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Supplementary figureS1 - Representative cases of pancreatic NEN-G3

Supplementary Table S1. Breakdown of chemotherapy response regimens for PanNEN-G3 (55 cases)

Purpose: Patients with pancreatic neuroendocrine neoplasm grade-3 (PanNEN-G3) show variable responses to platinum-based chemotherapy. Recent studies indicated that PanNEN-G3 includes well-differentiated neuroendocrine tumor with G3 (NET-G3). Here, we examined the clinicopathologic and molecular features of PanNEN-G3 and assessed the responsiveness to chemotherapy and survival.Experimental Design: A total of 100 patients with PanNEN-G3 were collected from 31 institutions, and after central review characteristics of each histologic subtype [NET-G3 vs. pancreatic neuroendocrine carcinoma (NEC-G3)] were analyzed, including clinical, radiological, and molecular features. Factors that correlate with response to chemotherapy and survival were assessed.Results: Seventy patients analyzed included 21 NETs-G3 (30%) and 49 NECs-G3 (70%). NET-G3 showed lower Ki67-labeling index (LI; median 28.5%), no abnormal Rb expression (0%), and no mutated KRAS (0%), whereas NEC-G3 showed higher Ki67-LI (median 80.0%), Rb loss (54.5%), and KRAS mutations (48.7%). Chemotherapy response rate (RR), platinum-based chemotherapy RR, and prognosis differed significantly between NET-G3 and NEC-G3. Chemotherapeutic outcomes were worse in NET-G3 (P < 0.001). When we stratified PanNEN-G3 with Rb and KRAS, PanNENs-G3 with Rb loss and those with mutated KRAS showed significantly higher RRs to platinum-based chemotherapy than those without (Rb loss, 80% vs. normal Rb, 24%, P = 0.006; mutated KRAS, 77% versus wild type, 23%, P = 0.023). Rb was a predictive marker of response to platinum-based chemotherapy even in NEC-G3 (P = 0.035).Conclusions: NET-G3 and NEC-G3 showed distinct clinicopathologic characteristics. Notably, NET-G3 does not respond to platinum-based chemotherapy. Rb and KRAS are promising predictors of response to platinum-based chemotherapy for PanNEN-G3, and Rb for NEC-G3. Clin Cancer Res; 23(16); 4625–32. ©2017 AACR.

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Some situations may require endoscopy during the COVID-19 (Coronavirus Disease 2019) pandemic. Here, we describe the necessary precautions in the form of clinical questions and answers (Q&A) regarding the safe deployment of gastrointestinal endoscopy in such situations while protecting endoscopy staff and patients from infection. Non-urgent endoscopy should be postponed. The risk of infection in patients should be evaluated in advance by questionnaire and body temperature. The health of staff must be checked every day. Decisions to employ endoscopy should be based on the institutional conditions and aims of endoscopy. All endoscopic staff need to wear appropriate personal protective equipment (PPE). The endoscope and other devices should be cleaned and disinfected after procedures in accordance with the relevant guidelines. Optimal management of the endoscopy unit is required. Endoscopy for infected patients or those with suspected infection demands exceptional caution. When a patient who undergoes endoscopy is later found to have COVID-19, the members of staff involved are considered exposed to the virus and must not work for at least 14 days if their PPE is considered insufficient. When PPE resources are limited, some equipment may be used continuously throughout a shift as long as it is not contaminated. Details of the aforementioned protective measures are described.

