Israel Medical Association Journal

The cause for gender differences in the epidemiology, natural history and response to therapy in many diseases is unknown and has seldom been investigated in depth. Sex hormones are blamed for many of these changes, mostly without any scientific evidence. In this review I will describe some of the evidence for gender differences in gastrointestinal diseases. Gender medicine and its application for gastroenterology is a new field and one warranting research.
 

Background: Increased cardiovascular morbidity has become a leading cause of mortality in rheumatoid arthritis (RA). Tumor necrosis factor-alpha (TNFα) inhibitors may influence flow-mediated vasodilation (FMD) of the brachial artery, common carotid intima-media thickness (ccIMT) and arterial stiffness indicated by pulse-wave velocity (PWV) in RA.

Objectives: To assess the effects of adalimumab treatment on FMD[1], ccIMT[2] and PWV[3] in early RA[4].

Methods: Eight RA patients with a disease duration ≤ 1 year received 40 mg adalimumab subcutaneously every 2 weeks. Ultrasound was used to assess brachial FMD and ccIMT. PWV was determined by arteriograph. These parameters were correlated with C-reacive protein, vonWillebrand factor (vWF), immunoglobulin M (IgM)-rheumatoid factor (RF), anti-CCP levels and 28-joint Disease Activity Score (DAS28).

Results: Adalimumab therapy successfully ameliorated arthritis as it decreased CRP[5] levels (P = 0.04) and DAS28[6] (P < 0.0001). Endothelial function (FMD) improved in comparison to baseline (P < 0.05). ccIMT decreased after 24 weeks, indicating a mean 11.9% significant improvement (P = 0.002). Adalimumab relieved arterial stiffness (PWV) after 24 weeks. Although plasma vWF[7] levels decreased only non-significantly after 12 weeks of treatment, an inverse correlation was found between FMD and vWF (R = -0.643, P = 0.007). FMD also inversely correlated with CRP (R = -0.596, P = 0.015). CRP and vWF also correlated with each other (R = 0.598, P = 0.014). PWV and ccIMT showed a positive correlation (R = 0.735, P = 0.038).

Conclusions: Treatment with adalimumab exerted favorable effects on disease activity and endothelial dysfunction. It also ameliorated carotid atherosclerosis and arterial stiffness in patients with early RA. Early adalimumab therapy may have an important role in the prevention and management of vascular comorbidity in RA.

Background: Meningiomas are frequently detected incidentally. Their natural history has not yet been established because it is difficult to predict the growth pattern. Therefore, the management, after the radiological diagnosis, is still controversial.

Objectives: To evaluate the clinical outcome and growth rate of conservatively treated meningiomas at our tertiary center, identify prognostic factors of tumor growth, and suggest guidelines based on the available data and our experience.

Methods: We reviewed the clinical records of 56 patients with 63 untreated meningiomas. Most were diagnosed incidentally. Clinical features and imaging findings at diagnosis and during follow-up were compared between growing and non-growing tumors. Potential patient- and tumor-related predictive factors for growth were analyzed.

Results: The study group included 46 women (52 meningiomas) and 10 men (11 meningiomas) aged 39–83 years. Mean tumor size was 18 ± 11 mm (range 3–70 mm) at diagnosis and 22 ± 11 mm (range 8–70 mm) at last follow-up; mean follow-up time was 65 ± 34 months (range 15–152 months). During follow-up 24 tumors (38%) grew at a rate of 4 mm per year; none became symptomatic. Only two prognostic factors were statistically significantly associated with low growth rate: older age and tumor calcifications.

Conclusions: Given our finding of a low growth incidence of meningiomas in the elderly, we support conservative management in patients aged 70 years or older. Calcifications into the meningioma are also indicative of slow growth, suggesting a conservative strategy. Surgery is recommended in younger patients in whom tumor growth occurs more often and a longer follow-up is necessary.
 

Background: Survival in T cell lymphoblastic lymphoma has improved over the past 30 years, largely due to treatment protocols derived from regimens designed for children with acute lymphoblastic leukemia.

Objectives: To assess the outcome of the NHL-BFM-95 protocol in children and adolescents hospitalized during the period 1999–2006.

Methods: We conducted a retrospective multi-institutional, non-randomized study of children and adolescents up to age 21 with T cell lymphoma admitted to pediatric departments in six hospitals in Israel, with regard to prevalence, clinical characteristics, pathological characteristics, prognostic factors, overall survival (OS) and event-free survival (EFS). All patients had a minimal follow-up of one year after diagnosis. The study was based on the NHL[1]-BFM[2]-95 protocol.

