BACKGROUND:Little is known about the prognostic significance of pancreatic duct (PD) dilation following pancreatoduodenectomy for intraductal papillary mucinous neoplasms (IPMN). Although PD dilation is typically the hallmark radiographic feature of IPMN, other causes of PD dilation exist, including anastomotic stricture, pancreatitis, senescence, and postsurgical passive dilation. Therefore, PD dilation after pancreatoduodenectomy for IPMN represents a diagnostic and management dilemma. The purpose of this study was to evaluate the significance of PD dilation after pancreatoduodenectomy for noninvasive IPMN. METHODS:All patients who underwent pancreatoduodenectomy for noninvasive IPMN at 9 pancreatic academic centers between 2013 and 2018 were included. Variables were entered prospectively into institutional databases and retrospectively reviewed for the purpose of this study. Dilation of the PD remnant was defined as a duct diameter of ≥5 mm, according to international guidelines. RESULTS:Four hundred and eighty-one patients were included in this study. The mean age of the patients was 66 years (range 30-90). Patients were surveilled for a median of 4.5 (+/-2.3; max 10.6) years. During follow-up, 132 patients (27.4%) developed PD dilation in the remnant pancreas after a median of 3.3 years. Multivariable analysis demonstrated that older age at the time of pancreatoduodenectomy ( P =0.01) and longer surveillance duration ( P =0.002) were predictors of PD dilation. Interestingly, neither the pathological IPMN subtype (branch-duct vs main duct/mixed, P =0.96) nor the preoperative PD diameter ( P =0.14) was associated with an increased risk of PD dilation in the remnant. During follow-up, IPMN recurrence was suspected in the remaining 72 patients (18.4%), solely because of ductal dilation on cross-sectional imaging in 97% (70/72). Completion pancreatectomy was performed in only 16 patients (3.3%), of whom only 4 (0.8%) had invasive carcinoma. Three of these 4 patients had high-grade dysplasia in the original pancreatoduodenectomy specimen, whereas only one had a low-grade dysplastic lesion initially. On multivariable analysis, no variable was predictive of IPMN recurrence in the remnant. CONCLUSIONS:New main duct dilation in the pancreatic remnant after pancreatoduodenectomy for IPMN is common, occurring in 27% of the patients. The duration of surveillance is the main factor associated with remnant PD dilation, suggesting that this is likely a physiologic phenomenon. Although recurrence of IPMN in the remnant is often suspected, only 0.8% of patients develop an invasive carcinoma in the pancreatic remnant requiring completion pancreatectomy.

Purpose: Bile leakage belong to the most harmful complications after hepato-pancreato-biliary (HPB) surgery, associated with high morbidity and mortality. The incidence for clinically relevant bile leakage (type B and C bile leakage as defined by the ISGLS) varies in literature, with incidence rates between 6.5% and 27.2%. Another feared complication after hepatic resections are postoperative bleeding events, also described as post-hepatectomy hemorrhage (PHH). Incidence ranges up to 8%. None of the available sealants can significantly reduce the incidence of postoperative bile leakage and bleeding events. We developed a new biodegradable sealant to reduce bile leakage and to achieve bleeding control. In a preclinical porcine model the patch was able to reduce bile leakage and was superior to the standard of care. The aim of the ongoing first-in-human study is to clinically assess safety and performance in HPB surgery.

