The effect of internal mammary lymph node biopsy on the therapeutic decision and survival of patients with breast cancer.

BACKGROUND: The role of internal mammary lymph node biopsy (IMLNB) is still being discussed in breast cancer treatment. The aim of this study was to investigate the role of IMLNB on adjuvant therapy and survival of patients with breast cancer. PATEINTS AND METHODS: The data of 72 patients with clinically negative axilla and IMLNB were evaluated. IMLNB was performed either through a small separate intercostal incision or from the same incision for tumor resection or mastectomy by using both blue dye and radioisotope. Pathological analysis was performed on formalin-fixed paraffin-embedded tissues. RESULTS: Ten of the patients (14%) were IMLNB-positive. The axillary sentinel lymph node and IMLN were negative in most of the patients (52.8%). In one patient (1.4%), the axilla was negative but the IMLNB was positive. IMLNB changed the pathologic stage in eight patients (11%). Adjuvant internal mammary radiotherapy was added to the treatment protocol for 10 patients due to IMLNB positivity and adjuvant chemotherapy was added in for only one patient with negative axilla. The factors found to be related with IMLN positivity were SLN positivity (p = 0.033), mastectomy (p = 0.022), and the number of resected IMLN ≥2 (p = 0.040). The median follow-up time was 115.5 months (range, 30-162 months). The ten-year overall survival (OS) rate was 86%. Systemic metastasis (p = 0.007), SLNB positivity (p < 0.001), and IMLNB positivity (p = 0.005) were statistically related to overall survival. CONCLUSION: IMLNB positivity in patients with breast cancer changed the pathologic stage and adjuvant treatment modalities of patients and also adversely affected the overall survival.

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.

Phase II study of lapatinib in combination with vinorelbine in patients with HER2 positive recurrent or metastatic breast cancer: a multicentric Turkish Oncology Group (TOG) trial.

BACKGROUND: The aim of this explorative phase II study was to evaluate the activity and safety of lapatinib in combination with intravenous vinorelbine in women with HER2 positive metastatic or recurrent breast cancer. METHODS: Twenty-nine patients were enrolled. The primary objectives were response and clinical benefit (CB) rates, secondary objectives were toxicity, response duration and progression free survival. Patients received 1250 mg oral lapatinib continuously once daily and intravenous vinorelbine 20-25 mg/m(2) on days 1 and 8, every 3 weeks. RESULTS: Although 25 patients were evaluable for response, according to intend to treat analysis of 28 patients; 14% had confirmed partial response (PR) and 36% had stable disease more than 24 weeks with a CB rate of 50%. Sixty four percent of the patients suffered from grade 3-4 hematologic and 18% from grade 3 extra-hematologic toxicities. CONCLUSION: The results of this trial provide evidence to further investigate the potential of this combination for patients unsuitable for trastuzumab or who become refractory to trastuzumab.

Glutathione S-transferase P1 polymorphisms are associated with time to tumor progression in small cell lung cancer patients.

PURPOSE: Many of commonly used chemotherapeutics in lung cancer treatment are metabolized by glutathione-S transferases (GSTs). The placental isoform of GST (GSTP1) is the most abundant isoform in the lung. Polymorphisms within the GSTP1 may result in alterations in enzyme activity and change sensitivity to platinum-based chemotherapy. We investigated whether the polymorphism within the exons 5 and 6 of GSTP1 gene may change response to therapy, time to tumor progression (TTP) and overall survival in small cell lung cancer (SCLC) patients. METHODS: Ninety-four histologically confirmed patients with SCLC were enrolled in this study during 1995-2006. GSTP1 Ile105Val polymorphism in exon 5 and GSTP1 Ala- 114Val polymorphism in exon 6 were determined by using PCR-RFLP techniques. Associations between the GSTP1 polymorphisms and treatment response were evaluated using the chi-square test. Associations between the GSTP1 polymorphisms and TTP and overall survival were compared using Kaplan-Meier survival curves. RESULTS: We found no significant associations between exon 5 and exon 6 GSTP1 gene polymorphisms and response to therapy or overall survival. Patients carrying both variant exon 5 (Ile/Val or Val/Val) and variant exon 6 (Ala/Val) genotypes had significantly shorter TTP (5 vs. 8 months, p = 0.04). Moreover, patients with heterozygote exon 6 variant had presented with extensive-stage disease. CONCLUSION: No individual effect of variant alleles was found in relation to chemotherapy response, median TTP and overall survival. The carriage of both types of variant alleles may predict worse outcome.

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.

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.

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.

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.

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.

