Comparison of genomic profiling of circulating tumor DNA in pancreaticobiliary malignancies in plasma and bile.

BACKGROUND: Obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug-matched mutations. METHODS: This study created a panel of 60 significantly mutated genes specific to pancreaticobiliary cancer (PBCA) and used it for genomic analysis of 212 deoxyribonucleic acid (DNA) samples (87 bile supernatant, 87 bile precipitate, and 38 plasma) from 87 patients with PBCA. The quantity of extracted DNA from bile and plasma was compared, as were genomic profiles of 38 pairs of bile and plasma from 38 patients with PBCA. Finally, we investigated 87 bile and 38 plasma for the ability to detect druggable mutations. RESULTS: The amount of DNA was significantly lower in plasma than in bile (p < .001). Oncogenic mutations were identified in 21 of 38 (55%) patients in bile and nine (24%) in plasma samples (p = .005). Bile was significantly more sensitive than plasma in identifying druggable mutations (p = .032). The authors detected 23 drug-matched mutations in combined bile and plasma, including five ERBB2, four ATM, three BRAF, three BRCA2, three NF1, two PIK3CA, one BRCA1, one IDH1, and one PALB2. CONCLUSIONS: Liquid biopsy using bile may be useful in searching for therapeutic agents, and using the obtained genomic information may improve the prognoses of patients with PBCA. PLAIN LANGUAGE SUMMARY: Genomic profiling of formalin-fixed paraffin-embedded tissues may provide actionable targets for molecular and immuno-oncological treatment. However, most pancreaticobiliary malignancies are unresectable and formalin-fixed paraffin-embedded tissues cannot be obtained. Although comprehensive genomic profiling tests using plasma have been used in recent years, the utility of those using bile is not clear. Our study revealed that bile identified more drug-matched mutations than plasma in advanced pancreaticobiliary cancer patients. Bile may help widen the patient population benefiting from targeted drugs.

Efficacy and Safety of Electrohydraulic Lithotripsy Using Peroral Cholangioscopy under Endoscopic Retrograde Cholangiopancreatography Guidance in Older Adults: A Single-Center Retrospective Study.

Background and objectives: The safety of electrohydraulic lithotripsy (EHL) in older adults remains unclear. We aimed to investigate the efficacy and safety of EHL using peroral cholangioscopy (POCS) under endoscopic retrograde cholangiopancreatography (ERCP) guidance in older adults aged ≥80 years. Materials and Methods: This retrospective clinical study was conducted at a single center. Fifty patients with common bile duct stones who underwent EHL using POCS under ERCP guidance at our institution, between April 2017 and September 2022, were enrolled in this study. The eligible patients were divided into an elderly group (n = 21, age ≥80 years) and a non-elderly group (n = 29, age ≤79 years), and were analyzed. Results: A total of 33 and 40 EHL procedures were performed in the elderly and non-elderly groups, respectively. After excluding cases in which stone removal was performed at other institutions, complete removal of common bile duct stones was confirmed in 93.8% and 100% of the elderly and non-elderly groups, respectively (p = 0.20). The mean number of ERCPs required for complete removal of bile duct stones was 2.9 and 4.3 in the elderly and non-elderly groups, respectively (p = 0.17). In the EHL session, the overall occurrence of adverse events was eight and seven in the elderly (24.2%) and non-elderly (17.5%) groups, respectively; however, the difference was insignificant (p = 0.48). Conclusions: EHL using POCS under ERCP guidance is effective in patients aged ≥80 years and there was no significant increase in adverse event rates compared to those aged ≤79 years.

Genomic profiling amplifies the utility of endoscopic ultrasound-guided fine needle biopsy by identifying clinically applicable druggable mutations in pancreatic cancer.

