記述言語：英語   掲載種別：研究論文（学術雑誌）  

Transpapillary gallbladder biopsy has been reported for the diagnosis of gallbladder disease, and this procedure requires special biopsy forceps or a large-diameter pusher catheter. We retrospectively examined consecutive patients who underwent transpapillary gallbladder biopsy using a newly designed device delivery system (Endosheather; Piolax Medical Device, Kanagawa, Japan). We evaluated 11 patients (median age, 71 years [28-85]) who underwent transpapillary gallbladder biopsy from June 2021 to July 2022. The selective gallbladder cannulation and delivery system insertion success rate was 90.9% (10/11). The target lesion biopsy success rate was 63.6% (7/11). The biopsy time (i.e., time to completion of biopsy after successful guidewire placement) was 8.7 (5.4-32.7) min. In 1 patient in whom all 6 gallbladder bile juice cytology results were benign, the biopsy result was suspicious of adenocarcinoma. The final diagnosis for this patient was gallbladder cancer. Adverse events occurred in 2 patients. In 1 patient, acute cholecystitis occurred and required emergency surgery. Transpapillary gallbladder biopsy using the Endosheather is a potential option for the diagnosis of gallbladder disease. A good indication for this technique is considered to be wall thickening at the gallbladder fundus, where it is difficult to differentiate between benign and malignant lesions by imaging modalities such as ultrasonography or endoscopic ultrasound. The addition of transpapillary gallbladder biopsy may be advantageous when performing bile juice cytology using a nasogallbladder drainage tube for the diagnosis of gallbladder disease.

DOI： 10.1055/a-2095-0098

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 75-year-old woman visited our hospital with constipation. Colonoscopy revealed a submucosal tumor in the rectum. She was followed up as a case of mucosal prolapse syndrome. Six years later, she was referred to our hospital due to hematochezia and abdominal pain. Colonoscopy revealed that the submucosal tumor had an ulcerative appearance with bleeding. Low anterior resection was performed. Amyloid protein deposition was detected from the submucosa to subserosa. Other organs showed no evidence of amyloidosis; we therefore diagnosed the patient with localized rectal amyloidosis. This is a rare case of symptomatic localized rectal amyloidosis whose long-term progression was able to be endoscopically observed.

DOI： 10.2169/internalmedicine.9648-22

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/den.14376

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Artificial intelligence (AI) is rapidly developing in various medical fields, and there is an increase in research performed in the field of gastrointestinal (GI) endoscopy. In particular, the advent of convolutional neural network, which is a class of deep learning method, has the potential to revolutionize the field of GI endoscopy, including esophagogastroduodenoscopy (EGD), capsule endoscopy (CE), and colonoscopy. A total of 149 original articles pertaining to AI (27 articles in esophagus, 30 articles in stomach, 29 articles in CE, and 63 articles in colon) were identified in this review. The main focuses of AI in EGD are cancer detection, identifying the depth of cancer invasion, prediction of pathological diagnosis, and prediction of Helicobacter pylori infection. In the field of CE, automated detection of bleeding sites, ulcers, tumors, and various small bowel diseases is being investigated. AI in colonoscopy has advanced with several patient-based prospective studies being conducted on the automated detection and classification of colon polyps. Furthermore, research on inflammatory bowel disease has also been recently reported. Most studies of AI in the field of GI endoscopy are still in the preclinical stages because of the retrospective design using still images. Video-based prospective studies are needed to advance the field. However, AI will continue to develop and be used in daily clinical practice in the near future. In this review, we have highlighted the published literature along with providing current status and insights into the future of AI in GI endoscopy.

DOI： 10.1007/s10620-021-07086-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report on two patients with stasis symptoms, including vomiting and nausea that were caused by deformity, stenosis, and decreased gastric peristalsis associated with artificial ulcers after endoscopic submucosal dissection (ESD). In both cases, the symptoms remained unresolved despite repetitive endoscopic balloon dilation (EBD). Therefore, laparoscopic gastrojejunostomy was performed. Soon after the procedure, their food intake was improved. Laparoscopic gastrojejunostomy can be an option for the treatment of gastric outlet obstruction induced by a large field of gastric ESD that is refractory to EBD.

DOI： 10.1002/deo2.18

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIMS: This study aimed to assess the efficacy of a novel aerosol-exposure protection (AP) mask in preventing coronavirus disease in healthcare professionals during upper gastrointestinal endoscopy and to evaluate its clinical feasibility. METHODS: In Study 1, three healthy volunteers volitionally coughed with and without the AP mask in a cleanroom. Microparticles were visualized and counted with a specific measurement system and compared with and without the AP mask. In Study 2, 30 patients underwent endoscopic resection with the AP mask covering the face, and the SpO2 was measured throughout the procedure. RESULTS: In Study 1, the median number of microparticles in volunteers 1, 2, and 3 with and without the AP mask was 8.5 and 110.0, 7.0 and 51.5, and 8.0 and 95.0, respectively (p<0.01). Using the AP mask, microparticles were reduced by approximately 92%. The median distances of microparticle scattering without the AP mask were 60, 0, and 68 in volunteers 1, 2, and 3, respectively. In Study 2, the mean SpO2 was 96.3%, and desaturation occurred in three patients. CONCLUSION: The AP mask could provide protection from aerosol exposure and can be safely used for endoscopy in clinical practice.

