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Purpose: Postoperative venous thromboembolism (VTE) risk is pronounced after abdominal cancer surgery. Enoxaparin shows promise in preventing VTE in gastrointestinal, gynecological, and urological cancers, but its application after surgery for hepatobiliary-pancreatic malignancy has been under-evaluated due to bleeding concerns. We confirmed the safety of enoxaparin administration in patients undergoing curative hepatobiliary-pancreatic surgery for malignancies in a prospective, multi-center, phase I study. Methods: The study was conducted from April 2015 to May 2021 across eight specialized centers. Patients (n = 262) were randomized to enoxaparin prophylaxis given postoperatively for 8 days (n = 131) or control (n = 131). The primary endpoint was the efficacy in reducing VTE. Secondary endpoints examined safety. Results: The full analysis set included 259 patients (131 control, 129 enoxaparin). The per-protocol population included 233 patients (117 control, 116 enoxaparin). Most cases were hepatic malignancies (111 control, 111 enoxaparin). The median administration duration of enoxaparin was 7 days, with 92% receiving 4000 units/day. Despite a reduction in the relative risk (RR) of VTE due to postoperative enoxaparin administration, the results were not significant (control: four cases, 3.4% vs. treatment: two cases, 1.7%; RR 0.50, 95% CI 0.09-2.70; p = 0.6834). No significant difference was found in the incidence of bleeding events (control: five cases, 4.3% vs. treatment: five cases, 4.3%, RR 1.00, 95% CI 0.53-1.89; p = 1.0000). Conclusions: The perioperative administration of enoxaparin in hepatobiliary-pancreatic malignancies is feasible and safe. However, further case accumulation and investigation are necessary to assess its potential in reducing the occurrence of VTE.

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A 57-year-old man with a background of chronic pancreatitis presented with acutely worsening abdominal pain and vomiting. He previously had a pancreatic duct stent in situ which had been removed 1 year prior to presentation. Initially suspected to be acute-on-chronic pancreatitis, a computed tomography (CT) scan of the abdomen and pelvis revealed an atrophic pancreas and a new mass in the pancreatic head, raising the suspicion of pancreatic malignancy. An urgent endoscopic ultrasound (EUS)-guided fine needle biopsy of the pancreatic head mass surprisingly revealed the presence of actinomyces colonies on histological evaluation. Prompt initiation of a prolonged antibiotic course led to significant clinical and radiological improvement. This case highlights the rare presentation of pancreatic actinomycosis which can often masquerade as malignancy. Although a gut commensal, actinomyces can elicit pathogenic effects if allowed to enter tissues through a breach in the mucosal lining such as following abdominal surgery or pancreatic duct intervention as observed in this case. Early recognition and appropriate treatment with antibiotics can lead to clinical recovery and complete resolution of the infection.

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Background: The diagnostic and prognostic clinical value of circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) in pancreatic malignancies are unclear. Herein, we aimed to perform a meta-analysis to evaluate ctDNA and cfDNA as potential diagnostic and prognostic biomarkers. Methods: PRISMA reporting guidelines were followed closely for conducting the current meta-analysis. The PubMed/Medline, Scopus, and Web of Science (WoS) databases were scanned in detail to identify eligible papers for the study. A quality assessment was performed in accordance with the REMARK criteria. The risk ratios (RRs) of the diagnostic accuracy of ctDNA compared to that of carbohydrate antigen 19.9 (CA 19.9) in all disease stages and the hazard ratios (HRs) of the prognostic role of ctDNA in overall survival (OS) were calculated with 95% confidence intervals (CIs). Results: A total of 18 papers were evaluated to assess the diagnostic accuracy and prognostic value of biomarkers related to pancreatic malignancies. The pooled analysis indicated that CA19.9 provides greater diagnostic accuracy across all disease stages than ctDNA or cfDNA (RR = 0.64, 95% CI: 0.50-0.82, p < 0.001). Additionally, in a secondary analysis focusing on prognosis, patients who were ctDNA-positive were found to have significantly worse OS (HR = 2.00, 95% CI: 1.51-2.66, p < 0.001). Conclusion: The findings of this meta-analysis demonstrated that CA19-9 still has greater diagnostic accuracy across all disease stages than KRAS mutations in ctDNA or cfDNA. Nonetheless, the presence of detectable levels of ctDNA was associated with worse patient outcomes regarding OS. There is a growing need for further research on this topic. Systematic review registration: https://doi.org/10.37766/inplasy2023.12.0092, identifier INPLASY2023120092.

