Endoscopic Removal of Premalignant Lesions Reduces Long-Term Colorectal Cancer Risk: Results From the Japan Polyp Study.

BACKGROUND & AIMS: To date, no regional evidence of long-term colorectal cancer (CRC) risk reduction after endoscopic premalignant lesion removal has been established. We aimed to analyze this over a long-term follow-up evaluation. METHODS: This was a prospective cohort study of participants from the Japan Polyp Study conducted at 11 Japanese institutions. Participants underwent scheduled follow-up colonoscopies after a 2-round baseline colonoscopy process. The primary outcome was CRC incidence after randomization. The observed/expected ratio of CRC was calculated using data from the population-based Osaka Cancer Registry. Secondary outcomes were the incidence and characteristics of advanced neoplasia (AN). RESULTS: A total of 1895 participants were analyzed. The mean number of follow-up colonoscopies and the median follow-up period were 2.8 years (range, 1-15 y) and 6.1 years (range, 0.8-11.9 y; 11,559.5 person-years), respectively. Overall, 4 patients (all males) developed CRCs during the study period. The observed/expected ratios for CRC in all participants, males, and females, were as follows: 0.14 (86% reduction), 0.18, and 0, respectively, and 77 ANs were detected in 71 patients (6.1 per 1000 person-years). Of the 77 ANs detected, 31 lesions (40.3%) were laterally spreading tumors, nongranular type. Nonpolypoid colorectal neoplasms (NP-CRNs), including flat (<10 mm), depressed, and laterally spreading, accounted for 59.7% of all detected ANs. Furthermore, 2 of the 4 CRCs corresponded to T1 NP-CRNs. CONCLUSIONS: Endoscopic removal of premalignant lesions, including NP-CRNs, effectively reduced CRC risk. More than half of metachronous ANs removed by surveillance colonoscopy were NP-CRNs. The Japan Polyp Study: University Hospital Medical Information Network Clinical Trial Registry: University Hospital Medical Information Network Clinical Trial Registry, C000000058; cohort study: UMIN000040731.

Randomised comparison of postpolypectomy surveillance intervals following a two-round baseline colonoscopy: the Japan Polyp Study Workgroup.

OBJECTIVE: To assess whether follow-up colonoscopy after polypectomy at 3 years only, or at 1 and 3 years would effectively detect advanced neoplasia (AN), including nonpolypoid colorectal neoplasms (NP-CRNs). DESIGN: A prospective multicentre randomised controlled trial was conducted in 11 Japanese institutions. The enrolled participants underwent a two-round baseline colonoscopy (interval: 1 year) to remove all neoplastic lesions. Subsequently, they were randomly assigned to undergo follow-up colonoscopy at 1 and 3 years (2-examination group) or at 3 years only (1-examination group). The incidence of AN, defined as lesions with low-grade dysplasia ≥10 mm, high-grade dysplasia or invasive cancer, at follow-up colonoscopy was evaluated. RESULTS: A total of 3926 patients were enrolled in this study. The mean age was 57.3 (range: 40-69) years, and 2440 (62%) were male. Of these, 2166 patients were assigned to two groups (2-examination: 1087, 1-examination: 1079). Overall, we detected 29 AN in 28 patients at follow-up colonoscopy in both groups. On per-protocol analysis (701 in 2-examination vs 763 in 1-examination group), the incidence of AN was similar between the two groups (1.7% vs 2.1%, p=0.599). The results of the non-inferiority test were significant (p=0.017 in per-protocol, p=0.001 in intention-to-treat analysis). NP-CRNs composed of dominantly of the detected AN (62%, 18/29), and most of them were classified into laterally spreading tumour non-granular type (83%, 15/18). CONCLUSION: After a two-round baseline colonoscopy, follow-up colonoscopy at 3 years detected AN, including NP-CRNs, as effectively as follow-up colonoscopies performed after 1 and 3 years.

Safety and efficacy of endoscopic submucosal dissection of rectal tumors extending to the dentate line.

