Israel Medical Association Journal

Artificial intelligence in ophthalmology is used for automatic diagnosis, data analysis, and predicting responses to possible treatments. The potential challenges in the application and assimilation of artificial intelligence include technical challenges of the algorithms, the ability to explain the algorithm, and the ability to diagnose and manage the medical course of patients. Despite these challenges, artificial intelligence is expected to revolutionize the way ophthalmology will be practiced. In this review, we compiled recent reports on the use and application of deep learning in various fields of ophthalmology, potential challenges in clinical deployment, and future directions.

Background: Computed tomography (CT) is the main diagnostic modality for detecting pancreatic adenocarcinoma.

Objectives: To assess the frequency of missed pancreatic adenocarcinoma on CT scans according to different CT protocols.

Methods: The medical records of consecutive pancreatic adenocarcinoma patients were retrospectively collected (12/2011–12/2015). Patients with abdominal CT scans performed up to a year prior to cancer diagnosis were included. Two radiologists registered the presence of radiological signs of missed cancers. The frequency of missed cancers was compared between portal and pancreatic/triphasic CT protocols.

Results: Overall, 180 CT scans of pancreatic adenocarcinoma patients performed prior to cancer diagnosis were retrieved; 126/180 (70.0%) were conducted using pancreatic/triphasic protocols and 54/180 (30.0%) used portal protocols. The overall frequency of missed cancers was 6/180 (3.3%) in our study population. The frequency of missed cancers was higher with the portal CT protocols compared to the pancreatic/triphasic protocols: 5/54 (9.3%) vs. 1/126 (0.8%), P = 0.01. CT signs of missed cancers included small hypodense lesions, peri-pancreatic fat stranding, and dilated pancreatic duct with a cut-off sign.

Conclusions: The frequency of missed pancreatic adenocarcinoma is higher on portal CT protocols. Physicians should consider the cancer miss rate on different CT protocols.

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: Acquired hepatocerebral degeneration (AHD) is a neurologic complication of severe chronic liver disease (CLD) with portosystemic shunts. The proposed etiology is manganese accumulation in the brain tissue, especially in the basal ganglia. Combination of clinical manifestation, mostly extrapyramidal movement disorders, and hyperintensities on T1-weighted brain magnetic resonance imaging (MRI) is diagnostic. Although liver transplantation controversial, it is suggested for AHD.

Objectives: To depict clinical and neuroimaging characteristics and response to treatments in patients diagnosed with AHD at Sheba Medical Center.

Methods: Review of patients with AHD diagnosis at the Liver Diseases Center at Sheba Medical Center between 2012 and 2017, data of clinical and neuroimaging, follow-up, and response to treatments, including liver transplantation were recorded.

Results: Five patients with diagnosis of AHD were identified, median age at diagnosis 55 years (range 45–64 years). Four patients had cirrhosis at the time of AHD diagnosis. The main risk factor for AHD was the presence of portosystemic shunts. The most prevalent clinical manifestations were movement disorders, specifically a combination of extrapyramidal and cerebellar signs including instability, rigidity, tremor, bradykinesia, and cognitive impairment. Brain MRI revealed hyperintensities on T1-weighted images in the basal ganglia in all patients. Administration of antiparkinsonian drugs showed clinical improvement, whereas liver transplantation performed in two patients was not associated to neurological improvement.

Conclusions: AHD is related to portosystemic shunts. The combination of Parkinsonism and cerebellar signs and MRI pallidal lesions should alert physicians to the diagnosis. The role of liver transplantation in AHD is still controversial.

Background: No specific clinical or histological factors are recognized to be associated with the development of pericardial effusion in non-small cell lung cancer (NSCLC) other than a metastatic disease.

Objectives: To assess whether specific clinical and histological features are associated with development of pericardial effusion in patients with NSCLC.

Methods: A consecutive cohort of patients with NSCLC who presented with symptomatic pericardial effusion 2014–2017 was compared to a control group of patients with advanced NSCLC without pericardial effusion.

