Incidental detection of upper gastrointestinal epithelial neoplasia by screening endoscopy prior to endoscopic ultrasonography in patients with pancreaticobiliary disease.

BACKGROUND: Screening esophagogastroduodenoscopy plays an important role in the early detection of upper gastrointestinal cancer. To provide more opportunities for patients with pancreaticobiliary disease to undergo this screening, we have performed esophagogastroduodenoscopy prior to endoscopic ultrasonography. However, the usefulness of this protocol is not elucidated. This study aimed to investigate the utility of screening esophagogastroduodenoscopy in this protocol in the detection of upper gastrointestinal epithelial neoplasms. METHODS: The outcomes of screening esophagogastroduodenoscopy performed prior to endoscopic ultrasonography in patients with pancreaticobiliary disease at our hospital between April 2020 and September 2022 were investigated. A logistic regression model was used to identify factors affecting the detection of epithelial neoplasms. Additionally, we compared the detection rate of gastric epithelial neoplasms between screening esophagogastroduodenoscopy performed prior to endoscopic ultrasonography and that performed at our medical checkup center. RESULTS: A total of 615 screening esophagogastroduodenoscopies prior to endoscopic ultrasonography were performed, and 12 (2.0%) epithelial neoplasms were detected, including esophageal lesions (n = 2) and gastric lesions (n = 10). Of these lesions, 75% (9/12) underwent curative endoscopic resection. A multivariate analysis showed that open-type gastric mucosal atrophy (odds ratio, 7.7; 95% confidence interval, 1.5-38.4; p = 0.01) and the use of magnification endoscopy (odds ratio, 7.3; 95% confidence interval, 1.9-27.9; p < 0.01) independently affected the detection of epithelial neoplasms. The detection rate of gastric epithelial neoplasms was significantly higher using this protocol than that in our medical checkup center (1.6% versus 0.2%, p < 0.01). CONCLUSIONS: A protocol of screening esophagogastroduodenoscopy prior to endoscopic ultrasonography may be recommended because epithelial neoplasms could be detected at a non-negligible rate.

[Gallbladder carcinosarcoma associated with pancreaticobiliary maljunction with biliary dilation:a case report].

A 68-year-old female patient was referred to our hospital with acute cholangitis. Computed tomography revealed common bile duct dilatation, gallbladder fundal tumor, and gallbladder wall thickening attached to the tumor. Cholangiography revealed pancreaticobiliary maljunction with biliary dilation. The patient was diagnosed with pancreaticobiliary maljunction with biliary dilation and gallbladder cancer and underwent liver S4b+5 and bile duct resection and reconstruction. Pathological results revealed that the gallbladder fundal tumor included sarcoma, and the gallbladder wall thickening had adenocarcinoma;thus, the patient was diagnosed with gallbladder carcinosarcoma.

IFN/STAT signaling controls tumorigenesis and the drug response in colorectal cancer.

Colorectal cancer (CRC) is caused by genetic alterations, and comprehensive sequence analyses have revealed the mutation landscapes. In addition to somatic changes, genetic variations are considered important factors contributing to tumor development; however, our knowledge on this subject is limited. Familial adenomatous polyposis coli (FAP) is an autosomal-dominant inherited disease caused by germline mutations in the adenomatous polyposis coli (APC) gene. FAP patients are classified into two major groups based on clinical manifestations: classical FAP (CFAP) and attenuated FAP (AFAP). In this study, we established 42 organoids from three CFAP patients and two AFAP patients. Comprehensive gene expression analysis demonstrated a close association between IFN/STAT signaling and the phenotypic features of FAP patients. Genetic disruption of Stat1 in the mouse model of FAP reduced tumor formation, demonstrating that the IFN/STAT pathway is causally associated with the tumor-forming potential of APC-deficient tumors. Mechanistically, STAT1 is downstream target of KRAS and is phosphorylated by its activating mutations. We found that enhanced IFN/STAT signaling in CFAP conferred resistance to MEK inhibitors. These findings reveal the crosstalk between RAS signaling and IFN/STAT signaling, which contributes to the tumor-forming potential and drug response. These results offer a rationale for targeting of IFN/STAT signaling and for the stratification of CRC patients.

Laparoscopic cholecystectomy and laparoscopic common bile duct exploration for cholecystolithiasis and choledocholithiasis in a patient with situs inversus totalis: A case report.

Situs inversus complicates diagnosis and treatment due to the mirrored organ placement in relation to normal anatomy. This report describes a 78-year-old female patient with situs inversus totalis who underwent laparoscopic cholecystectomy and laparoscopic common bile duct exploration for cholecystolithiasis and choledocholithiasis. Utilizing the "French mirror technique" for port placement, the surgeon adeptly mirrored standard maneuvers with a 2-mm needle forceps in the left hand and a 5-mm forceps in the right in a reversed anatomical setting. This technique maintained familiar hand movements, despite the patient's unique anatomy. The surgeon applied transcystic ductal bile duct exploration, using choledochoscopy for duct exploration and a basket catheter for stone removal. Laparoscopic cholecystectomy and common bile duct exploration through the transcystic ductal route are viable and effective for patients with situs inversus.

Endoscopic ultrasound-guided fine needle biopsy diagnosis of circumferentially extraluminal mucosa-associated lymphoid tissue lymphoma in the transverse colon: a case report.

