Cutaneous nodes in a patient with advanced papillary carcinoma of the thyroid

Cutaneous metastasis from thyroid carcinoma is infrequent. Leukemia as a second malignancy after treatment of thyroid cancer is also rare. We present a patient with a relapsed thyroid carcinoma treated with thyroid ablation with I 131 and loco-regional radiotherapy, who consulted by global worsening, weight lost, and multiple cutaneous nodes. Our patient is unusual in that she showed multisystem involvement at the time of hospital admission, and the specific skin lesions were the first sign of her acute monocytic leukemia.     

The interval from surgery to chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

BACKGROUND: To study the effect of the interval between surgery and the start of chemotherapy in the treatment of patients with advanced ovarian cancer. METHODS: We stratified patients according to the start of platinum-based chemotherapy in group 1 (within 4 weeks from surgery), group 2 (between 4 and 8 weeks) and group 3 (between 8 and 12 weeks). RESULTS: Three hundred and ninty-four stage III ovarian cancer patients were analysed. In the multivariate analysis there were no differences in survival according to the interval between surgery and chemotherapy among the three groups. The independent prognostic variables were type of procedure (p = 0.014), performance status (p = 0.040) and post-chemotherapy CA-125 (p < 0.0001). CONCLUSIONS: The interval between surgery and chemotherapy does not affect outcome.     

Whole brain irradiation and temozolomide based chemotherapy in melanoma brain metastases

Introduction Whole brain irradiation (WBRT) remains a recommended treatment for patients with brain metastases from malignant melanoma in terms of symptom palliation, especially when extracranial systemic disease is present. Temozolomide (TMZ) has shown efficacy in the treatment of metastatic melanoma. The objective was to evaluate the potential benefit in survival of two different schedules of total dose and fractionation (20 Gy/5 fractions vs 30 Gy/10 fractions) and further TMZ based chemotherapy. Materials and method We have conducted a retrospective study in a group of twenty-one patients (RTOG Recursive Partitioning Analysis class II) of the use of WBRT with 20 Gy/5 fractions (n=11) and 30 Gy/10 fractions (n=10). All patients received further TMZ based chemotherapy administered as a single chemotherapeutic agent or in combination with chemo-immunotherapy. Results Prognostic variables such as: age, Karnofsky performance status, extracranial metastases and number of brain metastases, were analyzed in both groups of treatment without statistically significant differences. The median survival time (MST) for WBRT 20 Gy group was 4 months (CI 95%: range 2–6 months) and for WBRT 30 Gy group was 4 months (CI 95%: range 0–7 months) without statistically significant differences (Log rank p=0.74). There was one complete response and two partial responses. Conclusions The results suggest that MST was not significantly affected by the total dose/fractionation schedule.     

Cesarean section as a cause of chronic pelvic pain.

OBJECTIVE: To determine if the history of cesarean section was associated with chronic pelvic pain, independent of the presence of other conditions such as pelvic adhesions, endometriosis, sequelae of pelvic inflammatory disease, leiomyoma and pelvic varices. METHODS: Retrospective case-control study conducted on 199 patients consecutively admitted from January 1998 to January 2000, 116 of them submitted to laparoscopy for the diagnosis of chronic pelvic pain and 83 asymptomatic patients submitted to tubal ligation by laparoscopy. A logistic regression analysis was used to verify the association between chronic pelvic pain and the history of previous cesarean section. RESULTS: In women with chronic pelvic pain, a history of cesarean section was observed in 67.2% of cases, adhesions in 51.7%, endometriosis in 33.6%, sequelae of pelvic inflammatory disease in 31.9%, leiomyoma in 6.9% and pelvic varices in 11.2%. In asymptomatic women, a history of cesarean section was observed in 38.5%, adhesions in 24.1%, endometriosis in 9.6%, sequelae of pelvic inflammatory disease in 4.8%, leiomyoma in 7.2% and pelvic varices in 3.6%. In a logistic model, chronic pelvic pain was associated with a history of cesarean section (O.R.=3.7), as well as with endometriosis (O.R.=8.5), sequelae of pelvic inflammatory disease (O.R.=10.5). CONCLUSIONS: In the present study cesarean section was associated with chronic pelvic pain. This fact may be the cause of a public health problem in the coming years, due to the raised rates of cesarean section in Brazilian women.     

Cooperative role of telomerase activity and p16 expression in the prognosis of non-small-cell lung cancer.

