Intraoperative ultrasonography-guided surgery: An effective modality for breast conservation after neo-adjuvant chemotherapy.

Margin status is one of the significant prognostic factors for recurrence in breast-conserving surgery (BCS). The issue that merits consideration for oncologic safety and cost-effectiveness about the modalities to assure clear margins at initial surgical intervention remains controversial after neo-adjuvant chemotherapy (NAC). The presented study aimed to assess the impact of intraoperative ultrasound (IOUS)-guided surgery on accurate localization of tumor site, adequacy of excision with clear margins, and healthy tissue sacrifice in BCS after NAC. Patients who had IOUS-guided BCS ater NAC were reviewed. No patient had preoperative localization with wire or radiotracer. Intraoperative real-time sonographic localization, sonographic margin assessment during resection, macroscopic and sonographic examination of specimen, and cavity shavings (CS) were done as the standard procedure. No frozen assessment was performed. One hundred ninety-four patients were included, in which 42.5% had pCR. IOUS-guided surgery accomplished successful localization of the targeted lesions in all patients. Per protocol, all inked margins on CS specimens were reported to be tumor-free in permanent histopathology. No re-excision or mastectomy was required. For a setting without CS, the negative predictive value (NPV) of IOUS rate was 96%. IOUS was found to over and underestimate tumor response to NAC both in 2% of patients. IOUS-guided surgery seems to be an efficient modality to perform adequate BCS after NAC with no additional localization method. Especially, when CS is integrated as a standard to BCS, IOUS seems to provide safe surgery for patients with no false negativity and a high rate of NPV.

Comparison of Gemcitabine monotherapy with Gemcitabine and Cisplatin combination in metastatic pancreatic cancer: a retrospective analysis.

PURPOSE: Gemcitabine is among the standard first-line agents for the treatment of metastatic pancreatic cancer. However, as the median survival with gemcitabine monotherapy is 6 months, different combinations are being studied for better, prolonged survival. In this multicenter study, we aimed to compare the results of gemcitabine monotherapy with those of gemcitabine and cisplatin combination therapy as first-line treatments for metastatic pancreatic cancer. METHODS: Data of 664 patients diagnosed with metastatic pancreatic cancer between January 2007 and December 2016 from seven oncology centers in Turkey were retrospectively evaluated, and 319 patients with gemcitabine alone (n=138) or gemcitabine and cisplatin combination (n=181) as first-line treatment were included. RESULTS: The median patient age was 62 years (range 42-79), being 60 years (42-75) in the gemcitabine/cisplatin arm and 67 years (52-79) in gemcitabine alone arm. no complete response was observed in either arm, whereas partial response rates were 30.1% in gemcitabine/cisplatin arm and 15.3% in gemcitabine alone arm (p=0.001). median overall survival was 8 months (95% CI:7.7-10.2) and was significantly longer in the gemcitabine/cisplatin arm than in the gemcitabine alone arm (10 vs. 6 months, p=0.004). CONCLUSION: The cemcitabine and cisplatin combination therapy as first-line treatment of metastatic pancreatic cancer yields significantly prolonged survival over gemcitabine monotherapy. In patients with favorable performance conditions, the combination therapy should be preferred.

The effects of zoledronic acid on ECG: a prospective study on patients with bone metastatic cancer.

INTRODUCTION: There are controversial results in the risk of atrial fibrillation as well as arrhythmogenic potential of bis-phosphonates. METHOD: 37 patients and 40 healthy controls were evaluated prospectively with regard to the cardiac side effects related to the use of zoledronic acid (ZA) and its effects on electrocardiography (ECG) parameters. RESULT: As the basal ECG results of the patients diagnosed with cancer compared with the control group, it was determined that QT maximum was significantly lower, QT minimum was significantly higher. However; it was determined that QT disp, P max, P min, and P disp values were not significantly different. There was no statistically significant difference in P max, P min, P disp, QT max, QT min, QT disp values of the ECG parameters measured from cancer patients, before and 60 minutes after ZA therapy. CONCLUSION: There were no significant alterations in ECG in the acute period, indicated that ZA had no arrhythmia potential in the early period in patients with no underlying cardiac disease. However: patients receiving ZA should be monitored more closely because of the risk of arrhythmia which may ensue due to hypocalcemia, hypomagnesemia, or other chemotherapeutics.

