Reappraising imaging features of pancreatic acinar cystic transformation: be aware of differential diagnoses.

OBJECTIVES: Imaging features of pancreatic acinar cystic transformation (ACT) have been published. We aimed to describe the clinical and radiological characteristics of patients with a presumed pancreatic ACT diagnosis, reappraising the value of these published imaging criteria. MATERIALS AND METHODS: Single-center retrospective study (2003-2021) of consecutive patients with a presumed diagnosis of ACT as suggested by the local expert multidisciplinary case review board. Patients without available imaging (CT or MRI) for review were excluded. Patients were classified into "certain" ACT (if ≥ 2 imaging criteria and no differential diagnosis) or "uncertain" ACT (if ≥ 1 imaging criteria and suggested differential diagnoses). RESULTS: Sixty-four patients (35 males, [55%]) were included. ACT was considered "certain" for 34 patients (53%) and "uncertain" for 30 patients (47%). The number of ACT criteria did not differ between groups, with 91.2% of patients with ≥ 3 ACT imaging criteria in the "certain" group vs 93.3% in the "uncertain" group (p = 0.88). In the "uncertain" group, the main suggested differentials were branch-duct intraductal papillary mucinous neoplasm (18/30 patients, 60%), calcifying chronic pancreatitis (8/30 patients, 27%), both (three patients, 10%) and serous cystadenoma (one patient, 3%). Calcifications were significantly more frequent in the "uncertain" group (89% vs 63% in the "certain" group, p = 0.02). CONCLUSION: Published ACT imaging criteria are frequently associated with features suggesting differential diagnoses. They appear insufficient to reach a final diagnosis in a subset of patients. CLINICAL RELEVANCE STATEMENT: ACT displays a heterogeneous morphological imaging presentation challenging the non-invasive diagnostic work-up. Physicians' and radiologists' awareness of this entity is important to better understand its natural history and improve non-invasive diagnostic criteria. KEY POINTS: The criteria to help diagnose ACT are frequently associated with features suggestive of differentials. The main alternatives suggested when ACT diagnosis was "uncertain" were branch-duct intraductal papillary mucinous neoplasm and calcifying chronic pancreatitis. Published ACT diagnostic imaging criteria can be insufficient for a definite non-invasive diagnosis.

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.

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.

Role of the fatty pancreatic infiltration in pancreatic oncogenesis.

Although pancreatic precancerous lesions are known to be related to obesity and fatty pancreatic infiltration, the mechanisms remain unclear. We assessed the role of fatty infiltration in the process of pancreatic oncogenesis and obesity. A combined transcriptomic, lipidomic and pathological approach was used to explore neoplastic transformations. Intralobular (ILF) and extralobular (ELF) lipidomic profiles were analyzed to search for lipids associated with pancreatic intraepithelial neoplasia (PanINs) and obesity; the effect of ILF and ELF on acinar tissue and the histopathological aspects of pancreatic parenchyma changes in obese (OB) and non-obese patients. This study showed that the lipid composition of ILF was different from that of ELF. ILF was related to obesity and ELF-specific lipids were correlated to PanINs. Acinar cells were shown to have different phenotypes depending on the presence and proximity to ILF in OB patients. Several lipid metabolic pathways, oxidative stress and inflammatory pathways were upregulated in acinar tissue during ILF infiltration in OB patients. Early acinar transformations, called acinar nodules (AN) were linked to obesity but not ELF or ILF suggesting that they are the first reversible precancerous pancreatic lesions to occur in OB patients. On the other hand, the number of PanINs was higher in OB patients and was positively correlated to ILF and ELF scores as well as to fibrosis. Our study suggests that two types of fat infiltration must be distinguished, ELF and ILF. ILF plays a major role in acinar modifications and the development of precancerous lesions associated with obesity, while ELF may play a role in the progression of PDAC.

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.

[Hereditary and familial forms of pancreatic adenocarcinoma: Genetic determinism, patients eligible for systematic screening, screening methods and results]. / Les formes héréditaires et familiales des adénocarcinomes pancréatiques : déterminisme génétique, population éligible à un dépistage systématique, modalités et résultats du dépistage.

Systematic screening for pancreatic cancer in high risk individuals is justified by the poor prognosis of the majority of cases diagnosed at a symptomatic stage that are mostly advanced and unresectable Individual risk assessment is based on both genetic data and family history. The screening of a panel of susceptibiility genes should be offered to any affected individual when a genetic predisposition is suspected. An international consortium has proposed a definition of the at risk population, candidate for screening, and there is a consensus on the target lesions of this screening: early adenocarcinoma and benign lesions with a high potential for malignant transformation: Intraductal Papillary Mucinous Neopasm (IPMN) and Pancreatic Intraepithelial Neoplasia (PanIN) with high-grade dysplasia. Its modalities currently consist of an annual pancreatic MRI and/or endoscopic ultrasound (EUS), associated with screening for diabetes mellitus. The main limitation of screening, the effectiveness of which has not yet been demonstrated, is its lack of sensitivity, which results in a non-negligible rate of interval cancers and sometimes advanced diagnoses. Insufficient specificity is also imperfect, in particular with regard to benign lesions with a low potential for degeneration, and can lead to the proposal of unjustified surgeries. This situation makes the future integration of new imaging techniques and promising new biological approaches that are being explored highly desirable.

Diagnosis and treatment of bacterial peritonitis in patients with gastrointestinal cancer: an observational multicenter study.

Background: Bacterial peritonitis (BP) in patients with gastrointestinal (GI) cancer has been poorly described, and its prevalence is unknown. Objectives: This study aimed to evaluate in patients with both GI cancer and ascites the prevalence of BP, associated features, mechanisms, prognosis, and the diagnostic performance of neutrophil count in ascites. Design: A retrospective, multicenter, observational study. Methods: All patients with GI cancer and ascites who underwent at least one paracentesis sample analyzed for bacteriology over a 1-year period were included. BP was defined by a positive ascites culture combined with clinical and/or biological signs compatible with infection. Secondary BP was defined as BP related to a direct intra-abdominal infectious source. Results: Five hundred fifty-seven ascites from 208 patients included were analyzed. Twenty-eight patients had at least one episode of BP and the annual prevalence rate of BP was 14%. Among the 28 patients with BP, 19 (65%) patients had proven secondary BP and 17 (59%) patients had multi-microbial BP, mainly due to Enterobacterales. A neutrophil count greater than 110/mm3 in ascites had negative and positive predictive values of 96% and 39%, respectively, for the diagnosis of BP. The median survival of patients with BP was 10 days (interquartile range 6-40) after the diagnosis. Conclusion: BP is not rare in patients with GI cancer and is associated with a poor short-term prognosis. When a patient with GI cancer is diagnosed with BP, a secondary cause should be sought. Further studies are needed to better define the best management of these patients.

SEC16A Variants Predispose to Chronic Pancreatitis by Impairing ER-to-Golgi Transport and Inducing ER Stress.

Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next-generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26-2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67-4.50) and in a biobank meta-analysis (OR, 1.16; 95% CI, 1.04-1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9-edited HEK293T cell lines show that loss-of-function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/- mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein-stimulated pancreatitis models, Sec16a+/- mice display heightened pancreatic inflammation and fibrosis compared to wild-type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.