Efficacy and Safety of Endoscopic Removal for Asymptomatic Common Bile Duct Stones in Comparison with Symptomatic Stones.

OBJECTIVE: Endoscopic removal is recommended for common bile duct stones (CBDs). However, in patients with asymptomatic CBDs, follow-up without treatment may be recommended because of the increased complication risks associated with asymptomatic CBDs removal. The objective of our study was to investigate the efficacy and safety of CBDs removal in asymptomatic patients. METHODS: Consecutive patients with naive papilla who underwent endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of CBDs from April 2016 to August 2020 were retrospectively analyzed. We compared the efficacy and safety of CBDs removal in asymptomatic and symptomatic patients. RESULTS: We enrolled 300 patients, 53 asymptomatic and 247 symptomatic patients. Endoscopic CBDs removal was successful in all patients, except one symptomatic patient. However, the complete stone removal rate in a single session was significantly higher in the asymptomatic group than that in the symptomatic group. ERCP-related complications did not differ between the asymptomatic and symptomatic patients. The incidence of post-ERCP pancreatitis was similar and liver cirrhosis was the only significant risk factor for pancreatitis. CONCLUSION: Complication risks associated with endoscopic CBDs removal was not significantly different between asymptomatic and symptomatic patients. Liver cirrhosis was a significant risk factor of ERCP-related pancreatitis.

[A case of simultaneous multicentric cancer in the gallbladder duct and the common bile duct without pancreaticobiliary maljunction].

A 68-year-old man who underwent cholecystectomy for acute cholecystitis and was diagnosed with gallbladder duct carcinoma was referred to our hospital. Postoperative computed tomography showed thickening of the middle to lower bile duct without any tumorous lesions. Endoscopic retrograde cholangiopancreatography and intraductal ultrasonography revealed irregular wall thickening of the lower bile duct and apparent infiltration of gallbladder duct tumor to the common bile duct without pancreaticobiliary maljunction. Subtotal stomach-preserving pancreaticoduodenectomy was performed. Pathological examination showed papillary adenocarcinoma and tubular adenocarcinoma in the gallbladder duct and BilIN-3 lesion in the distal bile duct. The final diagnosis was biliary simultaneous multicentric cancer without pancreaticobiliary maljunction.

Rapid Regression of B-Cell Non-Hodgkin's Lymphoma after Eradication of Hepatitis C Virus by Direct Antiviral Agents.

A 47-year-old woman visited Tokai University Hospital complaining of left cervical lymph node swelling in 2007. The laboratory data were almost normal except for slight anemia (Hgb 10.5 g/dL), elevation of serum soluble interleukin (IL)-2 receptor levels (645 U/mL [normal range 220-530 U/mL]), and positive hepatitis C virus (HCV) antibody. Serum transaminase and lactated dehydrogenase levels were normal. Contrast-enhanced computed tomography (CT) showed lymph node swelling with a diameter of 3 cm at the left supraclavicular fossa and mild splenomegaly, and 18F-fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT) revealed abnormal uptake in the left supraclavicular fossa. The patient was diagnosed as having indolent nodal marginal zone B-cell lymphoma by lymph node biopsy. After 9 years with no progression of lymphoma, the patient received 12-week ledipasvir/sofosbuvir therapy for HCV infection and achieved sustained virologic response without any adverse effects. The left supraclavicular mass disappeared in the FDG-PET/CT performed 5 months after antiviral therapy indicating complete response. The serum soluble IL-2 receptor concentration decreased to 244 U/mL. Thereafter, her lymphoma was in remission for 3 years.

A Case of Endoscopic Mucosal Resection of Carcinoma in Adenoma at the Minor Duodenal Papilla.

Here, we describe a case of minor papillary adenocarcinoma in adenoma that was treated with endoscopic mucosal resection (EMR). In a 67-year-old woman, sigmoid colon cancer was incidentally detected on preoperative upper gastrointestinal endoscopy. Endoscopy revealed a slightly elevated lesion at the minor duodenal papilla. The findings of a histopathologic examination were suggestive of adenocarcinoma. Computed tomography and magnetic resonance images identified a minute tumor, whereas endoscopic ultrasonography revealed that the tumor did not spread to the pancreas. We performed EMR of this lesion. There were no complications, and relapse has not occurred in 3 years. Cases of minor papillary adenocarcinoma treated with EMR are quite rare.

An Autopsy Case of Anaplastic Pancreatic Ductal Carcinoma (Spindle Cell Type) Multiple Onset in the Pancreas.

This is a case of a 75-year-old man who was diagnosed with anaplastic pancreatic ductal carcinoma (spindle cell type). His image findings showed pancreatic head cysts and pancreatic head, body, and tail tumors respectively. EUS-FNA was performed to the pancreatic head and pancreatic body tumors, and the same high atypical type cells suspected of cancer were obtained from either specimen, and finally total pancreatectomy was performed. On the specimen, there were 4 lesions in the pancreas; histology showed that the same anaplastic pancreatic ductal carcinoma (spindle cell type) was obtained from the pancreatic head cyst and the pancreatic tumors.

