Background factors of idiopathic peptic ulcers and optimal treatment methods: a multicenter retrospective Japanese study.

This study investigated the trends in idiopathic peptic ulcers, examined the characteristics of refractory idiopathic peptic ulcer, and identified the optimal treatment. The characteristics of 309 patients with idiopathic peptic ulcer were examined. We allocated idiopathic peptic ulcers that did not heal after 8 weeks' treatment (6 weeks for duodenal ulcers) to the refractory group and those that healed within this period to the healed group. The typical risk factors for idiopathic peptic ulcer (atherosclerosis-related underlying disease or liver cirrhosis complications) were absent in 46.6% of patients. Absence of gastric mucosal atrophy (refractory group: 51.4%, healed group: 28.4%; p = 0.016), and gastric fundic gland polyps (refractory group: 17.6%, healed group: 5.9%; p = 0.045) were significantly more common in the refractory group compared to the healed group. A history of H. pylori eradication (refractory group: 85.3%, healed group: 66.0%; p = 0.016), previous H. pylori infection (i.e., gastric mucosal atrophy or history of H. pylori eradication) (refractory group: 48.5%, healed group: 80.0%; p = 0.001), and potassium-competitive acid blocker treatment (refractory group: 28.6%, healed group, 64.1%; p = 0.001) were significantly more frequent in the healed group compared to the refractory group. Thus, acid hypersecretion may be a major factor underlying the refractoriness of idiopathic peptic ulcer.

Clinical characteristics and long-term prognosis of type 1 gastric neuroendocrine tumors in a large Japanese national cohort.

OBJECTIVES: Optimal management of type 1 gastric neuroendocrine tumors (T1-GNETs) remains unknown, with few reports on their long-term prognosis. This study investigated the clinical characteristics and long-term prognosis of T1-GNETs. METHODS: We reviewed the medical records of patients diagnosed with T1-GNET during 1991-2019 at 40 institutions in Japan. RESULTS: Among 172 patients, endoscopic resection (ER), endoscopic surveillance, and surgery were performed in 84, 61, and 27, respectively, including 27, 77, and 2 patients with pT1a-M, pT1b-SM, and pT2 tumors, respectively. The median tumor diameter was 5 (range 0.8-55) mm. Four (2.9%) patients had lymph node metastasis (LNM); none had liver metastasis. LNM rates were significantly higher in tumors with lymphovascular invasion (LVI) (15.8%; 3/19) than in those without (1.1%; 1/92) (P = 0.016). For tumors <10 mm, LVI and LNM rates were 18.4% (14/76) and 2.2% (2/90), respectively, which were not significantly different from those of tumors 10-20 mm (LVI 13.3%; 2/15, P = 0.211; and LNM 0%; 0/17, P = 1.0). However, these rates were significantly lower than those of tumors >20 mm (LVI 60%; 3/5, P = 0.021; and LNM 40%; 2/5, P = 0.039). No tumor recurrence or cause-specific death occurred during the median follow-up of 10.1 (1-25) years. The 10-year overall survival rate was 97%. CONCLUSIONS: Type 1 gastric neuroendocrine tumors showed indolent nature and favorable long-term prognoses. LVI could be useful in indicating the need for additional treatments. ER for risk prediction of LNM should be considered for tumors <10 mm and may be feasible for tumors 10-20 mm. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Information Network (UMIN) under the identifier UMIN000029927.

Endoscopic features and clinical importance of autoimmune gastritis.

Autoimmune gastritis (AIG) is a special type of chronic gastritis characterized by autoimmune disorders caused by cellular immunity, resulting in the destruction of parietal cells and production of antiparietal cell antibodies. Endoscopic findings of AIG are mainly characterized by corpus-dominant advanced atrophy. The antral area is generally considered to have no or mild atrophy; however, there are cases wherein the gastric mucosa is red or faded due to past infection with Helicobacter pylori or bile reflux. Currently, there are no diagnostic criteria for AIG in Japan, and it is important to make a diagnosis based on the presence of gastric autoantibodies and characteristic endoscopic and histological findings. AIG is associated with gastric cancer, neuroendocrine tumors (NETs), and other autoimmune diseases, such as thyroid diseases, anemia, and neurological symptoms due to impaired absorption of iron and vitamin B12 , and thus requires systemic treatment. The significance of diagnosing AIG is to include patients as a high-risk group for the development of gastric cancer and gastric NETs, provide an opportunity to detect autoimmune endocrine diseases, and initiate therapeutic intervention before anemia and neurological symptoms develop. It is important to pay close attention to the occurrence of AIG comorbidities not only at the time of AIG diagnosis but also during follow-up after detection.

