[Hepatic MALT lymphoma associated with chronic hepatitis B in a patient on trial therapy of Entecavir and H. pylori eradication therapy - case report].

A 65-year-old woman with a history of chronic hepatitis B was referred to our hospital for the examination of abdominal lymphadenopathy and diffuse lesions in the liver. Endoscopic ultrasound-guided fine-needle aspiration biopsy and liver biopsy were performed, and mucosa-associated lymphoid tissue (MALT) lymphoma was found in both. Based on the results of various images, a diagnosis of primary hepatic MALT lymphoma, Ann Arbor classification stage IV was reached at. Entecavir administration, H. pylori eradication therapy, and chemotherapy were performed, and remission was induced. The tumor condition remained unchanged after H. pylori eradication therapy and Entecavir administration. Subsequently, she became symptomatic, so chemotherapy was performed, leading to remission. We herein report a case of hepatic MALT lymphoma associated with chronic hepatitis B.

A multicenter prospective study of the treatment and outcome of patients with gastroduodenal peptic ulcer bleeding in Japan.

Gastroduodenal peptic ulcers are the main cause of nonvariceal upper gastrointestinal bleeding (UGIB). We believe that recent advances in endoscopic techniques and devices for diagnosing upper gastrointestinal tract tumors have advanced hemostasis for UGIB. However, few prospective multicenter studies have examined how these changes affect the prognosis. This prospective study included 246 patients with gastroduodenal peptic ulcers treated at 14 participating facilities. The primary endpoint was in-hospital mortality within 4 weeks, and the secondary endpoints required intervention and refractory bleeding. Subsequently, risk factors affecting these outcomes were examined using various clinical items. Furthermore, the usefulness of the risk stratification using the Glasgow-Blatchford score, rockall score and AIMS65 based on data from the day of the first urgent endoscopy were examined in 205 cases in which all items were complete there are two periods. Thirteen (5%) patients died within 4 weeks; and only 2 died from bleeding. Significant risk factors for poor outcomes were older age and severe comorbidities. Hemostasis was required in 177 (72%) cases, with 20 cases of refractory bleeding (2 due to unsuccessful endoscopic treatment and 18 due to rebleeding). Soft coagulation was the first choice for endoscopic hemostasis in 57% of the cases and was selected in more than 70% of the cases where combined use was required. Rockall score and AIMS65 predicted mortality equally, and Glasgow-Blatchford score was the most useful in predicting the requirement for intervention. All scores predicted refractory bleeding similarly. Although endoscopic hemostasis for UGIB due to peptic ulcer had a favorable outcome, old age and severe comorbidities were risk factors for poor prognosis. We recommend that patients with UGIB should undergo early risk stratification using a risk scoring system.

Low potency of fecal immunological surveillance testing soon after negative colonoscopy or resection of low-risk adenoma in average-risk patients.

BACKGROUND: Postcolonoscopy surveillance colonoscopy based on positive fecal occult blood testing (FOBT) is often performed, although its long-term efficacy has not been established. The aim of this study was to clarify the low potency of FOBT surveillance at short intervals after colonoscopy. METHODS: Colonoscopy was performed in 1308 average-risk patients, based on positive results of immunological FOBT [fecal immunological test (FIT)]. Patients were stratified according to the length of time since their last colonoscopy and their colonoscopy results [no adenoma or 1-2 small (<10 mm) adenomas]. Tumor detection rates were determined. RESULTS: The baseline patients characteristics did not differ between the groups. The advanced lesion detection rate (ALDR) among the patients who had never undergone a colonoscopy was 21.9% [95% confidence interval (CI), 19.1-25.0%]. Among the patients who had no adenoma detected in the previous colonoscopy within the past 5 years, the past 5-10 years and over 10 years, the ALDRs were 2.5% (95% CI, 1.0-5.5%), 4.1% (95% CI, 1.5-9.4%) and 9.3% (95% CI, 3.1-22.2%), respectively. Among the patients who had 1-2 small adenomas, the ALDRs were 7.4% (95% CI, 3.4-14.8%), 12.1% (95% CI, 4.2-27.9%) and 27.8% (95% CI, 12.2-51.2%), respectively. Invasive cancer was not observed in any patients within 5 years since the prior colonoscopy. CONCLUSION: In average-risk patients whose prior colonoscopy detected no adenomas or low-risk adenomas, postcolonoscopy surveillance by FIT has a low positive predictive value within a 5-year interval.

