Colorectal cancer screening at age 45 years in Israel: Cost-effectiveness and global implications.

BACKGROUND: Colorectal cancer (CRC) incidence at ages <50 years is increasing worldwide. Screening initiation was lowered to 45 years in the United States. The cost-effectiveness of initiating CRC screening at 45 years in Israel was assessed with the aim of informing national policy and addressing internationally relevant questions. METHODS: A validated CRC screening model was calibrated to Israeli data and examined annual fecal immunochemical testing (FIT) or colonoscopy every 10 years from 45 to 74 years (FIT45-74 or Colo45-74) versus from 50 to 74 years (FIT50-74 or Colo50-74). The addition of a fourth colonoscopy at 75 years was explored, subanalyses were performed by sex/ethnicity, and resource demands were estimated. RESULTS: FIT50-74 and Colo50-74 reduced CRC incidence by 57% and 70% and mortality by 70% and 77%, respectively, versus no screening, with greater absolute impact in Jews/Other versus Arabs but comparable relative impact. FIT45-74 further reduced CRC incidence and mortality by an absolute 3% and 2%, respectively. With Colo45-74 versus Colo50-74, CRC cases and deaths increased slightly as three colonoscopies per lifetime shifted to 5 years earlier but mean quality-adjusted life-years gained (QALYGs) per person increased. FIT45-74 and Colo45-74 cost 23,800-53,900 new Israeli shekels (NIS)/QALYG and 110,600-162,700 NIS/QALYG, with the lowest and highest values among Jewish/Other men and Arab women, respectively. A fourth lifetime colonoscopy cost 48,700 NIS/QALYG. Lowering FIT initiation to 45 years with modest participation required 19,300 additional colonoscopies in the first 3 years. CONCLUSIONS: Beginning CRC screening at 45 years in Israel is projected to yield modest clinical benefits at acceptable costs per QALYG. Despite different estimates by sex/ethnicity, a uniform national policy is favored. These findings can inform Israeli guidelines and serve as a case study internationally.

Place of Death for Israeli Cancer Patients Over a 20-Year Period: Reducing Hospital Deaths, but Barriers Remain.

BACKGROUND: Cancer remains a leading cause of mortality worldwide. While the main focus of palliative care (PC) is quality of life, the elements that comprise the quality of death are often overlooked. Dying at home, with home-hospice-care (HHC) support, rather than in-hospital, may increase patient satisfaction and decrease the use of invasive measures. We examined clinical and demographic characteristics associated with out-of-hospital death among patients with cancer, which serves as a proxy measure for HHC deaths. METHODS: Using death certification data from the Israel Central Bureau of Statistics, we analyzed 209,158 cancer deaths between 1998 and 2018 in Israel including demographic information, cause of death, and place of death (POD). A multiple logistic regression model was constructed to identify factors associated with out-of-hospital cancer deaths. RESULTS: Between 1998 and 2018, 69.1% of cancer deaths occurred in-hospital, and 30.8% out-of-hospital. Out-of-hospital deaths increased by 1% annually during the study period. Older patients and those dying of solid malignancies were more likely to die out-of-hospital (OR = 2.65, OR = 1.93, respectively). Likelihood of dying out-of-hospital varied with area of residency; patients living in the Southern district were more likely than those in the Jerusalem district to die out-of-hospital (OR = 2.37). CONCLUSION: The proportion of cancer deaths occurring out-of-hospital increased during the study period. We identified clinical and demographic factors associated with POD. Differences between geographical areas probably stem from disparity in the distribution of PC services and highlight the need for increasing access to primary EOL care. However, differences in age and tumor type probably reflect cultural changes and suggest focusing on educating patients, families, and physicians on the benefits of PC.

Coexistence of malignancies in pemphigus vulgaris.

