YAP/WNT5A/FZD4 axis regulates osteogenic differentiation of human periodontal ligament cells under cyclic stretch.

OBJECTIVE: To verify the role of YAP/WNT5A/FZD4 axis in stretch-induced osteogenic differentiation of hPDLCs. BACKGROUND: During orthodontic tooth movement, differentiation of human periodontal ligament cells (hPDLCs) at the tension side of the periodontal ligament mediates new bone formation. WNT5A promotes osteogenesis and its regulator Yes-associated protein (YAP) is responsive to mechanical stimulation in hPDLCs. However, the mechanisms of YAP and WNT5A in alveolar bone remodeling remain unclear. METHODS: Cyclic stretch was applied to hPDLCs to mimic the orthodontic stretching force. Osteogenic differentiation was determined by alkaline phosphatase (ALP) activity, Alizarin Red staining, qRT-PCR and western blotting. To detect activation of YAP and expression of WNT5A and its receptor Frizzled-4 (FZD4), western blotting, immunofluorescence, qRT-PCR and ELISA were performed. Verteporfin, Lats-IN-1, small interfering RNAs and recombinant protein were used to explore the relationship of YAP, WNT5A and FZD4, and the effect of their relationship on stretch-induced osteogenesis of hPDLCs. RESULTS: WNT5A, FZD4 and nuclear localization of YAP were upregulated by cyclic stretch. YAP positively regulated WNT5A and FZD4 expression and osteogenic differentiation of hPDLCs under cyclic stretch by YAP inhibition or activation assay. Knockdown of WNT5A and FZD4 attenuated YAP-induced and stretch-induced osteogenic differentiation. Recombinant WNT5A rescued the suppressed osteogenic differentiation by YAP inhibitor in hPDLCs, whereas knockdown of FZD4 weakened the effect of WNT5A and amplified the suppression. CONCLUSIONS: WNT5A/FZD4 could be positively regulated by YAP and the YAP/WNT5A/FZD4 axis mediated osteogenic differentiation of hPDLCs under cyclic stretch. This study provided further insight into the biological mechanism of orthodontic tooth movement.

Submucosal tunneling endoscopic septum division for esophageal diverticulum with a median follow-up of 39 months: a multicenter cohort study.

BACKGROUND AND AIMS: Submucosal tunneling endoscopic septum division (STESD) is an endoscopic minimally invasive technique for treating esophageal diverticulum. The objectives of this study were to evaluate the safety and efficacy of STESD and its impact on patients' quality of life. METHODS: This study included consecutive patients who underwent STESD for esophageal diverticulum from April 2016 to August 2020 in 2 centers (Zhongshan Hospital, Fudan University and Tianjin First Central Hospital). Esophagogram and endoscopic examination were performed before STESD and 30 days after STESD. Patients completed the 36-item Short Form survey (SF-36) before STESD and 1 year after surgery. Clinical symptoms were assessed via telehealth every 6 months until August 2021. Costamagna and Eckardt scores were used to evaluate changes in symptoms. RESULTS: Twenty-one patients were included. Mucosal injury 1 to 2 cm below the septum occurred in 2 patients. No severe surgical adverse events were observed. Median duration of follow-up was 39 months (range, 12-63). Total SF-36 scores increased from 118.7 ± 18.6 before STESD to 132.4 ± 9.1 at 1 year after the procedure (P = .007). SF-36 subscales of general health (P = .002), vitality (P = .004), social functioning (P = .030), and mental health (P = .020) improved significantly after STESD. The mean Costamagna score decreased from 3.83 ± 1.33 to 1.67 ± 1.51 (P = .010), whereas the mean Eckardt score decreased from 3.50 ± .90 to 1.25 ± 1.76 (P = .002). One patient developed symptom recurrence at 10 months after STESD. CONCLUSIONS: STESD is a safe and valid endoscopic minimally invasive surgery for esophageal diverticulum, which can reduce symptoms and improve quality of life.

