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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.

Background: HER2 expression in the primary tumor and its lymph node metastases vary in gastric cancer, reflecting intratumoral heterogeneity. This finding also suggests that proliferation of a different clone in metastatic nodes is possible. In the current study, we aimed to determine the cause of discordance in HER-2 expression in the primary tumor and lymph node metastases for patients with gastric cancer., Materials and Methods: Eighty-one patients with gastric cancer who had undergone radical gastrectomy and were found to have lymph node metastasis upon pathological examination were included. Histopathological samples were obtained from biopsies obtained during patient gastrectomies and lymph node dissection. HER2 status was evaluated by both immunohistochemistry (IHC) and silver in situ hybridization (SISH)., Results: Sixty-four (79%) patients were SISH (-), while 17 (21%) were SISH (+) in the primary tumor. However, in metastatic lymph nodes, HER2 status was SISH positive in 5 (28.3%) of the 64 SISH (-) primary tumor specimens. One of the 17 SISH (+) primary tumors was SISH (-) in the metastatic lymph nodes. Thus, SISH results for HER2 in both primary tumors and lymph node metastases were comparable, showing a concordance of 92.5%. In total, six patients demonstrated discordance between the primary tumor and lymph node metastases. The prevalence of HER2 discordance was significantly higher for patients in the pN2 and N3 stages (p=0.007). Although discordant patients had worse survival rates than concordant patients, the differences were not significant (p>0.05)., Conclusions: Our study indicates that the frequency of concordance in HER2 status, as determined by IHC or SISH, is high in primary tumors and their corresponding lymph node metastases for patients with gastric cancer. If there is a discrepancy in HER2 status, its evaluation by both IHC and SISH may be useful for detecting patients who would benefit from trastuzumab, and it would therefore help guide decision-making processes in administering treatment.

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.

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: 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.

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.

Objectives: Multifocal/multicentric breast cancers have been comprehensively studied and their outcomes have been compared with unifocal tumors. We evaluated the impact of multifocality and multicentricity on the disease-free survival (DFS) and overall survival of breast cancer patients and tried to analyze the correlation between multifocality/multicentricity (M/M) and other prognostic factors., Material and Methods: Between 1994 and 2009, we analyzed retrospectively 697 breast cancer patients. Multicentric and multifocal breast cancer were defined as the presence of 2 or more invasive tumor foci within the different quadrants of the same breast or within a same quadrant of the breast, respectively. M/M and other prognostic factors were evaluated using univariate and multivariate analyses., Results: Multifocal/multicentric tumors were seen in 107 (15.4%) of the 697 breast cancer patients. pT and pN stage were related with the presence of multifocal/multicentric tumors. As tumor size increased and the number of axillary lymph nodes metastasis increased, the incidence of M/M increased significantly (P=0.003 vs. P=0.02, respectively). Overall, the median DFS time of patients with multifocal/multicentric tumors was significantly worse than that of the unifocal tumors (55 vs. 137 mo, P<0.001). Multivariate analysis showed that the presence of M/M was the most important prognostic factor for DFS (P=0.001, hazard ratio (HR): 0.33; 95% confidence interval (CI), 0.18-0.58), as were pN stage and extracapsular extension of the tumor (P=0.01, HR: 1.74; 95% CI, 1.13-2.69) (P=0.03, HR: 1.9; 95% CI, 1.04-3.47, respectively). M/M were not also statistically significant prognostic factors in breast cancer for overall survival (P=0.06)., Conclusions: M/M imparts an unfavorable prognosis on the DFS of breast cancer patients in comparison to unifocal tumors and the presence of multifocal/multicentric tumors were associated with advanced pT and pN stages.

Background and Purpose: To investigate the role of postoperative concomitant chemo-radioimmunotherapy in gastric adenocarcinoma patients., Patients and Methods: 59 patients, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m(2)/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m(2)/day 5-FU and 25 mg/m(2)/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7-112 months)., Results: Median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment., Conclusion: Although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care.

CA-125, a commonly used tumor marker for epithelial ovarian cancer, is a glycoprotein found in normal tissues derived from coelomic epithelia. Increased serum levels of CA-125 have also been found in nongynecologic tumors and nonmalignant diseases involving the peritoneum. A few recent studies and sporadic case reports have reported increased CA-125 levels in patients with non-Hodgkin's lymphoma (NHL). In our study, we aimed to evaluate the serum levels of CA-125 in patients with NHL and determine its potential role to show disease activity in NHL. Serum levels of CA-125 were measured in 61 patients with NHL and were found to be correlated with clinical stage, site of involvement, and disease activity.

Metastases to the breast are rare. Secondary breast involvement from an epithelial ovarian cancer heralds widespread dissemination and a very poor prognosis. We report an unusual case of a patient who had epithelial ovarian cancer and who showed signs of recurrence with inflammatory metastases to both breasts, 2 years after her diagnosis of ovarian cancer. She died within 3 months of breast involvement. Our case has unique features, with both bilateral breast metastases and also with its inflammatory pattern of metastasis, which is extremely rare.

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.

