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Background: A new circulating biomarker superior to carbohydrate antigen 19–9 (CA19-9) is needed for diagnosing pancreatobiliary cancer (PBca). The aim of this study was to identify serum microRNA (miRNA) signatures comprising reproducible and disease-related miRNAs. Methods: This multicenter study involved patients with treatment-naïve PBca and healthy participants. The optimized serum processing conditions were evaluated using t-distributed stochastic neighbor embedding (t-SNE) visualization. Serum miRNA candidates for disease association were selected using weighted gene coexpression network analysis (WGCNA). A miRNA signature combining multiple serum miRNAs was tested in exploratory, validation, and independent validation sets. The synthesis and secretion of diagnostic miRNAs were evaluated using human pancreatic cancer cells. Results: In total, 284 (150 healthy and 134 PBca) of 827 serum samples were processed within 2 h of blood collection before freezing, distributed in the same area as that in the t-SNE map, and assigned to an exploratory set. The 193 optimized samples were assigned to either the validation (50 healthy, 47 PBca) or independent validation (50 healthy, 46 PBca) set. Index-1, a combination of five serum miRNAs (hsa-miR-1343-5p, hsa-miR-4632-5p, hsa-miR-4665-5p, hsa-miR-665, and hsa-miR-6803-5p) with disease association in WGCNA, showed a sensitivity and specificity of > 80% and an AUC outperforming that of CA19-9 in the exploratory, validation, and independent validation sets. The AUC of Index-1 was superior to that of CA19-9 (0.856 vs. 0.649, p = 0.038) for detecting T1 tumors. miR-665, a component of Index-1, was expressed in human pancreatic cancer cells, and its transfection inhibited cell growth. Conclusions: The serum miRNA signature Index-1 is useful for detecting PBca and could facilitate the early diagnosis of PBca. These findings can help improve clinical PBca detection by providing an optimized biomarker that overcomes the limitations of the current standard. [ABSTRACT FROM AUTHOR]

The natural history of branch-duct intraductal papillary mucinous cystic neoplasms (BD-IPMNs) in the pancreas remains unclear. This study aimed to answer this clinical question by focusing on the development of concomitant pancreatic ductal adenocarcinomas (cPDAC). The Japan Pancreas Society conducted a prospective multicenter surveillance study of BD-IPMN every six months for five years. The primary endpoints were progression of BD-IPMN, progression to high-grade dysplasia/invasive carcinoma (HGD/IC), and cPDAC. Factors predicting the progression of BD-IPMN to HGD/IC and development of cPDAC were also assessed as secondary endpoints. Among the 2104 non-operated patients, 348 (16.5 %) showed progression of primary BD-IPMN. Cumulative incidences of BD-IPMN with HGD/IC and cPDAC during the 5.17-year surveillance period were 1.90 % and 2.11 %, respectively, and standard incidence ratios of BD-IPMN with HGD/IC and cPDAC were 5.28 and 5.73, respectively. Of 38 cPDACs diagnosed during surveillance, 25 (65.8 %) were resectable. The significant predictive characteristics of BD-IPMN for progression to HGD/IC were larger cyst size (p = 0.03), larger main pancreatic duct size (p < 0.01), and mural nodules (p = 0.02). Significant predictive characteristics for the development of cPDAC were male sex (p = 0.03) and older age (p = 0.02), while the size of IPMN was not significant. Careful attention should be given to "dual carcinogenesis" during BD-IPMN surveillance, indicating the progression of BD-IPMN to HGD/IC and development of cPDAC distinct from BD-IPMN, although the establishment of risk factors that predict cPDAC development remains a challenge (UMIN000007349). [ABSTRACT FROM AUTHOR]

