Clinicopathologic Analysis and Prognostic Factors for Survival in Patients with Operable Ampullary Carcinoma: A Multi-Institutional Retrospective Experience.

Background and Objectives: In ampullary cancer, 5-year survival rates are 30-50%, even with optimal resection and perioperative systemic therapies. We sought to determine the important clinicopathological features and adjuvant treatments in terms of the prognosis of patients with operable-stage ampullary carcinomas. Materials and Methods: We included 197 patients who underwent pancreaticoduodenectomy to treat ampullary carcinomas between December 2003 and May 2019. Demographics, clinical features, treatments, and outcomes/survival were analyzed. Results: The median disease-free survival (mDFS) and median overall survival (mOS) were 40.9 vs. 63.4 months, respectively. The mDFS was significantly lower in patients with lymphovascular invasion (p < 0.001) and lymph node involvement (p = 0.027). Potential predictors of decreased OS on univariate analysis included age ≥ 50 years (p = 0.045), poor performance status (p = 0.048), weight loss (p = 0.045), T3-T4 tumors (p = 0.018), surgical margin positivity (p = 0.01), lymph node involvement (p = 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p = 0.007), and poor histological grade (p = 0.042). For the multivariate analysis, only nodal status (hazard ratio [HR]1.98; 95% confidence interval [CI], 1.08-3.65; p = 0.027) and surgical margin status (HR 2.61; 95% CI, 1.09-6.24; p = 0.03) were associated with OS. Conclusions: Nodal status and a positive surgical margin were independent predictors of a poor mOS for patients with ampullary carcinomas. Additional studies are required to explore the role of adjuvant therapy in patients with ampullary carcinomas.

Effects of hormone receptor status on patient clinic and survival in HER2 positive breast cancer.

BACKGROUND: In the current study, the effect of hormone receptor (HR) status on clinical and survival in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer was investigated. METHODS: Two hundred ninety-one patients with HER2- positive were examined in two categories as HR-positive and HR-negative. RESULTS: Of these, 197 (68%) were HR-positive and 94 (32%) were HR-negative with a mean follow-up period of 68 ± 2.7 months. The groups were found to be similar in terms of age, menopausal status, comorbidity, pathologic type, stage, T stage, N stage, lymphovascular invasion, presence and percentage of intraductal component, multicentricity/focality and extracapsular invasion. Family history (P = 0.038), stage 2 tumor rate (P < 0.001), and perineural invasion (P = 0.005) were significantly higher in the HR-positive group. In the HR-negative group, mean Ki-67 value (P = 0.014), stage 3 tumor rate (P < 0.001), tumor necrosis (P = 0.004) and strong (3+) HER2 staining on immunohistochemical staining (P = 0.003) were higher. The incidence of relapse and metastasis, and the localization of metastasis were similar in both patient groups. The rate of locoregional relapse during the first 2 years was higher in the HR-negative patients than in the HR-positive patients (P = 0.023). Overall survival (OS) and disease-free survival (DFS) did not differ between the groups in univariate analysis. However, HR status was determined as an independent prognostic factor (HR: 2.11, 95% CI: 1.17-3.79; P = 0.012) for OS was not found to be significant for DFS in multivariate analysis. CONCLUSION: Both clinicopathologic features and OS outcomes of HR-negative patients were worse than those of HR-positive patients.

"Evaluation of quality of life in patients with gastric adenocarcinoma receiving chemoradiotherapy: a cross-sectional study".