Peroral endoscopic myotomy: 10-year outcomes from a large, single-center U.S. series with high follow-up completion and comprehensive analysis of long-term efficacy, safety, objective GERD, and endoscopic functional luminal assessment.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is becoming the treatment of choice for achalasia. Data beyond 3 years are emerging but are limited. We herein report our 10-year experience, focusing on long-term efficacy and safety including the prevalence, management, and sequelae of postoperative reflux. METHODS: This was a single-center prospective cohort study. RESULTS: Six hundred ten consecutive patients received POEM from October 2009 to October 2019, 160 for type 1 achalasia (26.2%), 307 for type II (50.3%), 93 for type III (15.6%), 25 for untyped achalasia (4.1%), and 23 for nonachalasia disorders (3.8%). Two hundred ninety-two patients (47.9%) had prior treatment(s). There was no aborted POEM. Median operation time was 54 minutes. Accidental mucosotomies occurred in 64 patients (10.5%) and clinically significant adverse events in 21 patients (3.4%). No adverse events led to death, surgery, interventional radiology interventions/drains, or altered functional status. At a median follow-up of 30 months, 29 failures occurred, defined as postoperative Eckardt score >3 or need for additional treatment. The Kaplan-Meier clinical success estimates at years 1, 2, 3, 4, 5, 6, and 7 were 98%, 96%, 96%, 94%, 92%, 91%, and 91%, respectively. These are highly accurate estimates because only 13 patients (2%) were missing follow-up assessments. One hundred twenty-five patients (20.5%) had reflux symptoms more than once per week. At a median of 4 months, the pH study was completed in 406 patients (66.6%) and was positive in 232 (57.1%), and endoscopy was completed in 438 patients (71.8%) and showed reflux esophagitis in 218 (49.8%), mostly mild. CONCLUSIONS: POEM is exceptionally safe and highly effective on long-term follow-up, with >90% clinical success at ≥5 years.

Learning Curve for Endoscopic Submucosal Dissection With an Untutored, Prevalence-Based Approach in the United States.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is widely used in Asia to resect early-stage gastrointestinal neoplasms, but use of ESD in Western countries is limited. We collected data on the learning curve for ESD at a high-volume referral center in the United States to guide development of training programs in the Americas and Europe. METHODS: We performed a retrospective analysis of consecutive ESDs performed by a single operator at a high-volume referral center in the United States from 2009 through 2017. ESD was performed in 540 lesions: 449 mucosal (10% esophageal, 13% gastric, 5% duodenal, 62% colonic, and 10% rectal) and 91 submucosal. We estimated case volumes required to achieve accepted proficiency benchmarks (>90% for en bloc resection and >80% for histologic margin-negative (R0) resection) and resection speeds >9cm2/hr. RESULTS: Pathology analysis of mucosal lesions identified 95 carcinomas, 346 premalignant lesions, and 8 others; the rate of en bloc resection increased from 76% in block 1 (50 cases) to a plateau of 98% after block 5 (250 cases). The rate of R0 resection improved from 45% in block 1 to >80% after block 5 (250 cases) and ∼95% after block 8 (400 cases). Based on cumulative sum analysis, approximately 170, 150, and 280 ESDs are required to consistently achieve a resection speed >9cm2/hr in esophagus, stomach, and colon, respectively. CONCLUSIONS: In an analysis of ESDs performed at a large referral center in the United States, we found that an untutored, prevalence-based approach allowed operators to achieve all proficiency benchmarks after ∼250 cases. Compared with Asia, ESD requires more time to learn in the West, where the untutored, prevalence-based approach requires resection of challenging lesions, such as colon lesions and previously manipulated lesions, in early stages of training.

A novel technique of endoscopic submucosal dissection for circumferential ileocecal valve adenomas with terminal ileum involvement: the "doughnut resection" (with videos).

BACKGROUND: Ileocecal valve (ICV) lesions are difficult to resect endoscopically and patients are often referred for laparoscopic colectomy. ICV involvement has been shown to be related to technical failure and tumor recurrence after endoscopic mucosal resection (EMR) and represents a challenge for endoscopic submucosal dissection (ESD). Few publications have focused specifically on endoscopic management of ICV lesions. METHODS: We developed a novel ESD technique, the "doughnut resection," for circumferential ICV adenomas with terminal ileum involvement. Two circumferential mucosal incisions are performed, one in the ileum and the other in the cecum, followed by submucosal dissection of the disk of tissue between the two incisions around a guiding stent placed across the valve that helps guide the dissection as it crosses the valve orifice. The lesion is removed en bloc in the shape of a "doughnut" with two concentric assessable lateral margins. The underwater ESD technique and a gastroscope were used to facilitate the resection. RESULTS: Seven patients received the doughnut resection. The median patient age was 67 years. All patients had prior biopsy and three had prior endoscopic resection (1-6 times). The median specimen diameter was 4.5 cm (range 3-8). All resections were en bloc and R0. There was no perforation, delayed bleeding, or other clinically significant adverse events. After a median follow-up of 21 months (range 12-32), there was no tumor recurrence. CONCLUSION: The "doughnut resection" is a feasible, safe, and effective method to remove circumferential ICV lesions endoscopically even for patients with multiple prior tumor manipulations.

