Kazunari Kanke

Adsorptive granulocyte and monocyte apheresis for refractory Crohn's disease : an open multicenter prospective study

BackgroundActive Crohn’s disease (CD) is often associated with elevated levels of platelets, granulocytes, and monocytes that are activated and resistant to apoptosis. The level of neutrophils in the intestinal mucosa has been quantitatively related to the severity of intestinal inflammation in CD. We postulated that patients with CD that is refractory to conventional medications might respond to a reduction of granulocytes and monocytes by adsorptive apheresis.MethodsTwenty-one patients with a CD activity index (CDAI) of 200–399 and unresponsive to standard medication, which included nutritional intervention, received granulocyte and monocyte adsorptive apheresis (GCAP) as an adjunct to their ongoing medication. GCAP was performed with an Adacolumn, which adsorbs granulocytes, monocytes, and a small fraction of lymphocytes (FcγR and complement receptor-bearing leucocytes). Patients received one GCAP session/week for 5 consecutive weeks. CDAI, International Organization for the Study of Inflammatory Bowel Disease (IOIBD), and IBD questionnaire (IBDQ) scores were evaluated.ResultsDuring the initial conventional/nutritional therapy, no significant improvement was seen in any patient. However, at week 7 of GCAP therapy, significant improvements in CDAI, IOIBD, and IBDQ scores were observed. The CDAI, IOIBD, and IBDQ scores before GCAP were 275.6 ± 54.2, 3.4 ± 1.4, and 152 ± 22, respectively. The corresponding values after GCAP were 214.8 ± 89.2 (P = 0.0005), 2.54 ± 1.5 (P = 0.0224), and 165 ± 29 (P = 0.0327), respectively.ConclusionsGCAP could be effective for inducing remission and improving quality of life in patients with active CD that is refractory to conventional therapy.

Treatment of gastric tumors by endoscopic mucosal resection with a ligating device.

BACKGROUND This study attempted to determine the indication for endoscopic mucosal resection with a ligating device (EMRL) and to assess the efficacy of radical (complete) resection of early gastric carcinoma and adenoma. METHODS Sixteen patients with early gastric carcinoma (17 lesions) and 21 patients with gastric adenoma (23 lesions) underwent EMRL with an endoscope with a ligating device. After epinephrine solution was injected into the submucosa, the lesions were aspirated, ligated, and resected. RESULTS Twelve of 17 early carcinomas (70.6%) and 18 of 23 adenomas (78.3%) were radically resected by EMRL. The average size of the resected specimens was 12.8 x 11.0 mm. The rate of successful radical resection by EMRL, including piecemeal resection, was 100% (15/15) for lesions located in the antrum, 80% (4/5) in the angle, 61.1% (11/18) in the body, and 0% (0/2) for lesions at the cardia. Repeat EMRL was performed successfully in cases of partial resection (n = 3). No serious complication was encountered. No recurrence of the tumors was identified in cases of radical resection during a median follow-up period of 22.8 months. CONCLUSION EMRL is suitable for the treatment of gastric tumorous lesions. For the treatment of early carcinoma, well-differentiated mucosal carcinomas smaller than 10 mm located in the distal stomach represent the best indication for EMRL.

Prediction of Colorectal Neoplasia by Quantitative Methylation Analysis of Estrogen Receptor Gene in Nonneoplastic Epithelium from Patients with Ulcerative Colitis

Purpose: The incidence of colorectal neoplasia has increased among patients with longstanding and extensive ulcerative colitis (UC). Therefore, surveillance colonoscopy has been widely recommended. However, there is controversy about the impact of cancer surveillance, and ways to improve its effectiveness are being sought. The estrogen receptor (ER) gene shows age-related methylation in the colorectal epithelium and is frequently methylated in colorectal neoplasia, suggesting that ER methylation occurs early in the process of colorectal tumorigenesis. Experimental Design: To clarify whether methylation analysis of the ER gene in nonneoplastic epithelium can help predict an increased risk for UC-associated neoplasia, a total of 105 nonneoplastic colorectal epithelia from 18 patients with longstanding and extensive UC, including 8 patients with neoplasia and 10 patients without neoplasia, were analyzed. In all patients, multiple samples were taken from six regions of the colorectum. The combined bisulfite restriction analysis method was used to determine the methylation status of the ER gene. Results: The mean methylation level of the ER gene was 25.4% in the nonneoplastic epithelia from UC patients with neoplasia, whereas it was only 4.0% in those without neoplasia (P < 0.001). The methylation level of the ER gene in UC patients with neoplasia was significantly higher than in UC patients without neoplasia throughout the colorectum except for the cecum. In UC patients with neoplasia, the mean ER methylation level in the distal colon (36.1%) was significantly higher than in the proximal colon (14.6%; P < 0.001). Conclusions: These results suggest that the analysis of ER gene methylation in nonneoplastic colorectal epithelium could have the potential to be a useful adjunct for identifying individuals with longstanding and extensive UC who are at increased risk of neoplasia and contribute to more effective cancer surveillance.

