Israel Medical Association Journal

Background: The contribution of the abnormal DNA mismatch repair system to non-small cell lung cancer tumorigenesis is controversial and has not been reported in Jewish Israeli patients. Similarly, the involvement of 3p deletions in NSCLC[1] in the same population has not been assessed.

Objectives: To assess the contribution of the DNA-MMR[2] system to NSCLC pathogenesis by analyzing microsatellite instability, and evaluate loss of heterozygosity at 3p rates in Israeli NSCLC patients.

Methods: Paired DNA from tumorous and non-tumorous tissue was extracted, and genotyping for MSI[3] determination was carried out using the five Bethesda markers and for determining LOH[4] two 3p markers were used. Genotyping was performed using polymerase chain reaction amplification and size separation on an ABI semiautomatic DNA sequencer, and the allelic patterns of tumorous and non-tumorous tissue were compared.

Results: Forty-four NSCLCs from 35 smokers and 9 non-smokers were analyzed, with 26 of the 44 (59%) at stage I disease. Using five microsatellite markers (D17S250, D5S346, D2S123, BAT-25, BAT-26) (known as Bethesda markers) for MSI determination, 6 of the 44 tumors (13.6%) exhibited MSI in at least one marker. Similarly, genotyping for LOH at chromosome 3p was performed using two markers (D3S4103, D3S1234) located at 3p14.2 l. With D3S4103, 33 of the 44 patients successfully analyzed were homozygous and therefore non-informative with respect to LOH. Using D3S1234, 33 of 36 patients (91.7%) were heterozygous, and 23 of these individuals' tumors (69.7%) displayed LOH. Unexpectedly, 4 of 33 tumors (12.1%) genotyped by D3S4103, and 16 of 36 tumors (44.5%) genotyped by D3S1234 showed a pattern of MSI, even though only one of these tumors showed a similar pattern when genotyped with the five consensus markers. Overall, 23 of 44 tumors (52.3%) demonstrated MSI on at least one marker, and 5 of these 23 tumors (21.7%) had MSI on two or more markers.

Conclusions: MSI using 3p markers and not the Bethesda markers occurs at a high rate and in early stages in Jewish NSCLC patients.

Background: Thyroidectomy for goiter is a common surgical procedure performed in most hospitals in Israel. Both general and ear, nose and throat surgeons are familiar with thyroidectomy for cervical goiters. In about 1–15% of thyroidectomies, the goiter is intrathoracic and requires somewhat different management. This topic has not been reviewed in the literature recently.

Objective: To evaluate the clinical presentation, preoperative workup, surgical complications and risk of malignancy in retrosternal goiters.

Methods: We retrospectively reviewed the records of 75 patients who underwent thyroidectomy for retrosternal goiter in the General Thoracic Surgical Department of our institution during a 15 year period, January 1990 to January 2005.

Results: All the patients (41 women and 34 men) were symptomatic at presentation, with choking and dyspnea being the most common complaint. Computerized tomography scan of the neck and chest were obtained before the operation in 71 patients (95%). Ten patients (13%) had a previous partial thyroidectomy. A cervical approach was used in 68 patients (91%). Seven patients (9%) required median sternotomy to complete the operation. One patient (1.3%) died from postoperative respiratory failure. Transient recurrent laryngeal nerve palsy occurred in 5 patients (7%) and permanent RLNP[1] in 3 (4%). The incidence of transient and permanent hypoparathyroidism was 10% and 2.6% respectively. Sixty-six lesions (88%) were benign and 9 (12%) were malignant.

Conclusions: Choking and dyspnea are the most common presenting symptoms of retrosternal goiter. CT scan is an important component of the preoperative evaluation and operative planning. Surgical removal of the thyroid is the treatment of choice and most patients have symptomatic improvement following the operation. Since a substernal thyroidectomy may be technically different from cervical thyroidectomy, a surgical team familiar with its unique pitfalls should perform the procedure.

