Potential significance of uncovered self-expandable metal stents for distal malignant biliary obstruction: A propensity score-adjusted competing risk regression analysis.

Objectives: Selection criteria for self-expandable metal stents (SEMSs) with or without cover during palliative treatment of distal malignant biliary obstruction (DMBO) remain unclear. We evaluated factors associated with time to recurrent biliary obstruction (TRBO) in fully covered SEMSs (FCSEMSs) and uncovered SEMSs (UCSEMSs). Methods: We retrospectively analyzed consecutive patients with DMBO who received a SEMS. TRBO was determined using the Kaplan-Meier analysis, and complications were compared between the FCSEMS and UCSEMS groups. After TRBO-associated factors were extracted using multivariate competing-risks regression (CRR), propensity score-adjusted CRRs were performed to verify their robustness. Results: There were 180 patients (66 FCSEMSs and 114 UCSEMSs) enrolled in this study. There was no significant difference between median TRBO in the FCSEMS and UCSEMS groups (275 vs. 255 days, p = 0.67). Complications were more frequent in the FCSEMS than UCSEMS group (21.2% vs. 8.8%; p = 0.023). Multivariate CRR for TRBO-associated factors revealed that "pancreatic ductal carcinoma (PDAC) treated with UCSEMS" was the only independent predictor of TRBO (p = 0.03). Similarly, the propensity score-adjusted CRRs showed no significant difference in TRBO in "FCSEMS" vs "UCSEMS" (p = 0.96); however, there was a significant difference in "PDAC using UCSEMS" vs "other" (p = 0.043). In the palliative care group including any DMBO without chemotherapy, the first quartile of the TRBO of UCSEMS was 100 days. Conclusions: UCSEMSs are a possible option for both patients with DMBO arising from PDAC and for patients with any DMBO receiving palliative care who should avoid SEMS-related complications.

Impact of qualitative endoscopic ultrasonography on fatty pancreas at a referral medical center.

BACKGROUND: Taking advantage of the current advances in diagnostic imaging modalities, including endoscopic ultrasonography (EUS), and due to the increased attention to ectopic fat accumulation in the pancreas following the rising trend of metabolic syndrome, we qualitatively assessed the clinical implication of pancreatic steatosis by EUS in this study. METHODS: The study included 243 patients that were divided into four groups. The correlation between the average echogenicity of the pancreas and that of the control organs and the key clinical data of all study patients were collectively analyzed. The cut-off point of the pancreas-control (PC) ratio in EUS and liver-control (LC) ratio on abdominal ultrasound were determined from the population distribution and the obtained median values. RESULTS: With the cut-off point of 1.30 for the PC ratio and 1.20 for the LC ratio, sex, the Brinkman index, habitual alcohol drinkers, and fatty pancreas were significant factors. The associations between each relevant factor in fatty pancreas, metabolic syndrome in the fatty liver group, and age in the pancreatic cancer group were all significant in the analysis. In addition, we investigated whether the PC ratio differed according to age and staging in pancreatic cancer patients. Interestingly, the PC ratio was lower in the advanced stage group than in the early-stage group. CONCLUSION: Our results suggest that, irrespective of the degree, ectopic fat infiltration in the pancreas could be a specific clinical phenotype of serious pancreatic diseases, including pancreatic cancer, especially in high-risk patients.

Endoscopic ultrasound-guided fine-needle biopsy histology with a 22-gauge Franseen needle and fine-needle aspiration liquid-based cytology with a conventional 25-gauge needle provide comparable diagnostic accuracy in solid pancreatic lesions.

BACKGROUND AND AIM: Fine-needle biopsy (FNB) needles obtain more core samples and support the shift from cytologic to histologic evaluation; however, recent studies have proposed a superior diagnostic potential for liquid-based cytology (LBC). This study compared the diagnostic ability of endoscopic ultrasound (EUS)-guided FNB histology with a 22-gauge Franseen needle (22G-FNB-H) and fine-needle aspiration (FNA) LBC with a conventional 25-gauge needle (25G-FNA-LBC). METHODS: We analyzed 46 patients who underwent both 22G-FNB-H and 25G-FNA-LBC in the same lesion during the same endoscopic procedure. This study evaluated the diagnostic ability of each needle, diagnostic concordance between needles, and incremental diagnostic effect of both needles compared to using each needle alone. RESULTS: The agreement rate for malignancy between both techniques was 93.5% (kappa value = 0.82). There was no significant difference in the diagnostic ability of both methods. 22G-FNB-H and 25G-FNA-LBC provided an incremental diagnostic accuracy in two (4.3%) cases and one (2.2%) case, respectively. CONCLUSION: Our study demonstrated that the diagnostic accuracy of 25G-FNA-LBC and 22G-FNA-H for solid pancreatic lesions were comparable. A conventional 25-gauge needle that punctures lesions with ease can be used in difficult cases and according to the skill of the endoscopist.

