A comparison between non-sedation and general endotracheal anesthesia for retrograde endoscopic common bile duct stone removal: A tertiary center experience.

BACKGROUND: Conscious sedation is not routinely administered for therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in many countries. The aim of our retrospective study was to compare the safety and rate of success and complications during common bile duct (CBD) stone extraction using ERCPs performed with no-sedation (NS) or under general endotracheal anesthesia (GET). METHODS: The medical records of all patients who underwent ERCP for biliary stone extraction between January 2010 and September 2013 were reviewed, and patients classified to the NS and GET groups. The primary outcomes were the rate of success of complete stone removal and rate of complications, including post-ERCP pancreatitis (PEP), perforation, bleeding, pneumonia, and mortality within 30 days post-ERCP. Operative time was recorded for analysis. RESULTS: During the study period, 630 patients underwent ERCP, 402 with NS and 105 with GET. Among the 402 patients in the NS group, 37 (9.2%) could not complete the procedure due to an inability to tolerate the procedure. The success rate of complete stone extraction was higher among patients in the GET group than the NS group (94.3% versus 75.6%, respectively; p < 0.001). The rate of contrast injection into the pancreatic duct was higher for the NS than GET group (24.9% versus 15.2%, respectively; p = 0.008). Although non-significant, there was a higher incidence of post-ERCP pancreatitis (PEP) in the NS than in the GET group (10.4% versus 5.7%, respectively; p = 0.105), while the incidence of pneumonia was higher for the GET group. Biliary pancreatitis, contrast injection into the pancreatic duct and an operation time ≥30 min were independent risks factors for PEP. CONCLUSIONS: ERCP under GET is effective for CBD stone removal, but with slightly higher pneumonia rate after the procedure than non-sedated ERCP.

Bridging the Gap between Advancements in the Evolution of Diagnosis and Treatment towards Better Outcomes in Achalasia.

Over the past few decades, there was an encouraging breakthrough in bridging the gap between advancements in the evolution of diagnosis and treatment towards a better outcome in achalasia. The purpose of this review is to provide updated knowledge on how the current evidence has bridged the gap between advancements in the evolution of diagnosis and treatment of esophageal achalasia. The advent of high-resolution manometry and standardization based on the Chicago classification has increased early recognition of the disease. These 3 clinical subtypes of achalasia can predict the outcomes of patients, and the introduction of POEM has revolutionized the choice of treatment. Previous evidence has shown that laparoscopic Heller myotomy (LHM) and anterior fundoplication were considered the most durable treatments for achalasia. Based on the current evidence, POEM has been evolving as a promising strategy and is effective against all 3 types of achalasia, but the efficacy of POEM is based on short- and medium-term outcome studies from a limited number of centers. Types I and II achalasia respond well to POEM, LHM, and PD, while most studies have shown that type III achalasia responds better to POEM than to LHM and PD. In general, among the 3 subtypes of achalasia, type II achalasia has the most favorable outcomes after medical or surgical therapies. The long-term efficacy of POEM is still unknown. The novel ENDOFLIP measures the changes in intraoperative esophagogastric junction dispensability, which enables a quantitative assessment of luminal patency and sphincter distension; however, this technology is in its infancy with little data to date supporting its intraoperative use. In the future, identifying immunomodulatory drugs and the advent of stem cell therapeutic treatments, including theoretically transplanting neuronal stem cells, may achieve a functional cure. In summary, it is important to identify the clinical subtype of achalasia to initiate target therapy for these patients.

Endosonographic surveillance of 1-3 cm gastric submucosal tumors originating from muscularis propria.

