Israel Medical Association Journal

Background: Intrathoracic cancer can cause hyponatremia, but it is uncertain whether mild hyponatremia in the outpatient setting should be regarded as an early sign of intrathoracic cancer.

Objectives: To evaluate the risk of undiagnosed intrathoracic cancer in patients with new persistent mild hyponatremia.

Methods: We conducted a retrospective cohort study using the electronic health record database of a large healthcare organization. The hyponatremia group included patients with sodium concentration of 130–134 mmol/L twice, after a previous normal value and without previous history of cancer or diseases related to hyponatremia. A control group with normal sodium concentration was matched by sex, age, and year of testing. We measured specific intrathoracic cancer incidence during 3 years of follow-up after sodium concentration test date. A logistic regression was used to adjust for further clinical information including smoking history, symptoms, and medications.

Results: The study comprised 1539 participants with mild hyponatremia and 7624 matched controls. New intrathoracic cancer diagnosis was more common in the hyponatremia group during a 3-year follow-up; 1.49% in the hyponatremia group and 0.39% in the control group, crude odds ratio (OR) 3.84, 95% confidence interval (95%CI) 2.22–6.63. After adjustment, hyponatremia remained a significant risk factor for the diagnosis of intrathoracic cancer; adjusted OR 3.61, 95%CI 2.08–6.28.

Conclusions: New mild persistent hyponatremia might be a significant predictive marker to a yet undiagnosed intrathoracic cancer.

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: Hepatitis D virus may cause a disease at various severities in the presence of hepatitis B virus, using hepatitis B surface antigen (HBsAg) on the external envelope in its replication process. Thus, people identified with HBsAg in blood tests should also be tested for hepatitis D virus.

Objectives: To describe the situation of performance of blood tests for detection of hepatitis D virus in patients positive for hepatitis surface antigen during 9 years in a population with heterogeneous origins in the north region of Israel.

Methods: We conducted a retrospective study using the database of Clalit Health Services.

Results: We found 3367 people were positive for HBsAg during the study period; 613 (18%) were tested for hepatitis D. People who tested for hepatitis D were younger (47.3 ± 15 years vs. 50.5) and showed a higher rate of visiting the gastroenterology clinic (80.6% vs. 41%). The rate of positive blood tests for hepatitis D was too small for analysis, but it still demonstrated tendency for higher rates in the Ethiopian Jewish group.

Conclusion: The recommendation for performance of blood test for hepatitis D virus was followed to a small extent. Considering the ethnic diversity of the population in Israel, activities to raise rates of performance should be considered.

Background: Medical imaging and the resultant ionizing radiation exposure is a public concern due to the possible risk of cancer induction.

Objectives: To assess the accuracy of ultra-low-dose (ULD) chest computed tomography (CT) with denoising versus normal dose (ND) chest CT using the Lung CT Screening Reporting and Data System (Lung-RADS).

Methods: This prospective single-arm study comprised 52 patients who underwent both ND and ULD scans. Subsequently AI-based denoising methods were applied to produce a denoised ULD scan. Two chest radiologists independently and blindly assessed all scans. Each scan was assigned a Lung-RADS score and grouped as 1 + 2 and 3 + 4.

Results: The study included 30 men (58%) and 22 women (42%); mean age 69.9 ± 9 years (range 54–88). ULD scan radiation exposure was comparable on average to 3.6–4.8% of the radiation depending on patient BMI. Denoising increased signal-to-noise ratio by 27.7%. We found substantial inter-observer agreement in all scans for Lung-RADS grouping. Denoised scans performed better than ULD scans when negative likelihood ratio (LR-) was calculated (0.04–-0.08 vs. 0.08–0.12). Other than radiation changes, diameter measurement differences and part-solid nodules misclassification as a ground-glass nodule caused most Lung-RADS miscategorization.

Conclusions: When assessing asymptomatic patients for pulmonary nodules, finding a negative screen using ULD CT with denoising makes it highly unlikely for a patient to have a pulmonary nodule that requires aggressive investigation. Future studies of this technique should include larger cohorts and be considered for lung cancer screening as radiation exposure is radically reduced.

Background: The incidence of congenital cytomegalovirus (CMV) infection in Israel is 0.7%. Only 10–15% are symptomatic. Valganciclovir has been shown to improve hearing and neurodevelopmental outcomes in neonates with symptomatic congenital CMV infection. Targeted examination of infants who fail routine neonatal hearing screening or have clinical or laboratory findings suggestive of symptomatic congenital CMV infection may be a cost-effective approach.

