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Continuous duodenal levodopa/carbidopa intestinal gel delivery by a gastrostomy infusion system improves control of Parkinson’s disease. The overall complication rates of percutaneous endoscopic gastrojejunostomy were reported to be 41% and 59% for immediate and delayed adverse events, respectively. A 72-year-old woman underwent percutaneous endoscopic gastrojejunostomy using the delivery system noted above. Abdominal pain and vomiting occurred 3 months later. Esophagogastroduodenoscopy showed a longitudinal ulcer extending from the lower gastric body to the ileum end, with small intestinal telescoping. Colonoscopy showed a large bezoar of food residue that was attached around the tip of the tube, reaching the ascending colon, which may have acted as an anchor. Thus, the gastric antrum and small intestine were shortened with telescoping. This complication was resolved by crushing the bezoar with forceps during colonoscopy and can be prevented by consuming a fiber-free diet and periodic exchanges of the tube using esophagogastroduodenoscopy.

The present study aimed to elucidate the association between post-vascular–phase (Kupffer-phase) images from contrast-enhanced ultrasonography (CEUS) with perfluorobutane microbubbles and metastatic recurrences after the resection of hepatocellular carcinoma (HCC). The study examined 73 patients with solitary HCC ≤5 cm in diameter who underwent CEUS before resection. HCC was defined as irregular type (including an irregular defect on Kupffer-phase images) or non-irregular type. Intrahepatic metastatic recurrence was defined as >3 intrahepatic recurrences. Metastatic recurrence included both extrahepatic and intrahepatic recurrences. Frequencies of microscopic portal invasion and intrahepatic metastasis were significantly higher in the irregular group than in the non-irregular group. Cumulative 5-y metastatic recurrence rates in the irregular and non-irregular groups were 43% and 7% (p = 0.028), respectively. Multivariate analyses identified Kupffer-phase findings as a factor significantly related to metastatic recurrence. In conclusion, HCCs with an irregular defect during Kupffer-phase CEUS are characterized by more frequent microscopic vascular invasion and intrahepatic metastasis and are significantly associated with metastatic recurrence after resection.

Internal stents used during pancreaticoduodenectomy (PD) are generally spontaneously passed through the rectum by defecation. However, we encountered six patients with internal stents that migrated into the bile duct after PD. We herein report the outcomes of these six patients and the usefulness of double-balloon enteroscopy (DBE) for removal of such stents from the bile duct. An internal stent was placed across pancreaticojejunostomy in 416 (68.8%) of 605 consecutive patients undergoing PD between 2005 and 2015. This study evaluated the characteristics and outcomes of the six patients whose internal stent migrated into the bile duct. Migration of an internal stent into the bile duct was found during follow-up computed tomography (CT) in 6 (1.4%) of 416 patients who had an internal stent placed during PD. Three patients developed stent-induced cholangitis, and two had bile duct stones. Excluding one patient whose internal stent spontaneously slipped out and disappeared from the bile duct, all patients underwent successful removal of a stent from the bile duct by a single instance of biliary intervention involving DBE. Removal of a stent from the bile duct using DBE is a feasible and useful procedure that should be considered if an internal stent is detected during follow-up CT after PD.

Background Glioblastoma-initiating cells (GICs) comprise a tumorigenic subpopulation of cells that are resistant to radio- and chemotherapies and are responsible for cancer recurrence. The aim of this study was to identify novel compounds that specifically eradicate GICs using a high throughput drug screening approach. Methods We performed a cell proliferation/death-based drug screening using 10 560 independent compounds. We identified dihydroorotate dehydrogenase (DHODH) as a target protein of hit compound 10580 using ligand-fishing and mass spectrometry analysis. The medical efficacy of 10580 was investigated by in vitro cell proliferation/death and differentiation and in vivo tumorigenic assays. Results Among the effective compounds, we identified 10580, which induced cell cycle arrest, decreased the expression of stem cell factors in GICs, and prevented tumorigenesis upon oral administration without any visible side effects. Mechanistic studies revealed that 10580 decreased pyrimidine nucleotide levels and enhanced sex determining region Y–box 2 nuclear export by antagonizing the enzyme activity of DHODH, an essential enzyme for the de novo pyrimidine synthesis. Conclusion In this study, we identified 10580 as a promising new drug against GICs. Given that normal tissue cells, in particular brain cells, tend to use the alternative salvage pathway for pyrimidine synthesis, our findings suggest that 10580 can be used for glioblastoma therapy without side effects. Key Points 1. Chemical screening identified 10580 as a novel GIC-eliminating drug that targets DHODH, an essential enzyme for the de novo pyrimidine synthesis pathway. 2. Compound 10580 induced cell cycle arrest, apoptosis, and differentiation in GICs.

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.

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.

Entecavir requires long-term administration. Pegylated interferon (PEG-IFN) therapy leads to significant reduction of hepatitis B surface antigen (HBs Ag) levels. This study aimed to assess the safety and efficacy of adding PEG-IFN-α-2a to entecavir toward cessation of entecavir. A total of 23 patients treated with entecavir underwent add-on PEG-IFN-α-2a therapy (90 μg per week) for 48 weeks. Viral response (VR) was defined as more than 50% reduction of baseline hepatitis B surface antigen (HBs Ag) level at 72 weeks from the start of therapy. Complete response (CR) was defined as the decline of HBs Ag levels α-2a to entecavir has limited efficacy. The percentage reduction of HBs Ag level at week 12 may be a useful predictor for VR.

