Mark P. Hanna

Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists

The reliability of a diagnostic test depends on the reproducibility of the result. Many clinical diagnostic tests can be quantified with established ranges and standard deviations. Other tests are more subjective, such as those that depend on analysis of a visual image with an increased possibility of variance in the result. To study this variance, the authors analyzed the performance of expert pathologists in the interpretation of cutaneous melanocytic tumors. A panel of expert pathologists was convened to review anatomic pathology specimens from melanocytic tumors. Each pathologist submitted five specimens, from which 37 were selected for review. Only one slide was used for each case. All specimens were interpreted by each pathologist without consultation with each other. In addition to standard diagnostic terms, each specimen was designated as benign, malignant, or indeterminate. Statistical analysis was used to determine the degree of concordance. The combined kappa statistic for the eight observers and three possible outcomes (benign, malignant, or indeterminate) was 0.50. A kappa statistic of this magnitude, is defined as being moderate. In 62% of the specimens, there was unanimous agreement or only one discordant designation. Thirty-eight percent had two or more discordant interpretations. No single pathologist had a disproportionate number of discordant designations. This study mimics the consultation practice of anatomic pathology and shows the variability and discordance in diagnostic language and designation of biological behavior. The results suggest the criteria for the diagnosis of melanomas and melanocytic nevi need to be refined and more consistently applied.

Reduced utilization and cost of primary care clinic visits resulting from self-care education for patients with osteoarthritis of the knee

OBJECTIVE To determine the extent to which the cost of an effective self-care intervention for primary care patients with knee osteoarthritis (OA) was offset by savings resulting from reduced utilization of ambulatory medical services. METHODS In an attention-controlled clinical trial, 211 patients with knee OA from the general medicine clinic of a municipal hospital were assigned arbitrarily to conditions of self-care education (group E) or attention control (group AC). Group E (n = 105) received individualized instruction and followup emphasizing nonpharmacologic management of joint pain. Group AC (n = 106) received a standard public education presentation and attention-controlling followup. A comprehensive clinical database provided data concerning utilization and cost of health services during the following year. RESULTS Only 25 subjects (12%) were lost to followup. The 94 subjects remaining in group E made 528 primary care visits during the year following intervention, compared with 616 visits by the 92 patients remaining in group AC (median visits 5 versus 6, respectively; P < 0.05). Fewer visits translated directly into reduced clinic costs in group E, relative to controls (median costs [1996 dollars]

Serum Angiotensinogen Concentration in Relation to Gonadal Hormones, Body Size, and Genotype in Growing Young People

229 versus

Chemotherapy, early surgical reassessment, and hyperfractionated abdominal radiotherapy in stage III ovarian cancer: Results of a gynecologic oncology group study

305, respectively; P < 0.05). However, self-care education had no significant effects on utilization and costs of outpatient pharmacy, laboratory, or radiology services over the ensuing year. The cost per patient to deliver the self-care intervention was estimated to be

Studies of iodixanol in the rabbit lung and peritoneum

58.70. CONCLUSION Eighty percent of the cost of delivering effective self-care education to the knee OA patients in this study was offset within 1 year by the reduced frequency and costs of primary care visits. For >50% of patients receiving the intervention, the savings associated with fewer primary care visits exceeded the cost of self-care education.

Effect of breathing on the detection of in vivo simulated pulmonary nodules by spiral CT.

Multiple factors are thought to influence the level of circulating angiotensinogen (AGT). We showed previously that the serum AGT concentration was significantly related to body mass index (BMI) in a cohort of young people. In the present study, we studied whether levels of the gonadal hormones estradiol and testosterone might also predict the AGT level and might contribute to the BMI effect, since both the production of these hormones and BMI increase with age. In boys (n=127; mean+/-SD age, 14.7+/-1.9 years) and girls (n=104; age, 14.8+/-1.9 years) studied as a single group, we found a significant association of AGT level with level of estradiol (P=0.015) after adjustment for haplotype, age, race, testosterone concentration, and BMI. In girls studied alone, the level of AGT showed a significantly positive relation to level of testosterone (P=0.043), possibly a result of peripheral conversion of testosterone to estradiol, after adjustment for haplotype, age, race, estradiol concentration, and BMI. In boys, on the other hand, the level of testosterone was inversely related to AGT concentration (P=0.019), again after making adjustments for the other variables. Finally, in pairs of subjects matched for BMI, age, race, and gender where 1 member of each pair had either 1 or 2 copies of an AGT gene haplotype (T235 and -1074t) and the other member had no copy, the level of AGT was higher in the carrier of a haplotype in 24 of the 34 pairs (P<0.001). In conclusion, gonadal hormones are an additional influence on the circulating level of AGT in growing young people. In addition, with matching for BMI and other covariates, there is a strong association of AGT genotype with the serum level of AGT, emphasizing the importance of AGT gene expression as a determinant of the circulating level of AGT.

