Fine-needle aspiration cytology of sarcomatoid renal cell carcinoma: A morphologic and immunocytochemical study of 15 cases

Sarcomatoid renal cell carcinoma (SRCC), which accounts for 5% of all renal cell carcinomas (RCC), has a worse prognosis than conventional nonsarcomatoid RCC. making accurate diagnosis important. This study reports on the morphologic and immunocytochemical features of 15 cases of SRCC (9 primary tumors and 6 metastases) diagnosed by fine-needle aspiration (FNA) biopsy. All but three cases showed a dimorphic cell population consisting of varying proportions of a high-grade epithelial component, either clear or granular-cell type and a spindle cell (sarcomatoid) component, of either fibrosarcomatous, malignant fibrous histiocytoma (MFH), or unclassified types. The sarcomatoid component in the biphasic and monophasic tumors stained positively for cytokeratin in 12 of 14 (85%) cases, for vimentin in 10 of 11 (91 %) cases, and for muscle-specific action in 4 of 11 (36%) cases. Of note, the three cases that demonstrated a purely sarcomatoid morphology stained positively for cytokeratin. Unlike in studies performed on surgically resected specimens, neither the proportion of the sarcomatoid component nor the presence of necrosis had prognostic significance, the discrepancy most likely being related to the sampling. We conclude that SRCC, both primary and metastatic, can be accurately diagnosed by FNA when cytologic features are evaluated in conjunction with immunocytochemical findings.     

Hemorrhagic complications in patients treated with anticoagulant doses of a low molecular weight heparin (enoxaparin) in routine hospital practice.

Low molecular weight heparins (LMWHs) are a rapidly growing class of anticoagulant drug. Their efficacy has been demonstrated in several clinical settings where they are rapidly becoming the anticoagulant of choice. Controlled clinical studies in patients with deep vein thrombosis, pulmonary embolism, and unstable angina have documented that the frequency of major hemorrhage is 0.5-4%. The purpose of the study was to determine the frequency of minor and major hemorrhage occurring in patients receiving anticoagulant doses of an LMWH (enoxaparin) during routine clinical practice. A prospective, observational study of consecutive patients receiving enoxaparin 1 mg/kg twice daily for at least 24 hours in five internal medicine wards of a university teaching hospital was performed. Five hundred forty-nine patients were studied. The mean age was 67.5+/-15.5 years and the mean duration of enoxaparin therapy was 3.8+/-1.5 days. Hemorrhage was documented in a total of 94 patients (17.3%). Major hemorrhage occurred in 14 patients (2.6%), injection-site hemorrhage occurred in 55 patients (10%), and minor hemorrhage (noninjection site) was documented in 25 patients (4.7%). There were two deaths attributed to hemorrhage. Patients with major hemorrhage were older than patients with minor or no hemorrhage (75.5+/-10.4 versus 66.8+/-15.2 years; p=0.03) and occurred in patients receiving enoxaparin for a longer period (5.14+/-3.8 days) than those with minor (4+/-2.5 days) or no hemorrhage (2.9+/-2.1 days). Major hemorrhage was significantly associated with impaired renal function, chronic liver disease, and concomitant treatment with warfarin or a proton pump inhibitor. Enoxaparin used in anticoagulant doses in unselected medical patients is not associated with more major hemorrhagic complications than observed in controlled clinical trials. Major hemorrhage may be more likely in older patients, in patients with chronic liver disease and impaired renal function, in patients receiving prolonged enoxaparin therapy, and in patients receiving warfarin or proton pump inhibitors.     

Chairing the internal medicine department- analysis of current state and future trends in Israel

Background

Professional skills and academic records of the highest degree are essential requirements for the chairmanship of internal medicine departments. Whether the new generation and future successors of Israeli chairmen is endowed with these attributes is not known.

Purpose

To determine whether there is a lack of future suitable successors for the current heads of internal medicine departments in Israel and to compare the demographic, academic and professional characteristics of the older and newer generations of department heads.

Methods

An online anonymous questionnaire was nationally distributed during 2016 to all active heads of internal medicine departments in Israel (n?=?101). First round was followed by two runs of personal phone calls to promote participation.