DOI： 10.5946/ce.2021.178-IDEN

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: In patients with average risk of bleeding, second-look endoscopy does not reportedly reduce bleeding after gastric endoscopic submucosal dissection. However, effectiveness of second-look endoscopy for patients with a high risk of bleeding, such as those who are taking antithrombotic agents, is unclear. Hence, this study aims to clarify the effectiveness of second-look endoscopy for patients with antithrombotic therapy. METHODS: We studied 142 consecutive patients with 173 gastric epithelial neoplasms who were routinely taking antithrombotic agents and were treated by endoscopic submucosal dissection at Tonan Hospital between November 2013 and December 2019. They were classified into two groups: those with second-look endoscopy (SLE group, 69 patients with 85 lesions) and those without second-look endoscopy (non-SLE group, 73 patients with 88 lesions). The incidence of post-endoscopic submucosal dissection bleeding was compared between the SLE and non-SLE groups. RESULTS: There were no statistical differences in the rate of patients undergoing single antiplatelet therapy, single anticoagulant therapy, and multiple therapy between the SLE and non-SLE groups (SLE group vs. non-SLE group; 32 [46.4%], 16 [23.2%], and 21 [30.4%] patients vs. 37 [50.7%], 20 [27.4%], and 16 [21.9%] patients, respectively; p = 0.50). Post-endoscopic submucosal dissection bleeding incidence was 21.7% (15/69) and 21.9% (16/73) in the SLE and non-SLE groups, respectively, and did not significantly differ between the two groups (p = 0.98). CONCLUSIONS: For patients taking antithrombotic agents, the incidence of post-endoscopic submucosal dissection bleeding was not reduced by second-look endoscopy.

DOI： 10.1186/s12885-021-08679-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1055/a-1216-1167

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/jjco/hyab009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Recent studies have shown that mixed predominantly differentiated-type (MD) early gastric cancer (EGC) might have more malignant potential than pure differentiated-type (PD) EGC. However, no study has analyzed all differentiated-type EGC cases treated endoscopically and surgically. This study aimed to compare the differences in clinicopathological features and long-term prognosis between MD- and PD-EGC. METHODS: We evaluated all patients with differentiated-type EGCs who were treated endoscopically and surgically in our hospital between January 2010 and October 2014. The clinicopathological features and long-term prognosis of MD-EGC were compared with those of PD-EGC. RESULTS: A total of 459 patients with 459 lesions were evaluated in this study; of them, 409 (89.1%) and 50 (10.9%) were classified into the PD and MD groups, respectively. Submucosal invasion was found in 96 (23.5%) patients of the PD group and in 33 (66.0%) patients of the MD group (p < 0.01). The rates of positive lymphatic and vascular invasion and ulceration were significantly higher in the MD group than in the PD group (p < 0.01). The proportion of patients with lymph node metastasis was also significantly higher in the MD group than in the PD group (5 (10%) vs 6 (1.5%), p < 0.01). The 5-year overall and EGC-specific survival rates in the PD group were 88.3 and 99.5%, respectively, while they were 94.0 and 98.0% in the MD group, respectively. CONCLUSIONS: MD-EGC has more malignant potential than PD-EGC. However, the long-term prognosis of MD-EGC is good and is not significantly different from that of PD-EGC when treated appropriately.

DOI： 10.1186/s12885-021-07962-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.5590-20

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.cgh.2019.03.041

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIMS: The adenoma detection rate (ADR) of screening colonoscopies performed by trainees is often lower than that of colonoscopies performed by experts. The effcacy of cap-assisted colonoscopy (CAC) in adenoma detection is well documented, especially that of CACs performed by trainees. Endocuff, a new endoscopic cap, is reportedly useful for adenoma detection; however, no trials have compared the effcacy of Endocuff-assisted colonoscopy (EAC) and CAC conducted by trainees. Therefore, the present study retrospectively compared the effcacy between EAC and CAC in trainees. METHODS: This was a single-center, retrospective study involving 305 patients who underwent either EAC or CAC performed by three trainees between January and December 2018. We evaluated the ADR, mean number of adenomas detected per patient (MAP), cecal intubation rate, cecal intubation time, and occurrence of complications between the EAC and CAC groups. RESULTS: The ADR was significantly higher in the EAC group than in the CAC group (54.3% vs. 37.3%, p=0.019), as was the MAP (1.36 vs. 0.74, p=0.003). No significant differences were found between the groups with respect to the cecal intubation rate or cecal intubation time. No major complications occurred in either group. CONCLUSION: Our results suggest that EAC exhibits increased ADR and MAP compared to CAC when performed by trainees.

DOI： 10.5946/ce.2019.124

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Although there have been established guidelines for first surveillance colonoscopy (FSC) after a polypectomy, there is no consensus on performing a second surveillance colonoscopy (SSC), especially in Asian countries. This study aimed to investigate the association of SSC findings with index total colonoscopy (TCS) and FSC results. METHODS: This was a single-center retrospective cohort study involving 1928 consecutive Japanese patients who had received three or more colonoscopies. High-risk colonoscopic findings were defined as advanced adenoma (≥10 mm in size, with a villous histology or high-grade dysplasia) or more than three adenomas, whereas low-risk findings were defined as one to two non-advanced adenomas. On the basis of index TCS results, the patients were divided into three groups: no adenomas (NA) (n = 888), low-risk (LR) (n = 476), and high-risk (HR) (n = 564) groups, respectively. RESULTS: In the NA group, the rate of high-risk findings on SSC was significantly higher in patients with high-risk or low-risk findings on FSC than in those with no adenoma (7.7% and 7.9% vs 2.2%, P < 0.05). Patients in the LR and HR groups with high-risk findings on FSC had a significantly higher risk on SSC than those with low-risk findings or no adenoma on FSC (LR group: 28.6%, 9.4%, and 5.9%, respectively, P < 0.01; HR group: 34.5%, 18.8%, and 7.9%, respectively, P < 0.01). CONCLUSIONS: Index TCS and especially FSC findings were predictive of SSC results. The study results may be useful for determining appropriate intervals for surveillance colonoscopy in Asian countries.

