Israel Medical Association Journal

Background: Polyp detection rate (PDR) is a convenient quality measure indicator. Many factors influence PDR, including the patient's background, age, referral (ambulatory or hospitalized), and bowel cleansing.

Objectives: To evaluate whether years of professional experience have any effect on PDR.

Methods: A multivariate analysis of a retrospective cohort was performed, where both patient- and examiner-related variables, including the experience of doctors and nurses, were evaluated. PDR, as the dependent variable was calculated separately for all (APDR), proximal (PPDR), and small (SPDR) polyps.

Results: Between 1998 and 2019, 20,996 patients underwent colonoscopy at a single center. After controlling for covariates, the experience of both doctors and nurses was not found to be associated with APDR (odds ratio [OR] 0.99, 95% confidence interval [95%CI] 0.98–1.00, P = 0.15 and OR 1.03, 95%CI 1.02–1.04, P < 0.0001, respectively). However, after 2.4 years of colonoscopy experience for doctors, and 9.5 years of experience for nurses, a significant increase in APDR was observed. Furthermore, results revealed no association for PPDR and SPDR, as well.

Conclusions: Years of colonoscopy experience for both doctors and assisting nurses were not associated with APDR, PPDR, and SPDR. In doctors with 2.4 years of experience and nurses with 9.5 years of experience, a significant increase in APDR was observed.

Background: Advances in examination techniques have improved routine assessment of non-gynecological structures in the pelvis.

Objectives: To describe the sonographic features of incidental urological abnormalities found during gynecological transvaginal ultrasound.

Methods: A retrospective descriptive analysis of patients who underwent gynecological ultrasound and were diagnosed with urologic findings was performed. The sonographic features of the findings including size, echogenicity, and vascularity were examined.

Results: Gynecological ultrasound diagnosed urological findings in nine women. Two had primary neoplasms of the urinary bladder, one had metastases to the urinary bladder, one had polyps in the distal ureters, four presented with calculus in the distal ureters (one of them was 19 weeks pregnant), and one showed diverticulum of the urethra. At presentation five women (56%) had urinary complaints. Two patients (22%) with abdominal pain with distal ureteral calculi had normal transabdominal ultrasound targeted to the urinary system prior to the gynecological sonography.

Conclusions: Transvaginal ultrasound is useful in the diagnosis of urological abnormalities, mainly in the urinary bladder and the distal ureters. We suggest adding transvaginal assessment for female patients with urinary complains in whom transabdominal ultrasound of urinary system was unremarkable.

Background: There has been a rapid increase in vulnerable subpopulations of very old with co-morbidity, dementia, frailty, and limited life expectancy. Being treated by many specialists has led to an epidemic of inappropriate medication use and polypharmacy (IMUP) with negative medical and economic consequences. For most medications there are no evidence-based studies in older people and treatments are based on guidelines proven in much younger/healthier populations.

Objectives: To evaluate whether the benefits of reducing IMUP by poly-de-prescribing (PDP) outweighs the negative outcomes in older people with polypharmacy.

Methods: The Garfinkel method and algorithm were used in older people with polypharmacy (≥ 6 prescription drugs).

Results: We found that in nursing departments, of 331 drugs de-prescribed only 32 (10%) had to be re-administered. Annual mortality and severe complications requiring referral to acute care facility were significantly reduced in PDP (P < 0.002). In community dwelling older people, successful de-prescribing was achieved in 81% with no increase in adverse events or deaths. Those who de-prescribed ≥ 3 prescription drugs showed significantly more improvement in functional and cognitive status, sleep quality, appetite, serious complications, quality of life, and general satisfaction compared to controls who stopped ≤ 2 medications (P < 0.002). Rates of hospitalization and mortality were comparable. Clinical improvement by polydeprescribing was usually evident within 3 months and persisted for several years. The main barrier to polydeprescribing was physician’s unwillingness to deprescribe (P < 0.0001)

Conclusions: Applying the Garfinkel method of PDP may improve the lives of older people and save money.

Background: Decisions on medication treatment in children dying from cancer are often complex and may result in polypharmacy and increased medication burden. There is no information on medication burden in pediatric cancer patients at the end of life (EOL).

