We identified glides as segments where the absolute value of the

We identified glides as segments where the absolute value of the Hilbert transform of the pitch rate signal was <0.05 (Woodward

et al. 2006a), and visually checked these sequences. Based on previously described gliding behaviors in right whales (Nowacek et al. 2001, Woodward et al. 2006a), we defined the minimum glide duration as 5 s. Following Wilson et al. (2006) find more and Fahlman et al. (2008), we calculated Overall Dynamic Body Acceleration (ODBA, g) by smoothing accelerometer measurements in three separate axes, with a window size of 3 s. We then subtracted these smoothed data (static acceleration) from the unsmoothed data to estimate the dynamic acceleration in each axis. Finally, we then calculated ODBA as the sum of the absolute value of dynamic acceleration in each axis. We observed peaks and identified outliers in ODBA at each surfacing event, and therefore

calculated mean ODBA values within dives, between dives, and during descent and ascent periods of each dive. We defined three phases of the sedation and disentanglement of Eg 3911 (Table 2) hereafter referred to as (1) Sedation/Entangled: animal towing gear and attached buoys, and sedative injection; (2) Disentangled: following removal of most of trailing gear and buoys, administration of antibiotics, and attachment of the satellite LIMPET tag (Andrews et al. 2008); and (3) Recovery: retrieval of injection darts, this website dart tethers and floats (Moore et al. 2010), and the end of active boat approaches. To determine the behavioral effects of sedation on an entangled whale, we used Wilcoxon rank sum

tests to compare dive parameters and respiration rates within the Sedation/Entangled phase, between the 21 min prior to and the 50 min following sedative injection, but prior to removal of the gear and buoys. We used Three-sample Kruskal-Wallis single factor analysis of variance tests with tied ranks and post hoc Bonferroni-corrected (α =  0.05/3 = 0.0167) Wilcoxon rank sum tests to compare the distributions of various dive click here parameters between Sedation/Entangled, Disentangled and Recovery phases. To compare the observed vs. expected ratio of time spent above and below the wave drag limit between phases, we used Chi-square contingency tables. We compared fluke stroke rate, RMS, and the frequency and duration of glides across phases within the single tag deployment to infer changes in thrust intensity and power requirements. As propulsive (thrusting) forces should equal resistive forces (net buoyancy and drag), we expect thrusting intensity (stroke rate and RMS) to be greater and for fewer and shorter glides to occur in entangled vs. nonentangled conditions.

In vitro, S100-MPs are released from human T cells after activati

In vitro, S100-MPs are released from human T cells after activation (and apoptosis) and fuse with the cell membranes of HSCs and transfer membrane molecules (CD147, Emmprin), which triggers up-regulation of fibrolytic MMP-1, MMP-3, MMP-9, and MMP-13. Of note,

the circulating CD4+ and CD8+ S100-MPs found in patients’ plasma mainly derive from activated T cells, and their equivalent generated ex vivo by PHA stimulation of donor CD4+ and CD8+ T cells most strongly up-regulated putatively fibrolytic MMPs in HSCs (Table 1). This finding will likely have relevance in vivo, because activated HSCs are the principal driving force of liver Proteasome inhibitor drugs fibrogenesis. MPs were described as a product of various kinds of cell types, including T cells, as a product of activation or early apoptosis. However, characterization of the biological effects of these MPs has been limited. A prior study implicated MPs from the Jurkat T cell line in fibrolytic activation of synovial fibroblasts.8 Questions relevant to liver disease or diseases of other epithelial-mesenchymal organs have not been addressed. We demonstrated that increased T cell activation (and apoptosis) in active hepatitis C19 is paralleled by

excess release of T cell–derived buy Vadimezan MPs, which can be detected in the circulation. Using T cell subpopulations and HSCs, both of which are key players in liver inflammation and fibrogenesis, we demonstrated the functional relevance of these MPs in vitro. Therefore, T cell MPs ameliorated or even blunted the fibrogenic response that is usually prevalent in chronic hepatitis,1 including the neutralization of fibrogenic activation of HSCs by TGFβ1, the strongest profibrogenic cytokine in hepatic fibrosis and other fibrotic diseases.2 Of note, not all T cell–derived MPs were equally potent inducers of fibrolytic MMP expression selleck chemicals llc in HSCs. Therefore, MPs derived from apoptotic and activated CD8+ T cells were the strongest inducers compared with MPs from activated CD4+

