Israel Medical Association Journal

Background: There is a rising incidence of bladder cancer (BC) in Israel and worldwide. BC is currently the fourth most common cancer in Israeli males. There are large variations in the incidence of BC observed in different populations, both in Israel and worldwide.

Objectives: To characterize the time trends and epidemiologic profile of BC in Israel regarding various population demographics.

Methods: All cases of BC reported to the Israeli National Cancer Registry between 1996 and 2016 were included. We calculated age standardized rates for BC. Joinpoint regression analysis was used to study trends in incidence as expressed by annual percent change (APC) in incidence.

Results: Between 1996 and 2016, 28,953 cases of BC were diagnosed in Israel. BC rates in Jewish males peaked in 2006 and subsequently declined (APC = -1.69, P < 0.05). Between 1996 and 2011, in-situ BC rates increased for both Jewish (APC = 28.2, P < 0.05) and Arab males (APC = 16.76, P < 0.05). Invasive BC incidence in Jewish males declined from 2005 to 2016 (APC = -7.6, P< 0.05) as well as in Arab males from 2006 to 2011 (APC = -12.0, P < 0.05).

Conclusions: In the past two decades, in situ BC rates have risen, while invasive BC rates have decreased. BC epidemiology mirrors lung cancer trends, which is expected as smoking is a significant risk factor for both. These trends are important to identify as they can affect clinical guidelines regarding screening in high-risk populations and health care planning.

Background: Locally advanced gastric adenocarcinomas are treated with neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy. Since 2019 the standard of care for perioperative chemotherapy has been FLOT protocol. Concerns regarding the use of FLOT in elderly patients ≥ 65 years of age emerged due to the relatively high toxicity of this protocol.

Objectives: To evaluate the toxicity profile of FLOT and clinical outcome in elderly patients.

Methods: We conducted a retrospective analysis of patients with locally advanced gastric adenocarcinomas treated with FLOT between 2017–2023 at the Sheba Medical Center. The cohort was stratified by age (≥ or < 65 years). The primary outcome was overall survival (OS). Secondary outcomes were treatment-related toxicity. Kaplan-Meier analysis and Cox proportional hazard regression model were used to analyze the effect of exposure variables on OS.

Results: The study cohort included 91 patients. The median age was 60 years (IQR 50–67); 32 patients were included in the ≥ 65 years group, and 59 patients were included in the < 65 years group. Median follow-up was 40 months (IQR 17–58). Patients ≥ 65 years old received fewer cycles of FLOT compared to those < 65 years old (4.5 vs. 7 cycles, respectively, P = 0.03). Despite the difference in treatment intensity and cumulative chemotherapy dose, there was no difference in median OS between patients ≥ 65 years old compared with those < 65 years old (P = 0.68).

Conclusions: Elderly patients with locally advanced gastric adenocarcinomas received fewer cycles of perioperative FLOT without compromising clinical outcomes.

Background: Hypofractionation regimens shorten the overall duration of treatment, thereby reducing the risk of accelerated tumor cell repopulation following the initiation of radiotherapy. These regimens have been shown to improve overall survival and locoregional control in patients with laryngeal cancer. The toxic effects from radiotherapy for laryngeal squamous cell carcinoma (SCC) include dysphagia, mucositis, laryngeal edema, weight loss, and pain.

Objectives: To evaluate early toxicity and opioid usage associated with hypofractionation treatment of the larynx compared to standard fractionated radiotherapy.

Methods: We retrospectively analyzed 127 laryngeal SCC patients who underwent radiotherapy. Among these, 50% with early glottic cancer received hypofractionation (2.25 Gy per fraction, totaling 63 Gy) directed at the larynx, while 50% with advanced-stage disease underwent standard fractionation (2 Gy per fraction, totaling 70 Gy) targeting both the larynx and bilateral neck, with or without concurrent chemotherapy.

Results: Patients in the hypofractionation group required significantly higher dosages of opioids due to increased pain and swallowing discomfort (P < 0.05). Those in the hypofractionation group who received dexamethasone boluses experienced significantly less weight loss compared to hypofractionation patients who did not receive steroids, with some even experiencing weight gain (P < 0.005). Patients with advanced-stage cancer treated with chemoradiotherapy exhibited greater toxicity than those receiving radiotherapy alone.

