Large Cell Neuroendocrine Carcinoma of the Ovary and Its Skin Metastases: A Case Report and Review of the Literature.

Large cell neuroendocrine carcinoma in the gynaecological organs affects the uterine cervix and ovary. Large cell neuroendocrine carcinoma of the ovary is extremely rare, and prognosis is quite poor even when diagnosed at an early stage. These tumours respond poorly to standard chemotherapy regimens. The clinical observation of skin metastasis in patients with epithelial ovarian cancer is relatively uncommon, occurring in only 3.5% of patients. These lesions are observed mostly in skin of the abdominal wall adjacent to the primary ovarian tumours. Metastatic skin lesions on extremities are much more rare; it is reported that only 12% of epithelial ovarian carcinoma skin metastases occur on the limbs. Skin metastasis due to large cell neuroendocrine carcinoma of the ovary has not been previously reported. We report the case of a large cell neuroendocrine tumour of the ovary with skin metastases on extremities appearing two months after surgery in a 68-year old woman.

Chemopreventive efficacies of rosiglitazone, fenretinide and their combination against rat mammary carcinogenesis

INTRODUCTION: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) and retinoic acid receptors (RAR/RXR) belong to the nuclear steroid receptor family. In vitro studies have suggested that PPAR-gamma ligands are highly effective in preventing mammary tumours and these effects are enhanced by some retinoids. However, in vivo anti-initiator and anti-promoter efficacies of this combination are not clear. AIM AND METHODS: The present study aimed to investigate the chemopreventive efficacies of the PPAR-gamma ligand rosiglitazone (200 microg/kg/day), synthetic retinoid fenretinide (0.3 mg/kg/day) and their combination on a DMBA-induced rat mammary carcinogenesis model. RESULTS: In the rosiglitazone group, no malignant tumour developed, apart from the lowest proliferative mammary lesions. In the fenretinide group, 30% developed a malignant tumour but there were no benign tumours. Cancer incidences were 61.5% and 10% in the control and combination groups respectively. CONCLUSIONS: Our results showed that the PPAR-gamma ligand rosiglitazone and synthetic retinoid fenretinide have potent chemopreventive properties against in vivo mammary carcinogenesis; however, the efficacies were not enhanced by their combination (AU)

A pilot study for human tumor/DNA banking: returned more questions than answers.

A pilot study was performed for setting up the Dokuz Eylül University Breast Tumor DNA Bank (DEUBTB) to facilitate the sharing of tumor DNA/RNA samples and related data from cases collected by collaborators specializing in the breast cancer diseases between 2004 and 2006. The pilot study aimed to provide answers for certain questions on: (1) ethical concerns (informing the volunteer for donating specimen, anonymizing the sample information, procedure on sample request), (2) obtaining and processing samples (technical issues, flowchart), (3) storing samples and their products (storing forms and conditions), (4) clinical database (which clinical data to store), (5) management organization (quality and quantity of personnel, flowchart for management relations), (6) financial issues (establishment and maintenance costs). When the bank had 64 samples, even though it is quite ready to supply samples for a research project, it revealed many questions on details that may be answered in more than one way, pointing that all biobanks need to be controlled by a higher degree of management party which develops and offers quality standards for these establishments.

Bax, bcl-2 and c-kit expression in non-small-cell lung cancer and their effects on prognosis.

In non-small-cell lung cancer (NSCLC), stage of the disease is still the most important prognostic factor. Other than stage, many biological markers and many other prognostic factors are studied to define their effects on prognosis of lung cancer. In this study, we aimed to evaluate the expressions of Bax and bcl-2 genes which are important in apoptosis and c-kit, which is a tyrosine kinase transmembrane receptor, as well as searched their response to treatment modalities and effects on survival. Sixty-nine NSCLC cases' pathological samples were stained with specific Bax, bcl-2 and c-kit dyes by immunohistochemical (IHC) methods. IHC evaluation was done by the semichantitative method according to the distribution and intensity of the staining. Twelve of 69 cases (17.4%) were stage I, 28 (40.5%) were stage II, 17 were (24.6%) stage IIIA, nine cases were (13.1%) stage IIIB and three cases (4.4%) were stage IV patients. Their histological subtypes were as follows: of 69 cases, 36 (52.2%) were squamous cell carcinoma, 28 (40.6%) were adenocarcinoma, five (7.2%) were adenosquamous cell carcinoma (two patients) and large-cell carcinoma (three patients). The positive immunostaining rates for Bax and bcl-2 in whole group, squamous cell carcinoma and adenocarcinoma groups were 40.6%/36.2%, 55.6/69.4% and 25.0/0.0%, respectively. The positive immune staining rates for c-kit in whole group, squamous cell carcinoma and adenocarcinoma groups were 7.2, 5.6 and 7.1%, respectively. We didn't find any correlation with Bax, bcl-2 and c-kit expressions and clinicopathological parameters such as age, tumour size, lymph node involvement, smoking, stage of the disease, response to radiotherapy and chemotherapy. Results are interpreted according to survival; bax and bcl-2 expressions were not so effective both in whole group and histologically subgrouped patients. C-kit expression was also found not related with survival in whole group whereas found as a bad prognostic factor in patients with squamous cell carcinoma. These findings could indicate that the expression of apoptotic pathway markers and c-kit may have a role in the prognosis of early stage NSCLC, especially with squamous cell carcinoma subtype.

Myelotoxicity of Cyclophosphamide, Methotrexate and 5-fluorouracil Regimen in the Early Stage Breast Cancer Patients with Diabetes Mellitus.