Apolipoprotein A2-ATQ/AT (apoA2-ATQ/AT) is a new biomarker for diagnosing pancreatic cancer (PC). In this study, the value of blood carbohydrate antigen 19-9 (CA19-9) and apoA2-ATQ/AT levels in diagnosing stage 0 and IA PC was evaluated. During 2014–2021, 12 patients with stage 0 PC and 12 patients with IA PC (average age: 73.8 years) underwent resection at JA Onomichi General Hospital. In addition, the data of 200 healthy controls were collected from a community-based cohort study. Levels of two apoA2-isoforms were measured using enzyme-linked immunosorbent assay (ELISA) with specific antibodies to calculate the apoA2-i Index as a surrogate value for apoA2-ATQ/AT. The cutoff value for the apoA2-i Index was determined to be 62.9 μg/mL. CA19-9 levels were also measured through ELISA. Among all 24 patients with PC, the positivity rates for apoA2-i and CA19-9 were 33.3% and 25.0%, respectively. The positivity rates for apoA2-i and CA19-9 were 16.7% and 8.3% in patients with stage 0 PC and 50.0% and 41.7% in those with stage IA, respectively. For CA19-9-negative patients, the apoA2-i positivity rate was 9.1% in stage 0 and 42.9% in stage IA. The combined positivity rate for both markers was 16.7% in stage 0 and 66.7% in stage IA. Imaging findings in apoA2-i- and CA19-9-positive patients included pancreatic duct dilatation (87.5%/100%), duct stenosis (75.0%/50%), and atrophy (87.5%/66.7%). The imaging findings of this study suggest that apoA2-i may enhance the sensitivity for detecting CA19-9-negative stage 0 and IA PC, and complementary measurements with CA19-9 may be valuable for diagnosing early-stage PC. Therefore, minute PC with pancreatic duct dilation, duct stenosis, and atrophy may exhibit a high positivity rate, aiding differential diagnosis. [ABSTRACT FROM AUTHOR]

Several prognostic scoring systems based on cancer-related inflammation have been developed. We aimed to evaluate the efficacy of a novel physiobiological parameter-based grading system (PGS) for predicting the long-term prognosis after curative-intent surgery for pancreatic ductal adenocarcinoma. One-hundred fifty-nine consecutive patients with pancreatic ductal adenocarcinoma were enrolled. Univariate and multivariate analyses were performed to identify variables associated with overall survival and recurrence-free survival. Patients were stratified according to the PGS score with a cut-off value of 40.5 being estimated by receiver-operating characteristic curve analysis. Propensity score matching analysis (PSM) was performed to compare between patients with low and high scores in the physiobiological parameter-based grading system. Univariate analysis showed that CEA elevation (p = 0.032), tumor size ≥20 mm (p < 0.001), lymph node metastasis (p < 0.001), high-PGS (p < 0.001), CA19-9 elevation (p < 0.001), Prognostic nutritious index (PNI) ≤40 (p = 0.002) and positive Glasgow prognostic score (GPS) (p = 0.001) were risk factors for poor overall survival. CEA elevation (p = 0.006), Tumor size ≥20 mm (p < 0.001), lymph node metastasis (p < 0.001), high-PGS (p < 0.001), CA19-9 elevation (p < 0.001), PNI ≤40 (p = 0.017) and positive GPS (p < 0.001) were identified as risk factors for poor recurrence-free survival. The multivariate analysis revealed that tumor size ≥20 mm (p = 0.007, p = 0.008, respectively) and high PGS score (p = 0.041, p = 0.018, respectively) were independently associated with poor overall survival and recurrence-free survival. Patients with high-PGS showed a significantly worse long-term prognosis even after PSM. The PGS is a novel nomogram that could effectively predict long-term outcomes following curative surgery in patients with pancreatic ductal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Abstract Background The neutrophil-to-lymphocyte ratio (NLR), which reflects the cancer-induced systemic inflammation response, has been proposed as a risk factor for poor long-term prognosis in cancer. We investigated the prognostic role of the NLR and the relationship between the NLR and TNM stage in pancreatic ductal adenocarcinoma (PDAC) patients following curative resection. Methods One-hundred thirty-eight consecutive patients with resected PDAC were enrolled between 2004 and 2014. Univariate and multivariate analyses identified variables associated with overall survival (OS) and recurrence-free survival (RFS). Patients were stratified according to the NLR, with an NLR cut-off value of 2.2 being estimated by receiver operating characteristic curve. Results Compared to patients with a low NLR (≤2.2), those with a high preoperative NLR (>2.2) had worse OS and RFS (P = 0.017, P = 0.029, respectively). For early-stage tumors, tumor size ≥20 mm and a high NLR were independent risk factors for poor OS (hazard ratio (HR): 3.255, 95% confidence interval (CI): 1.082–9.789, P = 0.036; HR: 3.690, 95% CI: 1.026–13.272, P = 0.046, respectively) and RFS (HR: 3.575, 95% CI: 1.174–10.892, P = 0.025; HR: 5.380, 95% CI: 1.587–18.234, P = 0.007, respectively). The NLR was not correlated with prognosis in patients with advanced stages. Conclusions An elevated preoperative NLR was an important prognosticator for early TNM stage PDAC. The NLR, which is calculated using inexpensive and readily available biomarkers, could be a novel tool for predicting long-term survival in patients, especially those with early stage PDAC. [ABSTRACT FROM AUTHOR]

