Sequential therapy for 10†days versus triple therapy for 14†days in the eradication of Helicobacter pylori in the community and hospital populations: a randomised trial.

OBJECTIVE: Significant heterogeneity was observed in previous trials that assessed the efficacies of sequential therapy for 10 days (S10) versus triple therapy for 14 days (T14) in the first-line treatment of Helicobacter pylori. We aimed to compare the efficacy of S10 and T14 and assess the factors affecting their efficacies. DESIGN: We conducted this open-label randomised multicentre trial in eight hospitals and one community in Taiwan. 1300 adult subjects with H pylori infection naïve to treatment were randomised (1:1) to receive S10 (lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, clarithromycin and metronidazole for another 5 days) or T14 (lansoprazole, amoxicillin and clarithromycin for 14 days). All drugs were given twice daily. Successful eradication was defined as negative 13C-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test. RESULTS: The eradication rates of S10 and T14 were 87.2% (567/650, 95% CI 84.4% to 89.6%) and 85.7% (557/650, 95% CI 82.8% to 88.2%) in the ITT analysis, respectively, and were 91.6% (556/607, 95% CI 89.1% to 93.4%) and 91.0% (548/602, 95% CI 88.5% to 93.1%) in the PP analysis, respectively. There were no differences in compliance or adverse effects. The eradication rates in strains susceptible and resistant to clarithromycin were 90.7% and 62.2%, respectively, for S10, and were 91.5% and 44.4%, respectively, for T14. The efficacy of T14, but not S10, was affected by CYP2C19 polymorphism. CONCLUSIONS: S10 was not superior to T14 in areas with low clarithromycin resistance. TRIAL REGISTRATION NUMBER: NCT01607918.

Levofloxacin Sequential Therapy vs Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori: A Randomized Trial.

OBJECTIVES: The efficacy of levofloxacin triple therapy has fallen below 80% in the second-line treatment of Helicobacter pylori (H. pylori). We aimed to assess whether the levofloxacin sequential therapy is more effective than levofloxacin triple therapy in the second-line treatment. METHODS: This open-label, randomized, multicenter trial was conducted between 2012 and 2015. H. pylori-infected subjects who failed from clarithromycin-based regimens (N=600) were randomized (1:1) to receive levofloxacin sequential therapy (LS: lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, levofloxacin, and metronidazole for another 5 days) or levofloxacin triple therapy (LT: lansoprazole, amoxicillin, and levofloxacin for 10 days). Successful eradication was defined as negative (13)C-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test. RESULTS: The prevalence of clarithromycin, levofloxacin, and metronidazole resistance was 60, 17.6, and 36.9%, respectively. The eradication rates of LS and LT were 84.3% (253/300) and 75.3% (226/300), respectively, in the ITT analysis (P=0.006) and 86.3% (253/293) and 78.8% (223/283), respectively, in the PP analysis (P=0.021). The efficacies of both LS and LT were affected by levofloxacin resistance. The secondary resistance of levofloxacin was 66.7 and 73.9% after LS and LT, respectively. The efficacies of LS and LT were not affected by the CYP2C19 polymorphism. CONCLUSIONS: Levofloxacin sequential therapy was more effective than levofloxacin triple therapy, and it is recommended in the second-line treatment for H. pylori ( TRIAL REGISTRATION NUMBER: NCT01537055).

Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria.