Pemphigus vulgaris (PV) is a rare autoimmune intraepidermal bullous disease. PV has a major effect on morbidity as well as quality of life. There is sparse literature regarding the association between pemphigus vulgaris (PV) and comorbid malignancies. In this study we aimed to assess the risk of malignancy in a cohort of patients with PV and characterize PV-associated malignancies. Data were collected from two tertiary referral centers between the years 2008 and 2019 and compared with the national cancer registry. Of 164 patients with PV, 19 were diagnosed with malignancy: seven prior to PV diagnosis and 12 after. All cancers, solid and hematological, displayed higher incidences compared to the general population (p <0.001). In conclusion, we demonstrated higher rates of malignancies among patients with PV than in the general population. These observations suggest the need for careful assessment and follow up of patients with PV, given the possibility of associated malignancies.

Occupational Exposure to Nonionizing Radiation and Risk for Malignancy in Young Adults.

INTRODUCTION: Nonionizing radiation (NIR) is considered "possibly carcinogenic to humans," and therefore, exposure of young military personnel raises concerns regarding increased risk for cancer. The aim of our study was to compare the cancer incidence in exposed and nonexposed populations in order to gain better understanding of their risk. MATERIALS AND METHODS: A longitudinal retrospective cohort study, between 2009 and 2018, was conducted. Israel Defense Forces (IDF) aerial defense units service members, with NIR exposure (range of 2-300 GHz, below the International Commission of Non-Ionizing Radiation Protection guidelines), were compared with a similar sociodemographic group of service members without NIR exposure. Both groups were followed for cancer incidence (all-cause and specific malignancies). Kaplan-Meier analysis of cancer-free survival and univariate and multivariable logistic regressions for possible confounders and risk factors were performed. This analysis was repeated on a matched 1:1 control group. RESULTS: Exposure and comparison groups included 3,825 and 11,049 individuals, respectively. Forty-one cases diagnosed with cancer were identified during the follow-up time (mean 4.8 [±2.7] years), 13 (0.34%) of which were reported in the exposure group, and 28 (0.25%) were reported in the comparison group. The odds ratio (OR) for cancer incidence in the exposure vs. control groups was 1.34 (95%CI, 0.70-2.60), P-value = 0.3807. The results remained unchanged after adjustment for sex, age at enrollment, service length, socioeconomic status, and military occupation (adjOR = 1.38 [95%CI, 0.67-2.82], P = 0.3818). CONCLUSIONS: Our study did not find an increased short-term risk for cancer in young adults exposed to NIR radiation as compared with unexposed young adults.

Secondary cancer after meningioma diagnosis: an Israeli national study.

BACKGROUND: There are limited data on whether primary diagnosis of meningioma may be associated with development of secondary primary cancer (SPC). METHODS: All meningioma cases (ICD-O-3 morphology codes 9530/0-9539/3) diagnosed in Jewish Israelis ≥ 20 years 1990 through 2015 registered in the Israel National Cancer Registry (INCR) were retrieved. All subsequent cancers occurring more than 6 months after meningioma diagnosis were identified. Risk of secondary cancer (SPC) was compared to cancer risk in the general population through the calculation of standardized incidence ratios (SIRs) and excess absolute risks (EARs). SIRs were stratified by type of second cancer, sex, and age group. Cox regression models were used to estimate hazard ratios of developing SPC. RESULTS: Overall, 8044 meningioma cases were identified: mean age at diagnosis was 64.0 ± 14.1 years. Of these, 927 (11.5%) were diagnosed with SPC (SIR 1.6, 95% CI 1.5-1.7). SPC risk was elevated in men (SIR 1.6, 95% CI 1.5-1.9) and women (SIR 1.6, 95% CI 1.5-1.8) diagnosed with meningioma in univariable analyses. Cancers most commonly encountered in the studied population were breast (17.6%), colorectal (13.4%), lung (8.1%), prostate (5%), and bladder (4.6%) cancer. In multivariable analyses, 10+ year increment in age at meningioma diagnosis was significantly associated with higher risk for SPC in individuals diagnosed with meningioma between 20 and 64 years, with an inverse association in the older age group (65+ years). CONCLUSIONS: Meningioma diagnosis is associated with an increased risk for developing secondary cancers. This risk should be discussed with patients treated for meningioma.

Risk of Cancer in Paediatric onset Inflammatory Bowel Diseases: A Nation-wide Study From the epi-IIRN.