T cells or from the CD4-expressing Jurkat T cell line (Table 1). In this regard, it is noteworthy that CD8+ cells predominate in livers with hepatitis C, and the presence of CD8+ rather than CD4+ T cells has been correlated with the progression of liver fibrosis.20-22 These contrast with circulating MPs in inflammatory intestinal diseases where CD4+ T cell–derived MPs predominate (unpublished data). Therefore, MPs derived from activated (and apoptotic) CD8+ and CD4+ T cells may represent a negative feedback loop that counteracts the yet ill-defined profibrogenic activity of T cells once they become highly stimulated (as reproduced in vitro with PHA) with or without subsequent deletion by apoptosis. Human T cell–derived MPs could also potently induce MMP expression in primary HSCs from rats, suggesting a conserved mechanism, which is working beyond species boundaries.

We cannot

We cannot ICG-001 rule out NASH cases being excluded (e.g., those with NASH and steatosis <5%), but, as a result of the workup to exclude other etiologies, all included cases were managed clinically as NAFLD. Logistically, it was not possible to match every patient with NAFLD by age and gender with patients with HCV infection; however, only age was shown

to have an independent effect on outcomes. We also adjusted the comparisons by age, sex, BMI, and the presence of diabetes and dyslipidaemia without discernible differences. There may be residual confounding by some parameters: For example, diabetes status differed significantly between NALFD and HCV, and even though this was adjusted for, this cannot account for severity of disglycemia. Moreover, follow-up for medical problems that

may have an effect, such as de novo diabetes see more mellitus, were not assessed systematically (although insulin resistance may play a role in HCV as well as in NAFLD).17 Nor can we rule out effects of later medications for the treatment of comorbidities, although no pharmacological treatments have been shown reliably to have a substantive effect on liver fibrosis in NAFLD.18 This also applies to any effects of nonpharmacological treatments, such as exercise or diet.19 Practice and follow-up obviously varied between the centers, although this does not affect the systematic prospective methodology used, nor should it significantly affect the event predictors. Compared to the general population, NAFLD has been associated with an increased risk of overall death (standardized mortality ratio: 1.34; 95% CIs: 1.003-1.76) in a community-based study of 420 patients selleck chemicals from the United States.20 In a similar Swedish study, just over 5% of

the 129 NAFLD patients enrolled went on to develop end-stage liver disease.21 In both studies, there was a higher vascular- and liver-related mortality in patients with NAFLD (as compared to the general population of the same age and sex). In contrast to patients with other liver diseases, the short-term prognosis of NAFLD is largely excellent, but longer term prognosis depends crucially on histological stage at presentation.6, 22 In patients with bland steatosis, two studies have reported either nil23 or minimal progression24 to advanced disease over a median of 11.5 and 16.7 years, respectively. For those with NASH on baseline liver biopsy, 11% went on to develop cirrhosis and ∼40% of patients die from any cause within 15 years (of which 7.3% are from liver-related complications, especially in those with advanced fibrosis or cirrhosis).6 Studies with subsequent liver biopsy have also prospectively evaluated the risk of fibrosis progression over time. One hundred three patients underwent two liver biopsies 1-21 years apart: Baseline low fibrosis stage, diabetes, and greater BMI were independently associated with fibrosis progression.

Conclusions— The Pediatric Migraine Disability Assessment provid

Conclusions.— The Pediatric Migraine Disability Assessment provides a simple tool to measure the impact of RG7420 molecular weight headaches in adolescents. Adolescents with migraine headaches suffered the greatest level of disability. Higher depression scores were associated with more severe headache-related disabilities in adolescents, independent of headache frequency and severity. “
“Migraine is a chronic, episodic, often disabling, neurological condition that affects more than 12% of the US population, 3 times more in women than men. It has widespread effects on cerebral function and appears to be inherited. There are many types of therapy including

behavioral, complementary, acute pharmacologic care, preventive pharmacologic care, and physical techniques. General treatment principles include

