Novel physiological analysis using blood flow velocity for colonic polyps: Pilot study.

Real-time visualization of red blood cell flow inside subepithelial microvessels is performed with magnifying endoscopy. However, microvascular blood flow velocity in the colorectum has not been investigated. Here, we aimed to evaluate the blood flow velocity of microvessels of colonic polyps and to compare it with that of surrounding mucosa. We examined 50 lesions, including 30 adenomas (ADs) and 20 hyperplastic polyps (HPs). Blood flow velocities of lesions and their surrounding mucosa were evaluated using magnifying blue laser imaging (BLI) prior to endoscopic resection. Calculation of mean blood flow velocities was based on mean movement distance of one tagged red blood cell using split video images of magnifying BLI. Mean microvascular blood flow velocity was significantly lower in ADs (1.65±0.66 mm/sec; range 0.46-2.90) than in HPs (2.83±1.10 mm/sec; 1.07-4.50) or the surrounding mucosa (3.73±1.11 mm/sec; 1.80-6.20; P <0.001). The blood flow velocity rate compared with the surrounding mucosa was significantly lower in ADs (0.41±0.16; 0.10-0.82) than in HPs (0.89±0.25; 0.46-1.51; P <0.001). We found that mean microvascular blood flow velocity was significantly lower in ADs than in HPs and the surrounding non-neoplastic mucosa. These findings indicate that a novel dynamic approach with microvascular blood flow velocity using magnifying endoscopy may be useful in assessing physiological differences between ADs and HPs.

Validation study for development of the Japan NBI Expert Team classification of colorectal lesions.

BACKGROUND AND AIM: The Japan narrow-band imaging (NBI) Expert Team (JNET) was organized to unify four previous magnifying NBI classifications (the Sano, Hiroshima, Showa, and Jikei classifications). The JNET working group created criteria (referred to as the NBI scale) for evaluation of vessel pattern (VP) and surface pattern (SP). We conducted a multicenter validation study of the NBI scale to develop the JNET classification of colorectal lesions. METHODS: Twenty-five expert JNET colonoscopists read 100 still NBI images with and without magnification on the web to evaluate the NBI findings and necessity of the each criterion for the final diagnosis. RESULTS: Surface pattern in magnifying NBI images was necessary for diagnosis of polyps in more than 60% of cases, whereas VP was required in around 90%. Univariate/multivariate analysis of candidate findings in the NBI scale identified three for type 2B (variable caliber of vessels, irregular distribution of vessels, and irregular or obscure surface pattern), and three for type 3 (loose vessel area, interruption of thick vessel, and amorphous areas of surface pattern). Evaluation of the diagnostic performance for these three findings in combination showed that the sensitivity for types 2B and 3 was highest (44.9% and 54.7%, respectively), and that the specificity for type 3 was acceptable (97.4%) when any one of the three findings was evident. We found that the macroscopic type (polypoid or non-polypoid) had a minor influence on the key diagnostic performance for types 2B and 3. CONCLUSION: Based on the present data, we reached a consensus for developing the JNET classification.

Narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team.

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.

Optimal timing for resuming antithrombotic agents and risk factors for delayed bleeding after endoscopic resection of colorectal tumors.

Aim. To examine optimal timing for resuming antithrombotic agents and risk factors for delayed bleeding after endoscopic resection of colorectal tumors. Method. Of 1,970 polyps larger than 10 mm removed by polypectomy, endoscopic mucosal resection, or endoscopic submucosal dissection, delayed bleeding, which was designated as bleeding that occurred 6 or more hours after endoscopic treatment, occurred in 52 cases (2.6%); 156 nonbleeding cases matched for age and gender were controls in this single-institution retrospective case-control study. We investigated (1) patient-factors: resuming antithrombotic agents within 5 days following endoscopic resection, hypertension, and diabetes mellitus; and (2) tumor-factors: morphology, size, location, and resection technique by conditional logistic regression. Results. By multivariate analysis resumption of anticoagulants within 5 days was a significant risk factor for delayed bleeding (OR 10.2; 95% CI = 2.7-38.3; P = 0.0006). But resuming a thienopyridine within 5 days was not (OR 0.9; 95% CI = 0.1-2.6; P = 0.40). Other patient- and tumor-factors were not significant. Conclusion. Resuming anticoagulants within 5 days after endoscopic treatment was associated with delayed bleeding whereas resuming thienopyridines was not.

