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Introduction: Risk prediction of gastric cancers is important to implement appropriate screening procedures. Although aberrant DNA methylation is deeply involved in gastric carcinogenesis, its induction by Helicobacter pylori, a strong gastric carcinogen, is unclear. Here, we analyzed the effect of H. pylori infection on the quantity of methylated DNA molecules in noncancerous gastric mucosae and examined its association with gastric cancer risk.Experimental Design: Gastric mucosae were collected from 154 healthy volunteers (56 H. pylori negative and 98 H. pylori positive) and 72 cases with differentiated-type gastric cancers (29 H. pylori negative and 43 H. pylori positive) by endoscopy. The numbers of DNA molecules methylated and unmethylated for eight regions of seven CpG islands (CGI) were quantified by quantitative PCR after bisulfite modification, and fractions of methylated molecules (methylation levels) were calculated.Results: Among healthy volunteers, methylation levels of all the eight regions were 5.4- to 303-fold higher in H. pylori positives than in H. pylori negatives (P < 0.0001). Methylation levels of the LOX, HAND1, and THBD promoter CGIs and p41ARC exonic CGI were as high as 7.4% or more in H. pylori–positive individuals. Among H. pylori–negative individuals, methylation levels of all the eight regions were 2.2- to 32-fold higher in gastric cancer cases than in age-matched healthy volunteers (P ≤ 0.01). Among H. pylori–positive individuals, methylation levels were highly variable, and that of only HAND1 was significantly increased in gastric cancer cases (1.4-fold, P = 0.02).Conclusions: It was indicated that H. pylori infection potently induces methylation of CGIs to various degrees. Methylation levels of specific CGIs seemed to reflect gastric cancer risk in H. pylori–negative individuals.

Supplementary Table S1 from High Levels of Aberrant DNA Methylation in Helicobacter pylori–Infected Gastric Mucosae and its Possible Association with Gastric Cancer Risk

Supplementary Data from Locked Nucleic Acid In situ Hybridization Analysis of miR-21 Expression during Colorectal Cancer Development

Supplementary Figure 1 from Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

Supplementary Figure 4 from Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

Supplementary Figure 2 from Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

Supplementary Figure Legends 1-8 from Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

Supplementary Tables S1-S2, Figures 1-7 from Frequent Loss of Brm Expression in Gastric Cancer Correlates with Histologic Features and Differentiation State

Supplementary Figure 3 from Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

Supplementary Figure 5 from Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

Supplementary Tables1-4 from Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

The mammalian SWI/SNF chromatin remodeling complex, an essential epigenetic regulator, contains either a single Brm or BRG1 molecule as its catalytic subunit. We observed frequent loss of Brm expression but not of BRG1 in human gastric cancer cell lines. Treatment with histone deacetylase inhibitor rescued Brm expression, indicating epigenetic regulation of this gene, and an RNA interference–based colony formation assay revealed antioncogenic properties of Brm. Brm immunostaining of 89 primary gastric cancers showed an obvious reduction in 60 cases (67%) and a severe decrease in 37 cases (42%). Loss of Brm is frequent in the major gastric cancer types (well- or moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma) and positively correlates with the undifferentiated state. Among the minor gastric cancer types, Brm expression persists in signet-ring cell carcinoma and mucinous adenocarcinoma, but a marked decrease is observed in papillary adenocarcinoma. Intestinal metaplasia never shows decreased expression, indicating that Brm is a valid marker of gastric oncogenesis. In contrast, BRG1 is retained in most cases; a concomitant loss of BRG1 and Brm is rare in gastric cancer, contrary to other malignancies. We further show that Brm is required for villin expression, a definitive marker of intestinal metaplasia and differentiation. Via regulating such genes important for gut differentiation, Brm should play significant roles in determining the histologic features of gastric malignancy. [Cancer Res 2007;67(22):10727–35]

Supplementary Figures 6-8 from Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