The influence of cisplatin, doxorubicin, pegylated doxorubicin, oxaliplatin and gemcitabine on mahlavu cell line.

PURPOSE: Hepatocellar carcinoma (HCC) remains a major health problem being the third leading cause of deaths due to cancer worldwide. Because HCC is known to be highly resistant to conventional systemic therapies, single-agent or combination of systemic therapies have been investigated. Today, sorafenib, a multikinase inhibitor, is the only approved systemic agent for the first line treatment of advanced HCC. In this study, we aimed to investigate the influence of different concentrations of cisplatin, doxorubicin, pegylated doxorubicin (PLD), oxaliplatin and gemcitabine by applying these agents either single or in combinations on mahlavu cell line. METHODS: HCC mahlavu cell line was used for the experiments. Cell death was measured by flow cytometry at 48 hrs after incubation with various concentrations (0.1 µg/ml, 1.0 µg/ml and 10 µg/ml) of the drugs. RESULTS: Cell death due to gemcitabine was found to be significantly higher than cell deaths caused by the other single agents including cisplatin, oxaliplatin, doxorubicin and PLD (p<0.001, p<0.001, p<0.001 and p=0.0049, respectively). There was no significant difference between gemcitabine and both the gemcitabine combination with doxorubicin and PLD (p=0.992 and p=0.441, respectively). CONCLUSION: This is a preliminary analysis evaluating the effect of the conventional chemotherapeutic agents on mahlavu cell line in vitro. The findings of this study suggest that gemcitabine-based therapies keep on being the prefered therapeutic approach for the treatment of HCC.

Cutaneous melanoma in Turkey: analysis of 1157 patients in the Melanoma Turkish Study.

PURPOSE: To develop a large Turkish National Melanoma registry in order to define demographic and clinicopathologic characteristics of patients with melanoma. METHODS: The data was collected from 1635 patients with melanoma through a web-based registry system in 22 centers. Herein we present the results of 1157 patients with cutaneous melanoma. RESULTS: The patient median age was 56.4 years and 646 (55.8%) were males. The commonest subtype was superficial spreading type (357, 30.9%). The commonest primary site was the lower extremities (N=353, 30.5%). The most common Breslow thickness was 1-2 mm (361 patients, 43.5%). Only 104 (12.5%) patients had a thickness <1mm. Among 694 patients with available data, 136 (19.6%) presented with stage 4 disease while the most frequent stage was stage 3, encountered in 393 (56.6% patients). CONCLUSION: Our melanoma registry is the largest in our country providing a snapshot view of cutaneous melanoma and its care. Our patients presented with more advanced stages and they had worse prognosis compared to SEER database.

MELD-sodium score and its prognostic value in malignancy-related ascites of pancreatic and gastric cancer.

BACKGROUND: Malignant ascites is a manifestation of end-stage events in a variety of cancers. There is significant lack of possible survival predictors in patients with malignancy-related ascites. Since the Model for End-Stage Liver Disease (MELD)-Na score has been shown to be a feasible and independent prognostic predictor for both short- and long-term outcome in HCC patients, we decided to test its prognostic role in other cancer types with ascites. MATERIAL AND METHODS: This is a retrospective study. The outpatient oncology clinic's records were screened for the period between 2004 and 2011. Eighty-two pancreatic and gastric cancer patients were enrolled into the study. RESULTS: The median age of patients was 59 (±12). Fifty-nine patients had gastric cancer and 23 had pancreatic cancer. Overall survival (OS) was 16.8 (IR, 1-98) months in gastric cancer and 16.3 (IR, 0.5-81) months in pancreatic cancer. There was no statistically significant difference between OS of gastric and pancreatic cancer. Progression-free survival (PFS) was statistically significantly longer in gastric cancer than pancreatic cancer with 16.5 (IR, 0.5-90) vs 6.5 (IR, 0.4-34) months (P = 0.04). Further analysis of data included stepwise multiple regression analysis with the dependent variable "overall survival." The model had two independent predictors and an R(2) of 82 % and a predicted R(2) of 81 %. Predictors for time to remission were PFS and MELD-Na. The regression equation for the model was: Overall survival =17.4- 0.522 MELD-Na + 0.902 PFS CONCLUSION: In this study we showed that progression-free survival and MELD-Na score are significantly related with overall survival. MELD-Na score can be one of the predictors of the survival and PFS in pancreatic and gastric cancer patients with ascites.

