Israel Medical Association Journal

Background: Colorectal cancer is the second leading cause of cancer mortality in Israel. Unfortunately, compliance  with annual fecal occult blood testing is very low.

Objective: To assess the effectiveness of interventions to increase FOBT[1] screening in primary care clinics in Israel.

Methods: A prospective, randomized study included all 50–75 year old enrollees of six family physicians in two primary care clinics. The register of two physicians, one from each clinic, was allocated to one of three groups. Two FOBT reminder strategies were tested: a physician reminder (753 patients), and a patient reminder that was either a phone call (312 patients) or a letter (337 patients). The control group (913 patients) of physicians continued administering their regular level of care. The main outcome measure was the percentage of patients undergoing FOBT screening in each study arm at the conclusion of the one year study period.

Results: In the intervention groups 14.3% (201/1,402) were screened using the FOBT over the course of the study year. Using an intent-to-screen analysis, the screening rate in the physician and patient reminder groups was significantly higher than in the control group(16.5 and 11.9%,vs. 1.2% respectively, P < 0.0001). Phone reminders were significantly more efective as compared to letters (14.7 vs. 9.2%, P = 0.01).

Conclusions: Our study has shown the benefit of various FOBT reminder systems, especially those centered around the family physician. Further research should focus on this area, in conjunction with other novel approaches.

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[1] FOBT = fecal occult blood testing

Background: Carcinoma of the gallbladder is diagnosed in 0.3–1.5% of all cholecystectomy specimens.

Objectives: To establish the overall rate of gallbladder carcinoma and unexpected gallbladder carcinoma based on our experience.

Methods: We retrospectively evaluated all consecutive cholecystectomies performed in our ward during a 6 year period in order to determine the incidence of gallbladder carcinoma and to identify common characteristics of this particular group of patients.

Results: Of the 1,697 cholecystectomies performed in our ward during the 6 years, gallbladder carcinoma was diagnosed in six patients (0.35%), but was not suspected prior to surgery in any of them. In accordance with the literature, the occurrence in women (5/6) was higher than in men (1/6). The mean age was 70 years (range 55–90). The most common symptom was abdominal pain; the majority (5/6) had cholelithiasis, and the pathologic report confirmed the diagnosis of adenocarcinoma in all six patients.

Conclusions: The overall incidence of unsuspected gallbladder carcinoma in our series was 0.35%. We could not find any common characteristics for this particular group of patients when compared to patients with non-malignant pathology.

Background: Matrix metalloproteinases are proteolytic enzymes that degrade extracellular matrix components. Numerous studies have demonstrated that individual MMPs[1] play a crucial role in tumor invasion and metastasis.

Objective: To examine the expression of MMPs and their inhibitor TIMP-2 in neoplastic and normal thyroid tissues.

Methods: We examined 33 cases of thyroid tumor (papillary, follicular and medullary carcinoma, follicular adenoma and multinodular goiter). MMP protein content and activity were measured by enzyme-linked immunosorbent assay and gel zymography. Immunohistochemistry was also performed.

Results: The thyroid tissues examined secreted MMP-2 and 9 as well as TIMP-2, but only MMP-2 was significantly higher in papillary carcinoma cases compared to the adjacent normal tissue or to the other tumor entities. Increased MMP-2 immunohistochemical staining was demonstrated in the neoplastic papillary epithelial component. No significant difference was seen between papillary carcinomas with lymph node metastases and those without.

Conclusions: Increased MMP-2 expression may be useful as a diagnostic marker to differentiate papillary carcinoma from other thyroid neoplasms, but it cannot serve as a useful prognostic marker.

Background: Extensive necrosis is rare in primary renal cell carcinoma. This finding may reflect the biological characteristics of the carcinoma and therefore could be of prognostic and clinical value.

Objectives: To assess the incidence of necrosis in renal cell carcinoma and its potential prognostic value.

Methods: We conducted a consecutive retrospective study of 173 patients after radical nephrectomy for renal cell carcinoma. Clinical and pathological data were collected from hospital medical records and compiled into a computerized database.

Results: Extensive necrosis was found in 31 tumor specimens (17.9%). Univariate analysis showed that the specimens with extensive necrosis were significantly larger and manifested more perirenal and venous extension than the tumors without necrosis. The size of the renal tumor was the only parameter that remained significant in multivariate analysis (P=0.0001). Overall disease-free survival did not differ significantly between patients with necrotic tumors and those without (68% and 66% respectively).

Conclusions: The finding of extensive necrosis in renal cell carcinoma specimens does not seem to be related to tumor biology but rather may reflect the relation between size and vascularity of the tumor.

Paraneoplastic syndromes are disorders associated with cancer but without a direct effect of the tumor mass or its metastases on the nervous system. Small cell carcinoma of lung associated with paraneoplastic sensory neuronopathy and/or paraneoplastic encephalomyelitis with the presence of anti-Hu antibodies has been termed “anti-Hu syndrome. Anti-­Hu associated PSN-PEM is an immune disorder in which both cell-mediated and humoral mechanisms are involved. Patients are consiaered affected by Anti-Hu associated PSN-PEM when they develop clinical signs and symptoms of CNS dysfunction and/or sensory neuropathy not caused by metas­tases or other disorders, and serum or cerebrospinal fluid is positive for Hu abs. SCLC is found in more than 90% of patients with cancer and positive Hu abs. Individual patients with Hu abs associated to SCLC may suffer PSN-PEM, Iimbic encephalitis, brainstem encephalopathy, opsoclonus-myoclo­nus, paraneoplastic cerebellar degeneration or myelopathy. Hu abs have a specificity of 99% and sensitivity of 82% in detecting paraneoplastic neurological syndromes. There are two types of treatment: the first is to treat the cancer, the second is to suppress the immune reaction with the use of corticosteroids, cyclophosphamide, azathioprine, plasma ex­change, intravenous immunoglobulin and immunoadsorption however, treatment of paraneoplastic syndromes is generally unsatisfactory.

Objective: To evaluate the feasibility of using combined clinical and histomorphometric features to construct a prognostic score for the individual patient with localized renal cell carcinoma.

Patients and Methods: We studied 39 patients with pT1 and pT2 RCC who underwent radical nephrectomy between 1974 and 1983. Univariate and multivariate analyses were used to determine the association between various prognostic features and patient survival.

Results: The most important and independent predictors of survival were tumor angiogenesis (P=0.009), nuclear DNA ploidy (P=0.0071), mean nuclear area (P=0.013), and mean elongation factor (P=0.0346). Combination of these variables enabled prediction of outcome for the individual patient at a sensitivity and specificity of 78% and 89% respectively.

Conclusion: Our results indicate that no single parameter can accurately predict the outcome for patients with localized RCC. Combination of neovascularity, DNA content and morphometric shape descriptors enabled a more precise stratification of the patients into different risk categories.