PURPOSE: The aim of this study was to evaluate quality of life (QoL) in patients with gastric adenocarcinoma receiving adjuvant chemoradiotherapy (CRT). METHODS: The European Organization for Cancer Research and Treatment Quality of Life Questionnaire-Core 30 (QLQ-C30) and site-specific module for gastric cancer (QLQ-STO22) were administered at four time points to 156 patients admitted to Cumhuriyet University Oncology Center between 2011 and 2018. RESULTS: The patient group comprised 76% men and 24% women with a median age of 61 years (range, 18-88). During CRT, 12 patients (8%) discontinued treatment, 25 (16%) lost weight, and 42 (27%) had reduced performance. There was significant worsening in QLQ-C30 global health status and all functional and symptom scale scores at CRT completion. These changes were also clinically significant except for physical functioning scores and were supported by minimal clinically important difference measurements. In the QLQ-STO22, all symptoms except dry mouth and hair loss were negatively affected at CRT completion. In general, scores were improved at 1 month after CRT and almost all scores reached baseline level by 6 months. Certain scores were more adversely affected in women (global health status, physical functioning, role functioning, fatigue, pain, and insomnia), those who lost weight during CRT (emotional functioning), and those with CRT interruption (emotional functioning and anxiety). CONCLUSION: Although CRT reduces QoL in patients with gastric cancer, the effects tend to resolve within 6 months after completing treatment. Female sex, weight loss, and CRT interruption negatively affected some QoL scores.

Is SUVmax of 18F-FDG PET/CT Predictive Factor for Malignancy in Gastrointestinal Tract?

BACKGROUND: Increasing use of 18F-FDG PET/CT in cancer patients, has led to more common detection of 18F- FDG uptake in the gastrointestinal tract (GIT). AIMS: The objective of this study was to assess 18F-FDG uptake in incidental and known GIT malignancy. METHODS: A total of 6500 patients followed-up in a single and tertiary center between January 2010 and September 2016 were retrospectively reviewed. Of 2850 patients assessed with 18FDG-PET/CT, known GIT malignancy and 18F-FDG uptake cases during follow-up were included in the study. RESULTS: Of 658 patients with 18F-FDG uptake, 150 patients who underwent endoscopy were included in the study. Seventy-seven of these patients had known GIT malignancy and 73 had incidental 18F-FDG uptake. Among these 73 patients; 7 (9.6%) had malignancy, 20 (27,2%) adenoma and 24 (32.9%) inflammation that were confirmed. Endoscopy was normal in 22 (30.2%) patients. One hundred forty-three (95.3%) patients had focal and 7 (4.7%) had diffuse uptake. While no malignancy was detected in patients with diffuse uptake, 58.7% (84/143) of the patients with focal uptake presented malignancy. Mean the standardized uptake value (SUV) max values were found as 15.0 ± 10.6 (range, 3.8-56.5) in malignant disease, 10.2 ± 4.3 (range, 2.4-19.7) in adenoma, 7.3 ± 3.6 (range, 3.6-18.7) in inflammation, and 9.8 ± 4.2 (range, 3.8-19.9) in normal endoscopy groups (p < 0.001, rho = 0.378). CONCLUSION: Although this study demonstrated high probability of malignant disease with increased 18F-FDG uptake in the GIT, it would be a more appropriate approach to confirm all patients with 18F-FDG uptake through endoscopy as SUVmax values vary in a wide range.

[Relation of cervical cancer with the results of human papillomavirus (HPV) screening carried out via hybrid capture 2 method on 52.000 women in Erzurum]. / Erzurum ilinde 52.000 kadinda hybrid capture 2 yöntemi kullanilarak yapilan insan papilloma virüs (HPV) tarama sonuçlarinin serviks kanseri ile iliskisi.

