Progression of duodenal neoplasia to advanced adenoma in patients with familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) have a lifetime risk of developing duodenal adenomas approaching 100%, and the relative risk for duodenal cancer compared with the general population is high. We conducted a retrospective study to investigate the progression of non-ampullary duodenal adenomas (NADAs) and risk factors for advanced lesions in patients with FAP. METHODS: Of 248 patients with 139 pedigrees at 2 institutes, we assessed 151 patients with 100 pedigrees with a pathogenic germline variant in the adenomatous polyposis coli gene, excluding mosaic variants. We evaluated the prevalence of NADAs in patients with FAP, the progression of these adenomas to advanced adenoma during the observation period, and the risk factors for the lifetime development of high-grade dysplasia (HGD), large (≥ 10 mm) duodenal adenomas, and Spiegelman stage IV. RESULTS: During the median observation period of 7 years, the incidences of patients with NADAs, with more than 20 polyps, with polyps ≥ 10 mm, with HGD, and with stage IV at the last esophagogastroduodenoscopy were increased 1.6-fold, 1.7-fold, 5-fold, 22-fold, and 9-fold, respectively. Intramucosal cancer occurred in three patients (2%), but no patients developed invasive cancer during the observation period because we performed endoscopic intervention for advanced adenomas. Stage progression was observed in 71% of 113 patients. Stage IV was more common in women, patients with a history of colectomy, and those with a 3' side mutation in their adenomatous polyposis coli gene. CONCLUSIONS: NADAs in patients with FAP frequently become exacerbated. Our findings suggest that patients with FAP who develop duodenal adenomas should be surveyed to prevent the development of duodenal cancer.

Genotype-phenotype correlation for extracolonic aggressive phenotypes in patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) patients develop various life-threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype-phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high-grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398-1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required.

Feasibility of underwater endoscopic mucosal resection for endoscopic management of gastric neoplasms in patients with familial adenomatous polyposis.

BACKGROUND: Underwater endoscopic mucosal resection (UEMR) has been developed as an effective endoscopic intervention for colon, rectum, and duodenum neoplasms. However, there are no comprehensive reports regarding the stomach, and its safety and efficacy are unknown. We aimed to examine the feasibility of UEMR for gastric neoplasms in patients with familial adenomatous polyposis (FAP). METHODS: We retrospectively extracted data of patients with FAP who underwent endoscopic resection (ER) for gastric neoplasms at Osaka International Cancer Institute from February 2009 to December 2018. Elevated gastric neoplasms of ≤ 20 mm in diameter were extracted, and conventional endoscopic mucosal resection (CEMR) and UEMR were compared. Furthermore, outcomes after ER until March 2020 were examined. RESULTS: 91 endoscopically resected gastric neoplasms were extracted from 31 patients with 26 pedigrees, and 12 neoplasms underwent CEMR and 25 neoplasms underwent UEMR was compared. The procedure time was shorter for UEMR than for CEMR. There was no significant difference between en bloc resection and R0 resection rates by EMR methods. CEMR and UEMR showed postoperative hemorrhage rates of 8% and 0%, respectively. Residual/local recurrent neoplasms were identified in four lesions (4%), but additional endoscopic intervention (three UEMR and one cauterization) resulted in a local cure. CONCLUSION: UEMR was feasible in gastric neoplasms of FAP patients, especially in elevated lesions and those of ≤ 20 mm in diameter.