In a previous population-based case-control study, we demonstrated an elevated risk of colorectal neoplasia with Helicobacter pylori (H. pylori) infection. The present study investigated the effects of H. pylori-associated chronic gastritis on the development of colorectal neoplasia by analyzing the recurrence of colorectal neoplasia subsequent to endoscopic resection. Ninety-nine patients who had undergone endoscopic resection of colorectal neoplasia were monitored under colonoscopy, and the recurrence of colorectal neoplasia was prospectively investigated. The stage of H. pylori-associated chronic gastritis in each subject was evaluated using a combination of two serum tests: H. pylori antibody and pepsinogen. In the present cohort, colorectal neoplasia recurred at a rate of 15,296/100,000 person-years during the study period. After adjusting for the confounding factors, chronic atrophic gastritis (CAG) was identified as an independent risk factor [adjusted hazard ratio (HR), 2.72; 95% confidence interval, 1.33-5.57], while H. pylori-infected non-atrophic gastritis was not identified as an independent risk factor for recurrent colorectal neoplasia. Colorectal neoplasia recurred earlier and was significantly more frequent in patients with CAG (22,573/100,000 person-years) compared to patients without CAG (11,089/100,000 person-years; P=0.029, log-rank test). Patients with more extensive CAG showed a higher risk of recurrence. These results demonstrated a significant elevation of the risk of recurrent colorectal neoplasia with the establishment and progression of CAG, indicating the involvement of H. pylori infection in the development of colorectal neoplasia. The two serum tests were useful clinical markers for noninvasively evaluating the risk of each individual for recurrent colorectal neoplasia subsequent to endoscopic resection.

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.

Background Both double-balloon enteroscopy (DBE) and video capsule endoscopy (VCE) have similar diagnostic yields for patients with overt obscure gastrointestinal bleeding (OGIB). However, the choice of initial modality is still controversial. The aim of this study was to show the clinical outcome of the strategy of initial VCE, followed by DBE. Methods Eighty-nine consecutive overt OGIB patients who had undergone VCE as the initial examination were analyzed. The interpreters of VCE evaluated the necessity of performing DBE, and the antegrade or retrograde route was chosen, depending on the transit time of the capsule. Results Thirty-seven patients (42 %) underwent DBE depending on the findings of VCE. Of these, bleeding sites in the small bowel were identified in 29 patients with the initially selected route (21 antegrade and 8 retrograde). The remaining 8 later underwent DBE by the other route, but 7 had no bleeding lesion, which was confirmed by second-look VCE. One remaining patient had a jejunal varix found by VCE, but DBE from either side could not reach the lesion. The sensitivity and negative predictive value of VCE were 100 %, both for the presence of small bowel lesions and the requirement of hemostasis in the small bowel; this indicated that VCE never misses relevant findings in the small bowel, and that negative VCE findings correspond to the lack of necessity for further examination. Conclusions VCE as the initial examination can efficiently identify overt OGIB patients who require DBE. The strategy of initial VCE for overt OGIB appears to be reasonable.

OBJECTIVES The role of contrast-enhanced sonography in the diagnosis of recurrent hepatocellular carcinoma is still unclear. This study aimed to clarify the usefulness and limitations of contrast-enhanced sonography with a perfluorobutane microbubble contrast agent (Sonazoid; Daiichi-Sankyo, Tokyo, Japan) after contrast-enhanced computed tomography (CT) for diagnosis of recurrent hepatocellular carcinoma and to establish its optimal use. METHODS A total of 514 patients, who were suspected to have recurrent hepatocellular carcinoma on contrast-enhanced CT, underwent contrast-enhanced sonography. Of 514 suspicious lesions, 484 were diagnosed as recurrent hepatocellular carcinomas, including 142 recurrent hepatocellular carcinomas measuring 1 cm or smaller in diameter. The largest lesion was evaluated in each patient. A final diagnosis of recurrent hepatocellular carcinoma after contrast-enhanced CT was reached on the basis of the typical hallmarks of hepatocellular carcinoma on any of the other contrast imaging modalities or by resected tissue or tumor enlargement during follow-up. RESULTS The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of contrast-enhanced CT were 68%, 93%, 99%, 15%, and 70%, respectively, and the values of contrast-enhanced sonography were 91%, 100%, 100%, 31%, and 91%, excluding 60 unassessable lesions on contrast-enhanced sonography. The diagnostic rate for recurrent hepatocellular carcinoma on contrast-enhanced sonography for lesions with an atypical enhancement pattern on contrast-enhanced CT was 71%. On multivariate analysis of factors contributing to the unassessability of contrast-enhanced sonography, lesion size, location, and abdominal wall thickness were independent factors. CONCLUSIONS Although the assessability of contrast-enhanced sonography depends on lesion size, location, and abdominal wall thickness, contrast-enhanced sonography after contrast-enhanced CT is useful for confirmative diagnosis of small recurrent hepatocellular carcinoma with an atypical enhancement pattern on contrast-enhanced CT, even for lesions measuring 1 cm or smaller in diameter.

