Israel Medical Association Journal

Background: The prevalence of aortic stenosis increases with advancing age. Once symptoms occur the prognosis in patients with severe aortic stenosis is poor. The current and recommended treatment of choice for these patients is surgical aortic valve replacement. However, many patients, mainly the very elderly and those with major comorbidities, are considered to be at high surgical risk and are therefore denied treatment. Recently, a transcatheter alternative to surgical AVR[1] has emerged.

Objectives: To describe the first year experience and 30 day outcome of transcatheter aortic self-expandable CoreValve implantation in Israel.

Methods: Transcatheter aortic valve implantation using the CoreValve system has been performed in Israel since September 2008. In the following year 55 patients underwent CoreValve TAVI[2] in four Israeli centers.

Results: Patients' mean age was 81.7 ± 7.1 years; there were 35 females and 20 males. The mean valve area by echocardiogram was 0.63 ± 0.16 cm². The calculated mean logistic Euroscore was 19.3 ± 8%. Following TAVI, mean transvalvular gradient decreased from baseline levels of 51 ± 13 to 9 ± 3 mmHg. The rate of procedural success was 98%. One patient died on the first day post-procedure (1.8%) and all-cause 30 day mortality was 5.5% (3 of 55 patients). One patient had a significant post-procedural aortic regurgitation of > grade 2. Symptomatic improvement was evident in most patients, with reduction in functional capacity grade from 3.2 ± 0.6 at baseline to 1.4 ± 0.7. The most common post-procedural complication was complete heart block, which necessitated permanent pacemaker implantation in 37% of patients.

Conclusions: The Israeli first year experience of transcatheter aortic valve implantation using the CoreValve self-expandable system demonstrates an effective and safe procedure for the treatment of severe aortic stenosis in patients at high surgical risk.

Background: An accurate preoperative definition of tumor and lymph node status is needed for reaching the correct decision regarding rectal cancer treatment. Transrectal ultrasonography is the most commonly used diagnostic modality for the local staging of rectal cancer.

Objectives: To determine the accuracy of TRUS[1] in the staging of rectal cancer.

Methods: We conducted a retrospective study on 95 patients evaluated by TRUS. The rectum was subdivided into two parts (lower and upper).

Results: Sixty patients underwent radical surgery. Of these, 34 received no preoperative chemo-irradiation owing to µT1, µT2 tumor or the patient’s choice (neo-adjuvant treatment was suggested to patients with adenocarcinoma that proved to be µT3). The overall accuracy rate was 80% for T stage. Overstaging was found in 13.3% and understaging in 6.7%.The N-stage was correctly assessed in 70%. The overall accuracy rate for tumors was 73.9% in the lower part and 90.9% in the upper. A trend towards a lower accuracy rate for low-lying tumors compared to high-located rectal tumors was found (P = 0.532), which did not reach statistical significance.

Conclusions: TRUS gave better results for T1 and T3 stage rectal tumors but was inaccurate for stage T2, indicating the possible need for local excision in order to base the final treatment for T2 tumors on pathologic staging.
[1] TRUS = transrectal ultrasonography
 

Background: Hypocalcaemia following thyroid and parathyroid surgery is a well-recognized potential complication.

Objectives: To determine the utility of intraoperative quick parathormone assay in predicting severe hypocalcemia development following parathyroidectomy for a single-gland adenoma causing primary hyperparathyroidism.

Methods: A retrospective cohort study was performed. IO-QPTH[1] values were measured at time 0 (T0) before incision, and 10 (T10) and 30 minutes (T30) following excision of the hyperfunctioning gland. Percent decrease in IO-QPTH at 10 minutes (T10), maximum percent decrease of IO-QPTH value, and lowest actual IO-QPTH value obtained at surgery were used to determine any correlation with the development of postoperative hypocalcemia requiring treatment.

Results: Percent decrease in IO-QPTH at 10 minutes, maximum percent decrease in IO-QPTH and lowest IO-QPTH value did not correlate with the lowest postoperative calcium levels measured 18 hours after surgery (r = 0.017, P = 0.860 r = 0.018, P = 0.850 and r = 0.002, P = 0.985 respectively). For the purposes of our analysis, patients were subdivided into three groups. Group 1 comprised 68 patients with normal calcium levels (serum Ca 8.6¨C10.3 mg/dl) Group 2 had 28 patients with hypocalcemia (8.1¨C8.6 mg/dl) Group 3 included 12 patients with severe hypocalcemia (calcium level ¡Ü 8.0 mg/dl) requiring calcium supplementation due to symptoms of hypocalcemia. There was no difference between the three groups in the lowest IO-QPTH value (P = 0.378), percent decrease in IO-QPTH (P = 0.305) and maximum percent decrease in IO-QPTH (P = 0.142).

