Role of hepatitis B surface antigen in hepatitis B virus relapse after entecavir or tenofovir prophylaxis in patients undergoing cancer chemotherapy.

BACKGROUND AND AIM: This study investigated whether hepatitis B surface antigen (HBsAg) could predict hepatitis B virus (HBV) relapse after cessation of entecavir or tenofovir disoproxil fumarate (TDF) prophylaxis for chronic hepatitis B cancer patients who are undergoing chemotherapy. METHODS: The study enrolled 122 hepatitis B e-antigen-negative cancer patients who underwent chemotherapy with entecavir or TDF for antiviral prophylaxis and posttreatment follow-up for at least 6 months. RESULTS: Of the 122 patients, 52 and 18 experienced virological and clinical relapse, which had 3-year cumulative incidences of 46.6% and 18.6%, respectively. Multivariate analysis showed that end-of-treatment HBsAg levels and baseline HBV-DNA ≥ 2000 IU/mL were independent predictors of virological relapse. The best HBsAg cutoff value was 500 IU/mL. An end-of-treatment HBsAg of 500 IU/mL was useful for predicting virological relapse in patients with baseline HBV-DNA < 2000 IU/mL (3-year rate: 21.3% vs 46.4%, P = 0.038, in patients with HBsAg < 500 and ≥ 500 IU/mL, respectively), but not in patients with baseline HBV-DNA ≥ 2000 IU/mL. Of the 52 patients who experienced virological relapse, 13 experienced transient virological relapse. Patients with baseline HBV-DNA level < 2000 IU/mL experienced a higher rate of transient virological relapse (42.1% vs 15.2%, P = 0.031). Three patients experienced hepatic decompensation upon alanine aminotransferase flares, and no patient died after timely retreatment. Ten patients experienced posttreatment HBsAg loss, and the 3-year HBsAg loss rate was 30.7% in patients with end-of-treatment HBsAg < 100 IU/mL. CONCLUSIONS: The baseline HBV-DNA and end-of-treatment HBsAg levels could predict virological relapse after withdrawal of entecavir and TDF prophylaxis for chemotherapy.

The validation of the 2010 American Association for the Study of Liver Diseases guideline for the diagnosis of hepatocellular carcinoma in an endemic area.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) diagnosis could be made with one typical imaging study in a cirrhotic liver by the guideline of the American Association for the Study of Liver Diseases (AASLD) in 2010. Patients with hepatitis B who may not have fully developed cirrhosis could be applied. We aim to retrospectively analyze and validate the diagnostic power of the 2010 guideline in an HCC endemic area (Taiwan). METHODS: From January 2006 to December 2010, a total of 648 patients with liver tumor post-surgical resection were reviewed. The fibrotic scores were verified by METAVIR score 4. Among the 648 patients, 569 (87.8%) were HCC patients. Hepatitis B accounts for 54.5%, hepatitis C 21.9%, hepatitis B + C 2.8%, and non-hepatitis B or C 20.7% of patients. Two hundred eighty-eight of 648 (44%) patients were with cirrhotic liver. RESULTS: The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy of the 2010 AASLD guideline f are 99.1%, 36.7%, 91.9%, 85.3%, and 91.5%, respectively. Cirrhotic liver exhibited a higher PPV (P < 0.001) but lower specificity (P = 0.0479) than non-cirrhotic liver. In both cirrhotic and non-cirrhotic condition, no difference existed in patients with hepatitis B or hepatitis C (P > 0.05). CONCLUSIONS: Similar sensitivity of HCC diagnosis existed between cirrhotic and non-cirrhotic liver, and across different fibrotic stages. But cirrhotic liver exhibited a higher PPV. Hepatitis B or C has no decisive effect in HCC diagnosis.

Telbivudine and adefovir combination therapy for patients with chronic lamivudine-resistant hepatitis B virus infections.

We evaluated second-line salvage therapy with adefovir + telbivudine (group 1), adefovir followed by adefovir + telbivudine (group 2), or lamivudine + adefovir followed by adefovir + telbivudine (group 3) in hepatitis B patients with an inadequate virologic response to lamivudine treatment. Simple linear regression analysis showed that for each additional month of treatment, the most significant reduction in viral load occurred in group 1 (HBV DNA [Log10 IU/mL]: group 1, -0.149; group 2, -0.081; group 3, -0.123). Generalized estimating equation analysis revealed that compared to group 1, hepatitis B virus (HBV) DNA levels were 1.203 and 0.443 Log10 IU/mL higher in groups 2 and 3, respectively. Overall, a significant reduction in viral load (-0.060 Log10 IU/mL) was observed for each additional month of treatment. Adefovir + telbivudine treatment resulted in a significant reduction in HBV DNA levels. Moreover, telbivudine treatment resulted in a significant reduction in viral load (-0.050 Log10 IU/mL) compared to lamivudine treatment after the emergence of lamivudine resistance.