Efficacy and safety of intensive downstaging polypectomy (IDP) for multiple duodenal adenomas in patients with familial adenomatous polyposis: a prospective cohort study.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) risk developing multiple duodenal adenomas (MDAs), leading to duodenal cancer and death. We investigated the efficacy and safety of intensive downstaging polypectomy (IDP) for MDAs integrated with new-generation procedures. METHODS: This prospective phase II study, conducted at a tertiary cancer center, enrolled patients with FAP who had MDAs. We performed IDP including cold snare/forceps polypectomy (CSP/CFP) and underwater endoscopic mucosal resection (UEMR). The primary end point was the downstaging of Spigelman stage at 1-year follow-up. RESULTS: 2424 duodenal polyps in 58 patients with FAP underwent IDP, including 2413 CSPs in 57 patients, seven CFPs in one patient, and four UEMRs in four patients. Only one major adverse event was observed (grade 3 hyperamylasemia) without clinical manifestations. We performed additional UEMR, CSP, and CFP for one, 12, and 22 patients, respectively, during initial follow-up. Overall, 55 patients completed protocol examination; the Spigelman stage was significantly reduced at the 1-year follow-up endoscopy (P < 0.001), with downstaging observed in 39 patients (71 %). Among the 26 patients with Spigelman stage IV at initial examination and protocol completion, 23 (88 %) showed downstaging. There was no major change in Spigelman stages from 1-year follow-up esophagogastroduodenoscopy to a median of 37 months (range 3-56). CONCLUSIONS: IDP, including new-generation procedures, showed significant downstaging with acceptable adverse events for MDA in patients with FAP, even those with advanced-stage disease. Lesion selection for different resection techniques may be important for suitable and sustainable management of MDA in patients with FAP.

Gastric neoplasms in patients with familial adenomatous polyposis: endoscopic and clinicopathologic features.

BACKGROUND AND AIMS: Gastric neoplasms in patients with familial adenomatous polyposis (FAP) occur at a high rate and can cause death. The endoscopic findings of gastric neoplasms in these patients are characteristic but not well recognized. To identify the relevant characteristics to enable early detection, we retrospectively investigated endoscopic findings of gastric neoplasms in patients with FAP and then compared the clinical, histopathologic, and genetic features among subgroups. METHODS: Of 234 patients with 171 pedigrees at 2 institutes, 56 cases (24%, 133 gastric neoplasms) with 44 pedigrees were examined. Immunostaining was performed for histopathologic evaluation by 1 blinded pathologist. According to the endoscopic findings, gastric neoplasms were divided into 4 types based on location (L: antrum and pylorus, UM: the rest of the stomach) and color (W: white, T: translucent, R: reddish) and their clinicopathologic features examined. RESULTS: Of the cases, 93% could be classified into a single type. Among histologic phenotypes, high-grade dysplasia was present in 26% (type L), 41% (type UM-W), 0% (type UM-T), and 22% (type UM-R). The immunologic phenotype comprised the gastric type in 69% (93% in Type UM) and the intestinal phenotype, including the mixed type, in 31% (61% in type L). Moreover, 96% of patients had concurrent duodenal neoplasms. Adenomatous polyposis coli gene status was identified in 93% of patients; the pathogenic variant was detected in 98% but did not influence any endoscopic features. CONCLUSIONS: Gastric neoplasms in patients with FAP were stratified into 4 types according to their endoscopic findings. The endoscopic phenotype was related to the histopathologic phenotype but not to germline variants.

Chemoprevention with low-dose aspirin, mesalazine, or both in patients with familial adenomatous polyposis without previous colectomy (J-FAPP Study IV): a multicentre, double-blind, randomised, two-by-two factorial design trial.