Results: The 27 patients in the effusion group were generally younger, more often female, and with a higher percentage of never-smokers, compared to the 54 patients of the control group. Epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) mutation tumors were found in 48% of patients in the effusion group vs. 25% in the control group. In the multivariate analysis, the unadjusted odds ratio (OR) for the development of pericardial effusion in patients with somatic mutations was significantly higher compared to wild type tumors (OR 2.65, 95% confidence interval 1.00–7.00). However, a suspected association between pericardial effusion and mutation status was found to be confounded by age. While a high rate of recurrence was observed when pericardiocentesis was initially performed (9/17, 53%), no recurrence was documented when pericardial window procedure was performed (total of 17 patients).

Conclusions: Patients with EGFR/ALK mutations may be at higher risk for the development of pericardial effusion; therefore, attending physicians need to be aware and have a high index of clinical suspicion

Background: New direct acting antiviral agent (DAA) therapies are associated with a high sustained virological response rate (SVR) in hepatitis C virus (HCV) patients. The understanding of the impact of SVR on fibrosis stage is limited.

Objectives: To determine the effect of treatment with the DAAs on long-term liver fibrosis stages, as determined by shear-wave elastography (SWE) or FibroTest©.

Methods: Fibrosis stage was determined at baseline and at 6-month intervals after end of treatment (EOT), using two‐dimensional SWE or FibroTest©; APRI and FIB-4 scores.

Results: The study comprised 133 SVR12 patients. After a median follow-up of 15 months (range 6–33), liver fibrosis stage decreased by at least 1 stage in 75/133 patients (56%). Cirrhosis reversal was observed in 24/82 (29%). Repeated median liver stiffness SWE values in cirrhotic patients were 15.1 kPa at baseline (range 10.5–100), 13.4 kPa (range 5.5–51) at 6 months, and 11.4 kPa (range 6.1–35.8) at 12 months after EOT, P = 0.01. During the second year after EOT, no statistically significant differences in liver fibrosis stage in 12, 18, and 24 months were found. Splenomegaly was the only significant negative predictor of liver fibrosis regression during all time points of repetitive noninvasive assessment.

Conclusions: Following successful DAA treatment, the majority of our HCV patients with advanced fibrosis demonstrated significant improvement, as assessed by non-invasive methods. Advanced fibrosis stage was a negative predictor of fibrosis regression. Longer follow-up periods are required to further establish the impact of DAAs treatment in HCV patients with advanced fibrosis

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: Prophylactic cranial irradiation (PCI) exclusion in favor of brain magnetic resonance imaging (MRI) staging and surveillance in the management of small cell lung cancer (SCLC) is controversial yet accepted by some centers. The use of MRI suggests performing stereotactic radiosurgery (SRS) treatment for limited brain metastases. Data regarding SRS efficacy in this setting is limited.

Objectives: To assess intracranial objective response rate (iORR), progression-free survival (iPFS), intracranial failure patterns, overall survival (OS) and time-to-whole-brain radiation therapy (WBRT)/death, whichever occurred first (TTWD) with SRS in SCLC.

Methods: The study comprised 10 consecutive SCLC patients with brain metastases treated with SRS and followed-up at Davidoff Cancer center between Aug 2012 and March 2019. Brain MRI images were reviewed by a neuro-radiology specialist.

Results: iORR was 57% as assessed by response assessment in neuro-oncology brain metastases. Intracranial progression developed in 8 patients. Median iPFS was 4.0 months (95% confidence interval [95%CI] 1.7–7.2). In-site, off-site and combined pattern of intracranial failure was seen in 0, 5, and 3 patients, respectively; median number of new brain lesions following SRS was 4 (range, 1–12). SRS was performed 10 additional times in 6 patients (median number of lesions irradiated per round was 1, range 1–5). WBRT was administered in 3 patients. Median TTWD was 20.9 months (95% CI, 1.9–26.8). Median OS since SRS administration was 23.2 months (95% CI, 4.2–not reached).

Conclusions: MRI surveillance with multiple rounds of SRS may serve a reasonable alternative to PCI or therapeutic WBRT in SCLC. 

Background: In Israel, coronary heart disease mortality rates are significantly higher among the Arab population than the Jewish population. Dyslipidemia prevention should begin in childhood.

Objectives: To identify sociodemographic disparities in the preventive health measurement of lipid profile testing and lipoprotein levels among Israeli children and adolescents.

Methods: A cross-sectional analysis of 1.2 million children and adolescents insured by Clalit Health Services between 2007 and 2011 was conducted using sociodemographic data and serum lipid concentrations.

