Pancreaticopleural fistula is a rare complication of pancreatitis. We present a rare case of pancreaticopleural fistula in a 43-year-old alcoholic male. He presented with recurrent episodes of left pleural effusion that were managed with aspiration and chest tube placement. An MRI of the chest and upper abdomen revealed a pancreaticopleural fistula. The patient underwent distal pancreatectomy with splenectomy and Roux-en-Y pancreaticojejunostomy. The surgical approach was our first-line management due to the unavailability of octreotide and endoscopic retrograde cholangiopancreatography. His recovery was complicated by an empyema that was managed by tube thoracostomy and IV antibiotics. There was no issue detected at his 3-month follow-up clinic visit.

In this editorial, we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer. Cancer of the pancreas remains one of the deadliest cancer types. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends of pancreatic cancer incidence and mortality vary considerably worldwide. A better understanding of the etiology and identification of the risk factors is essential for the primary prevention of this disease. Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche. In this editorial, we highlight the foundational studies that have driven our understanding of these processes. In our experimental center, we have carefully studied the mechanisms of that link pancreatic inflammation and pancreatic cancer. We focused on the role of mast cells (MCs). MCs contain pro-angiogenic factors, including tryptase, that are associated with increased angiogenesis in various tumors. In this editorial, we address the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue and adjacent normal tissue. The assessment includes the density of c-Kit receptor-positive MCs, the density of tryptase-positive MCs, the area of tryptase-positive MCs, and angiogenesis in terms of microvascularization density.

BACKGROUND: Isoniazid-induced pancreatitis is a potentially serious adverse drug reaction, however, the frequency of its occurrence is unknown. We conducted a systematic review to explore this adverse drug reaction comprehensively.
METHODS: We performed an advanced search in PubMed, Web of Science, Scopus, Ovid, and Embase for studies that reported isoniazid-induced pancreatitis. From the extracted data of eligible cases, we performed a descriptive analysis and a methodological risk of bias assessment using a standardized tool.
RESULTS: We included 16 case reports from eight countries comprising 16 patients in our systematic review. Most of the isoniazid-induced pancreatitis cases were extrapulmonary tuberculosis cases. We found the mean age across all case reports was 36.7 years. In all the cases, discontinuation of isoniazid resulted in the resolution of pancreatitis.
CONCLUSIONS: We found the latency period for isoniazid-induced pancreatitis to be ranged from 12 to 45 days after initiation of isoniazid therapy. A low threshold for screening of pancreatitis by measuring pancreatic enzymes in patients on isoniazid presenting with acute abdominal pain is recommended. This would facilitate an early diagnosis and discontinuation of isoniazid, thus reducing the severity of pancreatitis and preventing the complications of pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a common emergency condition with high morbidity, mortality, and socio-economic impact. Soluble urokinase plasminogen activator receptor (suPAR) is a potential biomarker for AP prognosis. This study systematically reviews the literature on suPAR\'s prognostic roles in assessing AP severity, organ failure, mortality, and other pathological markers.
METHODS: A comprehensive search of 5 databases up to March 19, 2023, was conducted, selecting cohort studies that examined suPAR\'s relationship with AP outcomes. Outcome variables included AP severity, organ failure, mortality, hospital stay length, and suPAR\'s association with other inflammatory markers. Our paper has been registered on Prospero (ID: CRD42023410628).
RESULTS: Nine prospective observational studies with 1033 AP patients were included. Seven of eight studies found suPAR significantly elevated in severe acute pancreatitis (P < .05). Four studies showed suPAR effectively predicted organ failure risk, and 4 studies concluded suPAR significantly predicted mortality (P < .05). The review had no high-risk studies, enhancing credibility.
CONCLUSIONS: suPAR is a valuable prognostic marker in AP, significantly predicting severity, organ failure, hospital stay length, and mortality. Further large-scale studies are needed to explore suPAR\'s role in other clinical outcomes related to AP disease course, to establish it as a mainstay of AP prognosis.

