Diagnostic yield of repeat genetic testing in idiopathic chronic pancreatitis.

Genetic testing is performed for unexplained pancreatitis. The aim of this study was to evaluate the diagnostic value of repeating genetic testing in idiopathic pancreatitis when new predisposing genes are identified. We investigated 330 patients who were initially screened for PRSS1, SPINK1 and CFTR genes. A new analysis was performed by Next-Generation Sequencing (NGS) for PRSS1, SPINK1, CFTR, CTRC, CASR, CPA1, TRPV6 genes and the CEL-HYB1 allele in clinical practice, and patients were included in our cohort study. Additional rare variants were identified in 7.3 % of the patients. Screening for new pancreatitis genes is recommended when initial screening is limited. Routine use of NGS is a useful diagnostic tool in these cases.

Outcome and survival were similar with laparoscopic and open pancreatectomy in 102 solid pseudopapillary neoplasms.

BACKGROUND: Solid pseudopapillary neoplasms of the pancreas (SPNP) are rare tumors predominantly in young women. We report the largest single-center cohort study comparing resection of SPNP by laparoscopic approach (LA) and the open approach (OA). METHOD: Between 2001 and 2021, 102 patients (84% women, median age: 30) underwent pancreatectomy for SPNP and were retrospectively studied. Demographic, perioperative, pathological, early and the long-term results were evaluated between patients operated by LA and those by OA. RESULTS: Population included 40 LA and 62 OA. There were no significant differences in demographics data between the groups. A preoperative biopsy by endoscopic ultrasound was performed in 45 patients (44%) with no difference between the groups. Pancreatoduodenectomy (PD) was less frequently performed by LA (25 vs 53%, p = 0.004) and distal pancreatectomy (DP) was more frequently performed by LA (40 vs 16%, p = 0.003). In the subgroup analysis by surgical procedure, LA-PD was associated with one mortality, less median blood loss (180 vs 200 ml, p = 0.034) and fewer harvested lymph nodes (11 vs 15, p = 0.02). LA-DP was associated with smaller median tumor size on imaging (40 vs 80mm, p = 0.048), shorter surgery (135 vs 190 min, p = 0.028), and fewer complications according to the median comprehensive complication index score (0 vs 8.7, p = 0.048). LA-Central pancreatectomy was associated with shorter surgery (160 vs 240, p = 0.037), less median blood loss (60 vs 200, p = 0.043), and less harvested lymph nodes (5 vs 2, p = 0.025). After a median follow-up of 60 months, two recurrences (2%) were observed and were unrelated to the approach. CONCLUSIONS: The LA for SPNP appears to be safe, should be applied cautiously in case of PD for large lesion, and was not associated with recurrence.

Epidemiology, treatment and outcomes of infected pancreatic necrosis in France: a bicenter study.

INTRODUCTION: Acute necrotizing pancreatitis (ANP) mortality increases when pancreatic necrosis is infected (IPN). Current treatment of IPN relies on prolonged antibiotic therapies associated with a step-up strategy of drainage. The objective of this study was to analyze IPN treatment outcomes in two referral centers in France. METHODS: Data of consecutive patients with documented IPN hospitalized in two expert centers in France between 2014 and 2019 were retrospectively reviewed. The composite primary outcome was the proportion of unsuccessful management outcome, defined as new emergency drainage to treat sepsis with organ failure, an unplanned new antibiotic course, an unplanned prolongation of antibiotic course and/or death by septic shock, within three months following the diagnosis of ANP. RESULTS: All in all, 187 patients (138 males; 74.0%), with documented IPN were included. The most frequently identified microorganism was Escherichia coli (26.2%). Ninety-eight patients (52.4%) were admitted to an intensive care unit or resuscitation ward within the first two days of ANP care. Overall, 126 patients (67.4%) endured an unsuccessful outcome: new emergency drainage to treat acute sepsis (62.0%), unplanned new antibiotic course (47.1%), unplanned prolongation of antibiotic course (44.9%) and/or death by septic shock complicating IPN (8.0%). CONCLUSION: The unfavorable evolution in two thirds of patients shows that determination of optimal drainage timing and choice of antibiotic therapy remain major challenges in 2024.

Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

Long-term quality of life is better after laparoscopic compared to open pancreatoduodenectomy.