BACKGROUND AND OBJECTIVE: Whether there is distinct pathogenesis in subgroups of functional dyspepsia (FD), the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) remains controversial. We aimed to identify the risk factors of FD and its subgroups in the Chinese population. METHODS: Patients with dyspepsia and healthy subjects who underwent gastric cancer screening were enrolled in this multicentre study from 2010 to 2012. All patients were evaluated by questionnaire, oesophagoduodenoscopy, histological examination and Helicobacter pylori tests. Subgroups of FD were classified according to the Rome III criteria. Psychiatric stress was assessed by the short form Brief Symptom Rating Scale. CagA and VacA genotypes were determined by PCR. RESULTS: Of 2378 patients screened for eligibility, 771 and 491 fulfilled the diagnostic criteria of uninvestigated dyspepsia and FD, respectively. 298 (60.7%) and 353 (71.9%) individuals were diagnosed with EPS and PDS, respectively, whereas 169 (34.4%) had the overlap syndrome. As compared with 1031 healthy controls, PDS and EPS shared some common risk factors, including younger age (OR 0.95; 99.5% CI 0.93 to 0.98), non-steroidal anti-inflammatory drugs (OR 6.60; 99.5% CI 3.13 to 13.90), anxiety (OR 3.41; 99.5% CI 2.01 to 5.77) and concomitant IBS (OR 6.89; 99.5% CI 3.41 to 13.94). By contrast, H. pylori (OR 1.86; 99.5% CI 1.01 to 3.45), unmarried status (OR 4.22; 99.5% CI 2.02 to 8.81), sleep disturbance (OR 2.56; 99.5% CI 1.29 to 5.07) and depression (OR 2.34; 99.5% CI 1.04 to 5.36) were associated with PDS. Moderate to severe antral atrophy and CagA positive strains were also more prevalent in PDS. CONCLUSIONS: Different risk factors exist among FD subgroups based on the Rome III criteria, indicating distinct aetiopathogenesis of the subdivisions that may necessitate different therapeutic strategies.

Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial.

BACKGROUND: Whether sequential treatment can replace triple therapy as the standard treatment for Helicobacter pylori infection is unknown. We compared the efficacy of sequential treatment for 10 days and 14 days with triple therapy for 14 days in first-line treatment. METHODS: For this multicentre, open-label, randomised trial, we recruited patients (≥20 years of age) with H pylori infection from six centres in Taiwan. Using a computer-generated randomisation sequence, we randomly allocated patients (1:1:1; block sizes of six) to either sequential treatment (lansoprazole 30 mg and amoxicillin 1 g for the first 7 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg for another 7 days; with all drugs given twice daily) for either 10 days (S-10) or 14 days (S-14), of 14 days of triple therapy (T-14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg for 14 days; with all drugs given twice daily). Investigators were masked to treatment allocation. Our primary outcome was the eradication rate in first-line treatment by intention-to-treat (ITT) and per-protocol (PP) analyses. This trial is registered with ClinicalTrials.gov, number NCT01042184. FINDINGS: Between Dec 28, 2009, and Sept 24, 2011, we enrolled 900 patients: 300 to each group. The eradication rate was 90·7% (95% CI 87·4-94·0; 272 of 300 patients) in the S-14 group, 87·0% (83·2-90·8; 261 of 300 patients) in the S-10 group, and 82·3% (78·0-86·6; 247 of 300 patients) in the T-14 group. Treatment efficacy was better in the S-14 group than it was in the T-14 group in both the ITT analysis (number needed to treat of 12·0 [95% CI 7·2-34·5]; p=0·003) and PP analyses (13·7 [8·3-40], p=0·003). We recorded no significant difference in the occurrence of adverse effects or in compliance between the three groups. INTERPRETATION: Our findings lend support to the use of sequential treatment as the standard first-line treatment for H pylori infection. FUNDING: National Taiwan University Hospital and National Science Council.

Clinical presentations of patients from different age cohorts with biliary tract stone diseases.

BACKGROUND AND AIM: The role of clinical symptoms, transabdominal ultrasound scan (USS), and liver function tests (LFTs) in evaluating common bile duct (CBD) stones in patients suspected to have pancreatobiliary disease has been studied. However, it is unclear whether these predictive models are useful in different age cohorts. The aim of this study is to investigate the clinical presentations from different age cohorts with and without CBD stones. METHODS: Four hundred and forty-three patients with pancreatobiliary diseases were divided into cohorts according to decades as follows: young (Y, 18-64 years old, n = 143), young-old (YO, 65-74 years old, n = 168), old-old (OO, 75-84 years old, n = 97), and very old (VO, ≥ 85 years old, n = 35). The clinical symptoms, LFTs, and USS findings were demonstrated and compared among patients. RESULTS: Y- and YO-group patients were more likely to develop symptoms such as biliary colic in the presence of CBD stones. The proportion of abnormal serum aspartate aminotransferase and alanine aminotransferase were significantly greater in Y-, YO-, and OO-group patients with than in those without CBD stones. Sensitivity of USS for CBD stones in Y: 0.15; YO: 0.45; OO: 0.57; and VO: 0.68. Accuracy of USS for detected CBD stone in Y: 48%; YO: 62.5%; OO: 70.1%; and VO: 71.4%. CONCLUSION: Combined evaluation of clinical symptoms, biochemical and USS findings may help predict the presence of CBD stones. In Y, YO, and OO patients with CBD stones, the incidences of abnormal LFTs were higher. The sensitivity and accuracy of USS in detecting CBD stones were increased according to age.