Long-term comparisons of the durability of 6 months versus 12 months antiviral therapy for hepatitis B after chemotherapy cessation.

BACKGROUND: Prophylaxis antiviral therapy is recommended for patients with hepatitis B receiving chemotherapy but the ideal treatment duration after chemotherapy cessation needs more evidence for clarification. AIMS: This study aimed to compare the relapse rate of short finite intervals of 6 months and 12 months of -nucleos(t)ide analogue (NA) therapy in patients stratified by low hepatitis B virus (HBV)-DNA of < 2000 IU/ml or high HBV DNA of ≥ 2000 IU/ml. METHODS: Patients started tenofovir or entecavir treatment 1 week before chemotherapy and were assigned to different treatment duration groups randomly after stratified by HBV DNA pretreatment: (1) HBV DNA of < 2000 IU/ml at 6-month or 12-month duration; (2)HBV DNA of ≥ 2000 IU/ml at 6-month or 12-month duration. Virological relapse (VR) was defined as HBV DNA of > 2000 IU/ml, and clinical relapse (CR) was defined as HBV DNA of > 2000 IU/ml and alanine aminotransferase of > 80 IU/L during the follow-up period. The primary endpoint was to compare the durability between groups 1 year after antiviral therapy cessation. The secondary endpoint was VR and CR rate at long-term follow-up after antiviral therapy cessation. RESULTS: This study enrolled 61 patients, and 5 patients were lost to follow-up or tumor recurrence. VR and CR rates were 46.4% and 14.3% at 1-year and 55.3% and 16.1%, at long-term follow-up, respectively. VR and CR rates demonstrated no difference between the groups. Pretreatment HBV DNA at ≥ 2000 IU/ml and end-of-treatment hepatitis B surface antigen (HBsAg) at ≥ 500 IU/ml were the predictor of VR (hazard ratio [HR]: 2.98; p = 0.010 and HR: 2.38; p = 0.037). CONCLUSIONS: Prolongation from 6 months to 12 months of NA consolidation after chemotherapy cessation did not affect the VR or CR of HBV. High pretreatment HBV DNA and end-of-treatment HBsAg levels could predict VR after antiviral therapy cessation for chemotherapy.

Blockade of phospholipid scramblase 1 with its N-terminal domain antibody reduces tumorigenesis of colorectal carcinomas in vitro and in vivo.

BACKGROUND: Membrane-bound phospholipid scramblase 1 (PLSCR1) is involved in both lipid trafficking and cell signaling. Previously, we showed that PLSCR1 is overexpressed in many colorectal carcinomas (CRCs). In the present study, we investigated the tumorigenic role of PLSCR1 in CRC and suggest that it is a potential therapeutic target. METHODS: To identify PLSCR1 as a therapeutic target, we studied the tumorigenic properties of CRC cell lines treated with a monoclonal antibody (NP1) against the N-terminus of PLSCR1 in vitro and in vivo. We also investigated cell cycle status and epidermal growth factor receptor-related pathways and downstream effectors of PLSCR1 after blocking its function with NP1. RESULTS: Treating CRC cells with NP1 in vitro and in vivo decreased cell proliferation, anchorage-independent growth, migration, and invasion. Adding NP1 to the CRC cell line HT29 caused arrest at G1/S. Treating HT29 cells with NP1 significantly decreased the expression of cyclin D1 and phosphorylation levels of Src, the adaptor protein Shc, and Erks. The reduced level of cyclin D1 led to an increase in the activated form of the tumor suppressor retinoblastoma protein via dephosphorylation. These actions led to attenuation of tumorigenesis. CONCLUSIONS: Therefore, PLSCR1 may serve as a potential therapeutic target for CRC.

Randomized comparison of two non-bismuth-containing second-line rescue therapies for Helicobacter pylori.

