Tyrosine kinase inhibitors in the treatment of metastatic renal cell cancer patients with early cytokine intolerance: TURCOS, a Turkish national, prospective observational study.

OBJECTIVE: Cytokines have been the mainstay of treatment in metastatic renal cell cancer (mRCC) for decades before the introduction of tyrosine kinase inhibitors (TKIs), which dramatically changed the therapeutic landscape in these patients. This observational study was designed to evaluate use of TKIs in the treatment of cytokine-intolerant mRCC patients. METHODS: A total of 151 cytokine-intolerant mRCC patients who were treated with TKIs (sunitinib, pazopanib and sorafenib) were enrolled in this prospective, non-interventional, multi-center observational study at 16 oncology centers across Turkey. Mean (SD) age was 61.3 (11.1) years and 74.8% were males. Data on duration of TKI treatment was the primary outcome measure. Additionally, overall response rate (ORR), progression free survival (PFS), overall survival (OS) and safety data were recorded. RESULTS: Median duration of treatment was 8.2 months at a median follow up of 17.9 months. ORR and disease control rate were 12.5% and 70.8%, respectively. Median PFS and OS were 7.5 months (95%CI: 6.4-10.4) and 27.3 months (95%CI: 17.6-27.3) with no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS. The most common adverse events excluding progression-which was the protocol requirement were diarrhea (13.6%), asthenia (13.6%) and hand-foot syndrome (12.6%). Dose modifications were required in 30.5% of the patients and 15% discontinued TKIs because of toxicity. CONCLUSIONS: Our findings confirm the efficacy and safety profile of TKIs in the first-line treatment of mRCC patients intolerant to cytokine treatment. There was no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS.Trial registration: TURCOS ClinicalTrials.gov Identifier: NCT01585974. Registered April 25, 2012.

Efficacy and safety of bevacizumab in Turkish patients with metastatic and recurrent cervical cancer.

OBJECTIVE: To evaluate the efficacy of bevacizumab a monoclonal, antivascular endothelial growth factor antibody in combination with cytotoxic chemotherapy in Turkish patients with recurrent and metastatic cervical cancer. MATERIALS AND METHODS: Data of 64 patients with metastatic or recurrent cervical cancer, receiving bevacizumab with first-line cisplatin or carboplatin and paclitaxel chemotherapy between 2013 and 2017 were retrospectively evaluated. RESULTS: The mean age of the patients was 49 years (range, 28-68), the median follow-up time was 12 months (range, 2-53), the median progression-free survival (PFS) was eight months, and the median overall survival (OS) was 23 months. All 64 patients received a median of 6 (range, 1-12) bevacizumab and 6 (range, 2-12) chemotherapy cycles. The chemotherapy regimens used with bevacizumab were cisplatin and paclitaxel in 31 (48%) and carboplatin and paclitaxel in 33 (52%) patients. The survival in patients treated with bevacizumab and cisplatin plus paclitaxel was better-particularly in patients with no previous cisplatin-based radiosensitizer therapy-than those treated with carboplatin, paclitaxel, and bevacizumab (p=0.023). The bevacizumab dose was 7.5 mg/kg in 30 patients (47%) and 15 mg/kg in 34 patients (53%) every 21 days. No significant difference was reported in the OS and the PFS between the two groups. While the most common all-grades adverse events were nausea, neutropenia, anemia, and peripheral sensory neuropathy, the most common grade ≥3 adverse events were neutropenia, anemia, and peripheral sensory neuropathy. CONCLUSION: Adding bevacizumab to platinum and paclitaxel chemotherapy in a case of metastatic or recurrent cervical cancer is an effective and tolerable treatment for Turkish patients.