BACKGROUND AND STUDY AIMS: Unique anatomical features render endoscopic resection for rectal tumors extending to the dentate line (RTDL) technically challenging. The aim of this study was to evaluate the feasibility of endoscopic submucosal dissection (ESD) for RTDLs. PATIENTS AND METHODS: This retrospective study compared ESD for RTDLs with proximal rectal tumors between September 2002 and June 2012. En bloc resection rate, R0 resection rate, complications, and tumor recurrences were assessed. RESULTS: A total of 45 RTDLs (median age 69 years; 15 males; median lesion size 38.4 mm) and 94 proximal rectal tumors were identified. En bloc resection and R0 resection rates were 95.6 % (43/45) and 53.3 % (24/45), respectively. The perforation rate was 4.4 %. Compared with proximal rectal ESD, ESD for RTDLs showed longer procedure time (104 vs. 60 minutes; P < 0.001), lower R0 resection rate (53.3 % vs. 70.2 %; P = 0.019), and more frequent high grade fever (22.2 % vs. 4.3 %; P = 0.002). No residual adenoma was observed at the first surveillance colonoscopy. Recurrence rate did not differ significantly between the two groups. CONCLUSIONS: ESD for RTDLs demonstrated safety and effectiveness comparable to ESD in proximal rectal lesions.

Long-term outcomes after resection for submucosal invasive colorectal cancers.

BACKGROUND & AIMS: Little is known about the long-term outcomes of patients with submucosal invasive colorectal cancer who undergo endoscopic or surgical resection. We performed a retrospective analysis of long-term outcomes of patients treated for submucosal colon and rectal cancer. METHODS: We collected data on 549 patients with submucosal colon cancer and 209 patients with submucosal rectal cancer who underwent endoscopic or surgical resection at 6 institutions over a median follow-up period of 60.5 months. Patients were classified into one of 3 groups: low-risk patients undergoing only endoscopic resection (group A), high-risk patients undergoing only endoscopic resection (group B), and high-risk patients undergoing surgical resection that included lymph node dissection (group C). We assessed recurrence rates, 5-year disease-free survival, and 5-year overall survival. Cox regression analysis was used to compare recurrences. RESULTS: The rates of recurrence, disease-free survival, and overall survival in group A for submucosal colon and rectal cancer were 0% versus 6.3% (P < .05), 96% versus 90%, and 96% versus 89%, respectively. For group B, these values were 1.4% versus 16.2% (P < .01), 96% versus 77% (P < .01), and 98% versus 96%, respectively; local recurrence was observed in 5 patients (one with submucosal colon cancer and 4 with submucosal rectal cancer). Tumor location was the only factor that contributed significantly to disease recurrence and death (hazard ratio, 6.73; P = .045). For group C, these values were 1.9% versus 4.5%, 97% versus 95%, and 99% versus 97%, respectively. CONCLUSIONS: The risk for local recurrence was significantly higher in high-risk patients with submucosal rectal cancer than in patients with submucosal colon cancer when treated with only endoscopic resection. The addition of surgery is therefore recommended for patients with submucosal rectal cancer with pathologic features indicating a high risk of tumor progression; University Hospital Medical Network Clinical Trials Registry, Number: UMIN 000008635.

A large-scale multicenter study of long-term outcomes after endoscopic resection for submucosal invasive colorectal cancer.

BACKGROUND AND STUDY AIMS: Patients with submucosal invasive colorectal cancer (SM-CRC) treated with endoscopic resection who are at low risk of lymph node metastasis and local recurrence may be followed up with observation alone, while additional surgery is recommended for those with high risk features. However, the long-term outcomes that these strategies offer are still unclear. The objective of our study was to retrospectively evaluate the long-term outcomes of patients with SM-CRC managed with endoscopic resection. PATIENTS AND METHODS: We retrospectively analyzed all patients with SM-CRC treated by endoscopic resection at six institutions between 2000 and 2007. SM-CRCs with (i) negative vertical margin, (ii) well or moderately differentiated adenocarcinoma, (iii) absence of lymphovascular invasion, and (iv) invasion depth < 1000 µm were classified as low risk. Patients with SM-CRCs without these characteristics were classified as high risk. Outcomes were assessed by 5-year recurrence-free survival (RFS) and recurrence rate. RESULTS: During the study period, 428 patients with SM-CRC (low risk, 126; high risk, 302) who underwent endoscopic resection as their first treatment were enrolled (median follow-up 61 months). Among the 120 patients with low risk features treated by endoscopic resection alone, the 5-year RFS and recurrence rates were 98 % and 0.8 %, respectively. Of the 302 patients with high risk features, 196 underwent additional surgery and 106 were managed with endoscopic resection alone. For those who underwent additional surgery, the 5-year RFS and recurrence rates were 97 % and 3.6 %, respectively. Among the 106 patients managed with endoscopic resection alone, RFS and recurrence rates were 89 % (P < 0.05 vs. low risk patients treated by endoscopic resection alone) and 6.6 % (P < 0.05), respectively. CONCLUSIONS: Endoscopic resection alone is adequate for the management of patients with SM-CRC and low risk features. However, in those patients with SM-CRC and high risk features, surgery should be considered in addition to endoscopic resection.

