Effect of letrozole on the lipid profile in postmenopausal women with breast cancer.

Hormonal therapy plays a central role in the overall treatment of breast cancer. Aromatase inhibitors can inhibit the aromatase enzyme system resulting in a reduction of oestrogens. Letrozole is a non-steroidal aromatase inhibitor that effectively blocks aromatase activity without interfering with adrenal steroid biosynthesis. The drug can significantly reduce the levels of plasma oestrogens, which remain suppressed throughout the treatment. Data are scarce concerning the influence of these drugs on serum lipid levels. In the present study, we evaluated the effects of letrozole on the serum lipid profile in postmenopausal women with breast cancer. A total of 20 patients with breast cancer were treated with letrozole, 2.5 mg once daily. After an overnight fast, serum lipid parameters (total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, apolipoproteins A1, B and E and lipoprotein (a)) were measured before treatment and at 8 and 16 weeks afterwards. A significant increase in total cholesterol (P=0.05), LDL cholesterol (P<0.01) and apolipoprotein B levels (P=0.05) in the serum, as well as in the atherogenic risk ratios total cholesterol/HDL cholesterol (P<0.005) and LDL cholesterol/HDL cholesterol (P<0.005) was noticed after letrozole treatment. We conclude that letrozole administration in postmenopausal women with breast cancer has an unfavourable effect on the serum lipid profile.

Tamoxifen-induced severe hypertriglyceridemia and pancreatitis.

Tamoxifen exhibits favorable effects on the lipid and lipoprotein profile since it decreases the total and LDL cholesterol levels as well as the Lp(a) levels. Additionally, a small increase in serum triglycerides is commonly found after tamoxifen administration. However, severe hypertriglyceridemia which can sometimes be associated with life-threatening complications is occasionally noticed. Herein, we describe a patient who developed tamoxifen-induced severe hypertriglyceridemia and pancreatitis. An analysis of the underlying pathogenetic mechanisms as well as a review of the relevant literature is also provided.

Endobronchial metastases secondary to solid tumors: report of eight cases and review of the literature.

Endobronchial metastases (EBM) secondaries to extrapulmonary solid malignant tumors are rare. Breast, colon and renal adenocarcinomas are the most frequent tumors associated with EBM. Since 1990 we have treated eight patients with EBM secondary to renal adenocarcinoma (three cases), colon adenocarcinoma (two cases), gastric adenocarcinoma (one case), bladder carcinoma (one case) and basal cell carcinoma (one case). Endobronchial lesions were detected by bronchoscopy and their metastatic nature was confirmed histopathologically in all eight cases. We also conducted a review of EBM reporting studies published in English language. The median interval from the diagnosis of the primary tumour was 41 months. Symptoms and radiological findings were indistinguishable from those of primary lung cancer. Five patients were treated with external radiotherapy with symptomatic improvement while two patients had chemotherapy and one patient underwent surgical resection of the metastasis. Systemic treatment was used in six cases with no significant effect on EBM. Median survival after EBM diagnosis was 9 months with one patient surviving 3.5 years and two patients still alive at 1 year. In conclusion, EBM usually represent a late manifestation requiring differential diagnosis from a primary lung cancer. Local treatment may result in symptomatic improvement but prognosis is generally poor averaging 1-2 years in most series.

Serum soluble interleukin-2 receptors in epithelial ovarian cancer patients.

The levels of soluble interleukin-2 receptors (sIL-R2) were measured in the serum of 52 patients with epithelial ovarian carcinoma as well as in 25 age and sex-matched normal controls. The mean serum level of sIL-R2 was increased in 37 patients (71.2%). Comparison of these levels to those of normal controls showed a highly statistically significant difference (p < 0.001). Serum sIL-R2 levels were not related to histology, clinical stage or the presence of ascites (p = 0.58, p = 0.32 and p = 0.67, respectively), nor did they follow disease activity or response to chemotherapy. However, patients with higher pretreatment sIL-2R levels (more than 1200 U/ml) were found to have a longer survival (p < 0.02), possibly explained by the presence of activated lymphocytes and a better immune surveillance. We conclude that the serum level of sIL-R2: a) is elevated in ovarian cancer patients, b) has no relationship with histological subtypes, tumor burden or the presence of ascites, c) cannot serve as a valuable tumor marker for the monitoring of patient treatment, and d) has a prognostic value for survival.