BACKGROUND: Paediatric onset IBD [PIBD] is characterised by a more extensive phenotype than adult-onset IBD and a higher utilisation of immunosuppressive medications; both may be associated with malignancy. We aimed to assess the risk of cancer in a nationwide cohort of PIBD and to explore the risks associated with medical treatments. METHODS: PIBD patients [<18 years old] were included from the epi-IIRN cohort, covering 98% of the Israeli population from 2005, linked to the national cancer registry. We matched PIBD children to non-IBD children for calculating the cumulative incidence of cancer. RESULTS: In all, 3944 PIBD cases were included (2642 [67%] Crohn's disease, 1302 [33%] ulcerative colitis) translating into 23 635 person-years of follow-up, individually matched to 13 005 non-IBD children. By 30 years of age, 14 IBD patients [0.35%, 5.9/10 000 patient-years] were diagnosed with cancer and one [0.03%] with haemophagocytic-lymphohistiocytosis [HLH], compared with 14 [0.11%, 1.9/10 000 patient-years] cases of cancer {relative risk (RR) 2.5 (95% confidence interval [CI] 1.05-6.2); p = 0.04} and no HLH in the comparison-group. There were no cases of hepatosplenic T cell lymphoma, adenocarcinoma, or cholangiocarcinoma. Cancer risk was 15.6 cases/10 000 person-years in those treated with thiopurines alone (RR compared with IBD patients never exposed to either thiopurines or anti-tumuor necrosis factor [TNF] 1.8 [95% CI 0.6-6.1]; p = 0.2), 11.1/10 000 in those treated with anti-TNF alone (RR 1.3 [95% CI 0.3-6.6]; p = 0.5), and 23.1/10 000 treated with combination therapy of anti-TNF and thiopurines (RR 2.8 [95% CI 0.6-13.8]; p = 0.2). CONCLUSIONS: PIBD confers an increased risk for malignancy compared with non-IBD in children. However, the absolute risk is very low and no differences in risk with specific therapies were apparent in our data.

Increased incidence with improved survival of gynecologic carcinosarcoma: A population-based study.

OBJECTIVE: To evaluate trends in the incidence and survival of gynecologic carcinosarcoma over the last 35 years and to explore ethnic disparities. STUDY DESIGN: Using the Israeli National Cancer Registry database, all cases of gynecologic carcinosarcoma were included (1980-2014). Age at diagnosis, patient's ethnicity and anatomical site were extracted. Age-standardized incidence rates (ASRs) were calculated for 3 time periods (1980-1994, 1995-2004 and 2005-2014). Relative survival was calculated using the Pohar-Perme method. RESULTS: Overall, 935 cases of gynecologic carcinosarcomas were diagnosed during 1980-2014. The most common gynecologic anatomical site was the uterus (83.4%). Most cases (66%) were diagnosed at ages 60-80, with median age of 69 years. There was a steady increase in ASRs from 5.6 to 8.2 per million women. Throughout 1980-1994 and 2005-2014, ASRs were significantly higher in the Jewish compared to the Arab population (5.8 vs. 3.1, p = 0.02 and 8.5 vs. 5.2, p = 0.002, respectively). Relative survival rates increased throughout the study period. No significant differences were noted in relative survival between the Jewish and Arab populations (p = 0.18). CONCLUSION: The incidence of gynecologic carcinosarcoma increased significantly from 1980 through 2014. Nevertheless, survival rates increased during this time, with no difference in survival between the Jewish and Arab populations.

Pre-diagnosis thyroid hormone dysfunction is associated with cancer mortality.