To investigate the effects of Japanese apricot (JA) consumption on gastroesophageal reflux disease (GERD)-related symptoms.Participants included individuals living in Minabe-cho, a well-known JA-growing region, who received specific medical check-ups by the local community health service in 2010. GERD-related symptoms were examined in 1303 Japanese individuals using a validated questionnaire, the Frequency Scale for Symptoms of GERD (FSSG), which consists of 7 questions associated with acid reflux symptoms and 5 questions asking about gastrointestinal dysmotility symptoms. Each question was answered using a 4-point scale, with higher scores indicating more severe GERD-related symptoms. Subjects were divided into two groups according to their intake of dried and pickled JA: daily intake (≥ 1 JA daily) (392 subjects) and none or occasional intake (1 JA daily) (911 subjects). FSSG scores were compared between subjects who consumed JA daily and those who did not. Next, subjects were stratified by age, gender and Helicobacter pylori (H. pylori) status for subanalyses.Those who ate JA daily were significantly older than those who did not (60.6 ± 10.5 years vs 56.0 ± 11.0 years, P0.001). Total FSSG scores were significantly lower in subjects with daily JA intake than in those with none or only occasional intake (2.13 ± 3.14 vs 2.70 ± 3.82, P = 0.005). In particular, subjects who consumed JA daily showed significantly improved FSSG dysmotility scores compared with subjects who did not (1.05 ± 1.58 vs 1.46 ± 2.11, P0.001). In contrast, the FSSG reflux score did not differ between subjects with and without daily intake of JA (1.08 ± 1.90 vs 1.24 ± 2.11, P = 0.177). Subanalysis indicated that improvement in dysmotility by JA intake was specifically observed in non-elderly (1.24 ± 1.68 vs 1.62 ± 2.22, P = 0.005) and H. pylori-negative subjects (0.99 ± 1.58 vs 1.57 ± 2.06, P0.001). GERD patients (total FSSG score ≥ 8) were less frequently observed among subjects with daily intake of JA as compared to those without daily intake of JA (6.1% vs 9.7%, P = 0.040).Daily JA intake may improve digestive dysmotility symptoms, resulting in relief of GERD symptoms. The effect is more obvious in non-elderly and H. pylori-negative subjects.

Background and Aim Esophageal varices are usually treated with endoscopic injection sclerotherapy (EIS) or endoscopic band ligation (EBL). However, frequent recurrences of varices after those procedures have been problematic. Argon plasma coagulation (APC) after EIS may be effective for preventing varix recurrence and, in recent years, we have routinely carried out APC after EIS. The aim of the present study was to verify the effectiveness of APC for preventing recurrence of varices after EIS. Methods A case–control study was carried out using a historical control cohort in a single center. The varix recurrence rate in 62 patients (34 men and 28 women, median age; 69 years) who underwent APC after EIS for hemorrhagic or risky esophageal varices (APC group) was compared with that of control patients who did not undergo APC after EIS (control group). Age-, sex-, and liver function-matched two control subjects were selected for one case subject (control group). Recurrence of varices was defined as rupture of varices or reappearance of risky varices. Results The 1-year and 2-year recurrence rates of the APC group were 9.7% and 11.3%, respectively. In contrast, the rates of the control group were 29.0% and 34.7%, respectively. Kaplan–Meier curves showed a significantly lower recurrence rate in the APC group (P = 0.013, log–rank test). No APC-related severe adverse events were observed. Conclusion APC after EIS was safe and could significantly prevent recurrence of esophageal varices. Therefore, the addition of APC should be routinely carried out after EIS.

Objectives An ultrasound contrast agent consisting of perfluorobutane microbubbles (Sonazoid; Daiichi Sankyo, Tokyo, Japan) accumulates in Kupffer cells, which thus enables Kupffer imaging. This study aimed to elucidate the association of defect patterns of hepatocellular carcinoma during the Kupffer phase of Sonazoid contrast-enhanced sonography with outcomes after radiofrequency ablation (RFA). Methods For this study, 226 patients with initial hypervascular hepatocellular carcinoma, who could be evaluated by contrast-enhanced sonography with Sonazoid before RFA, were analyzed. Patients were divided into 2 groups according to the tumor defect pattern during the Kupffer phase. The irregular-defect group was defined as patients with hepatocellular carcinoma that had a defect with an irregular margin, and the no-irregular-defect group was defined as patients with hepatocellular carcinoma that had either a defect with a smooth margin or no defect. Critical recurrence was defined as more than 3 intrahepatic recurrences, vascular invasion, dissemination, or metastasis. Results The irregular-defect and no-irregular-defect groups included 86 and 140 patients, respectively, and had cumulative 5-year critical recurrence rates of 49% and 17% (P < .01). Multivariate analysis indicated that the tumor diameter, lens culinaris agglutinin– reactive α-fetoprotein level, and defect pattern were independent factors related to critical recurrence. The cumulative 5-year overall survival rates for the irregular-defect and no-irregular-defect groups were 46% and 61% (P< .01). Multivariate analysis indicated that the Child-Pugh class, tumor diameter, lens culinaris agglutinin–reactive α-fetoprotein level, and defect pattern were independent factors related to survival. Conclusions The defect pattern of hepatocellular carcinoma during the Kupffer phase of Sonazoid contrast-enhanced sonography is associated with critical recurrence and survival after RFA.

A 69-year-old woman undergoing medical treatment for liver cirrhosis with chronic hepatic encephalopathy developed consciousness disturbance. Emergency blood analysis revealed hyperammonemia, and abdominal CT demonstrated a large splenorenal shunt as the cause of her symptoms. The splenic vein was embolized at the portal side of the shunt entrance via the percutaneous transhepatic route, while preserving the splenorenal shunt and preventing retrograde flow to the splenorenal shunt from the superior mesenteric vein. The temporary balloon occlusion of the outflow pathway of the shunt allowed safe and accurate embolization with detachable coils under the flow control of the shunt. After the interventional procedure, her blood NH3 level decreased markedly, and the hepatic encephalopathy immediately disappeared. Postprocedural elevation of portal blood pressure was slight.

