Fatih Kose

Promising efficacy of sorafenib in a relapsed thymic carcinoma with C-KIT exon 11 deletion mutation

Advanced thymic carcinoma (TC) is a very aggressive disease. To date there are no established treatment options for the refractory and recurrent disease and only a few prospective trials have been conducted in patients with TC. Here we present a case of a relapsed TC patient, who, by using combination chemotherapy, showed a positive response to sorafenib with C-KIT exon 11 mutation.

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.

Squamous cell carcinoma of the renal pelvis

A 61-year-old patient presented with 2-month long left flank pain. The patient had history of pyelolithotomy 35 years previously. The CT scan results are shown in Fig. 1a for left nephrolithiasis with left grade 4 hydronephrosis, solid mass in the renal pelvis, and retroperitoneal lymphadenopathy. Histopathological examination revealed squamous cell carcinoma of the renal pelvis which had pathological stage pT3 (Fig. 1b, c). The patient was treated with platinum-based chemotherapy, after three cycles of treatment control CT scan showed progression of disease with liver metastasis. The patient had grave prognosis and died at the fifth month of diagnosis with disease progression. Sivaramakrishna et al. reported a case of a patient with squamous metaplasia identified at percutaneous nephrolithotomy. This patient was progressed to invasive overt renal pelvis squamous cell carcinoma (RSCC) in the 8 months after PCNL at the same location where squamous metaplasia was found [1]. The incidence of coexisting urinary stone was 87, 18, and 100% at different series [2–4]. The prognosis of RSCC was very poor, with a median survival of 3.5 months. Early metastatic spread was the main reason for this grave prognosis. Holmang et al. reported a clinical and histopathological review of 65 patients with RSCC and compared it to 743 patients with transitional cell carcinoma (TCC) [5]. They reported that RSCC were larger than TCC and macrohematuria was more common in patients with TCC than RSCC at the time of diagnosis. Interestingly, disease-specific survival of patients with the same stage RSCC and TCC was similar and there was no statistical difference. Unfortunately, most RSCC had pT3 or higher at diagnosis. Only 2–4% of RSCC had a stage of pT2 or lower at diagnosis, whereas 62% TCC had a stage of pT2 or lower at diagnosis. Our patient had pT3 with renal pelvis invasion and retroperitoneal lymph node involvement at CT scan, so he had stage 4 disease at the time of diagnosis. Surgical treatment may sometimes result in cure in low stage patients. Systemic chemotherapy seems to have marginal benefit [3]. The patient had taken 3 cycle of platinumbased chemotherapy without any benefit and died at the fifth month of diagnosis with disease progression. Therefore we should be more careful about the incidence of RSCC of the renal pelvis in patients with a long history of renal calculus.

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.

Procalcitonin as a biomarker for infection-related mortality in cancer patients.

PURPOSE OF REVIEW Infectious diseases are the second leading cause of death following direct cancer-related complications in the field of oncology. Clinical studies using the classic inflammatory biomarkers, C-reactive protein, erythrocyte sedimentation rate, leukocytosis, and thrombocytosis fail to show a significant correlation between these biomarkers and infection-related mortality. It is therefore crucial to define new biomarkers that are not affected by the primary cancer and precisely show the severity of the infection to help in the decision-making process. RECENT FINDINGS A significant increase in the number of cancer patients in the past decades has created an exponential increase in the number of immunocompromised patients. Preemptive and typically unnecessary usage of broad-spectrum antibiotics is common during the treatment of these patients and may result in an increase in multidrug-resistant microbial strains. Recent clinical studies suggest that a significant reduction in antibiotic consumption may be achieved by procalcitonin-guided algorithms without sacrificing the outcome of patients with severe infection. SUMMARY In this article, we focus on procalcitonin and its potential role in differentiating cancer and infection-induced inflammation. Using this strategy may significantly reduce the usage of empirical broad-spectrum antibiotics and result in earlier discharge of patients.

Little dose, huge toxicity: profound hematological toxicity of intrathecal methotrexate

A 60-year-old man presented with complaints of blurred vision and inability to raise the right eyelid 15 days after the last cycle of the planned six cycles R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone) for stage IV follicular lymphoma. Complete remission was confirmed after the fourth cycle by positron emission tomography. On physical examination, he had third and fourth cranial nerve palsies, whereas the remainder of the neurological examination was unremarkable. Magnetic resonance imaging of cranium and orbital region with gadolinium enhancement were normal. Upon detection of lymphocytic infiltration in the cerebrospinal fluid (CSF) by cytology, isolated leptomeningeal relapse of follicular lymphoma was diagnosed without any sign of systemic relapse. Treatment with intrathecal methotrexate 12.5 mg twice a week was planned. After the second dose of the intrathecal methotrexate, he developed a grade IV neutropenia, grade IV thrombocytopenia and grade IV oral mucositis. Intrathecal chemotherapy was then stopped. He also developed neutropenic fever and had to receive prolonged antibiotic administration. Intrathecal chemotherapy withmethotrexate, Ara-C, or both with or without hydrocortisone is considered the standard of care for prophylaxis and treatment of central nervous system (CNS) lymphoma [1]. Although, intrathecal methotrexate can cause some neurological complications [2,3], it is quite unusual to observe grade IV hematological toxicity. To the best of our knowledge, profound hematological toxicity has not been reported. Intrathecal methotrexate is not altered by metabolic processes in the CSF and it passes through the systemic circulation slowly via choroid plexus [4]. Its metabolism after intrathecal administration probably resembles the one in the presence of large volume of ascitis or pleural effusions where it is redistributed to the systemic circulation slowly. Even the small amounts at 10–15 mg of intrathecal methotrexate which pass to the systemic circulation can therefore cause the myelosuppression and other feared methotrexate complications. Bruce et al. [5] showed in pediatric patients that systemic methotrexate exposure can be greater after intrathecal than oral route. Our patient had none of the unfavorable factors that predispose for methotrexate toxicity such as renal insufficiency, third spacing of fluid in the body, anatomic abnormality of CSF flow or a history of using albumin bound drugs. In summary, one should be aware that intrathecal methotrexate administration may cause some unexpected toxicities. To our knowledge, this is the first case of profound hematological toxicity reported after intrathecal administration of methotrexate in the adult 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.

