Sabri Barutca

Oral Versus Intramuscular Cobalamin Treatment in Megaloblastic Anemia: A Single-Center, Prospective, Randomized, Open-Label Study

BACKGROUND Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost. OBJECTIVE This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency. METHODS This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection. RESULTS Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p.o. group, at days 30 and 90, all hematologic parameters changed significantly versus day 0 (mean hemoglobin levels increased [both P<0.001]; mean corpuscular volume decreased [both P<0.001]; mean white blood cell count increased [day 30, P<0.01; day 90, P<0.001]; and mean platelet count increased [both P<0.001]). The mean serum vitamin B12 concentration increased significantly from day 0 to 90 (P<0.001). These hematologic parameters and the recovery patterns were similar between the 2 groups. Neurologic findings included sensitive peripheral neuropathy in 9 patients (15.0%), alteration of cognitive function (loss of memory, impaired concentration) in 7 patients (11.7%), and loss of sense of vibration in 5 patients (8.3%). Neurologic improvement was detected in 7 of 9 patients (77.8%) in the p.o. group and 9 of 12 patients (75.0%) in the i.m. group at day 30. CONCLUSIONS In this study of patients with megaloblastic anemia due to cobalamin deficiency, p.o. cobalamin treatment was as effective as i.m. cobalamin treatment. P.o. treatment also was better tolerated and less expensive compared with IM treatment. However, because of the small sample size and the short term of this study, further long-term studies are needed to determine the efficacy of p.o. cobalamin treatment.

Biological subtypes of breast cancer: Prognostic and therapeutic implications.

Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient-tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors.

NF-KappaB expression correlates with apoptosis and angiogenesis in clear cell renal cell carcinoma tissues

BackgroundClear cell renal cell carcinoma (ccRCC) is the most frequently encountered tumor in the adult kidney. Many factors are known to take part in the development and progression of this tumor. Nuclear factor kappa B (NF-κB) is a family of the genes that includes five members acting in events such as inflammation and apoptosis. In this study, the role of NF-κB (p50 subunit) in ccRCC and its relation to angiogenesis and apoptosis were investigated.MethodsFormalin-fixed and paraffin embedded tissue blocks from 40 patients with ccRCC were studied. Expressions of NF-κB (p50), VEGF, EGFR, bc1-2 and p53 were detected immunohistochemically. The relationship of NF-κB with these markers and clinicopathological findings were evaluated.ResultsThe expression of NF-κB was detected in 35 (85%), VEGF in 37 (92.5%), EGFR in 38 (95%), bc1-2 in 33 (82.5%) and p53 in 13 (32.5%) of 40 ccRCC patients. Statistical analyses revealed a significant relation between NF-κB expression and VEGF (p = 0.001), EGFR (p = 0.004), bc1-2 (p = 0.010) and p53 (p = 0.037). There was no significant correlation between NF-κB and such parameters as tumor grade, stage, age and sex.ConclusionThe results of this study indicated that in ccRCC cases NF-κB was associated with markers of angiogenesis and apoptosis such as VEGF, EGFR, bc1-2 and p53. In addition, the results did not only suggest a close relationship between NF-κB and VEGF, EGFR, bc1-2 and p53 in ccRCC, but also indicate that NF-κB was a potential therapeutic target in the treatment of ccRCC resistant to chemotherapy.

Urinary Stone Disease in Diabetes Mellitus

Objective: Diabetes mellitus (DM) and urinary stone disease (USD) are common diseases in the community. The prevalence of USD has not previously been studied in DM patients. Material and Methods: We evaluated 286 diabetics and 111 age-matched controls by means of direct urinary system X-ray, ultrasonography and/or intravenous pyelography. We also examined the history, risk factors and clinical aspects of USD in DM patients. Results: The prevalence of USD (21% vs 8%; p r < r 0.05) and the rate of recurrence (2.1 r - r 2.2 vs 1.3 r - r 0.5 stones/case; p r < r 0.05) were higher in the diabetics compared to the controls. Family history and male gender were significant risk factors for the development of USD in the DM patients. Increased daily total fluid consumption was not preventive for USD in the DM patients, and the type of fluid consumed did not have an impact on the risk of USD. Alcohol consumption was a significant risk factor for the development USD in the DM patients (odds ratio 3.68; 95% confidence interval 1.29-10.45; p r < r 0.05). Crystaluria (10% vs 1%; p r < r 0.05) and positive urine culture (8% vs 1%; p r < r 0.05) were also more prominent in the diabetics compared to the controls. Conclusions: The results of this study suggest that DM is a risk factor for the development USD.

Biological characteristics of breast cancer at the primary tumour and the involved lymph nodes

Diminished oestrogen receptor (ER) expression in the involved axillary lymph nodes (ALN) in breast cancer compared with the primary tumour has been reported in previous studies. We have assessed a wider spectrum of tumour markers (ER, progesterone receptor (PgR), p53, Ki‐67 and HER‐2/neu) and compared extent and staining intensities at the primary tumour and the involved ALN on specimens of 22 cases with invasive ductal breast cancer. At the involved ALN, both the quantity of positive staining cells and the staining intensities for ER and PgR were decreased (p < 0.001 and p = 0.003, respectively). In contrast, the quantity of positive staining cells (p < 0.004) and the staining intensities for Ki‐67 were increased. The differences for HER‐2/neu and p53 staining at both sites were insignificant. The immunohistochemical staining properties of both the primary tumour and the ALN metastases showed no correlation with the number of involved ALN (p > 0.05). This study suggested that ALN metastasis might indicate a more unfavourable expression pattern of ER, PgR and Ki‐67 in invasive ductal breast cancer.