Comparison between endoscopic papillary balloon dilatation and endoscopic sphincterotomy for the treatment of common bile duct stones

BackgroundThis study was designed to evaluate the therapeutic outcome and early postoperative complications, especially pancreatitis, of endoscopic papillary balloon dilation (EPBD) and endoscopic sphincterotomy (EST) in patients with common bile duct stones in our department.MethodsOne hundred eighty patients with common bile duct stones were randomized to undergo EPBD or EST. An 8-mm dilatation balloon was used for EPBD. Modified Cotton’s criteria, in which relatively mild pancreatitis is also included as a complication, were used to determine the incidence of postoperative complications.ResultsThe rate of complete removal of stones was significantly higher in the EST group (95.6%) than in the EPBD group (86.6%); for stones less than 10 mm in diameter, however, the rate with EPBD (93.8%) was almost equivalent to that with EST (98.1%). According to modified Cotton’s criteria, the incidence of postoperative pancreatitis was significantly higher in the EPBD group (16.7%) than in the EST group (6.7%). Bleeding was encountered in one patient (1.1%) in the EST group, but in none in the EPBD group. No fatal complication occurred in either the EPBD or the EST group.ConclusionsAlthough EPBD appears to be comparable to EST for removal of small common bile duct stones, mild postoperative pancreatitis is more likely to occur with EPBD than with EST.

Efficacy, safety and cost analyses in ulcerative colitis patients undergoing granulocyte and monocyte adsorption or receiving prednisolone

BackgroundPatients with ulcerative colitis (UC) are treated with prednisolone (PSL), which causes adverse side effects. Extracorporeal granulocyte/monocyte adsorption (GMA) with an Adacolumn depletes elevated/activated myeloid lineage leucocytes as sources of inflammatory cytokines. We were interested to evaluate the efficacy, safety and the treatment cost for PSL and GMA.MethodsForty-one patients with active UC had achieved remission with GMA, at 1 or 2 sessions/week, up to 10 sessions (n=24) or with orally administered PSL (1mg/kg bodyweight, n=17). Clinical activity index (CAI) ≤4 was considered clinical remission. Following remission, patients received 5-aminosalicylic acid (2250-3000mg/day) or sulphasalazine (4000-6000mg/day) as maintenance therapy and were followed for 600 days. The total treatment cost was assessed based on 1€=150JPY.ResultsPSL was tapered after two weeks, and discontinued when a patient achieved remission. The average time to the disappearance of at least one major UC symptom (haematochezia, diarrhoea, or abdominal discomfort) was 15.3 days in the GMA group and 12.7 days in the PSL group, while time to remission was 27.9 days in the GMA group and 27.6 days in the PSL group, CAI 0.8 and 2.0, respectively. The Kaplan-Meier plots showed similar remission maintenance rates over the 600 days follow-up period. The average medical cost was 12739.4€/patient in the GMA group and 8751.3€ in the PSL group (P<0.05). In the GMA group, 5 transient adverse events were observed vs 10 steroid related adverse events in the PSL group (P<0.001).ConclusionsIn appropriately selected patients, GMA has significant efficacy with no safety concern. The higher cost of GMA vs PSL should be compromised by good safety profile of this non-pharmacological treatment intervention.

IPMN penetration of the stomach.

An 83‐year old Japanese man was transferred to our hospital due to a 1‐week history of melena and signs of disordered awareness. Esophagogastroduodenoscopy showed a villous tumor associated with massive white mucous discharge in the posterior wall of the gastric corpus, where pathologically identified mucin‐producing epithelium with nuclear atypia had developed into a papillary form. An abdominal enhanced computed tomography scan demonstrated communication between the dilated main pancreatic duct and the gastric lumen. Based on these findings, we reached a diagnosis of gastric penetration by an intraductal papillary mucinous neoplasm (IPMN) of the main pancreatic duct. IPMN is partly characterized by expansive mucinous growth that may result in penetration into adjacent organs.

Selection of Anticoagulants for Leukocytapheresis Therapy in Cases of Active Ulcerative Colitis

Background and Aim: Leukocytapheresis (LCAP) is an extracorporeal leukocyte removal therapy that removes immunocompetent leukocytes from the peripheral blood. Nafamostat mesilate (NM) is the most commonly used anticoagulant for LCAP due to various benefits associated with its use, such as a reduced likelihood of bleeding and minimization of adverse reactions caused by contact between blood and the LCAP device. However, adverse reactions have also been reported with NM administration. We reviewed the safety of anticoagulants other than NM, from the perspective of bradykinin production and the consequent drop in blood pressure during treatment. Methods: For each of 10 patients with ulcerative colitis, we used four types of anticoagulants sequentially [NM (30–50 mg), heparin, low-molecular-weight heparin (LMWH) and NM (1 mg), and LMWH] for LCAP. We then examined the changes in the blood bradykinin concentrations from the perspective of adverse reactions during LCAP. Results: The bradykinin production levels from Cellsorba EX varied, depending on the type of anticoagulant used. NM alone (30–50 mg) or LMWH + NM (1 mg) inhibited bradykinin production, whereas heparin alone or LMWH alone significantly accelerated it. However, an excessive fall of blood pressure was not noted in any of the cases. Use of LMWH alone was frequently associated with pressure elevations in the column. Conclusions: Given the significant benefits of minimized adverse reactions of LCAP and of continuation of LCAP, we suggest that an appropriate selection of the anticoagulant(s) may allow safer execution of LCAP.

