Israel Medical Association Journal

Background: Several studies have addressed the issue of undetected uterine pathology in women undergoing hysterectomy for pelvic organ prolapse (POP). However, these studies differ largely with respect to the incidence of malignancy found, study population, and preoperative evaluation.

Objectives: To assess the risk of unexpected pre-malignant and malignant uterine pathological findings after vaginal hysterectomy for POP repair, in a single medical center in Israel.

Methods: A retrospective study was performed of all patients who underwent vaginal hysterectomy due to symptomatic POP between January 1990 and April 2015 in a single tertiary medical center. Selected clinical and pathological data were retrieved from the computerized medical records. All specimens were routinely sent for histopathological assessment. All women were managed according to a uniform protocol that required the presence of a preoperative normal Pap smear, and included preoperative transvaginal sonography and endometrial biopsy when indicated. Patients in whom premalignant or malignant lesions were found preoperatively were not included in the study.

Results: The study comprised 667 patients. The overall rate of malignant or significant premalignant pathologies (6 cases) was 0.89%, including one (0.14%) case of endometrial carcinoma. All premalignant and malignant pathologies were found only in post-menopausal patients. The rate of significant endometrial pathological lesions found in asymptomatic post-menopausal women was only 0.35%.

Conclusions: The rate of preoperatively undetected abnormal histopathological findings in patients who undergo vaginal hysterectomy due to POP is very low, and therefore more extensive preoperative evaluation is not warranted in them.

Ovarian cancer is a major cause of cancer death among women worldwide, and particularly in Israel. Although the disease at stage IA has 5 year survival rates of over 90%, early detection methods are not sufficiently accurate. Consequently, ovarian cancer is typically diagnosed late, which results in high fatality rates. An excellent candidate for early ovarian cancer detection would be in vivo magnetic resonance spectroscopy (MRS) because it is non-invasive and free of ionizing radiation. In addition, it potentially identifies metabolic features of cancer. Detecting these metabolic features depends on adequate processing of encoded MRS time signals for reconstructing interpretable information. The conventional Fourier-based method currently used in all clinical scanners is inadequate for this task. Thus, cancerous and benign ovarian lesions are not well distinguished. Advanced signal processing, such as the fast Padé transform (FPT) with high-resolution and clinically reliable quantification, is needed. The effectiveness of the FPT was demonstrated in proof-of-concept studies on noise-controlled MRS data associated with benign and cancerous ovaries. The FPT has now been successfully applied to MRS time signals encoded in vivo from a borderline serous cystic ovarian tumor. Noise was effectively separated out to identify and quantify genuine spectral constituents that are densely packed and often overlapping. Among these spectral constituents are recognized and possible cancer biomarkers including phosphocholine, choline, isoleucine, valine, lactate, threonine, alanine, and myoinositol. Most of these resonances remain undetected with Fourier-based in vivo MRS of the ovary. With Padé optimization, in vivo MRS could become a key method for assessing ovarian lesions, more effectively detecting ovarian cancer early, thereby improving survival for women afflicted with this malignancy.

Background: Biallelic BLM gene mutation carriers are at an increased risk for cancer, including colorectal cancer (CRC). Whether heterozygous BLM gene mutations confer an increased cancer risk remains controversial.

Objectives: To evaluate CRC and endometrial cancer risk in BLM heterozygous mutation carriers.

Methods: Jewish Ashkenazim at high risk for colon or endometrial cancer and endometrial cancer cases unselected for family history were genotyped for the BLM^Ash predominant mutation.

Results: Overall, 243 high-risk individuals were included: 97 men CRC patients (55.12 ± 12.3 years at diagnosis), 109 women with CRC (56.5 ± 13.7 years), 32 women with endometrial cancer (58.25 ± 13.4 years) and 5 women with both CRC and endometrial cancer. In addition, 120 unselected Ashkenazi women with endometrial cancer (64.2 ± 11.58 years) were genotyped. The BLM^Ash mutation was present in 4/243 (1.65%) high-risk patients; 2 CRC (0.97%) 2 endometrial cancer (5.4%), and 1/120 unselected endometrial cancer patients (0.84%). Notably, in high-risk cases, BLM^Ash mutation carriers were diagnosed at a younger age (for CRC 47.5 ± 7.8 years; P = 0.32 ; endometrial cancer 49.5 ± 7.7 years; P = 0.36) compared with non-carriers.