PTK-7 Expression in Gastric Cancer: A Prognostic Determinant

Background: Protein tyrosine kinase-7, a regulatory protein in the Wnt signaling pathway, was highly overexpressed in various cancer types and assumed to be related to prognosis. Aims: The purpose of this study is to assess whether protein tyrosine kinase-7 expression status in curatively resected gastric carcinoma would independently identify patients with a high risk of recurrence and death. Study Design: Retrospective cohort study. Methods: We included patients who were at least 18 years of age and diagnosed with gastric cancer. The exclusion criterion was a metastatic disease at the time of diagnosis or operation. Data on clinicopathological prognostic determinants and clinical courses, including the date of disease relapse and survival status, were collected with the use of medical records. Surgically removed tumor tissue specimens were examined by two independent pathologists at the pathology department of our institution. Protein tyrosine kinase-7 expression status was assessed with immunohistochemical processing and stratified on a scale ranging from 0 to +3 according to the extent of stained tumor cells. It was then further categorized into two groups, one being + (positive), including +1, +2, and +3 scores, another was-(negative), including-and +/− scores. Results: A total of 114 patients were analyzed. Protein tyrosine kinase-7 expression was present in 66.7% of the surgical tumor specimens. There was no statistically significant difference in almost all relevant parameters between the protein tyrosine kinase-7 positive and negative groups. The estimated median survival in the protein tyrosine kinase-7 positive group was significantly better than the protein tyrosine kinase-7 negative group (60 vs 22 months, p<0.001). Disease-free survival was found to be 55 months in the protein tyrosine kinase-7 positive group, whereas it was 21 months in the negative group (p=0.015). In the multivariate analysis, along with negative protein tyrosine kinase-7 expression, poor performance status, and advanced stage were significantly associated with the risk of death (p<0.001 for each). Conclusion: Compared to patients with negative PTK-7 expression, patients with positive PTK-7 expression have better disease-free survival and overall survival rates. Efforts should be made to enhance this finding and translate it into clinical practice.

Molecular subtypes are prognostic for N3 breast cancer patients in the modern therapeutic era.

Nodal (N) status and molecular subtypes are well-known prognostic factors for breast cancer patients. The aim of the present study was to evaluate whether there was a prognostic role of molecular subtypes for pN3a breast cancer patients in the modern therapeutic era. The present study retrospectively evaluated a total of 521 breast cancer patients who had 10 or more metastatic lymph nodes and received adjuvant systemic therapy at the Oncology Department of four different centers in Turkey between 2000-2015. Patients were divided into four molecular subtypes by immunohistochemical staining. There were no significant differences in relapse rates according to the molecular subtypes (P=0.07). The five year disease free survival rate was 62% for the whole study population, 67% for Luminal A tumors, 53% for Luminal B tumors, 64% for human epidermal growth factor receptor 2-positive tumors and 56% for triple negative tumors. Luminal A patients had a better progression free survival when compared with Luminal B (P=0.026) and triple negative (P=0.07) patients. pT stage (P<0.001), and breast cancer subtype (P<0.001), remained significant independent factors for disease free survival. Therefore, breast cancer subtypes are still prognostic for patients with pN3 breast cancer.

Effectiveness and Safety of LMWH Treatment in Patients With Cancer Diagnosed With Non-High-Risk Venous Thromboembolism: Turkish Observational Study (TREBECA).

We compared the efficacy and safety of low-molecular-weight heparins (LMWHs) in patients with cancer who are at low risk of venous thromboembolism (VTE). Patients were treated by medical oncologists in Turkey at 15 sites, where they were enrolled and followed up for a period of 12 months. Due to the study design, there was no specific treatment protocol for LMWH. Primary end points were efficacy and the time to change in VTE status. Of the included 250 patients, 239 (95.6%), 176 (70.4%), 130 (52.0%), and 91 (36.4%) completed their day 15, month 3, month 6, and month 12 visits, respectively. Number of patients treated with enoxaparin, bemiparin, and tinzaparin were 133, 112, and 5, respectively. Anticoagulant therapy provoked thrombus resolution in 1.2% and 12.7% of patients using enoxaparin and bemiparin, respectively ( P = .004). Thrombus resolution was observed in 81 more patients at month 3 visit. This ratio was 35 (40.2%) of 87 and 46 (54.1%) of 85 patients administered enoxaparin and bemiparin at the third visit, respectively ( P = .038). Thrombus resolution was observed in 21 more patients during month 6 visit. This ratio was 5 (7.7%) of 65 and 15 (23.4%) of 64 patients administered enoxaparin and bemiparin at the fourth visit, respectively ( P = .022). The LMWH was discontinued in only 2 patients due to gastrointestinal bleeding. This pioneering study shows bemiparin is more effective than enoxaparin in thrombosis resolution and has a similar tolerability profile.

