Israel Medical Association Journal

Objectives: To examine the effect of postoperative loco-regional radiotherapy on local and regional recurrence and survival in breast cancer patients with four or more involved lymph nodes or extracapsular tumor extension.

Methods: This controlled clinical trial included 258 breast cancer patients with four or more involved nodes or ECE[1]. Eighty-nine patients in the control group had modified radical mastectomy and received adjuvant chemotherapy with melphalan and 5FU, but no radiation therapy. The 169 patients in the study group (87 with MRM[2] and 82 with lumpectomy and axillary dissection) received various adjuvant chemotherapy regimes and radiation therapy to the chest wall/breast, supraclavicular region and full axilla.

Results: With an average follow-up of more than 5 years, loco-regional radiation significantly reduced local and regional disease recurrence. The median disease-free survival was significantly longer in radiated patients (59.2 months and 63.3 months in the MRM and L+AXLND[3] groups, respectively, vs. 28.4 months in the control group; P < 0.01). There was no difference in the rate of systemic recurrence and overall survival. The median overall survival was 71.2 and 67.5 months in the study groups (MRM and L+AXLND, respectively) and 70.5 months in the control group (P = 0.856).

Conclusions: Radiotherapy to the breast/chest wall and to the draining lymphatics, in addition to surgery and adjuvant therapy, significantly reduced the risk of local and regional recurrence in high risk breast cancer patients with four or more involved lymph nodes or ECE.

Objectives: To assess the relative efficacy of clinical and laboratory methods in the diagnosis of Bordetella pertussis by patient age and immunization status.

Methods: We compared the clinical and laboratory diagnosis of B. pertussis in 87 pre-vaccinated, 78 recently vaccinated, and 75 post-vaccinated children with suspected pertussis. Serum and nasopharyngeal swabs were obtained for serology, culture and polymerase chain reaction.

Results: PCR[1] and culture identified 41% and 7% of patients with B. pertussis, respectively (P < 0.001). All positive cultures were PCR-positive. Positive PCR was less common among those recently vaccinated than among those in the pre- (P < 0.001) and post-vaccinated groups (P < 0.05). Positive culture was more common among those pre-vaccinated than among those recently vaccinated (P < 0.01). Positive tests for immunoglobulin M and A were more common among the post-vaccinated than the pre- and recently vaccinated (P < 0.001), respectively. Logistic regression analyses revealed that clinical criteria have no significant association with infection in recently and post-vaccinated children. Among the pre-vaccinated children, whoop and cough duration were associated with a positive PCR (odds ratio 7.66 and 0.5, P < 0.001). Seventy-six percent of pre-vaccinated, 39% of recently vaccinated and 40% of post-vaccinated children with positive PCR did not meet the U.S. Centers for Disease Control diagnostic criteria for B. pertussis.

Conclusions: PCR is a useful tool for pertussis diagnosis, particularly in pre-vaccinated infants. The yield of culture and serology is limited, especially among pre- and recently vaccinated children. In pre-vaccinated infants with whoop and less than 2 weeks of cough, PCR testing should be implemented promptly.

Objectives: To characterize the demographic and clinical features of malaria acquired in Kenya, and to assess the adequacy of preventive measures.

Methods: Data were collected from investigation forms at the Ministry of Health. All persons who acquired malaria in Kenya during the years 1999–2001 were contacted by phone and questioned about use of chemoprophylaxis, attitudes towards malaria prevention, and disease course. Further information was extracted from hospital records.

Results: Kenya accounted for 30 of 169 (18%) cases of malaria imported to Israel, and was the leading source of malaria in the study period. Of 30 malaria cases imported from Kenya, 29 occurred after short (1–2 weeks) travel to holiday resorts in Mombassa. Average patient age was 43 ± 12 years, which is older than average for travelers to tropical countries. Only 10% of the patients were fully compliant with malaria chemoprophylaxis. The most common reason for non-compliance was the belief that short travel to a holiday resort carries a negligible risk of malaria. Only 3 of 13 patients (23%) who consulted their primary physician about post-travel fever were correctly diagnosed with malaria. Twenty percent of cases were severe enough to warrant admission to an intensive care unit; one case was fatal.

