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PDF - 85K, Table breakdown comparing the location of the primary tumor (GEJ or stomach) in males and females between the Japanese and US cohorts.

PDF - 87K, Table breakdown comparing the genotype frequency of the LMTK3 polymorphisms analyzed (rs99896661 and rs8108419) in the Japanese and US cohorts.

PDF - 86K, Plasma estradiol (E2) levels and body mass index comparison between males and females in the Japanese and US cohorts.

PDF - 62K, Breakdown by genotype of the LMTK3 polymorphisms analyzed and their correlation with survival (disease-free survival and overall survival) in the Japanese and US cohorts.

Endoscopic bilateral self-expandable metallic stent (SEMS) placement for unresectable malignant hilar biliary obstruction (MHBO) is widely performed; however, re-intervention after recurrent biliary obstruction (RBO) is often challenging. We compared stent-in-stent (SIS) and side-by-side (SBS) SEMS placement for MHBO considering re-intervention for RBO.One hundred five consecutive patients with MHBO who underwent endoscopic bilateral SEMS placement in our hospital and its affiliated institutions were enrolled in this study; 75 patients underwent partial SIS deployment between December 2005 and December 2012; and 30 underwent SBS deployment between January 2013 and March 2019. Initial treatments and re-interventions in each group were retrospectively evaluated.Technical success rate (92% vs 100%, P = 0.179), procedure duration (46 vs 35 min, P = 0.382), functional success rate (97.1% vs 100%, P = 1.00), complication rate (24.6% vs 20.0%, P = 0.797), time to RBO (260 vs 312 days; Gray test, P = 0.815), and rate of RBO (59.4% vs 70.0%, P = 0.371) were not significantly different between the SIS and SBS groups. However, bilateral re-stenting with plastic stents through SEMS was successful in 63.4% of patients in the SIS group compared with 100% of patients in the SBS group (P = 0.0013). Median time to RBO upon first re-stenting with a plastic stent was 75 days (range, 11-195 days).Endoscopic re-stenting after RBO was significantly more successful in the SBS group than in the SIS group. SBS method is suitable for MHBO considering revisionary stent placement.

The concept of BRCAness has been proposed as a homologous recombination repair dysfunction triggered by a genetic defect in the BRCA pathway including the BRCA1/2 mutations. A certain number of pancreatic ductal adenocarcinoma (PDAC) patients have BRCAness. However, a large-scale analysis of BRCAness in PDAC has not been performed. In addition, no basic studies have examined the significance of BRCAness in PDAC cell lines.Ninety-two patients who underwent surgery for PDAC were enrolled. Formalin-fixed and paraffin-embedded specimens of resected PDACs were used to analyze BRCAness by multiplex ligation-dependent probe amplification. We also analyzed BRCAness in pancreatic cancer cell lines and the sensitivity to cisplatin and olaparib using a colony formation assay.Of the 92 patients with PDAC, 6 were detected to have BRCAness-positive PDAC (6.5%). No significant differences in overall survival and progression-free survival were observed between the BRCAness-positive and BRCAness-negative groups. One PDAC cell line, KP-2, was positive for BRCAness and was more sensitive to cisplatin and olaparib than the BRCAness-negative cell lines.Our results revealed that a considerable number of PDACs are positive for BRCAness, suggesting that BRCAness status could be a useful biomarker for selecting anticancer treatments for advanced or relapsed PDAC.

CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, whose expression is upregulated in some types of malignant tumors. High levels of CD109 in tumor cells have been reported to correlate with poor prognosis; however, significance of CD109 stromal expression in human malignancy has not been elucidated. In this study, we investigated the tumorigenic properties of CD109 in pancreatic ductal adenocarcinoma (PDAC). Immunohistochemical analysis of 92 PDAC surgical specimens revealed that positive CD109 expression in tumor cells was significantly associated with poor prognosis (disease-free survival, p = 0.003; overall survival, p = 0.002), and was an independent prognostic factor (disease-free survival, p = 0.0173; overall survival, p = 0.0104) in PDAC. Furthermore, CD109 expression was detected in the stroma surrounding tumor cells, similar to that of α-smooth muscle actin, a histological marker of cancer-associated fibroblasts. The stromal CD109 expression significantly correlated with tumor progression in PDAC (TNM stage, p = 0.033; N factor, p = 0.024; lymphatic invasion, p = 0.028). In addition, combined assessment of CD109 in tumor cells and stroma could identify the better prognosis group of patients from the entire patient population. In MIA PaCa-2 PDAC cell line, we demonstrated the involvement of CD109 in tumor cell motility, but not in PANC-1. Taken together, CD109 not only in the tumor cells but also in the stroma is involved in the progression and prognosis of PDAC, and may serve as a useful prognostic marker in PDAC.