BACKGROUND: The only established treatment for preventing colorectal cancer in patients with familial adenomatous polyposis (FAP) is colectomy, which greatly reduces patient quality of life. Thus, an alternative method is warranted. In this trial, we aimed to clarify the individual and joint effects of low-dose aspirin and mesalazine on the recurrence of colorectal polyps in Japanese patients with FAP. METHODS: This was a randomised, double-blind, placebo-controlled, multicentre trial with a two-by-two factorial design done in 11 centres in Japan. Eligible patients were aged 16-70 years and had a history of more than 100 adenomatous polyps in the large intestine, without a history of colectomy. Before the study, patients underwent endoscopic removal of all colorectal polyps of at least 5·0 mm in diameter. Randomisation was done with a minimisation method with a random component to balance the groups with respect to the adjustment factors of sex, age (<30 years vs ≥30 years), or smoking status at the time of entry. Patients and researchers were masked to the treatment group. There were four groups: aspirin (100 mg per day) plus mesalazine (2 g per day), aspirin (100 mg per day) plus mesalazine placebo, aspirin placebo plus mesalazine (2 g per day), or aspirin placebo plus mesalazine placebo. Treatment was continued until 1 week before 8 month colonoscopy. The primary endpoint was the incidence of colorectal polyps of at least 5·0 mm at 8 months and was assessed in the intention-to-treat population. Safety was assessed in the ITT population. We also did a per-protocol analysis including only patients who took at least 70% of the allocated study drug. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000018736, and is complete. FINDINGS: Between Sept 25, 2015, and March 13, 2017, 104 patients were randomly assigned to receive either aspirin or aspirin placebo (n=52) or mesalazine or mesalazine placebo (n=52). Two patients withdrew from the aspirin plus mesalazine placebo group. 26 (50%) of 52 patients who received no aspirin had colorectal polyps of at least 5·0 mm at 8 months, as did 15 (30%) of the 50 patients who received any aspirin, 21 (42%) of the 50 patients who received no mesalazine, and 20 (38%) of the 52 patients who received any mesalazine. The adjusted odds ratio for polyp recurrence was 0·37 (95% CI 0·16-0·86) in the patients who received any aspirin and 0·87 (95% CI 0·38-2·00) in any who received mesalazine. The most common adverse events were grade 1-2 upper gastrointestinal symptoms in three (12%) of 26 patients who received aspirin plus mesalazine, one (4%) of 24 patients who received aspirin plus mesalazine placebo, and one (4%) of 26 patients who received mesalazine plus aspirin placebo. There was one grade 4 event in the mesalazine plus aspirin placebo group, but not related to the treatment. INTERPRETATION: Low-dose aspirin safely suppressed the recurrence of colorectal polyps larger than 5·0 mm in patients with FAP. These results suggest an effect of low-dose aspirin for FAP and could be an alternative method for preventing colorectal cancer in FAP. FUNDING: Japan Agency for Medical Research and Development.

Diagnostic yield of conventional endoscopy with endoscopic ultrasonography for submucosal invasion of superficial esophageal squamous cell carcinoma: a post hoc analysis of multicenter prospective confirmatory study (JCOG0508).

BACKGROUND: Endoscopic ultrasonography (EUS) is reportedly the reliable modality to predict the depth of esophageal squamous cell carcinoma (ESCC), however, most previous studies are retrospective or single-centered. We aimed to evaluate the diagnostic ability of conventional endoscopy and EUS using the data from a multicenter prospective study of endoscopic resection (ER) followed by chemoradiotherapy for cSM1-2N0M0 ESCC (JCOG0508). METHODS: All lesions were evaluated as cSM cancer with both conventional endoscopy and EUS before enrollment and judged as cSM1 or cSM2 in real time. We compared the clinical and pathological diagnoses for tumor depth and assessed the positive predictive value (PPV) for pSM (pSM/cSM) as the primary endpoint. We also investigated the clinical factors affecting the pathological depth of SM. RESULTS: 175 lesions were examined, and clinical diagnosis was SM1 in 114 and SM2 in 61 lesions. The pathological diagnoses of the epithelium, lamina propria mucosa, muscularis mucosae, SM1, and SM2 were 3, 31, 55, 17, and 69. The PPV for pSM was 49.1% (86/175) in all lesions, 34.2% (39/114) in cSM1 lesions, and 77.0% (47/61) in cSM2 lesions. Multivariable analysis demonstrated that cSM2 (vs. cSM1, OR 6.79) was an independent clinical factor associated with pSM. CONCLUSIONS: While the accurate depth diagnosis in cSM ESCC was difficult to make, the clinical diagnosis of SM2 with both conventional endoscopy and EUS was significantly associated with pSM. Furthermore, diagnostic ER could be recommended to confirm the pathological diagnosis especially in cSM1 lesions with both conventional endoscopy and EUS.

Utility of Mesalazine in Familial Adenomatous Polyposis: Clinical Report of Reduction of Polyp Size in Patients with Ulcerative Colitis, and Safety Examination in Familial Adenomatous Polyposis Patients.

Mesalazine is the gold standard drug for treatment of ulcerative colitis (UC). Here, we describe 4 cases of familial adenomatous polyposis (FAP) patients with UC that showed reduction of intestinal polyp diameter by mesalazine treatment. Of note, the effects of mesalazine on the development of intestinal polyps in FAP patients have not been reported, and we further investigated whether the short-term use of high-dose mesalazine (4 g/day) has harmful effects on FAP patients or not. The authors found that the treatment showed slightly adverse events in FAP patients. However, mesalazine tended to reduce the number of colon polyps in male subjects with FAP. This report provides basic information for planning a double-blind, randomized, clinical trial that aims to show mesalazine's potential to suppress intestinal polyp development in FAP.