Objectives: To characterize medication burden during the last hospitalization in children dying from cancer

Methods: We performed a retrospective cohort study based on medical records of 90 children who died from cancer in hospital between 01 January 2010 and 30 December 2018. Demographic and clinical information were collected for the last hospitalization. We compared medication burden (number of medication orders) at hospitalization and at time of death and examined whether changes in medication burden were associated with clinical and demographic parameters.

Results: Median medication burden was higher in leukemia/lymphoma patients (6 orders) compared to solid (4 orders) or CNS tumor patients (4 orders, P = 0.006). Overall, the median number of prescriptions per patient did not change until death (P = 0.42), while there was a significant reduction for some medication subgroups (chemotherapy [P = 0.035], steroids [P = 0.010]).Patients dying in the ICU (n=15) had a higher medication burden at death (6 orders) than patients dying on wards (3 orders, P = 0.001). There was a trend for a reduction in medication burden in patients with “Do not resuscitate” (DNR) orders (P = 0.055).

Conclusions: Polypharmacy is ubiquitous among pediatric oncology patients at EOL. Disease type and DNR status may affect medication burden and deprescribing during the last hospitalization.

Background: Evaluation of mismatch repair (MMR) deficiency is conducted via immunohistochemistry or by microsatellite instability (MSI) analysis. Heterogeneous immunohistochemistry staining for MMR proteins may show different patterns; however, according to current guidelines, all of those patterns should be interpreted as MMR proficient. This conclusion might lead to false negative results because although most cases of heterogeneity stem from technical factors and biological variability, other types of heterogeneity represent true MMR deficiency.

Objectives: To identify a unique heterogeneity pattern that is associated with true MMR loss.

Methods: We analyzed 145 cases of colorectal carcinoma. Immunohistochemistry staining for MLH1, PMS2, MSH2, and MSH6 were performed. We defined geographic heterogeneity as areas of tumor nuclear staining adjacent to areas of loss of tumor nuclear staining with intact staining in the surrounding stroma. All cases were evaluated for the presence of geographic heterogeneity. In addition, 24 cases were also evaluated by MSI testing.

Results: Of the 145 cases, 24 (16.5%) were MMR deficient. Of the 24 cases for which MSI analysis was also available, 10 cases (41.7%) demonstrated biological heterogeneity, 5 (20.8%) demonstrated technical heterogeneity, and 2 (8.3%) demonstrated geographic heterogeneity. Only the two cases with geographic heterogeneity were MSI-high via MSI analysis. In addition, a germline mutation in MSH-6 was identified in one of these cases.

Conclusions: Geographic heterogeneity may raise a suspicion for a MMR-deficient case, which should be further analyzed using additional methodologies such as MSI analysis.

Background: Nasal polyps are three-dimensional structures arising from the mucosa of the upper airway. Due to their complexity, the reliability of single-layer cell cultures and animal systems as research models is limited.

Objectives: To evaluate the feasibility of an ex vivo organ culture of human polyps, preserving tissue structure and function.

Methods: Nasal polyps were excised during routine endoscopic sinus surgery for chronic rhinosinusitis and polyposis. Fresh tissue samples were used for pathological evaluation and for the preparation of 250–500 µm sections, which were incubated in culture media. Tissue viability was assessed by visualisation of cilia motility, measurement of glucose uptake, and an infectivity assay. Cytokine secretion was evaluated by enzyme-linked immunosorbent assay and real-time polymerase chain reaction before and after the introduction of steroids.

Results: Polyp tissue viability was retained for 2–3 days as demonstrated by cilia motility, glucose uptake and preserved cellular composition. Tissue samples maintained their capacity to respond to infection by herpes simplex virus 1 and adenovirus. Introduction of dexamethasone to cultured tissue samples led to suppression of interferon-g production.

Conclusions: The ex vivo nasal polyp organ culture reproduces the physiological, metabolic, and cellular features of nasal polyps. Furthermore, it shows a preserved capacity for viral infection and response to drugs. This system is a useful tool for the investigation nasal-polyps and for the development of novel therapies.

Background: Medication reconciliation (MR) at hospital admission, transfer, and discharge has been designated as a required hospital practice to reduce adverse drug events.

