Yoshitaka Murakami

Long-term Outcomes After Resection for Submucosal Invasive Colorectal Cancers

BACKGROUND & AIMSnLittle 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.nnnMETHODSnWe 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnThe 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.

Diagnostic accuracy of narrow-band imaging and pit pattern analysis significantly improved for less-experienced endoscopists after an expanded training program

BACKGROUNDnPrevious reports assessing diagnostic skill using narrow-band imaging (NBI) and pit pattern analysis for colorectal polyps involved only highly experienced endoscopists.nnnOBJECTIVEnTo evaluate diagnostic skills of less-experienced endoscopists (LEE group) for differentiation of diminutive colorectal polyps by using NBI and pit pattern analysis with and without magnification after an expanded training program.nnnDESIGNnProspective study.nnnPATIENTSnThis study involved 32 patients with 44 colorectal polyps (27 adenomas and 17 hyperplastic polyps) of < or =5 mm that were identified and analyzed by using conventional colonoscopy as well as non-magnification and magnification NBI and chromoendoscopy followed by endoscopic removal for histopathological analysis.nnnINTERVENTIONnBefore a training course, 220 endoscopic images were distributed in randomized order to residents with no prior endoscopy experience (NEE group) and to the LEE group, who had performed colonoscopies for more than 5 years but had never used NBI. The 220 images were also distributed to highly experienced endoscopists (HEE group) who had routinely used NBI for more than 5 years. The images were distributed to the NEE and LEE groups again after a training class. Magnification NBI and chromoendoscopy images were assessed by using the Sano and Kudo classification systems, respectively.nnnMAIN OUTCOME MEASUREMENTSnDiagnostic accuracy and interobserver agreement for each endoscopic modality in each group.nnnRESULTSnDiagnostic accuracy was significantly higher, and kappa (kappa) values improved in the LEE group for NBI with high magnification after expanded training. Diagnostic accuracy and kappa values when using high-magnification NBI were highest among endoscopic techniques for the LEE group after such training and the HEE group (accuracy 90% vs 93%; kappa = 0.79 vs 0.85, respectively).nnnLIMITATIONSnStudy involved only polyps of < or =5 mm.nnnCONCLUSIONnUsing high-magnification NBI increased the differential diagnostic skill of the LEE group after expanded training so that it was equivalent to that of the HEE group.

Effects of prehypertension and hypertension subtype on cardiovascular disease in the Asia-Pacific Region

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure defined blood pressure (BP) levels of 120 to 139/80 to 89 mm Hg as prehypertension and those of ≥140/90 mm Hg as hypertension. Hypertension can be divided into 3 categories, isolated diastolic (IDH; systolic BP <140 mm Hg and diastolic BP ≥90 mmHg), isolated systolic (systolic BP ≥140 mm Hg and diastolic BP <90 mmHg), and systolic-diastolic hypertension (systolic BP ≥140 mm Hg and diastolic BP ≥90 mmHg). Although there is clear evidence that isolated systolic hypertension and systolic-diastolic hypertension increase the risks of future vascular events, there remains uncertainty about the effects of IDH. The objective was to determine the effects of prehypertension and hypertension subtypes (IDH, isolated systolic hypertension, and systolic-diastolic hypertension) on the risks of cardiovascular disease (CVD) in the Asia-Pacific Region. The Asia Pacific Cohort Studies Collaboration is an individual participant data overview of cohort studies in the region. This analysis included a total of 346570 participants from 36 cohort studies. Outcomes were fatal and nonfatal CVD. The relationship between BP categories and CVD was explored using a Cox proportional hazards model adjusted for age, cholesterol, and smoking and stratified by sex and study. Compared with normal BP (<120/80 mmHg), hazard ratios (95% CIs) for CVD were 1.41 (1.31–1.53) for prehypertension, 1.81 (1.61–2.04) for IDH, 2.18 (2.00–2.37) for isolated systolic hypertension, and 3.42 (3.17–3.70) for systolic-diastolic hypertension. Separately significant effects of prehypertension and hypertension subtypes were also observed for coronary heart disease, ischemic stroke, and hemorrhagic stroke. In the Asia-Pacific region, prehypertension and all hypertension subtypes, including IDH, thus clearly predicted increased risks of CVD.

