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AIMS AND BACKGROUND: To review false-negative or underreported (reactive changes, squamous or glandular atypia) smears performed in women developing histologically proven CIN2 or more severe lesions within 24 months and evaluate error causes. The study setting was the Florence District cervical cancer population-based screening: about 60,000 women age 25-60 years screened per year. METHODS: 118 false-negative or underreported cases were identified at screening files-cancer Registry matching, and the original smears were reviewed by six independent readers to judge smear adequacy and error type. RESULTS: Sampling errors (reported as inadequate, negative or less severe than CIN1 at review) accounted for 74% and screening/interpretation errors (reported as CIN1 or more severe at review) accounted for 26% of studied cases. Screening/interpretation errors were more likely ascribed to misinterpretation and underreporting than to misperception of cellular abnormalities. CONCLUSIONS: Quality control should above all address the problem of sampling adequacy. Due to the rarity of misperceived abnormalities (true screening errors), manual or automated rescreening of negative smears would not be an effective procedure for quality control.

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BACKGROUND: A previous pilot study from our group suggested that: (1) adoptive immunotherapy (A1) with tumor-infiltrating lymphocytes (TIL) and recombinant interleukin-2 (rIL-2) may be applied with safety to more than 80% of the patients who had surgery for Stage III nonsmall cell lung carcinoma (NSCLC); and (2) AI could be useful in patients with locally advanced disease. The present randomized study was planned to assess the efficacy of AI in the postoperative treatment of Stage II, IIIa, or IIIb NSCLC: METHODS: TIL were expanded in vitro from tissue samples obtained from the surgically removed specimens of 131 patients. Eighteen cultures yielded no growth of TIL. The remaining 113 patients were stratified according to disease stage and randomized to receive AI or standard chemoradiotherapy. TIL were infused intravenously 6 to 8 weeks after surgery, rIL-2 was administered subcutaneously at escalating doses for 2 weeks, and then at reduced doses for 2 weeks and then for 2 to 3 months. RESULTS: Three-year survival was significantly better (P < 0.05) for patients who underwent AI than for controls. AI was of no benefit to patients with Stage II NSCLC, potentially useful to patients with Stage IIIa NSCLC (P = 0.06), and significantly advantageous to patients with Stage IIIb (T4) NSCLC (P < 0.01). For patients with Stage III NSCLC, local relapse (but not distant relapse) was significantly reduced following AI (P < 0.05). CONCLUSIONS: AI should be considered when designing future adjuvant therapy protocols for the treatment of NSCLC:

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This study assesses the feasibility and toxicity of adoptive immunotherapy with tumor infiltrating lymphocytes and recombinant interleukin-2 in 29 patients who underwent resection for stage III non-small-cell lung cancer. In five patients cultures yielded no growth of tumor infiltrating lymphocytes. In the remaining 24 patients (stage IIIa, 14 cases; stage IIIb, 10 cases) tumor infiltrating lymphocytes were in vitro expanded from surgically obtained tissue samples, including samples from both the tumor and surrounding lung. A number of tumor infiltrating lymphocytes, ranging from 4 to 70 billion cells, were reinfused intravenously 4 to 6 weeks after operation. Interleukin-2 was administered subcutaneously at escalating does for 2 weeks and then at reduced doses for 2 to 3 months. Median survival was 14 months, and the 2-year survival was 40%. Three patients remain alive and disease-free at more than 2 years after operation. Two of these patients did not have complete resection at thoracotomy. Multivariate analysis showed no correlation between the factor of incomplete resection and survival. Intrathoracic recurrence without concomitant distant failure was documented in two patients only and none of the patients with incomplete resection (12 cases) had relapse within the thorax. The present experience demonstrates that adoptive immunotherapy may be applied with safety in patients operated on for stage III non-small-cell lung cancer and suggests that it can be useful, notably in patients with locally advanced disease.

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In order to evaluate the agreement and accuracy of cervical (vaginal) cytologic diagnoses, 16 cytologists from a large laboratory in Florence, Italy, with experience ranging from 2 to 25 years, independently examined a set of 100 slides. A common reporting form based on a seven-category classification system was used. Concordance was calculated for each pairwise comparison between the 16 cytologists and between each cytologist and the target diagnosis. The values of the kappa statistic for the whole laboratory were .49 for the multiple raters comparison and .59 for the target diagnosis comparison, showing a relatively good degree of agreement.

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An internal quality control system which is used in the centralized cytology laboratory of a population-based cervical cancer screening programme in Florence is described. It includes a peer review procedure. Abnormal cervical smears are circulated among all the cytologists and a consensus on the final diagnosis is reached. This daily procedure is designed to evaluate the performance of each cytologist and of the laboratory as a whole but can also be considered a valuable training opportunity. During an 18-month period 1197 smears were reviewed by 15 readers using a reporting form with six main categories of reporting (from 'negative' to 'invasive carcinoma'), plus an 'unsatisfactory' category. Overall the concordance between the 15 cytologists, assessed using the kappa statistic (range 0.46-0.71; median 0.60), was good. The level of agreement increased when a weighted kappa statistic (range 0.55-0.78; median 0.68) was used. Kappa values were also calculated for specific categories and suggested an increasing concordance with increasing severity of the lesions, the categories of 'severe dysplasia' and 'invasive carcinoma' showing the highest agreement. The poor results for the 'moderate dysplasia' confirmed the need for combining this group with the 'severe dysplasia', as proposed in the Bethesda system.

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The effect of L-arginine methylester (L-Arg-Me) was studied in the isolated heart of the guinea-pig perfused with hypoxic substrate-free medium for 30 min and subsequently reoxygenated with normal saline solution for 30 min. The administration of L-Arg-Me in basal conditions decreases dose-dependently heart rate without any changes in the myocardial structure. On the other hand, the administration of L-Arg-Me (5-10 mM) decreases ventricular arrhythmias, especially during reoxygenation; in fact ventricular fibrillation is abolished. L-Arg-Me treatment increases the recovery of normal electrical and mechanical activity at the end of reoxygenation and reduces the increase in basal tone. Treatment with 10 mM L-Arg-Me decreases lactate dehydrogenase (LDH) release in the effluent and lysosomal fragility in cardiac tissue, while it does not influence calcium gain. L-Arginine (L-Arg) does not mimic any of the effects of L-Arg-Me.

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