BACKGROUND: Classical second-line anti-Helicobacter pylori includes proton-pump inhibitor, tetracycline, metronidazole, and bismuth salts, but alternative therapies are required owing to the restricted availability of the latter. Levofloxacin-containing triple therapy is recommended but is expensive. Besides, quinolone resistance in an endemic tuberculosis infection area like Taiwan is concerned. The low in vitro antibiotic resistance to amoxicillin and tetracycline in Taiwanese H. pylori strains implies that in vivo esomeprazole/amoxicillin/tetracycline (EAT) second-line rescue therapy may be effective. This study compared the efficacy of esomeprazole/amoxicillin/levofloxacin (EAL) and EAT second-line eradication therapies and determines the clinical factors influencing the efficacy of salvage regimens. MATERIALS AND METHODS: One hundred and twenty-eight patients who failed H. pylori eradication using the standard triple therapy for 7 days are randomly assigned to either EAL group (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, and levofloxacin 500 mg once daily) for 7 days or EAT group (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, tetracycline 500 mg four times daily) for 14 days. Follow-up endoscopy or urea breath test was performed 8 weeks later to assess treatment response. RESULTS: The eradication rates of EAL and EAT groups were 78.1 versus 75.0%, p = .676 (in intention-to-treat analysis) and 80.3 versus 80%, p = .0964 (per-protocol analysis). Both groups exhibited similar drug compliance (95.3 vs 96.9%, p = .952) but more adverse events in the EAT group (6.3 vs 12.5%, p = .225). CONCLUSIONS: Despite low in vitro drug resistances to amoxicillin and tetracycline, the efficacy of 14-day EAT regimens attained an unacceptable report card of 75% eradication rates in intention-to-treat analysis and was not even superior to the 7-day EAL regimen. Drug-drug interaction between combined antibiotics should be considered other than in vivo drug resistances.

The efficacy of second-line anti-Helicobacter pylori therapy using an extended 14-day levofloxacin/amoxicillin/proton-pump inhibitor treatment--a pilot study.

BACKGROUND: Large meta-analyses of second-line Helicobacter pylori eradication with fluoroquinolone triple therapy have shown that neither 7-day nor 10-day therapy provides 90% or better treatment success. Reports describing second-line H. pylori eradication using 14-day fluoroquinolone-containing triple therapy are few. Current study aimed to determine the efficacy of a 14-day levofloxacin/amoxicillin/proton-pump inhibitor regimen as second-line therapy and the clinical factors influencing the outcome. MATERIALS AND METHODS: One-hundred and one patients who failed H. pylori eradication using the standard triple therapy for 7 days were randomly assigned to either a levofloxacin/amoxicillin/esomeprazole group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 14 days) or a esomeprazole/metronidazole/bismuth salt/tetracycline group (esomeprazole 40 mg twice daily, metronidazole 250 mg four times daily, tripotassium dicitrate bismuthate 300 mg four times daily, and tetracycline 500 mg four times daily for 14 days). Follow-up to assess treatment response consisted of either endoscopy or a urea breath test, which were carried out 8 weeks later. RESULTS: Eradication rates attained by levofloxacin/amoxicillin/esomeprazole and esomeprazole/metronidazole/bismuth salt/tetracycline treatments in the per-protocol analysis were 44/47 (93.6%; 95% CI = 86-99.8) and 43/47 (91.8%; 95% CI = 83.2-98.5). In the intention-to-treat analysis, these were 43/47 (86.3%; 95% CI = 76.5-96.1) in the LAE group (four lost to follow-up) and 43/50 (86%; 95% CI = 76-96) in the EMBT groups. The observed adverse events were 25.5% and 38.5% among the two groups. There was 100% drug compliance among the levofloxacin/amoxicillin/esomeprazole group. Levofloxacin-resistant strains occurred at a frequency of 32.3%. H. pylori eradication rates for the levofloxacin-susceptible strains and levofloxacin-resistant strains were 92% (11/12) and 33% (1/3) in the per-protocol analysis. CONCLUSIONS: A 14-day levofloxacin/amoxicillin/esomeprazole triple therapy approach provides a >90% per-protocol report card with the caveat that this approach is markedly less effective in the presence of fluoroquinolone resistance. Levofloxacin-resistant strains are increasing in Taiwan.

Intravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole in preventing rebleeding among low risk patients with a bleeding peptic ulcer after initial endoscopic hemostasis.