Results: Overall, 10.1% individuals had undergone lipid testing. Those with male sex (odds ratio [OR] = 0.813, 95% confidence interval [95%CI] 0.809–0.816), Arab ethnicity (OR = 0.952, 95%CI 0.941–0.963), and low socioeconomic status (SES) (OR = 0.740, 95%CI 0.728–0.752) were less likely to be tested. By 2010, differences among economic sectors narrowed and Arab children were more likely to be tested (OR = 1.039, 95%CI 1.035–1.044). Girls had higher total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels compared to boys (P < 0.001). Jewish children had higher cholesterol and low-density and high-density lipoprotein-cholesterol, as well as lower triglyceride levels than Arabs (P < 0.001). Children with low SES had lower cholesterol, low-density and high-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels (P < 0.001).

Conclusions: We found that boys, Arab children, and those with low SES were less likely to be tested. Over time there was a gradual reduction in these disparities. Publicly sponsored healthcare services can diminish disparities in the provision of preventive health among diverse socioeconomic groups that comprise the national population.

Background: Pregnant women with acute abdominal pain pose a diagnostic challenge. Delay in diagnosis may result in significant risk to the fetus. The preferred diagnostic modality is magnetic resonance imaging (MRI), since ultrasonography is often inconclusive, and computed tomography (CT) would expose the fetus to ionizing radiation

Objectives: To describe the process in setting up an around-the-clock MRI service for diagnosing appendicitis in pregnant women and to evaluate the contribution of abdominal MR in the diagnosis of acute appendicitis.

Methods: We conducted a retrospective study of consecutive pregnant women presenting with acute abdominal pain over a 6 year period who underwent MRI studies. A workflow that involved a multidisciplinary team was developed. A modified MRI protocol adapted to pregnancy was formulated. Data regarding patients' characteristics, imaging reports and outcome were collected retrospectively. 

Results: 49 pregnant women with suspected appendicitis were enrolled. Physical examination was followed by ultrasound: when positive, the patients were referred for MR scan or surgery treatment; when the ultrasound was inconclusive, MR scan was performed. In 88% of women appendicitis was ruled out and surgery was prevented. MRI diagnosed all cases with acute appendicitis and one case was inconclusive. The overall statistical performance of the study shows a negative predictive value of 100% (95%CI 91.9–100%) and positive predictive value of 83.3% (95%CI 35.9–99.6%).

Conclusions: Creation of an around-the-clock imaging service using abdominal MRI with the establishment of a workflow chart using a dedicated MR protocol is feasible. It provides a safe way to rule out appendicitis and to avoid futile surgery in pregnant women.

Background: Cardiac patients express elevated levels of B-type natriuretic peptide and the amino terminal segment of its prohormone (NT-proBNP). However, there are non-cardiac causes of NT-proBNP level elevation.

Objectives: To determine the upper limit of NT-proBNP for pediatric patients with acute non-cardiac disease.

Methods: We compared NT-proBNP concentrations in healthy children and children with acute non-cardiac, mostly febrile, and acute cardiac disease. We used the Student t-test and Mann-Whitney test for group comparisons, and Pearson's and Spearman's correlation coefficients to test relationships between variables. 

Results: In 138 patients with acute non-cardiac diseases (mean age 3.7 years, 53% male), median NT-proBNP concentration was 162 pg/ml, upper limit (95% percentile) 1049 pg/ml. The level did not vary significantly by disease category; was negatively correlated with weight, weight percentile, age and hemoglobin level; and positively correlated with creatinine level. Multivariant analysis showed weight to be the only factor influencing NT-proBNP level. Levels were higher in children with acute non-cardiac diseases versus healthy children (median 88 pg/ml, P < 0.001, n= 59), and lower than levels in patients with acute cardiac disease (median 29,986 pg/ml, P < 0.001, n=29). Receiver operating characteristic analysis showed good NT-proBNP performance for differentiation between children with acute cardiac versus non-cardiac disease (area under the curve 0.958), at a cutoff of 415 pg/ml.

Conclusions: NT-proBNP levels are higher in children with acute non-cardiac diseases than in healthy children, but lower than in children with acute cardiac disease. NT-proBNP negatively correlated with weight and weight percentile.
 

Background: The effect of anti-platelet drugs on surgical blood loss and perioperative complications has not been studied in depth and the management of surgical patients taking anti-platelet medications is controversial.

