Israel Medical Association Journal

Background: Local recurrences after breast-conserving surgery occur mostly at the site of the primary carcinoma. The main objective of postoperative radiotherapy is sterilization of residual cancer cells. Whole-breast radiotherapy is the standard of care, but its utility has recently been challenged in favor of radiotherapy limited to the area at highest risk of recurrence. Intraoperative electron radiotherapy (IOeRT) is an innovative technique for accelerated partial breast irradiation (APBI) that is applied to selected patients affected by early breast cancer.

Objectives:  To describe our experience with IOeRT at the Rambam Health Care Campus in Haifa since we began utilizing this modality in 2006.

Methods: From April 2006 to September 2010, 31 patients affected by unifocal invasive duct breast carcinoma ≤ 2 cm diameter received wide local resection followed by intraoperative radiotherapy with electrons. Patients were evaluated for early and late complications, and other events, 1 month after surgery and every 3 months thereafter for the duration of the first 2 years.

Results: After a mean follow-up of 36 months, seven patients developed mild breast fibrosis and three suffered from mild postoperative infection. Rib fractures were observed in four patients before routine lead shielding was initiated. Additional whole-breast irradiation was given to four patients. None of the patients developed local recurrences or other ipsilateral cancers. Similarly, no contralateral cancers or distant metastases were observed.

Conclusions: Intraoperative electron radiotherapy may be an alternative to external beam radiation therapy in an appropriate selected group of early-stage breast cancer patients. However, long-term results of clinical trials are required to better evaluate the indications and utility of this technique in the management of breast cancer.
 

Background: Although the comprehensive evaluation of the fetal heart includes echocardiography by an experienced pediatric cardiologist, economic constraints sometimes dictate the need to select patients.

Objectives: To analyze the usefulness of fetal echocardiography in the detection of congenital heart disease according to the referral indication.

Methods: This retrospective survey relates to all 3965 FE studies performed in our center from January 2000 to December 2004. The diagnosed cardiac anomalies were classified as significant and non-significant malformations. All FE[1] studies were done by a single operator (A.L.) at Meir Medical Center, a referral center for a population of about 400,000. The 3965 FE studies were performed for the following indications: abnormal obstetric ultrasound scans, maternal and family history of cardiac malformations, medication use during the pregnancy, and maternal request. The relative risk of detecting CHD[2] was calculated according to the various referral indications.

Results: Overall, 228 (5.8%) cases of CHD were found. The most common indication for referral was suspicion of CHD during a four-chamber view scan in a basic system survey or during a level II ultrasound survey. No correlation was found between maternal age and gestational age at the time of scanning and the likelihood of finding CHD.

Conclusions: Our data suggest that a suspicious level-II ultrasound or the presence of polyhydramnios is an important indication for FE in the detection of significant CHD.

For centuries skin pigmentation has played a major societal role. Genetic disorders of skin pigmentation have therefore always evoked the curiosity of both laypersons and physicians. Normal skin pigmentation is a complex process that begins with the synthesis of melanin within the melanocytes, followed by its transfer to neighboring keratinocytes where it is translocated to the upper pole of the nucleus and degraded as the keratinocyte undergoes terminal differentiation. Mutations in various genes involved in melanocyte migration during embryogenesis, melanin synthesis and melanosomal function and transfer have been shown to cause pigmentation disorders. In the present review, we discuss normal skin pigmentation and the genetic underpinning of selected disorders of hypo- and hyperpigmentation.

Objectives: To analyze our 8 year experience using TEM[1] for the management of rectal cancer.

Methods: Local resection by TEM was performed in patients with benign tumors and early rectal cancer. In addition, selected patients with T2 and T3 rectal cancers who were either medically unfit or unwilling to undergo radical surgery were also treated with this modality. Radical surgery was offered to all patients with incomplete tumor excision by TEM.

Results: Overall, 116 TEM operations for rectal tumors were carried out between 1995 and 2003, including 74 patients with rectal adenomas and 42 patients with rectal carcinomas. Twenty-five patients had T1 tumors that were all successfully removed, with clear tumor margins, by TEM. Fourteen patients had T2 cancer and 3 of them (21%) required additional radical surgery due to incomplete excision. Local recurrence was observed in one patient with T2 cancer. There was no mortality. Major surgery, or radiotherapy-related complications requiring additional surgical intervention was needed in five patients with T2 cancer.

Conclusions: Local excision by TEM is a safe surgical procedure and should be offered to highly selected patients with early rectal cancer.

Background: The histologic status of axillary lymph nodes is one of the most important prognostic factors in breast cancer, influencing the management of these patients. Axillary lymph node dissection was traditionally performed in all patients to obtain this information but this procedure carries a considerable rate of complications. Recently, sentinel lymph node biopsy has emerged as an accurate and minimally invasive tool for predicting the axillary nodal status and has become the standard of care in selected patients with breast cancer.

Objective: To examine the accuracy of SLN[1] biopsies performed by surgical residents during surgical resident training.

Methods: This prospective, randomized controlled study included 100 consecutive patients with clinically early breast cancer (T1-T2, N0, M0) study. Lymphatic mapping was performed using radiotracers, blue dye, or both. Formal axillary lymph node dissection completed the operations in all patients. All operations were performed by surgical residents under the supervision of senior surgeons.

Results: The overall rate of identification of sentinel lymph nodes was 92%. The accuracy of SLN biopsy in reflecting the axillary nodal status was 96% with a false negative rate of 5.7%.

Conclusions: Sentinel lymph node biopsy is an accurate method for the evaluation and staging of regional lymph nodes in breast cancer patients. A dedicated instruction program for surgical residents may increase the standard of care and lead to highly trained surgeons in the management of early breast cancer.