Efficacy of Endoscopic Resection and Selective Chemoradiotherapy for Stage I Esophageal Squamous Cell Carcinoma.

BACKGROUND & AIMS: Esophagectomy is the standard treatment for stage I esophageal squamous cell carcinoma (ESCC). We conducted a single-arm prospective study to confirm the efficacy and safety of selective chemoradiotherapy (CRT) based on findings from endoscopic resection (ER). METHODS: We performed a prospective study of patients with T1b (SM1-2) N0M0 thoracic ESCC from December 2006 through July 2012; 176 patients underwent ER. Based on the findings from ER, patients received the following: no additional treatment for patients with pT1a tumors with a negative resection margin and no lymphovascular invasion (group A); prophylactic CRT with 41.4 Gy delivered to locoregional lymph nodes for patients with pT1b tumors with a negative resection margin or pT1a tumors with lymphovascular invasion (group B); or definitive CRT (50.4 Gy) with a 9-Gy boost to the primary site for patients with a positive vertical resection margin (group C). Chemotherapy comprised 5-fluorouracil and cisplatin. The primary end point was 3-year overall survival in group B, and the key secondary end point was 3-year overall survival for all patients. If lower limits of 90% confidence intervals for the primary and key secondary end points exceeded the 80% threshold, the efficacy of combined ER and selective CRT was confirmed. RESULTS: Based on the results from pathology analysis, 74, 87, and 15 patients were categorized into groups A, B, and C, respectively. The 3-year overall survival rates were 90.7% for group B (90% confidence interval, 84.0%-94.7%) and 92.6% in all patients (90% confidence interval, 88.5%-95.2%). CONCLUSIONS: In a prospective study of patients with T1b (SM1-2) N0M0 thoracic ESCC, we confirmed the efficacy of the combination of ER and selective CRT. Efficacy is comparable to that of surgery, and the combination of ER and selective CRT should be considered as a minimally invasive treatment option. UMIN-Clinical Trials Registry no.: UMIN000000553.

[Evaluation of the safety and efficacy of endoscopic treatment for early gastric cancers in patients aged over 80 years].

Endoscopic treatments, including endoscopic mucosal resection or endoscopic submucosal dissection, are well accepted as standard treatments for early gastric cancers. However, there are few studies evaluating the safety and efficacy of this approach for early gastric cancers in patients aged over 80 years, and the post-treatment prognosis remains unclear. Here, we retrospectively analyzed the medical records and evaluated the safety and efficacy of endoscopic treatment for early gastric cancers in patients aged over 80 years (group A) compared with non-elderly patients aged 65-79 years (group B) and under 65 years (group C). In this study, we enrolled 53 patients (mean age, 82 years) in group A, 217 patients (mean age, 73 years) in group B, and 89 patients (mean age, 60 years) in group C who received endoscopic treatment at Kyoto University Hospital between 2001 and 2010. The incidence of treatment-related complications including aspiration pneumonia, bleeding, and perforation was 19% (10/53) in group A, 9.7% (21/217) in group B, and 6.7% (6/89) in group C, respectively. In particular, only the incidence of aspiration pneumonia was significantly higher in group A [11% (6/53) ] than in the other two groups [1.8% (4/217) in group B and 1.1% (1/89) in group C]. There was no significant difference in the curative resection rate and recurrence rate including metachronous lesions among the three groups. In group A, the median survival calculated using the Kaplan-Meier method was 8.0 years, and the 5-year survival rate was 73%. No gastric cancer-related deaths were observed in all groups. In conclusion, endoscopic treatment for early gastric cancers may contribute to an improvement in life expectancy, even among patients aged over 80 years, provided an experienced gastroenterologist selects the appropriate patients based on not only the endoscopic findings for the lesion but also the severity of any comorbidities. However, it is noteworthy that our elderly group aged over 80 years had a high risk of developing aspiration pneumonia.

An integrated analysis of hyponatremia in cancer patients receiving platinum-based or nonplatinum-based chemotherapy in clinical trials (JCOG1405-A).