Relationship between endoscopic findings and clinical severity in ischemic colitis.

BACKGROUND AND AIM: The incidence of ischemic colitis (IC) in Japan has been increasing due to the westernization of diet and the aging population. The aim of this study was to evaluate the relationship between endoscopic findings and clinical severity in IC. METHODS: This retrospective analysis included 106 cases diagnosed with IC that were divided into two groups based on endoscopic findings in the acute stage: redness and erosion (RE) versus longitudinal and circumferential ulcers (LCU). The clinical variables were compared between the two groups. In addition, we investigated the risk factors of IC associated with the severity of the endoscopic findings by multivariate logistic regression analysis. RESULTS: The percentage of cases presenting abdominal pain was significantly higher in the LCU group than that in the RE group (p=0.002), as were the baseline serum CRP levels (p=0.0001). The periods of hospitalization in LCU group were longer than in the RE group (p=0.0001). Multivariate logistic regression analysis indicated that ischemic heart disease (IHD) and connective tissue disease were the independent explanatory factor associated with the endoscopic severity of IC (p<0.05). CONCLUSION: We showed clearly that the two endoscopic classifications were accurate indicators of severity and could be used to anticipate severity of IC. Furthermore, we confirmed that IHD and connective tissue disease were the exacerbating factor associated with the severity of endoscopic findings in IC.

Multiple primary malignant neoplasms of three early cancer lesions: a case report.

Multiple primary malignant neoplasms (MPMNs) are rarely reported and it is important to give early diagnosis and proper therapy for these patients. Here reported a case of 62-year-old man with concomitant three early stage cancer lesions in upper gastrointestinal tract, all of which were detected by endoscopy. The first one was an IIc-type lesion at angular part of stomach under endoscopy, which was histologically confirmed to be a mucosal well-differentiated adenocarcinoma. The patient underwent a standard radical gastrectomy for the lesion after the failure of endoscopic treatment. The other two neoplasms were observed during follow-up and were indicated as early stage lesions by synthesizing information from endoscopy, endoscopic ultrasonography, computed tomography and biopsy. One displayed as a hyperemic patch (3 cm×4 cm in size) located at the part of esophagus 27 cm away from the incisor teeth and was proved to be moderately differentiated squamous cancer by histopathological examination. The other was an IIc-type lesion (3.0 cm×3.5 cm in size) located at the part of esophagus 36 cm away from the incisor teeth, and the biopsy result showed a poorly differentiated squamous carcinoma. Both the two lesions were treated with radical radiation because the patient refused surgery management. No recurrence of former lesions or occurrence of novel lesions were observed during post-treatment follow-up, suggesting radical radiation might be effective for this patient.

Evaluation of new subclassification of type V(I) pit pattern for determining the depth and type of invasion of colorectal neoplasm.

