北村 昌史

We herein report a kidney transplant recipient with recurrent bleeding due to multiple ileal ulcerations associated with mycophenolate mofetil (MMF). Symptoms persisted despite surgical resection and embolization. Double-balloon enteroscopy revealed multiple ulcerations, and a biopsy helped exclude other causes. The discontinuation of MMF led to rapid symptom resolution and healing of the ulceration. Intestinal complications after renal transplantation vary, and MMF-induced enteritis, although rare, should be considered. This case highlights the diagnostic value of enteroscopy in identifying drug-induced small intestinal injuries and underscores the importance of including MMF in the differential diagnosis of post-transplant gastrointestinal bleeding.

BACKGROUND: Primary small intestinal lymphoma (PSIL) is a rare disease, and its clinical characteristics and prognostic factors remain insufficiently defined because of limited large-scale data. METHODS: We conducted a nationwide multicenter retrospective study of 686 patients diagnosed with PSIL between January 2008 and December 2017 at 44 institutions in Japan. Clinical characteristics, histological subtypes, and overall survival were analyzed. RESULTS: B-cell lymphoma was the predominant immunophenotype (n = 623, 91%), whereas T-cell lymphoma was uncommon (n = 50, 7%). Diffuse large B-cell lymphoma (DLBCL) was the most frequent histological subtype (n = 330, 48%), followed by follicular lymphoma (FL) (n = 224, 33%). Compared with other B-cell lymphomas, FL was more common in women and more frequently involved the jejunum (P < 0.001). The 5-year overall survival rate was significantly higher in patients with B-cell lymphoma than in those with T-cell lymphoma (81% vs. 23%, P < 0.001). Multivariate Cox regression analysis identified age > 60 years and T-cell lymphoma as independent adverse prognostic factors, whereas FL was an independent predictor of favorable overall survival. CONCLUSIONS: This nationwide multicenter analysis delineates the clinicopathological features and survival outcomes of PSIL in Japan. FL represents the second most common subtype after DLBCL and is associated with a favorable prognosis among PSIL subtypes.

BACKGROUND: Although endoscopic diagnosis of primary small intestinal lymphoma (PSIL) is important, the association between endoscopic findings and histologic types remains unclear. This study aimed to evaluate the diagnostic accuracy of endoscopic classifications and biopsies in PSIL. METHODS: We retrospectively reviewed 100 lesions from 49 patients with PSIL who underwent double-balloon enteroscopy between 2005 and 2020. Endoscopic findings were classified into six macroscopic types: polypoid, ulcerative, multiple nodules, diffuse, concentric stenosis, or unclassified. RESULTS: Of the 100 lesions, 47 were multiple nodules, 32 were ulcerative, 8 were polypoid, 7 were diffuse, 4 were concentric stenosis, and 2 were unclassified. Diffuse large B-cell lymphoma (DLBCL) was mainly ulcerative (72%) or polypoid (75%), whereas follicular lymphoma appeared as multiple nodules (98%) or concentric stenosis (100%) (p<0.001, Cramér's V=0.41). The ulcerative type was associated with DLBCL (sensitivity, 0.74; specificity, 0.87), and multiple-nodule type were associated with follicular lymphoma (sensitivity, 0.75; specificity, 0.97). The overall diagnostic yield of the biopsy was 95%. Interobserver agreement was substantial (κ=0.69; agreement, 78%). CONCLUSIONS: Endoscopic findings were significantly associated with histologic types. Endoscopic findings and biopsies provide a high diagnostic yield, supporting their central role in the diagnostic management of PSIL.