MEFV gene testing may guide physicians for early diagnosis of familial Mediterranean fever.

INTRODUCTION: Familial Mediterranean fever (FMF) is characterized by recurrent attacks of polyserositis. Even though clinical assessment is accepted to be the most important factor in the diagnosis of FMF, some diagnostic procedures may help the physician. In this study, we aimed to compare the number of diagnostic procedures performed and number of physician referrals in early diagnosed and late diagnosed cases. Furthermore, we assessed which diagnostic approaches would affect the decision-making of physicians in the early diagnosed patients. MATERIALS AND METHODS: We enrolled into the study 143 FMF patients who met the Tel-Hashomer Criteria. Demographic variables, MEFV mutations (when available), diagnostic procedures (if performed) and specialist referrals were evaluated. Early diagnosis was defined as establishment of definite diagnosis within a 5-year period after the appearance of the first symptom. RESULTS: Early diagnosed were referred to physicians less often, and except for genetic testing, had fewer diagnostic procedures. In addition to clinical features, MEFV testing was found to be the only method that might influence the diagnosis by a physician. CONCLUSIONS: MEFV gene assessment, unlike other diagnostic procedures, might support physicians in the early diagnosis of FMF. Especially in atypical cases, MEFV gene assessment might be considered for diagnosis of FMF.

The clinicopathologic characteristics and prognostic factors of gastroesophageal junction tumors according to Siewert classification.

OBJECTIVE: The treatment of gastroesophageal junction tumors remains controversial due to confusion on whether they should be considered as primary esophageal or as gastric tumors. The incidence of these tumors with poor prognosis has increased, thus creating scientific interest on gastroesophageal cancers. Esophagogastric cancers are classified according to their location by Siewert, and the treatment of each type varies. We evaluated the prognostic factors and differences in clinicopathologic factors of patients with gastroesophageal junction tumor, who have been treated and followed-up in our clinics. MATERIAL AND METHODS: We retrospectively analyzed 187 patients with gastroesophageal junction tumors who have been operated and treated in the Oncology Department between 2005 and 2014. The chi-square test was used to evaluate differences in clinicopathologic factors among Siewert groups I, II and III. Prognostic factors were analyzed by univariate and multivariate analysis. RESULTS: The median age of our patients was 62 years, and approximately 70% was male. Nineteen patients (10.2%) had Siewert I tumors, 40 (21.4%) II, and the remaining 128 (64.4%) had Siewert III tumors. Siewert III tumors were at more advanced pathologic and T stages. Preoperative chemoradiotherapy was mostly applied to Siewert group I patients. There was no difference between the 3 groups in terms of recurrence. While the median overall survival and 2-year overall survival rate were 26.6 months and 39.6%, the median disease free survival and disease free survival rates were 16.5 months and 30.1%, respectively. The N stage, pathologic stage, vascular invasion, lymphatic invasion, perineural invasion, surgical margin, and grade were associated with both overall survival and disease free survival, while pathologic stage and presence of recurrence were significant factors for overall survival. The median disease free survival for Siewert III tumors was 20 months, 11.3 month for Siewert I tumors, and 14 months for Siewert II tumors, but the finding was not statistically significant (p=0.08). CONCLUSION: Although gastroesophageal junction tumors were grouped according to their location and they exerted different clinicopathologic properties, their prognosis was similar.

Correlation of Caveolin-1 Expression with Prognosis in Patients with Gastric Cancer after Gastrectomy.

