Israel Medical Association Journal

Background: The safe completion of cholecystectomy is dependent on proper identification and secure closure of the cystic duct. Effecting this closure poses a great challenge when inflammatory changes obscure the anatomy. Subtotal cholecystectomy allows for near complete removal of the gallbladder and complete evacuation of the stones while avoiding dissection in the hazardous area.

Objectives: To describe experience with laparoscopic subtotal cholecystectomy.

Methods: Subtotal cholecystectomy was performed when the critical view of safety could not be achieved. Surgical technique was similar in all cases and included opening the Hartmann’s pouch, removing stones obstructing the gallbladder outlet, and identifying the opening of the cystic duct, as well as circumferential transection of the gallbladder neck, closure of the gallbladder stump, and excision of the gallbladder fundus. Data retrieved from patient charts included demographics, pre-operative history, operative and postoperative course, and late complications. No bile duct injuries were observed in this series.

Results: A total of 53 patients underwent laparoscopic subtotal cholecystectomy (2010–2018). Ten patients were operated during the acute course of the disease and 43 electively. Acute cholecystitis was the leading cause for gallbladder removal. Cholecystostomy tube was placed in 18 patients during acute hospitalization. The gallbladder remnant was closed and a drain was placed in most patients. Of the 53 patients, 42 had an uneventful postoperative course.

Conclusions: Laparoscopic subtotal cholecystectomy is an effective surgical technique to avoid bile duct injury when the cystic duct cannot safely be identified. Subtotal cholecystectomy has acceptable morbidity and obviates the need for conversion in these difficult cases.

Background: In 2006, the International Society for Heart and Lung Transplantation amended the guidelines for the upper age limit of heart transplantation (HTx) from 55 years to 70 years and older for carefully selected patients. However, the relation of age to outcomes following of HTx has not been well studied.

Objectives: To investigate the impact of recipient age on the occurrence of rejections, vasculopathy, and mortality after HTx.

Methods: Study population comprised all consecutive 291 patients who underwent HTx between 1991–2016 and were followed at our center. Patients were categorized by age tertiles: < 46 years (mean 31.4 ± 11.7, range 16–45, n=90), 46–57 years (mean 51.4 ± 3.2, range 46–56, n=92), and ≥ 57 years (mean 61.6 ± 3.4, range 57–73, n=109).

Results: Patients aged ≥ 57 years were more often males and had more pre-HTx co-morbidities including hypertension, diabetes, dyslipidemia, and history of smoking (P < 0.05) compared to the younger age groups. Kaplan-Meier analysis by age tertiles showed the rates of major rejections and vasculopathy at 15 years were similar among the three age groups. Mortality rates at 15 years were directly related to the age groups (39%, 52%, 62% log-rank, P = 0.01). However, the association between age and mortality was no longer statistically significant after multivariate analysis (hazard ratio 1.01, 95% confidence interval 1.00–1.03).

Conclusions: In a contemporary cohort of patients undergoing HTx, recipient age does not significantly impact the risk of major rejections, vasculopathy, and long-term mortality.

Background: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment.

Objectives: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development.

Methods: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD.

Results: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e’ septal (P < 0.001).

Conclusions: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment

Background: The incidence of gestational diabetes mellitus (GDM) is increasing in parallel to the worldwide obesity and type 2 diabetes pandemic. Both GDM and pre-gestational diabetes mellitus (PGDM) are associated with short- and long-term consequences in the offspring. There are few recent studies addressing outcomes of newborns born to women diagnosed with GDM and PGDM in Israel.

Objectives: To assess perinatal complications in offspring of women with GDM and PGDM.

Methods: The authors conducted a single-center retrospective case-control study of outcomes of all newborns whose mothers had been diagnosed with diabetes in pregnancy compared to randomly assigned controls born on the same date, whose mothers had no diabetes.

Results: In the study period 2015–2017, 526 mothers diagnosed with GDM or PGDM and their newborn infants were identified. The authors randomly assigned 526 control infants. The rate of women with diabetes in pregnancy was 5.0%. Mothers with GDM and PGDM had higher rates of pre-eclampsia, multiple pregnancies, and preterm deliveries. Mothers with PGDM had significantly higher rates of intrauterine fetal demise (4.3%), congenital anomalies (12.8%), and small-for-gestational-age neonates (10.6%) compared to controls (0%, 3.2%, and 4.2%, respectively, P < 0.001). The risks for preterm or cesarean delivery, large-for-gestational-age neonate, respiratory morbidity, hypoglycemia, and polycythemia were increased in offspring of mothers with diabetes, especially PGDM.

