Biological Subtypes and Distant Relapse Pattern in Breast Cancer Patients After Curative Surgery (Study of Anatolian Society of Medical Oncology).

PURPOSE: The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergone curative surgery. METHODS: We retrospectively evaluated 1,350 breast cancer patients with relapses after curative surgery between 1998 and 2012 from referral centers in Turkey. Patients were divided into 4 biological subtypes according to immunohistochemistry and grade: triple negative, HER2 overexpressing, luminal A and luminal B. RESULTS: The percentages of patients with luminal A, luminal B, HER2-overexpressing, and triple-negative breast cancer were 32.9% (n = 444), 34.9% (n = 471), 12.0% (n = 162), and 20.2% (n = 273), respectively. The distribution of metastases differed among the subgroups: bone (66.2% and 53.9% in luminal A and B vs. 38.9% in HER2-overexpressing and 45.1% in triple negative, p < 0.001), liver (40.1% in HER2-overexpressing vs. 24.5% in luminal A, 33.5% in luminal B, and 27.5% in triple negative, p < 0.001), lung (41.4% in triple negative and 35.2% in HER2-overexpressing vs. 30.2% and 30.6% in luminal A and B, p = 0.008) and brain (25.3% in HER2-overexpressing and 23.1% in triple negative vs. 10.1% and 15.1% in luminal A and B, p < 0.001). CONCLUSIONS: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer should be considered.

Efficacy and tolerability of weekly docetaxel, cisplatin, and 5-fluorouracil for locally advanced or metastatic gastric cancer patients with ECOG performance scores of 1 and 2.

BACKGROUND: Docetaxel, cisplatin, 5-fluorouracil (DCF) given every three weeks is an effective, but palliative regimen and significantly toxic especially in patients who have a low performance score. Here, we aimed to evaluate the efficacy and tolerability of a weekly formulation of DCF in locally advanced and metastatic gastric cancer patients. MATERIALS AND METHODS: 64 gastric cancer patients (13 locally advanced and 51 metastatic) whose ECOG (Eastern Cooperative Oncology Group) performance status (PS) was 1-2 and who were treated with at least two cycles of weekly DCF protocol as first-line treatment were included retrospectively. The weekly DCF protocol included 25mg/m2 docetaxel, 25mg/m2 cisplatin, and 24 hours infusion of 750mg/m2 5-fluorouracil, repeated every week. Disease and patient characteristics, prognostic factors, treatment response, grade 3-4 toxicity related to treatment, progression free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Of the patients, 41 were male and 23 were female; the median age was 63 (29-82) years. Forty-one patients were ECOG-1 and 23 were ECOG-2. Of the total, 81.2% received at least three cycles of chemotherapy. Partial response was observed in 28.1% and stabilization in 29.7%. Overall, the disease was controlled in 57.8% whereas progression was noted in 42.2%. The median time to progression was 4 months (95%CI, 2.8-5.2 months) and median overall survival was 12 months (95%CI, 9.2-14.8 months). The evaluation of patients for grade 3-4 toxicity revealed that 10.9% had anemia, 7.8% had thrombocytopenia and 10.9% had neutropenia. Non-hematologic toxicity included renal toxicity (7.8%) and thrombosis (1.6%). CONCLUSIONS: In patients with locally advanced or metastatic gastric cancer who were not candidates for DCF administered every-3-weeks, a weekly formulation of DCF demonstrated modest activity with minimal hematologic toxicity, suggesting that weekly DCF is a reasonable treatment option for such patients.

Investigation of ErbB-2 overexpression on patients with gastric cancer in Eastern Anatolia of Turkey.