Conclusions: Patients undergoing hypofractionation treatment generally require significantly higher doses of opioids than those treated with standard fractionation. Treatment protocols for patients receiving hypofractionation should include effective pain management strategies and, where feasible, the use of corticosteroids.

Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin tumor with an increasing incidence in Western countries. Predominantly affecting older individuals, MCC represents less than 1% of malignant skin tumors.

Objectives: To characterize the clinical presentation, therapeutic interventions, and follow-up outcomes of MCC patients. To promote heightened clinical awareness regarding the early recognition and diagnosis of MCC.

Methods: We conducted a retrospective cohort study analyzing medical records of MCC patients at the Shaare Zedek Medical Center between 2015–2022. From 19 initially identified patients, 17 met the inclusion criteria. Data collection included demographic, epidemiological, clinical, and pathological characteristics.

Results: The study included 17 patients, predominantly of Jewish origin, with a mean age of 70.06 years; 58.8% female. Medical co-morbidities included 64.7% hypertension and 35.3% diabetes. MCC tumors were predominantly left-sided (58.8%), with varied locations including limbs, trunk, and face. Surgical treatment consisted of excision and primary closure (64.7%) or skin grafting (23.5%). The average tumor diameter was 3.41 cm clinically and 3.83 cm pathologically. Lymph node involvement occurred in 29.4% of cases; 23.5% showed metastatic disease at diagnosis, with metastases diffused in different body areas. Kaplan-Meier survival analysis showed no statistically significant differences across most variables, except for a significantly lower survival rate in patients with ischemic heart disease (P = 0.009).

Conclusions: Our study reveals unique characteristics of MCC, predominance of female patients, and a slightly younger average diagnosis age compared to existing literature. The 2-year survival rate in our cohort was 82%. The study underscores the importance of early detection and diagnosis of MCC, thereby enhancing clinical awareness and improving patient outcomes.

Background: Breast edema, characterized by fluid accumulation in breast tissue, is a common yet understudied complication following breast-conserving surgery (BCS) and radiotherapy for breast cancer. Its impact on physical and emotional well-being highlights the need for deeper exploration of its prevalence, risk factors, and clinical management.

Objectives: To evaluate the prevalence of breast edema following breast surgery, investigate its association with arm lymphedema, and explore links to surgical interventions.

Methods: We analyzed 105 breast cancer patients treated with BCS and axillary interventions, including sentinel lymph node biopsy (SLNB), lymph node sampling, or axillary lymph node dissection (ALND). Comprehensive evaluations included physical exams, arm circumference measurements, and a thorough review of patient demographics, medical history, and disease progression to assess the presence and severity of breast and arm lymphedema.

Results: Breast edema prevalence was 7.6%, with rates significantly influenced by surgical extent. None of the SLNB patients exhibited breast edema, compared to 23.5% of ALND patients. Significant predictors included arm lymphedema (OR 57.54, P = 0.024), body mass index (OR 0.65, P = 0.016), and tumor grade (OR 51.78, P = 0.040). Co-occurrence of breast and arm lymphedema was observed in 50% of cases.

Conclusions: Breast edema is a significant postoperative complication influenced by surgical extent and lymphatic disruption. Improved diagnostic methods, multidisciplinary care, and innovative surgical strategies are essential for mitigating this condition and enhancing patient outcomes.

Background: Breast reconstruction following oncological resection offers psychosocial benefits. Various factors influence patient reconstruction decisions, including ethnicity, socioeconomic status, and education. We investigated disparities in breast reconstruction among Bedouin and non-Bedouin women in the Negev region.

Objectives: To investigate the influence of ethnicity in breast reconstruction decisions between Bedouin and non-Bedouin women in Israel and to identify factors influencing the choice of reconstruction following oncological breast surgery.

Methods: In this retrospective cohort study, we examined women undergoing breast cancer surgery, with or without reconstruction, between 2015 and 2021 in a breast cancer referral center. Demographics and detailed medical data were collected from electronic health records. We analyzed the factors that influenced decisions regarding breast reconstruction.

Results: The study included 1415 patients who underwent breast resection. Age was a significant factor in breast reconstruction choices, with younger patients being more likely to choose reconstruction. Marital status and education level influenced the decision, whereas socioeconomic status and number of children did not. Ethnicity analysis highlighted distinct demographic and socioeconomic differences between Bedouin and non-Bedouin women. Despite these disparities, surgical choices did not differ significantly between ethnicities.

