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Abstract Objective We aimed to investigate the prevalence and type of BRAF V600 mutations and the associations with clinicopathological variables in primary skin nodular melanoma cases in Yogyakarta and Central Java, Indonesia using pyrosequencing. Results BRAF V600 mutations of the V600E type were found in 21 (53.85%) specimens. The variant allele frequencies (VAFs) ranged from 5.07 to 94.70%, averaging 29.05%. However, most cases had low VAFs, with 13 (61.9%) specimens below 20% and 4 (19.05%) below 10%.

Abstract Background Melanoma is a lethal skin malignancy with a high risk of metastasis, which prompts a need for research on treatment targets and prognostic factors. Recent studies show that the presence of neuroblastoma RAS viral oncogene homolog (NRAS) mutation can influence cell growth in melanomas. The NRAS mutation, which stimulates the mitogen‐activated protein kinase (MAPK) signaling pathway, is associated with a lower survival rate. However, evidence from Indonesia population is still very rare. Further understanding of the role of NRAS mutations in Indonesian melanoma cases will be crucial in developing new management strategies for melanoma patients with NRAS mutations. Aims To explore the frequency of NRAS mutations and their clinicopathological associations in patients with primary nodular cutaneous melanoma in Central Java and Yogyakarta, Indonesia. Methods and results Fifty‐one paraffin‐embedded tissue samples were collected from primary nodular skin melanoma cases between 2011 and 2019 from the two largest referral hospitals in Yogyakarta and Central Java, Indonesia. The NRAS mutation status was evaluated using qualitative real‐time polymerase chain reaction (qRT‐PCR). The association of NRAS mutation was analyzed with the following: age, gender, location, lymph node metastasis, ulceration, mitotic index, tumor‐infiltrating lymphocytes (TILs), necrosis, tumor thickness, lymphovascular invasion (LVI), and tumor size. NRAS mutations were detected in 10 (19.6%) samples and predominantly observed (60%) in exon 2 (G12). These mutations were significantly correlated with lymph node metastases (p = .000); however, they were not associated with other variables analyzed in this study. Conclusions The prevalence of NRAS mutations in primary nodular cutaneous melanoma cases from Indonesia is consistent with previous studies and is significantly associated with increased lymph node metastases. However, the predominant mutation detected in exon 2 (G12) is different from previous studies conducted in other countries. This suggests that melanoma cases in Javanese people have different characteristics from other ethnicities.

Abstract Background Cutaneous melanoma is a rare, aggressive skin malignancy with a high mortality rate. Although only contributing 7.6% of the cases worldwide, Asia is responsible for 18.6% of deaths from cutaneous melanoma. BRAF V600 mutation presents a potential prognostic predictor in melanoma. Unfortunately, studies on that mutation in melanoma, particularly nodular subtype, in Indonesia are still scarce. This research aimed to investigate the prevalence of BRAF V600 mutation in primary skin nodular melanoma in Yogyakarta and Central Java, Indonesia. Its association with clinicopathological parameters was also analyzed. Methods Forty paraffin-embedded tissue samples from primary skin nodular melanoma cases in 2011–2018 were collected from the two biggest referral hospitals in Yogyakarta and Central Java, Indonesia. The BRAF V600 mutation status was assessed using qualitative real-time PCR and its associations with age, sex, anatomic location, lymph node metastasis, tumor thickness, ulceration, mitotic index, necrosis, lymphovascular invasion, and tumor-infiltrating lymphocytes were analyzed. Results BRAF V600 mutations were found in 4 (10%) samples. These mutations were significantly associated with the central (non-extremity) region (p = 0.013) and presence of lymphovascular invasion (p = 0.005). However, it was not associated with any other variables analyzed in this study. Conclusion The prevalence of BRAF V600 mutation in Indonesian primary skin nodular melanoma cases is low and significantly associated with anatomic location and lymphovascular invasion. It is lower than prevalences in other Asian populations as well as in Caucasian populations and suggests that melanoma cases in Javanese people may have distinct clinicopathological characteristics from other Asian ethnicities.