Evidence that crystalline silica is associated with an increased rate of lung cancer led the International Agency for Research on Cancer to conclude in 1997 that crystalline silica is a known human carcinogen. In Israel too, crystalline silica is considered as such. The decision raised a debate in the scientific arena, and a few scientists have questioned the basis upon which causality was determined. We review the literature regarding the level of evidence of crystalline silica carcinogenicity.

Background: The cause of cerebral palsy remains unknown in most cases. Factor V Leiden mutation, a common cause of hereditary thrombophilia, has been associated with CP[1].

Objectives: To analyze the prevalence of factor V Leiden (G1691A), prothrombin (G20210A), and methylenetetrahydrofolate reductase (C677T) mutations in children with CP.

Methods: Sixty-one children with CP were studied for the presence of the three gene mutations associated with thrombophilia.

Results: We found that 41% of the children with CP and 33% of the controls carry one or more of the studied mutations (P = 0.348). The prevalence of the factor V mutation was 27.9% in CP and 16.4% in controls (P = 0.127). The frequency of the other two genetic factors was even less significant. The FVL[2] mutation was found in 35% of the Arab CP patients (15/42) and in 22% of the controls from the same population (9/40) (P = 0.067).

Conclusions: Each of the genetic factors studied was shown to be related to CP. Despite the high frequency of FVL among the studied patients, we were unable to prove a significant correlation between FVL and CP, mainly because this factor is frequent in the Arab control group. In this population a trend toward significance can be seen (P = 0.067). Larger studies are needed to validate the significance of these results.

Objectives: To determine the prevalence of different pathogens in patients presenting to our sexually transmitted disease clinic with hematospermia.

Methods: Between January 1999 and January 2000, 16 patients presented to our STD[1] clinic with hematospermia after other non-infectious pathologies had been excluded by a referring physician. After obtaining informed consent, subjects completed a questionnaire addressing symptoms and sexual behavior. First void urine samples, as well as genitourinary and serum specimens were tested for Chlamydia trachomatis, Ureaplasma urealyticum and Herpes simplex virus. Standard bacterial cultures were also performed.

Results: Laboratory testing detected a pathogen in 12 of the 16 males presenting with hematospermia. The sexually transmitted pathogens detected were Herpes simplex virus in 5 patients (42%), Chlamydia trachomatis in 4 (33%), Enterococcus fecalis in 2 (17%), and Ureaplasma urealyticum in 1 (8%). In all cases in which a pathogen was identified, the appropriate antimicrobial agent was administered. Symptoms resolved for each patient following antimicrobial therapy. During a 1 year follow-up, all 12 patients remained free of disease.

Conclusions: Recent advances in microbiologic diagnostic techniques have facilitated the detection of pathogens in patients with hematospermia, thereby enhancing the efficacy of treatment.

____________________

[1] STD = sexually transmitted disease

Background: An organ sharing system should achieve fairness and optimal graft longevity. Balancing between social and utilitarian considerations is a sensitive ethical, public and medical issue that requires a means to examine the consequences of any allocation policy or planned changes thereof.

Objective: To evaluate the performance and applicability of a computerized simulation model by examining the impact of two opposing organ allocation policies (social or utilitarian) on predicted organ distribution regarding age, waiting time, recipient sensitization measured by panel reactive antibody level and overall donor-recipient tissue matching (measured by the number of HLA antigen mismatches).

Methods: Using a computerized simulation model, virtual donors and recipients were emulated and organs were allocated according to either social algorithms or utilitarian policies. The resulting number of HLA mismatches, PRA[1], age, and waiting time distributions were compared between allocation strategies.

Results: Simulating allocation of 7,000 organs to 17,000 candidate recipients and implementing social policies yielded donor-recipient compatibility comparable to utilitarian policies (0–1 mm: 19.4% vs. 28%) while allocating 66.7% of organs to long waiters (>48 months).

