Hakan Sakalli

Impact of Helicobacter pylori on the clinical course of recurrent aphthous stomatitis

BACKGROUND Recurrent aphthous stomatitis is one of the most common lesions of oral mucosa. Helicobacter pylori is suggested as one of the etiological agents of recurrent aphthous stomatitis. Here, we conduct a study for evaluating the impact of H. pylori eradication on clinical course of recurrent aphthous stomatitis. METHODS Forty-six patients with minor aphthous lesions were enrolled. The number of RAS lesions at last 6 months and vitamin B(12) levels were recorded. All patients were detected for H. pylori with endoscopic biopsy. H. pylori was positive in 30 patients and negative in 16 patients. H. pylori-positive 30 patients received eradication therapy. Three months after therapy, patients were re-evaluated with urea breath test; 18 patients were negative (eradicated), and the remainders (12 patients) were positive (non-eradicated) for H. pylori. 6 months after eradication, vitamin B(12) levels and number of aphthous lesions at 6 months were recorded. RESULTS Vitamin B(12) levels were significantly increased in H. pylori-eradicated group (P = 0.001), whereas no significant change was found in non-eradicated group (P = 0.638). Mean number of aphthous lesions (per 6 months) of H. pylori-eradicated group was significantly decreased after eradication (P = 0.0001); in the non-eradicated group, no significant change was found (P = 0.677). In Hp-positive group, number of RAS lesions and vitamin B(12) levels were negatively correlated when evaluated both before and after eradication. CONCLUSIONS This study provides evidence to support the beneficial effect of H. pylori eradication in patients with recurrent aphthous stomatitis. The underlying mechanism might be the increase in vitamin B(12) levels after eradication.

The effect of HER2 expression on cisplatin-based chemotherapy in advanced non-small cell lung cancer patients

IntroductionThe prognostic value of HER2 expression in patients with advanced non-small cell lung cancer remains controversial. The relationship between HER2 expression, and platinum resistance and patient survival, was investigated.MethodsSeventy-three consecutive patients (median age, 61 years) with stage IIIB and IV non-small cell lung cancer, admitted between February 2004 and December 2006, were included in this study. Sixty-one patients received gemcitabine, given as two 1250 mg/m2 doses on days 1 and 8 and, cisplatin, given as a 75 mg/m2 dose on day 8. Twelve patients received vinorelbine, given as two 25 mg/m2 doses on day 1 and 8, and cisplatin, given as a 75 mg/m2 dose on day 1. Both treatment paradigms were repeated on a 21-day cycle. Tumor response was evaluated by comparing tumor size on computerized tomography scans before and after three cycles of chemotherapy. HER2 status was examined by immunohistochemical analysis of paraffin-embedded specimens.ResultsHER2 was positive in 21 of 73 patients (28.8%). Of the 21 patients with HER2 positivity, 13 (61.9%) responded to chemotherapy with either a complete response, partial remission, or evidence of stable disease. Of 52 HER2-negative patients, 48 (92.3%) exhibited a response to chemotherapy. The difference in response to therapy between HER2-positive and -negative patients was statistically significant (p = 0.003). The median overall survival duration for all patients was 13 months. Median overall survival time was 14 months for HER2-negative patients and 10 months for HER2-positive patients (log-rank p = 0.007).ConclusionNon-small cell lung cancer patients with high expression of HER2 exhibited resistance to cisplatin-based chemotherapies that are the standard treatment for this disease. Our results indicate that HER2 status may be a predictive and prognostic factor for cisplatin- based therapy response and disease survival.

Primary Renal Lymphoma: Report of Four Cases

Background: Although secondary renal involvement from systemic lymphoma is very frequent, primary renal lymphoma is a rare entity. It is characterized by aggressive histopathology, very early extra-renal infiltration and poor prognosis. Case Reports: Here, we report 4 cases of primary renal lymphoma presenting with unilateral renal masses, which after radiological and clinical examination were assumed to be renal cell carcinoma. 3 patients were diagnosed with Non-Hodgkin’s lymphoma by nephrectomy and one patient was diagnosed by open renal biopsy. Histopathological subtypes were diffuse large B cell lymphoma in 2 cases and non-Hodgkin’s lymphoma of small B cell type in the others. While 3 of the patients were treated with systemic chemotherapy, the fourth patient refused chemotherapy. 2 patients (no. 2 and 3) were still in complete remission and were followed regularly in the second and first year after diagnosis, respectively. Conclusions: Since it is difficult to diagnose primary renal lymphoma, most patients with this kind of tumor undergo radical nephrectomy, and diagnosis of primary renal lymphoma is delayed. The authors believe that both the delayed diagnosis due to anatomical difficulties and the histological aggressive characteristics of this disease are equally responsible for the poor outcome in the case of primary renal lymphoma.