BACKGROUND: Hyponatremia is a common electrolyte abnormality in cancer patients who receive chemotherapy. Among anticancer agents, platinum-based agents are reported to cause chemotherapy-induced hyponatremia. However, the actual incidence and risk factors remain unknown. RESULTS: The reports of 29 trials were analyzed. The incidence of grade 3/4 hyponatremia was 11.9% in patients treated with platinum-based chemotherapy and 3.8% in those treated with nonplatinum-based regimens (P < 0.01). Univariable analysis revealed a high incidence of hyponatremia in patients receiving cisplatin, three-drug combination regimen, two-drug combination regimen with amrubicin or irinotecan, or high-dose cisplatin (weekly equivalent cisplatin dose ≥20 mg/m2), and in patients with small-cell lung cancer. CONCLUSION: This is the first report of the actual incidence and the potential risk factors of chemotherapy-induced hyponatremia. Careful monitoring of serum sodium level is needed when platinum-based chemotherapy is administered. METHODS: This study included all clinical trials of systemic chemotherapies for solid cancers that were conducted by the Japan Clinical Oncology Group (JCOG) after January 2000 and of which the patient enrolment was completed by January 2014. The latest reports of each trial were used for analysis. The incidence of chemotherapy-induced grade 3/4 hyponatremia and the potential risk factors were investigated with univariable analysis.

Multiple convex demarcation line for prediction of benign depressed gastric lesions in magnifying narrow-band imaging.

BACKGROUND AND STUDY AIMS: With magnifying narrow-band imaging (M-NBI) of the gastric mucosa, a characteristic demarcation line (DL) is occasionally found in non-cancerous depressed lesions. This DL forms multiple convex shapes along the edge of the epithelia of surrounding mucosa. We have termed this novel finding a multiple convex DL (MCDL). In this study, we clarified the prevalence of an MCDL in depressed gastric lesions detected in patients at high risk for gastric cancer and determined the diagnostic yield necessary to distinguish between cancer and non-cancer. PATIENTS AND METHODS: This was a post hoc analysis of a multicenter prospective trial. In total, 362 small (≤ 10 mm) depressed lesions were detected in 1353 patients. Presence or absence of a DL in target lesions was evaluated on M-NBI images. The proportion of MCDLs among lesions with a DL was evaluated. RESULTS: Images of 347 lesions (39 cancerous and 308 non-cancerous) were evaluable. A DL was present in 252/347 lesions (73 %). When the cutoff value for the proportion of MCDLs needed to distinguish non-cancer from cancer was set at two-thirds, an MCDL was observed in 86/252 lesions (34 %). In 86 lesions with an MCDL, 83 (97 %) were non-cancerous. The sensitivity, specificity, positive predictive value, and negative predictive value of an MCDL for non-cancerous lesions were 38 %, 91 %, 97 %, and 19 %, respectively. CONCLUSIONS: Presence of an MCDL had high specificity and positive predictive value for non-cancerous lesions. Evaluating the shape of the DL is useful for differentiation between cancer and non-cancerous lesions.

Safety of cold snare polypectomy for duodenal adenomas in familial adenomatous polyposis: a prospective exploratory study.

BACKGROUND: Cold snare polypectomy (CSP) to remove multiple duodenal adenomas (MDAs) in patients with familial adenomatous polyposis (FAP) could be an effective and less invasive method than more extensive surgery. The aim of the present study was to determine the safety of this procedure. METHODS: This prospective exploratory study included 10 consecutive patients with FAP and MDAs who underwent CSP for as many as 50 duodenal adenomas. The primary outcome was the incidence of severe adverse events. RESULTS: 10 patients were enrolled and underwent 332 CSPs from June 2016 to January 2017. The median procedure time was 33 minutes (range 25 - 53), and the median number of polyps removed during a single session was 35 (range 10 - 50). Most of the removed polyps were ≤ 10 mm. None of the 10 patients experienced a severe adverse event. One patient developed arterial bleeding during the procedure, but it was easily managed using hemoclips. CONCLUSIONS: CSP for MDAs in patients with FAP was safe. The long-term efficacy of this procedure should be investigated.