Conclusions: IO-QPTH evaluation was not useful in predicting the group of patients susceptible to develop severe postoperative hypocalcemia.  

[1] IO-QPTH = intraoperative quick parathormone

Background: Cancer is a leading cause of mortality worldwide. The most effective way to combat cancer is by prevention and early detection.

Objectives: To evaluate the outcome of screening an asymptomatic population for the presence of benign and neoplastic lesions.

Methods: Routine screening tests for prevention and/or early detection of 11 common cancers were conducted in 300 consecutive asymptomatic, apparently healthy adults, aged 25–77 years. Other tests were performed as indicated.

Results: Malignant and benign lesions were found in 3.3% and 5% of the screenees, respectively, compared to 1.7% in the general population. The most common lesions were in the gastrointestinal tract followed by skin, urogenital tract and breast. Advanced age and a family history of a malignancy were associated with increased risk for cancer with an odds ratio of 9 and 3.5, respectively (95% confidence interval 1.1–71 and 0.9–13, respectively). Moreover, high serum C-reactive protein levels and polymorphisms in the APC and CD24 genes indicated high cancer risk. When two of the polymorphisms existed in an individual, the risk for a malignant lesion was extremely high (23.1%; OR[1] 14, 95% CI[2] 2.5–78).

Conclusions: Screening asymptomatic subjects identifies a significant number of neoplastic lesions at an early stage. Incorporating data on genetic polymorphisms in the APC and CD24 genes can further identify individuals who are at increased risk for cancer. Cancer can be prevented and/or diagnosed at an early stage using the screening facilities of a multidisciplinary outpatient clinic.

Background: Down syndrome is one of the most common chromosomal abnormalities. Children and adults with DS[1] have significant medical problems and require life-long medical follow-up.

Objectives: To determine the adequacy of medical surveillance of individuals with DS as recommended by the American Academy of Pediatrics.

Methods: The study was conducted at a multidisciplinary center specializing in the care of DS during the period 2004–2006. At their first visit to the Center, caregivers of individuals with DS were questioned about the medical status of their child including previous evaluations. Medical records brought in by the parents were reviewed.

Results: The caregivers of 150 individuals with DS (age ranging from newborn to 48 years old, median age 5 years) were interviewed and medical records were reviewed. The prevalence of specific medical problems differed between our population and the reported prevalence from other surveys. For example, 39.3% of our population had documented auditory deficits while the reported prevalence is 75%. For gastrointestinal and thyroid disease, the prevalence was higher in the studied population than that reported in the literature. In terms of compliance with the AAP[2] recommendations, most children (94%) underwent echocardiography, but only 42.7% and 63.3% had been tested for auditory or visual acuity respectively. Only 36.3% over the age of 3 years had cervical spine films.
Discussion: Many individuals with DS are not receiving appropriate medical follow-up and the implications of inadequate surveillance can be serious

Background: Fine needle aspiration is the main diagnostic tool used to assess thyroid nodules.

Objectives: To correlate FNA[1] cytology results with surgical pathological findings in two teaching medical centers across the Atlantic.

Methods: We retrospectively identified 484 patients at Hadassah University Hospital, Jerusalem and Mount Sinai Hospital, New York, by means of both preoperative FNA cytology and a final histopathological report. Results compared FNA diagnosis, histological findings and frozen section results (Mt. Sinai only).

Results: The sensitivity value of FNA at Hadassah was 83.0% compared with 79.1% at Mt. Sinai (NS). Specificity values were 86.6 vs. 98.5% (P < 0.05), negative predictive value 78.7 vs. 77.6% (NS) and positive predictive value 89.7 vs. 98.6% (P < 0.05), respectively. "Follicular lesion" was diagnosed on FNA in 33.1% of the patients at Hadassah and in 21.5% at Mt Sinai (P < 0.005) with a malignancy rate of 42.5 vs. 23.1% (P < 0.05), respectively. Frozen section was used in 190 patients at Mt. Sinai (78.5%) with sensitivity and specificity values of 72.3% and 100%. Frozen section results altered the planned operative course in only 6 patients (2.5%). Follicular carcinoma was diagnosed in 12 patients at Hadassah vs. 2 patients at Mt. Sinai (P p <0.05).