Cervical cancer is a common female cancer that could be diagnosed early with screening methods. Almost all cases are caused by human papilloma virus (HPV) infection. Therefore, detecting the presence of HPV DNA is important for early diagnosis and treatment. Regular determination of screening tests enables early detection of patients with the risk of cervical cancer. For this purpose, since August 2014 a new screening program has been carried out by Early Diagnosis, Screening and Training of Cancer Centers (KETEM). The aims of our study were to detect the HPV prevalence in Erzurum and determine the major HPV types under the scope of population based cervical cancer screening program. Female patients between the ages of 30-65 were included in the study. Pap-smear and HPV DNA samples were taken simultaneously. The samples were examined in a national central laboratory. The study was performed using conventional methods in pap-smear samples. Pap-smear samples from HPV (-) patients were not included in the pathological evaluation. Pathological results of the pap-smear samples, which were taken from the HPV (+) cases, were sent to KETEM by national central laboratory and then these results were used. Within the scope of this study, 52.000 women were screened. Among all these women 2.4% of the cases were HPV DNA positive. HPV DNA samples were screened by Hybrid capture 2 (Qiagen, Germany) method. The highest positivity was observed at age 40 with 65 cases (5.1%) and the lowest positivity was observed at age 65 with 2 cases (0.1%). 60.1% of the HPV positive cases were at 30-45 age group, 35.2% were at 45-60 age group and 4.6% were at 65 and above age group. The most common type was HPV 16 with the frequency of 12.2% and this was followed by HPV 31 with 7.4% and HPV 51 with 6.7%,HPV 52 with 4.4% and HPV 68 with 4.3% frequencies. The rate of the HPV 18, which is the type of HPV that carries high risk for causing cervical cancer, was 3.0%. 49.2% of the HPV positive cases had single and 50.8% of them contained more than one type of HPV. The most common pathological appearance was "low grade cervical intraepithelial lesion" (LGSIL) detected in 115 cases (9.2%) and "atypical squamous cells of unknown significance" (ASC-US) detected in 93 cases (7.4%). Cases that had abnormal cytology were referred to colposcopy. Consequently, it was concluded that regional screening is important in terms of the determination of the HPV type for the early diagnosis of cervical cancer and vaccination so prevalence studies should be increased and supported.

Biweekly cisplatin and gemcitabine with two different doses in non small cell lung cancer patients: A retrospective singlecenter experience.

PURPOSE: Non-small-cell lung cancer (NSCLC) constitutes 80-85% of all lung cancers. Patients with advanced-stage NSCLC may benefit from chemotherapy. Gemcitabine and cisplatin is a well-established therapy for this malignancy. Recently, biweekly administration is becoming more acceptable, but the most effective and tolerable dose remains unclear. The purpose of this study was to compare the toxicity and efficacy of 1000 mg/m2 gemcitabine (GEM 1000) and 1500 mg/m2 gemcitabine (GEM 1500) in combination with 50 mg/m2 cisplatin. METHODS: Gemcitabine was administered at a dose of 1000 or 1500 mg/m2 with cisplatin administered at a dose of 50 mg/m2 on day 1. The treatment was repeated every 2 weeks for a total of 4 courses. Response rates, progression-free survival (PFS), overall survival (OS) and toxicities were assessed. RESULTS: 114 patients with IIIB and IV stages of NSCLC were included. Seventy two patients (63%) received GEM 1000 and 42 (37%) received GEM 1500. The overall reponse rate (ORR), PFS and OS were 24%, 6 months and 13 months respectively in the GEM 1000 group and 36%, 6 months and 15 months in the GEM 1500 group, respectively. Grade 3-4 neutropenia and thrombocytopenia were observed in 4% of the GEM 1000 group and 9% of the GEM 1500 group (p=0.41). CONCLUSION: Biweekly administration of GEM 1000 and 1500 is a well tolerated regimen. Although the GEM 1000 group showed a lower response rate than the GEM 1500 group, PFS and OS were similar.

Is Change in Hemoglobin Level a Predictive Biomarker of Tyrosine Kinase Efficacy in Metastatic Renal Cell Carcinoma? A Turkish Oncology Group Study.

BACKGROUND: There are insufficient predictive markers for renal cell carcinoma (RCC). METHODS: A total of 308 metastatic RCC patients were analyzed retrospectively. RESULTS: The increased hemoglobin (Hb) group had significantly higher progression-free survival and overall survival (OS) compared with the decreased Hb group at 11.5 versus 6.35 months (p < .001) and 21.0 versus 11.36 months (p < .001) respectively. The 1- and 3-year OS rates were higher in the Hb increased group, i.e., 84% versus 64% and 52% versus 35% respectively. CONCLUSIONS: The present study showed that increased Hb levels after tyrosine kinase inhibitor therapy could be a predictive marker of RCC.