DOI： 10.1111/1751-2980.12869

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a rapidly progressive malignancy that exhibits an extremely poor prognosis, with most cases diagnosed at an advanced stage. To date, few reports have explored the natural history of PDAC, and the period leading up to the detection of PDAC as a tumor with contrast-enhanced computed tomography (CECT) remains unclear. Here, we report 3 PDAC cases diagnosed incidentally by repeating imaging examinations during observation of other organ cancers. CASE REPORT Two patients were undergoing postoperative follow-up for colorectal cancer; owing to the elevation of serum CA19-9 or dilatation of the main pancreatic duct, both cases were finally diagnosed with PDAC. Another patient was administered neoadjuvant chemotherapy for a gastrointestinal stromal tumor; the fluorodeoxyglucose uptake in the pancreas with fluorodeoxyglucose positron emission tomography for the treatment assessment led to the diagnosis of PDAC. All patients underwent frequent CECT for assessment of other diseases, and PDAC became visible with CECT within 3-4 months of the appearance of indirect findings of PDAC. CONCLUSIONS The period leading up to the detection of PDAC as a tumor with CECT was approximately 3-4 months. These cases suggest that additional imaging examinations should be performed when the indirect findings of PDAC are noted. This report adds value to the literature by elucidating the natural course of PDAC.

DOI： 10.12659/AJCR.917197

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cisplatin plus 5-fluorouracil is regarded as standard neoadjuvant chemotherapy for esophageal squamous cell carcinoma (ESCC) in Japan, but the prognosis remains poor. We have previously described how definitive chemoradiotherapy with docetaxel, nedaplatin, and 5-fluorouracil (DNF) led to a very high response rate and promising survival times. We therefore undertook a phase II trial to evaluate the feasibility and efficacy of neoadjuvant DNF. The study included patients with clinical stage Ib-III ESCC. Chemotherapy consisted of i.v. docetaxel (30 mg/m2 ) and nedaplatin (50 mg/m2 ) on days 1 and 8, and a continuous infusion of 5-fluorouracil (400 mg/m2 /day) on days 1-5 and 8-12, every 3 weeks. After three courses of chemotherapy, esophagectomy was carried out. The primary end-point was the completion rate of the protocol treatment. Twenty-eight patients were enrolled (cStage Ib/II/III, 2/3/23) and all received at least two cycles of chemotherapy. Twenty-five patients underwent surgery, all of whom achieved an R0 resection, leading to a completion rate of 89.3%. The overall response rate was 87.0%. A pathological complete response was confirmed in eight (32.0%) cases. Grade 3/4 adverse events included leukopenia (32.1%), neutropenia (39.3%), febrile neutropenia (10.7%), thrombocytopenia (10.7%), and diarrhea (14.3%), but were manageable. Treatment-related deaths and major surgical complications did not occur. Estimated 2-year progression-free and overall survival rates were 70.4% and 77.2%, respectively. Thus, DNF therapy was well tolerated and deemed feasible, with a strong tumor response in a neoadjuvant setting for ESCC. This trial is registered with the University Hospital Medical Information Network (UMIN ID: 000014305).

DOI： 10.1111/cas.13772

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

AIM: This study aimed to retrospectively evaluate the efficacy and safety of capecitabine plus oxaliplatin(CapeOX)for heavily pretreated advanced gastric cancer(AGC)refractory to S-1, cisplatin, irinotecan, and taxanes. METHODS: Twelve patients with AGC refractory to S-1, cisplatin, irinotecan, and taxanes were enrolled in this study.Treatment comprised capecitabine(1,000mg/m / 2 twice a day on days 1-14)and oxaliplatin(130mg/m2 on day 1).Cycles were repeated at 3- week intervals. RESULTS: The overall response rate was 16.7%, and the disease control rate at 6 weeks was 75.0%. The progression free survival was 3.1 months, and the overall survival was 8.3 months after initiation of CapeOX therapy. The most common hematological toxicity was grade 3 neutropenia(50%).Peripheral neuropathy of Grade 1 or 2 was found in 50%of cases, but no Grade 3 or 4 neuropathy was found. CONCLUSIONS: CapeOX showed some activities as salvage therapy for heavily pretreated AGC patients.We suggest that CapeOX therapy should be considered a treatment option for pretreated AGC with good performance status.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 66-year-old man underwent follow-up colonoscopy after colon polypectomy. The retroflexed view of the anal canal with white-light imaging revealed a whitish, slightly elevated lesion on the dentate line and an ill-defined flat lesion. A biopsy of the whitish elevation revealed squamous cell carcinoma (SCC), and endoscopic submucosal dissection (ESD) was planned. The lateral margin of the SCC was identified by spraying with Lugol's iodine, and the tumor was resected en bloc with no complications. The pathological findings were SCC in situ with parakeratosis in the whitish elevation and high-grade intraepithelial neoplasia in the ill-defined flat lesion, which exhibited a wide iodine-unstained area by chromoendoscopy. Early SCC in the anal canal is a rare gastrointestinal cancer, and Lugol chromoendoscopy helped visualize the tumor margin for ESD.