Efficacy of genotypic resistance-guided sequential therapy in the third-line treatment of refractory Helicobacter pylori infection: a multicentre clinical trial.

OBJECTIVES: The efficacy of sequential therapy and the applicability of genotypic resistance to guide the selection of antibiotics in the third-line treatment of Helicobacter pylori have not been reported. We aimed to assess the efficacy of genotypic resistance-guided sequential therapy in third-line treatment. METHODS: Genotypic and phenotypic resistances were determined in patients who failed at least two eradication therapies by PCR with direct sequencing and agar dilution test, respectively. The patients were retreated with sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole plus clarithromycin, levofloxacin or tetracycline for another 7 days (all twice daily), according to genotypic resistance determined using gastric biopsy specimens. Eradication status was determined by the (13)C-urea breath test. Trial registered at clinicaltrials.gov (identifier: NCT01032655). RESULTS: The overall eradication rate was 80.7% (109/135, 95% CI 73.3%-86.5%) in the intention-to-treat analysis. The presence of amoxicillin resistance (OR 6.83, 95% CI 1.62-28.86, P = 0.009) and prior sequential therapy (OR 4.77, 95% CI 1.315-17.3, P = 0.017), but not tetracycline resistance (tetracycline group), were associated with treatment failure. The eradication rates in patients who received clarithromycin-, levofloxacin- and tetracycline-based sequential therapies were 78.9% (15/19), 92.2% (47/51) and 71.4% (25/35) in strains susceptible to clarithromycin, levofloxacin and tetracycline, respectively. CONCLUSIONS: A simple molecular method guiding sequential therapy can achieve a high eradication rate in the third-line treatment of refractory H. pylori infection.

Perforated peptic ulcer in southeastern Taiwan.

BACKGROUND: No studies focus on the population with perforated peptic ulcer in southeastern Taiwan. The present study aimed to assess the differences between the different races and the risk factors related to mortality and morbidity in postoperative patients in southeastern Taiwan. METHODS: The medical records of 237 patients were reviewed retrospectively. The following factors were analyzed: patient profiles, coexisting illnesses, diagnostic method, fever, preoperative shock, clinical data at emergency room, delay operation, site of perforation, operative method, positive ascites culture, species of microbes in ascites culture, postoperative complications, death and the length of hospital stay. RESULTS: Aborigines were significantly different from non-aborigines in the ratio of female cases and in the habits of alcohol drinking and betel nut chewing. There were also four significantly different variables between them: fever, hemoglobin value, site of perforation and operative method. Total postoperative complication rate was 41.3% and 39 patients (16.6%) died. In multivariate analysis, age > or = 65 years, lipase > upper normal limit and preoperative shock were independent predictors of mortality. Significant risk factors associated with morbidity were NSAIDs use, creatinine > 1.5 mg/dL and preoperative shock. CONCLUSION: Aborigines were different from non-aborigines in several categories. In southeastern Taiwan, NSAIDs use, creatinine > 1.5 mg/dL and preoperative shock were independent risk factors of morbidity, and age > or = 65 years, lipase > upper normal limit and preoperative shock were independent risk factors of mortality in postoperative perforated peptic ulcer. Lipase > upper normal limit is needed for further research on the influence on mortality.

Acquired hyperplastic gastric polyps after treatment of ulcer.