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An adult male cadaver, approximately 60 years of age, was dissected as part of an eight-week didactic course. It was found that the subject had evidence of pancreatic cancer with signs of metastasis as well as significant bilateral pulmonary artery clotting. In particular, a saddle embolism was observed, and the cause of death was listed as sudden pulmonary failure. Malignant tumors are often accompanied by hypercoagulable states and increased risk of thromboembolism. Because the clots showed lines of Zahn on histology, we can infer that this hypercoagulable state preceded death and may have been related to the presence of pancreatic carcinoma. There are few recorded cases of pulmonary saddle embolism being the fatal event in cases of underlying pancreatic cancer. The extensive clotting observed in the inferior vena cava and pulmonary arteries demonstrates to clinicians that patients, especially those with pancreatic cancer, are at higher risk for thromboembolic events. This case report also serves as a reminder that instances of pulmonary failure or sudden death because of pulmonary saddle embolism may be caused by underlying visceral neoplasms, such as pancreatic cancer.

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Aim The study aims to determine the incidence of malignancy at presentation and subsequent risk of malignancy (at 12 months follow-up) in a cohort of patients with double duct sign (DDS) on cross-sectional imaging but no visible stigmata of jaundice. The study also correlates malignancy with liver enzyme dysfunction and estimates the resource burden incurred during the investigation of these patients. Methods A search for the key term "double duct sign" was undertaken in the radiological database of a tertiary hepatopancreatobiliary (HPB) centre between March 2017 and March 2022. Radiological reports, clinic letters, blood results, and multidisciplinary team meeting (MDT) outcomes were reviewed during this period and at one year. The national tariff payment system was reviewed to identify tariffs for different investigations required for the cohort and to calculate the total cost incurred. Results Ninety-seven patients with DDS were identified. Sixty-four patients (66%) had a normal bilirubin (0-21 µmol/L) at presentation and were included in the analysis. Seven patients (10.9%) were diagnosed with malignant peri-ampullary tumours, and 21 (32.8%) were diagnosed with benign diseases. In 34 patients (53%) with DDS, the underlying cause remained uncharacterised. Most patients had mild abnormalities of liver enzymes, but two patients (4.3%) were diagnosed with malignant peri-ampullary tumours despite having normal serological values. Patients who had a benign diagnosis and/or who had cancer excluded without a definitive diagnosis did not go on to develop a malignancy at 12 months follow-up. However, in those patients where the underlying aetiology could not be characterised, extended surveillance was required with a total of 80 MDT discussions and multiple surveillance scans (103 CT and 65 MRI scans). Twenty-six patients underwent endoscopic ultrasound (EUS) with three patients requiring more than one EUS examination (29 investigations in total). The cost of these investigations was £38,926.89. Conclusion This study confirms that DDS even in patients without clinical jaundice or with normal liver enzymes requires careful investigation to exclude malignancy despite the resource burden this entails. This supports previously reported results in the literature, and despite the increased use of cross-sectional imaging, DDS remains a clinically significant finding. Large cohort risk stratification studies would be useful to determine clinical urgency and allow the appropriate allocation of resources.

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In this report we present a rare case of pancreatoblastoma in an adult patient. Whilst they are amongst the most common malignant pancreatic tumours in children, presentations in adults are exceedingly rare, with a small number of reported cases. Its presentation is often non-specific in terms of clinical examination, and subsequent imaging can show similar findings to those seen in benign neoplasms. This report highlights the difficulty of achieving a diagnosis and subsequent treatment of such an uncommon disease. Biopsy and resultant histology are essential in diagnosis and surgical resection remains the preferred modality of treatment. However, the use of chemotherapy and its efficacy in adults remains unclear, and the prognosis documented in existing literature for adults is worse when compared to paediatric presentations. This case emphasises the need to consider pancreatoblastoma as a differential diagnosis when suspecting pancreatic or abdominal malignancies to achieve early detection and diagnosis, in order to provide optimal treatment and improve patient outcomes.

