Israel Medical Association Journal

The ubiquitin-proteasome pathway has a central role in selective degradation of intracellular proteins. Among the key proteins degraded by the system are those involved in the control of inflammation, cell cycle regulation and gene expression. With numerous important cellular pathways affected, derangements in the ubiquitin system were shown to result in a variety of human diseases including malignancies, neurodegenerative diseases and hereditary syndromes, and proteasome inhibition was implicated as a potential treatment for cancer and inflammatory conditions. Two proteasome inhibitors are currently under clinical evaluation for multiple myeloma and acute ischemic stroke. The ubiquitin system also has an important function in the immune and inflammatory response. It is involved in antigen processing and presentation to cytotoxic T cells, and the activation of nuclear factor-kappa B – the central transcription factor of the immune system. Since the proteasome is the central source of antigenic peptides that are presented to the immune system, some viruses, such as the Epstein-Barr virus, developed escape mechanisms that manipulate the ubiquitin-proteasome system in order to persist in the infected host. Understanding the mechanisms underlying the production of viral antigens by the ubiquitin-proteasome system may have therapeutic applications such as future development of vaccines.

Background: Major efforts are being directed at the early diagnosis of breast cancer. The diagnosis rate of non-palpable tumors is steadily growing as a result of increased screening by mammography. In most patients with non-palpable lesions, percutaneous image-guided biopsies have replaced wire localization with surgical excision for obtaining tissue diagnosis. In recent years the Israel Ministry of Health initiated a mammograpy screening program. Percutaneous image-guided biopsies have also become widely available.

Objective: To assess the impact of these changes on breast cancer surgical treatment in our hospital.

Methods: The charts of 483 patients operated on in our department for primary breast carcinoma during the years 1997 to mid-2001 were reviewed. Data on the mode of diagnosis, tumor stage, resection margins, and number and types of operations were recorded and analyzed. The term non-palpable tumors relates to tumors necessitating wire localization for surgical excision.

Results: The percentage of patients diagnosed with non-palpable tumors rose from 16.2% in 1997 to 47.4% in 2001, with an average size of 2.6 cm for palpable and 1.7 cm for non-palpable tumors. The rate of preoperative diagnosis for non-palpable tumors rose from 6.2% in 1997 to 96.4% in 2001. The rate of involved or very close margins was reduced by 73% in the patient group diagnosed preoperatively as compared to those without a preoperative diagnosis (10.6% vs. 39.4%). Finally, the percentage of patients who had two operations fell from 56.2% in 1997 to 11.1% in 2001.

Conclusions: The mammography screening program in Jerusalem in 1997–2001 was effective in increasing the relative percentage of non-palpable breast cancers with reduced tumor size at diagnosis. The improved availability of preoperative tissue diagnosis in these patients reduced the number of surgical procedures needed.

Background: The role of prostatic fossa radiation as salvage therapy in the setting of a rising prostate-specific antigen following radical prostatectomy is not well defined.

Objectives: To study the efficacy and safety of pelvic and prostatic fossa radiation therapy following radical prostatectomy for adenocarcinoma.

Methods: A retrospective review of 1,050 patient charts treated at the Sheba Medical Center for prostate cancer between 1990 and 2002 identified 48 patients who received post-prostatectomy pelvic and prostatic fossa radiotherapy for biochemical failure. Two patients were classified as T-1, T2A-9, T2B-19, T3A-7 and T3B-11. Gleason score was 2–4 in 9 patients, 5–6 in 22 patients, 7 in 10 patients and 8–10 in 7 patients. Positive surgical margins were noted in 28 patients (58%) of whom 18 had single and 10 had multiple positive margins. Radiation was delivered with 6 mV photons using a four-field box to the pelvis followed by two lateral arcs to the prostatic fossa.

Results: At a median follow-up of 34.3 months (25th, 75th) (14.7, 51,3) since radiation therapy, 32 patients (66%) are free of disease or biochemical failure. Exploratory analysis revealed that a pre-radiation PSA[1] less than 2 ng/ml was associated with a failure rate of 24% compared with 66% in patients with a pre-radiation PSA greater than 2 ng/ml (chi-square P < 0.006).

Conclusions: For patients with biochemical failure following radical prostatectomy early salvage radiation therapy is an effective and safe treatment option.

Background: Although the home is perceived to be a safe haven, it is a scene of numerous injuries.

Objectives: To characterize home injury in Israel, the victims, injury circumstances and outcomes, and to identify groups at high risk for injury in order to focus future interventions and thus effectively prevent these injuries and their associated hospitalizations.

Methods: We analyzed 5 year records (1997–2001) from the National Trauma Registry of all patients arriving at eight trauma centers following home injury and admitted to hospital, transferred to another medical center or died in the emergency department.