BACKGROUND: Three randomized controlled trials have reported improved functional recovery after Laparoscopic pancreatoduodenectomy (LPD), as compared to open pancreatoduodenectomy (OPD). Long-term results regarding quality of life (QoL) are lacking. The aim of this study was to compare long-term QoL of LPD versus OPD. METHODS AND PATIENTS: A monocentric retrospective cross-sectional study was performed among patients < 75 years old who underwent LPD or OPD for a benign or premalignant pathology in a high-volume center (2011-2021). An electronic three-part questionnaire was sent to eligible patients, including two diseases specific QoL questionnaires (the European Organization for Research and Treatment in Cancer Quality of Life Questionnaire for cancer (QLQ-C30) and a pancreatic cancer module (PAN26) and a body image questionnaire. Patient demographics and postoperative data were collected and compared between LPD and OPD. RESULTS: Among 948 patients who underwent PD (137 LPD, 811 OPD), 170 were eligible and 111 responded (58 LPD and 53 OPD). LPD versus OPD showed no difference in mean age (51 vs. 55 years, p = 0.199) and female gender (40% vs. 45%, p = 0.631), but LPD showed lower BMI (24 vs 26; p = 0.028) and higher preoperative pancreatitis (29% vs 13%; p = 0.041). The postoperative outcome showed similar Clavien-Dindo ≥ III morbidity (19% vs. 23%; p = 0.343) and length of stay (24 vs. 21 days, p = 0.963). After a similar median follow-up (3 vs. 3 years; p = 0.122), LPD vs OPD patients reported higher QoL (QLQ-C30: 49.6 vs 56.3; p = 0.07), better pancreas specific health status score (PAN20: 50.5 vs 55.5; p = 0.002), physical functioning (p = 0.002), and activities limitations (p = 0.02). Scar scores were better after LPD regarding esthetics (p = 0.001), satisfaction (p = 0.04), chronic pain at rest (p = 0.036), moving (p = 0.011) or in daily activities (p = 0.02). There was no difference in digestive symptoms (p = 0.995). CONCLUSION: This monocentric study found improved long-term QoL in patients undergoing LPD, as compared to OPD, for benign and premalignant diseases. These results could be considered when choosing the surgical approach in these patients.

Efficacy and tolerance of LV5FU2-carboplatin chemotherapy in patients with advanced pancreatic ductal adenocarcinoma after failure of standard regimens.

Background: Chemotherapy options in patients with advanced pancreatic ductal adenocarcinoma (PDAC) after failure of standard chemotherapies are limited. Objectives: We aimed to report the efficacy and safety of the leucovorin and 5-fluorouracil (LV5FU2) and carboplatin combination in this setting. Design: We performed a retrospective study including consecutive patients with advanced PDAC who received LV5FU2-carboplatin between 2009 and 2021 in an expert center. Methods: We measured overall survival (OS) and progression-free survival (PFS), and explored associated factors using Cox proportional hazard models. Results: In all, 91 patients were included (55% male, median age 62), with a performance status of 0/1 in 74% of cases. LV5FU2-carboplatin was mainly used in third (59.3%) or fourth line (23.1%), with three (interquartile range: 2.0-6.0) cycles administered on average. The clinical benefit rate was 25.2%. Median PFS was 2.7 months (95% CI: 2.4-3.0). At multivariable analysis, no extrahepatic metastases (p = 0.083), no ascites or opioid-requiring pain (p = 0.023), <2 prior treatment lines (p < 0.001), full dose of carboplatin (p = 0.004), and treatment initiation >18 months after initial diagnosis (p < 0.001) were associated with longer PFS. Median OS was 4.2 months (95% CI: 3.48-4.92) and was influenced by the presence of extrahepatic metastases (p = 0.058), opioid-requiring pain or ascites (p = 0.039), and number of prior treatment lines (0.065). Prior tumor response under oxaliplatin did not impact either PFS or OS. Worsening of preexisting residual neurotoxicity was infrequent (13.2%). The most common grade 3-4 adverse events were neutropenia (24.7%) and thrombocytopenia (11.8%). Conclusion: Although the efficacy of LV5FU2-carboplatin appears limited in patients with pretreated advanced PDAC, it may be beneficial in selected patients.

Outcomes and predictors of delayed endoscopic biliary drainage for severe acute cholangitis due to choledocholithiasis in an intensive care unit.

