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Background While outcomes after spleen-preserving distal pancreatectomy (SP-DP) are widely reported, the impact on splenic parenchyma is poorly studied. This study aimed to assess splenic imaging after SP-DP with splenic vessels removal or preservation, and to compare postoperative outcomes especially spleen-related.Methods All patients undergoing SP-DP with splenic vessels removal (Warshaw technique, WDP) or preservation (Kimura technique, KDP) between 2010 and 2022 in two tertiary centres were retrospectively analysed. Splenic ischemia and volume at early/late imaging and postoperative outcomes were reviewed.Results Ninety-five patients were included, 57 in WDP and 38 in KDP groups. The median age and Charlson’s Comorbidity Index were significantly higher in WDP group compared with KDP group. Postoperative morbidity was similar between groups. There was more splenic ischemia at early imaging in WDP compared to KDP groups (53% vs. 14%, p = 0.007), especially severe ischemia (22% vs. 0). Splenic partial atrophy was observed in 30% and 0% of WDP and KDP groups, respectively (p Conclusions Splenic ischemia appeared in one half of patients undergoing SP-DP with splenic vessels removal at early imaging, and partial splenic atrophy in 30% at late imaging, without clinical impact neither complete splenic atrophy. Charlson Comorbidity Index and postoperative day 6 platelets levels could help to predict the occurrence of splenic atrophy.

Background It is of interest to determine the incidence and molecular characteristics of NTRK gene fusions in patients with bilio-pancreatic cancers, because of possible treatment with TRK inhibitors for advanced tumors. The aim of the present study was to apply the guidelines for NTRK testing algorithm to a series of patients with bilio-pancreatic cancers. Methods Immunohistochemistry screening was applied on formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies, or cytological samples of biliary tract and pancreatic adenocarcinomas. The presence of at least a weak staining in rare tumor cells led to testing by 2 RNA-based NGS panels. Results For biliary tract tumors, 153 samples have been selected. A total of 140 samples were suitable to perform IHC, and 17 samples were IHC positive. RNA NGS testing of the 17 IHC-positive samples revealed a single NTRK3 gene fusion (ETV6(4)-NTRK3(14)) that was detected by both NGS panels. In this perihilar cholangiocarcinoma, IHC performed on a biopsy showed a weak focal cytoplasmic and nuclear staining. No other NTRK fusion was detected on the 16 other samples with both panels. Overall in the patients screened by IHC and confirmed by NGS, the percentage of NTRK fusions was 0.7%. For pancreatic cancers, 319 samples have been selected and 297 were suitable to perform IHC. Nineteen samples were IHC positive. No fusion was detected by NGS. Conclusion NTRK gene fusions are rare in bilio-pancreatic cancers but testing is of high interest due to possible treatment with specific TRK inhibitors.

Background Concomitant venous resection during pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma with mesenterico-portal vein involvement is increasingly performed to achieve oncological resection. This study aims to report a single centre experience in peritoneal patch (PP) as autologous graft for vascular reconstruction (VR) during PD. Methods A retrospective analysis of all patients who underwent PD + VR with PP between December 2019 and September 2020 was performed, using a prospective collected database. Postoperative outcome and pathological margins were evaluated. Venous patency was assessed by computed tomography at day 7 and week 12 post surgery. Results Fifteen patients underwent PD + VR with PP reconstruction for pancreatic cancer, including one total pancreatectomy. VR consisted of lateral (n = 14) or tubular (n = 1) patch. The median PP length was 30 mm [26.3-33.8] and venous clamping time 30 min [27.5-39.0]. Computed tomography showed a patent VR in 93.3% and 53.3% after 7 days and 12 weeks, respectively; venous patency loss was always asymptomatic. The only postoperative VR-related complication was one mesenteric venous thrombosis. Five other patients experienced VR-unrelated complications: septic shock (n = 3), biliary fistula (n = 1) and post-traumatic subdural hematoma (n = 1). Mortality was nihil. At pathology, R0 resection (≥1 mm) was observed in 40.0% (6/15), venous margin was free in 46.7% (7/15), and venous wall was involved in 40.0% (6/15). Conclusions Use of PP as venous substitute during PD + VR is safe and feasible with an acceptable postoperative morbidity, and a decreased but asymptomatic venous patency after 12 weeks which should question the role of anticoagulation therapy.

Given the lack of direct comparative evidence, we aimed to compare the oncological outcomes of localized pancreatic ductal adenocarcinoma (PDAC) treated in the same tertiary cancer center with isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) or conventional chemoradiotherapy (CRT). Biopsy-proven borderline/locally advanced patients treated with iHD-SBRT (35 Gy in 5 fractions with a simultaneous integrated boost up to 53 Gy) or CRT (45–60 Gy in 25–30 fractions) were retrospectively included from January 2006 to January 2021. The median overall survival (mOS) was evaluated trough uni- and multivariate analyses. The progression free survival (PFS) and the 1-year local control (1-yLC) were also reported. Eighty-two patients were included. The median follow-up was 19.7 months. The mOS was in favour of the iHD-SBRT group (22.5 vs. 15.9 months, p < 0.001), including after multivariate analysis (HR 0.39 [CI95% 0.18–0.83], p = 0.014). The median PFS and the 1-yLC were also significantly better for iHD-SBRT (median PFS: 16.7 vs. 11.5 months, p = 0.011; 1-yLC: 75.8 vs. 39.3%, p = 0.004). In conclusion, iHD-SBRT is a promising RT option and may offer an improvement in OS in comparison to CRT for localized PDAC. Further validation is required to confirm the exact role of iHD-SBRT and the optimal therapeutic sequence for the treatment of localized PDAC.

