Israel Medical Association Journal

Background: Esophageal cancer is comprised of adenocarcinoma and squamous cell carcinoma and is the sixth leading cause of cancer-related mortality worldwide. Upper endoscopy may reveal a partially or completely lumen-occluding mass at diagnosis, yet the prognostic significance of such a presentation is not clear.

Objectives: To investigate whether endoscopic obstructing lesions have a meaning regarding patient prognosis.

Methods: We reviewed upper gastrointestinal endoscopic studies performed over a 20-year period (2000–2020). We compared overall survival, disease stage, histologic criteria, and anatomic location of the lesions in esophagus lumen-obstructing and non-obstructing tumors. Differences between the two groups were statistically evaluated.

Results: Sixty-nine patients were diagnosed with histologically confirmed esophageal cancer. As assessed through endoscopy, 32/69 (46%) patients had obstructive and 37/69 (54%) had non-obstructive cancers. Median survival was significantly shorter in the lumen-obstructing lesions compared with the non-obstructing lesions (3.5 months vs. 10 months, P = 0.001). Female median survival displayed a trend toward shorter survival compared to males (3.5 months vs. 10 months, P = 0.059). There was no statistically significant difference in the percentages of advanced, stage IV disease in the obstructive group and the non-obstructive group (11/32 [34.3%] and 14/37 [37.8%], respectively P = 0.80).

Conclusions: Obstructive esophageal cancers predict shorter median overall survival compared with non-obstructive cancers, without any correlation between obstruction of the lesion and tumor metastatic stage.

Background: Recent studies show a high risk of developing malignancy in patients with Fanconi anemia. The most common solid tumor in this condition is head and neck squamous cell carcinoma (HNSCC) and there is often uncertainty and about disease behavior as well as chemotherapy and radiation response.

Objectives: To describe and characterize HNSCC among Fanconi anemia patients on the Israeli Fanconi Registry

Methods: Our study population included patients in Israel's inherited bone marrow failure registry who were diagnosed with Fanconi anemia between1980 and 2016. Demographic, clinical, and laboratory data were collected from patient charts.

Results: From the collected data, HNSCC was confirmed in 6/111 (5.4%) Fanconi anemia patients; 1 (17%) had classic HNSCC risk factors of tobacco abuse and 4 (56%) had undergone primary surgery. The 3 (50%) receiving concurrent chemoradiotherapy had mild side effects, while half developed metachronous primary malignancy, and all developed > 2 primary malignancies. The overall median survival of the patients in our study was 14 (0.5–57) months.

Conclusions: Fanconi anemia patients have a very high risk of developing HNSCC. Proactive screening for malignancies is needed for the head and neck regions. We also found that chemoradiotherapy can be used safely in high-stage cancers.

Background: Immune cell counts in blood in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may be useful prognostic biomarkers of disease severity, mortality, and response to treatment.

Objectives: To analyze sub-populations of lymphocytes at hospital admission in survivors and deceased from severe pneumonia due to coronavirus disease-2019 (COVID-19).

Methods: We conducted a cross-sectional study of healthcare workers confirmed with SARS-CoV-2 in convalescents (control group) and healthy controls (HC) diagnosed with severe COVID-19. Serum samples were taken at hospital admission and after recovery. Serum samples ≥ 25 days after onset of symptoms were analyzed for lymphocyte subpopulations through flow cytometry. Descriptive statistics, Kruskall-Wallis test, receiver operating characteristic curve, calculation of sensitivity, specificity, predictive values, and Kaplan-Meier analysis were performed.