PURPOSE: Telomerase activity and p16 expression can be considered two of the most important molecular markers implicated in tumorigenesis. Our main aim was to study the cooperative role of both molecular alterations in the prognosis of patients surgically resected for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We have determined telomerase activity and p16 expression in a series of 98 prospectively collected NSCLC specimens obtained from patients who had undergone surgery without other treatment. Telomerase activity was investigated by a telomeric repeat amplification protocol enzyme-linked immunosorbent assay-based procedure, and p16 expression was examined by Western blot. Associations with survival were evaluated. RESULTS: Positive results for telomerase activity were found in 82% of the cases, and this variable correlated with poor differentiation and recurrence of tumors. Lack of p16 expression was observed in 61% of tumors, and a significant association with tumor recurrence was also observed. By univariate analysis, both negative telomerase activity and p16-positive expression were significantly correlated with a better prognosis. Moreover, statistics for equality of survival distributions for telomerase, adjusted for p16, indicated a positive interaction between both parameters. For telomerase-positive tumors, p16 expression emerged as a significant independent protective variable, as indicated by Cox multivariate analysis (relative risk [RR], 0.214; P =.014). This protective effect was maintained only for stage I and II tumors (RR, 0.108; P =.046). CONCLUSION: These results suggest that the combined telomerase activity and p16 expression analyses may be of prognostic importance in NSCLC, especially for patients affected by stage I and II tumors.     

A phase I-II study on a gemcitabine-cyclophosphamide-fluorouracil/folinic acid triplet combination in anthracycline- and taxane-refractory breast cancer patients.

PURPOSE: To define the cyclophosphamide (CTX) maximal tolerated dose when combined with fixed doses of gemcitabine, fluorouracil (5-FU) and folinic acid (leucovorin, LFA) in metastatic breast cancer patients pretreated with anthracyclines and taxanes. METHODS: Metastatic breast cancer patients aged < or = 75 years, with ECOG performance status 0-2, were eligible, provided that they had received previous anthracycline- and taxane-based chemotherapy for the advanced disease. Chemotherapy consisted of gemcitabine 1,000 mg/m(2), 5-FU 425 mg/m(2), LFA 100 mg/m(2) and escalating doses of CTX, starting from 500 mg/m(2), on days 1 and 8 every 3 weeks. The dose escalation was stopped if dose-limiting toxicity (DLT) occurred in > 33% of patients of a given cohort. After the definition of DLT, a further escalation with the addition of granulocyte colony-stimulating factor (G-CSF; on days 3-5 and 10-12) was planned. RESULTS: Since March 1999, 69 patients have entered this trial through seven different cohorts. The dose escalation was stopped at the CTX dose of 600 mg/m(2) since 3/6 patients showed DLT. A further dose escalation was attempted in the presence of G-CSF support. A CTX dose of 800 mg/m(2) proved to be safe and was chosen for the phase II. A total of 33 patients were treated at this dose level. The treatment was fairly well tolerated, grade 3-4 neutropenia and thrombocytopenia occurring in 38 and 16% of patients, respectively. No cases of sepsis or bleeding were registered. Four patients required a packed red blood cell transfusion. Severe nonhematologic toxicity was also uncommon, occurring in 10 patients. Three complete and 24 partial responses were recorded for an overall response rate of 38% (95% CI = 26-50). Two complete and 12 partial responses were recorded in the 33 patients treated in the phase II for an overall response rate (ORR) of 42% (95% CI = 25-61). CONCLUSIONS: The gemcitabine-CTX-5-FU/LFA combination is a well-tolerated treatment for poor-prognosis breast cancer patients with previous exposure to anthracyclines and taxanes. With the addition of G-CSF, a cumulative CTX dose of 1,600 mg/m(2) can be safely delivered every 3 weeks. The evidence of an ORR approaching 40% is very promising and justifies further evaluations in this subset of patients.     

Expression of epidermal growth factor receptor correlates with disease relapse and progression to androgen-independence in human prostate cancer.

PURPOSE: The transforming growth factor alpha-epidermal growth factor receptor (EGFR) autocrine pathway has been implicated in prostate cancer cell growth. Amplification and/or overexpression of c-erbB-2, a receptor closely related to the EGFR, has been recently involved in prostate cancer progression. We investigated EGFR and c-erbB-2 expression in primary androgen-dependent and in advanced androgen-independent prostate cancer and their potential role as markers of disease progression. EXPERIMENTAL DESIGN: EGFR and c-erbB-2 expression were evaluated by immunohistochemistry in a consecutive series of 74 prostate cancer patients with the following characteristics: 29 patients (group 1) treated with radical prostatectomy; 29 patients (group 2) treated with luteinizing hormone-releasing hormone analogues and antiandrogen therapy followed by radical prostatectomy; and 16 patients with hormone-refractory metastatic disease. In all patients we evaluated: association between EGFR and/or c-erbB-2 expression and clinicopathological parameters; and disease-free survival according to EGFR and c-erbB-2 expression in univariate analysis (Kaplan-Meier product-limit method) and in multivariate analysis (Cox proportional hazards regression model). RESULTS: EGFR expression was found in 12 of 29 (41.4%) group 1 patients, in 22 of 29 (75.9%) group 2 patients (P < 0.0005), and in 16 of 16 (100%) metastatic patients (P < 0.005), whereas c-erbB-2 expression was found in 11 of 29 (37.9%) group 1, in 10 of 29 (34.5%) group 2 patients, and in 9 of 16 (56.3%) metastatic patients. A significant association was found between EGFR expression and a high Gleason score (P < 0.01) and between EGFR expression and higher serum prostate-specific antigen values (P < 0.02) in all groups of patients. Among the 58 patients treated with radical prostatectomy, 23 of 34 EGFR-positive patients (67.6%) relapsed, whereas only 2 of 24 EGFR-negative patients (8.3%) relapsed (P < 0.00004). c-erbB-2 expression did not significantly correlate with disease relapse (P = 0.07). In a Cox multivariate analysis, the only parameter with an independent prognostic effect on disease-free survival was EGFR expression (relative hazard, 11.23; P = 0.0014). CONCLUSIONS: EGFR expression increases during the natural history of prostate cancer. Correlation with disease progression and hormone-refractory disease suggests that EGFR-targeted drugs could be of therapeutic relevance in prostate cancer.     