Introduction: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, liver resection (LR) is recommended for early-stage (BCLC-A) hepatocellular carcinoma (HCC) but is not a standard treatment for intermediate-stage (BCLC-B). The study aim was to assess surgical and oncological outcomes of LR in BCLC-A and B patients. Methods: This retrospective multicenter study included HCC patients with LR between January 2010 and December 2020 in four tertiary referral centers. Surgical outcomes of LR were assessed according to the Clavien classification. The overall survival (OS) and disease-free survival (DFS) were calculated by the Kaplan-Meier method. Results: Among 614 patients included, 564 were classified as BCLC-A and 50 as BCLC-B. Despite a higher clinically relevant complication (≥3b) rate in BCLC-B group (20.0 vs 8.0%, p=0.009), the incidence of overall complications (56.0 vs 41.5%, p=0.053) and mortality (0.0 vs 1.6%, p=1.000) did not differ between the two groups. Length of stay was significantly longer in BCLC-B group (12.9 vs 9.8 days, p<0.001). DFS was similar between BCLC-A and BCLC-B group (1-, 3-, and 5-year DFS: 66%, 24%, and 15% vs 67%, 35%, and 24%; p=0.766). OS was longer in BCLC-A group (1-, 3-, and 5-year OS of 93%, 70%, and 39% vs 83%, 48%, and 32%; p=0.015). Conclusions: LR for early and intermediate-stage HCC is safe providing careful preoperative selection. Despite better OS in BCLC-A patients, results of surgery in BCLC B patients were acceptable. These results will help to refine the BCLC staging system, which is probably too restrictive for surgery.

Pancreatic fistulas (POPF) still belong to the most harmful complications following hepato-pancreato-biliary (HPB) surgery. The incidence for clinically relevant POPF (type B and C pancreatic fistulas as defined by the ISGPS) vary in literature, around 21% (type B) and 3% (type C). However, none of the available sealants can significantly reduce POPF. In order to reduce POPF and to achieve bleeding control a new biodegradable sealant has been developed. In a preclinical porcine distal pancreatectomy model the sealant was able to reduce POPF and was superior to the standard of care. The aim of the ongoing first-in-human study is to clinically assess safety and performance in HPB surgery. Patients eligible to this pan-European multicenter, single-arm, prospective study receive a distal pancreatectomy. 40 patients are included at 8 European high-volume centers. The defect is closed as per usual. Afterwards, the resection surface is covered with the sealant. The primary endpoint evaluates the incidence of POPF up to 30-days post-operatively. The secondary endpoints integrate the assessment of bleeding control, leak associated comorbidities as well as re-interventions and device usability. Preliminary interim results of the 30-day analysis indicate that four pancreas patients presented with a type B POPF post-operatively (10%). There were no patients presenting with a type C POPF. Patch handling and application were straightforward. The preliminary results demonstrate that the device is safe to use and indicate excellent performance of the new sealant regarding the reduction of POPF. Compared to the standard-of-care the patch performance indicates to be non-inferior.

Introduction: Lymph node ratio (LNR) was proven to be predictive of survival in several gastrointestinal cancers. Its predictive role in pancreatic ductal adenocarcinoma (PDAC) remains unknown. This study aimed to assess if LNR predicted overall survival (OS) after pancreatoduodenectomy for PDAC. Method: Data were collected from six international tertiary centers. Patients with PDAC who underwent upfront pancreatoduodenectomy were included (2000-2018). LNR (positive lymph nodes/harvested lymph nodes) was calculated for all patients based on pathology reports. Prognostic OS factors were assessed using multivariable Cox regression. Results: In total, 1513 patients were included. Ninety-day mortality rate was 5.9% (89/1513). Lymph node invasion (pN+) was present in 1175 patients (77%). Median number of harvested lymph nodes and positive lymph nodes were 18 (IQR 12-24) and 3 (IQR 2-6). Median LNR was 0.148 (IQR 0.042-0.333) in the entire cohort and 0.214 (IQR 0.107-0.372) in pN+ patients. Best LNR threshold to predict OS in pN+ patients was 0.043 (C-index 0.562). A total of 368 and 1101 patients had LNR< 0.043 and LNR≥0.043 (44 missing data). Patients with LNR≥0.043 had worse median OS (23 vs. 50 months, p< 0.001). On multivariable analysis, LNR was an independent OS predictor (HR 4.7, 95% CI 1.1-19.2, p=0.033). In the pN+ group, patients with LNR≥0.043 also had worse median OS (23 vs. 44 months, p=0.037). In N1 and N2 subgroups, LNR was also an independent OS predictor. Conclusions: In this international, multicenter cohort study, LNR was a strong independent prognostic factor of OS in patients with PDAC who underwent pancreatoduodenectomy.