BACKGROUND: Many studies have shown that high-dose proton-pumps inhibitors (PPI) do not further reduce the rate of rebleeding compared to non-high-dose PPIs but we do not know whether intravenous non-high-dose PPIs reduce rebleeding rates among patients at low risk (Rockall score < 6) or among those at high risk, both compared to high-dose PPIs. This retrospective case-controlled study aimed to identify the subgroups of these patients that might benefit from treatment with non-high-dose PPIs. METHODS: Subjects who received high dose and non-high-dose pantoprazole for confirmed acute PU bleeding at a tertiary referral hospital were enrolled (n = 413). They were divided into sustained hemostasis (n = 324) and rebleeding groups (n = 89). The greedy method was applied to allow treatment-control random matching (1:1). Patients were randomly selected from the non-high-dose and high-dose PPI groups who had a high risk peptic ulcer bleeding (n = 104 in each group), and these were then subdivided to two subgroups (Rockall score ≥ 6 vs. < 6, n = 77 vs. 27). RESULTS: An initial low hemoglobin level, serum creatinine level, and Rockall score were independent factors associated with rebleeding. After case-control matching, the significant variables between the non-high-dose and high-dose PPI groups for a Rockall score ≥ 6 were the rebleeding rate, and the amount of blood transfused. Case-controlled matching for the subgroup with a Rockall score < 6 showed that the rebleeding rate was similar for both groups (11.1% in each group). CONCLUSION: Intravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole when treating low risk patients with a Rockall sore were < 6 who have bleeding ulcers and high-risk stigmata after endoscopic hemostasis.

The Impact of Weight Loss during Chemoradiotherapy for Unresectable Esophageal Cancer: Real-World Results.

Weight loss is a common phenomenon presented in unresectable esophageal cancer (EC) patients during their definitive chemoradiotherapy (dCRT) treatment course. This study explored the prognostic value of weight changes during dCRT in unresectable EC patients. From 2009 to 2017, 69 cT4b thoracic EC patients undergoing complete curative dCRT without baseline malnutrition were included. Clinical factors were analyzed via the Cox proportional hazards model and survival was analyzed by the Kaplan−Meier method. During dCRT, the median weight loss percentage was 5.51% (IQR = 2.77−8.85%), and the lowest body weight was reached at 35 days (IQR = 23−43 days). Median OS of these patients was 13.5 months. Both univariate and multivariate analysis demonstrated that weight loss ≤ 4% during dCRT was significantly associated with superior OS with a hazard ratio of 2.61 (95% CI: 1.40−4.85, p = 0.002). The median OS for patients with weight loss ≤ 4% and >4% during dCRT was 59.6 months and 9.7 months, respectively (p = 0.001). Our study demonstrated that weight loss ≤ 4% during dCRT course is a favorable prognostic factor for cT4b EC patients. This index could serve as a nutrition support reference for unresectable EC patients receiving dCRT in the future.

Clinical outcomes of endoscopic submucosal dissection for colorectal neoplasms: A single-center experience in Southern Taiwan.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) as an advanced endoscopic procedure can be considered for the removal of colorectal lesions with high suspicion of limited submucosal invasion or cannot be optimally removed by snare-based techniques. We aimed to analyze the clinical outcomes of ESD for colorectal neoplasms in our hospital. METHODS: We retrospectively enrolled 230 patients with 244 colorectal neoplasms who received ESD procedures from April 2012 to October 2020 at Kaohsiung Chang Gung Memorial Hospital. Clinicopathological data were collected by chart review. We also recorded ESD-related complications and clinical outcomes. RESULTS: The average age was 64 years old, with a mean follow-up time of 22.59 months. There was a loss of follow-up in 34 lesions. Most lesions were lateral spreading tumors of the non-granular type. The average ESD time was 51.9 minutes. Nine cases (3.7%) had procedure-related complications, including two intra-procedure perforations (0.8%) and seven delayed bleeding (2.9%) without procedure-related mortality. 241 lesions (98.8%) achieved en-bloc resection, while 207 lesions (84.8%) achieved R0 resection. Most lesions were tubulo-(villous) adenoma. Malignancy included 35 adenocarcinomas and 5 neuroendocrine tumors. No local recurrence was developed during follow-up. Multivariate analysis for long ESD time revealed significance in size ≥ 10 cm2 and endoscopist's experience < 3 years. Pre-ESD endoscopic ultrasound revealed good prediction in discrimination of mucosal (sensitivity: 0.90) and submucosal lesion (specificity: 0.67). CONCLUSIONS: ESD for colorectal neoplasms is an effective and safe technique. Size ≥ 10 cm2 and endoscopist's experience < 3 years were significantly associated with long procedure time. Pre-ESD EUS provided a good prediction for colorectal neoplasms in invasion depth.