Piperacillin-tazobactam versus carbapenem therapy with and without amikacin as empirical treatment of febrile neutropenia in cancer patients: results of an open randomized trial at a university hospital.

OBJECTIVE: Empirical beta-lactam monotherapy has become the standard therapy in febrile neutropenia. The aim of this study was to compare the efficacy and safety of piperacillin-tazobactam versus carbapenem therapy with or without amikacin in adult patients with febrile neutropenia. METHODS: In this prospective, open, single-center study, 127 episodes were randomized to receive either piperacillin-tazobactam (4 x 4.5 g IV/day) or carbapenem [meropenem (3 x 1 g IV/day) or imipenem (4 x 500 mg IV/day)] with or without amikacin (1 g IV/day). Doses were adjusted according to renal function. Clinical response was determined during and at completion of therapy. RESULTS: One hundred and twenty episodes were assessable for efficacy (59 piperacillin-tazobactam, 61 carbapenem). Mean duration of treatment was 14.8 +/- 9.6 days in the piperacillin-tazobactam group and 14.7 +/- 8.8 days in the carbapenem group (P > 0.05). Mean days of fever resolution were 5.97 and 4.48 days for piperacillin-tazobactam and carbapenem groups, respectively (P > 0.05). Similar rates of success without modification were found in the piperacillin-tazobactam (87.9%) and in the carbapenem groups (75.4%; P > 0.05). Fungal infection occurrence rates were 30.5 and 18% in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.05). Antibiotic modification rates were 30.5 and 13.1% (P = 0.02) and the addition of glycopeptides to empirical antibiotic regimens rates were 15.3 and 44.3% for piperacillin-tazobactam and carbapenem groups, respectively (P = 0.001). The rude mortality rates were 14% (6/43) and 29.3% (12/41) in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.08). CONCLUSIONS: The effect of empirical regimen of piperacillin-tazobactam regimen is equivalent to carbapenem in adult febrile neutropenic patients.

Serum Sulphate Levels in Hemodialysis Patients.

OBJECTIVE: Sulphur, similar to phosphorus, is easily attached to organic compounds. The inadequate elimination of sulphate may cause high sulphate concentrations in hemodialysis (HD) patients because sulphate is low in free form in plasma. Although we are well aware of the accumulation of phosphorus in chronic dialysis patients, we do not have an adequate knowledge database about the sulphur compounds. This study was designed to determine the level of sulphate in hemodialysis patients. MATERIALS AND METHODS: Ninety-four prevalent HD patients and 33 patients without renal failure were included in the study. The serum inorganic sulphate levels were measured by turbidimetric technique. Moreover, the serum level of urea, creatinine, albumin, calcium, phosphorus, and parathyroid hormone concentrations was simultaneously recorded. RESULTS: Mean levels of plasma sulphate were significantly higher (0.56 ± 0.17 mM vs 0.31 ± 0.13 mM, p < 0.001) in HD patients. Serum sulphate level correlated with patient's age, serum albumin, serum BUN and creatinine, and serum phosphorus level in HD patients. Serum sulphate levels were not associated with serum parathyroid hormone levels. CONCLUSION: Serum sulphate levels were approximately twofold higher in HD patients than in the normal control group. Inorganic sulphate does not seem to accumulate in long-term dialysis patients, and mild increased serum levels of sulphate has no poor clinical outcome in these patients.

Neural cell adhesion molecule-180 expression as a prognostic criterion in colorectal carcinoma: feasible or not?