Background/Aims: Intestinal fibrosis is a major complication of Crohn’s disease (CD). The profibrotic protein transforming growth factor-β (TGF-β) has been considered to be critical for the induction of the fibrotic program. TGF-β has the ability to induce not only the expression of extracellular matrix (ECM) including collagen, but also the production of plasminogen activator inhibitor-1 (PAI-1) that prevents enzymatic degradation of the ECM during the onset of fibrotic diseases. However, the significance of PAI-1 in the developing intestinal fibrosis has not been fully understood. In the present study, we examined the actual expression of PAI-1 in fibrotic legion of intestinal inflammation and its correlation with the abnormal ECM deposition.Methods: Chronic intestinal inflammation was induced in BALB/c mice using 8 repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). TM5275, a PAI-1 inhibitor, was orally administered as a carboxymethyl cellulose suspension each day for 2 weeks after the sixth TNBS injection.Results: Using a publicly available dataset (accession number, GSE75214) and TNBS-treated mice, we observed increases in PAI-1 transcripts at active fibrotic lesions in both patients with CD and mice with chronic intestinal inflammation. Oral administration of TM5275 immediately after the onset of intestinal fibrosis upregulated MMP-9 (matrix metalloproteinase 9) and decreased collagen accumulation, resulting in attenuation of the fibrogenesis in TNBS-treated mice.Conclusions: PAI-1-mediated fibrinolytic system facilitates collagen degradation suppression. Hence, PAI-1 inhibitor could be applied as an anti-fibrotic drug in CD treatment.

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.

A 49-year-old man was referred to our hospital for an abnormality of the hepatobiliary enzyme. The patient was diagnosed with primary sclerosing cholangitis 9 years ago, and he had a biliary stent with a string placed as an inside stent. We attempted to remove the stent 6 months later, but the string was cut off, so the stent could not be removed. Removal was attempted again, but the patient cancelled the outpatient appointments. During the examination performed at the present visit, we discovered that the biliary stent had migrated into the bile duct, and a stone had formed around the stent. We attempted to remove the stent-stone complex by endoscopic retrograde cholangiopancreatography, but it was difficult; thus, we decided to implant a new biliary stent and remove the other stent later. When we performed endoscopic retrograde cholangiopancreatography again 2 days later, the bile duct axis was linearized thanks to the additional stent, enabling us to grab the migrated stent with stent-stone complex using grasping forceps and to successfully pull it out. By implanting an additional plastic stent temporarily, we were able to straighten the biliary axis and endoscopically remove the biliary stent that migrated and caused the development of stent-stone complex in a 2-staged approach.

AIMS Rifaximin (RFX), a non-systemic antibiotic, improves liver/neuropsychological functions in patients with hepatic encephalopathy (HE). We aimed to investigate the clinical profiles associated with gut bacterial loads using exploratory data analysis and the effects of RFX on the gut microbiota of patients with HE. METHODS We analyzed the data from 17 patients with HE who underwent fecal microbiota examination in phase II/III trials in Japan. Profiles associated with genera Streptococcus, Veillonella, and Lactobacillus loads were analyzed using classification and regression trees (CART). Changes in gut microbial consortia of seven patients with HE were then assessed 2 weeks after RFX treatment by principal component analysis. RESULTS In the CART, the first and second divergence variables for each higher bacterial load were as follows: (i) in Streptococcus, the number connection test-A ≥39.55 s and presence of portal-systemic shunt; (ii) in Veillonella, serum potassium levels

BACKGROUND Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide (TAP) concentration have been reported as prognostic markers for the diagnosis of acute pancreatitis. AIM To reconfirm the validity of all these markers in the diagnosis of acute pancreatitis by undertaking a multi-center study in Japan. METHODS Patients with acute abdominal pain were recruited from 17 medical institutions in Japan from April 2009 to December 2012. Urinary and serum samples were collected twice, at enrollment and on the following day for measuring target markers. The diagnosis and severity assessment of acute pancreatitis were assessed based on prognostic factors and computed tomography (CT) Grade of the Japanese Ministry of Health, Labour, and Welfare criteria. RESULTS A total of 94 patients were enrolled during the study period. The trypsinogen-2 dipstick test was positive in 57 of 78 patients with acute pancreatitis (sensitivity, 73.1%) and in 6 of 16 patients with abdominal pain but without any evidence of acute pancreatitis (specificity, 62.5%). The area under the curve (AUC) score of urinary trypsinogen-2 according to prognostic factors was 0.704, which was highest in all parameter. The AUC scores of urinary trypsinogen-2 and TAP according to CT Grade were 0.701 and 0.692, respectively, which shows higher than other pancreatic enzymes. The levels of urinary trypsinogen-2 and TAP were significantly higher in patients with extended extra-pancreatic inflammation as evaluated by CT Grade. CONCLUSION We reconfirmed urinary trypsinogen-2 dipstick test is useful as a marker for the diagnosis of acute pancreatitis. Urinary trypsinogen-2 and TAP may be considered as useful markers to determine extra-pancreatic inflammation in acute pancreatitis.

