Language：English   Publishing type：Research paper (scientific journal)  

We report the rare case of severe cognitive disorder and ataxia caused by entrectinib in a patient with NTRK1 fusion gene-positive intrahepatic cholangiocarcinoma. The case was a 56-year-old woman after nine courses of GCS therapy. The patient experienced grade 1 muscle weakness on day 4 and grade 3, cognitive disorder on day 7 after receiving entrectinib, which led to hospitalization. The symptoms were reversible and tended to improve after withdrawal of entrectinib. It is crucial to increase awareness of TRKi-specific adverse events and their proper management.

DOI： 10.1007/s12328-024-02076-w

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: The role of long noncoding RNAs (lncRNAs) in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Extracellular vesicle (EV)-encapsulated RNAs could be effective targets for liquid biopsy. We aimed to identify previously unknown EV-encapsulated lncRNAs in PDAC and establish highly accurate methods for isolating EVs. MATERIALS AND METHODS: Extracellular vesicles were isolated using existing and newly developed methods, namely, PEViA-UC and PEViA-IP, from serum samples of 20 patients with PDAC, 22 patients with intraductal papillary mucinous neoplasms, and 21 healthy individuals. Extracellular vesicle lncRNA expression was analyzed using digital PCR. RESULTS: Gene expression analysis using cDNA microarray revealed a highly expressed lncRNA, HEVEPA , in serum EVs from patients with PDAC. We established PEViA-UC and PEViA-IP using PEViA reagent, ultracentrifugation, and immunoprecipitation. Although detection of EV-encapsulated HEVEPA using existing methods is challenging, PEViA-UC and PEViA-IP detected EV HEVEPA , which was highly expressed in patients with PDAC compared with non-PDAC patients. The detection sensitivity for discriminating PDAC from non-PDAC using the combination of HEVEPA and HULC , which are highly expressed lncRNAs in PDAC, and carbohydrate antigen 19-9 (CA19-9), was higher than that of HEVEPA , HULC , or CA19-9 alone. CONCLUSIONS: Extracellular vesicle lncRNAs isolated using PEViA-IP and CA19-9 together could be effective targets in liquid biopsy for PDAC diagnosis.

DOI： 10.1097/MPA.0000000000002315

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BACKGROUND: Visualization of the pancreatobiliary junction is one of the challenges faced by endoscopic ultrasonography (EUS). The water-filling technique, which allows for the observation of the ampulla at a suitable distance by injecting water into the lumen of the duodenum, was used for this purpose. However, a new gel immersion technique has recently been introduced for visualizing the gastrointestinal tract. This study investigated the effectiveness of visualizing the pancreatobiliary junction in EUS by comparing both water filling and the new gel immersion technique in identical cases. METHODS: The study ran from June to December 2021. Ten images from each technique were retrospectively compared by three independent researchers. The primary result of the study was the number of images depicting the "Pancreatic and Biliary Ducts Penetrating the Duodenal Muscularis Propria" (defined as Excellent observation) in each technique. The secondary outcome was defined as gel immersion technique's safety and impact on duodenal lumen distension. RESULTS: Ten patients used the gel immersion technique. All patients underwent the water-filling technique first, followed by gel injection after the water was completely aspirated. The average number of pictures rated as "Excellent observation," which is the primary outcome, was significantly higher with the gel immersion technique than with water filling, and no adverse events were observed. The subanalysis revealed that both convex and radial echoendoscopes are equally effective at depicting the ampulla with the gel immersion technique. CONCLUSIONS: The ability to depict the pancreatobiliary junction using the gel immersion technique is superior to that of the water-filling method, which may allow for a more detailed assessment of the ampullary region with both radial and convex echoendoscopes. This can be a useful EUS technique for diagnosing pancreaticobiliary maljunction or periampullary tumors.