BACKGROUND/AIMS: In the present study, the frequency of ErbB-2 overexpression and its relationship with pathologic parameters on patients with gastric cancer in Eastern Anatolia of Turkey was studied. MATERIALS AND METHODS: A total of 32 newly diagnosed patients were enrolled in the study. DNA isolation was performed on paraffinized tumor tissues obtained from patients by endoscopy or surgical resection. ErbB-2 overexpression was investigated from the isolated DNA by "Real Time Polymerase Chain Reaction". RESULTS: ErbB-2 positivity was detected in five (15.6%) of 32 gastric cancer patients. The correlation between distant metastases and ErbB-2 positivity was found to be statistically significant (p=0.04). Additionally, no statistically significant correlation was noted between ErbB-2 positivity and parameters such as level of differentiation (p=0.7), the depth of tumor invasion (p=0.08), lymph node metastases (p=0.6), Lauren's classification (p=0.4), World Health Organization classification (p=0.3), tumor, node, metastasis staging (p=0.3) and tumor localization (p=0.2). Lymph node involvement was present in all ErbB-2 positive patients, the depth of tumor invasion was T3 (one case) and T4 (four cases) with the cardia being the most common location, which was remarkable, though not statistically significant (p>0.05). All ErbB-2 positive patients were detected with intestinal-type gastric cancer according to Lauren's classification and with the tubular-type according to World Health Organization classification. CONCLUSION: According to our findings, given the rates of ErbB-2 overexpression (15.6%) in gastric cancer, the investigation of ErbB-2 overexpression as an important biomarker in humanized monoclonal-antibody treatment in patients with gastric cancer was considered appropriate.

Effect of mirtazapine on MNNG-induced gastric adenocarcinoma in rats.

OBJECTIVE: In this study, anticancer effects of mirtazapine on rats were investigated in an adenocarcinoma model induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and compared with those of cisplatin. MATERIALS AND METHODS: For this purpose, 10 mg/kg doses of mirtazapine were administered orally to one group of rats, while 1 mg/kg doses of cisplatin were administered intraperitoneally to another group. At 1 hour after administration, 200 mg/kg doses of MNNG were given orally to both groups. MNNG administration was repeated once every 10 days through 3 months, after which period, gastric tissue was taken and pathologically evaluated. RESULTS: Mirtazapine prevented adenocarcinoma induction by MNNG in rats to a greater extent than cisplatin. Some of the rats receiving cisplatin demonstrated severe dysplasia in gastric samples and others exhibited mild dysplasia. Rats given mirtazapine were not observed to suffer severe dysplasia, only mild dysplasia being observed. CONCLUSION: For adenocarcinoma induced by MNNG on rats, mirtazapine was determined more effective than cisplatin. In order to make statement about mechanism of anticancer activity of mirtazapine, wider studies are required.

Adjuvant chemoradiation for gastric cancer: multicentric study of the Anatolian Society of Medical Oncology.

BACKGROUND/AIMS: The aims of this study were to report the clinical outcomes of adjuvant chemo-radiotherapy after curative resection in 637 patients with gastric cancer. METHODOLOGY: The retrospective analysis included 637 patients with resectable gastric cancer and stage IB-IV (M0) from 8 medical centers between 2003 and 2010. The patients were treated with 5FU-leucovorin and radiotherapy according to Schema for INT-0116. RESULTS: Of the 637 patients, the median of overall survival (OS) was 43.7 months and relapse free survival (RFS) was 36.6 months. OS rates were 84%, 45%, 40% while RFS rates were 81%, 45% and 35% at 1, 3 and 5-years, respectively. Hematological and gastrointestinal toxicities (grade 1-4) were observed in 35% and 36.5% of patients, respectively. In univariate analysis, according to the Lauren classification, tumor grade, T stage, N stage, type of operation (total gastrectomy or subtotal) and surgery resection margin (R0 or R1) were found as prognostic factors on RFS and OS (p<0.05). In multivariate analysis, T stage, N stage and surgical margins were found as effective factors on OS. T stage, N stage and Lauren classification were factors affecting RFS. CONCLUSIONS: Adjuvant chemo-radiotherapy after curative resection of gastric cancer was feasible, with acceptable toxicities in the Turkish population.