Ten‐eleven translocation 1 (TET1) is an essential methylcytosine dioxygenase of the DNA demethylation pathway. Despite its dysregulation being known to occur in human cancer, the role of TET1 remains poorly understood. In this study, we report that TET1 promotes cell growth in human liver cancer. The transcriptome analysis of 68 clinical liver samples revealed a subgroup of TET1‐upregulated hepatocellular carcinoma (HCC), demonstrating hepatoblast‐like gene expression signatures. We performed comprehensive cytosine methylation and hydroxymethylation (5‐hmC) profiling and found that 5‐hmC was aberrantly deposited preferentially in active enhancers. TET1 knockdown in hepatoma cell lines decreased hmC deposition with cell growth suppression. HMGA2 was highly expressed in a TET1high subgroup of HCC, associated with the hyperhydroxymethylation of its intronic region, marked as histone H3K4–monomethylated, where the H3K27‐acetylated active enhancer chromatin state induced interactions with its promoter. Collectively, our findings point to a novel type of epigenetic dysregulation, methylcytosine dioxygenase TET1, which promotes cell proliferation via the ectopic enhancer of its oncogenic targets, HMGA2, in hepatoblast‐like HCC., Ten‐eleven translocation 1 (TET1), a methylcytosine dioxygenase of the DNA demethylation pathway, is overexpressed in the subgroup of hepatocellular carcinoma with the hepatoblast‐like expression pattern. Comprehensive epigenome profilings revealed the ectopic enhancer activation of HMGA2 through cytosine hydroxymethylation, H3K27 acetylation, H3K4 monomethylation, and promoter‐enhancer interaction in a TET1‐dependent manner.

The numbers of Helicobacter pylori (HP)-infected individuals and deaths due to gastric cancer are decreasing in Japan. We aimed to determine whether the serological test for chronic gastritis (the ABC method) is still useful for gastric cancer risk stratification in the 2010s and to analyze risk factors for developing gastric cancer in Japan.In this prospective study, we monitored 20773 individuals for the incidence of gastric cancer from 2010 to 2019. The relationships between blood sampling results, physical examination, and lifestyle in 2010 and the cumulative incidence of gastric cancer were analyzed.A total of 19343 participants who met the study criteria were analyzed. Overall, 0.08% of participants in group A (9/11717), 0.63% in group B (28/4452), 2.05% in group C (43/2098), 1.52% in group D (1/66), and 0.30% in group E (3/1010) developed gastric cancer. Cox hazard analysis showed that age ≥ 50 years; groups B, C, and D according to the ABC method; and current smoking habits were independent risk factors for gastric cancer. The hazard ratios (HRs) of the incidence of gastric cancer were 6.7 in group B and 21.7 in groups C and D, while the HRs of group E was 2.8, which was not significantly different from that of group A. The incidence of gastric cancer was not statistically significantly different between those with and without successful HP eradication in groups B, C, and D during follow-up.The ABC method was still useful for gastric cancer risk stratification in the 2010s.

The mechanism behind the pathogenesis and carcinogenesis of these neoplasms is not fully understood. The objective of this study was to identify genetic markers and pathways specific to precancerous duodenal adenomas and early stage adenocarcinomas through gene expression analysis. Gene expression profiling was performed in 4 pairs of duodenal adenoma/adenocarcinomas and corresponding matched normal tissue. Genes with consistent expression differences were identified and confirmed in 7 independent pairs. Gene set enrichment analysis (GSEA) was performed to characterize gene expression profiles of duodenal adenoma/adenocarcinomas, together with immunohistochemical staining of candidate oncogenic genes. 626 probes consistently demonstrated over a twofold expression difference between tumor–normal pairs. Reverse transcriptase polymerase chain reaction of genes with the most prominent difference in expression between tumors and normal mucosa (KLK7, KLK6, CEMIP, MMP7, KRT17, LGR5, G6PC, S100G, APOA1) validated the results of gene expression analysis. GSEA demonstrated a strong association between duodenal adenoma/adenocarcinomas with colorectal adenomas (p