Objectives: To perform MR among elderly patients admitted to the hospital and to determine factors that influence differences between the various lists of prescribed drugs as well as their actual consumption.

Methods: We studied patients aged 65 years and older who had been admitted to the hospital and were taking at least one prescription drug.

Results: The medication evaluation and recording was performed within 24 hours of admission (94%). The mean number of medications was 7.8 per patients, 86% consumed 5 or more medications. Mismatching between medication prescribed by a primary care physician (PCP) and by real medication use (RMU) was found in 82% of patients. In PCP the most common mismatched medications were cardiovascular drugs (39%) followed by those affecting the alimentary tract, metabolism (24%), and the nervous (12%) system. In RMU, the most commonly mismatched medications were those affecting the alimentary tract and metabolism (36%). Among all causes of mismatched medications, discrepancies in one drug were found in 67%, in two drugs in 21%, and in three drugs in 13%. The mismatching was more common in females (85%) than in males (46%, P = 0.042).

Conclusions: This study provided evidence in a small sample of patients on differences of drug prescription and their use on admission and on discharge from hospital. MR processes have a high potential to identify clinically important discrepancies for all patients.

Background: Hyperplastic polyps (HPs) of the colon are the most common colorectal polyps. Metabolic syndrome components such as obesity and hyperlipidemia are considered the most common etiological factors for HPs as well contributing to the pathogenesis of fatty liver disease. Objectives: To determine the possible association between biopsy-proven steatohepatitis and hyperplastic colonic polyps. 

Methods: This retrospective cohort observational study conducted at the Holy Family Hospital in Nazareth, Israel, included subjects who underwent screening colonoscopy over a 2 year period. Data were extracted from the patient charts and included demographics, anthropometric measurements, vital signs, underlying diseases, medical therapy, laboratory data, and results of the liver biopsy. The colonoscopy report and pathological report of each extracted polyp were also evaluated.

Results: A total of 223 patients were included in the study: 123 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) and 100 patients without NASH who served as the control. Fourteen colonic adenomas (11% of patients) were found in the NASH group vs. 16 (16%) in the control group (P = 0.9); 28 HPs were found in the NASH group (22.7%) vs. 8 in the control group (8%) (P < 0.05). The multivariate analysis, after adjusting for, age, C-reactive protein and smoking, showed that the presence of NASH (OR 1.69, 95%CI 1.36–1.98, P < 0.01) was associated with increased risk for HP. 

Conclusions: Our study found an association between biopsy-proven steatohepatitis and the burden of hyperplastic polyp.

 

Background: Recently we observed patients with chronic liver disease (CLD) or chronic reflux symptoms (CRS) who developed gastric polyps (GPs) while undergoing surveillance gastroscopies for the detection of either esophageal varices or Barrett's esophagus, respectively.

Objectives: To identify risk factors for GP growth and estimate the gastric polyp growth rate (GPGR).

Methods: GPGR was defined as the number of days since the first gastroscopy (without polyps) in the surveillance program, until the gastroscopy when a GP was discovered.

Results: Gastric polyp growth rates in CLD and CRS patients were similar. However, hyperplastic gastric polyps (HGPs) were detected more often (87.5% vs. 60.5%, P = 0.051) and at a higher number (2.57 ± 1.33 vs. 1.65 ± 0.93, P = 0.021) in the CLD patients. Subgroup analysis revealed the following findings only in CLD patients with HGPs: (i) a positive correlation between the GPGR and the patient's age; the older the patient, the longer the GPGR (r = 0.7, P = 0.004). (ii) A negative correlation between the patient's age and the Ki-67 proliferation index value; the older the patient, the lower the Ki-67 value (r = -0.64, P = 0.02). No correlation was detected between Ki-67 values of HGPs in CLD patients and the presence of portal hypertension, infection with Helicobacter pylori, or proton pump inhibitor use.

Conclusions: In comparison with CRS patients, CLD patients developed HGPs more often and at a greater number. Young CLD patients may have a tendency to develop HGPs at a faster rate than elderly CLD patients.

