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Background/aims: The prognostic importance of perineural invasion (PN) in colorectal cancer (CRC) is unclear. The aim of this study to find out whether the PN was an independent stratification factor of postoperative relapse in curatively resected high-risk stage II & III CRC patients who were treated with adjuvant therapy., Methodology: Data of patients with high risk stage II & all stage III CRCs treated with adjuvant chemotherapy were retrospectively analyzed. Pathological features of final surgical specimen were noted. Disease-free survival was determined by Kaplan-Meier estimator, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test., Results: PN was found to be positive in 26% in the files of 593 eligible patients. In 21% of the reports PN status was not reported. Presence of PN in the resected primary tumors did not have independent effect on DFS. Further analyses for importance of PN on DFS of colon or rectal cancers did not show any effect., Conclusions: This study had failed to demonstrate any prognostic effect of PN for DFS in surgically resected stage II and III CRC patients who received adjuvant treatments.

In certain cell culture studies, significant CEA expression was observed in K-ras mutant cells. However, the relationship between high CEA levels and K-ras status has not been sufficiently investigated. In the present study, we aimed to determine the prognostic role of initial CEA and CA 19-9 values in metastatic colorectal cancer patients according to the status of K-ras. Between 2000 and 2010, a total of 215 patients with metastatic colorectal cancer who were treated and followed up in our oncology center were analyzed. Smokers were excluded from the study. The clinicopathological findings and initial CEA and CA19-9 values were determined. K-ras mutation analysis was performed using quantitative PCR evaluation of the DNA from the tumor tissues. Eighty-two patients (38.1 %) were female and 133 (61.9 %) were male, with a median age of 59 years (range 27-83). Based on tumor localization, 127 patients (59 %) were classified as colon cancer patients and 88 patients (41 %) were classified as rectal cancer patients. The majority of patients (83.3 %) had pure adenocarcinoma histology, while 36 cases (16.7 %) had mucinous adenocarcinoma. The initial CEA levels were detected to be high (>5 ng/mL) in 108 of the patients (50.2 %), while high levels of initial CA 19-9 (>37 ng/mL) were found in 90 patients (41.8 %). K-ras mutations were detected in 99 of the patients (46 %). K-ras was found to be wild type in 116 patients (54 %). Significant differences were detected between the K-ras wild-type and mutant groups with respect to age and the initial serum CEA levels. Patients with K-ras mutations were younger (p = 0.04) and had higher initial CEA levels (p = 0.02) compared to patients with K-ras wild type. The median overall survival (OS) time and 3-year OS rate for patients with a high initial CEA level (>5 ng/mL) were significantly shorter than those of patients with a low initial CEA level (<5 ng/mL) (50.5 months and 61.8 % vs. 78.6 months and 79.1 %, p = 0.014). Furthermore, the patients with low initial CA 19-9 levels (<37 ng/mL) had a significant better median OS interval and 3-year OS rate (76.1 months and 80.1 %) compared to patients with high initial CA 19-9 levels (>37 ng/mL) (37.6 months and 55.7 %, p = 0.04). Multivariate analysis indicated that stage at the time of diagnosis (p < 0.001) and low initial serum CEA level (p = 0.037) were independent prognostic factors of OS. For K-ras mutant patients, the stage at diagnosis (p = 0.017), low initial serum CEA level (p = 0.001), and low initial serum CA 19-9 level were found to be independent prognostic indicators of OS. Our findings demonstrate for the first time that the presence of a K-ras mutation correlated with high initial CEA and CA 19-9 levels in patients with metastatic colorectal cancer. Patients with high initial CEA and CA 19-9 levels may potentially predict the presence of a K-ras mutation, and this prediction may guide targeted therapies in these patients.

