Israel Medical Association Journal

Background: Multiple primary malignancies are increasingly being detected among cancer patients. Objectives: To investigate the co-occurrence of primary bladder cancer and primary lung cancer, two established smoking-related neoplasms characteristically associated with increased risk of secondary cancers.

Methods: A retrospective search of the patient registry in our institution identified 25 patients (23 men and two women) who were diagnosed with both bladder cancer and lung cancer during the period 1990–2005. Medical records were reviewed and clinical and pathological data were extracted.

Results: In 21 patients (84%) bladder cancer was the first primary tumor and in 4 (16%) the second primary tumor. More than 90% of the patients had a history of smoking. Mean smoking exposure was 62.1 pack years (range 30–120). All bladder cancers were transitional cell carcinomas with the majority being superficial at presentation. Most lung cancers were of the non-small cell type. Second primary lung cancers were significantly more advanced at diagnosis. Overall, mean follow-up was 105.8 months (range 6–288). Seven patients (28%) were alive at the time of evaluation; 68% died of lung cancer, while none died of bladder cancer.

Conclusions: Second primary lung cancer may occur in patients with bladder carcinoma and vice versa. In view of the relatively frequent involvement of the genitourinary tract as a site of multiple primary tumors, urologists may have a key role in the detection of second primary tumors arising in the genitourinary tract, or second primary tumors that occur in patients with primary genitourinary tract malignancies.
 

Background: Interleukin-8 is a prototypical inflammatory chemokine that induces leukocyte migration to inflammatory sites. Leukocyte recruitment in response to gradients of this chemokine is attenuated at advanced stages of inflammation to prevent damage to surrounding healthy tissues. Our published studies suggest that over-phosphorylation of focal adhesion kinase in migration-desensitizing conditions is involved in cessation of cell motility. This over-phosphorylation of FAK[1] was induced by IL-8[2] only when the receptor transmitting the chemokine signals was CXCR2, and not CXCR1, indicating that the two IL-8 receptors diverge in their signaling properties.

Objectives: To analyze the regulation of FAK in CXCR2-expressing hematopoietic cells under conditions of migratory desensitization, focusing on the roles played by adhesion-related components in this process.

Methods: Under conditions of migratory desensitization, we determined IL-8-induced cell spreading and FAK localization following disruption of actin filaments, and evaluated the role of integrins in FAK phosphorylation.

Results: The disturbance of intact activity of actin filaments resulted in inhibition of cell spreading and modification of FAK intracellular localization upon IL-8 stimulation. Also, adhesion-dependent pre-stimulation of integrins was required for IL-8-induced FAK phosphorylation.
Conclusions: Intact actin filaments and integrins are required for optimal IL-8-induced FAK phosphorylation in conditions of migratory desensitization. These observations suggest that lack of adequate activity/regulation of adhesion-related components may give rise to FAK activities that are not appropriately controlled, possibly leading to pathological conditions that are associated with perturbed leukocyte migration phenotypes

Background: Patients with severe persistent asthma despite GINA 2002 step 4 treatment are at risk for asthma-related morbidity and mortality. This study constitutes the Israeli arm of the international INNOVATE study.

Objectives: To determine the efficacy and safety of Xolair® as an add-on treatment in patients with severe persistent asthma.

Methods: Asthma patients (age 12–75 years) not controlled with high dose inhaled corticosteroids and long-active beta-2 agonists were randomized to receive either Xolair® or placebo for 28 weeks in a double-blind study in two Israeli centers.

Results: Thirty-three patients, 20 females and 13 males, mean age 54 ± 11.7 years, were included in the Israeli arm of the INNOVATE study. There were neither major adverse events nor withdrawals from the study. Xolair® (omalizumab) significantly reduced the rate of clinically significant asthma exacerbations (55% reduction) and all asthma-related emergency visits (53% reduction).
Conclusions: In patients with severe persistent difficult-to-treat asthma, despite regular treatment with LABA[1] and inhaled corticosteroids (GINA 2002 step 4), Xolair® is a safe and effective treatment

Background: Radiofrequency ablation has been suggested as first-line therapy in the management of accessory pathways. There are limited data on the results of ablation over years of experience.

Objectives: To assess the results and complications following RFA[1] of APs[2] performed in our institution over a 14 year period.