BACKGROUND: Upregulation of caveolin-1 (Cav-1) expression is correlated with histopathological grade and poor prognosis in several human cancers. However, in gastric cancer, its clinical utility as a useful prognostic molecular marker remains unclear. METHODS: The prognostic importance of Cav-1 expression was retrospectively analyzed by immunohistochemistry in 148 patients with gastric cancer who had undergone radical gastrectomy. RESULTS: Cav-1 expression was positive in 23 (15.5%) patients and negative in 125 (84.5%) patients. Tumor location, tumor grade, lymph node involvement, pT stage, pTNM stage, and the presence of recurrence were found to be significantly associated with Cav-1 expression. The median disease-free survival (DFS) of patients with negative Cav-1 expression was significantly better than that of patients with positive Cav-1 expression (not reached vs. 10.2 months, p < 0.001). Moreover, patients with positive Cav-1 expression had a worse median overall survival (OS) compared to patients with negative Cav-1 expression (14.2 vs. 40.3 months, p = 0.004). In the multivariate analysis, Cav-1 expression (positive vs. negative) was an independent prognostic factor for DFS (p < 0.001, hazard ratio (HR) 2.58) and OS (p = 0.031, HR 1.87), as was lymph node metastasis. CONCLUSION: Our results suggest that positive Cav-1 expression is associated with progression and poor prognosis in gastric cancer patients after radical gastrectomy. Targeting Cav-1 would be a potential option for future gastric cancer treatment.

Evaluation of Bevacizumab in Advanced Small Bowel Adenocarcinoma.

BACKGROUND: Small bowel adenocarcinomas (SBAs) are rarely seen tumors. Data regarding the use of chemotherapy together with bevacizumab in patients with advanced SBA are lacking. The aim of this study was the evaluation of treatment with bevacizumab in advanced SBA. MATERIALS AND METHODS: Twenty-eight patients from 5 centers with a diagnosis of advanced SBA who received first-line treatments with modified FOLFOX6 (mFOLFOX6; oxaliplatin, leucovorin, and 5-fluorouracil) and FOLFIRI (leucovorin, 5-fluorouracil, and irinotecan) chemotherapy regimens were involved in the study. All patients were divided into 2 groups; those who received bevacizumab together with these chemotherapy regimens (Chemo+Bev group) and those who did not receive bevacizumab (Chemo group). RESULTS: The median progression-free survival (PFS) and overall survival (OS) times of all population were 8.7 months and 16.9 months, respectively. The overall response rate was 43.7% in the Chemo group and 58.3% in the Chemo+Bev group. The median PFSs in the Chemo and Chemo+Bev groups were found to be 7.7 months and 9.6 months, respectively, and the median OSs were 14.8 months and 18.5 months, respectively. There was not a significant difference between the groups in terms of overall response rate, PFS, and OS. CONCLUSION: Although there was no significant difference in any of the outcomes, use of bevacizumab together with chemotherapy is a more effective treatment approach compared with chemotherapy alone, and it does not cause an excess of significant toxicity.

Pretreatment PET/CT Standardized Uptake Values Play a Role in Predicting Response to Treatment and Survival in Patients with Small Cell Lung Cancer.

BACKGROUND: We investigated the role of standardized uptake values (SUVs) of the primary tumor in small cell lung cancer (SCLC) patients. PATIENTS AND METHODS: The relationship between SUV and response to treatment was investigated using receiver operating characteristic (ROC) curve analysis, and the efficient cut-off value for detecting response to treatment was determined. The effects of SUV on response to treatment and survival were investigated. RESULTS: 90 patients with a median age of 58 years (range 39-83 years) were included. Median follow-up was 11 months. The suitable cut-off SUV for determination of response was found to be 10 in ROC analysis. The sensitivity and specificity of this value were 85.7% (95% confidence interval (95% CI) 63-96) and 61.8% (95% CI 49-73) (area under the curve 0.783; p = 0.0001), respectively. The overall objective response rate in patients with involvement above the cut-off value was 93.3% compared to 59.1% in those with involvement below the cut-off value (p < 0.0001). In uni- and multivariate analysis, favorable effects of limited-stage disease on response to treatment were established (p < 0.05). The effect of an SUV higher than the cut-off value on progression-free survival was borderline (p = 0.085). CONCLUSION: These data may contribute to identifying prognostic disease characteristics and response to treatment.

Comparison of efficacy and safety of three different chemotherapy regimens delivered with concomitant radiotherapy in inoperable stage III non-small cell lung cancer patients.