Background The recent COVID-19 pandemic has led several countries worldwide to confine the population. Consequently, people’s mobility and physical activity are limited in addition to a negative psychosocial effect. The aim of this study was to assess the impact of COVID-19 crisis on short-term weight loss and the remission of obesity-associated comorbidities in patients undergoing sleeve gastrectomy (SG). Methods A case-control study was conducted comparing percentage of total weight loss (%TWL), excess weight lost (%EWL), and the remission rate of obesity-related comorbidities at the first postoperative year between patients who underwent primary SG between June 2019 and October 2019 (1-year postoperative period affected by COVID-19 lockdown; COV-group), and a control group operated between June 2018 and October 2018 (1-year postoperative period not affected by COVID-19 lockdown; CONTROL-group). Results In total, 45 patients from COV-group were compared to 57 patients from CONTROL-group. Demographic data were similar between groups. The follow-up rate at 1 year was 100%. The mean %TWL and %EWL was lower at 28.2 ± 12.7% and 67.6 ± 23.5% in COV-group patients compared to 34.3 ± 14.1% and 78.3 ± 27.2% in CONTROL-group patients at 1 year from SG (p=0.025 and p=0.036, respectively). The remission rate of obesity-related comorbidities at 1 year from SG including type 2 diabetes mellitus, hypertension, dyslipidemia, and obstructive sleep apnea syndrome was 57.1%, 60.0%, 71.4%, and 41.7% in COV-group and 66.7%, 72.4%, 85.3%, and 52.9% in CONTROL-group, respectively, without any statistically significant difference between groups. Conclusions The COVID-19 lockdown had a negative effect on weight loss in the first year after SG. Larger studies are needed to confirm these results, and we are expecting for a longer follow-up to evaluate the long-term impact on weight loss and comorbidities.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) became the most frequently performed bariatric procedure worldwide, gaining rapidly popularity thanks to its technical simplicity and the relatively good results. The aim of this Belgian-French study was to evaluate postoperative complications, weight loss, and resolution of obesity-related comorbidities after LSG, and identify predictive factors of weight loss failure. PATIENTS AND METHODS: A prospective multicenter study was conducted on all LSG performed during 2014 in 7 centers. Their demographic, preoperative, and postoperative data were prospectively collected and analyzed statistically. RESULTS: Overall 529 patients underwent LSG, with a mean preoperative weight and body mass index (BMI) of 118.9 ± 19.9 kg and 42.9 ± 5.5 kg/m2, respectively. Postoperative mortality was null and early postoperative morbidity was 6%, including 2.5% of gastric leakage. BMI significantly decreased to 31.1 kg/m2 and 30.0 kg/m2 at 1 and 3 years, respectively (p < .001). The mean %EWL was 77.2 and 74.6% at 1 and 3 years. A significant reduction in dyslipidemia (28.0-16.8%), obstructive sleep apnea (OSAS) (34.6-23.3%) and arterial hypertension (HTN) (30.4-20.2%) was observed after 3 years, but it does not concern diabetes and gastroesophageal reflux disease (GERD). At multivariate analysis, age > 50 years old, BMI >50 kg/m2 and previous laparoscopic adjustable gastric banding (LAGB) remained independent predictors of weight loss failure. CONCLUSIONS: LSG for morbid obesity is safe and effective. Satisfactory outcome after 3 years can be achieved regarding %EWL and some comorbidities such as dyslipidemia, OSAS, and HTN, but not diabetes and GERD. Age > 50 years old, BMI > 50 kg/m2 and previous LAGB were independent predictors of weight loss failure.

Pancreatic tumours are frequently associated with obstructive jaundice requiring preoperative biliary drainage (PBD) before pancreatoduodenectomy (PD), exposing patients to infectious complications. This study aims to compare postoperative complications after PD with or without PBD and to analyse bile bacteriology and antibiotic susceptibility.All patients undergoing PD between 2014 and 2019 were retrospectively evaluated, and postoperative outcomes were compared according to PBD use. Prophylactic narrow-spectrum antibiotic therapy was given for 24 h, then adapted according to bacteriologic profile. Intraoperative bile cultures and antibiograms were collected.Among 164 patients with intraoperative bile culture during PD (75 PBD+, 89 PBD-), an infected bile was observed in 95% and 70% of PBD + and PBD- groups, respectively (PBD exposes nearly 100% of patients undergoing PD to bile infection and an increased duration of postoperative antimicrobial therapy, without increasing infectious complications in this study. Adaptation of antimicrobial prophylaxis should be further evaluated according to performance of PBD and local epidemiology, in order to avoid overuse of antibiotics.

Background: Our aim was to evaluate the feasibility and safety of isotoxic high-dose (iHD) stereotactic body radiation therapy (SBRT) in a total neoadjuvant sequence for the treatment of localized pancreatic adenocarcinoma. Materials and methods: Biopsy-proven borderline resectable/locally advanced pancreatic cancer (BR/LAPC) patients were included in this observational prospective analysis from August 2017 to April 2020 without excluding tumours showing a radiological direct gastrointestinal (GI) invasion. An induction chemotherapy by modified fluorouracil, irinotecan and oxaliplatin was performed for a median of six cycles. In case of non-progression, an isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) was delivered in 5 fractions followed by a surgical exploration. The primary endpoint was acute/late gastrointestinal grade ⩾3 toxicity. Secondary endpoints were overall survival (OS), progression-free survival (PFS) and local control (LC). Results: A total of 39 consecutive patients (21 BR and 18 LAPC) were included: 34 patients (87.2%, 18 BR and 16 LAPC) completed the planned neoadjuvant sequence. After iHD-SBRT, 19 patients [55.9% overall, 13/18 BR (72.2%) and 6/16 LAPC (37.5%)] underwent an oncological resection among the 25 patients surgically explored (73.5%). The median follow up was 18.2 months. The rates of acute and late GI grade 3 toxicity were, respectively, 2.9% and 4.2%. The median OS and PFS from diagnosis were, respectively, 24.5 and 15.6 months. The resected patients had improved median OS and PFS in comparison with the non-resected patients (OS: 32.3 versus 18.2 months, p = 0.02; PFS: 24.1 versus 7.1 months, p Conclusions: iHD-SBRT displays an excellent toxicity profile, also for potentially high-risk patients with radiological direct GI invasion at diagnosis and can be easily integrated in a total neoadjuvant strategy. The oncological outcomes are promising and emphasise the need for further exploration of iHD-SBRT in phase II/III trials.