UNASSIGNED: While most patients with acute pancreatitis (AP) fulfill diagnostic criteria with characteristic abdominal pain and serum lipase levels of at least 3 times the upper limit of normal (reference range) at presentation, early imaging is often used for confirmation. A prior prediction model and corresponding point-based score were developed using nonimaging parameters to diagnose AP in patients presenting to the emergency department (ED).
UNASSIGNED: To evaluate the performance of the prediction model to diagnose AP in a prospective patient cohort.
UNASSIGNED: This prospective diagnostic study included consecutive adult patients presenting to the ED between January 1, 2020, and March 9, 2021, at 2 large academic medical centers in the northeastern US with serum lipase levels at least 3 times the upper limit of normal. Patients transferred from outside institutions or with malignant disease and established intra-abdominal metastases, acute trauma, or altered mentation were excluded. Data were analyzed from October 15 to October 23, 2023.
UNASSIGNED: Participants were assigned scores for initial serum lipase level, number of prior AP episodes, prior cholelithiasis, abdominal surgery within 2 months, presence of epigastric pain, pain of worsening severity, duration from pain onset to presentation, and pain level at ED presentation.
UNASSIGNED: A final diagnosis of AP, established by expert review of hospitalization records.
UNASSIGNED: Prospective scores in 349 participants (mean [SD] age, 53.0 [18.8] years; 184 women [52.7%]; 66 Black [18.9%]; 199 White [57.0%]) demonstrated an area under the receiver operating characteristics curve of 0.91. A score of at least 6 points achieved highest accuracy (F score, 82.0), corresponding to a sensitivity of 81.5%, specificity of 85.9%, positive predictive value of 82.6%, and negative predictive value of 85.1% for AP diagnosis. Early computed tomography or magnetic resonance imaging was performed more often in participants predicted to have AP (116 of 155 [74.8%] with a score ≥6 vs 111 of 194 [57.2%] with a score <6; P < .001). Early imaging revealed an alternative diagnosis in 8 of 116 participants (6.9%) with scores of at least 6 points, 1 of 93 (1.1%) with scores of at least 7 points, and 1 of 73 (1.4%) with scores of at least 8 points.
UNASSIGNED: In this multicenter diagnostic study, the prediction model demonstrated excellent AP diagnostic accuracy. Its application may be used to avoid unnecessary confirmatory imaging.

Endoscopic retrograde cholangiopancreatography-guided transpapillary gallbladder drainage has emerged as an effective alternative for management of acute cholecystitis in nonoperable candidates. Delayed acute pancreatitis has not been previously described as an adverse event with this procedure. In this article, we describe 3 patients who developed acute pancreatitis between 2 and 6 weeks after stent insertion with no alternative inciting cause. Delayed acute pancreatitis may represent a rare and previously uncharacterized adverse event related to transpapillary gallbladder drainage.

Inflammation and tissue damage associated with pancreatitis can precede or occur concurrently with pancreatic ductal adenocarcinoma (PDAC). We demonstrate that in PDAC coupled with pancreatitis (ptPDAC), antigen-presenting type I conventional dendritic cells (cDC1s) are specifically activated. Immune checkpoint blockade therapy (iCBT) leads to cytotoxic CD8+ T cell activation and elimination of ptPDAC with restoration of life span even upon PDAC rechallenge. Using PDAC antigen-loaded cDC1s as a vaccine, immunotherapy-resistant PDAC was rendered sensitive to iCBT with elimination of tumors. cDC1 vaccination coupled with iCBT identified specific CDR3 sequences in the tumor-infiltrating CD8+ T cells with potential therapeutic importance. This study identifies a fundamental difference in the immune microenvironment in PDAC concurrent with, or without, pancreatitis and provides a rationale for combining cDC1 vaccination with iCBT as a potential treatment option.

Background and Objectives: The risk of developing glycemic dysregulation up to overt diabetes mellitus (DM) after an episode of acute pancreatitis (AP) is increasingly being analyzed. We aimed to assess the changes in serum glucose levels associated with the first episode of AP, as well as the impact of dysglycemia on outcomes such as the severity of inflammation, the length of hospitalization, mortality, and the persistence of hyperglycemia at follow-up. Materials and Methods: All patients experiencing their first episode of AP, who presented to the Emergency Room (ER) between 1 January 2020 and 31 December 2023, were retrospectively included. On-admission serum glucose and peak serum glucose during hospitalization were the biological markers used to assess glucose metabolism impairment, and they were correlated with outcomes of AP. Results: Our study included 240 patients, 46.67% (112 patients) having a biliary etiology for an AP flare. Patients with COVID-19-associated AP exhibited the highest on-admission and peak serum glucose levels (244.25 mg/dL and 305.5 mg/dL, respectively). A longer hospital stay was noted in patients with peak serum glucose levels of ≥100 mg/dL (9.49 days) compared to normoglycemic patients (6.53 days). Both on-admission and peak glucose levels were associated with elevated CRP levels during hospitalization. A total of 83.78% of patients who received antibiotics exhibited on-admission hyperglycemia, and 72.07% had peak serum glucose levels of ≥100 mg/dL. The presence of hyperglycemia at follow-up was associated with both on-admission and peak serum glucose levels of ≥100 mg/dL, as well as with a longer stay, higher CRP levels, and antibiotic use during index admission. Conclusions: On-admission hyperglycemia predicts a higher inflammatory response in patients at the first episode of AP, while the presence of hyperglycemia during hospitalization is associated with imaging and biological severity and longer hospitalizations, indicating a more severe disease course. Both on-admission and peak in-hospital hyperglycemia were identified as risk factors for sustained hyperglycemia at follow-up.