An autopsy case of primary extranodal NK/T cell lymphoma (extranodal NK/T-cell lymphoma) of the bile duct.

We reported the case of a 50-year-old man diagnosed with extrinsic NK/T-cell lymphoma. He was initially diagnosed with locally advanced unresected pancreatic duct carcinoma and was treated with combination chemotherapy using gemcitabine and nabpaclitaxel. One month after treatment, he developed bleeding. Upper gastrointestinal endoscopy showed a deep ulcer lesion from the duodenal bulb to the inner wall of the descending section that was not observed before treatment. Coil embolization was performed, but the necrotic area widened after treatment; the patient died of disseminated intravascular coagulation after 1 week. Autopsy showed a soft white-tone lesion that extended from the ulcer wall to the gallbladder wall and around the intrahepatic bile duct. Lesions were also found in the spleen, lungs, kidney, and bone marrow, and immunohistochemistry confirmed extrinsic NK/T-cell lymphoma (extranodal NK/T-cell lymphoma, nasal type). In conclusion, histological diagnosis of NK/T-cell lymphoma is difficult at an early stage, and the clinical course often shows rapid tumor progression, particularly bleeding in the digestive organs or widespread perforation and penetration. NK/T-cell lymphoma should be ruled out in patients with bile duct and pancreatic tumors in whom tissue diagnosis via biopsy cannot be performed.

Gene expression profile of fibrovascular membranes from patients with proliferative diabetic retinopathy.

BACKGROUND/AIMS: The purpose of this study was to generate a profile of genes expressed in preretinal fibrovascular membranes (FVMs) from patients with proliferative diabetic retinopathy. METHODS: A PCR-amplified complementary DNA (cDNA) library was constructed using the RNAs isolated from FVMs obtained during vitrectomy. The sequence from the 5' end was obtained for randomly selected clones and used to generate expressed sequence tags (ESTs). Functional annotation was retrieved from Ensemble database and analysed by FatiGO. The web-based VisANT software was used to identify the molecular networks within the FVMs. RESULTS: A total of 2816 ESTs were assembled in 625 non-redundant clusters. Among these, 515 matched the human cDNA database. The 515 clusters were subdivided by functional subsets of genes related to ribosomal activity, oxidative phosphorylation, focal adhesion, cell adhesion and other functions. Querying against the VisANT database yielded 3175 possible physical relationships to other genes/proteins, which included an additional 2480 genes that were not detected in the FVM library. CONCLUSIONS: The cDNA library constructed from human FVMs will be a valuable source of information. It should facilitate a wide range of studies that can establish the molecular mechanisms underlying the development of FVMs.

TEM7 (PLXDC1) in neovascular endothelial cells of fibrovascular membranes from patients with proliferative diabetic retinopathy.

PURPOSE: Proliferative diabetic retinopathy (PDR) results from the formation of fibrovascular membranes (FVMs) in the posterior fundus that can lead to a severe decrease of vision. Tumor endothelial marker 7 (TEM7) is a protein that is highly expressed in the endothelial cells of tumors, but whether it plays a role in FVMs is unknown. The purpose of this study was to determine whether TEM7 is associated with the formation of FVMs. METHODS: FVMs were obtained during vitrectomy from patients with PDR. RT-PCR was performed to determine the level of expression of the mRNA of TEM7. The splice variants of TEM7 were identified by direct sequencing. Immunohistochemical analyses and in situ hybridization was performed to determine the sites of TEM7 in the FVMs. RESULTS: The level of the mRNA of TEM7 was high in 10 of 10 FVMs but was barely detectable in the five idiopathic epiretinal membranes. Direct sequencing of subcloned TEM7 PCR products revealed several splice variants (intracellular, secreted, and membrane-bound forms of TEM7) in the FVMs. Immunohistochemical analysis showed a colocalization of TEM7 and CD34, an endothelial cell marker, in most of the neovascular endothelial cells in the FVMs. Immunoelectron microscopy revealed that membrane-bound TEM7 was expressed on the luminal surfaces of the vascular endothelial cells of FVMs. CONCLUSIONS: This study indicates that TEM7 may play a significant role in the proliferation and maintenance of neovascular endothelial cells in the FVMs. If correct, TEM7 may be a molecular target for new diagnostic and therapeutic strategies for PDR.

Prognostic DNA testing and counselling for dominant optic atrophy due to a novel OPA1 mutation.

CASE REPORT: To report the case of a 26-year-old woman with a family history of dominant optic atrophy who requested DNA testing and counselling. Ophthalmologic examination showed her affected father had bilateral temporal papillary pallor. Direct genomic sequencing of the OPA1 gene revealed a novel heterozygous nonsense mutation (Arg879stop). Because no mutation in OPA1 was detected in the daughter, we could counsel her that the possibility was very low that she was a carrier or would pass the disease-causing gene to her children. COMMENTS: Our study provides evidence of the apparent value of molecular genetic analysis of OPA1 gene as predictive DNA testing, although the exact risk and benefit of this type of analysis awaits further study.

Rapid detection of SAG 926delA mutation using real-time polymerase chain reaction.

