Israel Medical Association Journal

Background: Metastatic melanoma is an aggressive and highly malignant cancer. The 5 year survival rate of patients with metastatic disease is less than 5% with a median survival of only 6–10 months. Drugs like dacarbazin (DTIC) as a single agent or in combination with other chemotherapy agents have a response rate of 15–30%, but the duration of response is usually short with no impact on survival. Interleukin-2-based immunotherapy has shown more promising results. The National Institutes of Health recently reported that lymphodepleting chemotherapy, followed by an adoptive transfer of large numbers of anti-tumor specific tumor-infiltrating lymphocytes, resulted in an objective regression in 51% of patients.

Objectives: To introduce the TIL[1] technology to advanced metastatic melanoma patients in Israel.

Methods: We generated TIL cultures from tumor tissue, choosing those with specific activity against melanoma and expanding them to large numbers.

Results: TIL cultures from nine patients were established and examined for their specific activity against the patients' autologous tumor cells. Twelve TIL cultures derived from 5 different patients showed the desired anti-tumor activity, making those 5 patients potential candidates for the therapy.

Conclusions: Pre-clinical studies of the TIL technology in a clinical laboratory set-up were performed successfully and this modality is ready for treating metastatic melanoma patients at the Sheba Medical Center's Ella Institute.

Objectives: To evaluate the outcome of this procedure and to compare the complication rate following circumcisions performed by ritual circumcisers and by physicians.

Methods: In 2001, of the 19,478 males born in four major medical centers in Israel 66 had circumcision-related complications. All the children were circumcised in non‑medical settings within the community. The patients were medically evaluated either urgently due to immediate complications or electively in outpatient clinics later on. Upon the initial assessment a detailed questionnaire was filled to obtain data regarding the procedure, the performer and the subsequent complications.

Results: All the circumcisions were performed during the early neonatal life, usually on day 8 of life (according to Jewish law). In 55 cases (83%) it was part of a ritual ceremony conducted by a ritual circumciser (Mohel), while in 11 babies (17%) physicians were involved. Acute bleeding after circumcision was encountered in 16 cases (24%), which required suturing in 8. In addition, we found two cases of wound infection and one case of partial amputation of glans penis in which the circumcision was performed by a ritual circumciser. Among the late complications, the most common was excess of skin in 38 cases (57%); 5 children (7.5%) had penile torsion and 4 children (6%) had shortages of skin, phimosis and inclusion cyst. The overall estimated complication rate of circumcision was 0.34%.

Conclusions: Complications of circumcision are rare in Israel and in most cases are mild and correctable. There appears to be no significant difference in the type of complications between medical and ritual circumcisions.

Objective: To investigate hemodynamic variables, including small and large artery compliance, in cirrhotic patients during total paracentesis.

Methods: The study included 15 cirrhotic patients admitted for an episode of tense diuretic-resistant ascites. Hemodynamic variables including vascular compliance were measured using an HDI pulse wave cardiovascular profiling instrument CR-2000. The variables were measured in these patients before, immediately after and 24 hours following large volume (mean 5.6 L) paracentesis.

Results: Cardiac output increased immediately after paracentesis due to increment in stroke volume, with no change in heart rate. However, 24 hours later the cardiac output decreased to below the basal level. The fluctuation was statistically significant (P < 0.05). There was no change in large artery compliance, but small artery compliance increased after paracentesis (P < 0.05) and partially returned to the basal level after 24 hours. Systemic vascular resistance measurement showed the same pattern of change: vasodilatation occurred during paracentesis and was attenuated 24 hours later.

Conclusions: Large volume paracentesis with albumin replacement caused an accentuation of the vasodilatation (small but not large artery) already present in these patients. This may be the first sign of enhanced vasodilatation due to large volume paracentesis before the clinical expression of impaired hemodynamics and deterioration of renal function.

Background: Bladder exstrophy is a severe congenital defect that requires a multidisciplinary treatment approach. Soft tissue repair may be successful during the first few days after birth but a combination of pelvic osteotomies and bladder reconstruction is necessary later in life. The combination of externally fixed anterior and posterior osteotomies has biomechanical advantages over previous techniques for achieving primary bladder closure.

Objectives: To describe our experience with a combined vertical and horizontal pelvic osteotomy approach for the repair of bladder exstrophy.

Methods: Four children underwent bladder exstrophy closure; the mean age at surgery was 19 months (range 9–33 months)... We stabilized the osteotomies with a small Synthes AO external fixator, 4.0 mm rod diameter.

Results: All four patients had successful bladder repair with no dehiscence; two of them achieved partial continence, and bladder neck reconstruction is planned for the other two. Three of the four patients sustained neurologic injury; two completely recovered, and the third continues to suffer from right drop foot. The average follow-up was 39 months (range 10–60 months).

Conclusions: Vertical and horizontal pelvic osteotomies stabilized by external fixator and bladder repair is an effective treatment for bladder exstrophy.

Background: An estimated 10% of all children are subject to recurrent attacks of abdominal pain of unknown origin. When no organic cause is found, the working diagnosis is usually functional abdominal pain.

Objectives: To investigate the possible causative role of occult constipation.

Methods: We defined occult constipation as the absence of complaints of constipation on initial medical history or of symptoms to indicate the presence of constipation. The diagnosis was made by rectal examination and/or plain abdominal X-ray.

Results: Occult constipation was found to be the cause of RAP[1] in 42.6% of children examined. Treatment consisted of paraffin oil and phosphate enema. In 82.84% of cases the abdominal pain subsided considerably or disappeared within 2 weeks to 3 months of treatment. On telephone interview of the parents at 1–1.5 years after discharge, 96.5% reported that both the abdominal pain and constipation had subsided or disappeared.