Results: At a median follow-up of 4 years (range 1–9 years), OS and EFS for all patients was 86.5% and 83.8%, respectively. OS was 86.7% and 83.3% for patients with stage III and stage IV, respectively, and EFS was 83.3% and 83.3%, respectively. EFS was 62.5% for Arab patients and 89.7% for Jewish patients (P = 0.014). Patients who did not express CD45 antigen showed superior survival (P = 0.028). Five (13.5%) patients relapsed, four of whom died of their disease. Death as a consequence of therapy toxicity was documented in one patient while on the re-induction protocol (protocol IIA).

Conclusions: Our study shows that OS and EFS for all patients was 86.5% and 83.8%, respectively.

Background: During military escalations emergency departments provide treatment both to victims of conflict-related injuries and to routine admissions. This requires special deployment by the hospitals to optimize utilization of resources.

Objectives: To evaluate “routine” visits to the ED[1] during Operation Cast Lead in Israel in 2008–2009.

Methods: We obtained data regarding routine visits to the ED at Soroka University Medical Center throughout OCL[2]. The visits one month before and after OCL and the corresponding periods one year previous served as controls.

Results: The mean number of daily visits throughout the study period (126 days) was 506 ± 80.9, which was significantly lower during OCL (443.5 ± 82) compared with the reference periods (P < 0.001). Compared to the reference periods, during OCL the relative rates were higher among Bedouins, visitors from the region closest to the Gaza Strip (< 30 km), patients transported to the ED by ambulance and patients of employment age; the rates were lower among children. No difference in the different periods was found in the rate of women patients, distance of residence from Beer Sheva, rate of patients referred to the ED by a community physician, and hour of arrival. The overall in-hospital admission rate increased during OCL, mainly in the internal medicine and the obstetric departments. There was no change in the number of in-hospital births during OCL; however, the rate of preterm labors (32–36 weeks) decreased by 41% (P = 0.013).

Conclusions: Throughout OCL the number of routine ED visits decreased significantly compared to the control periods. This finding could help to optimize the utilization of hospital resources during similar periods.

Background: Uterine sarcoma constitutes a highly malignant group of uterine tumors. It accounts for 2–6% of uterine malignancies and its incidence is 1.7 in 100,000 women. The three most common variants of uterine sarcoma are endometrial stromal sarcoma, leiomyosarcoma and carcinosarcoma. Based on relatively small case series, the literature provides little information on the risk factors, the natural course of the disease and the preferred treatment.

Objectives: To evaluate uterine sarcoma patients treated in a tertiary referral center in Israel over a 20 year period (1980–2005).

Methods: We conducted a retrospective review of the charts of 40 uterine sarcoma patients, including their tumor characteristics, stage at diagnosis, treatment modalities, follow-up and survival.

Results: The patients’ mean age was 53 years (range 32–76); 30% of the patients had carcinosarcoma, 55% had leiomyosarcoma and 15% had ESS[1]. Half of the patients presented with stage I disease, 23% stage II, 10% stage III and 15% stage IV. Thirty-nine patients were treated by surgery. Adjuvant radiotherapy was administered to 39% of the patients, adjuvant chemotherapy to 21% and combined radiotherapy and chemotherapy to 9%. The mean follow-up period was 44 months, at which time disease had recurred in 44% of the patients. The disease stage was correlated with the 5-year survival rate, which was 73.1% for stages I-II and 22.2% for stages III- IV.

Conclusions: In accordance with other larger studies our data show that the only prognostic factor that was significantly correlated with prognosis was the stage of the disease at diagnosis. Despite advances in diagnosis and treatment, survival has not improved over the last 25 years.

Background: Routine histopathological analysis of bone extracted during total joint replacement is controversial.

Objectives: To evaluate the utility of routine histopathological analysis in total joint replacement.

Methods: We calculated the risk for discrepant diagnosis between the pre- and postoperative histopathological results by performing a meta-analysis of 11 studies (including our data). We also calculated the risk for significant discrepancies.

Results: The discrepant diagnoses analysis showed a random effect of 3% discrepancies (95% confidence interval 1.2–3.7%). Funnel plot indicates a publication bias; consequently, the conclusions from this analysis should be interpreted with caution. Regarding the significant discrepancy in diagnosis, we performed a meta-analysis of nine studies. Fixed-effects analysis of all the studies resulted in 0.16% significant discrepancies (95% CI[1] 0.02–0.30%) with no heterogeneity (Q = 3.93, degrees of freedom = 9, P = 0.14, I² = 49.2%), and appropriate fixed-effects models.