Introduction: SMAD4, the central mediator of the Transforming Growth-Beta (TGF-Beta) signaling pathway, is inactivated in 50-55% of pancreatic ductal adenocarcinomas (PDACs). SMAD4 loss of expression has been described as a negative prognostic factor in PDAC and associated with increased rate of metastasis and resistance to adjuvant therapy. However, the impact of SMAD4 inactivation in patients receiving neoadjuvant therapy (NAT) is not well characterized. The aim of our study is to investigate if SMAD4 loss is a prognostic factor in a cohort of patients who underwent surgery for PDAC and, more specifically, in patients receiving NAT. Material and methods: We analyzed a single center retrospective series of 204 patients who underwent surgical resection for PDAC between 2004-2021. SMAD4 nuclear expression was semi-quantitively assessed by immunohistochemistry (IHC) on tumor samples and related to clinical variables including overall survival (OS) and disease free survival (DFS). Results: Among the 204 patients, 64 (31,37%) received NAT and 140 (68,63%) did not. In the NAT cohort, 33 (51,47%) tumors were SMAD4-positive and 31 (48,43%) were SMAD4-negative and in the non-NAT group, 84 (60%) and 56 (40%) patients presented SMAD4-positive and -negative tumors, respectively (p=0.28). Both in the NAT and non-NAT cohort of patients, SMAD4 status was not associated with clinico-pathological variables and did not impact OS. However, regarding DFS, in patients without NAT, SMAD4 loss seems to be associated with shorter DFS (p=0.073). In a multivariate analysis including the significant clinico-pathological variables, SMAD4 status showed a tendency to remain an independent prognostic variable (p=0.052). Moreover, in patients that received NAT, univariate analysis indicated that SMAD4 loss was associated with worse DFS (p=0.018). However, in a multivariate analysis, only vascular invasion (p=0.02) and the subtype of administrated NAT (FOLFIRINOX or GEMCITABINE-based) (p=0.0004) were independent prognostic factors for DFS. We therefore evaluated the prognostic significance of SMAD4 loss in a homogenous group of patients receiving FOLFIRINOX-based therapy (n=45). Univariate and multivariate analysis indicated that in these patients, SMAD4 loss was an independent negative prognostic factor (p=0.009) as well as vascular invasion (p=0.003). Conclusion: This study highlights the potential prognostic role of SMAD4 loss in the DFS of PDAC patients, more specifically in patients receiving NAT. Citation Format: Marie-Lucie Racu, Dana Bernardi, Aniss Chaouche, Egor Zindy, Julie Navez, Patrizia Loi, Calliope Maris, Jean Closset, Jean-Luc Van Laethem, Christine Decaestecker, Isabelle Salmon, Nicky D'Haene. Impact of SMAD4 loss in patients with pancreatic ductal adenocarcinoma receiving neoadjuvant therapy [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B043.

Summary Malpractice claims are a regularly increasing concern in gastrointestinal surgery. The goal of this study was to compare the current status of claims in two different French-speaking communities by a retrospective descriptive study of surgeons’ experiences, from the beginning of their practice up until December 31 2014. Data included the number, the reasons, and the results of medicolegal claims and their jurisdictions. Forty-three surgeons participated in this study. Two hundred medicolegal claims were analyzed. The mean number was 5.8 per surgeon. Bariatric surgery, colorectal surgery and parietal surgery were the most exposed. Forty-six (23%) faults were noted, while no fault was pronounced in 139 (69.5%) cases. The main reasons for lodging complaints were nosocomial infections, anastomotic leaks, poor postoperative care, hollow organ perforation, peripheral neurologic complication, and insufficient preoperative information. Forty-four percent of the complaints were analyzed by the conciliation and compensation commissions and 43.5% by the High Court. In the French-speaking group, there were 13 complaints, two of which gave rise to compensation. French surgeons are highly exposed to complaints: in French law, clumsiness or technical maladdress is considered as a fault. The patient should be informed preoperatively of all possible severe risks of a medical procedure. In Belgium, complications are exceptional and are considered random therapeutic events. Adhering to the recommendations emanating from the French High Authority of Health and Learned Societies as well as accreditation issued by the same High Authority should allow to decrease the number of undesirable events related to care and malpractice.

Resume La sinistralite en chirurgie viscerale constitue un sujet preoccupant et sa frequence augmente regulierement. Le but de cette etude est de realiser au sein d’un groupe de 50 chirurgiens un etat des lieux avec comparaison de 2 groupes francophones. Il s’agit d’une etude retrospective descriptive realisee depuis l’installation des 50 chirurgiens jusqu’au 31 decembre 2014. Les donnees principales repertoriees etaient le nombre, les motifs, les resultats des plaintes et les juridictions concernees. Quarante-trois chirurgiens ont participe a cette etude. Dans le groupe « francais », 200 plaintes ont ete analysees. Le nombre moyen de plainte etait de 5,8 par chirurgien. Les interventions chirurgicales les plus exposees ont ete la chirurgie bariatrique, la chirurgie colo-rectale et la chirurgie parietale. Aucune faute n’a ete retrouvee dans 69,5 % des cas. Quarante-six fautes ont ete notees et representent 23 % des plaintes). Les motifs principaux des plaintes etaient : infection nosocomiale, fistule anastomotique mauvaise prise en charge postoperatoire, perforation d’un organe creux, complication neurologique peripherique, information preoperatoire insuffisante. Quarante-quatre pour cent des plaintes ont ete analysees par la commission de conciliation et d’indemnisation (CCI) et 43,5 % par le tribunal de grande instance (TGI). Dans le groupe « francophone », il a ete retrouve 13 plaintes dont seules 2 ont fait l’objet d’une indemnisation. Les chirurgiens francais sont tres exposes aux plaintes : pour le droit francais, une maladresse est consideree comme une faute et le patient doit etre informe en preoperatoire de tout risque grave d’un acte medical. En Belgique, les complications exceptionnelles sont des aleas therapeutiques. Le respect des recommandations donnees par la haute autorite de sante (HAS) et les societes savante et l’accreditation par l’HAS des chirurgiens francais doivent permettre de diminuer les evenements indesirables lies aux soins et la sinistralite.

Background Sleeve gastrectomy (SG) is the most frequently performed bariatric procedure in the world. Our purpose was to evaluate the percentage of excess weight loss (%EWL), resolution of obesity-related comorbidities after SG, and identify predictive factors of weight loss failure. Methods A prospective cohort study of adults who underwent SG during 2014 in 7 Belgian-French centers. Their demographic, preoperative, and postoperative data were prospectively collected and analyzed statistically. Results Overall, 529 patients underwent SG, with a mean preoperative weight and body mass index (BMI) of 118.9 ± 19.9 kg and 42.9 ± 5.5 kg/m2, respectively. Body mass index significantly decreased to 32.2 kg/m2 at 5 years ( P < .001). The mean %EWL was 63.6% at 5 years. A significant reduction in dyslipidemia (28.0%-18.2%), obstructive sleep apnea (OSAS) (34.6%-25.1%), and arterial hypertension (HTN) (30.4%-21.5%) was observed after 5 years, but not for diabetes and gastroesophageal reflux disease (GERD). At multivariate analysis, age >50 years old, BMI >50 kg/m2, and previous laparoscopic adjustable gastric banding (LAGB) remained independent predictors of weight loss failure. Conclusions Five years after SG, weight loss was satisfactory; the reduction of comorbidities was significant for dyslipidemia, OSAS, and HTN, but not diabetes and GERD. Age >50 years old, BMI >50 kg/m2, and previous LAGB were independent predictors of weight loss failure.