The Radiation Dose to the Left Supraclavicular Fossa is Critical for Anastomotic Leak Following Esophagectomy - A Dosimetric Outcome Analysis.

Purpose: For locally advanced esophageal cancer, definitive concurrent chemoradiotherapy (CCRT) with a radiation dose of 50-50.4 Gy/25-28 Fx is prescribed, followed by adjuvant esophagectomy for better local control or salvage treatment if locoregional recurrence occurs. However, radiation injury before surgery may delay wound healing. We performed cervical anastomosis directly inside the left supraclavicular fossa (SCF), the irradiation target for esophageal cancer. The significance of radiation injury in patients with cervical anastomotic leak (AL) remains unclear. Thus, we assessed the influence of radiation on cervical AL in patients undergoing preoperative CCRT followed by esophagectomy. Patients and Methods: We defined the SYC zone, a portion of the region overlapping the left SCF. The radiation dose to the SYC zone was analyzed and correlated with AL in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were administered preoperative CCRT (radiation dose with 50-50.4 Gy/25-28 Fx to the primary esophageal tumor) followed by esophagectomy between October 2009 and January 2018. Receiver operating characteristic curve analysis and logistic regression were used to identify the optimal radiation factor to predict AL and the cutoff value. Results: The optimal radiation factor to predict AL was the mean dose to the SYC zone (area under the curve (AUC)=0.642), and the cutoff point of the mean dose was 48.55 Gray (Gy). For a mean SYC zone dose ≥48.55 Gy, the AL risk was sevenfold greater than that for <48.55 Gy (OR = 7.805; 95% CI: 1.184 to 51.446; P value = 0.033). Conclusion: Recognizing the SYC zone as an organ at risk and performing radiation evaluation are meaningful. A reduced mean dose of the SYC zone below 48.55 Gy results in a lower cervical AL rate following esophagectomy.

Detection of annexin A autoantibodies in sera from colorectal cancer patients.

BACKGROUND: Annexins (ANXAs) belong to a superfamily of closely related calcium and membrane-binding proteins and are overexpressed in some carcinomas. The overexpression of ANXAs presumably induces an autoantibody response, but this has not been demonstrated for sera from colorectal cancer (CRC) patients. STUDY: We examined serum samples from 220 CRC patients and 216 healthy volunteers to evaluate the ANXA autoantibody response in patients by using an enzyme-linked immunosorbent assay with recombinant ANXA A4 as the antigen. RESULTS: The sensitivity of the anti-ANXA response from CRC patient sera was about 85% and the specificity was about 61.6%. When a cut-off value of 5.0 ng/mL was chosen for carcinoembryonic antigen (CEA) in the same sera samples, the sensitivity and specificity values were 43.2% and 85.2%, respectively. Combined detection using ANXA autoantibodies and CEA produced better sensitivity (71.8%) and specificity (79.2%) compared with CEA sensitivity (43.2%) and anti-ANXA specificity (61.6%). The area under a receiver operating characteristic curve was 0.794 for ANXA autoantibodies, 0.666 for CEA, and 0.84 for both markers together. Importantly, in comparison to CEA (27.5% seropositivity), ANXA autoantibody showed a remarkable change (81.3% seropositivity) at the early stage of CRC. CONCLUSIONS: Measurement of ANXA autoantibody levels may provide an alternative detection indicator for CRC, particularly among early-stage patients.

Definitive chemoradiotherapy for clinical T4b esophageal cancer - Treatment outcomes, failure patterns, and prognostic factors.