BACKGROUND: Acute cholangitis (AC) is an infection of the biliary tract secondary to biliary obstruction requiring biliary drainage through endoscopic retrograde cholangiopancreatography. This study aims to compare the outcome between the early and delayed ERCP in patients with severe AC. METHODS: Patient with severe AC due to choledocholithiasis admitted to intensive care unit were included. Early ERCP was defined was as ERCP performed within 24 h following hospital admission. Propensity-score matching was used to reduce the imbalance between groups. The primary outcome was 30-day mortality. Secondary outcomes included length of hospital and ICU stay, onset or persistent organ failure. RESULTS: The delayed ERCP group had a higher mortality rate at 30 days (45,5 versus 13%, <0.001) and at 1 year (59,7% versus 15,6%, p <0.001). Delayed ERCP had also a higher rate of respiratory adverse events (54,5 versus 27,8%, p = 0,002), longer ICU (7.41 versus 4.61, p = 0,004) and hospital (11,88 versus 9,22, p = 0,042) length of stay. Predictors of delayed ERCP were cardiac arrythmias, liver disease, creatinine value and white blood cell count at baseline. CONCLUSIONS: Delays in ERCP for patients with severe AC appear to be associated with higher mortality rate and prolonged ICU and hospital stays.

Dilatation of the main pancreatic duct of unknown origin: causes and risk factors of pre-malignancy or malignancy.

INTRODUCTION: A dilatation of the main pancreatic duct (MPD) is mainly due to obstructive causes (pancreatic tumor, chronic pancreatitis) or intraductal papillary mucinous neoplasm (IPMN). This study aims to assess the risk of pre-malignancy or malignancy in case of MPD dilatation with no visible mass nor obstructive calcification on computed tomography scan (CT-scan) in a population operated for it. PATIENTS AND METHODS: All patients operated on from November 2015 to December 2019 in our center for a significant dilatation of the MPD without visible obstructive cause on CT-scan were included. Preoperative work-up included at least CT-scan, magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). Primary endpoint was the final pathological diagnosis. Secondary endpoints were predictive factors of malignancy. RESULTS: 101 patients were included, mean age 68 years-old. Final pathological data were pancreatic adenocarcinoma (n = 2), IPMN with high-grade dysplasia (n = 37), high-grade Pancreatic Intraepithelial Neoplasia (PanIN) (n = 2) (total of pre-malignant or malignant lesions: n = 41), neuroendocrine tumor (n = 6), IPMN with low-grade dysplasia (n = 45), low-grade PanIN (n = 5), chronic pancreatitis (n = 3), and benign stenosis (n = 1). On preoperative explorations, the median diameter of MPD was 7 mm [3-35]. MRI and/or EUS showed intraductal material, nodule, or cyst in 22, 32, and 52 patients, respectively; 22 patients without nodule visible on MRI or EUS had still a pre-malignant or malignant lesion. In multivariate analysis, predictive factors for pre-malignancy or malignancy were symptoms before surgery (p = 0.01), MPD dilatation without downstream stenosis (p = 0.046), and the presence of nodule (p = 0.009). CONCLUSION: A dilatation of the MPD without detectable mass or obstructive calcification on CT-scan was associated with a pre-malignant or malignant lesion in 41 patients. Symptoms before surgery, MPD dilatation without duct narrowing, and the presence of nodules on MRI/EUS were associated with the risk of  pre-malignancy or malignancy.

Paroxysmal dyskinesia and electrodermal volatility: The role of mindfulness, self-compassion and psychophysiological interventions.

To date, there are no behavioral or psychophysiological treatment studies on paroxysmal dyskinesia (PD). PD is a group of debilitating movement disorders that present with severe episodes of dystonia, chorea, and/or ballistic like movements. This is a first case report of a 50-year-old male who received behavioral interventions (e.g., mindfulness, CBT, and biofeedback interventions) to manage his PD episodes in tandem with multidisciplinary treatments (e.g., neurology, psychiatry, etc.). The paper primarily discusses the serendipitous observation of galvanic skin response (GSR) elevations and spikes immediately before and after the onset of PD episodes. GSR volatility was noted in wave amplitude and wave morphology. Graphs are presented to illustrate GSR volatility associate with PD episodes and the reduction of GSR volatility in response to behavioral approaches. The discussion highlights the feasibility of using GSR biofeedback as an adjunct to mindfulness and CBT to manage PD as part of a multidisciplinary treatment approach. Peripherally, issues that related to misclassification of somatic symptoms and related disorders (e.g., psychogenic non-epileptic seizures) and aspects of neurocognitive disorders are discussed. The paper reviews neurological findings, MRI, neuropsychological data, and psychiatric assessment to highlight the dilemma clinician's face and clarify behavioral practices to further the management of PD.

WITHDRAWN: Clinical interpretation of PRSS1 gene variants in patients with pancreatitis.