Open vs Laparoscopic Vertical Banded Gastroplasty: A case control study with 1-year follow-up

Background: Vertical Banded Gastroplasty (VBG) is one of the most common bariatric operations. It can be performed by open or laparoscopic methods. The purpose of this study was to analyze and compare the 1-year results of 40 patients who underwent laparoscopic (20) and open (20). Methods: The initial 20 patients undergoing LaparoscopicVBG and the initial 20 patients in whom an Open VBG were performed in our Institution were comparatively evaluated. Demography, surgical details, complications, and 1-year weight loss were analyzed. Results: Both groups were highly comparable in terms of age, sex and body mass index. Laparoscopic VBG was a more prolonged procedure (median 4 hr) than the open VBG (median 3 hr). On the other hand, hospital stay was significantly shorter in the laparoscopic procedure (median 10 days for the open and 6 days for the laparoscopic). One year weight loss and complications were similar in both groups. Conclusions: Laparoscopic VBG is a safe procedure for the treatment of morbid obesity. This initial series shows comparable results.     

Loosening and osteolysis with the press-fit condylar posterior-cruciate-substituting total knee replacement

BACKGROUND: Aseptic loosening and osteolysis are rarely associated with cemented posterior-cruciate-substituting total knee replacements. Consequently, there is a paucity of information on this topic. METHODS: After a mean follow-up interval of fifty-six months (range, thirty-seven to eighty-nine months), sixteen (2.9%) of 557 posterior-cruciate-substituting primary total knee replacements were revised by a single surgeon because of loosening and osteolysis. Clinical, radiographic, and retrieval analyses were conducted to determine the mechanism of loosening and to identify associated risk factors. RESULTS: All sixteen knees (fifteen patients) were rated as good or excellent at one year after the primary replacement, with mean clinical and functional Knee Society scores of 95 and 86 points, respectively. Nine of the fifteen patients who had a revision because of loosening and osteolysis had had a total knee arthroplasty on the contralateral side compared with only 18% of the patients who did not have a revision (p = 0.026). No evidence of transmission of substantial anteroposterior stresses from the posterior-cruciate-substituting mechanism was found. All twelve retrieved knee implants, however, had damage to the lateral and medial side walls of the polyethylene posterior-cruciate-substituting post. Damage to the inferior surface of the polyethylene inserts had a rotational pattern, with the axis of rotation in the medial compartment. Surface damage in a rotational pattern was also present on the superior and inferior surfaces of the titanium tibial base-plates. CONCLUSIONS: In the knees in our study, rotational forces were generated by impingement of the side walls of the intercondylar box on the polyethylene post. Such box-post impingement can occur throughout the range of motion. Rotational stresses are transmitted to the modular interfaces and to the metal-cement interfaces, resulting in loosening and osteolysis. A reduction in rotational constraint would be desirable. Patients with bilateral total knee replacement may be at increased risk for this type of loosening.     

Th1-like and Th2-like cytokines in patients undergoing open versus laparascopic cholecystectomy

The advantages of laparoscopic (LC versus, open cholecystectomy (OC) seems to be related to minimal invasive procedure and to the moderate inflammatory response. The aim of this study is to define the involvement of Th1 (IFN-gamma) and Th2 (IL-4, IL-6, IL-10, IL-13) cytokines production in vivo and in vitro in patients undergoing OC or LC. In 42 patients undergoing LC (n = 22) and OC (n = 20) Th1-like and Th2-like was evaluated before operation and at 6, 24 and 48 hours after operation for white blood cell counting and cytokines (IL-4, IL-6, IL-10, IL-13, IFN-gamma, TNF-alpha) in the sera and in the supernatants from circulating mononuclear cells stimulated with phytohemagglutinin or lipopolysaccharide. The acute phase response cytokine, IL-6, appeared significantly increased following OC than after LC. All other cytokines did not very significantly. In vitro data shows a reduction of IFN-gamma and increase in Th2-like cytokines in OC patients compared with the basal value. In LC subjects we observed an high production of IFN-gamma associated to an increase of Th2-like cytokines, like IL-10 and IL-13, even though IL-4 and IL-6 were unmodified. In contrast to OC, LC did not significantly affect immunocompetence, maintaining a moderate inflammatory response and an adequate balance between Th1 and Th2 cytokine. Furthermore, the strong activation of cells producing Th1-like cytokines in LC patients following mitogen activation indicated a consistent anti-microbial activity, that was not detectable in OC patients, that showed after activation only a Th2 response.