Microscopic positive tumor margin does not increase the rate of recurrence in endoscopic resected gastric mesenchymal tumors compared to negative tumor margin.

BACKGROUND: The endoscopic resection of gastrointestinal mesenchymal tumors (GIMTs) is widely accepted because of its minimal invasiveness. However, one major concern is the high rate of positive microscopic margins remaining following endoscopic resection, which was thought to be related to a higher risk of recurrence. This study aimed to determine whether positive margins affect the recurrence rate of gastric GIMTs and the factors associated with positive margins. METHODS: Patients with gastric GIMTs were recruited retrospectively from January 2008 to December 2013. Clinical and pathological features, endoscopic procedure information, and follow-up data were collected and analyzed. RESULTS: The study included 777 patients. All tumors were removed along with the pseudocapsule without macroscopic residual (ER0), and the median tumor size was 15.2 mm (range 3-100 mm). Pathological evaluation revealed 371(47.7%) GISTs. The rate of microscopic R1 resection rate was 47.0% (443/777). In a stepwise multivariate analysis, a significantly increased incidence of R1 resection was recorded for the GISTs (OR 11.13, 95% CI 3.00-41.37). In a subgroup analysis of GISTs, a univariate analysis revealed that EFTR achieved a higher rate of R0 resection (OR 0.56, 95% CI 0.31-1.00), but it was proven insignificant in a stepwise multivariate analysis. Local recurrence occurred in two patients (0.3%) during a mean follow-up time of 34.2 months. Differences in the recurrence rates between the R0 and R1 groups were statistically insignificant (P = 0.841). CONCLUSIONS: R1 resection for gastric GIMTs is not related to a higher recurrence rate than R0 resection, and ER0 resection is sufficient for gastric GIMTs.

The effect of prior treatment on clinical outcomes in patients with achalasia undergoing peroral endoscopic myotomy.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a treatment option for patients with previous surgical or endoscopic treatment. We aimed to evaluate the influence of prior treatment on perioperative and follow-up outcomes in patients undergoing POEM. METHODS: From August 2010 to December 2014, a total of 1384 patients with achalasia underwent POEM at our center. We retrospectively reviewed 849 patients who completed follow-up. Patients with an Eckardt score ≥ 4 after POEM were considered to have a clinical failure. We compared variables between patients with and without prior treatment. We analyzed risk factors for perioperative major adverse events, and clinical reflux and failure during follow-up.  RESULTS: 245 patients (28.9 %) had undergone prior treatment, and 34 patients (4.0 %) experienced a major adverse event associated with the POEM procedure. During a median follow-up of 23 months (range 1 - 71), clinical reflux occurred in 203 patients (23.9 %) and clinical failure was recorded for 94 patients (11.1 %). Patients with prior treatment had a longer procedure duration (P = 0.001) and longer hospital stay after POEM (P = 0.001). Prior treatment was not an independent risk factor for major adverse events or clinical reflux (odds ratio [OR] 1.19, P = 0.65; OR 1.26, P = 0.19; logistic regression), but it did increase the rate of clinical failure during follow-up (hazard ratio 1.90, P = 0.002; Cox regression). CONCLUSIONS: POEM was performed safely with a low rate of major adverse events in patients with achalasia who had undergone prior surgical or endoscopic treatment. However, prior treatment increased the risk of clinical failure after POEM.

Comprehensive Evaluation of the Learning Curve for Peroral Endoscopic Myotomy.

