Israel Medical Association Journal

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: Hyperthermia combined with radiation therapy was shown to be more effective in local recurrent breast cancer than radiotherapy alone, but it use is limited due to technical difficulties, stringent reimbursement policies and because it is time consuming.

Objectives: To report our experience with a simple and convenient XRT+HT[1] delivery system.

Methods: XRT was delivered through either electron or photon beams (total dose 30–40 Gy in previously irradiated fields or 50–70 Gy in non-irradiated fields). Hyperthermia was delivered by a dedicated HT device operating at 915 MHz. The heating session lasted 45 minutes. The maximal tumor surface temperature was set at 45°C and modified according to patient comfort. No intratumoral (invasive) thermometry was used. At least two HT sessions were scheduled to each HT field during the entire XRT treatment period. Tumor response was evaluated every 3 months after completion of treatment. The overall survival was measured from XRT+HT initiation until the last follow‑up.

Results: Fifteen women underwent 114 HT treatments delivered through 28 HT fields. Twenty-four HT fields (15 patients) were previously irradiated. There was complete infield response in 10 fields (6 patients), partial response in 8 fields (4 patients), no response or progressive disease in 4 fields (3 patients), and no parameters in 6 fields (5 patients). Eighteen (64%) fields had complete or partial response. Seven patients had outfield recurrence despite wide XRT+HT fields. Ulceration was the only major side effect (three patients, three fields).

Conclusions: The combined HT+XRT delivery system, with no invasive thermometry, is a simple and effective method for treating local recurrent breast cancer.

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: 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.

Background: Arterial involvement in Behçet's syndrome is rare. Aneurysms are common among the arterial lesions, affecting various arteries but mostly the abdominal aorta. Surgical interposition graft insertion is the treatment of choice for large aneurysms. However, vasculitis in these patients is the reason for the notorious surgical complications that result in up to 50% false aneurysms in anastomotic sites. Recently, endovascular repair for abdominal aortic aneurysms has been established.

Objectives: To learn more about vascular Behçet and, specifically, to compare the results of surgical treatment and endovascular repair of AAA[1] in patients with Behçet's syndrome.

Methods: We retrieved the medical records of all 53 patients with Behçet disease admitted to Rambam Medical Center during the years 1985 and 2001 and analysed the results and follow-up of open surgery versus endovascular repair of AAA in patients with known Behçet's syndrome.

Results: Of the 53 patients with Behçet's disease 18 had vascular manifestations (34%). AAAs were encountered in 8 patients (15%) and 5 were treated. Open surgery (group 1), under general anesthesia, lasted less than 3 hours with an average aortic clamping time of 34 minutes (range 26–41 min) after which the patients were transferred to the intensive care unit for 24–48 hours. Endovascular treatment (group 2), although lasting about the same time without the need for intensive care, necessitated contrast media and fluoroscopy. The length of hospital stay was considerably shorter for patients after endovascular repair compared to open surgery (3 days vs. 6 days). Combined mortality and morbidity was higher in patients who underwent open surgery compared to endovascular repair (one death, one major amputation and three anastomotic pseudoaneurysms compared to one temporary contrast-induced nephropathy).

Conclusions: Vasculo-Behçet patients with AAA are better candidates for endovascular treatment than atherosclerotic patients. Combined morbidity (especially anastomotic pseudoaneurysms) and mortality of Behçet patients after endovascular repair is considerably lower than after open surgery.

Background: Unexplained pulmonary hypertension is assumed to occur mainly in young adults.

Objectives: To describe the features of the disease in older patients and compare them to those in PHT[1] patients of all ages.

Methods: We conducted a retrospective evaluation of the files of patients over 65 years of age in whom UPHT[2] was diagnosed between 1987 and 1999 at two PHT centers serving a population of 4 million. Patients were followed for survival until March 2003. Clinical variables of the study patients were compared to those in PHT patients of all ages.

Results: The study group included 14 patients, 10 females and four males, with a mean age of 70.5 ± 6.7 years. The calculated mean annual incidence of UPHT for the study population was one new case per year per million persons. Seven patients (50%) had systemic hypertension. The mean interval from onset of symptoms to diagnosis was 8.3 months. At diagnosis, 64% of patients had functional capacity of III-IV according to the New York Heart Association classification, and 43% had right heart failure. Mean systolic pulmonary artery pressure was 80 ± 21 mmHg, peripheral vascular resistance 11.7 ± 7 mmHg/L/min, cardiac index 2.16 ± 0.81, and mean right atrial pressure 10.5 ± 5.9 mmHg. Median survival time was 43 months; survival rates for 1 year, 3 years and 5 years were 92.6%, 50%, 40%, respectively. Compared to data from the U.S. National Institute of Health Registry, UPHT in older patients is more common in females, but the incidence as well as clinical, hemodynamic and survival parameters are similar to those in PHT patients at any age.