We herein report a rare case of cartilage-hair hypoplasia (CHH) complicated with liver cirrhosis. A 20-year-old Japanese man with CHH was found incidentally to have liver cirrhosis and an esophageal varix. This patient had been treated for infections due to immunodeficiency since early childhood. He ultimately died of liver failure at 31 years of age. An autopsy revealed an abnormality of the interlobular bile ducts and intrahepatic cholestasis. Liver cirrhosis was thought to have been caused by chronic intrahepatic cholestasis due to biliary duct hypoplasia and changes in the intestinal microbiome. Therefore, CHH may cause biliary cirrhosis due to multiple effects.

The process of gastric ulcer healing includes cell migration, proliferation, angiogenesis and re‐epithelialization. Platelets contain angiogenesis stimulating factors that induce angiogenesis. Thromboxane A2 (TXA2) not only induces platelet activity but also angiogenesis. This study investigated the role of TXA2 in gastric ulcer healing using TXA2 receptor knockout (TPKO) mice. Gastric ulcer healing was suppressed by treatment with the TXA2 synthase inhibitor OKY‐046 and the TXA2 receptor antagonist S‐1452 compared with vehicle‐treated mice. TPKO showed delayed gastric ulcer healing compared with wild‐type mice (WT). The number of microvessels and CD31 expression were lower in TPKO than in WT mice, and TPKO suppressed the expression of transforming growth factor beta (TGF‐β) and vascular endothelial growth factor A (VEGF‐A) in areas around gastric ulcers. Immunofluorescence assays showed that TGF‐β and VEGF‐A co‐localized with platelets. Gastric ulcer healing was significantly reduced in WT mice transplanted with TPKO compared with WT bone marrow. These results suggested that TP signalling on platelets facilitates gastric ulcer healing through TGF‐β and VEGF‐A.

Background: Data regarding the additional effect on the recurrence of hepatic encephalopathy (HE) after oral L-carnitine administration are scarce. Objective: This study aimed to assess the additional effects of L-carnitine in patients who were receiving rifaximin for HE. Methods: This randomized study comprised a screening visit and a 12-week treatment period. Patients who fulfilled the eligibility criteria were randomized to either group A (additional rifaximin) or group B (additional L-carnitine and rifaximin). Group A received 1,200 mg/day of rifaximin. Group B received 1,500 mg/day of L-carnitine and rifaximin at 1,200 mg/day. The endpoints were the changes in the portal systemic encephalopathy (PSE) index and the admission rate from the baseline for the duration of the study in both groups. Results: Eighty-three patients were randomized to either group A (n = 42) or group B (n = 41). In group A, the PSE index decreased from 0.35 ± 0.09 at baseline to 0.27 ± 0.11 on the final evaluation day (p = 0.001). In group B, the PSE index decreased from 0.37 ± 0.09 at baseline to 0.24 ± 0.11 on the final evaluation day (p = 0.001). Although there was not a significant reduction in the PSE index in group A compared to that in group B (p = 0.202), the admission rates were 30.9% and 9.8% in groups A and B, respectively. Additional L-carnitine significantly reduced the admission rate (p = 0.028). Conclusion: L-Carnitine addition reduced the risk of hospitalization for patients who received rifaximin for HE.