BACKGROUND: Genomic profiling of tumors is available, but whether the small fragment obtained via endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is sufficient for these examinations is unknown. Here we investigated whether EUS-FNB specimens are suitable for genomic profiling to identify oncogenic and drug-matched mutations. METHODS: We constructed a pancreatobiliary cancer panel for targeted panel sequencing that covered 60 significantly mutated genes and compared the results with those of whole-exome sequencing (WES). In total, 20 and 53 formalin-fixed paraffin-embedded tissues obtained via surgery and EUS-FNB were analyzed, respectively. First, we examined the DNA quality and genomic profiles of 20 paired samples from 20 malignant lesions obtained via surgery and EUS-FNB. We then tested 33 samples obtained via EUS-FNB from 24 malignant and 9 benign lesions for the discrimination of malignancy. Finally, we explored drug-matched mutations from EUS-FNB specimens. RESULTS: Although the DNA quantity obtained via surgery was higher than that obtained via EUS-FNB (P = 0.017), the DNA quality and mean depth were equivalent (P = 0.441 and P = 0.251). Panel sequencing of EUS-FNB specimens identified more oncogenic mutations than WES (90 % vs. 50 %). Furthermore, the number of oncogenic mutations did not differ between EUS-FNB and surgically resected specimens. Genomic profiling of EUS-FNB specimens enabled the discrimination of malignancy with 98 % accuracy. Of 44 malignant lesions, drug-matched alterations were identified in 14 % (6/44) of malignant lesions. CONCLUSION: EUS-FNB specimens can be widely utilized for diagnostic purposes, discrimination of malignancy, and detection of drug-matched mutations for the treatment of pancreatic cancer.

Detection of actionable mutations in cytological specimens obtained by endoscopic ultrasound-guided fine needle aspiration with rapid onsite evaluation in pancreatic cancer.

BACKGROUND: It is not clear whether archived cytological specimens (ACSs) obtained with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with rapid onsite evaluation (ROSE) can be used for genomic profiling of tumors. We used ACSs to perform genomic analysis of specimens to identify oncogenic and druggable mutations. METHODS: A panel of 60 significantly mutated genes specific to pancreatobiliary cancer was created and used for genomic analysis of 113 specimens of 44 formalin-fixed paraffin-embedded (FFPE) tissues and 69 ACSs obtained by EUS-FNA with ROSE were included. The quantity and quality of DNA extracted from FFPE tissues and ACSs were compared. We also compared DNA from spray and touch ACSs. Next, genomic profiles were compared. We also evaluated detection of target gene mutations in each specimen. RESULTS: The amount of DNA in FFPE tissues was greater than in ACSs (P = 0.014), but the quality of DNA was comparable (P = 0.378). There was no quantitative or qualitative difference between spray and touch ACSs (P = 0.154 and P = 0.734, respectively). Oncogenic mutations were shared at 82 % in FFPE tissues and ACSs and 82 % in spray and touch ACSs. The sensitivity of genomic analysis in ACSs was 97 % (67 of 69), which was comparable to that of cytology (62 of 69, 90 %; P = 0.165), and was significantly higher than that of histology (32/44, 73 %; P < 0.001). Drug-matched mutations were identified in five of the 44 lesions (11 %). CONCLUSION: Genomic analysis of ACSs is useful in the prognosis of pancreatic cancer because detection of driver mutations is similar to detection in FFPE tissues.

Analysis of circulating cell-free DNA after endoscopic ultrasound-guided fine needle aspiration in pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVES: Recently, increase in cell-free DNA (cfDNA) concentration or newly detected KRAS mutation after endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy were reported to be related to the occurrence of new distant metastasis. In this study, we investigated whether cfDNA concentration increased with the release of tumor components into the blood after EUS-FNA and whether its increase was related to prognosis. METHODS: Sixty-eight patients underwent EUS-FNA and were pathologically confirmed as having pancreatic ductal adenocarcinoma (PDAC). We measured plasma cfDNA concentration and the copy number of KRAS mutation in 68 patients and circulating tumor cells in 8 before and after EUS-FNA. RESULTS: The average cfDNA concentration after EUS-FNA (672.5 ± 919.6 ng/mL) was significantly higher than that before EUS-FNA (527.7 ± 827.3 ng/mL) (P < 0.001). KRAS mutation in plasma was detected in 8 patients (11.8%), however a significant increase in cfDNA concentration after EUS-FNA was not related to the change in KRAS-mutant copy number. Minimal increase in circulating tumor cells was observed in 3 of 8 patients. New distant metastasis was observed within 286 days to initial metastasis detection in 6 of 12 patients with ≥2-fold increase in cfDNA concentration and 26 of 56 patients with <2-fold increase within 185 days. In 32 patients who underwent surgery, ≥2-fold increase in cfDNA did not affect early recurrence. CONCLUSIONS: The increase in cfDNA concentration after EUS-FNA was not caused by tumor cell components released into blood vessels. Hence, the risk of seeding via the blood stream after EUS-FNA may need not be considered.