BACKGROUND & AIMS: Peroral endoscopic myotomy (POEM) is a minimally invasive endoscopic surgical procedure that is effective in treatment for spastic esophageal motility disorders. However, little is known about the learning curve for endoscopists. We aimed to evaluate the effects of various factors on the POEM learning curve. METHODS: We performed a retrospective study of 1346 patients who underwent POEM for achalasia at Shanghai Zhongshan Hospital in China from August 2010 through July 2015. We used risk-adjusted cumulative sum and moving average methods to evaluate outcomes. The primary outcome was a composite of technical failure and adverse events. Secondary outcomes included procedure time and the composite outcome of technical failure, adverse events, and clinical failure of the first 192 cases performed by only the original, training surgeon. RESULTS: The primary composite outcome occurred in 54 (4%) of the 1346 patients: 10 technical failures and 44 adverse events. This composite outcome was independently associated with the case number (P = .010), full-thickness myotomy (P = .002), and procedure time (P = .001). After we adjusted for these risk factors, cumulative sum analysis showed that the primary composite outcome decreased gradually after 100 cases. The procedure time was high during the first few cases and decreased after endoscopists performed 70 cases. The secondary composite outcome of technical failure, adverse events, and clinical failure for the 192 cases performed by only the original surgeon gradually decreased after 90-100 cases. CONCLUSIONS: In a retrospective analysis of POEM procedures, we found that 100 cases were required to decrease the risk of technical failure, adverse events, and clinical failure (the learning curve). Seventy cases can be considered the threshold for decreasing procedure time.

Per-oral endoscopic myotomy in patients with or without prior Heller's myotomy: comparing long-term outcomes in a large U.S. single-center cohort (with videos).

BACKGROUND AND AIMS: Heller's myotomy (HM) is one of the most effective treatments for esophageal achalasia. However, failures do exist, and the success rate tends to decrease with time. The efficacy of rescue treatments for patients with failed HM is limited. A few small-scale studies have reported outcomes of per-oral endoscopic myotomy (POEM) in these patients. We conducted this study to systematically assess feasibility, safety, and efficacy of POEM on patients who have had HM. METHODS: Patients at least 3 months out from POEM were selected from our prospective database: 318 consecutive POEMs performed from October 2009 to October 2016. The efficacy and safety of POEM were compared between the 46 patients with prior HM and the remaining 272 patients. RESULTS: Patients with prior HM had longer disease history, more advanced disease, more type I and less type II achalasia, lower before-POEM Eckardt scores, and lower before-POEM lower esophageal sphincter (LES) pressure (all P < .01). Procedure parameters and follow-up results (clinical success rate, Eckardt score, LES pressure, GERD score, esophagitis, and pH testing) showed no significant difference between the 2 groups. For the 46 HM-POEM patients, no clinically significant perioperative adverse events occurred. Their overall clinical success rate (Eckardt score ≤3 and no other treatment needed) was 95.7% at a median follow-up of 28 months. CONCLUSION: POEM as a rescue treatment for patients with achalasia who failed HM is feasible, safe, and highly effective. It should be the treatment of choice in managing these challenging cases at centers with a high level of experience with POEM.

Outcomes of per-oral endoscopic myotomy for treatment of esophageal achalasia with a median follow-up of 49 months.

BACKGROUND AND AIMS: Per-oral endoscopic myotomy (POEM) has received wide acceptance as a highly effective and safe treatment for esophageal achalasia. Short-term and small-scale studies are ample, but long-term large-scale studies are few. The aim of the study was to systematically analyze our long-term results of POEM, with particular emphasis on POEM failures and associated risk factors. METHODS: In this single-center study, consecutive patients treated with POEM between August 2010 and December 2012 were included. The Kaplan-Meier survival function was used to estimate clinical success rate at each year. The Cox proportional hazards model was used to analyze risk factors related to recurrence. RESULTS: A total of 564 patients were included. Major perioperative adverse events occurred in 36 patients (6.4%). After a median follow-up of 49 months (range, 3-68), the Eckardt score and lower esophageal sphincter (LES) pressure were significantly decreased (median Eckardt score, 8 to 2 [P < .05]; median LES pressure, 29.7 mm Hg to 11.9 mm Hg [P < .05]). Fifteen failures occurred within 3 months, 23 between 3 months and 3 years, and 10 after 3 years. The estimated clinical success rates at 1, 2, 3, 4, and 5 years were 94.2%, 92.2%, 91.1%, 88.6%, and 87.1%, respectively. Multivariate Cox regression revealed long disease duration (≥10 years) and history of prior interventions to be risk factors for recurrence. Clinical reflux occurred in 37.3% of patients (155/ 416). CONCLUSIONS: POEM is a highly safe and effective treatment for esophageal achalasia with favorable long-term outcomes.

Submucosal fibrosis in achalasia patients is a rare cause of aborted peroral endoscopic myotomy procedures.