PURPOSE: Mutation 926delA of the arrestin/S-antigen SAG gene is the main cause of Oguchi disease in the Japanese. The purpose of this study was to develop a rapid diagnostic assay to detect mutations in the SAG gene. METHODS: Two sequence-specific primers and fluorophore-labeled probes for exon 11 of the SAG gene were designed, and the region spanning the mutations was amplified by polymerase chain reaction (PCR) using the LightCycler detection system (Roche Diagnostics, Mannheim, Germany). The mutations were then identified by melting curve analyses of the hybrid formed between the PCR product and a specific fluorescent probe. RESULTS: We clearly distinguished each SAG genotype (homozygous and heterozygous 926delA and wild type) by the distinct melting peaks at different temperatures. One thermal cycling required approximately 54 min to process, and the results were 100% in concordance with the genotypes determined by DNA sequencing. CONCLUSIONS: We have succeeded in developing a rapid method to detect the most frequent mutation in the SAG gene. This method will help in identifying gene mutations associated with Oguchi disease with a rapid and reliable identification or the exclusion of the frequent mutations in the SAG gene.

Novel triple missense mutations of GUCY2D gene in Japanese family with cone-rod dystrophy: possible use of genotyping microarray.

PURPOSE: To report a novel mutation in the GUCY2D gene in a Japanese family with autosomal dominant cone-rod dystrophy (adCORD), and to examine the possible use of arrayed primer extension (APEX)-based genotyping chip in detecting mutations. METHODS: Genomic DNA was extracted from the peripheral blood of family members with adCORD. It was PCR-amplified, fragmented, and hybridized to APEX-based genotyping microarrays on which known disease-associated sequence variations were arrayed for patients with early-onset retinal dystrophy. All coding exons of the GUCY2D gene were directly sequenced. The PCR amplicon carrying a novel mutation was subcloned, and each clone was sequenced. RESULTS: Five single nucleotide polymorphisms in AIPL1, RPGRIP1, and GUCY2D were detected in the proband by microarray screening, and all were validated by direct sequencing. A novel heterozygous triple missense mutation of c.2540_2542delinsTCC (p.Gln847_Lys848delinsLeuGln amino acid substitutions) was found in both the proband and his father, and the three nucleotide changes were located on the same chromosome. Electroretinography (ERGs) demonstrated a significant reduction in rod function and a complete absence of cone function in both affected individuals. CONCLUSIONS: A novel heterozygous triple consecutive missense mutation in the GUCY2D gene has been linked to adCORD. Our study demonstrates that the APEX-based gene screening can be used to identify simultaneously disease-modifying sequence changes as well as disease-causing mutations, once proper and comprehensive sites of sequence variations of the disease are arrayed.

De novo insG619 mutation in PAX2 gene in a Japanese patient with papillorenal syndrome.

PURPOSE: To describe a Japanese patient with papillorenal syndrome (PRS) and to identify the genetic defect responsible for the disease. DESIGN: Interventional case report. METHODS: Complete ophthalmologic and systemic examinations were performed, and direct genomic sequencing of the PAX2 gene. RESULTS: Fundus examination of a 3-year-old Japanese girl showed atypical coloboma bilaterally. At 6 years of age, she presented with proteinuria, and renal ultrasonography showed hypoplastic kidneys bilaterally. Molecular genetic analysis of the PAX2 gene revealed a de novo heterozygous insertion of a G at position 619. CONCLUSIONS: Our findings suggest that an abnormal development of the optic stalk led to the optic disk dysplasia in PAX2-associated PRS. This indicates that we should consider renal abnormalities when an atypical round coloboma is present. Molecular genetic analysis of the PAX2 gene in combination with renal ultrasonography can help in making an earlier diagnosis of the disease.

Rapid genotyping for most common TGFBI mutations with real-time polymerase chain reaction.

Recent studies of the corneal dystrophies (CDs) have shown that most cases of granular CD, Avellino CD, and lattice CD type I are caused by mutations in the human transforming growth factor beta-induced (TGFBI) gene. The aim of this study was to develop a rapid diagnostic assay to detect mutations in the TGFBI gene. Sixty-six patients from 64 families with TGFBI-associated CD were studied. A primer probe set was designed to examine the genome from exons 4 and 12 of the TGFBI gene in order to identify mutant and wild-type alleles. A region spanning the mutations was amplified by the polymerase chain reaction (PCR) in a commercial cycler. Mutations were then identified by melting curve analysis of the hybrid formed between the PCR product and a specific fluorescent probe. Using this system, we clearly distinguished each CD genotype (homozygous and heterozygous 418G-->A, heterozygous 417C-->T, heterozygous 1710C-->T, and wild-type) of all the patients by means of the clearly distinct melting peaks at different temperatures. One thermal cycling took approximately 54 min, and all results were completely in concordance with the genotypes determined by conventional DNA sequencing. Thus, the technique is accurate and can be used for routine clinical diagnosis. We expect that our new method will help in making precise diagnoses of patients with atypical CDs and aid the revision of the clinical classification of inherited corneal diseases based on the genetic pathogenesis.