Conclusions: Despite all the advancements in prenatal care, diabetes in pregnancy, both PGDM and GDM, is still associated with significant morbidities and complications in offspring. Better preconception and inter-pregnancy care might reduce these risks

Background: Dependence on technology and electronic media devices (EMDs) is a significant phenomenon of modern life with many people experiencing adverse symptoms during abstention. Orthodox Jews abstain from using all forms of EMDs for 25 consecutive hours every week on the Sabbath but do not appear to experience significant adverse reactions during this abstention.

Objectives: To better examine whether Sabbath observant Jews experience fewer and less severe adverse symptoms while abstaining from EMDs on the Sabbath compared to weekdays.

Methods: Ten Sabbath observant Jews abstained from using all forms of EMDs for 25 hours on a Sabbath and again on a weekday. At the end of each 25-hour period participants completed a 12-item Likert-type scale self-assessment of 1–5, once as a report of their condition at 10:00 and again after 25 hours of abstaining. The authors compared the mean results of Sabbath and weekday using Wilcoxon signed ranks test. P ≤ 0.05 was considered significant.

Results: Overall, discomfort on Sabbath was less than on weekdays. A statistically significant decrease on the Sabbath was found at both the 10:00 reporting time and after 25 hours in anxiety, restlessness, thoughts and plans of using devices, and overall difficulty to abstain. Significance was found for feelings of not knowing what to do with time (10:00) and moodiness and irritability, being drawn to devices, and cravings achieved significance (after 25 hours).

Conclusions: Sabbath observant Jews reported statistically significant less adverse reactions while abstaining from EMDs on the Sabbath compared to on a weekday.

Background: Belimumab was the first biological drug approved for the treatment of systemic lupus erythematosus (SLE) patients. Phase II/III randomized controlled trials and real-life studies identified patients with musculoskeletal involvement as best responders.

Objective: To evaluate the effectiveness of belimumab in SLE-related joint involvement.

Methods: The cohort comprised SLE patients receiving belimumab for musculoskeletal indications. Belimumab was intravenously administrated according to protocols; all the patients were evaluated at baseline (T0) and after 3 (T1), 6 (T2), and 12 (T3) months. We assessed joint activity by disease activity score 28, simple disease activity index (SDAI), clinical disease activity index (CDAI), and swollen tender ratio. Each patient underwent musculoskeletal ultrasound of 34 joints to assess synovial effusion synovial hypertrophy, and power Doppler; by using a semi-quantitative scale (0–3) we obtained the total inflammatory score (0–216).

Results: We evaluated 20 patients (males/females 1/19, median age 45 years [interquartile range (IQR) 12], median disease duration 144 months [IQR 144]). CDAI and SDAI significantly decreased at T1 (P = 0.02 and P = 0.01 respectively) and this improvement was maintained at the following time-points (CDAI: T2 P = 0.008, T3 P = 0.004; SDAI: T2 P = 0.006, T3 P = 0.01). A significant reduction of median ultrasound score was identified at T1 (T0 20.5 [IQR 13.5] vs. T1 7.5 [IQR 4.7], P < 0.001), and maintained at T2 (7.0 [IQR 5], P < 0.0001), and T3 (7.0 [IQR 9.0], P < 0.0001).

Conclusions: Belimumab induces a sustained improvement of ultrasound-detected inflammatory status at the articular level.

Background: While the ratio of male to female births (sex-ratio at birth [SRB]) in humans is remarkably stable on the population level, there are many families with multiple same-sex offspring.

Objectives: To identify a putative sub-population with skewed SRB and explore potential factors affecting the SRB.

Methods: A retrospective cohort study including 66,054 families with up to nine same-sex offspring evaluated between 2003 and 2015 at Hadassah-Hebrew University Medical Center. Outcome measures were observed prevalence and SRB of families with up to nine same-sex offspring in a single family. Analyses included the effect of parity, month and year of delivery, inter-delivery interval, and presence of a sequence of previous same-sex offspring on the SRB.

Results: The study comprised 193,411 live-born babies with SRB of 1.057 in favor of males. The proportion of SRB in families with up to nine same-sex offspring did not differ from the calculated presumed proportion. Furthermore, none of the tested factors (parity, month and year of delivery, inter-delivery interval, and the sequence of previous same-sex offspring) were significantly associated with SRB.