BACKGROUND/PURPOSE: Healing of gastric ulcers requires repair by epithelial migration and proliferation. We have found a small proportion of patients with acquired hyperplastic polyps at the healed ulcer site. The aim of this study was to identify clinical characteristics that might be associated with the development of hyper-plastic polyps at the site of healed gastric ulcers. METHODS: This was a retrospective review of 86 patients with gastric ulcers from April 2006 to September 2008. After initial endoscopy, the patients were all treated with proton pomp inhibitors, after which a second endoscopy was performed. Demographic data, polyp characteristics (endoscopic and histological), Helicobacter pylori status, and duration of treatment were analyzed. RESULTS: A total of 24 hyperplastic gastric polyps were found in 18 patients; all at the site of the healed ulcer (20 in the antrum and 4 in the corpus). The mean size of the ulcers prior to treatment was 14.5 +/- 9.1 mm. Hyperplastic gastric polyps were more likely to occur at the site of ulcers larger than 10 mm (odds ratio = 9.57, 95% confidence interval =2.50-36.65). Age, sex, H. pylori status, ulcer location and duration of treatment did not differ significantly between patients with and without polyps. CONCLUSION: Hyperplastic polyps that develop after healing of gastric ulcers are likely to be extensive mucosal injury. A gastric ulcer larger than 10 mm is associated with a significantly increased risk of hyperplastic polyps.

Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism is associated with choledocholithiasis in Taiwanese patients.

BACKGROUND AND AIMS: The gene product of the uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) is crucial to bilirubin metabolism. Mutations in this gene subsequently result in disease presented with unconjugated hyperbilirubinemia. A previous study showed that a TA-repeat polymorphism in the promoter region of this gene might play a role in the metabolism of bilirubin. Whether this polymorphism might predispose choledocholithiasis is unclear. METHODS: We recruited 32 patients who were diagnosed with pigment choledocholithiasis (common bile duct stones) by endoscopic retrograde cholangiopancreatography (ERCP) morphology and 107 population controls. The TA-repeat in the UGT1A1 promoter was genotyped. RESULTS: We found that among the 32 patients, 15 (46.9%) were wild type (A[TA](6)TAA homozygous); 15 (46.9%) were a heterozygous variation (A[TA[(6)TAA/A[TA](7)TAA) and 2 (6.2%) were a homozygous variation (A[TA](7)TAA). Among the controls, 81 (75.7%) were wild type, 23 (21.5%) were a heterozygous variation and 3 (2.8%) were a homozygous variation. The genotype distribution was significantly different between patients and controls. CONCLUSIONS: The results suggest that the UGT1A1 promoter TA-repeat polymorphism is associated with choledocholithiasis in Taiwanese patients.

Abdominal tuberculosis in southeastern Taiwan: 20 years of experience.

BACKGROUND/PURPOSE: Abdominal tuberculosis (TB) is a rare manifestation of extrapulmonary TB. This disease entity can be overlooked, and its early diagnosis is difficult because of its variable manifestations and lack of specific symptoms. METHODS: The clinical and diagnostic features, treatment, and outcome of patients with abdominal TB at a major hospital in southeastern Taiwan from January 1987 to December 2006 were investigated. RESULTS: Twenty-one patients with abdominal TB identified during the 20-year period were included. A predominance of male (13/21, 61.9%) and Taiwanese aborigine (15/21, 71.4%) patients was noted. Middle-aged (30-50 years) patients with alcoholic liver cirrhosis had the highest risk. Common presenting features included abdominal pain (18/21, 85.7%), fever (16/21, 76.2%), ascites (13/21, 61.9%), and weight loss (12/21, 57.3%). The mean time to reach a diagnosis was 48 +/- 10 days. Tuberculous peritonitis was noted in 11 patients, with a high correlation with liver cirrhosis (p = 0.0237, Fisher's exact test). The other patients were diagnosed with TB of the gastrointestinal tract (n = 6), urinary tract (n = 2), and pelvis (n = 2). Abdominal sonography and abdominal computed tomography were helpful for diagnosis, by revealing ascites and thickening of the peritoneum. Pulmonary involvement was noted in 11 patients. Most of the patients (16/21, 76.2%) improved with anti-tuberculosis therapy, and five patients died from sepsis and respiratory failure. CONCLUSION: Abdominal TB is a rare manifestation of extrapulmonary TB, even in southeastern Taiwan where TB is prevalent. Delay in diagnosis is common and abdominal TB should be included in the differential diagnosis of middle-aged aborigine men with alcoholic liver cirrhosis and peritonitis.