Since the description of the PRSS1 gene encoding the cationic trypsinogen as being involved in dominant hereditary pancreatitis, more than 50 PRSS1 gene variants have been reported. Among those that have been classified as pathogenic, some have a high penetrance and others have a low penetrance. Assessing the clinical relevance of PRSS1 variants is often complicated in the absence of functional evidence and interpretation regarding rare variants is not very easy in clinical practice. The aim of this study was to review the PRSS1 variants and to classify them according to their degree of deleterious effect. This classification was based on the results of in vitro experiments and on population data, in comparing the allelic frequency of each variant in patients with pancreatitis and in unaffected individuals. This review should help geneticists and clinicians in charge of patient...s care and genetic counseling to interpret results of genetic studies.

Laparoscopic-assisted liver transplantation: A realistic perspective.

Laparoscopic approach was rarely described in recipients for liver transplantation (LT). We report the feasibility and safety of laparoscopic-assisted LT (LA-LT) in patients with unresectable liver metastases of neuroendocrine tumors. Total hepatectomy was performed laparoscopically with graft implantation through an upper midline incision. Liver grafts were retrieved from deceased donors. From July 2019 to July 2021, six patients (4 women, 2 men) underwent LA-LT. Median age and BMI were 46 (29-54) and 24 (19-35) kg/m2 , respectively. Implanted grafts were reduced (n = 3), full (n = 2), and a right split liver (n = 1). Median surgical time was 405 min (390-450) and median blood loss was 425 ml (250-600). Median cold and warm ischemia times were 438 min (360-575) and 35 min (30-40), respectively. Median anhepatic phase was 51 min (40-67) and midline incision was 14 cm (13-20) long. On postoperative day 5, median prothrombin index and serum bilirubin levels were 95% (70-117) and 11 (10-37) µmol/L, respectively. No Clavien-Dindo > III complications were encountered. Median hospital stay was 12 days (10-14). After a median follow-up of 8 (8-32) months, all patients were alive without tumor recurrence or adverse event. This preliminary series suggests that in selected patients, LA-LT is a safe and effective option.

Guidelines for the management of patients with severe acute pancreatitis, 2021.

OBJECTIVE: To provide guidelines for the management of the intensive care patient with severe acute pancreatitis. DESIGN: A consensus committee of 22 experts was convened. A formal conflict-of-interest (COI) policy was developed at the beginning of the process and enforced throughout. The entire guideline construction process was conducted independently of any industrial funding (i.e. pharmaceutical, medical devices). The authors were required to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. METHODS: The most recent SFAR and SNFGE guidelines on the management of the patient with severe pancreatitis were published in 2001. The literature now is sufficient for an update. The committee studied 14 questions within 3 fields. Each question was formulated in a PICO (Patients Intervention Comparison Outcome) format and the relevant evidence profiles were produced. The literature review and recommendations were made according to the GRADE® methodology. RESULTS: The experts' synthesis work and their application of the GRADE® method resulted in 24 recommendations. Among the formalised recommendations, 8 have high levels of evidence (GRADE 1+/-) and 12 have moderate levels of evidence (GRADE 2+/-). For 4 recommendations, the GRADE method could not be applied, resulting in expert opinions. Four questions did not find any response in the literature. After one round of scoring, strong agreement was reached for all the recommendations. CONCLUSIONS: There was strong agreement among experts for 24 recommendations to improve practices for the management of intensive care patients with severe acute pancreatitis.

MRI is useful to suggest and exclude malignancy in mucinous cystic neoplasms of the pancreas.

OBJECTIVES: To evaluate the value of MRI in differentiating benign (b-MCN) and malignant (m-MCN) MCN. European guidelines suggest that certain mucinous cystic neoplasms (MCN) of the pancreas can be conservatively managed. METHODS: A retrospective single-center study of consecutive patients with resected MCN. MRIs were independently reviewed by two readers blinded to the pathological results. The authors compared b-MCN (i.e., mucinous-cystadenoma comprising high-grade dysplasia (HGD)) and m-MCN (i.e., cystadenocarcinoma). RESULTS: Sixty-three patients (62 women [98%]) with 63 MCN (6 m-MCN, 2 HGD) were included. m-MCN tumors had a tendency to be larger than b-MCN (median 86 [25-103] vs. 45 [17-130] mm, p = .055). The combination of signal heterogeneity on T2-weighted imaging, wall thickness ≥ 5 mm, the presence of mural nodules ≥ 9 mm, and enhancing septa had an area under the ROC curve of 0.97 (95% CI 0.91-1.00) for the diagnosis of m-MCN. A total of 24 (37%), 20 (32%), 10 (16%), 5 (8%), and 4 (6%) out of 63 MCNs showed 0, 1, 2, 3, and 4 of these features, respectively. The corresponding rate of m-MCN was 0%, 0%, 10%, 20%, and 100%, respectively, with a good-to-excellent inter-reader agreement. Patterns with a high NPV for m-MCN included an absence of enhancing septa or walls (NPV 97% and 100%, respectively), wall thickness < 3 mm (NPV 100%), and no mural nodules (NPV 100%). CONCLUSIONS: A combination of 4 imaging features suggests malignant MCN on MRI. On the other hand, visualization of a thin non-enhancing wall with no mural nodules suggests benign MCN. KEY POINTS: • A heterogenous signal on T2-weighted MRI, a ≥ 5-mm-thick wall, mural nodules ≥ 9 mm, and/or enhancing septa suggest malignant MCNs. • A thin non-enhancing wall with no mural nodules suggests benign MCNs. • MRI should be performed in the pre-therapeutic evaluation of MCN to help determine the therapeutic strategy in these patients.

