Israel Medical Association Journal

Melanoma is the leading cause of death from skin tumors worldwide, with an annual increase in incidence over the past decade. The molecular mechanisms involved in melanoma pathogenesis are beginning to be unraveled. While a family history of melanoma and exposure to ultraviolet irradiation have been known for years as risk factors in melanoma development, the precise genes involved in inherited predisposition were defined only in the past decade. Germline mutations in two genes that play a pivotal role in controlling cell cycle and division – CDKN2A and cyclin-dependent kinase 4 (CDK4) – have been detected in autosomal, dominant, high penetrance familial melanoma cases. In addition to these two highly penetrant genes, germline mutations and polymorphisms in a few low penetrance genes have been reported in familial melanoma cases: melanocortin-1 receptor, epidermal growth factor, glutathione s-transferase M1, cytochrome p450 debrisoquine hydroxylase locus (CYP2D6) and vitamin D receptor.

The world now faces the dreadful possibility of biological weapons attacks by terrorists. Healthcare systems would have to cope with such emergencies should all preemptive measures fail. Information gained from the Global Mercury exercise and the SARS outbreak has shown that containing an outbreak at the start is more effective than reacting to it once it has spread and that containment should be treated both nationally and internationally. On the national level this entails developing rapid and effective methods to detect and identify infected cases, and implementing isolation and control measures to lower the risk of further transmission of the disease while assuring the safety of medical teams and laboratory workers. Strategic contingency plans should incorporate well-defined procedures for hospitalization and isolation of patients, providing regional backup of medical personnel and equipment and maintaining close cooperation between the various bodies in the healthcare system. Quarantine is an effective containment measure, especially if voluntarily imposed. Modern communication systems can help by sending professional teams timely instructions and providing the public with information to reduce panic and stress during quarantine procedures. Informing the public poses a dilemma: finding a balance between giving advance warning of an imminent epidemic outbreak and ascertaining the likelihood of its occurrence. Containment of international bioterrorist attacks depends entirely on close international cooperation to implement national and international strategic contingency plans with free exchange of information and recognition of procedures.

Background: Advances in surgical techniques and retractor-stabilizer devices allowing access to all coronary segments have resulted in increased interest in off-pump coronary artery bypass. The residual motion in the anastomotic site and potential hemodynamic derangements, however, render this operation technically more demanding.

Objectives: To evaluate the OPCAB[1] experience in a single Israeli center.

Methods: Between 2000 and 2003 in our institution, 1,000 patients underwent off-pump operations. Patients were grouped by the type of procedure, i.e., minimally invasive direct coronary artery bypass or mid-sternotomy OPCAB.

Results: One hundred MIDCAB[2] operations were performed. Of the 900 OPCAB, 767 patients received multiple grafts with an average of 2.6 ± 0.6 grafts per patient (range 2–4) and the remaining patients underwent single grafting during hybrid or emergency procedures. In the multiple-graft OPCAB group, complete revascularization was achieved in 96%. Multiple arterial conduits were used in 76% of the patients, and total arterial revascularization without aortic manipulation, using T-graft (35%) or in situ configurations, was performed in 61%. The respective rates for early mortality, myocardial infarction and stroke in the MIDCAB were 1%, 0% and 2%, and 2%, 1.3% and 0.9% in the multiple-vessel OPCAB groups. Multivariate analysis identified renal dysfunction (odds ratio 11.5, confidence interval 3.02–43.8; P < 0.0001) and emergency operation (OR[3] 8.74, CL[4] 1.99–38.3; P = 0.004) as predictors of mortality. The proportion of off-pump procedures increased from 9% prior to the study period to 59%.

Conclusions: The use of OPCAB does not compromise the ability to achieve complete myocardial revascularization. Our procedure of choice is OPCAB using arterial conduits, preferably the 'no-touch' aorta technique.

Background: The prognosis of patients with fulminant hepatic failure without timely liver transplantation is dismal. Given the limited availability of cadaveric organs for urgent transplantation in Israel, adult-to-adult living-donor segmental liver transplantation may be the only alternative.

Objectives: To report our initial experience with urgent lifesaving LDLT[1] in this unique scenario.

Methods: Three adult patients with FHF[2] (two of unknown etiology, one with paracetamol intoxication) were transferred from other institutions and admitted to our intensive care unit. Initial treatment and monitoring included intracranial pressure monitoring and hepatic dialysis using the Molecular Adsorbent Recirculating System. Expeditious potential donor selection included medical, psychosocial and surgical evaluation. Liver volume and vascular anatomic compatibility were assessed with computed tomography angiography.

Results: Between July and October 2003 we performed three procedures of urgent adult-to-adult LDLT. The donors (two uncles, one sister) underwent hepatic resection (two right lobes, one left lateral segment) and recovered well. The recipients underwent total hepatectomy with caval preservation, followed by lobar grafting. All recipients recovered and are alive with good liver function and without any neurologic complications.

Conclusions: Urgent adult-to-adult living-donor segmental liver transplantation can be performed safely and timely as a lifesaving procedure in the setting of comatose patients with FHF.

Background: Cystoscopy, the principal means of diagnosis and surveillance of bladder tumors, is invasive and associated with unpleasant side effects

Objectives: To determine the early complications of rigid cystoscopy and the impact on patients' quality of life and sexual performance.