Large-Scale Investigation into Dumping Syndrome after Gastrectomy for Gastric Cancer

BACKGROUNDnThe aim of this study was to investigate early and late dumping syndromes in a large number of patients after gastrectomy for gastric cancer.nnnSTUDY DESIGNnResponses to questions on a visual analogue scale survey completed by 1,153 gastrectomy patients were analyzed for associations between clinical factors and occurrence of dumping syndrome. Types of gastrectomy included distal gastrectomy with Billroth I or with Roux-Y reconstruction, pylorus preserving gastrectomy, proximal gastrectomy, and total gastrectomy.nnnRESULTSnBased on the visual analogue scale rating of symptomatic discomfort, patients were categorized into 1 of 2 groups: symptom-free or symptomatic. Incidences of early or late dumping syndrome in all patients were 67.6% and 38.4%, respectively. Patients in whom early dumping syndrome developed were significantly more likely to experience late dumping syndrome than those in whom it did not develop (p < 0.001). According to multivariate analyses, factors that decreased the risk for developing early dumping syndrome were reduced weight loss (p < 0.01), old age (p < 0.01), pylorus preserving gastrectomy (p < 0.01), distal gastrectomy with Roux-Y reconstruction (p < 0.01), and distal gastrectomy with Billroth I (p = 0.019). In addition, factors that decreased the risk of developing late dumping syndrome were reduced weight loss (p = 0.03), being male (p < 0.01), pylorus preserving gastrectomy (p < 0.01), and distal gastrectomy with Roux-Y reconstruction (p < 0.01). No other clinical factors (lymph node dissection, vagal nerve preservation, and postoperative period) showed a substantial association with the occurrence of dumping syndrome in multivariate analyses.nnnCONCLUSIONSnSubstantially more patients suffered from early dumping syndrome than late dumping syndrome after gastrectomy. Two clinical factors, surgical procedures and amount of body weight loss, associated significantly with the occurrence of both early and late dumping syndrome.

The genetics underlying acquired long QT syndrome: impact for genetic screening

AIMSnAcquired long QT syndrome (aLQTS) exhibits QT prolongation and Torsades de Pointes ventricular tachycardia triggered by drugs, hypokalaemia, or bradycardia. Sometimes, QTc remains prolonged despite elimination of triggers, suggesting the presence of an underlying genetic substrate. In aLQTS subjects, we assessed the prevalence of mutations in major LQTS genes and their probability of being carriers of a disease-causing genetic variant based on clinical factors.nnnMETHODS AND RESULTSnWe screened for the five major LQTS genes among 188 aLQTS probands (55 ± 20 years, 140 females) from Japan, France, and Italy. Based on control QTc (without triggers), subjects were designated true aLQTS (QTc within normal limits) or unmasked cLQTS (all others) and compared for QTc and genetics with 2379 members of 1010 genotyped congenital long QT syndrome (cLQTS) families. Cardiac symptoms were present in 86% of aLQTS subjects. Control QTc of aLQTS was 453 ± 39 ms, shorter than in cLQTS (478 ± 46 ms, P < 0.001) and longer than in non-carriers (406 ± 26 ms, P < 0.001). In 53 (28%) aLQTS subjects, 47 disease-causing mutations were identified. Compared with cLQTS, in true aLQTS, KCNQ1 mutations were much less frequent than KCNH2 (20% [95% CI 7-41%] vs. 64% [95% CI 43-82%], P < 0.01). A clinical score based on control QTc, age, and symptoms allowed identification of patients more likely to carry LQTS mutations.nnnCONCLUSIONnA third of aLQTS patients carry cLQTS mutations, those on KCNH2 being more common. The probability of being a carrier of cLQTS disease-causing mutations can be predicted by simple clinical parameters, thus allowing possibly cost-effective genetic testing leading to cascade screening for identification of additional at-risk family members.

Proportion of Flat- and Depressed-Type and Laterally Spreading Tumor Among Advanced Colorectal Neoplasia

BACKGROUND & AIMSnFlat- and depressed-type neoplasias along with laterally spreading tumors (LSTs) have been reported in colorectal neoplasias. We estimated the prevalence of flat and depressed types and LSTs along with their proportion among advanced neoplasias in a large average-risk population undergoing screening colonoscopy.nnnMETHODSnThis was a cross-sectional study performed at a single, general community institution, with subjects who were 40 to 79 years old, asymptomatic, and who had undergone their first colonoscopy for screening between 2003 and 2009 (n = 4910). Among the neoplasias detected, advanced neoplasias were morphologically classified as the polypoid type, flat and depressed type, or LST. We determined the prevalence and proportion for each type among the advanced neoplasias, with morphologies defined according to the Japanese endoscopic classification.nnnRESULTSnAdvanced neoplasias were detected in 7.9% of men, 4.7% of women, and 6.1% of overall subjects. The polypoid type, the flat and depressed types, and the LSTs accounted for 75.3%, 7.5%, and 17.2% of advanced neoplasia, respectively. There was a high proportion of T1 cancers among the depressed types (40%). Approximately 80% of LSTs were located on the right side of the colon and more than 30% of LSTs showed high-grade dysplasia or T1 cancer.nnnCONCLUSIONSnMost advanced neoplasias detected were of the polypoid type. LSTs accounted for a considerable proportion among advanced neoplasia and tended to be located on the right side of the colon. The influences of any LSTs need to be taken into consideration for preventing colorectal cancer.