Methods: RFA was performed using deflectable electrode catheters positioned at the mitral or tricuspid annulus. The site of the AP was localized by electrophysiological study and radiofrequency energy was applied via the tip of the catheter

Results: The study cohort comprised 508 consecutive patients (64.2% males, mean age 33.6 ± 15.1 years) who underwent 572 RFA procedures for ablating 534 APs. A single AP was found in 485 (95.5%) patients while multiple APs were noted in 23 patients (4.5%). The APs were manifest, concealed or intermittent in 46.8%, 44.4% and 8.8% of cases, respectively. AP distribution was as follows: left free wall (56.6%), posteroseptal (23%), right anteroseptal (7.9%), right free wall (6.2%), midseptal (3.4%) and right atriofascicular (3.0%). Acute successful rates for a first or multiple ablation attempts were 93.1% and 95.3%, respectively. At a first ablation attempt, acute success and failure rates were the highest for midseptal (100%) and right atriofascicular (12.5%) APs respectively. Right anteroseptal APs were associated with the highest rate (23.9%) of discontinued or non-attempted procedures. Recurrent conduction in an AP after an initial successful ablation was observed in 9.9% of cases; it was the highest (24.2%) for right free wall APs and the lowest (5.0%) for left free wall APs. During follow-up (85 ± 43 months), definite cure of the AP was achieved in 94.9% of cases following a single or multiple procedures: midseptal (100%), left free wall (98%), right free wall (97%), posteroseptal (92.7%), right atriofascicular (87.5%) and right anteroseptal (78.5%). A non-fatal complication occurred in 18 patients (3.5%), more frequently in females (6.6%) than in males (1.8%) (P < 0.01). The two major complications (pericardial effusion and myocardial ischemic events) mainly occurred during RFA of a left free wall AP using a retrograde aortic approach. Catheter-induced mechanical trauma to APs was observed in 56 cases (10.5%). Mechanical trauma mainly involved right atriofascicular (43.8%) and right anteroseptal (38.1%) APs and contributed to the low success rate of RFA at these AP locations. During the 14 year period, our learning curve was achieved quickly in terms of success rate, although the most significant complications were observed at the beginning of our experience.

Conclusions: The results of this study confirm the efficacy and safety of RFA and suggest that it is a reasonable first-line therapy for the management of APs at any location.

Objectives: To compare the neonatal outcome (survival, intraventricular hemorrhage and bronchopulmonary dysplasia) of inborn and outborn very low birth weight infants, accounting for sociodemographic, obstetric and perinatal variables, with reference to earlier published data.

Methods: We compared 129 premature infants with birth weights of 750–1250 g delivered between 1996 and 2000 in a hospital providing neonatal intensive care to 99 premature babies delivered in a referring hospital. In the statistical analysis, variables with a statistical significant association with the outcome variables and dissimilar distribution in the two hospitals were identified and entered together with the hospital of birth as explanatory variables in a logistic regression.

Results: Accounting for the covariates, the odds ratios (outborns relative to inborns) were 0.31 (95% confidence interval = 0.11–0.86, P = 0.03) for mortality, 1.37 (95%CI[1] = 0.64–2.96, P = 0.42) for severe intraventricular hemorrhage, and 0.86 (95%CI = 0.38–1.97, P = 0.78) for bronchopulmonary dysplasia. The odds ratio for survival without severe intraventricular hemorrhage was 1.10 (95%CI = 0.55–2.20, P = 0.78). Comparing the current results with earlier (1990–94) published data from the same institution showed that mortality decreased in both the outborn and inborn infants (OR[2] = 0.23, 95%CI = 0.09–0.58, P = 0.002 and 0.46; 95%CI = 0.20–1.04, P = 0.06, respectively), but no significant change in the incidence of severe intraventricular hemorrhage or brochopulmonary dysplasia was observed. Increased survival was observed also in these infants receiving surfactant, more so among the outborn. The latter finding could be attributed to the early, pre-transport surfactant administration, implemented only during the current study.

Conclusions: Our data suggest that very low birth weight outborn infants may share an outcome comparable with that of inborn babies, if adequate perinatal care including surfactant administration is provided prior to transportation to a tertiary center.

Objectives: To compare leukocyte counts and blood levels of various inflammatory cytokines in children and adults diagnosed with community-acquired bronchopneumonia.

Methods: We prospectively evaluated all pediatric and adult patients admitted for bronchopneumonia based on clinical and chest X-ray findings.. Blood was drawn for complete blood count and serum concentration of the following cytokines: granulocyte colony-stimulating factor, interleukins-6, 8 and 10, interferon-gamma, tumor necrosis factor, as well as matrix metalloproteinase-9 and intercellular adhesion molecule-1.

Results: There were 31 children and 32 adults. The patients in both groups had similar parameters of infection severity. None of them required admission to the Intensive Care Unit. Mean (± SD) leukocyte counts in the pediatric and adult groups were 21,018/mm (± 10,420) and 12,628/mm (± 6735) respectively (P = 0.02). Age was inversely correlated with leukocytes in the pediatric group (P = 0.0001). A significant inverse correslation was also found between age and platelet counts. Although cuytokine levels in both groups were not significantly different, age was

Conclusions: The immune response in community-aquired bronchopneumonia is, at least partly, age-dependent.