A new perspective on cardiotoxicity of 5-fluorouracil. A novel research tool 'cardiac ultrasonic integrated backscatter analysis' indicates transient, subclinical myocardial dysfunction due to high-dose leucovorin and infusional 5-fluorouracil regimen.

Background: The pathophysiology of 5-fluorouracil (5-FU) cardiotoxicity is still controversial. The objective of this study was to assess the influence of high-dose leucovorin and infusional 5-FU regimen (HDLV5FU) on cardiac tissues. Methods: We monitored 28 patients (median age 68 years) under HDLV5FU chemotherapy with complete blood counts, cardiac enzymes, C-reactive protein, coagulation tests, Holter electrocardiogram, and conventional echocardiography. Cardiac ultrasonic tissue characterization with integrated backscatter (IBS) analysis was performed in the 16 last enrolled patients. Results: The magnitude of both anterior and posterior cardiac IBS values significantly decreased at the 48th hour of treatment compared to both 0th hour and day 15 (p < 0.003). Cardiac IBS values on the 15th day were not different from the 0th hour. Clinical cardiotoxicity was not observed and other monitored parameters did not change significantly in any patient (p > 0.5 for all). Conclusion: Cardiac IBS analysis suggests that 5-FU might cause reversible subclinical myocardial dysfunction.

Topical Heparin: A Promising Agent for the Prevention of Tracheal Stenosis in Airway Surgery

BACKGROUND The protective effects of topical mitomycin-C (MMC) have been well documented for tracheal stenosis; however, to the best of our knowledge, the use of heparin as an anti-inflammatory agent to support wound healing in upper airway surgery was not studied before. The aim of this study was to investigate the efficacy of topical heparin for healing of tracheal re-implants in a rabbits model and its resultant histological changes compared with that of MMC. METHODS In a rabbit model (n = 21), an elliptically shaped portion of the anterior tracheal wall was excised (3-4 tracheal cartilages) under anesthesia and immersed in an isotonic saline solution containing 0.4 mg/mL (0.04%) MMC (n = 7), heparin (liquemine) 5000 U/mL (n = 7), or none (n = 7) for 2 min and then re-implanted. The follow-up period was 2 wk for all animals and then both the larynx and the trachea were excised for histological evaluation. Hematoxylin-eosin (H and E) staining was applied to the excised tissues for microscopic evaluation. RESULTS Compared with controls, the granulation tissue formation score in MMC group (P = 0.03), and epithelial regeneration and inflammation scores in heparin group (P = 0.032 and P = 0.022, respectively) were more favorable. The fibrosis index and tracheal lumen ratio values were also more favorable in both MMC (P = 0.019 and P = 0.0028, respectively) and heparin (P = 0.023 and P = 0.0021, respectively) groups compared with controls on the 15th d. CONCLUSIONS Topical heparin application may have favorable effects on healing of tracheal autografts in a rabbit model. We suggest that heparin therapy should be further researched for the prevention of tracheal stenosis in airway surgery.

Extravasation of paclitaxel into breast tissue from central catheter port.

Abstract. A 53-year-old woman with advanced-stage ovarian cancer experienced extravasation of paclitaxel into the breast tissue as a result of inappropriate needle insertion and/or dislodgement; it came from a central catheter port (CCP) that was found to be intact under radiological examination with contrast material. The breast became tender and oedematous with erythema, and local warming was observed within a few hours. The patient improved in the next few days during nonsteroidal anti-inflammatory medication and close observation, and the breast healed with thickened and darkened skin and central scarring in the 6th month of follow-up. To the best of our knowledge, extravasation into breast tissue is rare in the literature. Extravasation of vesicant drugs from CCP can cause tissue necrosis; it is therefore essential that ports be carefully assessed and used by experienced staff to lessen the likelihood of such an unpleasant complication.

Influence of high-dose leucovorin and 5-fluorouracil chemotherapy regimen on P wave duration and dispersion

Background:  Although 5‐fluorouracil (5‐FU)‐related cardiotoxicity is well known, atrial arrhythmia, as a potentially serious complication has not been studied in detail. The aim of this study was to determine the P max and Pd in the electrocardiograms (ECG) of patients receiving 5‐FU treatment.

Anti-Yo Antibody-mediated Paraneoplastic Cerebellar Degeneration in a Female Patient with Pleural Malignant Mesothelioma

Paraneoplastic cerebellar degeneration is a rare non-metastatic complication of malignancies. It presents with acute or subacute onset of ataxia, dysarthria and intention tremor. Paraneoplastic cerebellar degeneration is most commonly associated with malignancies of the ovary, breast and lung. The anti-Yo (anti-Purkinje cells) antibodies that specifically damage the Purkinje cells of the cerebellum are found in the serum and cerebrospinal fluid. Anti-Yo-related paraneoplastic cerebellar degeneration is most commonly found in women with gynecological and breast cancers, but it is reported in other malignancies. Patients with paraneoplastic syndromes most often present with neurologic symptoms before an underlying cancer is detected. We report a case of anti-Yo-related paraneoplastic cerebellar degeneration associated with pleural malignant mesothelioma in a 51-year-old female patient. She presented to our department with a 2-week history after the last chemotherapy of progressive dizziness related to head movement, nausea, vomiting, ataxia and unsteady gait. A western blot assay was negative for anti-Hu, anti-Ri, anti-Ma2, anti-CV2 and anti-amphiphysin paraneoplastic antibody markers but positive for anti-Yo. In conclusion, we report a case of paraneoplastic cerebellar degeneration in a patient with pleural malignant mesothelioma because of the rarity of this neurologic presentation after the diagnosis of malignant mesothelioma and of the association with anti-Yo antibodies.