Favorable outcome with sentinel lymph node biopsy alone after neoadjuvant chemotherapy in clinically node positive breast cancer at diagnosis: Turkish Multicentric NEOSENTI-TURK MF-18-02-study.

PURPOSE: Factors affecting local outcome were evaluated in patients with clinically node-positive (cN+) breast cancer at diagnosis, who underwent sentinel lymph node biopsy (SLNB) alone after neoadjuvant chemotherapy (NAC). METHODS: Between 2004 and 2018, 303 cytopathology-proven cN (+) patients in a multicentric registry, who received NAC and underwent SLNB alone were analysed. All patients had regional nodal irradiation. RESULTS: Median age was 46 (23-70). Of those, 211 patients had ypN0 disease (69.6%), whereas 92 patients had ypN (+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastases (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 36 months (24-172), one patient (0.3%) with macrometastatic SLN was found to have locoregional recurrence as chest wall and supraclavicular LN metastases at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were 87% and 95%, respectively. Patients with cT3/4 (HR = 2.41, 95% CI; 1.14-5.07), non-luminal molecular pathology (HR = 2.60, 95% CI, 1.16-5.82), and non-pCR in the breast (HR = 2.11, 95% CI, 0.89-5.01) were found to have an increased HR compared to others in 5-year DFS. However, no difference could be found between ypN0 and ypN ITC and micrometastasis (HR = 1.23, 95% CI, 0.44-3.47), whereas there was a slight increase in HR of patients with ypN macrometastasis versus ypN0 (HR = 1.91, 95% CI, 0.63-5.79). CONCLUSION: ALND could be avoided in meticulously selected cN (+) patients who underwent SLNB after NAC having breast and/or nodal pCR, cT1-2, or low volume residual nodal disease with luminal pathology, as long as axillary radiotherapy is provided.

TWIST1 Gene Expression as a Biomarker for Predicting Primary Doxorubicin Resistance in Breast Cancer.

Doxorubicin is one of the most commonly used chemotherapeutic agents for adjuvant chemotherapy of breast cancer. In the studies focused on finding biomarkers to predict the response of the patients and tumors to the drugs used, the Twist transcription factor has been suggested as a candidate biomarker for predicting chemo-resistance of breast tumors. In this study, we aimed to investigate the relationship between TWIST transcription factor expression and the effectiveness of doxorubicin treatment on directly taken primary tumor samples from chemotherapy-naive breast cancer patients. Twenty-six primary breast tumor samples taken from 26 different breast cancer patients were included in this study. Adenosine triphosphate tumor chemo-sensitivity assay (ATP-TCA) has been used to determine tumor response to doxorubicin and real-time reverse-transcription polymerase chain reaction (RT-PCR) was used for analyzing the TWIST1 gene expression of tumors. There was a significant difference in TWIST gene expression between responder and non responder tumors (p <0.05). The TWIST gene expression of the drug-resistant group was higher than the responsive group. This difference was not dependent on the histopathological features of tumors. In conclusion, compatible with earlier studies that have been performed with cell lines, the current study supports the role of higher TWIST gene expression as a biomarker for predicting the response of breast tumors to chemo-therapeutic agent doxorubicin.

Preoperative chemotherapy for T2 breast cancer is associated with improved surgical outcome.

BACKGROUND: The aim of this study is to compare the clinical outcome in T2 breast cancer patients who underwent preoperative chemotherapy (PC) and who did not. The study also tried to define a subgroup of patients, who are more beneficial after PC in terms of lower re-excision rates, better cosmetic results and local recurrence free survival. MATERIALS AND METHODS: 251 consecutive patients treated for nonmetastatic T2 invasive breast cancer were analyzed retrospectively. Of those; 141 underwent primary surgery (PS) followed by chemotherapy, whereas 110 were treated with combination of PC and surgery. RESULTS: The patients who were treated with PC had a significantly higher incidence of negative margins and lower rate of re-excision (5% vs. 16%, p = 0.02). Of all patients attempted breast conserving surgery (BCS), patients in the PC group were more likely to undergo BCS as their definitive operation compared to patients with PS group (BCS rates; PC group: 99% vs. PS group: 92%, p = 0.05). Multifocal disease (OR: 7, 95% Cl, 2.7-18.4, p = 0.0001) and PC (OR = 0.2; 95% CI, 0.06-0.72, p = 0.01) were factors associated with margin positivity in patients treated with BCS. There was no statistically significant difference in 5 year local-recurrence free survival rates between 2 groups. CONCLUSIONS: Our study shows that PC significantly decreases the re-excision in patients undergoing BCS with primary T2 breast tumors. This data suggests that any patient with a tumor greater than 2 cm might be considered for PC to increase BCS success with final negative margins.