Conclusions: Ashkenazi high risk CRC/endometrial cancer, and women with endometrial cancer have a higher rate of BLM^Ash heterozygous mutation compared with the general population. BLM^Ash heterozygous mutation carriers are diagnosed with CRC and endometrial cancer at a younger age compared with non-carriers. These observations should be validated and the possible clinical implications assessed.

Background: The number of cancer survivors has been increasing worldwide and is now approximately 32.6 million and growing. Cancer survivors present a challenge to health care providers because of their higher susceptibility to long-term health outcomes related to their primary disease and treatment.

Objective: To report on the number of cancer survivors and incident cancer cases in the period 1960–2009 in Israel, in order to provide data on the scope of the challenge Israel’s health care funds face.

Methods: The Israel National Cancer Registry (INCR) database was used to identify new cancer cases diagnosed during the period 1960–2009. Lifetable analysis was used to assess changes in cumulative survival and population prevalence of cancer survivors throughout the 50 year study period.

Results: Almost 600,000 invasive cancer cases were diagnosed during the period 1960–2009 (overall absolute survival rate 54%). Within this time period, the number of new patients diagnosed with cancer increased fivefold and that of cancer survivors ninefold. The absolute survival of cancer patients and the prevalence of cancer survivors in the general population significantly increased with time from 34% and 0.5%, respectively (1960–1969), to 62% and 1.9%, respectively (2000–2009). Cumulative absolute survival for 5, 10 and 15 years following diagnosis increased with time as well.

Conclusions: The INCR database is useful to assess progress in the war against cancer. The growing numbers of cancer survivors in Israel present a challenge to the national health and social services system.

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease which refers to the presence of hepatic steatosis. Breast cancer is now the most common cancer in women and is the leading cause of death from cancer among women.

Objectives: To assess the relationship between NAFLD and newly diagnosed cases of breast cancer.

Methods: The results of mammography screening examinations in women referred to the Breast Center, Holy Family Hospital, Nazareth during a 4 year period were collected. We identified cases of women who were newly diagnosed with breast cancer and who underwent abdominal computed tomography (CT) within 1 month of the diagnosis. The control group comprised 73 women with normal mammography and breast ultrasonography who underwent abdominal CT within 3 months from the date of the breast cancer screening during the same study period. The control cases were matched by age and body mass index (BMI). We compared the cases with the controls in terms of the presence of diffuse hepatic fatty liver and other known risk factors for breast cancer.

Results: Of the 133 women who were screened, 73 with new diagnosis of breast cancer were eligible for the study. NAFLD was found in 33 of the women with breast cancer and in 12 in the control group (45.2% vs.16.4%, respectively, P = 0.002). Multivariate analysis showed NAFLD (odds ratio 2.82, 95% confidence interval 1.2–5.5, P = 0.016) to be associated with breast cancer.

Conclusions: NAFLD is associated with breast cancer.

A flowering plant of variegated ingredients and psychoactive qualities, cannabis has long been used for medicinal and recreational purposes. Currently, cannabis is approved in several countries for indications of symptomatic alleviation. However, limited knowledge on the benefits and risks precludes inclusion of cannabis in standard treatment guidelines. This review provides a summary of the available literature on the use of cannabis and cannabinoid-based medicines in palliative oncology. Favorable outcomes are demonstrated for chemotherapy-induced nausea and vomiting and cancer-related pain, with evidence of advantageous neurological interactions. Benefit in the treatment of anorexia, insomnia and anxiety is also suggested. Short- and long-term side effects appear to be manageable and to subside after discontinuation of the drug. Finally, cannabinoids have shown anti-neoplastic effects in preclinical studies in a wide range of cancer cells and some animal models. Further research is needed before cannabis can become a part of evidence-based oncology practice.