INTRODUCTION: Follicular lymphoma is an indolent B-cell lymphoma that can involve the gastrointestinal tract, most commonly the small intestine. Although rituximab-based therapy is effective, transformation to diffuse large B-cell lymphoma (DLBCL) can occur and becomes difficult to diagnose after CD20 loss. CASE PRESENTATION: We report the case of a 64-year-old woman initially diagnosed with primary small intestinal follicular lymphoma who subsequently developed transformation to DLBCL 2 years after rituximab therapy. Double-balloon enteroscopy revealed progression of mucosal lesions, raising suspicion of histologic transformation. However, endoscopic biopsy was inconclusive because of the loss of CD20 expression, likely resulting from prior rituximab therapy. Surgical resection was performed to relieve intestinal obstruction and to establish a definitive diagnosis. Histopathological examination confirmed transformation to CD20-negative DLBCL. CONCLUSION: This case highlights the diagnostic limitation of endoscopic biopsy following rituximab therapy. Therefore, clinicians should be cautious in relying solely on endoscopic findings and remain open to surgical intervention to achieve a timely and accurate diagnosis.

BACKGROUND: The pocket-creation method (PCM) was developed to overcome the technical difficulties of endoscopic submucosal dissection (ESD), although opening the pocket remains challenging. We developed a novel technique of PCM with single-clip traction (PCM-CT), which uses a reopenable clip as a traction device to maintain stability during the procedure. No prospective study has compared the efficacy of PCM-CT and PCM. This study aimed to investigate the effectiveness of PCM-CT vs. PCM in a randomized controlled trial. METHODS: This randomized controlled clinical trial was conducted at four Japanese institutions. Patients with superficial colorectal neoplastic lesions were included following Japanese guidelines for colorectal cancer. Seven moderately experienced endoscopists performed the ESD procedures using either PCM-CT or PCM. RESULTS: 100 patients were enrolled in the study. Compared with PCM, PCM-CT achieved significantly faster mean (SD) dissection speed (21.4 [10.8] vs. 27.0 [14.5] mm2/min [95%CI 0.5 to 10.7], P = 0.03), and reduced the mean procedure time (81.8 [57.9] vs. 64.8 [47.6] minutes [95%CI -38.2 to 4.3], P = 0.12) and pocket-opening time (37.8 [33.0] vs. 30.0 [28.9] minutes [95%CI -20.2 to 4.6], P = 0.22). En bloc and R0 resection rates were not significantly different between the two groups (100% vs. 100%, P >0.99; 100% vs. 96%, P = 0.50, respectively). No significant differences were observed in adverse events between the two groups. CONCLUSION: ESD facilitated by the novel PCM-CT method appeared to be significantly faster than PCM. Both methods achieved high R0 resection rates.

Background and study aims  Intussusception caused by intestinal polyps in patients with Peutz-Jeghers syndrome usually requires laparotomy. Patients following successful endoscopic reduction using double-balloon endoscopy (DBE) have been reported. The aim of this study was to evaluate the feasibility of endoscopic treatment of intussusception. Patients and methods  We retrospectively reviewed patients who underwent DBE for intussusception due to small intestine polyps in patients with Peutz-Jeghers syndrome from January 2004 to June 2020. Results  Twenty-seven (antegrade 22, retrograde 5) DBEs were performed in 19 patients with 25 sites of intussusception identified during the study period. If the intussusception remained once the endoscope reached the site, endoscopic reduction of the intussusception was performed as needed (15 sites). Ultimately, endoscopic resections (8 sites) or ischemic polypectomies (16 sites) of the polyp causing the intussusception were completed at 24 sites. Only one site could not be treated endoscopically and was treated surgically. The final per-site and per-patient success rates of endoscopic treatment were 96 % (24/25) and 95 % (18/19) respectively. Two patients developed mild acute pancreatitis and one patient developed intussusception after the procedures, both of which were treated non-operatively. Conclusions  Endoscopic treatment of intussusception is feasible to avoid laparotomy in patients with Peutz-Jeghers syndrome.