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Pancreatic ductal adenocarcinoma (PDAC) is a significant challenge due to its silent progression and well-advanced, unresectable, complicated presentation. Detecting this disease early on is crucial, and researchers have been investigating various potential biological markers, such as carbohydrate antigen 19-9 (CA 19-9), hoping to find indicators that can aid in its early detection. The primary focus of this review is on the diagnostic usefulness of CA 19-9 in detecting pancreatic cancer (PC) in the beginning stage and its usefulness in predicting progression. The database search of articles from PubMed, PMC, the Cochrane Library, and Google Scholar identified 227 articles published from 2013 to 2023. The keyword mix used in the search technique included terms like "CA 19-9," "pancreatic cancer," "diagnosis," and "early detection." This study provides evidence of CA 19-9's ability in detecting PDAC in the pre-diagnostic stage. But since the outcomes were inconsistent among the included trials, further analysis is required to develop standardized diagnostic criteria and methodologies. Furthermore, because of the variability of the study, it is not easy to make firm conclusions on CA 19-9's sensitivity as well as specificity in the first stage of pancreatic neoplasm. This in-depth overview of the available literature provides new insights into using CA 19-9 as a biological marker for detecting undiagnosed PC before progressing into the advanced stage, and was proven beneficial. However, this has to be shown in broader research with adequate sample size. Although it shows promise as a diagnostic tool, further study is required to confirm these findings.

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Biliary pancreatic malignancy has an occultic onset, a high degree of malignancy, and a poor prognosis. Most clinical patients miss the opportunity for surgical resection of the tumor. Systemic chemotherapy is still one of the important methods for the treatment of biliary pancreatic malignancies. Many chemotherapy regimens are available, but their efficacy is not satisfactory, and the occurrence of chemotherapy resistance is a major reason leading to poor prognosis. With the advancement of studies on intestinal flora, it has been found that intestinal flora is correlated with and plays an important role in chemotherapy resistance. The application of probiotics and other ways to regulate intestinal flora can improve this problem. This paper aims to review and analyze the research progress of intestinal flora in the chemotherapy resistance of biliary pancreatic malignancies to provide new ideas for treatment.

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Primary pancreatic lymphoma (PPL) is an extremely rare type of non-Hodgkin's lymphoma (NHL). It accounts for 0.1% of all lymphomas and less than 1% of pancreatic tumors. Within this subtype, T-cell lymphomas only account for up to 6.7% of pancreatic lymphomas. In this study, we present the case of a 78-year-old Hispanic man who presented with obstructive jaundice associated with a mass within the head of the pancreas; pathologic analysis of the tumor revealed a mature T-cell lymphoma, not otherwise specified (NOS).

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Although acinar cells comprise a large volume of the pancreas, they rarely transform into malignant neoplasms. Once they arise, they rapidly metastasize via hematogenous spread to other organs such as the brain, liver, lung, and skeletal system. Cutaneous involvement, however, is rarely seen in all patients with primary pancreatic neoplasms. The most frequently reported site of cutaneous manifestations is the umbilicus, with the other sites including the trunk, lower extremities, head, and neck. Here, we report a case of metastatic pancreatic acinar cell carcinoma with cutaneous involvement of the patient's scalp.

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Primary squamous cell carcinoma of pancreas is a rare malignant neoplasm. It has been reported as case reports only, hence clinical information is limited. Here, we present a case of primary squamous cell carcinoma of pancreas in a 47-year-old female with a background history of chronic pancreatitis. Patient was treated with systemic chemotherapy; however, she did not respond to the treatment protocol. Follow-up CT scan showed increase in the size and extension of the lesion. It is an aggressive tumor and does not respond well to chemotherapy or radiotherapy.

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Primary pancreatic sarcomas are rare malignancies with an incidence of 0.1%. This case report is of a 48-year-old man who presented with this condition. The patient's treatment plan consisted of distal pancreatectomy and splenectomy with intraoperative immunohistochemistry and adjuvant chemotherapy. To correctly identify and treat undifferentiated pleomorphic sarcoma, a stepwise strategy involving cross-sectional imaging and extensive histopathology analysis is necessary.

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Pancreatic malignancy is still the most lethal gastrointestinal malignancy. It has a very poor prognosis with low survival rate. Surgery is still the main treatment option for pancreatic malignancy. Most patients already have locally advanced and even late stage disease due to non-specific abdominal symptoms. Even though some cases are still suitable for surgical treatment, due to its aggressiveness adjuvant chemotherapy is becoming the standard treatment for controlling the disease. Radiofrequency ablation (RFA) is a thermal therapy that has been used as one of the standard treatments for liver malignancy. It can also be performed intraoperatively. There are several reports on percutaneous RFA treatment for pancreatic malignancy using transabdominal ultrasound and guided by computed tomography scan. However, due to its anatomical location and the risk of high radiation exposure, these methods seem to be very limited. Endoscopic ultrasound (EUS) has been widely used for pancreatic abnormality evaluation due to its ability to detect more accurately, especially small pancreatic lesions, compared to other imaging modalities. By the EUS approach, it is easier to achieve good visualization of tumor ablation and necrosis as the echoendoscope position is closer to the tumor area. Based on studies and a recent meta-analysis, EUS-guided RFA is a promising treatment approach for most pancreatic malignancy cases, but most studies only collected data from a small sample size. Larger studies are needed before clinical recommendations can be made.