Évaluation de la valeur du PET scanner au 18F-FDG dans la différenciation des formes bénignes et malignes des tumeurs intracanalaires papillaire et mucineuse du pancréas. Les TIPMP malignes ou de haut risque nécessitent une résection chirurgicale mais cette chirurgie devrait être évitée en cas de TIPMP à faible risque de malignité. Le PET scanner au 18F-FDG a été étudié dans de nombreuses séries rétrospectives monocentriques. Il s’agit d’une étude multicentrique française prospective non comparative. L’objectif principal de cette étude était d’analyser la spécificité du PET scanner au 18F-FDG pour l’identification des formes malignes des TIPMP (carcinome invasif ou in situ). Le diagnostic final était obtenu sur l’analyse anatomopathologique de la pièce d’exérèse. Sur 120 patients analysés, 99 présentaient une confirmation de TIPMP, incluant 24 lésions malignes, 9 carcinomes in situ et 15 cancers invasifs. Le PET scanner au 18F-FDG était positif dans 44 et 31 cas respectivement dans l’ensemble de la série et sur la population de TIPMP. Chez les 99 patients présentant une TIPMP les résultats du PET scanner retrouvaient 13 vrais positifs, 18 faux positif, 57 vrais négatifs et 11 faux négatifs. La sensibilité, spécificité, valeur prédictive négative et valeur prédictive positive était respectivement de 54,2 %, 76 %, 83,8 % et 41,9 %. Nous n’avons pu identifier une valeur de cut-off de SUVmax permettant la distinction entre une lésion bénigne maligne. Les imageries conventionnelles comportaient un scanner abdominal, une imagerie par résonance magnétique nucléaire et une écho-endoscopie. Dans le groupe des patients présentant une TIPMP qui avaient reçu les trois techniques d’imagerie, la sensibilité, spécificité, valeur prédictive positive et négative étaient respectivement de 66,7 %, 84,4 %, 84,4 %, et 66,7 %. Dans cette étude, le PET scanner au 18F-FDG n’améliorait pas la distinction entre les formes bénignes et malignes des TIPMP par rapport aux examens d’imagerie conventionnelle. To assess the value of 18F-FDG PET/CT in differentiating between benign and malignant intraductal papillary mucinous neoplasms (IPMN) of the pancreas. Data Malignant or high-risk IPMN require surgical resection but surgery should be avoided in patients with IPMN carrying a low risk of malignancy. 18F-FDG PET has been studied mostly in small, single center, retrospective series. Prospective, non-comparative, multicenter French study. The primary endpoint was the specificity of PET/CT for identifying malignant IPMN (in situ or invasive carcinoma). Final diagnosis was obtained from pathological examination of the resected specimen. Among 120 patients analyzed, 99 had confirmed IPMN, including 24 with malignant lesions, namely 9 with carcinoma in situ and 15 with invasive carcinoma. The 18F-FDG PET/CT was positive in 44 and 31 patients in the overall and IPMN populations respectively. In the 99 IPMN patients, PET/CT showed 13 true positive, 18 false positive, 57 true negative and 11 false negative results. The sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were 54.2%, 76.0%, 83.8% and 41.9% respectively, versus 64.9%, 75.9%, 82.9% and 54.5% in the overall population. We could not identify a cut-off value for SUVmax to distinguish between benign and malignant lesions. Conventional imaging consisted of computed tomography, magnetic resonance cholangiopancreatography and endoscopic ultrasound. In IPMN patients who underwent the 3 techniques, sensitivity, specificity, NPV and PPV were 66.7%, 84.4%, 84.4% and 66.7% respectively. In this study, 18F-FDG PET/CT did not perform better than conventional imaging to differentiate benign and malignant IPMN.