info:eu-repo/semantics/published

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive solid tumours with an estimated 5-year overall survival rate of 7% for all stages combined. In this highly resistant disease that is located in the vicinity of many radiosensitive organs, the role of radiotherapy (RT) and indications for its use in this setting have been debated for a long time and are still under investigation. Although a survival benefit has yet to be clearly demonstrated for RT, it is the only technique, other than surgery, that has been demonstrated to lead to local control improvement. The adjuvant approach is now strongly challenged by neoadjuvant treatments that could spare patients with rapidly progressive systemic disease from unnecessary surgery and may increase free margin (R0) resection rates for those eligible for surgery. Recently developed dose-escalated RT treatments, designed either to maintain full-dose chemotherapy or to deliver a high biologically effective dose, particularly to areas of contact between the tumour and blood vessels, such as hypofractionated ablative RT (HFA-RT) or stereotactic body RT (SBRT), are progressively changing the treatment landscape. These modern strategies are currently being tested in prospective clinical trials with encouraging preliminary results, paving the way for more effective treatment combinations using novel targeted therapies. This review summarizes the current literature regarding the use of RT for the treatment of primary PDAC, describes the limitations of conventional RT, and discusses the emerging role of dose-escalated RT and heavy-particle RT., SCOPUS: re.j, info:eu-repo/semantics/published

BACKGROUND Goal-directed fluid therapy (GDFT) has been associated with improved patient outcomes. However, implementation of GDFT protocols remains low despite growing published evidence and the recommendations of multiple regulatory bodies in Europe. We developed a closed-loop-assisted GDFT management system linked to a pulse contour monitor to assist anaesthesiologists in applying GDFT. OBJECTIVE To assess the impact of our closed-loop system in patients undergoing major abdominal surgery in an academic hospital without a GDFT programme. DESIGN A case-control study with propensity matching. SETTING Operating rooms, Erasme Hospital, Brussels. PATIENTS All patients who underwent elective open major abdominal surgery between January 2013 and December 2016. INTERVENTION Implementation of our closed-loop-assisted GDFT in April 2015. METHODS A total of 104 patients managed with closed-loop-assisted GDFT were paired with a historical cohort of 104 consecutive non-GDFT patients. The historical control group consisted of patients treated before the implementation of the closed-loop-system, and who did not receive GDFT. In the closed-loop group, the system delivered a baseline crystalloid infusion of 3 ml kg h and additional 100 ml fluid boluses of either a crystalloid or colloid for haemodynamic optimisation. MAIN OUTCOME MEASURES The primary outcome was intra-operative net fluid balance. Secondary outcomes were composite major postoperative complications, composite minor postoperative complications and hospital length of stay (LOS). RESULTS Baseline characteristics were similar in both groups. Patients in the closed-loop group had a lower net intra-operative fluid balance compared with the historical group (median interquartile range [IQR] 2.9 [1.6 to 4.4] vs. 6.2 [4.0 to 8.3] ml kg h; P

Objectives: Postoperative complications after Laparoscopic sleeve gastrectomy (LSG) can dramatically compromise patient’s outcome. The aim of this study is to analyze the per- and postoperative short-term outcomes after LSG and to assess predictive risk factors of complications.Methods: The study group consisted of 790 patients (610 women and 180 men) who underwent LSG In 2014. All interventions were performed by 18 experienced surgeons members of the Club Coelio. Data about preoperative work-up, surgical techniques, 30-days postoperative morbidity and mortality were collected. Endpoints were perioperative morbidity and mortality and assessment of potential risk factors for complications.Results: Mean age and body mass index were respectively 39 years and 41.5kg/m2. Ninety-one patients (11.5%) had previous bariatric surgery. Morbidity rate was 4.7% (37/790) including 16 leaks (2.0%) and 9 bleedings (1.1%) and no deaths. Risk factors for leak were: previous adjustable banding (p = .0051), with no d...

Background While distal pancreatectomy with splenectomy (DPS) is the reference treatment for pancreatic body and tail neoplasia, oncological benefits of splenectomy have never been demonstrated. Involvement of spleen, splenic hilum and lymph nodes (LN) was therefore assessed on DPS specimens. Methods All DPS pancreatic neoplasia specimens obtained in 2 Brussels University Hospitals over 15 years (2004–2018) were reviewed retrospectively, using both preoperative radiological imaging and postoperative pathological analyses of splenic parenchyma, hilar tissue and LN. Results The total of 130 DPS specimens included 85 adenocarcinomas, 37 neuroendocrine neoplasms and 8 other carcinomas. Tumours involved the pancreatic body without tail invasion for 59 specimens (B, Body group), and the pancreatic tail with/without body for 71 (T, Tail group). At pathology, direct splenic and/or hilar involvement was observed in 13 T specimens (13/71, 18.3%), but in none belonging to the Body group. The observed numbers of splenic hilar LN (only reported in 49/130 patients) were low, only one T adenocarcinoma had positive splenic LN in addition to direct splenic involvement. Conclusion Splenectomy remains justified during pancreatectomy for neoplasia involving the pancreatic tail, but in case of pancreatic body tumours, its benefits should be questioned in the light of absent splenic LN/parenchymal involvement.

e16664 Background: Gene fusions involving one of the 3 neurotrophic tyrosine receptor kinases ( NTRK) have been identified in approximately 1% of solid tumors and inhibitors of TRK have been shown to have anti-tumor activity regardless of tumor type. NTRK gene fusions have been previously reported in bilio-pancreatic tumors. It is of interest therefore to determine incidence and molecular characteristics of NTRK gene fusions in these patients. Methods: Formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies or cytological samples of biliary tract tumors (BTC) including intra-hepatic (IH), extra-hepatic (EH), perihilar cholangiocarcinoma (PH) and gallbladder tumors (G), and pancreatic adenocarcinoma (PA) were retrieved from the tumor bank of CUB Hôpital Erasme between JAN 2010 and OCT 2019. A two-step diagnostic method incorporating immunohistochemistry (IHC) screening followed by NGS analysis was used. Pan–TRK IHC (monoclonal antibody clone EPR17341 [AbCam, Cambridge, MA]) was used for the screening method. Staining intensity (negative, weak, moderate or strong) pattern (diffuse, focal or rare positive cells), and localization (cytoplasmic or nuclear) were evaluated. The presence of at least weak staining tumor cells led to testing by a RNA-based NGS panel (Oncomine Focus Assay ThermoFisher Scientific). Results: For BTC, 162 archival tumors samples have been selected. 149 samples were suitable to perform IHC.17 samples were IHC positive including 9 IH, 3 PH, 2 EH and 3 G tumor samples. Intensity of staining was weak in 16 samples and moderate in one. Staining location was cytoplasmic (14/17), nuclear (2/17), and nuclear+cytoplasmic (1/17). Pattern of staining was rare positive cells (2/17), focal (4/17) and diffuse (11/17). NGS testing of the 17 IHC positive samples revealed a single NTRK3 gene fusion ( ETV6(4)- NTRK3(14)). In this PH tumor, IHC had a weak focal cytoplasmic and nuclear staining. Overall in the patients screened by IHC and confirmed by NGS, percentage of NTRK fusions was 0.67 %. For PA, 319 archival tumor samples have been selected and 297 were suitable for IHC. 19 samples were IHC positive. Intensity of staining was weak in 18 samples and moderate in one. Staining location was cytoplasmic (18/19) and nuclear (1/19). Pattern of staining was focal in 2 cases and diffuse in 17 cases. No fusion was detected by NGS. Conclusions: NTRK gene fusions are rare in bilio-pancreatic cancers but testing is of high interest due to the emergence of possible treatment with specific TRK inhibitors. These results support the use of NGS to confirm positive IHC results during diagnostic screening.