Background and study aims: Early gastric cancers show gastric and/or intestinal phenotypes with specific mucin production profiles, and the phenotypes can vary with tumor progression. The aim of this study was to evaluate the correlation between tumor invasion patterns and phenotypes in the mucosa and submucosa of early gastric cancers. Methods: Phenotypic expressions of 44 endoscopically resected gastric cancers with submucosal invasion were evaluated immunohistochemically using MUC5AC and MUC6 as gastric and MUC2 and CD10 as intestinal phenotypic markers. Results: Cancers were classified into two patterns by invasion pattern: 19 collapsing pattern (C-pattern) tumors had cancer cells that invaded to the submucosa with expansive destruction of the muscularis mucosae, while 25 passing-through pattern (P-pattern) tumors formed focal cancer cell aggregations in the submucosa without massive destruction of the muscularis mucosae. Cancers with C-pattern invasion were likely to show similar phenotypes between the mucosa and submucosa, while phenotypes of cancers with P-pattern invasion were likely to differ between the two layers (rate of the same phenotypes: C-pattern 68% vs. P-pattern 28%, p = 0.008). Of 22 cancers with P-pattern invasion that included the intestinal phenotype component in the mucosa, 13 (59%) expressed the gastric phenotype alone in the submucosa. Conclusions: Phenotype presentation in the mucosa and submucosa differ by the invasion pattern in early gastric cancer. Tumors with P-pattern invasion are likely to express the gastric phenotype in the submucosa, regardless of phenotype in the mucosa, suggesting that such cancers might achieve submucosal invasion prior to intestinalization occurring in the mucosa.

Termitomyces-related symbiotic basidiomycetes in the nests of fungus-growing termites (Macrotermitinae) of several genera in Thailand were cultivated and analyzed phylogenetically based on the DNA sequence of nuclear ribosomal RNA genes. The relationships of the symbiotic fungi with host termites and their locality were apparently complex, supporting intricate mechanisms for the termites to acquire the symbionts.

A gene encoding a manganese-dependent peroxidase (MnP) of the oriental mushroom Elfvingia applanata has been cloned into λgt10 and characterized. This gene, Ea.mnp1, consists of a 1, 095 bp open reading frame coding for 364 amino acid residues. Northern blot analysis revealed that transcription of the Ea.mnp1 gene was elevated by an increase in Mn2+ to 200 mM or 0.1 g 2, 5-xylidine l−1. The Ea.mnp1 mRNA transcript levels changed in parallel with the observed changes in activity of MnP in E. applanata.

A 57-year-old Japanese man was admitted to our hospital with diarrhea, weight loss and malabsorption. Due to a high serum IgA level, we suspected α-heavy chain disease (α-HCD). However, no monoclonal IgA was detected on protein electrophoresis or immunofixation. Immunohistochemical staining of intestinal biopsy specimens showed proliferation of CD138(+)IgA(+) cells, compatible with a diagnosis of α-HCD. Most α-HCD patients exhibit M-proteins in the serum on electrophoresis or immunoelectrophoresis; however, some patients lack detectable M-proteins, similar to our patient. Therefore, when α-HCD is suspected based on the clinical features, immunohistochemistry is required to make a diagnosis.

The aim of the present study was to predict sustained virological response (SVR) to telaprevir with pegylated interferon (PEG-IFN) and ribavirin using viral response within 2 weeks after therapy initiation. Thirty-six patients with genotype 1 hepatitis C virus (HCV) and high viral load were treated by telaprevir-based triple therapy. SVR was achieved in 72% (26/36) of patients. Significant differences between the SVR group and non-SVR group were noted regarding response to prior PEG-IFN plus ribavirin, interleukin (IL)28B polymorphism, amino acid substitution at core 70, cirrhosis, hyaluronic acid level, and HCV-RNA reduction within 2 weeks. Setting 4.56 logIU/mL as the cut-off value for HCV-RNA reduction at 2 weeks, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 77%, 86%, 95%, 50%, and 79%, respectively, and for neither the IL28B minor allele nor core 70 mutant were 80%, 71%, 91%, 50%, and 78%, respectively. In conclusion, evaluation of viral reduction at 2 weeks or the combination of IL28B polymorphism and amino acid substitution at core 70 are useful for predicting SVR to telaprevir with PEG-IFN and ribavirin therapy.

Gastrectomy (GX) is thought to result in osteomalacia due to deficiencies in Vitamin D and Ca. Using a GX rat model, we showed that GX induced high turnover of bone with hyperosteoidosis, prominent increase of mineralization and increased mRNA expression of both osteoclast-derived tartrate-resistant acid phosphatase 5b and osteocalcin. The increased 1, 25(OH)2D3 level and unchanged PTH and calcitonin levels suggested that conventional bone and Ca metabolic pathways were not involved or changed in compensation. Thus, GX-induced bone pathology was different from a typical osteomalacia. Gene expression profiles through microarray analysis and data mining using Ingenuity Pathway Analysis indicated that 612 genes were up-regulated and 1,097 genes were down-regulated in the GX bone. These genes were related functionally to connective tissue development, skeletal and muscular system development and function, Ca signaling and the role of osteoblasts, osteoclasts and chondrocytes. Network analysis indicated 9 genes (Aldehyde dehydrogenase 1 family, member A1; Aquaporin 9; Interleukin 1 receptor accessory protein; Very low density lipoprotein receptor; Periostin, osteoblast specific factor; Aggrecan; Gremlin 1; Angiopoietin-like 4; Wingless-type MMTV integration site family, member 10B) were hubs connected with tissue development and immunological diseases. These results suggest that chronic systemic inflammation might underlie the GX-induced pathological changes in bone.