Rapidly declining trend of signet ring cell cancer of the stomach may parallel the infection rate of Helicobacter pylori.

BACKGROUND: Studies indicate that gastric cancer (GC) incidence has decreased, whereas signet ring cell carcinoma (SRC) incidence has increased. However, recent trends in GC incidence are unclear. We used our hospital cancer registry to evaluate the changes in the incidence of GC, SRC, and non-SRC (NSRC) over time in comparison to changes in the H. pylori infection rates over time. METHODS: We identified 2532 patients with GC enrolled in our registry between January 2007 and December 2018 and statistically analyzed SRC and NSRC incidence. The H. pylori infection rate in patients with SRC was determined by serum anti-H. pylori antibody testing, urea breath test, biopsy specimen culture, and immunohistochemical analysis (IHC) of gastric tissue. Additionally, genomic detection of H. pylori was performed in SRCs by extracting DNA from formalin-fixed paraffin-embedded gastric tissue and targeting 16S ribosomal RNA of H. pylori. RESULTS: Overall, 211 patients had SRC (8.3%). Compared with patients with NSRC, those with SRC were younger (P <  0.001) and more likely to be female (P <  0.001). Time series analysis using an autoregressive integrated moving average model revealed a significant decrease in SRC (P <  0.001) incidence; NSRC incidence showed no decline. There was no difference in H. pylori infection prevalence between the SRC and NSRC groups. IHC and genomic methods detected H. pylori in 30 of 37 (81.1%) SRCs. CONCLUSIONS: Reduction in H. pylori infection prevalence may be associated with the decrease in the incidence of SRC, which was higher than that of NSRC.

Immunohistochemical analysis of IMP3 and p53 expression in endoscopic ultrasound-guided fine needle aspiration and resected specimens of pancreatic diseases.

BACKGROUND: Insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3) is a valuable marker that distinguishes malignant from benign lesions and predicts prognosis. METHODS: First, we evaluated IMP3 expression in 77 resected specimens of pancreatic ductal adenocarcinoma (PDAC), intraductal papillary mucinous neoplasm (IPMN), and chronic pancreatitis (CP). Eleven PDAC patients preoperatively underwent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Survival analysis of IMP3 and clinicopathological factors was performed. IMP3 and p53 expression was evaluated in another 127 EUS-FNA samples of solid pancreatic masses to compare the diagnostic value of routine and immunohistochemical staining. RESULTS: IMP3 expression was detected in 72.3%, 50%, 20%, and 0% of PDAC, malignant IPMN, benign IPMN, and CP, respectively. Evaluation of IMP3 expression in EUS-FNA specimens coincided with that in resected specimens in 10 of 11. IMP3 expression correlated with tumor differentiation in PDAC samples (p = .006) and with poor prognosis through univariate analysis (p = .045). Tumor differentiation and lymph node metastasis were significantly associated with poor prognosis through multivariate analysis. In EUS-FNA specimens, the sensitivity, specificity, and accuracy of cytohistological analysis were 80.8%, 100%, and 85.0%, respectively. IMP3 and p53 expression were detected in 80.8% and 44.9% of malignant and 0% and 5% of benign lesions. Combined with IMP3 immunostaining, the sensitivity, specificity and accuracy of cytohistological analysis significantly increased to 87.9%, 100%, and 90.8% (p = .016), respectively. Meanwhile, p53 staining had no impact on the results. CONCLUSIONS: IMP3 immunohistochemical staining can improve the diagnostic accuracy of EUS-FNA for malignant pancreatic tumors.

Stent Deployment Without Tract Dilation in Endoscopic Ultrasound-Guided Hepaticogastrostomy Using a Novel Partially Covered Metal Stent With a Super-Slim Stent Delivery System: A Case Report.

Endoscopic ultrasound-guided hepaticogastrostomy is performed when transpapillary biliary drainage using endoscopic retrograde cholangiopancreatography is difficult due to surgically altered anatomy, an inaccessible papilla, or difficult biliary cannulation. This procedure consists of puncturing the intrahepatic bile duct from the stomach, inserting a guidewire into the bile duct, dilating the puncture tract, and placing a stent. Recently, a novel partially covered self-expandable metal stent with a super-slim stent delivery system of 5.9 Fr has become available. With this stent, endoscopic ultrasound-guided hepaticogastrostomy can be performed without using a dilator to expand the puncture tract. Herein, we describe a technique for dilator-free stent deployment for endoscopic ultrasound-guided hepaticogastrostomy using this novel stent. We performed an endoscopic ultrasound-guided hepaticogastrostomy with this stent in a 65-year-old patient with obstructive jaundice due to pancreatic head cancer without adverse events and with satisfactory improvement in jaundice. This procedure is expected to reduce bile leakage into the abdominal cavity and shorten the procedure time.