[Pyogenic granuloma in small intestine associated with Cowden's disease in a patient with gastrointestinal bleeding:a case report].

A 57-year-old female with a history of Cowden's disease was referred to our hospital because of black stool, loss of consciousness, and severe anemia. Upper and lower gastrointestinal endoscopy findings could not confirm the source of hemorrhage. Capsule endoscopy (CE) of the small intestine showed an active exudative hemorrhagic site near the ileum, although a definitive diagnosis was difficult. In a double balloon enteroscopy examination, it was difficult to observe the entire small intestine due to adhesions and the responsible lesion could not be confirmed, even when ink spots were applied to the deepest observation points through the mouth and anus. Hemostasis spontaneously occurred, and then anemia occurred again approximately 1 month later and a second CE examination was performed including passage of an ink stick through the oral side, which revealed an exudative elevated polyp with erosion and a white moss appearance in the ileum. Partial ileal resection was performed and pyogenic granuloma of the small intestine was the diagnosis. We report here a case of pyogenic granuloma of the small intestine associated with Cowden's disease.

Relationship between colonic diverticulosis and colon neoplasms in Japanese patients.

BACKGROUND AND AIM: Colonic diverticulosis (CD) has been reported to be associated with presence of colon neoplasms (CNs) in Western patients, since most of the associated risk factors are common between them. However, such correlation has not been fully investigated in Asian patients. In this study, the association of CNs with CD was evaluated in a multicenter investigation. METHODS: We enrolled 5633 patients who underwent both colonoscopy and esophagogastroduodenoscopy due to annual follow-up, screening for positive occult blood testing and abdominal symptoms between January 2016 and December 2017 at three institutions. The relationship between the presence of CNs and CD was investigated, and predictors for presence of CNs were determined by multivariate logistic analysis. RESULTS: The enrolled patients consisted of 1799 (31.9%) with CD (average age 70.0 years, male 64.0%) and 3834 without CD (66.0 years, male 52.9%), with the prevalence of CNs in those groups 46.6% and 44.2%, respectively (P = 0.090). Predictors for early colon cancer were shown to be age (OR 1.02, 95% CI 1.01-1.04, P = 0.010), laxatives use (OR 1.76, 95% CI 1.17-2.64, P = 0.007), gastric neoplasms (OR 2.16, 95% CI 1.23-3.81, P = 0.008), and CD (OR 1.64, 95% CI 1.16-2.31, P = 0.005). Early colon cancer in the distal colon was most frequently detected in patients with right-sided CD (RR 2.50, P = 0.001). CONCLUSION: In Japanese patients, early colon cancer was more frequently found in those with as compared to those without CD. The presence of CD may be an important indicator for an index colonoscopy examination to detect colon cancer. (Clinical-trial-registry: UMIN000038985).

Initial Computed Tomography Findings of Long and Distended Colon Are Risk Factors for the Recurrence of Sigmoid Volvulus.

BACKGROUND: Sigmoid volvulus is a common condition in elderly patients with elongated colons. Although endoscopic de-torsion is effective as the primary treatment of sigmoid volvulus, elective surgery is recommended because of the high risk of recurrence and high mortality rate. AIM: The aim of this study was to determine the risk factors for the recurrence of sigmoid volvulus. METHODS: Clinical records of patients treated at Shimane Prefectural Central Hospital were reviewed retrospectively. Among 41 sigmoid volvulus patients who were successfully treated by endoscopic de-torsion and followed up, 30 were observed over 1 year. Among the 30 patients, eight (26.7%) did not experience recurrence, while 22 (73.3%) did. Initial computed tomography (CT) findings indicating the sigmoid colon extending to the diaphragm or ventral to the liver were defined as "extension findings." Extension findings and sigmoid diameter were evaluated in relation to sigmoid volvulus recurrence. RESULTS: Extension findings were significantly more frequent in the recurrent group (77.3%) than in the nonrecurrent group (25.0%) (P = 0.009). Distended sigmoid colon diameter was significantly larger in the recurrent group (11.7 ± 3.8 cm) than in the nonrecurrent group (7.1 ± 1.1 cm) (P = 0.044). Receiver operating characteristic curve analysis demonstrated that the performance threshold was greater than 8.9 cm. Kaplan-Meier analysis showed the significantly high sigmoid volvulus recurrence rate in the patients with extension findings and a distended sigmoid colon greater than 8.9 cm. CONCLUSIONS: CT findings of a long and distended sigmoid colon in initial sigmoid volvulus are risk factors for the recurrence of sigmoid volvulus.

