Israel Medical Association Journal

Background: Intrathoracic cancer can cause hyponatremia, but it is uncertain whether mild hyponatremia in the outpatient setting should be regarded as an early sign of intrathoracic cancer.

Objectives: To evaluate the risk of undiagnosed intrathoracic cancer in patients with new persistent mild hyponatremia.

Methods: We conducted a retrospective cohort study using the electronic health record database of a large healthcare organization. The hyponatremia group included patients with sodium concentration of 130–134 mmol/L twice, after a previous normal value and without previous history of cancer or diseases related to hyponatremia. A control group with normal sodium concentration was matched by sex, age, and year of testing. We measured specific intrathoracic cancer incidence during 3 years of follow-up after sodium concentration test date. A logistic regression was used to adjust for further clinical information including smoking history, symptoms, and medications.

Results: The study comprised 1539 participants with mild hyponatremia and 7624 matched controls. New intrathoracic cancer diagnosis was more common in the hyponatremia group during a 3-year follow-up; 1.49% in the hyponatremia group and 0.39% in the control group, crude odds ratio (OR) 3.84, 95% confidence interval (95%CI) 2.22–6.63. After adjustment, hyponatremia remained a significant risk factor for the diagnosis of intrathoracic cancer; adjusted OR 3.61, 95%CI 2.08–6.28.

Conclusions: New mild persistent hyponatremia might be a significant predictive marker to a yet undiagnosed intrathoracic cancer.

Background: Population screening for the BRCA mutations in Ashkenazi Jewish women was recently implemented in Israel and is expected to lead to a 10-fold increase in the diagnosis of asymptomatic carriers. Performing the screening follow-up within multidisciplinary dedicated clinics for carriers is recommended for early detection and risk reduction.

Objectives: To determine the availability, capacity, and practices of dedicated screening clinic for BRCA carriers in Israel.

Methods: A telephone-based survey of all public hospitals in Israel was conducted October 2020 to August 2021 to determine whether they had a dedicated clinic. Dedicated clinics were defined as multidisciplinary screening clinics offering at least breast and gynecological screening and risk reducing services on site. The clinic director or nurse navigator answered a questionnaire about screening practices followed by a semi-structured interview.

Results: Of the ten dedicated BRCA clinics found in Israel, nine participated. Approximately 4500 BRCA carriers are currently being followed. No specialized clinics are available in the southern district or in the northernmost half of the northern district of Israel, leading to a disparity between periphery and center. Screening recommendations, although asserted as adhering to international guidelines, vary among clinics including age at initiating of clinical exam, use of adjunct imaging modalities, and follow-up during lactation and after risk reducing surgery.

Conclusions: There is a suboptimal distribution of dedicated clinics for BRCA carriers in Israel. Nationally centralized attempt to create guidelines that will unify screening practices is warranted, especially considering the expected increase in demand.

Background: The Israel National Cancer Registry (INCR) was established in 1960. Reporting has been mandatory since 1982. All neoplasms of uncertain/unknown behavior, in situ and invasive malignancies (excluding basal and squamous cell carcinomas of the skin), and benign neoplasms of the brain and central nervous system (CNS) are reportable.

Objectives: To assess completeness and timeliness of the INCR for cases diagnosed or treated in 2005.

Methods: Abstractors identified cases of in situ and invasive malignancies and tumors of benign and uncertain behavior of the brain and CNS diagnosed or treated in 2005 in the files of medical records departments, pathology and cytology laboratories, and oncology and hematology institutes in 39 Israeli medical facilities. Cases were linked to the INCR database by national identity number. Duplicate cases, and those found to be non-reportable were excluded from analysis. Completeness was calculated as the percent of reportable cases identified by the survey that were present in the registry. Timeliness was calculated as the percent of reportable cases diagnosed in 2005, which were incorporated into the registry prior to 31 December 2007.

Results: The INCR’s completeness is estimated at 93.7% for all reportable diseases, 96.8% for invasive solid tumors, and 88.0% for hematopoietic tumors. Incident cases for the calendar year 2005 were less likely to be present in the registry database than those diagnosed prior to 2005.