Research on the association between thyroid hormone levels and cancer mortality remains limited and inconclusive. We determined the relation of thyroid stimulating hormone (TSH), free T4 (FT4), and free T3 (FT3) levels with mortality in overall cancer and specific tumor types. Thyroid hormone levels 1-5 years prior to cancer diagnosis, as well as multiple clinical and demographic parameters, were retrospectively collected for 10,325 Israeli cancer patients, diagnosed between 2000 and 2016. Patients treated with thyroid altering medications were excluded. Cancer diagnosis was determined via the Israel National Cancer Registry. Multivariate-adjusted Cox proportional hazards model was used to assess the hazard ratios (HRs) based on thyroid hormone function for cancer mortality. A total of 5265 patients died during the follow-up period (median of 4.4 years). TSH, FT4, and FT3 levels in the hypothyroid range were associated with increase in overall mortality (adjusted HR 1.20, 1.74, 1.87, respectively). We further analyzed the association between TSH and mortality in 14 cancer subgroups. Specifically, TSH in both the hyperthyroid and hypothyroid range was associated with melanoma mortality (adjusted HR 2.20, 4.47, respectively). In conclusion, pre-diagnosis of thyroid dysfunction is associated with increased cancer mortality, a relation likely driven by specific cancer types. These findings suggest that thyroid hormones may potentially serve as prognostic markers in cancer.

Breast cancer survivors: physical and mental quality of life 10 years following diagnosis, a case-control study.

PURPOSE: Improvements in diagnosis and treatment of Breast Cancer (BC) have resulted in an increase in the life expectancy of survivors and in the importance of quality of life in BC survivorship care. The current study aimed to assess the Health-Related Quality Of Life (HRQOL) of BC survivors and to investigate the association of comorbidities with HRQOL compared to a group of women with no history of cancer. METHODS: Women were residents of the central district in Israel, the case group included 250 women diagnosed with BC between 1999 and 2003, with no prior cancer history and no evidence of disease after 8-12 years. The comparison group included 250 women with no cancer history, individually matched to cases by age and area of residence. Data were collected through in-person interviews, and HRQOL was assessed using the Short Form-36 (SF-36) questionnaire. Regression analyses were performed evaluating the influence of demographic, socioeconomic, lifestyle characteristics and comorbidities on physical and mental HRQOL. RESULTS: The physical and mental summary scores means, were 48.5 ± 11.1 and 49.2 ± 10.8 compared to 51.5 ± 10.2 and 50.9 ± 10.6, in BC survivors and the comparison group, respectively (p = 0.002 and p = 0.097). BC survivors and controls did not differ in number and type of comorbidities and for both groups a negative association was seen with HRQOL. Controlling for age, income, number of comorbidities, BMI and physical activity, BC survivor had decreased physical (b = -2.49, p = 0.001) and mental summary scores (b = -1.27, p = 0.18). CONCLUSION: HRQOL of BC survivors should gain more attention in the area of cancer care, especially when comorbidities are present.

An Assessment of the Completeness and Timeliness of the Israel National Cancer Registry.

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.

Opposing effects of thyroid hormones on cancer risk: a population-based study.

OBJECTIVE: The association between dysregulated thyroid hormone function and cancer risk is inconclusive, especially among different age groups and uncommon malignancies. We sought to determine the relation of TSH and free T4 levels with overall cancer risk as well as risk of specific cancer types. DESIGN AND METHODS: Data on thyroid hormone profile was collected from 375 635 Israeli patients with no prior history of cancer. Cancer cases were identified via the Israel National Cancer Registry. Cox proportional hazards model was used to assess hazard ratios for overall cancer as well as 20 cancer subgroups. RESULTS: In this study, 23 808 cases of cancer were detected over median follow up of 10.9 years. Among patients younger than 50 at inclusion, TSH in the hyperthyroid range, elevated free T4 and subclinical hyperthyroidism were associated with increased cancer risk (HR: 1.3, 1.28 and 1.31, respectively). In contrast, patients 50 or older with clinical hyperthyroidism were at lower cancer risk (HR: 0.64). Elevated TSH was associated with decreased risk of prostate cancer (HR: 0.67). Log-TSH elevation was associated with decreased risk of thyroid cancer (HR: 0.82) and increased risk of melanoma (HR: 1.11) and uterine cancer (HR: 1.27). Elevated free T4 was associated with increased lung cancer risk (HR: 1.54), while free T4 levels above the normal range and clinical hyperthyroidism were related to lower colorectal cancer risk (HR: 0.59 and 0.08, respectively). CONCLUSIONS: Thyroid hormones display opposing effects on cancer risk, based on patient age and cancer type.

Sarcoma incidence and subtype distribution in Israel - A population-based study.