Is sunitinib-induced hypothyroidism a predictive clinical marker for better response in metastatic renal cell carcinoma patients?

BACKGROUND: The main goal of this study was to examine whether the occurrence of hypothyroidism during sunitinib therapy in patients with metastatic renal cell carcinoma (mRCC) is associated with a better outcome. METHODS: The study enrolled 81 patients with pathologically proven mRCC who were treated with sunitinib between March 2008 and June 2013.Thyroid function evaluation comprised (free-thyroxine) FT4 and thyroid-stimulating hormone (TSH) before treatment and at day 1 of each 6-week cycle. Survival analysis was performed using the Kaplan-Meier method, and the differences among the groups were determined using the log-rank test. RESULTS: Hypothyroidism occurred in 30 (37%) of 81 patients within a median 3 months (range 1-18) of treatment initiation. There was a statistically significant correlation between the occurrence of hypothyroidism during treatment and the rate of objective remission (ORR) (hypothyroid patients vs euthyroid patients: 46.7 vs 13.7%, respectively; P = 0.001). Median progression-free survival (PFS) was 10 (95% CI 6.13-13.8) months in the euthyroid patients, and 17 (95% CI 9.33-24.6) months in the hypothyroid patients (P = 0.001). The median overall survival (OS) was 39 (95% CI 25.4-52.5) months in the hypothyroid patients and 20 (95% CI 14.7-25.2) months in the euthyroid patients (P = 0.019). CONCLUSIONS: The occurrence of hypothyroidism during treatment in patients was significantly associated with longer PFS, OS and better ORR in the current study.

Hepatic steatosis is associated with higher incidence of liver metastasis in patients with metastatic breast cancer; an observational clinical study.

PURPOSE: To investigate the relationship between hepatic steatosis (HS) (at the time of diagnosis) and hepatic metastasis (at the time of diagnosis and follow-up) in metastatic breast cancer (BC) patients by using computed tomography (CT). METHODS: A total of 107 metastatic BC patients who had an abdominal CT were retrospectively enrolled in this study. Patients without HS (N=79) were regarded as the control group and those with HS constituted the HS study group (N-28). RESULTS: Hepatic metastases at diagnosis and during follow-up were more common in patients with HS (p=0.018 and p=0.041, respectively) and in the premenopausal group (p<0.001 and p=0.004, respectively), whereas they were similar in patients with and without HS in the postmenopausal group (p=0.655 and p=0.656, respectively). Overall survival rates were similar in patients with and without HS (p=0.606). CONCLUSION: Hepatic metastases at diagnosis and during follow-up were more frequent in patients with HS, especially in premenopausal patients. Survival was similar in both groups.

Is Late Recurrence a Predictive Clinical Marker for Better Sunitinib Response in Metastatic Renal Cell Carcinoma Patients?

BACKGROUND: We investigated the clinicopathological features in patients with recurrent renal cell carcinoma (RCC) within 5 years or more than 5 years after nephrectomy and determined predictors of overall survival (OS) and progression-free survival (PFS) after disease recurrence in the administration of first-line sunitinib in the treatment of metastatic RCC (mRCC). PATIENTS AND METHODS: In this study we enrolled 86 Turkish patients with mRCC who received sunitinib. Univariate analyses were performed using the log rank test. RESULTS: Fifty-six patients (65%) were diagnosed with disease recurrence within 5 years after radical nephrectomy (early recurrence) and 30 patients (35%) were diagnosed with recurrence more than 5 years after radical nephrectomy (late recurrence). Fuhrman grade was statistically significantly different between the 2 groups (P = .013). The late recurrence patients were significantly associated with the Memorial Sloan Kettering Cancer Center favorable risk group compared with patients with early recurrence (P = .001). There was a statistically significant correlation between recurrence time and the rate of objective remission (ORR) (the late recurrence group vs. the early recurrence group: 43.3% vs. 14.3%, respectively; P = .004). From the time of disease recurrence, the median OS was 42.0 (95% confidence interval [CI], 24.4-59.5) months in the late recurrence group, and 16 (95% CI, 11.5-20.4) months in the early recurrence group (P = .001). Median PFS was 8 (95% CI, 4.05-11.9) months in the early recurrence group, and 20 (95% CI, 14.8-25.1) months in the late recurrence group (P ≤ .001). CONCLUSION: The study demonstrated a potential prognostic value of late recurrence in terms of PFS, OS, and ORR.