All gastrointestinal endoscopic procedures have a high risk of aerosol contamination of the coronavirus disease 2019 (COVID‐19) to endoscopists, nurses, and healthcare assistants. Given the current pandemic situation of COVID‐19, the Japan Gastroenterological Endoscopy Society issued the recommendation for gastrointestinal (GI) endoscopy based on the status of COVID‐19 as of April 9, 2020, in Japan: (i) indications for GI endoscopy in the pandemic of COVID‐19; (ii) practical protective equipment for medical personnel depending on the risk for COVID‐19; (iii) preprocedural management, such as pharyngeal local anesthesia using lidocaine spray which has a potential to generate the aerosols; (iv) ideal settings of the endoscopy room including the numbers of the staff and the patients; (v) postprocedural management, such as undressing and follow‐up of the patients, as well as the involved staff, were documented to fit the practical scenarios in GI endoscopy, with the available data in Japan and the world. We believe that certain measures will prevent further spread of COVID‐19.

Background and Objective Tolvaptan, an oral vasopressin V2 receptor antagonist, has been widely used for the treatment of patients with cirrhosis and ascites. However, its efficacy in patients with renal dysfunction remains unknown. The objective of this study was to investigate the efficacy and safety of tolvaptan in patients with decompensated cirrhosis and severe chronic kidney disease (s-CKD). Methods We studied 43 patients with liver cirrhosis who received tolvaptan (7.5 mg/day) for refractory ascites. s-CKD was defined as an estimated glomerular filtration rate (eGFR)

Purpose: Patients with pancreatic neuroendocrine neoplasm grade-3 (PanNEN-G3) show variable responses to platinum-based chemotherapy. Recent studies indicated that PanNEN-G3 includes well-differentiated neuroendocrine tumor with G3 (NET-G3). Here, we examined the clinicopathologic and molecular features of PanNEN-G3 and assessed the responsiveness to chemotherapy and survival. Experimental Design: A total of 100 patients with PanNEN-G3 were collected from 31 institutions, and after central review characteristics of each histologic subtype [NET-G3 vs. pancreatic neuroendocrine carcinoma (NEC-G3)] were analyzed, including clinical, radiological, and molecular features. Factors that correlate with response to chemotherapy and survival were assessed. Results: Seventy patients analyzed included 21 NETs-G3 (30%) and 49 NECs-G3 (70%). NET-G3 showed lower Ki67-labeling index (LI; median 28.5%), no abnormal Rb expression (0%), and no mutated KRAS (0%), whereas NEC-G3 showed higher Ki67-LI (median 80.0%), Rb loss (54.5%), and KRAS mutations (48.7%). Chemotherapy response rate (RR), platinum-based chemotherapy RR, and prognosis differed significantly between NET-G3 and NEC-G3. Chemotherapeutic outcomes were worse in NET-G3 (P < 0.001). When we stratified PanNEN-G3 with Rb and KRAS, PanNENs-G3 with Rb loss and those with mutated KRAS showed significantly higher RRs to platinum-based chemotherapy than those without (Rb loss, 80% vs. normal Rb, 24%, P = 0.006; mutated KRAS, 77% versus wild type, 23%, P = 0.023). Rb was a predictive marker of response to platinum-based chemotherapy even in NEC-G3 (P = 0.035). Conclusions: NET-G3 and NEC-G3 showed distinct clinicopathologic characteristics. Notably, NET-G3 does not respond to platinum-based chemotherapy. Rb and KRAS are promising predictors of response to platinum-based chemotherapy for PanNEN-G3, and Rb for NEC-G3. Clin Cancer Res; 23(16); 4625–32. ©2017 AACR.

