Fazil Aydin

The efficacy of octreotide in the therapy of acute radiation-induced diarrhea: a randomized controlled study.

PURPOSE Although the somatostatin analog octreotide is currently used in the treatment of chemotherapy-induced diarrhea and secretory diarrhea associated with various disorders, its role in the management of radiation enteritis is not well defined. We performed a randomized study that compared octreotide acetate with diphenoxylate hydrochloride plus atropine sulfate, the drug commonly used as therapy for acute radiation-induced diarrhea (ARID). METHODS AND MATERIALS Sixty-one patients with Grade 2 (four to six stools per day) or Grade 3 (> or = seven stools per day, National Cancer Institute Common Toxicity Criteria) diarrhea associated with pelvic radiotherapy were assigned randomly to receive octreotide s.c., 100 microg three times daily (n = 33) or diphenoxylate and atropine orally, 2.5 mg four times daily (n = 28). Radiotherapy was delivered to all patients in a conventional manner, with high-energy photons in a total dose > or =45 Gy, which exceeds the tolerance of intestine. Overall, there was no significant difference in patient characteristics or radiotherapy applied between the two arms. Patients were evaluated daily for the primary study end point, resolution of diarrhea, as well as for interruption of pelvic radiotherapy. RESULTS Within 3 days, ARID completely resolved in 20 patients in the octreotide arm (2 within the first day, 11 within the second day, and 7 within the third day) vs. only 4 (all within the second day of therapy) in the diphenoxylate arm (p = 0.002). On the diphenoxylate arm, 15/28 patients were required to discontinue pelvic radiotherapy; on the octreotide arm, 6/33 patients were required to discontinue pelvic radiotherapy for an average of 1.89 +/- 0.5 and 0.45 +/- 0.2 days, respectively (p = 0.003). No side effects were observed in either arm. Three patients on the diphenoxylate arm and only 1 on the octreotide arm required further treatment for parenteral replenishment of fluids and electrolytes or other antidiarrheal treatments. CONCLUSION Octreotide seems to be more effective than conventional therapy with diphenoxylate and atropine in controlling ARID and eliminating the need for radiotherapy interruptions.

Correlation of serum IL-2, IL-6 and IL-10 levels with International Prognostic Index in patients with aggressive non-Hodgkin's lymphoma.

Cytokines play important roles in the pathogenesis of lymphomas. The aim of this study was to determine the relations between serum levels of interleukin-2 (IL-2), IL-6, and IL-10 and parameters of International Prognostic Index (IPI). Serum levels of IL-2, IL-6, and IL-10 were measured using a sensitive enzyme-linked immunosorbent assay in the pretreatment frozen sera from 43 patients with non-Hodgkin’s lymphoma. The patients we included in the study were divided into two groups, one with high risk and the other with low risk according to the IPI in regard to their ages, stages, performance status, extranodal involvements, and serum levels of lactate dehydrogenase. In the high-risk group, serum levels of IL-2 (0.852 ± 0.268 ng/ml), IL-6 (0.461 ± 0.206 ng/ml), and IL-10 (0.816 ± 0.240 ng/ml) were found to be higher than serum levels of IL-2 (0.667 ± 0.170 ng/ml), IL-6 (0.355 ± 0.075 ng/ml), and IL-10 (0.643+0.177 ng/ml) in the low-risk group (p < 0.05). There was a correlation between the patients with high risk according to the IPI criteria and high levels of serum cytokines (IL-2, IL-6, IL-10). Knowledge of the serum levels of these cytokines in patients with newly diagnosed aggressive non-Hodgkin’s lymphoma may help us to have some information about the possible prognosis, the activation of disease, and to decide on appropriate therapeutic approaches for individual patients.

Primary intraspinal primitive neuroectodermal tumor: case report of a tumor arising from the sacral spinal nerve root and review of the literature.

Primary spinal primitive neuroectodermal tumor (PNET) is a rare condition, 18 cases of which have been reported in the literature. In general, this tumor is treated with surgery followed by radiotherapy and chemotherapy, but prognosis is still poor. An 18-year-old female patient with an intradural, extramedullary mass at L3–L5 levels is presented in this report. This is the first female patient with primary spinal PNET at lumbar region, second patient with spinal nerve root origin, and third one with intradural, extramedullary localization ever reported in the literature. After surgery, she was treated with craniospinal radiotherapy and four cycles of combination chemotherapy regimen consisting of vincristine, cyclophosphamide, doxorubicin alternated with ifosfamide, and VP-16. Currently, she is asymptomatic and alive at 25 months. The histopathologic, radiologic, and clinical findings of the patient are presented and relevant literature is reviewed.