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Background: Musculoskeletal complaints represent the second most common reason for visits to a physician, second only to the common cold. The limited capability of medical treatment for musculoskeletal disease requires modification of communication with patients by attending to their perception of the disease.

Objectives: To assess patients’ satisfaction with care provided by their primary physicians, and the relationship of patients' satisfaction to their expectations of that care, perceptions of physician performance, and perceived severity of musculoskeletal disease.

Methods: Questionnaires were administered to 90 community-dwelling elderly patients (mean age 76+-8 years) presenting for follow-up appointments with their primary care physicians. Patients were asked to report on their satisfaction with the medical care provided by the primary physicians for musculoskeletal symptoms, their expectations of that care, their perceptions of their primary physicians' interaction (regarding competence, performance, and communication), and their perceptions of disease severity (based on the number of areas involved, pain frequency and intensity, and impact on daily activity). The effects on the degree of satisfaction were assessed with regard to demographic variables, co-morbidity, site involved, and response to recommended treatment.

Results: Most patients (> 85%) expressed overall satisfaction with their doctor's interpersonal skills. Fewer (76.9%) were satisfied with the amount of effort their doctors spend evaluating their musculoskeletal symptoms, the information received regarding their musculoskeletal symptoms (75%), the degree of pain relief (75%), and the degree of functional improvement (61.8%). Level of education and response to recommended treatment for musculoskeletal disease were the only parameters associated with degree of satisfaction (higher education P = 0.005, lower education P = 0.059, medication P = 0.008, rehabilitation P = 0.076). A high level of expectations (regarding physician's care and musculoskeletal disease treatment) was noted.

Conclusions: The high level of patient satisfaction with their primary physicians' care for musculoskeletal symptoms may reflect the overall tendency of the elderly population to be satisfied with its primary care physicians. However, their high level of expectations (related to perceived efficacy of medical treatment) and their unrealistic perceptions of disease may lead to disappointment and non-compliance with their doctor's recommendations. Management of musculoskeletal disease in the elderly should address the patients’ disease perceptions, as well as their therapeutic and functional needs.
 

Background: Rectal administration of iodoacetamide induces colitis by blocking sulphhydryl groups and generating inflammatory mediators. Thalidomide, a non-barbiturate hyp­notic, also has an anti-inflammatory effect, presumably by suppressing the production of tumor necrosis factor alpha. In patients with Crohn’s disease, neutralization or suppression of TNFá reduces inflammation.

Objectives: To evaluate the effects of thalidomide in a model of experimental colitis.

Methods: Colitis was induced in rats by intracolonic administration of 3% iodoacetamide. In the treatment group, thalidomide 50 mg/kg was given daily by gavage and continued for 7 days until the rats were sacrificed. Their colons were then processed for wet weight, lesion area, weight of mucosal scraping, myeloperoxidase activity and histology. Serum levels of TNF were determined.

Results: Colonic wet weight, lesion area, myeloperoxidase activity and serum levels of TNFá were significantly lower (P<0.05) in the treatment group (iodoacetamide + thalido­mide) than the control group (iodoacetamide only). Histologi­cally, colonic inflammation in the treated group was markedly decreased.

Conclusions: Thalidomide effectively decreases colitis induced by iodoacetamide. The mechanism is probably associated with inhibition of TNFá, and should be further studied.
 

Background: Cell-mediated immunity is impaired in uremia. Cell-matrix interactions of immune cells such as CD4+T lymphocytes with extracellular matrix are an important requirement for an intact immune response. The adherence of CD4+T cells of healthy subjects (normal T cells) to ECM components is inhibited in the presence of uremic serum. Such decreased adhesive capacity is also found in T cells of dialysis patients. Various chemokines and cytokines affect the attachment of CD4+T cells to ECM.

Objective: To evaluate chemokine (MIP-1β and RANTES) and tumor necrosis factor α-induced adhesion of CD4+T cells to ECM in a uremic milieu.

Methods: We examined adhesion of normal CD4+T cells (resting and activated) to intact ECM in response to soluble or bound chemokines (MIP-1β and RANTES) and to TNF-α following incubation in uremic versus normal serum. Thereafter, we evaluated the adhesion of resting CD4+T cells from dialysis patients in a similar fashion and compared it to that obtained from a healthy control group.

Results: Addition of uremic serum diminished soluble and anchored chemokine-induced attachment of normal resting and activated CD4+T cells to ECM compared to a normal milieu (a peak response of 10–11% vs. 24–29% for soluble chemokines, P<0.001; 12–13% vs. 37–39% for bound chemokines on resting cells, P<0.01; and 18–20% vs. 45–47% for bound chemokines on activated cells, P<0.02). The same pattern of response was noted following stimulation with immobilized TNF-α (7 vs. 12% for resting cells, P<0.05; 17 vs. 51% for activated cells, P<0.01).  Adherence of dialysis patients’ cells to ECM following stimulation with both bound chemokines was reduced compared to control T cells (15–17% vs. 25–32%, P<0.0000). In contrast, adherence following stimulation by TNF-α was of equal magnitude.

Conclusions: Abnormal adhesive capacity of T lymphocytes to ECM in uremia may, in part, be related to a diminished response to MIP-1β, RANTES and TNF-α. However, whereas reduced adhesion to chemokines was present in both normal CD4+T cells in a uremic environment and in dialysis patients’ T cells, TNF-α-induced adhesion was found to be inhibited only in normal cells in a uremic milieu.

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ECM = extracellular matrix

TNF-α = tumor necrosis factor-a