Postpolypectomy bleeding of colorectal polyps in patients with continuous warfarin and short-term interruption of direct oral anticoagulants.

BACKGROUND AND AIMS: Postpolypectomy bleeding (PPB) is the most common adverse event after colorectal polypectomy. Use of anticoagulants is an important risk factor for PPB. This study aimed to evaluate PPB in patients receiving treatment with warfarin and direct oral anticoagulants (DOACs). METHODS: Between August 2017 and July 2019, 5449 patients with 12,601 polyps who underwent endoscopic snare resection of colorectal polyps were enrolled. Endoscopic snare resection was performed in patients receiving continuous warfarin (C-warfarin) and in patients who experienced 1 day cessation of (O-) of DOACs in accordance with the Japanese Gastroenterological Endoscopy Society guidelines. RESULTS: The PPB rate in the group receiving anticoagulants was statistically higher than that in the group without anticoagulants (8.5% [33/387] vs 1.2% [63/5,062], respectively; P < .001). By multivariate logistic regression analysis, male gender (odds ratio [OR], 2.17; P = .007), warfarin (OR, 4.64; P < .001), DOACs (OR, 6.59; P < .001), and multipolyp removal (OR, 1.77; P = .007) were significant risk factors for PPB. PPB was observed in 9 and 21 patients in the C-warfarin and O-DOACs groups, respectively: C-warfarin (8.0% [9/113]), O-dabigatran (6.1% [2/33]), O-rivaroxaban (14.8% [9/61]), O-apixaban (9.8% [9/92]), and O-edoxaban (1.8% [1/56]). The PPB rate with the O-edoxaban group was significantly lower than that with the O-rivaroxaban group (P < .05). CONCLUSIONS: Use of anticoagulant therapy was an independent risk factor for PPB. The rates of PPB in patients receiving C-warfarin and O-DOACs were also higher than those in patients not receiving anticoagulants. Edoxaban may be safe through short-term withdrawal in patients undergoing endoscopic snare resection of colorectal polyps.

Mid-esophageal Diverticular Bleeding in a Patient with Kyphosis.

Mid-esophageal diverticulum is a rare disease, formed by the traction caused by inflamed bronchial lymph nodes or by pulsion induced by motility disorder. We herein report a case of mid-esophageal diverticular bleeding in a patient with kyphosis who was taking an anti-platelet drug. She was successfully treated with endoscopic hemostasis. An 80-year-old woman presented to our emergency department with hematemesis. She had kyphosis and was taking dipyridamole for her chest pain. Emergent upper endoscopy revealed bleeding from a mid-esophageal diverticulum; hemostasis was achieved via clipping. Mid-esophageal diverticula can cause upper gastrointestinal bleeding. An endoscopic examination and hemostasis are effective treatments.

Intravascular Large B-cell Lymphoma Mimicking Hepatobiliary Infection: A Case Report and Literature Review.

Intravascular large B-cell lymphoma (IVLBCL) frequently involves the hepatobiliary system, but its clinical course and pathophysiology are still not fully known. We herein describe a case of IVLBCL mimicking acute hepatobiliary infection. An 85-year-old woman was admitted because of fever and epigastric pain, and she was diagnosed to have acute acalculous cholecystitis based on gallbladder wall thickening with fluid collection. The gallbladder swelling regressed within several days, and areas of intrahepatic hypoperfusion appeared. Inflammation continued despite treatment with antibiotics, and she died within 21 days. An autopsy examination revealed IVLBCL. IVLBCL can present as acute cholecystitis with an improvement in the imaging findings and the presence of a subsequent liver mass.

Relationship between Barrett's esophagus and colonic diseases: a role for colonoscopy in Barrett's surveillance.