Multicenter study of autoimmune gastritis in Japan: Clinical and endoscopic characteristics.

BACKGROUND AND AIM: In Japan, the prevalence of autoimmune gastritis (AIG) is assumed to be very low. With the recent rapid decrease in Helicobacter pylori (Hp) prevalence, reports on AIG are increasing. This multicenter registry study aimed to clarify the characteristics of AIG, especially its endoscopic appearance. METHODS: A total of 245 patients with AIG from 11 institutions in Japan from January 2010 to October 2016 were included, and their clinical and endoscopic findings were evaluated. RESULTS: Mean age was 67.2 ± 11.4 years, and 63.7% of the participants were women. The most common approach to diagnose AIG was endoscopic examination. Repeated incorrect treatment for Hp infection, due to a false-positive result in 13 C-urea breath test, ranked third among the basis for diagnosis of AIG. Associated gastric lesions were type 1 neuroendocrine tumor (11.4%), adenocarcinoma (9.8%), and hyperplastic polyps (21.1%). Corpus pan-atrophy was the most common appearance (90.1%); however, remnant oxyntic mucosa was found in 31.5% of the patients (flat, localized type, 48.6%). Sticky adherent dense mucus and scattered minute whitish protrusions were also observed in approximately 30% of the patients. Despite the prevailing presumption of the antral mucosa remaining normal, 42.3% of the patients presented with various extents of atrophy, and patchy redness and circular wrinkle-like patterns were both observed in approximately 20% of the patients. CONCLUSIONS: The present study showed some prominent clinical characteristics and endoscopic findings of AIG. We believe that our study will facilitate the diagnosis of potential AIG.

Hypophosphatemia predicts a failure to recover from adefovir-related renal injury after dose reduction in lamivudine-resistant hepatitis B patients.

AIM: In chronic hepatitis B patients receiving 10 mg adefovir, dose reduction is recommended when renal injury appears. However, recovery is not always achieved and markers that recommend switching to another antiviral agent are unknown. We investigated adefovir-related renal injury, recovery after dose reduction, and their predictors. METHODS: The renal injury in 77 chronic hepatitis B patients receiving 10 mg adefovir and recovery after dose reduction to alternate day administration in those with adefovir-related renal injury were assessed. The predictors for >20% estimated glomerular filtration rate (eGFR) decline following treatment with 10 mg adefovir and for >20% eGFR recovery after dose reduction were investigated. RESULTS: The adefovir dose was reduced in 26 patients (34%) at 59 ± 30 (mean ± standard deviation) months of 10 mg adefovir treatment because of decreases in eGFR (cumulative incidence 27%), serum phosphorus (9%), and uric acid (16%) levels, and increases in alkaline phosphatase (20%), bone type alkaline phosphatase (18%), urinary α1-microglobulin (18%), and urinary N-acetyl-ß-D-glucosaminidase (18%) levels. The only significant predictor for >20% eGFR decline was age ≥50 years at the start of 10 mg adefovir treatment. The cumulative eGFR recovery rate was 42% at 42 ± 27 months after dose reduction, and ≥2.5 mg/dL serum phosphorus level at dose reduction was the only significant predictor for >20% eGFR recovery after dose reduction. CONCLUSION: Patients aged ≥50 years are predisposed to adefovir-related renal injury and switching to another antiviral agent rather than adefovir dose reduction is recommended when hypophosphatemia is observed.

Characteristics of Colonic Diverticulitis and Factors Associated With Complications: A Japanese Multicenter, Retrospective, Cross-Sectional Study.