Conclusions: We recommend no further routine histological examination, reserving this tool for cases with a controversial primary diagnosis and unexpected findings during the operation.

Background: The age-standardized incidence rate of invasive cervical cancer in Israeli Jewish women is persistently low. Selected demographic characteristics of Israeli Jewish women with cervical squamous cell carcinoma (SCC) were reported recently. 

Objectives: To assess selected clinical characteristics of Israeli Jewish women with cervical SCC.

Methods: Included were all Israeli Jewish women with SCC diagnosed during the 3-year period 2002­–2004. Data were obtained from the Israel National Cancer Registry and the Central Population Registry. Discharge summaries of the patients were reviewed and clinical data were abstracted.

Results: The study was based on 350 Israeli Jewish women with histologically confirmed cervical SCC diagnosed during the 3-year study period. The median age of the patients was 50.3 years. The most common main complaint was discharge/bleeding (35.7%) and only a small percentage (7.4%) was diagnosed subsequent to an abnormal cytological smear. The rate of patients diagnosed in stage I was 47.7%. The overall absolute 5-year survival and survival in stage I was 70% and 83.8% respectively. The rate of Israeli born patients diagnosed in stage I and their overall absolute 5-year survival was significantly higher than in the other ethnic groups.

Conclusions: Age, the most frequent main complaint, the percent of patients diagnosed in stage I and the 5-year survival (overall and in stage I) are similar to data in other countries. The survival of Israeli born women seems to be better than that of other ethnic groups.
 

Background: The diagnostic and therapeutic approach to hilar cholangiocarcinoma and thus the prognosis have changed significantly over the last two decades. Nonetheless, hilar  cholangiocarcinoma  presents a complex surgical challenge.

Objectives: To assess the outcome of the radical approach for the management of types III and IV hilar  cholangiocarcinoma.

Methods: We conducted a retrospective single-center study. Preoperative diagnosis was based on ultrasound, computed tomography and selective percutaneous cholangiography without tissue diagnosis. Surgery was radical and included en-bloc liver, extrahepatic biliary tree and hilar lymph nodes resection, followed by biliary reconstruction with hepatico-jejunostomy.

Results: Fifteen patients (mean age 49 years, range 24–72) were managed accordingly. Anatomic classification of the biliary involvement was Bismuth-Corlette type IIIA (n=4), type IIIB (n=3) and type IV (n=8). The surgical procedures performed included four right hepatic lobectomies, five left hepatic lobectomies and six trisegmentectomies (all extended to the caudate lobe). Complete negative resection margins (R0) were accomplished in 12 cases (80%). Regional lymph node metastases were detected in five cases. There were two perioperative mortalities. Long-term follow-up (mean 30 months, range 6–72) revealed local recurrences in two cases, distant metastases in three, and both local and distant in two cases. Eleven patients are alive and 6 are without evidence of disease. The overall 2- and 5-year survival is 78% and 38% respectively.

Conclusions: In selected patients, the aggressive surgical approach to hilar cholangiocarcinoma is justified and can result in long-term survival.
 

Background: Concomitant human immunodeficiency virus and human papillomavirus infection increases both HPV[1] persistence and the risk of invasive cervical cancer. An estimation of HPV prevalence among HIV[2]-positive women in Israel would contribute to improving care for this population and preventing morbidity and mortality related to cervical cancer.

Objectives: To determine the prevalence of HPV infection and cervical cytology abnormalities, and to assess the possible influence of HIV infection on HPV carriage in HIV-positive women attending the Infectious Disease Clinic at Soroka University Medical Center.

Methods: The study population included 84 HIV-seropositive women. They were examined by a gynecologist and screened for HPV genotyping, and Pap smears were obtained for cervical cytology. Demographic, behavioral, and HIV infection variables were also recorded and analyzed.

Results: Forty-nine (58.3%) of the study participants were HPV-positive; 34 of them had oncogenic genotypes. Young age (< 16 years) at first sexual intercourse was the only variable significantly associated with HPV infection (P < 0.05). Abnormal cervical cytology was present in 17 women (20.3%); 21 women were referred to colposcopy, which was abnormal in 9 (10.7%).

Conclusions: The prevalence of HPV carriage among HIV-positive woman in our study was slightly higher than published elsewhere. The prevalence of pathological cervical cytology was much higher than in the general population. An extremely high prevalence of pathological colposcopies requiring further treatment was found. Screening for HPV and premalignant changes in the uterine cervix is highly recommended in the HIV-seropositive population. We suggest that colposcopy be considered part of the routine workup in HIV-seropositive woman.