Israel Medical Association Journal

Background: Uterine carcinosarcoma (UCS) is a rare tumor with a poor prognosis. An elevated thrombocyte count and thrombocytosis were found to be associated with poor prognosis in several gynecological tumors. Data regarding an elevated thrombocyte count and thrombocytosis, particularly in UCS, are scarce.

Objectives: To assess the frequency of a preoperative elevated thrombocyte count and of thrombocytosis in UCS patients and their association with clinicopathological prognostic factors and survival.

Methods: The preoperative thrombocyte count of 29 consecutive verified USC patients diagnosed in our medical center from January 2000 to July 2015 was recorded, and clinicopathological data of these patients were abstracted from hospital files. 

Results: Thrombocytosis was found in two patients (6.8 %) and both died of the disease. An elevated thrombocyte count was found in nine patients (31.0%). The percentage of patients with the poor prognostic factors who had a preoperative elevated thrombocyte count was not statistically different from those without these risk factors. The cumulative survival of patients with an elevated count was 22.1 months and that of those without an elevated count was 31.1 months. This difference was statistically not significant (P = 0.85). There was also no difference between the groups regarding the progression free survival.

Conclusions: No association between an elevated thrombocyte count and prognosis was found. Larger studies are needed to clarify this issue.

Background: The human papillomavirus (HPV) test has proven to be efficient in triaging women with abnormal Pap findings in women with low cytological atypia, but there is no data about the accuracy for large loop excision of transformation zone in cases of recurrent atypia.

Objectives: To assess the clinical correlation between results of HPV typing and conization histology in women who had recurrent abnormal Pap test results with no colposcopy findings.

Methods: Our retrospective cohort study included 138 women enrolled in the Maccabi Healthcare Services who had consecutive atypical Pap test results for 2 years in which no abnormal colposcopic findings were detected. These women had an HPV typing and then conization.

Results: Among the total study population (n=138), 71.7% had negative histology, 19.6% had ≤ cervical intraepithelial neoplasia grade 1 (≤ CIN1), and 8.7% had CIN2+. With regard to HPV typing, 34.8% were negative and 65.2% were positive. Of those testing positive, 34.4% were positive for HPV 16 or 18. Sensitivity, specificity, positive predictive value, and negative predictive values of HPV typing for women were 89.7%, 44.4%, 38.9%, and 91.7%, respectively, and for HPV 16 or 18: 71.4%, 67.7%, 32.3%, and 100.0%, respectively. After stratification by cytological grades, for women with high-grade cervical cytology, the sensitivity and negative predictive values of the HPV typing were higher than among low-grade cervical cytology, while specificity and positive predictive values were lower.

Conclusions: HPV typing is a useful tool for the management of patients with persistently abnormal Pap test results.

Background: Elevated serum levels of the epithelial marker CA125 are occasionally observed in leiomyosarcoma (LMS) patients.

Objectives: To assess the immunohistochemical expression of this marker in the tissue of LMS.

Methods: The consecutive unselected records of all patients with LMS diagnosed during the period 1995–2012 were located and abstracted. After verification of the diagnosis, 4 µm unstained slides were prepared from each case for immunohistochemical staining for CA125. Sections of ovarian carcinoma known to express CA125 were used as positive controls.

Results: We located 17 LMS patients from the period under study. Bleeding was the presenting symptom in 9 patients; the diagnosis was established prior to treatment in 11 patients. The tumor was in an advanced stage in 6 patients, and in 7 unstaged patients it was grossly confined to the uterus. Ten patients died within 14 months after the diagnosis. Serum CA125 levels prior to treatment were assessed in only 8 patients and were above normal limits (> 35 U/ml) in 3 of them. Two of the three with elevated serum levels were in stage III, and the third was an unstaged apparent stage I patient. None of the LMS tissue specimens demonstrated immunohistochemical expression of CA125.

Conclusions: CA125 was not immunohistochemically expressed in the tissue of any LMS tumors examined by us. The origin of elevated serum CA125 in some of these tumors is therefore not in its tissue and remains unknown. 

Background: Serum lactate dehydrogenase (LDH) is elevated in various diseases. 

Objectives: To analyze serum LDH as a distinguishing clinical biomarker and as a predictor of in-hospital outcome in admitted medical patients.

Methods: We analyzed a cohort of all 158 patients with very high isolated LDH (LDH ≥ 800 IU/ml – without concomitant elevations of alanine aminotransferase and aspartate aminotransferase) – admitted to our internal medicine department during a 3 year period. Epidemiologic and clinical data, as well as the final diagnosis and outcome were recorded and compared with those of a cohort of all 188 consecutive control patients.

