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.

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: Delayed diagnosis of choroidal neovascularization (CNV) in age-related macular degeneration (AMD) adversely affects visual outcome.

Objectives: To identify factors associated with early detection of CNV in the clinic setting.

Methods: Demographic and clinical data and lesion characteristics were retrospectively collected from 76 consecutive AMD patients who had a history of CNV in one eye and presented with CNV in the second eye. These data were evaluated for association with visual acuity (VA) at the time of presentation.

Results: Better VA was associated with a history of CNV in the fellow eye (P < 0.0001), adherence to follow-up every 4 months (P = 0.015), younger age (P = 0.03), smaller lesion (P < 0.0001), and non-subfoveal location (P = 0.048). VA of the fellow eye did not correlate with VA at presentation with CNV.

Conclusions: These data suggest that patients’ experience of CNV, regardless of VA, facilitates early diagnosis in the fellow eye. Adherence to follow-up in the routine clinic setting also facilitates early detection of CNV.

There are major dilemmas regarding the optimal modalities for breast cancer screening. This is of particular relevance to Israel because of its high-risk population. It was suggested that an avenue for further research would be to incorporate advances in signal processing through the fast Padé transform (FPT) to magnetic resonance spectroscopy (MRS). We have now applied the FPT[1] to time signals that were generated according to in vitro MRS[2] data as encoded from extracted breast specimens from normal, non-infiltrated breast tissue, fibroadenoma and cancerous breast tissue. The FPT is shown to resolve and precisely quantify the physical resonances as encountered in normal versus benign versus malignant breast. The FPT unambiguously delineated and quantified diagnostically important metabolites such as lactate, as well as phosphocholine, which very closely overlaps with glycerophosphocholine and phosphoethanolamine, and may represent a magnetic resonance-visible molecular marker of breast cancer. These advantages of the FPT could clearly be of benefit for breast cancer diagnostics via MRS. This line of investigation should continue with encoded data from benign and malignant breast tissue, in vitro and in vivo. We anticipate that Padé-optimized MRS will reduce the false positive rates of MR-based modalities and further improve their sensitivity. Once this is achieved, and given that MR entails no exposure to ionizing radiation, new possibilities for screening and early detection emerge, especially for risk groups. For example, Padé-optimized MRS together with MR imaging could be used with greater surveillance frequency among younger women with high risk of breast cancer.

Background: Cancer is a leading cause of mortality worldwide. The most effective way to combat cancer is by prevention and early detection.

Objectives: To evaluate the outcome of screening an asymptomatic population for the presence of benign and neoplastic lesions.

Methods: Routine screening tests for prevention and/or early detection of 11 common cancers were conducted in 300 consecutive asymptomatic, apparently healthy adults, aged 25–77 years. Other tests were performed as indicated.

Results: Malignant and benign lesions were found in 3.3% and 5% of the screenees, respectively, compared to 1.7% in the general population. The most common lesions were in the gastrointestinal tract followed by skin, urogenital tract and breast. Advanced age and a family history of a malignancy were associated with increased risk for cancer with an odds ratio of 9 and 3.5, respectively (95% confidence interval 1.1–71 and 0.9–13, respectively). Moreover, high serum C-reactive protein levels and polymorphisms in the APC and CD24 genes indicated high cancer risk. When two of the polymorphisms existed in an individual, the risk for a malignant lesion was extremely high (23.1%; OR[1] 14, 95% CI[2] 2.5–78).

Conclusions: Screening asymptomatic subjects identifies a significant number of neoplastic lesions at an early stage. Incorporating data on genetic polymorphisms in the APC and CD24 genes can further identify individuals who are at increased risk for cancer. Cancer can be prevented and/or diagnosed at an early stage using the screening facilities of a multidisciplinary outpatient clinic.

Pancreatic cancer is not a common malignancy in Israel, but it is the third most common cause of cancer mortality, attributable to a lack of screening tests, inaccessibility of the pancreas, and late cancer stage at diagnosis. We reviewed the epidemiology, known risk factors and screening methods available in Israel and describe the Israeli national consortium that was established to identify persons at risk and decide on screening methods to detect and treat their early-stage pancreatic cancer. In collaboration with the Israel National Cancer Registry, we evaluated the incidence and trends of the disease in the Jewish and non-Jewish populations. The consortium reviewed known lifestyle risk habits and genetic causes, screening methodologies used and available in Israel. Overall, there are about 600 new patients per year, with the highest incidence occurring in Jewish men of European birth (age-standardized rate 8.11/10⁵ for 2003–06). The 5 year survival is about 5%. The consortium concluded that screening will be based on endoscopic ultrasonography. Pancreatic cancer patients and families at risk will be enrolled, demographic and lifestyle data collected and a cancer pedigree generated. Risk factors will be identified and genetic tests performed as required. This concerted national program to identify persons at risk, recommend which environmental risk factors to avoid and treat, and perform endoscopic ultrasound and genetic screening where appropriate, might reduce their incidence of invasive pancreatic cancer and/or improve its prognosis

Background: Early detection of malignant melanoma of the skin is the most important factor in patient survival. Naked-eye diagnostic sensitivity and specificity are low. Patients with multiple nevi are at high risk to develop melanomas and the clinical follow-up of such patients is difficult, resulting in missed melanomas on the one hand and unnecessary biopsies on the other.