Concomitant administration of chemotherapy and radiotherapy is currently recognized as the standard of treatment in locally advanced inoperable non-small cell lung cancer (NSCLC). Our study aimed to compare the efficacy and toxicities of three different chemotherapy regimens delivered concurrently with radiotherapy. We retrospectively reviewed the clinical records of patients who received the PE (cisplatin, 50 mg/m(2), on days 1, 8, 29, and 36 plus etoposide, 50 mg/m(2), on days 1 to 5 and 29 to 33), PD (docetaxel, 20 mg/m(2), on day 1 plus cisplatin, 20 mg/m(2), on day 1, every week), and PC (carboplatin, AUC 2 plus paclitaxel, 45 mg/m(2), on day 1, every week) regimens concurrently with radiotherapy. A total of 227 patients were evaluated in the study. Median follow-up time was 13 months (2-101). There were 27 females (11.9 %) and 200 males (88.1 %) with a median age of 61 (38-82) years. The PD group had higher rates of esophagitis, mucositis, and anemia (p < 0.05). The PC group had higher rates of neuropathy (p = 0.000). The progression-free survival (PFS) time was 10 months for patients in the PC group, 15 months for patients in the PD group, and 21 months for the PE group (p = 0.010). Patients in the PC group had a median overall survival time of 23 months, those in the PD group 27 months, and those in the PE group 36 months (p = 0.098). Combination of cisplatin-etoposide with radiotherapy led to a more favorable outcome compared with the other two regimens. It shows generally manageable toxicity profile and compliance to treatment is noticeable.

Evaluation of prognostic factors in localized high-grade undifferentiated pleomorphic sarcoma: report of a multi-institutional experience of Anatolian Society of Medical Oncology.

Most data on prognostic factors for patients with high-grade undifferentiated pleomorphic sarcoma (HGUPS) is obtained from analyses of soft tissue sarcomas. The purpose of this study was to evaluate the clinicopathologic features and their impact on outcomes specifically in patients diagnosed with HGUPS. In this multicenter trial, we retrospectively analyzed 112 patients who were diagnosed and treated at 12 different institutions in Turkey. We collected data concerning the patients, tumor characteristics, and treatment modalities. There were 69 males (61.6 %) and 43 females (38.4 %). Median age was 56 years (19-90). The most common anatomic site of tumor origin was the upper extremity. Pleomorphic variant was the predominant histological subtype. Median tumor size was 8.2 cm (0.6-30 cm). Tumors were mainly deeply seated (57.1 %). Fifty-seven patients (50.9 %) were stage II and the remainder were stage III at the time of diagnosis. Median follow-up was 30 months (2-160). The primary site of distant metastasis was the lung (73.5 %) and the second most common site was the liver (11.7 %). The 5-year overall survival, distant metastasis-free survival, and local recurrence-free survival rates were 56.3, 53.4, and 67.2 %, respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) performance score of II (p = 0.033), deep tumor location (p = 0.000), and development of distant metastasis (p = 0.004) were negatively correlated with overall survival, and perioperative radiotherapy and negative microscopic margins were significant factors for local control rates (p = 0.000 for each). Deep tumor location (p = 0.003) was the only adverse factor related to distant metastasis-free survival. Deep tumor location, ECOG performance score of II, and development of distant metastasis carry a poor prognostic implication on overall survival. These will aid clinicians in predicting survival and treatment decision.

Is second-line systemic chemotherapy beneficial in patients with non-small cell lung cancer (NSCLC)? A multicenter data evaluation by the Anatolian Society of Medical Oncology.

Patients with advanced non-small cell lung cancer (NSCLC) generally require second-line treatment although their prognosis is poor. In this multicenter study, we aimed to detect the characteristics related to patients and disease that can predict the response to second-line treatments in advanced NSCLC. Data of 904 patients who have progressed after receiving first-line platinum-based chemotherapy in 11 centers with the diagnosis of stage IIIB and IV NSCLC and who were evaluated for second-line treatment were retrospectively analyzed. The role of different factors in determining the benefit of second-line treatment was analyzed. Median age of patients was 57 years (range 19-86). Docetaxel was the most commonly used (20.9 %, n = 189) single agent, while gemcitabine-platinum was the most commonly used (6.7 %, n = 61) combination chemotherapy regimen in second-line setting. According to survival analysis, median progression-free survival after first-line treatment (PFS2) was 3.5 months (standard error (SE) 0.2; 95 % confidence interval (CI), 3.2-3.9), median overall survival (OS) was 6.7 months (SE 0.3; 95 % CI, 6.0-7.3). In multivariate analysis, independent factors affecting PFS2 were found to be hemoglobin (Hb) level over 12 g/dl and treatment-free interval (TFI) longer than 3 months (p = 0.006 and 0.003, respectively). Similarly, in OS analysis, Hb level over 12 g/dl and time elapsed after the first-line treatment that is longer than 3 months were found to be independent prognostic factors (p = 0.0001 and 0.045, respectively). In light of these findings, determining and using the parameters for which the treatment will be beneficial prior to second-line treatment can increase success rate.