Conclusion: The sensitivity of FNA at the two institutions was comparable. While malignancy on frozen section is highly specific, it should be used selectively for suspicious FNA results. Follicular lesions and the rate of malignancy in such lesions were more common at Hadassah, favoring a more aggressive surgical approach.

Background: Sickle cell anemia is a hemolytic anemia caused by a single mutation in position 6 of the β globin molecule. About 80 patients with SCA[1] in northern Israel are currently receiving treatment.

Objectives: To assess a screening program in northern Israel aimed at detecting couples at risk for having offspring with SCA.

Methods: Since 1987, screening for β thalassemia in pregnant women in northern Israel has been conducted, and from 1999 all the samples were also tested for hemoglobin S, Hgb C, Hgb D, Hgb O Arab and others.

Results: During the 20 year period 1987–2006 a total of 69,340 women were screened; 114 couples who carried Hgb S were detected and 187 prenatal diagnoses were performed in couples at risk for having an offspring with Hgb S. The mean gestational age was 13 ± 4 weeks. Fifty-four of those diagnoses revealed affected fetuses and in 4 cases the couple declined to perform therapeutic abortion.

Conclusions: The economic burden to the health services for treating SCA patients is about U.S.$ 7000 per year, and the institution of prevention programs has proven cost-effective in populations with a high frequency of carriers. Since our program is aimed to also detect β thalassemia, a disease that is more frequent in this area (> 2.5%), the added cost for the prevention of SCA is less significant in spite a low incidence of the S gene in our population, namely < 1%.

Background: Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of the human gastrointestinal tract.

Objectives: To review our accumulated experience using surgery to treat gastrointestinal stromal tumors.

Methods: We reviewed all patient charts and histological diagnoses of leiomyomas, leiomyosarcomas, leiomyoblastomas and schwannomas. Only tumors that displayed c-kit (CD117) immunopositivity were defined as GISTs[1].

Results: The study group comprised 40 female and 53 male patients (age 26–89 years); 40.9% of the tumors were classified as malignant, 39.8% as benign, and 19.4% as of uncertain malignancy. Fifty-six GISTs were located in the stomach (60.2%), 29 in the small bowel (31.2%), 4 in the duodenum (4.3%), 2 in the colon (2.1%) and 2 in the rectum (2.1%). Incidental GISTs were found in 23.7% of our patients. Mean overall survival time for malignant gastric GISTs was 102.6 months (95% confidence interval 74.2–131.1) as compared to 61.4 months mean overall survival for malignant small bowel GISTs (95% CI[2] 35.7–87) (P = 0.262). The mean disease-free survival period for patients with malignant gastric GISTs was 97.5 months (95% CI 69.7–125.2) as compared to only 49.6 months (95% CI 27.4–71.7) for patients with small bowel malignant GISTs (P = 0.041).

Conclusions: We found a high percentage of incidental GISTs. Gastric GISTs are more common than small bowel GISTs. Patients with malignant gastric GISTs have a significantly better prognosis than patients with malignant small bowel GISTs. A statistically significant correlation was found between age and malignant potential of the GIST.

Background: There is currently no standard salvage chemotherapy for the 40–50% of patients with non-Hodgkin’s lymphoma who fail first-line treatment.

Objectives: To review the experience of a major tertiary medical center with DVIP (dexamethasone, etoposide, ifosfamide and cisplatin) salvage therapy for primary refractory/relapsing NHL[1].

Methods: We reviewed the records of all patients with NHL who received DVIP salvage therapy during the period 1993 to 2005.