Stone removal using endoscopic papillary large balloon dilation (EPLBD) is extremely effective. However, limited research exists regarding the risk factors for perforation of the duodenal papilla and bile duct, which may be fatal. We aimed to investigate the risk factors for perforation during EPLBD + stone removal. We included patients who underwent EPLBD + stone removal at four medical facilities between January 2008 and December 2018. We retrospectively analyzed the risk factors for perforation and their relationship between overdilation and adverse events. Overdilation was defined as a ratio of the balloon diameter to the diameter of the bile duct that exceeded 100%. The diameter of the distal bile duct was measured using the diameter of the intrapancreatic bile duct at a point 10 mm toward the liver from the narrow distal segment on a cholangiogram. We included 310 patients (177 males; median age: 79 years [range: 46–102 years]). Perforation occurred in five patients (1.6%). Multivariate analysis indicated that no surrounding-pancreas (half or less of the circumference of the intrapancreatic bile duct was surrounded by the pancreatic parenchyma) was a significant risk factor (perforation rate: 8.3%, p = 0.011, odds ratio: 12.7 [95% confidence interval: 1.8–90.5]). No significant difference was found between the overdilation and non-overdilation groups regarding the occurrence of pancreatitis, bleeding, and cholangitis. Perforation rate in patients with no surrounding pancreas + overdilation was 16.7% (2/12). Patients with perforation underwent conservative therapy, which improved their conditions. EPLBD + stone removal should be avoided in patients with no surrounding pancreas. Overdilation is not a risk factor for adverse procedural events; however, it should be limited in patients with surrounding pancreas.

A schwannoma is a tumor originating from Schwann cells. It is occasionally observed in the abdominal viscera in the form of a submucosal tumor derived from the gastric or duodenal muscularis propria. To date, only a few studies have reported on pancreatic schwannomas. Furthermore, very few patients are preoperatively diagnosed with pancreatic schwannoma because of the lack of established imaging characteristics distinguishing this type of schwannoma from other conditions. We herein report the first English publication of pancreatic schwannoma in which surgery was avoided because a pathological diagnosis was made solely on the basis of endoscopic ultrasound-guided fine-needle aspiration findings.

We herein report the first case of metastatic pancreatic leiomyosarcoma derived from the urinary bladder diagnosed by an endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) in a 65-year-old woman. The patient had undergone total cystectomy for bladder leiomyosarcoma. Four years thereafter, a nodule was observed in her left lung on chest computed tomography. Suspecting primary lung cancer, pulmonologists at our hospital recommended a thoracoscopic lung biopsy, which the patient refused. Five years post-cystectomy, fluorodeoxyglucose positron emission tomography revealed enlargement of the left lung nodule and a new mass in the pancreatic head. She was referred to our department for the pathological diagnosis of a pancreatic head mass by an EUS-FNB. The EUS-FNB yielded adequate pancreatic tissue for an immunohistochemical analysis. A diagnosis of metastatic pancreatic lesion originating from the urinary bladder was made. In atypical pancreatic tumors, the utilization of an EUS-FNB and immunohistochemical analysis can help establish an accurate diagnosis.

BACKGROUND Information on whether a fine-needle biopsy (FNB) needle can improve histopathological specimen quality or the amount of core tissue collected in the diagnosis of subepithelial lesions (SELs) remains insufficient. In this study, we aimed to compare the procedure outcomes and adequacy of histopathological specimens of fine-needle aspiration (FNA) and FNB needles in endoscopic ultrasound-guided tissue acquisition (EUS-TA) using sample isolation processing by stereomicroscopy (SIPS) in patients with SELs. METHODS We performed a retrospective comparison of SEL cases registered in two previously conducted prospective studies. Of 61 cases, we identified 56 cases of SELs that involved the muscularis propria layer. Of these, 27 patients who underwent EUS-TA using a 22-gauge FNA needle between July 2016 and December 2017, and 29 patients who underwent the procedure using a 22-gauge FNB needle between March 2018 and January 2019 were included in the FNA and FNB group, respectively. RESULTS Patient background characteristics did not differ between the groups. The technical success rate was 100% in both groups. The median adequacy score was significantly higher in the FNB group than in the FNA group (P