A 61-year-old man present to us with continued abdominal pain without abdominal tenderness for 1 month. Blood testing showed elevated biliary enzymes and inflammation. Contrast-enhanced computed tomography (CT) revealed thickening of the transverse colon with relatively strong enhancement but no bile duct dilatation. Colonoscopy revealed localized edema and granular mucosa in the transverse colon. Fluoroscopic endoscopy exhibited the absence of haustra. Multiple biopsies were performed, but differentiation between mild inflammation and mucosa-associated lymphoid tissue (MALT) lymphoma was inconclusive. To establish a definitive diagnosis, transgastric endoscopic ultrasound-guided fine needle biopsy of the hypoechoic mass was performed. Histopathological analysis exhibited the proliferation of small-sized lymphocytes. Fluorescence in situ hybridization revealed the characteristic API2-MALT1 translocation of MALT lymphoma. We performed liver biopsy to investigate biliary enzyme elevation. Histopathology confirmed lymphocytic infiltration within Glisson's capsule. Immunohistochemistry showed positive for CD20 and negative for CD3 and CD5, signifying the infiltration of MALT lymphoma in the liver. Based on these findings, we diagnosed MALT lymphoma, Lugano classification Stage IV. We performed bendamustine-rituximab (BR)-combined therapy. After six courses of BR-combined therapy, colonoscopy revealed improvement in the lead pipe sign and CT revealed disappearance of the mass.

Gallbladder perforation following peroral cholangioscopy-guided lithotripsy: A case report.

Peroral cholangioscopy-guided lithotripsy is highly effective in clearing difficult bile duct stones. It can cause adverse events, such as cholangitis and pancreatitis; however, gallbladder perforation is extremely rare. Herein, we describe the case of a 77-year-old woman who developed gallbladder perforation following peroral cholangioscopy -guided lithotripsy. She was referred to our hospital to treat multiple large bile duct stones. She underwent peroral cholangioscopy-guided lithotripsy because of conventional lithotripsy failure. After a cholangioscope was advanced into the bile duct, saline irrigation was used for visualization. Electronic hydraulic lithotripsy was performed, but it took time for fragmentation because the calculus was hard. The 2-h endoscopic procedure did not completely remove the stone, and treatment was discontinued after placing a biliary plastic stent and nasobiliary tube. After the endoscopic procedure, she started experiencing right hypochondrial pain, which worsened the next day. Computed tomography showed a gallbladder wall defect in the gallbladder fundus with pericholecystic fluid. She was diagnosed with gallbladder perforation and underwent emergency surgery. A perforation site was found at the gallbladder fundus. Open cholecystectomy, choledochotomy, and extraction of residual bile duct stones were performed. The patient was discharged 9 days post-surgery without any complications. The saline irrigation used for visualization may have caused a surge in intra-gallbladder pressure, resulting in gallbladder perforation. Therefore, endoscopists may need to conserve irrigation water during peroral cholangioscopy-guided lithotripsy.

Comparative Analysis of Patient-Matched PDOs Revealed a Reduction in OLFM4-Associated Clusters in Metastatic Lesions in Colorectal Cancer.

Metastasis is the major cause of cancer-related death, but whether metastatic lesions exhibit the same cellular composition as primary tumors has yet to be elucidated. To investigate the cellular heterogeneity of metastatic colorectal cancer (CRC), we established 72 patient-derived organoids (PDOs) from 21 patients. Combined bulk transcriptomic and single-cell RNA-sequencing analysis revealed decreased gene expression of markers for differentiated cells in PDOs derived from metastatic lesions. Paradoxically, expression of potential intestinal stem cell markers was also decreased. We identified OLFM4 as the gene most strongly correlating with a stem-like cell cluster, and found OLFM4+ cells to be capable of initiating organoid culture growth and differentiation capacity in primary PDOs. These cells were required for the efficient growth of primary PDOs but dispensable for metastatic PDOs. These observations demonstrate that metastatic lesions have a cellular composition distinct from that of primary tumors; patient-matched PDOs are a useful resource for analyzing metastatic CRC.

Evaluation of the RAS signaling network in response to MEK inhibition using organoids derived from a familial adenomatous polyposis patient.

RAS signaling is a promising target for colorectal cancer (CRC) therapy, and a variety of selective inhibitors have been developed. However, their use has often failed to demonstrate a significant benefit in CRC patients. Here, we used patient-derived organoids (PDOs) derived from a familial adenomatous polyposis (FAP) patient to analyze the response to chemotherapeutic agents targeting EGFR, BRAF and MEK. We found that PDOs carrying KRAS mutations were resistant to MEK inhibition, while those harboring the BRAF class 3 mutation were hypersensitive. We used a systematic approach to examine the phosphorylation of RAS effectors using reverse-phase protein array (RPPA) and found increased phosphorylation of MEK induced by binimetinib. A high basal level of ERK phosphorylation and its rebound activation after MEK inhibition were detected in KRAS-mutant PDOs. Notably, the phosphorylation of EGFR and AKT was more closely correlated with that of MEK than that of ERK. Transcriptome analysis identified MYC-mediated transcription and IFN signaling as significantly correlated gene sets in MEK inhibition. Our experiments demonstrated that RPPA analysis of PDOs, in combination with the genome and transcriptome, is a useful preclinical research platform to understand RAS signaling and provides clues for the development of chemotherapeutic strategies.