Results: Very high isolated LDH was a distinguishing biomarker for the presence of cancer (27% vs. 4% in the LDH group and controls respectively, P < 0.0001), liver metastases (14% vs. 3%, P < 0.0001), hematologic malignancies (5% vs. 0%, P = 0.00019), and infection (57% vs. 28%, P < 0.0001). Very high isolated LDH was a marker for a severe prognosis, associated with more admission days (9.3 vs. 4.1, P < 0.0001), significantly more in-hospital major complications, and a high mortality rate (26.6% vs. 4.3%, P < 0.0001). Finally, very high isolated LDH was found in a multivariate regression analysis to be an independent predictor of mortality.

Conclusions: The presence of very high isolated LDH warrants thorough investigation for the presence of severe underlying disease, mostly metastatic cancer, hematologic malignancies and infection. Moreover, it is a marker for major in-hospital complications and is an independent predictor of mortality in admitted medical patients. 

Background: A growing number of Eritrean and Sudanese refugees seek medical assistance in the labor and delivery ward of our facility. Providing treatment to this unique population is challenging since communication is limited and pregnancy follow-up is usually absent.

Objectives: To compare the perinatal outcome of refugees and Israeli parturients.

Methods: The medical and financial records of all refugees delivered between May 2010 and April 2011 were reviewed. Perinatal outcome was compared to that of native Israeli controls.

Results: During this period 254 refugees were delivered (2.3% of deliveries). Refugees were significantly younger and leaner. They had significantly more premature deliveries under 37 weeks (23 vs. 10, P = 0.029) and under 34 weeks gestation (9 vs. 2, P = 0.036) with more admissions to the neonatal intensive care unit (15 vs. 5, P = 0.038). Overall cesarean section rate was similar but refugees required significantly more urgent surgeries (97% vs. 53%, P = 0.0001). Refugees had significantly more cases of meconium and episiotomies but fewer cases of epidural analgesia. There were 2 intrauterine fetal deaths among refugees, compared to 13 of 11,239 deliveries during this time period (P = 0.036), as well as 7 pregnancy terminations following sexual assault during their escape. Sixty-eight percent of refugees had medical fees outstanding with a total debt of 2,656,000 shekels (US$ 767,250).

Conclusions: The phenomenon of African refugees giving birth in our center is of unprecedented magnitude and bears significant medical and ethical implications. Refugees proved susceptible to adverse perinatal outcomes compared to their Israeli counterparts. Setting a pregnancy follow-up plan could, in the long run, prevent adverse outcomes and reduce costs involved in treating this population.

Objectives: To describe the phenotypic and genotypic features in five Bulgarian Jewish patients, from different families, with autosomal dominant OPMD.

Methods: We performed clinical follow-up, electrodiagnostic tests and mutation detection. Blood samples were obtained after informed consent and DNA was extracted; measurement of GCG repeats in both PABPN1 alleles and sequencing of OPMD mutations were performed according to standard techniques.

Results: We identified five patients (four females), aged 58 to 71 years, with bilateral ptosis, dysphagia, dysphonia (n=3) and myopathic motor units by electromyography. In all patients we noticed proximal weakness of the upper limbs with winging scapulae in three of them. All cases shared the (GCG)13-(GCG)10 PABPN1 genotype.

Conclusions: OPMD among Bulgarian Jews is produced by a (GCG)13 expansion, identical to the mutation in Uzbek Jews and French Canadians. In addition to the classical neurological and neuro-ophthalmological features, early shoulder girdle weakness is common in Bulgarian Jewish patients; this is an unusual feature during the early stages of OPMD produced by the same mutation in other populations. We suggest that besides the disease-producing GCG expansion, additional ethnicity-related genetic factors may influence the OPMD phenotype. OPMD is a rare disease, and the identification of five affected families in the rather small Bulgarian Jewish community in Israel probably represents a new cluster; future haplotype studies may elucidate whether a founder effect occurred. 

Objectives: To investigate the occurrence and to classify sport-related eye trauma in northern Israel.

Methods: We analyzed the records of the ophthalmology emergency department for the years 2007–2011 and classified the admissions according to type, severity of injury and demographic data.

Results: In 2% of the patients the injuries occurred during a sport activity. Most of the injuries occurred during soccer, basketball or school sport activity (74%). The majority of patients were young males.

Conclusions: Most sports-related eye injuries can be prevented with adequate eye protection.

Background: Hypovitaminosis D is common worldwide, even in sunny regions.

Objectives: To assess the prevalence and determinants of vitamin D deficiency in toddlers.

Methods: A cross-sectional prospective study was conducted in healthy Jewish children aged 1.5–6 years at five primary care pediatric clinics in the Jerusalem area during the period October 2009 to November 2010. Parents were interviewed regarding personal and demographic data and sun exposure. Blood samples were obtained for serum 25-hydroxyvitamin D [25-OHD] level. Vitamin D deficiency and insufficiency were defined as 25-OHD < 20 ng/ml and < 30 ng/ml, respectively.

