Huseyin Abali

Association of the ABCB1 3435C>T polymorphism with antiemetic efficacy of 5‐hydroxytryptamine type 3 antagonists

Resistance to antiemetic treatment with 5‐hydroxytryptamine type 3 (5‐HT3) receptor antagonists is still a major problem resulting in patient discomfort and poor compliance to chemotherapy. We hypothesized that clinical resistance to 5‐HT3 antagonists is associated with the single‐nucleotide polymorphism (3435C > T) in the gene that codes for the drug efflux transporter adenosine triphosphate–binding cassette subfamily B member 1 (ABCB1).

Old antihypertensives as novel antineoplastics: angiotensin-I-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists

Angiogenesis, cellular growth and invasion of a cancer cell are attractive targets for new treatment strategies of malignancies in recent years. The evidences are accumulating that ACE inhibitors and angiotensin II type 1 antagonists could be novel anti-angiogenic, anti-invasive, and even anti-growth agents against neoplastic tissues: The renin-angiotensin system promotes angiogenesis directly or indirectly and growth of neoplastic cell. Some tumors carry angiotensin II type 1 receptors. Angiotensin II antagonists and angiotensin-I-converting enzyme inhibitors have shown some anti-neoplastic actions. Angiotensin II receptor blocker losartan antagonises platelets, which are thought to modulate via vascular endothelial growth factor. They may even protect the patient from the major toxicity of chemotherapy and/or radiotherapy, myelotoxicity, enabling us to give higher doses and end up with higher success rate. We believe that these agents can be useful on clinical grounds and suggest their incorporation into clinical studies.

Disclosure of cancer diagnosis to patients and their relatives in Turkey: views of accompanying persons and influential factors in reaching those views.

Aims and Background In Turkey, it is a common belief that most family members of patients with cancer would not want them to be informed of a diagnosis of cancer. Our aim was to evaluate the attitudes and opinions of people accompanying cancer patients, regarding cancer diagnosis disclosure. Methods In a cross-sectional study 270 caregivers accompanying cancer patients during outpatient chemotherapy sessions were asked to fill in a questionnaire to determine their opinions regarding whether the diagnosis of cancer should be disclosed to the patients and their relatives or not. Timing of telling the diagnosis and from whom it should be learned were queried as well. Possible influential factors for the answers were analyzed with the chi-square test. Results Of the 270 accompanying persons, 130 (48.2%) said that the patients should be informed of the diagnosis, whereas a greater number (236, 87.4%) believed that the patients relatives should be informed. Being younger than 40 years old (P = 0.0005), being unmarried (P = 0.002), having a higher educational status (P = 0.0001) and having passed less than four months since the diagnosis (P = 0.005) positively affected opinions regarding telling the truth to the patient. Higher education (P = 0.012) and high monthly income (P = 0.002) positively affected opinions regarding disclosing a diagnosis of cancer to the patients relatives. Conclusion As a result, in a survey of caregivers’ points of view, more than half of the accompanying persons did not agree with disclosing a cancer diagnosis to patients, whereas the majority agreed with disclosing it to the relatives, and educational level seemed to be the major influential factor.

Which One Is Better: AIDS Related or HIV Associated?

TO THE EDITOR: We have read the article by Francois Boue et al on AIDS-related lymphoma. The authors stated that rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is a simple and effective schedule for HIV-associated lymphoma. The authors used the terms HIV-associated and AIDS-related interchangeably throughout their article. Although everybody who read it surely understood that they are more or less the same entity, it is crucial to use the most correct terminology for scientific communication, in our point of view. Which one defines malignancies developing in individuals infected with HIV better? We have some comments. Caused by HIV, AIDS is the profound immunodeficiency state characterized by opportunistic infections and Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical cancer—the AIDS-defining cancers. By definition, when they are diagnosed in a patient infected with CD4 count less than 200 cells/uL that patient has AIDS. Therefore, the term AIDS-related seems better suited for AIDS-defining cancers. However, non–AIDS-defining cancers do occur in individuals infected with HIV. Several population-based studies indicated that relative risks for such malignancies with the exception of anal cancer is minimally increased during the pre-AIDS period, meaning that HIV positivity does not substantially increase risk of malignancy before inducing AIDS. Therefore, the term AIDS related seems more correct for non–AIDS-defining cancers, as well. Furthermore, highly active antiretroviral therapy prevents immunodeficiency and decreased incidences of malignancies, but can not eradicate HIV. This observation means that AIDS is necessary for the development of most cancers. In conclusion, we kindly suggest that AIDS related be preferred over HIV associated when referring to all malignancies in individuals with HIV infection.