BACKGROUND: Colorectal neoplasms with a type V(I) pit pattern include various lesions, such as adenomas, intramucosal cancers, and submucosal carcinomas. METHODS: We analyzed 96 colorectal neoplasms with a type V(I) pit pattern and identified six different variants: (1) unclear outline of the pit; (2) irregular margins of the pit; (3) narrowing of the pit; (4) ragged array of the pit; (5) high residual density of the pit; (6) abnormal branching of the pit. We examined the relationship between the appearance of each V(I) pit pattern and histology, including the depth of invasion. RESULTS: In univariate logistic regression analysis the unclear outline, irregular margins, and narrowing of the pit were significantly associated with a submucosal (SM) invasion ≥1000 µm (P < 0.01). In multivariate logistic regression analysis, unclear outline of the pit was shown to be the only significant predictor of highly invasive submucosal cancer (odds ratio = 24.20, P < 0.0001). Regarding tumor morphology, the following were significantly associated with an SM invasion ≥1000 µm: in protruded type, ragged array (P = 0.022), irregular margins of the pit (P = 0.011), and unclear outline of the pit (P < 0.01); in flat type, irregular margins of the pit (P < 0.01) and unclear outline of the pit (P < 0.01); and in the depressed type, narrowing of the pit (P = 0.015) and unclear outline of the pit (P < 0.01). CONCLUSIONS: Subclassification of the type V(I) pit pattern is useful for determining the depth of invasion of colorectal neoplasms.

Asymptomatic anisakiasis of the colon incidentally found by colonoscopy.

Asymptomatic anisakiasis of the colon is a rare condition that is difficult to diagnose. A 42-year-old man with no symptoms was referred to our department because of elevated serum carcinoembryonic antigen (CEA) levels detected previously at another hospital. A colonoscopy was performed to find the reason for these elevated CEA levels, and Anisakis larvae were identified by chance in the ascending colon wall. This is only the fourth case of asymptomatic anisakiasis of the colon to be reported worldwide.

Clinicopathological characteristics of colorectal cancer less than 10 mm in diameter and invading submucosa and below.

BACKGROUND AND AIMS: Identifying the invasive depth of cancers less than 10 mm in diameter remains a challenge. This study examines the clinicopathological characteristics of colorectal cancers less than 10 mm in diameter and invading submucosal layer (SM)3 and below, which require surgery and must never be treated by endoscopic mucosal resection. METHODS: We studied 54 cases of colorectal cancer less than 10 mm in diameter and invading the submucosa and deeper tissues, by dividing them into two groups: those invading SM1 and SM2 versus those invading SM3 and below. We investigated the clinicopathological characteristics of cancers invading SM3 and below by comparing them with cancers invading SM1 and SM2. Similarly, 38 cases, whose endoscopic findings could be analyzed, were selected and examined. RESULTS: In cases invading SM3 and below, the rates of moderately to poorly differentiated adenocarcinoma, lymphatic and venous permeation and lymph node metastasis were significantly higher than those invading SM1 and SM2. Among cases invading SM3 and below, the presence of endoscopic findings-including white spots of the protruded type, and fullness, white spots, hardness and protruded lesions in the depressed area of the depressed type-was significantly higher than among those invading SM1 and SM2. CONCLUSION: Colorectal cancers less than 10 mm in diameter and invading SM3 and below have high malignant potential. Cancers of this invasive depth can be identified by looking for characteristics such as white spots, fullness, hardness and protruded lesions in the depressed area. Careful endoscopic observation for these signs aids in determining the appropriate treatment.

Colonic mucosal lesions associated with long-term or short-term administration of nonsteroidal anti-inflammatory drugs.

AIM: The effects of short- or long-term administration of nonsteroidal anti-inflammatory drugs (NSAIDs) on the colon have not been well characterized. We assessed the risk of developing colonic mucosal lesions according to the duration of exposure to NSAIDs: short-term and/or long-term use. METHOD: A case-controlled study was performed by reviewing medical records for endoscopic findings, underlying disease, pre-endoscopic symptoms, category of NSAIDs used and duration of use. The patients underwent colonoscopy between January and October 2004, and 75 colitis cases and 1801 non-colitis controls were identified. The prevalence of NSAID use was compared between the cases and controls. The age- and sex- adjusted odds ratios (OR) were estimated using multiple logistic regression models. RESULTS: NSAIDs had been used in colitis cases and non-colitis controls for over six months in 20.0% and 12.7%, and for one week in 4.0% and 2.1%. Overall 76.0% and 85.2% had not received NSAIDs. The adjusted OR (95% confidence interval) for colonic mucosal lesions with short- and long term NSAID administration combined vs. non-use was 2.04 (1.16-3.61). When determined separately for short- and long-term NSAID users, the adjusted ORs were 1.48 (0.42-5.25) and 2.21 (1.19-4.11), compared to non-users. These values signify a trend toward an increased frequency of colonic mucosal lesions with longer use of NSAIDs (P=0.011 for trend). CONCLUSION: Long-term use of NSAIDs increased the risk of colonic mucosal lesions, suggesting that NSAIDs may contribute to the pathogenesis of colonic ulcer or colitis.

