Shinichi Katsuki

Aberrant Crypt Foci of the Colon as Precursors of Adenoma and Cancer

Background Aberrant crypt foci of the colon are possible precursors of adenoma and cancer, but these lesions have been studied mainly in surgical specimens from patients who already had colon cancer. Methods Using magnifying endoscopy, we studied the prevalence, number, size, and dysplastic features of aberrant crypt foci and their distribution according to age in 171 normal subjects, 131 patients with adenoma, and 48 patients with colorectal cancer. We also prospectively examined the prevalence of aberrant crypt foci in 11 subjects (4 normal subjects, 6 with adenoma, and 1 with cancer) before and after the administration of 100 mg of sulindac three times a day for 8 to 12 months and compared the results with those in 9 untreated subjects (4 normal subjects and 5 with adenoma). All 20 subjects had aberrant crypt foci at base line. Results We identified 3155 aberrant crypt foci, 161 of which were dysplastic; the prevalence and number increased with age. There were significant (P<0.001) correlations between...

Argon plasma coagulation for successful treatment of early gastric cancer with intramucosal invasion.

Background: In recent years, there has been an increasing number of cases of early gastric cancer (T1, NX) with intramucosal invasion, which are untreatable by surgical or endoscopic mucosal resection (EMR) because of their high risk. Currently, no adequate treatment is available for such patients. Aim: The main objective of this study was to evaluate whether argon plasma coagulation (APC) is an effective and safe modality for treating early gastric cancer untreatable by surgical resection or EMR. Methods: The study group comprised 20 men and seven women diagnosed with gastric cancer with intramucosal invasion who were considered poor candidates for surgical resection or EMR due to risk factors such as severe cardiac failure or thrombocytopenia. Irradiation conditions for APC treatment were determined using swine gastric mucosa. We used an argon gas flow of 2 l/min at a power setting of 60 W and a maximum irradiation time of 15 s/cm2. The follow up period of the 27 patients ranged from 18 to 49 months (median 30 months). Results: All lesions were irradiated easily, including areas anatomically difficult for EMR such as the gastric cardia or the posterior wall of the upper gastric body. In 26 of 27 patients (96%) there was no evidence of recurrence during the follow up period (median 30 months). One patient showed recurrence six months after the treatment but was successfully retreated. No serious complications were found in any of the 27 patients but three patients (11%) experienced a feeling of abdominal fullness. Interpretation: APC is a safe and effective modality for treatment of early gastric cancer with intramucosal invasion untreatable by surgical resection or EMR. However, further observations are necessary to determine the long term prognosis of patients undergoing this treatment.

Aberrant Crypt Foci as Precursors of the Dysplasia-Carcinoma Sequence in Patients with Ulcerative Colitis

Purpose: Long-standing ulcerative colitis (UC) predisposes patients to the development of colorectal cancer, but surveillance of colitis-associated cancer by detecting the precancerous lesion dysplasia is often difficult because of its rare occurrence and normal-looking appearance. In sporadic colorectal cancer, aberrant crypt foci (ACF) have been reported by many investigators to be precursor lesions of the adenoma-carcinoma sequence. In the present study, we analyzed the genetic background of ACF to determine whether they could be precursors for dysplasia, and we examined the usefulness of endoscopic examination of ACF as a surrogate marker for surveillance of colitis-associated cancer. Experimental Design: ACF were examined in 28 UC patients (19 patients with UC alone and 9 patients with UC and dysplasia; 2 of those patients with dysplasia also had cancer) using magnifying endoscopy. K-ras, APC, and p53 mutations were analyzed by two-step PCR RFLP, in vitro–synthesized protein assay, and single-strand conformation polymorphism, respectively. Methylation of p16 was analyzed by methylation-specific PCR. Results: ACF that appeared distinct endoscopically and histologically were identified in 27 out of 28 UC patients. They were negative for K-ras, APC, and p53 mutations but were frequently positive for p16 methylation (8 of 11; 73%). In dysplasia, K-ras and APC mutations were negative but p53 mutation (3 of 5; 60%) and p16 methylation (3 of 5; 60%) were positive. There was a significant stepwise increase in the number of ACF from patients with UC alone to patients with dysplasia and to patients with cancer. Univariate and multivariate analyses showed significant correlations between ACF and dysplasia. Conclusions: We have disclosed an ACF-dysplasia-cancer sequence in colitis-associated carcinogenesis similar to the ACF-adenoma-carcinoma sequence in sporadic colon carcinogenesis. This study suggests the use of ACF instead of dysplasia for the surveillance of colitis cancer and warrants further evaluation of ACF as a surveillance marker in large-scale studies.