Conclusions: Occult constipation can be easily identified and treated in a large number of children with RAP who were diagnosed as having functional abdominal pain.

Background: The role of prostatic fossa radiation as salvage therapy in the setting of a rising prostate-specific antigen following radical prostatectomy is not well defined.

Objectives: To study the efficacy and safety of pelvic and prostatic fossa radiation therapy following radical prostatectomy for adenocarcinoma.

Methods: A retrospective review of 1,050 patient charts treated at the Sheba Medical Center for prostate cancer between 1990 and 2002 identified 48 patients who received post-prostatectomy pelvic and prostatic fossa radiotherapy for biochemical failure. Two patients were classified as T-1, T2A-9, T2B-19, T3A-7 and T3B-11. Gleason score was 2–4 in 9 patients, 5–6 in 22 patients, 7 in 10 patients and 8–10 in 7 patients. Positive surgical margins were noted in 28 patients (58%) of whom 18 had single and 10 had multiple positive margins. Radiation was delivered with 6 mV photons using a four-field box to the pelvis followed by two lateral arcs to the prostatic fossa.

Results: At a median follow-up of 34.3 months (25th, 75th) (14.7, 51,3) since radiation therapy, 32 patients (66%) are free of disease or biochemical failure. Exploratory analysis revealed that a pre-radiation PSA[1] less than 2 ng/ml was associated with a failure rate of 24% compared with 66% in patients with a pre-radiation PSA greater than 2 ng/ml (chi-square P < 0.006).

Conclusions: For patients with biochemical failure following radical prostatectomy early salvage radiation therapy is an effective and safe treatment option.

Background: Laryngeal obstruction due to bilateral vocal cord immobility in adduction may cause dyspnea, hoarseness and dysphagia and can lead to dependence on a tracheostomy. Treatment poses a challenge because of the opposing functions of the larynx and the risk of neck and laryngeal tissue damage.

Objectives: To describe our experience with endoscopic CO₂-laser-assisted posterior ventriculocordectomy without tracheostomy for the treatment of bilateral vocal cord immobility in adduction.

Method: The study group consisted of five male and five female patients aged 17–81 years. The procedure was performed with an endoscope and operating microscope connected to a CO₂ laser. A C-shaped incision was made, and the posterior third of one vocal cord, the vocal process of the arytenoid, and the posterior third of the false vocal cord were excised. Tracheostomy was not performed.

Results: The technique allowed for a convenient approach to the difficult-to-view areas of the larynx. The procedure was short and bloodless, with minimal damage to laryngeal tissue and no local edema. Hospitalization time was short. Postoperatively, patients had sufficient breathing and mostly fair to good voice quality. None of the patients had severe aspirations and only three patients had mild aspirations.

Conclusions: We recommend this procedure for patients with bilateral vocal cord immobility prior to tracheostomy. Delaying surgery beyond the time of possible re-innervation may place the patient at risk of decompensation, which requires tracheostomy.

Background: Hyperhomocysteinemia is a well-recognized risk factor for accelerated atherosclerosis in hemodialysis patients.

Objectives: To examine the effects of two doses of vitamins B6 and B12 and folic acid on homocysteine levels in hemodialysis patients and assess the functional impact of the methylenetetrahydrofolate reductase genotype on the response to treatment.

Methods: In a randomized prospective study, we assessed the effects of folic acid and two doses of B-vitamins in 50 hemodialysis patients with hyperhomocysteinemia. Patients were divided into two groups: 26 patients (group A) who received 25 mg of vitamin B₆ daily and one monthly injection of 200 µg vitamin B12, and 24 patients (group B) who received 100 mg of vitamin B6 daily and one monthly injection of 1,000 µg vitamin B12. In addition, both groups received 15 mg folic acid daily. Patients were evaluated for homocysteine levels as well as for coagulation and a thorough lipid profile. Baseline Hcy[1] levels were determined after at least 4 weeks washout from all folic acid and B-vitamins that were given. MFTHR[2] alleles were analyzed, as were activated protein C resistance, von Willebrand factor and lupus anticoagulant.

Results: Basal plasma Hcy levels were significantly elevated in hemodialysis patients compared with normal subjects (33.8 ± 4.3 vs. 4.5 to 14.0 mmol/L). Following treatment, Hcy levels were significantly reduced to 21.2 ± 1.6 in group A and 18.6 ± 1.4 mmol/L in group B (P < 0.01). There was no difference in Hcy reduction following the administration of either high or low dosage of vitamins B6 and B12 utilized in the present study. There was no correlation between Hcy levels or thrombophilia and high incidence of thrombotic episodes in hemodialysis patients. Genotypic evaluation of MTHFR revealed that the presence of homozygous thermolabile MTHFR (n = 5) was associated with higher Hcy levels and better response to treatment (Hcy levels decreased by 58%, from 46.2 ± 14.6 to 19.48 ± 4.1 mmol/L following treatment). In patients with heterozygous thermolabile MTHFR (n = 25), Hcy levels decreased by 34%, from 31.2 ± 3.7 to 18.1 ± 1.1 mmol/L following treatment. The efficacy of high and low doses of B-vitamins on the reduction of homocysteine levels was comparable.

Conclusions: Treatment with B-vitamins in combination with folic acid significantly decreased homocysteine levels in hemodialysis patients, independently of the tested doses. In addition, mutations in MTHFR were associated with elevated plasma levels of Hcy. Neither vascular access nor.