Identification of a predictive factor for distant metastasis in esophageal squamous cell carcinoma after definitive chemoradiotherapy.

BACKGROUND AND PURPOSE: Distant metastasis (DM) after definitive chemoradiotherapy has not been a focus of research in esophageal carcinoma. At present, local-regional control is improving following advances in salvage treatments after definitive chemoradiotherapy. There is a need to focus on suppressing the development of DM. The aim of this study was to identify pre-treatment factors associated with DM after definitive chemoradiotherapy. MATERIALS AND METHODS: This study included 144 patients with thoracic esophageal squamous cell carcinoma (Stage I/II/III/IV; 35/17/69/23) (TNM 7th) who underwent definitive chemoradiotherapy; >50 Gy was prescribed to all gross tumors with concurrent administration of 5-fluorouracil ± platinum. Pre-treatment factors included age, gender, performance status, tumor location, T/N/M status, tumor length, size of metastatic lymph nodes (LN size), and the presence of intramural metastasis or multiple primary tumors. The effects of pre-treatment factors on overall survival (OS) and DM were evaluated. RESULTS: The median follow-up period was 48 months. DM occurred as an initial progression in 21 % of patients, and LN size correlated with DM development (hazard ratio [HR] = 5.12; p = 0.0013) and poor OS (HR = 2.20; p = 0.0076) in univariate and multivariate analyses. CONCLUSIONS: LN size is a quantitative pre-treatment prognostic factor that should be assessed prior to definitive chemoradiotherapy. Patients with large metastatic lymph nodes are at high risk of DM and should be monitored.

Factors affecting dilation force in balloon dilation of severe esophageal strictures: an experiment using an artificial stricture model.

BACKGROUND: The multidiameter balloon catheter is used widely for severe esophageal stricture dilation. However, the relationships between inflation pressure, balloon size, and radial dilation force at the stricture site have not been examined fully. METHODS: We performed an experiment using phantom models to investigate the relationships between inflation pressure, balloon size, and radial dilation force. The balloon dilation procedure was performed for each stricture model using three sizes of balloon: 10-11-12, 12-13.5-15, and 15-16.5-18 mm. RESULTS: A positive association between inflation pressure and dilation force was observed for each balloon size. In balloons inflated by targeting the same diameter, the dilation force was higher for smaller balloons than for larger balloons. An inverse association between stricture size and dilation force was observed in the 12-13.5-15 mm balloon (3 vs 5 mm, P = .002; 5 vs 7 mm, P < .001). CONCLUSIONS: We found relationships between inflation pressure, balloon size, severity of strictures, and dilation force. To perform safe and effective esophageal balloon dilation, the inflation pressure and balloon size should be selected after considering the stricture size and target diameter.

Endoscopic management of familial adenomatous polyposis in patients refusing colectomy.

BACKGROUND AND STUDY AIMS: Colectomy protects against colorectal cancer in familial adenomatous polyposis (FAP); however, some patients with FAP refuse surgery. The aim of this study was to evaluate the feasibility and safety of endoscopic management of these patients. PATIENTS AND METHODS: A retrospective review of medical records was performed to identify adult patients with FAP who refused colectomy and were managed by repeated colonoscopies to remove numerous polyps between 2001 and 2012. Polyps were removed by hot snare polypectomy or endoscopic mucosal resection. Polyps of < 10 mm in size and without endoscopic features suggesting cancer were discarded without histological examination; the remaining polyps were examined histologically. RESULTS: Of the 95 eligible patients, five (5.3 %) were excluded. The remaining 90 patients (median age at first visit 29 years [range 16 - 68 years]; 46 males) were followed for a median of 5.1 years (interquartile range [IQR] 3.3 - 7.3 years). During this period, a total of 55 701 polyps were resected without adverse events such as bleeding or perforation. The median numbers of endoscopic treatment sessions and polyps removed per patient were 8 (IQR 6 - 11) and 475 (IQR 211 - 945), respectively. Five patients had noninvasive carcinoma (Category 4.2 according to the revised Vienna classification), detected within 10 months from the start of the follow-up period. All of these patients were treated endoscopically, without signs of recurrence during a median follow-up of 4.3 years (IQR 2.0 - 7.1 years). No invasive colorectal cancer was recorded during the study period. Two patients (2.2 %) underwent colectomy because the polyposis phenotype had changed to dense polyposis. CONCLUSION: Endoscopic management of FAP is feasible and safe in the medium term.