Conclusions: Significant disparities exist between Bedouin and non-Bedouin women in terms of sociodemographic factors. However, these disparities did not affect their breast reconstruction decisions. Age, marital status, and education level influenced the decision to reconstruct the breast.

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by hamartomatous polyps throughout the gastrointestinal tract, with an estimated prevalence of 1 in 100,000 individuals. While most cases follow an autosomal dominant inheritance pattern, some are caused by de novo mutations [1].

The age of onset for JPS is typically during childhood or adolescence, with a mean age at diagnosis of 18.5 years [2]. A major concern in JPS is the increased risk of colorectal cancer (CRC), requiring close lifelong surveillance. The cumulative lifetime risk for CRC ranges from 38% to 68%, with a mean age at diagnosis between 34 and 44 years [3].

Although juvenile polyps were initially considered to have low malignant potential, studies have identified two pathways of carcinogenesis in JPS: progression from hamartomatous polyps to adenoma and then to adenocarcinoma or direct transformation of hamartomatous polyps into adenocarcinoma. The management of JPS is tailored to each patient's specific manifestations and clinical presentation. The primary treatment goal is to prevent morbidity associated with gastrointestinal polyps, such as bleeding and intestinal obstruction.

Background: BRCA1/BRCA2 female pathogenic sequence variant (PSV) carriers in Israel are offered semiannual cancer antigen 125 (CA125) serum level determination and transvaginal ultrasound until performing risk reducing salpingo-oophorectomy (RRSO), even with the lack of proven efficacy of these procedures in providing adequate early detection of ovarian cancer.

Objectives: To report the results of longitudinal CA125 measurements in BRCA1/BRCA2 carriers as a tool for ovarian cancer detection in a single medical center in Israel.

Methods: Asymptomatic BRCA1/BRCA2 PSV carriers attending the Meirav High Risk Clinic at Sheba Medical Center for more than 3 years were eligible. Data on specific PSV, risk reducing surgeries, and cancer diagnoses were obtained from participant records. We used chi-square and Wilcoxon-Rank tests for statistical analyses.

Results: Overall, 739 (399 BRCA1, 336 BRCA2, 4 BRCA1 + BRCA2) PSV carriers were included. Mean age at the start of follow-up was 38.96 ± 11.13 years, mean follow-up time was 7.93 ± 2.34 years, (5860.80 women/years). Most participants (490/739 [66.3%]) had stable CA125 levels (± 5 U/µl). Of participants, 61 had CA125 levels > 35 U/µl at least twice (n=42) or at least doubling of marker levels to a minimum of 20 U/µl (n=19), results that have led to further cancer defining investigations. Of these, 14 and 4 were diagnosed with breast and ovarian cancer, respectively.

Conclusions: Longitudinally stable CA125 levels were noted in most BRCA1/BRCA2 PSV carriers and elevated levels were a poor marker for ovarian cancer development.

Background: Colorectal cancer (CRC) is the third most commonly occurring cancer worldwide. There are conflicting reports on whether colonoscopies performed during the morning shift have higher adenoma detection rates.

Objectives: To investigate the differences in polyp detection rate (PDR) in colonoscopies between morning and afternoon shifts.

Methods: In a retrospective, multicenter study involving a large cohort, we analyzed all colonoscopies conducted between 2016 and 2023 across seven endoscopy departments. The PDR was compared between morning and afternoon shifts.

Results: We included 368,997 colonoscopies: 213,795 (57.9%) performed during the morning shift and 155,202 (42.1%) during the afternoon shift. Patients undergoing colonoscopies during the morning shift were more frequently female (53.8% vs. 51%, P < 0.001) and tended to be older compared to those in the afternoon shift (average age of 56.97 ± 12.6 vs. 55.6 ± 12.9, P < 0.001). Colonoscopies conducted during the morning shift exhibited a higher cecum intubation rate (CIR) (96.7% vs. 95.6%, P < 0.001). During the morning shift, higher rates of PDR (32.9% vs. 29.9%, P < 0.001) were observed. In the multivariate analysis, after adjusting for other variables, age, male sex, polyp follow-up, fecal occult blood test, morning shift, familial history of CRC, and rectal bleeding demonstrated statistically significant associations (P < 0.001) for PDR.