Objective The aim of this retrospective study is to evaluate the usefulness of upper gastrointestinal endoscopy and the ValsamouthⓇ by an otolaryngologist in patients with hypopharyngeal cancer to assess the risk. Methods The study group comprised 41 patients with untreated hypopharyngeal cancer that was precisely diagnosed by an otolaryngologist using upper gastrointestinal endoscopy and the ValsamouthⓇ at our hospital from January 2016 to December 2017. With upper gastrointestinal endoscopy and the ValsamouthⓇ, the oral cavity, oropharynx, larynx, hypopharynx, and esophagus were observed in this order. Narrow-band imaging, and subsequently, white-light observation were performed. At the hypopharynx, vocalization, and subsequently, the Valsalva maneuver were performed. After observing the esophagus, Lugol chromoendoscopy of the esophagus was performed. Results The mean age of the 38 men and 3 women included in the study was 69.7 ± 10.0 years (range, 51–94 years). As for the T category of hypopharyngeal cancer, T1 cancer was observed in 9 patients, T2 cancer in 14, T3 cancer in 11, and T4 cancer in 7. With vocalization, the grade of visualization in the hypopharynx was 1 in 30 patients (73.2%), 2 in 11 patients (26.8%), and 3 or more in 0 patients (0.0%). With the Valsalva maneuver, the grade of visualization in the hypopharynx was 1 in 1 patient (2.4%), 2 in 15 patients (36.6%), 3 in 8 patients (19.5%), 4 in 11 patients (26.8%), and 5 in 6 patients (14.6%). The grade of visualization in the hypopharynx on average was 1.27 after vocalization and 3.15 after the Valsalva maneuver (p Conclusion The examination with upper gastrointestinal endoscopy and the ValsamouthⓇ by an otolaryngologist is feasible in patients with hypopharyngeal cancer. This procedure can detect synchronous esophageal cancer, allowing the risk of metachronous cancer in the head and neck or the esophagus to be recognized after the treatment.

Endoscopic retrograde cholangiopancreatography (ERCP) is associated with complications such as post-ERCP pancreatitis (PEP). Protease inhibitors, including nafamostat mesylate (NM), have been evaluated for prophylaxis against PEP. We describe the first multicenter randomized controlled trial assessing the prophylactic efficacy of NM against PEP. In this multicenter prospective study, we aimed to enroll 800 patients aged ≥ 20 years with a planned ERCP between December 2012 and March 2019. The primary outcome was the incidence and severity of PEP in patients who did not receive NM (non-NM) versus those who did (NM; 20 mg). Secondary outcomes included the incidence of PEP by NM initiation (pre- and post-ERCP), risk factors for PEP, and NM-related adverse events. Only 441 of the planned 800 patients were enrolled (non-NM: n = 149; NM: n = 292 [pre-ERCP NM: n = 144; post-ERCP NM: n = 148]). Patient characteristics were balanced at baseline with no significant differences between groups. PEP occurred in 40/441 (9%) patients (non-NM: n = 15 [10%]; NM: n = 25 [9%]), including 17 (12%) and eight (8%) in the pre-ERCP and post-ERCP NM groups, respectively. In the NM group, the incidence of PEP was lower in the low-risk group than in the high-risk group. Pancreatic injection and double-guidewire technique were independent risk factors for PEP. NM-related adverse events of hyperkalemia occurred in two (0.7%) patients. We found no evidence for the prophylactic effect of NM against PEP, regardless of the timing of administration; however, further studies are needed.

Sample isolation processing by stereomicroscopy (SIPS) was recently introduced as an alternative to rapid on-site cytologic evaluation and showed high accuracy for use in pathologic diagnoses. SIPS is a useful, but slightly complicated procedure; therefore, a new, more straightforward method for the objective estimation of the core tissue amount required during the sampling is desirable. We evaluated the usefulness of the automated multiband imaging system (AMUS) for calculating whitish core amounts in EUS-FNA biopsy (EUS-FNAB) samples from patients with subepithelial lesions (SELs).Four EUS-FNAB specimens per patient were obtained from 20 patients with upper gastrointestinal SELs. The correlation between the whitish core amount calculated by AMUS, length of the manually measured whitish cores (stereomicroscopically visible white core [SVWC]), and sample suitability for pathologic evaluation were analyzed.We identified 13 patients with gastrointestinal stromal tumors, five with leiomyomas, one with a schwannoma, and one with an ectopic pancreas. The histological diagnostic accuracy was 100%, median SVWC length was 9 mm, and median whitish core area, calculated using AMUS, was 10 mmAMUS, a simple on-site verification instrument, is an alternative to SIPS for determining the appropriate SEL tissue sampling quantity with high diagnostic accuracy.