ObjectiveTo assess the value of 18F-FDG PET/CT in differentiating between benign and malignant intraductal papillary mucinous neoplasms (IPMN) of the pancreas.Summary background dataMalignant or high-risk IPMN require surgical resection but surgery should be avoided in patients with IPMN carrying a low risk of malignancy. 18F-FDG PET has been studied mostly in small, single center, retrospective series.MethodsProspective, non-comparative, multicenter French study. The primary endpoint was the specificity of PET/CT for identifying malignant IPMN (in situ or invasive carcinoma). Final diagnosis was obtained from pathological examination of the resected specimen.ResultsAmong 120 patients analyzed, 99 had confirmed IPMN, including 24 with malignant lesions, namely 9 with carcinoma in situ and 15 with invasive carcinoma. The 18F-FDG PET/CT was positive in 44 and 31 patients in the overall and IPMN populations respectively. In the 99 IPMN patients, PET/CT showed 13 true positive, 18 false positive, 57 true negative and 11 false negative results. The sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for the diagnosis of malignancy were 54.2%, 76.0%, 83.8% and 41.9% respectively, versus 64.9%, 75.9%, 82.9% and 54.5% in the overall population. We could not identify a cut-off value for SUVmax to distinguish benign from malignant lesions. Conventional imaging included computed tomography, magnetic resonance cholangiopancreatography and endoscopic ultrasound. In IPMN patients who underwent the 3 techniques, sensitivity, specificity, NPV and PPV were 66.7%, 84.4%, 84.4% and 66.7% respectively.ConclusionsIn this study, 18F-FDG PET/CT did not perform better than conventional imaging to differentiate malignant from benign IPMN.

Background: The prognosis of Invasive intraductual papillary mucinous neplasms (IPMNinv) was often considered more favorable compared to pancreatic adenocarcinoma (PDAC). However, recent reports suggest a comparable long term outcome between PDAC and advanced stages of IPMNinv. Methods: One thousand, eight hundred eighty-four patients underwent surgery for IPMNinv (n=198) or PDAC (n=1686) were included. Clinical, biochemical, and pathological features and follow up after resection were recorded. Patients with IPMNinv (n=169) were matched with patients with PDAC (n=169), according to age, TNM stages, perineural invasion, margin and surgical procedure. Results: Overall median survival of IPMNinv was 70 months compared with 28 months of PDAC (p<0.001). early stages were significantly increased in patients with IPMNinv (78% vs 98%, p<0.001). On multivariate analysis, IPMNinv demonstrated a 39% lower hazard than PDAC. For patients with IPMNinv, positive lymph nodes (HR, 2.51; 95% CI, 1.17-5.41, p=0.018) was the only predictor of survival. When patients were matched by age, TNM stages, perineural invasion, margin and surgical procedure, overall (70 vs 34 months, p=0.09) and free disease survivals (21 vs 17 months, p=0.9) were similar. Conclusion: The more favorable pathological factors of IPMNinv and early diagnosis suggested the less aggressive behavior of this tumor. However, the prognosis of IPMNinv is as poor as PDAC.

The aim of this study was to assess oncological outcomes in patients treated with pancreaticoduodenectomy for advanced pancreatic head adenocarcinoma after preoperative chemoradiotherapy and to compare these with outcomes in patients treated with surgery alone.From 2004 to 2009, patients treated with pancreaticoduodenectomy for pancreatic head adenocarcinoma were included in a retrospective comparative study. Patients with locally advanced adenocarcinoma were treated with preoperative chemoradiotherapy (CRT group) and were compared with those treated with surgery alone (SURG group).A total of 111 patients were included; these comprised 72 patients in the SURG group and 39 patients in the CRT group. The median follow‐up was 21 months. Patients in the CRT group presented with a more advanced tumoral status. Microscopic resection rates were similar in both groups, but nodal status and vascular or lymphatic emboli were lower in the CRT group. At 3 years, the SURG and CRT groups exhibited similar overall (36% and 51%, respectively) and disease‐free (35% and 37%, respectively) survival (P = 0.10).In patients with advanced pancreatic head adenocarcinoma, a good response after preoperative chemoradiotherapy results in a survival rate similar to that in patients treated with surgery alone in whom the initial prognosis is better.