The efficacy of combination chemotherapy including intraperitoneal cisplatinum and mitoxantrone with intravenous ifosfamide in patients with FIGO stage I C ovarian carcinoma.

OBJECTIVE: Patients with stage I ovarian cancer show a high incidence of recurrent disease ranging from 30% to 50%, which may be associated with a shortened survival. Therefore, a subset of early-stage patients with poor prognostic factors who are most likely to present with recurrent disease in the next few years may benefit from adjuvant treatment. PATIENTS AND METHOD: In this pilot study, we evaluated the efficacy of combination chemotherapy including intraperitoneal mitoxantrone (12 mg/ml) and cisplatinum (75 mg/ml) on day 1, in addition to intravenous ifosfamide (4000 mg/m2) given on day 15 with mesna protection. Thirteen patients with a median age of 44 years were included in the study. RESULTS: Following a median of 5 cycles of chemotherapy, 12 patients had a complete response (92.3%), while one patient had progressive disease. At the latest follow-up, ten patients were alive with no evidence of disease, two patients had died and one patient was lost to follow-up. Overall and progression-free survival rates at eight years were 82.5+/-11.3% and 83.9+/-10.5%, respectively. Excluding grade 3 and 4 abdominal pain in three (23.1%) patients, there were no serious complications associated with this combination. Dose delay not longer than one week was observed in 3 cycles (5.6%). Port-related complications observed in three patients were colonic perforation, hematoma and leakage. CONCLUSION: This combination has moderate efficacy and tolerable toxicity. However, further studies are required to make definite conclusions regarding the efficacy of this combination in the adjuvant setting in patients with high-risk early stage ovarian carcinoma.

The role of chemotherapy in malignant mixed mullerian tumors of the female genital tract.

Thirteen patients with malignant mixed mullerian tumor of the female genital tract, treated and followed in our clinic from 1989 to 1999 were retrospectively evaluated. Seven patients (53.8%) with advanced disease or postoperative residual tumor were treated with adjuvant chemotherapy. The median age at diagnosis was 64 years (range: 26-79). All patients underwent primary surgical cytoreduction. Tumors were localized to the endometrium in five (62.5%), to the ovaries in two (25%) and to the fallopian tube in one (12.5%) patient. One patient with endometrial carcinosarcoma had a simultaneous second primary ovarian epithelial carcinoma. Two patients (25%) had a heterologous sarcomatous component. Myometrial involvement included less than half the thickness in one patient, while there was no myometrial invasion encountered in two patients. Five patients (38.5%) had more than 50% of the myometrium invaded. Two patients received additional radiotherapy. Six patients received cisplatinum-based chemotherapy (4 had doxorubicin including combinations), while one patient was treated with a doxorubicin+ifosphamide combination. Five patients (71.4%) had a complete response (CR) to chemotherapy. Response duration in patients with a CR was +13, +67, +10, +14 and +2 months, respectively. After a median follow-up period of 20 months (3-115 months), six patients have died, five are being followed-up with no evidence of disease, one is alive with metastatic disease and one patient is under treatment. Malignant mixed mullerian tumor of the female genital tract is highly responsive to multimodality treatment strategies. Further prospective studies are required to identify distinct prognostic groups that may benefit from various treatment modalities.

Treatment of aggressive non-Hodgkin's lymphoma with dose-intensified epirubicin in combination of cyclophosphamide, vincristine, and prednisone (CEOP-100): a phase II study.

Epirubicin is an agent with a lower incidence of cardiotoxicity and myelotoxicity compared with doxorubicin; and it is active in patients with non-Hodgkin's lymphoma (NHL). Our aim was to define the therapeutic efficacy and toxicity of dose-intensified epirubicin in combination with cyclophosphamide, vincristine, and prednisone (CEOP) in patients with diffuse large-cell NHL. Previously untreated patients aged between 15 and 75 years, with at least one measurable lesion, adequate liver, renal, cardiac functions, and no central nervous system involvement were included in the study. The planned chemotherapy regimen CEOP consisted of cyclophosphamide 750 mg/m2, epirubicin 100 mg/m2, and vincristine 1.4 mg/m2 intravenously on day 1 and 100 mg prednisone taken orally on days 1 to 5. Courses were repeated every 21 days. Patients with stage I and II received four cycles of chemotherapy followed by involved-field radiotherapy, and patients with stage III and IV received six cycles of chemotherapy followed by radiotherapy to bulky lymph node sites. Seventy-five patients were enrolled in the study. The complete response rate was 83.8%, and 72 patients were assessable for toxicity. The most common toxicity was myelosuppression; 13.9% of the patients had grade III-IV neutropenia. Severe mucositis, diarrhea, and emesis were uncommon (<10%). At a median follow-up period of 41 months, the 5-year progression-free survival and overall survival rates were 63.5% and 65.3%, respectively. Increasing the dose intensity of epirubicin can yield a similar complete response rate compared with the regimens used in NHL without significantly increasing the toxicity rate associated with chemotherapy. The role of dose-intensive epirubicin should be investigated further in future randomized trials.