Metastasis to the breast from nonmammarian solid neoplasms: a report of five cases.

Primary breast carcinoma is the commonest neoplasm in women. Although rare, metastases of solid tumors from elsewhere to the breast may occur. Apart from cross-lymphatic metastasis from contralateral primary breast carcinoma, hematopoietic neoplasms occasionally involve the breast. As far as we know, less than 500 patients with secondary extramammary solid neoplasms involving the breasts have been reported in the English literature, of which malignant melanoma and lung tumors constitute the leading cause. Herein, five additional adult cases are reported and literature is reviewed. Two of the patients had primary rhabdomyosarcomas, two ovarian carcinomas, and one colon carcinoma. In one case with ovarian carcinoma, breast mass was the only manifestations of the disease relapse. All, except one with disseminated disease, had pathological diagnosis. Two of the patients died soon after the detection of breast metastasis. As a result, breast mass can be the first manifestation of relapse or part of a disseminated disease, and usually predicts poor survival.

Circulating and Local Bone Marrow Renin - angiotensin System in Leukemic Hematopoiesis: Preliminary Evidences

Abstract Until last the decade, the renin-angiotensin system (RAS) was considered as a circulating endocrine system. It is now known that there are local RASs in many tissues. It has also recently been hypothesized that there exists a local bone marrow (BM) RAS with paracrine/autocrine pathobiological functions. The aim of this study was to detect BM and peripheral blood levels of the essential RAS components in normal and leukemic hematopoiesis. Concentrations of renin and angiotensin-converting enzyme (ACE) were assayed in BM aspirates and in simultaneously drawn peripheral blood samples of 16 pre-chemotherapy leukemic and 10 post-treatment megaloblastic anemia patients with normal blood counts, as controls. In the leukemia group, the ACE concentration was found to be significantly higher in the BM (38±6.2 U/l) than in the peripheral blood (29.5±5.3 U/l), (p=0.029). In the leukemia group, although the BM renin concentration was higher than the peripheral blood levels (21.3±8.3 vs. 18.6±6.2 U/l), this difference was not statistically significant (p=0.196). In the control group, mean BM renin levels were insignificantly lower than in the peripheral blood (8.6±3 vs. 12.1±4.6 pg/ml) (p=0.059). In the leukemia group, serum ACE levels positively correlated with BM and peripheral blood blast percentages (p<0.05). Serum LDH level (p<0.01), BM blast (p<0.05) and peripheral blast percentages (p<0.01) were inversely correlated with serum potassium in the leukemia group. The results of this study can be considered as the preliminary evidence supporting the hypothesis of the presence of a local BM RAS. Further, molecular biologic and immunohistochemical studies are needed to shed light on this important subject. A better understanding of the interrelationships of RAS and hematopoiesis will bring new insights into the pathobiology and even novel therapies for such neoplastic diseases.

Metastatic granular cell tumor: A case report and review of the literature

To the EditorGranular cell tumors (GCT) are uncommon benigntumors. They may occur in various sites. The tongueand breast comprise the two most common loca-tions, while a lesion in the digestive and respiratorytracts is not unusual. Laryngeal involvement is fairlyuncommon and is present in approximately 10% ofall cases [1]. Malignant GCTs represent less than2% of all granular cell tumors [2]. As with theirbenign counterparts, malignant GCT have a wideanatomic distribution. However, they carry a poorprognosis, with recurrence and metastasis typicallywithin one year of diagnosis [3].We present a case of malignant granular celltumor arising from larynx, which has metastasizedto lungs and bones. We also conducted a search onthe MEDLINE database (National Library ofMedicine, Bethesda, MD) and identified 52 pre-viously reported cases of metastatic GCT whosesurvival data were reported. Basic characteristics ofthese cases together with ours are described in thefollowing sections. We also review the metastaticGCT in literature.Case ReportA 43-year-old woman was admitted to the hospitalfor long-standing cough and recent hemoptysis. Inher past history, she had undergone right verticallaryngectomy in another institution two years ago.The diagnosis was laryngeal GCT. Physicalexamination was unremarkable except for decreasedbreath sounds in the apex of the right lung. Chestx-ray revealed infiltration of right upper lung region.Computed tomography (CT) of the thorax showedmediastinal lymphadenopathies as well as a lesionthat partially obstructed the upper lobe bronchusand invaded the inferior vena cava. Bronchoscopyrevealed a bright, smooth and vascularized mass,obstructing the right upper lobe entrance. Punchbiopsy was performed. Histopathological examina-tion showed a GCT. The lesion appeared inoperabledue to the invasion of large vessels. Ultrasound andCT of the abdomen showed a giant hemangioma inthe right lobe of the liver. This finding was con-firmed by biopsy. Sixty Gy of external radiotherapywas administered to the pulmonary lesion.This intervention resulted in the palliation of he-moptysis, but the size of the lesion remained stable.As no other effective treatment modality wasavailable, a decision to administer chemotherapywas made. She received three cycles of cisplatinand fluorouracil. Toxicity was acceptable, however,the pulmonary lesion remained unchanged whilemultiple osteoblastic lesions appeared on directx-rays and radionuclide bone scan. Chemotherapywas discontinued, and she was given radiotherapy tothe right distal femur for pain palliation. Oraletoposide 50 mg/day was prescribed, but patientcould not tolerate and refused to use it after onlyten days of treatment.

