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: The correlation between epidural analgesia and successful Trial of Labor After Cesarean delivery (TOLAC) remains controversial.

Objectives: To explore this correlation considering the indication for previous cesarean section (CS).

Methods: We accessed an electronic database of an obstetrics department at a university tertiary medical center. All patients admitted for a TOLAC at term with a live singleton fetus with cephalic presentation between January 2015 and December 2021 were included. The primary outcome was the mode of delivery, based on the previous CS indication. Univariate and multivariate analyses were performed to identify the effect of epidural analgesia on TOLAC success.

Results: Overall, 1522 candidates for TOLAC were included, with previous CS due to arrest of descent in 261 cases (17.1%). Epidural analgesia was administered in 1098 deliveries (72.1%), and 282 women (18.5%) underwent a repeat CS. Women in the epidural group were younger, had higher body mass index, lower parity, and more frequent induction of labor. Prior vaginal birth after cesarean was more common in the non-epidural group. Univariate analysis showed a higher rate of epidural analgesia in repeat CS cases. However, in multivariable logistic regression, epidural analgesia was not significantly associated with the risk of repeat CS, both among women whose prior CS was for arrest of descent and among those with other indications.

Conclusions: The employment of epidural analgesia seems to have no observable influence on successful outcomes of TOLAC, regardless of the indication for the preceding CS. These findings imply that epidural anesthesia in TOLAC is safe.

Background: Fetal macrosomia is a risk factor for operative vaginal delivery (VD), shoulder dystocia, obstructed labor, and cesarean section (CS). Induction of labor (IOL) may decrease these risks but also leads to longer labor, increasing the risk of CS. No data exist regarding the optimal method of IOL in macrosomic fetuses, and most studies are limited to the efficacy of medical induction.

Objective: To compare medical and mechanical IOL in macrocosmic fetuses.

Methods: This retrospective case-control study included pregnant women who underwent IOL and delivered macrosomic neonates at a tertiary center between 2010 and 2020.

Women with non-cephalic presentation, prior CS, and multiple pregnancies were excluded. The primary outcome was the mode of delivery. Secondary outcomes included neonatal and maternal complications.

Results: A total of 247 women were included in the study, 188 underwent cervical ripening with prostaglandin E2 (PGE2) regimens and 59 with a double-balloon catheter. Higher rates of prior deliveries over 4000 grams and Oxytocin use during delivery were found in the mechanical induction group. No other clinically significant differences in demographic or clinical characteristics were identified. There were no statistically significant differences in the rates of VD or CS between the groups. The indications for CS were similar. Maternal and neonatal secondary outcomes were comparable.

Conclusion: PGE2 vaginal regimens and double catheter balloons are safe and effective methods for cervical ripening during IOL in term pregnancies with macrosomic neonates. The choice of cervical ripening method did not impact the mode of delivery or maternal and neonatal outcomes.

Background: Despite a significant advance in prevention and treatment of heart failure (HF), patients still struggle with decreased quality of life, high mortality, and recurrent hospitalizations. Several inflammatory cytokines have been widely investigated in the pathogenesis of HF.

Objectives: To investigate the prognostic value of fibrinogen on clinical outcomes of patients admitted with acute HF.

Methods: This retrospective study was based on data of patients hospitalized with acute HF. Demographics, laboratory, and clinical outcomes including length of stay and readmissions were obtained. We compared outcomes of patients with normal (< 430 mg/dl) and high (> 430 mg/dl) fibrinogen levels.

Results: We included 149 patients (mean age 67.6 ± 12.3 years, 73.8% male). In our cohort, 24 (16.1%) had normal fibrinogen (< 430 mg/dl) and 125 (83.9%) had high fibrinogen levels (> 430 mg/dl). Among patients with readmissions for HF, fibrinogen levels were higher (622 ± 136 vs. 470 ± 68, P < 0.001) and were associated with longer hospital stay. Fibrinogen remains an independent risk factor after adjusting to age, diabetes status, and left ventricular ejection fraction.

Conclusions: High fibrinogen levels may predict readmissions in patients with HF.

Background: Rising rates of antibiotic resistance pose a major challenge in the treatment of Helicobacter pylori (H. pylori) infection. Current treatment guidelines emphasize the importance of acquiring local resistance data to select an effective empirical regimen.

Objectives: To analyze trends in H. pylori antibiotic resistance over two decades in Israel.

Methods: Data from Clalit Health Services for H. pylori isolates cultured from gastric biopsies between January 2007 and December 2023 were included. Susceptibility to clarithromycin, amoxicillin, metronidazole, tetracycline, and levofloxacin was determined using E-tests. Demographic and clinical variables were retrieved to identify predictors of resistance.