Aim: To evaluate the location, histopathology, stages, and treatment of gastric cancer and to conduct survival analysis on prognostic factors., Methods: Patients diagnosed with of stomach cancer in our clinic between 2000 and 2011, with follow-up or a treatment decision, were evaluated retrospectively. They were followed up by no treatment, adjuvant therapy, or metastatic therapy. We excluded from the study any patients whose laboratory records lacked the operating parameters. The type of surgery in patients diagnosed with gastric cancer was total gastrectomy, subtotal gastrectomy or palliative surgery. Patients with indications for adjuvant treatment were treated with adjuvant and/or radio-chemotherapy. Prognostic evaluation was made based on the parameters of the patient, tumor and treatment., Results: In this study, outpatient clinic records of patients with gastric cancer diagnosis were analyzed retrospectively. A total of 796 patients were evaluated (552 male, 244 female). The median age was 58 years (22-90 years). The median follow-up period was 12 mo (1-276 mo), and median survival time was 12 mo (11.5-12.4 mo). Increased T stage and N stage resulted in a decrease in survival. Other prognostic factors related to the disease were positive surgical margins, lymphovascular invasion, perineural invasion, cardio-esophageal settlement, and the levels of tumor markers in metastatic disease. No prognostic significance of the patient's age, sex or tumor histopathology was detected., Conclusion: The prognostic factors identified in all groups and the proposed treatments according to stage should be applied, and innovations in the new targeted therapies should be followed.

Background: This study was designed to examine changing trends in localization of gastric cancer in Turkey in recent years., Materials and Methods: A total of 796 adult patients with newly diagnosed, histologically proven adenocarcinomas, treated and followed up at our oncology center between 2000-2011, were examined retrospectively. In all cases tumor localization were identified and recorded with clinicopathological features., Results: The median age was 58 with a range between 22-90 for the 552 men and 244 women. Median follow up was 12 months (1-276) and median overall survival was also 12 months (11.5-12.4). There was a trend for a change in tumor localization from distal to proximal. Survival of patients was low with advanced T and N stage tumours. Positive surgical margins, lymphovascular invasion, perineural invasion, cardioesophageal localization were predisposition factors for metastatic disease in gastric cancer. There was no relation between age or sex and histopathological type of gastric cancer., Conclusions: There is a trend in our country for a change in gastric tumour localization from distal to proximal, with clear significance for treatment choices.

First described by Hirsch and Helwig in 1961, chondroid syringomas (CSs) are rare, benign tumors of the skin arising from the eccrine sweat glands with tumor differentiation in the epithelial and mesenchymal tissues. They most commonly occur in the head and neck, although they may be also found in the axilla, trunk, limbs, and genitalia. The incidence of CS is <0.01% of all primary skin tumors. Malingnant chondroid syringomas (MCS), which are also called malignant mixed tumors of the skin, are extremely uncommon. MCSs commonly involve the limbs and rarely head and neck. In this article, we present a case of malignant chondroid syringoma localized in the face at the left nasolabial region in the light of literature review.

Background: Primary aim of this study is to assess whether or not there is an increase at rate of HPV positive oropharyngeal cancers during 1996-2011 in Turkey, for comparison with prior reports from Western countries., Materials and Methods: A total of 138 newly diagnosed patients with oropharyngeal cancer were identified, 39 of which had no primary tumor specimen available and 18 patients with invalid HPV status, therefore HPV status for remaining 81 patients was evaluated. The presence and type of HPV DNA were determined with formalin- fixed paraffin embedded specimens, using an HPV DNA-based multiplex PCR assay. Associations between HPV status and clinicopathological characteristics were evaluated using a two-sample t-test for the continuous variables and the categorical variables were compared by chi-square test. Overall survival (OS) periods were calculated with Kaplan-Meier method., Results: The proportion of HPV-positive cancer has continued to increase during 2004-2011 as compared with 1996-2003. Notably, 33% (6/18) of the cases were HPV-positive in 1996-1999, 43% (9/21) in 2000-2003, 55% (11/20) in 2004-2007 and 70% (16/23) in 2008-2011. Thus, when we compared the results obtained during the 2004-2011with results of 1996-2003 period, we found that increase at HPV-positivity ratio was statistically significant (38% vs 64% p=0.012)., Conclusions: This study demonstrated that HPV positive oropharyngeal cancers are increasing in Turkish patients as in the Western world.