Pyogenic liver abscess with Prevotella species and Fusobacterium necrophorum as causative pathogens in an immunocompetent patient.

Pyogenic liver abscess of odontogenic origin in an immunocompetent patient is extremely rare. We report an immunocompetent 25-year-old male hepatitis B carrier with severe dental disease that led to the development of liver abscess. A periapical abscess in the upper left molar area was seen on his dental X-ray. Two sets of blood cultures grew Prevotella species, bacteria that are commonly found inside the oral cavity. Bacterial culture of the liver abscess drainage sample grew both Prevotella and Fusobacterium necrophorum. This led to our diagnosis of pyogenic liver abscess of dental origin, since we found no other source of infection in our patient except for his dental disease. After antibiotic therapy with drainage, abdominal sonography showed resolution of the abscess. The diseased teeth were also extracted. During 1 year of follow-up, there was no sign of abscess recurrence. A diagnosis of pyogenic liver abscess necessitates a complete evaluation to rule out possible biliary, colonic or other associated diseases. However, when a liver abscess is thought to be cryptogenic, we also recommend a careful dental examination to help identify the source of infection.

Proposed scoring system to determine small bowel mass lesions using capsule endoscopy.

BACKGROUND/PURPOSE: Capsule endoscopy is a highly sensitive method for the detection of small bowel lesions. False-positive findings are important confounding factors. This study reports on a scoring system for evaluating the role of capsule endoscopy in small bowel tumors. METHODS: Ten men and two women (age, 23-79 years) with suspected small bowel tumors were included from 120 patients referred for capsule endoscopy between March 2004 and March 2008. The indications were gastrointestinal bleeding (n = 9), melanoma workup (n = 1), physical checkup (n = 1), and iron deficiency anemia (n = 1). The proposed tumor score was composed of five components: bleeding, mucosal disruption, an irregular surface, color, and white villi. These can be scored for probability of mass lesions seen at capsule endoscopy. Small bowel mass lesions were probably present in those with a score of >or= 4, and a score of

Clinical presentation and outcome of hepatic subcapsular fluid collections.

BACKGROUND/PURPOSE: Bile, blood or pus may rupture into or extend to the hepatic subcapsular space, but most descriptions in the literature are from isolated case reports. When fluid collections are limited by the size of the subcapsular space, they rarely present with abrupt symptoms and signs. We reviewed our experience with hepatic subcapsular fluid collections, including diagnostic studies and outcome. METHODS: Two radiologists independently assessed imaging database from computed tomography (CT) with the letter strings "subcapsule", "subcapsular", "liver" or "hepatic". Subcapsular fluid collection was defined as fluid deep in the liver capsule and superficial to the liver parenchyma without rupture into the peritoneum. The demographic data, clinical presentation, laboratory and imaging results, length of hospital stay, final diagnosis, and outcome were reviewed and recorded. RESULTS: From January 2002 to December 2004, 60 patients (33 males, 27 females; age range, 4-92 years) were diagnosed by CT to have a subcapsular fluid accumulation in liver. Etiologies included traumatic hematoma in 10, tumor-related hematoma in 18, ruptured liver abscess in 20, biloma in 8, and 4 miscellaneous causes. CT typically showed a lenticular-shaped fluid collection compressing the liver parenchyma. The fluid accumulation was connected in over half the cases to an intrahepatic lesion with a visible tract. Conservative management was adequate in 32 patients, while 9 had surgery and 19 underwent either percutaneous drainage (by CT or ultrasound guidance) or transarterial therapy. Of the 60 patients, 49 (82%) survived the episode, including all 10 with traumatic hematoma. The shortest mean length of hospital stay was 7.8 +/- 6.7 days in the tumor-related hematoma group, and the longest was 50.7 +/- 41.7 days in the abscess group. The international normalized ratio for coagulation for those who died and those who survived was 1.8 +/- 1.4 and 1.4 +/- 0.2 respectively (p = 0.027). CONCLUSION: If these fluid collections are limited in the subcapsular space, they are rarely associated with abrupt hemodynamic instability and usually not lethal. The only characteristic that differed significantly between those who died and those who survived was the international normalized ratio, meaning that good liver function and normal coagulation has the ability to recover from this dismal episode.