Prenatal nicotine exposure affects cardiovascular function and growth of the developing fetus.

AIM: Effects of nicotine on fetal hemodynamics are not well known, especially in the first trimester fetus. We investigated the acute and chronic effects of nicotine on hemodynamics in pregnant mice and their fetuses using ultrasound. Postnatal health status including growth and hemodynamics was also examined. METHODS: To investigate the acute effects of nicotine on fetal hemodynamics, we injected nicotine 0.2 mg/kg subcutaneously into pregnant mice on gestational days (GD) 9.5, 11.5 and 13.5 and compared with saline-injected group. To determine the chronic effects of nicotine on fetal hemodynamics, we administered nicotine in drinking water (0.1 mg/mL) to pregnant mice from GD 6.5 until they gave birth and compared hemodynamics with water-administered mice. RESULTS: Regarding the acute effects of nicotine, we found no intergroup difference in maternal hemodynamics; however, fetal blood flow through the dorsal aorta, carotid artery and umbilical artery tended to decrease, particularly on GD 11.5. Regarding the chronic effects of nicotine, we observed no intergroup difference in maternal body weight changes and hemodynamics; however, blood flow to all fetal organs tended to be lower in the nicotine water group than in the water group with significant difference on GD 13.5. The offspring of the nicotine water group had significantly low birth weights and continued to have low body weight until 9 weeks of age. In addition, these offspring developed postnatal cardiac hypertrophy. CONCLUSION: Nicotine adversely affects fetal hemodynamics acutely and chronically in early pregnancy, potentially leading to fetal tissue hypoxia, intrauterine growth restriction and adverse postnatal health effects.

Pancreatic cancer screening in patients with presumed branch-duct intraductal papillary mucinous neoplasms.

Because delayed diagnosis is one of the causes of poor prognosis in pancreatic ductal adenocarcinoma (PDAC), early detection is a key for overall improvement of prognosis. Towards this end, periodic screening is recommended for individuals considered high-risk for PDAC. Advances in diagnostic imaging modalities have increased the frequency of incidental findings of pancreatic cysts, including the intraductal papillary mucinous neoplasm (IPMN) - a major risk factor of PDAC, having 1% annual prevalence of concomitance with IPMN. Proper retainment of patients with IPMN and regular follow-up by routine imaging examination will likely improve early detection and better prognosis of PDAC. Unfortunately, current guidelines only address management of PDAC derived from IPMN and overlook PDAC concomitant with IPMN. Screening of patients with IPMN, by endoscopic ultrasonography (currently the most reliable modality for detecting small PDAC), may facilitate early detection of both IPMN-derived and -concomitant PDAC. Prospective studies to evaluate the usefulness of endoscopic ultrasonography in screening of IPMN-concomitant PDAC will also help in determining the optimal surveillance strategy for more widespread applications.

Mouse models for investigating the underlying mechanisms of nonalcoholic steatohepatitis-derived hepatocellular carcinoma.

As the incidence of hepatocellular carcinoma (HCC) caused by infection with the hepatotropic viruses hepatitis B and hepatitis C decreases, greater attention has become focused on HCC caused by nonalcoholic steatohepatitis (NASH), an advanced form of nonalcoholic fatty liver disease which has shown increasing prevalence in correspondence with the overall increase in metabolic syndrome over the recent decades. Several clinical population studies have shown a positive relationship between NASH and HCC, while also providing initial insights into the underlying mechanisms of HCC development from NASH. Research into the pathological progression of NASH to HCC has advanced by use of several beneficial rodent models. In this review, we summarize the established mouse models for preclinical research of NASH-associated HCC and discuss the underlying hepatic mechanisms of NASH-related tumorigenesis identified to date that could lead to new targets for treatment and prevention.

An Appraisal of Current Guidelines for Managing Malignancy in Pancreatic Intraductal Papillary Mucinous Neoplasm.