PURPOSE: The management of cT4b thoracic esophageal cancer (EC) is challenging. The optimal treatment remains unclear, and prospective or large-scale retrospective reports on treatment outcomes are lacking. The present study was conducted to investigate the treatment outcomes, failure patterns, treatment responses, and prognostic factors focusing on cT4b thoracic EC treated by definitive concurrent chemoradiotherapy (dCRT). METHODS: A retrospective review of cT4b thoracic EC patients treated with curative intent dCRT at our institution between 2009 and 2017 was conducted. Survival analysis was calculated using the Kaplan-Meier method, and prognostic factors were examined by the Cox proportional hazards model. RESULTS: A total of 95 cT4b EC patients were included, and the median survival was 11.4 months. The 1-year, 3-year, and 5-year survival rates were 49.4%, 22.2%, and 19.0%, respectively. Forty-six patients (48.4%) experienced locoregional failure, 3 patients (3.2%) developed distant metastasis, and 11 patients had synchronous locoregional and distant failure. The corresponding 1-year, 3-year, and 5-year locoregional failure rates were 62.6%, 74.5%, and 79.2%, respectively. The treatment response rate was 76.9%, and clinical complete response was achieved in 25.3% of patients. Multivariable analysis revealed that age ≤ 65 (p = 0.003), pre-dCRT body mass index (BMI) > 21 (p < 0.001), clinical N stage 0-1 (p = 0.014), and tumor length ≤ 6 cm (p = 0.026) were independent prognosticators for better survival. CONCLUSION: Our study revealed that long-term survival is achievable for cT4b EC patients treated by dCRT, with a 3-year survival rate of more than 20%. Locoregional recurrence was the most common failure pattern. Age, BMI, N stage, and tumor length were significant prognosticators for survival in this group of patients.

The efficacies of non-bismuth containing quadruple therapies in the treatment of first-line anti-Helicobacter pylori across 4-year time interval with changing antibiotics resistance.

BACKGROUND: Non-bismuth containing quadruple therapy (concomitant therapy) is an alternative treatment for Helicobacter pylori (H. pylori) eradication with increasing clarithromycin-resistant strains over times. This study compared the efficacies of non-bismuth containing quadruple therapy (concomitant therapy) in the treatment of first-line anti-Helicobacter Pylori between two time intervals (January 2013 to June 2014 and June 2016 to December 2017). METHODS: H. pylori-infected patients were recruited in the intention-to-treat (ITT analysis) and divided into EACM-A group (enrolled from January 2013 to June 2014, N = 98) and EACM-B group (enrolled from June 2016 to December 2017, N = 99). Patients were prescribed with 7-day esomeprazole 40 mg bid., clarithromycin 500 mg bid., amoxicillin 1 g bid. and metronidazole 500 mg bid. Ninety patients and 93 patients were analyzed in the per protocol (PP) analysis (8 and 6 patients lost follow-up in each group). Urea breath tests were performed 4-8 weeks thereafter. RESULTS: The eradication rates for EACM-A and EACM-B groups were 87.8% (95% confidence interval [CI] = 79.7%-93.5%) and 84.8% (95% CI = 76.2%-91.2%) (p = 0.55) in intention-to-treat (ITT) analysis; 95.6% (95% CI = 89.1%-98.8%) and 90.3% (95% CI = 82.4%-95.5%) (p = 0.17) in per protocol (PP) analysis. The adverse event rates were 16.7% vs. 10.8% in the 2 groups (p = 0. 0.24). The antibiotic resistance rates between the 2 groups were amoxicillin (0%), tetracycline (0%); clarithromycin (11.8% vs. 17.8%, p = 0.46); metronidazole (32.4% vs. 33.3%, p = 0.93) and levofloxacin (14.7% vs. 37.8%, p = 0.02). CONCLUSION: The success rate of 7-days concomitant therapy encountered an approximately 5% decrease across 4-year time interval (2013-2017) with the changes of clarithromycin resistance from 11.8% to 17.8% in Taiwan.

Gastric metastasis of hepatocellular carcinoma via a possible existing retrograde hematogenous pathway.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) tends to metastasize to extrahepatic organs. Stomach involvement has been seldom reported and has always been considered as direct invasion. This study aims to propose a possible existing pathway for the hematogenous metastasis of HCC to the stomach. METHODS: Only seven cases with stomach involvement were found from 8267 HCC patients registered at our hospital between 2000 and 2007. Their laboratory data, the findings of computed tomography and upper endoscopy, therapeutic procedures, such as esophageal variceal banding ligation (EVL), and transhepatic arterial embolization (TAE) were further studied. RESULTS: All seven patients were male. Liver cirrhosis was found in six patients (6/7 = 85.7%), HCC with portal vein thrombosis (PVT) in six patients (6/7 = 85.7%), splenomegaly in five patients (5/7 = 71.4%) and esophageal varices in five patients (5/7 = 71.4%). Six patients underwent TAE and one patient underwent EVL before the development of HCC in the stomach. Four patients had HCC at the cardia, one patient at the anterior wall of the high body and two patients at the greater curvature of the high body, far away from the original HCC. Six patients eventually developed distant metastasis. HCC with gastric metastasis developed 53-126 days after TAE in five patients and 74 days after EVL in one patient. CONCLUSIONS: When cirrhotic patients with portal hypertension have HCC with PVT, a hematogenous pathway can exist for gastric metastasis of tumor thrombi involving hepatofugal flow to the stomach after TAE or EVL apart from the major pathway of direct invasion.