Colon Adenocarcinoma and Solitary Tibia Metastasis: Rare Entity

IntroductionColorectal cancer is the third leading cause of cancer-related deaths in the world. Mostly, death occurs with complications of distant metastases.DiscussionEffective systemic chemotherapy regimen and resultant improved survival for patients are associated with an increased incidence of metastases at uncommon sites. Therefore, incidences of osseous metastases are rising at the last decade. Osseous metastases are mostly diffuse, along with visceral metastases.ConclusionMost common osseous metastatic sites are lumbal, sacral vertebrae, and pelvis region, probably because of colonic anatomical proximity to the paravertebral venous plexus. Herein, we report an uncommon case of isolated solitary tibia metastasis in the colorectal cancer patient and management of disease course.

Gemcitabine and cisplatin treatment of advanced-stage non-small-cell lung cancer in patients given cisplatin on day 8.

Aims and Background Gemcitabine and cisplatin treatment were administered to patients with advanced-stage, non-small-cell lung cancer. During phase II studies, the treatment is performed using a 28-day cycle, with gemcitabine administered on days 1, 8, and 15. Although it is advised that cisplatin not be administered on the first day, gemcitabine and cisplatin treatment is usually performed using a 21-day cycle, with gemcitabine administered on days 1 and 8, and cisplatin is given on the first day in most phase III studies. In contrast with previous phase III studies, cisplatin was administered on day 8 in our study. Dose density, drug toxicity, and efficacy were analyzed. Methods and Study Design Chemonaive patients with stage IIIB or stage IV non-small-cell lung cancer received gemcitabine (1250 mg/m2) on days 1 and 8 plus cisplatin (75 mg/m2) on day 8 every 3 weeks (1 cycle contained 2 applications). Results Sixty-seven patients received a total of 293 applications. Dose densities were 92.3% for gemcitabine and 93.9% for cisplatin. The types and rates of grade 3 and grade 4 hematologic toxicities were anemia (6%), granulocytopenia (46%), and thrombocytopenia (6%). Complete remission was seen in 2 patients (3%); partial remission was 40%, stable disease was 39%, and progression of disease, 10%. The median overall survival time was 13 months. The median progression-free survival time was 9.5 months. One-year survival rate was 54% and 2-year survival, 10.4%. Conclusions In this 21-day treatment regimen, overall survival was longer than 1 year and the 1-year survival rate was more than 50%. Both the severity and rate of observed thrombocytopenia in the study were very low. Other adverse effects in the current study were comparable to those reported in the literature.

Concurrent Chemoradiotherapy with Vinorelbine plus Split-Dose Cisplatin may be an Option in Inoperable Stage III Non-Small Cell Lung Cancer: A Single-Center Experience