Methods: One hundred consecutive patients undergoing diagnostic rigid cystoscopy filled in questionnaires including anxiety and pain levels (0–5 visual analogue scale), adverse events, short-form health survey, International Prostate Symptom Score, and functional sexual performance. Questionnaires were administered before, immediately after, and 1, 2 days, 2 and 4 weeks following cystoscopy.

Results: The pre-cystoscopy anxiety level was 2.01. The average pain during the examination was 1.41. SF-36[1] score was not affected by cystoscopy. The subjective impact on patients' quality of life was 0.51. The mean IPSS[2] increased following cystoscopy (6.75 vs. 5.43, P = 0.001) and returned to baseline 2 weeks later. A decline in libido was reported by 55.6% (25/45) and 50% (3/6) of the sexually active men and women, respectively. Cystoscopy was associated with a decreased Erectile Dysfunction Intensity Score, from 15.6 to 9.26 during the first 2 weeks (P = 0.04). The overall complication rate was 15% and included urethrorrhagia and dysuria. None of the patients had fever or urinary retention and none was hospitalized. The complication rate was higher in patients with benign prostatic hyperplasia (24% vs. 9.7%, P = 0.001).

Conclusions: Rigid cystoscopy is well tolerated by most patients and has only a minor impact on quality of life. However, cystoscopy transiently impairs sexual performance and libido. The early complications are mild and correlate with a diagnosis of BPH[3].

Background: The ¹³C-urea breath test is the best non-invasive test to validate Helicobacter pylori eradication. Serology is unreliable for this purpose due to the slow and unpredictable decline in the antibodies titer.

Objectives: To characterize a specific group of patients who were treated for H. pylori and tested for successful eradication by ¹³C-UBT[1] in our central laboratory and to correlate the eradication success rate with specific drug combinations, and to evaluate other factors that may influence eradication success.

Methods: ¹³C-UBT for H. pylori was performed in the central laboratory of Clalit Health Services. The breath test was performed by dedicated nurses in 25 regional laboratories and the samples were analyzed by a mass spectrometer (Analytical Precision 2003, UK). The physician who ordered the test completed a questionnaire computing demographic data (age, gender, origin), indication, use of non-steroidal anti-inflammatory drugs or proton pump inhibitor, and combination of eradication therapy.

Results: Of the 1,986 patients tested to validate successful H. pylori eradication, 539 (27%) had a positive test (treatment failure group) and 1,447 (73%) had a negative test (successful treatment group). Male gender, older age and European-American origin predicted better eradication rates. Dyspeptic symptoms and chronic PPI[2] therapy predicted treatment failure. Combination therapy that included clarithromycin had a higher eradication rate than a combination containing metronidazole. The combination of omeprazole, amoxicillin and clarithromycin achieved an eradication rate of 81.3%, which was better than the combination of omeprazole, metronidazole and clarithromycin (77.2%) (not significant), or of omeprazole, amoxicillin and metronidazole (66.1%) (P < 0.01).

Conclusion: Gender, age, origin, dyspepsia and PPI therapy may predict H. pylori eradication results. Our findings also support an increase in metronidazole resistance of H. pylori strains in Israel, as described in other countries. We recommend combination therapy with omeprazole, amoxicillin and clarithromycin and avoidance of metronidazole as one of the first-line eradication drugs.

Background: Despite advances in cancer therapy the treatment of liver tumors remains a challenge. Most patients are poor candidates for surgical resection; both chemotherapy and irradiation have a low success rate and neither is without complications. New minimally invasive techniques for ablation of unresectable tumors have gained attention as effective treatment alternatives. Among these are percutaneous ethanol injection and radiofrequency ablation; both are effective for primary liver tumors and RFA is also effective for hepatic metastases.

Objective: To report our experience with PEI and RFA in the treatment of hepatic lesions.

Methods: The study included 49 lesions in 27 patients: 23 primary lesions in 13 patients treated with PEI and 26 lesions (22 secondary and 4 primary) in 14 patients treated with RFA. PEI was performed on an outpatient basis in the ultrasound suite; RFA was done in hospitalized patients (9 in the ultrasound suite and 4 in the operating room). Patients were followed with triphasic spiral computerized tomography 1 month after treatment and every 3±6 months thereafter.

Results: Complete necrosis was achieved with PEI on the first attempt in 11 of 23 primary lesions (91.3%). In 8.7% (2/23) a second series of treatments was required. Using RFA, complete necrosis was achieved in 85% of lesions (22/26) and partial necrosis in 15% (4/26). Complications included low fever (3 patients), high fever and abscess formation (1 patient), peri-tumoral necrosis (1 patient ) and portal vein thrombosis (1 patient ).

Conclusions: Our preliminary results confirm that PEI and RFA are an effective and safe option for treating hepatic tumors in patients unfit for surgery.
 

The threat of a disease outbreak resulting from biologic warfare has been of concern for the Israeli health system for many years. In order to be prepared for such an event the health system has formulated doctrines for various biologic agents and defined the logistic elements for the procurement of drugs. During the last 4 years, and especially after the West Nile fever epidemic in 2000, efforts to prepare the healthcare system and the relevant organizations were accelerated. The Director-General of the Ministry of Health nominated a Supreme Steering Committee to fill in the gaps and upgrade the preparedness of the health system for an unusual disease outbreak. This committee and its seven subcommittees established appropriate guidelines, communication routes among different organizations, and training programs for medical personnel. The anthrax outbreak in the United States found the healthcare system in the hub of the preparation process, and all modes of action were intensified. Further work by hospitals, primary care clinics and all other institutes should be initiated to maintain a state of proper preparedness.