Spleen tyrosine kinase (Syk) is essential for downstream pathways in signaling from B-cell receptor (BCR) in B cells and Fc-gamma receptors in macrophages. Because of the essential roles it plays in signaling, Syk has been targeted in drug development for autoimmune and allergic diseases, in which B cells and macrophages have pivotal roles in the pathophysiology. In addition, accumulated data suggest that aberrant BCR signaling is deeply involved in the pathogenesis of B-cell malignancies. Here we report the pharmacological profile of a novel and highly selective Syk inhibitor, FF-10102-01 (FF-10102 hydrochloride). FF-10102-01 was evaluated in the following in vitro assays: Kinase inhibitory activities were performed with ProfilerPro Kit (PerkinElmer, USA). The effects on cell signaling and functions were studied using THP-1, a human monocyte-derived cell line, after differentiation with human recombinant interferon gamma (IFNγ). The effects on CD69, an activated B-cell marker, expression on B cells were evaluated using whole blood samples from healthy volunteers and mice, and on lymphoma cell growth using SU-DHL-6, a human diffuse large B-cell lymphoma-derived cell line. FF-10102-01 was also evaluated in vivo in animal models of antigen-induced antibody production, anti-platelet antibody-induced thrombocytopenia, and collagen-induced arthritis (CIA). FF-10102-01 showed high potency against recombinant human Syk enzyme activity, with a 50% inhibitory concentration (IC50) value of 1.2 nmol/L. Kinase profiling assay in a panel of 216 kinases revealed that FF-10102-01 is highly selective for Syk, with an IC50 value more than 25 times lower than those of the other kinases. FF-10102-01 exhibited suppressive effects on phosphorylation of downstream molecules of Syk, SLP76, and ERK1/2 in THP-1 cells. FF-10102-01 inhibited tumor necrosis factor α secretion under stimulation by immunoglobulin (Ig) G and phagocytosis of IgG-opsonized beads in IFNγ-induced differentiated THP-1 cells. CD69 expression under stimulation with anti-BCR antibodies in human and mouse blood was also inhibited by FF-10102-01, with IC50 values of 314 nmol/L and 307 nmol/L, respectively. FF-10102-01 was the most potent inhibitor of the growth of SU-DHL-6 cells among other known Syk, JAK, and Bruton's tyrosine kinase inhibitors compared, with an IC50 value of 318 nmol/L. FF-10102-01 is orally available with a good PK profile, and showed inhibitory effect at daily doses 50 mg/kg (as free base) on specific antibody production in ovalbumin-immunized mouse model. Orally administered FF-10102-01 showed significant effects in a mouse model of thrombocytopenia and a rat model of rheumatoid arthritis (CIA) at 25 mg/kg and 10 mg/kg (as free base), respectively. In the thrombocytopenia model, the prevention of platelet decrease by FF-10102-01 was well correlated with suppressions of platelet-phagocytotic macrophages in spleen and CD69-positive B cells in blood. These data indicate that FF-10102-01 is a potent and highly selective orally available Syk inhibitor, with pharmacological effects through inhibition of both B-cell and macrophage activities represented in inhibitions of cell signaling and functions in vitro, and in animal models of autoimmune diseases in vivo. The results suggest that FF-10102-01 is a promising agent for treatment of autoimmune diseases such as immune thrombocytopenia, rheumatoid arthritis, and B-cell malignancies. A clinical trial of FF-10102-01 is planned to commence in 2017. Disclosures Kinouchi: FUJIFILM Corporation: Employment. Taguchi:FUJIFILM Corporation: Employment. Shimoyama:FUJIFILM Corporation: Employment. Ioroi:FUJIFILM Corporation: Employment. Ogura:FUJIFILM Corporation: Employment. Yamamoto:Toyama Chemical Co., Ltd.: Employment. Iino:Toyama Chemical Co., Ltd.: Employment. Maeda:Toyama Chemical Co., Ltd.: Employment. Kato:Toyama Chemical Co., Ltd.: Employment. Fujiwara:FUJIFILM Corporation: Employment. Hagiwara:FUJIFILM Corporation: Employment. Iwamura:FUJIFILM Corporation: Employment. Kuter:Rigel: Consultancy, Research Funding; Genzyme: Consultancy; Bristol-Myers Squibb: Research Funding; GlaxoSmithKline: Consultancy; ONO: Consultancy; Amgen: Consultancy, Paid expert testimony; Protalex: Research Funding; MedImmune: Consultancy; Pfizer: Consultancy; Syntimmune: Consultancy; Shire: Consultancy; Eisai: Consultancy; 3SBios: Consultancy; CRICO: Other: Paid expert testimony; Shionogi: Consultancy. Nakamura:Toyama Chemical Co., Ltd.: Employment. Shimada:FUJIFILM Corporation: Employment.