Predictive model for length of hospital stay of patients surviving surgery for perforated peptic ulcer.

BACKGROUND/PURPOSE: Many studies have assessed the major risk factors for mortality or morbidity in surgical patients with perforated peptic ulcer (PPU). The aim of our study was to focus on survivors and to investigate the predictive factors for length of hospital stay (LOHS) for surgical patients. METHODS: The medical records of 195 patients who survived surgery were reviewed retrospectively. The following factors were analyzed: patient profile, associated medical illnesses, diagnostic methods, fever, preoperative shock, clinical data from the emergency room, delays in surgery, sites of perforation, operative methods, positive ascites culture and species of microorganism, postoperative infection, and noninfective postoperative complications. RESULTS: Univariate analysis showed that the following factors were significantly related to longer LOHS: age > 65 years, liver cirrhosis, diabetes mellitus, history of peptic ulcer disease, number of comorbid diseases, preoperative shock, creatinine > 1.5 mg/dL, surgical delay of > 12 hours, and all postoperative factors except species of microorganisms in ascites culture. In a multivariate linear regression model, catheter infection, pneumonia, urinary tract infection, wound infection, bacteremia, non-infective abdominal complications, other infections, surgical delay of > 12 hours, and comorbidity were major factors associated with longer LOHS. CONCLUSION: A predictive model was established with nine factors that explained 71.6% of the variation in LOHS of patients who survived surgery for PPU. Several corrective methods based on the model can be devised by attending physicians to shorten LOHS.

Spontaneous clearance of Helicobacter pylori colonization in patients with partial gastrectomy: correlates with operative procedures and duration after operation.

BACKGROUND/PURPOSE: For patients undergoing gastric surgery because of complications of peptic ulcers, such as bleeding or perforation in the pre-Helicobacter pylori eradication era, their infection status was not surveyed or it was neglected altogether. Previous reports have shown spontaneous clearance of H. pylori in these patients but the determining factors remain ill-defined. METHODS: Seventy-six patients with previous partial gastrectomy for complicated peptic ulcers were enrolled prospectively. Patients with peptic ulcers but without gastrectomy were selected as a control group. Gastric biopsy specimens were obtained from each patient for histological H. pylori staining and rapid urease test on endoscopic evaluation. Spontaneous clearance of H. pylori colonization was defined when patients who were positive for H. pylori prior to operation became negative, without eradication treatment. RESULTS: The prevalence of H. pylori colonization was significantly lower in patients with partial gastrectomy (22.4%, 17/76 vs. 67.1%, 51/76, p < 0.001). There was a trend towards decreasing prevalence of H. pylori colonization as time after operation increased: 1-15 years, 29.5% (13/44); 16-30 years, 13.6% (3/22); and > 31 years, 10% (1/10). The spontaneous clearance rate of H. pylori after partial gastrectomy was 43% (13/30). The time after operation in the spontaneous clearance group was longer than that in those without (20.8 +/- 11.7 vs. 12.1 +/- 11.0 years, p = 0.048). Billroth-II procedure had a higher bile reflux rate and a lower H. pylori infection prevalence than the Billroth-I procedure. CONCLUSION: Spontaneous clearance of H. pylori develops in a certain number of patients who undergo distal gastrectomy. The clearance rate is related to operative procedures and time after operation.

Caffeic acid phenethyl ester induces apoptosis of human pancreatic cancer cells involving caspase and mitochondrial dysfunction.