Background Concurrent chemoradiotherapy is the current standard treatment for inoperable stage III non-small cell lung cancer (NSCLC). In this study we aimed to investigate the efficacy and toxicity of CCRT with split dose of cisplatin (30 mg/m2) and vinorelbine (20 mg/m2) in patients with inoperable stage III NSCLC followed in our oncology clinic. Material/Methods Medical records of 97 patients with inoperable stage III NSCLC treated with concurrent chemoradiotherapy with cisplatin-vinorelbine were retrospectively analyzed. Cisplatin (30 mg/m2) and vinorelbine (20 mg/m2) were administered on days 1, 8, 22, and 29 during radiotherapy. Two cycles of consolidation chemotherapy were given. All patient data, including pathological, clinical, radiological, biochemical, and hematological data, were assessed retrospectively using our database system. Results Our study included 97 unresectable stage III NSCLC patients who were treated with CCRT. Median age was 58 years old (range 39–75) and 87 (89.7%) of the patients were men. ECOG performance score was 0–1 in 93 patients (95.9%). Squamous histology, the most common histology, was diagnosed in 46 patients (47.4%). Median follow-up time was 23.8 months. Median progression-free survival (PFS) and median overall survival time (OS) were 10.3 months and 17.8 months, respectively. Objective response rate and clinical benefit rate were 75.3% and 83.5%, respectively. Distant and local relapse rate were 57.1% and 42.9%, respectively. Hematological and non-hematological grade 3–4 toxicities were seen in 13 (13.4%) and 16 (16.5%) patients, respectively. Six (6.1%) patients died due to toxicity. Conclusions The results of this study suggest that split-dose cisplatin may offer fewer grade III–IV toxicities without sacrificing efficacy and could be an option in patients with inoperable stage III NSCLC during CCRT. Similar to past studies, despite high response rate during CCRT, distant relapse is the major parameter that influences patient survival in long-term in NSCLC.

Serum cancer antigen 15-3 concentrations in patients with sickle cell disease

Cancer antigen (CA) 15-3, which is associated with breast carcinoma, is an epithelial mucin and a product of the MUC1 gene (MUC1) (Hayes et al, 1986). Elevated levels of CA 15-3 also occur in patients with benign conditions such as inflammatory disease (Colomer et al, 1989; Valerio Marzano et al, 1998). Sickle cell disease (SCD) is an inflammatory disorder characterised by chronic haemolysis, endothelial activation and vaso-occlusion (Hebbel et al, 2004). Recent evidence showed that MUC1 was also expressed in the haematopoietic lineages (Rughetti et al, 2003), which prompted us to examine the possible association of CA 15-3 with SCD. Fifty-one patients with homozygous SCD, 15 patients with previously treated active metastatic breast carcinoma, and 20 healthy volunteers, sex and age-matched, were enrolled in the study. The SCD patients were divided into two subgroups: individuals with painful vaso-occlusive crises (n 1⁄4 17) and those with steady-state disease (n 1⁄4 34). Patients with active infection, cirrhosis, severe organ dysfunction, cancer, pregnancy or fibrocystic breast disease were excluded from the study. All subjects provided informed consent. Serum CA 15-3 levels were measured with a microparticle immunoassay. Differences were analysed by the Student’s t-test, analysis of variance, and the chi-squared test for statistical analysis. Two patients with steady-state SCD had experienced a prior cerebrovascular event. No difference was found among patients with or without painful crisis with respect to transfusion requirement, bone necrosis, hepatomegaly, seropositivity for hepatitis B or hepatitis C virus or the median value of alanine aminotransferase, bilirubin or creatinine peak levels (P > 0Æ05). All patients had been pretreated with an avarage of three substances (usually hydroxycarbamide, zinc and folic acid). There was no difference between the groups regarding the treatment with hydroxycarbamide (P > 0Æ05). In both SCD groups and the metastatic breast cancer group, serum CA 15-3 concentrations were elevated when compared with controls (P < 0Æ001 for all). The subjects with metastatic breast cancer were found to have significantly higher serum CA 15-3 concentrations when compared with the patients with SCD (steady-state disease or painful crisis) (P < 0Æ001 for both). There was no difference between the serum CA 15-3 levels of the patients with SCD in steady state or painful crisis (P > 0Æ05) (Table I). Twenty-eight patients (82%) with steady-state SCD and 13 patients (76%) with SCD in painful crisis had CA 15-3 values >30 U/ml. This difference was not statistically significant (P > 0Æ05). When both groups of patients with SCD were compared with controls, the percentage of CA 15-3 levels ‡30 IU/l was significantly higher than patients with SCD (P < 0Æ001 for both). However, this percentage in the SCD groups was lower than patients with breast cancer (P < 0Æ001 for both) (Table I). Among the patients with SCD, serum CA 15-3 levels were not affected by the use of hydroxycarbamide. Possible explanations of our findings, based on the current literature are: (i) in the past two decades, it has been established that SCD is an inflammatory state with abnormal endothelial cell activation (Hebbel et al, 2004). Previous reports have shown that elevated CA 15-3 levels are associated with connective tissue diseases, such as systemic lupus erythematosus (SLE), and systemic sclerosis (Colomer et al, 1989; Valerio Marzano et al, 1998). One study showed that 7% of patients with SLE had serum CA 15-3 concentrations >40 U/ml (Colomer et al, 1989). Pathogenetic mechanisms that cause the elevation of CA 15-3 in patients with an inflammatory disease can also explain the elevation of CA 15-3 in both SCD groups in our study. (ii) In bone marrow differentiating cells, the increase in MUC1 expression