Results: We identified 37 adult patients (mean age 56.3 years): 29 with aggressive lymphoma and 8 with indolent lymphoma. Mean event-free survival was 13.5 months (range 0–82 months), mean time between diagnosis and DVIP treatment 18.5 months (range 2–101), and mean number of DVIP cycles 1.9. Four patients (11%) achieved a complete response and 9 (24%) a partial response (overall response 35%). Consolidation with stem cell transplantation was used in 14 patients with aggressive lymphoma and 4 with indolent lymphoma; 14 patients, all with aggressive lymphoma, responded (12 complete, 2 partial). Of the 10 patients who underwent SCT[2] despite no response to salvage DVIP, 6 achieved a complete response. Five year overall survival from diagnosis for the whole sample was 39.4 ± 8.7%, and 5 year post-DVIP overall survival 37.6 ± 8.0%. On multivariate analysis, SCT was the strongest predictor of survival (relative risk 0.73, P < 0.0001) followed by a high score on the International Prognostic Index (RR[3] 3.71, P = 0.032).

Conclusions: DVIP salvage therapy for NHL was associated with a low response rate of 35% but a 5 year post-DVIP survival rate of 37.6%. Patients who are refractory to salvage treatment with DVIP might still be salvaged with SCT.

Background: Multi-detector computed tomography has advanced enormously and now enables non-invasive evaluation of coronary arteries as well as cardiac anatomy, function and perfusion. However, the role of cardiac MDCT[1] is not yet determined in the medical community and, consequently, many clinically unnecessary scans are performed solely on a self-referral basis.

Objectives: To prospectively evaluate the role of a cardiologist consultation and recommendation prior to the scan, and the influence on the diagnostic yield of cardiac MDCT.

Methods: In our center, a CT service was initiated, but with the prerequisite approval of a cardiologist before performance of the CT. Each individual who wanted and was willing to pay for a cardiac CT was interviewed by an experienced cardiologist who determined whether cardiac MDCT was the most appropriate next test in the cardiovascular evaluation. Subjects were classified into three groups: a) those with a normal or no prior stress test, no typical symptoms and no significant risk factors of coronary artery disease were recommended to perform a stress test or to remain under close clinical follow-up without MDCT; b) those with an equivocal stress test, atypical symptoms and/or significant risk factors were allowed to have cardiac MDCT; and c) those with positive stress test or clinically highly suspected CAD[2] were advised to go directly to invasive coronary angiography. CT findings were categorized as normal CAD (normal calcium score and no narrowings), < 50% and > 50% CAD.

Results: A total of 254 people were interviewed, and in only 39 cases did the cardiologist approve the CT. However, 61 of the 215, despite our recommendation not to undergo CT, decided to have the scan. Assessment of the 100 cases that underwent MDCT showed a statistically significant better discrimination of significant CAD, according to the cardiologist’s recommendation: MDCT not recommended in 3/54 (6%) vs. MDCT recommended in 12/39 (31%) vs. recommended invasive coronary angiography in 4/7 (57%) (P < 0.001).

Conclusions: Detection of coronary calcification, as well as MDCT angiography can provide clinically useful information if applied to suitable patient groups. It is foreseeable that MDCT angiography will become part of the routine workup in some subsets of patients with suspected CAD. Selection of patients undergoing MDCT scans by a cardiologist improves the ability of the test to stratify patients, preventing unnecessary scans in both high and low risk patients

Background: With regard to ethnic predilections for Gaucher disease, the most common storage disorder, Ashkenazi Jews are at risk for the non-neuronopathic form (type I), Norbottnian Swedes are at risk for the sub-acute neuronopathic form (type III), and perhaps Arabs are at risk for the very rare cardiac variant of the sub-acute neuronopathic form (type IIIc) for which there is a relatively tight genotype-phenotype correlation. Type II, the acute infantile form, being the rarest form, has not been associated with any ethnic predilection.

Objectives: To examine whether Arab ethnicity influences the Gaucher phenotype.

Methods: We reviewed the records of all Arab patients in a referral clinic of 586 patients in Israel.

Results: There were 46 patients (7.8%) of Arab ethnicity: 23 (50%) had type I disease, 16 (34.8%) had type IIIc disease, 4 (8.7%) had type IIIb disease, and 3 (6.5%) had type II disease. Type IIIc disease was characterized by genotype-phenotype correlation with homozygosity for the D409H (1342C) mutation. All five Bedouin patients (10.9%) had the R48W (C259T) mutation on at least one allele.

Conclusions: For all genotypes, disease severity among Arab patients was relatively similar to that reported among other Caucasian patients. Apparently Arab ethnicity does not impact phenotypic expression in Gaucher disease in a unique manner. The predilection for type IIIc may be a result of consanguinity.