BACKGROUND: Little is known about the epidemiology of diverticulitis in Japan. Additional information is needed about its clinical characteristics and the factors associated with complications of diverticulitis. OBJECTIVE: This study was designed to determine the clinical characteristics of diverticulitis and factors associated with its complications in Japanese patients. DESIGN: This was a retrospective, multicenter, large-scale, cross-sectional study. SETTINGS: All of the consecutive patients in 21 Japanese hospitals with a final diagnosis of acute colonic diverticulitis were included in this study. PATIENTS: A total of 1112 patients, including 658 men and 454 women, with a mean age of 54.8 years, who were diagnosed by CT and/or ultrasonography between January 2006 and May 2011, were included in this study. INTERVENTIONS: Data on medical history, investigations, treatments, and prognosis were collected using a standard form to create a dedicated database. MAIN OUTCOME MEASURES: Clarification of the clinical characteristics of Japanese patients with acute diverticulitis was the main outcome measured. RESULTS: Diverticulitis was detected mainly in men and women aged 40 to 60 years. Although diverticulitis more frequently affected the right colon (70.1%), diverticulitis of the left colon was significantly more frequent (61.0%) in elderly patients. Of the 1112 patients with diverticulitis, 179 (16.1%) developed complications, including abscess formation, perforation, stenosis, and/or fistula, some of which required surgical treatment, such as drainage or colonic resection. The duration of hospitalization (24.1 ± 19.5 days) and mortality rate (2.8%) were significantly higher in patients with versus without complications. Factors associated with complications were fever (>38.5°C), involvement of the left colon, higher age, and delayed diagnosis. LIMITATIONS: Limitations included the nonconsideration of diverticulitis treatment, the effect of dietary fiber, and the retrospective design of the study. CONCLUSIONS: Complications were more frequent in elderly men with left-sided diverticulitis, although diverticulitis was more common in middle-aged people and on the right side of the colon. Factors associated with complications were fever, site of involvement, older age, and longer time until diagnosis.

Diagnostic criteria and endoscopic and histological findings of autoimmune gastritis in Japan.

The Japanese diagnostic criteria for autoimmune gastritis (AIG) were established by the "Study Group on the establishment of diagnostic criteria for type A gastritis," which is related to a workshop associated with the Japan Gastroenterological Endoscopy Society (JGES) and the Committee of AIG Research Group (CARP). The criteria were set as follows: the cases of confirmed diagnosis are patients in whom either the endoscopic or histological findings, or both, meet the requirements for AIG and who are confirmed to be positive for gastric autoantibodies (either anti-parietal cell or anti-intrinsic factor antibodies, or both). The presentation of endoscopic findings of early-stage AIG in the diagnostic criteria was withheld owing to the need for further accumulation and characterization of endoscopic clinical data. Therefore, diagnosis of early-stage AIG only requires histological confirmation and gastric autoantibody positivity. Suspected cases are patients in whom either the endoscopic or histological findings, or both, meet only the requirements for AIG. Histological findings only meet the requirements for early stage. AIG has been underdiagnosed in the past, but our study group's newly proposed diagnostic criteria will enable a more accurate and early diagnosis of AIG. The criteria can be used to stratify patients into various high-risk groups for gastric tumors and pernicious anemia. They would allow the establishment of an appropriate surveillance system in the coming years. Nevertheless, issues such as establishing the endoscopic findings of early-stage AIG and obtaining Japanese insurance coverage for gastric autoantibody tests require attention.

Gastric epithelial neoplasm of fundic-gland mucosa lineage: proposal for a new classification in association with gastric adenocarcinoma of fundic-gland type.

BACKGROUND: Gastric adenocarcinoma of fundic-gland type (GA-FG) is a rare variant of gastric neoplasia. However, the etiology, classification, and clinicopathological features of gastric epithelial neoplasm of fundic-gland mucosa lineage (GEN-FGML; generic term of GA-FG related neoplasm) are not fully elucidated. We performed a large, multicenter, retrospective study to establish a new classification and clarify the clinicopathological features of GEN-FGML. METHODS: One hundred GEN-FGML lesions in 94 patients were collected from 35 institutions between 2008 and 2019. We designed a new histopathological classification of GEN-FGML using immunohistochemical analysis and analyzed via clinicopathological, immunohistochemical, and genetic evaluation. RESULTS: GEN-FGML was classified into 3 major types; oxyntic gland adenoma (OGA), GA-FG, and gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM). In addition, GA-FGM was classified into 3 subtypes; Type 1 (organized with exposure type), Type 2 (disorganized with exposure type), and Type 3 (disorganized with non-exposure type). OGA and GA-FG demonstrated low-grade epithelial neoplasm, and GA-FGM should be categorized as an aggressive variant of GEN-FGML that demonstrated high-grade epithelial neoplasm (Type 2 > 1, 3). The frequent presence of GNAS mutation was a characteristic genetic feature of GEN-FGML (7/34, 20.6%; OGA 1/3, 33.3%; GA-FG 3/24, 12.5%; GA-FGM 3/7, 42.9%) in mutation analysis using next-generation sequencing. CONCLUSIONS: We have established a new histopathological classification of GEN-FGML and propose a new lineage of gastric epithelial neoplasm that harbors recurrent GNAS mutation. This classification will be useful to estimate the malignant potential of GEN-FGML and establish an appropriate standard therapeutic approach.