AIM: To evaluate the frequency of neural cell adhesion molecule (NCAM)-180 expression in fresh tumor tissue samples and to discuss the prognostic value of NCAM-180 in routine clinical practice. METHODS: Twenty-six patients (16 men, 10 women) with colorectal cancer were included in the study. Fresh tumor tissue samples and macroscopically healthy proximal margins of each specimen were subjected to flow-cytometric analysis for NCAM-180 expression. RESULTS: Flow-cytometric analysis determined NCAM-180 expression in whole tissue samples of macroscopically healthy colorectal tissues. However, NCAM-180 expression was positive in only one case (3.84%) with well-differentiated Stage II disease who experienced no active disease at 30 mon follow-up. CONCLUSION: As a consequence of the limited number of cases in our series, it might not be possible to make a generalisation, nevertheless the routine use of NCAM-180 expression as a prognostic marker for colorectal carcinoma seems to be unfeasible and not cost-effective in clinical practice due to its very low incidence.

Dyskeratosis congenita associated with hypocellular myelodysplastic syndrome: a case report.

A 16-year-old female patient presented with complaints of malaise, dizziness, syncope, and nausea of 1-week duration. On dermatologic examination there were telangiectasias, atrophic areas, and poikiloderma with both hypopigmentation and hyperpigmentation on the neck and the proximal parts of the thighs. The bone marrow biopsy specimen showed hypocellularity and dysplastic megakaryocytic and erythroid elements, findings consistent with hypocellular myelodysplastic syndrome, which was further confirmed by cytogenetic studies. Thereafter, she was referred for allogeneic bone marrow transplantation.

Gastric wall calcification in gastric cancer relapse: case report.

We present the case of a 53-year-old male with subtotal gastrectomy and gastrojejunostomy due to gastric cancer who later developed cancer relapse and diffuse plaque-like calcification in the residual gastric tissue. As far as we know, this is the first case in the English literature in whom gastric tumor calcification developed one year after gastric cancer operation. We also discuss possible mechanisms of gastric wall calcification in such cases.

Red Cell Distribution Width Has a Predictable Value for Differentiation of Provoked and Unprovoked Venous Thromboembolism.

Venous thromboembolism (VTE) is generally classified as provoked or unprovoked. This dichotomy is important for following patients, mortality rate, prognosis and whether more efficient therapy is needed. In VTE patients, during initial diagnosis, it is not known exactly whether red cell distribution width (RDW) have a predictable value for this differentiation and pathogenesis. In this study, 298 patients with VTE and 197 control subjects were included. Patients with VTE were defined as provoked or unprovoked with respect to physical examination findings and laboratory values. Changes in RDW were tested between VTE patients and control subjects, provoked and unprovoked VTE patients, and separately with control subjects. RDW was found to be high in provoked and unprovoked groups compared with control group (p < 0.001, p = 0.003 respectively). RDW was significantly high in provoked VTE patients group compared with unprovoked patients (p < 0.001) and a cut-off value was found to be 13.6 %. In ROC analysis, sensitivity was 90.19 % and specificity was 82 % (95 % CI 85.4-93. 8 % and 95 % CI 72.3-89. 6 % respectively). RDW could be used as a simple, costeffective and a reliable test independent of age in differentiation of provoked and unprovoked VTE. In order to better understand its role, prospective large homogenized population studies in different regions are necessary.

Using Interferon Alfa Before Tyrosine Kinase Inhibitors May Increase Survival in Patients With Metastatic Renal Cell Carcinoma: A Turkish Oncology Group (TOG) Study.

BACKGROUND: We aimed to investigate the outcomes of interferon alfa and sequencing tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: This multicenter study assessing the efficacy of TKIs after interferon alfa therapy in the first-line setting in patients with metastatic renal cell carcinoma. Patients (n = 104) from 8 centers in Turkey, who had been treated with interferon alfa in the first-line setting, were included in the study. Prognostic factors were evaluated for progression-free survival (PFS). RESULTS: The median age of the patients was 57 years. The median PFS of the patients treated with interferon alfa in the first-line was 3.6 months. A total of 61 patients received TKIs (sunitinib, n = 58; sorafenib, n = 3) after progression while on interferon alfa. The median PFS among the TKI-treated patients was 13.2 months. In the univariate analysis for interferon alfa treatment, neutrophil and hemoglobin level, platelet count, and Karnofsky performance status were the significant factors associated with PFS. In the univariate analysis for TKI treatment, neutrophil and hemoglobin levels were the significant factors for PFS. The median total PFS of the patients who had been treated with first-line interferon alfa and second-line TKIs was 24.9 months. CONCLUSION: This study showed that first-line interferon alfa treatment before TKIs may improve the total PFS in patients with metastatic renal cell carcinoma.