Primary extranodal non-Hodgkin's lymphoma: clinicopathological features, survival and treatment outcome in two cancer centers of southern Turkey.

BACKGROUND The aim of this study was to assess the epidemiological and clinicopathological characteristics of primary extranodal non-Hodgkins lymphoma (pENL) patients, focusing on treatment and survival outcome. MATERIALS AND METHODS Between October 2003 and March 2012, 802 patients with non-Hodgkins lymphoma (NHL) were diagnosed and treated in two different cancer centers of Southern Turkey. RESULTS pENL, constituted 12.4% (100/802) of all NHL studied during this period. Median age of the patients was 56 years (range 17-87 years) and the male: female distribution was 3:2. Eighty-five of 100 patients (85%) were in stage I/II, 9/100 (9%) in stage III, whereas 6/100 (6%) were in stage IV. Head and neck constituted the most common site (51/100, 51%), followed by gastrointestinal tract (GIL) (37/100, 37%), and cerebrum (CL) (5/100, 5%). Diffuse large B cell lymphoma (DLBCL) was the most common histological type, observed in 53% of patients, followed by marginal zone extranodal lymphoma (13%). Most of patients (76%) received a CHOP containing regimen. Complete remission (CR) were achieved in 71% of patients. The median follow-up duration of all patients was reported as 37.6 months (range, 0.8-165 months). This period was reported as 137.5 months (range, 117.5- 1578.6 months) in gastrointestinal lymphoma (GIL) patients, 119.0 months (range, 91.8-146.1 months) in head and neck lymphoma (HNL) patients, and 18.4 months (range, 12.6-24.1 months) in cerebral lymphoma (CL) patients. CONCLUSIONS Head and neck, and the gastrointestinal tract were the two most common extranodal sites observed. Histologically DLBC accounted for the majority of cases. Most patients were on earlier stages, had low-low intermediate IPI scores and had a favorable prognosis.

Can serial monitoring of serum Vascular Endothelial Growth Factor (VEGF), Nitric Oxide (NO), and Angiotensin II (ANGII) levels have predictive role during Bevacizumab treatment?

Background Standard treatment of colorectal cancer includes both cytostatic chemotherapy and targeted therapies. Bevacizumab, targeting the VEGF receptor, is one of the primary targeted therapies that achieve better response rate and survival rate as compared to combination chemotherapy. To the best of our knowledge, there is no established single marker that can be used as a predictive marker in bevacizumab therapy. Material/Methods We enrolled 24 patients with the diagnosis of metastatic colorectal cancer in our study. During the study, 2 blood samples were drawn from patients before the first cycle and after the sixth cycle of bevacizumab therapy. Serum levels of VEGF, ANG II, and NO were recorded. Results While the change across VEGF levels was found to be a statistically significant decreasing trend (p=0.009), this decrease was not found to be correlated with treatment response and hypertension development. Additionally, no statistically significant difference was found in terms of NO and ANG II levels. Conclusions This study showed a significant decrease in serum VEGF, but failed to show a significant change in NO and ANG II levels during bevacizumab treatment. Although no significant correlation was found between the presence of hypertension and markers, most patients (83%) had an increase in their blood pressure. Our results suggest that dynamic monitoring of NO and ANG II, along with VEGF, may not be useful as predictive markers for bevacizumab treatment in colorectal cancer.

Effectiveness of percutaneous metal stent placement in cholangiocarcinoma patients with midterm follow-up: Single center experience

PURPOSE Patients with advanced cholangiocarcinoma present with high rate of local complications. The primary aim of this study is to report clinical course of advanced cholangiocarcinoma patients those who were presented with biliary obstruction and treated with percutaneous biliary stenting. MATERIAL AND METHODS Patients with unresectable locally advanced or metastatic cholangiocarcinoma followed by our center for a period of 4 years were analyzed. For statistical analysis demographic and clinical characteristics of patients, primary biliary drainage method, metal stent occlusion rate, time to stent occlusion, and overall survival rates were recorded. RESULTS A total of 34 eligible patients were analyzed. 27 patients had metal stent placement. These 27 patients formed the basis of this study. Median overall survival (OS) was 6.0 months. After metal stent deployment bilurubin levels were normalized within a mean of 10 days. During the follow-up period, 13 patients were experienced metal stent occlusion. Median TtSO was 10 weeks. Cytotoxic chemotherapy was administered to 14 (52%) patients. Patients without stent dysfunction had significantly higher rate of chemotherapy exposure rate (p=0.021). Statistical analysis, however, failed to exhibit significant effect of stent dysfunction on OS. CONCLUSION In advanced cholangiocarcinoma, relief of bile duct obstruction is an important part of the initial patient management. This study therefore described the clinical value of percutaneous metal stent in cholangiocarcinoma patients and raises the question about patency of metal stent in cholangiocarcinoma whether we can expect success similar to the success achieved in pancreas carcinoma.