Background and study aims  Underwater endoscopic mucosal resection (UEMR) does not always result in en bloc resection of large colorectal lesions. The aim of this study was to demonstrate the feasibility of en bloc resection with progressive polyp contraction with underwater endoscopic mucosal resection (PP-CUE) of large, superficial colorectal lesions. The advantage of PP-CUE is to enable resection of a superficial non-polypoid lesion that is larger than the snare diameter. Patients and methods  Eleven consecutive lesions in ten patients who underwent UEMR with PP-CUE of large superficial colorectal lesions (20 mm or greater) were included. Results  The median lesion diameter was 24 mm (interquartile range [IQR], 20-24 mm). All lesions were larger than the 15-mm rotatable snare that was used. Median procedure time and PP-CUE time were 11 minutes (IQR, 8.5-12.3) and 2.3 minutes (IQR, 1.9-3.4), respectively. Pathological diagnoses of resected specimens included six adenomas, three sessile serrated lesions, and two slightly invasive submucosal carcinomas. En bloc and R0 resection rates were both 91 % (10/11). No adverse events occurred. Conclusions  PP-CUE is useful to resect superficial non-polypoid colorectal lesions 20 to 25 mm in diameter in an en bloc fashion.

BACKGROUND: Endoscopic submucosal dissection (ESD) of superficial gastric lesions located along the lesser curvature at the gastric angle is a challenging situation due to paradoxical movement and a protruding angle. The pocket-creation method (PCM) can overcome this difficulty by stabilizing the tip of the endoscope in the pocket and minimizing insufflation of the stomach, which enables horizontal and straight dissection. This study aims to clarify whether the PCM improves the technical outcomes of ESD of superficial gastric neoplasms along the lesser curvature at the angle. METHODS: From October 2006 to June 2021, 158 gastric lesions along the lesser curvature at the angle were resected with needle-type knives. We retrospectively reviewed the records and divided them into the PCM group (n = 61) and the conventional method (CM) group (n = 97). The primary outcome measurement was dissection speed (in mm2/min). RESULTS: The two groups were not significantly different for baseline characteristics such as macroscopic type and size except for the proportion of adenomas. The proportion of expert endoscopists was not significantly different between the two groups (P = 0.141). The dissection speed was significantly faster in the PCM group than in the CM group (P = 0.001). There were no holes in the resected specimens in the PCM group, while five lesions in the CM group (5%) had a hole (P = 0.182). There were no significant differences in the incidence of adverse events. CONCLUSIONS: This is the first study to show that the PCM outperforms the CM for ESD of lesions located along the lesser curvature at the gastric angle. The PCM facilitated ESD of these lesions by significantly increasing dissection speed when a needle-type knife is used with no increase in adverse events.

BACKGROUND AND STUDY AIMS: The resection strategy for rectal neuroendocrine tumors (NET) < 10 mm is not uniform. We compared the utility of underwater endoscopic mucosal resection (UEMR) to endoscopic submucosal resection with a ligation device (ESMR-L) to resect rectal NETs. PATIENTS AND METHODS: Patients with rectal NET < 10 mm treated with UEMR or ESMR-L were included. Their medical records were retrospectively reviewed. RESULTS: Thirty-two patients were divided into a UEMR group (n = 7) and an ESMR-L group (n = 25). Histopathological diagnosis of NET by biopsy was known before resection in 43% (3/7) in the UEMR group and 68% (17/25) in the ESMR-L group, (p = 0.379). UEMR was performed on an outpatient basis for all patients, and 92% of ESMR-L (23/25) were performed as inpatient procedures (p < 0.001). The procedure time was significantly shorter in the UEMR group than in the ESMR-L group [median (IQR), min, 6 (5-8) vs. 12 (9-14), p = 0.002]. En bloc resection and R0 resection rates were 100% in both groups. Pathological evaluations were predominantly NET G1 in both groups (UEMR: 7/7, 100% and ESMR-L: 23/25, 92%). Two patients in the ESMR-L group developed delayed bleeding, controlled by endoscopic hemostasis. Device costs were significantly higher in the ESMR-L group than the UEMR group by approximately US$180 [median (IQR), $90.45 (83.64-108.41) vs. $274.73 (265.86-292.45), P < 0.001]. CONCLUSION: UEMR results in similar resection quality with shorter procedure time and lower costs compared to ESMR-L. We recommend UEMR for the resection of rectal NET < 10 mm.