DOI： 10.1055/a-0584-7060

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Gastrointestinal stromal tumors (GIST) typically appear as solid masses, and cystic formation is uncommon. Most stomach GISTs with cystic formation progress outside the gastric wall and are frequently misdiagnosed as epigastric cystic tumors derived from pancreas or liver. An asymptomatic 72-year-old male underwent esophagogastroduodenoscopy, which revealed a submucosal tumor (SMT), approximately 50 mm in diameter, at the anterior wall of the gastric angle. The SMT was very soft with positive cushion sign. Endoscopic ultrasonography and contrast-enhanced computed tomography revealed that the SMT was a cystic tumor with solid component. Laparoscopic and endoscopic cooperative surgery were performed to remove the tumor. Histopathological analysis revealed that the tumor was a GIST with cystic formation. To the best of our knowledge, this the first documented case of a cushion sign-positive stomach GIST with cystic formation, which had mainly developed inside the stomach. This case suggests that we should keep in mind the possibility of cystic formation of GIST when the tumor has a solid component, even if it appears as a cushion sign-positive SMT.

DOI： 10.3892/mco.2018.1639

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10120-016-0643-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Conversion therapy is an option for unresectable metastatic gastric cancer when distant metastases are controlled by chemotherapy; however, the feasibility and efficacy remain unclear. This study aimed to assess the feasibility and efficacy of conversion therapy in patients with initially unresectable gastric cancer treated with docetaxel, cisplatin, and S-1 (DCS) chemotherapy by evaluating clinical outcomes. METHODS: One hundred unresectable metastatic gastric cancer patients, enrolled in three DCS chemotherapy clinical trials, were retrospectively evaluated. The patients received oral S-1 (40 mg/m2 b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m2) and docetaxel (50-60 mg/m2) on day 8 every 3 weeks. Conversion therapy was defined when the patients could undergo R0 resection post-DCS chemotherapy and were able to tolerate curative surgery. RESULTS: Conversion therapy was achieved in 33/100 patients, with no perioperative mortality. Twenty-eight of the 33 patients (84.8 %) achieved R0 resection, and 78.8 % were defined as histological chemotherapeutic responders. The median overall survival (OS) of patients who underwent conversion therapy was 47.8 months (95 % CI 28.0-88.5 months). Patients who underwent R0 resection had significantly longer OS than those who underwent R1 and R2 resections (P = 0.0002). Of the patients with primarily unresectable metastases, 10 % lived >5 years. Among patients who underwent conversion therapy, multivariate analysis showed that the pathological response was a significant independent predictor for OS. CONCLUSIONS: DCS safely induced a high conversion rate, with very high R0 and pathological response rates, and was associated with a good prognosis; these findings warrant further prospective investigations.

DOI： 10.1007/s10120-016-0633-1

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

An 87-year-old woman was admitted to our hospital for paralytic ileus, and she was treated using an ileus tube. Although her symptoms improved, abdominal fullness developed again on day 3 after ileus tube insertion. Abdominal computed tomography indicated intussusceptions at the ileum and the terminal part of the ileum;therefore, an emergency surgery was performed. During the surgery, antegrade intussusceptions were found in the ileum 60cm from the ileocecal valve and the terminal part of the ileum into the ascending colon. The intussusception of the anal side was resolved by manual reduction, but the oral side needed a partial resection of small bowel because of the presence of necrosis. There were no lesions, such as tumors, at the intussusceptions sites. Therefore, the two intussusceptions were thought to be caused by the ileus tube. We diagnosed a rare case of intussusceptions in the two parts of the ileum as a complication of the placement of an ileus tube.

DOI： 10.11405/nisshoshi.114.1001

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 65-year-old man was admitted under emergency to our hospital because of abdominal pain. His current medication history did not include steroids or nonsteroidal antiinflammatory drugs. He had taken an eradication agent for Helicobacter pylori, and his serum was negative for H. pylori IgG antibody. Abdominal computed tomography indicated gastric perforation;therefore, emergency surgery was performed. Two weeks later, esophagogastroduodenoscopy revealed a gastric ulcer on the lesser curvature of the gastric angle and bezoars. The gastric perforation was thought to be caused by the bezoars. The bezoars were successfully treated with endoscopic therapy using Coca-Cola®. The bezoars included over 98% tannin, and the patient had frequently consumed chestnuts. We thus diagnosed a rare case of gastric perforation caused by chestnut bezoars.