Carbon-14 urea breath test: does it work in patients with partial gastric resection?

OBJECTIVE: The diagnostic value of Carbon-14 urea breath test (C-14 UBT) in the detection of Helicobacter pylori (H. pylori) infection in non-operated patients has been proved. However, the efficacy of C-14 UBT in patients with partial gastric resection (PGR) has not been evaluated yet. Herein, the results of the C-14 UBT and H. pylori stool antigen test (HpSAT) in this patient group were compared with the endoscopic findings. METHODS: Multi-breath samples C-14 UBT and HpSAT were performed in all patients on the same day. Histology was used as a gold standard for testing C-14 UBT and HpSAT diagnostic efficacies. RESULTS: 30 patients (mean age: 54.6 ± 11 year) with PGR were included. The sensitivity and specificity of standard C-14 UBT were 29 and 100 %, respectively. When breath samples were collected at 20th min, and >35 CPM was selected as radioactivity threshold, the sensitivity raised to 86 % without any loss of specificity. The specificity and sensitivity of the HpSAT were 71 and 96 %, respectively. CONCLUSIONS: The sensitivity of the standard C-14 UBT was very poor for patients with PGR, and results of HpSAT were superior in this population. Certain modifications are needed if C-14 UBT is to be used in PGR patients.

The changing of serum vitamin B12 and homocysteine levels after gastrectomy in patients with gastric cancer: do they associate with clinicopathological factors?

After total (TG) or distal subtotal gastrectomy (DG), patients are at high risk of vitamin B12 (vit-B12) deficiency, which results in elevation of homocysteine levels. The changing of serum vit-B12 and homocysteine levels in patients with gastric cancer is not well known. Seventy-two patients with gastric cancer who had undergone currative gastrectomy and 50 healthy controls were included. Serum vit-B12 and homocysteine levels were analyzed in gastric cancer patients. In addition, these parameters were compared with those of healthy control subjects. While serum vit-B12 levels in gastrectomized patients were significantly lower than that of healthy controls (221.8 ± 125.6 pg/mL vs. 309.9 ± 174.3 pg/mL, p = 0.002), homocysteine levels were significantly higher in patients with gastric cancer (14.2 ± 6.7 µmol/L vs. 12.5 ± 6.1 µmol/L, p = 0.016). Mean serum folate level was found to be high in healthy controls (7.3 ng/mL) compared to patients (9.2 ng/mL, p = 0.027). Out of 72 patients, 40 patients (55.6 %) with gastric cancer developed vit-B12 deficiency after gastrectomy. Vit-B12 deficiency was found to be related with gastrectomy type (p = 0.02) and homocysteine levels (p = 0.014). In patients who underwent TG, the incidence of vit-B12 deficiency was significantly higher compared with those with DG (67.5 vs. 32.5 %). In addition, serum vit-B12 level in patients with DG was significantly higher than that of patients with TG (248.3 ± 122.0 pg/mL vs. 200.8 ± 126.7 pg/mL, p = 0.041), whereas homocysteine levels were significantly lower in DG group compared with TG group (12.1 ± 6.1 µmol/L vs. 15.8 ± 6.9 µmol/L, p = 0.014). A logistic regression analysis showed that the extent of gastrectomy was found to be an independent factor for predicting the occurrence of vit-B12 deficiency (p < 0.001, odds ratio 1.38). Our results showed that cumulative vit-B12 deficiency rate was significantly higher after TG compared with that after DG, while homocysteine levels were significantly higher in TG group compared with DG group. The extent of gastrectomy was found to be an independent factor for predicting the occurrence of vit-B12 deficiency. Vit-B12 deficiency and hyperhomocysteinemia are imperious clinical situation for patients with gastric cancer after surgery. Hence, both preoperative and regular postoperative monitoring of vit-B12 and homocysteine levels for all gastrectomized patients with gastric cancer are important and necessary for early detection and prevention of vit-B12 deficiency and hyperhomocysteinemia as a risk factor for cardiovascular diseases.