AIM: To observe the natural course of 1-3 cm gastric submucosal tumors originating from the muscularis propria (SMTMPs). METHODS: By reviewing the computerized medical records over a period of 14 years (2000-2013), patients with 1-3 cm gastric SMTMPs who underwent at least two endoscopic ultrasound (EUS) examinations were enrolled. Tumor progression was defined as a ≥ 1.2 times enlargement in tumor diameter observed during EUS surveillance. All patients were divided into stationary and progressive subgroups and further analyzed. We also reviewed the patients in the progressive subgroup again in 2016. RESULTS: A total of 88 patients were studied, including 25 in the progressive subgroup. The mean time of EUS surveillance was 24.6 mo in the stationary subgroup and 30.7 mo in the progressive subgroup. Risk factors for tumor progression included larger tumor size and irregular border. Initial tumor size > 14.0 mm may be considered a cut-off size for predicting tumor progression. Seventeen patients underwent surgery, of whom 13 had gastrointestinal stromal tumors (GISTs) and 4 had leiomyomas. Tumor progression was found only in patients with GISTs. All of the tumors exhibited benign behaviors without metastasis until 2016. CONCLUSION: Most 1-3 cm gastric SMTMPs (71.6%) are indolent. Tumor progression was found only in GISTs, and it is a good predictor for differentiating GISTs from leiomyomas. Predictors of tumor progression include larger tumor size (> 14.0 mm) and irregular border.

Limited precut sphincterotomy combined with endoscopic papillary balloon dilation for common bile duct stone removal in patients with difficult biliary cannulation.

BACKGROUND: Difficult biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) can result in failure of common bile duct (CBD) stone removal and pancreatitis. The present study aimed to report the efficacy and safety of limited precut sphincterotomy (PS) combined with endoscopic papillary balloon dilation (EPBD) for CBD stone removal in patients with difficult biliary cannulation, and the complications associated with this combined procedure. METHODS: A total of 3305 patients underwent ERCP in our hospital between October 2009 and September 2014 and 258 were diagnosed with difficult biliary cannulation. Of these 258 patients, 58 underwent limited PS combined with EPBD for CBD stone removal, and these 58 patients were included in this retrospective study. RESULTS: The overall success rate was 94.8 % (55/58), and the success rate for single-session removal was 87.9 % (51/58). The mean procedure time was 41 ± 11.48 min (range, 20-72 min). Mechanical lithotripsy was needed in 10.3 % (6/58) of patients. Procedure-related complications included bleeding in 3.4 % (2/58), pancreatitis in 8.6 % (5/58) and biliary tract infection (BTI) in 1.7 % (1/58) of patients. CONCLUSIONS: The therapeutic outcome of limited PS combined with EPBD for CBD stone removal in patients with difficult biliary cannulation was good with an acceptable complication rate. It could be an alternative to PS and "early" limited PS should be used for prompt identification of the bile duct. Limited PS combined with EPBD is safe and effective for CBD stone removal in patients with difficult biliary cannulation.

Comparison of treatment outcomes of endoscope-guided pneumatic dilation and laparoscopic Heller myotomy.

The debate on which is the better choice between laparoscopic Heller myotomy (LHM) and endoscopic pneumatic dilation (PD) for esophageal achalasia has been ongoing for decades. This study aims to compare the results of endoscope-guided PD and LHM in 42 patients with achalasia between May 1996 and August 2011. Twenty-one patients who had received PD and 21 who had received LHM were enrolled. The cumulative remission rate was analyzed using the Kaplan-Meier method with the assessment of symptom scores between grades before and after PD or LHM done at 6 weeks, 6 months, 1 year, and then every year thereafter. Possible confounding factors related to the remissions were analyzed by Cox's proportional hazard model. For PD, the cumulative remission rates were 81.0% (1 year), 76.2% (2), 66.7% (3), 61.9% (4), and 47.6% (5). For LHM, the cumulative remission rates were 90.5% every year from the 1(st) to the 5(th). The LHM patients had significantly better remission rates than the PD patients (p = 0.033, by log-rank test). The LHM group had a longer hospital stay than the PD group [median (interquartile range): 8 (6.5-10) days vs. 3 (2-3) days, p < 0.001) and had more reflux complications (52.4% vs. 19.0%, p = 0.024). No perforation occurred in either group. In conclusion, the 5-year cumulative effectiveness of LHM is better than that of PD despite the association of LHM with more reflux events (52.4%).

Combining age and HBsAg level predicts post-treatment durability of nucleos(t)ide analogue-induced HBeAg seroconversion.