Analyses of multiple factors for determination of "selected patients" who should receive rechallenge treatment in metastatic colorectal cancer: a retrospective study from Turkey.

BACKGROUND: Repeating a prior chemotherapy (rechallenge therapy) is an option for selected patients with metastatic colorectal cancer, but there is very little evidence in the literature for this approach. Thus, we reviewed our registry to evaluate prognostic factors and survival of patients who received irinotecan and oxaliplatin- based regimens as rechallenge third and fourth-line therapy. MATERIALS AND METHODS: Patients who received irinotecan-based or oxaliplatin-base regimen as first-line had been rechallenged with third-line or fourth-line therapy. These patients were selected from the database of Turkish mCRC registry archives between October 2006 and June 2013 and evaluated retrospectively for factors effecting progression free survival (PFS) and overall survival (OS) by the Kaplan-Meir and Cox-regression methods. RESULTS: Thirty-nine patients were enrolled. The median duration of follow-up was 36 months (14-68 months). Thirty-one patients (76%) died during follow-up. In terms of rechallenge treatments, 29 patients had received third-line and 10 patients had received fourth-line. Response rate (RR) was found to be 12.9%, with stable disease in 19 (48.7%) patients. The median PFS was 6 months (95%CI=4.64-7.35 months) and the median OS was 11 months (95%CI=8.31-13.7 months). The factors effecting survival (PFS and OS) were only being PFS after first-line chemotherapy≥12 months (p=0.007, 95% CI=1.75-35.22 and p=0.004, 95%CI=1.44-7.11), both in univariate and multivariate analyses. CONCLUSIONS: This study indicates that rechallenge treatment could be a good option as a third or later line therapy in patients who had ≥12 months PFS on receiving first line therapy.

Predicting the role of the pretreatment neutrophil to lymphocyte ratio in the survival of early triple-negative breast cancer patients.

PURPOSE: Increasing evidence supports an association between systemic inflammation and cancer development and progression. The neutrophil to lymphocyte ratio (NLR) is used as a basic parameter of systemic inflammation in some tumors. The aim of this study was to examine the association between the pretreatment NLR, disease-free survival (DFS), and overall survival (OS) in patients with early triple-negative breast cancer (TNBC). METHODS: We retrospectively studied patients diagnosed with stage I-III TNBC who had completed all phases of primary treatment from 2002 to 2013. The association between the pretreatment NLR and survival was analyzed. The difference among variables was calculated by chi-square test. OS and DFS were assessed using the Kaplan-Meier method. Multivariate Cox proportional hazards models were used to analyze the prognostic impact of clinical parameters. RESULTS: Eighty-five patients were eligible for study inclusion. There were no statistically significant differences among the pretreatment NLR and clinicopathological variables. Patients with an NLR of > 2 had significantly lower DFS (p=0.002) and OS (p=0.03) than patients with an NLR of ≤ 2. Multivariate Cox proportional hazards models showed that a higher pretreatment NLR was independently correlated with poor DFS and OS, with a hazard ratio 5.46 (95% confidence interval [CI] 1.61-18.85, p=0.006) and 2.86 (95% CI 1.04-7.86, p=0.04), respectively. CONCLUSION: Patients with early TNBC and with elevated pretreatment NLR showed poorer DFS and OS than patients without elevated NLR. However, this finding needs to be confirmed in a large prospective study.

Clinicopathological characteristics and prognosis of patients according to recurrence time after curative resection for colorectal cancer.