Objectives: To assess the possibility of targeted examination for the detection of newborns with symptomatic congenital CMV infection.

Methods: A prospective observational study was conducted in 2014–2015 at two medical centers in northern Israel. Included were all newborns who were tested in the first 3 days of life by polymerase chain reaction (PCR) for urine CMV DNA (n=692), either for failure the hearing screening (n=539, 78%), clinical or laboratory findings suggestive of symptomatic congenital CMV infection, or primary CMV infection during pregnancy (n=153, 22%).

Results: During the study period 15,433 newborns were born. The predicted rate of infection was 10–15% (symptomatic) of 0.7% of newborns, namely 0.07–0.105% or 10–15 infants. In fact, 15 infants (0.11%, 95% confidence interval 0.066–0.175) were diagnosed with symptomatic congenital CMV infection, 2/539 (0.37%) in the failed hearing group and 13/153 (8%) in the clinical/laboratory findings group. The incidence of symptomatic congenital CMV infection was within the predicted range.

Conclusions: Targeted examination of only 4.5% (n=692) of newborns detected the predicted number of infants with symptomatic congenital CMV infection in whom valganciclovir therapy is recommended

Background: The sentinel lymph node (SLN) biopsy procedure is a well-known method for identifying solid tumors such as breast cancer, vulvar cancer, and melanoma. In endometrial and cervical cancer, SLN has recently gained acceptance.

Objectives: To evaluate the detection rate of SLN with an indocyanine green and near-infrared fluorescent imaging (ICG/NIR) integrated laparoscopic system in clinically uterine-confined endometrial or cervical cancer.

Methods: Patients with clinically early-stage endometrial or cervical cancer were included in this retrospective study. ICG was injected into the uterine cervix and an ICG/NIR integrated laparoscopic system was used during the surgeries. The National Comprehensive Cancer Network (NCCN) protocol was followed. SLN and/or suspicious lymph nodes were resected. Side-specific lymphadenectomy was performed when mapping was unsuccessful. Systematic lymphadenectomy was completed in patients with high-grade histology or deep myometrial invasion. Enhanced pathology using ultra-staging and immunohistochemistry were performed in all cases.

Results: We analyzed 46 eligible patients: 39 endometrial and 7 cervical cancers. Of these, 44 had at least one SLN (93.6%). In 41 patients (89%) we detected bilateral SLN, in 3 (7%) only unilateral, and in 2 (4%) none were detected. Seven patients presented with lymph node metastasis. All were detected by NCCN/SLN protocol. Of these cases, two were detected with only pathological ultra-staging.

Conclusions: SLN mapping in endometrial and cervical cancer can easily be performed with a high detection rate by integrating ICG/NIR into a conventional laparoscopic system. Precision medicine in patients evaluated by SLN biopsy changes the way patients with endometrial or cervical cancer are managed.

Background: Ureaplasma species (Usp) are the most prevalent genital Mycoplasma isolated from the urogenital tract of both men and women. Usp may be commensals in the genital tract but may also be contributors to a number of pathological conditions of the genital tract. Because they can also just colonize the genital tract of healthy people, their pathogenic role can be difficult to prove.

Objectives: The aim of the study was to evaluate the efficacy of a quantitative polymerase chain reaction (qPCR) method for the discrimination between infection and colonization by measuring prevalence of Usp in asymptomatic versus symptomatic patients.

Methods: Urine samples were tested for U. parvum and U. urealyticum using a semi-quantitative multiplex PCR technique for sexually transmitted diseases (Anyplex™ STI-7 Detection Kit, Seegene, South Korea). A total of 250 symptomatic and 250 asymptomatic controls were included.

Results: A strong positive result for U. parvum was significantly more prevalent in symptomatic compared to asymptomatic patients. This finding was observed especially in women and in the young group (15–35 years of age). No significant differences were observed between the prevalence in symptomatic and asymptomatic patients of U. parvum with low strength of positivity and for U. urealyticum in all groups by age, gender, and strength of positivity.

Conclusions: The significant difference between the symptomatic and asymptomatic group in the highest positivity group for U. parvum using the Anyplex™ STI-7 detection kit in urine may indicate a high probability of infection rather than colonization, especially in women and young patients.

