Israel Medical Association Journal

Background: Antimicrobial resistance is the main determinant for Helicobacter pylori treatment failure. Regional antimicrobial susceptibility testing is essential for appropriate antibiotic selection to achieve high eradication rates.

Objectives: To assess primary and secondary H. pylori resistance in isolates recovered from Israeli naïve and treatment failures. To identify predictors of resistance.

Methods: In this retrospective study, in vitro activity of isolated H. pylori in Israel was tested against metronidazole, clarithromycin, tetracycline, amoxicillin, and levofloxacin in 128 isolates: 106 from treatment failures and 22 from naïve untreated patients. The minimal inhibitory concentration values were determined according to the Etest instructions. Treatment failures previously failed at least one treatment regimen.

Results: No resistance to amoxicillin and tetracycline was detected. Resistance to metronidazole and clarithromycin was high in H. pylori isolates both from treated and untreated patients: 68.9%, 68.2% for metronidazole (P = 0.95); 53.8%, 59.1% for clarithromycin (P = 0.64), respectively. Dual resistance to clarithromycin and metronidazole was seen in 45.3% and 50%, respectively (P = 0.68). Resistance to levofloxacin was detected in two (1.9%) isolates from treated patients. Simultaneous resistance to clarithromycin, metronidazole, and levofloxacin was seen in an isolate from a treated patient. Age was the only predictor of resistance to metronidazole and clarithromycin.

Conclusion: The resistance rates to both single and dual metronidazole and clarithromycin in isolates recovered from both Israeli naïve and treated patients is high. Low resistance renders levofloxacin an attractive option for second or third line treatment. Therapeutic outcome would benefit from susceptibility testing after treatment failure.

Background: Surgery is considered the mainstay of treatment for esophageal carcinoma. Transhiatal esophagectomy with cervical esophagogastric anastomosis is considered relatively safe with an oncological outcome comparable to that using the transthoracic approach.

Objectives: To review the results of the first 100 transhiatal esophagectomies performed in a single Israeli center.

Methods: The records of all patients who had undergone transhiatal esophagectomy during the period 2003–2009 were reviewed. The study group comprised the first 100 patients. All patients who had undergone colon or small bowel transposition were excluded. Indications for surgery included esophageal cancer, caustic injury and achalasia.

Results: The median follow-up period was 19.5 months. The anastomotic leakage rate was 15% and all were managed successfully with local wound care. The benign stricture rate was 10% and all were managed successfully with endoscopic balloon dilation. Anastomotic leakage was found to be a risk factor for stricture formation. Overall survival was 54%. Response to neoadjuvant therapy was associated with a favorable prognosis.

Conclusions: Transhiatal esophagectomy is a relatively safe approach with adequate oncological results, as long as it is performed in a high volume center.
 

Background: Vitamin A and its derivative retinoic acid regulate various aspects of cell behavior as growth, differentiation, and proliferation. Retinoic acid derivatives have been suggested to play a role in processes such as hepatic regeneration and fibrosis.

Objectives: To evaluate the influence of vitamin A on rat liver epithelial cell proliferation.

Methods: We performed common bile duct ligation in rats that had been subjected to differing vitamin A diets and compared their livers to control rats. Proliferation, apoptosis, and retinoic acid receptors were evaluated by histology and immunohistochemistry in bile duct cells and hepatocytes.

Results: Vitamin A deficiency was found to be associated with enhanced proliferation of bile duct epithelial cells following CBD[1] ligation. The proliferation was manifested by increased numbers of ducts, by aberrant extended ductal morphology, and by elevated numbers of nuclei expressing the proliferation marker Ki67. The amount of vitamin A in the rat diet did not affect detectably ductal cell apoptosis. We observed up-regulated expression of the retinoid X receptor-alpha in the biliary epithelium of vitamin A-deficient rats that had undergone CBD ligation, but not in vitamin A-sufficient rats.

Conclusions: We speculate that the mechanism underlying the ductal proliferation response involves differential expression of RXR[2]-alpha. Our observations suggest that deficiency of vitamin A may exacerbate cholestasis, due to excessive intrahepatic bile duct proliferation.