Results: We identified 2521 H. pylori isolates (71.6% females, mean age 44.4 ± 15.8 years). Most individuals were residents of central Israel (84.6%) and of Jewish ethnicity (87.8%). Antibiotic resistance was observed in 71.6% of isolates for clarithromycin, 64.3% for metronidazole, and 19.4% for levofloxacin. Resistance to tetracycline and amoxicillin was minimal (0.2% and 1.2%, respectively). Dual clarithromycin-metronidazole resistance occurred in 50.4%, and triple resistance (clarithromycin-metronidazole-levofloxacin) was found in 12.0%. Between 2007 and 2012, clarithromycin resistance increased 5.3% annually, then tapered (odds ratio [OR] 1.05, 95% confidence interval [95%CI] 3.84–6.85, P < 0.001). Age and prior antibiotic use were predictors of resistance for all antibiotics, with the greatest effect observed for drugs in the same class. Female sex was associated with higher resistance to levofloxacin (OR 1.62, 95%CI, 1.28–2.05, P < 0.001).

Conclusions: Antibiotic resistance to H. pylori is high in our geographical region. Nevertheless, resistance rates have remained steady over recent years.

Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare tumors arising from pancreatic tissue, predominantly affecting young women and possessing low malignant potential. Extrapancreatic SPNs are exceedingly uncommon. According to data from the English literature, only 30 cases of extrapancreatic SPNs had been reported by 1990, accounting for less than 1% of all reported SPNs from 2004 to 2018. The testis, paratesticular region, and ovary are the more frequently documented sites of these tumors [1,2]. Notably, to the best of our knowledge, no cases of SPN originating in the diaphragm have been reported in the English literature to date. The prevailing theory suggests that SPNs behave similarly regardless of whether they originate in the pancreas or in extrapancreatic locations.

We present the case of a 79-year-old female with a history of lung and endometrial cancer, who was diagnosed with a liver lesion during a routine follow-up ¹⁸F-fluorodeoxyglucose positron-emission tomography/computed tomography (¹⁸F-FDG PET/CT). During surgery, the lesion was resected from the diaphragm and was confirmed to be consistent with the pathological findings of SPN.

Background: Increased utilization of imaging modalities has led to a significant rise in the detection of incidental thyroid nodules (ITN). Discrepancies in the prevalence of thyroid nodules with malignant potential exist worldwide.

Objectives: To analyze demographic and clinical data among patients with thyroid nodules in our geographic region.

Methods: The medical records of patients diagnosed with symptomatic or incidental thyroid nodules at the Galilee Medical Center between 2018 and 2023 were reviewed. Demographic and clinical data were collected and analyzed.

Results: The study population included 402 patients with thyroid nodules, 292 females. Symptomatic patients were younger (mean age 55.9 vs. 60.8 years) and had larger nodules (mean size 2.5 vs. 2.1 cm) compared to incidentally diagnosed patients (P < 0.001, P < 0.001, respectively). Male patients demonstrated a higher rate of malignancy for both symptomatic and incidental nodules compared to females (P < 0.05). Pathological examination revealed that malignant nodules were smaller (mean size 2.10 cm vs. 2.87 cm) and detected at a younger age (mean age 48.56 years vs. 56.5 years), compared to benign nodules (P < 0.05, P < 0.01, respectively).

Conclusions: We found a higher prevalence of both symptomatic and ITN among females. However, malignant thyroid nodules were more frequently observed in males. Notably, malignant nodules tended to be smaller and were more commonly diagnosed in younger individuals compared to benign nodules. These findings highlight significant sex and age disparities in the occurrence and characteristics of thyroid nodules, emphasizing the need for tailored diagnostic and management strategies.

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: Epidemiological studies have demonstrated an association between sleep deprivation (SD) and ischemic heart disease.

Objectives: To determine the effect of SD on the endothelial function and on the inflammatory profile of young healthy men following 24 hours of work without sleep.

Methods: Fourteen healthy men (age 31.3 ± 2.4 years) participated in our prospective study. Endothelial function was evaluated by the brachial artery method, measuring flow medicated percent change (FMD%) of the brachial artery by a linear array ultrasound early in the morning. Interleukin 1 (IL-1) and interleukin 6 (IL-6) were measured in saliva by ELISA.

Results: Basic FMD% was 6.7 ± 6.8%, and following SD 1.7 ± 3.3% (P = 0.009). A 5.0 ± 6.1% decrease was measured after SD. IL-1 levels increased after SD from 36 ± 21 pg/ml to 47 ± 24 pg/ml (P = 0.004), and IL-6 levels increased from 22 ± 07 pg/ml to 36 ± 11 pg/ml (P = 0.0005). A negative correlation was found between the change (decrease) in FMD% and the change (increase) in IL-1 level (r = -0.813; P = 0.001). A negative correlation was found between the decrease in FMD% and the increase in IL-6 level (r = -0.735; P = 0.003).

Conclusions: SD led to endothelial dysfunction with increase in markers of inflammation (IL-1 and IL-6), with an inverse correlation between the change (decrease) in endothelial function and the change (increase) in IL-1 and in IL-6.