Purpose: Unlike cetuximab, there is a paucity of biomarkers for bevacizumab as predictors of outcome in metastatic colorectal cancer (mCRC) patients. Obviously exploring the worth of some potential markers in this setting is warranted. The purpose of this study was to investigate the predictive value of the presence of K-RAS and B-RAF mutations on the outcome of patients with mCRC treated with FOLFIRI and bevacizumab combination therapy., Methods: A total of 172 patients with mCRC were evaluated. K-RAS and B-RAF mutations were analyzed by quantitative PCR. Median progression-free survival (PFS) and overall survival (OS) were compared utilizing chi-square and Mann-Whitney U tests, respectively., Results: Forty-four percent (N=77) of the patients were found to harbor K-RAS mutations and 6 (7.5%) were positive for B-RAF mutations. In baseline no difference in PFS and OS was observed between the groups with or without K-RAS mutation. No relationship was established between K-RAS and B-RAF mutation status and baseline CEA and CA19-9 tumor markers levels., Conclusion: K-RAS and B-RAF mutations do not seem to be predictive of treatment outcome as potential biomarkers for bevacizumab therapy in mCRC. However, not only the presence of K-RAS and B-RAF mutations but also the different biological behavior of the various subtypes of mutations should be considered as potential determinants in the final outcome of this disease.

Background: Helicobacter pylori (H. pylori) is one of the risk factors for gastric cancer (GC). Any prognostic effect of HER-2 status in gastric lymph node metastasis in H. pylori positive cases is unknown., Materials and Methods: A total of 74 patients, 47 (64%) male, and 27 (34%) female, who had subtotal or total gastrectomy and also positive lymph nodes, were included in the study. Age range was 29-87 years, and median age was 58 years. HER-2 expression was assessed in both gastric resection samples and lymph node material with carcinoma metastasis of the same patient by immunohistochemistry (IHC) and silver in situ hybridization (SISH) methods. H. pylori status was examined in gastric materials of all patients. Relationships between HER-2 status in gastric cancers and lymph nodes and H. pylori status were investigated., Results: H. pylori was positive in 40 cases (54%), and negative in 34 (46%). While in the primary tissues of H. pylori positive cases, SISH positivity for HER-2 was observed in 13 cases (86%), SISH negativity was observed in 2 (14%), in metastatic lymph nodes 21 cases (72%) were SISH positive and 8 cases (28%) were SISH negative (P=0.005 and P=0.019, respectively). Initial CEA values were high in 18 cases (78%) with positive H. pylori and in 5 cases (22%) with negative H. pylori (P=0.009). While SISH data of patients were negative in 59 cases (80%) and positive in 15 cases (20%) in primary tissues, they were negative in 56 cases (75%) and positive in 18 cases (25%) in lymph nodes. Discrepancy between primary tissue and lymph node results was detected in 3 cases, in which SISH was negative in the primary tissue and HER-2 expression was positive in the lymph nodes., Conclusions: Clinical progression was poor in H. pylori positive cases with HER-2 negativity in primary gastric tissue, but HER-2 positivity in the lymph nodes. SISH positivity can be expected in H. pylori positive cases, and it may be predicted that these cases can benefit from trastuzumab treatment.

Background: We aimed to test the hypothesis that whether FDG-PET/CT which was ordered for various purposes can predict suspected or particularly unsuspected bone marrow metastasis (BMM) from the complete blood count and therefore can change the management of these patients., Methods: In this retrospective study, the study sample consisted of 68 subsequent patients presented to our institution's pathology department with bone marrow metastases of solid tumors. PET/CT was found to have been ordered in 10 out of 68 patients (6.8%) for various purposes. All patients gave informed consent about the PET/CT examinations and bone marrow biopsies., Result: FDG-PET/CT was ordered in 10 out of 68 solid tumor patients with pathologically proven BMM. Of these 10 patients, 3 were female and 7 were male; mean age was 54.7 years. While FDG PET/CT showed bone and BMM in 4 of 10 patients (40%), the rest of the patients had BMM without bone involvement. Five patients (50%) who had probable bone marrow involvement on their FDG PET/CT scans had unsuspected complete blood counts with regard to BMM., Conclusion: PET/CT has the ability to detect a substantial number of metabolically active tumor cells in the bone marrow in all of our patients which we proved by bone marrow biopsies. We think that this cohort of patients with solid tumors is hypothesis-generating with regard to detecting early bone marrow metastases by FDG PET/CT., Competing Interests: The authors have declared no conflicts of interest.