The Effects of Adherence to Antidepressant Treatment Guidelines on Relapse and Recurrence of Depression

PURPOSE To determine outcomes and treatment toxicities in patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma treated with three courses of cisplatin-cyclophosphamide, surgical reassessment (SRA), and hyperfractionated whole abdominal irradiation (WAI). METHODS AND MATERIALS Forty-two eligible patients entered this prospective Phase II study conducted by the Gynecologic Oncology Group (GOG). Disease characteristics were as follows: age range, 32-76 years (median 58); Stage IIIA (n = 1, 2%), IIIB (n = 2, 5%), IIIC (n = 39, 93%); histology-serous papillary (n = 21, 50%); other (n = 21, 50%); Grade 1 (n = 1, 2%); 2 (n = 14, 33%); 3 (n = 27, 54%); residual disease after initial surgery (present: n = 23, 55%; absent: n = 19, 45%). Five patients progressed while on chemotherapy, could not be effectively cytoreduced, and were not eligible for WAI. Of the remaining 37 patients, 35 received WAI. Surgical reassessment was not performed in five patients. RESULTS Of 37 patients with known SRA status after chemotherapy, 21 (57%) were grossly positive, 4 (11%) were microscopically positive, and 12 (32%) were negative. Based on measurements recorded following initial laparotomy and surgical reassessment, progression during chemotherapy was noted in 40%, stage disease in 37%, and objective response in 23%. Toxicity during hyperfractionated WAI was limited and reversible. No patient beginning WAI failed to complete or required a significant treatment break. Following WAI, six patients underwent laparotomies for abdominal symptoms; five had recurrent disease. Five additional patients were managed conservatively for small bowel obstruction (SBO) or malabsorption, of whom three subsequently developed recurrence. Twenty-two patients having pelvic boosts were significantly more likely to require management for gastrointestinal morbidity (p = 0.0021). Considering all eligible patients, median disease-free and overall survivals were 18.5 and 39 months, respectively. Considering patients completing chemotherapy and WAI, median disease-free and overall survivals were 24 and 46 months, respectively. CONCLUSIONS (a) Disease progression occurred within three cycles of cisplatin and cyclophosphamide chemotherapy in 40% of patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma. (b) Following limited chemotherapy, hyper-fractionated WAI was acutely well tolerated. (c) Late radiation-related toxicity was observed in only three patients (8.6%) in the absence of recurrent disease. Late gastrointestinal morbidity was significantly associated with the administration of a pelvic radiotherapy (RT) boost. (d) Short duration chemotherapy followed by SRA and hyperfractionated WAI without a pelvic boost is a promising management option for patients with optimal Stage III ovarian cancer. A Phase III trial will be necessary to determine how this treatment strategy compares with chemotherapy or RT alone in this patient population.

Racial Variation in Antidepressant Treatment in a Medicaid Population

Objective. To evaluate a new water-soluble contrast agent, iodixanol. The study evaluates absorption from the peritoneal cavity and toxicity in the lung. Materials and methods. Thirty New Zealand white rabbits were given the study agent and comparative agents into an endotracheal tube. Serial chest radiographs were evaluated for development of pulmonary edema. All lungs were evaluated histopathologically for toxic inflammatory response. Fifteen different rabbits were given intraperitoneal injection of the study and comparative contrast agents. Serial abdomen radiographs, taken up to 24 h after injection, were evaluated for contrast absorption from the peritoneal cavity. Results. Evaluation of indicators of pulmonary edema demonstrated that iodixanol caused the same or less pulmonary edema than comparative agents. Histopathologic analysis showed that iodixanol caused less macrophage response than saline (P = 0.010), the same lymphocyte infiltration as saline (P = 0.472), the same neutrophil response as saline (P = 0.297), and the same vasculitic reaction as saline (P = 0.128). Compared to iohexol 270, iodixanol caused the same macrophage infiltrate (P = 0.924), the same lymphocyte infiltration (P = 0.523), more neutrophil reaction (P = 0.007), and less vasculitic reaction (P = 0.042). Iodixanol was rapidly absorbed from the peritoneal cavity. Conclusion. Iodixanol is a new contrast agent that is isotonic at all clinically useful iodine concentrations. It appears safe in the lung and is absorbed from the peritoneal cavity.

Effects of self-care education on the health status of inner-city patients with osteoarthritis of the knee

OBJECTIVE To determine the effect of breathing on the detection of small dense pulmonary nodules of threshold conspicuity by spiral computed tomography (SCT). MATERIALS AND METHODS Forty pulmonary nodules of high density were created by endobronchial deployment of 2 and 4mm diameter beads in the peripheral airways of five anaesthetized dogs. SCT was performed during induced breath-hold and quiet breathing, using 5 mm collimation, pitch 2 and reconstruction of contiguous 5 mm slices. Scans were reviewed by six radiologists. Detection rates were measured as the number of nodules seen by at least one reader. The data was modelled using ordinal logistic regression for repeated measures, and the Wald Chi-square statistic used to test if there was a breath-hold vs. breathing effect on reader confidence level. RESULTS There was no difference in detection rates for breath-hold vs. breathing SCT (28 vs. 25, respectively; P=0.48). This was also true when only the 2 mm nodules (n=24) were considered (12 vs. 11, respectively; P=0.77). Reader confidence level was significantly higher for breath-hold vs. breathing SCT (Wald Chi-square statistic with 6 degrees of freedom=19.0; P=0.0041). CONCLUSION SCT can be performed during quiet breathing without a significant reduction the overall detection rate for small dense pulmonary nodules, though reader diagnostic confidence level is reduced.