Ultrasound-guided percutaneous drainage may decrease the mortality of severe acute pancreatitis.

OBJECTIVES: To evaluate the efficacy and safety of ultrasound-guided percutaneous catheter drainage (PCD) treatment for severe acute pancreatitis compared to conservative and conventional surgical treatments. METHODS: Eighty-one patients with severe acute pancreatitis (SAP) were admitted and divided into three groups: forty-nine cases in the conservative therapy group; nineteen cases in the surgery group; and thirteen cases in the PCD therapy group. Forty-five patients with a CT severity index (CTSI) < or = 8.0 received conservative treatment. One patient with CTSI = 7.0 underwent surgery. Thirty-five patients with a CTSI > 8.0 were randomly selected for surgery or PCD treatment. After randomization, six patients (four patients in the surgery group and two patients in the PCD group) were dropped from the study. The total number of patients included in the surgery and PCD groups was sixteen and thirteen, respectively. RESULTS: Four patients (8.2%) in the conservative therapy group died, five patients (31.3%) in surgery group with a CTSI > 8.0 died, and all patients in the PCD group survived. The mortality rate was lower in the PCD group than in the surgery group (P = 0.048). The serum C-reactive protein (CRP) level recovered more quickly in patients in the PCD group compared to those in the surgery group (P < 0.001). CONCLUSIONS: Patients with SAP and a CTSI < or = 8.0 could be treated with conservative therapy, while patients with a CTSI > 8.0 should be treated with surgery or PCD therapy if the life-threatening complications of extensive fluid collection or necrosis are a factor. However, PCD therapy used in a timely manner for drainage may decrease mortality in patients with SAP, decrease inflammatory mediator release, and avoid incidence of severe sepsis or acute respiratory distress syndrome (ARDS) and emergency surgery.

Correlations among total colonoscopic findings, clinical symptoms, and laboratory markers in ulcerative colitis.

BACKGROUND AND AIM: Colonoscopy plays an integral role in the diagnosis, management and surveillance of ulcerative colitis (UC). In the present study we assessed the relationship between endoscopic and histological findings, clinical symptoms, and laboratory data. METHODS: We performed total colonoscopy examinations in 54 consecutive patients with UC. Seven segments (appendiceal region, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum) were scored for endoscopic and histological activity. The patients were also evaluated using a symptom-activity index and laboratory markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) and platelet (plt) counts. RESULTS: There was a significant positive correlation between endoscopic and histological scores (r(s)=0.738), and between symptom activity score, endoscopic score (r(s)=0.444), and histological score (r(s)=0.557). Although the endoscopic and histological scores of distal colonic lesions (rectum-sigmoid, endoscopic: r(s)=0.515, histological: r(s)=0.624) correlated with clinical symptoms, there was no similar correlation for the proximal colon (appendiceal region-descending; endoscopic, r(s)=0.268, histological, r(s)=0.329). CRP, ESR, and WBC count also correlated with the sum of endoscopic and histological scores (CRP, r(s)=0.447, r(s)=0.369; ESR, r(s)=0.483, r(s)=0.589; WBC, r(s)=0.338, r(s)=0.330), whereas platelet count did not (r(s)=0.171, r(s)=0.210). In particular, CRP and ESR were well correlated with the activity of proximal colonic lesions (CRP, r(s) = 0.474, r(s)=0.480; ESR, r(s) = 0.423, r(s)=0.529) rather than with that of distal lesions (CRP, r(s)=0.236, r(s)=0.212; ESR, r(s)=0.368, r(s)=0.497). CONCLUSIONS: In this study, clinical symptoms reflected the activity of distal colonic lesions, whereas CRP and ESR reflected the activity of proximal lesions. Therefore, total colonoscopy may be indicated when CRP or ESR is elevated in UC patients in clinical remission.