DOI： 10.1007/s00464-024-10762-6

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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BACKGROUND: Gemcitabine plus nab-paclitaxel (GnP) has been a standard treatment for unresectable pancreatic cancer (uPC); however, the current treatment status and usefulness in older adults with uPC remain unclear. Therefore, we aimed to investigate the patient background and compare the efficacy and safety of GnP versus other treatments in older adults with uPC. PATIENTS AND METHODS: In this prospective observational study, we enrolled 233 eligible patients aged ≥76 years with pathologically proven, clinically uPC, and no history of chemotherapy from 55 Japanese centers during September 2018-September 2019. The main endpoints were overall survival (OS), progression-free survival (PFS), and safety. Geriatric assessments were performed upon registration and after 3 months. To adjust for confounders, we conducted propensity score-matched analyses. RESULTS: GnP, gemcitabine alone (Gem), best supportive care, and other therapies were administered to 116, 72, 16, and 29 patients, respectively. In the propensity score-matched analysis, 42 patients each were selected from the GnP and Gem groups. The median OS was longer in the GnP group than in the Gem group (12.2 vs. 9.4 months; hazard ratio [HR], 0.65; 95% CI, 0.37-1.13). The median PFS was significantly longer in the GnP group than in the Gem group (9.2 vs. 3.7 months; HR, 0.38; 95% CI, 0.23-0.64). The incidence of severe adverse events was higher with GnP than with Gem; however, the difference was not significant. CONCLUSION: GnP is more efficacious than Gem in patients aged ≥76 years with uPC despite demonstrating a higher incidence of severe adverse events.

DOI： 10.1093/oncolo/oyac157

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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BACKGROUND: Chemotherapy for advanced gastric cancer is recommended in the guidelines; however, later-line treatment remains controversial. Since immune checkpoint inhibitors have been used for the treatment of various malignancies, trials have been performed for gastric cancer. A phase 3 trial indicated the survival benefit of nivolumab monotherapy for gastric cancer patients treated with prior chemotherapy regimens. PATIENTS AND METHODS: A regional cohort study was undertaken to determine the real-world data of nivolumab treatment for patients with advanced or recurrent gastric cancer. The patients were enrolled for 2 years from October 2017 to October 2019 and were prospectively followed for 1 year to examine the overall survival (OS). The patient characteristics were analyzed in a multivariate analysis and a nomogram to predict the probability of survival was generated. RESULTS: In total, 70 patients who received nivolumab as ≥third-line chemotherapy were included in the Asahikawa Gastric Cancer Cohort. The median OS was 7.5 (95% CI, 4.8-10.2) months and the response rate was 18.6%. Diffuse type classification, bone metastasis, high neutrophil/lymphocyte ratio, and high CRP were associated with poor OS/prognosis in the multivariate analysis. A nomogram was developed based on these clinical parameters and the concordance index was 0.80 (95% CI, 0.68-0.91). The responders were aged and were frequently diagnosed with intestinal type gastric cancer, including patients with a HER2-positive status (27.3%) or microsatellite instability-high (27.3%) status. CONCLUSIONS: The regional cohort study of nivolumab monotherapy for gastric cancer patients revealed prognostic factors and a nomogram was developed that could predict the probability of survival.

DOI： 10.1002/cam4.4461

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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The role of long noncoding RNAs (lncRNAs) in the epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) is unclear. Some lncRNAs can be transferred by extracellular vesicles (EVs) and have potential as biomarkers. Here, we identify an lncRNA that could serve as a biomarker for PDAC and show the functional roles of the lncRNA. Expression profiling of lncRNAs revealed that highly upregulated in liver cancer (HULC) was highly expressed, and induced, by transforming growth factor-β in PDAC cells and their EVs. Knockdown of HULC decreased PDAC cell invasion and migration by inhibiting the EMT. Thus, HULC could be transferred by EVs, and promote EMT, invasion, and migration in recipient PDAC cells. To assess the roles of HULC, PDAC cell xenografts in nude mice were established. Knockdown of HULC in PDAC cells implanted in mice inhibited tumor growth. Moreover, microRNA-133b suppressed PDAC cell invasion and migration by inhibiting the EMT through targeting HULC. Furthermore, serum samples were obtained from 20 PDAC and 22 intraductal papillary mucinous neoplasm (IPMN) patients, as well as 21 healthy individuals. Analysis of serum EV HULC expression by digital PCR showed that HULC expression was significantly increased in PDAC patients compared to healthy individuals or IPMN patients. Additionally, HULC showed good predictive performance for discriminating PDAC, suggesting that the analysis of EV-encapsulated HULC would contribute to the diagnosis for human PDAC. Extracellular vesicle-transported HULC promotes cell invasion and migration by inducing the EMT, and microRNA-133b suppresses the EMT by targeting HULC. Extracellular vesicle-encapsulated HULC could be a potential circulating biomarker for human PDAC.