Conclusions: SRB was not associated with any of the tested demographic characteristics. We could not identify a skew in SRB even in families with up to nine consecutive same sex offspring. This finding suggests that in the majority of the population the chance of a male or female fetus in each pregnancy remains similar in every pregnancy, regardless of any of the tested variables.

Background: Stress hyperglycemia (SH) is a common finding in patients in pediatric emergency departments (PED) and has been related to increased morbidity and mortality.

Objectives: To assess the incidence of SH among children visiting the PED. To identify which diseases predispose patients to SH and whether they indicate a worse outcome.

Methods: Data were collected retrospectively from the medical records of all children aged 0–18 years who visited the PED during the years 2010–2014 and who had a glucose level of ≥ 150 mg/dl. Data collected included age, gender, weight, blood glucose level, presence or absence of a pre-existing or a new diagnosis of diabetes mellitus, and previous treatment with medications affecting blood glucose levels or with intravenous fluids containing dextrose. Data were collected regarding hospitalization, duration of hospitalization, discharge diagnosis, and survival status.

Results: The study population included 1245 children with SH, which comprised 2.6% of all patients whose blood glucose level was measured in the PED during the study period. The mean age of children with SH was 49 months; 709 (56.9%) were male. The mean blood glucose level was 184 mg/dl. The rate of hospitalization was 57.8%. The mean duration of hospital stay was 5.6 days and mortality rate was 0.96%. The majority were diagnosed with a respiratory illness.

Conclusions: SH is a common phenomenon among children evaluated in the PED and is associated with a high incidence of hospitalization. It may serve as an additional clinical indicator of disease severity.

Background: Abdominal tumors invading the inferior vena cava (IVC) present significant challenges to surgeons and oncologists.

Objectives: To describe a surgical approach and patient outcomes.

Methods: The authors conducted a retrospective analysis of surgically resected tumors with IVC involvement by direct tumor encasement or intravascular tumor growth. Patients were classified according to level of IVC involvement, presence of intravascular tumor thrombus, and presence of hepatic parenchymal involvement.

Results: Study patients presented with leiomyosarcomas (n=5), renal cell carcinoma (n=7), hepatocellular carcinoma (n=1), cholangiocarcinoma (n=2), Wilms tumor (n=1), neuroblastoma (n=1), endometrial leiomyomatosis (n=1), adrenocortical carcinoma (n=1), and paraganglioma (n=1). The surgeries were conducted between 2010 and 2019. Extension of tumor thrombus above the hepatic veins required a venovenous bypass (n=3) or a full cardiac bypass (n=1). Hepatic parenchymal involvement required total hepatic vascular isolation with in situ hepatic perfusion and cooling (n=3). Circular resection of IVC was performed in five cases. Six patients had early postoperative complications, and the 90-day mortality rate was 10%. Twelve patients were alive, and six were disease-free after a mean follow-up of 1.6 years.

Conclusions: Surgical resection of abdominal tumors with IVC involvement can be performed in selected patients with acceptable morbidity and mortality. Careful patient selection, and multidisciplinary involvement in preoperative planning are key for optimal outcome.

Background: The effect of weight reduction following bariatric surgery is already well known.

Objectives: To investigate the effects of abdominoplasty on metabolic markers indicative of weight loss.

Methods: The authors prospectively enrolled consecutive obese patients after laparoscopic sleeve gastrectomy. They were candidates for post-bariatric surgery abdominoplasty. The authors measured metabolic markers one day prior to surgery, 24 hours after, and 3 months following surgery. They recorded medical and demographic parameters.

Results: Sixteen patients were recruited for participation in the study. Mean age was 47 years and 88% of the patients were female. Bariatric surgery achieved a mean decline in body mass index of 13.8 kg/m². All patients underwent abdominoplasty. Leptin and insulin levels were slightly increased at 3 months postoperative. No significant changes were observed in glucose, hemoglobin, or triglycerides throughout the study.

Conclusions: In a cohort of obese patients undergoing laparoscopic sleeve gastrectomy followed by abdominoplasty, no significant changes were noted in a patient’s metabolic profiles. The results suggest that abdominoplasty has no effect on the metabolic markers tested in contrast to other reports; however, the cosmetic, behavioral, and psychological advantages of abdominoplasty are well established.

Background: Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Several viral and host factors related to viral response have been reported in the era of treatment with pegylated (PEG)-interferon and ribavirin.

Objectives: To quantify histological findings from patients with chronic HCV using computerized morphometry and to investigate whether the results can predict response to medical treatment with peg-interferon and ribavirin.