Pancreatic adenosquamous cell carcinoma (PASC) is a rare histological type of pancreatic malignancy with a particularly poor prognosis, even after curative surgery. Here, we describe the long-term prognosis of PASC in a patient who developed delayed local recurrence of the remnant pancreas after successful distal pancreatectomy, together with a literature review. A 59-year-old woman had a history of hepatitis C. Computed tomography revealed a hypointense mass in the pancreatic body in the arterial phase of the study. Magnetic resonance imaging revealed a tumor (20 mm) in the pancreatic body and dilatation of the main pancreatic duct at the periphery of the tumor. The patient was diagnosed with resectable pancreatic ductal adenocarcinoma and underwent distal pancreatectomy with lymphadenectomy; her postoperative course was uneventful. Immunohistochemical analysis of the resected specimen confirmed the diagnosis of tumor node metastasis [TNM] classification T2N1M0 stage IIB. Five years after curative surgery, following adjuvant systemic chemotherapy with S-1, local recurrence in the remnant pancreas occurred, which invaded the common hepatic artery and celiac pleural plexus. Systemic chemotherapy with gemcitabine and abraxiane is currently underway. Curative surgery significantly affects the prognosis of patients with PASC. Adjuvant chemotherapy may prolong the survival of these patients. Delayed remnant pancreatic recurrence should be considered during the surveillance of pancreatic cancer after curative resection. We present a case of PASC in a patient who developed local recurrence in the remnant pancreas 5 years after successful distal pancreatectomy. Special attention should be paid not only to early recurrence but also to delayed local recurrence in PASC. • Pancreatic adenosquamous cell carcinoma (PASC) is a rare histological type of pancreatic malignancy • We describe the long-term prognosis of PASC in a patient who developed delayed local recurrence of the remnant pancreas after distal pancreatectomy. • Delayed remnant pancreatic recurrence should be considered during the surveillance of pancreatic cancer after curative resection. [ABSTRACT FROM AUTHOR]

Background: Endoscopic transpapillary biliary drainage (EBD) or stenting is the gold standard treatment for inoperable malignant biliary obstruction. When the papilla cannot be traversed because of pyloric or duodenal stenosis, or the catheter cannot be introduced, or because of previous surgery, the usual alternative method is considered to be percutaneous transhepatic biliary drainage (PTBD). We herein report our experiences with four cases with inoperable pancreatic head carcinoma associated with obstructive jaundice treated by endoscopic ultrasonography-guided biliary drainage (EUS-BD). Methods: Between September 2006 and December 2007, methods of EUS-BD were performed in four cases with inoperable pancreas head carcinoma. In three out of four cases, EBD and PTBD were unsuccessful because of previous surgery, or duodenal stenosis, or nondilated intrahepatic bile ducts. In one case, although PTBD was successful, internal drainage could not be established. Results: EUS-BD was successful for all cases. The obstructed biliary system was successfully decompressed by the creation of a choledochoduodenal fistula and the insertion of a transduodenal biliary plastic stent. No complication was encountered in all cases. Conclusions: EUS-BD may have the potential of replacing PTBD in cases with inoperable pancreatic head carcinoma associated with obstructive jaundice. [ABSTRACT FROM AUTHOR]