Malignant lymphoma in the ileum diagnosed by double-balloon enteroscopy.

A 73-year old man presented with abdominal pain. A tumor with central ulceration was observed in the ileum using double-balloon enteroscopy. Histological findings of the biopsy specimens were consistent with malignant lymphoma. Double-balloon enteroscopy confirmed the diagnosis of a malignant lymphoma tumor which was surgically resected. The patient is still in complete remission now.

Increased esophageal sensitivity to acid and saline in patients with nonerosive gastro-esophageal reflux disease.

GOALS: To investigate the features of nonerosive reflux disease (NERD). BACKGROUND: NERD is not considered as a milder form of erosive gastro-esophageal reflux disease (eGERD). Although the prevalence of NERD was reported to be high in our country, there have been very few studies about NERD. STUDY: We performed upper gastrointestinal endoscopy to confirm the diagnosis of GERD. The modified acid perfusion test and saline perfusion test were performed in 7 control subjects, 14 NERD, and 11 eGERD patients. The stimulus-response function to acid and saline was quantified by the duration of typical symptom perception (minutes), total sensory intensity rating (0 to 10), and the perfusion sensory score (SS), which was defined as the product of minutes and the sensory intensity rating. RESULTS: The mean value of SS by saline was 0 in control subjects, 12.0 in NERD patients, and 1.5 in eGERD patients (P<0.01 control vs. NERD, P<0.01 NERD vs. eGERD). The mean SS with acid was 0.9 in control subjects, 52.5 in NERD patients, and 23.0 in eGERD patients (P<0.01 control vs. NERD, control vs. eGERD, P<0.05 NERD vs. eGERD). A statistically significant association was shown between the acid and saline perfusion SSs with a correlation coefficient value of r=0.57 in the NERD group (P<0.05). CONCLUSIONS: Both eGERD and NERD, but especially NERD, exhibited esophageal hypersensitivity not only to acid but also saline perfusion, suggesting that hyperalgesia to acid and other factors (eg, psychologic and/or autonomic nerve disturbance) may play some roles in symptom generation in NERD.

Clinicopathological features of nonpolypoid colorectal tumors as viewed from the patients' background.

BACKGROUND: This study was performed to characterize the clinicopathological features of colorectal tumors with flat-, depressed-, or protruded-type morphology (hereafter referred to simply as flat, depressed, or protruded lesions). METHODS: There are two major types of colorectal tumor: polypoid (protruded) and nonpolypoid (flat and depressed). A total of 130 lesions from 130 patients with colorectal submucosal invasive cancer were classified into three groups according to their macromorphology seen during endoscopy: flat (laterally spreading) and depressed nonpolypoid tumors and protruded polypoid tumors. The following factors in the patients' background were evaluated: indication for colonoscopy, age, and family history of colorectal cancer in first-degree relatives (i.e., parents, siblings, children). We also compared the following characteristics of the tumors: size, location, depth of submucosal invasion, vascular invasion, and frequency of synchronous and metachronous tumor lesions. RESULTS: The incidence of abnormal findings on follow-up studies after polypectomy as an indication for colonoscopy was significantly higher among patients with flat lesions (4/24, 16.7%) and depressed lesions (3/22, 13.6%) than among those with protruded lesions (1/84, 1.2%) (P < 0.01, P < 0.01). Patients with flat lesions (65.8 +/- 7.6 years old) were significantly older than those with protruded lesions (P < 0.05). The patients with flat tumors had a significantly higher rate of a family history of colorectal cancer (6/24, 25.0%) than patients with protruded or depressed lesions (P < 0.01, P < 0.05). The protruded lesions were significantly larger than the depressed lesions (size 13.3 +/- 6.7 mm) (P < 0.05), and the flat lesions (24.1 +/- 10.1 mm) were significantly larger than either the protruded or depressed lesions (P < 0.01, P < 0.01). Seventy-five percent (18/24) of the flat lesions were located in the right colon, and this proportion was significantly higher than that among the protruded or depressed lesions (P < 0.01, P < 0.01). The mean +/- SD depth of submucosal invasion was 1218 +/- 1034 microm in the flat lesions, 2392 +/- 1869 microm in the depressed lesions, and 2761 +/- 1929 microm in the protruded lesions, representing a significant difference (P < 0.05, P < 0.0001). Of the 24 patients with flat lesions, 9 (37.5%) showed vascular invasion; this proportion was significantly lower than that among patients with the depressed or protruded lesions (P < 0.01, P < 0.01). Patients with depressed lesions tended to have higher incidence of synchronous and metachronous malignant polyps than those with protruded or flat lesions. CONCLUSION: It is important to examine the morphology of colorectal tumors when diagnosing them and planning the treatment strategy, including follow-up, after resection of nonpolypoid tumors. It is useful to know the patient's family history so nonpolypoid tumors can be accurately diagnosed.