This prospective cohort study searched for factors associated with a response to nucleos(t)ide analogue/peg-interferon (NUC/peg-IFN) sequential therapy. A total of 95 patients with chronic hepatitis B being treated with NUCs were enrolled. Immediately following NUC cessation, peg-IFN was administered at 180 µg/dose weekly for 48 weeks. Twenty-six patients (27%) were judged to be responders at 48 weeks after the completion of peg-IFN. Analysis of baseline factors revealed that hepatitis B surface antigen (HBsAg)

Accessory spleens (ASs), ectopic splenic tissue at intrapancreatic and extrapancreatic sites, rarely contain epidermoid cysts. Our aim was to analyze the incidence of epidermoid cysts in ASs and perform an immunohistochemical analysis of its epithelial lining. We included in the study 148 ASs from 135 patients, for which pathological data were available. Eleven were intrapancreatic ASs (IPASs) and 137 were extrapancreatic ASs (EPASs). Six of the eleven (55%) IPASs contained epidermoid cysts, but they were not detected in EPASs. Immunohistochemical analysis showed that both the superficial/luminal and basal layer of the epithelial lining of epidermoid cysts in IPASs are negative for MUC2, MUC5AC, MUC6, WT-1, calretinin, thrombomodulin, uroplakin-II, and uroplakin-III. The superficial/luminal layer was positive for MUC4, CK7, and CA19-9 in all cases (100%), for CEA and HBME-1 in three cases (50%), and for MUC1, CK5/6, and CK20 in two cases (33%). The superficial/luminal layer was negative for p63 and D2-40 in all cases. The basal layer was positive for MUC1, CK5/6, p63, and HBME-1 in all six cases (100%), for CK7 and D2-40 in two cases (33%), and for CEA in one case (17%). The basal layer was negative for MUC4, CK20, and CA19-9 in all cases. Epidermoid cysts are a characteristic feature of IPASs but not of EPASs. Immunohistochemical analysis showed that the epithelial lining of epidermoid cysts in IPASs has a mixed character of glandular, squamous, mesothelial, and urothelial epithelium.

Background and study aims Positive horizontal margins in resected specimens are sometimes encountered after endoscopic submucosal dissection (ESD) for early gastric cancers, and appropriate treatment strategies for these cases are not established. The aim of this study was to evaluate current empirical treatments for patients with positive horizontal or indeterminable margins after ESD. Patients and methods We performed a multicenter survey and data from 14 hospitals were collected. The pooled proportions of positive horizontal or indeterminable margins and those of patients followed up without early intervention were calculated using a logistic-normal random-effects model. For calculating pooled estimates, subgroup analyses of high- and non-high-volume centers were conducted. Results A total of 11,796 ESD cases were enrolled and 229 patients (2 %) had positive horizontal or indeterminable margins. Ninety-eight cases were treated within 30 days of ESD and 131 cases were followed up without early treatments. Pooled estimates of positive margins in high- and non-high-volume centers were 1 % (95 % CI: 1 % – 2 %) and 2 % (95 % CI: 1 % – 4 %), respectively, and were not heterogeneous (P = 0.191). The proportion of patients followed up without early intervention ranged from 30 % to 100 %. The pooled estimate was 68 % (95 % CI: 50 % – 83 %). The pooled estimates of high- and non-high-volume centers were 65 % (95 % CI: 38 % – 85 %) and 72 % (95 % CI: 44 % – 89 %), respectively, and were not heterogeneous (P = 0.692). Conclusion There was insufficient consensus regarding treatment strategies used for early gastric cancer with positive horizontal or indeterminable margins after ESD. Further studies are required to establish a consensus.

A 45-year-old woman was found to have a pancreatic tumor by abdominal ultrasound performed for a medical check-up. Abdominal contrast-enhanced computed tomography showed a hypovascular tumor measuring 30 mm in diameter in the pancreatic tail. Endoscopic ultrasound-guided fine needle aspiration was performed. An extragastric growing gastrointestinal stromal tumor was thereby diagnosed preoperatively, and surgical resection was planned. Laparoscopic surgery was attempted but conversion to open surgery was necessitated by extensive adhesions, and distal pancreatectomy, splenectomy, and partial gastrectomy were performed. The histological diagnosis was an intra-abdominal desmoid tumor. A desmoid tumor is a fibrous soft tissue tumor arising in the fascia and musculoaponeurotic tissues. It usually occurs in the extremities and abdominal wall, and only rarely in the abdominal cavity. We experienced a case with an intra-abdominal desmoid tumor that was histologically diagnosed after laparotomy, which had been preoperatively diagnosed as an extragastric growing gastrointestinal stromal tumor. Although rare, desmoid tumors should be considered in the differential diagnosis of intra-abdominal tumors. Herein, we report this case with a literature review.