BACKGROUND: Given that risk factors for Barrett's carcinogenesis are predictive, appropriate management and surveillance of Barrett's esophagus (BE) may be provided. The presence of colorectal neoplasms (CRNs) is a possible predictor of the development of BE and the progression to esophageal adenocarcinoma (EAC). We evaluated the relationship between BE or EAC and colonic diseases, including neoplasms and diverticulosis. METHODS: Patients (N = 5606) who underwent both colonoscopy and esophagogastroduodenoscopy between January 2016 and December 2017 at three institutions were enrolled. The relationships between the presence of colonic diseases and BE or EAC and other clinical or endoscopic predictors of the presence of BE were investigated retrospectively. RESULTS: The prevalence of BE ≥ 1 cm and ≥ 3 cm in length was 13.0% and 0.52%, respectively. BE was closely related with the presence of colorectal adenoma (48.4% vs. 37.2% in non-BE; P < 0.001), adenocarcinoma (16.6% vs. 8.4%, P < 0.001) and colonic diverticulosis (CD) (34.1% vs. 29.3%, P < 0.001). In patients with long-segment BE, CRNs (79.3%, P < 0.001) and CD (48.2%, P = 0.038) were more common. EAC patients also had a statistically significantly higher incidence of CRNs than non-BE patients (87.5% vs. 45.6%, P = 0.027). Diverticulosis at the distal colon correlated significantly with EAC and BE (50.0%, P = 0.010 and 15.4%, P = 0.024, vs. 12.0% in non-BE). Multivariate analysis showed that CRNs (t = 8.55, P < 0.001), reflux esophagitis (t = 5.26, P < 0.001) and hiatal hernia (t = 11.68, P < 0.001) were predictors of BE. CONCLUSIONS: The presence of CRNs was strongly associated with BE and EAC. Therefore, colonoscopy may be useful for establishing a strategy for the surveillance of BE.

Circumferential distribution and clinical characteristics of esophageal cancer in lower esophagus: differences related to histological subtype.

BACKGROUND: Esophageal adenocarcinoma (EAC) is frequently found on the right-anterior wall of the distal esophagus in short-segment Barrett's esophagus (SSBE) patients. However, the endoscopic characteristics of EAC in cases with long-segment BE (LSBE) and squamous cell carcinoma (ESCC) in the lower esophagus remain to be fully evaluated. Here, we determined the circumferential distribution and clinical characteristics of esophageal cancer occurring in the lower esophagus based on histological subtype. METHODS: We retrospectively reviewed the medical records of 150 patients with esophageal cancer (ESCC, n = 100; EAC, n = 50) diagnosed at our hospital or a related facility between January 2002 and June 2017, including information regarding endoscopic findings, etiology, and clinical parameters. RESULTS: Of the 100 patients with ESCC, 28 lesions were located in the lower esophagus, though characteristic circumferential distribution was not seen regardless of location. Those showed a greater frequency of smoking and drinking habit and gastric mucosal atrophy as compared to patients with EAC. Consistent with the previous reports, EAC in SSBE (n = 41) was frequently located on the right-anterior wall. Likewise, EAC at the esophagogastric junction (EGJ) in LSBE was frequently located on the right-anterior wall, while EAC distant from the EGJ showed no characteristic circumferential distribution. CONCLUSION: Our results showed no circumferential predilection for ESCC in the lower esophagus, suggesting that development of this type of lesion may be less affected by gastroesophageal reflux. In addition, EAC at the EGJ was frequently found on the right-anterior wall irrespective of BE length.

Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy.

PURPOSE: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. METHODS: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. RESULTS: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). CONCLUSIONS: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.

Endoscopic submucosal dissection of early gastric cancer via inverted overtube in a patient with situs inversus totalis: a case report.

Background and study aims A 72-year-old man with complete situs inversus presented with early gastric cancer on the lesser curvature wall of the antrum of the stomach. Endoscopic submucosal dissection (ESD) was selected as a treatment. When the patient was positioned in the left decubitus position, the lesion was hidden by blood and gastric fluid because it was located on the gravitational side. Therefore, we decided to perform ESD with the patient in the right lateral decubitus position and use an inverted overtube, which provided a good endoscopic view without the need to rearrange the endoscopist, assistants, or endoscopic system. ESD was safe and feasible using the inverted overtube.

Large-cell neuroendocrine carcinoma arising from a gastritis cystica polyposa.