Diagnostic markers are desperately needed for the early detection of pancreatic ductal adenocarcinoma (PDA). We describe sets of markers expressed in temporal order in mouse models during pancreatitis, PDA initiation and progression. Cell type specificity and the differential expression of PDA markers were identified by screening single cell (sc) RNAseq from tumor samples of a mouse model for PDA (KIC) at early and late stages of PDA progression compared to that of a normal pancreas. Candidate genes were identified from three sources: (1) an unsupervised screening of the genes preferentially expressed in mouse PDA tumors; (2) signaling pathways that drive PDA, including the Ras pathway, calcium signaling, and known cancer genes, or genes encoding proteins that were identified by differential mass spectrometry (MS) of mouse tumors and conditioned media from human cancer cell lines; and (3) genes whose expression is associated with poor or better prognoses (PAAD, oncolnc.org). The developmental progression of PDA was detected in the temporal order of gene expression in the cancer cells of the KIC mice. The earliest diagnostic markers were expressed in epithelial cancer cells in early-stage, but not late-stage, PDA tumors. Other early markers were expressed in the epithelium of both early- and late-state PDA tumors. Markers that were expressed somewhat later were first elevated in the epithelial cancer cells of the late-stage tumors, then in both epithelial and mesenchymal cells, or only in mesenchymal cells. Stromal markers were differentially expressed in early- and/or late-stage PDA neoplasia in fibroblast and hematopoietic cells (lymphocytes and/or macrophages) or broadly expressed in cancer and many stromal cell types. Pancreatitis is a risk factor for PDA in humans. Mouse models of pancreatitis, including caerulein treatment and the acinar-specific homozygous deletion of differentiation transcription factors (dTFs), were screened for the early expression of all PDA markers identified in the KIC neoplasia. Prognostic markers associated with a more rapid decline were identified and showed differential and cell-type-specific expression in PDA, predominately in late-stage epithelial and/or mesenchymal cancer cells. Select markers were validated by immunohistochemistry in mouse and human samples of a normal pancreas and those with early- and late-stage PDA. In total, we present 2165 individual diagnostic and prognostic markers for disease progression to be tested in humans from pancreatitis to late-stage PDA.

We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P (n = 9 studies, N = 1375) involved as a starting point parathyroid NETs (n = 7) or pancreatitis (n = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three reports of parathyroid carcinoma (female/male ratio of 2/1, ages of 34 in women, men of 56). MEN1-NET studies (n = 7) included MEN1-related insulinomas (n = 2) or MEN1-associated PHP (n = 2) or analyses of genetic profile (n = 3), for a total of 877 MEN1 subjects. In MEN1 insulinomas (N = 77), the rate of associated PHP was 78%. Recurrence after parathyroidectomy (N = 585 with PHP) was higher after less-than-subtotal versus subtotal parathyroidectomy (68% versus 45%, p < 0.001); re-do surgery was 26% depending on surgery for pancreatic NETs (found in 82% of PHP patients). MEN1 pathogenic variants in exon 10 represented an independent risk factor for PHP recurrence. A single pediatric study in MEN1 (N = 80) revealed the following: a PHP rate of 80% and pancreatic NET rate of 35% and 35 underlying germline MEN1 pathogenic variants (and 3/35 of them were newly detected). The co-occurrence of genetic anomalies included the following: CDC73 gene variant, glucokinase regulatory protein gene pathogenic variant (c.151C>T, p.Arg51*), and CAH-X syndrome. IR/metabolic feature-focused analysis identified (n = 10, N = 1010) a heterogeneous spectrum: approximately one-third of adults might have had prediabetes, almost half displayed some level of IR as reflected by HOMA-IR > 2.6, and serum calcium was positively correlated with HOMA-IR. Vitamin D deficiency was associated with a higher rate of metabolic syndrome (n = 1). Normocalcemic and mildly symptomatic hyperparathyroidism (n = 6, N = 193) was associated with a higher fasting glucose and some improvement after parathyroidectomy. This multilayer pancreas/parathyroid analysis highlighted a complex panel of connections from pathogenic factors, including biochemical, molecular, genetic, and metabolic factors, to a clinical multidisciplinary panel.