Conclusions: Measures aimed at preventing malaria and its severe sequelae among travelers should concentrate on increasing awareness of risks and compliance with malaria chemoprophylaxis.

Objective: To investigate the effectiveness of preoperative chemoradiation in increasing the resectability rates of rectal cancer and increasing the anal sphincter preservation rate.

Methods: The study group included 66 patients aged 33–84 years with T₂–T₃ rectal carcinoma who were treated in our institute from 1997 to 2002 with preoperative chemoradiation followed by surgery 6 weeks later. All patients underwent preoperative transrectal endoscopic ultrasound for tumor staging and localization. The duration of follow-up was 25 months.

Results: Chemoradiation led to tumor downstaging in 61 patients (92.4%), all of whom underwent low anterior resection. Only 11.4% of this group needed a temporary (6 weeks) loop colostomy/ileostomy. None of the 16 patients with post-treatment T₀ tumors had evidence of malignant cells on pathologic study. Five patients (7.6%) failed to respond to chemoradiation and underwent APR[1]. There were no major complications, such as leakage, and no deaths.

Conclusions: Neoadjuvant chemoradiation is an effective modality to downstage advanced rectal cancer, improving patient quality of life by significantly reducing the need for a terminal permanent colostomy, or even a temporary one.

Objectives: To assess the effect of a vaginal ring delivering estradiol and progesterone in postmenopausal women and to determine whether continuous administration can relieve climacteric symptoms, produce an acceptable pattern of vaginal bleeding and control endometrial proliferation.

Methods: Twenty-nine postmenopausal women with an intact uterus were studied. All had climacteric symptoms. The vaginal rings contained 0.36 g estradiol and either 3.6 g progesterone (high dose progesterone) or 1.8 g (low dose progesterone), and were kept in place for 4–6 months. Serum progesterone, estradiol and estrone were measured and endometrial thickness determined. All women kept a daily diary of bleeding/spotting and completed a questionnaire on climacteric symptoms at monthly intervals. The low dose progesterone group comprised 14 women and the high dose progesterone group 15 women.

Results: A total of 18 patients (9 in each group) completed the study. Mean levels of estradiol, estrone and progesterone were at their peak after 2 to 4 weeks. All rings were effective in alleviating vasomotor symptoms, although there was evidence of the "escape from effect" in month 6. Endometrial thickness increased in 6 of the 29 women but biopsy in each case showed no evidence of hyperplasia. Of the 18 women who completed the study, 5 had amenorrhea throughout, 7 had amenorrhea after 3 months, and the remainder had one or two bleeding episodes after 3 months. Therapy was discontinued in 11 women.

Conclusions: A vaginal ring delivering estradiol and progesterone controlled climacteric symptoms, prevented endometrial proliferation, and provided an acceptable bleeding pattern. It should be viewed as a promising alternative for short-term estrogen-progesterone therapy.

Objectives: To describe the role of wireless capsule endoscopy in diagnosing isolated small intestinal Crohn’s disease in two adolescents.

Methods: Wireless capsule endoscopy was performed in two adolescents with severe protein-losing enteropathy and negative standard diagnostic workup.

Results: Wireless capsule endoscopy successfully diagnosed Crohn’s disease with uncharacteristic presentations and negative radiographic and endoscopic findings in both patients.

Conclusions: The non-invasiveness and ease in performance of capsule endoscopy on an ambulatory basis make this diagnostic modality especially advantageous for children.

Objective: To present our algorithm of urgent and elective donor selection.

Methods: Urgent selection is expeditious and protocol‑based. Elective selection permits a comprehensive process. Both include medical, psychosocial and surgical-anatomic evaluations. Liver volumes and vascular anatomy are evaluated with computerized tomographic angiography. Informed consent is obtained after painstaking explanations. Independent institutional committees review and approve all cases.