In a previous population-based case-control study, we demonstrated an elevated risk of colorectal neoplasia with Helicobacter pylori (H. pylori) infection. The present study investigated the effects of H. pylori-associated chronic gastritis on the development of colorectal neoplasia by analyzing the recurrence of colorectal neoplasia subsequent to endoscopic resection. Ninety-nine patients who had undergone endoscopic resection of colorectal neoplasia were monitored under colonoscopy, and the recurrence of colorectal neoplasia was prospectively investigated. The stage of H. pylori-associated chronic gastritis in each subject was evaluated using a combination of two serum tests: H. pylori antibody and pepsinogen. In the present cohort, colorectal neoplasia recurred at a rate of 15,296/100,000 person-years during the study period. After adjusting for the confounding factors, chronic atrophic gastritis (CAG) was identified as an independent risk factor [adjusted hazard ratio (HR), 2.72; 95% confidence interval, 1.33–5.57], while H. pylori-infected non-atrophic gastritis was not identified as an independent risk factor for recurrent colorectal neoplasia. Colorectal neoplasia recurred earlier and was significantly more frequent in patients with CAG (22,573/100,000 person-years) compared to patients without CAG (11,089/100,000 person-years; P=0.029, log-rank test). Patients with more extensive CAG showed a higher risk of recurrence. These results demonstrated a significant elevation of the risk of recurrent colorectal neoplasia with the establishment and progression of CAG, indicating the involvement of H. pylori infection in the development of colorectal neoplasia. The two serum tests were useful clinical markers for noninvasively evaluating the risk of each individual for recurrent colorectal neoplasia subsequent to endoscopic resection.

Epithelial linings of 170 post operative maxillary cysts (POMCs) were microscopically examined, and correlations between lining epithelia and clinical findings were investigated. Then, using 45 of 170 POMCs (including ciliated (38), squamous (4), and composite lining epithelia (3 cases)), 30 radicular cysts (composed of ciliated (2), non-keratinized squamous (25) and of these composite epithelia (2), and keratinized epithelium (1)), and also using 25 dentigerous cysts revealing keratinized or non-keratinized epithelia in 8 and 17 cases, respectively, lectin-bindings and keratin localization were histochemically examined.Ninety walls of the subjected POMCs were lined with ciliated columnar epithelium, and linings of cuboidal, squamous and their combinations were seen in 6, 19, and 20 cases, respectively. Many POMCs lined with squamous epithelium revealed infection during past history, and a correlation between squamous lining and the infection was noted. RKSE60 keratin (56. 5 KD) only existed in the keratinized layer of squamous linings, while RGE 53 keratin (45 KD) was detected not only in all columnar epithelia, but also in all POMCs lined with squamous epithelia and 4 cases of maxillary radicular cysts. Tissue culture study of rabbit respiratory ciliated epithelium revealed that squamous cells, seemingly derived from originally columnar epithelium, and some newly proliferated squamous cells, induced with prostaglandin E1, E2 and dibutyryl cyclic AMP, reacted with RGE53 antibody. RGE53 keratin was therefore considered to be continuously maintained even after squamous metaplasia. From these results, it seems certain that epithelial linings of maxillary radicular cysts are sometimes derived from the respiratory epithelium associated with squamous metaplasia, and that RGE53 keratin is a useful marker for identification of metaplastic squamous cells.Most squamous epithelia bound strongly with SBA, Con A and UEA-I, while columnar epithelia showed weak bindings. Only a few linings of the tested cysts bound with SVGA. Among these lectins tested, SBA bindings revealed the most contrastive dramatic difference between both epithelia. Con A bound most prominently to squamous linings, and binding of UEA-I and SBA followed in this order. RKSE60 keratin-positive (i.e. keratinized squamous) epithelia had no glycoconjugates with SBA on basal cells. Contrarily, basal cells negative for this keratin had some lectin-binding sugar residues in most cases. From the above findings and other previous reports regarding keratin localization and lectin-binding in reduced enamel epithelium and dental lamina, it seems likely that keratinized lining of some dentigerous cysts may be derived from the early stage of tooth germ development. Metaplastic squamous epithelia intensely bound with SBA, Con A and UEA-I throughout the whole layer, and ciliated epithelium coexisting with squamous cells had similar staining patterns to those of metaplastic squamous epithelium. Ciliated epithelia of radicular cysts were also positive for SBA, Con A and UEA-I. Additionally, cultured respiratory epithelium gradually increased SBA binding ability corresponding to the degree of metaplastic change. Taking these facts into consideration, it is therefore likely that lectin binding sugar residues are expressed in advance on squamous metaplasia-ready columnar cell surfaces.

Keratins and secretory component (SC) were immunohistochemically examined in fresh tissue samples from 45 odontogenic and 35 non-odontogenic cysts. Lining epithelia of almost all cases contained keratins which reacted with polyclonal antibodies (Dako, Bio-Science), and no difference could be found between the two groups of lesions. By staining with two monoclonal antibodies against keratins, i.e., RGE53 (Bio-Science) and RKSE60 (Bio-Science), it was revealed that the epithelia of non-odontogenic cysts, which were columnar epithelium in most cases, had fully and positively reacted with RGE53, while none of the cases was positive for RKSE60. In contrast, the squamous linings of odontogenic cysts except for two cases did not react with RGE53, and few cases possessed RKSE60-reactive keratin. SC was also contradictory. All non-odontogenic cysts were proven to be positive for SC, but only 21 of the odontogenic cysts exhibited SC. Regarding each pair of non-odontogenic and odontogenic cysts covered with RGE53 and SC-positive, and RKSE60-negative squamous epithelium, it seemed reasonable from the staining results to conclude that the squamous linings were metaplastic from the columnar epithelium. Based on the results, concomitant examinations of SC with keratins will be helpful in deciding the epithelial derivation of jaw cysts.