DOI： 10.11405/nisshoshi.114.1830

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Fucose is utilized for the modification of different molecules involved in blood group determination, immunological reactions, and signal transduction pathways. We have recently reported that enhanced activity of the fucosyltransferase 3 and/or 6 promoted TGF-ß-mediated epithelial mesenchymal transition and was associated with increased metastatic potential of colorectal cancer (CRC), suggesting that fucose is required by CRC cells. With this in mind, we examined requirement of L-fucose in CRC cells and developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specific to CRC. METHODS: In this study, we first examined the expression of fucosylated proteins in 50 cases of CRC by immunochistochemical staining with biotinylated Aleuria aurantia lectin (AAL). Then we carried out an L-fucose uptake assay using three CRC cell lines. Finally, we developed fucose-bound nanoparticles as vehicles for the delivery of an anticancer drug, SN38, and examined tumor growth inhibition in mouse xenograft model (n = 6 mice per group). All statistical tests were two-sided. RESULTS: We found a statistically significant relationship between vascular invasion, clinical stage, and intensity score of AAL staining (P ≤ .02). L-fucose uptake assay revealed that L-fucose incorporation, as well as fucosylated protein release, was high in cells rich in fucosylated proteins. L-fucose-bound liposomes effectively delivered Cy5.5 into CRC cells. The excess of L-fucose decreased the efficiency of Cy5.5 uptake through L-fucose-bound liposomes, suggesting an L-fucose receptor dependency. Intravenously injected, L-fucose-bound liposomes carrying SN38 were successfully delivered to CRC cells, mediating efficient tumor growth inhibition (relative tumor growth ratio: no treatment group [NT], 8.29 ± 3.09; SN38-treated group [SN38], 3.53 ± 1.47; liposome-carrying, SN38-treated group [F0], 3.1 ± 1.39; L-fucose-bound, liposome-carrying, SN38-treated group [F50], 0.94 ± 0.89; F50 vs NT, P = .003; F50 vs SN38, P = .02, F50 vs F0, P = .04), as well as prolonging survival of mouse xenograft models (log-rank test, P < .001). CONCLUSIONS: Thus, fucose-bound liposomes carrying anticancer drugs provide a new strategy for the treatment of CRC patients.

DOI： 10.1093/jnci/djw210

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Fucose is utilized for the modification of different molecules involved in blood group determination, immunological reactions, and signal transduction pathways. We have recently reported that enhanced activity of the fucosyltransferase 3 and/or 6 promoted TGF-ß-mediated epithelial mesenchymal transition and was associated with increased metastatic potential of colorectal cancer (CRC), suggesting that fucose is required by CRC cells. With this in mind, we examined requirement of L-fucose in CRC cells and developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specific to CRC. METHODS: In this study, we first examined the expression of fucosylated proteins in 50 cases of CRC by immunochistochemical staining with biotinylated Aleuria aurantia lectin (AAL). Then we carried out an L-fucose uptake assay using three CRC cell lines. Finally, we developed fucose-bound nanoparticles as vehicles for the delivery of an anticancer drug, SN38, and examined tumor growth inhibition in mouse xenograft model (n = 6 mice per group). All statistical tests were two-sided. RESULTS: We found a statistically significant relationship between vascular invasion, clinical stage, and intensity score of AAL staining (P≤ .02). L-fucose uptake assay revealed that L-fucose incorporation, as well as fucosylated protein release, was high in cells rich in fucosylated proteins. L-fucose-bound liposomes effectively delivered Cy5.5 into CRC cells. The excess of L-fucose decreased the efficiency of Cy5.5 uptake through L-fucose-bound liposomes, suggesting an L-fucose receptor dependency. Intravenously injected, L-fucose-bound liposomes carrying SN38 were successfully delivered to CRC cells, mediating efficient tumor growth inhibition (relative tumor growth ratio: no treatment group [NT], 8.29 ± 3.09; SN38-treated group [SN38], 3.53 ± 1.47; liposome-carrying, SN38-treated group [F0], 3.1 ± 1.39; L-fucose-bound, liposome-carrying, SN38-treated group [F50], 0.94 ± 0.89; F50 vs NT,P= .003; F50 vs SN38,P= .02, F50 vs F0,P= .04), as well as prolonging survival of mouse xenograft models (log-rank test,P< .001). CONCLUSIONS: Thus, fucose-bound liposomes carrying anticancer drugs provide a new strategy for the treatment of CRC patients.

DOI： 10.1093/jnci/djw038

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Complete remission by induction therapy in acute myelogenous leukemia (AML) can be achieved due to improvements in supportive and optimized therapy. However, more than 20% of patients will still need to undergo salvage therapy, and most will have a poor prognosis. Determining the specificity of drugs to leukemia cells is important since this will maximize the dose of chemotherapeutic agents that can be administered to AML patients. In turn, this would be expected to lead to reduced drug toxicity and its increased efficacy. We targeted Notch-1 positive AML cells utilizing fucose-bound liposomes, since activation of Notch-1 is required for O-fucosylation. Herein, we report that intravenously injected, L-fucose-bound liposomes containing daunorubicin can be successfully delivered to AML cells that express fucosylated antigens. This resulted in efficient tumor growth inhibition in tumor-bearing mice and decreased proliferation of AML patient-derived leukemia cells. Thus, biological targeting by fucose-bound liposomes that takes advantage of the intrinsic characteristics of AML cells could be a promising new strategy for Notch-1 positive-AML treatment.

DOI： 10.18632/oncotarget.9558

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: ST6GalNAc I is a sialyltransferase controlling the expression of sialyl-Tn antigen (STn), which is overexpressed in several epithelial cancers, including gastric cancer, and is highly correlated with cancer metastasis. However, the functional contribution of ST6GalNAc I to development or progression of gastric cancer remains unclear. In this study, we investigated the effects of suppression of ST6GalNAc I on gastric cancer in vitro and in vivo. METHODS: Gastric cancer cell lines were transfected with ST6GalNAc I siRNA and were examined by cell proliferation, migration, and invasion assays. We also evaluated the effect of ST6GalNAc I siRNA treatment in a peritoneal dissemination mouse model. The differences in mRNA levels of selected signaling molecules were analyzed by polymerase chain reaction (PCR) arrays associated with tumor metastasis in MKN45 cells. The signal transducer and activator of transcription 5b (STAT5b) signaling pathways that reportedly regulate the insulin-like growth factor-1 (IGF-1) were analyzed by Western blot. RESULTS: ST6GalNAc I siRNA inhibited gastric cancer cell growth, migration, and invasion in vitro. Furthermore, intraperitoneal administration of ST6GalNAc I siRNA- liposome significantly inhibited peritoneal dissemination and prolonged the survival of xenograft model mice with peritoneal dissemination of gastric cancer. PCR array confirmed that suppression of ST6GalNAc I caused a significant reduction in expression of IGF-1 mRNA. Decreased IGF-1 expression in MKN45 cells treated with ST6GalNAc I siRNA was accompanied by reduced phosphorylation of STAT5b. CONCLUSION: ST6GalNAc I may regulate the gene expression of IGF-1 through STAT5b activation in gastric cancer cells and may be a potential target for treatment of metastasizing gastric cancer.