A multicenter, prospective trial of total colonoscopy using a short double-balloon endoscope in patients with previous incomplete colonoscopy

BACKGROUND There is no specific insertion method for patients who previously underwent an incomplete colonoscopy. No multicenter prospective study using a double-balloon endoscope (DBE) for total colonoscopy was previously performed. OBJECTIVE To demonstrate the effectiveness and safety of using short DBEs in patients who previously underwent incomplete colonoscopies. DESIGN A multicenter, prospective trial. SETTING Four tertiary care academic centers and 6 community hospitals. PATIENTS Patients with a history of incomplete colonoscopy, ages 20 to 79 years, were included. Exclusion criteria were colonoscopy performed by endoscopists with experience in fewer than 1000 cases, history of colectomy, poor bowel preparation, inflammatory bowel disease, active bowel obstruction, and active bleeding. INTERVENTION Total colonoscopies using short DBEs were attempted in all patients. MAIN OUTCOME MEASUREMENTS Primary endpoint was the cecal intubation rate. Secondary endpoints were time to cecal intubation, complications, and tolerability. RESULTS A total of 110 patients (62 males, median age 66.5 years) were included. Fifty-four patients had a history of abdominal surgery. The cecal intubation rate was 100% (110/110). Median intubation time was 12 minutes (range 4-47 minutes). Mild mucosal tears without symptoms occurred in 1 patient. For 64.5% of patients, intravenous sedatives and/or analgesics were used during examinations. Based on questionnaires, 50.9% had no pain, 31.8% slight pain, and 17.3% tolerable pain. Moreover, 96.4% of patients answered that their examination was more comfortable than their previous colonoscopy. LIMITATION Uncontrolled trial. CONCLUSION The use of a short DBE is an effective and safe method for total colonoscopy in patients who previously underwent incomplete colonoscopies. ( CLINICAL TRIAL REGISTRATION NUMBER UMIN3464.).

Diagnostic and Therapeutic Endoscopic Retrograde Cholangiography Using a Short-Type Double-Balloon Endoscope in Patients With Altered Gastrointestinal Anatomy: A Multicenter Prospective Study in Japan

OBJECTIVES:To evaluate the utility and safety of a short-type double-balloon endoscope (DBE) in the treatment of biliary disease in patients with surgically altered gastrointestinal (GI) anatomy.METHODS:This study was conducted as a multicenter, single-arm, prospective trial at five tertiary academic care centers and three community-based hospitals in Japan. Consecutive patients with biliary disease with altered GI anatomy were prospectively included in this study.RESULTS:A total of 311 patients underwent double-balloon endoscopic retrograde cholangiography (ERC). The success rate of reaching the target site, the primary end point, was 97.7% (95% confidence interval (CI): 95.4–99.1). The success rate of biliary cannulation and contrast injection of the targeted duct, the secondary end point, was 96.4% (95% CI: 93.6–98.2), and the therapeutic success rate was 97.9% (95% CI: 95.4–99.2). Adverse events occurred in 33 patients (10.6%, 95% CI: 7.1–14.0) and were managed conservatively in all patients with the exception of 1 in whom a perforation developed, requiring emergency surgery.CONCLUSIONS:ERC using a short-type DBE resulted in an excellent therapeutic success rate and a low rate of adverse events. This treatment can be a first-line treatment for biliary disease in patients with surgically altered GI anatomy.

Exacerbation of bloody diarrhea as a side effect of mesalamine treatment of active ulcerative colitis.

Mesalamine has been used as the first-line therapy for the treatment of ulcerative colitis (UC) because of its efficacy and fewer side effects. However, earlier study showed that mesalamine occasionally causes diarrhea. We are presenting a patient with active UC in whom bloody diarrhea accompanied by abdominal pain and fever occurred and the symptoms were aggravated after administration of mesalamine. In order to clarify the reason of symptoms aggravation, drug lymphocyte stimulation test and rechallenge trial with mesalamine were performed. The results indicated the possibility that aggravation was related to allergic reaction and was dose-dependent. Furthermore, we examined colonoscopic views but there was no remarkable change in before and after rechallenge trial. Based on the above result, the patient was diagnosed with mesalamine intolerance. In order to differentiate whether the exacerbation of bloody diarrhea is due to the side effects of the mesalamine or a true relapse of UC, taking careful history before and after increasing mesalamine dosage as well as being aware of side effects of mesalamine are required. Clinicians should be aware of diarrhea as a side effect of mesalamine particularly after onset of mesalamine formulation, change in mesalamine formulation, or change in mesalamine dose.