Results: Of 247 children studied, 188 (76%) were ultra-Orthodox and 59 (24%) were Orthodox, traditional or secular. Mean (± SD) 25-OHD level was 25.7 ± 10 ng/ml. Only 73 children (29.6%) had sufficient 25-OHD levels, 104 (42.1%) had insufficiency, and 70 (28.3%) had 25-OHD deficiency. The difference between ultra-Orthodox and others was insignificant (25 ± 10 vs. 27.8 ± 10.5 ng/ml respectively, P = 0.062). Children aged 1.5–3 years had higher 25-OHD levels than those aged 3–6 years (28.6 ± 10.7 and 24 ± 9.2 ng/ml respectively, P < 0.001). Vitamin D deficiency was more common in winter (53%) and autumn (36%) than in summer (19%) and spring (16%). Toddlers attending long-day kindergartens had higher 25-OHD level than those staying at home or at short-day kindergartens (28.8 ± 11.5 and 24.7 ± 9.6 ng/ml respectively, P < 0.05).

Conclusions: A high prevalence of vitamin D deficiency was found in toddlers in our study, mainly in older children and in the winter and autumn. We recommend routine supplementation of vitamin D for children beyond the agear.

Background: The number of patients treated with intravitreal injections has increased significantly over the past few years, mainly following the introduction of anti-vascular endothelial growth factor antibody intraocular medications. Bevacizumab is mostly used in this group of medications.

Objectives: To describe persistent elevation of intraocular pressure (IOP) following intravitreal injection of bevacizumab.

Methods: We reviewed consecutive cases of persistent IOP elevation after intravitreal bevacizumab injection for exudative age-related macular degeneration (AMD). A total of 424 patients (528 eyes) met the inclusion criteria and received 1796 intravitreal injections of bevacizumab. Persistent IOP elevation was found in 19 eyes (3.6%, 19/528) of 18 patients (4.2%, 18/424) with IOP elevated 30–70 mmHg, 3–30 days after injection.

Results: Mean IOP was 42.6 mmHg (range 30–70); IOP elevations occurred after an average of 7.8 injections of bevacizumab (range 3–13). Injected eyes (19/528) had a significantly higher incidence of elevated IOP than uninjected eyes (fellow eyes), 1/328, P < 0.001.

 Conclusions: Like other anti-vascular endothelial growth factor (VEGF) substances reported in a few recent studies, intravitreal injection of bevacizumab for neovascular AMD may be associated with persistent IOP elevation. Providers should be aware that significant IOP elevation might occur after repeated treatments. 

Objectives: To describe the outcomes of radical prostatectomy as perceived by the patients, and their ways of coping with them.

Methods: We conducted a qualitative study of 22 men with localized prostatic cancer 1 year after surgery. The key questions related to the effect of the disease and the surgery on their lives and their view on the value of the surgery.

Results: The surgery was perceived as a necessary solution for the diagnosed cancer. All the participants suffered from varying degrees of urinary incontinence and erectile dysfunction. Urinary incontinence caused severe suffering. The impaired sexual ability affected relations with partners and led to feelings of shame and guilt and a decreased sense of self-esteem. In retrospect, the participants still viewed the surgery as a life-saving procedure. Faith in the surgeon contributed to their affirmation of the decision to undergo surgery despite the difficulties.

Conclusions: Patients were prepared to suffer the inevitable physical and psychological sequelae of radical prostatectomy because they believed the surgery to be a definitive solution for cancer. Surgeons advising patients with localized prostatic cancer on treatment options should address these difficult issues and provide psychological support, either themselves or in collaboration with professionals.

Background: Corneal haze is a significant complication of photorefractive keratectomy (PRK) and laser-assisted sub-epithelial keratectomy (LASEK).

Objectives: To evaluate the effect of ascorbic acid supplementation in addition to perioperative topical mitomycin-C for the prevention of haze after LASEK.

Methods: We performed a retrospective, non-randomized case series study of two groups of 48 consecutive patients (96 myopic eyes) who had LASEK surgery. The treatment group was given ascorbic acid (vitamin C) orally 500 mg twice daily from 1 week before to 2 weeks after surgery. The control group was not offered any additional treatment. Ascorbate supplementation was the only difference in the postoperative treatment protocol between the treatment and control groups. Haze was assessed on a scale from 0 to 4 at the 1 year visit.

Results: Overall, 33.3% and 37.5% of the patients in the treatment and control groups respectively developed corneal haze. The trend of increased haze severity in the control group did not reach statistical significance.

Conclusions: Our results showed that systemic ascorbate supplementation does not have an additional effect on the prevention of haze after LASEK compared to the effect of topical mitomycin-C alone.