DOI： 10.1007/s10120-014-0454-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The prognosis of advanced hepatocellular carcinoma (HCC) is dismal, underscoring the need for novel effective treatments. The α1,6-fucosyltransferase (fucosyltransferase 8, FUT8) has been reported to accelerate malignant potential in HCC. Our study aimed to investigate the regulation of FUT8 expression by p53 and develop a novel therapeutic strategy for targeting HCC cells using L-fucose-mediated drug delivery. METHODS: Binding sites for p53 were searched for within the FUT8 promoter region. FUT8 expression was assessed by immunoblotting. Chromatin immunoprecipitation (ChIP) assays were performed to analyze p53 binding to the FUT8 promoter. The delivery of Cy5.5-encapsulated L-fucose-liposomes (Fuc-Lip-Cy5.5) to a Lens Culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3)-expressing HCC cells was analyzed by flow cytometry. The induction of FUT8 by histone deacetylase inhibitor (HDACi) -inducing acetylated -p53 was evaluated by immunoblotting. Flow cytometric analysis was performed to assess whether the activation of p53 by HDACi affected the uptake of Fuc-Lip-Cy5.5 by HCC cells. The cytotoxicity of an L-fucose-bound liposome carrying sorafenib (Fuc-Lip-sorafenib) with HDACi was assessed in vivo and in vitro. RESULTS: The knock down of p53 with siRNA led to decreased FUT8 expression. ChIP assays revealed p53 binds to the FUT8 promoter region. Flow cytometric analyses demonstrated the specific uptake of Fuc-Lip-Cy5.5 into AFP-L3-expressing HCC cells in a p53- and FUT8-dependent manner. HDACi upregulated the uptake of Fuc-Lip-Cy5.5 by HCC cells by increasing FUT8 via acetylated -p53. The addition of a HDACi increased apoptosis induced by Fuc-Lip-sorafenib in HCC cells. CONCLUSIONS: Our findings reveal that FUT8 is a p53 target gene and suggest that p53 activated by HDACi induces Fuc-Lip-sorafenib uptake by HCC cells, highlighting this pathway as a promising therapeutic intervention for HCC.

DOI： 10.1371/journal.pone.0168355

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). METHODS AND MATERIALS: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m(2)) and nedaplatin (50 mg/m(2)) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m(2)/day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. RESULTS: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m(2). In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. CONCLUSIONS: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC.

DOI： 10.1016/j.ijrobp.2015.05.041

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 60s-year-old woman with metastatic colorectal cancer was treated using mFOLFOX6 plus bevacizumab. Zoledronic acid was also administered owing to the presence of bone metastasis. The patient was admitted to our hospital with progressive hypokalemia, hypocalcemia, hypophosphatemia, and proximal renal tubular dysfunction. A diagnosis of Fanconi syndrome was made, and was believed to be induced by zoledronic acid treatment. This treatment was discontinued, and the patient's renal tubular function recovered. Denosumab was subsequently administered to treat the bone metastasis, and no renal tubular dysfunction occurred. It was possible to continue chemotherapy, and a complete response was obtained. Fanconi syndrome induced by zoledronic acid is rare, but it may hinder chemotherapy. Therefore, monitoring renal tubular function is recommended during therapy with zoledronic acid.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The aim of this study was to determine the recommended dose (RD) of a triweekly capecitabine, oxaliplatin, irinotecan, and bevacizumab (XELOXIRI/bevacizumab) regimen that was easier to administer than FOLFOXIRI/bevacizumab, using capecitabine instead of 5-fuorouracil (5-FU), in patients with metastatic colorectal cancer (mCRC). METHODS: Patients received oxaliplatin (100 mg/m(2), day 1), capecitabine (1,700 mg/m(2) per day from day 2 to 15), irinotecan (100, 120, 150 mg/m(2) for dose levels 1, 2, 3, day 1), and bevacizumab (7.5 mg/kg, day 1), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first two cycles to determine the maximum tolerated dose (MTD). RESULTS: Twelve patients received a median of 6.5 cycles of therapy (range 2-12). The DLT was grade 4 neutropenia, observed in one of six patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m(2). The most common grade ≥3 toxicities were neutropenia (41 %), anemia (17 %), diarrhea (8 %), and febrile neutropenia (8 %). The response rate and median progression-free survival were 83 % and 15 months, respectively. CONCLUSIONS: XELOXIRI/bevacizumab is a feasible regimen for patients with mCRC, neutropenia was the DLT, and the RD of irinotecan is 150 mg/m(2). The response rate observed is very promising and warrants further investigation.

