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Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been suggested as an effective therapy for liver cirrhosis. The efficacy and safety of autologous BM-MSC transplantation in the treatment of alcoholic cirrhosis were investigated. Seventy-two patients with baseline biopsy-proven alcoholic cirrhosis who had been alcohol-abstinent for more than 6 months underwent a multicenter, randomized, open-label, phase 2 trial. Patients were randomly assigned to three groups: one control group and two autologous BM-MSC groups that underwent either one-time or two-time hepatic arterial injections of 5 × 107 BM-MSCs 30 days after BM aspiration. A follow-up biopsy was performed 6 months after enrollment, and adverse events were monitored for 12 months. The primary endpoint was improvement in fibrosis quantification based on picrosirius red staining. The secondary endpoints included liver function tests, Child-Pugh score, and Model for End-stage Liver Disease score. Outcomes were analyzed by per-protocol analysis. In terms of fibrosis quantification (before versus after), the one-time and two-time BM-MSC groups were associated with 25% (19.5 ± 9.5% versus 14.5 ± 7.1%) and 37% (21.1 ± 8.9% versus 13.2 ± 6.7%) reductions in the proportion of collagen, respectively (P 0.05). The Child-Pugh scores of both BM-MSC groups (one-time 7.6 ± 1.0 versus 6.3 ± 1.3 and two-time 7.8 ± 1.2 versus 6.8 ± 1.6) were also significantly improved following BM-MSC transplantation (P < 0.05). The proportion of patients with adverse events did not differ among the three groups. Conclusion: Autologous BM-MSC transplantation safely improved histologic fibrosis and liver function in patients with alcoholic cirrhosis. (Hepatology 2016;64:2185-2197)

The measurement of the hepatic venous pressure gradient (HVPG) for the estimation of portal hypertension (PH) in cirrhosis has some limitations, including its invasiveness. Hepatic vein arrival time (HVAT), as assessed by microbubble contrast-enhanced ultrasonography (CEUS), is negatively correlated with the histological grade of liver fibrosis because of the associated hemodynamic abnormalities. Anatomical and pathophysiological changes in liver microcirculation are the initial events leading to PH. However, the direct relationship between HVAT and PH has not been evaluated. The present study measured both HVPG and HVAT in 71 consecutive patients with compensated cirrhosis and analyzed the relationship between the two parameters (i.e., the derivation set). Results were validated in 35 compensated patients with cirrhosis at another medical center (i.e., the validation set). The derivation set had HVPG and HVAT values of 11.4 ± 5.0 mmHg (mean ± standard deviation; range, 2-23) and 14.1 ± 3.4 seconds (range, 8.4-24.2), respectively; there was a statistically significant negative correlation between HVPG and HVAT (r(2) = 0.545; P < 0.001). The area under the receiver operating characteristic curve (AUROC) was 0.973 for clinically significant PH (CSPH; HVPG, ≥ 10 mmHg), and the sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios for CSPH for an HVAT cut-off value of 14 seconds were 92.7%, 86.7%, 90.5%, 89.7%, 6.95, and 0.08, respectively. In addition, a shorter HVAT was associated with worse Child-Pugh score (P < 0.001) and esophageal varices (P = 0.018). In the validation set, there was also a significant negative correlation between HVAT and HVPG (r(2) = 0.538; P < 0.001), and AUROC = 0.953 for CSPH. HVAT was significantly correlated with PH. These results indicate that measuring HVAT is useful for the noninvasive prediction of CSPH in patients with compensated cirrhosis.

OBJECTIVE The aim of this study was to evaluate the prevalence of Barrett's esophagus (BE) in the general Korean population by evaluating screening esophagogastroduodenoscopy. In addition, the risk factors for BE were identified. METHOD An esophagogastroduodenoscopy examination was performed in 25,536 subjects who had upper endoscopy screening from January 2006 to July 2006. RESULTS Two hundred and fifteen subjects were confirmed to have BE by pathology, thus the prevalence of BE was calculated to be 0.84%. The endoscopic findings were subdivided into 2 groups: BE without reflux esophagitis (RE), which included 167 (77.7%), and BE with RE, which included 48 (22.3%). The analysis of symptoms showed that only 60.1% of the subjects with BE had reflux symptoms. Chest pain [odds ratio (OR): 1.48, 95% confidence interval (CI): 1.04-2.11] and epigastric soreness (OR: 1.42, 95% CI: 1.05-1.93) were found more frequently in the subjects with BE compared with the normal subjects. The multivariate analysis showed that the risk factors for all subjects with BE were a male sex (OR: 1.82, 95% CI: 1.32-2.50), nonsteroidal anti-inflammatory drug use (OR: 2.02, 95% CI: 1.28-3.20), hiatal hernia (OR: 5.66, 95% CI: 3.70-8.66), and an age > or = 60 compared with an age < 40 (OR: 1.81, 95% CI: 1.07-3.09). There was no significant difference associated with RE. CONCLUSIONS The prevalence of BE in Korean patients presenting for a routine health check-up was 0.84%, lower than reported in Western countries. Among the subjects with BE 77.7% did not have endoscopic erosions and there were no reflux symptoms in 39.9%. These results suggest that regular endoscopic screening with a high index of suspicion is necessary for the diagnosis of BE.

We present the first report of ovarian dysgerminoma in Cowden syndrome, presenting in a 7-year-old girl. In her second decade, a hamartomatous soft tissue extremity mass and diffuse gastrointestinal hamartomatous polyposis with pathologic features suggestive of either juvenile, Peutz-Jeghers, or Cowden polyps were identified, along with diffuse esophageal glycogenic acanthosis and skin manifestations. During regular thyroid cancer surveillance under the provisional diagnosis of Cowden syndrome, papillary thyroid carcinoma and benign follicular nodules were diagnosed at age 23. PTEN mutational analysis revealed a novel germline nonsense point mutation of Q219X. Loss of PTEN heterozygosity was also present in the ovarian dysgerminoma. Parental mutation testing and phenotype screening were negative. The correct classification of Cowden syndrome is difficult because of its protean manifestations and overlapping phenotypes with other genetic and noninherited pathologies, particularly regarding various gastrointestinal polyposis syndromes. Despite the challenges, correct classification is critical to patient care because of the associated cancer predispositions and necessary surveillance programs. This is the first report of Cowden syndrome presenting with ovarian dysgerminoma, which implicates PTEN in the molecular pathogenesis of dysgerminoma and adds it to the phenotypic manifestations of Cowden syndrome.

The serrated neoplasia pathway of colorectal carcinogenesis is characterized by BRAF mutation and aberrant DNA methylation, which have not been reported on Korean patients. The aim of this study was to investigate BRAF mutation and DNA methylation in colorectal serrated polyps and the right colon. Between 2005 and 2013, 146 colon polyps (47 tubular adenomas [TAs], 53 traditional serrated adenomas [TSAs], 17 sessile serrated adenomas/polyps [SSAs], and 29 hyperplastic polyps in the proximal colon [PHPs]) were collected from patients. Paraffin-embedded colon polyp tissue was used for DNA extraction. BRAF V600E mutation was identified through polymerase chain reaction (PCR) and pyrosequencing assay. The methylation status of the long interspersed nucleotide element-1, insulin-like growth factor binding protein 7 (IGFBP7), mutL homolog 1 (hMLH1), and CD133 genes were evaluated through disulfite conversion, PCR, and pyrosequencing assay. BRAF V600E mutation was found in 2.1% of TAs, 47.2% of TSAs, 41.2% of SSAs, and 20.7% of PHPs. TSA and SSA had higher BRAF mutation rates than did TA (P