Nil Molinas Mandel

The correlation of angiogenesis with metastasis in primary cutaneous melanoma: a comparative analysis of microvessel density, expression of vascular endothelial growth factor and basic fibroblastic growth factor

Aim: To establish whether there is a correlation between angiogenesis and metastasis in primary cutaneous melanoma (PCMM). Methods: We studied the microvessel density and the expression of vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) in 22 cases of PCMM with metastasis at presentation (metastatic group) and 28 cases of PCMM without metastasis for 24 months or more (non‐metastatic group). Microvessels were stained with CD31/PECAM‐1 antibody and counted. We assessed the proportion of VEGF expression in tumour cells, lymphocytes infiltrating the tumour (TIL) and lymphocytes at the periphery of the tumour, as well as the proportion of bFGF expression in tumour cell cytoplasms, nuclei and intra‐ and peritumoral vessels. Results: An increased microvessel density was detected in the metastatic group (15–33 [24.09±5.55] versus 2–24 [12.96±6.02]). Moreover, enhanced expression of VEGF in tumour cells and peritumoral lymphocytes (Chi‐square p = 0.038 and p = 0.018) and bFGF in peritumoral vessels (&khgr;2p = 0.013) correlated with the simultaneous presence of melanoma metastasis in PCMM. Furthermore, microvessel density was correlated with the expression of bFGF in peritumoral vessels (rs = 0.53, p = 0.049) and VEGF in tumour cells (rs = 0.37, p = 0.019). Conclusion: Microvessel density as well as the expression of both VEGF and bFGF might be informative concerning the progression of melanoma.

Serum erythropoietin level in anemic cancer patients

Anemia is a frequent complication of cancer and its treatment. A defect in erythropoietin production has been advocated as being the main cause of anemia in cancer patients. We studied serum erythropoietin levels in 74 patients with solid tumors and in a control group consisting of 20 otherwise healthy individuals without any malignancy, who have only iron deficiency anemia. Serum erythropoietin levels were measured by enzyme immunoassay in cancer patients without anemia (n=34), and in anemic cancer patients (n=40); either receiving chemotherapy (n=21) or not (n=19). Anemic cancer patients were found to have decreased response of erythropoietin for a given hemoglobin level (mean, 40.1±34.7 u/ml), compared with the patients having only iron deficiency anemia (mean, 69.7±68.6 u/ml) (P<0.05). In patients with iron deficiency anemia having no malignancy, erythropoietin response was remarkably high and inversely correlated with the level of hemoglobin (r=−0.69;P=0.05). Although there was no correlation between hemoglobin and erythropoietin response in cancer anemia (r=−0.07), serum levels of erythropoietin were found to be higher in anemic cancer patients (mean, 40.1±34.7 u/ml), compared with cancer patients with normal hemoglobin values (mean, 19.96±18.4 u/ml). There was not any statistically significant difference between erythropoietin levels in anemic cancer patients with or without chemotherapy (mean, 43.7±37.7 u/ml and 41.9±30.08 u/ml respectively;P>0.05). No difference in serum erythropoietin levels were noted in patients treated with cisplatin or non-cisplatin containing regimens (mean, 48.36±33.12 u/ml and 38.55±43.52 u/ml, respectively;P>0.05). In this study, we demonstrated that anemia in cancer patients was caused by blunted erythropoietin response, rather than its quantitative deficiency. Serial measurements, however, should be considered in patients receiving chemotherapy.