Clinical and endoscopic characteristics of eosinophilic esophagitis in Japan: a case-control study.

BACKGROUND: Eosinophilic esophagitis (EoE) is an allergy-associated clinicopathologic condition gaining an increasing amount of recognition in various areas of the world. While the clinical definition and characteristics may differ depending on country and region, sufficient studies have not yet been performed in Japan. OBJECTIVE: To assess the prevalence of EoE among the Japanese population and the clinical features associated with the disease. METHODS: Endoscopic data from January 2012 to October 2018 was gathered from 9 Japanese clinical institutes. EoE, defined as esophageal mucosal eosinophilia of at least 15 eosinophils per high-power field, was determined based on esophageal biopsies. Clinical and endoscopic patterns in the cases with EoE were investigated and compared with 186 age- and sex-matched controls. RESULTS: From 130,013 upper endoscopic examinations, 66 cases of EoE were identified (0.051%; mean age, 45.2 years [range, 7-79 years]; 45 males). Twenty-five patients (37.9%) with EoE were diagnosed by endoscopy during a medical check-up. Patients with EoE had more symptoms (69.7% vs. 10.8%, p < 0.01) such as dysphagia and food impaction, and more allergies (65.2% vs. 23.7%, p < 0.01) compared with the controls. The prevalence of atrophic gastritis was lower in EoE patients than in the controls (20.0% vs. 33.3%, p < 0.05). CONCLUSION: The prevalence of EoE in the Japanese population was 0.051% which was comparable with previous reports in Japan. History of allergies and the absence of atrophic gastritis were associated with EoE.

Two independent families with strongly suspected hereditary diffuse gastric cancer based on the probands' endoscopic findings.

Hereditary diffuse gastric cancer (HDGC) is the most famous of hereditary gastric cancer syndromes with an autosomal dominant inheritance pattern, and its diagnosis can be made by identifying a pathogenic germline variant in CDH1. We report two independent families that were strongly suspected of having HDGC based on endoscopic findings (multiple tiny, pale areas) obtained in the probands; the probands were pathologically diagnosed as having signet ring cell carcinoma (SRCC) and were genetically confirmed to have a pathogenic CDH1 germline variant. Although the updated International Gastric Cancer Linkage Consortium (IGCLC)'s clinical guidelines for HDGC (2015) state that screening/surveillance endoscopy should be performed (Cambridge protocol), the endoscopic findings obtained in the two presently reported families suggest that pale areas should be suspected as indicating the presence of SRCCs, and biopsies should be performed in addition to obtaining a precise family history in cases suspected of having HDGC.

Long-term prognosis of patients after endoscopic sphincterotomy for choledocholithiasis.

INTRODUCTION: The aims of the present study were to clarify the long-term prognosis of endoscopic sphincterotomy (EST) for choledocholithiasis and to evaluate the need for cholecystectomy after EST. METHODS: Between 1993 and 2007, 262 patients who underwent successful EST for choledocholithiasis were followed up for more than 6 months). Eighteen patients had previously undergone cholecystectomy (Group A), 129 had a calculous gallbladder (GB) and underwent cholecystectomy after EST (Group B), 46 had a calculous GB in situ (Group C), and 69 had an acalculous GB in situ (Group D). Late complications, including recurrence of choledocholithiasis, acute cholecystitis and biliary carcinoma, were evaluated. RESULTS: Of the 262 patients, late complications occurred in 34 patients (13.0%) and recurrence of choledocholithiasis occurred in 29 patients (11.1%). The rate of late complications was higher in Group C (23.9%) than in Group B (7.8%) (P < 0.001). The rate of recurrent choledocholithiasis was higher in Group C (17.4%) than in Group B (7.8%) (P < 0.05). Univariate analysis indicated that pneumobilia after EST was associated with the recurrence of choledocholithiasis (P < 0.001). Acute cholecystitis occurred in eight (7.0%) of 115 patients with intact GB. A gallbladder carcinoma was found after EST. Late complications were not serious and endoscopically or surgically manageable. CONCLUSIONS: EST for choledocholithiasis is safe and effective. Cholecystectomy after EST is recommended in patients with calculous GB, but is not necessary in patients with acalculous GB. Pneumobilia was associated with the recurrence of choledocholithiasis.

