Well-differentiated thyroid carcinoma: comparison of microscopic and macroscopic disease.

BACKGROUND: The rapid increase in the incidence of well-differentiated thyroid cancer in recent years is the result of smaller thyroid tumors (1 cm or less) being diagnosed more frequently. Few studies are available regarding the appropriate approach to this previously known postmortem incidental finding, and their results remain controversial. METHODS: In 2005, our center started a registry of all patients with nonmedullary thyroid carcinoma who were followed at our institute. In the present study, data on the background, clinical, and outcome characteristics were collected from the registry for 225 patients with microscopic disease and 543 patients with macroscopic disease. RESULTS: Patients with microscopic disease were slightly older (51 vs. 47.5 years, p = 0.003), had a higher female to male ratio (189:37 vs. 419:123; p = 0.06), and were affected more by papillary carcinoma (98.2% vs. 85.5%; p < 0.001). Multifocal disease was documented in 50.2% of the patients with microscopic disease and 46.8% of the patients with macroscopic disease (NS), and bilateral disease, in 42.6% and 36.8%, respectively (NS). Corresponding rates for the two groups for other tumor-related factors were as follows: lymph node involvement at initial treatment, 25.7% and 30% (NS); distant metastases, 2.4% and 5.1% (p = 0.16); persistent/recurrent disease, 11% and 32% (p < 0.001); and new distant metastases, 2.65% and 6.5% (p = 0.07). At a median follow-up of 5 years, 96% of the microscopic carcinoma group were disease free compared to 77% of the macroscopic group (p < 0.001). CONCLUSION: The differences between patients with microscopic and macroscopic well-differentiated thyroid carcinoma may not justify a different therapeutic approach.

Weekly infusional high-dose 5-fluorouracil and leucovorin and biweekly cisplatin: a convenient treatment option in advanced gastric cancer.

BACKGROUND: To summarize our experience using a regimen of weekly 5-FU and leucovorin (LV) and biweekly cisplatin (CDDP) in advanced gastric cancer (AGC). MATERIAL/METHODS: Patients had previously untreated histologically confirmed AGC. Treatment consisted of intravenous weekly infusional 5-FU and LV and biweekly CDDP, given for 6 weeks followed by a 2-week rest. Initially, a lower dose level was used (5-FU 2000 mg/m(2), LV 500 mg/m(2), CDDP 40 mg/m(2)), which was later increased (5-FU 2600 mg/m(2), LV 500 mg/m(2), CDDP 50 mg/m(2)). RESULTS: Forty-five patients were treated, 18 at the lower dose level and 27 at the higher dose level. The median age was 67 years and 55% were male. Grade > or =3 toxicity was documented in 37% of patients but toxicity related hospitalizations or treatment discontinuation occurred in only 22% and 13%, respectively. There were no toxic deaths. The most common hematological toxicities were anemia and neutropenia and the most common non-hematological toxicities were nausea, vomiting and fatigue. Of the 39 patients evaluable for response, 13 (33%) had partial response (PR) and 11 (28%) had stable disease (SD). Control of disease (PR+SD) was achieved in 61%. The higher dose level was associated with a higher response rate (p=0.07) and an increased toxicity (p=0.01), mostly hematological and gastrointestinal. Median progression-free survival and overall survival were 3.5 and 9.2 months, respectively. CONCLUSIONS: This regimen appears safe, with a manageable toxicity profile. Efficacy data resemble those reported for more complex and toxic regimens. The higher dose level had enhanced activity, at the expense of increased toxicity.

Deleted in colorectal cancer protein expression as a possible predictor of response to adjuvant chemotherapy in colorectal cancer patients.

PURPOSE: The deleted in colorectal cancer (DCC) gene predicts a poor outcome for patients with colorectal carcinoma. This study was designed to investigate whether the expression of the DCC protein also can predict response to adjuvant chemotherapy. METHODS: The expression of DCC was evaluated immunohistochemically in 74 paraffin-embedded tumor samples from patients with Stage II (n = 41) and Stage III (n = 33) colorectal carcinomas. Follow-up time was at least 60 (median, 64) months. Follow-up was at least five years for all patients who are alive. End points of the study were recurrence of disease and death. Forty-eight patients received adjuvant therapy of 5-fluorouracil + levamisole; 28 were not treated. RESULTS: Fifty percent of tumors were deleted in colorectal cancer-positive (DCC+). Proportion of survival and disease-free survival were higher in the DCC+ patients (83 percent) than in deleted in colorectal cancer-negative (DCC-; 54 percent). In the DCC+ group, adjuvant treatment was a strong positive predictive factor for survival and disease-free survival. All DCC+ patients who received adjuvant chemotherapy (CHEMO+) are alive with no evidence of disease, whereas without chemotherapy (CHEMO-) only 54 percent are alive ( P = 0.0001). When stratification was performed by stage, patients in Stage II who were DCC+/CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO- survival rate was 75 percent and disease-free survival rate 62 percent ( P = 0.042). Patients in Stage III who were DCC+/ CHEMO+ had survival and disease-free survival of 100 percent, whereas in DCC+/CHEMO- both dropped to zero ( P = 0.0002). On the other hand, in the DCC- tumors, there was no statistical significant relationship between chemotherapy and survival or disease-free survival (DCC-/CHEMO- had 57 percent survival; DCC-/CHEMO+ had 52 percent survival). CONCLUSIONS: DCC is a prognostic factor for colorectal cancer. Positive expression of DCC identifies a subgroup of patients who respond favorably to adjuvant chemotherapy, which resulted in our cases, in 100 percent survival and disease-free survival rates. Without treatment, the survival rate of DCC+ patients dropped significantly. We suggest that DCC immunostaining should be performed routinely. All DCC+ patients should receive adjuvant chemotherapy. For DCC- tumors, a larger cohort of patients should be studied before definitive conclusions can be drawn; however, clinical trials of new drug combinations should focus on DCC- patients.