Extraskeletal Ewing's Sarcoma Family of Tumors in Adults: Prognostic Factors and Clinical Outcome

OBJECTIVE The aim of this study was to evaluate prognostic factors, survival rate and the efficacy of the treatment modalities used in patients with extraskeletal Ewings sarcoma. METHODS Data of patients with extraskeletal Ewings sarcoma followed up at our center between 1997 and 2010 were retrospectively analyzed. RESULTS The median age of 27 patients was 24 years (range, 16-54 years). The median follow-up was 31.8 months (range, 6-144 months). Tumor size was between 1.5 and 14 cm (median: 8 cm). Eighty-five percent of patients had localized disease at presentation and 15% had metastatic disease. Local therapy was surgery alone in 16% of patients, surgery combined with radiotherapy in 42% and radiotherapy alone in 27%. All patients were treated with vincristine, doxorubicin, cyclophosphamide and actinomycin-D, alternating with ifosfamide and etoposide every 3 weeks. In patients with localized disease at presentation, the 5-year event-free survival and overall survival were 59.7 and 64.5%, respectively. At univariate analysis, patients with tumor size ≥ 8 cm, high serum lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy and positive surgical margin had significantly worse event-free survival. The significant predictors of worse overall survival at univariate analysis were tumor size 8 ≥ cm, high lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy, radiotherapy only as local treatment and positive surgical margin. CONCLUSIONS Prognostic factors were similar to primary osseous Ewings sarcomas. Adequate surgical resection, aggressive chemotherapy (vincristine, doxorubicin, cyclophosphamide and actinomycin-D alternating with ifosfamide and etoposide) and radiotherapy if indicated are the recommended therapy for patients with extraskeletal Ewings sarcoma.

Ultrasonographic appearance of endometrium in postmenopausal breast cancer patients receiving tamoxifen.

OBJECTIVES To assess the ultrasonographic appearance and associated pathological changes of the endometrium in postmenopausal breast cancer patients with tamoxifen therapy. STUDY DESIGN Forty-eight postmenopausal breast cancer patients receiving 20 mg/day tamoxifen for 6-84 months (mean 29) and 38 control breast cancer patients without any hormonal treatment were examined by transvaginal ultrasonography and endometrial biopsy. Any thickening of the endometrium with cystic formations or homogeneous endometrial thickening > 10 mm detected by ultrasonography was defined as abnormal endometrial appearance. Homogeneous endometrial thickening < 10 mm without cystic formations was accepted as normal. Statistical analysis was performed using the Students t-test and Mann-Whitney U test. RESULTS The two groups were similar in age and menopausal period. The patients on tamoxifen therapy had a thicker endometrium (8.6 +/- 6.6 mm) than the non-treated women (4.8 +/- 3.1 mm), which was found to be a statistically significant difference (P < 0.01). The sonographic evaluations showed abnormal endometrial appearance in 8 cases of tamoxifen treated women while the others revealed homogeneous thickness < 10 mm without cystic formations or a thin linear echo with or without fluid in the endometrial cavity. All 8 patients with cystic appearance had endometrial thickness > 10 mm. Only 1 patient had endometrial cancer on biopsy and no pathology was observed in the remaining 7 patients. In the control group, only 1 patient had abnormal ultrasonographic finding who had insufficient endometrial tissue on biopsy. CONCLUSIONS Tamoxifen can produce a sonographic image of the endometrium that resembles endometrial neoplasia. It is suggested that the discrepancy between the sonographic findings and histology may be the result of the stromal edema of the endometrium from tamoxifen treatment. Until more data are gathered, all postmenopausal breast cancer patients who are being treated with tamoxifen should have a periodic ultrasonographic examination and those presenting with a sonogram suggestive of endometrial pathology should undergo biopsy.

Usefulness of the epithelial tumor marker CA-125 in Non-Hodgkin's lymphoma

CA-125, a commonly used tumor marker for epithelial ovarian cancer, is a glycoprotein found in normal tissues derived from coelomic epithelia. Increased serum levels of CA-125 have also been found in nongynecologic tumors and nonmalignant diseases involving the peritoneum. A few recent studies and sporadic case reports have reported increased CA-125 levels in patients with non-Hodgkins lymphoma (NHL). In our study, we aimed to evaluate the serum levels of CA-125 in patients with NHL and determine its potential role to show disease activity in NHL. Serum levels of CA-125 were measured in 61 patients with NHL and were found to be correlated with clinical stage, site of involvement, and disease activity.