Background: More than 90% of all thyroid cancers are differentiated thyroid carcinomas (DTC) with a 10 year survival rate greater than 90%. The commonly used risk stratification systems for DTC include: European Organization for Research and Treatment of Cancer (EORTC), AGES (Age, histologic Grade, Extent of tumor, Size), AMES (Metastasis) and MACIS (Completeness of resection, local Invasion). Other systems are also utilized. Several new factors that may be involved in DTC risk stratification have emerged in recent studies, with other "traditional" factors being challenged. 

Objectives: To present recent updates in the literature on new potential prognostic factors for DTC.

Methods: We conducted a literature review and analysis of publications regarding DTC prognostic factors or risk stratification published in the last 10 years. 

Results: Several new factors with potential prognostic implications for DTC were noted, including family history, lymph node involvement parameters, positive PET-CT findings, multifocal disease, thyroglobulin level and several molecular markers including BRAF. Increasing age is associated with poorer outcome in DTC; however, recent studies suggest that the cutoff point of 45 years may be contested. Furthermore, several studies have shown contradictory results regarding male gender as a negative prognostic factor, thus questioning its prognostic significance. 

Conclusions: A number of new factors with potential prognostic implications for DTC have emerged and should be addressed. However, their role and possible inclusion in new staging systems has yet to be determined.

 

Background: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer. 

Objectives: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009.

Methods: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009–2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method.

Results: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2–69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47–69%) and local control was 88% (95%CI 78–94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1–2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%.

Conclusions: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.

 

Background: Automated breast volumetric sonography (ABVS) is a new technology with various possible applications.

Objectives: To compare ABVS and breast magnetic resonance imaging (MRI) in the surveillance of women with BRCA1/2 gene mutation carriers.

Methods: We conducted a prospective study in Jewish female BRCA1/2 mutation carriers who underwent breast MRI and ABVS. The results of both exams performed 6 months apart or less, and relevant clinical data, were reviewed. The BIRADS results were divided into three subgroups according to subsequent expected management: BIRADS 1-2 (normal study), BIRADS 3 (probably benign finding), and BIRADS 4 and 5 (suspicious findings). BIRADS 0 and 6 scores were excluded from the study. Distribution of ABVS and MRI BIRADS scores were compared using McNemar's test, and concordance was calculated using the Cohen kappa test.

Results: Overall, 68 women, 40 BRCA1 and 28 BRCA2 mutation carriers, age range 26–69 (mean 44.55 ± 12.1 years), underwent 79 paired ABVS and MRI examinations. McNemar's test calculations showed no significant difference between MRI and ABVS BIRADS score distribution. Cohen’s kappa test resulted in k = 0.158, an agreement that can be described as only "slight agreement" between both modalities. Of 14 discordant cases there was one cancer, revealed by MRI and not by ABVS performed 6 months prior to MRI.

Conclusions: ABVS showed slight agreement with MRI in BRCA1/2 mutation carriers. These preliminary results on a small group of healthy high risk patients suggest that the diagnostic abilities of ABVS are inferior to MRI. Further studies encompassing larger groups are needed.

 

Background: Gastrointestinal malignancies comprise a broad spectrum of neoplasms and have a high overall incidence. The incidence rates in Israel vary among ethnic groups due to different risk factors.

Objectives: To investigate incidence trends of these cancers in Israel in both Jewish and Arab ethnic groups in order to better understand the risks in those groups.

Methods: This study is based on data published by the Israel National Cancer Registry and the Central Bureau of Statistics. We compared statistics between ethnicities and genders. We examined the eight most common gastrointestinal cancers, focusing on colon, rectal and gastric cancers.

Results: Between 1980 and 2012 there was a decline in the incidence of gastric cancer in the Jewish population; in contrast, a significant increase occurred in Arab women, but there was no significant change in Arab men. Colon cancer showed a relative decrease in incidence in the Jewish population, but an increase in the Arab population. A decrease in the incidence of rectal cancer in the Jewish population and an increase in the Arab population was observed. 

Conclusions: Gastric, colon and rectal cancers exhibit differences in incidence and outcome between Jewish and Arab populations in Israel. These differences were not observed in the other five types of less common gastrointestinal cancers.