The optimal timing for cholecystectomy in patients with acute cholecystitis remains controversial. The aim of this study is to assess prospectively the impact of the duration of symptoms on outcomes in early laparoscopic cholecystectomy (ELC) for acute cholecystitis. The series consisted of 276 consecutive patients who underwent ELC for acute cholecystitis in 2016. The patients were divided into three groups according to the timing of surgery: within the first 3 days (group 1), between 4 and 7 days (group 2) and beyond 7 days (group 3) from the onset of symptoms. The percentage of surgical procedure rated as difficult was respectively: 12% in G1, 18% in G2 and 38% in G3 (p

Since redo surgery is associated with a high risk of morbidity and mortality after bariatric surgery in case of leakage, we sought to evaluate whether endoscopic drainage and debridement of collections following bariatric surgery is an efficient step-up approach to the management of these complications. From 2007 to 2011, we retrospectively studied our cohort of nine cases treated by endoscopic drainage and debridement of abdominal abscesses secondary to postbariatric surgery leaks performed via the transluminal or percutaneous route. Three patients were treated by percutaneous endoscopic debridement of abscesses knowing that their leak was already closed by other endoscopic means and that their collection did not improve despite external drain in place. Six patients were treated by transluminal endoscopic drainage to perform necrosectomy as a first-line option or after failure of improvement after endoscopic treatment. The number of sessions required ranged from 1 to 3. Most severe patients had rapid improvement of their hemodynamic and respiratory conditions. In eight of the nine patients, we were able to close the fistula by stent, fistula plugs, or a macroclip. Resolution of collections was seen in seven out of nine patients, but two required further surgery. Endoscopic necrosectomy via the transluminal or percutaneous route is a feasible option in postbariatric surgery patients with necrotic abscesses not adequately managed by the classical combination of percutaneous drainage and stenting. Further wide-scale studies are needed to compare this non-surgical method with surgical necrosectomy in postbariatric surgery patients.

La chirurgia antireflusso costituisce un trattamento efficace e duraturo del reflusso gastroesofageo (RGE), i cui risultati sono superiori alla terapia medica in termini di controllo dei sintomi e di miglioramento della qualita di vita. Tuttavia, la chirurgia e gravata da un tasso di effetti secondari e di reinterventi non trascurabile. I candidati a una chirurgia antireflusso devono essere correttamente selezionati e informati. Un’endoscopia, dimostrando l’esistenza di un’esofagite, permette da sola di porre la diagnosi di RGE in un paziente che presenta dei sintomi tipici. La pH-metria e indispensabile in caso di dubbio diagnostico. La manometria esofagea e il test di svuotamento gastrico non sono necessari di routine. Rispetto alla laparotomia, la laparoscopia presenta numerosi vantaggi ed e diventata la via d’accesso di elezione. I principi della chirurgia sono: riduzione della giunzione gastroesofagea nella cavita addominale, chiusura dei pilastri del diaframma e creazione di una valvola antireflusso senza tensione. La scelta tra fundoplicatio di tipo Nissen, Rossetti, Toupet o Dor e una questione di scuola, in quanto nessuna tecnica ha dimostrato la sua superiorita sulle altre in modo perentorio. Benche una valvola di 1-2 cm sia sufficiente in caso di fundoplicatio completa, e raccomandata una valvola di un’altezza di 3 cm in caso di fundoplicatio parziale. La disfagia postoperatoria e frequente ma transitoria. Si deve ricercare una causa meccanica solo se essa persiste per piu di tre mesi. I sintomi tipo gas bloat possono essere anteriori o secondari alla chirurgia. Con un follow-up di cinque-dieci anni, il tasso di recidiva dei sintomi del RGE e inferiore al 12%, ma un reintervento e necessario nel 3-6% dei pazienti. La causa principale di insuccesso e la risalita della valvola nel torace, legata a una chiusura inadeguata dei pilastri o a un brachiesofago misconosciuto.

La cirugia antirreflujo constituye un tratamiento eficaz y duradero del reflujo gastroesofagico (RGE) cuyos resultados son superiores a los del tratamiento medico en terminos de control de los sintomas y de mejora de la calidad de vida. No obstante, la cirugia conlleva una tasa no despreciable de efectos secundarios y de reintervenciones. Es necesario seleccionar e informar apropiadamente a los pacientes candidatos para cirugia antirreflujo. Una endoscopia que demuestre la existencia de una esofagitis permite, por si sola, realizar el diagnostico de RGE en un paciente que presente los sintomas tipicos. En caso de duda diagnostica, es imprescindible la realizacion de una pH-metria. La manometria esofagica y la prueba de vaciamiento gastrico no son necesarias de rutina. En comparacion con la laparotomia, la laparoscopia presenta numerosas ventajas y se ha convertido en la via de acceso de eleccion. Los principios de la cirugia son: reduccion de la union esofagogastrica a la cavidad abdominal, cierre de los pilares del diafragma y creacion de una valvula antirreflujo sin tension. La eleccion entre la fundoplicatura de tipo Nissen, Rossetti, Toupet o Dor es una cuestion de escuela, ya que ninguna tecnica ha demostrado su superioridad sobre las otras de forma concluyente. Aunque para una fundoplicatura completa es suficiente una valvula de 1-2 cm, en caso de fundoplicatura parcial se aconseja una valvula de unos 3 cm de altura. La disfagia postoperatoria es frecuente, pero transitoria. No hay que buscar una causa mecanica, salvo si persiste mas de 3 meses. Los sintomas de tipo distension abdominal (gas bloat) pueden ser anteriores o secundarios a la cirugia. Con un seguimiento de 5-10 anos, la tasa de recidiva de los sintomas del RGE es inferior al 12%, aunque en el 3-6% de los pacientes es necesaria una reintervencion. La causa principal de fracaso es el ascenso de la valvula en el torax, relacionada con un cierre inadecuado de los pilares o un braquiesofago no diagnosticado.