Results: We included 337 patients: 120 HC, 127 convalescents, and 90 severe COVID-19 disease patients (50 survivors, 40 deceased). For T cells, total lymphocytes ≥ 800/μL, CD3+ ≥ 400/μL, CD4+ ≥ 180/μL, CD8+ ≥ 150/μL, B cells CD19+ ≥ 80/μL, and NK ≥ 34/μL subsets were associated with survival in severe COVID-19 disease patients. All subtypes of lymphocytes had higher concentrations in survivors than deceased, but similar between HC and convalescents. Leukocytes ≥ 10.150/μL or neutrophils ≥ 10,000/μL were associated with increased mortality. The neutrophil-to-lymphocyte ratio (NLR) ≥ 8.5 increased the probability of death in severe COVID-19 (odds ratio 11.68).

Conclusions: Total lymphocytes; NLR; and levels of CD3+, CD4+, CD8+, and NK cells are useful as biomarkers of survival or mortality in severe COVID-19 disease and commonly reach normal levels in convalescents.

Background: Peritoneal dialysis (PD) is a treatment option for patients with end-stage renal disease (ESRD) and cardiorenal syndrome (CRS).

Objectives: To evaluate the outcome of this patient population.

Methods: A retrospective study was conducted of patients who underwent an open or laparoscopic insertion of a PD catheter at our institution between 2009 and 2017. Data included demographics, peri-operative parameters, and long-term outcome. Patient and technique survival curves are presented, including subgroup analysis by method of catheter insertion and techniques for infection prevention.

Results: The study population included 95 men and 42 women, aged 65.7 ± 12.4 years. Mean follow-up was 34.6 ± 27.3 months. Open insertion was performed in 113 cases, while 24 underwent laparoscopic insertion. There was no difference in technique survival between these groups (P = 0.943). Removal of the catheter was required in 66% of patients. Median technique survival was 12.1 months. Two-year technique survival was 37% and 5-year technique survival was 12%. The leading cause for catheter removal was infection (69%). Application of measures for prevention of infections were significantly associated with prolonged technique survival (P = 0.001). Technique survival after 2 years was 38% with the application of a single measure and 57% with the application of two measures (P = 0.001). CRS patients (n=24) had a significantly lower overall survival rate (2-year survival 20% vs. 74%, P = 0.001).

Conclusions: The method of catheter insertion has no effect on technique survival. Prevention of infections is the most significant factor for improving the technique survival rates.

Background: The impact of revascularization of coronary chronic total occlusion (CTO) on survival is unknown. Several studies, which included subjects with varied coronary anatomy, suggested that CTO revascularization improved survival. However, the contribution of CTO revascularization to improved outcome is unclear since it was more commonly achieved in subjects with fewer co-morbidities and less extensive coronary disease.

Objectives: To study the association between CTO revascularization and survival in patients with uniform coronary anatomy consisting of isolated CTO of the right coronary artery (RCA).

Methods: A registry of 16,832 coronary angiograms was analyzed. We identified 278 patients (1.7%) with isolated CTO of the RCA who did not have lesions within the left coronary artery for which revascularization was indicated. Survival of 52 patients (19%) who underwent successful percutaneous coronary intervention was compared to those who did not receive revascularization.

Results: Revascularized patients were younger (60.2 vs. 66.3 years, P = 0.001), had higher creatinine clearance (106 vs. 83 ml/min, P < 0.0001), and had fewer co-morbidities than those who did not receive revascularization. Lack of CTO revascularization was a univariable predictor of mortality (hazard ratio [HR] = 2.65, 95% confidence interval [95%CI] 1.06–6.4) over 4.3 ± 2.5 years of follow-up. On multivariable analysis, the only predictors of mortality were increased age (HR 1.04, 95%CI 1.01–1.07), reduced creatinine clearance (HR 1.02, 95%CI 1.01–1.03), and ejection fraction below 55% (HR 2.24, 95%CI 1.22–4.11).

Conclusions: Among patients with isolated RCA CTO who underwent extended follow-up, revascularization was not an independent predictor of increased survival.

Background: The treatment of elderly patients with advanced stage ovarian carcinoma is challenging due to a high morbidity.