Sporadic nonampullary duodenal epithelial tumors (NADETs) are uncommon, and thus their clinicopathological features have not been fully assessed. In this study, we have analyzed a series of early sporadic NADETs, focusing on various immunohistological features. We conducted a multicenter retrospective analysis of 68 patients with endoscopically resected sporadic NADETs. Associations between immunohistological features and clinicopathological features were statistically analyzed. The 68 patients consisted of 46 men (68%) and 22 women (32%) with a mean age of 60.7 ± 12.2 years (range 37–85 years). The 68 tumors were composed of 39 adenomas (57%) and 29 early-stage adenocarcinomas (43%). Duodenal adenocarcinomas were larger in size than adenomas and had papillary architecture in their pathological diagnosis with statistical significance. Duodenal adenocarcinomas also demonstrated a significantly higher expression of gastric markers (MUC5AC and MUC6) and a higher MIB-1 index. Duodenal adenomas were contrastively apt to express intestinal markers (MUC2, CDX1 and CDX2). Of the 68 cases analyzed, there were only 3 tumors positive for p53 staining, all of which were adenocarcinoma. When 7 submucosal invasive cancers and 21 intramucosal cancers were compared, submucosal invasion was positively associated with expression of MUC5AC. Also, submucosal invasion showed strong association with double-positivity of MUC5AC and MUC6. Our results indicate that immunohistochemical evaluation is useful for predicting malignant potential of NADETs, especially focusing on the expression of gastrointestinal markers.

Background and aim Nodular gastritis is caused by Helicobacter pylori infection and is associated with the development of diffuse-type gastric cancer. This study examined the clinical characteristics of patients with nodular gastritis, including cancer incidence before and after H. pylori eradication. Methods This was a retrospective study of patients who underwent upper endoscopy and were positive for H. pylori infection. We examined the clinical findings and follow-up data after H. pylori eradication in patients with and without nodular gastritis. Results Of the 674 patients with H. pylori infections, nodular gastritis was observed in 114 (17%). It was more prevalent in women (69%) and young adults. Among patients with nodular gastritis, six (5%) had gastric cancer, all of which were of the diffuse type. Among the 19 (4%) patients with gastric cancer and no nodular gastritis, 16 had intestinal-type cancer. White spot aggregates in the corpus, a specific finding in patients with nodular gastritis, were more frequently observed in patients with gastric cancer than in those without (83% vs 26%, P = 0.0025). Of 82 patients with nodular gastritis who had H. pylori eradicated successfully, none developed gastric cancer over a 3-year follow-up period, while 7 (3%) of 220 patients without nodular gastritis developed gastric cancer after H. pylori eradication. Conclusions In patients with nodular gastritis, white spot aggregates in the corpus may indicate a higher risk of developing diffuse-type gastric cancer. Nodular gastritis may be an indication for eradication therapy to reduce the risk of cancer development after H. pylori eradication.

ObjectivesWe previously demonstrated that lansoprazole provided hepatoprotection in a drug-induced hepatitis animal model partially through the Nrf2/HO-1 pathway. Here, we examined whether lansoprazole could also provide hepatoprotection in a rat model of non-alcoholic steatohepatitis (NASH).MethodsSix-week-old rats were fed a normal chow or a choline-deficient amino acid-defined (CDAA) diet to establish a rat model of NASH. The groups fed a CDAA diet for 5 weeks were subcutaneously administered either a vehicle or a lansoprazole suspension for 4 weeks beginning the second week of the experiment.Key findingsBridging fibrosis was observed in the livers of almost all the NASH model rats (six of seven), but it was not always observed in NASH model rats (one of seven) continuously administered lansoprazole. The serum aspartate aminotransferase level elevated by the CDAA diet was significantly decreased following lansoprazole administration. Lansoprazole also increased the expression of Nrf2, but not HO-1, in the liver of NASH model rats. Lansoprazole decreased the level of activated TGF-β protein. Furthermore, interleukin-6 gene and protein expression were decreased.ConclusionsLansoprazole inhibits hepatic fibrogenesis, at least during the early stages, in CDAA diet-induced NASH model rats. The mechanisms might be associated with cytokine suppression but not the inhibition of reactive oxygen species.

Background/aims Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been used to diagnose gastrointestinal submucosal tumors (SMTs). Although rapid on-site evaluation (ROSE) has been reported to improve the diagnostic accuracy of EUS-FNA for pancreatic lesions, on-site cytopathologists are not routinely available. Given this background, the usefulness of ROSE by endosonographers themselves for pancreatic tumors has also been reported. However, ROSE by endosonographers for diagnosis of SMT has not been reported. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA with ROSE by endosonographers for SMT, focusing on diagnosis of gastrointestinal stromal tumor (GIST), compared with that of EUS-FNA alone. Methods Twenty-two consecutive patients who underwent EUS-FNA with ROSE by endosonographers for SMT followed by surgical resection were identified. Ten historical control subjects who underwent EUS-FNA without ROSE were used for comparison. Results The overall diagnostic accuracy for SMT was significantly higher in cases with than without ROSE (100% vs. 80%, p=0.03). The number of needle passes by FNA with ROSE by endosonographers tended to be fewer, although accuracy was increased (3.3±1.3 vs. 5.9±3.8, p=0.06). Conclusions ROSE by endosonographers during EUS-FNA for SMT is useful for definitive diagnosis, particularly for GIST.