Introduction There are very few case reports of metastasis on a mesh prosthesis following laparoscopic hernia repair in the literature and its incidence is completely unknown. Case report A 76-year-old male patient presented in December 2013 with a suspicious malignant lesion of the pancreatic tail on the MRI. He was also complaining of a painful mass in the right para-rectal area. An exploratory laparoscopy performed in December 2013 revealed microscopic whitish peritoneal implants in the left hypochondrium and a massive metastasis involving a mesh prosthesis placed é years before in the right para-rectal area. The pathology report of biopsies of the mesh confirmed a metastasis compatible with a pancreatic tumor. Discussion Possible modes of metastasis and limited published data to date on mesh prosthesis metastasis are presented. This situation can be assimilated to port-site metastasis after laparoscopy. Conclusion A mesh prosthesis metastasis after laparoscopic hernia repair is very rare.

International audience; Microsatellite instability (MSI) caused by mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical analyses of a 445 PDAC specimens, collected from consecutive patients at multiple centers, to identify those with dMMR, based on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2. We detected dMMR in 1.6% of tumor samples; we found dMMR in a larger proportion of intraductal papillary mucinous neoplasms-related tumors (4/58, 6.9%) than non- intraductal papillary mucinous neoplasms PDAC (5/385, 1.3%) (P = .02). PDACs with dMMR contained potentially immunogenic mutations because of MSI in coding repeat sequences. PDACs with dMMR or MSI had a higher density of CD8+ T cells at the invasive front than PDACs without dMMR or MSI (P = .08; Fisher exact test). A higher proportion of PDACs with dMMR or MSI expressed the CD274 molecule (PD-L1, 8/9) than PDACs without dMMR or MSI (4/10) (P = .05). Times of disease-free survival and overall survival did not differ significantly between patients with PDACs with dMMR or MSI vs without dMMR or MSI. Studies are needed to determine whether these features of PDACs with dMMR or MSI might serve as prognostic factors.

OBJECTIVES This study investigates the factors that could influence the development of delayed gastric emptying (DGE) after pancreatoduodenectomy (PD). Delayed gastric emptying is a common complication after PD. The postoperative course is affected by a lengthened hospital stay, a decrease of the patients' quality of life, and a delayed adjuvant treatment. METHODS From January 2000 to December 2012, 257 patients underwent PD in the same center. Forty-six variables were retrospectively extracted from medical records. Delayed gastric emptying (grades A, B, and C) was defined by the International Study Group of Pancreatic Surgery classification. Univariate and multivariate analyses were performed to identify factors associated with DGE. RESULTS Delayed gastric emptying occurred in 133 patients (51.8%), 89 grade A (66.9%), 27 grade B (20.3%), and 17 grade C (12.8%). Biliary fistula (odds ratio [OR], 8.87; 95% confidence interval [CI], 2.07-37.99, P = 0.003), sepsis (OR, 8.02; 95% CI, 3.22-19.99; P < 0.0001), and intra-abdominal collection (OR, 3.43; 95% CI, 1.06-11.06; P = 0.039) were identified as independent risk factors for DGE, whereas pancreaticogastrostomy (OR, 0.32; 95% CI, 0.16-0.64; P < 0.001) decreased the occurrence of DGE. CONCLUSIONS Delayed gastric emptying was linked to the occurrence of postoperative intra-abdominal complications, and reconstruction by pancreaticogastrostomy was beneficial by decreasing its incidence.

Background and study aims: Paraduodenal pancreatitis is histologically well defined but its epidemiology, natural history, and connection with chronic pancreatitis are not completely understood. The aim of this study was to review the endoscopic and medical management of paraduodenal pancreatitis. Patients and methods: Medical records of all patients with paraduodenal pancreatitis diagnosed by magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasonography (EUS) between 1995 and 2010 were retrospectively reviewed. Clinical features, imaging procedures, and treatments were investigated. The primary end point was the rate of clinical success, and the secondary end points were the radiological or endoscopic improvement, complication rate, and overall survival rate. Results: A total of 51 patients were included in the study (88.2 % alcohol abuse; median age 49 years [range 37 – 70]; 50 men). The most frequent symptoms at presentation were pain (n = 50; 98.0 %) and weight loss (n = 36; 70.6 %). Chronic pancreatitis was present in 36 patients (70.6 %), and 45 patients (88.2 %) had cysts. Other findings included stricture of the pancreatic duct (n = 37; 72.5 %), common bile duct (n = 29; 56.9 %), and duodenum (n = 24; 47.1 %). A total of 39 patients underwent initial endoscopic treatment: cystenterostomy (n = 20), pancreatic and/or biliary duct drainage (n = 19), and/or duodenal dilation (n = 6). For the patients with available follow-up (n = 41), 24 patients required repeat endoscopy and 9 patients required surgery after the initial endoscopic management. After a median follow-up of 54 months (range 6 – 156 months), complete clinical success was achieved in 70.7 % of patients, and the overall survival rate was 94.1 %. Conclusions: This is the largest series concerning the management of paraduodenal pancreatitis using endotherapy as the first-line intervention. Although repeat endoscopic procedures were required in half of the patients, no severe complication was observed and surgical treatment was ultimately needed in less than 25 % of the patients.

Background Prognosis of patients with pancreatic adenocarcinoma (PAC) remains poor. S100A2 has been recently suggested as a negative prognostic biomarker in PAC. We aimed to investigate its prognostic and/or predictive value in a large independent multicentric cohort of patients with resected PAC. Methods Sequential samples of 471 patients were retrospectively collected; 142 patients did not receive adjuvant treatment (30%) and 329 (70%) received an adjuvant treatment. We measured protein levels of S100A2 by semiquantitative immunohistochemistry with tissue microarrays and correlated with patients’ overall survival (OS) and disease-free survival (DFS). Results S100A2 protein status was obtained in 462 (98%) patients. Its expression was low, moderate or high in 59%, 12% and 2% of cases, respectively. It was not correlated with DFS or OS in the whole population, neither in the subgroup of patients who did not receive adjuvant treatment. However among patients who received an adjuvant therapy, moderate/high levels of S100A2 were significantly associated with longer OS and DFS in multivariate analysis (hazard ratios of 0.63, p = 0.022 and 0.67, p = 0.017, respectively), whereas low S100A2 was not. Interaction tests for adjuvant therapy were statistically significant both for the OS and the DFS ( p = 0.001 and p = 0.023, respectively). On multivariate analysis, S100A2 retained independent predictive values (OS: p p = 0.003) with a significant benefit of adjuvant therapy for those patients with moderate/high S100A2. Conclusions S100A2 expression predicts longer DFS and OS in patients treated with adjuvant therapy and should be evaluated as a predictive biomarker.