INTRODUCTION: This report aimed to describe sarcoma incidence and subtype distribution in Israel, as well as evaluate accuracy of registration for sarcoma cases diagnosed at a single institution. METHODS: Incidence reports were issued for all sarcomas diagnosed between 1996-2017. Concordance between the WHO classification used in pathology reports and the diagnoses in the national registry were evaluated. Sarcoma subtype distribution was analysed. RESULTS: Between 1996-2017 sarcomas had an annual percent change of -2.1 in men and -1.5 in women. Concordance between the pathology report coding and registry in the INCR were 90 %. The most common subtypes were Kaposi sarcoma (KS), liposarcoma and leiomyosarcoma accounting for 21 %, 14.4 % and 10.8 % of all sarcomas, respectively. KS had the highest incidence with 1.6/100,000 persons. CONCLUSION: This is the first description of sarcoma incidence and subtype distribution in Israel. Sarcoma incidence in Israel has declined in the past two decades.

Rising Incidence of Lung Cancer in Arab Females, Jewish Females, and Arab Males from 1990 to 2014 in Israel.

BACKGROUND: Lung cancer is the most common cause of cancer-related death. OBJECTIVES: To identify changing patterns of lung cancer and its histologic subtypes among different population groups in Israel over a 25 year period. METHODS: Primary lung cancers, all types and all stages, diagnosed during 1990-2014 were recorded in the Israel National Cancer Registry database. Demographic information was retrieved from the National Population Register. Age-standardized rates for the different subgroups were calculated for each year. Joinpoint software was used to analyze trends in incidence. RESULTS: We identified 42,672 lung cancer cases. The most common histology was adenocarcinoma (34%), followed by squamous cell carcinoma (19%), large cell/not-otherwise-specified (19%), other histologies (15%), and small cell lung cancer (11%). The adenocarcinoma incidence rose from 25.7% to 48.2% during the examined period. Large cell/not-otherwise-specified incidence peaked around 2005-2006 and declined after. Lung cancer incidence increased significantly for the population overall and specifically in Arab females, followed by Jewish females and by Arab males. Adenocarcinoma and small cell lung cancer increased in Jewish females and in Arab males. A younger age of diagnosis was seen in Arab compared to Jewish patients. CONCLUSIONS: Jewish females and Arab males and females living in Israel demonstrated a constant increase in lung cancer incidence, mostly in adenocarcinoma and small cell lung cancer incidence. In addition, a younger age of diagnosis in Arabs was noted. Smoking reduction interventions and screening should be implemented in those populations.

Rituximab is not associated with increased risk of second primary malignancies in Israeli patients with diffuse large B cell lymphoma treated with RCHOP regimen.

It is unknown whether rituximab increases the risk of second primary malignancies (SPMs) in patients with diffuse large cell B-cell lymphoma (DLBCL). We assessed SPMs in DLBCL patients diagnosed between 1996 and 2014 in comparison with the general Israeli population and dependent on rituximab treatment. Jewish patients had no increased risk for SPMs. Arab-DLBCL females had a higher SPMs rate compared to the general Arab-females population [SIR (95%CI) 1.86 (1.08-2.98)]. Incidence and time to SPMs, in both Jewish and Arab patients, were unaffected by rituximab. Risk for breast and thyroid cancers, in Arab and Jewish females respectively, were higher in the pre-rituximab era [SIR(95%CI) 5.25 (1.41-13.43) and SIR(95%CI) 3.85 (1.41-8.38), respectively]. Age ≥60 years was the only predictor for increased risk of SPM (HR = 2.5, p < .01). The increased risk of SPMs in specific subgroups of patients that were treated in the pre-rituximab era may reflect stringent medical surveillance employed in these populations.

A modified Prevalence Incidence Analysis Model method may improve disease prevalence prediction.