DOI： 10.1007/s00280-014-2672-9

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The risks of myelodysplastic syndrome (MDS) and acute leukemia are increased in patients previously treated for other malignancies. Therapy-related MDS (t-MDS) occurs after exposure to certain cytotoxic agents or radiation used for cancer treatment. We report a case of t-MDS following curative chemoradiotherapy (CRT) for esophageal and oropharyngeal cancer. An 80-year-old male diagnosed with double cancers of the esophagus and oropharynx underwent definitive CRT and achieved a complete response. Six years later, he became anemic, and bone marrow examination showed 3.4% blast cells with fine chromatin structures and basophilic cytoplasm. Cytogenetic analysis indicated a complex karyotype that included chromosome 5 and 7 abnormalities. These findings were consistent with t-MDS. Subsequently, he developed acute myeloid leukemia and died 8 months later. This case indicates that long-term surveillance is needed to closely monitor the risk of t-MDS in patients treated with CRT.

DOI： 10.11405/nisshoshi.112.1664

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND STUDY AIMS: The clinical utility of computed virtual chromoendoscopy with flexible spectral imaging color enhancement (FICE) in capsule endoscopy (CE) remains controversial. To clarify the clinical utility of FICE-enhanced CE in evaluating small bowel lesions, we quantitatively assessed white light (WL), FICE, and blue mode (BM) images and examined the sensitivity of these 3 imaging modes of small-bowel lesions from patients who underwent CE. METHODS: The CIELAB color difference (∆E) and visual analogue scales (VAS) were measured in 261 CE images (3 different lesion categories) using WL and FICE set 1, 2, and 3, and BM images, respectively. Three endoscopists reviewed CE videos with WL, 3 FICE mode settings, and BM, and compared the sensitivity and detectability for small intestinal diseases from 50 patients who underwent CE. RESULTS: In the assessment of visibility in the 152 vascular lesion images, the ∆E and VAS of FICE set 1, 2, and BM images were significantly higher than that of WL images. In 88 erosion/ulceration images, the ∆E and VAS of FICE set 1 and 2 images were significantly higher than that of WL images. In 21 tumor images, there were no significant differences in ∆E among these modalities. When analyzed on a per-patient basis, FICE settings 1 and 2 had the highest sensitivity (100 %) and specificity (97.3 - 100 %) for vascular lesions. As for erosive/ulcerative lesions, FICE setting 2 had the highest sensitivity (100 %) and specificity (97.2 %). For tumors or polyps, WL had the highest sensitivity (90.9 %) and specificity (87.1 %). In per-lesion analysis, FICE settings 1 and 2 showed significantly superior detection ability over WL for vascular lesions. In the detection of erosive/ulcerative lesions, FICE setting 2 was significantly superior to WL. In tumor images, there was no significant improvement with any of the settings relative to WL images. CONCLUSIONS: FICE is most useful for improving CE image quality and detection in cases of angioectasia and erosion/ulceration of the small intestine.

DOI： 10.1055/s-0034-1365526

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Reactivation of hepatitis B virus (HBV) has recently been reported as a fatal complication in patients undergoing cytotoxic chemotherapy. We herein describe a case of reactivation in a 76-year-old man who had undergone pelvic exenteration for colorectal cancer (CRC). He was treated with a modified FOLFOX6 chemotherapy regimen after the operation. Thirteen months later, his laboratory data showed severe liver dysfunction. His hepatitis B surface antigen (HBsAg) test was positive, and his HBV-DNA level was elevated. We diagnosed the patient with HBV reactivation as his HBsAg test was negative before starting chemotherapy. His liver dysfunction improved after administration of entecavir. This is the first report describing HBV reactivation following chemotherapy for an HBsAg-negative CRC patient.

PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We describe a patient with transformed follicular lymphoma(FL), expressing p53 but remaining in complete remission(CR) due to bendamustine-rituximab(BR)therapy. She was a 64-year-old female diagnosed with stage IV FL(grade 3A)in July 2007 when she was admitted with right lower abdominal pain and body weight loss. Colonoscopy revealed Bauhin' valve lymphoma of the terminal ileum, and computed tomography(CT)scan showed lymphadenopathy, involving the cervical, mediastinal para-aortic lymph nodes and right tonsil. She received chemotherapy with eight courses of CHOP therapy with rituximab and achieved CR. Two and a half years later, mediastinal lymph node swelling relapsed, and ibritumomab tiuxetan therapy induced the second CR. After ten months, however, a third relapse occurred as a submucosal tumor(SMT)of the stomach. Gastric SMT biopsy showed diffuse large B cell lymphoma(DLBCL)transformation with immunohistochemical expression of p53. Although gastric SMT disappeared after radiotherapy, which achieved the third CR, lymph node swelling was detected again in the para-aortic and-iliac artery lymph nodes in September 2011. Subsequently, she was treated with five courses of BR therapy, because bendamustine had been reported to be effective for p53 gene-deficient B cell neoplasms. The therapy was successful and achieved the fourth CR, demonstrating that BR therapy was effective for p53-expressing DLBCL.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