Objective: To evaluate the clinical course and outcome of elderly patients with advanced stage ovarian carcinoma receiving neoadjuvant chemotherapy (NACT).

Methods: A retrospective study of all patients with stage IIIC and IV ovarian carcinoma receiving NACT in one medical center (between 2005 and 2017). The study group criteria age was above 70 years. The control group criteria was younger than 70 years old at diagnosis. Demographics and treatment outcomes were compared between groups. Primary outcomes were progression-free survival (PFS) and overall survival (OS).

Results: Overall, 105 patients met the inclusion criteria, 71 patients (67.6%) were younger than 70 years and 34 patients (32.4%) older. Rates of interval cytoreduction were significantly higher in younger patients (76.1% vs. 50.0%, P = 0.01). Of those who underwent interval cytoreduction, no difference was found in rates of optimal debulking between groups (83.35% vs. 100%, P = 0.10). Using a Kaplan-Meier survival analysis, no significant differences were observed between groups in PFS or OS, P > 0.05. Among the elderly group alone, patients who underwent interval cytoreduction had significantly longer PFS than those without surgical intervention (0.4 ± 1.7 vs. 19.3 ± 19.4 months, P = 0.001).

Conclusions: Elderly patients with ovarian carcinoma who received NACT undergo less interval cytoreduction than younger patients, with no difference in PFS and OS. However, among the elderly, interval cytoreduction is associated with significantly higher PFS.

Background: Heart failure centers with specialized nurse-supervised management programs have been proposed to improve prognosis. The Heart Failure Center in Beit Shemesh, Israel, is located within a large primary care facility. The specialist team supervised the managememt of patients both within the frame of the center and while they were hospitalized.

Objectives: To evaluate the health services utilization by heart failure patients treated at a heart failure center and their clinical outcome.

Methods: In this retrospective study, we compared the clinical outcome of patients treated at a heart failure center to patients who received the standard care in 2013–2014. The clinical outcome included primary care visits, emergency room visits, hospitalizations, and death.

Results: The study comprised 430 heart failure patients; 82 were treated at the heart failure center and 348 under standard care. At baseline, no significant differences were seen in clinical parameters between the groups. Healthcare utilization was higher among the study group. No significant changes in healthcare utilization were found. During follow-up, patients treated in a heart failure center were more likely to get recommended heart failure medications. Mortality was significantly lower in patients treated in the heart failure center compared with those receiving standard care 3.6% vs. 24%, respectively (P = 0.001), hazard ratio 0.19, 95% confidence interval 0.06–0.62, P = 0.005.

Conclusions: Joint management of heart failure by primary clinics and a specialized community heart failure center reduced mortality. There was no decrease in healthcare utilizations among heart failure center patients, despite the reduction in mortality.

Background: Endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA) is associated with decreased perioperative morbidity and mortality.

Objectives: To report the outcomes of EVAR among patients older than 80 years of age.

Methods: In this retrospective study, we reviewed patients older than 80 years of age who underwent elective EVAR at our institution between 2007 and 2017. The demographics, perioperative morbidity and mortality, and long-term results are reported.

Results: During the study period, 444 patients underwent elective EVAR for AAAs. Among them 128 patients (29%) were > 80 years of age. Mean age was 84 ± 3.4 (range 80–96) years, and 110 patients (86%) were male. The EVAR was technically successful in 127 patients (99%) and there were intraoperative mortalities. Within 30 days of the surgery, nine patients (7%) died. Major and minor adverse events occurred in 26 (20%) and 59 (46%) patients, respectively. Factors associated with increased risk of perioperative morbidity and mortality included chronic kidney disease, peripheral artery disease, and the existence of three or more co-morbidities.

Conclusions: EVAR in the elderly can be performed with a high rate of success; however, it is associated with a substantial rate of morbidity and mortality, particularly when patients present with multiple co-morbidities. When performing EVAR in this population group, the risk of rupture must be considered opposed to the life expectancy of these patients and the risk of perioperative morbidity and mortality.