Tardive Peritonitis After Endoscopic Ultrasound-Guided Pancreatic Pseudocyst Drainage: A Case Report.

Here, we report a case of tardive peritonitis after endoscopic ultrasound (EUS)-guided transmural pancreatic pseudocyst drainage. A 50-year-old man was diagnosed with acute pancreatitis and a pancreatic pseudocyst measuring 5 cm. Ten months later, his pancreatic pseudocyst was 10 cm. We performed EUS-guided transmural drainage using a lumen-apposing metal stent. After two months, the stent was replaced with a double-pigtail plastic stent. Two months later, the patient developed fever and abdominal pain, and computed tomography revealed abdominal free air. He was diagnosed with peritonitis due to free air caused by a fistula rupture. The double-pigtail plastic stent was removed, and clipping was performed at the fistula site to achieve closure. The patient's symptoms subsequently improved. Long-term placement of a plastic stent for pancreatic pseudocysts makes recurrence less likely, but late adverse events due to stent placement can occur. Notably, fistula rupture can occur even when the fistula is well-formed several months after the initial drainage.

Asymptomatic Pneumoperitoneum With a Large Amount of Gas Appeared During Endoscopic Ultrasound-Guided Biliary Drainage.

We report a case in which a large amount of intraperitoneal free gas developed during endoscopic ultrasound-guided biliary drainage with the rendezvous technique. A 62-year-old woman presented with obstructive jaundice caused by a pancreatic head tumor. Endoscopic retrograde cholangiopancreatography was attempted but failed due to difficulty cannulating the bile duct. Consequently, endoscopic ultrasound-guided hepaticogastrostomy was performed using a fully covered metal stent. Subsequently, the rendezvous technique was employed to access the biliary system and perform an endoscopic sphincterotomy. Finally, a fully covered metal stent was placed transpapillary. Fluoroscopic imaging during the procedure revealed a large amount of gas between the liver and diaphragm. Despite the pneumoperitoneum, the patient experienced no abdominal pain or fever. One week later, a computed tomography scan confirmed the disappearance of free air in the intraperitoneal cavity. The patient's subsequent clinical course remained uneventful, and she was discharged from the hospital. This case highlights the potential for pneumoperitoneum to develop during endoscopic ultrasound-guided biliary drainage, particularly when using the rendezvous technique. It is crucial to differentiate this finding from gastrointestinal perforation based on clinical presentation and imaging features.

Parathyroid Hormone-Related Peptide-Producing Gallbladder Cancer Presenting With Humoral Hypercalcemia of Malignancy: A Case Report.

Humoral hypercalcemia of malignancy (HHM) is often reported in cancers derived from the squamous epithelium; however, there are very few reports of HHM in patients with gallbladder cancer. We report a case of a parathyroid hormone-related protein (PTHrP)-producing gallbladder cancer presenting with HHM. A 43-year-old woman presented with appetite loss, nausea, and brown-colored urine. Blood tests revealed that she had hypercalcemia, high serum bilirubin, and high serum parathyroid hormone. Contrast-enhanced computed tomography revealed a gallbladder tumor, liver metastasis, and bile duct obstruction caused by the gallbladder tumor in the hilar region. No bone metastasis was observed. Endoscopic retrograde cholangiopancreatography revealed pancreaticobiliary maljunction. Metal biliary stents were placed, and a transpapillary biopsy of the gallbladder tumor revealed a pathological diagnosis of adenocarcinoma. The patient was diagnosed with HHM due to gallbladder cancer with liver metastasis. Although her hypercalcemia and jaundice improved, her appetite loss and nausea did not improve. Subsequently, the patient developed disseminated intravascular coagulation, and her general condition gradually deteriorated. Due to her poor general condition, chemotherapy could not be administered. The patient died six weeks after visiting our hospital. Although rare, some gallbladder cancers cause HHM due to PTHrP production.

Natural history of asymptomatic gallbladder stones in clinic without beds: A long-term prognosis over 10 years.