The diagnostic, predictive, and prognostic role of serum epithelial cell adhesion molecule (EpCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in breast cancer.

The purpose of this study was to determine the clinical significance of vascular cell adhesion molecule-1 (VCAM-1) and epithelial cell adhesion molecule (EpCAM) in breast cancer (BC) patients. Ninety-six BC patients and 30 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich (enzyme-linked immunosorbent assay (ELISA)). The median age at diagnosis was 48 years (range 29-80 years). Majority of the patients (71 %) had luminal subtype, and 38.5 % had metastatic disease. Twenty-nine (30 %) patients showed tumor progression, and 20 (21 %) patients died during follow-up. Median progression-free survival (PFS) and overall survival (OS) were 8.6 ± 1.7 and 35.5 ± 1.5 months, respectively. The baseline serum EpCAM levels of the patients were significantly higher than those of the controls (p < 0.001). There was no significant difference in the serum levels of VCAM-1 between the patients and controls (p = 0.47). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p > 0.05). Patients with HER-2-positive and triple-negative tumors had significantly poorer PFS (p = 0.04 and p = 0.001, respectively), while metastatic disease and chemotherapy unresponsiveness had significantly adverse effect on OS analysis (p < 0.001 and p < 0.001, respectively). Neither serum VCAM-1 levels nor serum EpCAM levels were identified to have a prognostic role on either PFS or OS (VCAM-1 p = 0.76 and p = 0.32; EpCAM p = 0.16 and p = 0.69, respectively). Even though any predictive or prognostic role could not be determined for both markers, serum levels of EpCAM were found to have diagnostic value in BC patients.

Is there any diagnostic value of serum protease-activated receptor-1 (PAR1) levels on determination of epithelial ovarian carcinoma?

The role of molecular markers in ovarian cancer is still a matter of debate. Protease-activated receptor-1 (PAR1) might be a good marker in some types of malignant tumors and might provide useful information in diagnosis and prognosis. The objective of this study was to evaluate the serum levels of PAR1 in regard to diagnostic, predictive, and prognostic value in epithelial ovarian cancer (EOC) patients. Forty-four EOC patients were enrolled in this study. Serum PAR1 levels were determined by enzyme-linked immunosorbent assay (ELISA) method. Twenty-five age- and sex-matched healthy controls were included in the analysis. The median age of patients was 58 years old, ranging from 22 to 83 years, where most of them had advanced disease (stage III-IV) (n = 40, 91%). The median serum PAR1 values were significantly elevated in patients compared to healthy controls (1.52 ng/ml vs. 1.13 ng/ml) (p = 0.03), whereas any clinical variables including response to chemotherapy did not associate with serum assay (p > 0.05). Progression-free survival (PFS) and overall survival (OS) of patients who did not respond to chemotherapy nor had platinum resistance in relapsed disease were poorer in the analyses. On the other hand, serum PAR1 levels showed no significant adverse effect on either PFS or OS (p = 0.43 and p = 0.49, respectively). These results proved that baseline serum PAR1 levels of patients with EOC were significantly higher than those of healthy people. However, these assays suggested no predictive or prognostic value in this group of patients.

Detection of human papillomavirus DNA by polymerase chain reaction and southern blot hybridization in colorectal cancer patients.

PURPOSE: The molecular mechanisms related to colorectal carcinogenesis are controversial. The purpose of this study was to evaluate the possible role of high-risk oncogenic human papillomavirus (HPV) types in the pathogenesis of colorectal cancer. PATIENTS AND METHODS: Tumor, and corresponding normal mucosal tissue specimens were obtained soon after surgery from 56 patients with colorectal adenocarcinoma. We studied both neoplastic and normal colon tissues for the presence of HPV types 6, 11, 16, 18, and 33. After the isolation of DNA, the presence of specific types of HPV DNA was determined by polymerase chain reaction (PCR) and southern blot hybridization. RESULTS: HPV DNA was detected in 46 (82.14 %) of 56 colorectal adenocarcinomas and in 18 (32 %) of 56 normal colonic mucosal tissue samples. Two or more HPV types were detected in 32 carcinoma samples. HPV type 18 (n= 40) and 33 (n= 32) were the most frequently detected types of HPVs in the tumor tissues. None of the normal mucosal specimens revealed HPV 18 DNA. The expression rate of HPV DNA in tumor tissue was significantly higher than that encountered in normal colonic mucosa (p <0.001). CONCLUSION: Detection of HPV DNA types 18 and 33 in most of the colorectal adenocarcinoma specimens suggests that HPVs may be related to carcinogenesis in glandular cells of the colorectal mucosa of our patient population.