AIMS: This study aimed to investigate the effect of caffeic acid phenethyl ester (CAPE), an active component isolated from honeybee propolis, in inducing apoptosis in human pancreatic cancer cells. METHODS: Inhibition of viability of BxPC-3 and PANC-1 cell lines induced by CAPE was estimated by a trypan blue dye exclusion test. The type of cell death in BxPC-3 after CAPE treatment was characterized by observation of morphology, sub-G1 DNA content, annexin-V/PI staining, caspase-3 and caspase-7 assay, and DNA agarose gel electrophoresis. RESULTS: CAPE (10 microg/ml) resulted in marked inhibition of viability of BxPC-3 (80.4 +/- 4.1%) and PANC-1 (74.3 +/- 2.9%) cells. CAPE induced a time-dependent increase in hypodiploid percentage and a significant decrease in mitochondrial transmembrane potential in BxPC-3 cells. It induced morphological changes of typical apoptosis, but no DNA fragmentation was noted by DNA electrophoresis. The inhibition of growth and increased in the proportion of sub-G(1) cells was partially blocked by pretreatment with the pan-caspase inhibitor Z-VAD-fmk (50 microM) in BxPC-3 cells indicating a caspase-related mechanism in CAPE-induced apoptosis. Caspase-3/caspase-7 activity was approximately 2 times greater in CAPE-treated BxPC-3 cells compared with control cells. CONCLUSIONS: These results suggest that CAPE is a potent apoptosis-inducing agent. Its action is accompanied by mitochondrial dysfunction and activation of caspase-3/caspase-7.

Gastric carcinoid tumor in a patient with a past history of gastrointestinal stromal tumor of the stomach.

Gastrointestinal stromal tumor is the most common mesenchymal tumor in the gastrointestinal tract. It may coexist with other type of cancers, and if so, the tumors usually involve the stomach. The most common associated cancers are gastrointestinal carcinomas. We report a 65-year-old woman with a history of gastric gastrointestinal stromal tumor who had undergone subtotal segmental gastrectomy. New polypoid lesions were detected on a follow-up gastroscopy one year later. The lesions were biopsied and found to be carcinoid tumors. There was serum hypergastrinemia, and type 1 gastric carcinoid tumor was diagnosed. A total gastrectomy was performed. Pathologic examination revealed both carcinoid tumors and a recurrent gastrointestinal stromal tumor.

Simultaneous Klebsiella pneumoniae and amoebic liver abscess in an immunocompetent patient.

Simultaneous Klebsiella pneumoniae and amoebic liver abscess is rarely reported in immunocompetent patients. A 47-year-old man was hospitalized with abdominal pain, fever, chills, and hypotension. Physical examination revealed right upper quadrant tenderness. Abdominal computed tomography showed an area of low attenuation with some liquefaction in the liver. Echo-guided aspiration revealed 30 mL of pus, which grew Klebsiella pneumoniae, and the same organism was isolated from the blood. Cytology examination of the pus showed scattered amoeba. The patient gradually improved over 1 month on treatment with cefmetazole and metronidazole, along with repeated drainage of the abscess. His amoebic indirect hemagglutination titer was 1:128, but no parasite ova or amoeba were found in the stool. He had no evidence of immunocompromise. Parasitic diseases may be a predisposing factor for bacterial infections, including pyogenic liver abscess. The possible coexistence of amoebae and bacteria in a liver abscess should not be discounted.

Potentiation of the immunotherapeutic effect of autologous dendritic cells by pretreating hepatocellular carcinoma with low-dose radiation.

PURPOSE: To determine whether exposing hepatocellular carcinoma (HCC) to low dose radiation increases the efficacy of dendritic cell-mediated immunotherapy for HCC. METHODS: Tumour specimens collected from 20 recruited patients with HCC were cultured in primary culture (half successfully) and then exposed to low-dose radiation (0.5 Gy). Immature DCs derived from peripheral blood monocytes of patients were pulsed with autologous HCC cell lysates and matured with a cytokine cocktail. Autologous tumour lysate-pulsed DCs (TLP-DCs) were used to stimulate mixed lymphocytes, which were then tested for inhibitory effect on the growth of HCC cells. Surface markers of immunogenicity on primary HCC cells, MHC, and Fas were investigated before and after low-dose irradiation. RESULTS: Exposing HCC cells to low-dose (0.5 Gy) radiation enhanced the immunotherapeutic effect of TLP-DC-stimulated lymphocytes. Growth inhibition increased from 50.6+/-7.5% without irradiation to 74.3+/-4.3% with radiation. The expression of MHC class ll and Fas was upregulated after irradiating HCC cells. CONCLUSION: Exposing tumour cells to a low dose of radiation can enhance the immunotherapeutic effect of the autologous tumor lysate-pulsed DC vaccine.