The prognostic role of inflammation and hormones in patients with metastatic cancer with cachexia.

We wanted to investigate the possible etiologic factors of cachexia. Forty-six patients diagnosed with cancer cachexia and 34 healthy controls were included in the study. Serum total testosterone, free testosterone, interleukin 1 (IL) alpha and beta, IL6, tumor necrosis factor (TNF) alpha, orexin, galanin, neuropeptide Y, tumor necrosis factor-like weak inducer of apoptosis and tumor necrosis factor receptor-associated factor 6, and C-reactive protein (CRP) levels were investigated. There were 36 male and 10 female patients in the cachexia group, and 24 male and 10 female patients in the control group. Median overall survival (OS) of the cachexia group after the diagnosis of cachexia was 8 (1-25) months. There were statistically significant relationships between OS and BMI, serum CRP, TRAF-6, albumin, and LDH levels in the cachexia group. In addition to cachexia, serum CRP, testosterone, and TNF alpha levels were statistically significantly correlated with OS in refractory cachexia. TRAF-6 levels was significantly correlated with type of cancer (P = 0.02). Although cachexia presents with a multifactorial ethio-pathogenesis, few of them affect the OS. Our novel results were that serum CRP, albumin, LDH, and TRAF-6 levels have a higher association with OS in patients with cancer cachexia compared to the many other parameters. An ongoing cachexia also called refractory cachexia is a recent definition. This end-stage term of cancer duration may be predicted by decreasing serum testosterone and increasing serum TNF alpha levels, as well as serum CRP levels.

Increased serum tumor necrosis factor receptor-associated factor-6 expression in patients with non-metastatic triple-negative breast cancer.

Obesity appears to be associated with an increased risk of breast cancer (BC) and an inferior oncological outcome at the time of diagnosis, with poor outcomes most prominent in cases of triple-negative BC (TNBC). The present study analyzed serum tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and TNF receptor associated factor-6 (TRAF) protein expression levels in 48 patients with non-metastatic BC and 26 obese control patients (without BC). The mean age of the cohort was 52.5 years (range, 35-78 years) and the patients had a median body mass index of 33.5 kg/m2 (range, 30-47 kg/m2). In the study population, 27.1% of BC patients were triple negative and 70.8% were hormone receptor (HR)-positive. Median serum TRAF6 expression was 0.90 ng/ml (range, 0.55-1.53 ng/ml) in the 13 TNBC patients and 0.63 ng/ml (range, 0.49-1.22 ng/ml) in the 35 HR-positive BC patients; thus, TRAF6 expression was significantly higher in the TNBC patients compared with the obese control group (0.90 vs. 0.73 ng/ml; P=0.033). Furthermore, median serum TRAF6 expression levels were significantly higher in HR-negative patients compared with HR-positive patients (0.83 vs. 0.62 ng/ml; P=0.002). The present study demonstrated that serum TRAF6 expression levels were increased in TNBC and HR-negative patients with non-metastatic BC compared with HR- and human epidermal growth factor receptor 2-positive cases or the obese healthy control group. Therefore, elevated TRAF6 expression may be a poor prognostic factor in non-metastatic BC. In addition, we propose that progesterone (PR) negativity may be a more useful poor prognosis factor than estrogen receptor (ER) negativity, as TRAF6 expression levels were higher in the PR-negative patients compared with the ER-negative patients.

Prospective study of combined modality treatment or radiotherapy alone in the management of early-stage adult Hodgkin's disease.