Background and Aims: Duodenoscopes have been implicated in the transmission of multidrug-resistant organisms (MDRO). We compared the frequency of duodenoscope contamination with MDRO or any other bacteria after disinfection or sterilization by 3 different methods., Methods: We performed a single-center prospective randomized study in which duodenoscopes were randomly reprocessed by standard high-level disinfection (sHLD), double high-level disinfection (dHLD), or standard high-level disinfection followed by ethylene oxide gas sterilization (HLD/ETO). Samples were collected from the elevator mechanism and working channel of each duodenoscope and cultured before use. The primary outcome was the proportion of duodenoscopes with an elevator mechanism or working channel culture showing 1 or more MDRO; secondary outcomes included the frequency of duodenoscope contamination with more than 0 and 10 or more colony-forming units (CFU) of aerobic bacterial growth on either sampling location., Results: After 3 months of enrollment, the study was closed because of the futility; we did not observe sufficient events to evaluate the primary outcome. Among 541 duodenoscope culture events, 516 were included in the final analysis. No duodenoscope culture in any group was positive for MDRO. Bacterial growth of more than 0 CFU was noted in 16.1% duodenoscopes in the sHLD group, 16.0% in the dHLD group, and 22.5% in the HLD/ETO group (P = .21). Bacterial growth or 10 or more CFU was noted in 2.3% of duodenoscopes in the sHLD group, 4.1% in the dHLD group, and 4.2% in the HLD/ETO group (P = .36). MRDOs were cultured from 3.2% of pre-procedure rectal swabs and 2.5% of duodenal aspirates., Conclusions: In a comparison of duodenoscopes reprocessed by sHLD, dHLD, or HLD/ETO, we found no significant differences between groups for MDRO or bacteria contamination. Enhanced disinfection methods (dHLD or HLD/ETO) did not provide additional protection against contamination. However, insufficient events occurred to assess our primary study end-point. ClinicalTrials.gov no: NCT02611648., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Recent data suggest that effective control of gastroesophageal reflux improves outcomes associated with endoscopic eradication therapy (EET) for Barrett's esophagus (BE). However, the impact of reflux control on preventing recurrent intestinal metaplasia and/or dysplasia is unclear. The aims of the study were: (a) to determine the effectiveness and durability of EET under a structured reflux management protocol and (b) to determine the impact of optimizing anti-reflux therapy on achieving complete eradication of intestinal metaplasia (CE-IM)., Methods: Consecutive BE patients referred for EET were enrolled and managed with a standardized reflux management protocol including twice-daily PPI therapy during eradication. Primary outcomes were rates of CE-IM and IM or dysplasia recurrence., Results: Out of 221 patients enrolled (46.0% with high-grade dysplasia/intramucosal carcinoma, 34.0% with low-grade dysplasia, and 20.0% with non-dysplastic BE) an overall CE-IM of 93% was achieved within 11.6±10.2 months. Forty-eight patients did not achieve CE-IM in 3 sessions. After modification of their reflux management, 45 (93.7%) achieved CE-IM in a mean of 1.1 RFA sessions. Recurrence occurred in 13 patients (IM in 10(4.8%), dysplasia in 3 (1.5%)) during a mean follow-up of 44±18.5 months. The only significant predictor of recurrence was the presence of a hiatal hernia. Recurrence of IM was significantly lower than historical controls (10.9 vs. 4.8%, P=0.04)., Conclusions: The current study highlights the importance of reflux control in patients with BE undergoing EET. In this setting, EET has long-term durability with low recurrence rates providing early evidence for extending endoscopic surveillance intervals after EET.

Background: The clinical utility of performing esophagogastroduodenoscopy (EGD) before linear endoscopic ultrasonography (L-EUS) to evaluate the luminal upper gastrointestinal (GI) tract is not well established., Goals: The study was aimed to determine the prevalence of clinically meaningful luminal abnormalities (any luminal finding requiring further evaluation with mucosal biopsy or initiation of treatment) in patients undergoing L-EUS. The study also sought to compare the ability of the gastroscope and the linear echoendoscope in identifying these lesions., Study: A prospective, multicenter cohort study enrolled patients undergoing L-EUS for nonluminal indications. All patients underwent EGD followed by L-EUS by 2 different endoscopists. The second endoscopist was blinded to the results of the initial EGD. The identification of clinically meaningful luminal lesions and quality of endoscopic visualization of the upper GI tract were measured., Results: In the cohort of 175 patients, 52 (29.7%) patients had clinically meaningful luminal findings seen in the upper GI tract. There was no significant difference in the number of clinically meaningful lesions identified on EGD and L-EUS (25.1% vs. 22.9%, P=0.39). No significant difference was found in the miss rate of clinically meaningful lesions between the 2 modalities (EGD: 4.5% vs. EUS: 6.9%, P=0.39)., Conclusions: A substantial minority of patients undergoing L-EUS for nonluminal indications will have clinically meaningful luminal findings. The endoscopic evaluation of the luminal upper GI tract can be adequately achieved using the linear echoendoscope.