Background This study evaluated the association between early tumor response at 8 weeks, previously reported as a positive outcome prognosticator, and health-related quality of life (HRQOL) in advanced gastric cancer (AGC) patients enrolled in the ABSOLUTE trial. Methods HRQOL was assessed using the EuroQol-5 Dimension (EQ-5D) utility index score in patients with complete response (CR) + partial response (PR) and progressive disease (PD) at 8 weeks, and time-to-deterioration (TtD) of the EQ-5D score, with the preset minimally important difference (MID) of 0.05, was compared between these populations. Among the enrolled patients, 143 and 160 patients were assessable in weekly solvent-based paclitaxel (Sb-PTX) arm and weekly nanoparticle albumin-bound paclitaxel (nab-PTX) arm, respectively. Results Changes of the EQ-5D score from baseline to 8 weeks in the nab-PTX arm were 0.0009 and − 0.1229 in CR + PR and PD patients, respectively; the corresponding values for the Sb-PTX arm were − 0.0019 and − 0.1549. For both treatments, changes of the EQ-5D score from baseline at 8 weeks were significantly larger in patients with PD than in those with CR + PR. The median TtD was 3.9 and 2.2 months in patients with CR + PR and PD, respectively, for nab-PTX [hazard ratio (HR) = 0.595, 95% confidence interval (CI) 0.358–0.989]. For Sb-PTX, the corresponding values were 4.7 and 2.0 months (HR = 0.494, 95% CI 0.291–0.841). Conclusions Early tumor shrinkage was associated with maintained HRQOL in AGC patients on the second-line chemotherapy with taxanes.

Abdominal ultrasound in a 50-year-old Japanese man revealed a cystic lesion on the caudate lobe of the liver. Four-month follow-up imaging showed a rapid increase in the size of the cystic lesion. The patient underwent laparoscopic partial hepatectomy because of a suspicion and perceived risk that the lesion might be malignant. The initial histological diagnosis was a hepatic cyst. Eleven months later, computed tomography showed a giant cystic lesion in the abdominal cavity and multiple liver metastases. The patient underwent excision of the giant cystic lesion and a partial hepatectomy. Immunohistochemistry for the recurring lesion revealed undifferentiated embryonal sarcoma of the liver.

AIM Lenvatinib is an oral, multitargeted, tyrosine kinase inhibitor, which suppress tumor angiogenesis and tumor progression. It was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma (HCC). Sorafenib had a beneficial effect on portocollateral circulation with portal hypertension in translating and clinical studies. However, the hemodynamic effects of lenvatinib appear to be different from those of sorafenib because the efficacy of lenvatinib for vascular endothelial growth factor receptors and fibroblast growth factor receptors is different from that of sorafenib. This study was prospectively performed to evaluate the portal hemodynamic effect of lenvatinib in patients with advanced HCC using duplex Doppler ultrasonography. METHODS In total, 28 Child-Pugh class A or B patients with advanced HCC received lenvatinib depending on body weight daily for 2 weeks. Primary outcomes were changes in the hemodynamics of the portal venous system using duplex Doppler ultrasonography before and after the 2-week administration of lenvatinib. RESULTS The portal venous flow velocity (cm/s) significantly reduced (27 ± 12.1 vs. 22.6 ± 8.0, P = 0.019), while portal venous area (cm2 ) did not change after the 2-week administration (0.80 ± 0.36 vs. 0.82 ± 0.27, P = 0.665). Therefore, the congestion index (portal venous area/portal venous flow velocity), which reflects the pathophysiological hemodynamics of the portal venous system significantly worsened (0.037 ± 0.025 vs. 0.043 ± 0.024, P = 0.045). CONCLUSIONS Considering that this was a short-term study, because lenvatinib could be an agent that aggravates portal hypertension, it will be necessary to verify its clinical effects for portal hypertension in future studies.

The purpose of this study is to evaluate the long-term survival outcomes of KDOG1001 trial after a minimum follow-up of 3 years. Patients with bulky N2 lymph nodes, linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) received up to four 28-day cycles of DCS neoadjuvant chemotherapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 lymphadenectomy plus adjuvant S-1 therapy for 1 year. The final preplanned analysis of long-term outcomes including overall survival and relapse-free survival was conducted after minimum follow-up of 3 years. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN 000003642, and has been completed. From May 2010 through January 2017, 40 patients were enrolled. All included patients underwent neoadjuvant chemotherapy with DCS followed by gastrectomy with D2 lymphadenectomy, and 32 (80%) completed adjuvant S-1 therapy for 1 year. After a median follow-up for surviving patients of 68 months at the last follow-up in January 2020, 3-year overall survival rate was 77.5% (95% confidence interval 62.1–87.9%), while 3-year relapse-free survival rate was 62.5% (95% confidence interval 46.8–76.0%). Neoadjuvant chemotherapy with 4 cycles of DCS followed by D2 gastrectomy plus adjuvant S-1 was associated with relatively good long-term oncologic outcomes for patients with the high-risk gastric cancer.