BACKGROUND: Several studies have explored the long-term prognosis of patients with asymptomatic gallbladder stones. These reports were primarily conducted in facilities equipped with beds for addressing symptomatic cases. AIM: To report the long-term prognosis of patients with asymptomatic gallbladder stones in clinics without bed facilities. METHODS: We investigated the prognoses of 237 patients diagnosed with asymptomatic gallbladder stones in clinics without beds between March 2010 and October 2022. When symptoms developed, patients were transferred to hospitals where appropriate treatment was possible. We investigated the asymptomatic and survival periods during the follow-up. RESULTS: Among the 237 patients, 214 (90.3%) remained asymptomatic, with a mean asymptomatic period of 3898.9279 ± 46.871 d (50-4111 d, 10.7 years on average). Biliary complications developed in 23 patients (9.7%), with a mean survival period of 4010.0285 ± 31.2788 d (53-4112 d, 10.9 years on average). No patient died of biliary complications. CONCLUSION: The long-term prognosis of asymptomatic gallbladder stones in clinics without beds was favorable. When the condition became symptomatic, the patients were transferred to hospitals with beds that could address it; thus, no deaths related to biliary complications were reported. This finding suggests that follow-up care in clinics without beds is possible.

Development of a molecular barcode detection system for pancreaticobiliary malignancies and comparison with next-generation sequencing.

BACKGROUND: Obtaining sufficient tumor tissue for genomic profiling is challenging in pancreaticobiliary cancer (PBCA). We determined the utility of molecular barcoding (MB) of liquid biopsies (bile, duodenal fluid, and plasma) for highly sensitive genomic diagnosis and detection of druggable mutations for PBCA. METHODS: Two in-house panels of 60 genes (non-MB panel) and 21 genes using MB (MB panel) were used for the genomic analysis of 112 DNA samples from 20 PBCA patients. We measured the yield of DNA and compared the genomic profiles of liquid samples obtained using the non-MB panel and the MB panel. The utility of the panels in detecting druggable mutations was investigated. RESULTS: A significantly greater amount of DNA was obtained from bile supernatants and precipitates compared to tumor samples (P < 0.001 and P = 0.001, respectively). The number of mutations per patient was significantly higher using the MB panel than using the non-MB panel (2.8 vs. 1.3, P = 0.002). Tumor-derived mutations were detected more frequently using the MB panel than the non-MB panel (P = 0.023). Five drug-matched mutations were detected in liquid samples. CONCLUSIONS: Liquid biopsy with MB may have utility in providing genomic information for the prognosis of patients with PBCA.

Liquid biopsy of wash samples obtained via endoscopic ultrasound-guided fine-needle biopsy: Comparison with liquid biopsy of plasma in pancreatic cancer.

OBJECTIVES: Pancreatic cancer (PC) has a poor prognosis and limited treatment options. Liquid biopsy, which analyzes circulating tumor DNA (ctDNA) in blood, holds promise for precision medicine; however, low ctDNA detection rates pose challenges. This study aimed to investigate the utility of wash samples obtained via endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) as a liquid biopsy for PC. METHODS: A total of 166 samples (42 formalin-fixed paraffin-embedded [FFPE] tissues, 80 wash samples, and 44 plasma samples) were collected from 48 patients with PC for genomic analysis. DNA was extracted and quantified, and 60 significantly mutated genes were sequenced. The genomic profiles of FFPE tissues, wash samples, and plasma samples were compared. Finally, the ability to detect druggable mutations in 80 wash samples and 44 plasma samples was investigated. RESULTS: The amount of DNA was significantly lower in plasma samples than in wash samples. Genomic analysis revealed a higher detection rate of oncogenic mutations in FFPE tissues (98%) and wash samples (96%) than in plasma samples (18%) and a comparable detection rate in FFPE tissues and wash samples. Tumor-derived oncogenic mutations were detected more frequently in wash samples than in plasma samples. Furthermore, the oncogenic mutations detection rate remained high in wash samples at all PC stages but low in plasma samples even at advanced PC stages. Using wash samples was more sensitive than plasma samples for identifying oncogenic and druggable mutations. CONCLUSIONS: The wash sample obtained via EUS-FNB is an ideal specimen for use as a liquid biopsy for PC.

The efficacy of bile liquid biopsy in the diagnosis and treatment of biliary tract cancer.