Objectives: To describe the set-up of a special clinic aimed at early detection of melanoma and follow-up of high risk patients and preliminary results from 20 months of operation.

Methods: We established a pigmented lesions clinic based on a digital photography studio enabling documentation and comparison over time of full body photography and dermoscopy.

Results: In the first 20 months of work, 895 patients were seen, 206 of them for follow-up visits. A total of 29,254 photos were taken. Altogether, 236 lesions were suspicious (either clinically or dermoscopically) and the patients were advised to excise them. Seven melanomas were found in this initial examination (which did not include long-term follow-up).

Conclusions: With multimode photographic cutaneous surveillance, early detection of melanoma in high risk patients has been reported. Our clinic utilizes the same techniques and diagnostic algorithm as other leading clinics throughout the world, thus enabling us to deliver better follow-up for those patients.
 

Background: Syndromic surveillance systems have been developed for early detection of bioterrorist attacks, but few validation studies exist for these systems and their efficacy has been questioned.

Objectives: To assess the capabilities of a syndromic surveillance system based on community clinics in conjunction with the WSARE[1] algorithm in identifying early signals of a localized unusual influenza outbreak.

Methods: This retrospective study used data on a documented influenza B outbreak in an elementary school in central Israel. The WSARE algorithm for anomalous pattern detection was applied to individual records of daily patient visits to clinics of one of the four health management organizations in the country.

Results: Two successive significant anomalies were detected in the HMO’s[2] data set that could signal the influenza outbreak. If data were available for analysis in real time, the first anomaly could be detected on day 3 of the outbreak, 1 day after the school principal reported the outbreak to the public health authorities.

Conclusions: Early detection is difficult in this type of fast-developing institutionalized outbreak. However, the information derived from WSARE could help define the outbreak in terms of time, place and the population at risk.

Israel has a National Screening Program for early detection of breast cancer. The need to continue and even expand this program was recently stressed in light of the high risk in the population. However, the optimal modalities for breast cancer screening are controversial, especially for women at risk. Mammography, the established screening method, is critically examined, and molecular imaging techniques, such as magnetic resonance spectroscopy and spectroscopic imaging are explored, especially for primary breast cancer detection. MRS[1] and MRSI[2] are currently limited by their reliance on the conventional framework for data analysis in biomedical imaging, i.e., the fast Fourier transform. Recent mathematical advances in signal processing via the fast Pade transform can extract diagnostically important information, which until now has been unavailable with in vivo MRS. A clinical MRS signal illustrates the rapid and stable convergence provided by FPT[3], yielding accurate information about key metabolites and their concentrations at short acquisition times. We suggest that the next step would be to apply the FPT to in vivo MRS/MRSI signals from patients with breast cancer and to compare these to findings for normal breast tissue. The potential implications of such an optimized MRS/MRSI for breast cancer screening strategies are discussed, especially for younger women at high risk.

The appearance of “new” infectious diseases, the reemergence of “old” infectious diseases, and the deliberate introduction of infectious diseases through bioterrorism has highlighted the need for improved and innovative infectious disease surveillance systems. A review of publications reveals that traditional current surveillance systems are generally based on the recognition of a clear increase in diagnosed cases before an outbreak can be identified. For early detection of bioterrorist-initiated outbreaks, the sensitivity and timeliness of the systems need to be improved. Systems based on syndromic surveillance are being developed using technologies such as electronic reporting and the internet. The reporting sources include community physicians, public health laboratories, emergency rooms, intensive care units, district health offices, and hospital admission and discharge systems. The acid test of any system will be the ability to provide analyses and interpretations of the data that will serve the goals of the system. Such analytical methods are still in the early stages of development.

Background: First-degree relatives of colorectal cancer patients are the largest groups of individuals at increased risk for colorectal cancer.

Objective: To assess the knowledge, attitudes and behavior to disease prevention and colorectal cancer screening among first-degree relatives of colon cancer patients.

Methods: A descriptive, point-prevalence epidemiological study was conducted among 215 first-degree relatives of survivors of colorectal cancer in the southern (Negev) region of Israel. Variables included perceived health status, knowledge about cancer screening, compliance rates with colorectal cancer screening, and interest in participation in early detection programs in the future.

Results: The mean age of the respondents was 47.9111.2 years, and 54% were males. Only 58 (27%) remembered having been encouraged to undergo an early detection test. In the previous year only 15% underwent fecal occult blood tests, while 9% had a barium enema and 14% an endoscopic examination of the colon by sigmoidoscopy or colonoscopy. A total of 49% of the asymptomatic respondents were unaware of recommendations for screening, and only 38.3% expressed any interest in participating in early detection programs in the future. Only 19% of respondents over the age of 50 and 8% of respondents over age 60 were interested in participating compared with 49% under the age of 50 (P0.0001).

Conclusion: A minority of first-degree relatives of colorectal cancer patients reported having been counseled to undergo screening, although most had seen their family physician in the previous 3 years. Primary care physicians should be more active in informing at-risk patients and encouraging them to undergo periodic screening.