Summary Background Postoperative pancreatic fistula is the leading cause of death and morbidity after pancreaticoduodenectomy. However, the best reconstruction method to reduce occurrence of fistula is debated. We did a multicentre, randomised superiority trial to compare the outcomes of different reconstructive techniques in patients undergoing pancreaticoduodenectomy for pancreatic or periampullary tumours. Methods Patients aged 18–85 years with confirmed or suspected neoplasms of the pancreas, distal bile duct, ampulla vateri, duodenum, or periampullary tumours were eligible for inclusion. An internet-based platform was used to randomly assign patients to either pancreaticojejunostomy or pancreaticogastrostomy as reconstruction after pancreaticoduodenectomy, using permuted blocks with six patients per block. Within each centre the randomisation was stratified on the pancreatic duct diameter (≤3 mm vs >3 mm) measured at the time of surgery. The primary endpoint was the occurrence of clinical postoperative pancreatic fistula (grade B or C) as defined by the International Study Group on Pancreatic Fistula. The study was not masked and analyses were done by intention to treat. Patient follow-up was closed 2 months after discharge from the hospital. This study is registered with ClinicalTrials.gov, number NCT00830778. Findings Between June, 2009, and August, 2012, we randomly allocated 167 patients to receive pancreaticojejunostomy and 162 to receive pancreaticogastrostomy. 33 (19·8%) patients in the pancreaticojejunostomy group and 13 (8·0%) in the pancreaticogastrostomy group had clinical postoperative pancreatic fistula (OR 2·86, 95% CI 1·38–6·17; p=0·002). The overall incidence of postoperative complications did not differ significantly between the groups (99 in the pancreaticojejunostomy group vs 100 in the pancreaticogastrostomy group), although more events in the pancreaticojejunostomy group were of grade ≥3a than in the pancreaticogastrostomy group (39 vs 35). Interpretation In patients undergoing pancreaticoduodenectomy for pancreatic head or periampullary tumours, pancreaticogastrostomy is more efficient than pancreaticojejunostomy in reducing the incidence of postoperative pancreatic fistula. Funding Funding Johnson & Johnson Medical Devices, Belgium.

Sleeve gastrectomy (SG) has been used as the first step of a staged malabsorptive procedure for high-risk patients. More recently SG was proposed as an stand alone procedure in the treatment of morbidly obese patients. The aim of this study is to analyze perioperative outcome of morbid obese patients after SG.301 patients, 201 women and 100 men, undergoing SG were retrospectively analyzed. SG was performed by 17 surgeons all member of the Club Coelio. The mean BMI was 44.7kg/m2 (27.4-70.3 kg/m2). 34 patients (11.3%) of our series had SG as revisional surgery. These revisional procedures consisted of 32 conversions from gastric banding, 1 conversion from vertical gastroplasty (VBG) and 1 from transoral endoscopic gastroplasty. Among the 32 patients that had revisional SG after a gastric banding, 13 bands were removed at least 3 months before the revisional SG and 19 bands were removed during the SG procedure. Endpoints were perioperative morbidity and mortality and potential risk factors for complications, mainly per or postoperative bleeding or leakage.Overall mortality was 0% and morbidity was 10.3%. Perioperative bleeding occurred in 10 patients (3.3%), leakage in 12 patients (4%) patients and stenosis in 3 patients (1%). The risk of leakage was significantly higher after revisional bariatric surgery and in case of gastric perforation during surgery (p = 0.0001). Previous gastric banding is also associated with a higher risk of postoperative bleeding (p = 0.0006).SG can be safely performed but patients and surgeons must be aware of a higher risk of postoperative complications when SG is proposed as a revisional surgery.

Prognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients.A total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-β receptor, CXCR4, and LKB1.High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR) = 1.74; P0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR = 2.19; P0.0001) and was the strongest prognostic factor compared with clinicopathological factors. In patients who did not received adjuvant treatment, there was a trend toward decrease in the overall survival for negative Smad4 expression. Loss of Smad4 expression was not correlated with recurrence pattern but was shown to be predictive for adjuvant chemotherapy (CT) benefit (HR = 0.59; P = 0.002).CXCR4 is a strong independent prognostic biomarker associated with distant metastatic recurrence and appears as an attractive target to be evaluated in pancreatic adenocarcinoma. Negative SMAD4 expression should be considered as a potential predictor of adjuvant CT benefit.

The World Health Organization defines obesity as “an abnormal or excessive accumulation of fat that poses a risk to health”. In the general population, high levels of exercise capacity are associated with lower levels of total body fat and higher levels of lean body mass. But it is not clear

To prospectively determine whether dynamic contrast material-enhanced (DCE) magnetic resonance (MR) quantitative parameters correlate with fibrosis and microvascular density (MVD) in malignant and benign solid pancreatic focal lesions and nontumoral pancreatic tissue.The institutional review board approved the study; written informed consent was obtained. DCE MR was performed in 28 patients with surgically resectable focal pancreatic lesions. DCE MR quantitative parameters derived from one-compartment (OC) (transfer rate constant [K(trans)] and distribution fraction [ƒ]) and two-compartment (TC) (K(trans), tissue volume fraction occupied by extravascular extracellular space [v(i)], and tissue volume fraction occupied by vascular space [v(p)]) pharmacokinetic models were correlated with fibrosis content and MVD counts in focal lesions and nontumoral tissue (Spearman correlation coefficient [SCC]). Pharmacokinetic parameters were compared (Mann-Whitney test) between tumoral and nontumoral tissue. Diagnostic performance of DCE MR fibrosis detection was assessed (receiver operator characteristic curve analysis).K(trans) OC and K(trans) TC were significantly lower in primary malignant tumors compared with benign lesions (P = .023) and nontumoral pancreatic tissue downstream (P.001) and upstream (P = .006); ƒ and v(i) were significantly higher in primary malignant tumors compared with nontumoral pancreatic tissue downstream (P = .012 and .018, respectively). Fibrosis was correlated negatively with K(trans) OC (SCC, -0.600) and K(trans) TC (SCC, -0.564) and positively with ƒ (SCC, 0.514) and v(i) (SCC, 0.464), with P.001 (all comparisons). MVD was positively correlated with ƒ (SCC, 0.355; P = .019) and v(i) (SCC, 0.297; P = .038) but not with K(trans) OC (SCC, -0.140; P = .33) and K(trans) TC (SCC, -0.194; P = .181). Sensitivity and specificity for fibrosis detection were 65% (24 of 37) and 83% (10 of 12) for K(trans) OC (cutoff value, 0.35 min(-1)) and 76% (28 of 37) and 83% (10 of 12) for K(trans) TC (cutoff value, 0.29 min(-1)), respectively.Quantitative DCE MR parameters, derived from pharmacokinetic models in malignant and benign pancreatic solid lesions and nontumoral pancreatic tissue, were significantly correlated with fibrosis and MVD.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11103515/-/DC1.