A 76-year-old man had a diagnosis of double primary cancers consisting of poorly differentiated esophageal squamous cell carcinoma (ESCC) invading the submucosa and poorly differentiated gastric adenocarcinoma (GAC) invading the submucosa. The clinical stage of both ESCC and GAC was T1N0M0 stage I. The tumor diameter of ESCC and GAC was 20 mm and 25 mm, respectively. We performed chemoradiotherapy for ESCC. Chemotherapy consisted of nedaplatin in an intravenous dose of 90 mg/m2 on day 1 and 5-fluorouracil in an intravenous dose of 800 mg/m2 on days 1–5, repeated every 4 weeks for two cycles. Radiotherapy consisted of 50.4 Gy in 28 fractions for ESCC. GAC was down-staged after chemoradiotherapy for ESCC and was treated by endoscopic submucosal dissection (ESD). The tumor was histopathologically confirmed to be down-staged to intramucosal cancer with a diameter of 18 mm and no evidence of lymphovascular invasion and ulceration. Multiple metastasis occurred in the stomach, the small intestine and the colorectum after ESD. ESD is not a curative treatment even if chemotherapy is effective for poorly differentiated GAC invading the submucosa. Multiple gastrointestinal metastasis may be a unique recurrence pattern after ESD for such a lesion.

The optimal dose of each drug used in the docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy remains to be clarified for the Japanese population. The purpose of this study was to determine a recommended dose for a combination neoadjuvant DOS chemotherapy for Japanese patients with locally advanced adenocarcinoma of the esophagogastric junction (AEG). Patients with cT3 or more advanced AEG without distant metastasis were eligible for this study. The planned dosages of docetaxel (mg/m2, day 1), oxaliplatin (mg/m2, day 1), and S-1 (mg/day, days 1–14) were: 50/100/80–120 at level 1, and 60/100/80–120 at level 2, respectively. The treatment cycle was repeated every 3 weeks, and patients were assessed for response to the treatment after 2 and 3 cycles. This study was registered in the UMIN Clinical Trial Registry (UMIN 000022210). We enrolled 12 patients with locally advanced AEG in this study. At dose level 1, one of the six patients experienced dose-limiting toxicity (DLT) of grade 3 diarrhea and grade 3 febrile neutropenia. Two of the next six patients also experienced DLT of need for more than 2-week delay of the start of the second cycle due to adverse events at dose level 2. Based on these results, level 2 was considered the recommended dose for this regimen. Recommended doses of docetaxel (mg/m2), oxaliplatin (mg/m2), and S-1 (mg/day) were 60/100/80–120. This chemotherapy scheme showed good preliminary efficacy with acceptable toxicity warranting a further phase II trial to investigate the efficacy of this regimen.

Background Autotaxin (ATX) has been reported as a direct biomarker for estimating the evaluation of liver fibrosis. But available data on ATX as a useful biomarker for the complications of liver cirrhosis (LC) are scant. Aim To assess the clinical usefulness of ATX for assessing the complications of LC. Methods This multicenter, retrospective study was conducted at six locations in Japan. We include patients with LC, n = 400. The ATX level was evaluated separately in men and women because of its high level in female patients. To assess the clinical usefulness of ATX for the complications of LC, the area under the curve (AUC) of ATX assessing for the severe complications was analyzed in comparison with the model for end-stage liver disease score, albumin-bilirubin (ALBI) score, fibrosis-4 index, and aspartate aminotransferase-to-platelet ratio index. Results The mean age was 68.4 ± 11.4 years, 240 patients (60.0%) were male. A total of 213 (53.3%) and 187 (46.8%) patients were compensated and decompensated, respectively. The numbers of patients with varix rupture, hepatic ascites, and hepatic encephalopathy were 35 (8.8%), 131 (32.8%), and 103 (25.8%), respectively. The AUCs of ATX in men for hepatic encephalopathy, hepatic ascites, and varix ruptures were 0.853, 0.816, and 0.706, respectively. The AUCs of ATX in women for hepatic encephalopathy, hepatic ascites, and varix rupture were 0.759, 0.717, and 0.697, respectively. The AUCs of ATX in men were higher than those in women, as were all the other biomarkers used to detect encephalopathy and varix ruptures. However, for detecting ascites, the AUC of ALBI in men was more effective than using ATX. Conclusion ATX in men was more effective than any other biomarkers for detecting hepatic encephalopathy and varix ruptures.