lifestyle changes and using rapidly acting PD-0332991 purchase acute care medications alone or in combination early in the migraine attack. Migraine-specific medications such as triptans and non steroidal anti-inflammatory drugs should be used when possible. There are several promising medications and devices in the migraine pipeline. “
“Background.— One of the genome-wide linkage studies performed in migraine has yielded a significant linkage of migraine (with and without aura) with markers located at 6p12.2-21.1. This locus (named MIGR3) has not been replicated in the only genome-wide association check details scan

study performed to date or in previous genome-wide linkage studies. Objective.— Our objective had been to replicate the MIGR3 locus performing a family-based association study. Methods.— A sample of 594 subjects belonging to 134 migraine families of diverse complexity underwent genotyping for the markers previously published as linked at 6p12.2-21.1 migraine locus. Family-based association test, under different models of inheritance, and also the model-free TDT analysis were performed. Results.— The best result was obtained with the D6S1650 marker under the additive model (rank [S observed] = 265.0; permuted P = .0006), using family-based association test program (HBAT subprogram). Similar results were obtained with the model-free TDTPHASE algorithm (P < .0001, corrected). Nominal significant P values were obtained for D6S1630, D6S452, and D6S257. After correction for multiple testing with the stratified false-discovery rate, all markers showed significant association (P < .0001). Conclusion.— We corroborated that the MIGR3 locus at 6p12 is a genetic risk for migraine with and without aura. (Headache 2012;52:393-399) "
“This article describes a single case of migraine headaches misdiagnosed as idiopathic intracranial hypertension in a young woman. The implications of such a diagnosis are discussed. Literature regarding normal intracranial pressure is reviewed.

Because the Alb-TLR4−/− mice were significantly protected, we fur

Because the Alb-TLR4−/− mice were significantly protected, we further investigated the mechanisms by which this was taking place. Among the most proximal inflammatory signaling events after I/R is the activation of mitogen-activated protein (MAP) kinases.23, 24 To determine whether HC TLR4 was involved in the activation of MAP kinase signaling, we performed western blotting analysis on liver lysates from WT, Alb-TLR4−/−, selleck compound and global TLR4−/− mice after I/R. Phosphorylation of the MAP kinases, JNK and ERK, were substantially reduced at 3 hours of reperfusion in both Alb-TLR4−/− and global TLR4−/− mice, when

compared to WT mice (Fig. 5). We found no role for HC TLR4 in p38 phosphorylation at this time point; however, p38 phosphorylation occurs very early after reperfusion.23 buy Alectinib This may account for the lack of difference noted at 3 hours of reperfusion. Notably, we did not observe major differences in MAP

kinase activation at either the 1-hour or 6-hour time points. To confirm that these findings were related to the local effects of I/R and not systemic inflammatory mediators, we demonstrated no increased phosphorylation of these proteins in the nonischemic lobes (Fig. 5). Therefore, HC TLR4 seems to be an important mediator of MAP kinase activation after I/R. Our above-described experiments found that HC TLR4 was involved in the activation of JNK signaling in the liver after I/R. JNK is activated click here by exposure of cells to cytokines and environmental stress and has previously been demonstrated to be activated in HCs by both hypoxia and liver I/R.25, 26 Therefore, we exposed WT HCs to hypoxia and rapidly observed increased phosphorylation of JNK and p38, compared to normoxia (Fig. 6A). When TLR4−/− HCs were exposed to hypoxia, the phosphorylation of JNK, c-Jun (the downstream target of JNK),

and p38 was substantially reduced, compared to WT HCs (Fig. 6B). We observed no increase in NF-κB (p65) or ERK phosphorylation with hypoxia exposure (Fig. 6B). To confirm that this response was, in fact, the result of the lack of functional TLR4 and not some other mechanism, HCs from TLR4−/− mice were then transfected with either a control adenoviral vector (AdLacZ) or recombinant adenovirus encoding TLR4 (AdTLR4). TLR4 expression using AdTLR4 was confirmed by western blotting (Fig. 6C). Transfection of TLR4−/− HCs with AdTLR4 restored JNK and p38 phosphorylation in response to hypoxia (Fig. 6D), indicating that this is, in fact, a TLR4-dependent response. Thus, these results demonstrate that HCs respond to hypoxic stress with a rapid activation of JNK and p38 in a TLR4-dependent manner. We next sought to determine whether the release of HMGB1 was mediated by JNK phosphorylation. Therefore, we added the JNK inhibitor (SP600125) to the media of HCs exposed to hypoxia. Phosphorylation of the target of JNK, c-Jun, was inhibited with the addition of the JNK inhibitor (Fig. 7A).