Introduction. Interferon is a glycoprotein produced by assigned cells of immune system. It has been used in many different diseases. Although flu-like syndrome, myalgia, rash, hypotension, thrombocytopenia and peripheral neuropathy due to interferon use are encountered frequently, ocular side effects are rare, generally mild and transient. Case Report. 47-year-old female patient, presented with a mass lesion in right renal pelvis. Right radical nephrectomy was applied and the histopathological examination was consistent with papillary renal cell carcinoma. Interferon alpha treatment was started subcutaneously at the dose of 5 MIU/3 times in a week. Four weeks after the interferon therapy, suddenly bilateral visual loss developed. We discussed the diagnosis, followup, and treatment of the patient who developed irreversible ischemic optic neuropathy and had no previous known primary systemic disease to cause this condition. Conclusion. We suggest that patients should be screened for risk factors causing optic ischemic neuropathy, before interferon therapy. Although there was no adequate information in the literature for the followup, patients should be monitorized before, 1 month after, and 2 months after the treatment. And if there is no complication, we suggest that they should be followed up at 3-month intervals.

Introduction: Carcinosarcoma is a rare malignant biphasic tumor which has sarcomatous and carcinomatous components. Stomach localization is very rare. We discuss the diagnosis, follow-up and treatment of patients diagnosed with gastric carcinosarcoma in company with the literature review., Presentation of Case: A 73-year-old white male patient applied to hospital with dyspeptic complaints lasting for 2months. His endoscopic examination revealed an ulcero-vegetating mass in the cardiac region of his stomach. Total gastrectomy and D2 lymph node dissection were performed for the patient. In the pathologic evaluation, the tumor was found consistent with Stage IIA stomach adenocarcinoma in accordance with AJCC (7edt, 2010) classification. Pathologic specimen was reevaluated by an expert pathologist for the patient with progression and liver metastasis under adjuvant chemotherapy and concomitant radiotherapy. The new pathology was consistent with gastric carcinosarcoma, and 90% of the tumor was identified as osteosarcoma whereas 10% was identified as carcinoma. Cisplatin doxorubicine-based chemotherapy was given considering the fact that sarcomatous component was dominant.(1) The patient was given 3 courses of chemotherapy. However, as the patient showed progression under therapy, he died after 14months of the diagnosis., Discussion: Gastric carcinosarcoma is a very rare and clinically aggressive malignancy. Recurrence is likely to occur with a rate of more than 50% in patients who have undergone resection within the first year following surgery, and overall survival time is 10-15months., Conclusion: In refractory gastric carcinoma cases with rapid progression, we suggest that gastric carcinosarcoma with biphasic component should be taken into consideration and the pathological evaluation should be performed by an expert pathologist., (Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Neuroendocrine tumors originate from neuroendocrine cells and occur in a wide spectrum from carcinoid tumors to small cell carcinomas. Although the World Health Organization determined clinical and histological features to predict prognosis for such tumors, they may not be valid on an individual basis. This study investigates the clinical, pathologic and prognostic characteristics of gastroenteropancreatic neuroendocrine tumors that presented to the Medical Oncology Outpatient Clinic, İstanbul University, Cerrahpaşa School of Medicine from 1995 to 2006 (n=86). The mean age of the patients was 52±14 and the male-to-female ratio was 0.87. The most common site of involvement was the stomach. Midgut intestinal tumors seemed to have significant female predominance compared to hindgut intestinal tumors (P=0.016). Most of the patients had metastatic disease with a prevalence of 34.9%. Poorly differentiated tumors and mixed neuroendocrine carcinomas were significantly larger than 2 cm (P=0.0001). The median survival was 139 months and the highest mortality was for colorectal tumors (36%). While univariate analysis revealed that the number of lymph nodes (P=0.008), multiple foci (P=0.034), metastases (P=0.022) and stage (P=0.034) correlated significantly with survival, there was no independent variable in the multivariate analysis. Hindgut tumors had significantly more Ki-67, mitosis and necrosis compared to others (P≤0.05). In this retrospective study, the clinical, pathologic and prognostic characteristics of gastroenteropancreatic tumors from a single center from Turkey were analyzed and compared with the current medical literature.