Clinical importance of discordance of hormone receptors and Her2/neu status after neoadjuvant chemotherapy in breast cancer.

PURPOSE: The aim of this study was to compare the hormone receptors' (HR) and HER2/neu status between core needle biopsy (CNB) and residual tumor after surgery of breast cancer treated with neoadjuvant chemotherapy (NAC), and also to evaluate the impact of discordance and other clinicopathological factors on survival. METHODS: Oestrogen receptor (ER), progesterone receptor (PR) and HER2/neu status were evaluated by immunohistochemistry (IHC) on 90 CNBs of primary tumors and surgical specimens after NAC (study group); 53 patients without NAC served as control group, and discordance was compared between the two groups. The association between discordance of HR status after NAC and various other clinicopathological factors was tested with Spearman's test. RESULTS: Pathological complete response (PCR) was achieved in 10 (11.1%) patients after NAC. ER and PR changed significantly more in the study than in the control group. ER and PR discordance was detected in 10 (12.5%) and 17 (21.2%) patients in the NAC group and in 1 (1.8%) and 2 (3.7%) patients in the control group (p=0.04 and p=0.005, respectively). ER discordance was related with HER2/neu change. Furthermore, PR discordance correlated with CNB, ER and treatment response, while HER2/ neu discordance was associated with treatment response (p=0.05). ER discordance was found to be an independent prognostic factor for progression-free survival (PFS) (p=0.02). CONCLUSION: NAC might cause alterations in ER, PR or HER2//neu status in breast cancer, and they should be re-tested in the residual tumor after NAC to optimize adjuvant therapy.

Important Factors Affecting Adjuvant Treatment Decision in Stage IA Breast Cancer Patients in Turkey.

INTRODUCTION: In Turkey, the gene expression profile test is not standard, so adjuvant treatment is planned according to clinicopathological factors. Therefore, we retrospectively analyzed important parameters that affect the decision on adjuvant chemotherapy, and also factors related to survival in stage IA breast cancer patients in Turkey. METHODS: We retrospectively evaluated 347 stage IA patients. The relationship between the clinicopathological parameters and adjuvant chemotherapy was analyzed. RESULTS: The median age and follow-up time were 52 years (range: 25-86) and 22.6 months (range: 1-113), respectively. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 87.9% and 98.7%, respectively, but the median DFS was not reached. Age, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, and the presence of triple-negative breast tumor (TNBC) were related to DFS, and lymphovascular invasion (LVI), perineural invasion (PNI), HER2 status, the presence of TNBC, and recurrence were related to OS (p > 0.05). Furthermore, age, menopausal status, multicentricity, grade, tumor size, necrosis, ER, the presence of TNBC, and HER2 were found to be related to adjuvant therapy decision (p > 0.05). All these parameters, in addition to LVI and PNI, were independent factors for chemotherapy by logistic regression analysis. CONCLUSIONS: In decisions about adjuvant therapy in stage IA breast cancer patients, clinicopathological factors should be kept in mind.

Assesment of the patients presenting with severe anemia to the emergency internal medicine clinic.

OBJECTIVE: Etiological evaluation of the patients who were hospitalized with the diagnosis of severe anemia (Hb<7 gr/dl) in the emergency internal medicine clinic between January and July, 2013. METHODS: In this study, 112 patients who were hospitalized in Dr. Lutfi Kirdar Kartal Education and Research Hospital emergency internal medicine clinic with severe anemia between January and July 2013 were retrospectively analyzed. Patients' initial complaints, underlying causes of their anemia and prognosis of the patients were evaluated. RESULTS: The etiology of anemia was iron deficiency in 60 (53.6%), chronic kidney failure in 16 (14.2%), hematologic malignancies in 12 (10.7%), liver cirrhosis in 12 (10.7%) and other non-malignant hematologic disorders in 4 (3.6%) patients. CONCLUSION: The most common cause of anemia in patients who apply to emergency internal medicine clinic with severe anemia is iron deficiency. The most common complaints on admission are subjective ones such as weakness, fatigue and lassitude. Chronic disease anemia does not cause severe anemia as much as iron deficiency.

