Saadettin Kilickap

Rituximab-related viral infections in lymphoma patients.

Recently, a human/mouse chimeric monoclonal antibody, rituximab, has been successfully used to treat cases of B-cell non-Hodgkins lymphoma and some autoimmune diseases. However, several viral infections related to rituximab have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 64 previously reported cases of serious viral infection after rituximab treatment. The median age of the cases was 61 years (range: 21 – 79). The median time period from the start of rituximab treatment to viral infection diagnosis was 5.0 months (range: 1 – 20). The most frequently experienced viral infections were hepatitis B virus (HBV) (39.1%, n = 25), cytomegalovirus infection (CMV) (23.4%, n = 15), varicella-zoster virus (VZV) (9.4%, n = 6), and others (28.1%, n = 18). Of the patients with HBV infections, 13 (52.0%) died due to hepatic failure. Among the 39 cases that had viral infections other than HBV, 13 died due to these specific infections. In this study, about 50% of the rituximab-related HBV infections resulted in death, whereas this was the case in only 33% of the cases with other infections. Close monitoring for viral infection, particularly HBV and CMV, in patients treated with rituximab should be recommended.

Platelet size has diagnostic predictive value for bone marrow metastasis in patients with solid tumors

Though not very common, solid tumor involvement of the bone marrow (BM) may have serious consequences. Recent studies have shown that mean platelet volume (MPV) is a good indicator for BM disease in the differential diagnosis of thrombocytopenia. We investigated the significance of MPV in the diagnosis of BM metastasis in patients with solid tumors. Patients with histologically‐verified solid tumors for whom BM biopsy specimens were available (n = 121) and healthy controls (n = 62) were included in this retrospective study. A total of 183 individuals were analyzed. Of the patients, 61 had a diagnosis of BM metastasis (Group A), 60 did not have BM metastasis (Group B). Group B and C (healthy controls) constituted the control group without BM metastasis (n = 122). The mean MPV was 7.0 ± 0.8 fl in patients with BM metastasis and 8.4 fl in the control group (P < 0.001). A cut‐off point of <7.4 fl was found to have significant predictive value according to receiver‐operating characteristics curve analysis. This cut‐off point had 85% positive predictive value and 90% negative predictive value in the diagnosis of BM metastasis (odds ratio: 53; 95% confidence interval: 20–135), and a sensitivity of 82.7% and specificity of 89.6%. MPV can be used as a reliable marker to guide the clinician as to the likely presence or absence of BM metastasis in patients with solid tumors.

Could the Neutrophil to Lymphocyte Ratio be a Poor Prognostic Factor for Non Small Cell Lung Cancers

BACKGROUND Although many prognostic factors have been identified for lung cancers, new ones are needed to determine the course of the disease. Recently, a high neutrophil to lymphocyte ratio (NLR) prior to surgery or treatment has been shown to be an indicator of prognosis for cancer. The aim of this study was to investigate the value of NLR as a prognostic factor and the correlation between NLR and other probable clinical prognostic factors in non small cell lung cancer patients prior to treatment. MATERIALS AND METHODS Data of patients who were diagnosed with non-small cell lung cancer in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR was calculated before the application of any treatment. RESULTS A total of 299 patients, 270 (90%) males and 29 (10%) females, were included in the study. Age (p<0.001) stage (p<0.001), Eastern Cooperative Oncology Group performance status (p<0.001), weight loss (p<0.001), anemia (p<0.001), histopatology (p<0.001), NLR ≥ 3 (p=0.048), NLR ≥ 4 (p=0.025) and NLR ≥ 5 (p=0.018) were found to be the prognostic factors. Age, anemia, Eastern Cooperative Oncology Group performance status, the stage, NLR (≥ 5) were an independent prognostic factors. There was a positive correlation between NLR and the Eastern Cooperative Oncology Group performance status (0.23, p=0.001), the C reactive protein levels (r=0.36, p<0.001). CONCLUSIONS Prior to treatment high NLR was found as an independent poor prognosis factor. Besides, NLR correlated with Eastern Cooperative Oncology Group performance status and the C reactive protein levels.

Characteristics of Breast Cancer Patients with Central Nervous System Metastases: A Single-Center Experience

The aim of this study was to assess the characteristics of breast cancer patients with central nervous system (CNS) metastases and factors associated with survival after development of CNS metastasis. One-hundred-forty-four patients with brain metastases were retrospectively analyzed. Median age at the time of brain metastasis diagnosis was 48.9. Median time between initial diagnosis and development of brain metastasis was 36 months. Fourteen cases had leptomeningeal involvement. Twenty-two patients (15.3%) had single metastasis. Ten percent of the patients had surgery, 94% had radiotherapy and 63% had chemotherapy. Median survival after development of brain metastasis was 7.4 months. Survival of patients with single metastasis was significantly longer than those with multiple metastases (33.5 vs. 6.5 months, p = 0.0006). Survival of patients who received chemotherapy was significantly longer than those who received radiotherapy alone (9.9 vs. 2 months, p < 0.0001). In multivariate Cox regression analyses, presence of single metastasis and application of chemotherapy were the only significant factors associated with better survival (p = 0.047 and p < 0.0001, respectively). Age at initial diagnosis or at the time of brain metastasis, time from initial diagnosis to development of brain metastasis, menopausal status, tumor stage, grade, hormone receptor or HER2 status individually were not associated with survival. In this study, survival after the diagnosis of CNS metastases appeared to be affected by patient characteristics rather than biologic characteristics of the tumor. This is probably secondary to the lack of effective treatment options in these patients and overall poor prognosis.