BACKGROUND AND AIMS: Previous studies have indicated that lamivudine-induced hepatitis B e antigen (HBeAg) seroconversion may not be durable in the Asian population. We investigated the useful predictors of post-treatment hepatitis B virus (HBV) relapse in patients with nucleos(t)ide analogue (NA)-induced HBeAg loss/seroconversion. METHODS: A total of 157 non-cirrhotic patients with NA-induced HBeAg loss/seroconversion (78, lamivudine; 68, entecavir; 11, telbivudine) were retrospectively analyzed. All patients had at least 12 months of post-treatment follow-up and consolidation therapy duration. RESULTS: The cumulative rate of post-treatment HBV relapse at 5 years was 57.1%. Multivariate analysis revealed that age and baseline hepatitis B surface antigen (HBsAg) levels independently predicted post-treatment HBV relapse. The post-treatment HBV relapse rate was significantly higher in patients aged > 40 years than in those < 40 years (P < 0.001). A baseline HBsAg level of 2000 IU/mL was the optimal cut-off value for predicting post-treatment HBV relapse (P = 0.002). The post-treatment HBV relapse risk further increased with the presence of both risk factors (age ≥ 40 years and baseline HBsAg level ≥ 2000 IU/mL; P < 0.001). A prolonged consolidation therapy period of ≥ 18 or 24 months had no positive effect on sustained viral suppression. There was no significant difference in post-treatment HBV relapse rates between patients with lamivudine- and entecavir-induced HBeAg loss/seroconversion during the off-treatment follow-up (P = 0.31). CONCLUSION: The combination of an age of 40 years and a baseline HBsAg level of 2000 IU/mL was a useful marker for predicting post-treatment HBV relapse in patients with NA-induced HBeAg loss/seroconversion.

High risk of hepatitis B virus reactivation in nucleos(t)ide analogue-induced hepatitis B e antigen seroconverters older than 40 years.

BACKGROUND: A recent study showed that chronic hepatitis B virus (HBV) carriers with nucleos(t)ide analogue (NA)-induced hepatitis B antigen (HBeAg) seroconversion occurring before the age of 30 years have a higher risk of HBV reactivation. AIM: To compare the risk of HBV reactivation and HBeAg seroreversion between patients with spontaneous and NA-induced HBeAg seroconversion. METHODS: A total of 135 and 251 non-cirrhotic patients with NA-induced and spontaneous HBeAg seroconversion, respectively, were analyzed. RESULTS: NA-induced HBeAg seroconverters faced higher risks of HBV reactivation and HBeAg seroreversion than spontaneous HBeAg seroconverters (P < 0.001). In spontaneous HBeAg seroconverters, age at HBeAg seroconversion, sex, HBV DNA levels before HBeAg seroconversion, HBV genotype C, and pre-S deletions were independent predictors of HBV reactivation. In NA-induced HBeAg seroconverters, only age at baseline was an independent predictor of HBV reactivation. To determine whether the difference in the incidence of HBV reactivation or HBeAg seroreversion between two groups was age-specific, we analyzed these patients according to their age at HBeAg seroconversion (20-29, 30-39, and ≥40 years). Our data showed that NA-induced HBeAg seroconversion was an independent predictor of HBV reactivation and HBeAg seroreversion than spontaneous HBeAg seroconversion in patients older than 40 years at HBeAg seroconversion, but not in patients between 20-29 and 30-39 years of age. CONCLUSIONS: NA-induced HBeAg seroconverters are associated with higher risks of HBV reactivation and HBeAg seroreversion compared to spontaneous HBeAg seroconverters, especially in patients who are older than 40 years at HBeAg seroconversion.

The role of hepatitis B surface antigen quantification in predicting HBsAg loss and HBV relapse after discontinuation of lamivudine treatment.