Pomegranate seed extract attenuates chemotherapy-induced acute nephrotoxicity and hepatotoxicity in rats.

Cisplatin (CDDP), one of the most active cytotoxic agents against cancer, has adverse side effects, such as nephrotoxicity and hepatotoxicity. The present study was designed to investigate the potential protective effect of pomegranate seed extract (PSE) against oxidative stress caused by CDDP injury of the kidneys and liver by measuring tissue biochemical and antioxidant variables and immunohistochemically testing caspase-3-positive cells. Twenty-four Sprague-Dawley rats were divided into 4 groups: control; CDDP: injected intraperitoneally with CDDP (7 mg/kg body weight, single dose); PSE: treated for 15 consecutive days by gavage with PSE (300 mg/kg per day); and PSE+CDDP: treated by gavage with PSE 15 days after a single injection of CDDP. The degree of protection against CDDP injury afforded by PSE was evaluated by determining the levels of malondialdehyde as a measure of lipid peroxidation. The levels of glutathione and activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase were estimated from liver and kidney homogenates; the liver and kidney were also histologically examined. PSE elicited a significant protective effect toward liver and kidney by decreasing the level of lipid peroxidation; elevating the levels of glutathione S-transferase; and increasing the activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase. These biochemical observations were supported by immunohistochemical findings and suggested that PSE significantly attenuated nephrotoxicity and hepatotoxicity by the way of its antioxidant, radical-scavenging, and antiapoptotic effects. This PSE extract could be used as a dietary supplement in patients receiving chemotherapy medications.

Malignancies diagnosed during pregnancy and treated with chemotherapy or other modalities (review of 27 cases): multicenter experiences.

BACKGROUND: Cancer is the second leading cause of death in women of reproductive age. The most common tumors diagnosed during pregnancy are breast and cervix cancer, Hodgkin lymphoma and non-Hodgkin lymphoma, leukemias, and malignant melanoma. The aim of therapy in pregnancy is to give optimal treatment to the mother without harm to the fetus. In the first trimester, organogenesis continues, so chemotherapy should not be given because of increasing risk of spontaneous abortion, fetal malformation, and mortality. We evaluated mostly seen tumors during pregnancy and assessed treatment type and outcome of pregnancy after chemotherapy in our population. METHODS: We retrospectively analyzed 27 patients who have been treated during pregnancy or after the delivery because of several malignancies. RESULTS: The tumors associated with pregnancy were breast cancer, hematologic malignancies,gynecologic malignancies, sarcomas, and others. The chemotherapy regimens were given in 17 of 27 patients in the second or third trimester of pregnancy. Four of the patients were diagnosed with cervical cancer, hemangiopericytoma, chronic myeloid leukemia,and breast cancer during the first trimester, so their pregnancies were ended by therapeutic abortion. Although 1 of the 3 fetuses who were exposed to chemotherapy in utero at the second or third trimester was born prematurely and low birth weight was diagnosed in the other 2 fetuses, fetal malformation was not seen in any of them. There were 7 normal and 9 cesarean deliveries. Twenty-three healthy babies survived from 27 pregnancies, of whom 17 babies were exposed to chemotherapeutic agents. CONCLUSIONS: We reported herein 27 patients with malignancies diagnosed during pregnancy; 17 patients received chemotherapy during the gestational period without any fetal or maternal abnormalities. Because of the low incidence of malignancy during pregnancy, our report is noteworthy.

Salivary gland function in continuous ambulatory peritoneal dialysis patients by 99mTc-pertechnetate scintigraphy.