Family history and hepatitis B virus (HBV) infection have been identified as risk factors for hepatocellular carcinoma. We report hepatocellular carcinoma (HCC) diagnosed at the same time in identical twin brothers. Serological analyses of the patients showed that both were chronically infected with HBV. Molecular analyses of the tumor specimens confirmed loss of heterozygocity of the Rb gene region. Both of the patients were unresponsive to chemotherapy and died within the same month with an interval of I wk. With a review of the current literature, we discuss the role of HBV infection and genetic factors on hepatic carcinogenesis.

The first Phase I Trial with a combination of IL-2 and IFN-alpha was published in 1989. There are still some questions though, concerning the in vivo effects of this combination on lymphocytes. We designed a prospective pilot study to evaluate in vivo effects of low dose IL-2 and IFN-alpha combination on expression of Bcl-2, FAS (Apo-1/CD 95), Fas Ligand, IL-2 receptor (CD25), and HLA-DR on peripheral lymphocytes in patients with advanced renal cell carcinoma. After initiation of the immunomodulating therapy, Bcl-2 expressing lymphocytes increased significantly on day 3 (p < 0.025), Fas (Apo-1/CD95) expressing lymphocyte increased significantly on day 5 (p < 0.003), Fas ligand expressing lymphocytes increased significantly on day 3 (p < 0.004), HLA-DR expressing lymphocytes increased significantly on day 5 (p < 0.003), and IL-2 receptor (CD25) expressing cells increased significantly on day 5 (p < 0.01). We conclude that immunomodulating therapy induces in vivo expression of Bcl-2, Fas (Apo-1) and Fas Ligand in lymphocytes significantly.

Mitoxantrone (Novantrone, N) is a new anthracenedione derivative with structural similarities to doxorubicin (Adriamycin, A). It has shown significant activity during phase I and II clinical trials in the treatment of advanced breast cancer. The present trial compares the CNF regimen to CAF. All patients received cyclophosphamide (500 mg/m2) and 5-fluorouracil (500 mg/m2), with either N (10 mg/m2) or A (50-60 mg), repeated every three weeks. There were 30 patients in the mitoxantrone group and 30 patients in the doxorubicin group. The results presented are based on 60 patients: 70% were postmenopausal; 25% had received adjuvant chemotherapy; 29% had prior hormonal therapy in an adjuvant setting or for relapse. There were no significant differences between the pretreatment characteristics of each group. The response rate (complete + partial) for CNF was 57% and for CAF was 40%. The dose limiting toxicity was granulocytopenia seen after the 3rd cycle in the CNF group. Thrombocytopenia was not seen. There was less nausea and vomiting in the CNF group. No cardiotoxicity was seen in CNF; only 2 patients suffered from congestive heart failure in CAF. These preliminary data indicate that CNF seems to be an effective regimen for patients with advanced breast cancer and has fewer adverse effects than CAF.

Most previous studies of lymphocyte-mediated cytotoxicity to animal and human hepatocytes have not taken into account the ability to human lymphoid cells to kill spontaneously cultured cell lines, particularly those of malignant origin (the natural killer or NK effect). We have studied spontaneous killing to a human target (erythromyeloid cell line K562) in patients with biopsy-proven liver disease and from normal controls. Patients with chronic active hepatitis were shown to have a significant reduction in NK activity unrelated to immunosuppressive therapy (P less than 0.01). Other groups showed normal values. These results imply that cytotoxic effectors reported active in chronic liver disease are K cells and not NK cells, with which they share many characteristics, and suggest that a cytotoxic mechanism considered to be of importance in immunosurveillance may be reduced in chronic aggressive hepatitis.