Tropisetron, Ondansetron, and Granisetron for Control of Chemotherapy-Induced Emesis in Turkish Cancer Patients: A Comparison of Efficacy, Side-Effect Profile, and Cost

Background: Tropisetron, ondansetron, and granisetron are considered equally efficacious, supported by several international studies. However, there are interindividual variations in their metabolism that could affect efficacy. The clustering of such variations may change from one to another nation. Therefore, their equality must be validated in Turkish patients. The aim of this study was to compare their efficacies, side-effect profiles, and costs in the prophylaxis of emesis induced by moderate to high emetogenic chemotherapies. Methods: A total of 158 patients with a median age of 48 years, 115 (72.8 percent) female and 43 (27.2 percent) male, were included, respectively. Fifty-one, 61, and 46 patients were allocated to tropisetron (5 mg), ondansetron (8 mg), and granisetron (3 mg IV) in combination with 8 mg dexamethasone, which were continued 5 mg once a day, 8 mg b.i.d. and 1 mg b.i.d. PO for 5 days, respectively. Results: The complete response (CR) rates in the control of acute emesis were 80.4 percent with tropisetron, 72.1 percent with ondansetron, and 71.7 percent granisetron (p = 0.877). CR rates in delayed emesis (Days 2–5) were 68.6 percent, 68.9 percent, and 76.1 percent, respectively (p = 0.527). Rates of freedom from nausea in the same period were 37.3 percent, 35.9 percent, and 33.9 percent (p = 0.949). Nausea control rates, side-effect profile did not differ. However, headache seemed to be encountered higher (45.6 percent) in Turkish patients than others (3.9–9 percent). Tropisetron is the least expensive one (

Capecitabine and Cisplatin Combination Is an Active and Well-Tolerated Doublet in the Treatment of Metastatic Breast Carcinoma Patients Pretreated with Anthracycline and Taxanes

95.3 per cycle) according to current prices in Turkey. Conclusions: There were no differences among the 3 serotonin antagonists with respect to efficacy and frequency of side-effects in our patients. Tropisetron is the least expensive at current prices. The choice may be based on other parameters, such as ease of administration and patient preference.

Laryngeal Involvement of Rhabdomyosarcoma in an Adult.

Our aim was to evaluate the activity and toxicity of capecitabine and cisplatin (CapCisp) combination in anthracycline- and taxane-pretreated metastatic breast cancer patients. Thirty-three patients, 20–61 years of age (median 41), were included. They received Cap 2,000 mg/m2 on days 1–14 and Cisp 60 mg/m2 on day 1, repeated every 3 weeks. Twelve nonprogressive patients continued single-agent Cap therapy until progression or until intolerable toxicity after Cisp cessation. The disease control rate in 154 cycles was 81.8%: complete response 3.0% (n = 1), partial response 48.5% (n = 16) and stable disease 30.3% (n = 10). The median time to disease progression was 6.3 months (95% CI 3.8–8.8). The median overall survival was 11.5 months (95% CI 6.9–16.1). The only grade 3 toxicity was neutropenia, observed in 4 patients (12.1%). CapCisp has an encouraging anti-tumor activity with a low toxicity rate in anthracycline- and taxane-pretreated metastatic breast cancer patients.