RADIATION THERAPY AND CONCURRENT FIXED DOSE AMIFOSTINE WITH ESCALATING DOSES OF TWICE-WEEKLY GEMCITABINE IN ADVANCED PANCREATIC CANCER

PURPOSE To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of twice-weekly gemcitabine (TW-G) when administered in conjunction with fixed dose amifostine (A) during external radiotherapy (RT) in patients with advanced pancreatic cancer. METHODS AND MATERIALS Ten patients with previously untreated, locally advanced, or asymptomatic-metastatic pancreatic adenocarcinoma were enrolled in this study. RT was delivered by using the standard four-field technique (1.8 Gy daily fractions, 45 Gy followed by a boost of 5.4 Gy, in 5-1/2 weeks). The starting dose of TW-G was 60 mg/m(2) (i.v., 30-min infusion), which is equal to the upper limit of previously reported MTD of TW-G when given without A during RT. A was given just before the TW-G, at a fixed dose of 340 mg/m(2) (i.v., rapid infusion). TW-G doses were escalated by 30-mg/m(2) increments in successive cohorts of 3 to 6 additional patients until DLT was observed. Toxicities were graded using the Radiation Therapy Oncology Group and National Cancer Institute Common Toxicity Criteria, version 2.0. RESULTS In general, therapy was well tolerated in patients treated at the first two dose levels of 60 mg/m(2) and 90 mg/m(2). The DLT of TW-G given in conjunction with A during RT were neutropenia, thrombocytopenia, and nausea/vomiting at the dose level of 120 mg/m(2). Of the 10 patients eligible for a median follow-up of 10 months, 5 remain alive; 1 complete responder, 3 partial responders, and 1 with stable disease. CONCLUSION A dose of TW-G at a level of 90 mg/m(2) produced tolerable toxicity and it may possess significant activity when delivered in conjunction with 340 mg/m(2) dose of A during RT of the upper abdomen. Due to the higher MTD of TW-G seen in our study, we consider that the A supplementation may optimize the therapeutic index of TW-G-based chemoradiotherapy protocols in patients with pancreatic carcinoma.

Thrombin activatable fibrinolysis inhibitor and thrombin-antithrombin-III-complex levels in patients with gastric cancer.

The relation between cancer and coagulation is the subject of investigation since a relation between tumor and thrombosis has been determined. Antithrombin III is an important thrombin inhibitor, and increased thrombin–antithrombin (TAT) complex levels activate coagulation. Activated thrombin activatable fibrinolysis inhibitor (TAFI) inhibits the conversion of plasminogen to plasmin. In addition, it directly inactivates plasmin. Defective fibrinolysis increases the risk of thrombosis. In this study, we evaluated homeostatic parameters, TAFI, and TAT levels in patients with gastric cancer applying to the medical oncology outpatient clinic. Fifty-two patients and 35 healthy controls were included. ELISA was used to measure TAFI and TAT complex levels. These were statistically higher in the patient group (p < 0.05 and p = 0.001, respectively). D-dimer levels were higher in stage IV (p = 0.05). Correlations between lymph nodes and TAFI and TAT levels were examined. Weak but positive correlation between lymph nodes and TAFI was detected (R = 0.452, p = 0.027). TAFI and TAT levels were evaluated using relative operating characteristic analysis to differentiate the disease. TAT was more specific than TAFI according to this analysis (TAFI area under curve (AUC), 0.676; TAT AUC, 0.874). Thrombotic events and bleeding disorders need to be borne in mind in gastric cancer. This situation is due to the impairment of the balance between coagulation and fibrinolysis. Further studies are now needed to evaluate the effects of TAFI and TAT on survey and prognosis as well as the potential of these parameters as tumor markers for gastric cancer.

Hemostatic and Fibrinolytic Response to Nasal Desmopressin in Hemodialysis Patients

Objective: To evaluate the effect of desmopressin (DDAVP) on hemostatic parameters during dialysis and in the interval between dialysis sessions. Subjects and Methods: Fifteen patients dialyzed twice weekly at least for 1 year and 15 healthy volunteers serving as a control group were enrolled in the study. Bleeding time, platelet count, prothrombin time, activated partial thromboplastin time, tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), euglobulin clot lysis time, protein C, protein S, fibrinogen, D-dimer, factor V, VII, VIII, IX, X and von Willebrand factor (VWF) values were studied at the beginning, at 2 and 4 h of dialysis with and without administration of DDAVP at a dose level of 2 µg/kg intranasally. Results: After dialysis, bleeding time shortened, PAI-1 and fibrinogen levels were lower, while VWF and D-dimer levels were higher. After DDAVP administration, bleeding time, PAI-1 levels were significantly lower (p < 0.01), while tPA, factor VIII and VWF levels increased significantly (p < 0.001). Conclusion: The findings indicate that DDAVP can be used for patients on dialysis with serious bleeding.