[18, 22-24] Previous studies have shown that pretreatment IP-10 c

[18, 22-24] Previous studies have shown that pretreatment IP-10 concentrations were closely associated with SVR rate in response to PEG IFN and RBV in patients with HCV genotype 1, with high systemic IP-10 concentrations at the onset of treatment predictive of poorer outcomes.[17, 18, 25] IL28B genotype in combination with IP-10 concentration

is useful for predicting SVR in patients with HCV genotype 1 with PEG IFN and RBV.[26] It has not been determined, however, whether IL28B genotype in combination with baseline IP-10 Navitoclax is useful in predicting outcomes in HCV-infected patients treated with TVR-based triple therapy.[27] This study was therefore designed to determine whether baseline serum IP-10 concentration is predictive of response to TVR-based triple therapy in patients with HCV genotype 1, and to examine the association between pretreatment

serum IP-10 concentration and other baseline patient characteristics. Between January 2012 and April 2013, 105 DAA-naïve patients with CHC were treated with TVR-based triple therapy at the Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Japan; the Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Quizartinib concentration Hyogo, Japan; and the Department of Hepatology, Osaka City University Hospital, Osaka, Japan. Pretreatment serum samples had been obtained from 100 of these patients and stored at −80°C. Three patients co-infected with HCV and hepatitis B virus were excluded; thus, 97 patients were analyzed.

All patients analyzed had compensated liver disease, were infected with HCV genotype 1, were naïve to DAA treatment, had no evidence of HIV infection, and had a serum learn more HCV RNA concentration of more than 5.0 log IU/mL. Liver biopsy samples obtained from 85 patients (87.6%) before treatment were coded and scored using the METAVIR scoring system by a single pathologist in each hospital.[28] Advanced fibrosis was defined as the presence of F3 or F4 fibrosis. The associations between baseline serum IP-10 concentration and the clinical characteristics and virological responses of patients were analyzed retrospectively. This study was conducted according to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the ethics committee of each participating facility. Written informed consent was obtained from all patients prior to treatment. All patients analyzed were scheduled to receive TVR (Telavic; Mitsubishi Tanabe Pharma, Osaka, Japan) in combination with PEG IFN-α-2b (Peg-Intron; MSD, Tokyo, Japan; 1.5 μg/kg per week) and weight-based RBV (Rebetol; MSD; total doses of 600 mg/day, 800 mg/day and 1000 mg/day for patients weighing less than <60 kg, 60–80 kg and >80 kg, respectively, according to Japanese guidelines) for 12 weeks, followed by PEG IFN-α-2b and RBV for 12 weeks.

Becoming familiar with the strengths and the potential limitation

Becoming familiar with the strengths and the potential limitations click here of EUS may improve detection of early pancreatic cancer. “
“We read with great interest the American Association for the Study of Liver Diseases practice guideline1 showing the current central status of anticoagulation for portal vein thrombosis (PVT), although anticoagulation should never be stereotyped for all patients with PVT. It is very important for clinicians to distinguish between noncirrhotic

and cirrhotic PVT because of its association with therapeutic strategy selection. Nonmalignant and noncirrhotic PVT is mainly caused by inherited and acquired prothrombotic disorders, except for some local factors, so the treatment should be focused on correction of these disorders and not on the creation of a hepatic parenchymal shunt and thrombectomy, which may be just a temporary rescue. According to our data for the period of December 2001 to September 2008, the outcome of noncirrhotic selleck screening library PVT by transjugular intrahepatic portosystemic shunt (TIPS) was unsatisfactory with respect to the technical success rate (9/23) and follow-up in patients with successful recanalization. In contrast, the outcome by anticoagulation therapy was inspiring, as many recent reports have shown.2, 3 The primary cause of cirrhotic PVT is portal flow reduction

and its secondary hemostasis, even if other check details factors play a role, such as the decline of coagulation inhibitors synthesized by the liver and inherited coagulation abnormalities. Variceal rebleeding is one of the most common clinical presentations in patients with decompensated cirrhosis and PVT, at least in our aforementioned data (52/61). Therefore, the goal of treatment in theory is to deal with the portal hypertension and smooth portal vein. Benefits lie not only in a successful recanalization rate (43/61) but also in postoperative follow-up in our experience