OBJECTIVES: The Prevalence Incidence Analysis Model method is used for predicting disease prevalence, using past data on incidence and relative survival. Our objective was to propose and evaluate a modified approach for choosing the Prevalence Incidence Analysis Model. STUDY DESIGN AND SETTING: Instead of the standard approach using the likelihood ratio statistic, we find the model that predicts most successfully the prevalence in the last available Y years using data up to but not including those Y years and then use that model to predict future prevalence another Y years ahead using all the data. We also make an "alignment" adjustment using the last known prevalence level. We evaluate the relative performance of the modified and standard methods using data on cancer from Israel in 1983-2013. RESULTS: In this example, the modified approach gave as good or better predictions than the standard. Using the modified approach, we forecast cancer prevalence in Israel for 2014-2024 to increase at a gradually accelerating rate from the current 10,000 per year to 12,000 per year by 2020, reaching a total of 380,000 by 2024. CONCLUSION: The modified approach may offer improved forecasting, but further methodological work on forecasting cancer prevalence is needed.

Characteristics and outcomes of patients with cancer presenting with acute myocardial infarction.

BACKGROUND: Limited data are available regarding the optimal management of patients with cancer in the acute myocardial infarction (AMI) setting. PATIENTS AND METHODS: We studied consecutive patients with AMI included in a national registry (years 2010, 2016) with the diagnosis of past or active malignancy and followed them for 1 year. RESULTS: Our cohort consisted of 2937 cancer-naive patients and 152 patients with cancer, of whom 35% presented with active malignancies. Compared with cancer-naive patients, patients with cancer were older, with female predominance, and presented more often with a history of hypertension and chronic kidney disease (P<0.001 for all comparisons). The rate of ST-elevation AMI was comparable (P=0.067). GRACE score more than 140 was more common in the cancer group (P<0.001). Most patients with cancer were referred to coronary angiography, though less than cancer-naive patients (87 vs. 93%; P=0.004). The rate of percutaneous coronary intervention was similar (P=0.265). Propensity score matching demonstrated similar rates of in-hospital complications between groups, and no mortality or major cardiac adverse event differences were noted at 30 days. Moreover, short-term mortality was similar between patients with active versus past malignancies, and between patients with solid and nonsolid tumors. However, cancer in patients with AMI was found to predict an increased mortality risk at 1 year by multivariable analysis (hazard ratio=2.52; P<0.001). CONCLUSION: Patients with cancer and AMI have a more complicated clinical presentation, yet their short-term prognosis is similar to cancer-naive patients. Nevertheless, 1-year outcome is worse.

Increased Risk for Cancer in Young Patients with Severe Obstructive Sleep Apnea.

BACKGROUND: Several studies in animal models and human with obstructive sleep apnea syndrome (OSAS) demonstrated an increase in cancer aggressiveness and mortality. However, there is a need for further clinical evidence supporting a correlation between OSAS and cancer incidence. OBJECTIVES: To reveal whether OSAS presence and severity is correlated with cancer incidence in a large homogenous patients' cohort. METHODS: We analyzed a cohort of over 5,000 concurrently enrolled patients, age > 18, with suspected OSAS, from a tertiary medical academic center. Patients underwent whole night polysomnography, the gold standard diagnostic tool for OSAS, and were classified for severity according to the Apnea Hypopnea Index (AHI). Data on cancer incidence were obtained from the Israel National Cancer Registry. A multivariate Cox proportional-hazards analysis, adjusted for age, gender, and BMI, was performed to estimate the hazard-ratio of new cancer incidence. RESULTS: Among 5,243 subjects with a median follow-up of 5.9 years, 265 were diagnosed with cancer. The most prevalent cancers were prostate (14.7%), hematological (12.8%), urothelial (9.4%), colorectal (9%), and breast (8.3%). In subjects who were diagnosed at age below 45 years (n = 1,533), a high AHI (> 57/h) was significantly associated with cancer (HR 3.7, CI 1.12-12.45, p = 0.008). CONCLUSIONS: Patients younger than 45 with severe OSAS have a significantly higher all-type cancer incidence than the general population. These results should encourage clinicians to detect and diagnose young patients with suspected OSAS and to recommend cancer screening methods in this high-risk population.

Deliveries following fertility preservation by ovarian tissue cryopreservation without autotransplantation-what should be expected?