DOI： 10.1111/cas.14232

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Language：English   Publishing type：Research paper (scientific journal)  

Although non-coding RNAs (ncRNAs) are involved in disease pathogenesis, their contributions to pancreatic ductal adenocarcinoma (PDAC) remain unclear. Recently, the interrelationship between two classes of ncRNA, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), has been reported to contribute to the epigenetic regulation of gene expression in several diseases including cancers. Moreover, some ncRNAs can be transferred by extracellular vesicles (EVs) from their donor cells to recipient cells. We previously verified that lncRNA HULC is up-regulated in PDAC cells and the intercellular transfer of HULC by EVs can promote PDAC cell invasion and migration through the induction of epithelial-mesenchymal transition (EMT). Therefore, we identified the miRNA that could target HULC and investigated the functional contributions of the miRNA-HULC interaction and EV transfer of miRNA to the EMT pathway in PDAC. Microarray analysis revealed 187 miRNAs that were decreased to <0.87-fold in Panc-1 cells treated with TGF-β compared with the control. Of these, miR-622 was predicted to target HULC directly by bioinformatics analysis. Expression of miR-622 was significantly down-regulated by TGF-β in a panel of PDAC cells. miR-622 overexpression by a miRNA mimic significantly decreased HULC expression, increased E-cadherin expression, and decreased expression of Snail, N-cadherin, and vimentin. Moreover, overexpression of miR-622 significantly reduced cell invasion and migration whereas inhibition of miR-622 increased HULC expression and promoted EMT signaling, invasion, and migration of PDAC cells. Furthermore, incubation with miR-622-overexpressing EVs could transfer miR-622, which significantly elevated miR-622 expression and decreased cell invasion and migration via inhibition of the EMT pathway in recipient PDAC cells. These results provide mechanistic insights into the development of PDAC by demonstrating that miR-622, as a miRNA downregulated by TGF-β, could target HULC and suppress invasion and migration by inhibiting EMT signaling via EV transfer. These observations may identify EV-encapsulated miRNA as a novel therapeutic target for human PDAC.

DOI： 10.3389/fonc.2020.01013

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(一社)日本内科学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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57歳女。腹部エコー検査を受けたところ、肝S3、S7に肝腫瘍を指摘された。同結節は造影CTにてリング状濃染を呈し、転移性肝腫瘍が疑われた。精査目的に紹介入院となった。原発巣の精査目的にPET・CTを施行したが、肝S3、S7病変に集積を認める他、肝外に集積は認めなかった。診断目的に肝腫瘍生検を施行した。S3病変からの生検の結果、壊死組織とその周囲の炎症細胞浸潤が認められたが悪性細胞は認めず、病理所見上は炎症性偽腫瘍が疑われた。しかし、腫瘍辺縁部からのサンプリングエラーの可能性も否定しきれず、再度生検を施行した。S3およびS7病変より腫瘍生検を行ったところ、前回と同様の壊死組織の他に、クチクラの存在が認められ肝エキノコックス症と診断した。治療は、両葉多発であり小さな嚢胞性病変の散在も認められ、アルベンダゾールの内服とし、現在経過観察中である。

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Language：Japanese   Publisher：(一社)日本インターベンショナルラジオロジー学会  