Effect of oral administration of kefir on serum proinflammatory cytokines on 5-FU induced oral mucositis in patients with colorectal cancer.

In order to investigate the effect of kefir consumption on mucositis induced by 5-FU based chemotherapy (CT), we monitored the systemic immune response by measurement of the serum proinflammatory cytokine levels and we evaluated the anti-microbial effect of kefir with an agar diffusion method. Forty patients with colorectal cancer were included in this randomized prospective study. On the first 5 days of each CT cycle, the study group received oral lavage with kefir and then swallowed 250 ml of kefir while control group received oral lavage with 0.09% NaCl twice a day. Before and after every cycle of CT, the oral mucosa was assessed. Serum proinflammatory cytokine levels were evaluated before the initiation and after the third and the sixth cycle. Kefir was administered in 99 out of 205 courses. Mucositis developed in 27.3% of the courses given with kefir administration and in 21.7% of the courses given with 0.9% NaCl oral rinses. The difference between the two groups was not statistically significant (p > 0.05). When we compared the serum proinflammatory cytokine levels of the two groups at the baseline and following the third and the sixth cycles, we again found no statistically significant difference (p > 0.05). Kefir consumption at the mentioned doses made no statistically significant effect on serum proinflammatory cytokine levels and on the incidence of mucositis development in cancer patients. Under in vitro conditions, kefir inhibits only Staphylococcus epidermidis.

MAPK overexpression is associated with anthracycline resistance and increased risk for recurrence in patients with triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer is estimated to account for 15%-20% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular factors in patients with triple-negative breast cancer. PATIENTS AND METHODS: Tumor specimens from 109 patients with receptor-negative (estrogen receptor and progesterone receptor) breast cancer were analyzed for mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR) and phosphoinositol-3-kinase (PI3K) expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables, was investigated. RESULTS: Fifteen (13.8%), 38 (34.9%) and 33 patients (30.3%) had positive staining for EGFR, MAPK and PI3K, respectively. MAPK was associated with anthracycline resistance (P = 0.008) and lower MAPK score was significantly associated with shorter disease-free survival (P = 0.029). Survival following relapse was significantly worse for those with a higher MAPK score (P = 0.03). CONCLUSION: MAPK is a significant prognostic and predictive factor in patients with triple-negative breast cancer. Furthermore, the level of staining among those with a positive MAPK expression may play a prognostic role at different stages of relapse. Further translational research is required to elucidate molecular mechanisms of tumor proliferation in this subset of patients.

Isolated lung perfusion with Paclitaxel and docetaxel: comparison of the early effects on pulmonary physiology.

BACKGROUND: This study was designed to compare the early effects of docetaxel and paclitaxel on pulmonary physiology after isolated lung perfusion. METHODS: Rats underwent isolated left lung perfusion with docetaxel in group 1 (n = 5), paclitaxel in group 2 (n = 5), and 0.9 %NaCl in the control group (n = 5). Ventilation pressures, compliance of the lungs, blood gas analysis and histopathological results were compared between the groups. RESULTS: In group 1 and group 2, the decrease in PaO (2) (p = 0.008) and increase in ventilation pressures were significantly higher than in the control group ( P = 0.016). In group 2, pCO (2) retention was higher compared to the docetaxel perfusion group ( P = 0.016). In the histochemical assessment, intra-alveolar hemorrhage and mononuclear cell infiltration were dense and perivascular edema was not present in group 1. In group 2, perivascular and intraalveolar edema were found to be dense. CONCLUSION: Perfusion by either of the chemotherapeutics resulted in an alteration of lung physiology in rat lungs. If isolated lung perfusion is administered using chemotherapeutics from the taxanes group, it is suggested that docetaxel could be the first choice for isolated lung perfusion.

Prognostic factors and survival in patients with metastatic or recurrent carcinoma of the uterine cervix.