Background: Statins and selective serotonin reuptake inhibitors (SSRIs) have beneficial effects on health outcomes in the general population. Their effect on survival in debilitated nursing home residents is unknown.

Objectives: To assess the relationships between statins, SSRIs, and survival of nursing home residents.

Methods: Baseline patient characteristics, including chronic medications, were recorded. The association of 5-year survival with different variables was analyzed. A sub-group analysis of survival was performed according to baseline treatment with statins and/or SSRIs.

Results: The study comprised 993 residents from 6 nursing homes. Of them, 285 were males (29%), 750 (75%) were fully dependent, and 243 (25%) were mobile demented. Mean age was 85 ± 7.6 years (range 65–108). After 5 years follow-up, the mortality rate was 81%. Analysis by sub-groups showed longer survival among older adults treated with only statins (hazard ratio [HR] for death 0.68, 95% confidence intervals [95%CI] 0.49–0.94) or only SSRIs (HR 0.6, 95%CI 0.45–0.81), with the longest survival among those taking both statins and SSRIs (HR 0.41, 95%CI 0.25–0.67) and shortest among residents not taking statins or SSRIs (P < 0.001). The survival benefit remained significant after adjusting for age and after conducting a multivariate analysis adjusted for sex, functional status, body mass index, mini-mental state examination, feeding status, arrhythmia, diabetes mellitus, chronic kidney disease, and hemato-oncological diagnosis.

Conclusion: Treatment with statins and/or SSRIs at baseline was associated with longer survival in debilitated nursing home residents and should not be deprived from these patients, if medically indicated. 

Background: Reports of longevity in Holocaust survivors (HS) conflict with excess prevalence of chronic diseases described among them. However, data on their long-term risk of cardiovascular diseases (CVD) are limited. Clinical data on large representative groups of HS who were exposed to severe persecution are also limited.

Objectives: To determine the prevalence of CVD and the risk factors in a large cohort of elderly HS compared to elderly individuals who were not exposed to the Holocaust (NHS).

Methods: CVD prevalence rates and risk factors data from the computerized system of the central district of Clalit Health Services, the largest Israeli health maintenance organization (HMO) in Israel were evaluated in a retrospective observational study. The study was comprised of 4004 elderly HS who underwent direct severe persecution. They were randomly matched by identification numbers to 4004 elderly NHS.

Results: HS were older than NHS and 51% of them were older than 85 years. The prevalence rate of ischemic heart disease (IHD) was significantly higher among HS. HS underwent significantly more cardiac interventions (20% vs. 15.7%, P < 0.05). HS status was an independent risk factor for increased IHD and for more coronary interventions.

Conclusions: Despite having a higher prevalence of CVD, a substantial number of HS live long lives. This finding may imply both unique resilience and ability to cope with chronic illness of the survivors as well as adjusted medical services for this population. These findings may help in planning the treatment of other mass trauma survivors.

Background: The lack of organs for liver transplantation has prompted transplant professionals to study potential solutions, such as the use of livers from donors older than 70 years. This strategy is not widely accepted because potential risks of vascular and biliary complications and recurrence of hepatitis C.

Objectives: To examine the efficacy and safety of liver grafts from older donors for transplantation.

Methods: A retrospective analysis of data on 310 adults who underwent deceased donor liver transplantation between 2005 and 2015 was conducted. We compared graft and recipient survival, as well as major complications, of transplants performed with grafts from donors younger than 70 years (n=265, control group) and those older than 70 years (n=45, older-donor group), followed by multivariate analysis, to identify risk factors.