NBI magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team (JNET)

Many clinical studies on narrow‐band imaging (NBI) magnifying endoscopy classifications advocated so far in Japan (Sano, Hiroshima, Showa, and Jikei classifications) have reported the usefulness of NBI magnifying endoscopy for qualitative and quantitative diagnosis of colorectal lesions. However, discussions at professional meetings have raised issues such as: (i) the presence of multiple terms for the same or similar findings; (ii) the necessity of including surface patterns in magnifying endoscopic classifications; and (iii) differences in the NBI findings in elevated and superficial lesions. To resolve these problems, the Japan NBI Expert Team (JNET) was constituted with the aim of establishing a universal NBI magnifying endoscopic classification for colorectal tumors (JNET classification) in 2011. Consensus was reached on this classification using the modified Delphi method, and this classification was proposed in June 2014. The JNET classification consists of four categories of vessel and surface pattern (i.e. Types 1, 2A, 2B, and 3). Types 1, 2A, 2B, and 3 are correlated with the histopathological findings of hyperplastic polyp/sessile serrated polyp (SSP), low‐grade intramucosal neoplasia, high‐grade intramucosal neoplasia/shallow submucosal invasive cancer, and deep submucosal invasive cancer, respectively.

Diagnosis of depth of invasion for early colorectal cancer using magnifying colonoscopy.

Background and Aims:u2002 Early colorectal cancer (CRC) with submucosal deep (s.m.‐d.) invasion should not be treated with endoscopic mucosal resection due to the higher incidence of lymph‐node metastasis. It is, therefore, clinically important to accurately diagnose s.m.‐d. lesions before treatment.

Trends in Disability-Free Life Expectancy in Japan, 1995–2004

Background In Japan, life expectancy at birth is currently the highest in the world. However, recent trends in disability-free life expectancy in Japan have not been examined. Methods We used data from Japanese national surveys for the period 1995–2004. These surveys included information on activity status measured by common self-reported instruments. The numbers of expected years with and without activity limitation were estimated by using the Sullivan method. Results The numbers of expected years of life without activity limitation, at birth, in 1995 and 2004 were 68.5 and 69.7, respectively, in males and 72.1 and 73.0 in females. As a proportion of total life expectancy, at birth, these values represent a decrease from 89.7% to 88.6% in males and from 87.1% to 85.3% in females. The proportion of expected years with a limitation of some activities except activities of daily living (ADL) increased in males and females. The proportion of those with an ADL limitation increased in females, but not in males. Conclusions The trends in expected years with and without activity limitation suggest that the duration of life with a light or moderate disability increased in Japanese males and females during the period 1995–2004.

Risk of lymph node metastasis in patients with pedunculated type early invasive colorectal cancer: A retrospective multicenter study

Depth of invasion in early invasive colorectal cancer is considered an important predictive factor for lymph node metastasis. However, no large‐scale reports have established the relationship between invasion depth of pedunculated type early invasive colorectal cancers and risk of lymph node metastasis. The aim of this retrospective cohort study was to clarify the risk of lymph node metastasis in pedunculated type early invasive colorectal cancers in a large series. Patients with pedunculated type early invasive colorectal cancer who underwent endoscopic or surgical resection at seven referral hospitals in Japan were enrolled. Haggitt’s line was used as baseline and the invasion depth was classified into two groups, head invasion and stalk invasion. The incidence of lymph node metastasis was investigated between patients with head and stalk invasion. We analyzed 384 pedunculated type early invasive colorectal cancers in 384 patients. There were 154, 156, and 74 endoscopic resection cases, endoscopic resection followed by surgical operation, and surgical resection cases, respectively. There were 240 head invasion and 144 stalk invasion lesions. Among the lesions treated surgically, the overall incidence of lymph node metastasis was 3.5% (8/230). The incidence of lymph node metastasis was 0.0% (0/101) in patients with head invasion, as compared with 6.2% (8/129) in patients with stalk invasion. Pedunculated type early invasive colorectal cancers pathologically diagnosed as head invasion can be managed by endoscopic treatment alone. (Cancer Sci 2011; 102: 1693–1697)