Conclusions: UPHT occurs in the elderly more frequently than previously thought, with similar features in PHT patients of all ages. The coexistence of systemic and pulmonary hypertension warrants further investigation.

Background: Pyoderma gangrenosum is an uncommon ulcerative cutaneous condition associated with inflammatory bowel disease. PG[1] occurs rarely in IBD[2] patients and there are insufficient data on the clinical manifestations of this disease with IBD.

Objective: To determine the incidence, clinical manifestations and treatment of PG in patients with IBD and the connection to IBD, its activity and extent.

Methods: All patients hospitalized with IBD at a university hospital during a 20 year period were evaluated for the occurrence of PG.

Results: Of 986 patients hospitalized for IBD 6 suffered from PG (0.6% incidence). Their average age was 37 with equal sex distribution and equal distribution of Crohn’s disease and ulcerative colitis. PG appeared 6.5 years on average after diagnosis of IBD in all patients. The development of PG correlated with significant clinical exacerbation of IBD, the majority having active colitis at the onset of the PG. Extra-intestinal manifestations of IBD occurred in half the patients (sacroiliitis, peripheral arthritis and erythema nodosum). Pathergy was not elicited in any patients. Four patients had multiple skin lesions, frequently on the lower extremities. Diagnosis was made by skin biopsy in four patients. There was little correlation between amelioration of IBD and the skin lesions. Treatment consisted of high dose steroids and immunomodulatory drugs (cyclosporine, azathioprine and dapsone) in conjunction with topical treatment.

Conclusions: PG is a rare extra-intestinal manifestation of IBD that coincides with the exacerbation of the intestinal disease but does not always respond to treatment of the bowel disease.

Background: Screening for celiac disease is based on the sequential evaluation of serologic tests and intestinal biopsy; an optimal screening protocol is still under investigation. The screening policy of one of the main healthcare providers in Israel (Maccabi) consists of measuring total immunoglobulin A and tissue transglutaminase IgA[1] antibodies and confirming positive results by endomysial antibodies. For IgA-deficient patients antigliadin IgG is measured.

Objectives: To evaluate the use of tTGA[2] as a first-level screening test in patients suspected of having celiac disease

Methods: The results of tTGA and EMA[3] tests over a 3 month period were obtained from the laboratory computer. Letters were sent to the referring physicians of patients with positive tests, requesting clinical information and small intestinal biopsy results. tTGA was performed using an anti-guinea pig tTG-IgA enzyme-linked immunosorbent assay kit.

Results: Overall, 2,505 tTGA tests were performed: 216 (8.6%) were tTGA-positive of which 162 (75%) were EMA-negative (group 1) and 54 (25%) EMA-positive (group 2). Clinical information was obtained for 91 patients in group 1 and 32 in group 2. Small intestinal biopsy was performed in 33 (36%) and 27 patients (84%) in groups 1 and 2, respectively. Celiac disease was diagnosed in 4 biopsies (12%) in group 1 and 23 (85%) in group 2 (P < 0.0001). The positive predictive value was 45% for tTGA and 85% for EMA.

Conclusions: Symptomatic patients with positive tTGA and negative EMA have a low rate of celiac disease compared to those who are tTGA-positive and EMA-positive. Confirmation with EMA is advised when tTGA is performed as a first-level screening for suspected celiac disease.

Background: The Israeli Blood Pressure Control program was initiated to enhance the control of modifiable risk factors among high risk hypertensive patients followed by general practitioners in Israel.

Objective: To report the baseline results of the state of the treatment regarding blood pressure management, lipid and glucose control as well as obesity and smoking cessation among the patients.

Methods: Hypertensive patients were screened in 30 general practice clinics supervised by family medicine specialists seeing 1,000–5,000 patients each. Between 50 and 250 hypertensive patients were diagnosed at each participating clinic. Blood pressure levels, body mass index, lipid and glucose levels, as well as target organ damage and medications were recorded for all patients.

Results: Of the 4,948 patients registered, 2,079 were males (42%). Mean age was 64.8 ± 12. Blood pressure control was achieved in only 33.1% of total hypertensive patients. Low density lipoprotein control was achieved in 31.1% of all patients, and glucose control in only 28.5%% of diabetic patients (glucose < 126 mg/dl); 20.7% of the diabetics had glucose levels above 200 mg/dl. In this group of patients 38.9% were obese (BMI[1] >30 kg/m²). While there were more obese females than males (48.0% vs. 35.6%), no difference was found in blood pressure, lipid or glucose control between the genders.

Conclusion: Risk factor management of hypertensive patients attending general practice clinics in Israel is not optimal, especially among those with diabetes or in need of secondary prevention measures. A long-term intervention program for high risk patients in the community is needed to improve the current situation.