Conclusion: This computerized simulation model is a valuable tool for decision-makers establishing or modifying organ allocation policies.

Background: Primary hyperparathyroidism in elderly patients is usually associated with additional co-morbidity that increases operative risk, and thus many geriatric patients are denied the benefit of surgery for a single parathyroid adenoma.

Objectives:  To evaluate the safety and efficacy of accurate single photon emission computed tomography sestamibi scintigraphy, enabling precise localization of a single adenoma, in the geriatric population

Methods: Twenty-two patients aged 70 years and over with biochemically proven PHPT[1] and with a single parathyroid adenoma identified by localization studies (sestamibi SPECT[2] scan and ultrasonography) underwent 23 operations over 29 months (out of a total of 140 patients operated upon during the same period). Immediate preoperative sestamibi scintigraphy and marking of focal adenoma uptake followed by intraoperative hand-held gamma probe were used for the removal of the parathyroid adenoma by unilateral minimal access surgery. Associated major co-morbid conditions and pre- and postoperative calcium, phosphorus and parathormone levels were recorded. Indications for surgery were listed and operative and postoperative complications were noted. The patients were followed for a mean period of 17.7 months using the same parameters.

Results: The 22 patients with PHPT had a mean age of 76.3 ± 5.9 years (range 70–88 years)  and a female to male ratio of 13:9. Associated co-morbidity included ischemic heart disease (n=15), hypertension (n=22), non-insulin-dependent diabetes mellitus (n=9), chronic obstructive pulmonary disease (n=3), and previous neck surgery (n=3). Mean preoperative serum calcium, phosphorous and PTH[3] were 11.7 ± 1.3 mg/dl, 2.5 ± 0.5 mg/dl and 160.9 ± 75.4 pg/ml respectively. In 20 of the 22 patients, surgery was successful in curing PHPT (91%). One patient had persistent hypercalcemia due to a missed adenoma, and repeat operation (by focused minimal access surgery) was successfully performed 2 weeks later. There were no complications and no morbidity postoperatively. Mean postoperative serum calcium, phosphorous and PTH were 9.6 ± 1.2 mg/dl, 3.0 ± 0.5 mg/dl and 35.2 ± 24 pg/ml respectively. In all patients, serum calcium levels remained normal (9.7 ± 1.3 mg/ml) after long-term follow-up (mean 17.7 ± 9.6 months).

Conclusions: Minimally invasive, radio-guided focused parathyroidectomy for a single adenoma is a safe and effective method to cure hyperparathyroidism in the elderly. Success of surgery is directly related to the surgeon's experience and to the precise localization marking provided by sestamibi scintigraphic SPECT localization and concurrent sonographic findings.

Background: During a period of 13 months - 1 October 2000 to 31 October 2001 – 586 terror assault casualties were treated in the trauma unit and emergency department of Hadassah University Hospital (Ein Kerem campus); 27% (n = 158) were hospitalized and the rest were discharged within 24 hours.

Objectives: To analyze the special requirements of a large number of victims who received treatment during a short period.

Methods: Data were attained from the main admitting office and the trauma registry records. Analysis was conducted of: age, gender, mechanism of injury, anatomic site of injury, Injury Severity Score (ISS), and length of stay.

Results: Males comprised 81% of the hospitalized patients. The majority of the injuries (70%) were due to gunshot wounds and 31% of the hospitalized patients were severely injured (ISS ≥ 16). Twelve patients died, yielding a mortality rate of 7.5%.

Conclusion: The nature of the injuries was more complex and severe than trauma of other etiologies, as noted by the mean length of stay (10.2 vs. 7.2 days), mean intensive care unit stay (2.8 vs. 0.9 days), and mean operations per patient (0.7 vs. 0.5). The mean insurance cost for each hospitalized terror casualty was also higher than for other trauma etiologies (US$ 3,200 vs. 2,500).