Location of early colorectal cancers at fold-top may reduce the risk of lymph node metastasis.

PURPOSE: This study was designed to look for significant correlations between location of early colorectal cancer, distance from muscularis mucosae to muscularis propria, and the frequency of lymph node metastasis. METHODS: A total of 166 early colorectal cancers, including 67 surgically resected lesions, were evaluated. The cancers were divided into two groups: metastatic and nonmetastatic. Cancer lesions were further subtyped at the fold-top or fold-bottom. Macroscopic classifications and histology were performed. Absolute invasive depth and distance from muscularis mucosae to muscularis propria was measured. Multivariate analysis was used to assess relationships among the variables. RESULTS: The percentage of polypoid cancer lesions at fold-bottom was higher than at fold-top (74.5 vs. 51.8 percent), whereas flat-type cancer lesions at fold-bottom occurred less often than at fold-top (8.2 vs. 30.4 percent). Logistic regression showed that deep absolute invasive depth, lymphatic and vessel invasion, and cancer location (at fold-bottom) were the significant risk factors for early colorectal cancers leading to lymph-node metastasis. The distance from muscularis mucosae to muscularis propria with lymph-node metastasis (1,396.7 +/- 728.4 microm) was shorter than without lymph-node metastasis (3,533.9 +/- 2,507.8 microm; P < 0.01). Multivariate analysis showed that distance from muscularis mucosae to muscularis propria was a statistically significant factor for early colorectal cancers leading to lymph node metastasis (P = 0.0054). CONCLUSIONS: We conclude that early colorectal cancers at the fold-top or with a long distance from muscularis mucosae to muscularis propria have less tendency to metastasize to lymph nodes. Clinically, these results provide evidence of a new indicator of endoscopic mucosal resection for early colorectal cancers at the fold-top.

Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up.

OBJECTIVE: It is proposed that Fusobacterium varium might be one of the elusive pathogenic factors in ulcerative colitis (UC). Our goal was to assess whether an antibiotic combination therapy against F. varium is effective for induction and maintenance of remission of UC. MATERIAL AND METHODS: Twenty chronic, active UC patients with F. varium infection were enrolled consecutively and were randomly assigned to receive amoxicillin, tetracycline or metronidazole per os for 2 weeks (treatment group; n=10), or no antibiotics (control group; n=10). F. varium was sensitive to the antibiotics. Symptom assessment, endoscopic and histological evaluations were performed blind before enrollment at 3-5 months and 12-14 months after the treatment. Serum immunoglobulins to F. varium were measured using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemical detection of F. varium in biopsy specimens was carried out using the avidin-biotin complex method. RESULTS: The clinical activity, endoscopic and histological scores in the treatment group decreased significantly at 3-5 and 12-14 months after the end of treatment compared with those in the control group (p=0.001-0.036). The remission rate in the treatment group was higher than that in the control group (p=0.037). In addition, the titers of antibody to F. varium and the F. varium density in the mucosa decreased at both the short- and long-term follow-ups in the treatment group (p=0.0002-0.049). No serious drug-related toxicity was observed during the trial. CONCLUSIONS: The 2-week antibiotic combination therapy against F. varium was effective and safe in patients with chronic, active ulcerative colitis in this long-term follow-up study.