Pancreatic neuroendocrine neoplasms (PENs) are rare neoplasms that comprise only 5% of all pancreatic malignancies 1. PENs usually appear radiologically as solid tumors but may rarely manifest as cystic lesions of the pancreas 2. Cystic pancreatic endocrine neoplasms (CPENs) have been reported to represent 11–17% of resected PENs 3, 4, 5. In this study, which described laparoscopic splenopancreatectomy for a CPEN, the biological behavior of the CPEN was found to be less aggressive than that of PENs.

Background: Although there is evidence about the beneficial effects of probiotics, their effects on aspirin-induced small bowel injuries have not been well examined. We evaluated the effects of the probiotic Lactobacillus gasseri OLL2716 (LG) on aspirin-induced small intestinal lesions, such as ulcers, erosions, reddened lesions, and bleeding. Summary: This study enrolled 64 patients who received aspirin for more than 1 month and provided written informed consent to be part of the study. The patients received 112 ml of yogurt containing LG or placebo twice daily for 6 weeks. Small bowel injuries were evaluated by capsule endoscopy before and after consuming the yogurt. The effect of LG on patient symptoms was also assessed using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires before and after 6 weeks of treatment. There was no significant difference in any baseline characteristics and the number of small bowel mucosal breaks between the 2 groups. In contrast with the placebo group, the LG group had significantly fewer small bowel mucosal breaks and reddened lesions after 6 weeks (p < 0.01). The FSSG and GSRS scores were also significantly improved in the LG group but not in the placebo group. Key Messages: This double-blind, placebo-controlled study found that LG may be useful in reducing aspirin-induced small bowel injuries and in mitigating gastrointestinal symptoms.

AimsThe loss, or decreased expression, of nectin-like molecule 4 (Necl-4; an immunoglobulin-like cell adhesion molecule) is reported to be associated with the development and progression of certain types of cancer. We investigated the clinicopathological significance of Necl-4 expression in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsImmunohistochemical analyses of Necl-4 (n=258) and E-cadherin (n=256) expression were performed using tissue microarray blocks of PDAC samples. Necl-4 expression of 38 pancreatic intraepithelial neoplasia (PanIN) lesions included in tissue microarray cores was also evaluated. Necl-4 and E-cadherin expression was considered positive if >30% of cells were stained, and negative if ≤30% of cells were stained.ResultsNecl-4 expression was positive in 45.7% (n=118) and negative in 54.3% (n=140) of PDAC cases. Necl-4 staining was positive in 96.7% (n=29) and negative in 3.3% (n=1) of low-grade PanIN cases, and positive in 62.5% (n=5) and negative in 37.5% (n=3) of high-grade PanIN cases. The number of cases with positive Necl-4 expression decreased in the order low-grade PanIN>high-grade PanIN>PDAC (p30 mm, perineural invasion, lymphatic involvement, lymph node metastasis (pN1), an advanced TNM (tumour, node, metastases) stage (stage IIB–IV), an advanced histological grade (G2/3), and shorter overall survival. E-cadherin staining was positive in 46.1% (n=118) and negative in 53.9% (n=138) of PDAC cases. Necl-4 expression correlated positively with E-cadherin expression (r=0.405, pConclusionsThe results suggest that Necl-4 is associated with carcinogenesis and aggressiveness of PDAC.