Background/Aims This study aimed to predict sustained viral response (SVR) to low-dose pegylated interferon (PEG-IFN) plus ribavirin of elderly and/or cirrhotic patients with genotype 2 hepatitis C virus (HCV) using viral response within 2 weeks. Methods Low-dose PEG-IFN-α-2b plus ribavirin was administered to 50 elderly and/or cirrhotic patients with genotype 2 HCV for 24 weeks. The dynamics of HCV RNA and HCV core antigen levels within 2 weeks were measured. Results The patients’ median age was 66 years. There were 21 male and 29 female patients. The median baseline HCV RNA level was 5.7 log IU/mL. Rapid viral response was achieved in 17 patients (34%), SVR in 28 (56%), and two (4%) discontinued treatment. Univariate analysis of factors contributing to SVR showed significant differences for sex, baseline virus level, and response within 4 weeks. When 40 fmol/L was set as the cutoff value for the core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 93%, 75%, 84%, 88%, and 85%, respectively. Conclusions Low-dose PEG-IFN plus ribavirin was a safe and cost-effective treatment for elderly and/or cirrhotic patients with genotype 2 HCV, and the viral response within 2 weeks was a useful predictor of SVR.

Background/Aims Transpapillary forceps biopsy is an effective diagnostic technique in patients with biliary stricture. This prospective study aimed to determine the usefulness of the wire-grasping method as a new technique for forceps biopsy. Methods Consecutive patients with biliary stricture or irregularities of the bile duct wall were randomly allocated to either the direct or wire-grasping method group. In the wire-grasping method, forceps in the duodenum grasps a guide-wire placed into the bile duct beforehand, and then, the forceps are pushed through the papilla without endoscopic sphincterotomy. In the direct method, forceps are directly pushed into the bile duct alongside a guide-wire. The primary endpoint was the success rate of obtaining specimens suitable for adequate pathological examination. Results In total, 32 patients were enrolled, and 28 (14 in each group) were eligible for analysis. The success rate was significantly higher using the wire-grasping method than the direct method (100% vs 50%, p=0.016). Sensitivity and accuracy for the diagnosis of cancer were comparable in patients with the successful procurement of biopsy specimens between the two methods (91% vs 83% and 93% vs 86%, respectively). Conclusions The wire-grasping method is useful for diagnosing patients with biliary stricture or irregularities of the bile duct wall.

We have previously reported that serum pepsinogen (PG) can quantify the level of gastric mucosal atrophy, and that H. pylori eradication reduces cancer development in subjects with mild atrophy identified by serum PG levels. The aim of this study was to elucidate the predictive ability of serum PG levels for the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) of primary cancer in association with H. pylori eradication. A retrospective chart review was performed, and 330 patients who underwent ER for initial early gastric cancer were enrolled. Presence or absence of H. pylori, serum PG levels, and endoscopic atrophy at ER were evaluated. H. pylori eradication was performed at the patient's request after ER. The incidence of MGC in these patients was analyzed. Of 330 patients, 47 developed MGC. Endoscopic extensive atrophy was observed more frequently in patients with MGC (p = 0.001). Although PG I or PG II alone did not significantly differ according to development of MGC, the proportion of PG I/II ≤ 3.0, which is one of the criteria of PG test-positive, was significantly higher in patients with MGC (83 vs. 69%, p = 0.04). H. pylori eradication after ER did not affect MGC development (p = 0.2). On multivariate analysis, serum PG I/II ratio ≤ 3.3 was significantly associated with the development of MGC (hazard ratio: 3.66, 95% confidence interval: 1.47-12.25, p = 0.004). The risk of MGC after ER could be quantitatively predicted by the PG I/II ratio regardless of H. pylori status.