An 85-year-old male was admitted to a hospital with abdominal discomfort in October, 2010. Severe splenomegaly and mild para-aortic lymphoadenopathy were detected. In addition, an increase in atypical lymphocytes was noticed by bone marrow analyses with weak positive staining of cyclin D1. Subsequently, the fluorescence in situ hybridization(FISH)method confirmed cyclin D1 reconstruction, and the fusion signals of the BCL1 and IgH genes were detected, thus providing a definitive diagnosis of leukemic mantle cell lymphoma. After treatment with rituximab monotherapy, the Ki-67 index was stabilized to within 10%, and complete response was obtained.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Hepatic involvement by chronic lymphocytic leukemia(CLL)is common, but rarely presents with liver injury. We report a case of chronic hepatitis C(CH-C)in a patient who had suffered from liver injury as a result of hepatic involvement by CLL. A 74-year-old man was hospitalized because of an examination confirming him positive for leukocytosis. Computer tomography scan showed mild hepatosplenomegaly, lymph node swelling of the neck and axilla, and abdominal lymphadenopathy. He was diagnosed as CLL by bone marrow examination. His laboratory data revealed hepatis C virus(HCV)antibody-positive, and elevated levels of both aminotransferase and HCV-RNA. Liver biopsy demonstrated significant CLL involvement of portal areas and a mild T lymphocyte invasion of centrilobular and portal areas. After treatment with polyethylene glycol interferon (PEG-IFN)-α-2b for CH-C, the CLL count was decreased in both peripheral blood and the liver. The hematological response was significantly correlated with the disappearance of HCV-RNA. The patient has maintained a sustained virological response(SVR)status for the past 9 months after PEG-IFN-α-2b administration. Thus, PEG-IFN-α-2b therapy could be effective not only for CH-C but also for hepatic involvement of CLL as seen in our patient.

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記述言語：日本語   出版者・発行元：一般社団法人 日本消化器がん検診学会  

大腸CTは欧米のみならず本邦でもその評価が高まっている。一般に, 大腸CTではC-RADS評価により6mm以上あるいは10mm以上のピックアップ病変を大腸内視鏡検査に推奨している。今回, 当院で内視鏡的あるいは外科的に切除された大腸癌299病変の切除病理結果について後方視的再検討を加え, C-RADS評価により経過観察と判断される可能性のある進行癌の有無について検討した。299病変のうち, 10mm以下の進行癌を2病変に認めた。いずれも径10mmの病変であり, 6mm以下の進行癌は認めなかった。この2病変について, 大腸CT所見を検討するといずれもC2以上の病変として指摘可能であった。6mm以上の病変, あるいは10mm以上の大腸CTピックアップ病変に大腸内視鏡検査を推奨するC-RADS評価は概ね妥当と考えられた。

その他リンク:： https://ndlsearch.ndl.go.jp/books/R000000004-I030089275

DOI： 10.11404/jsgcs.57.1153

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記述言語：日本語   出版者・発行元：一般社団法人 日本消化器がん検診学会  

大腸がん検診において, 大腸CT読影解析時間の短縮化は重要な課題である。近年その解析ソフトは進歩しており, フライスルー法のみならず, 展開像や多画面同時読影などの読影時間を短縮する試みが行われている。今回, 同一症例に対し従来のフライスルー読影法と多画面同時読影法による大腸CT解析を行い, その結果を比較検討した。対象は53例で, 前処置として全例に腸液を標識し, 大腸CTデータをフライスルー法と多画面同時読影法にて読影した。読影時間の検討では多画面同時読影法はフライスルー法に比し有意に短縮されていた。しかし, レポート作成を含めた総読影時間では有意差を認めなかった。また多画面同時読影法では, 1症例で見落としを認めた。大腸CTにおいて多画面同時読影法では短時間で読影することが可能となると考えられる。反面, 一度に多画面を認識することは難しく習熟が必要と考えられ, フライスルー法との使い分けが重要と考えられた。

その他リンク:： https://ndlsearch.ndl.go.jp/books/R000000004-I028918998

DOI： 10.11404/jsgcs.56.130

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記述言語：日本語   出版者・発行元：一般社団法人 日本消化器内視鏡学会  

症例は70歳男性．十二指腸球部にポリープを認め，精査加療目的に当科紹介．上部消化管内視鏡検査では，十二指腸球部に基部を持ち，頭部は発赤調で茎部は頭部と同等の太さの，茸状の外観を呈した山田IV型病変を認めた．拡大観察では，頭部に胃上皮化生または異所性胃粘膜と考えられる所見と微小な開口部を認めた．診断的治療目的にpolypectomyを施行したところ，組織学的には表層粘膜に胃上皮化生を伴う成熟脂肪組織の豊富な十二指腸Brunner腺過誤腫であった．Brunner腺過誤腫は，過形成性のBrunner腺に脂肪組織など他の要素が混在するもので，しばしば胃上皮化生を伴う¹⁾とされる．本例では，拡大内視鏡観察によりBrunner腺由来病変に特徴的な所見の指摘が可能であった．

DOI： 10.11280/gee.57.2441

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記述言語：日本語   出版者・発行元：一般社団法人 日本肝臓学会  

症例は40歳代女性．検診の腹部超音波検査で肝血管腫が疑われ当科を紹介受診．造影CT検査で肝血管腫以外に多発肝腫瘍を認め，精査目的に入院となった．Gd-EOB-MRI検査では，S2, S5に腫瘤像が認められ，T1WIで低信号，動脈相で等信号，門脈相，平衡相及び肝細胞相で低信号であった．画像検査では確定診断に至らず，腫瘍生検を施行した．細胞密度の高い異型の乏しい腫瘍細胞で，肝細胞腺腫や高分化型肝細胞癌が疑われ，肝部分切除術と術中RFAを施行した．摘出標本の免疫染色にてliver fatty acid binding protein（L-FABP）の発現低下を認め，Hepatocyte nuclear factor 1α-inactivated type（HNF1α-inactivated type）の多発肝細胞腺腫と診断した．多発肝細胞腺腫は稀であり文献的考察を加え報告する．

その他リンク:： https://ndlsearch.ndl.go.jp/books/R000000004-I026944750

DOI： 10.2957/kanzo.56.584

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