This study was undertaken to investigate a possible association of anticardiolipin antibodies (ACLAs) in cancer patients with thromboembolic events. Twenty-five patients with solid tumors complicated with acute thrombosis, 36 cancer patients without any thrombotic events, and a group of 20 healthy volunteers without thrombosis or malignancy were included. The mean age of the cancer patients with and without thrombosis and healthy subjects were 50 years (range 20-75), 45 years (range 23-66), and 40 years (range 20-68), respectively. Deep venous thrombosis (n = 16) and thrombosis of the central venous port-catheter systems (n = 9) were confirmed by Doppler sonography in all patients. IgG and IgM isotypes of ACLAs were quantitated by enzyme-linked immunosorbent assay with normal levels of < 23 GPL and < 11 MPL, respectively. Mean values of IgG ACLAs were found similar in cancer patients with acute thrombosis (13.8 +/- 4.9 GPL), without thrombosis (12.8 +/- 5.4 GPL) or in healthy subjects (14.8 +/- 5.5 GPL). Although the mean values of IgM ACLAs were within normal limits in all groups, cancer patients with thrombotic events had higher levels of IgM ACLAs (mean = 10.5 +/- 2.2 MPL) than cancer patients without thrombosis (mean = 4.6 +/- 2.4 MPL) (p = .01). Healthy subjects also had lower levels of IgM ACLAs (mean = 7.1 +/- 3.2 MPL) than cancer patients with thrombosis (p = .16). In addition, a higher percentage of cancer patients with or without thrombosis had IgM and IgG ACLA levels above normal limits compared with healthy controls. In conclusion, our study suggests an association between ACLAs or IgG and particularly IgM isotypes and venous thrombosis in malignancy. Identification of cancer patients who are at higher risk for developing thromboembolic events might lead to a better selection of patients for prophylactic anticoagulant therapy.

Anaphylactic reactions to platinum compounds and paclitaxel are well-recognized complications during their systemic administration. Although there have been reports describing anaphylaxis during intravesical instillation of chemotherapeutic agents, to the best of the authors' knowledge, no hypersensitivity reactions after intraperitoneal administration of chemotherapeutic drugs has been reported in the English literature. The authors report an unusual case of anaphylaxis occurring in a 33-year-old woman who has been treated with paclitaxel and cisplatin for ovarian cancer. She developed a hypersensitivity reaction during her ninth cycle of chemotherapy, immediately after institution of intraperitoneal infusion of cisplatin. It is important to be aware of the possibility of anaphylaxis during chemotherapy administration other than the systemic route so that appropriate premedication or effective treatment can be promptly instituted.

Bone marrow involvement is a frequent finding in malignant lymphoma. Bone marrow biopsy of the posterior iliac crest is routinely performed for staging. Abnormal magnetic resonance imaging (MRI) signals of bone marrow was also reported to be indicative of bone marrow involvement. This study included 60 patients with malignant lymphoma. Unilateral bone marrow biopsy of the posterior iliac crest was performed. MRI of lumbar spine was studied within 24 hours of bone marrow biopsy. 22 healthy controls were used for the detection of MRI objectivity during visual evaluation. In 83% of patients (50/60), biopsy and MRI results agreed completely. In two patients, histologic sections failed to show any evidence of bone marrow involvement despite abnormal MRI signals suggestive of involvement. In three patients, MRI was completely normal despite biopsy proven bone marrow infiltration. False negativity (3/60) and false positivity (2/60) rates were very low. Negative biopsy findings with positive or equivocal MRI results should not exclude bone marrow involvement and needs further evaluation with bilateral or guided biopsy. Thus, we conclude that MRI of bone marrow is a fairly sensitive, noninvasive modality and might be of potential value in detecting bone marrow infiltration in malignant lymphoid neoplasms which can be utilized as a useful adjunct to standard staging procedures.

The effects of different chemotherapy protocols on survival were evaluated in 197 small cell lung cancer patients followed-up between 1974 and 1987 in our unit. Of these, 170 patients had Stage IV disease and 24 had Stage III disease. Thoracic radiotherapy was given to 73 patients of whom 63 had Stage IV disease. Cytotoxic chemotherapy was given in four main protocols consisting of cyclophosphamide (CYC): CYC + vincristine (VCR); CYC + VCR + adriamycin (ADM) and CYC + VCR + ADM + lomustine (CCNU). The latter protocol was associated with the highest survival rates and differed significantly (p less than 0.05) from the others. In patients with extensive disease, both radiotherapy to the primary site and adjuvant immunomodulation in conjunction with the above chemotherapy regimens lacked any beneficial effect on survival.

The effect on long-term survival of immunomodulation adjuvant to various cytotoxic chemotherapy regimens in non-small cell lung cancer (NSCLC) was evaluated in 669 patients followed up between 1974 and 1987. Four hundred seventeen patients were treated only by cytotoxic chemotherapy and served as controls. Two hundred fifty-two patients received warfarin (W), levamisole (L) and tranexamic acid (T) for adjuvant immunomodulation. These drugs, especially when given in combination (W + L + T), led to a significant (p less than 0.05) enhancement of survival in patients with advanced NSCLC, independent of the cytotoxic regimen used.