BACKGROUND & AIMS: We investigated whether the quantification of hepatitis surface antigen (HBsAg) could predict HBsAg loss or hepatitis B virus (HBV) relapse after stopping lamivudine treatment. METHODS: A total of 188 naive chronic hepatitis B patients (83 HBeAg-positive, 105 HBeAg-negative patients), who were previously treated with lamivudine (treatment duration: 89.3 ± 35.9 weeks, range: 52-243 weeks) but stopped the treatment for at least 12 months were recruited. RESULTS: The cumulative incidence of HBsAg loss and HBV relapse at year 6 after stopping lamivudine treatment was 24% and 65.9% respectively. Cox regression analysis revealed that lower alanine aminotransferase (ALT) at baseline, lower HBsAg levels at the end of treatment, and longer treatment duration were independent predictors for HBsAg loss, and old age, male sex and higher HBsAg levels at the end of treatment were independent predictors for post-treatment HBV relapse. At the end of treatment, the HBsAg cut-off value of 300 IU/ml could predict 55.6% (5/9) HBsAg loss in HBeAg-positive patients. In HBeAg-negative patients, the HBsAg cut-off values of 120 and 200 IU/ml could predict 79.2% (19/24) HBsAg loss and 93.3% (28/30) post-treatment sustained response respectively. Further HBsAg reduction (>0.22 log IU/ml) at month 6 after stopping treatment was an independent predictor for HBsAg loss after adjusting for HBsAg level at the end of treatment. CONCLUSIONS: Serum HBsAg level at the end of treatment is a useful predictor to guide the timing of stopping lamivudine treatment in chronic hepatitis B patients.

Current status in the treatment options for esophageal achalasia.

Recent advances in the treatment of achalasia include the use of high-resolution manometry to predict the outcome of patients and the introduction of peroral endoscopic myotomy (POEM). The first multicenter randomized, controlled, 2-year follow-up study conducted by the European Achalasia Trial group indicated that laparoscopic Heller myotomy (LHM) was not superior to pneumatic dilations (PD). Publications on the long-term success of laparoscopic surgery continue to emerge. In addition, laparoscopic single-site surgery is applicable to advanced laparoscopic operations such as LHM and anterior fundoplication. The optimal treatment option is an ongoing matter of debate. In this review, we provide an update of the current progress in the treatment of esophageal achalasia. Unless new conclusive data prove otherwise, LHM is considered the most durable treatment for achalasia at the expense of increased reflux-associated complications. However, PD is the first choice for non-surgical treatment and is more cost-effective. Repeated PD according to an "on-demand" strategy based on symptom recurrence can achieve long-term remission. Decision making should be based on clinical evidence that identifies a subcategory of patients who would benefit from specific treatment options. POEM has shown promise but its long-term efficacy and safety need to be assessed further.

Virological response to entecavir reduces the risk of liver disease progression in nucleos(t)ide analogue-experienced HBV-infected patients with prior resistant mutants.

OBJECTIVES: This study investigated the influence of virological response (VR) to entecavir on clinical liver disease progression in nucleos(t)ide analogue (NA)-naive and -experienced patients. METHODS: We investigated 487 chronic hepatitis B patients (323 NA-naive, 164 NA-experienced) treated with entecavir monotherapy for at least 12 months. VR was defined as hepatitis B virus DNA level <300 copies/mL during entecavir therapy. Clinical events were defined as hepatic decompensation, hepatocellular carcinoma (HCC), death and liver transplantation. RESULTS: Of the 487 patients, 49 developed clinical events during entecavir treatment. Of those, 36 developed HCC. For all patients, Cox regression analysis showed that age, baseline cirrhosis, alanine aminotransferase level ≤200 U/L, albumin level and no VR during entecavir treatment were independent predictors for clinical events and HCC development. However, the benefit of VR to entecavir was significant for clinical events and HCC only in NA-experienced patients, but not in NA-naive patients. For the further analysis of the different subgroups of NA-experienced patients, the benefit of VR to entecavir was significant for clinical events or HCC only in patients with prior lamivudine- or adefovir-resistant mutants, but not in NA-experienced patients who had never developed lamivudine- or adefovir-resistant mutants. VR at month 12 (but not early VR at month 6) remained a significant predictor associated with the development of clinical events and HCC in NA-experienced patients. CONCLUSIONS: VR to entecavir was associated with a reduced risk of clinical events and HCC in NA-experienced patients, particularly in those who had prior lamivudine- or adefovir-resistant mutants.

The effect of systemic antibiotic prophylaxis for cirrhotic patients with peptic ulcer bleeding after endoscopic interventions.