PURPOSE: To determine the efficacy and toxicity of combined modality treatment (CMT) or radiotherapy (RT) alone in the management of clinical Stage I-IIA adult Hodgkin's disease patients. METHODS AND MATERIALS: Forty-seven patients with supradiaphragmatic clinical Stage I-IIA Hodgkin's disease without bulky mediastinal lymphadenopathy were enrolled into this prospective study between September 1997 and February 2002. Patients with very favorable criteria presenting with one or two nonbulky nodal areas involved, an erythrocyte sedimentation rate of <50 mm/h, age <40 years, and either lymphocyte predominant or nodular sclerosing histologic findings were treated by RT alone. Patients missing any of these favorable criteria were classified as the other favorable group and were treated with three courses of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy followed by involved-field RT. The median age was 36 years (range, 19-53 years). Of the 47 patients, 15 were women and 32 were men. Only 3 patients were classified as the most favorable group and treated with mantle RT alone; the remaining 44 were treated with CMT. RESULTS: The median follow-up was 51 months (range, 20-74 months). Only 2 patients developed recurrence, both out of the irradiated field, one in the contralateral neck and the other in the abdomen. The 5-year relapse-free and overall survival rate was 95.4% and 97.8%, respectively. Although none of the prognostic factors were statistically significant for relapse-free survival, a trend was noted for the response to chemotherapy (p = 0.06). Only 2 patients developed treatment-related complications. One patient treated with mantle RT alone developed severe ischemic heart disease and one in the CMT arm developed subclinical hypothyroidism. CONCLUSION: Despite the short follow-up, CMT or RT alone tailored according to the clinical prognostic factors were successful in terms of disease control in clinical Stage I-IIA Hodgkin's disease. Longer follow-up is required to make definitive conclusions.

Cardiac tuberculosis with multiple intracardiac masses: a case report.

In this report, clinical, echocardiographic, and pathologic findings of a patient with multiple masses caused by tuberculosis both in the left and right side of the heart are presented. After antituberculosis treatment some of the masses disappeared and some became smaller. Although an intracardiac mass caused by tuberculosis is very rare, it should be considered in the list of masses detected by echocardiography.

Generalized lymphadenopathy: a rare presentation of disseminated prostate cancer.

Prostate cancer most often metastases to regional lymph nodes and bones by hematogenous or lymphatic spread. Metastases to the supradiaphragmatic nodes are rare. A 56-yr-old male smoker with generalized lymphadenopathy was referred to our center with the complaints of weight loss of 15 kg and severe back and leg pain. On computed tomography of the thorax and abdomen, massive mediastinal, intra-abdominal, retroperitoneal, and inguinal lymphadenopathies with hydroureteronephrosis of the left kidney were noted. Excisional biopsy of left cervical lymph node revealed metastasis of prostatic adenocarcinoma and transrectal biopsy of the prostate disclosed poorly differentiated adenocarcinoma. Bone marrow aspiration biopsy, done for the differential diagnosis of anemia, also showed infiltration with prostate-specific antigen positive neoplastic cells. Supradiaphragmatic spread of prostate cancer has been postulated to be by a hematogenous route via the vertebral venous system, or Batson's plexus, accessible via direct extension from the primary cancer site.

Old antihypertensives as novel antineoplastics: angiotensin-I-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists.

Angiogenesis, cellular growth and invasion of a cancer cell are attractive targets for new treatment strategies of malignancies in recent years. The evidences are accumulating that ACE inhibitors and angiotensin II type 1 antagonists could be novel anti-angiogenic, anti-invasive, and even anti-growth agents against neoplastic tissues: The renin-angiotensin system promotes angiogenesis directly or indirectly and growth of neoplastic cell. Some tumors carry angiotensin II type 1 receptors. Angiotensin II antagonists and angiotensin-I-converting enzyme inhibitors have shown some anti-neoplastic actions. Angiotensin II receptor blocker losartan antagonises platelets, which are thought to modulate via vascular endothelial growth factor. They may even protect the patient from the major toxicity of chemotherapy and/or radiotherapy, myelotoxicity, enabling us to give higher doses and end up with higher success rate. We believe that these agents can be useful on clinical grounds and suggest their incorporation into clinical studies.