Second-line treatment for Helicobacter pylori infection in Japan: proton pump inhibitor-based amoxicillin and metronidazole regimen.

BACKGROUND: Recent studies have reported that proton pump inhibitor (PPI)/amoxicillin (A) metronidazole (M) therapy for Helicobacter pylori infection provides a sufficient cure rate in Japan in patients who have failed first-line treatment with PPI/amoxicillin and clarithromycin (AC). To validate the efficacy of this regimen as second-line therapy, our experience with second-line treatment using a PPI/AM regimen was reviewed. METHODS: We analyzed data on 151 patients who had been prescribed a 10-day PPI/AM re-treatment regimen after eradication failure of 1 to 2 weeks' first-line PPI/AC therapy. The PPI/AM regimen was given according to results of susceptibility testing (S+) in 31 patients. The group that had undergone susceptibility testing was further divided into two subgroups according to dosage: standard dose of omeprazole (O)/AM (n = 11) and double dose of lansoprazole (L)/AM (n = 20). The PPI/AM regimen was given without susceptibility testing (S-) to 120 patients. These patients were also divided into two subgroups according to whether they received omeprazole or lansoprazole: OAM (n = 61) and LAM (n = 59). Cure rates and adverse effects in each group were analyzed. RESULTS: The intention-to-treat (ITT)-based cure rate with/without susceptibility testing was 93.5% (95% confidence interval [CI], 79%-99%) and 87.5% (95% CI, 80%-93%), respectively (not significant [NS]). The ITT-based cure rate in S+/S- for OAM and S+/S- for LAM was 90.9% (95% CI, 59%-100%)/82% (95% CI, 70%-91%), and 95% (95% CI, 75%-100%)/93.2% (95% CI, 84%-98%), respectively (NS). Adverse effects were seen in 26.3% and 32.5% of patients in the OAM group and the LAM group, respectively (NS). CONCLUSIONS: The 10-day PPI/AM re-treatment regimen is safe and effective, suggesting its usefulness as second-line treatment in Japan in patients who have failed initial treatment with the PPI/AC regimen.

Frequent hypermethylation of RASSF1A in early flat-type colorectal tumors.

Flat colorectal tumors, characterized by high-grade dysplasia from early small flat mucosal lesions, exhibit a relatively aggressive clinical behavior and are known for their infrequent K-ras mutations. In this study, we investigated the methylation status of the RASSF1A promoter in association with 3p LOH and K-ras mutations in 48 flat colorectal tumors (39 early carcinomas and nine intramucosal high-grade dysplasias). RASSF1A hypermethylation was detected in 39 of 48 (81.3%) tumors and RASSF1A methylation was also detected in 19 of 39 (49%) normal colonic mucosal tissues. 3p21.3 LOH was detected in 20 of 42 (47.6%) cases, but RASSF1 methylation was detected in cases with LOH (14 cases) and retention of 3p21.3 (20 cases). K-ras mutations were detected in seven of 48 (14.6%) tumors and the concordant occurrence of K-ras mutation and RASSF1A methylation was detected in three of 48 cases (6.3%). Overall, there was a statistically significant mutually exclusive relationship between K-ras mutations and RASSF1A methylation. In conclusion, promoter hypermethylation of RASSF1A is a frequent event and may start early in the background normal mucosa in this tumor type. An alternative cascade of abnormalities in RAS transduction pathways may be responsible for the flat morphology and aggressive nature of flat colorectal neoplasms.