Surgical treatment and prognosis of primitive neuroectodermal tumors of the thorax.

Introduction: Primitive neuroectodermal tumors (PNETs) are rare, rapidly progressive, small- round cell tumors with a poor prognosis despite multimodal therapy, including surgery and chemoradiotherapy. The treatment of choice was unknown since no clinical series with surgical therapy had been reported. We evaluated the impact of multimodal treatment in patients with PNETs located in the thoracic region. Methods: Between 1998 and 2006, 25 patients with PNETs in the thoracic region were treated in 3 tertiary-care hospitals. The patients consisted of 15 males and 10 females with a mean age of 27.2 years (range, 6-60). The tumor was in the chest wall in 20 (involving the costovertebral junction in 9), the lung in four, and the heart in one patient. Twelve patients received neoadjuvant chemotherapy (54.5%), and 22 of 25 patients underwent surgery. Results: In patients who received neoadjuvant treatment, the mean regression rate was 65.4% (range, 30-100%). Eighteen (82%) patients underwent chest wall resection, while 7 (32%) had vertebral resections, and the remaining 4 (16%) had pulmonary resections. A complete resection was possible in 18 of 22 patients (82%). Patients with incomplete and complete resections had 25% and 56% 5-year survival rates, respectively (p = 0.13). The progression-free 3-year survival rate was 36% and the median survival time was 13 months. The complete resection rate was significantly higher in patients receiving neoadjuvant therapy (p = 0.027). The 5-year survival rate of the patients with or without neoadjuvant therapy was 77% and 37%, respectively (p = 0.22) although it prolonged the disease-free survival (p = 0.01). The 5-year survival rate of patients without costovertebral junction involvement was 66%, whereas patients with PNETs involving the costovertebral junction had a 21% 3-year survival. The difference was statistically significant (p = 0.01). The 5-year progression-free survival rate of patients without costovertebral junction involvement was 58%, whereas patients with PNETs involving the costovertebral junction had a 14% 1-year progression-free survival (p = 0.004). Conclusions: PNET is an aggressive malignancy that often requires multimodal therapy. Induction chemotherapy leads to a greater complete resection rate and better disease-free survival, while involvement of the costovertebral junction indicates a poorer survival.

Serum Cardiolipin Antibodies in Cancer Patients with Thromboembolic Events

This study was undertaken to investigate a pos sible association of anticardiolipin antibodies (ACLAs) in can cer patients with thromboembolic events. Twenty-five patients with solid tumors complicated with acute thrombosis, 36 cancer patients without any thrombotic events, and a group of 20 healthy volunteers without thrombosis or malignancy were in cluded. The mean age of the cancer patients with and without thrombosis and healthy subjects were 50 years (range 20-75), 45 years (range 23-66), and 40 years (range 20-68), respec tively. Deep venous thrombosis (n = 16) and thrombosis of the central venous port-catheter systems (n = 9) were confirmed by Doppler sonography in all patients. IgG and IgM isotypes of ACLAs were quantitated by enzyme-linked immunosorbent as say with normal levels of <23 GPL and <11 MPL, respectively. Mean values of IgG ACLAs were found similar in cancer pa tients with acute thrombosis (13.8 ± 4.9 GPL), without throm bosis (12.8 ± 5.4 GPL) or in healthy subjects (14.8 ± 5.5 GPL). Although the mean values of IgM ACLAs were within normal limits in all groups, cancer patients with thrombotic events had higher levels of IgM ACLAs (mean = 10.5 ± 2.2 MPL) than cancer patients without thrombosis (mean = 4.6 ± 2.4 MPL) (p = .01). Healthy subjects also had lower levels of IgM ACLAs (mean = 7.1 ± 3.2 MPL) than cancer patients with thrombosis (p = .16). In addition, a higher percentage of cancer patients with or without thrombosis had IgM and IgG ACLA levels above normal limits compared with healthy controls. In con clusion, our study suggests an association between ACLAs or IgG and particularly IgM isotypes and venous thrombosis in malignancy. Identification of cancer patients who are at higher risk for developing thromboembolic events might lead to a better selection of patients for prophylactic anticoagulant therapy.