Objective: To assess the effect of anti-platelet therapy on perioperative blood loss in patients undergoing appendectomy either laparoscopically or via open surgery.

Methods: We reviewed the files of all patients > 40 years old who underwent open or laparoscopic appendectomies from 2007 to 2010. Excluded were patients with short hospitalization and no follow-up of hemoglobin level, patients on warfarin treatment and patients who underwent additional procedures. Estimation of blood loss was based on decrease in hemoglobin level from admission to discharge. Risk factors for blood loss, such as anti-platelet therapy, age, gender, surgical approach, surgical time, surgical findings and complications, were analyzed.

Results: The final cohort included 179 patients (mean age 61 ± 14 years, range 40–93) of whom 65 were males. The mean perioperative hemoglobin decrease was 1.59 ± 1.07 mg/dl (range 0–5 mg/dl). Thirty-nine patients received anti-platelet therapy prior to surgery and 140 did not. No significant differences in decrease of hemoglobin level were found between patients receiving anti-platelet therapy and those who were not (1.73 ± 1.21 vs. 1.55 ± 1.02 mg/dl, P = 0.3). In addition, no difference was found between patients on anti-platelet therapy operated laparoscopically and those operated in an open fashion (1.59 ± 1.18 vs. 2.04 ± 1.28 mg/dl, P = 0.29). Five patients required blood transfusions, two of whom were on anti-platelet therapy. Blood loss was significantly greater in patients with a perforated appendicitis and in those with an operative time of more than one hour.

Conclusions: Anti-platelet therapy does not pose a risk for increased blood loss following emergent appendectomy performed either laparoscopically or in an open fashion.
 

Background: Major changes in the evaluation and treatment of curable colorectal cancer (CRC) have emerged in the last two decades. These changes have led to better patient outcome over time.

Objectives: To evaluate the impact of these changes as reflected in the difference in long-term outcome of a consecutive group of recently laparoscopically operated curable CRC[1] patients and a consecutive group of patients operated 20 years earlier in the same department.

Methods: Data of the new group were taken from our prospectively collected data of patients who underwent elective laparoscopic surgery for CRC in recent years. Data regarding patients operated on 20 years ago were retrieved from previous prospectively collected data on the long-term survival of CRC patients operated in the same department.

Results: The recently operated group comprised 203 patients and the previous group 199 patients. Perioperative mortality was 0.5% in the new group versus 1.5% in the old group (not significant). There were more early-stage and more proximal tumors in the recently operated group. A Kaplan-Meier 5-year survival analysis revealed no difference between stage I patients of the two groups. However, there was a significant increase in 5-year survival in the new group for stage II (85% vs. 63%, P = 0.004) and for stage III patients (57% vs. 39%, P = 0.01). This trend was maintained after removing the rectal cancer patients from the calculated data.

Conclusions: We have demonstrated improved survival for stage II and III CRC patients over a 20-year period in the same medical center. This change most likely reflects advances both in imaging techniques leading to more accurate staging and in adjuvant treatments.

Background: Esophageal perforations and postoperative esophageal leaks are associated with substantial morbidity and mortality and pose a difficult therapeutic challenge. 

Objectives: To evaluate the outcome of removable self-expanding metallic stents (SEMS) as a treatment for postoperative leaks and perforations of the esophagus and stomach.

Methods: We conducted a retrospective study of all patients in one medical center who underwent temporary insertion of a covered plastic stent for postoperative leaks and perforations of the esophagus and stomach from June 2009 to February 2010. Data were retrieved from hospital and outpatient clinical data charts. Data included indication for insertion, post-insertion outcome including stent complications, and follow-up after stent removal.

Results: The indications for stent insertion were postoperative leak in four patients and postoperative esophagopleural fistula in one patient. Three of the patients had a leak at the gastro-esophageal junction following laparoscopic sleeve gastrectomy. In all cases the stent insertion was completed successfully. In three patients the stent migrated distally. In two of these three it was repositioned or replaced endoscopically, and in the third it was excreted in the feces. Stents were removed electively after 6 to 7 weeks. All patients recovered fully and were discharged from the hospital.

Conclusions: SEMS insertion may have an important role in the management of postoperative leaks and perforations of the esophagus and stomach and should be considered in such cases.