The Japanese Society of Gastroenterology (JSGE) revised the evidence-based clinical practice guidelines for peptic ulcer disease in 2014 and has created an English version. The revised guidelines consist of seven items: bleeding gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcer, non-H. pylori, non-nonsteroidal anti-inflammatory drug (NSAID) ulcer, surgical treatment, and conservative therapy for perforation and stenosis. Ninety clinical questions (CQs) were developed, and a literature search was performed for the CQs using the Medline, Cochrane, and Igaku Chuo Zasshi databases between 1983 and June 2012. The guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Therapy is initially provided for ulcer complications. Perforation or stenosis is treated with surgery or conservatively. Ulcer bleeding is first treated by endoscopic hemostasis. If it fails, surgery or interventional radiology is chosen. Second, medical therapy is provided. In cases of NSAID-related ulcers, use of NSAIDs is stopped, and anti-ulcer therapy is provided. If NSAID use must continue, the ulcer is treated with a proton pump inhibitor (PPI) or prostaglandin analog. In cases with no NSAID use, H. pylori-positive patients receive eradication and anti-ulcer therapy. If first-line eradication therapy fails, second-line therapy is given. In cases of non-H. pylori, non-NSAID ulcers or H. pylori-positive patients with no indication for eradication therapy, non-eradication therapy is provided. The first choice is PPI therapy, and the second choice is histamine 2-receptor antagonist therapy. After initial therapy, maintenance therapy is provided to prevent ulcer relapse.

Plasma medical research started late in Japan, but over the past 5 years has made truly remarkable progress, creating a flow of new research that leads the world. A foundation is steadily being built for the investigation of plasma’s effects on the body’s homeostatic mechanisms and therapeutic interventions in pathological conditions. As a result, we have reached the level of vigorous and detailed analyses of the effects of plasma on a diverse array of important life phenomena, including cell membrane transport, intracellular signaling systems, autophagy, apoptosis, and cell proliferation and differentiation. The results of these studies strongly suggest the possibility that plasma science will contribute not only to the resolution of major research questions in life science but also make unique contributions to the resolution of problems confronting modern clinical medicine, including wound healing, regenerative medicine, and cancer control. Among the series of findings that have been obtained in translational studies of plasma science and technology, one particularly worth noting is the concrete achievement of a practical plasma hemostasis device that allows less-invasive treatment. With a view toward medical applications, solid progress has also been made in investigations to improve the selectivity of plasma actions and control its biological effects, as well as investigations aimed at ensuring the safety of plasma medicine. From this series of research findings, one strongly feels not only the possibilities of plasma as a new option on the front lines of clinical medicine in the future, but also its development as a spectacular field of medical science that holds the potential to bring about far-reaching innovations.

Helicobacter pylori (H. pylori) represents an important factor in the development of atrophic gastritis, intestinal metaplasia (IM), and gastric cancer. Eradication of H. pylori has been reported to prevent gastric cancer only in cases without atrophy or IM. However, histological changes with eradication have yet to be fully clarified. We evaluated 38 H. pylori-positive cases before and after eradication at the gland level; pyloric glands were classified as showing gastric proper (G) and IM gland types, with the latter including gastric-and-intestinal mixed IM (GI-IM) and solely intestinal IM (I-IM), depending on the remaining gastric phenotypes. On eradication, acute and chronic inflammation attenuated rapidly and gradually, respectively, whereas levels of MUC5AC and MUC6 expression were not markedly altered. Gland width, size of nuclei and cytoplasm and their ratio in surface foveolar epithelium, the number of Ki-67-positive cells and the length of the proliferating zone in each gland were significantly decreased in G glands after eradication compared with those in GI-IM and I-IM. The number of mitotic phase cells, positive for phosphorylated histone H3 at serine 28, was increased in both types of IM compared to that in G glands in the H. pylori-infected state, but unexpectedly remained unchanged with eradication. These results suggest that GI-IM, as the beginning of IM, could represent a histological irreversible point with eradication and be considered as a “histological point of no return”.