Results

Sixty-seven (67%) of chairmen responded. The vast majority of current chairs of internal medicine departments are males (N?=?59, 88%) over 50 years of age (N?=?58, 86%) with established academic background with lecturer degree or higher (N?=?57, 85%).Only 19 (28%) of current heads assigned a future successor. Comparison of chairmen who did and did not assigned successors demonstrated that assignment of successors was associated with higher academic status (P?<?0.02) and longer chairmanship (p?<?0.01) but not with mean age of current chairmen (p?<?0.08). Nevertheless, most assignments (55%) were done by chairmen in the 61 to 67 years age group. As compared to current chairmen, the designated successors have lesser academic status (p?<?0.01) and are characterized by a higher female prevalence (P?<?0.03).

Conclusions

Significant demographic, professional and academic differences exist between the current chairs of internal medicine departments in Israeli hospitals and their future successors. This underscores the need for reassessment of the availability and requirements of this crucial position.

     

From the Cover: Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2

In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts (P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations.Inherited mutations in BRCA1 and BRCA2 predispose to high risks of breast and ovarian cancer. Among female mutation carriers, presymptomatic surgical measures significantly reduce morbidity and mortality (1, 2). In particular, risk-reducing salpingo-oophorectomy (i.e., the removal of ovaries and fallopian tubes from a woman without ovarian cancer) reduces risk both of breast cancer and of ovarian cancer, as well as overall mortality (1). However, for many mutation carriers identified following their first cancer diagnosis, genetic testing was not previously indicated because family history did not suggest inherited cancer predisposition (3–5, 6). From a prevention perspective, it is a missed opportunity to identify a woman as a BRCA1 or BRCA2 mutation carrier only after she develops cancer.Among Ashkenazi (European) Jews (AJ), three mutations, BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT, account for the great majority of inherited cancer risk due to BRCA1 and BRCA2 (7). In the AJ population, 2.5% of persons carry one of these three mutations (8), and the mutations account for 11% of breast cancer (3) and 40% of ovarian cancer (9, 10). These observations suggest that genetic testing in the AJ population for these mutations fulfills WHO criteria for population screening (11, 12): The disease is an important public health burden to the target population; prevalence and attributable risk of disease due to the mutations are known; and effective interventions exist. However, one necessary piece of information remains unknown: What is the disease risk to mutation carriers ascertained from the general population, rather than carriers identified based on family history (13)?Previous studies assessing cancer risks due to mutations in BRCA1 and BRCA2 ascertained carriers through high-incidence families (14), through a single index case with breast or ovarian cancer (3, 15) or through both affected and unaffected carriers (16). In a 1997 study of AJ volunteers, most index cases had no previous cancer diagnosis, but the percentage of index cases with a family history of breast cancer was approximately double that of unselected AJs (17). In principle, these strategies could have yielded risk estimates different from those of carriers ascertained from the local host population, if cancer risk in BRCA1 or BRCA2 carriers were influenced by familial factors other than the BRCA1 or BRCA2 mutation, such as modifier genes or shared environment (18). In addition, in almost all of these studies, risk estimates were based on imputing carrier status, rather than on direct genetic testing of BRCA1 and BRCA2. This year, the Recommendation Statement on BRCA Testing from the US Preventive Services Task Force recommended against population screening for BRCA1 and BRCA2 mutations, because cancer risk to mutation carriers in the general population was not yet known (19). To address this gap, in this study we assessed breast and ovarian cancer risks in confirmed carriers of BRCA1 and BRCA2 mutations ascertained from the general population. The study was undertaken in the AJ population, because screening for only three founder mutations is sufficient to capture nearly all inherited cancer risk in this population due to BRCA1 and BRCA2 (7).     

Association between alopecia and response to chemotherapy in patients with Hodgkin lymphoma

Alopecia and bone marrow suppression are prominent effects of doxorubicin-containing chemotherapy. The aim of the study was to validate our preliminary clinical observation that the lack of alopecia in Hodgkin lymphoma patients may predict poor response to chemotherapy and low rate of bone marrow suppression. Sixty-six patients with Hodgkin lymphoma were reviewed. They were treated between 1991 and 2001 with at least 4 courses of doxorubicin-containing chemotherapy (MOPP/ABV or ABVD) in 2 university-affiliated hematology departments. Thirty-four patients exhibited complete or near complete alopecia, and 32 retained their hair or had only minimal hair loss. The 2 groups were compared by response to treatment and episodes of bone marrow suppression. Alopecia was associated with a high rate of remission (OR 8.48, 95% CI 2.77-25.95), episodes of neutropenia (OR 3.55, 95% CI 1.28-9.84), leukopenia (OR 1.83, 95% CI 0.68-4.92), delays in scheduled treatments (OR 1.61, 95% CI 0.607-4.30), or number of courses with dose reduction (OR 1.63, 95% CI 0.56-4.74). Significantly more patients with alopecia had at least 1 of these parameters (88% versus 62%, P=0.015; OR 4.50, 95% CI 1.27-15.94). In conclusion, in patients with Hodgkin lymphoma treated with doxorubicin-containing chemotherapy, the absence of alopecia may predict poor response to treatment along with fewer episodes of bone marrow suppression. The absence of alopecia in such patients should alert clinicians to the possibility of treatment failure.     