Climatotherapy at the Dead Sea is a remittive therapy for psoriasis: combined effects on epidermal and immunologic activation.

BACKGROUND: The beneficial effect of climatotherapy at the Dead Sea (CDS) for psoriasis has been established clinically but there is a striking lack of studies assessing its in vivo effect at the molecular and cellular levels. OBJECTIVE: We sought to study the response of activated immunologic cells and keratinocytes in psoriatic lesions to CDS. METHODS: A total of 27 patients with chronic, stable, plaque-type psoriasis treated with CDS for 28 consecutive days were evaluated with the Psoriasis Area and Severity Index score and quantitative histologic measures. RESULTS: After 4 weeks of treatment, the overall Psoriasis Area and Severity Index score decreased by 81.5%. Complete clearance was achieved in 48% of the patients, and moderate to marked improvement in 41%. The average duration of remission was 3.3 months. Histologically, there was an overall reduction in malpighian layer thickness by 63.4%, and keratinocyte hyperplasia, assessed by Ki-67 cell cycle antigen expression, decreased by 78%; residual cell proliferation was confined mainly to the basal layer. These changes were accompanied by normalization of keratin 16 expression in 90% of the patients. T lymphocytes were almost totally eliminated from the epidermis (depletion of >90% of CD3(+) and CD25(+) cells), with only a low number remaining in the dermis (depletion of 69.4% of CD3(+) cells and 77.4% of CD25(+) cells). This reduction in activated T cells was accompanied by a marked reduction in HLA-DR expression by epidermal keratinocytes. CONCLUSIONS: CDS is a highly effective and remittive treatment for moderate to severe plaque-type psoriasis, leading to a reversal of both pathologic epidermal and immunologic activation.

Gynecologists' trends and attitudes toward prescribing hormone replacement therapy during menopause.

OBJECTIVE: To examine the attitudes and prescription practices of gynecologists in the United States and Israel with regard to hormone replacement therapy (HRT) for postmenopausal women. The current recommendations for the use of HRT for menopausal symptoms were reviewed. DESIGN: An eight-item questionnaire was sent by electronic mail or posted to randomly selected members of The North American Menopause Society ( = 250) and the Israeli Menopausal Society ( = 250), all of whom were physician gynecologists. RESULTS: Eighty-seven percent of the questionnaires ( = 435) were completed and were eligible for analysis. Results showed that 400 physicians (92%) routinely offered HRT to their menopausal patients. For women with an intact uterus, 72.5% preferred to use a continuous estrogen-progesterone regimen, and 27.5% preferred to use a sequential combined regimen. The treatment was prescribed for 10 years or more by 86.4% of the American gynecologists, compared with only 66.3% of the Israeli gynecologists ( = 0.001). Overall, the majority of physicians recommended alendronate for recalcitrant osteoporosis and dietary supplements for all women. However, significant differences were found between the American and Israeli groups: 71% of the Americans versus 55.6% of the Israelis prescribed alendronate ( = 0.02); 97.8% versus 71.33% recommended calcium and vitamin D; and 51.6% versus 38.8% recommended multivitamins ( = 0.001 for both groups). Phytoestrogens, alone or in combination with HRT, were recommended by 57.5% ( = NS between groups), and antidepressive drugs were prescribed by only 11% (15.1% of the Americans and 6.3% of the Israelis; = 0.001). CONCLUSION: Most gynecologists recommend HRT during menopause. For women with an intact uterus, the preferred regimen was continuous-combined HRT with estrogen and progesterone. The treatment duration is subject to wide variations, from no time limit to discontinuation after 5 to 10 years. Dietary supplements as well as alendronate, alone or in combination with HRT, are popular for severe osteoporosis. We suggest that, until definitive guidelines become available, an individualized approach should be applied, with careful consideration of both the benefits and risks of treatment.