Endoscopic findings of dyspeptic patients unresponsive to proton pump inhibitors.

OBJECTIVE: To evaluate the endoscopic findings of dyspeptic patients unresponsive to proton pump inhibitors (PPIs) and analyze if there is any correlation between these findings and dyspeptic symptoms via predetermined inquiry. METHODS: Patients between 18 and 45 years of age were selected among those referred to our unit for upper GI endoscopy due to failure to achieve improvement in dyspeptic complaints with PPI. Patients who consent to participate in and eligible for the study were questioned for their symptoms using questionnaires. RESULTS: A total of 446 patients with female preponderance (60%) were included in the study. Endoscopic results were listed as: 147 (32.9%) normal, 16 (3.6%) gastric ulcer, 36 (8.1%) duodenal ulcer, 216 (48.4%) gastritis, 7 (1.5%) duodenitis and 24 (5.4%) esophagitis. A total of 122 patients were classified as functional dyspepsia. While incidence of persistent bloating was distinctly higher in patients with gastritis compared to those with normal endoscopic findings (p:0.000), but its incidence was comparable between ulcer and normal patients. No statistical difference was detected between gastritis, ulcer and normal endoscopy patients considering incidence of early satiety. Compared to those with normal endoscopy patients, incidence of epigastric pain was significantly higher among patients with gastritis and ulcer (p: 0.002 and p: 0.000 respectively). Incidence of heartburn was higher in patients with gastritis compared to those with normal endoscopy findings, but it was similar to those with ulcer. CONCLUSION: Most (67.1%) of the patients between 18 and 45 years of age with no alarm symptoms had diagnoses that required use of a PPI. Hence, the patients should be carefully evaluated before referring for endoscopy.

The prognostic value of detecting symptomatic or asymptomatic recurrence in patients with gastric cancer after a curative gastrectomy.

BACKGROUND: Although studies have investigated whether a routine follow-up should be performed after a gastrectomy, no consensus has been reached on the significance of the follow-up or the optimal surveillance protocol. In the present study, we evaluated the significance of the presence or absence of symptoms in the detection of recurrences after curative gastrectomy for gastric cancer. METHODS: We retrospectively analyzed 173 patients with recurrent gastric cancer who underwent radical gastrectomy. We evaluated the prognostic significance of the presence of cancer-related symptoms at the diagnosis of recurrence, and the relationship between the presence of symptoms and other clinicopathological factors. RESULTS: We detected a symptomatic recurrence in 42.2% of patients. The presence of symptoms were significantly correlated with tumor size, pT stage, pN stage, pathologic stage, and short disease-free interval (<12 mo). The median disease-free survival (DFS), post-recurrence survival (PRS), and overall survival (OS) times for patients with asymptomatic recurrence were significantly longer than those of patients with symptomatic recurrence (disease-free survival was corrected as DFS, 11.1 versus 9.3 mo, P < 0.001; PRS, 4.9 versus 3.1 mo, P = 0.02; OS, 18.3 versus 12.3 mo, P = 0.001, respectively). Multivariate analysis showed that the presence of cancer-related symptoms (P = 0.033; hazard ratio [HR], 0.81) was an independent prognostic factor for PRS, as were short disease-free intervals (P < 0.001; HR, 2.42), age (P = 0.02; HR, 1.53), and the presence of chemotherapy in recurrence (P = 0.001; HR, 0.49). In addition, multivariate analysis indicated that the presence of symptoms, short disease-free interval, and age were also independent prognostic indicators for OS. CONCLUSIONS: Our results demonstrate that symptomatic recurrence is an important prognostic factor for PRS of patients with gastric cancer after a curative gastrectomy. The presence of symptomatic recurrence may be a new and beneficial prognostic marker to evaluate biologic aggressiveness, which is an important determinant of survival at the time of recurrence diagnosis during a follow-up for gastric cancer.