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BACKGROUND: The technical difficulties related to the insertion of a long intestinal tube into the jejunum under fluoroscopy present a considerable problem in patients with an intestinal obstruction. OBJECTIVE: To evaluate the usefulness of endoscopic long intestinal-tube placement with the ultrathin esophagogastroduodenoscope (UT-EGD). DESIGN: A prospective randomized clinical trial was conducted. PATIENTS: Twenty-eight consecutive patients who presented with an intestinal obstruction were included in the study. INTERVENTION: The UT-EGD was inserted nasally into at least the second portion of the duodenum or beyond. After a guidewire was introduced through the working channel, with fluoroscopic guidance, the UT-EGD itself was carefully removed with the guidewire left in place. Next, a hydrophilic intestinal tube was advanced over the guidewire into the jejunum, and then the guidewire was removed. MAIN OUTCOME MEASUREMENTS: Primary end points are the total procedure time, the radiation exposure time, and the rate of complications, all compared with the conventional method. RESULTS: The mean (+/-SD) total procedure time was 18.7 +/- 8.4 minutes for the UT-EGD method and 39.5 +/- 15.0 minutes for the conventional method, with a significant time difference between the 2 methods (P < .0005). The mean (+/-SD) radiation exposure time was also shorter with the UT-EGD method (11.1 +/- 6.0 minutes) than with the conventional method (30.3 +/- 13.7 minutes) (P < .0005). There were no complications, except for mild nasal bleeding with each method. CONCLUSIONS: The UT-EGD method has definite advantages in the placement of a long intestinal tube for patients with an intestinal obstruction in comparison with the conventional method.

DOI： 10.1016/j.gie.2008.01.043

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Language：Japanese   Publisher：(一社)日本インターベンショナルラジオロジー学会  

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CONTEXT: Autoimmune pancreatitis is an increasingly recognized type of chronic pancreatitis, but little is known about the long-term outcome of the disease. CASE REPORT: We report an autopsy case of autoimmune pancreatitis. The patient was an 81-year-old Japanese male. He was referred to our department with jaundice in February 1996. ERCP images revealed a severe stricture of the lower part of the common bile duct and irregular narrowing of the main pancreatic duct. A diagnosis of extrahepatic cholangiocarcinoma was made and endoscopic biliary drainage was performed. A stricture of the common bile duct and narrowing of the pancreatic duct had improved on ERCP images when a follow-up examination was performed in November 1998. He was followed up for chronic pancreatitis. The serum IgG and IgG4 levels were increased on serological examination. He died of interstitial pneumonia and congestive heart failure in May 2003. At the autopsy examination, fibrosis was found in the periductal, interlobular and intralobular parts of the pancreas. Focal atrophy of the acinar cells was also identified. There was little infiltration of inflammatory cells into the parenchyma or the stroma of the pancreas. These pathological findings were similar to those of 'conventional' chronic pancreatitis. CONCLUSION: We present an autopsy case of autoimmune pancreatitis which is a rare finding.

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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We studied the effect of iron chelators, 2,2'-dipyridyl and desferrioxamine, on cerulein-induced pancreatitis in rats. Acute pancreatitis was induced by a single subcutaneous injection of 100 micrograms/kg body weight of cerulein, which caused hyperamylasemia and edematous pancreatitis with neutrophilic infiltration. Blood samples were collected for determination of serum amylase values and the pancreas was removed for the histological examination 6 h after the cerulein injection. Intraperitoneal administration of a ferrous iron chelator, 2,2'-dipyridyl, prior to the cerulein injection resulted in amelioration of hyperamylasemia and histological abnormalities such as edema and inflammation but not of acinar cell vacuolization. In contrast, administration of a ferric iron chelator, desferrioxamine, did not show any beneficial effects. These results indicate that administration of 2,2'-dipyridyl ameliorates the pancreatitis induced by the supramaximal dose of cerulein.