Conclusions: Completeness and timeliness of the INCR are high and meet international guidelines. Fully automated reporting will likely improve the quality and timeliness of INCR data.

Background: Primary retroperitoneal neoplasms (PRN) arise from diverse retroperitoneal tissues. Soft tissue sarcomas (STS) comprise the majority and are well studied. Other non-sarcomatous PRN are very rare and less familiar.

Objectives: To evaluate the clinicopathologic and radiologic features of non-sarcomatous PRN, as well as the outcome of complete tumor resection (TR).

Methods: Retrospective data were collected on consecutive patients (June 2006 to January 2015) who underwent resection of retroperitoneal lesions at our department. Final pathology of non-sarcomatous PRN was included.

Results: The study population included 36 patients (26% with PRN). PRN were neurogenic (17%), fat-containing (3%), and cystic (6%). The preoperative diagnosis was correct in only 28%. All patients underwent TR via laparotomy (72%) or laparoscopy (28%), for mean operative time of 120 ± 46 minutes. En bloc organ resection was performed in 11%. Complete TR was achieved in 97%. Intra-operative spillage occurred in 8%. Intra-operative, 90-day postoperative complications, and mortality rates were 11%, 36%, and 0%, respectively. The mean length of stay was 6.5 ± 5.5 days. The median overall survival was 53 ± 4.9 months.

Conclusions: Familiarity with radiologic characteristics of PRN is important for appropriate management. Counter to STS, other PRN are mostly benign and have an indolent course. Radical surgery is not required, as complete TR confers good prognosis. Expectant management is reserved for small, asymptomatic, benign neoplasms.

Background: Thymectomy is a reliable surgical method for treating patients with myasthenia gravis (MG) and benign tumors of the thymus. Despite the advantages of minimally invasive surgical approaches for resection of thymic neoplasms, there are still controversies regarding the superiority of one type of surgery over another.

Objectives: To report the results of our initial Israeli experience with robotic thymectomy in 22 patients with MG and suspected benign thymic tumors.

Methods: We retrospectively analyzed 22 patients (10 men, 12 women) who underwent robotic thymectomy by a left-sided (16) or right-sided approach (6) using the da Vinci robotic system at Assaf Harofeh Medical Center. Seven patients were diagnosed with MG before surgery and 14 had suspected benign thymic neoplasms.

Results: Average operative time was 90 minutes. There were no deaths or intraoperative complications. Postoperative complications occurred in two patients (dyspnea and pleural effusion). Median blood loss was 12.3 cc (range 5–35 cc), median hospital stay 2.9 days (range 2–5 days), and mean weight of resected thymus 32.1 grams. Seven patients had thymic hyperplasia, six a lipothymoma, one a thymic cyst. Seven each had thymomas in different stages and one had a cavernous hemangioma.

Conclusions: Robotic thymectomy is a safe, technically effective surgical method for resection of thymic neoplasms. The advantages of this technique are safety, short hospitalization period, little blood loss, and low complications. We have included this surgical procedure in our thoracic surgery residency program and recommend a learning curve program of 10 to 12 procedures during residency.

Background: Janus kinase-2 (JAK2) is mutated in a high proportion of patients with polycythemia vera and in a smaller number with essential thrombocythemia and primary myelofibrosis. Mutated JAK2 is an important diagnostic marker for myeloproliferative neoplasm (MPN) and may also play a major role in the pathogenesis of MPN.

Objectives: To evaluate the prevalence of mutated JAK2 (JAK2-V617F) among patients with major intraabdominal vein thrombosis who had normal blood counts at diagnosis of the initial event.

Methods: The medical records of patients who presented with a major intraabdominal venous thrombosis and normal peripheral blood counts were obtained. JAK2-V617F mutation status was determined by real-time polymerase chain reaction.

Results: Twenty-two patients were available for this analysis and 9 (41%) were found to have JAK2-V617F. Patients with positive JAK2-V617F were younger and had more frequent clinical splenomegaly than those with wild-type JAK2.

Conclusions: A high proportion of patients presenting with “idiopathic” major intraabdominal vein thrombosis and normal blood counts carry JAK2-V617F. We recommend searching for the mutation in this clinical setting to detect patients with occult MPN.