A 73 years-old male presented with a giant cystic lesion developed in the pancreatic lodge. The MRI confirmed a 180/70 mm collection, with T2 enhancement, developed from the main pancreatic duct. Patient had always been asymptomatic and we suspected a giant mucinous tumour or a large walled off necrosis after a misdiagnosed acute pancreatitis.

Background:Hepatic surgery is appropriate for selected patients with colorectal liver metastases (CRLM). Advances in chemotherapy have led to modification of management, particularly when metastases disappear. Treatment should address all initial CRLM sites based on pretherapeutic cross-sectional imaging. This study aimed to evaluate pretherapeutic fiducial marker placement to optimize CRLM treatment.Methods:This pilot investigation included patients with CRLM who were considered for potentially curative treatment between 2009 and 2016. According to a multidisciplinary team decision, lesions smaller than 25 mm in diameter that were more than 10 mm deep in the hepatic parenchyma and located outside the field of a planned resection were marked. Complication rates and clinicopathological data were analysed.Results:Some 76 metastases were marked in 43 patients among 217 patients with CRLM treated with curative intent. Of these, 23 marked CRLM (30 per cent), with a mean(s.d.) size of 11·0(3·4) mm, disappeared with preoperative chemotherapy. There were four complications associated with marking: two intrahepatic haematomas, one fiducial migration and one misplacement. After a median follow-up of 47·7 (range 18·1-144·9) months, no needle-track seeding was noted. Of four disappearing CRLM that were marked and resected, two presented with persistent active disease. Other missing lesions were treated with thermoablation.Conclusion:Pretherapeutic fiducial marker placement appears useful for the curative management of CRLM.

Background: Posthepatectomy biliary leakage (PHBL) remains a major cause of morbidity after elective liver resection. Former prognostic studies on PHBL lacked power, population homogeneity, and model validation. The present study aimed to develop and validate a risk-score for predicting severe PHBL after hepatectomy. Methods: A prospective multicenter observational study included 2218 hepatectomies without hepatico-jejunostomy between 2012 and 2015. Procedures were randomly assigned with a 2:1 ratio to a training (n=1475) or validation cohort (n=743). A model predicting severe PHBL (defined as ISGLS grade B/C) was built in the training cohort and tested in the validation cohort. Results: Overall and severe PHBL occurred in 141 (6.4%) and 92 (4.1%) patients, respectively. In the training cohort, multivariate analysis identified blood loss >500ml, remnant ischemia >45min, anatomical resection including segment 8, transection along right aspect of left portal fissure, and ALPPS as predictors of severe PHBL. A risk-score (0-5 points) was built in the training cohort (c-statistic: 0.79, 95% CI: 0.74-0.85) and successfully tested upon the validation cohort (c-statistic: 0.70, 95% CI: 0.60-0.80). A score ≥3 predicted an increase of severe PHBL (19.4% versus 2.6%, p<0.001 in the training cohort; 15.1% versus 3.1%, p<0.001 in the validation cohort). Conclusion: The risk-score represents a multi-institutionally validated prognostic tool, allowing to identify patients at high-risk for severe PHBL after elective hepatectomy.

L’objectif de l’étude était de réévaluer les indications et les résultats de la pancréatectomie total (PT) dans la prise en charge des TIPMP à partir de la plus grande série à ce jour. Tous les patients opérés d’une PT élective ont été sélectionnés dans la base de données multicentrique de l’AFC sur les TIPMP et analysés. Quatre-vingt-treize sur 888 patients (10,5 %) ont eu une PT. La TIPMP était mixte dans 59 % et la PT décidée en peropératoire dans 33 %. La morbidité et la mortalité étaient de 47,3 % et 4,3 % respectivement, et plus élevées en cas de totalisation peropératoire (p < 0,001). Les erreurs diagnostiques étaient fréquentes concernant l’atteinte du CPP (12 %), la présence d’un cancer (33 %) ou de nodules muraux (50 %). Douze PT (13 %) étaient inappropriées. Cinquante-huit pour cent des patients présentaient un cancer (pT3 [68 %], N+ [60 %], R0 [74 %]) et la survie était alors fortement impactée (survie à 5 ans : 21,2 % versus 85,7 % si TIPMP non invasive, p < 0,0001). Cinquante-huit pour cent des patients avec cancer ont récidivé. La morbi-mortalité de la PT était acceptable mais un nombre important de PT inappropriées ont été observées. La survie est excellente en cas de TIPMP non invasive mais reste décevante en cas de cancer.