Surveillance culture of endoscope to monitor the quality of high-level disinfection of gastrointestinal reprocessing.

BACKGROUND/AIMS: Inadequate reprocessing of endoscopes or endoscopic accessories may result in iatrogenic infection and present a risk to public health. The aim of this study is to utilize microbiological cultures of endoscopes to assess the adequacy of standard reprocessing procedures. METHODOLOGY: A prospective study to randomly cultures of endoscopes and colonoscopies immediately after the completion of the decontamination cycle monthly. The samples were obtained by flushing 50 ml sterile distilled water to the internal channel and collected into a sterile container. These samples were incubated at 37 degrees C and examined for bacterial growth. RESULTS: A total of 49 cultures were obtained from June to December in year 2005. Three out of 7 were culture positive in the first month initially, but after prolonged the soaking duration to 25 minutes, the subsequent cultures were reduced to 1 positive sample only. The positive culture rate was 18.4% (9/49), and 44.4% (4/9) in Monoflora culture and 55.6% (5/9) in Multi-flora. Upper endoscopes decontaminated by automated endoscopic washing machine labeled as number 5 was found persistently culture positive with varied organisms despite vigorous manual cleaning and prolonged disinfectant soaking duration. At repair, the relief valve in the automated endoscopes washing machine was damaged and disconnected. After repair, subsequent cultures were negative. CONCLUSIONS: Endoscopy culturing is a useful method to assess the effectiveness of standard reprocessing procedures. Servicing of automated endoscope washer regularly is mandatory to minimize cross infection and quality assurance.

Elevated p21 expression is associated with poor prognosis of rectal stromal tumors after resection.

BACKGROUND AND OBJECTIVES: The pathogenic role of alteration of cell-cycle proteins in rectal stromal tumors (GISTs) remains unclear. This study aimed to elucidate the prognostic role of p21 to compare with p53, PCNA, and Ki-67 in rectal GISTs. METHODS: Forty-nine surgically resected CD117 (+) rectal GISTs were enrolled from 1986 to 2006. Immunohistochemical studies were performed with antibodies of p21, p53, PCNA, and Ki-67. RESULTS: The labeling index (LI) of immunoreactivities range from 0% to 65% for p53, 0% to 60% for p21, 0% to 67% for Ki-67, and 30% to 93% for PCNA. LI of four markers were positively correlated (P < 0.05). LI of four markers were also positively correlated with tumor mitosis and tumor size (P < 0.05). Tumors with high p53, p21, or Ki-67 LI were associated with increased NIH risk, non-spindle cell type, and high cell pleomorphism (P < 0.05). Survival analyses demonstrated that large tumor size (P = 0.012), high tumor mitosis (P < 0.001), increased NIH risk (P = 0.003), high cell pleomorphism (P = 0.004), high p53 LI (P = 0.005), high p21 LI (P = 0.009), high PCNA LI (P = 0.001), and high Ki-67 LI (P = 0.042) were poor prognostic factors for disease-specific survival. CONCLUSIONS: Elevated p21 expression is associated with poor prognosis of rectal stromal tumors after resection.

The abnormalities in the p53/p21WAF1 pathway have a significant role in the pathogenesis and progression of gastrointestinal stromal tumors.