PURPOSE: To investigate clinicopathological features in patients with recurrent colorectal cancer within 1 year and more than 1 year after curative resection. MATERIALS AND METHODS: We retrospectively evaluated 103 patients with disease recurrence before versus after 1 year of resection. Thirty-two patients (31%) were diagnosed with recurrence less than 1 year after curative resection for colorectal cancer (early recurrence) and 71 (69%) after more than 1 year (non-early recurrence). RESULTS: The early recurrence group displayed a significantly lower overall survival rate for both colon cancer (p=0, 01) and rectal cancer (p<0.001). Inadequate lymph node dissection was a significant predictor for early relapse. There were no statistically significant differences in clinicopathological variables such as age, sex, primary tumor localization, stage, depth of invasion, lymphovascular invasion and perineural invasion between the early and non-early recurrence groups. However, a K-ras mutation subgroup was significantly associated with early recurrence (p<0.001). CONCLUSIONS: Poor survival is associated with early recurrence for patients undergoing resection for non-metastatic colorectal cancer, as well as K-ras mutation.

Albumin-globulin ratio for prediction of long-term mortality in lung adenocarcinoma patients.

BACKGROUND: Prior studies showed a relationship between serum albumin and the albumin to globulin ratio with different types of cancer. We aimed to evaluate the predictive value of the albumin-globulin ratio (AGR) for survival of patients with lung adenocarcinoma. MATERIALS AND METHODS: This retrospective study included 240 lung adenocarcinoma patients. Biochemical parameters before chemotherapy were collected and survival status was obtained from the hospital registry. The AGR was calculated using the equation AGR=albumin/ (total protein-albumin) and ranked from lowest to highest, the total number of patients being divided into three equal tertiles according to the AGR values. Furthermore, AGR was divided into two groups (low and high tertiles) for ROC curve analysis. Cox model analysis was used to evaluate the prognostic value of AGR and AGR tertiles. RESULTS: The mean survival time for each tertile was: for the 1st 9.8 months (95%CI:7.765-11.848), 2nd 15.4 months (95%CI:12.685-18.186), and 3rd 19.9 months (95%CI:16.495-23.455) (p<0.001). Kaplan-Meier curves showed significantly higher survival rates with the third and high tertiles of AGR in comparison with the first and low tertiles, respectively. At multivariate analysis low levels of albumin and AGR, low tertile of AGR and high performance status remained an independent predictors of mortality. CONCLUSIONS: Low AGR was a significant predictor of long-term mortality in patients with lung adenocarcinoma. Serum albumin measurement and calculation of AGR are easily accessible and cheap to use for predicting mortality in patients with lung adenocarcinoma.

The relationship between CYP2C9 gene polymorphisms and upper gastrointestinal bleeding in patients who used warfarin.

AIM: Oral anticoagulants are the most common used substance for treatment and prophylaxis of warfarin venous and arterial thromboembolic disorders in the world. Therapeutic index of warfarin is narrow. CYP2C9 is a hepatic microsomal enzyme and has a primary role in metabolism of warfarin and genetic variations of CYP2C9 may cause a serious effect on the response to warfarin in patients. The aim of this study was to determine the efficiency of CYP2C9 gene polymorphisms on drug metabolism in patients who had upper gastrointestinal system bleeding while using warfarin. METHODS: There was a total of 67 patients in this study, 37 of whom had upper gastrointestinal system bleeding when INR was above 3 while using warfarin (group 1), 30 of whom had no bleeding and INR was stable under 3 (group 2). RESULTS: There was no difference in terms of warfarin dose used among the groups (p>0.05). Mutant genotype, INR and aspirin usage were found significantly different in the group with bleeding (p less 0.05). When analyzed in terms of drug interaction, there was no difference between the two groups (p>0.05). Logistic regression analysis was made in order to determine the risk factors that may cause bleeding. Aspirin usage (p= 0.016) and genetic polymorphism (p= 0.024) were related to the increased risk of bleeding. CONCLUSION: CYP2C9*2 and CYP2C9*3 polymorphisms were related to the increase of excessive anticoagulation and bleeding risk in the patients who used warfarin.