A significant feature of microvessels in magnifying narrow-band imaging for diagnosis of early gastric cancer.

BACKGROUND AND STUDY AIMS: Magnifying narrow-band imaging (NBI) is more useful than conventional endoscopy for diagnosing early gastric cancer (EGC). However, evaluation of irregular microvascular patterns is subjective and is often difficult, even with expert eyes. The aim of this study was to clarify the most important microvascular patterns in magnifying NBI for diagnosis of EGC. PATIENTS AND METHODS: This was a post-hoc analysis of a multicenter prospective trial among nine Japanese hospitals. A total of 1353 patients underwent screening with white-light endoscopy and 362 patients had small (≤ 10 mm) depressed lesions. They were randomly assigned to magnifying NBI or white-light endoscopy followed by magnifying NBI. During diagnosis, magnifying NBI images were recorded before biopsy. All magnifying NBI images were reviewed and evaluated for the association of four features of microvessels - that is, dilation, tortuosity, difference in caliber, and variation in shape - with cancer diagnosis. RESULTS: Images of 343 lesions (40 cancerous and 303 benign depression lesions) were evaluable. The diagnostic performance (sensitivity/specificity) of each finding was: dilation, 25/90 %; tortuosity, 55/24 %; difference in caliber, 13 /99 %; and variation in shape, 70/95 %. Multivariate analysis identified only variation in shape as being statistically significantly associated with diagnosis of cancer (odds ratio 38.0, 95 % confidence interval: 16.1 - 95.7, P < 0.001). All findings showed moderate agreement (κ values): dilation, 0.44; tortuosity, 0.33; difference in caliber, 0.26; and variation in shape, 0.48. CONCLUSIONS: A variation in shape was the most significant feature of microvessels observed in magnifying NBI for diagnosis of small depressed-type EGC. STUDY REGISTRATION: UMIN-CTR000001072.

The changing patterns of dispensing branded and generic drugs for the treatment of gastroesophageal reflux disease between 2006 and 2011 in Japan: a retrospective cohort study.

BACKGROUND: Despite rising healthcare costs, generic drugs are less frequently dispensed in Japan compared with other developed countries. This study aimed to describe changes in dispensing of branded and generic drugs and to explore possible factors that promote the use of generic drugs. METHODS: We conducted a retrospective cohort study using a Japanese medical and pharmacy claims database. All proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs) with indications for gastroesophageal reflux disease (GERD) described on Japanese labels were included. Patterns of dispensing branded and generic drugs for the treatment of GERD between 2006 and 2011 were analyzed. Multivariate logistic regression was applied to investigate factors associated with receiving generic drugs. RESULTS: The study cohort included 14,590 patients (male: 50.2%, mean age: 43.1 years). Branded drugs for GERD were still frequently dispensed despite an increase in the share of generic drugs. Only 4.3% of patients who initially received branded drugs switched to generic drugs. The percentage of patients who received only generic drugs increased over time (6.5% to 22.1%). The frequency of generic drug dispensing was the highest in the setting where both prescription and dispensing were implemented in clinics (43.3%), while the lowest in the setting where both prescription and dispensing were implemented in hospitals (11.5%). Factors associated with receiving generic drugs included year of dispensing (adjusted OR 2.22, 95% CI 1.94 to 2.55 for 2009-11 v 2006-8), prescription and dispensing setting (OR 1.81, 95% CI 1.44 to 2.26 for prescription in hospitals and dispensing in community pharmacies; OR 2.21, 95% CI 1.80 to 2.72 for prescription in clinics and dispensing in community pharmacies; and OR 4.55, 95% CI 3.68 to 5.62 for prescription and dispensing in clinics v prescription and dispensing in hospitals) and H2RAs (OR 1.64, 95% CI 1.49 to 1.81 compared to PPIs). CONCLUSIONS: The share of generic drugs for the treatment of GERD increased over time although branded drugs for GERD were still dispensed frequently. The use of generic drugs for GERD was influenced not only by government policies but also by changes in treatment approach and the setting of prescription and dispensing.