Background: The role of endoscopic ultrasound in evaluating the response of esophageal cancer to neoadjuvant chemotherapy is controversial.

Objectives: To evaluate the accuracy of EUS[1] in restaging patients who underwent NAC[2].

Methods: The disease stage of patients with esophageal cancer was established by means of the TNM classification system. The initial staging was determined by chest and abdominal computed tomography and EUS. Patients who needed NAC underwent a preoperative regimen consisting of cisplatin and fluouracil. Upon completion of the chemotherapy, patients were restaged and then underwent esophagectomy. The results of the EUS staging were compared with the results of the surgical pathology staging. This comparison was done in two groups of patients: the study group (all patients who received NAC) and the control group (all patients who underwent primary esophagectomy without NAC).

Results: NAC was conducted in 20 patients with initial stage IIB and III carcinoma of the esophagus (study group). Post-chemotherapy EUS accurately predicted the surgical pathology stage in 6 patients (30%). Pathological down-staging was noted in 8 patients (40%). However, the EUS was able to observe it in only 2 patients (25%). The accuracy of EUS in determining the T status alone was 80%. The accuracy for N status alone was 35%. In 65% of examinations the EUS either overestimated (35%) or underestimated (30%) the N status. Thirteen patients with initial stage I-IIA underwent primary esophagectomy after the initial staging (control group). EUS accurately predicted the surgical pathology disease stage in 11 patients (85%).

Conclusions: EUS is an accurate modality for initial staging of esophageal carcinoma. However, it is not a reliable tool for restaging esophageal cancer after NAC and it cannot predict response to chemotherapy.

Background: Current treatment for the eradication of Helicobacter pylori in patients with peptic disease is based on the combination of antibiotic and anti-acid regimens. Multiple combinations have been investigated, however no consensus has been reached regarding the optimal duration and medica­tions.

Objectives: To assess the efficacy of two treatment regimens in patients with peptic ulcer disease and non-ulcer dyspepsia, and to determine the need for gastric mucosal culture in patients failing previous treatment.

Methods: Ninety patients with established peptic ulcer and NUD (with previously proven ulcer) were randomly assigned to receive either bismuth-subcitrate, amoxycillin and metrnida­zole (8AM) or lansoprasole, clarithromycine and metronida­zole (LCM) for 7 days. Patients with active peptic disease were treated with ranitidine 300 mg/day for an additional month.

Results: Eradication failed in 8 of the 42 patients in the 8AM group and in 2 of the 43 patients in the LCM group, as determined by the ¹³C urea breath test or rapid urease test (19% vs. 5%, respectively, P=0.05). Five of these 10 patients were randomly assigned to treatment with lansoprazole, amoxycillin and clarithromycin (LAC) regardless of the culture obtained, and the other 5 patients were assigned to treatment with lansoprazole and two antibacterial agents chosen according to a susceptibility test. Eradication of H. pylon was confirmed by the ‘³C urea breath test. The same protocol (LAC) was used in all patients in the first group and in four of the five patients in the second group. The culture results did not influence the treatment protocol employed.

Conclusions: Combination therapy based on proton pump inhibitor and two antibiotics is superior to bismuth-based therapy for one week. Gastric-mucosal culture testing for sensitivity of H. pylon to antibiotics is probably unnecessary before the initiation of therapy for patients with eradication failure.

Background: Differentiating between benign and malignant submucosal tumors is difficult. Moreover, the natural course of benign-appearing SMTs is not clearly elucidated.

Objectives: To evaluate the natural course of upper gastrointestinal SMTs by endoscopic endosonography.

Methods: We followed 25 consecutive patients with small (<40 mm) SMTs for a mean period of 19 months. Evaluation included maximal tumor diameter, internal echo pattern, and outer margin of lesions.

Results: Follow-up revealed no change in echo features in 24 of 25 patients (96%). In only one patient a homogenous hypoechoic smooth margin lesion converted to a non-homogenous tumor with an irregular outer margin. This lesion also increased in size from 30 to 38 mm. On surgical removal this tumor was found to be a stromal tumor with high malignant potential.

Conclusions: Most small SMTs do not change during a period of 19 months and a conservative policy of surveillance is warranted.

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SMTs= submucosal tumors