Ovarian cancer is a major cause of cancer death among women worldwide, and particularly in Israel. Although the disease at stage IA has 5 year survival rates of over 90%, early detection methods are not sufficiently accurate. Consequently, ovarian cancer is typically diagnosed late, which results in high fatality rates. An excellent candidate for early ovarian cancer detection would be in vivo magnetic resonance spectroscopy (MRS) because it is non-invasive and free of ionizing radiation. In addition, it potentially identifies metabolic features of cancer. Detecting these metabolic features depends on adequate processing of encoded MRS time signals for reconstructing interpretable information. The conventional Fourier-based method currently used in all clinical scanners is inadequate for this task. Thus, cancerous and benign ovarian lesions are not well distinguished. Advanced signal processing, such as the fast Padé transform (FPT) with high-resolution and clinically reliable quantification, is needed. The effectiveness of the FPT was demonstrated in proof-of-concept studies on noise-controlled MRS data associated with benign and cancerous ovaries. The FPT has now been successfully applied to MRS time signals encoded in vivo from a borderline serous cystic ovarian tumor. Noise was effectively separated out to identify and quantify genuine spectral constituents that are densely packed and often overlapping. Among these spectral constituents are recognized and possible cancer biomarkers including phosphocholine, choline, isoleucine, valine, lactate, threonine, alanine, and myoinositol. Most of these resonances remain undetected with Fourier-based in vivo MRS of the ovary. With Padé optimization, in vivo MRS could become a key method for assessing ovarian lesions, more effectively detecting ovarian cancer early, thereby improving survival for women afflicted with this malignancy.

Background: Bowel ultrasound has several possible uses in inflammatory bowel disease (IBD), including the initial evaluation of suspected IBD, monitoring of therapeutic response, detection of relapse, and diagnosis of complications as well as of extra-intestinal manifestations. However, its use has been limited mainly to countries where it is performed by the attending physician. 

Objectives: To investigate the feasibility and sensitivity of bedside bowel ultrasound performed by a gastroenterologist for assessing disease activity and complications in IBD.

Methods: We performed a feasibility study to compare the results of bowel ultrasound examination with those of another cross-sectional imaging modality (computed tomographic enterography or magnetic resonance enterography) in Crohn's disease, or with colonoscopy in ulcerative colitis.

Results: Between May 2015 and March 2016, 178 bowel ultrasound examinations were performed in 178 patients with suspected or established diagnosis of IBD. In 79 cases the results of another cross-sectional imaging or endoscopic examination performed within 3 months prior to the ultrasound exam were available. The sensitivity for detection of intestinal bowel thickening (a surrogate of inflammation) was 90%, and for detection of Crohn's disease complications, namely bowel stenosis and inflammatory mass, was 94% and 75%, respectively.

Conclusions: Bowel ultrasound is a useful and feasible bedside imaging tool for the detection of inflammation and complications in IBD patients. Bedside bowel ultrasound can be a valuable non-invasive tool to assess disease activity and complications in IBD patients when performed by the attending physician.

 

Background: Early prenatal ultrasound is an important part of prenatal screening in Israel. No studies have described the rate of trisomy 21 [T21] identification at 14–17 weeks gestation.

Objectives: To describe the rate of T21 identification by transvaginal sonograms (TVS) at 14–17 weeks gestation. 

Methods: We conducted a historical prospective study. Since 1986, early TVS of 72,000 fetuses at 14–17 weeks gestation have been prospectively recorded together with prenatal screening data at a private ultrasound center (AL-KOL, Haifa). We calculated the fraction of T21 cases by dividing the total number of cases with abnormal sonographic findings by the total number of diagnosed T21 cases. We also examined the percentage of verified T21 cases that had completely normal prenatal screening tests prior to the early prenatal TVS, thus revealing the contribution of this examination to the existing prenatal screening. Fisher’s exact test was used to calculate odds ratios for each sonographic marker. 

Results: Of 137 T21 fetuses, 123 had sonographic markers on early TVS, yielding a prediction capability of at least 89.87%. Of all T21 cases, 14% had completely normal nuchal translucency/first-trimester screening prior to the abnormal 14–17 week TVS findings. Isolated abnormal sonographic findings, which were found to increase the risk for T21, were common atrioventricular septal canal (odds ratio 88.88), duodenal atresia (OR 88.23), nuchal edema (OR 39.14), and hydrocephalus (OR 15.78). Fetal hydronephrosis/pyelectasis was non-significant when isolated (OR 1), and cardiac echogenic focus was associated with a decreased risk (OR 0.13).

Conclusions: Early prenatal TVS at 14–17 weeks may identify almost 90% of T21 and adds 14% to the identification rate at the first-trimester screening.