The aim of this study is to identify the impact of various prognostic factors on survival in patients with recurrent carcinoma of the uterine cervix. Fifty-two patients who were treated with platinum-based chemotherapy for recurrent or metastatic disease were retrospectively evaluated. Twenty-seven patients (90%) had received pelvic radiation as primary treatment. Out of 45 evaluable patients, two (4.4%) had complete response (CR), three (6.7%) had a continuous CR after additional surgical treatment and irradiation. Five patients (11.1%) had partial response (PR). The majority of patients had progressive response to treatment (22 patients, 48.9%). After a median follow-up period of 19 months, 31 patients (60%) had died. Progression-free survival after initial diagnosis was observed to have a significant association with response to chemotherapy for recurrent disease (Fisher two-sided P = 0.027). The median survival duration for relapsed disease was 11.8 months. Those with a longer disease-free interval ( 8 months vs.

Combination chemotherapy with docetaxel and irinotecan in metastatic malignant melanoma.

AIM: The aim of the current trial was to assess the efficacy and toxicity of 3-weekly intravenous docetaxel and irinotecan in the treatment of patients with metastatic malignant melanoma. MATERIALS AND METHODS: Sixteen patients with no history of previous cytotoxic agents or immunological treatment for advanced disease were treated with docetaxel 50 mg/m2 and irinotecan 150 mg/m2 intravenously over 60 min every 21 days. Prior immunotherapy with interferon and chemotherapy for adjuvant therapies were accepted provided there was a minimum 4-week treatment-free interval. Response evaluation was performed after two cycles. RESULTS: None of the patients had chemotherapy-induced tumour response. Eight patients achieved stable disease and others had progression of disease. The median survival time was 136 days (95% CI: 30.2-241.8), and the 3-month survival rate was 62.5%. Patients with stable disease (n = 8) had a longer survival than non-responders (P = 0.023, Breslow test). Generally side effects were mild and tolerable. Grade III-IV haematological toxicity occurred in approximately 10%. Severe emesis, stomatitis and diarrhoea was seen in less than 20% of the patients. Alopecia was observed in all patients. CONCLUSION: A 3-weekly intravenous docetaxel and irinotecan combination appears to be inactive in the treatment of patients with malignant melanoma and has not been recommended.

Efficacy of cisplatin and cyclophosphamide combination for recurrent and metastatic carcinoma of the uterine cervix.

The efficacy of a combination of cyclophosphamide and cisplatin in patients with metastatic and recurrent carcinoma of the cervix, was tested. Thirty patients were included in the study. Initially, 27 patients (90%) had received pelvic radiation and intracavitary boost and one patient was additionally given paraaortic radiation. Cisplatin was given at 75 mg/m2 followed by cyclophosphamide at 750 mg/m2 on day 1 with three weekly intervals for a maximum of six cycles. All patients received a median of four cycles of chemotherapy. The overall response rate for all eligible patients was 20% (continuous CR: 1, CR: 1, PR: 4 patients). Overall response rate and progressive response in patients with relapse within the previous radiation field were 9.5% and 66.7%, respectively; while for patients who had recurrent disease outside any irradiated area both were 44.4%. Eighteen patients (60%) had early withdrawal from the planned schedule, which was due to patient incompliance in seven patients (23.3%), disease progression in ten (33.3%) and early death after the first cycle in one patient (3.3%). Anemia was the most frequent toxicity, necessiating 24 transfusions in nine patients (30%). WHO grade 3 and 4 toxicity were anemia: 13 (43.3%), leucopenia: one (3.3%), thrombocytopenia: two (6.6%), renal: one, emesis: nine (30.0%) patients. The median survival duration for all eligible patients was 11 months. Univariate analysis revealed that progressive response to chemotherapy was the only prognostic factor for survival (7.1 vs 16.8 months, p = 0.003). The combination of cisplatin and cyclophosphamide did not appear to be more active than single agent cisplatin in this patient group with a relatively poor prognosis. Further studies are required to determine a better therapeutic approach for patients with relapsed carcinoma of the cervix.

Acetaminophen modulations of chemotherapy efficacy in MDAH 2774 human endometrioid ovarian cancer cells in vitro.