Efficacy and tolerance of gemcitabine and nab-paclitaxel in elderly patients with advanced pancreatic ductal adenocarcinoma.

BACKGROUND: The efficacy and safety of gemcitabine and nab-paclitaxel (GnP) among elderly patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. We aimed to evaluate the safety and efficacy of GnP in this setting. PATIENTS AND METHODS: We retrospectively included all consecutive patients aged ≥65 years with histologically proven PDAC who received at least one cycle of GnP (January 2014 to May 2018) in four academic centers. The primary endpoints were toxicity and overall survival (OS). Secondary endpoints were progression-free survival (PFS) and objective response rate. We compared patients aged ≥ or <75 years. RESULTS: The study included 127 patients; among them 42 (33.1%) were aged ≥ 75 years. Fifty-seven and seventy patients received GnP as the first-line and the second-line treatment or beyond, respectively. Sixty-seven patients had at least one grade 3/4 adverse event, the most frequent being neutropenia and peripheral neuropathy. No deaths were related to toxicity. OS (median, 8.0 months; 95% confidence interval (CI), 5.8-10.2) and PFS (median, 5.5 months; 95% CI, 4.8-6.2) were similar for patients aged <75 or ≥75 years in the whole cohort and among patients receiving GnP as the first-line treatment. Cephalic PDAC, liver metastases, hypoalbuminemia, and GnP received beyond the first-line were associated with a significantly shorter OS on the multivariate analysis. CONCLUSION: GnP is well tolerated and effective in elderly patients with advanced PDAC, even patients aged ≥75 years. The data from daily clinical practice are consistent with the results reported with first-line treatment and highlight the relevance of GnP administration in elderly patients.

Serum phosphate is associated with mortality among patients admitted to ICU for acute pancreatitis.

BACKGROUND AND AIMS: Routine laboratory tests can be useful predictors in the early assessment of the severity and mortality of acute pancreatitis (AP). The aim of this study was to evaluate the accuracy of clinical and laboratory parameters for the prediction of mortality among patients admitted to the intensive care unit (ICU) for AP. METHODS: We conducted a retrospective analysis of prospectively collected data from Beth Israel Deaconess Hospital made publicly available to examine the relationship between routine clinical and laboratory parameters with respect to mortality for AP. Cox proportional hazard ratio was used to evaluate the impact of several routine laboratory markers on mortality. Receiver operation characteristic (ROC) curve was performed to determine the accuracy of diagnosis of laboratory tests by using area under curve (AUC) for the respective analysis. RESULTS: In total, 499 patients were admitted to the ICU for AP. Several factors for predicting mortality in AP at admission were identified in the multivariate analysis: alkaline phosphatase hazard ratio (HR) = 1.00 (1.00-1.00, p = 0.024), anion gap HR = 1.09 (1.00-1.20, p = 0.047), bilirubin total HR = 1.11 (1.06-1.17, p < 0.001), calcium total HR = 0.59 (0.42-0.84, p = 0.004), phosphate HR = 1.51 (1.18-1.94, p = 0.001), potassium HR = 1.91 (1.03-3.55, p = 0.041), white blood cells HR = 1.04 (1.00-1.07, p = 0.028). The AUC of serum phosphate level for mortality was 0.7 in the ROC analysis. The optimal cut-off value of serum phosphate level for prediction of mortality was 3.78 mg/dl (sensitivity, 0.58; specificity, 0.78). CONCLUSION: In this large cohort, we identified baseline serum phosphate as the most valuable single routine laboratory test for predicting mortality in AP. Future prospective studies are required to confirm these results.