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Lung injury is the most common secondary complication of pancreatitis and pancreatic malignancy. Around 60-70% of pancreatitis-related deaths are caused by lung injury; however, there is no animal model of the inflammation-mediated progressive pulmonary pathological events that contribute to acute lung injury in chronic pancreatitis (CP). Hence, we developed an inflammation-mediated mouse model and studied the pathological events that have a critical role in promoting the pathogenesis of lung injury. Our proteomic analysis of lung tissue revealed neutrophil-associated induction of neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase enzyme, further supporting a role for neutrophils in promoting IL-18-associated lung injury. We show that neutrophils released IL-18-induced p-NF-κB along with profibrotic and oncogenic proteins like TTF1, PDX1, and SOX9 in lung tissues of a mouse model of chronic pancreatitis. We also show that neutrophil infiltration induces TGF-ß and SMAD4 and activates epithelial cells to produce other profibrotic proteins like ZO-1 and MUC2, along with the fibroblast markers FGF-1 and αSMA, that cause mesenchymal transition and accumulation of extracellular matrix collagen. Most importantly, we present evidence that IL-18 inhibition significantly alleviates CP-induced lung injury. This was further established by the finding that IL-18 gene-deficient mice showed improved lung injury by inhibition of TGF-ß and fibroblast to mesenchymal transition and reduced collagen accumulation. The present study suggests that inhibition of IL-18 may be a novel treatment for CP-associated induced acute lung injury.

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We report a rare case of an incidental pancreatic lesion that proved to be Castleman disease in a peripancreatic lymph node, which mimicked a high-grade pancreatic neuroendocrine tumour (PNET) based on findings on positron emission tomography (PET). The disease was discovered as an incidental finding on CT imaging of the abdomen and was investigated and managed as PNET. Surgical resection was performed with distal pancreatectomy and splenectomy, however, histology revealed the lesion was a lymph node affected by Castleman disease. Often termed the great mimic, Castleman disease is a rare lymphoproliferative disorder that is often mistaken for other primary lesions of the organ due to its location and should be considered a differential of fluorodeoxyglucose (FDG)-avid PET lesions on imaging.

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Helicobacter pylori (H. pylori) bacterial infection has long been scrutinized as one of the potential risk factors for the development of pancreatic cancer with quite inconsistent and unequivocal data. Little is known about the risk factors involved with this malignancy. In this systematic review, we aimed to examine the relationship between H. pylori infection and pancreatic cancer based on the evidence from the existing observational studies across the world. We searched major electronic databases such as PubMed, MEDLINE, Science Direct, and Cochrane Library. After a careful and thorough screening process, we selected 15 observation studies for this systematic review. Six of 15 studies found a significant association between H. pylori infection and pancreatic cancer. Additionally, four of these studies found a significant relationship between the cytotoxin-associated gene A strain of H. pylori and pancreatic cancer. Based on the evidence from the selected studies, a weak association was observed between H. pylori infection and cancer of the pancreas, especially in European and Asian populations compared to the North American population. The cross-sectional evidence from the case-control studies only suggests the existence of an association but does not provide substantial evidence of the causative relationship. Further large-scale, prospective cohort studies are warranted in the future to understand this contradictory relationship better.

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Myeloid sarcoma (MS) is an extramedullary proliferation of immature myeloid cells which may occur as a progression of myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) and as acute myeloid leukemia (AML) relapse. Rarely may it be de novo. Lymph nodes, skin, lungs, intestine are the commonly involved sites. However, an isolated pancreatic MS is seldom reported in the literature. Herein, we report one such case which was misdiagnosed as pancreatic adenocarcinoma on the clinico-radiological examination which misled us away from preoperative diagnostic sampling, and a Whipple pancreaticoduodenectomy was performed. Histopathological examination in conjunction with immunohistochemistry revealed the final diagnosis of isolated MS of the pancreas. We emphasize that although rare, a clinical suspicion along with preoperative histopathological examination may lead to early diagnosis, targeted management, and a better clinical outcome in such cases.