Pancreatic intraductal papillary mucinous neoplasm was originally regarded as a benign mucinous cystic tumor but certainly has a marked malignant potential. With the array of high-resolution imaging modalities that are now available, more frequent incidental asymptomatic intraductal papillary mucinous neoplasm patients can be diagnosed. Until now, our clinicians have been managing intraductal papillary mucinous neoplasm patients by referring to the international consensus guidelines which have been revised twice or American Gastroenterological Association guidelines. The aim of this review is to reassess the current guidelines for the management of malignancy in intraductal papillary mucinous neoplasm. Furthermore, we specifically discuss the problems to be solved for establishing more refined guideline for the early detection, risk stratification and better management of pancreatic cancer in intraductal papillary mucinous neoplasm patients.

Aldehyde dehydrogenase 2 polymorphism for development to hepatocellular carcinoma in East Asian alcoholic liver cirrhosis.

BACKGROUND AND AIM: We aimed to clarify the influences of aldehyde dehydrogenase 2 (ALDH2), alcohol dehydrogenase 1B (ADH1B) polymorphisms, and ethanol consumption profile to hepatocellular carcinoma (HCC) development in alcoholic liver cirrhosis without chronic hepatitis B and C virus infection (non-B non-C). METHODS: Of 236 freshly diagnosed non-B non-C alcoholic liver cirrhosis patients, 67 were diagnosed as HCC and the remaining 169 as not having HCC. The relationship between the genetic polymorphisms and development to HCC were evaluated in well-matched patients with HCC (HCC group, n = 67) and without HCC (non-HCC group, n = 67) using propensity scores in age, sex, and prevalence of diabetes mellitus. RESULTS: Daily amount of ethanol consumption was significantly lower (P = 0.005), and consumptive period was significantly longer (P = 0.003) in HCC group than non-HCC group. Of 134 well-matched patients, 113 (84.3%) had ALDH2*1/*1 genotype and 21 (15.7%) had ALDH2*1/*2 genotype. In HCC development, consumptive long period (P = 0.007) and carrying ALDH2*1/*2 genotype (P = 0.026) were identified as significant factors independently participated, while there was no relation to ADH1B polymorphism. In addition, consumptive period was significantly longer in HCC group than non-HCC group in ALDH2*1/*1 genotype patients (P = 0.0005), while there was no difference in profile of ethanol consumption in ALDH2*1/*2 genotype patients. Among HCC group, daily (P = 3.78 × 10(-6) ) and cumulative amount (P = 4.89 × 10(-6) ) of ethanol consumption were significantly higher in ALDH2*1/*1 genotype patients than ALDH2*1/*2 genotype patients. CONCLUSION: In alcoholic liver cirrhosis, investigations of ALDH2 polymorphism and ethanol consumption profile are useful for prediction of HCC development.

Serum cytokeratin 18 fragment level as a noninvasive biomarker for non-alcoholic fatty liver disease.

BACKGROUND AND AIM: We evaluated the usefulness of serum cytokeratin 18 fragment (CK18-F) as a noninvasive biomarker in differentiating nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver (NAFL) since the prognosis of the 2 diseases differ. METHODS: 116 Japanese patients with nonalcoholic fatty liver disease (NAFLD) proven by liver biopsy were studied. Histological findings were classified according to the NAFLD activity score (NAS) proposed by the Nonalcoholic Steatohepatitis Clinical Research Network. The correlation between histological findings and serum CK18-F levels was investigated. RESULTS: Serum CK18-F levels showed a positive correlation with histologic steatosis (ρ = 0.271, P = 0.0033), inflammation (ρ = 0.353, P = 0.0005), ballooning (ρ = 0.372, P = 0.0001), and the total NAS (ρ = 0.474, P = 2.68 × 10-7). The serum CK18-F level was significantly lower for NAFL (NAS ≤ 2) than for borderline NASH (NAS of 3-4) or definite NASH (NAS ≥ 5) (P = 0.0294, P = 1.163 × 10-5, respectively). The serum CK18-F level was significantly higher for definite NASH than for borderline NASH (P = 0.0002). The area under the receiver operating characteristic curve of serum CK18-F to predict the presence of NAFL and definite NASH was 0.762 and 0.757, respectively. The optimal cut-off point of serum CK18-F for NAFL and definite NASH was 230 and 270 U/L, respectively. The sensitivity, specificity, positive predict value, and negative predict value of serum CK18-F for NAFL were 0.89, 0.65, 0.34, and 0.97, and those for definite NASH were 0.64, 0.76, 0.72, and 0.67, respectively. Accuracies of diagnosis for both NAFL and definite NASH were 0.70. CONCLUSIONS: Serum CK18-F could be a clinically useful biomarker to discriminate between NAFL and NASH.