To elucidate the prognostic role and relationship of the p53/p21/PCNA pathway in gastrointestinal stromal tumors (GISTs), a total of 167 resected gastric and small intestinal CD117-positive stromal tumor specimens were collected from January 1987 to December 2000. Immunohistochemical studies were performed on the paraffin sections with antibodies of p53, p21/WAF1, proliferating cell nuclear antigen (PCNA) and Ki-67. The immunoreactivity of four markers was recorded by labeling index (LI, %) for clinicopathologic and survival correlation. The labeling index was 0-83% for p53, 0-81% for p21/WAF1, 0-33% for Ki-67 and 12-92% for PCNA. Completely negative immunostaining (LI<1%) was found in 54.5% of p53, 25.8% of p21/WAF1 and 44.3% of Ki-67. The LI of four markers strongly correlate with each other (p<0.05). Furthermore, the LI of all four markers positively correlate to microscopic tumor mitotic counts (p<0.05). Only the LI of p53 and PCNA positively correlate to tumor sizes. Tumors with non-spindle cell type (versus spindle cell) and high cellular pleomorphism (versus low) exhibited a higher p53, p21/WAF1 and PCNA LI (p<0.05). Increased NIH risk significantly correlates to increased p53, PCNA and Ki-67 (p<0.05) LI. Survival analysis indicated that a large tumor size (> or =5 cm, p=0.003), increased tumor mitosis (> or =5/50 HPF, p<0.001), high NIH risk (p<0.001), non-spindle cell type (p=0.024), high p53 LI (p<0.001), high p21/WAF1 LI (p=0.007), high Ki-67 LI (p<0.001) and high PCNA LI (p<0.001) were prognostic factors for poor disease-free survival. Independent factors are tumor size, NIH risk, p53 and p21/WAF1 LI. We demonstrated the first evidence of the linear relationship and prognostic role of the p53/p21/PCNA pathway in gastrointestinal stromal tumors. Abnormalities of the p53/p21WAF1 pathway lead to increased proliferating states, thereby triggering the progression of GISTs.

Pseudoachalasia in a patient after truncal vagotomy surgery successfully treated by subsequent pneumatic dilations.

Pseudoachalasia is a difficult condition for the clinician to differentiate from idiopathic achalasia even by manometry, radiological studies or endoscopy. Its etiology is usually associated with tumors. In most cases, the diagnosis is made after surgical explorations. The proposed pathogenesis of the disease is considered as mechanical obstruction of the distal esophagus or infiltration of the malignancy that affects the inhibitory neurons of the meyenteric plexus in the majority of cases. Surgery has been reported as a cause of pseudoachalasia. We report a 70-year-old man who suffered from deglutination disorder caused by pseudo-achalasia after truncal vagotomy. The patient was symptom-free after a nine-year follow-up and complete recovery of esophageal motility status from pseudoachalasia after pneumatic dilations. We also reviewed the literature of pseudoachalasia.

A Randomized Control Trial Comparing 2 Levofloxacin-Containing Second-Line Therapies for Helicobacter pylori Eradication.

Summary of Trial Design.Lengthy exposure to quinolone-containing triple therapy in Helicobacter pylori eradication leads to the development of drug resistance. Sequential therapy with a quinolone and metronidazole -containing regimen appears to be an effective treatment option. This randomized controlled trial aimed to compare the efficacy of 5-plus 5 days' levofloxacin and metronidazole-containing sequential therapy (EALM) with that of 10-day levofloxacin-containing triple therapy (EAL) in second-line H pylori eradication treatment.One hundred and sixty-four patients who had failed the H pylori eradication attempts using the standard triple therapy (proton pump inhibitor bid, clarithromycin 500 mg bid, amoxicillin 1 g bid × 7 days) were randomly assigned to either an EALM therapy group (n = 82; esomeprazole 40 mg bid and amoxicillin 1 g bid for 5 days, followed by esomeprazole 40 mg bid, levofloxacin 500 mg qd, and metronidazole 500 mg tid, for 5 days) or a 10-day EAL therapy group (n = 82; levofloxacin 500 mg qd, amoxicillin 1 g bid, and esomeprazole 40 mg bid). One patient was lost to follow-up in each group. Follow-up for H pylori status was performed 4 to 8 weeks later.Eradication rates for the EALM and EAL groups were 90.2% (74/82, 95% confidence interval [CI] = 83.7%-96.8%) and 80.5% (66/82, 95% CI = 71.7%-89.2%, P = 0.077) in the intention-to-treat analysis; and 91.4% (74/81, 95% CI = 85.1%-97.6%) and 81.5% (66/81, 95% CI = 72.8%-90.1%, P = 0.067) in the per-protocol analysis. The adverse events for the EALM and EAL groups were 23.5% versus 11.1%, P = 0.038 but were all very mild and were well tolerated except for 1 patient with poor compliance. The compliances were 98.8% and 100%, respectively, between the 2 groups. An antibiotic resistance to levofloxacin was the clinical factor influencing the efficacy of H. pylori eradication therapy in the EAL group, and dual resistance to levofloxacin and metronidazole in the EALM group.Levofloxacin and metronidazole-containing sequential therapy achieved a >90% eradication rate as a second-line H pylori therapy. Dual antibiotic resistance to levofloxacin and metronidazole was the clinical factor influencing the efficacy of H pylori eradication therapy in the sequential therapy (ClinicalTrials.gov number: NCT02596620).