Background: Patients with multiple (< 100) colorectal adenomatous polyps are at increased risk for colorectal cancer. Genetic evaluation of those patients who test negative for APC gene mutation is both a clinical and economic burden but is critical for counseling and surveillance. In Israel, this is confounded by the fact that national health insurance does not fully cover genetic evaluation of APC gene exon 16.

Objectives: To perform a comprehensive genetic evaluation of APC gene mutation-negative polyposis patients with the aim of developing a future evaluation protocol.

Methods: Genetic analyses were performed in 29 APC gene mutation-negative Jewish individuals with 5 to ≥ 40 colonic adenomas who did not fulfill Amsterdam (clinical) criteria for Lynch syndrome. Analyses included completion of APC gene exon 16 sequencing, analysis for APC gene copy number variations (deletions or duplications), MUTYH gene sequencing, and microsatellite instability in CRC[1] patients fulfilling “Bethesda” (laboratory investigation) criteria for Lynch syndrome.

Results: Completion of APC gene exon 16 sequencing revealed one patient with the E1317Q polymorphism. All were normal by APC multiplex ligation-dependent probe amplification analysis. Pathogenic MUTYH mutations were found in three patients, all of North African origin; two additional patients had variants of unknown significance. One of six patients with Bethesda-positive criteria was MSI²-High with immunohistology consistent with MLH1 mutation.

Conclusions: Based on this small but well-characterized cohort with multiple colorectal adenomas, Lynch syndrome needs to be excluded if there are compatible criteria; otherwise MUTYH sequencing is probably the first step in evaluating APC-negative patients, especially for Jews of North African descent. Completing APC exon 16 sequencing and copy number variations analysis should probably be the last evaluations.

Background: Double balloon enteroscopy is a new technique that enables deep intubation of the endoscope into the small bowel lumen. Through a channel in the endoscope, invasive procedures such as biopsy, polypectomy and hemostasis can be performed, avoiding the need for surgery.

Objectives: To prospectively analyze our results of the first 124 DBEs[1] performed since February 2007.

Methods: The study group comprised all patients who underwent DBE at the Sheba Medical Center between February 2007 and February 2009. Recorded were the patients' demographic data, comorbidities, indications for the examination, results of previous non-invasive small bowel imaging (computed tomography enterography, capsule endoscopy, etc), investigation time, and results of the procedure including findings, endoscopic interventions, complications and pathological report.

Results: A total of 124 procedures were performed in 109 patients. Of the 124 examinations, 57 (46%) were normal and 67 (54%) showed pathology. The main pathologies detected on DBE were polyps (14%), vascular lesions (17.6%) and inflammation (12%). Endoscopic biopsies and therapeutic interventions were required in 58 examinations (46%). A new diagnosis was established in 15% of patients, diagnosis was confirmed in 29% and excluded or corrected in 12%. One complication was observed: a post-polypectomy syndrome that was treated conservatively.

Conclusions: DBE is a safe procedure and has a high diagnostic and therapeutic yield. Most of the examinations were performed under conscious sedation, and only a minority of patients required deeper sedation. 

Background: The incidence of cardiovascular disease increases with age, and visits by elderly patients to the outpatient cardiac clinic are becoming more frequent.

Objectives: To characterize cardiovascular pathologies of patients 70 years of age and over who visit the outpatient cardiac clinic.

Methods: We investigated cardiovascular pathologies, risk factors, and medications in new patients over a 2 month period.

Results: The study population comprised 290 patients: 139 (47.9%) were older than 70 years. Among the cardiovascular pathologies, aortic stenosis, angina pectoris, congestive heart failure, s/p coronary artery bypass graft, and stroke were more frequent in the elderly patients than in those under age 70. Among the risk factors for ischemic heart disease, only hypertension was more frequent in the elderly population, whereas fewer in this group were active smokers. The mean number of medications administered was 3.51 ± 1.63 among the elderly patients compared to 1.99 ± 1.71 among the younger ones (P = 0.0001). Beta-blockers were the most frequently used cardiovascular drugs both in the elderly (59.7%) and in the younger patients (43%) (P = 0.0046).

Conclusions: Patients over age 70 represent about half the visits in our outpatient clinic. Their multiple cardiovascular pathologies and therapeutic requirements raise the issue of developing the cardiology service to meet the special needs of geriatric patients.