BACKGROUND AND AIMS: The standard treatment for stage T1b colorectal cancers with 1,000µm or greater submucosal invasion is surgical resection. However, the risk of lymph node metastases is only 1-2% when excluding risk factors for metastases other than depth of submucosal invasion. The number of elderly patients with significant comorbidities is increasing with societal aging in Japan. Therefore, local endoscopic resection of T1b colorectal cancers needs more consideration in the future. We previously showed that the pocket-creation method (PCM) for endoscopic submucosal dissection (ESD) is useful regardless of the morphology, including large sessile tumors with submucosal fibrosis, or location of the colorectal tumor. However, some T1b colorectal cancers have pathologically positive margins even when using the PCM. We retrospectively investigated the causes of failure to achieve negative vertical margins. METHODS: We retrospectively analyzed 953 colorectal tumors in 886 patients resected with the PCM. Finally, 65 pathological T1b colorectal cancers after en bloc resection were included in this study. ESD specimens and recorded procedure videos of T1b cancer resections with pathologically positive vertical margins were reviewed. RESULTS: The 65 cancers were divided into positive vertical margin (VM+ group) and negative vertical margin (VM- group) groups with 10 [10/65 (15%)] and 55 [55/65 (85%)] patients in each group, respectively. There was a significant difference in the rate of submucosal fibrosis (P=0.012) and dissection speed (P=0.044). There were no significant differences between the two groups in other regards. When verifying 8/10 available videos in the VM+ group, endoscopic technical factors led to positive vertical margins in five patients, and essential pathological factors of ESD led to positive vertical margins in the other three. Six of these eight patients underwent additional surgical resection. No residual tumor was identified in six T1b cancers. None of these six resected specimens contained lymph node metastases on pathological examination. CONCLUSION: The PCM resulted in a high rate of negative-vertical-margin resections. The PCM resulted in complete resection of T1b cancers when examining additional surgical specimens. ESD using the PCM is a viable option for the endoscopic treatment of T1b colorectal cancers.

Video 1Demonstration of gastric endoscopic submucosal dissection using the pocket-creation method at the angle along the lesser curvature and fornix.

Background and study aims  Endoscopic submucosal dissection (ESD) of superficial gastric lesions involving the pyloric ring is difficult. The pocket-creation method (PCM) with a small-caliber-tip transparent hood can overcome this difficulty by compressing the pyloric sphincter applying both traction and counter-traction. The aim of this study is to clarify the usefulness of the PCM for ESD of superficial gastric neoplasms involving the pyloric ring compared to the conventional method (CM). Patients and methods  From October 2006 to August 2019, 66 gastric lesions requiring duodenal submucosal dissection beyond the pyloric ring in 66 patients were resected. The CM was mainly performed in the first period (CM group, n = 46) and the PCM in the second period (PCM group, n = 20). We retrospectively reviewed their medical records. Results  Although no significant differences were observed in en bloc resection rates between the two groups, the PCM group had a significantly higher R0 resection rate than the CM group ( P  = 0.047). There were no holes in resected specimens in the PCM group while three specimens in the CM group had a hole. The dissection speed in the PCM group tended to be higher than in the CM group, although it did not reach statistical significance ( P  = 0.148). No significant differences were observed for the incidence of adverse events. Conclusions  This is the first study reporting the advantages of the PCM over the CM for ESD of gastric lesions involving the pyloric ring. We believe that the PCM is an effective strategy to compress the pyloric sphincter and facilitates R0 resection.

We herein report the case of a 75-year-old man who developed an increased serum creatinine level (4.93 mg/dL) and oliguria with massive proteinuria (7.14 g/day) on the second day after a single oral administration of high-dose (56 mg) minodronate. The histology of a renal biopsy showed one area of glomerular sclerosis among 20 glomeruli with global foot process effacement of podocytes and mild infiltration of lymphocytes and eosinophils into the interstitial space. Acute kidney injury in nephrotic syndrome due to focal segmental glomerular sclerosis induced by minodronate was diagnosed. Following cessation of minodronate without the administration of immunosuppressive agents, the patient's renal function and proteinuria markedly improved.