Israel Medical Association Journal

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: Infiltrating ductal carcinoma and infiltrating lobular carcinoma account for more than 90% of all invasive breast cancer histological types. The rate of ILC[1] is reported to be increasing steadily in the United States and Europe.

Objectives: To describe the trend in the incidence of ILC in a large cohort of patients who underwent surgery in a single institution over an 18 year period.

Methods: Our comprehensive database of 2175 consecutive patients with invasive breast cancer diagnosed during the period 1992–2009 served for the analysis. Several potential factors associated with lobular carcinoma as compared with ductal carcinoma were evaluated.

Results: During this period, a 2.4-fold increase in the incidence of pure ILC was noted, from 4.6% in the years 1992–1994 to 10.9% in 2004–2006, followed by a modest decrease to 8.7% in 2007–2009. A significant association of lobular malignancies with external hormonal use was noted, including hormone replacement therapy exposure in patients diagnosed at age 50–64, and ovarian overstimulation during in vitro fertilization in those diagnosed at age 50 or less.  

Conclusions: Better diagnostic tools – such as the liberal use of ultrasound and magnetic resonance imaging – and more accurate pathological definition for ILC type appear to influence the changes in the incidence of ILC in the subgroups of invasive breast cancer.

The introduction of novel targeted therapies into the clinic in recent years has had a considerable impact on the management of several neoplastic diseases – such as gastrointestinal stromal tumors, hepatocellular carcinomas and renal cell carcinomas – considered until recently refractory to systemic therapies. We describe here two such novel biological agents, sunitinib and sorafenib, as a paradigm of the successful clinical application of new concepts. Sunitinib and sorafenib are small molecule tyrosine kinase inhibitors that target vascular endothelial growth factor receptor, platelet-derived growth factor receptor, C-Kit and others. Both agents are administered orally; sunitinib is typically given in cycles for 4 consecutive weeks with 2 weeks off, while sorafenib is given continually. Side effects occur in most patients, similar for both agents; they may affect several systems and organs but are mostly mild and easily manageable, rarely requiring discontinuation of the drug. However, these toxicities require prompt attention and intervention. The most frequently observed effects are hypertension, nausea, anorexia, asthenia and cutaneous manifestations; cardiac abnormalities may include congestive failure. Sunitinib, and markedly less frequently sorafenib, may cause thyroid gland dysfunction, mainly hypothyroidism. Antitumor activity has been shown for renal cell carcinoma in pivotal trials, for sunitinib as first-line treatment and for sorafenib in previously treated patients as second-line. Sunitinib is now approved as second-line therapy for patients with GIST[1] refractory to imatinib; sorafenib has resulted in a significant prolongation in median survival in patients with hepatocellular carcinoma. Ongoing clinical trials will further define the spectrum of these agents' antitumor activity, their role in combination with other drugs, as well as their optimal dose and schedule of administration.

Background: Professional volunteers play a crucial role in reinforcing emergency medical services in Israel. In order to encourage volunteers to return for additional shifts, the organization should provide conditions that will assure the return, particularly at a time of self-risk such as war. In 2009 Israeli emergency medical services (Magen David Adom) were required to increase preparedness in the southern part of the country due to missile attacks on civilian populations, while continuing their routine activities, i.e., responding promptly to emergency events. In order to perform these multiple functions, MDA[1] stations in the towns under attack were strengthened with volunteers from other regions of the country. These volunteers, trained as paramedics, served in 24–48 hour shifts.

Objectives: To identify the factors influencing the willingness of volunteers to return.

Methods: A questionnaire was used to assess the satisfaction of volunteers participating in the reinforcement with regard to their physical environment, job assignment and the actual activity they were involved in. Data were analyzed using SPSS statistical software.

Results: During the 10 days of the study, 121 volunteers reinforced southern MDA stations and 99 (81%) of them responded to the questionnaire. We found that volunteers' willingness to return to do more shifts was affected by their welcome and reception at the station, their job assignment, and their training and preparation for performing the necessary tasks. The sleeping conditions and the number of events they participated in were also contributing factors.

Conclusions: Factors that contribute to the willingness of volunteers to re-volunteer should be taken into account by organizations that rely on them.

Background: It is currently recommended that capillary glucose levels of non-critically ill hospitalized diabetic patients be maintained at between 140 and 180 mg/dl. Implementation of these recommendations and evaluation of their effectiveness require that data regarding the glucose control of these hospitalized patients be accessible.