Background and aims Peroral endoscopic myotomy (POEM) is now an established treatment for esophageal achalasia. The standard protocol ensures a smooth operation in most patients, but technical challenges and failures exist and little is known about the incidence, causes, and impact of aborted procedures. Here, using a large patient cohort, we attempted to answer these questions. Methods All patients admitted for planned POEM between August 2010 and July 2015 underwent chart review. Aborted POEM was defined as the inability to finish the procedure after submucosal injection. The cause of the failure, clinical course, management, and follow-up data were analyzed. Results Thirteen of the 1693 POEMs (0.77 %) were aborted. Out of the 13 failures, 12 (92.3 %) were due to severe submucosal fibrosis, which precluded tunneling, and one (7.7 %) was due to atrial fibrillation related to the electric current of the endoscopic knife. Submucosal fibrosis, prior Heller myotomy, and age ( ≥ 60 years) were related to technical failure, while a disease duration of ≥ 6 years, sigmoid esophagus, mucosal edema, and prior interventions were risk factors for the presence of fibrotic changes. In turn, fibrosis was correlated with a prolonged operation, longer hospital stay, more mucosal injuries, and more major perioperative adverse events. Finally, the yearly frequency of aborted POEMs decreased after the second year as operators became more experienced. Conclusions Aborted POEM is a rare event and is largely due to the presence of submucosal fibrosis, which not only causes increased procedural difficulties, but also gives rise to major adverse events.

Major perioperative adverse events of peroral endoscopic myotomy: a systematic 5-year analysis.

Background and study aims: Peroral endoscopic myotomy (POEM) is now a widely used treatment for esophageal achalasia, supported by several large cohort studies. Although major perioperative adverse events (mAE) are rare, in-depth investigations of related risks and preventive measures are lacking. The aim of this study was to systematically assess mAEs during POEM by analyzing their incidence, risks, prevention, and management. Patients and methods: This retrospective single-center analysis included all patients (n = 1680) undergoing POEM between August 2010 and July 2015 at Zhongshan Hospital. Major adverse events were defined as: vital-sign instability, intensive care unit (ICU) stay, hospital readmission, conversion to open surgery, invasive postoperative procedure, blood transfusion, or prolonged (> 5 days) hospitalization for functional impairment. Results: A total of 55 patients (3.3 %, 95 % confidence interval [CI] 2.5 % - 4.2 %) experienced mAEs: delayed mucosal barrier failure (n = 13, 0.8 %; 95 %CI 0.4 % - 1.3 %), delayed bleeding (n = 3, 0.2 %; 95 %CI 0.04 % - 0.5 %), hydrothorax (n = 8, 0.5 %; 95 %CI 0.2 % - 0.9 %), pneumothorax (n = 25, 1.5 %; 95 %CI 1.0 % - 2.2 %), and miscellaneous (n = 6, 0.4 %; 95 %CI 0.1 % - 0.8 %). Four patients (0.2 %) required ICU admission. No surgical conversion occurred, and 30-day mortality was zero. In stepwise multivariate regression, institution experience of < 1 year (odds ratio [OR] 3.85, 95 %CI 1.49 - 9.95), air insufflation (OR 3.41, 95 %CI 1.37 - 8.50), and mucosal edema (OR 2.01, 95 %CI 1.14 - 3.53) were identified as related risk factors. After introducing CO2 insufflation, the mAE rate declined to 1.9 % (95 %CI 1.2 % - 2.7 %) and seemed to plateau after 3.5 years at ~ 1 %. Conclusion: In general, POEM appears to be a safe procedure. Major adverse events were rare and could usually be prevented or anticipated, and were all managed effectively.

Diagnostic efficacy of endoscopic ultrasound-guided needle sampling for upper gastrointestinal subepithelial lesions: a meta-analysis.

BACKGROUND: An increasing number of studies have been conducted on the use of endoscopic ultrasound (EUS)-guided needle sampling for upper gastrointestinal subepithelial lesions (SEL). However, reported diagnostic efficacy varies greatly. OBJECTIVE: To summarize up current evidences on the diagnostic efficacy of EUS-guided needle sampling for upper GI SEL. METHOD: A reproducible strategy was used to search four databases. Search results were evaluated for eligibility, and the quality of eligible studies was assessed by QUADAS-2. Pooled efficacy of EUS-guided needle sampling in upper GI SEL was calculated. Procedure-related complications, diagnostic errors, and independent factors related to a higher success rate were also recorded and analyzed. RESULTS: Seventeen studies, comprising 978 attempts of EUS-guided needle sampling, were included in a meta-analysis. Pooled diagnostic rate of EUS-guided needle sampling was 59.9 %, with a heterogeneity I (2) of 55.2 %. Subgroup analysis showed no difference in diagnostic rate among fine needle aspiration (FNA), trucut needle biopsy (TCB), and fine needle biopsy (FNB), or among 19-, 22-, and 25-G needles. Subgroup analysis and meta-regression suggested that the cell block method might be correlated with a higher diagnostic rate. Few severe complications were reported. Diagnosis errors were rare. CONCLUSION: EUS-guided needle sampling is a safe, but only moderately effective method for pathology diagnosis of upper GI SEL. Choice of FNA/TCB/FNB, or 19 G/22 G/25 G does not seem to alter the overall diagnostic rate.

