Israel Medical Association Journal

Background: Heart rate variability is a sensitive marker of cardiac sympathetic activity.

Objectives: To determine whether long-term hyperthyroidism induced by thyroxine suppressive therapy affects HRV[1].

Methods: Nineteen patients treated with suppressive doses of thyroxin for thyroid cancer and 19 age-matched controls were enrolled. Thyroid function tests and 1 minute HRV were performed on all subjects and the results were compared between the groups. The 1 minute HRV was analyzed during deep breathing and defined as the difference in beats/minute between the shortest and the longest heart rate interval measured by eletrocardiographic recording during six cycles of deep breathing.

Results:  One minute HRV during deep breathing was significantly lower among thyroxine-treated patients compared to healthy controls (25.6 ± 10.5 vs. 34.3 ± 12.6 beats/min, P < 0.05). There were no significant differences in mean, maximal and minimal heart rate between the groups

Conclusions: Thyroxine therapy administered for epithelial thyroid cancer resulted in subclinical hyperthyroidism and significantly decreased HRV due to autonomic dysfunction rather than basic elevated heart rate.

Background: The frequency of colorectal cancer screening tests in Israel is poor, and is much lower than in the United States. This low rate has been attributed to health system failures as well as to barriers on the part of both physicians and patients.

Objectives: To further identify particular health system failures, physician and patient-based barriers, and the effectiveness of public lectures in improving the frequency of performance of CRC[1] screening tests.

Methods: Public lectures on colorectal cancer prevention were held. A gastroenterologist presented the lectures, which were followed immediately by a questionnaire and 4 months later by a telephone call.

Results: Of the 80% of attendees who had never undergone any CRC screening test, only 18% reported family physician recommendations for such tests. Eighty-four percent reported willingness to undergo fecal occult blood testing and 52% to undergo colonoscopy; 62% replied that they should undergo some CRC screening test and 90% believed that these tests save lives. Of the women, 47% expressed preference for a female gastroenterologist. Follow-up showed that 34% proceeded to undergo some CRC screening test: 60% chose colonoscopy and 40% FOBT[2].

Conclusions: Public lectures are effective at improving compliance with the CRC screening test. Physicians should recommend these tests to appropriate individuals. Same-gender gastroenterologists should be considered for individuals uneasy about someone from the opposite gender performing the test. Assessing the various health-promotion efforts can direct us in implementing finite resources to greatest effect. Local cancer institutes and societies may be supportive in disseminating screening information in this way.

Background: Occult breast cancer without clinically or mammographically detectable breast tumor is an uncommon presentation.

Objectives: To assess the role of breast MRI in women with metastatic carcinoma and an occult primary, and to define the MRI characteristics of the primary breast tumor.

Methods: This retrospective study evaluated 20 women with metastatic carcinoma of unknown origin who underwent breast MRI between 2000 and 2006. Four women were excluded, leaving 16 in the study group. Probability of malignancy was assessed according to BIRADS classification. MRI performance in detecting lesions and evaluating disease extent was assessed, with the gold standard being surgical or biopsy pathology.

Results: MRI detected suspicious lesions in 15 patients. Lesion size ranged from 0.4 to 7 cm (median 1.5 cm). MRI detected a single lesion in 6 patients (40%), multifocal disease in 3 (20%), multicentric disease in 4 (27%), and bilateral breast lesions in 2 (13%). In 13 patients MRI depicted the primary breast cancer. Initial treatment was surgical in nine; MRI correctly estimated disease extent in 6 (67%), underestimated disease extent in 1 (11%), and overestimated it in 2 (22%). Four patients had biopsy followed by chemotherapy; one had multicentric disease and one had multifocal disease. MR findings were false positive in two patients and false negative in one.

Conclusions: MRI is sensitive in detecting the primary tumor and beneficial in assessing tumor extent. Small size and multiple foci are common features. We suggest that bilateral breast MRI be part of the evaluation of women with metastatic carcinoma and an occult primary.
 

Background: Skin basal and squamous cell carcinomas together account for over half of all newly diagnosed cancer cases. Frozen  section control of surgical margins is often required in the head and neck region. A paraffin permanent section does not always confirm the results of a frozen section.

Objectives: To test the diagnostic accuracy of frozen section histopathological analysis in determining the free margins of excised tumors.

Methods: This was a retrospective study of 169 cutaneous basal and squamous cell carcinomas excised with surgical margins diagnosed by frozen section and confirmed by permanent paraffin sections. The data included patients' age, gender, clinical and histopathological diagnosis, as well as characteristics of the lesions.

Results: There were 149 (88%) basal cell carcinomas and 20 (12%) squamous cell carcinomas. False negative margins were found in 19 cases (11.2%) and false positive margins in 11 cases (6.6%). We did not find any correlation between false positive or false negative margins and patients' age, gender, tumor size, tumor location, or the presence of sun-damaged skin. A significantly lower rate of false negative results was found in the residual tumor group.

Conclusions: Our findings show support the use of frozen section margin control in selected patients suffering from non-melanoma skin cancer of the head and neck.
 