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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J-GLOBAL

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

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Language：Japanese   Publisher：(株)アークメディア  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(株)メディカルアイ  

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Language：Japanese   Publisher：(株)メディカルアイ  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(株)メディカルアイ  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：English   Publisher：日本癌学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2016&ichushi_jid=J02025&link_issn=&doc_id=20160304110005&doc_link_id=%2Fcq0pancr%2F2016%2F003101%2F006%2F0032-0040%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcq0pancr%2F2016%2F003101%2F006%2F0032-0040%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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症例は76歳女性で、B型肝炎で当院通院中、S8に18mmの中分化管癌を認めて肝切除術を行ったが、肝内再発を繰り返し、RFAやTACEが行われた。その後右肺転移を認め、肝癌Stage IVBの診断でSorafenib(SF)内服を開始した。Grade 2の下痢、食欲不振が出現し、SFを3週間休薬したが、造影USでS5に17mmの新規病変を認めてSF内服を再開し、投与再開1週後には腫瘍部の輝度は低下し、投与再開3週後の造影MRIではRECISTでSD、mRECISTでPRと判定され、その効果は33週後まで継続した。また経過中にSFの用量依存性に腫瘍血流の増減を認め、Real-time Tissue Elastographyによる組織弾性評価では、SF投与後弾性スコア、弾性比とも有意に低下し、B-modeによる形態評価では、投与12週後より腫瘍内部に低エコースポットが出現し、14週後には更に増加した。副作用に注意しながらSFの用量を調節したが、肝癌進行による肝不全にてSF開始後15ヵ月で死亡した。

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Language：Japanese   Publisher：北海道医学会  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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2007年1～7月に造影CTにて多血性肝細胞癌と診断された24症例43結節(腫瘍径10～80mm・平均28.4mm,体表よりの深さ2.2～11.4cm・平均6.0cm)を対象に、Bモード検出不能肝癌の存在診断におけるsonazoid造影エコーの有用性について検討した。その結果、肝癌43結節中16結節にマイクロコンベックス型プローブによる撮像が行われ、その内訳は横隔膜ドーム下病変8結節・肋間狭小化による観察不良の7結節であった。Bモードによる肝癌検出率は43結節中37結節(86.0%)で、Bモード検出不良となった原因は肝硬変による肝粗造が6結節中3結節と半数を占め、その他は治療による修飾や大きさ7mmの等輝度病変、高度肝萎縮症例各1結節であった。Sonazoid造影後の検出率は全体で97.7%まで上昇し、造影前のBモードに比べ11.7%の有意な増加を認めた。腫瘍径と腫瘍存在深部及びBモード検出の有無からみた存在診断能の検討では、SonazoidはBモード検出の有無に関係なく存在診断が可能であり、存在診断が行えなかった1結節は高度肝萎縮による消化管ガスの影響で物理的に描出不可能名病変であった。以上より、sonazoid造影エコーはBモード検出不能肝癌の存在診断に有用と考えられた。

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Language：Japanese   Publisher：(株)インナービジョン  

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Language：Japanese   Publisher：(株)メディカルアイ  

52歳男性。C型慢性肝炎であったが、6年経過して腹部膨満感が出現した。造影CTにより肝表面の凹凸不整、その周囲の腹水貯留を認めた。肝門部には内部に淡い造影効果を伴う低吸収域が存在し、それに接した門脈内にthread and streaks signを認めた。以上よりC型肝硬変症に合併した門脈腫瘍塞栓を伴う進行肝細胞癌と診断した。造影前カラードプラ検査所見より門脈右枝完全閉塞の診断で、attenuation differenceも認められた。Sonazoidを用いて低音圧Harmonic Imagingによる肝細胞癌門脈腫瘍塞栓の血流評価を行った結果、肝内の肝動脈より分岐して門脈腫瘍塞栓に流入している栄養動脈が観察された。さらにMicro Flow Imagingを用いて再度観察を行ったところ、その一部始終はより明瞭化し、いわゆるthread and streaks signがリアルタイムに映像化されたことを確認できた。さらにParametric Imagingによる血流速度評価にて正確さを証明できた。Sonazoid造影超音波はリアルタイム性の良さと空間分解能の高さを兼ね備えており、肝細胞癌門脈腫瘍塞栓の腫瘍内血流評価に大変有用であると考えられた。

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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