Criteria for non-surgical treatment of perforation during colorectal endoscopic submucosal dissection.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) has recently been applied in the treatment of large colorectal tumors. However, indications for emergent surgery and criteria for conservative treatment of perforation remain unclear. The aim of this study was to clarify the criteria for non-surgical treatment of perforation during colorectal ESD. METHODS: 219 colorectal tumors in 215 patients (136 men and 79 women; median age 69 years) were removed by performing ESD. The procedural outcomes, complications, prognoses, and criteria for non-surgical treatment of perforation were retrospectively analyzed by using our prospectively corrected database. RESULTS: The en-bloc and complete en-bloc resection rates were 92.7% (203/219) and 85.8% (188/219), respectively. The rate of discontinued ESD was 2.3% (5/219). The immediate and delayed perforation rates were 5.0% (11/219) and 0%, respectively. One of these patients required emergent surgery because of a residual lesion and localized peritonitis caused by an unsuccessful closure. The other 10 patients recovered with conservative treatment after successful closure with hemoclips and complete resection. The defects in all patients were successfully closed by using hemoclips. None of the patients had signs of diffuse peritonitis. The other factors, i.e. absence of localized peritonitis, high-grade fever, and acceleration of inflammatory reaction, were not associated with the success or the failure of the non-surgical treatment. CONCLUSIONS: The criteria for non-surgical treatment of perforation caused by colonic ESD were absence of diffuse peritonitis and successful closure.

A resected case of focal autoimmune pancreatitis with pancreatic duct wall thickening representing periductal lymphoplasmacytic infiltrate.

This case revealed that branch pancreatic duct wall thickening by endoscopic ultrasonography represented periductal lymphoplasmacytic infiltrate as a characteristic histopathological finding of autoimmune pancreatitis, which may help in the diagnosis of autoimmune pancreatitis. An 80-year-old man was referred because fluorodeoxyglucose-positron emission tomography for lung cancer indicated abnormal uptake in the pancreatic head. Computed tomography showed an enhanced mass with cystic structures in the pancreatic head. Magnetic resonance cholangiopancreatography revealed mild dilatation of the main pancreatic duct in the pancreatic body with no strictures. Endoscopic ultrasonography demonstrated a lobulated heterogeneous hypoechoic mass in the pancreatic head. A branch pancreatic duct with wall thickening connected the mass to the main pancreatic duct. An intraductal neoplasm filling and spreading into the branch pancreatic duct was considered, and surgery was performed. Histopathologically, the mass consisted of marked inflammatory cell infiltration, storiform fibrosis, and obliterative phlebitis. The branch pancreatic duct with wall thickening revealed a band-like inflammatory cell infiltration with mainly lymphocytes and plasma cells beneath the normal pancreatic duct epithelium. Immunohistological staining revealed abundant IgG4-positive plasma cells (> 10 cells/HPF) in the inflammatory cell infiltration. The definite diagnosis was type 1 focal autoimmune pancreatitis.

Local recurrence and surveillance after endoscopic resection of large colorectal tumors.

Local recurrence rates after endoscopic piecemeal mucosal resection (EPMR) typically range from 10 to 23%. In our previous study, the local recurrence rate after a piecemeal resection was significantly higher than that after an en bloc resection, irrespective of tumor size or macroscopic features. To reduce local recurrence after an EPMR, it is important to carefully note the circumferences of the edge and base of the ulcer. Recently, endoscopic submucosal dissection (ESD) was developed and recognized for its effectiveness in large, complete, en bloc resections and precise pathological assessments. ESD also showed lower local recurrence rates, ranging from 0 to 3% in previous, retrospective studies. However, ESD showed a higher perforation rate and longer procedure times; thus, it is necessary to improve ESD. An appropriate surveillance interval after EPMR was still controversial, and recommendations of some guidelines ranged from 2 to 9 months. In order to determine the appropriate interval, a randomized controlled study is necessary.

Learning curve for endoscopic submucosal dissection of large colorectal tumors.