Adenosquamous carcinoma (ASC) of the head and neck is extremely rare. We experienced ASC of the mandibular gingiva in a 64 year-old man having a history of lobectomy for pulmonary adenocarcinoma. The patient visited our clinic complaining of painless swelling on the mandibular gingiva in the central, lingual region. Soft, relatively smooth tumor measured 2.5×1.5cm in diameter was found on the gingiva. The overlying mucosa was deeply hyperemic and erosive in parts. One of the left submandibular lymphnodes solidly swelled to the size of the thumb-tip. Biopsied specimens exhibited both natures of squamous and adenomatous carcinoma microscopically, and the tumor was extirpated with no induction therapy. Histopathologic findings of the extirpated lesion were those of tumor nests consisted of proliferated peripheral basaloid cells and central squamous cells with necrotic spaces which gave a pseudoglandular picture. In some areas, mucous substance was observed in the ductlike structure, and mucous cells could be identified though being only few in number. Immunohistochemically, it was found that Total-Keratin was positive in the whole tumor cells, but RGE-53 Keratin existed only in basaloid cells. Metastatic lymphnode exhibited almost the same appearance as the primary lesion. From the above findings, the gingival tumor was considered as ASC but not a metastatic lesion from lung adenocarcinoma.

Fungus-growing termites efficiently decompose plant litter through their symbiotic relationship with basidiomycete fungi of the genus Termitomyces . Here, we investigated phenol-oxidizing enzymes in symbiotic fungi and fungus combs (a substrate used to cultivate symbiotic fungi) from termites belonging to the genera Macrotermes , Odontotermes , and Microtermes in Thailand, because these enzymes are potentially involved in the degradation of phenolic compounds during fungus comb aging. Laccase activity was detected in all the fungus combs examined as well as in the culture supernatants of isolated symbiotic fungi. Conversely, no peroxidase activity was detected in any of the fungus combs or the symbiotic fungal cultures. The laccase cDNA fragments were amplified directly from RNA extracted from fungus combs of five termite species and a fungal isolate using degenerate primers targeting conserved copper binding domains of basidiomycete laccases, resulting in a total of 13 putative laccase cDNA sequences being identified. The full-length sequences of the laccase cDNA and the corresponding gene, lcc1 - 2 , were identified from the fungus comb of Macrotermes gilvus and a Termitomyces strain isolated from the same fungus comb, respectively. Partial purification of laccase from the fungus comb showed that the lcc1 - 2 gene product was a dominant laccase in the fungus comb. These findings indicate that the symbiotic fungus secretes laccase to the fungus comb. In addition to laccase, we report novel genes that showed a significant similarity with fungal laccases, but the gene product lacked laccase activity. Interestingly, these genes were highly expressed in symbiotic fungi of all the termite hosts examined.

AIM: To compare the diagnostic performances of transnasal and standard transoral esophagogastroduodenoscopy (EGD) in gastric cancer screening of asymptomatic healthy subjects. METHODS: Between January 2006 and March 2010, a total of 3324 subjects underwent examination of the upper gastrointestinal tract by EGD for cancer screening, with 1382 subjects (41.6%) screened by transnasal EGD and the remaining 1942 subjects (58.4%) by standard transoral EGD. Clinical profiles of the screened subjects, detection rates of gastric neoplasia and histopathology of the detected neoplasias were compared between groups according to the stage of Helicobacter pylori (H. pylori)-related chronic gastritis. RESULTS: Clinical profiles of subjects did not differ significantly between the two EGD groups, except that there were significantly more men in the transnasal EGD group. During the study period, 55 cases of gastric mucosal neoplasias were detected. Of these, 23 cases were detected by transnasal EGD and 32 cases by standard transoral EGD. The detection rate for gastric mucosal neoplasia in the transnasal EGD group was thus 1.66%, compared to 1.65% in the standard transoral EGD group, with no significant difference between the two groups. Detection rates using the two endoscopies were likewise comparable, regardless of H. pylori infection. However, detection rates when screening subjects without extensive chronic atrophic gastritis (CAG) were significantly higher with standard transoral EGD (0.70%) than with transnasal EGD (0.12%, P < 0.05). In particular, standard transoral EGD was far better for detecting neoplasia in subjects with H. pylori-related non-atrophic gastritis, with a detection rate of 3.11% compared to 0.53% using transnasal EGD (P < 0.05). In the screening of subjects with extensive CAG, no significant differences in detection of neoplasia were evident between the two endoscopies, although the mean size of detected cancers was significantly smaller and the percentage of early cancers was significantly higher with standard transoral EGD. CONCLUSION: These results strongly suggest that the diagnostic performance of transnasal endoscopy is suboptimal for cancer screening, particularly in subjects with H. pylori-related non-atrophic gastritis.

A 66-year-old man developed dysphagia during dinner and was evaluated 2 d later in our hospital because of persistent symptoms. Upper gastrointestinal endoscopy showed no impacted food, but advanced esophageal cancer was suspected based on the presence in the upper esophagus of a large irregular ulcerative lesion with a thick white coating and stenosis. Further imaging studies were performed to evaluate for metastases, revealing circumferential esophageal wall thickening and findings suggestive of lung and mediastinal lymph node metastases. However, dysphagia symptoms and the esophageal ulcer improved after hospital admission, and histopathological examination of the esophageal mucosa revealed only nonspecific inflammation. At the time of symptom onset, the patient had been eating stewed beef tendon (Gyusuji nikomi in Japanese) without chewing well. Esophageal ulceration due to steakhouse syndrome was therefore diagnosed. The lung lesion was a primary lung cancer that was surgically resected. Although rare, steakhouse syndrome can cause large esophageal ulceration and stenosis, so care must be taken to distinguish this from esophageal cancer.