Results: Between July 2003 and June 2004 we evaluated 43 potential live donors for 12 potential recipients (fulminant hepatic failure, n=5; chronic end-stage liver disease, n=6); primary graft non-function, n=1). Thirty-three candidates (76%) were excluded due to blood type incompatibility (n=14, 42%), incompatible anatomy (n=8, 24%) – including problematic volume distribution (n=2) or vascular anatomy (n=6) – psychosocial issues (n=4, 12%), or medical co-morbidity (n=7, 22%). Five recipients (FHF[1], n=4; chronic ESLD[2], n=1) were successfully transplanted from living donors. In the acute setting, two patients (FHF, PGNF[3]) died in the absence of an appropriate donor (cadaveric or living donor). In the elective group, one patient died of unexpected variceal bleeding and one received a cadaveric graft just before the planned living donor transplantation was performed. One candidate was transplanted overseas and two cases are scheduled. The ratio of compatibility for donation was 34% (10/29) for blood type-compatible candidates.

Conclusions: Donor selection for living donor liver transplantation is a complex, labor-intensive multidisciplinary process. Most exclusions are due to blood type incompatibility or anatomic details. Psychosocial aspects of these donations warrant special attention.

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[1] FHF = fulminant hepatic failure

[2] ESLD = chronic end-stage liver disease

[3] PGNF = primary graft non-function

Background: Hypertension is considered resistant if blood pressure cannot be reduced to <140/90 mmHg with an appropriate triple-drug regimen, including an oral diuretic, with all agents administered at maximal dosages. This definition has evolved with the development of new therapies and evidence-based data supporting treatment to lower BP[1] goals.

Objective: To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia.

Methods: Forty-eight hyperlipidemic subjects with RH[2] (office systolic BP >140 mmHg and/or office diastolic BP >90 mm/Hg notwithstanding antihypertensive treatment with three medications in maximal doses) were randomized into three groups to receive additional medication for 8 weeks. Group VTC (n = 17) – mean 24 hour SBP[3] 150.6 ± 5.2 mmHg, DBP[4] 86.1 ± 3.3 mmHg, low density lipoprotein 158.1 ± 24.5 mg/dl) – received vitamin C 500 mg per day; Group ATR (n = 15) – mean 24 hour SBP 153.1 ± 4.8 mmHg, DBP 87.1 ± 6.7 mmHg, LDL[5] 162.6 ± 13.6 mg/dl) – received atorvastatin 20 mg/day; and Group PLA (n = 16) – mean 24 hour SBP 151.1 ± 7.4 mmHg, DBP 84.8 ± 5.9 mmHg, LDL 156.7 ± 26.1 mg/dl – received a placebo. High resolution ultrasound was used to calculate brachial artery flow-mediated dilation, and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks.

Results: In the ATR group there were significant reductions of SBP (DSBP1-2: 13.7 ± 5.6 mmHg, P < 0.001), DBP (DDBP1-2: 7.8 ± 5.7 mmHg, P < 0.01), LDL (DLDL1-2: 67.7 ± 28.3 mg/dl, P < 0.001) and improvement of brachial artery FMD[6] (DFMD2-1: 4.2 ± 2.6%). No significant changes in BP, LDL and FMD were observed in the other two groups.

Conclusions: In subjects with RH and dyslipidemia, atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period. A larger trial is needed to assess the drug's efficacy in this population for longer periods.

Background: Cardiac rupture is a rare but ominous complication of myocardial infarction.

Objectives: To study the clinical presentation, medical course, outcome and echocardiographic predictors of patients with myocardial rupture.

Methods: We evaluated 15 consecutive patients with cardiac rupture during a 4 year period in our department. The current report explores the presence of potential risk factors, timing, relation to the thrombolysis, coronary interventions and outcome.

Results: The index event in all patients was first ST elevation myocardial infarction. In seven patients rupture occurred in the first 24 hours. Pericardial effusion on admission with a clot was present in three patients. Five patients received thrombolytic therapy. Only three patients underwent coronary angioplasty, but in one case it was performed late and in two patients the culprit artery could not be opened. Six patients reached the operating room, of whom three survived.

Conclusions: The lack of early mechanical reperfusion in acute myocardial infarction and thrombolytic therapy are risk factors for cardiac rupture. Pericardial effusion on admission and evidence of a clot are echocardiographic indicators of cardiac rupture and should alert the medical team to further assess the possibility of cardiac rupture.