Cutaneous lymphocytic vasculopathy in lymphoproliferative disorders--a paraneoplastic lymphocytic vasculitis of the skin.

In this report the histopathology and the natural history of cutaneous lymphocytic vasculopathy (lymphocytic vasculitis) in patients with lymphoproliferative diseases, is described. Between January 1986 and June 1992, 116 patients with non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemias (CLL) were followed. Among them 3 patients with NHL, one with angioimmunoblastic lymphadenopathy/lymphoma and 7 with CLL developed cutaneous vasculitic changes during the course of their disease (incidence of 9.5%). All patients had advanced stage disease. Lymphomas were of B-cell origin and either low or intermediate grade. The median time between the diagnosis of NHL or CLL and the appearance of skin manifestations was 18 months. Recurrent vasculitic changes involving exclusively the skin, was characterized by a (maculo)papular rash, most commonly found in the upper and lower extremities. Pruritus of varying intensity was present in 82% of the patients. In the biopsy, all had perivascular and/or vessel wall lymphocytic infiltration of the dermis with occasional red cell extravasation. Immunohistochemical staining revealed that these infiltrates were mainly composed of T-lymphocytes. We conclude, that cutaneous lymphocytic vasculopathy is a relatively common paraneoplastic skin manifestation in patients with lymphoproliferative diseases and histologically is characterized as lymphocytic vasculitis with (peri)vascular infiltration by non-malignant T lymphocytes.

Docetaxel (Taxotere), a novel taxoid, in the treatment of advanced colorectal carcinoma: an EORTC Early Clinical Trials Group Study.

Docetaxel (Taxotere), a new semisynthetic taxoid, is a potentially important chemotherapeutic agent for the treatment of cancer. Forty patients with bidimensionally measurable advanced adenocarcinoma of the colon were treated with docetaxel 100 mg m-2 every 3 weeks as a 1 h infusion without routine premedication. Thirty-nine patients were eligible: 23 males and 16 females. Median age was 60 years (range 41-75) and WHO performance status 1 (0-2). Prior adjuvant chemotherapy was performed in four patients and prior radiotherapy in nine patients. Bidimensionally measurable disease sites included: liver in 26 patients, lymph nodes and abdominal/peritoneal masses in 13, lung/mediastinal masses in ten and subcutaneous nodes in four. The median number of cycles given was 2 (range 1-15). Thirty-three patients were evaluable for response. One patient (3%) achieved a complete response and two (6%) (95% confidence limits 0-14%) a partial response. Side-effects were similar to those observed in other studies. Docetaxel, given at this dosage and schedule, has minimal activity in the treatment of colorectal carcinoma.

Primary lymphoma of the pericardium: report on a "cured" case and review of the literature.

This report describes a 62-year-old man with a primary diffuse, immunohistochemically proven B-cell lymphoma of large non-cleaved cell (centroblastic) type of the pericardium. The patient responded completely to systemic chemotherapy and remains free of disease 30 months after diagnosis. The use of non-cardiotoxic drugs in divided doses as initial treatment is emphasized. In addition, the authors reviewed the literature of the last decade regarding the management and outcome of patients with primary cardiac lymphomas.

A phase II trial of carboplatin and vindesine in patients with non-small cell lung cancer. A Hellenic Cooperative Oncology Group study.

In an effort to investigate a regimen less toxic and more convenient than cisplatin combinations, 50 patients with non-small cell lung cancer (NSCLC) were treated in a Phase II study with carboplatin and vindesine. Carboplatin 300 mg/m2 every 28 days and vindesine 3 mg/m2 every 2 weeks were administered on an outpatient basis. Eight patients had a partial response of their disease (16%, confidence limits 7-29%). Mean duration of response was 4.5+ months (1 +/- 8). Toxicity, mainly of grade I-II, was noticed in 4-28% of the patients. The most common side effect was mild to moderate leukopenia (28%). The combination of carboplatin and vindesine at the above doses was very well tolerated. Although the response rate was relatively low, the survival in this patient population was similar to other cisplatin-containing regimens.