Gastritis cystica polyposa is a polypoid lesion that arises from the gastric mucosa at the gastrojejunal anastomotic site and is characterized by cystic dilation of the gastric glands. A 78-year-old man who underwent distal gastrectomy for a gastric ulcer with Billroth II reconstruction approximately 40 years previously, exhibited a gastritis cystica polyposa at the anastomotic site. Ulceration was observed on an annual endoscopic examination. Endoscopic ultrasonography revealed a submucosal hypoechoic mass with multiple cystic lesions. Gastrectomy was performed and histological examination revealed a large-cell neuroendocrine carcinoma with cystic dilation of the gastric glands. Here, we report the first case of a large-cell neuroendocrine carcinoma arising from a gastritis cystica polyposa. Endoscopic ultrasonography was effective at diagnosing a submucosal hypoechoic mass with cystic dilation of the gastric glands.

Efficacy and safety of Helicobacter pylori eradication therapy immediately after endoscopic submucosal dissection.

BACKGROUND AND AIMS: In the treatment of patients after endoscopic submucosal dissection (ESD), there is no consensus on the optimum time to start Helicobacter pylori eradication therapy or on whether eradication therapy improves ulcer healing rate after ESD. The aim of this study was to examine the effect of immediate eradication of H. pylori on ulcer healing after ESD in patients with early gastric neoplasms. METHODS: A total of 330 patients who underwent ESD for early gastric neoplasms were enrolled. Patients were assigned to either H. pylori eradication group (Group A: H. pylori eradication + proton pump inhibitor 7 weeks) or non-eradication group (Group B: proton pump inhibitor 8 weeks). The primary end point was gastric ulcer healing rate (Group A vs Group B) determined on week 8 after ESD. RESULTS: Patients in Group A failed to meet non-inferiority criteria for ulcer scarring rate after ESD compared with that in Group B (83.0% vs 86.5%, P for non-inferiority = 0.0599, 95% confidence interval: -11.7% to 4.7%). There were, however, neither large differences between the two groups in the ulcer scarring rate nor the safety profile. CONCLUSIONS: This study failed to demonstrate the non-inferiority of immediate H. pylori eradication therapy after ESD to the non-eradication therapy in the healing rate of ESD-caused ulcers. However, because the failure is likely to attribute to small number of patients enrolled, immediate eradication therapy may be a treatment option for patients after ESD without adverse effects on eradication therapy in comparison with the standard therapy.

Early esophageal cancer with epidermization diagnosed and treated with endoscopic resection.

The patient was a 57-year-old man who had undergone endoscopic submucosal dissection for early esophageal cancer (distance from incisor tooth, 30 cm) when he was 50 years of age. Pathological findings showed squamous cell carcinoma invading the lamina muscularis mucosae and mild lymphatic invasion. Considering the possibility of lymph node metastasis and distant metastasis, we administered radiation chemotherapy (CDDP+ 5-FU, total radiation 41.4 Gy) in the same year. Two years later, follow-up endoscopy revealed a white, flat, elevated lesion in the thoracic esophagus (distance from incisor tooth, 36 cm) that was not stained by Lugol's iodine. A biopsy of this lesion was performed. Although esophageal epidermization was seen, there were no findings suggestive of malignancy. The lesion grew slightly during four and a half years of follow-up after identification. We performed a repeat biopsy of the lesion, and the tissue was diagnosed as atypical epithelium, so we performed endoscopic mucosal resection for diagnostic and therapeutic purposes. The postoperative pathological diagnosis was squamous cell carcinoma of T1a-LPM with epidermization due to its histological features. To the best of our knowledge, this is the first report of esophageal cancer accompanied by epidermization.

[A case of long-term survival in stage IV squamous cell carcinoma of the anal canal with multidisciplinary treatment].

A 60-year-old female presented to our hospital with anal pain. Colonoscopy (CS) revealed a tumor in the anal canal, which was diagnosed as squamous cell carcinoma by biopsy. Computed tomography (CT) showed multiple liver metastases. From these findings, we diagnosed the anal tumor as stage IV squamous cell carcinoma of the anal canal. Although CS and CT indicated disappearance of the primary tumor and liver metastases following chemoradiotherapy, brain metastasis developed during the disease course and was treated with radiotherapy and surgical resection. Administration of S-1 as adjuvant chemotherapy was continued, and the patient has remained alive for approximately six years without recurrence. To the best of our knowledge, this case can be considered as having the longest-term survival in stage IV squamous cell carcinoma of the anal canal.

