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: In developed countries, the incidence of Sydenham’s chorea, a major sign of rheumatic fever has declined, but outbreaks are still encountered worldwide.

Objectives: To report the characteristics of a cohort of SC[1] patients in the Jerusalem area.

Methods: We conducted a prospective assessment of rheumatic fever and SC between 1985 and 2002. The diagnosis of rheumatic fever was based on the revised Jones criteria. Other etiologies of chorea were excluded. Recurrence was defined as the development of new signs, lasting more than 24 hours and separated by a minimum of 2 months from the previous episode. Patients were followed for 1 to 14 years following the initial SC episode, and at least one year after recurrence.

Results: Among 180 children with rheumatic fever, 24 had SC. Most of them came from large families of Ashkenazi origin. In 19 patients (79%) the chorea was associated with other rheumatic fever signs, while 5 had pure chorea. Due to the systematic use of two-dimensional color Doppler echocardiography, cardiac involvement was detected in 75% of the patients. Ten patients (42%, 7 females) developed 11 recurrent episodes of chorea 3 months to 10 years after the initial episode. At recurrence, chorea was the sole rheumatic sign in all nine patients who recurred once. None of the patients had persistent chorea.

Conclusions: SC is still prevalent in the pediatric population of Jerusalem, and may recur years later. Recognition of the disease and adequate treatment is necessary.

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: Mid- and lower rectum cancer is a technical challenge to the surgeon aiming to preserve the anal sphincter. The choice between abdominoperineal resection and anterior resection is often related to surgical skills.

Objectives: To evaluate the role of a specialized colorectal unit in preserving the anal sphincter mechanism in the treatment of rectal cancer.

Methods: Between 1991 and 1996, 75 patients with rectal cancer up to 12 cm from the anal verge were operated at the Sheba Medical Center. Among them, 21 patients (group 1) underwent surgery in the colorectal unit and 54 patients (group 2) in the other two surgical departments. All patients had a complete preoperative investigation and were followed for 12–90 months.

Results: Background and tumor parameters were similar for both groups. In group 1, 20 patients (95%) had low anterior resection and 1 patient (5%) had abdominoperineal resection as compared to 20 patients (37%) and 34 patients (63%), respectively, in group 2 (P < 0.005). There was no statistical difference in the systemic recurrence rate. Local recurrence was more frequent in group 2 (P < 0.05).

Conclusions: Special training in colorectal surgery enables the surgeon, in keeping with the principles of oncologic surgery, to preserve the anal sphincter mechanism in most patients with adenocarcinoma located in the mid- and lower third of the rectum.

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: Major efforts are being directed at the early diagnosis of breast cancer. The diagnosis rate of non-palpable tumors is steadily growing as a result of increased screening by mammography. In most patients with non-palpable lesions, percutaneous image-guided biopsies have replaced wire localization with surgical excision for obtaining tissue diagnosis. In recent years the Israel Ministry of Health initiated a mammograpy screening program. Percutaneous image-guided biopsies have also become widely available.

Objective: To assess the impact of these changes on breast cancer surgical treatment in our hospital.

Methods: The charts of 483 patients operated on in our department for primary breast carcinoma during the years 1997 to mid-2001 were reviewed. Data on the mode of diagnosis, tumor stage, resection margins, and number and types of operations were recorded and analyzed. The term non-palpable tumors relates to tumors necessitating wire localization for surgical excision.

Results: The percentage of patients diagnosed with non-palpable tumors rose from 16.2% in 1997 to 47.4% in 2001, with an average size of 2.6 cm for palpable and 1.7 cm for non-palpable tumors. The rate of preoperative diagnosis for non-palpable tumors rose from 6.2% in 1997 to 96.4% in 2001. The rate of involved or very close margins was reduced by 73% in the patient group diagnosed preoperatively as compared to those without a preoperative diagnosis (10.6% vs. 39.4%). Finally, the percentage of patients who had two operations fell from 56.2% in 1997 to 11.1% in 2001.

Conclusions: The mammography screening program in Jerusalem in 1997–2001 was effective in increasing the relative percentage of non-palpable breast cancers with reduced tumor size at diagnosis. The improved availability of preoperative tissue diagnosis in these patients reduced the number of surgical procedures needed.

The 50th anniversary of the Israel Diabetes Association this year is a time less for celebration than for concern. The prevalence of diabetes is rapidly and alarmingly increasing in Westernized and developing countries around the world. Unfortunately, the majority of patients with diabetes do not meet their treatment goals – i.e., glucose, blood pressure or lipid levels. Moreover, our clinical experience and large longitudinal studies have taught us that the mean glucose levels of diabetic patients tend to increase over the years regardless of their treatment modalities. The appropriate answer to these somewhat frustrating data is that the medical community responsible for the integrated health of our diabetic patients – namely, physicians, researchers, nurses and dieticians – must use its combined resources and available therapeutic tools to optimize treatment for these patients. We should also deepen our understanding of the mechanisms underlying the various forms of diabetes and its complications in order to devise more efficient preventive measures for this prevalent devastating chronic disease.

This issue of IMAJ dedicated to diabetes provides some glimpses into these approaches. It contains relevant clinical management debates such as how and when insulin therapy should be instituted and which antihypertensive drugs are more appropriate in the treatment of diabetic nephropathy; a current state-of-the-art review of gestational diabetes as well as how to recognize and manage the diabetic Charcot foot. It exposes the reader to modern prevention strategies against type 1 and type 2 diabetes, to the search for alternative insulin-producing tissue, to advanced understanding of diabetic dermopathy, and more. It also includes selected abstracts of ongoing studies to be presented at the 2004 annual meeting of the Israel Diabetes Association. Most of all, the high quality of the clinical and basic research presented herein strengthens our hope for a better future for our diabetic patients.

Micha Rapoport MD (Guest Editor)

Department of Internal Medicine C and the Diabetes Service, Assaf Harofeh Medical Center, Zerifin, Israel

Editorial Committee

Hilla Knobler MD (Debate Editor)

Eleazar Shafrir PhD

Efrat Wertheimer MD PhD