Background and Aim The preventive effect of Helicobacter pylori (HP) eradication on metachronous gastric cancer development after endoscopic resection remains controversial. The aim of the present study was to identify specific endoscopic features that correlated with the risk of metachronous gastric cancer development after endoscopic submucosal dissection (ESD) using both endoscopic findings before ESD and changes of findings after HP eradication. Methods This retrospective study investigated 122 consecutive patients who underwent ESD for early gastric cancer and successful HP eradication after ESD. Endoscopic findings linked with HP before ESD and changes after HP eradication were evaluated according to the development of metachronous cancer. Results Most patients showed severe atrophy and intestinal metaplasia (IM) before ESD (97% and 83%, respectively). Improvement of spotty redness, improvement of diffuse redness, emergence of patchy redness, and emergence of map-like redness were frequent findings after HP eradication (52%, 50%, 54%, and 32%, respectively). Kaplan–Meier curves indicated that patients without IM before ESD never developed metachronous cancer, whereas patients with emergence of map-like redness after HP eradication were significantly more likely to develop metachronous cancer (log–rank test, P = 0.031 and P

Aim The present study aimed to evaluate pathological features of hepatocellular carcinomas (HCC) appearing hypointense on the apparent diffusion coefficient (ADC) map, and to elucidate the association between the signal intensity on the ADC map and metastatic recurrences after hepatectomy. Methods In total, 52 consecutive patients with initial hypervascular HCC (solitary lesion ≤5 cm in diameter) without vascular invasion on imaging were examined by diffusion-weighted magnetic resonance imaging before hepatectomy. The signal intensities of HCC on the ADC map were visually compared with the surrounding liver and categorized as hypointense or non-hypointense. Intrahepatic metastatic recurrence was defined as more than three intrahepatic recurrences. Results The 52 HCC were evaluated as 26 hypointense and 26 non-hypointense tumors. No significant differences between the hypointense and non-hypointense groups were seen for age, sex, etiology, tumor size and tumor marker levels. However, in resected specimens, significant differences between the two groups were noted for histological grade and microscopic portal invasion. The percentages of poorly differentiated HCC and microscopic portal invasion in the hypointense group were significantly higher than those in the non-hypointense group. The cumulative 3-year metastatic recurrence rates of the hypointense and non-hypointense groups on the ADC map were 56% and 13% (P = 0.001), respectively. Multivariate analyses indicated that hypointensity on the ADC map was the only independent factor related to metastatic recurrence. Conclusion Hypointense HCC on ADC mapping are characterized by poor histological differentiation and more frequent microscopic portal invasion, and are significantly associated with metastatic recurrences after hepatectomy.

Critical recurrences after radiofrequency ablation for hepatocellular carcinoma (HCC), such as intrahepatic metastases or dissemination, and extrahepatic metastases or seeding, which are difficult to treat radically, almost certainly lead to primary cancer death. The present study aimed to clarify whether the arterial tumor enhancement pattern on contrast-enhanced computed tomography (CECT) is associated with critical recurrence and cancer death after RFA for small HCC. Between April 2001 and September 2011, 226 patients with initial small hypervascular HCC (≤3 cm in diameter and ≤3 tumors) were treated by RFA. Arterial tumor enhancement patterns on CECT before RFA were categorized by whether non-enhanced areas were included inside the tumor stain. The heterogeneous enhancement group included 44 patients, and the homogeneous enhancement group included 182 patients. The cumulative 5-year critical recurrence rates of the heterogeneous and homogeneous enhancement groups were 42 and 22 % (p = 0.005), respectively. Univariate analysis for factors related to critical recurrence showed significant differences in sex, arterial enhancement pattern, and response to antiviral therapy. These factors were independent on multivariate analysis. The cumulative 5-year primary cancer death rates of the heterogeneous and homogeneous enhancement groups were 29 and 13 % (p = 0.002), respectively. Univariate analysis for factors related to primary cancer death showed significant differences in arterial enhancement pattern and response to antiviral therapy. These factors were independent on multivariate analysis. Arterial heterogeneous tumor enhancement on CECT is associated with critical recurrence and cancer death after RFA for small HCC.

Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is the standard gastric cancer screening method in Japan. Atrophic gastritis and enlarged gastric folds are considered the two major features of Helicobacter pylori-induced chronic gastritis, but the clinical meaning of evaluating them by UGI-XR has not been elucidated. We analyzed healthy UGI-XR examinees without a history of gastrectomy, previous Helicobacter pylori eradication and usage of gastric acid suppressants. Of the 6433 subjects, 1936 (30.1 %) had atrophic gastritis and 1253 (19.5 %) had enlarged gastric folds. During the 3-year prospective observational follow-up, gastric cancer developed in seven subjects, six of whom (85.7 %) had atrophic gastritis with H. pylori infection and five of whom (71.4 %) had enlarged gastric folds with H. pylori infection. The Kaplan-Meier method with log-rank testing revealed that both UGI-XR-based atrophic gastritis (p = 0.0011) and enlarged gastric folds (p = 0.0003) are significant predictors for future gastric cancer incidence.