Background and Aims Although rapid on-site cytologic evaluation (ROSE) during EUS-guided FNA biopsy (EUS-FNAB) sampling may improve accuracy of pathologic analyses, cytopathologists are not widely available. We calculated the cutoff lengths required for accurate pathologic diagnoses from stereomicroscopically visible white cores (SVWCs) sampled using 22-gauge needles. Methods Overall, 118 patients with mediastinal or upper abdominal solid masses requiring pathologic diagnoses were included. EUS-FNAB sampling was performed using 22-gauge needles. SVWCs were isolated and measured using stereomicroscopy, and the utility of calculated cutoff lengths in diagnosis was investigated. Results The procedure success and SVWC sampling rates were both 100%, and the median SVWC length was 10 mm. Pathologic examination identified 75, 31, and 12 patients with pancreatic neoplasms (PNs), subepithelial lesions (SELs), and other lesions, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosing malignancy using EUS-FNAB sampling were 93.1%, 100%, 100%, 69.6%, and 94%, respectively. The final diagnostic accuracy in the entire cohort, PNs, and SELs was 92.4%, 90.7%, and 93.5%, respectively. Receiver operating characteristic curves demonstrated the overall SVWC cutoff length to be 11 mm (11 mm for PNs, 3.5 mm for SELs). The overall sensitivity according to SVWC cutoff length was 91.4% (87.6% for PNs, 98.8% for SELs). Compared with cutoff length, multivariate analysis confirmed SVWC length to be a stronger independent factor for tissue diagnosis in both groups. Conclusions Diagnosis improved significantly with SVWC cutoff lengths ≥11 mm. This may be a useful index for endoscopists, particularly where ROSE is unavailable. (Clinical trial registration number: UMIN000023013.)

CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, whose expression is upregulated in some types of malignant tumors. High levels of CD109 in tumor cells have been reported to correlate with poor prognosis; however, significance of CD109 stromal expression in human malignancy has not been elucidated. In this study, we investigated the tumorigenic properties of CD109 in pancreatic ductal adenocarcinoma (PDAC). Immunohistochemical analysis of 92 PDAC surgical specimens revealed that positive CD109 expression in tumor cells was significantly associated with poor prognosis (disease-free survival, p = 0.003; overall survival, p = 0.002), and was an independent prognostic factor (disease-free survival, p = 0.0173; overall survival, p = 0.0104) in PDAC. Furthermore, CD109 expression was detected in the stroma surrounding tumor cells, similar to that of α-smooth muscle actin, a histological marker of cancer-associated fibroblasts. The stromal CD109 expression significantly correlated with tumor progression in PDAC (TNM stage, p = 0.033; N factor, p = 0.024; lymphatic invasion, p = 0.028). In addition, combined assessment of CD109 in tumor cells and stroma could identify the better prognosis group of patients from the entire patient population. In MIA PaCa-2 PDAC cell line, we demonstrated the involvement of CD109 in tumor cell motility, but not in PANC-1. Taken together, CD109 not only in the tumor cells but also in the stroma is involved in the progression and prognosis of PDAC, and may serve as a useful prognostic marker in PDAC.

Background: Data regarding the influence of patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism for patients with liver cirrhosis (LC) are scarce. Objective: This study assesses the role of the PNPLA3 polymorphism for the development of LC and its complications by the findings of genetic examinations. Methods: Patients with LC caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33) and without LC (n = 128) were enrolled. LC was composed of the presence and absence of complications, such as variceal bleeding, hepatic ascites, and hepatic encephalopathy. To assess the role of the PNPLA3 polymorphism, odds ratio (OR) for the rs738409 variant was calculated for the patients between (i) with LC and without LC in the entire cohort and (ii) the presence and absence of complications in the patients with LC. Results: There was a significant difference among the patients without LC and those with alcohol, NAFLD-related LC in the frequency of G alleles (p < 0.001, both). According to complications of LC, the OR for NAFLD-related cirrhosis significantly increased in the presence of the two mutated alleles (OR = 3.165; p = 0.046) when the wild type was used as the reference. However, there were no significant risks for the complications in the virus and alcohol-related cirrhosis unless there was a presence of G alleles. Conclusion: The PNPLA3 polymorphism was associated with the risk of NAFLD-related LC and its complications.