Background: Fanconi anemia complementation group C and Bloom syndrome, rare autosomal recessive disorders marked by chromosome instability, are especially prevalent in the Ashkenazi* Jewish community. A single predominant mutation for each has been reported in Ashkenazi Jews: c.711+4A→T (IVS4 +4 A→T) in FACC[1] and BLM^Ash in Bloom syndrome. Individuals affected by both syndromes are characterized by susceptibility for developing malignancies, and we questioned whether heterozygote carriers have a similarly increased risk.

Objectives: To estimate the cancer rate among FACC and BLM^Ash carriers and their families over three previous generations in unselected Ashkenazi Jewish individuals.

Methods: We studied 42 FACC carriers, 28 BLM^Ash carriers and 43 controls. The control subjects were Ashkenazi Jews participating in our prenatal genetic screening program who tested negative for FACC and BLM^Ash. All subjects filled out a questionnaire regarding their own and a three-generation family history of cancer. The prevalence rates of cancer among relatives of FACC, BLM^Ash and controls were computed and compared using the chi-square test.

Results: In 463 relatives of FACC carriers, 45 malignancies were reported (9.7%) including 10 breast (2.2%) and 13 colon cancers (2.8%). Among 326 relatives of BLM^Ash carriers there were 30 malignancies (9.2%) including 7 breast (2.1%) and 4 colon cancers (1.2%). Controls consisted of 503 family members with 63 reported malignancies (12.5%) including 11 breast (2.2%) and 11 colon cancers (2.2%).

Conclusions: We found no significantly increased prevalence of malignancies among carriers in at least three generations compared to the controls.

Background: Colonoscopy is the gold standard procedure for screening for colorectal cancer and surveillance after polypectomy or colorectal cancer surgery, for diagnosis in symptomatic patients and patients with fecal occult blood, and for screening in the high risk population. The adherence of referring physicians to the accepted recommendations can prevent long waiting lists for colonoscopy and save lives, costs and resources.

Objectives: To evaluate the knowledge of primary care physicians and gastroenterologists in Israel about current guidelines for colonoscopy screening and surveillance.

Methods: A 10-item questionnaire on proper follow-up colonoscopy for surveillance after polypectomy and screening for colorectal cancer in various clinical and epidemiological situations was administered to 100 expert gastroenterologists and 100 primary care physicians at a professional meeting. Answers were evaluated for each group of physicians and compared using the chi-square test.

Results: The compliance rate was 45% for the gastroenterologists and 80% for the primary care physicians. The rate of correct answers to the specific items ranged from 18.7% to 93.75% for the gastroenterologists and from 6.2% to 58.5% for the primary care physicians (P < 0.001 for almost every item).

Conclusions: The knowledge of physicians regarding the screening and surveillance of colorectal cancer needs to be improved.

Background: Germline mutations in BRCA1 and BRCA2 genes account for only 20–40% of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase, involved in response to DNA damage, and hence is a candidate gene for breast cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was reported in a subset of mostly North European breast cancer families. The rate of the CHEK2*1100delC variant in the Ashkenazi* Jewish population was reported to be 0.3%.

Objectives: To evaluate whether CHEK2 germline mutations contribute to a breast cancer predisposition in Ashkenazi-Jewish high risk families.

Methods: High risk Ashkenazi Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were genotyped for germline mutations in the CHEK2 gene by exon-specific polymerase chain reaction followed by denaturing gradient gel electrophoresis and sequencing of abnormally migrating fragments.

Results: Overall, 172 high risk women were genotyped: 75 (43.6%) with breast cancer (average age at diagnosis 49.6 ± 9.6 years, mean ± SD) and 97 asymptomatic individuals (age at counseling 48.3 ± 8.2 years). No truncating mutations were noted and four previously described missense mutations were detected (R3W 1.2%, I157T 1.2%, R180C 0.6% and S428F 5%), one silent polymorphism (E84E 20.5%) and one novel missense mutation (Y424H 1.2%). Segregation analysis of the I157T and S428F mutations (shown to affect protein function) with the cancer phenotype showed concordance for the CHK2*I157T mutation, as did two of three families with the CHK2*S428F mutation.

Conclusions: CHEK2 missense mutations may contribute to breast cancer susceptibility in Ashkenazi Jews.

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.
 

Surgical resection offers the best opportunity for cure in patients with colorectal cancer metastasis to the liver, with 5 year survival rates of up to 58% following resection. However, only a small percentage of patients are eligible for resection at the time of diagnosis and the average recurrence rate is still high. Consequently, research endeavors have focused on methods aimed to increase the number of patients eligible for surgical resection, refine the selection criteria for surgery, and improve the disease-free and overall survival time in these patients. Improvements in imaging techniques and the increasing use of FDG-PET allow more accurate preoperative staging and superior identification of patients likely to benefit from surgical resection. Advances in the use of neoadjuvant chemotherapy allows up to 38% of patients previously considered unresectable to be significantly downstaged and eligible for hepatic resection. Many reports have critically evaluated the surgical techniques applied to liver resection, the concurrent or alternative use of local ablative therapies, such as radiofrequency ablation, and the subsequent utilization of adjuvant chemotherapy in patients undergoing surgical resection for hepatic metastases.