Methods: We followed 58 patients with chronic HCV infection with METAVIR score F1 and F2 in our liver unit who were grouped according to treatment response sustained viral response (SVR) and non-SVR. Liver needle biopsies from these patients were evaluated and histological variables, such as inflammatory cells, collagen fibers and liver architecture, were quantified using computerized morphometrics. The pathologist who performed the histomorphometric analysis was blinded to previous patient clinical and histological information.

Results: Histomorphometric variables including the density of collagen fibers were collected. The number of inflammatory cells in the portal space and textural variable were found to be statistically significant and could be used together in a formula to predict response to treatment, with a sensitivity of 93% and a 100% specificity.

Conclusions: Histomorphometry may help to predict a patient's response to treatment at an early stage.

Background: Pancreatic injuries during nephrectomy are rare, despite the relatively close anatomic relation between the kidneys and the pancreas. The data regarding the incidence and outcome of pancreatic injuries are scarce.

Objectives: To assess the frequency and the clinical significance of pancreatic injuries during nephrectomy.

Methods: A retrospective analysis was conducted of all patients who underwent nephrectomy over a period of 30 years (1987–2016) in a large tertiary medical center. Demographic, clinical, and surgical data were collected and analyzed.

Results: A total of 1674 patients underwent nephrectomy during the study period. Of those, 553 (33%) and 294 patients (17.5%) underwent left nephrectomy and radical left nephrectomy, respectively. Among those, four patients (0.2% of the total group, 0.7% of the left nephrectomy group, and 1.36% of the radical left nephrectomy) experienced iatrogenic injuries to the pancreas. None of the injuries were recognized intraoperatively. All patients were treated with drains in an attempt to control the pancreatic leak and one patient required additional surgical interventions. Average length of stay was 65 days (range 15–190 days). Mean follow-up was 23.3 months (range 7.7–115 months).

Conclusions: Pancreatic injuries during nephrectomy are rare and carry a significant risk for postoperative morbidity.

Background: Admission to an intensive care unit (ICU) is an objective marker of severe maternal morbidity (SMM).

Objectives: To determine the prevalence of obstetric ICU admissions in one medical center in Israel and to characterize this population.

Methods: In this retrospective study the files of women coded for pregnancy, birth, or the perinatal period and admission to the ICU were pulled for data extraction (2005–2013).

Results: During the study period, 111 women were admitted to the ICU among 120,279 women who delivered babies (0.09%). Their average age was 30 ± 6 years, most were multigravida, a few had undergone fertility treatments, and only 27% had complicated previous pregnancies. Most pregnancies (71.2%) were uneventful prior to admission. ICU admissions were divided equally between direct (usually hemorrhage) and indirect (usually cardiac disease) obstetric causes.

Conclusions: The indications for obstetrics ICU admission correlated with the proximate causes of maternal arrest observed worldwide. While obstetric hemorrhage is often unpredictable, deterioration of heart disease is foreseeable. Attention should be directed specifically toward improving the diagnosis and treatment of maternal heart disease during pregnancy in Israel.

Background: Male breast cancer (MBC) is a rare disease that is poorly understood. Treatment protocols are widely extrapolated from breast cancer in women.

Objectives: To review the experience with MBC of a single center in Israel over a period of 22 years.

Methods: This single center retrospective study evaluated all patients diagnosed with MBC over a period of 22 years (1993–2015). Data were extracted from patient medical charts and included demographics, clinical, surgical, and oncological outcomes.

Results: The study comprised 49 patients. Mean age at diagnosis was 64.1 ± 13.5 years. The majority were diagnosed at early stages (1A–2A) (54.4%), 30.6% were stage 3B mostly due to direct skin and nipple involvement, and 59.2% of the patients had node negative disease. All of the patients were diagnosed with invasive ductal carcinoma and 30.6% had concomitant ductal carcinoma in situ. Estrogen receptor (ER) status was predominantly positive and luminal B (HER2-) was the most common subtype. Of the patients, 18.4% were BRCA carriers. The majority of patients underwent mastectomy. Radiotherapy was delivered to 46.9% and hormonal therapy to 89.8%. Chemotherapy was administered to 42.9%. Overall survival was 79.6% with a median survival of 60.1 (2–178) months; 5- and 10-year survival was 93.9% and 79.6%, respectively. Progesterone receptor (PR)-negative patients had a significantly improved overall survival.

Conclusions: MBC has increasing incidence. PR-negative status was associated with better overall survival and disease-free interval. Indications to radiotherapy and hormonal therapy need standardization and will benefit from prospective randomized control trials.