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.

Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C

Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well‐documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV(+) patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High‐risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co‐infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels.

Nonconvulsive Status Epilepticus Due to Ifosfamide

Objective: To report 2 cases of nonconvulsive status epilepticus (NCSE) following infusion of ifosfamide. Case Summaries: Two patients who received ifosfamide-containing chemotherapy developed NCSE. One woman received ifosfamide 1000 mg/m2 (1 h infusion on days 1–5); confusion, lethargy, and speech deterioration developed on day 3. The second patient developed similar symptoms on day 3 of treatment with 2500 mg/m2. Both patients responded to intravenous administration of diazepam 10 mg and were given levetiracetam as maintenance therapy. Discussion: The severity and presentation of central nervous system toxicity due to ifosfamide varies greatly and involves a spectrum ranging from subclinical electroencephalogram changes to coma. NCSE, an epileptic disorder in which typical convulsive activity is absent, has previously been reported in only 4 patients receiving ifosfamide. Levetiracetam may be used for maintenance antiepileptic therapy after diazepam administration. Conclusions: Among the many presentations of ifosfamide neurotoxicity, clinicians should consider NCSE as a possible explanation for changes in consciousness in a patient receiving this agent. An objective causality assessment by use of the Naranjo probability scale revealed that NCSE due to ifosfamide was probable.

Bone Metastasis from Gastric Cancer: The Incidence, Clinicopathological Features, and Influence on Survival

Purpose To evaluate the incidence, clinicopathological characteristics, treatment outcomes, prognostic factors, and survival of gastric cancer patients with bone metastases. Materials and Methods Of 4,617 gastric cancer patients who were treated between 2001 and 2013, 176 patients with bone metastases were analyzed. Results The incidence of bone metastasis was 3.8%. The most common histopathological subtype was adenocarcinoma (79%) with poor differentiation (60.8%). The median interval from the diagnosis to bone metastasis was 11 months. The median survival time after bone metastasis was 5.4 months. Factors that were associated with longer median survival times included the following: isolated bone metastasis (P=0.004), well-differentiated tumors (P=0.002), palliative chemotherapy (P=0.003), zoledronic acid treatment (P<0.001), no smoking history (P=0.007), and no metastatic gastric cancer at the time of diagnosis (P=0.01). On the other hand, high levels of lactate dehydrogenase (LDH) (hazard ratio [HR]: 1.86; P=0.015), carcinoembryonic antigen (CEA) (HR: 2.04; P=0.002), and carbohydrate antigen (CA) 19-9 (HR: 2.94; P<0.001) were associated with shorter survival times. In multivariate analysis, receiving zoledronic acid (P<0.001) and performance status (P=0.013) were independent prognostic factors. Conclusions Smoking history, poor performance status, poorly differentiated adenocarcinoma, and high levels of LDH, CEA, and CA 19-9 were shown to be poor prognostic factors, while receiving chemotherapy and zoledronic acid were associated with prolonged survival in gastric cancer patients with bone metastases.

A Novel Immunosuppressive Agent, Sirolimus, in the Treatment of Kaposi's Sarcoma in a Renal Transplant Recipient

Renal transplant recipients are susceptible to Kaposis sarcoma (KS) because of treatment with immunosuppressive drugs. Sirolimus, a new immunosuppressive agent, has been successfully used for immune-suppression in kidney transplant recipients. Several studies have shown the potential role of sirolimus to inhibit progression of KS in kidney-transplant recipients. This report details a kidney-transplant recipient with cutaneous KS who had a complete remission in response to sirolimus therapy.

Higher Ki67 Expression is Associates With Unfavorable Prognostic Factors and Shorter Survival in Breast Cancer

BACKGROUND The prognostic value of the Ki67 expression level is yet unclear in breast cancer. The aim of this study was to investigate the association between Ki67 expression levels and prognostic factors such as grade, Her2 and hormone receptor expression status in breast cancers. MATERIALS AND METHODS Clinical and pathological features of the patients with breast cancer were retreived from the hospital records. RESULTS In this study, 163 patients with breast cancer were analyzed, with a mean age of 53.4±12.2 years. Median Ki67 positivity was 20% and Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001), estrogen receptor (ER) negativity (p=0.035), Her2 positivity (p=0.001), advanced stage (p<0.001) and lymph node positivity (p<0.003) . Lower Ki67 levels were significantly associated with longer median relapse-free and overall survival compared to those of higher Ki67 levels. CONCLUSIONS High Ki67 expression is associated with ER negativity, Her2 positivity, higher grade and axillary lymph node involvement in breast cancers. The level of Ki67 expression is a prognostic factor predicting relapse-free and overall survival in breast cancer patients.