OBJECTIVE: To evaluate the delivery rate and to characterize patients following ovarian tissue cryopreservation (OTCP) who did not undergo auto-transplantation. METHODS AND MATERIALS: All consecutive cancer patients admitted to our IVF unit, from January 2004 to December 2015, who underwent OTCP for the purpose of fertility preservation without autotransplantation were analyzed. The cohort included 338 patients and was linked to the National Live Birth registry of the Israel Ministry of Health in order to determine whether the women delivered following the cancer diagnosis. MAIN OUTCOME MEASURES: Delivery rate following OTCP without autotransplantation. RESULTS: During 6.4 years of follow-up, 30% of the patients delivered, with no differences in gravity, age at first diagnosis of cancer, type of malignancy, or the prevalence of relapse of malignancy between those who delivered and those who did not. Moreover, in multivariate analysis, those undergoing OTCP before the age of 30 and those suffering from breast cancer had significantly higher odds to conceive and deliver following cancer treatment without the need of autotransplantation. CONCLUSIONS: Further studies are required to elucidate the appropriate subgroup of patients with breast cancer under the age of 30 years, who will need OTCP. This information might aid both fertility specialists' counseling and their oncological patients in pursuing the appropriate fertility preservation strategy.

Uterine cancer in Jewish Israeli BRCA1/2 mutation carriers.

BACKGROUND: BRCA1/2 mutation carriers have an increased risk of developing ovarian cancer, leading to the recommendation of risk-reducing salpingo-oophorectomy (RRSO) at 35-40 years of age. The role, if any, that BRCA mutations play in conferring uterine cancer risk, is unresolved. METHOD: Jewish Israeli women, carriers of one of the predominant Jewish mutations in BRCA1/2 from 1998 to 2016, were recruited. Cancer diagnoses were determined through the Israeli National Cancer Registry. Uterine cancer risk was assessed by computing the standardized incidence ratio of observed-to-expected number of cases, using the exact 2-sided P value of Poisson count. RESULTS: Overall, 2627 eligible mutation carriers were recruited from 1998 to 2016, 2312 (88%) of whom were Ashkenazi Jews (1463 BRCA1, 1154 BRCA2 mutation carriers, 10 double mutation carriers). Among these participants, 1310 underwent RRSO without hysterectomy at a mean (± standard deviation) age of 43.6 years (± 4.4 years). During 32,774 women-years of follow up, 14 women developed uterine cancer, and the observed-to-expected rate of all histological subtypes was 3.98 (95% confidence interval [CI], 2.17-6.67; P < .001). For serous papillary (n = 5), the observed-to-expected ratio was 14.29 (95% CI, 4.64-33.34; P < .001), and for sarcoma (n = 4) it was 37.74 (95% CI, 10.28-96.62). These rates were also higher than those detected in a group of 1844 age- and ethnicity-matched women (53% with breast cancer). CONCLUSION: Israeli BRCA1 or BRCA2 mutation carriers are at an increased risk for developing uterine cancer, especially serous papillary and sarcoma. These elevated risks of uterine cancer should be discussed with BRCA carriers.

The risk of tuberculosis in cancer patients is greatest in lymphoma and myelodysplastic syndrome/myeloproliferative neoplasm: a large population-based cohort study.

Patients with cancer are at high risk for tuberculosis (TB). This study combined the Israeli databases of cancer and TB and examined the development of TB among all newly diagnosed cancer cases from 1993 to 2013. Patients were classified into groups according to their different malignancies. Among 495,335 cancer patients, 335 developed TB following cancer diagnosis. The cumulative incidence of TB following cancer diagnosis was highest among MDS/MPN (148.8/100,000 patients) and lymphoma (154.1/100,000 patients) (p = .023). The HR of TB following cancer among hematologic patients was 2.51 (p < .001), relative to patients with in situ carcinomas/skin cancer and highest among MDS/MPN and lymphoma patients (2.74, p = .012 and 2.70, p < .001, respectively). Among lymphoma patients, a significant increased HR was found only among NHL patients (2.72, p < .001). The limitations include lack of information regarding risk factors for TB and of anti-cancer treatments. In conclusion, these data may encourage a heightened awareness for TB among patients with a background of lymphoma and MDS/MPN.