BACKGROUND AND AIM: No studies have previously described the learning curve for colonic endoscopic submucosal dissection (ESD). The aim of the present study was to describe the learning curve for ESD of large colorectal tumors based on a single colonoscopist's experience. METHODS: ESD was carried out for 120 colorectal tumors in 115 patients (68 males, median age 70 years). All procedures were carried out by a single experienced colonoscopist. The cases were grouped chronologically into three periods: (1st): cases 1-40; (2nd): cases 41-80; and (3rd): cases 81-120. RESULTS: The learning curve was the changes in proficiency over time. Proficiency was expressed as procedure time per unit area of specimen. In the 1st, 2nd and 3rd periods, the proficiencies were 18.9, 12.6 and 12.9 (min/cm(2) ), respectively. The proficiencies in the 2nd and 3rd periods were significantly shorter than in the 1st period (t-test, P < 0.05). The en-bloc resection rates of the 1st, 2nd and 3rd periods were 92.5% (37/40), 90% (36/40) and 97.5% (39/40), respectively. The en-bloc and R0 resection rates of the 1st, 2nd and 3rd periods were 85% (34/40), 77.5% (31/40) and 92.5% (37/40), respectively. The perforation rates of the 1st, 2nd and 3rd periods were 12.5% (5/40), 5% (2/40) and 5% (2/40), respectively. CONCLUSION: Based on our analysis of the learning curve, approximately 80 procedures must be carried out to acquire skill with ESD for large colorectal tumors. However, approximately 40 procedures were sufficient to acquire skill in avoiding perforations during the ESD procedure.

Usefulness and Limitations of a Serum Screening System to Predict the Risk of Gastric Cancer.

Objective The aim of the present study was to evaluate the effectiveness and limitations of a serum screening system for predicting the risk of gastric cancer. Methods Serum pepsinogen I (PG I)/pepsinogen II (PG II) and Helicobacter pylori (HP) antibody levels were measured. Subjects were classified into four groupsaccording to their serological status (the ABC classification system). The grade of atrophic gastritis was assessed endoscopically. We evaluated gastric cancer detection rates according to the ABC classification system and the endoscopic grade of atrophy. Patients Individuals who underwent esophagogastroduodenoscopy (EGD) in a health check were prospectively enrolled in the present study. Results According to the ABC classification system, the gastric cancer detection rates in groups A, B, C, and D were 0.07% (4/6,105), 0.5% (8/1,739), 0.8% (16/2,010), and 1.1% (3/281), respectively. The gastric cancer detection rates in subjects with no atrophy, closed type (C-type) atrophy, and open type (O-type) atrophy were 0% (0/4,567), 0.2% (4/2,581), and 0.9% (27/2,987), respectively. In group A (HP(-)/PG(-)), the proportions of subjects with no atrophy, C-type atrophy, and O-type atrophy were 71.2%, 22.8%, and 6.0%, respectively. In group A, the gastric cancer detection rates in subjects with no atrophy, C-type atrophy, and O-type atrophy were 0%, 0.07%, and 0.8%, respectively. Conclusion The ABC classification system is useful for predicting the risk of gastric cancer. However, this system was limited in group A, which included individuals with a high risk of developing gastric cancer. An endoscopic diagnosis of atrophy may be more effective than the ABC classification system for predicting the risk of gastric cancer.

Progression of a sessile serrated adenoma to an early invasive cancer within 8 months.

Recent studies suggest that serrated polyps, including hyperplastic polyps, traditional serrated adenomas, and sessile serrated adenomas, may be morphologically and genetically distinct and linked to microsatellite unstable colorectal cancers, and thus the concept of a hyperplastic polyp-serrate adenoma-carcinoma pathway has been suggested. Furthermore, it has been suggested that transformation from serrated polyps to invasive cancers can be rapid and occurs when the lesions are small; however, direct evidence for this issue is scant. We herein describe a case of a sessile serrated adenoma showing rapid transformation into a submucosal invasive carcinoma with remarkable morphological change in a short period of 8 months. This case is unique and suggestive, as it provided information about the natural history of a sessile serrated adenoma.

Efficacy and Safety of Adsorptive Granulocyte and Monocyte Apheresis in Elderly and Pregnant Patients With Ulcerative Colitis.

In patients with active ulcerative colitis (UC), adsorptive granulocyte/monocyte apheresis (GMA) is expected to promote remission. We conducted a retrospective cohort study to evaluate the efficacy and safety of GMA in patients with active UC. Twenty-one UC patients including five pregnant or lactating mothers and four elderly patients (aged >60 years) received up to 10 GMA sessions. UC severity was evaluated at baseline and after GMA therapy according to Lichtiger's Clinical Activity Index (CAI). We defined clinical remission as CAI ≤4. Overall, the median CAI score after GMA therapy had decreased from 9 to 4 (P < 0.001). The clinical remission rate was 62%, but in the elderly and pregnant or lactating mothers, the remission rates were 100% and 60%, respectively. No severe adverse effects were seen in this study. Our results may support GMA as an effective and safe treatment for active UC patients, including elderly patients and pregnant cases.