Epidemiological data have correlated consumption of nonsteroidal antinflammatory drugs with lowered risk for many types of cancer, and some recent studies indicate a reverse correlation with acetaminophen consumption and ovarian malignancy. In this study we examined effects of acetaminophen on plating, S-phase and colony growth of MDAH 2774 human endometrioid ovarian carcinoma, as well as sensitivity of this cell line to carboplatin in all three tests, and paclitaxel to clonogenic assay. Acetaminophen significantly enhanced S-phase in first 72 hours and enhanced cell population in 96 hours of plating monitorization, but decreased one week colony growth by approximately 80%, which was in the range of cytotoxic drugs. Interestingly with low dose carboplatin in first 72 hours acetaminophen enhanced cell proliferation more profoundly, but only thereafter decreased cell growth synergistically with carboplatin. It did not effect paclitaxel colony growth inhibiting acitivity. MDAH-2774 cell line lack p-53 and MSH-2, which are both 'gatekeeper' apoptosis inducing genes against genome damaging insult. Thus, presence of lower doses of oxidizing drugs may help the induction of proliferative signals, but only their sustained presence may overcome such signals and ultimately bring to cell demise.

An atypical presentation of metastatic gestational choriocarcinoma with maxillary sinus and subcutaneous involvement; report of a case with literature review.

Extragonadal germ cell tumors are rare neoplasms with histologic features comparable to those of gonadal origin. In this case report we present a 21-year-old female patient with an atypical localization of metastatic gestational choriocarcinoma. She was admitted to our hospital with recurrent epistaxis, abnormal vaginal bleeding, rectal bleeding, subcutaneous nodules on both thighs and forearms and left maxillary mass with intranasal cavity invasion. Laboratory analysis revealed significant elevation in serum beta-human chorionic gonodotropin (beta-HCG) level. Abdominal computerized tomography (CT) revealed left renal and retroperitoneal masses and thoracic CT displayed multiple bilateral lung metastases. Histopathological evaluation of the biopsy specimen obtained from the maxillary sinus showed choriocarcinoma. Based on WHO criteria she was classified as high-risk metastatic choriocarcinoma and treated with combination chemotherapy. We believe that in young women with recurrent epistaxis, gross abnormal vaginal and rectal bleeding and atypical maxillary sinus tumor with multiple lung metastases, choriocarcinoma should be included in the differential diagnosis and previous history of pregnancy or abortion should be obtained.

Biological considerations in locally advanced breast cancer treated with anthracycline-based neoadjuvant chemotherapy: thymidine labelling index is an independent indicator of clinical outcome.

The present retrospective study aims to determine the clinical value of thymidine labelling index (TLI) together with other established clinical and biological factors in 116 locally advanced breast cancer (LABC) patients treated with anthracycline-based neoadjuvant chemotherapy, surgery, adjuvant chemotherapy and radiotherapy. TLI was determined in 71 LABC patients with a median of 2.62% (0-23.64%) and a mean of 4.71% +/- 5.54. As a result of neoadjuvant chemotherapy, 85 patients (73%) responded to chemotherapy (CT), whereas 31 patients were unresponsive (27%). No relationship has been found between the pretreatment biological variables including TLI, estrogen receptor (ER), progesteron receptor (PgR) status and clinical parameters such as the chemotherapy response rates and axillary lymph node involvement following chemotherapy. Median follow-up was 35 months (18-97 months) and the 3-year overall survival (OS) and disease free survival (DFS) rates were 71.6% and 52.2%, respectively. In univariate analysis, patients with inflammatory breast cancer, high TLI-index (> or = 2.62%), lymph node (LN) positivity or > 3 positive lymph nodes following neoadjuvant chemotherapy and without any response to neoadjuvant chemotherapy were found to have worse DFS and OS-rates and high local and systemic recurrence rates. In multivariate analysis, TLI was estimated as the most powerful independent factor affecting the OS in LABC patients among the other established clinical and biological parameters (p = 0.02). These results suggest that TLI is an important independent indicator of clinical outcome in patients with LABC and these patients with high TLI levels require more effective treatment modalities.

Vascularization pattern of C6 glioma is modified with medroxyprogesterone acetate and ibuprofen in Wistar rat brain.