[Case of pancreatic mucosa-associated lymphoid tissue (MALT) lymphoma].

A 77-year-old woman underwent abdominal ultrasonic diagnosis in a screening test for diabetes mellitus. A 65 x 45 mm tumor with low echo level was revealed and located from the uncinate process of the pancreas to the body. Contrast-enhanced computed tomography demonstrated the pancreas had a low density area in the arterial phase and a comparable area in the equilibrium phase, compared with the parenchyma of the normal pancreas. Gallium-scintigraphy showed strong accumulation, consistent with the tumor. Mucosa-associated lymphoid tissue (MALT) lymphoma was diagnosed by endosonography-guided fine-needle aspiration biopsy (EUS-FNAB). Complete remission was achieved after radiation therapy.

[Retroperitoneal fibrosis and Castleman disease in two patients with high IgG4 levels].

With the cumulative increase in the number of autoimmune pancreatitis cases, the disease is now widely accepted as a symptom of IgG4-related systemic disease. We recently experienced two cases of retroperitoneal fibrosis and Castleman disease presenting high IgG4 levels without evident pancreatic lesions. Both patients were successfully treated with steroid therapy. It is necessary to acknowledge that retroperitoneal fibrosis and Castleman disease, with or without pancreatic lesions, may have aspects of IgG4-related systemic disease and that the measurement of serum IgG4 and tissue immunostaining for IgG4 should be considered for diagnosing and treating the conditions.

[A case of colonic obstruction due to post-operative stenosis of the colon and multiple enteroliths].

An 81-year-old man who had under gone two abdominal surgeries and temporary colostomy 30 years previously was admitted due to lower abdominal pain and vomiting. An abdominal X-ray film and abdominal CT scan showed intestinal distension and multiple calcareous deposits in the colon. Gastrografin enema examination revealed smooth stenosis at the sigmoid colon and many additional defects. Endoscopy could not be performed due to the stenosis. He did not agree to surgery. Seven months later, he was admitted again, due to colonic obstruction. Surgery was performed which revealed colonic obstruction as the source of post-operative stenosis of the sigmoid colon and multiple enteroliths. The stones consisted of a core and a hull and contained ammonium magnesium phosphate.

[A case of Castlemans disease (plasma cell type) in which autoimmune pancreatitis developed 6 years later].

In 1998 a 74-year-old man, he had a medical checkup and mediastinal and hilar lymph node hyperplasia were discovered. Since the lymph nodes showed a tendency to increase in size, mediastinal lymph node biopsy was performed in the following year. Castlemans disease was diagnosed, and he was followed up. In 2005, autoimmune pancreatitis (AIP) developed. At this time, the mediastinal lymph node that had been biopsied was stained with anti-IgG4 antibody. Further examinations on pancreatic lesions associated with Castlemans disease and AIP are necessary in relation to IgG4-related systemic diseases.

Effects of adacolumn selective leukocytapheresis on plasma cytokines during active disease in patients with active ulcerative colitis.

AIM: To investigate the relationship between ulcerative colitis (UC) clinical activity index (CAI) and circulating levels of IL-1ra, IL-10, IL-6 and IL-18. METHODS: Blood levels of IL-1ra, IL-10, IL-6 and IL-18 were measured in 31 patients with active UC, the mean CAI was 11.1, ranging from 5-25; and 12 healthy individuals as controls. Patients were given granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn. Leucocytes which bear the FcgammaR and complement receptors were adsorbed to the column leucocytapheresis carriers. Each patient could receive up to 11 GMA sessions over 8 wk. RESULTS: We found strong correlations between CAI and IL-10 (r = 0.827, P < 0.001), IL-6 (r = 0.785, P < 0.001) and IL-18 (r = 0.791, P < 0.001). IL-1ra was not correlated with CAI. Following GMA therapy, 24 of the 31 patients achieved remission and the levels of all 4 cytokines fell to the levels in healthy controls. Further, blood levels of IL-1ra and IL-10 increased at the column outflow and inflow at 60 min suggesting release from leucocytes that adhered to the carriers.