BACKGROUND: Diagnosing biliary tract cancer is difficult because endoscopic retrograde cholangiopancreatography (ERCP) is performed fluoroscopically, and the sensitivity of bile cytology is low. Liquid biopsy of bile using targeted sequencing is expected to improve diagnosis and treatment, but few studies have been conducted. In this study, we examined whether liquid biopsy of bile improves the diagnostic sensitivity of biliary strictures. METHODS: A total of 72 patients with biliary strictures who underwent ERCP at Chiba University Hospital between April 2018 and March 2021 were examined. Of these, 43 and 29 were clinically and pathologically diagnosed as having malignant and benign biliary strictures, respectively. We performed targeted sequencing of bile obtained from these patients, and the sensitivity of this method was compared with that of bile cytology. Detection of at least one oncogenic mutation was defined as having malignancy. RESULTS: The sensitivity of bile cytology was 27.9%, whereas that of genomic analysis was 46.5%. Comparing bile cytology alone with the combination of cytology and genomic analysis, the latter was more sensitive (53.5%, p < .001). Among the 43 patients with malignant biliary strictures, mutations with FDA-approved drugs were detected in 11 (26%). CONCLUSIONS: Liquid biopsy of bile can potentially diagnose malignancy and detect therapeutic targets.

Genomic Analysis of Undifferentiated Carcinoma of the Pancreas with Squamous Differentiation: A Case Report.

Pancreatic cancer is an intractable malignancy associated with a dismal prognosis. Undifferentiated carcinoma, a rare subtype, poses a clinical challenge owing to a limited understanding of its molecular characteristics. In this study, we conducted genomic analysis specifically on a case of undifferentiated carcinoma of the pancreas exhibiting squamous differentiation. An 80-year-old male, previously treated for colorectal cancer, presented with a mass with central cystic degeneration in the pancreatic tail. The mass was diagnosed pathologically as undifferentiated carcinoma of the pancreas with squamous differentiation. Despite surgical resection and chemotherapy, the patient faced early postoperative recurrence, emphasizing the aggressive nature of this malignancy. Genomic analysis of distinct histologic components revealed some common mutations between undifferentiated and squamous components, including Kirsten rat sarcoma virus (KRAS) and TP53. Notably, the squamous component harbored some specific mutations in SMARCA4 and SMARCB1 genes that code for members of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. The common mutations in the undifferentiated and squamous cell carcinoma components from this analysis suggest that they originate from a common origin. The discussion also underscores the scarcity of genomic analyses on undifferentiated carcinoma of the pancreas, with existing literature pointing to SWI/SNF complex-related gene mutations. However, our case introduces chromatin remodeling factor mutations as relevant in squamous differentiation. In conclusion, this study provides valuable insights into the genomic landscape of undifferentiated pancreatic carcinoma with squamous differentiation. These findings suggest the importance of further research and targeted therapies to improve the management of undifferentiated carcinoma of the pancreas and enhance patient outcomes.

Penetration of duodenal wall by proximal end of biliary straight plastic stent in a patient with ampullary carcinoma.

A 70-year-old woman presented to our hospital with abdominal discomfort. Gastrointestinal endoscopy revealed an ampullary tumor, while a biopsy revealed a pathological diagnosis of adenocarcinoma. No distant metastases were observed and neoadjuvant chemotherapy and surgical resection were planned. Shortly thereafter, she developed obstructive jaundice due to the ampullary carcinoma. The patient underwent endoscopic retrograde cholangiopancreatography, during which a straight plastic stent was placed in the bile duct. The patient was discharged without complications. Neoadjuvant chemotherapy was initiated. Two months later, she was readmitted for surgery while asymptomatic. Endoscopic retrograde cholangiopancreatography was scheduled to replace the stent with a nasobiliary drainage tube for the surgery. Endoscopic imaging revealed that the proximal end of the stent had penetrated the duodenum on the oral side of the ampullary carcinoma. The distal end of the stent was grasped with forceps and the stent was successfully removed. A catheter was inserted into the bile duct orifice and cholangiography was performed, which revealed that the distal bile duct and the duodenum had formed a fistula. A guidewire was placed in the bile duct via the papilla and a nasobiliary drainage tube was placed. After endoscopic retrograde cholangiopancreatography, the patient exhibited smooth progress without issue. Pancreaticoduodenectomy was performed on the fourth day after the nasobiliary drainage tube placement, and the patient's postoperative course was uneventful. The proximal end of a biliary stent penetrating the duodenal wall is an infrequent phenomenon. This case report highlights a rare but noteworthy adverse event associated with straight biliary plastic stent placement.