PURPOSE: All previous studies reported the benefit of antibiotic prophylaxis in cirrhotic patients with either a mixture of nonvariceal and variceal bleeding or variceal bleeding alone. Reports on sole peptic ulcers bleeding are lacking. We aimed to assess the effect of antibiotic prophylaxis in cirrhotic patients with peptic ulcer bleeding after endoscopic interventions and the risk factors associated with recurrent bleeding. METHODS: A cross-sectional retrospective chart review study was conducted on 148 cirrhotic patients with acute peptic ulcer hemorrhage who underwent therapeutic endoscopic procedures. Patients who received prophylactic intravenous ceftriaxone were classified as group A (n = 38) and those who did not receive antibiotics were classified as group B (n = 110). The outcomes were prevention of infection, length of hospital stay, time of rebleeding, and death. RESULTS: More patients suffered from recurrent bleeding and infection in group B than those in group A (28.2 vs. 5.3 %; p = 0.003, and 26.4 vs. 10.5 %; p = 0.043, respectively). The risk factors associated with recurrent bleeding were being male (OR = 3.4; p = 0.024), those with advanced stage of cirrhosis with Child-Pugh's class C (OR = 3.8; p < 0.001), and those without antibiotic prophylaxis (OR = 8.9; p = 0.003). The observed 30-day survival was virtually identical for both groups (p = 0.279). CONCLUSIONS: Antibiotic prophylaxis in cirrhotic patients after endoscopic interventions for acute peptic ulcer hemorrhage reduced infections and decreased rebleeding. Male gender, cirrhosis Child-Pugh's class C, and no antibiotic prophylaxis were independent predictors of recurrent bleeding. Further studies should be directed to explore ways to improve the overall outcome of these patients.

Combination and evolution of HBV mutant strains in the HBeAg-positive status predict clinical outcomes after HBeAg seroconversion.

PURPOSE: We investigated whether the combined presence and evolution of hepatitis B virus (HBV) mutant strains in the hepatitis B e antigen (HBeAg)-positive status can predict clinical outcomes after HBeAg seroconversion. METHODS: One hundred and eighty-six patients with spontaneous HBeAg seroconversion were enrolled into this longitudinal study. The sequences of pre-S, core promoter, and precore regions were determined at study entry and at the visit immediately before HBeAg seroconversion. RESULTS: Age ≥40 years at HBeAg seroconversion, male sex, and higher HBV DNA levels at entry were independent predictors for HBeAg-negative chronic hepatitis B (CHB). Patients with combined mutations of pre-S deletions and T1762/A1764 had a significantly increased risk of cirrhosis and hepatocellular carcinoma (HCC) compared to patients with the wild type at both genomic regions. Combinations of pre-S deletions and T1762/A1764 were found on the same HBV genome by cloning analysis of full-length HBV genomes. Patients with a persistent presence of pre-S deletions and T1762/A1764 mutations, and new development of pre-S deletions in the HBeAg-positive status were significantly at an increased risk of HBeAg-negative CHB, cirrhosis, and HCC after HBeAg seroconversion than those with a persistent presence of the wild type at both genomic regions. After adjusting the other risk factors, the evolution of pre-S deletions was an independent predictor for cirrhosis [hazard ratio (HR): 1.52, 95 % confidence interval (CI) 1.02-2.25] and HCC (HR: 4.0, 95 % CI 1.6-10.1). CONCLUSIONS: The combined presence and evolution of pre-S deletions and T1762/A1764 in the HBeAg-positive status was a useful factor significantly predictive of clinical outcomes in patients with spontaneous HBeAg seroconversion.

Combining the HBsAg decline and HBV DNA levels predicts clinical outcomes in patients with spontaneous HBeAg seroconversion.

