60.3 %) (adjusted HR 1.1, 95  % CI 0.8-1.8). Rectal primary tumor (HR 1.4, 95 % CI 1.0-2.1) and metastasis ≥3 cm (HR 1.3, 95 % CI 1.1-2.7) were independently associated with RFS, but not OS, after RH.

Conclusion: Short-term outcomes of RH did not differ from IH. While recurrence was more frequent after RH than IH, it did not impact OS. Survival from the time of recurrence did not differ whether recurrence occurred after RH or after IH. CRLM recurrence can be treated with curative intent with excellent long-term outcomes.
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http://dx.doi.org/10.1245/s10434-016-5506-7DOI Listing
December 2016

Contribution of alpha-fetoprotein in liver transplantation for hepatocellular carcinoma.

World J Hepatol 2016 Jul;8(21):881-90

Bérénice Charrière, Charlotte Maulat, Bertrand Suc, Fabrice Muscari, Department of Visceral Surgery, Toulouse-Rangueil University Hospital, 31059 Toulouse, France.

Alpha-fetoprotein (AFP) is the main tumor biomarker available for the management of hepatocellular carcinoma (HCC). Although it is neither a good screening test nor an accurate diagnostic tool for HCC, it seems to be a possible prognostic marker. However, its contribution in liver transplantation for HCC has not been fully determined, although its use to predict recurrence after liver transplantation has been underlined by international societies. In an era of organ shortages, it could also have a key role in the selection of patients eligible for liver transplantation. Yet unanswered questions remain. First, the cut-off value of serum AFP above which liver transplantation should not be performed is still a subject of debate. We show that a concentration of 1000 ng/mL could be an exclusion criterion, whereas values of < 15 ng/mL indicate patients with an excellent prognosis whatever the size and number of tumors. Monitoring the dynamics of AFP could also prove useful. However, evidence is lacking regarding the values that should be used. Today, the real input of AFP seems to be its integration into new criteria to select patients eligible for a liver transplantation. These recent tools have associated AFP values with morphological criteria, thus refining pre-existing criteria, such as Milan, University of California, San Francisco, or "up-to-seven". We provide a review of the different criteria submitted within the past years. Finally, AFP can be used to monitor recurrence after transplantation, although there is little evidence to support this claim. Future challenges will be to draft new international guidelines to implement the use of AFP as a selection tool, and to determine a clear cut-off value above which liver transplantation should not be performed.
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http://dx.doi.org/10.4254/wjh.v8.i21.881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4958698PMC
July 2016

KRAS G12D Mutation Subtype Is A Prognostic Factor for Advanced Pancreatic Adenocarcinoma.

Clin Transl Gastroenterol 2016 Mar 24;7:e157. Epub 2016 Mar 24.

Department of Gastroenterology, CHU Toulouse Rangueil, University of Toulouse, Toulouse, France.

Objectives: There is no molecular biomarker available in the clinical practice to assess the prognosis of advanced pancreatic carcinoma. This multicenter prospective study aimed to investigate the role of KRAS mutation subtypes within the primary tumor to determine the prognosis of advanced pancreatic cancer.

Methods: The exon-2 KRAS mutation status was tested on endoscopic ultrasound-guided fine-needle aspiration biopsy material (primary tumor; restriction fragment-length polymorphism plus sequencing and TaqMan allelic discrimination) of patients with proven locally advanced and/or metastatic pancreatic ductal carcinoma. We used the Kaplan-Meier method, log-rank test, and Cox's model to evaluate the impact of KRAS status on the overall survival (OS), adjusting for age, stage of disease, clinical performance status, CA 19-9 levels, and treatment.

Results: A total of 219 patients (men: 116; mean age: 67±9.4 years) were included: 147 harbored a codon-12 KRAS mutation (G12D: 73; G12V: 53; G12R: 21) and 72 had a wild-type KRAS. There was no difference in the OS between patients with a mutant KRAS (8 months; 95% confidence interval (95% CI): 8.7-12.3) and the wild-type (9 months; 95% CI: 8.7-12.8; hazard ratio (HR): 1.03; P=0.82). However, the patients with a G12D mutation had a significantly shorter OS (6 months; 95% CI: 6.4-9.7) compared with the other patients (OS: 9 months; 95% CI: 10-13; HR: 1.47; P=0.003; i.e., wild type: 9 months, G12V: 9 months, G12R: 14 months). Similar results were observed in the subgroup of 162 patients who received chemotherapy (HR: 1.66; P=0.0013; G12D (n=49): 8 months, wild type (n=56): 10 months, G12V (n=38): 10 months, G12R (n=19): 14 months). Multivariate analyses identified KRAS G12D as an independent predictor for worse prognosis within the entire series (HR: 1.44; P=0.01) and in the subgroup of patients that received chemotherapy (HR: 1.84; P=0.02).

Conclusions: The KRAS G12D mutation subtype is an independent prognostic marker for advanced pancreatic ductal carcinoma. Codon and amino-acid-specific mutations of KRAS should be considered when evaluating the prognoses as well as in trials testing drugs that target RAS and downstream RAS pathways.
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http://dx.doi.org/10.1038/ctg.2016.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822095PMC
March 2016