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging but essential for improving its poor prognosis. We established a multicenter study to clarify the clinicopathological features, and to propose new algorithm for early diagnosis of PDAC. Ninety-six patients with stage 0 and IA PDAC were enrolled from 13 high-volume centers. Overall, 70% of the patients were asymptomatic. The serum pancreatic enzyme levels were abnormal in half of the patients. The sensitivity of endoscopic ultrasonography (EUS) for detecting small PDAC was superior to computed tomography and magnetic resonance imaging (MRI) (82%, 58%, and 38%, respectively). Indirect imaging findings were useful to detect early-stage PDAC; especially, main pancreatic duct stenosis on MRI had the highest positive rate of 86% in stage 0 patients. For preoperative pathological diagnosis, the sensitivity of endoscopic retrograde cholangiopancreatography (ERCP)-associated pancreatic juice cytology was 84%. Among the stage IA patients, EUS-guided fine-needle aspiration revealed adenocarcinoma in 93% patients. For early diagnosis of PDAC, it is essential to identify asymptomatic patients and ensure close examinations of indirect imaging findings and standardization of preoperative pathological diagnosis. Therefore, a new diagnostic algorithm based on tumor size and imaging findings should be developed. [ABSTRACT FROM AUTHOR]

Early diagnosis of pancreatic cancer (PC) can improve patients' prognosis. We aimed to investigate the utility of endoscopic ultrasonography (EUS) for the early diagnosis of PC. This study included 64 patients with PC at an early stage treated at Onomichi General Hospital between January 2007 and January 2020. Diagnostic procedures included contrast computed tomography (CT), magnetic resonance cholangiopancreatography, EUS fine-needle aspiration, and endoscopic retrograde cholangiopancreatography (ERCP) for pancreatic juice cytology. The mean age was 71.3 years. In all, 32 patients were stage 0, and 32 were stage I. As for image findings, the main pancreatic duct (MPD) stenosis was detected in several cases, although CT and MRCP seldom detected tumors. EUS had a high detection rate for stage 0 tumor lesions. The median observation period was 3.9 years. In cases with stage 0, the 1 year and 5 year survival rates were 100% and 78.9%, respectively. In cases with stage I, the 1 year and 5 year survival rates were 96.4% and 66.7%, respectively. EUS has the highest sensitivity among all imaging modalities for detecting small pancreatic tumors. Cases with MPD dilation or stenosis, especially with tumors that cannot be identified on CT and MRI, should have EUS performed. In some cases, EUS was not able to detect any tumor lesions, and ERCP-based pancreatic juice cytology should be useful for pathological diagnosis. [ABSTRACT FROM AUTHOR]

It has been reported that endoscopic retrograde cholangiopancreatography (ERCP) is of value in evaluating precise pancreatograms of the pancreatic duct (PD). Recently, institutions have tended to perform magnetic resonance cholangiopancreatography (MRCP) for the diagnosis of PD due to post-ERCP pancreatitis (PEP). In small pancreatic cancer (PC), including PC in situ (PCIS) which is undetectable on cross sectional images, endoscopic ultrasonography (EUS) and MRCP serve important roles in detecting local irregular stenosis of the PD or small cystic lesions. Subsequently, ERCP and associated serial pancreatic juice aspiration cytologic examination (SPACE) obtained by endoscopic nasopancreatic drainage (ENPD) may be useful in the diagnosis of very early-stage PC. Further prospective multicenter studies are required to establish a standard method of SPACE for the early diagnosis of PC. [ABSTRACT FROM AUTHOR]

Patients were stratified according to the physiobiological parameter-based grading system (PGS), with a PGS cut-off value of 40.5 being estimated by receiver operating characteristic curve. Patients with high-PGS had worse OS and RFS, rather than patients with low-PGS (P < 0.001, P < 0.001, respectively). [Extracted from the article]