PURPOSE: The aim was to investigate whether the quantitation of the hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels can predict HBV reactivation and advanced liver disease after spontaneous hepatitis B e antigen (HBeAg) seroconversion. METHODS: A total of 121 patients who experienced spontaneous HBeAg seroconversion were included in this longitudinal study. Serial HBsAg and HBV DNA levels were measured before and after HBeAg seroconversion. RESULTS: Of the 121 patients, 32 experienced HBV reactivation and six achieved an HBsAg loss after HBeAg seroconversion during the follow-up period. The decline in the HBsAg level was considerably more pronounced in patients without HBV reactivation when compared to those with HBV reactivation (p = 0.016). Multivariate analysis revealed that the age of >40 years at HBeAg seroconversion, male sex, and HBsAg decline, and HBV DNA levels at month 12 after HBeAg seroconversion were independent factors for the development of HBeAg-negative hepatitis. All the six patients who achieved HBsAg loss had HBsAg level of <1,000 IU/mL at month 12 after HBeAg seroconversion (p < 0.001). The risk of HBeAg-negative hepatitis, cirrhosis, and HCC was substantially increased in patients who had a combination of both, i.e., no decline in the HBsAg level and HBV DNA level of >10(4) copies/mL at month 12 after HBeAg seroconversion. CONCLUSIONS: Combining HBsAg reduction and HBV DNA levels at month 12 after HBeAg seroconversion was a useful marker to predict clinical outcomes in spontaneous HBeAg seroconverters. HBsAg level of <1,000 IU/mL at month 12 after HBeAg seroconversion could predict the HBsAg loss after HBeAg seroconversion.

A comparison of 4-year entecavir efficacy in nucleos(t)ide analog-naïve and -experienced adult Taiwanese chronic hepatitis B patients.

PURPOSE: To compare the efficacy of entecavir (ETV) monotherapy up to 4 years in nucleos(t)ide analog (NA)-experienced and -naïve subjects. METHODS: One hundred sixty NA-experienced and 282 naïve chronic hepatitis B patients who were treated with ETV were enrolled. Of the 160 NA-experienced patients, 49 had prior lamivudine (LAM)-resistant mutants, 18 had resistant mutants to LAM followed by adefovir (ADV) after switching to ADV sequential therapy (LAM/ADV resistance), and 9 had prior ADV-resistant mutants. NA-resistant mutants were detected by line probe assay. RESULTS: Four years of ETV therapy resulted in virological response (VR, HBV DNA < 300 copies/ml), HBeAg seroconversion, and ETV-resistant mutants development in 98.2, 45.2, and <1 % of naïve patients, respectively. LAM- and ADV-experienced patients who never developed LAM-resistant mutants had similar VR and ETV-resistant mutant rates to NA-naïve patients. In contrast, prior LAM-resistant mutants were significantly associated with higher ETV-resistant mutants development and reduced VR rates. Patients with prior LAM-resistant mutants but not at baseline had a lower rate of ETV-resistant mutants compared to those with baseline LAM-resistant mutants [hazard ratio (HR): 0.58, 95 % confidence interval (CI): 0.35-0.95] and those who had LAM/ADV resistance (HR:0.16, 95 % CI:1.0.03-0.76). Early add-on ADV achieved VR in eight of nine patients with ETV-resistant mutants when HBV DNA was <2 × 10(5) copies/ml. CONCLUSIONS: Entecavir was highly efficacious and low resistance in NA-naïve, LAM-, or ADV-experienced patients without LAM-resistant mutants. Patients with prior LAM-resistant mutants but not at baseline had lower ETV-resistant mutant rates compared to those with baseline LAM-resistant mutants or LAM/ADV resistance.

Endoscopic papillary balloon dilation for removal of bile duct stones: evaluation of outcomes and complications in 298 patients.

BACKGROUND: Endoscopic papillary balloon dilation (EPBD) is a therapeutic procedure for extraction of bile duct stones. GOALS: To evaluate the therapeutic outcomes, postoperative complications, and associated risk factors of EPBD in patients with bile duct stones. STUDY: A total of 298 patients with bile duct stones were treated with EPBD. Their immediate outcomes were assessed and they were followed up for late complications. The modified Cotton criteria were used to determine the incidence of post-EPBD pancreatitis. RESULTS: Complete removal of bile duct stones was achieved in 273 patients (91.6%). Removal was successful in 94.6% of stones ≤ 1 cm and 82.9% of stones >1 cm (P=0.001). Thirty patients (10.1%) had acute pancreatitis after EPBD with bile duct stone extraction, including 20 women (P=0.044), 20 patients under 60 years old (P=0.003) and 19 who received contrast medium injection to the pancreas (P=0.016). Symptomatic bile duct stones recurred in 12 patients (4%) 1 to 65 months after EPBD. The duration of balloon dilation was >3 minutes in 11 of these 12 patients (P=0.025) and all recurrent stones were brown and black pigment stones. CONCLUSIONS: EPBD is an effective and safe treatment for bile duct stone removal. Small bile duct stones (≤ 1 cm) can easily be extracted by EPBD. Contrast medium injection to the pancreas, female sex, and age under 60 years were significant risk factors for post-EPBD pancreatitis. Balloon dilatation duration >3 minutes was the only risk factor for recurrent symptomatic bile duct stones.