Delayed diagnosis of tracheoesophageal prosthesis aspiration

In 1980, Singer and Blom published the results of their study on use of the tracheoesophageal puncture prosthesis for restoration of voice after total laryngectomy. Since then, the placement of tracheoesophageal puncture prostheses has been an integral part of rehabilitation after laryngectomy. Complications of this procedure have been recognized and are usually minimal. Inadvertent aspiration of the prosthesis is rare. Usually, patients seek help immediately after the incident. We report a case of unnoticed aspiration of a Blom-Singer prosthesis in a patient with a laryngectomy.     

The use of otic powder in the treatment of acute external otitis

BACKGROUND: Acute external otitis (AEO) is a painful condition that results as a secondary infection of macerated skin and subcutaneous tissues of the external auditory canal. The most commonly causative microorganisms are Pseudomonas aeruginosa and Staphylococcus aureus. Classic management strategies include moisture prevention, cleansing of the canal and administration of topical antimicrobial agents in drop form, such as aminoglycosides and quinolones, at times in combination with steroid solutions. The objective of this study was to evaluate and compare the efficacy of topical otic powder, tobramycin drops and ciprofloxacin drops in patients suffering from AEO. MATERIALS AND MEASURES: A randomized prospective trial was performed to determine the efficacy of Auricularum powder (dexamethasone 10 mg, oxytetracycline HCl 90,000 U, polymyxin B Sulfate 100,000 U, nystatin 1,000,000 U; Trima, Serolam Laboratories, Germany) compared with ciprofloxacin (Ciloxan, Alcon Laboratories, Fort Worth, TX) and tobramycin (Tobrex, Alcon Laboratories) drops for the treatment of AEO. One hundred twenty patients who presented with signs and symptoms of AEO were enrolled. Inclusion criteria were: AEO diagnosed by an otolaryngologist, patient age 18 years, no prior treatment with other drops or systemic antibiotics, no sensitivity to any of the drugs used or their contents, and no perforation of the tympanic membrane. All patients were instructed to avoid moisture and wetness of the ear during the course of their treatment. After we received informed consent, a swab culture was taken, and the patient was randomly assigned topical treatment for 14 days. RESULTS: Eighty-six percent of those treated with Auricularum powder were cured at day 3-4 after initial treatment. Seventy-seven percent of those treated with ciprofloxacin drops, and fifty-six percent of those treated with tobramycin were cured at that time. All 120 patients were cured by day 14. CONCLUSION: The results show that topical treatment with Auricularum powder is an effective and rapid method for the treatment of AEO. Ciloxan also was effective in the treatment of AEO and relieved symptoms quickly and efficiently in a short period of time. Tobrex was effective in treating AEO, but our results show that relief of symptoms was slower than with the other drugs.     

Novel concepts in the staging of renal cell carcinoma

The incidence of renal cell carcinoma (RCC) continues to rise steadily; unfortunately, our ability to cure patients with metastatic RCC remains limited. When developing and evaluating new treatment protocols, it is important to consider the role of prognostic factors, often defined as pretreatment features, that are predictive of outcome. The complexity and variability of patients’ individual clinical outcome and the recently recognized limitation of conventional staging systems have lead to the formulation of integrated prognostic staging systems. In this review, we discuss the evolution of various clinically relevant integrated staging systems for RCC.     

High prevalence of low serum vitamin B12 in a multi-ethnic Israeli population

This study ascertained serum vitamin B12 levels among patients with Gaucher disease and among healthy Israelis. Serum B12 and metabolites' levels were studied in consecutive adult patients with Gaucher disease not treated with enzyme plus Ashkenazi Jewish neighbour-controls, together with healthy blood-donor volunteers of various ethnicities. Each group showed a high incidence of low serum B12 concentrations, with a 22.3% incidence among Ashkenazi Jews and 40% among patients with Gaucher disease. These findings raise questions on the individual and community levels of serum B12. We recommend evaluation of B12 levels among geographically contingent peoples.