Correlations of serum CA125 level and computerized tomography (CT) imaging with laparotomic findings following intraperitoneal chemotherapy in patients with ovarian cancer.

UNLABELLED: The aim of this study was to evaluate the role of serum CA125 levels and computerized tomography (CT) scans in predicting pathologic response of intraperitoneal chemotherapy in patients with ovarian cancer. We prospectively analyzed serum CA125 levels and abdominopelvic CT scans obtained after the completion of intraperitoneal chemotherapy in 52 patients with ovarian cancer and compared the results with subsequent laparotomic findings, which served as the gold standard for statistical analysis. Laparatomy revealed either microscopic or macroscopic residual disease in 20 patients, while 32 patients were completely tumor-free. CA125 levels correlated significantly with laparotomic findings (p=0.003, u=1405). Median CA125 values in patients with residual tumors and in tumor-free patients following intraperitoneal chemotherapy were 14.6 (1-775) and 7.2 (1-37) U/ml, respectively. Although CT-imaging and CA 125 levels had a high specificity (100% and 96.9%, respectively), they showed a low sensitivity rate (50% and 40%, respectively). Similarly, despite high positive predictive values (100% and 88.9%, respectively), the negative predictive values were 76.2% and 72.1%, respectively. CONCLUSION: Although highly specific, CT scans and CA125 levels do not accurately indicate the presence of disease. Due to a high false-negative rate, a normal CT scan or a normal CA125 value is not sufficient to replace a laparotomy.

Factors influencing the distribution of metastases and survival in extensive disease small cell lung cancer.

This study was conducted to investigate the distribution of metastatic lesions and their influence on survival, as well as other prognostic factors previously shown to have an impact on the outcome of patients with extensive small cell lung cancer (SCLC). Of the 207 patients were included and retrospectively analyzed; 124 patients had extended disease at initial presentation and the remaining 83 developed metastatic disease during follow-up. Patients who relapsed presented most frequently with distant metastases. The brain was the most frequent organ targeted for metastatic disease following the completion of chemotherapy (p<0.05). Serum LDH levels correlated significantly with the presence of liver metastasis (p<0.001). The site of involvement did not seem to have an impact on survival. Nevertheless, patients with multiple metastatic sites had a significantly poor survival rate (p = 0.001). Weight loss, performance status, gender, clinical stage, serum LDH and albumin levels were all shown to correlate with survival (p<0.05). Response to chemotherapy was determined to be the most important prognostic factor.

[Meta-analysis of determining the pathogen eradicating efficacy of various therapeutic regimens in Helicobacter pylori infection]. / Metaanalyse zur Feststellung der keimeradizierenden Potenz verschiedener Therapieschemata bei Helicobacter-pylori-Infektion.

Helicobacter pylori is the most common bacterial pathogen world-wide and has been identified in all countries. As long-term infection with H. pylori could potentially lead to duodenal or gastric ulcer disease, asymptomatic chronic gastritis, chronic dyspepsia, or gastric malignancy, including both adenocarcinoma and B-cell lymphoma, a large number of different treatment regimens aimed at eradicating H. pylori has been evaluated and reported. Despite numerous H. pylori treatment studies the optimum regimen for its eradication remains unclear. A treatment regimen, which is effective, safe and inexpensive could be used widespread and reduce the risks of the long-term complications of infection. In this study we compared the efficacy, side effects and cost-effectiveness of 12 different therapy regimens for H. pylori eradication by using meta-analysis methodology. 486 patients (256 male, 230 female; mean age 40.8 years) with H. pylori associated duodenal ulcer (n = 140), gastritis (n = 254), gastroduodenitis (n = 92) were treated with 12 different therapy-regimens. Endoscopy was performed at baseline and 6 weeks after discontinuation of eradication therapy. H. pylori status was assessed by urease test and histology. The therapy with a H2-receptor antagonist is less effective than the triple therapies with omeprazole or lansoprazole. Bismuth-based triple therapies have a mean overall eradication rate of 68%, but are limited by frequent side effects causing poor drug compliance.