Beneficial effects of medroxyprogesterone acetate (MPA) in cancer therapy is partly mediated via its antiangiogenic activity. The same is true for the antitumoral action of non-steroidal antiinflammatory drugs. We have studied two liposoluble drugs, MPA and the analgesic ibuprofen, on glioma vascularization in vivo. In this study we have shown that, until the sacrifice at 27. day after tumor inoculation in the right hemisphere, MPA had a slight though insignificant activity to reduce the fatality of C6 glioma, growing in right cerebral hemisphere of male Wistar rats. But ibuprofen both alone or with MPA had no effect on survival with gavage application of a 30 mg/kg/day dosing regime. On histological analysis, intra- and peritumoral vessels were counted. Progesterone seemed to lower intratumoral, but to increase peritumoral vessels, especially glomeruloids, around the tumor mass. Coadministration of ibuprofen acted to suppress the peritumoral vessel increase, and to enhance lymphomonocytic infiltration around tumor vessels.

Thymidine labeling index in epithelial ovarian cancer.

OBJECTIVE: The aim of this study is to determine the thymidine labeling index and its prognostic role in patients with ovarian cancer. METHODS: Tumor cell proliferation in 32 patients with primary ovarian cancer admitted to Istanbul Medical Faculty, Department of Obstetrics and Gynecology, between 1993 and 1997 was investigated using the [3H]thymidine labeling index (TLI). TLI results were compared with other clinical and histopathologic prognostic parameters. RESULTS: The mean and median TLI values of the patients were 9.3+/-6.2% and 9.20% (range: 0.4-23.0%), respectively. Sixteen patients showed high proliferation rates (mean TLI: 14.3%). These patients had an overall survival rate of 46.7% at 3 years. The mean TLI level and overall survival at 3 years in the low proliferation rate group were 4.4 and 68.8%, respectively. Patients with a high TLI had a significantly shorter survival compared to those with a low TLI (P<0.01). There was tendency towards a higher TLI with advanced stage (P>0.05). However, there was no statistically significant correlation between TLI and other prognostic parameters. CONCLUSION: TLI may have a predictive value in determining the outcome of patients with ovarian cancer. Further larger scale studies are needed before definite conclusions can be made about its role as a prognostic factor in this disease.

5-fluorouracil-induced balanitis in a patient with oesophageal carcinoma.

We have reported the case history of a patient with balanitis, who was treated with 5-FU. Although 5-FU has a wide toxicity profile, balanitis has not been reported in association with this therapy.

Stevens-Johnson syndrome in a patient receiving anticonvulsant therapy during cranial irradiation.

A 28-year-old female patient with a recent history of breast carcinoma was referred to our clinic with generalized necrotic skin eruptions and severe mucosal erosions, which developed right after the completion of cranial radiotherapy for brain metastases. She had been receiving prophylactic diphenylhydantoin treatment 100 mg three times daily during radiation therapy. The extensive involvement of the oral mucosa with conjunctivitis and synechiae of the eyelids, facial swelling, and extension of the rash over the trunk and shoulders with bullous detachment of less than 10% of the total body surface strongly suggested Stevens-Johnson syndrome caused by phenytoin treatment in our patient. There has been conflicting evidence on the role of radiotherapy in the increased risk of severe drug reactions. Although various authors have emphasized the augmented rate of severe mucocutaneous reactions caused by anticonvulsants given during radiotherapy and suggested discontinuing the prophylactic use of such drugs in patients with no history of seizures, others have argued in favor of prophylactic anticonvulsants. Given the high risk of seizures, reaching 20% in patients with brain tumors, and the low incidence of drug reactions, the suggestion of refraining from prophylactic anticonvulsants in the setting of primary or metastatic brain tumors is controversial.

Serum lactate dehydrogenase levels at presentation predict outcome of patients with limited-stage small-cell lung cancer.

Serum lactate dehydrogenase (LDH) is a biochemical parameter that is elevated in the majority of extensive-stage small-cell lung cancer (SCLC). In this study, distribution and prognostic importance of serum LDH in limited-disease SCLC were investigated. Serum concentrations of LDH were measured in 184 patients at initial examination. These results were compared with prospectively recorded clinicopathologic characteristics and patient outcome data. Significant positive association was found between LDH levels and weight loss, performance status, response to chemotherapy, and albumin but not between age, gender, and hemoglobin values. Patients with high concentrations of LDH had a significantly worse prognosis than did patients with normal levels. The probability of overall survival at 1 year was 60.2% in patients with normal serum LDH levels and 33.1% in patients with higher values (p = 0.0017). Also, the prognostic value of LDH on overall survival was shown in multivariate analysis (p = 0.05). At the time of diagnosis, serum levels of LDH appear to have a significant relation to outcome in patients with limited-stage SCLC.