Hodgkin’s Disease and Autoimmune Hemolytic Anemia: A Case Report

Objective: To report a case of Hodgkin’s disease presenting with immune hemolytic anemia. Clinical Presentation and Intervention: A 47-year-old man was admitted to hospital because of weight loss, fever, and inguinal lymph node adenopathy. Biopsy of the inguinal lymph node revealed mixed-cellularity Hodgkin’s disease. Three days after starting combined chemotherapy, the patient showed evidence of autoimmune hemolytic anemia, which responded well to prednisolone. Conclusion: This case shows that clinicians should be aware of the possibility of autoimmune hemolytic anemia in patients with Hodgkin’s disease presenting with anemia, and distinguish it from the anemia of chronic disease.

Carcinoma Erysipelatoides Resulting from Gastric Adenocarcinoma: An Unusual Clinical Presentation

Objective: To report a rare case of carcinoma erysipelatoides on the laryngeal skin caused by stomach adenocarcinoma. Clinical Presentation and Intervention: A 48-year-old male, who had undergone a gastrectomy 18 months prior to admission for stage IIIA gastric adenocarcinoma, presented with a reddish induration of the cervical skin, lymphadenopathy in both supraclavicular areas and widespread subcutaneous nodules. Abdominal computerized tomography and chest radiography did not reveal any organ metastasis or peritoneal carcinomatosis. A biopsy of the induration revealed atypical epithelial cells with edema and dilatation of lymphatics. The patient was given combination chemotherapy of etoposide, adriamycin, and cisplatin, and significant improvement was observed over the cervical area after three courses. The patient tolerated the systemic chemotherapy well and has been followed for two months. Conclusion: We recommend combination chemotherapy in patients with cutaneous metastasis of gastric adenocarcinoma as a safe and effective treatment.

Effects of Dexamethasone, All-Trans Retinoic Acid, Vitamin D3 and Interferon-α on FO Myeloma Cells

Background: Since multiple myeloma responds poorly to conventional chemotherapy or radiotherapy, new therapeutic approaches are needed. This study investigated the effects of dexamethasone, all-trans retinoic acid (ATRA), the active metabolite of vitamin D3 [1,25(OH)2D3] and interferon-α on FO mouse myeloma cells (non-immunoglobulin-secreting myeloma cell line) in single drug or drug combination groups in vitro. Methods: Apoptosis ratio and change in cell counts in 4 single drug groups (dexamethasone, ATRA, vitamin D3 and interferon-α) and 6 combination drug groups (dexamethasone + vitamin D3, dexamethasone + ATRA, dexamethasone + interferon-α, vitamin D3 + ATRA, vitamin D3 + interferon-α, interferon-α + ATRA) were compared with the control group. Results: When treatment groups were compared with the control group, there was a significant increase in apoptosis in all, but this was most prominent in the group treated with dexamethasone alone. The apoptosis ratios were 0.10 and 6.82% in the control and dexamethasone-only groups, respectively. We also found that there was a significant decrease in cell count, particularly in the dexamethasone-only, ATRA-only, and ATRA-vitamin D3 combination groups. Conclusion: ATRA, interferon-α, vitaminD3 and particularly dexamethasone have significant effects on FO mouse myeloma cells resulting in a decreased cell count and an increased apoptosis ratio. This study should be repeated with human myeloma cell lines for further information.

Elevated Serum Levels of SCUBE1, a Marker for Coagulation, in Patients with Breast Cancer

Breast cancer (BC) is the most common cancer among women and a major cause of death. Signal Peptide-Cub-Epidermal growth factor domain-containing protein-1 (SCUBE1) is secreted under hypoxia and inflammatory conditions from platelet alpha granules. Its biological function is uncertain, although it may be a procoagulant substance in cancer patients. SCUBE1 is useful for identifying thrombotic diseases, including cancers and acute coronary syndromes. D-dimer reflects the relationship between coagulation activation and fibrinolysis; namely, thrombosis and D-dimer levels are closely linked. This is the first investigation of the potential diagnostic and prognostic value of SCUBE1 levels in patients with BC. Fifty patients and 33 age-matched and body mass index-matched healthy controls were enrolled. Blood samples were collected before chemotherapy regimens commenced. Serum SCUBE1 and D-dimer levels were measured before adjuvant chemotherapy and were compared to the healthy controls. SCUBE1 levels were determined using an enzyme-linked immunosorbent assay (ELISA) method. SCUBE1 and D-dimer levels were significantly higher in patients than in the controls (p = 0.03 and p < 0.001, respectively). A cut-off value of 1.55 ng/mL for SCUBE1 was associated with 62% sensitivity and 72.7% specificity and with positive predictive value of 77.5% and negative predictive value of 55.8%. Two patients with high SCUBE1 and D-dimer levels also developed pulmonary embolism. SCUBE1 may indicate hypercoagulability in patients with BC and thus help identify patients at greater risk of thrombosis and requiring anti-thrombosis treatment. SCUBE1 may also be used as an assistant test for identifying patients at risk of BC.