Conclusions: Colonoscopies during the morning shift yielded a higher PDR and CIR than those in the afternoon. To improve this rate, endoscopists working the afternoon shift must be provided with the right conditions.

We presented the emergent development of pulmonary hypertension and right ventricular impairment in a 64-year-old woman with metastatic breast cancer undergoing carboplatin–gemcitabine combination therapy. The patient's acute decompensation, characterized by dyspnea and desaturation, occurred 2 days after chemotherapy initiation. Clinical assessments revealed right ventricular dilation and systolic dysfunction, a rare manifestation not previously associated with the administered drugs, but which may be associated with cardiopulmonary toxicity of gemcitabine therapy. Prompt discontinuation of chemotherapy and initiation of diuretic therapy resulted in clinical improvement and resolution of the right ventricular dysfunction within several weeks. While a definitive causal link to gemcitabine remains inconclusive, this report highlights a potential and under-reported side effect, emphasizing the need for increased awareness and further investigation into the cardiopulmonary effects of gemcitabine.

Colorectal cancer (CRC) is a major health concern, ranking as the third most common cancer in the United States. Screening programs, especially colonoscopy, play a crucial role in preventing CRC by removing and detecting polyps or early-stage cancers. Despite inherent risks, colonoscopy's effectiveness in saving lives is significant. In this review, we analyzed the outcomes of screening colonoscopies in an asymptomatic population for 15 years, focusing on detection rates and complications. We compared the data with previous meta-analyzes to evaluate changes in efficacy and safety. We conducted a systematic search of medical literature databases (1 January 2012 to 31 December 2023) for English-language studies on CRC screening colonoscopy. Our inclusion criteria comprised complete articles with over 500 participants with extractable data and a focus on screening colonoscopy outcomes in average-risk populations. In total, 2,897,025 people were screened, most (99.6%) were asymptomatic and were an average-risk population. Colonoscopy was complete and reached the cecum in 97–99% of the procedures. CRC was found in 0.5% (95% confidence interval [95%CI] 0.4–0.7%) of the participants. Advanced adenoma was found in 7.6% (95%CI 6.2–9.3%) of the cases. Complications were rare. Perforation developed in 0.022% of the cases and bleeding in 0.148%. Our findings exhibited a significant increase in the detection yield of adenomas and advanced adenomas with low complication rates, which shows that colonoscopy is feasible and suitable for screening for CRC in asymptomatic people.

Inflammatory myopathies include polymyositis, necrotizing autoimmune myositis, dermatomyositis, juvenile inflammatory myopathy, and inclusion body myositis. These diseases are classified based on the different clinical and pathological characteristics unique to each of them [1]. Dermatomyositis is a rare disease with an incidence of 6–10 cases/1,000,000 a year with the highest incidence in the 7th decade of life as reported by a Norwegian cohort in a Caucasian population [2].

Diagnosis of dermatomyositis is based on typical signs and symptoms combined with laboratory results, imaging, and electromyography findings and muscle biopsy. Historically, the diagnosis of dermatomyositis was based on the classification criteria named after Bohan and Peter published in 1975. Many other classification criteria were proposed subsequently, the latter by the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR), which were published in 2020 [3].

The clinical features of dermatomyositis are diverse. Skin manifestations can accompany or precede muscle weakness. Classical skin findings include periorbital heliotrope rash and a rash of the upper chest, back, and shoulders, known as the V sign and shawl sign respectively, as well as the Gottron's papules on the knuckles. Another skin appearance is subcutaneous calcifications that break periodically through the skin causing ulcerations. Dermatomyositis usually manifests as a symmetrical proximal muscle weakness but can present with preserved strength called amyopathic dermatomyositis [1].

Background: With age, colorectal cancer (CRC) prevalence rises. The elderly (> 75 years), and the very elderly (> 85 years) are especially vulnerable. The advantages of screening must be assessed in the context of diminished life span and co-morbidities.

Objective: To compare CRC findings in colonoscopies that were performed following a positive fecal occult blood test/fecal immunochemical test (FOBT/FIT) in both elderly and very elderly age groups with those of younger patients.

Methods: We identified colonoscopies conducted between 1998 and 2019 following a positive stool test for occult blood in asymptomatic individuals. A finding of malignancy was compared between the two patient age groups. Furthermore, a sub-analysis was performed for positive malignancy findings in FOBT/FIT among patients > 85 years compared to younger than < 75 years.