Toxicity and Survival Results of a Phase II Study Investigating the Role of Postoperative Chemo-radioimmunotherapy for Gastric Adenocarcinoma

Background and Purpose:To investigate the role of postoperative concomitant chemoradioimmunotherapy in gastric adenocarcinoma patients.Patients and Methods:59 patients, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m2/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m2/day 5-FU and 25 mg/m2/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7–112 months).Results:Median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment.Conclusion:Although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care.Hintergrund und Ziel:Untersuchung der Rolle der postoperativen Radiochemotherapie bei Patienten mit Adenokarzinom des Magens.Patienten und Methodik:59 total oder subtotal operierte Patienten mit Adenokarzinom des Magens, die eine Invasion der Serosaoberfläche, einen Befall der regionären Lymphknoten oder positive Resektionsränder aufwiesen, wurden in die Studie eingeschlossen. Postoperativ wurde eine simultane Radiochemotherapie begonnen. Die Bestrahlung wurde in „Extended-field“-Technik über zwei Felder (anterior-posterior und posterior-anterior) mit einer Gesamtdosis von 45 Gy in 25 Fraktionen zu 1,8 Gy appliziert. 28 Patienten (48%) mit positiven Resektionsrändern erhielten zusätzlich einen 10-Gy-Boost auf den Anastomosenbereich. Die adjuvante Chemotherapie mit einem 450-mg/m2-Bolus 5-Fluorouracil (5-FU) wurde an den ersten 3 Tagen verabreicht und am 20. Tag wiederholt. Nach der Strahlentherapie erhielten die Patienten 450 mg/m2 5-FU i.v. und 25 mg/m2 Leukovorin i.v. wöchentlich für weitere 6 Monate. Die Immunmodulation mit 40 mg Levamisol p.o. wurde am 1. Bestrahlungstag begonnen und für 6 Monate weitergeführt. Der mediane Nachuntersuchungszeitraum lag bei 37 Monaten (7–112 Monate).Ergebnisse:Die mediane Überlebenszeit betrug 23 Monate. Die 3- und 5-Jahres-Gesamtüberlebensraten lagen bei 35% und 14%. Patienten mit positiven Resektionsrändern wiesen eine mediane Überlebenszeit von 22 Monaten auf. Die lokoregionale Kontrollrate betrug 59% nach 3 Jahren und 55% nach 5 Jahren. Die häufigsten Nebenwirkungen der Behandlung waren gastrointestinale Beschwerden bei 42 Patienten (71%). Vier Patienten (7%) starben infolge der Nebenwirkungen. Sechs Patienten konnten die Behandlung aufgrund von Nebenwirkungen nicht beenden.Schlussfolgerung:Obwohl 48% der Patienten in dieser Studie einen mikroskopisch nachweisbaren Resttumor aufwiesen, war die beobachtete Überlebenszeit verhältnismäßig gut. Aufgrund der hohen Toxizität sollte die Behandlung jedoch sehr sorgfältig unter Einsatz angemessener supportiver Maßnahmen durchgeführt werden.

Simultaneous presentation of hepatocellular carcinoma in identical twin brothers.

Family history and hepatitis B virus (HBV) infection have been identified as risk factors for hepatocellular carcinoma. We report hepatocellular carcinoma (HCC) diagnosed at the same time in identical twin brothers. Serological analyses of the patients showed that both were chronically infected with HBV. Molecular analyses of the tumor specimens confirmed loss of heterozygocity of the Rb gene region. Both of the patients were unresponsive to chemotherapy and died within the same month with an interval of 1 wk. With a review of the current literature, we discuss the role of HBV infection and genetic factors on hepatic carcinogenesis.

Evidence-based medical oncology and interventional radiology paradigms for liver-dominant colorectal cancer metastases

Colorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is (limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non-surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharmacological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population.