Results: The study group included 26,921 patients, constituting 34% of all unintentional hospitalized trauma patients. Twenty-seven percent were children (0–4 years) and 37% were elderly (≥ 65 years) – the two age groups whose home injury accounted for most of the trauma injuries. Among children more boys (59%) than girls (41%) were injured, but the opposite was true for the elderly (30% males and 70% females). The share of females among the home-injured increased with age. Falls caused 79% of all home injuries (97% among the elderly) and burns 9%, increasing to 18% among children (0–4 years). Among non-Jewish home-injured patients, infants predominated (50% compared to 20% among Jews). Moderate to critical injuries amounted for 42%, with 38% of the home injured and 60% of the elderly requiring surgery. The clinical and economic consequences of home injuries differed according to the type of injury, with burns carrying the heaviest toll of prolonged intensive care and hospital stay. Overall, hospital stay averaged 6.2 days per patient (median 3 days).

Conclusions: Falls among the elderly, burns among children, and a high prevalence of hospitalization among non-Jewish children define groups at high risk for home injuries. Prevention programs should be based on these findings and should focus on the more vulnerable groups.

Background: Laryngeal obstruction due to bilateral vocal cord immobility in adduction may cause dyspnea, hoarseness and dysphagia and can lead to dependence on a tracheostomy. Treatment poses a challenge because of the opposing functions of the larynx and the risk of neck and laryngeal tissue damage.

Objectives: To describe our experience with endoscopic CO₂-laser-assisted posterior ventriculocordectomy without tracheostomy for the treatment of bilateral vocal cord immobility in adduction.

Method: The study group consisted of five male and five female patients aged 17–81 years. The procedure was performed with an endoscope and operating microscope connected to a CO₂ laser. A C-shaped incision was made, and the posterior third of one vocal cord, the vocal process of the arytenoid, and the posterior third of the false vocal cord were excised. Tracheostomy was not performed.

Results: The technique allowed for a convenient approach to the difficult-to-view areas of the larynx. The procedure was short and bloodless, with minimal damage to laryngeal tissue and no local edema. Hospitalization time was short. Postoperatively, patients had sufficient breathing and mostly fair to good voice quality. None of the patients had severe aspirations and only three patients had mild aspirations.

Conclusions: We recommend this procedure for patients with bilateral vocal cord immobility prior to tracheostomy. Delaying surgery beyond the time of possible re-innervation may place the patient at risk of decompensation, which requires tracheostomy.

Background: Contralateral exploration of the groin has been common practice among pediatric surgeons for nearly 50 years, based on the high incidence of patent processus vaginalis on the contralateral side with the potential for the subsequent development of a hernia.

Objectives: To evaluate transinguinal laparoscopic examination of the contralateral side during repair of inguinal hernia in children in order to reach a decision regarding exploration of the contralateral side.

Methods: Over a of 21 month period 124 children with unilateral inguinal hernia underwent laparoscopic evaluation of the contralateral groin. The operations were performed under general anesthesia as ambulatory procedures.

Results: Transinguinal contralateral laparoscopic exploration was positive (patent processus vaginalis) in 26 children (21%) and negative (closed processus vaginalis) in 88 (71%). Failure to introduce the telescope occurred in 10 patients (8%) due to a friable or narrow hernia sac. Twenty-five children below 2 years of age were spared exploration of the contralateral side as a result of the negative laparoscopic examination. On the other hand, 15 children aged 2–17 had their contralateral groin explored because of a positive finding at laparoscopy.

Conclusions: Transinguinal laparoscopic examination of the contralateral side during repair of inguinal hernia in children is a simple, safe and quick method to avoid systematic bilateral explorations and should be part of every pediatric surgeon's experience.

Background: Dysphagia is a common disorder among the elderly population. As many as 50% of nursing home residents suffer from dysphagia. It is important to identify patients at increased risk for colonization of dental and denture plaque by pathogenic organisms for prevention of associated disease.

Objectives: To quantify the prevalence and evaluate the effect of dental and denture plaque colonization by Candida albicans in hospitalized elderly dysphagic patients as a complication of stroke, as well as the effect of systemic antimicrobial therapy on C. albicans colonization in these patients.

Methods: We evaluated dysphagia and antibiotic therapy as risk factors for dental and denture plaque colonization by C. albicans in elderly stroke rehabilitating patients with dysphagia, as compared to elderly non-dysphagic stroke and non-stroke rehabilitating patients on days 0, 7 and 14 following admission to the Fliman Geriatric Rehabilitation Hospital.

Results: The risk of C. albicans colonization of dental plaque was greater in dysphagic patients than in those without dysphagia on day 0 (50% vs. 21%, P = 0.076), day 7 (58 vs. 15.2%, P = 0.008) and day 14 (58 vs. 15.2%, P = 0.08). Similarly, patients on antibiotic therapy were at greater risk for C. albicans colonization of dental plaque on day 0 (56 vs. 11%, P = 0.002), day 7 (44 vs. 14.8%, P = 0.04) and day 14 (39 vs. 19%, P = 0.18). The risk of C. albicans colonization of denture plaque as opposed to dental plaques in non-dysphagic patients was significantly greater on day 0 (45.7 vs. 21.2%, P = 0.03), day 7 (51.4 vs. 15.1%, P = 0.0016) and day 14 (54.3 vs. 15.1%, P = 0.0007). Dysphagia did not increase the risk of denture plaque colonization by C. albicans.

Conclusiona: Both dysphagia and antibiotic therapy are risk factors for C. albicans colonization of dental plaque, and although dysphagia does not significantly increase colonization of denture plaque, denture wearers are at greater risk of such colonization.