Clinical and endoscopic features of acute hemorrhagic rectal ulcer

BackgroundAcute hemorrhagic rectal ulcer (AHRU) has increasingly been reported in Japan, whereas it has rarely been reported in the English literature and is not yet established as a disease entity. The aim of this study was to elucidate clinical and endoscopic characteristics of patients with AHRU.MethodsWe enrolled 20 patients with 26 ulcers diagnosed as AHRU in our department between January 2001 and October 2005. Clinical features such as the underlying disorder, Karnofsky performance status (PS), and presence or absence of anticoagulant or antiplatelet therapy, as well as endoscopic findings and type of bleeding, were evaluated. Strategies for hemostasis were also reviewed.ResultsThe most prevalent underlying disorder was diabetes mellitus, and the number of bedridden patients with PS 4 was relatively high. In addition, more than half of the patients had been treated with anticoagulant or antiplatelet agents. Endoscopically, ulcers were characteristically solitary and irregularly shaped, and they did not show any typical localization pattern. As a hemostatic strategy, clipping alone showed a favorable result, with a hemostatic success rate as high as 76.9%.ConclusionsThis study may support the establishment of AHRU as a new clinical entity. In aged patients being treated with anticoagulant or antiplatelet agents, especially bedridden patients using aspirin, the possible appearance of this disease should be kept in mind.

Gastrografin as an alternative booster to sodium phosphate in colon capsule endoscopy: safety and efficacy pilot study.

Background and study aims: Sodium phosphate is a key component of bowel preparation regimen for colon capsule endoscopy (CCE), but may cause serious complications. The aim of this study is to evaluate the use of Gastrografin, substituted for sodium phosphate, in CCE bowel preparation. Patients and methods: In total, 29 patients (median age 64 years; 23 females) underwent CCE, covered by the national health insurance system of Japan. All had a history of laparotomy and/or previously incomplete colonoscopy. On the day before examination, patients ingested 1 L of polyethylene glycol + ascorbic acid with 0.5 L of water in the evening, and again the same laxative on the morning of examination. After capsule ingestion, 50 mL of Gastrografin diluted with 0.9 L of magnesium citrate was administered, and then repeated after 1 hour. Results: The capsule excretion rate was 97 % (28/29). The median colon transit time was 2 hours 45 minutes and rapid transit (< 40 minutes) through the colon occurred in one patient (3.4 %). Bowel cleansing level was adequate in 90 % of patients. The polyp (≥ 6 mm) detection rate was 52 %. Diluted Gastrografin was well tolerated by patients. No adverse events occurred. Conclusion: Gastrografin can be an alternative to sodium phosphate in CCE bowel preparation regimen.

Selective Embolization of the Splenic Vein in Patients with Hepatic Encephalopathy and Splenorenal Shunt

Obliteration of portal-systemic shunts is effective for portosystemic encephalopathy but is often associated with complications such as retention of ascites and worsening of esophageal varices. Selective embolization of the splenic vein was performed on six patients with hepatic encephalopathy and splenorenal shunts. Hepatic encephalopathy was not observed in four patients after the procedure. Neither retention of ascites nor rupture of esophageal varices was observed because postoperative elevation of portal venous pressure was not as great as that seen when shunt obliteration is performed. This procedure can be an effective and safe treatment option for hepatic encephalopathy with a splenorenal shunt.

Efficacy and safety of endoscopic interventions using the short double-balloon endoscope in patients after incomplete colonoscopy

We have previously reported excellent cecal intubation rates using a short double‐balloon endoscope in patients with a history of incomplete colonoscopy. However, data on the endoscopic treatment of colorectal tumors using a double‐balloon endoscope are limited. The aim of the present study was to evaluate the efficacy and safety of endoscopic intervention of colorectal tumors using a short double‐balloon endoscope.