Watering eyes is a common late adverse event associated with S-1 chemotherapy; however, the frequency and predictive factors are not known.This study included 304 consecutive gastric cancer patients treated with adjuvant S-1 monotherapy for 1 year at Shizuoka Cancer Center. We retrospectively evaluated the frequency of watering eyes, and explored other nonhematological adverse events during the first course of S-1 monotherapy which could become predictive factors for watering eyes.The severest grade of watering eyes during S-1 monotherapy was grade 2 in 41 patients (13.5 %) and grade 3 in 36 patients (11.8 %). The median time to onset of grade 2 and grade 3 watering eyes was 82 days (range 6-344 days) and 249 days (range 84-653 days), respectively, and the median cumulative S-1 dose at the onset of grade 2 and grade 3 watering eyes was 4174 mg/m(2) (range 491-16,095 mg/m(2)) and 10,243 mg/m(2) (range 4943-16,341 mg/m(2)), respectively. Multivariate analysis showed that anorexia (odds ratio 2.37, P = 0.008), oral mucositis (odds ratio 3.86, P = 0.0003), skin hyperpigmentation (odds ratio 3.84, P = 0.0001), and rash (odds ratio 3.76, P = 0.01) observed during the first course were significantly associated with watering eyes.The risk of watering eyes was higher in patients who also had anorexia, oral mucositis, skin hyperpigmentation, or rash during first course of S-1 monotherapy than in those without them.

In order to evaluate the Th1 and Th2 responses of Oral Squamous Cell Carcinoma (OSCC) patients, we investigated the cytokine producing capability of peripheral blood (PB), and compared it with clinicopathological appearances of OSCC patients. The production of a Th1-type cytokine, interferon (IFN)-γ, from lipopolysaccharide (LPS)-stimulated PB correlated positively with the frequency of lymph node metastasis. We also investigated the production of a Th2-type cytokine, IL-10, however, no significant correlation was observed with the clinicopathological appearances. Our results suggested that the IFN-γ producing capability was specifically regulated and dependent on the regional metastatic potencies of OSCCs.

We recently published in your journal a 3-year multicentre prospective cohort study demonstrating the usefulness of an epigenetic cancer risk marker for gastric metachronous cancers.1 This study achieved the first proof of concept of epigenetic cancer risk diagnosis in any type of cancer but, due to the short follow-up period, a relatively small number of events were observed, resulting in a marginally significant difference (p=0.042). It was anticipated that a longer follow-up could lead to a clearer difference and HR with a smaller 95% CI. We now report the 5-year follow-up data, which show highly significant results. Among the 826 enrolled patients, 795 patients received annual follow-ups by endoscopy for a median period of 5.46 years (IQR: 3.95–6.09). By the end, 133 patients had developed a metachronous gastric cancer. Among them, 116 patients developed a metachronous gastric cancer detected 1 year after the enrolment (authentic metachronous cancer). Statistical analyses were conducted in the same manner as previously …

Low energy ionized gas coagulation equipment (LE-IGCE) using low temperature nonthermal atmospheric pressure plasmas has been attracting special attention with the popularization of minimally invasive surgery. In this work, the thermal characteristics of a commercial high energy ionized gas coagulation equipment (HE-IGCE) and a specially designed LE-IGCE have been studied using an infrared camera and optical emission spectroscopy during their treatments. The four substrates used for the treatments were pork meats, copper (Cu) plates, wet tissues, and glass plates. In the HE-IGCE treatment, the surface temperature of the pork meat rose to 350°C, and the rotational temperatures of nitrogen molecules in plasmas were 450 to 1630 K, depending on which substrate was used during HE-IGCE treatments. In the LE-IGCE treatment, the surface temperature of pork meats was lower than 40°C, and the rotational temperatures of nitrogen molecules were lower than 350 K. The results show that the LE-IGCE can maintain the temperature of biological tissue below the threshold that would cause irreversible tissue damage.