Prognostically Favorable Abdominal Breast Cancer Metastases with Stomach Involvement

Background: Abdominal metastases with stomach involvement are rare in breast cancer. The median diseasefree interval from the time of breast cancer diagnosis to gastric metastasis is usually very long. Treatment is generally palliative, and expected survival time is less than 1 year. Case Report: A 59-year-old woman with breast cancer developed diffuse abdominal metastases involving stomach, abdominal lymph nodes, and omentum 9 years after she underwent mastectomy and adjuvant chemotherapy. The histopathologic diagnosis found by stomach specimen examination was invasive lobular carcinoma, and the cells expressed high levels of estrogen and progesterone receptors. The abdominal metastases were treated with surgery, postoperative chemotherapy, and further hormonal therapy. This was successful, and the patient has been in remission for more than 3 years. Conclusion: Once the definitive diagnosis of breast cancer metastases to the abdomen including the stomach is established, treatment that targets systemic breast cancer must be initiated. Our patient’s extended survival time suggests that surgical treatment could be considered for selected patients.

Mevalonate kinase gene mutations and their clinical correlations in Behçet's disease

Genetics is suggested to play a role in the development of Behçets disease (BD). Shared phenotipic features requires an approach to differential diagnosis from periodic febrile syndromes. We planned to study for mevalonate kinase (MVK) as a candidate for a susceptibility gene for Behçets disease.

Doksorubisin Kardiyotoksisitesinin Sinyal Ortalamali Elektrokardiyografi İle Değerlendirilmesi

AMAC: Sinyal ortalamali elektrokardiyografi miyokardiyal hasarla oldukca iliskili olan gec potansiyeller olarak adlandirlan dusuk amplitudlu sinyalleri saptar. Bu calismadaki amacimiz, doksorubisinin miyokardiyal yan etkileri ile sinyal ortalamali elektrokardiyogram arasindaki potansiyel iliskiyi arastirmaktir. YONTEM: Doksorubisin iceren kemoterapi alan 48 hasta calismaya dahil edildi. Sinyal ortalamali elektrokardiyografi, 3 parametre kullanilarak olculdu: filtrelenmis QRS (fQRS), fQRS suresinin son 40 milisaniyesi boyunca saptanan voltajin karekoku (RMS40), fQRS in son 40 milisaniyesinden baslayarak 40μV altina dustukten sonraki gecen sure (HFLA40). Hastalarin ejeksiyon fraksiyonlari, ekokardiyografi ile olculdu. SONUCLAR: Ortalama yas 44 (27-70) yil idi. Ortalama kumulatif doksorubisin dozu 475.56±98.45 mg idi. Olculen sinyal ortalamali elektrokardiyografik parametrelerin ortalama sureleri soyleydi: fQRS:78.27±10.74 milisaniye, RMS40: 115.10±50.23 ve HFLA: 21.95±8.39 mikrovolt idi. Doksorubisin dozu ile fQRS arasinda pozitif korelasyon saptanirken (r=0.28, p=0.02), RMS40 arasinda negatif korelasyon mevcuttu (r=-.31,p=0.03). Doksorubisin dozu ile ejeksiyon fraksiyonlari arasinda korelasyon saptanmadi (r=.18, p=0.22). TARTIŞMA: Bulgularimiz, kumulatif doksorubisin dozlari ile fQRS ve RMS40 arasinda anlamli korelasyon oldugunu dusundurmektedir. Bu yuzden sinyal ortalamali elektrokardiyografik parametreler doksorubisin iceren tedaviler alan hastalarinin prognozunu belirlemede degerli olabilir.