Objective: To analyze glucose control and monitoring of all the diabetic patients hospitalized in the general medicine wards of our medical center.

Methods: Capillary glucose measurements of all diabetic patients hospitalized in our departments of medicine between June and December 2008 were recorded by a central computerized institutional glucometer. Median glucose values and frequency of daily glucose checks per patient were analyzed in the internal medicine wards.

Results: We evaluated 14,366 capillary measurements from 2475 patients; 43% were taken before breakfast and 25% before dinner. A median of one daily determination per patient was obtained. This number increased 1.4-fold in patients with hyperglycemia > 200 mg/dl and 2.5-fold in patients with hypoglycemia. Seventy-five percent of the recorded glucose values were within the recommended target range, with a median daily level of 161 mg/dl and median fasting glucose of 142 mg/dl. A significant variance was found between wards.

Conclusions: The frequency of capillary glucose measurements in diabetic patients hospitalized in general medicine wards was low; most capillary glucose values, however, were within the recommended target range. The optimal monitoring of glucose in these patients remains to be determined.

Background: Health care workers bear the risk of both contracting influenza from patients and transmitting it to them. Although influenza vaccine is the most effective and safest public health measure against influenza and its complications, and despite recommendations that HCWs[1] should be vaccinated, influenza vaccination coverage among them remains low.

Objectives: To characterize influenza vaccination coverage and its determinants among employees in an Arab hospital in Israel.

Methods: An anonymous, self-administered questionnaire was distributed among employees involved in patient care in the winter of 2004–2005 at Nazareth Hospital in Israel. The questionnaire included items related to health demographic characteristics, health behaviors and attitudes, knowledge and attitude concerning influenza vaccination, and whether the respondent had received the influenza vaccine during the previous winter or any other winter.

Results: The overall rate of questionnaire return was 66%; 256 employees participated in the study. The immunization coverage rate was 16.4%, similar to that reported for other hospitals in Israel. Logistic regression analysis demonstrated a significant association only between influenza vaccination coverage and the presence of chronic illness and influenza vaccination in the past.

Conclusions: Influenza vaccination coverage among Nazareth Hospital health care workers was low. They did not view themselves as different to the general population with regard to vaccination. An intervention program was launched after the study period, aimed at increasing the knowledge on the efficacy and safety of the vaccine, stressing the importance of vaccinating HCWs, and administering the vaccine at the workplace. The program raised the vaccination coverage to 50%.

Background: Obstruction of urine outflow can result from mechanical blockade as well as from functional defects. In adults, urinary tract obstruction is due mainly to acquired defects, such as pelvic tumors, calculi, and urethral stricture. In childhood it is mostly due to congenital malformations. In this article we present two rare cases of acute obstructive renal failure that presented with hydronephrosis. These cases underline the wide range of causes that may lead to this clinical feature. 

Background: The prognostic significance of biologic markers in women with ductal carcinoma in situ is not fully understood. HER2/neu is a marker of prognostic significance that is routinely assessed in invasive cancer but its correlation with clinical outcome in DCIS[1] is still obscure.

Objectives: To evaluate the significance of HER-2/neu expression as a prognostic marker in DCIS.

Methods: Clinical and pathologic data from 84 patients treated for DCIS were analyzed. HER-2/neu expression was determined by immunohistochemical staining. Histopathologic parameters (nuclear grade, histologic subtype, necrosis, calcifications, margins) were reviewed by an experienced pathologist. Local recurrence and/or metastatic spread were used as endpoints to determine the prognostic significance of HER-2/neu expression.

Results: With a median follow-up of 94.8 months, nine recurrences were reported. Neither univariate nor multivariate analysis showed a significant correlation between HER-2/neu expression and disease recurrence or the time to disease recurrence. Although HER-2/neu expression demonstrated a significant association with high nuclear grade (P < 0.0001) and comedo subtype (P < 0.0001), there was no correlation between these histologic features and recurrence rate. The correlation between high nuclear grade and disease recurrence approached statistical significance (P = 0.07).

Conclusions: No significant association was found between HER-2/neu expression in DCIS and disease recurrence. However, HER-2/neu correlated with negative markers such as nuclear grading and comedo necrosis, and its role should therefore be investigated in larger studies.
 

[1] DCIS = ductal carcinoma in situ