Objectives: To evaluate the national Israeli experience with lung transplantation in patients with CF[1].

Methods: We reviewed the medical charts of all CF patients who underwent lung transplantation between January 1996 and June 2005 at the two Israeli centers that performed this procedure.

Results: Eighteen transplantations were performed in 17 patients. Mean patient age at transplantation was 25.3 ± 9.1 years, and mean duration of follow-up in survivors (n=14) was 37.2 months (range 1–113 months). The actuarial survival rate was 88% at 1 year and 74% at 5 years. Pulmonary function, expressed as percent of predicted normal forced expiratory volume in 1 sec, improved from 22.4 ± 8.1% to 76 ± 16.8% at one year after transplantation. Bronchiolitis obliterans syndrome was diagnosed in 5 patients (29%), of whom 2 died and 2 are currently candidates for retransplantation. Median time to onset of BOS[2] was 34.2 months (range 17–64 months).

Conclusion: In Israel, the early and intermediate-term results of lung transplantation for cystic fibrosis are encouraging. BOS remains a major complication that threatens long-term outcome.

The Ashkenazi-Jewish population is at increased risk for several recessively inherited disorders. While some of the disorders have severe or fatal symptom manifestations, others, such as non-neuronopathic Gaucher disease, do not usually pose a serious, life-threatening illness. Many healthcare centers in Israel offer prenatal panel screening. Controversy exists over the inclusion of Gaucher disease in the panel screening, especially since Gaucher disease screening lacks prognostic reliability. Most screening participants do not discriminate between the specific tests in the panel and are unable to discern between severe, life-threatening diseases and those that are less severe and even treatable. By including screening for Gaucher in the panel screening program, there is risk of a "panel effect," leading to termination of a pregnancy positive for Gaucher disease, without sufficient knowledge and understanding of the disease. Increasing medical and public awareness and knowledge of the disease, its prognosis and treatment options may reduce the rate of under-informed abortions associated with prenatal screening of Gaucher disease.

Background: The 5 year survival rate in patients with advanced epithelial ovarian cancer is 25–40% and treatment is mainly palliative once the disease recurs.

Objectives: To determine the time to progression, overall survival and toxicity of 1 year maintenance treatment with carboplatin in women with advanced EOC[1] after achieving complete remission with platinum‑based combination chemotherapy.

Methods: Twenty-two women with epithelial ovarian cancer stage III-IV previously treated with platinum‑based combinations who had achieved complete remission evidenced by symptoms, pelvic examination, computerized tomography and serum CA-125, were assigned to the study protocol consisting of: carboplatin of AUC=6, three cycles every 2 months, followed by two cycles once every 3 months for a total of five courses over 1 year.

Results: Median follow‑up in the 22 patients was 83 months (range 18–133 months), median disease‑free survival was 36 months (range 2.5–126.4, 95% confidence interval 16.39–56.34). The 5 year survival was 59.7% with a mean overall survival of 83 months (range 18–133, 95% CI[2] 39.11-127.29). Eleven patients have relapsed and died, 11 are alive, 6 are still in complete remission, and 5 are alive with recurrent disease. Grade III-IV toxicity was shown in some of the patients, anemia in 9%, thrombocytopenia in 9%, fatigue in 4.5%, and hypersensitivity in 4.5%.

Conclusions: A 1 year extension of treatment with a single‑agent carboplatin, administered to women with advanced EOC who had achieved complete recovery on platinum‑based chemotherapy as their first‑line therapy, has an acceptable toxicity. The disease-free survival and overall survival values noted in this study are encouraging and warrant further investigation.

Background: Sentinel lymph node mapping is the standard of care for patients with malignant melanoma and breast cancer. Recently, SLN[1] mapping was introduced to the field of gastric cancer.

Objectives: To evaluate SLN mapping in patients with gastric cancer.

Methods: In 43 patients with gastric cancer, open intraoperative subserosal dye injection in four opposing peritumoral points was used. Ten minutes following dye injection, stained LNs were located, marked and examined postoperatively from the surgical specimen.

Results: SLN mapping was performed in 43 with gastric cancer; 782 lymph nodes were harvested and evaluated. SLNs were stained in 34 of the patients (79.1%) with a mean of 2.85 SLNs per patient. The false negative rate was 20.9%, the positive predictive value 100%, the negative predictive value 78.6% and the sensitivity 86.9%.

Conclusions: SLN mapping in patients with gastric cancer is feasible and easy to perform. SLN mapping may mainly affect the extent of lymph node dissection, and to a lesser degree gastric resection. However, more data are needed.