Background: Multiple primary malignancies are increasingly being detected among cancer patients. Objectives: To investigate the co-occurrence of primary bladder cancer and primary lung cancer, two established smoking-related neoplasms characteristically associated with increased risk of secondary cancers.

Methods: A retrospective search of the patient registry in our institution identified 25 patients (23 men and two women) who were diagnosed with both bladder cancer and lung cancer during the period 1990–2005. Medical records were reviewed and clinical and pathological data were extracted.

Results: In 21 patients (84%) bladder cancer was the first primary tumor and in 4 (16%) the second primary tumor. More than 90% of the patients had a history of smoking. Mean smoking exposure was 62.1 pack years (range 30–120). All bladder cancers were transitional cell carcinomas with the majority being superficial at presentation. Most lung cancers were of the non-small cell type. Second primary lung cancers were significantly more advanced at diagnosis. Overall, mean follow-up was 105.8 months (range 6–288). Seven patients (28%) were alive at the time of evaluation; 68% died of lung cancer, while none died of bladder cancer.

Conclusions: Second primary lung cancer may occur in patients with bladder carcinoma and vice versa. In view of the relatively frequent involvement of the genitourinary tract as a site of multiple primary tumors, urologists may have a key role in the detection of second primary tumors arising in the genitourinary tract, or second primary tumors that occur in patients with primary genitourinary tract malignancies.
 

Background: Extensive necrosis is rare in primary renal cell carcinoma. This finding may reflect the biological characteristics of the carcinoma and therefore could be of prognostic and clinical value.

Objectives: To assess the incidence of necrosis in renal cell carcinoma and its potential prognostic value.

Methods: We conducted a consecutive retrospective study of 173 patients after radical nephrectomy for renal cell carcinoma. Clinical and pathological data were collected from hospital medical records and compiled into a computerized database.

Results: Extensive necrosis was found in 31 tumor specimens (17.9%). Univariate analysis showed that the specimens with extensive necrosis were significantly larger and manifested more perirenal and venous extension than the tumors without necrosis. The size of the renal tumor was the only parameter that remained significant in multivariate analysis (P=0.0001). Overall disease-free survival did not differ significantly between patients with necrotic tumors and those without (68% and 66% respectively).

Conclusions: The finding of extensive necrosis in renal cell carcinoma specimens does not seem to be related to tumor biology but rather may reflect the relation between size and vascularity of the tumor.

Background: The impact of repeated surgical resection on the survivorship of patients with malignant astrocytomas is an issue of some controversy in the medical literature.

Objectives: To clarify this issue through a retrospective analysis of treatment outcomes in a brain tumor clinic.

Methods: The patient records from the Brain Tumor Clinic at Hahnemann University Hospital for the period 1988 to 2000 were reviewed. From these, 112 cases of glioblastoma multiforme and 50 cases of anaplastic astrocytoma were chosen for analysis.

Results: The group of patients with glioblastomas showed a median survival of 415 days. When analyzed as subgroups based on the number of surgical resections, the median survival was 393 days in the group with biopsy only, 380 days in the group with one surgical resection, and 548 days in the group with two or three resections. Using the Kaplan-Meier method to generate survival plots and the log rank test to compare groups, repeat debulking was found to be a significant predictor of survival (P= 0.1 73). The group of patients with anaplastic astrocytomas showed a median survival of 1,311 days. When analyzed by subgroups, the patients with biopsy only had a median survival of 544 days, those with one debulking 1,589 days and those with two or three debulkings 1,421 days. There was a trend toward increased survival with debulking and the log rank test again showed statistical significance (P 0.1998).

Conclusions: This study indicates that repeated surgical resections offer increased survival for both glioblastomas and anaplastic astrocytomas.
 

Objectives: To present a case series of foyr patients with phenytion-induced severe CDRs, including toxic epidermal necrolysis (2 patients), exanthematous eruption (1 patient) and hypersensitivity syndrome (1 patient). In all patients the reactions appeared following the combined intake of phenytion, corticosteroids and H2 blockers.

Conclusions: Our case series may imply the role of drug interactions between phenytion, corticosteroids and H2 blockers in the induction of severe CDRs.