CMF (cyclophosphamide, methotrexate and 5-fluorouracil) is one of the most commonly used chemotherapy (CT) regimens in breast cancer. To the best of our knowledge there are no published studies on the toxicity of this regimen in the existence of diabetes mellitus (DM), in the literature. We retrospectively analyzed the myelotoxicity of CMF CT after 40 adjuvant cycles of 18 diabetics, according to WHO toxicity scala. Leucopenia/granulocytopenia was the most prominent toxicity (observed in overall 30% of the cycles), but it was relatively mild (5% grade III and 2.5% grade IV granulocytopenia). Anemia was only grade I (10% of the cycles), and there was no trombocytopenia. Two of the cases with grade III and IV granulocytopenia, had grade I and II urinary tract infections respectively, following the CT. The case with grade IV granulocytopenia and infection had received G-CSF. We conclude that CMF regimen is tolerable in DM as regard to its myelotoxicity. However, the patients should be closely monitored as infections may easily arise in parallel to deepening leucopenia in DM. Further extended studies would be appropriate on the toxicity of CMF as well as the other common CT regimens in DM.

Detection of bilateral multifocal breast cancer using Tc-99m sestamibi imaging. The role of delayed imaging.

PURPOSE: Early determination that breast cancer is bilateral and multifocal can change therapy strategy and, subsequently, mortality and morbidity rates. The authors present a case with bilateral, multifocal breast cancer detected only by Tc-99m sestamibi imaging. METHODS: Early and delayed Tc-99m sestamibi imaging and dynamic MRI were performed in a patient with a right-sided lesion shown on mammography. RESULTS: Although early Tc-99m sestamibi imaging detected bilateral breast cancer foci, both dynamic MRI and mammography missed the lesion in the left breast. Additional lesions seen on delayed Tc-99m sestamibi images of the left breast, which were initially thought to be benign, completely disappeared after concomitant chemotherapy and radiotherapy, suggesting multifocal malignant lesions in the left breast. CONCLUSION: This case suggests that Tc-99m sestamibi may be useful for detecting bilateral cancer, and delayed imaging may give additional information regarding the possible multifocal nature of the disease.

Flow cytometric analysis of circadian changes in platelet activation using anti-GMP-140 monoclonal antibody.

The hemostatic activity of blood shows a circadian variation with a higher frequency of acute coronary events in the morning. The thrombotic tendency of blood is influenced by many factors, including platelets. Diurnal changes of in vivo platelet activation were investigated by whole blood flow cytometry in 10 young healthy male volunteers using anti-GMP-140 (anti-alpha-granule membrane protein 140 kD) monoclonal antibody at 3h intervals from 06:00 to 24:00. We also studied circulating platelet aggregates to investigate whether there exists a similarity between the results of these methods. Results of flow cytometric analysis indicate that there is an increase in platelet activation during the period from 06:00 to 09:00. Platelet activation then decreases gradually during the period from noon to midnight. These changes are accompanied by a similar trend in circulating platelet aggregates. This suggests that GMP-140 expression on platelets is synchronized with or followed by platelet aggregate formation in vivo, and increased platelet activation may predispose individuals to thrombosis at this time.

Symptomatic hypocalcemia in a patient with latent hypoparathyroidism and breast carcinoma with bone metastasis following administration of pamidronate.

Pamidronate is an effective drug used not only in patients with tumor-associated hypercalcemia, but also in normocalcemic patients with metastatic bone disease to relieve pains. We describe a 39-year-old normocalcemic patient with subclinical hypoparathyroidism and bone metastasis due to breast carcinoma. Following parenteral administration of 60 mg pamidronate, the corrected serum level of calcium decreased from 2.12 mmol/l (=8.9 mg/dl) to 1.42 mmol/l (5.7 mg/dl), accompanied with carpal pedal spasm. The present case indicates that the hypocalcemia due to latent hypoparathyroidism was compensated by extensive osteolysis due to bone metastasis, and that overt hypocalcemia may develop after intravenous administration of pamidronate in such a patient.

CD44 expression in metastatic and non-metastatic non-small cell lung cancers.

CD44 is an integral membrane glycoprotein that functions as a receptor for the extracellular matrix glycan, hyaluronan. It exists as standard (CD44s) and variant (CD44v) isoforms which have been shown to be associated with metastasis in a range of tumors. Both CD44s and CD44v are found in normal respiratory epithelium and in non small cell lung cancers (NSCLCs). However, there isn't much information regarding their role in the metastatic process of NSCLCs. We examined the expression of CD44s in 30 NSCLCs using immunohistochemical techniques. Ten were non-metastatic (N0, M0), 5 were metastases to lymph nodes (N1, M0) and 15 were excised brain metastases. We found CD44s positivity in all non-metastatic tumors with varying degrees of expression, whereas 10 out of 15 metastatic tumors in brain and 3 out of 5 lymph node metastases were negative for CD44s. There was a statistically significant inverse relation between the CD44s expression and metastatic potential (P < 0.05). Our results support the hypothesis that diminished or lack of CD44s is the functional equivalent of CD44v which may be an accompaniment of enhanced metastatic potential. The value of CD44 in predicting metastatic behavior of NSCLCs remains to be established in a larger series.

Paraneoplastic cerebellar degeneration in association with Hodgkin's disease: a report of two cases.

Two patients with paraneoplastic cerebellar degeneration accompanying Hodgkin's disease were treated with plasma exchange in combination with chemotherapy or radiation therapy, respectively. Significant improvement in neurologic symptoms was obtained in 1 of them.