A 66-year-old woman underwent partial splenic embolization (PSE) for hypersplenism with idiopathic portal hypertension (IPH). One week later, contrast-enhanced CT revealed extensive portal vein thrombosis (PVT) and dilated portosystemic shunts. The PVT was not dissolved by the intravenous administration of urokinase. The right portal vein was canulated via the percutaneous transhepatic route under ultrasonic guidance and a 4 Fr. straight catheter was advanced into the portal vein through the thrombus. Transhepatic catheter-directed thrombolysis was performed to dissolve the PVT and a splenorenal shunt was concurrently occluded to increase portal blood flow, using balloon-occluded retrograde transvenous obliteration (BRTO) technique. Subsequent contrast-enhanced CT showed good patency of the portal vein and thrombosed splenorenal shunt. Transhepatic catheter-directed thrombolysis combined with BRTO is feasible and effective for PVT with portosystemic shunts.

The clinical investigations on the malar bone fractures treated in the past 5 years are reported with a proposal of the direct operative method for the arch fractures.Out of 31 malar fracture instances, 25 arches were involved. Persisting jaw trismus, however, was sometimes noticed immediately after the injury was observed in only a few cases. In 15 cases of the arch fractures complicated with the clear deformity, persistant jaw trismus or other fractures, the direct approach method was applied without sequence of facial nerve. Some merits of this surgical technique such as operative easiness, exact reduction and no requirement of the fixing equipment are advocated in view of the good results of the experience.

A modified method of Koele's technique reported in 1983 was applied to four cases of temporomandibular habitual luxation, while changes in the transplanted tissue with clinically used lyophilised dura (LYODURA) were observed in experimental animals. These results are summarised below.The modified procedure in brief is as follows. Formation of pedicle flap of dermis at the preaurecular region was almost same as the original method, however, the flap was strengthened with LYODURA. The dermic flap combined with LYODURA was introduced through the mandibular incision into the oral cavity. Both the flap and LYODURA were tightly sutured at the lateral portion of the coronoid process, i. e. to the lateral pterygoid muscle attachment for suppresing mandibular movements. The lower jaw was immobilized for about 3 weeks after surgery. This operation led to good results in four cases of habitual luxation of the mandible.Histologically, no foregin body reaction to grafted LYODURA was seen in dogs, and the planted LYODURA normally existed. From these clinical and experimental results, this surgical approach with potent LYODURA seemed to be applicable for treating temporomandibular habitual luxation.

We had the opportunity to treat a buccal angiomyoma in a woman who was operated for a uterine myoma. The buccal tumor, which was composed of smooth muscle and markedly dilated venous channels in the connective tissues, considered to be a cavernous type, was examined histochemically and evaluated concomitantly with the uterine myoma

Four cases of lateral cervical cysts were reported. All cyst walls were lined with keratinized stratified squamous epithelium, and contained lymph follicles with well-defined germinal centers. Ectopic salivary gland tissue was found in one case. Histochemical examination by the immunoperoxidase method revealed the existence of carcinoembryonic antigen (CEA). However, alpha-feto protein (AFP) and amylase were not detected in any of the cysts. The cyst fluid contained high levels of CEA and high titers of salivary type amylase, but AFP was negative. These results do not support any one of the theories concerning the etiology of cervical lymphoepithelial cysts. It seems likely that cysts derive from both epithelial remnants of the branchial apparatus and from salivary gland inclusions in lymph nodes.

Giantiform cementoma, a type of cementoma accorded to the WHO classifiction in 1971, is rarely seen in the literatures. A case of this tumor is reported with a summary as follows. A bony swelling as found on the body and ramus of the mandible of a refered 83-year-old woman. The smooth expansion covered with normal mucosa has persisted for about 40 yrs and slowly enlarged with no symptoms. In X-ray showed a demarcated radiopaque shadow with parts slightly radiolucent. The shadow seemed to be capsulated with healthy thin cortex. This was thought to be a benign tumor. A block dissection of the mandible was made. The dissected tumor was extremely hard with a yellowish cut-surface. The decarcified specimen was stained with H.E. for a subsequent microscopic examination.Connective tissue and infiltrated cells were nearly absent. In the central portion, basophilic hard tissue had formed and seemed to be primary cementum in such characteristics as dyeing fatigue and split spaces with no inclusion of cells. At the peripheral, and coexistence of the bone, fibrous and fat tissues could be seen. Substitution of bone by cementum and formation of cemeticles showing hematoxylin-line were also observed. On the basis of the above findings, a diagnosis of giantiform cementoma of the mandible was made.

Microscopic and clinical observations on 70 post-operative maxillary cysts were performed. Cysts of 47 cases were lined with the ciliatal epithelium, and 12 cases were composed of both squamous and ciliated cells. Squamous only and cuboidal lining were found in 9 and 2 cases, respectively. Duration after the antrum operation and the non-vital tooth related to the cyst did not affect the epithelial type, though many of the cases of squamous epithelium possessed infectious histories. From the results, the squamous change seemed to be acceralated by inflammatory irritations, and mucous cells in the lining epithelium were depleted as a part of the metaplastic sequence.

Hemangioma is a common lesion in the head and neck region, but Kasabach-Merritt syndrome,‘32 which is characterized by hemangioma with thrombocytopenia, is extremely rare. With large or multiple hemangiomas, consumption of coagulant factors may occur, and a consumptive coagulopathy similar to disseminated intravascular coagulation results.3-5 The syndrome has two therapeutic objectives. One is to control the coagulopathy,- and the other is to eradicate the hemangioma or reduce its size. 9310 To accomplish these purposes, many therapeutic treatment methods have been applied. This article reports a case of a 47-year-old woman with multiple hemangiomas, including many phleboliths, in the head and neck region, and suspected Kasabath-Merritt syndrome based on the hemostatic laboratory examinations.