The purpose of this study was to evaluate the alterations in salivary gland function in patients who receiving continuous ambulatory peritoneal dialysis (CAPD) for chronic renal failure (CRF) using technetium-99m pertechnetate ((99m)Tc-P) salivary gland scintigraphy. The study population consisted of 36 CAPD patients (16 males and 20 females, ranging in age from 19 to 73 years, mean age 44.94+/-15.01 years) and 20 healthy controls (11 males and 9 females, ranging in age from 31 to 51 years, mean age 41.25+/-5.62 years). All patients and healthy controls underwent salivary gland scintigraphy. After the intravenous administration of 185MBq of (99m)Tc-P, dynamic salivary gland scintigraphy was performed for 25min. On the basis of the time-activity curves, the following glandular function parameters were calculated for the parotid and submandibular salivary glands: uptake ratio, maximum accumulation, and ejection fraction. Our results showed: All functional parameters obtained for CAPD patients were significantly lower than for healthy controls (P<0.05). In conclusion, this study demonstrated that salivary gland function, an important determinant of oral health, is impaired among the CRF patients treated with CAPD compared with healthy controls, as evaluated by (99m)Tc-P salivary gland scintigraphy.

Distribution of HLA Tissue Groups in Patients with Gastric Cancer.

OBJECTIVE: Gastric cancer is an important disease that is seen all over the world and that threats public health. At the same time, gastric cancer is a heterogeneous disorder with multifactorial etiologies. Recent studies have shown a significant association between HLA antigens and gastric adenocarcinoma. The aim of the present study was to determine the distribution of HLA class I (HLA-A, B and C) and class II (HLA-DR, DQ and DP) antigens in Turkish patients with gastric adenocarcinoma. MATERIALS AND METHODS: HLA alleles or HLA haplotypes associated with gastric cancer were established in the Turkish population using PSR-SSP analysis in 71 unrelated patients with gastric cancer and in 82 unrelated healthy controls. The statistical significance of differences in allele frequencies between patients and controls was measured by the Chi-square test with Yates's correction. RESULTS: The study revealed that the HLA-Cw5 antigen is more prevalent in patients with gastric cancer (p=0.042) and that the HLA-DRB1*15 antigen is more prevelent in the control group (p=0.021). CONCLUSION: It is probable that HLA-Cw5 is a risk factor for gastric cancer whereas HLA-DRB1*15 plays a protective role for this disease. The results show that different loci on HLA may control resistance to or tendency for any disease in different societies; each society should determine its own tissue group.

Diffusion-weighted magnetic resonance imaging in evaluation of gastric cancer.

OBJECTIVE: To investigate the role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the diagnosis of gastric tumors and discuss the diagnostic importance and potential use of apparent diffusion coefficient (ADC) measurements. MATERIALS AND METHODS: Beginning in March 2009, DW-MRI was added to the routine abdominal and pelvic MR examination for all patients imaged at our institution. A total of 21 patients (12 men and 9 women; mean age 55±6.3SD, range: 39-74 years) with known gastric malignancy were referred to our MR unit. All MRI examinations were performed using a 1.5-T MRI scanner (Magnetom Avanto, Siemens Healthcare). The evaluation of the DW-MRI examinations was made by radiologists' consensus. Changes in the signal intensity of the lesions were determined by their appearance in images at b=50, 400, and 800 s/mm(2) and in ADC maps. Results were compared with histopathological findings. RESULTS: All of the gastric tumors in this study showed high signal intensity in DW-MRI and low signal intensity in ADC maps. Mean ADC values for gastric tumor and normal gastric wall were 0.892±0.23 SD mm(2)/s and 1.453±0.35 SD mm(2)/s respectively. The mean ADC values of gastric tumors were significantly lower than that of the normal gastric wall. CONCLUSION: DW-MRI and ADC values together can successfully differentiate gastric tumors from normal gastric wall.

Serum adiponectin levels in patients with esophageal cancer.