Results: There was no significant difference between the control and older-donor group at 1, 5, and 10 years of recipient survival (79.5% vs. 73.3%, 68.3% vs. 73.3%, 59.2% vs. 66.7%, respectively) or graft survival (74.0% vs. 71.0%, 62.7% vs. 71.0%, 54.8% vs. 64.5%, respectively). The rate of biliary and vascular complications was similar in both groups. Significant risk factors for graft failure were hepatitis C (hazard ratio [HR] = 1.92, 95% confidence interval [95%CI] 1.16–2.63), older donor age (HR = 1.02, 95%CI 1.007–1.031), and male gender of the recipient (HR = 1.65, 95%CI 1.06–2.55).

Conclusion: Donor age affects liver graft survival. However, grafts from donors older than 70 years may be equally safe if cold ischemia is maintained for less than 8 hours.

Background: With advances in myelodysplastic syndromes (MDS), patient cohorts from different time periods might be different.

Objectives: To compare presentation and outcomes between two cohorts.

Methods: Data were collected from George Washington University Medical Center, Washington, DC, USA 1986–1987 (DC), and Tel Aviv Medical Center, Israel 1999–2009 (TA).

Results: The study comprised 227 patients (139 TA, 88 DC). TA patients were older (75.4 ± 9.8 vs. 63.8 ± 14.3 years, P < 0.001) and had more cardiovascular diseases (56.8% vs. 14.8%, P < 0.001), fewer cytopenias (1.67 ± 0.82 vs. 2.0 ± 0.93, P = 0.003), and lower mean corpuscular volume (94.3 ± 9.9 fl vs. 100.5 ± 15.3 fl, P < 0.001). Hemoglobin, leukocyte, neutrophil, and platelet counts were similar. More TA patients had dysplasias. Bone marrow cellularity and cytogenetics were similar, but more TA patients had blasts < 5% (73.4% vs. 50.6%, P = 0.003). More TA patients had early French-American-British (FAB) disease (66.9% vs. 40.9%, P < 0.001) and lower risk disease per International Prognostic Scoring System (81% vs. 50%, P < 0.001). The 5 year survival (5YS) of TA patients was not significantly greater (62% vs. 55%). 5YS by FAB was also slightly greater for TA patients (77% vs. 65% for early FAB; 43% vs. 37% for advanced FAB, P > 0.05).

Conclusions: Although patients diagnosed with MDS at a later period were older and had more cardiovascular co-morbidities, they had fewer cytopenias, tended to have earlier disease, and had minimally greater, but not significant, 5YS.

The discovery of Jewish babies who were born in Nazi concentration camps and survived seems miraculous, but this phenomenon did occur toward the end of World War II. The lives of a small group of mothers and surviving children are of both historical and medical interests. Their survival shows additional support for the hypothesis that maternal nutrition can induce metabolic syndrome and bone demineralization in their offspring. Information obtained through direct contact with some of the surviving children is the basis for this article.

Background: Uterine carcinosarcoma (UCS) is a rare tumor with a poor prognosis. An elevated thrombocyte count and thrombocytosis were found to be associated with poor prognosis in several gynecological tumors. Data regarding an elevated thrombocyte count and thrombocytosis, particularly in UCS, are scarce.

Objectives: To assess the frequency of a preoperative elevated thrombocyte count and of thrombocytosis in UCS patients and their association with clinicopathological prognostic factors and survival.

Methods: The preoperative thrombocyte count of 29 consecutive verified USC patients diagnosed in our medical center from January 2000 to July 2015 was recorded, and clinicopathological data of these patients were abstracted from hospital files. 

Results: Thrombocytosis was found in two patients (6.8 %) and both died of the disease. An elevated thrombocyte count was found in nine patients (31.0%). The percentage of patients with the poor prognostic factors who had a preoperative elevated thrombocyte count was not statistically different from those without these risk factors. The cumulative survival of patients with an elevated count was 22.1 months and that of those without an elevated count was 31.1 months. This difference was statistically not significant (P = 0.85). There was also no difference between the groups regarding the progression free survival.

Conclusions: No association between an elevated thrombocyte count and prognosis was found. Larger studies are needed to clarify this issue.