Clear evidence that long-term, low-dose tamoxifen treatment can induce ocular toxicity. A prospective study of 63 patients.

The current study has prospectively investigated the incidence and course of ocular toxicity after low-dose tamoxifen treatment. Sixty-three patients with cancer who could be examined were analyzed. Tamoxifen was administered on a 20-mg daily dose. Median duration of treatment was 25 months. Median total tamoxifen dose was 14.4 gr. Four patients had retinopathy and/or keratopathy 10, 27, 31, and 35 months, respectively, after tamoxifen initiation (an incidence of 6.3%). Ophthalmologic findings consisted of decreased visual acuity, bilateral macular edema, yellow-white dots in the paramacular and fovea areas in all patients as well as corneal opacities in one patient. After tamoxifen withdrawal almost all ocular abnormalities were found to be reversible, except for the retinal opacities. This is the first prospective study in the literature indicating that even conventional low-dose tamoxifen treatment can induce ocular toxicity. In addition, the authors review and discuss the literature of the last decades.

Lymphoma in Sjogren's syndrome.

Sjogren's syndrome is an autoimmune disease with a known predisposition for lymphoma development. Eight of 120 patients with primary Sjogren's syndrome followed at the University of Ioannina over the past 7 years developed non-Hodgkin's lymphoma diagnosed according to the Kiel classification. The lymphomas differed by location and grading. Six were called low grade (immunocytoma) and two intermediate grade non-Hodgkin's lymphomas. Five of the immunocytomas involved the minor salivary or lacrimal glands. Immunoperoxidase staining for light chains revealed monoclonal populations. Two patients showed spontaneous regression not previously reported in Sjogren's syndrome. Thus, in Sjogren's syndrome, low grade non-Hodgkin's lymphomas and especially immunocytomas are the most common lymphomas. These lymphomas tend to evolve very slowly and may regress spontaneously. Given these facts, a conservative approach to treatment is indicated in those patients with only localized disease.

Serum-soluble interleukin-2 receptors in B-cell lymphoproliferative malignancies.

The levels of soluble interleukin-2 receptors (sIL-2R) were determined in the serum of 53 patients with B-cell lymphoproliferative malignancies, including 31 patients with non-Hodgkin lymphomas (NHL), 16 with chronic lymphocytic leukemia (CLL), and 6 with multiple myeloma. In addition, serum samples from 40 patients with various solid tumors as well as from 53 healthy individuals were used as controls. It was found that the mean serum levels of sIL-2R were significantly increased (P less than 0.001) in NHL (mean +/- standard error of the mean 2,327 +/- 320 units/ml) and CLL patients (2517 +/- 451 units/ml) as compared to normal controls (207 +/- 17 units/ml). No such difference was observed when the serum sIL-2R levels of patients with multiple myeloma or solid tumors were analyzed. Serum sIL-2R levels were closely related to the clinical stage, the presence of B-symptoms, and the disease activity of patients with NHL and CLL. In fact, response to chemotherapy was followed by marked decrease or normalization of sIL-2R levels, while in a number of patients sIL-2R values were even able to predict disease relapse. Finally, no association with histologic grade in NHL patients, could be demonstrated. We conclude that serum sIL-2R (1) are increased only in B-NHL and B-CLL but not in myeloma patients, (2) are related to the tumor burden, and (3) can serve as a valuable tumor marker for the monitoring of patients treatment.

Extraskeletal Ewing's sarcoma. Presentation of two cases and review of the literature.

We present here two cases of extraskeletal Ewing's sarcoma, the first in a 50-year-old female and the second in a 25-year-old male. We discuss the clinical picture, histopathology and therapeutic management. The literature is also reviewed, with major emphasis on the treatment of this rare disease.

High-dose epirubicin as a single agent in the treatment of patients with advanced breast cancer. A Hellenic Co-operative Oncology Group study.