2011 update on esophageal achalasia.

There have been some breakthroughs in the diagnosis and treatment of esophageal achalasia in the past few years. First, the introduction of high-resolution manometry with pressure topography plotting as a new diagnostic tool has made it possible to classify achalasia into three subtypes. The most favorable outcome is predicted for patients receiving treatment for type II achalasia (achalasia with compression). Patients with type I(classic achalasia) and type III achalasia (spastic achalasia) experience a less favorable outcome. Second, the first multicenter randomized controlled trial published by the European Achalasia Trial group reported 2-year follow-up results indicating that laparoscopic Heller myotomy was not superior to endoscopic pneumatic dilation (PD). Although the follow-up period was not long enough to reach a convincing conclusion, it merits the continued use of PD as a generally available technique in gastroenterology. Third, the novel endoscopic technique peroral endoscopic myotomy is a promising option for treating achalasia, but it requires increased experience and cautious evaluation. Despite all this good news, the bottom line is a real breakthrough from the basic studies to identify the actual cause of achalasia that may impede treatment success is still anticipated.

Treatment response and evolution of HBV resistance during lamivudine plus adefovir or entecavir therapy in patients with adefovir-resistant mutants.

BACKGROUND: Here, we investigated the treatment response and evolution of HBV resistance during lamivudine (LAM) plus adefovir (ADV) and entecavir (ETV) monotherapy in patients with ADV-resistant mutants. METHODS: Of the 53 patients with ADV-resistant mutants, 25 received combined LAM plus ADV therapy (LAM+ADV group) and 28 received ETV monotherapy (ETV group) for at least 12 months (median 24 months and range 12-67 months). RESULTS: During 24 months therapy, no significant difference was noted in HBV DNA reduction from baseline, HBV DNA<200 copies/ml, hepatitis B e antigen loss and ALT normalization between the two groups. In the LAM+ADV group, patients with single rtN236T resistant mutation had higher rates of undetectable HBV DNA than those with the double mutant rtA181T/V+rtN236T at months 3-18 of therapy. No virological breakthrough occurred except for one patient with rtN236T resistant mutation who experienced virological and biochemical breakthrough after the emergence of an additional rtA181T mutant under LAM+ADV therapy. Of the 28 patients receiving ETV monotherapy, ETV-resistant mutants developed in 8. The cumulative rates of ETV-resistant mutations and virological breakthrough at months 12, 24 and 36 were 3.6%, 25.7% and 46.8%, respectively. ADV-resistant mutations were rapidly replaced by LAM-resistant mutations (median 12 months) followed by ETV-resistant mutations. CONCLUSIONS: There was no significant difference in virological response between the LAM+ADV and ETV groups in patients with ADV-resistant mutants. LAM+ADV were less effective in patients with the double mutant rtA181T/V+rtN236T than the single rtN236T mutation. The incidence of ETV-resistant mutation was high in patients with LAM/ADV-resistant mutants treated with ETV monotherapy.

The effects of ginger on gallbladder motility in healthy male humans.