[Superior mesenteric arterial thrombosis complicating ulcerative colitis: A case report].

36-year-old men with ulcerative colitis was attacked by the colic. The thrombus in superior mesenteric artery was revealed by computed tomography. Because the effect of the thrombolysis under intrarterial angiography was insufficient, thrombectomy was enforced under the laparotomy in the same day. The arterial thrombosis is extremely rare in the complication of ulcerative colitis. The activity of ulcerative colitis as one of factors of the appearance of thrombus was suggested.

The Ulcerative Colitis Endoscopic Index of Severity More Accurately Reflects Clinical Outcomes and Long-term Prognosis than the Mayo Endoscopic Score.

BACKGROUND AND AIMS: The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and the Mayo endoscopic score (Mayo ES) are used to evaluate ulcerative colitis (UC) severity. This study compared UCEIS and the Mayo ES for evaluating UC severity and outcomes in patients undergoing remission induction during routine clinical practice with the aim of predicting medium- to long-term prognosis. METHODS: Forty-one UC patients who received colonoscopy before and after tacrolimus remission induction therapy were included. An index of clinical activity and endoscopic findings scored by both the UCEIS and the Mayo ES were determined. Changes in UCEIS and Mayo ES before and after induction therapy were compared. RESULTS: The mean UCEIS improved from 6.2±0.9 to 3.4±2.1 (p < 0.001). Based on the UCEIS, a significant reduction was reached in both the response and the remission groups. In contrast, the Mayo ES did not reflect a significant change in the response group. The discrepancy appeared to be due to ulcers becoming smaller and shallower during the early stages of mucosal healing; the Mayo ES seems to miss these early changes. In other words, whereas the UCEIS indicates improvements when ulcers shrink, the Mayo ES does not distinguish deep ulcers from shallow ulcers and is 3 (severe UC) for both deep and shallow ulcers. Additionally, better UCEIS strata after induction therapy were associated with lower incidences of colectomy (p = 0.0001) or relapse (p = 0.0008). CONCLUSIONS: The UCEIS accurately reflects clinical outcomes and predicts the medium- to long-term prognosis in UC patients undergoing induction therapy. These findings should support decision-making in clinical practice settings.

Decrease of reactive-oxygen-producing granulocytes and release of IL-10 into the peripheral blood following leukocytapheresis in patients with active ulcerative colitis.

AIM: To investigate the clinical efficacy of leukocytapheresis (LCAP) in patients with active ulcerative colitis (UC), and to elucidate the mechanisms by determining the changes in the cytokine levels in the peripheral blood and of the functions of the peripheral blood leukocytes in these patients. METHODS: The subjects were 19 patients with active UC, with a mean clinical activity index (CAI) of 9.2. The LCAP was conducted using Cellsorba E. In each session of LCAP, 2-3 L of blood at the flow rate of 30-50 mL/min was processed. The treatment was carried out in approximately 1-h sessions, once a week, for 5-10 wk. Blood samples for determination of the cytokine levels were collected from the inflow side of the column (site of dehematization; at the start of LCAP) and outflow side of the column (at the end of LCAP). Blood samples for the determination of reactive-oxygen-producing cells were collected from the peripheral blood before and after LCAP. RESULTS: LCAP resulted in clinical improvement in all the 19 patients of UC recruited for this study. Remission (CAI: < or = 4) was noted in 15 (79%) of the 19 patients. The blood level of the pro-inflammatory cytokine IL-6 was found to be decreased following treatment by LCAP, and the level of the anti-inflammatory cytokine IL-10 at the outflow side of the LCAP column was found to be significantly elevated as compared to that at the inflow side of the column. The reactive-oxygen-producing granulocytes in the peripheral blood of UC patients was increased as compared to that in healthy persons and the increase was found to be decreased following treatment by LCAP. CONCLUSION: LCAP exerted a high therapeutic efficacy in patients with active UC. Our findings suggest that LCAP is associated with enhanced production of the inhibitory cytokine IL-10 to indirectly inhibit the functions of the inflammatory leukocytes, and that inflammation is also considerably attenuated by the direct removal of reactive-oxygen-producing neutrophils from the peripheral blood.