(Table 1). It seems that TIPS with thrombectomy should be adopted more widely than anticoagulation therapy (Fig. 1), which is still challenged by the unresolved issue4 of whether to aggravate the risk of bleeding or not, especially for patients with thrombocytopenia and large varices. In addition, another point has to be emphasized: PVT with cirrhosis should never be regarded as cirrhotic PVT, and PVT without cirrhosis should never be regarded as noncirrhotic PVT. From our perspective if any one of the following conditions was identified, this further excluded cirrhotic PVT, even if cirrhosis had been diagnosed: 1 Definite primary thrombosis of the hepatic vessels was diagnosed. For example, Budd-Chiari syndrome had been recognized and treated a few years before the diagnosis of cirrhosis and PVT. The effect can be better only if we aim at the major etiology more accurately and choose a corresponding treatment.

Several authors have demonstrated that lithocholic acid is a phys

Several authors have demonstrated that lithocholic acid is a physiologic ligand of VDR33 and modulates bile acid detoxification. Han et al.22 identified VDR protein and messenger RNA in primary cultures of human hepatocytes and demonstrated that this receptor plays a critical role in the inhibition of the synthesis

of bile SCH727965 cell line acids, protecting the hepatocytes from cholestatic injury. VDR can be activated by either lithocholic acid acetate or 1α,25(OH)2D3 and exerts its activity through the transcriptional inhibition of CYP7A1, the initial and rate-limiting enzyme of bile acid synthesis, reducing the synthesis of bile acids in human hepatocytes.21 Interestingly, in selleck compound NASH patients, we found that VDR expression on cholangiocytes was inversely associated with NAS, suggesting a possible role of VDR, expressed on biliary cells, in modulating the inflammatory process in course of liver disease. Studies in animal models and in patients with biliary disorders and CHC have shown that the ductal epithelium can express several profibrogenic and chemotactic proteins, the latter capable of attracting

and activating inflammatory and fibrogenic cells.34-36 In this study, we demonstrated that liver expression of both CYP2R1 and CYP27A1 is preserved in NASH patients. This observation may question the hypothesis of a loss of hydroxylation capacity of hepatocytes in the course of NASH. Conversely, low 25(OH)D3 levels could favor, along with known risk factors, the intrahepatic accumulation of lipids, insulin resistance, progressive hepatic steatosis, and the development of steatohepatitis. Overall, the present study suggests that vitamin D may influence the inflammatory response to chronic liver injury both

in NASH and in CHC patients by means of its specific VDR, widely expressed on hepatic cell lines. In addition to the immunomodulator see more and antiproliferative activities on inflammatory cells, it is plausible to hypothesize that vitamin D exerts its action on cholangiocytes, in which the expression of VDR is particularly pronounced. Low hepatic VDR expression, closely associated with more severe liver histology in this study, could represent the primary event leading to progression of hepatitis. VDR polymorphisms have been investigated in the context of chronic liver diseases such as primary biliary cirrhosis and autoimmune hepatitis, where they seem to contribute to the risk of liver disease development.16, 17 Indeed, because serum 25(OH)D3 levels in our population of NASH patients are comparable to those observed in obese subjects without liver disease, it is plausible that VDR polymorphisms affecting liver VDR expression may play a role in the development and progression of NASH independently from serum vitamin D status.

A meta-analysis was carried out recently to determine whether H 

A meta-analysis was carried out recently to determine whether H. pylori eradication selleck chemicals can reduce the risk of GC.

A total of 6,695 patients were evaluated showing that H. pylori eradication reduces GC risk (relative risk, 0.65 [CI, 0.43–0.98]). Overall, 56 of 3,307 (1.7%) of untreated (control) participants developed GC compared with 37 of 3,388 (1.1%) of treated patients. The limitation of this meta-analysis is that most of the studies were performed in Asia. Moreover, only two studies were performed in a double-blinded fashion [19]. An interesting debate was provoked by the article of de Vries et al., who reported two cases of GC development 4 and 14 years after H. pylori eradication selleck chemical [20–22].