Background /Objectives: Severe acute pancreatitis (SAP) has a high mortality rate despite ongoing attempts to improve prognosis through a various therapeutic modalities. This study aimed to delineate etiology-based routes that may guide clinical decisions for the treatment of SAP. Methods Using data from a recent retrospective multicenter study in Japan, we analyzed the association between clinical outcomes, mainly in-hospital mortality and pancreatic infection, and various etiologies while considering confounding factors. We performed additional multivariate analyses and built decision tree models. Results The 1,097 participating patients were classified into the following groups by etiology: alcohol (n = 436, 39.7%); cholelithiasis (n = 230, 21.0%); idiopathic (n = 227, 20.7%); and others (n = 204, 18.6%). Mortality at hospital discharge was 8.4%, 12.2%, 16.7%, and 16.2% in the alcohol, cholelithiasis, idiopathic, and others groups, respectively. According to multivariable analysis, early enteral nutrition (EN) was significantly associated with reduced in-hospital mortality only in the cholelithiasis group. However, there was a consistent association between age and the need for mechanical ventilation and increased mortality, regardless of etiology. Our decision tree models presented different contributing factors depending on the etiology and patient background. Interaction analysis showed that EN and the use of prophylactic antibiotics may influence these results differently according to etiology. Conclusions No study has yet used comprehensive models to investigate etiology-related prognostic factors for SAP; our results can, therefore, be used as a reference for improving clinical decisions.

We aimed to characterize the mucosal immune microenvironment and immune checkpoint of Ulcerative colitis (UC) by immunohistochemistry with correlation to prognosis: requirement of second-line steroid-therapy within the 2-years after diagnosis (SR). A series of 72 cases included 56 UC, 43 non-SR (with first-line treatment 5-ASA) and 13 SR, 11 infectious colitis and 5 normal colonic biopsies. Normal mucosa was characterized by low infiltrates but high BTLA and TNFRSF14. Compared to normal, UC had increased pan-immune-markers of CD3, CD8, FOXP3, PD-1, CD68, CD16, CD163, PTX3 and CD11C but had decreased BTLA (P < 0.05); by GSEA analysis comparable results were found in an independent UC gene-expression-data set (GSE38713). Compared to infectious, UC had higher CD4, CD8, PTX3 and CD11C but lower BTLA (P < 0.05). Compared to non-SR, SR had lower FOXP3 + Tregs (Odds-Ratio = 0.114, P = 0.002), PD-1 (OR = 0.176, P = 0.002) and CD163/CD68 M2-ratio (OR, 0.019, P = 0.019) but higher CD68 + pan-macrophages (OR = 6.034, P = 0.002). Higher Baron endoscopic and Geboes histologic disease activity scores also correlated with SR. In summary, UC was characterized by increased pan-immune-markers, normal TNFRSF14 and low BTLA. SR had increased CD68 + pan-macrophages but lower immune inhibitors of FOXP3 + Tregs, PD-1 and CD163/CD68 M2-macrophage ratio. In conclusion, alterations of the immune homeostasis mechanisms are relevant in the UC pathogenesis and steroid-requiring situation.

Intratumoral ossification has been reported in a number of epithelial tumors, but its presence in intraductal papillary mucinous neoplasms (IPMNs) is very rare. Herein, we present a rare case of IPMN with marked ossification. A 56-year-old Japanese man was under follow-up for a previously diagnosed IPMN. Seven years later, he was found to have dilatation of the main pancreatic duct and an enlarged solid mass, for which pancreaticoduodenectomy was performed. Macroscopically, multiple and cystically dilated pancreatic branch ducts, as well as a dilated main pancreatic duct, were identified. There was a solid, polypoid hard mass measuring 15 × 12 mm in the cystically dilated branch of the duct in the pancreatic head. Histological examination revealed papillary proliferation of atypical cuboidal or columnar epithelial cells in the dilated main and branch pancreatic ducts. The solid mass included an invasive adenocarcinoma component with a tubular or trabecular structure that showed pronounced ossification. We diagnosed the patient with invasive IPMN accompanied by marked ossification. Immunohistochemically, tumor cells in both the non-invasive and invasive lesions expressed bone morphogenetic protein-2 (BMP-2). While the mechanism of intratumoral ossification is unclear, it may have involved BMP-2 in the present case.

Dyskeratosis congenita (DC) is a rare inherited disease in which the telomere complex cannot be maintained. Shortened telomeres can cause a number of clinical conditions. We herein report a case of unrelated bone marrow transplantation due to aplastic anemia associated with DC. The patient died of uncontrollable refractory intestinal bleeding. Three cases of DC with life-threatening hemorrhaging after transplantation have been reported; however, the bleeding origin could not be determined. Our case is the only patient in which a gastrointestinal bleeding point, jejunal multiple angioectasia, was determined.