OBJECTIVE: The aim of the study was to investigate a possible relationship between serum levels of adiponectin and clinicopathological characteristics in esophageal cancer. This is the first report evaluating serum adiponectin levels in patients with esophageal cancer. METHODS: Sixty-two patients with esophageal cancer and thirty healthy subjects were included in the study. Adiponectin levels were determined by an enzyme-linked immunosorbent assay kit. RESULTS: The mean serum adiponectin level in the cancer group was significantly low compared with the adiponectin level in the healthy control group. Furthermore, adiponectin levels of the patients gradually decreased with increase in tumor stage. The patients with adenocarcinoma of the esophagus had significantly lower values of serum adiponectin than patients with squamous cell carcinoma. CONCLUSION: We concluded that decreased circulating adiponectin levels may play a role in the progression and/or development of esophageal cancers. However, for clinical use of serum adiponectin in terms of early diagnosis and treatment, further studies should be performed.

Evaluation of nitric oxide synthase activity, nitric oxide, and homocysteine levels in patients with active Behcet's disease.

Behcet's disease (BD) is a chronic, progressive disorder that affects many systems of the body including the eye. The aim of this study was to examine the effects of nitric oxide synthase activity (NOS), nitric oxide (NO*), and homocysteine (Hcy) levels in patients with active BD. Included in this study were 18 male BD patients and 16 male healthy volunteers as controls. Erythrocyte NOS activity, (NO*) erythrocyte sedimentation rate, serum C-reactive protein, and plasma Hcy values in the patients with BD were significantly higher than those of the control group. Our results show that these parameters play a major role in the inflammatory reactions observed in BD.

Stereological Evaluation of Tumor Regression Rates in Lung Cancer Using CT Via the Cavalieri Method.

OBJECTIVE: The aims of this study were to analyze the relevant methods of computed tomography (CT) and stereology with respect to the estimation of tumor volume and to determine whether the response rates measured by the stereological method correlate with those of conventional morphometric techniques in lung cancer. MATERIALS AND METHODS: The study group was composed of 32 patients, including 25 males and 7 females. All the subjects included were non-small celled lung cancer patients (NSCLC), and they were all treated with either chemotherapy (n=12) or chemotherapy plus radiotherapy (n=20) for locally advanced disease (Stage III A and Stage III B). All patients underwent contrast enhanced CT of the thorax before and after treatment. Tumor diameters were measured according to stereological methods, the World Health Organization (WHO) criteria and the Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: With all three methods (stereological method, RECIST and WHO), an improvement was observed in the mean tumor size. The response rates were 11.8 ± 117.5% (stereological method), 27.4 ± 38.8% (RECIST), and 38.7 ± 68.1% (WHO). Although the response rates in RECIST and WHO criteria were statistically significant (P=0.02 and P=0.045 for RECIST and WHO, respectively), the response rates with stereological measurements were not statistically significant (P=0.21), showing that response rates obtained by the Cavalieri method differ from those obtained through WHO and RECIST. The comparison between response rates obtained with each method shows that the stereological response rate was not correlated with the response rate in either RECIST or WHO, (r=-0.15, P=0.59 and r=-0.27, P=0.33 for RECIST and WHO, respectively), while there was good correlation between the WHO and RECIST response rates (r=0.87 and P<0.001). CONCLUSION: The Cavalieri principle is more suitable for the evaluation of tumor volumes in response to treatment in the management of advanced malignancies, in particular in patients with tumors of irregular shape or when the determination of treatment response is not clear.

Rapidly developing giant sized lupus vulgaris on the chest associated with bilateral scrofuloderma on the neck.

Lupus vulgaris and scrofuloderma are the opposite poles of cutaneous tuberculosis. Lupus vulgaris of a giant size and scrofuloderma in the vicinity of this lesion were both present in a 70-year-old female patient. The purified protein derivative of tuberculin (PPD) skin test was strongly positive. In histopathological examination, granulomatous infiltration without caseation necrosis was seen in the dermis. The patient was treated with a four-drug therapy consisting of pyrazinamide (25 mg/kg), isoniazid (5 mg/kg), rifampin (10 mg/kg) and ethambutol (15 mg/kg) daily for 2 months, followed by dual therapy with isoniazid and rifampin for 6 months. Her cutaneous lesions significantly regressed after 4 months, leaving keloid scars.