Fifty-two women with advanced breast cancer were treated with 6 cycles of epirubicin. Even though the study was started with a dose schedule of 110 mg/m2 every 3 weeks, the average treatment interval was 26 days and the median weekly dose 78% of the protocol requirement. Forty-eight patients were evaluable for response; 3 achieved a complete remission which lasted for 17, 24 and 65 weeks, respectively, and 14 a partial remission. Median survival was 32 weeks. Toxicity included nausea/vomiting (68%), anemia (24%), leukopenia (37%), thrombocytopenia (8%), alopecia (81%), stomatitis (24%), diarrhea (14%), fever (19%) and fatigue (14%). Also 1 treatment-related death occurred and 2 cases of arrhythmia. Monotherapy with high doses of epirubicin has definite activity in advanced breast cancer and deserves further study in combination with hematopoietic growth factors which might allow a higher dose intensity.

Interdigitating Reticulum Cell Sarcoma Positive immunohistochemistry for HLA-DR and two other activation antigens, CD30(Ki-1) and CD25(IL2R).

This communication reports a case of the rare interdigitating reticulum cell (IDRC) sarcoma of lymph nodes in a 46-year-old man. Extensive immunophenotypic analysis on paraffin and frozen sections revealed positivity on the neoplastic cells for protein S-100 as well as for antigens CD1, HLA-DR, CD4, CD25 (IL2R) and CD30 (Ki-1). The simultaneous positivity for the three activation antigens CD30, HLA-DR, and IL2R, a phenomenon mostly described in H and S-R cells of Hodgkin's disease, is discussed in particular.

Monoclonal immunoglobulins and autoantibodies in lymphoid malignancies.

The presence of serum monoclonal or oligoclonal immunoglobulins (paraproteins) was investigated in 38 non-Hodgkin's lymphoma and chronic lymphocytic leukemia patients, 33 patients with solid tumors and 33 healthy individuals. Seventy two percent of non-Hodgkin's lymphoma and 31% of chronic lymphocytic leukemia patients had serum paraproteins, in contrast to 21% and 15% of solid tumor patients and normal controls respectively. There was no significant prevalence of a certain isotype or light chain in the non-Hodgkin's lymphoma, chronic lymphocytic leukemia and solid tumor groups. In the healthy individuals all bands were monoclonal of the IgG isotype. No correlation was found between histologic grading of lymphoid malignancy or disease stage and serum monoclonality. No serologic or histologic autoimmune features were demonstrated in non-Hodgkin's lymphoma and chronic lymphocytic leukemia patients. In addition, no correlation was found between serum autoantibody activity and mono- or oligoclonal immunoglobulins.

Neglected cases of papillary and follicular thyroid carcinoma. Occurrence of subcutaneous scalp metastases.

Three cases, two follicular and one of papillary thyroid carcinoma are reported. All three patients presented with subcutaneous cystic scalp metastases; they had a long-standing history of thyroid cancer, although two had never sought medical attention. We discuss this unusual clinical manifestation in patients with untreated well differentiated thyroid carcinoma.

A successfully treated case of multicentric angiofollicular hyperplasia with oral chemotherapy (Castleman's disease).

A case of angiofollicular lymph node hyperplasia of plasma cell type in a 60-year-old woman is reported. The patient presented with lymphadenopathy, splenomegaly, and fever. She responded dramatically to chlorambucil and corticosteroids and has remained free of disease for the last 30 months. The authors review and discuss the systemic cytotoxic treatment of this clinicopathologic entity.

[The natural course of primary Sjögren's syndrome (a clinical study)]. / Estestvennoe techenie pervichnogo sindroma Shegrena (klinicheskoe issledovanie).

In this work the authors analyzed the clinical course and diagnostic procedures of 104 patients with primary Sjogren's syndrome (pSS): 57 patients diagnosed and followed-up at Ioannina University and 47 similar patients treated at the National Institute of Health (USA). Both studies have shown that pSS is predominantly a female disease with a latent period of 6-8 yrs from the time of the first symptom to the time of final diagnosis. Although the syndrome begins almost exclusively with glandular manifestations (xerostomia, xerophthalmia or parotid gland enlargement), in a respectable percentage of patients it eventually progresses to extraglandular involvement. pSS can be potentially complicated by benign (pseudolymphoma) or malignant (lymphoma) lymphoproliferative disorders.