Background: Antiphospholipid syndrome (APS) is a common form of acquired thrombophilia associated with a high thrombotic risk. Fabry’s disease (FD) is an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A (GLA) gene and presents with a wide range of clinical manifestations, including a high rate of thrombosis. Previously reported, 45% of FD patients were found to have antiphospholipid autoantibodies.

Objectives: To determine the prevalence of FD in patients with APS.

Methods: We conducted a prospective study. Data were collected from 41 APS patients at our outpatient clinic at Meir Medical Center in Israel. We utilized chemical and genetic analyses to identify FD among APS patients. Dried blood spot (DBS) was used to assess GLA activity in males, and mutational analysis of the GLA gene was performed by sequencing exons and their flanking regions in women.

Results: Among 41 antiphospholipid patients, one male patient was diagnosed with FD. Gal variants were not detected in any of the tested female patients.

Conclusions: We found a low prevalence (2.4%) of FD in APS patients. Larger studies are needed to evaluate the clinical utility and cost-effectiveness of routine FD screening in this population.

Immune thrombocytopenia (ITP), driven by autoantibodies targeting platelet antigens, is an acquired disorder posing considerable challenges, particularly in pregnancy, where its prevalence escalates to 1–3 per 10,000 women, a tenfold increase compared to the general population [1]. Predominantly characterized by a heightened risk of bleeding, particularly during pregnancy, the incidence of significant hemorrhagic events stands at approximately 18%, mostly non-severe [1]. Despite its rarity, thrombosis can manifest as a complication, especially when accompanied by antiphospholipid antibodies, which amplify the propensity for arterial and venous thrombotic events alongside obstetric complications and thrombocytopenia [2,3].

In this case report, we present the case of a young female with primary unexplained infertility, complicated by ITP and antiphospholipid syndrome (APS), predisposing her to increased bleeding and thrombotic risks. During a multidisciplinary consultation, the medical staff navigated the intricate landscape of fertility treatments and pregnancy options, carefully considering the delicate balance between risks and benefits to optimize patient outcomes.

Recent publications based on newly available list of surgeries performed in Nazi concentration camps raised the question of motivation for thousands of procedures on internees incarcerated from occupied Europe. The performance of major surgeries would be suspicious in their intent, indicating, if not directly proving, their intention as an exercise for junior physicians or medical students. The concept of the Revier (infirmary) is discussed. The Revier (also known as Krankenrevier or infirmary) in Nazi concentrations camps was located next to the extermination unit. Procedures performed at the Revier were considered non-therapeutic, as the victims had a minimal chance of survival without appropriate postoperative facilities. A review of medical documents of major concentration camps (Auschwitz, Mauthausen, Gusen, Ebensee) indicates the criminal intention of the authorities. This unusual type of crime was raised in post-war trials, but no specific legal code was nominated.

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.

Background: Abdominoplasties are among the most common procedures in aesthetic plastic surgery. The target audience are patients after massive weight loss who are left with excess skin and post-partum patients. Due to the efficacy of abdominoplasties in improving the abdominal contour, it became a mainstay procedure in plastic surgery. Claims have been made that abdominal surgeries can be safely combined with breast surgeries, and thereby decrease the risk associated with anesthesia for two separate procedures as well as the recovery period. The benefits of the combined procedures led to a surplus of patients seeking consultations.

Objectives: To examine the safety of the mommy makeover procedure compared to sole abdominoplasty.

Methods: Patients who previously underwent abdominoplasty by the senior author were divided into two groups based on whether breast surgery was performed in addition to the abdominoplasty. Groups were compared based on demographical, clinical, and surgical variables.

Results: The study cohort included 726 patients, of whom 15% underwent "Mommy-makeovers". Groups differed only in liposuction volume, resection weight and number of drains. Regarding surgical outcomes, surgical site infections were seen at a greater rate in the isolated abdominoplasty procedure. Further analyses accounting for potential confounders found no difference between the groups in terms of adverse events.

Conclusions: Mommy makeovers do not display a safety concern when compared to isolated abdominoplasties. Surgeons must consider various patient characteristics to ensure optimal results.

Serotonin (5-hydroxytryptamin, 5-HT) is a vital monoamine neurotransmitter that modulates various physiological processes. Selective serotonin reuptake inhibitors (SSRIs) are commonly used for the management of depressive disorders. Prolonged administration of SSRIs may lead to reduced platelet aggregability due to the depletion of serotonin stores within platelets. However, the association between chronic SSRI use and the risk of postoperative bleeding remains a topic of debate, with no standardized guidelines for managing this risk in the field of plastic surgery. This literature review and case report highlights the importance of considering chronic SSRI use as a potential risk factor for postoperative bleeding in plastic surgery patients. Standardized guidelines for handling postoperative bleeding risk in patients using SSRIs are crucial for ensuring optimal surgical outcomes and patient safety.