Avoidance of platelet transfusion with readministration of lusutrombopag before radiofrequency ablation in hepatocellular carcinoma:a case report.

Platelet transfusions are generally administered to patients with liver cirrhosis and associated thrombocytopenia before radiofrequency ablation (RFA). Here, we describe a 77-year-old woman who was diagnosed with hepatitis C, liver cirrhosis, and hepatocellular carcinoma (HCC) in 2006. She underwent RFA in October 2014 and October 2015, with platelet transfusions. She was admitted to our hospital in July 2016 to receive RFA for recurrence of HCC. To avoid platelet transfusion before RFA, she was administered lusutrombopag. The platelet count increased, and she did not need a platelet transfusion. In November 2016, computed tomography revealed that HCC had recurred. Lusutrombopag was readministered to avoid platelet transfusion before performing RFA. Subsequently, her platelet count increased, platelet transfusion was avoided, with no side effects. The results obtained in this case are valuable because there is little information on readministration of lusutrombopag.

Bleeding Risk Related to Upper Gastrointestinal Endoscopic Biopsy in Patients Receiving Antithrombotic Therapy: A Multicenter Prospective Observational Study.

BACKGROUND: Although antithrombotic agents are widely used for cardiac and cerebrovascular disease prevention, they increase the risk of gastrointestinal (GI) bleeding. OBJECTIVE: To examine GI bleeding risk in association with an esophagogastroduodenoscopy (EGD) biopsy performed in patients without cessation of antithrombotic therapy. METHODS: This study was prospectively conducted at 14 centers. EGD biopsies were performed in patients receiving antithrombotic agents without cessation, as well as age- and sex-matched controls not receiving antithrombotic therapy. Patients treated with warfarin before the biopsy had a prothrombin time-international normalized ratio level <3.0. The proportion of GI bleeding events was compared between the groups. RESULTS: The patient group (n = 277) underwent a total of 560 biopsies while continuing antithrombotic therapy, of whom 24 were receiving multiple antiplatelet drugs, and 9 were receiving both antiplatelet and anticoagulant agents. The control patients (n = 263) underwent 557 biopsies. The upper-GI bleeding rate within 30 days after the EGD biopsy did not increase in patients without cessation of antithrombotic treatment, regardless of receiving single or multiple antithrombotic agents. CONCLUSIONS: We found no significant increase in upper-GI bleeding risk following an EGD biopsy in patients taking antithrombotic agents, suggesting its safety without the need for antithrombotic treatment interruption.

A Combined Deposition of Lanthanum and ß2-Microglobulin-Related Amyloid in the Gastroduodenal Mucosa of Hemodialysis-Dependent Patients: An Immunohistochemical, Electron Microscopic, and Energy Dispersive X-Ray Spectrometric Analysis.

Lanthanum carbonate (LC) is a new type of phosphate adsorbent used to treat patients with hyperphosphatemia caused by chronic kidney diseases. Recent studies have pointed out that lanthanum deposition can be found in the cytoplasm of histiocytes in the gastroduodenal mucosa of these patients. On the other hand, it is well known that patients on long-term hemodialysis can develop deposition of ß2-microglobulin-related amyloid (Aß2M) mainly around joints. However, involvement of the gastrointestinal tract by hemodialysis-associated amyloidosis has been thought to be rare, and therefore only Aß2M, if any, has been reported to accumulate in the vascular walls of the submucosa and muscularis propria. Thus, in contrast to AA amyloid, biopsy from gastrointestinal mucosa has long been considered to have little significance in detecting amyloid. We present unusual histologic findings on biopsy specimens taken from the gastroduodenal mucosa of 7 hemodialysis-dependent patients taking LC for more than a year. These findings were due to a combined deposition of lanthanum and ß2-microglobulin-related amyloid in the cytoplasm of histiocytes. The deposition of amyloid was confirmed by conventional histochemistry, immunohistochemistry, and transmission electron microscopy, and that of lanthanum by transmission electron microscopy and scanning electron microscopy/energy dispersive X-ray spectrometry. This is the first report of such a peculiar combined deposition of lanthanum and amyloid in the gastroduodenal mucosa of hemodialysis patients. Although the exact mechanism of combination and pathogenesis is unclear, we believe that histologic examination of the gastrointestinal mucosa should be considered in the careful follow-up and observation of hemodialysis patients taking LC.