Background: Plastic stents in patients with biliary obstruction caused by pancreatic adenocarcinoma are typically exchanged at 3-month intervals. Plastic stents may have reduced durability in patients receiving chemotherapy., Objective: To determine the duration of plastic biliary stent patency in patients undergoing chemotherapy for pancreatic adenocarcinoma., Design: Retrospective, multicenter cohort study., Setting: Three tertiary academic referral centers., Patients: A total of 173 patients receiving downstaging chemotherapy for locally advanced or borderline resectable pancreatic adenocarcinoma from 1996 to 2013., Interventions: Placement of 10F or larger plastic biliary stents., Main Outcome Measurements: Primary outcome was overall duration of stent patency. Secondary outcomes included the incidence of premature stent exchange (because of cholangitis or jaundice) and hospitalization rates., Results: A total of 233 plastic stents were placed, and the overall median duration of stent patency was 53 days (interquartile range [IQR] 25-99 days). Eighty-seven stents were removed at the time of surgical resection, and 63 stents were exchanged routinely per protocol. The remaining 83 stent exchanges were performed for worsening liver function test results, jaundice, or cholangitis, representing a 35.6% rate of premature stent exchange. The median stent patency duration in the premature stent exchange group was 49 days (IQR 25-91 days) with a 44.6% hospitalization rate. The overall rate of cholangitis was 15.0% of stent exchanges, occurring a median of 56 days after stent placement (IQR 26-89 days)., Limitations: Retrospective study., Conclusions: Plastic biliary stents placed during chemotherapy/chemoradiation for pancreatic adenocarcinoma have a shorter-than-expected patency duration, and a substantial number of patients will require premature stent exchange. Consideration should be given to shortening the interval for plastic biliary stent exchange., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Clinical esophageal manometry can be technically challenging. We investigated the prevalence and causes of technically imperfect, high-resolution esophageal pressure topography (EPT) studies at a tertiary referral hospital., Methods: We reviewed 2000 consecutive clinical EPT studies that had been performed with consistent technique and protocol. A study was considered technically imperfect if there was a problem with pressure signal acquisition, if the catheter did not pass through the esophagogastric junction (EGJ), or if there were fewer than 7 evaluable swallows (without double-swallowing, and so forth). Data from the technically imperfect studies were interpreted blindly to determine a diagnosis; this diagnosis was compared with the diagnosis based on chart review., Results: We identified 414 technically imperfect studies (21% of the series). These were attributed to fewer than 7 evaluable swallows (58%), inability to traverse the EGJ (29%), sensor or thermal compensation malfunction (7%), and miscellaneous artifacts (6%). The most frequent causes of failure to traverse the EGJ were a large hiatal hernia (50%) and achalasia (24%). The condition most frequently associated with an incomplete swallow protocol was achalasia (33%). Despite the limitations, the diagnosis of achalasia was achieved correctly by blinded interpretation in 77% of cases and nonblinded interpretation in 94% of cases., Conclusions: Technically imperfect EPT studies are common in a tertiary care center; large hiatal hernia and achalasia were the most frequent causes. However, despite the technical limitations, the data still could be interpreted, especially in the context of associated endoscopic and radiographic data., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The manometric diagnosis of distal esophageal spasm (DES) uses "simultaneous contractions" as a defining criterion, ignoring the concept of short latency distal contractions as an important feature. Our aim was to apply standardized metrics of contraction velocity and latency to high-resolution esophageal pressure topography (EPT) studies to refine the diagnosis of DES., Methods: Two thousand consecutive EPT studies were analyzed for contractile front velocity (CFV) and distal latency to identify patients potentially having DES. Normal limits for CFV and distal latency were established from 75 control subjects. Clinical data of patients with reduced distal latency and/or rapid CFV were reviewed., Results: Of 1070 evaluable patients, 91 (8.5%) had a high CFV and/or low distal latency. Patients with only rapid contractions (n = 186 [17.4%] using conventional manometry criteria; n = 85 [7.9%] using EPT criteria) were heterogeneous in diagnosis and symptoms, with the majority ultimately categorized as weak peristalsis or normal. In contrast, 96% of patients with premature contraction had dysphagia, and all (n = 24; 2.2% overall) were ultimately managed as spastic achalasia or DES., Conclusions: The current DES diagnostic paradigm focused on "simultaneous contractions" identifies a large heterogeneous set of patients, most of whom do not have a clinical syndrome suggestive of esophageal spasm. Incorporating distal latency into the diagnostic algorithm of EPT studies improves upon this by isolating disorders of homogeneous pathophysiology: DES with short latency and spastic achalasia. We hypothesize that prioritizing measurement of distal latency will refine the management of these disorders, recognizing that outcomes trials are necessary., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)