USP12 regulates ER stress-associated osteogenesis in human periodontal ligament cells under tension stress.

The bone formation (osteogenesis) of human periodontal ligament cells (hPDLCs) under tension stress is essential for alveolar bone remodeling during orthodontic tooth movement (OTM). Deubiquitinating enzymes (DUBs) remove ubiquitin from target proteins, affecting their function and mediating cell survival and differentiation. However, whether and how DUBs regulate hPDLC function under tension force is poorly understood. In this study, we first investigated the expression of DUBs in hPDLCs under cyclic tension stimulation (CTS). Up-regulation of USP12 was observed in hPDLCs and at the tension side of molar teeth in OTM C57BL6 mice models. Knockdown (KD) of USP12 led to enhanced osteogenesis of hPDLCs under CTS. RNA-seq analysis suggested that the unfolded protein response (UPR) was the prevailing biological process in hPDLCs with USP12 KD, indicating that USP12 depletion triggered endoplasmic reticulum (ER) stress. The three major UPR-related signaling branches, namely PERK/eIF2α/ATF4, IRE1α/XBP1s, and ATF6 axis, were activated in hPDLCs with USP12 KD. By utilizing specific inhibitors, we proved that the PERK/eIF2α/ATF4 axis predominantly mediated the enhanced osteogenesis in hPDLCs with USP12 KD under CTS. In summary, our study demonstrates that USP12 serves as a key regulator for CTS-induced osteogenesis in hPDLCs, suggesting that USP12 upregulation serves as an adaptive mechanism for hPDLCs to alleviate ER stress during OTM.

Portal vein thrombosis, hepatic decompensation, and survival in patients with porto-sinusoidal vascular disease and portal hypertension.

BACKGROUND: Porto-sinusoidal vascular disease (PSVD) is a novel nomenclature to describe non-cirrhotic portal hypertension and characteristic histology without portal vein thrombosis (PVT). It is a more inclusive definition than the previously well-recognized entity idiopathic non-cirrhotic portal hypertension. There is a paucity of data on PSVD patients. METHODS: A total of 33 patients diagnosed with PSVD and portal hypertension (PH) between 2005 and 2021 were included. Data were retrieved from electronic medical record system and analyzed. RESULTS: Of the 33 patients, 6 (18%) occurred in post-transplant allograft liver. After a median follow-up of 96 months (interquartile range, IQR [52, 139]), 14 deaths occurred (42%), 4 directly related to decompensated liver disease. The Kaplan-Meier survival estimates at 1, 5, and 10 years were 94%, 87% and 58%. PVT occurred in 10 patients (30%). The Nelson-Aalen cumulative risk estimate for PVT at 1, 5 and 10 years were 16%, 25% and 48%. The median model for end-stage liver disease and Child-Pugh score at initial presentation were 8 (IQR [7-12]) and 5 [5-6], and increased to 13 [8, 18] and 7 [5, 8], respectively, at the end of follow-up. Of the 11 patients who presented with splenomegaly and no specific sign of PH, 7 (64%) developed varices and 3 (27%) ascites at a median follow-up of 100 months. CONCLUSIONS: PSVD with PH is not a benign entity. Mortality, PVT and hepatic decompensation are common. Patients with PSVD must be closely monitored, including those who only have non-specific clinical signs (e.g., splenomegaly) of PH.

A Case of Erdheim-Chester Disease Causing Secondary Sclerosing Cholangitis.

Erdheim-Chester disease (ECD) is an exceedingly rare and aggressive disease characterized by foamy CD68 + CDa-histiocytic infiltration into multiple tissues and organs. Only 1,500 cases have been diagnosed since 1930 when ECD was first described. Biliary tract involvement of ECD has only been reported in the literature once. We report a case of ECD causing extrahepatic biliary obstruction without significant bile duct dilation, mimicking primary sclerosing cholangitis or IgG4 disease.