BACKGROUND/AIMS: Ginger has been used to treat a number of diseases including those affecting the digestive tract. This study was aimed to investigate the effects of ginger on gallbladder volume and gastrointestinal sensation in healthy male subjects. METHODS: Nineteen healthy male volunteers (age 21.3 ± 3.9 years, body mass index 21.6 ± 1.9 kg/m(2)) were studied on 2 occasions in a double blind randomized crossover design. After ingesting ginger (1,200 mg) or placebo capsules (starch), abdominal ultrasound was used to measure the gallbladder volume (calculated from gallbladder width, depth and diameter) and ejection fraction following a standard test meal. Gastrointestinal symptoms were also recorded at regular intervals by visual analogue scales. RESULTS: There were no differences in gallbladder volume or ejection fraction between ginger and placebo. Abdominal symptoms of bloating, fullness, nausea, discomfort and hunger was not different between the 2 occasions. CONCLUSIONS: Ginger (1,200 mg) may not affect gallbladder ejection fraction and possible relevant abdominal symptoms in healthy male human subjects.

Liver interleukin-8 messenger RNA expression and interferon sensitivity-determining region mutations relate to treatment response in hepatitis C 1b.

BACKGROUND: In vitro study has shown that mechanisms for inhibiting interferon (IFN)-α antiviral action by non-structural 5A protein include interaction with IFN-induced RNA-dependent protein kinase and induction of interleukin (IL)-8 expression. Mutations in the non-structural 5A IFN sensitivity-determining region (ISDR) were reported to correlate with sustained virological response (SVR). IL-8 is associated with the inhibition of IFN-α action. We investigated whether pretreatment ISDR mutations and hepatic IL-8 messenger RNA (mRNA) expression had an effect on the SVR rate under combination therapy. METHODS: A total of 53 HCV-1b patients who completed 24 weeks of pegylated-IFN-α2b plus ribavirin, a 24-week follow-up and had enough tissue specimens were enrolled. Liver biopsy was performed within 6 months before antiviral therapy. Hepatic IL-8 mRNA expression was measured by real-time reverse transcriptase PCR. RESULTS: Of 53 patients, 30 exhibited SVR. Multivariate analysis revealed that hepatic IL-8 mRNA expression <1.5×10(-4) (OR 6.66, 95% CI 1.77-25.05) and ISDR mutations ≥4 (OR 12.20, 95% CI 1.23-125.00) were independent predictors of SVR. Fibrosis scores and alanine aminotransferase levels were predictive of hepatic IL-8 mRNA expression by multiple linear regression analysis (r(2)=0.204). CONCLUSIONS: SVR to combination therapy in hepatitis C 1b patients was associated with down-regulated hepatic IL-8 mRNA expression and ISDR mutations. Fibrosis scores and alanine aminotransferase levels were predictive of hepatic IL-8 mRNA expression.

Congenital anomaly of low insertion of cystic duct: endoscopic retrograde cholangiopancreatography findings and clinical significance.

BACKGROUND/AIM: Low insertion of cystic duct (LICD) may be problematic during cholecystectomy. This study was performed retrospectively to assess the prevalence of LICD and identify the risk factors of stone recurrence between LICD and non-LICD (NLICD) after removal of stones. METHODS: Between January 1999 and November 2005, 3546 patients received endoscopic retrograde cholangiopancreatography examination for suspicion of biliary tract diseases. The age and sex-matched group with NLICD was enrolled to compare the clinical differences with LICD group. LICD was defined as "the orifice level of the cystic duct being below the low third of the extrahepatic duct." Recurrence was defined as "patients suffering from cholangitis or biliary stones 1 year later after the first intervention." RESULTS: Of the enrolled 3546 patients (male/female=1821/1725), 191 (5.4%) had LICD. Excluding cases of malignancy, nonbiliary stones, and incomplete data, 122 LICD patients were available. Periampullary diverticula and positive bacterial culture from bile were less common in the LICD group than the NLICD group (P=0.045; P<0.001, respectively). Lower recurrent rate of common bile duct (CBD) stones in the recurrent cases were found in the LICD group compared with the NLICD group (P=0.024; P=0.039, respectively). Univariate analysis revealed that LICD [odds ratio (OR)=0.284; P=0.032] and CBD stones (OR=4.496; P=0.006) were significantly correlated to stone recurrence. CONCLUSIONS: Our study clearly demonstrated the prevalence (5.4%) of LICD in cases with suspicion of biliary tract disease based on endoscopic retrograde cholangiopancreatography. Notably, the strongest predictors, NLICD and CBD stones, appeared to result in the higher stone recurrence.