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BACKGROUND: This study aimed to determine the prevalence of microsatellite instability (MSI)-high status in hepato-biliary-pancreatic malignancies in clinical practice and the clinical characteristics of and therapeutic results of pembrolizumab on patients with MSI-high cancers. METHODS: The subjects were 283 patients who had undergone MSI tests for unresectable, metastatic hepato-biliary-pancreatic malignancies at seven hospitals. The tests were polymerase chain reaction fragment analyses using the microsatellite markers consisting of BAT25, BAT26, NR21, NR24, and MONO27. Formalin-fixed, paraffin-embedded blocks, prepared according to the guidelines of the Japan Society of Pathology were used within 4 years after sampling. There were 13 patients with cancers high in MSI, including eight patients receiving pembrolizumab treatment. The clinical characteristics of these patients and therapeutic outcomes of their pembrolizumab treatment were investigated. RESULTS: MSI-high was detected in 13 (4.6%) of the 283 patients with hepato-biliary-pancreatic malignancies. None of these 13 patients had been diagnosed with Lynch syndrome. Of the Eight patients receiving pembrolizumab, a complete response was observed in three patients, a partial response in one patient, and stable disease in three patients. The objective response rate was 50% and the disease control rate was 87.5%. CONCLUSION: MSI-high was detected in 4.6% of patients with hepato-biliary-pancreatic malignancies. There was a 50% objective response rate to pembrolizumab treatment for MSI-high cancers. The evaluation of MSI status by the current method using appropriately prepared tissue samples was to be a reliable and accurate approach to both the determination of MSI status and estimation of the effectiveness of pembrolizumab.

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Background and Objects: An atypical cytologic diagnosis arises from inflammation or early neoplastic process. It is commonly found in EUS-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) tissue sampling of pancreatic malignancies. The aims of this study were to evaluate the diagnostic performance of EUS-FNA/FNB in patients with cytologic diagnosis of atypical cells and to develop a prediction model for malignant tumors of the pancreas in the atypical cytologic diagnostic category. Methods: Two hundred and twenty-six patients in the atypical cytologic diagnostic category were analyzed. Multivariate logistic regression analyses were performed to determine predictive factors for pancreatic malignancies. The final diagnoses were confirmed by repeat biopsy; surgical pathology, or clinical follow-up for at least 6 months. Results: The atypical cytologic diagnosis using EUS-FNA/FNB was associated with an absolute risk of malignancy (82.3%). Multivariate logistic regression analyses revealed that older age, long axis of the mass, and increased carbohydrate antigen 19-9 (CA19-9) were independent risk factors for true malignant pancreatic tumors among patients in the atypical cytologic diagnostic category. The calibration curve had a slope of 0.96, and a regression coefficient (R2) of 0.91. The area under the receiver operating characteristic curve of the validation group was 0.803. Conclusions: Atypical lesions of EUS-FNA/FNB have a higher risk of malignancy. Older age, the long axis of the mass, and elevated serum CA19-9 level were identified as independent risk factors for true malignant pancreatic tumors among patients in the atypical cytologic diagnostic category.

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BACKGROUND: Castleman disease is an uncommon nonclonal lymphoproliferative disorder, which frequently mimics both benign and malignant abnormalities in several regions. Depending on the number of lymph nodes or regions involved, Castleman disease (CD) varies in diagnosis, treatment and prognosis. It rarely occurs in the pancreas alone without any distinct clinical feature and tends to be confused with pancreatic paraganglioma (PGL), neuroendocrine tumors (NETs), and primary tumors, thus impeding proper diagnosis and treatment. CASE SUMMARY: A 28-year-old woman presented with a lesion on the neck of the pancreas, detected by ultrasound during a health examination. Physical examination and laboratory findings were normal. The mass showed hypervascularity on enhanced computed tomography (CT), significantly increased 18F-fluorodeoxyglucose uptake on positron emission tomography (PET)/CT, and slightly increased somatostatin receptor (SSTR) expression on 68Ga-DOTATATE PET/CT, suggesting no distant metastases and subdiagnoses such as pancreatic PGL, NET, or primary tumor. Intraoperative pathology suggested lymphatic hyperplasia, and only simple tumor resection was performed. The patient was diagnosed with the hyaline vascular variant of CD, which was confirmed by postoperative immunohistochemistry. The patient was discharged successfully, and no recurrence was observed on regular review. CONCLUSION: High glucose uptake and slightly elevated SSTR expression are potentially new diagnostic features of CD of the pancreas.