These patients presented at baseline already with gastric ulcer and preneoplastic changes (i.e. IM and gastric atrophy) and dysplasia at follow-up. It shows that eradication does not prevent GC in all cases, especially in those that already present with preneoplastic changes. The report further indicates that a close and effective endoscopic follow-up and surveillance are mandatory in patients at high risk of GC, even after successful H. pylori eradication. Based on the multifactorial process of gastric carcinogenesis and including genetic polymorphisms of the host, virulence determinants of H. pylori, and environmental factors, further diagnostic tools need to be studied for obtaining information about the single individual risk of a patient. Using the genome

wide germline analyses might offer the chance to identify high-risk groups of GC [23]. In an interesting study from Yanaoka et al. from Japan, individuals with high risk of GC were identified by the serum PG test and the risk of GC development after eradication therapy was related to the presence of extensive atrophy before the eradication [24]. In conclusion, H. pylori eradication prevents GC development, and it seems the earlier the bacteria gets eradicated, the more significant is the decrease of GC risk. A prophylactic vaccine as primary prevention, especially with infant vaccination, would represent an ideal strategy to eradicate H. pylori and prevent GC. From a socioeconomic selleck compound point of view, the use of a prophylactic vaccine is cost-effective, and the vaccine development is more than desirable, especially considering decreasing eradication rates using antibiotic regimens [25,26]. Only one novel agent (Trastuzumab) could be introduced into clinical use. The c-erbB2 (Her-2/neu) proto-oncogene encodes a transmembrane tyrosine kinase receptor and shows a high prevalence in malignant gastro intestinal neoplasias. In GC, overexpression is mainly mediated by gene amplification, and it is associated with advanced-stage disease and limited invasion [27,28].

In a retrospective study by Bae et al [11] on 1007 Korean patien

In a retrospective study by Bae et al. [11] on 1007 Korean patients who underwent endoscopic resection for early GC between November 2004 and December 2008, rates of metachronous cancer in the H. pylori-negative, Idasanutlin solubility dmso eradicated, and noneradicated groups were 10.9, 14.7, and 29.7 cases per 1000 person-years, respectively. The median time for metachronous recurrence was 18 months (range, 7–75 months). There were no significant differences in the recurrence rate and recurrence-free survival between the H. pylori-negative and eradicated groups, but the recurrence rate was significantly higher in the noneradicated than in the H. pylori-negative and eradicated groups.

The hazard ratios in the noneradicated group compared with the H. pylori-negative and eradicated groups were 2.5 (p < .01) and 1.9 (p = .02), respectively. On the basis of their results, the authors concluded that successful H. pylori eradication may reduce the occurrence of metachronous GC after endoscopic resection in patients with early GC. In a prospective,

randomized, open-label trial evaluating the effects of H. pylori eradication on the incidence of metachronous carcinoma after endoscopic resection of early GC, 901 consecutive Korean find more patients with H. pylori infection who had been treated with endoscopic resection for gastric dysplasia or cancer from April 2005 to February 2011 were randomly assigned to a PPI-based triple therapy (20 mg omeprazole, 1 g amoxicillin, and 500 mg clarithromycin twice daily for 1 week) or no therapy [12]. Patients underwent endoscopic examination learn more 3, 6, and 12 months after treatment and then yearly thereafter. During a median follow-up period

of 3 years, 10 patients who received H. pylori eradication and 17 controls developed metachronous carcinoma; this difference was not significant (p = .15). The incidence of metachronous carcinoma between the two groups did not differ significantly at 1, 2, 3, and 4 years after administration of the therapy. There were no significant differences in the development of metachronous carcinoma among patients who were positive (n = 16) or negative (n = 11) for H. pylori infection (p = .32). Thus, in contrast to the previous retrospective study, in the prospective trial, eradication of H. pylori did not reduce the incidence of metachronous gastric carcinoma after endoscopic resection of gastric tumors. A multicentre retrospective cohort study from 12 hospitals aimed at elucidating the time at which multiple GCs develop and determining whether scheduled endoscopic surveillance might control their development [13]; 1258 Japanese patients with early GC (EGC) who underwent endoscopic submucosa dissection (ESD) with en bloc margin-negative curative resection from April 1999 to December 2010 were included. Synchronous cancer was classified as concomitant cancer or missed cancer. Follow-up endoscopy was performed every 6–12 months. Synchronous or metachronous multiple cancers were detected in 175 patients (13.