Results: We compared the colonoscopy findings in 10,472 patients: 40–75 years old (n=10,146) vs. 76–110 years old (n=326). There was no significant difference in prevalence of CRC detection rate between the groups following positive FOBT/FIT (2.1% vs. 2.7%, P = 0.47). Similar results for non-significant differences were obtained in the sub-analysis compared to malignancy detection rates in the very elderly 0% (n=0) vs. 2.1% for < 75 years old (n=18), P = 0.59.

Conclusions: Although the prevalence of CRC increases with age, no significant increase in the detection rate of CRC by FOBT was found in either the elderly or very elderly age groups. Screening colonoscopies in elderly patients should be performed only after careful consideration of potential benefits, risks, and patient preferences.

Background: Perivascular cuffing as the sole imaging manifestation of pancreatic ductal adenocarcinoma (PDAC) is an under-recognized entity.

Objectives: To present this rare finding and differentiate it from retroperitoneal fibrosis and vasculitis.

Methods: Patients with abdominal vasculature cuffing were retrospectively collected (January 2011 to September 2017). We evaluated vessels involved, wall thickness, length of involvement and extra-vascular manifestations.

Results: Fourteen patients with perivascular cuffing were retrieved: three with celiac and superior mesenteric artery (SMA) perivascular cuffing as the only manifestation of surgically proven PDAC, seven with abdominal vasculitis, and four with retroperitoneal fibrosis. PDAC patients exhibited perivascular cuffing of either or both celiac and SMA (3/3). Vasculitis patients showed aortitis with or without iliac or SMA cuffing (3/7) or cuffing of either or both celiac and SMA (4/7). Retroperitoneal fibrosis involved the aorta (4/4), common iliac (4/4), and renal arteries (2/4). Hydronephrosis was present in 3/4 of retroperitoneal fibrosis patients. PDAC and vasculitis demonstrated reduced wall thickness in comparison to retroperitoneal fibrosis (PDAC: 1.0 ± 0.2 cm, vasculitis: 1.2 ± 0.5 cm, retroperitoneal fibrosis: 2.4 ± 0.4 cm; P = 0.002). There was no significant difference in length of vascular involvement (PDAC: 6.3 ± 2.1 cm, vasculitis: 7.1 ± 2.6 cm, retroperitoneal fibrosis: 8.7 ± 0.5 cm).

Conclusions: Celiac and SMA perivascular cuffing can be the sole finding in PDAC and may be indistinguishable from vasculitis. This entity may differ from retroperitoneal fibrosis as it spares the aorta, iliac, and renal arteries and demonstrates thinner walls and no hydronephrosis.

Background: In Israel, breast cancer prevalence is lower among Arab than Jewish women, but incidence is increasing among Arab women at a younger age.

Objectives: To explore differences between Arab and Jewish women with breast cancer with respect to age at diagnosis, associated risk factors, and use of hormonal medications.

Methods: We conducted a retrospective database study comparing Arab and Jewish women with breast cancer focusing on age at diagnosis, smoking history, obesity, and previous hormonal medication usage, including oral combined contraceptive pills (OCCP), progestogens, hormonal medications for treatment of infertility, and hormone replacement therapy (HRT).

Results: The study included 2494 women who were diagnosed with breast cancer during 2004–2015. Age at diagnosis was lower among Arab women (50.7 ± 13.1 years vs. 55.4 ± 12.6 years, P < 0.0001). The rate of smoking was higher among Jewish women (16.0% vs. 4.3%, P < 0.0001). The rate of obesity was higher in Arab women older than 50 years at diagnosis (59.0% vs. 42.4%, P < 0.0001). Arab women demonstrated a lower overall chance of previous use of all types of hormonal medications (odds ratio [OR] 0.6, 95% confidence interval [95%CI] 0.6–0.8) compared to Jewish women. Arab women were more likely to have used progestogens (OR 1.7, 95%CI 1.4–2.2) and medications for treatment of infertility (OR 2.3, 95%CI 1.5–3.4) and less likely OCCP (OR 0.4, 95%CI 0.3–0.6) and HRT (OR 0.4, 95%CI 0.3–0.5).

Conclusions: Previous use of hormonal medications may contribute to incidence of breast cancer in Arab women.