3558 Argon plasma coagulation for eradication of esophageal varices after treatment with endoscopic variceal banding ligation or sclerotherapy.

Background: Endoscopic variceal banding ligation (EVL) and sclerotherapy (EVS) have been used to prevent variceal hemorrhage. However, the rate of recurrence of esophageal varices after EVL or EVS is considerably high. Argon plasma coagulation (APC) is a new modality of electrosurgery to apply high frequency electric current into tissue to cause defined thermal effects. This study was conducted to determine whether APC is beneficial for eradication of residual esophageal varices after EVL or EIS. Methods: Cirrhotic patients with endoscopically assessed high-risk esophageal varices but no history of bleeding underwent EVL or EIS to reduce the risk of hemorrhage. When the size of varices was reduced 1 week later, the entire esophageal mucosae 4-5 cm proximal to the esophagogastric junction was coagulated with one session of APC in a total of 15 patients.APC was performed with the use of argon source APC300 and high frequency generator ICC 200 (ERBE, Germany). Follow-up endoscopy was performed 7 days and 1 month after the initial procedure and thereafter every 3 months, to check for recurrent/residual esophageal varices and its complications. Results: Ten to 14 days after APC, ulcerations with white coating were noted in all cases, whereas varices were completely eradicated. One month after APC, while the varices remained eradicated, coagulated esophageal mucosae became whitish and the ulcerations were nearly completely healed. During the course, no patients complained of dysphagia or retrosternal pain. Furthermore, neither development of gastric varices nor aggravation of portal hypertensive gastropathy was observed endoscopically. No serious complication such as bleeding necessitating endoscopic therapy and perforation or stricture of the esophagus was encountered. Over a maximum follow-up period of 5 months, neither recurrence of nor hemorrhage from esophageal varices was observed. Conclusions: APC ablation of residual esophageal varices in patients who have undergone prior EVL or EIS is safe and may be a novel approach to eradicate esophageal varices. It requires a long term follow-up of the eradicated varices to further evaluate its efficacy.

MANAGEMENT OF OBSCURE GASTROINTESTINAL BLEEDING BASED ON THE CLASSIFICATION OF CAPSULE ENDOSCOPIC BLEEDING FINDINGS

Background:  Double‐balloon endoscopy (DBE) and capsule endoscopy (CE) have been useful in managing obscure gastrointestinal bleeding (OGIB). However, DBE is invasive, complex and time‐consuming, therefore indications should probably be selective. The aim of this study was to evaluate the usefulness of the classification of the CE bleeding findings for determining the indications and timing of DBE in patients with OGIB.

Gastric mucosal congestion following endoscopic variceal ligation analysis using reflectance spectrophotometry

UNLABELLED Endoscopic variceal ligation (EVL) has been accepted as a new treatment for esophageal varices in cirrhotic patients, and evaluated to have a lower incidence of complications compared to sclerotherapy. Sclerotherapy may increase the risk of portal hypertensive gastropathy (PHG), which is recognized to be gastric mucosal congestion due to portal hypertension in cirrhotics. However, the gastric mucosal hemodynamics after EVL has not been established yet. The aim of this study is to assess whether EVL could affect the hemodynamics of the gastric mucosa. PATIENTS AND METHODS Eleven cirrhotic patients with severe esophageal varices, who underwent prophylactic EVL were enrolled in the trial. Age and sex-matched non-cirrhotic patients who had only gastric mucosal atrophy were entered as control to compare the mucosal hemodynamics to that of cirrhotic patient. EVL was performed as described by Stiegmann et al. The gastric mucosal hemodynamics was evaluated with both gastric mucosal blood volume (IHB) and hemoglobin O2 saturation (ISO2), which were measured by reflectance spectrophotometry during endoscopy. These parameters were measured in the three points of the stomach (gastric antrum, lower corpus and upper corpus) just before and after EVL. RESULT In all patients with cirrhosis, mild PHG was observed endoscopically. ISO2 in cirrhotic patients was significantly lower in all points of the stomach compared with control. IHB in cirrhotic patients was not significantly different from control. ISO2 of post-EVL was significantly lower than that of pre-EVL, whereas IHB of post-EVL revealed significantly higher than that of pre-EVL. However, endoscopic grade of PHG remained mild. The hemodynamics of the mucosa two weeks after the initial EVL showed improvement of the congestion. CONCLUSIONS The gastric mucosal hemodynamics showed increment of the gastric blood volume and decreased hemoglobin O2 saturation in cirrhotic patients, indicating that cirrhotic gastric mucosa is in congestive condition. EVL for esophageal varices makes the gastric mucosa more congestive soon after the procedure in spite of the same grade of endoscopic PHG. However, the worsened congestion improves within a few weeks.