Background: The question of intra-abdominal drainage after pancreaticoduodenectomy (PD) remains challenging and unsolved. Objectives: The aim of the study was to evaluate the effect of a selective drainage policy, based on the pancreas texture and the main pancreatic duct size, on the postoperative morbidity after PD. Methods: A no drain policy from January 2012 to September 2014 was compared to a selective drainage policy from October 2014 to May 2017 in patients undergoing PD. Drains were placed in case of soft/medium pancreas and/or in case of MPD size ≤3 mm. The primary endpoint was the postoperative morbidity graded according to Clavien-Dindo classification. Results: 134 patients were included: 74 in the no-drain group and 60 in the selective drain group. Postoperative morbidity was 82% in the no-drain group versus 75 % in the selective drain group (p=0.293). After selective drainage, uneventful postoperative course was more frequent (11% versus 25%; p=0.03), patients developed less complications grade III-IV (25% vs 50%; p=0.003) and less PPH (12% vs 30%; p=0.012). Selective drainage policy was associated with shorter length of stay (19.6 ± 11.6 vs 28.4 ± 16.9 days; p < 0.001) and lower reintervention rate (23% vs 53%; p < 0.001). Logistic regression analysis showed that pancreas texture was the only independent risk factor of postoperative pancreatic fistula (POPF) (OR=3.69; p=0.019). Conclusion: After PD, selective policy drainage in patients at high risk of POPF (soft/medium pancreas and MPD size ≤3 mm) appears to be a safe drainage policy.

Objectives: Specific enhanced recovery after surgery (ERAS) guidelines for duodenopancreatectomy were published, mostly by extrapolating data from colorectal surgery. This study aimed to assess the feasibility of an ERAS protocol by determining the compliance after duodenopancreatectomy according to the validated ERAS Society guidelines.

Background: The MDACC group recommends to extend the current borderline classification for pancreatic cancer into three groups: type A patients with resectable/borderline tumor anatomy, type B with resectable/borderline resectable tumor anatomy and clinical findings suspicious for extrapancreatic disease and type C with borderline resectable and marginal performance status/severe pre-existing comorbidity profile or age>80. This study intents to evaluate the proposed borderline classification system in a multicenter patient cohort without neoadjuvant treatment. Methods: Evaluation was based on a multicenter database of pancreatic cancer patients undergoing surgery from 2005 to 2016 (n = 1020). Complications were classified based on the Clavien-Dindo classification. chi(2)-test, Kaplan Meier estimator and Cox regression hazard model were used for statistical analysis. Results: Most patients (55.1%) were assigned as type A patients, followed by type C (35.8%) and type B patients (9.1%). Neither the complication rate, nor the mortality rate revealed a correlation to any subgroup. Type B patients had a significant worse progression free (p < 0.001) and overall survival (p = 0.005). Type B classification was identified as an independent prognostic marker for progression free survival (p = 0.005, HR 1.47). Conclusion: The evaluation of the proposed classification in a cohort without neoadjuvant treatment did not justify an additional medical borderline subgroup. A new subgroup based on prognostic borderline patients might be the main target group for neoadjuvant protocols in future. (C) 2018 Published by Elsevier Ltd.

Biliary leakage remains a major cause of morbidity after liver resection. Previous prognostic studies of posthepatectomy biliary leakage (PHBL) lacked power, population homogeneity, and model validation. The present study aimed to develop a risk score for predicting severe PHBL.