Clinical outcomes and reintervention after endoscopic retrograde cholangiopancreatography in primary sclerosing cholangitis in absence of cholangitis.

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) may help detect cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC), but it may be associated with complications. This study was aimed at determining the prognostic impact of ERCP on patients with PSC without cholangitis. METHODS: Patients with PSC without cholangitis were divided into two groups: those who underwent ERCP within three years after diagnosis (ERCP-performed group) and those who did not (non-ERCP group). These groups were compared in terms of clinical outcomes (liver-related death or liver transplantation, endoscopic treatment requirement and repeated cholangitis) and the composite outcome. RESULTS: Of 99 patients with PSC with detailed medical history, 49 were included in the ERCP-performed group and 21 in the non-ERCP group. In Kaplan-Meier analysis, the non-ERCP group was less likely to achieve the three outcomes and the composite outcome, showing statistical significance (endoscopic treatment requirement; p = 0.017 and composite outcome; p = 0.014). A Cox proportional hazards model indicated that ERCP in the asymptomatic state was a significant predictor of endoscopic treatment requirement (hazard ratio [HR]: 4.37, 95% confidence interval [CI]: 1.03-18.59) and the composite outcome (HR: 4.54, 95% CI: 1.07-19.28). CONCLUSION: ERCP in patients with PSC without cholangitis is likely to require further endoscopic treatment and may be associated with poor prognosis.

A Case of Primary Sclerosing Cholangitis Complicated With Liver Abscess Caused by Hyperviscous Klebsiella pneumoniae.

Liver abscesses caused by Klebsiella pneumoniae with a positive string test for hyperviscosity are more likely to develop invasive conditions than those with a negative string test. Here, we report the case of primary sclerosing cholangitis (PSC) who developed a treatment-resistant liver abscess caused by hyperviscous Klebsiella pneumoniae. A 67-year-old woman with PSC and a history of pancreaticoduodenectomy developed a fever. She had recurrent bacterial cholangitis after pancreaticoduodenectomy. This time, she was diagnosed with a liver abscess and bacterial cholangitis and then admitted to a local hospital. As her condition did not improve with intravenous administration of meropenem, she was transferred from another hospital to our hospital on the 7th day of admission. The percutaneous transhepatic abscess drainage was performed, and intravenous administration of cefepime and metronidazole was started. Klebsiella pneumoniae with a positive string test was detected in the blood culture test and the pus culture of the liver abscess. Although the liver abscess was reduced in size, the infection did not subside completely. Her general condition gradually deteriorated. She passed away on the 45th day of illness. In PSC patients, the formation of a liver abscess caused by hyperviscous Klebsiella pneumoniae can be life-threatening. In such cases, pus should be collected as soon as possible to identify the causative bacteria.

Distinct Genomic Profiles of Two Small Malignant Lesions Associated With an Intraductal Papillary Mucinous Neoplasm Co-occurring in a Patient.

Intraductal papillary mucinous neoplasm of the pancreas (IPMN) is characterized by cystic dilatation of the pancreatic duct system, intraductal papillary growth, and excessive mucin secretion. Although IPMN is basically a benign disease and surgical resection is not necessary, it has the potential to develop into pancreatic cancer. We recently encountered a rare case of synchronous development of two different types of malignant lesions in the pancreas associated with IPMN derived from different clones. A 74-year-old Japanese woman developed a cystic lesion in her pancreatic tail. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was performed on two low echoic lesions in the pancreatic tail (10 mm) and body (10 mm), which were then diagnosed as malignancies. After the surgically resected pancreas was carefully examined, in addition to the tail (10 mm) and body (10 mm) tumors, an intraductal papillary mucinous adenoma (IPMA) was observed, which was continuous to the tail tumor and extending toward the body of the pancreas but not contiguous to the body tumor. Genomic analysis using targeted sequencing revealed that the malignant lesion in the pancreatic tail and two sections of adjacent IPMA lesions in the pancreatic duct were almost identical. KRAS G12D, RNF43 G29fs, PBRM1 P1471R, and PIK3CA I1058L were shared, whereas only KRAS G12D was shared between the malignant lesion in the pancreatic body and others. Multiple pancreatic cancers may occur simultaneously and/or metachronously in the context of genomic alterations in IPMN.