Background Intragastric band migrations or dysfunctions are common long-term complications of both vertical banded gastroplasty (VBG) and laparoscopic adjustable gastric banding (Lap-Band) that classically require surgical treatment. Objective In this series, we describe the endoscopic removal of partially eroded Lap-Bands or Silastic rings and noneroded dysfunctioning rings after VBG. Design Case series. Setting A European, tertiary-care academic center. Patients This study involved 13 patients—3 with eroded Lap-Bands, 4 with eroded Silastic rings, and 6 with refractory outlet stoma stenosis after VBG. Intervention Endoscopic removal was performed within 1 or 2 sessions, according to the presence and extent of band erosion at presentation, including optional placement of a self-expandable plastic stent across the band, followed about 6 to 8 weeks later by extraction with transsection, if needed, by using a wire-cutting system. Main Outcome Measurements Technical success and safety. Results One failure was caused by huge adhesion formation around a Lap-Band on the lesser curvature of the stomach and the left liver lobe. Twelve of 13 endoscopic removals were successful in 1 (n = 2) and 2 (n = 10) sessions. Limitations Highly selected patients (tertiary-case academic center). Conclusion Endoscopic removal of dysfunctioning bands or rings is safe and feasible by the use of a 1- or 2-step endoscopic procedure.

Chemokines and their receptors are involved in tumourigenicity and clinicopathological significance of chemokines receptor expression in pancreatic adenocarcinoma (PA) is not fully understood. This study was conducted to determine patients' outcome according to the expressions of CXCR4, CXCR7 and HIF-1alpha after resection of PA. Immunohistochemistry for CXCR4, CXCR7 and HIF-1alpha expressions as well as cell proliferative index (Ki-67) was conducted in 71 resected (R0) PA and their 48 related lymph nodes (LN) using tissue microarray. CXCR4 and CXCR7 expressions were positively correlated to HIF-1alpha suggesting a potential role of HIF-1alpha in CXCR4 and CXCR7 transcription activation. Patients with CXCR4(high) tumour expression had shorter OS than those with low expression (median survival: 9.7 vs 43.2 months, P=0.0006), a higher risk of LN metastases and liver recurrence. In multivariate analysis, high CXCR4 expression, LN metastases and poorly differentiated tumour are independent negative prognosis factors. In a combining analysis, patients with CXCR4(low)/CXCR7(low) tumour had a significantly shorter DFS and OS than patients with a CXCR7(high)/CXCR4(high) tumour. CXCR4 in resected PA may represent a valuable prognostic factor as well as an attractive target for therapeutic purpose., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Clusterin is, in its major form, a secreted heterodimeric disulfide-linked glycoprotein (75-80 kDa). It was first linked to cell death in the rat ventral prostate after androgen deprivation. Recent studies have demonstrated that overexpression of clusterin in prostatic cells protects them against tumor necrosis factor-alpha (TNFalpha)-induced apoptosis. However the details of this survival mechanism remain undefined. Here, we investigate how clusterin prevents cells from undergoing TNFalpha-induced apoptosis. We established a double-stable prostatic cell line for inducible clusterin by using the Tet-On gene expression system. We demonstrated that 50% of the cells overexpressing clusterin escaped from TNFalpha- and actinomycin D-induced cell death. Moreover we demonstrated that the incubation of MLL cells with conditioned medium containing the secreted clusterin or the supplementation of purified clusterin in the extracellular medium decreased the TNFalpha-induced apoptosis significantly. This extracellular action implicates megalin, the putative membrane receptor for clusterin to mediate survival. Indeed clusterin overexpression up-regulated the expression of megalin and induced its phosphorylation in a dose-dependent manner. We interestingly showed that clusterin overexpression is associated with the up-regulation of the phosphorylation of Akt. Activated Akt induced the phosphorylation of Bad and caused a decrease of cytochrome c release. These results enable us to pinpoint one mechanism by which secreted clusterin favors survival in androgen-independent prostate cancer cells, implicating its receptor megalin and Akt survival pathway.

In mammals, thyrotropin, or thyroid-stimulating hormone (TSH), assay is used for the diagnosis of primary hypothyroidism. Hypothyroidism is the most common type of thyroid disorder in cattle. The aim of this study was to develop and validate, under physiologic and pathologic conditions, a radioimmunoassay (RIA) for bovine TSH (bTSH). Double RIA was performed with purified bTSH and specific bovine antiserum. Laboratory validation included research of minimal detection limit, accuracy, and reproducibility. The physiologic validation included a thyrotropin-releasing hormone (TRH) challenge performed on euthyroid cows and a follow-up of bTSH concentration over a 24-hour period. Furthermore, bTSH concentration was assayed in a large population of healthy dairy and beef cows to define reference interval. The pathologic validation was made by assaying bTSH and thyroid hormones on healthy and goitrous newborn calves. The minimum detection limit (MDL) for bTSH assay was 1.3 μU/ml. The recovery was 101% to 106%. The intra- and interassay coefficients of variation (CVs) ranged from 5% to 11% and 11% to 15%, respectively. The RIA covered the whole range of physiologic bTSH values, as shown by bTSH values induced by TRH-challenge. A pulsatile secretion of bTSH was observed, accompanied by a diurnal variation with lower night values than day values. Reference intervals of bTSH ranged from 1.3 to 13.0 μU/ml for beef and dairy breeds. Finally, bTSH easily discriminated goitrous newborn calves from healthy ones, leading to the definition of a cutoff value of 35 μU/ml. The bTSH assay positively reacted to physiologic and pathologic conditions. The accuracy and precision of the RIA were satisfying.