bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost of Insurance Policies for Investigator-Initiated Cancer Clinical Trials in Italy
Authors: Perrone Francesco , Marangolo Maurizio , Di Costanzo Francesco , Colucci Giuseppe , Repetto Lazzaro , Merlano Marco , De Placido Sabino , Torri Valter , Cornelia Giuseppe , Labianca Roberto , Parisi Valerio , Gallo Ciro 
Published: July 2019

Background Clinical trials with non-profit promoters are frequently performed in oncology and represent a highly valuable source of information. Methods To describe the costs of insurance policies and their determinants, data were collected from 12 Italian non-profit promoters of cancer trials. The cost of policies was expressed as per-patient premium. Results Sixty-two quotations issued by only two companies were collected, relative to 44 trials proposed for quotation between December 1998 and February 2003. Only the date of quotation was significantly associated with the cost (P = 0.0003) of quotations by Company A for policies with a deductible, with cost increasing over time. Date of quotation (P = 0.0002), sample size (P = 0.008) and number of study arms (P = 0.02) were independently associated with the cost of no-deductible policies quoted by Company A. Only the number of study arms was significantly associated with cost (P = 0.0001) in no-deductible policies quoted by Company B. Conclusion There is insufficient competition among companies for insurance of cancer trials with non-profit promoters. Many variables that affect the trial risk profile from a clinical perspective are not associated with insurance cost. Date of quotation is among the strongest determinants of the cost, which has sharply increased over time. This trend may become a serious problem for non-profit promoters of cancer clinical trials.
Elderly Patients with Advanced Colorectal Cancer: Tolerability and Activity of Chemotherapy
Authors: Berardi Rossana , Saladino Tiziana , Mari Davide , Silva Rosa Rita , Scartozzi Mario , Verdecchia Lorena , Onofri Azzurra , Cascini Stefano 
Published: July 2019

Aims and Background Colorectal cancer is the most common gastrointestinal tumor in Western countries and is increasing in elderly patients. In recent years, new treatments based on the use of 5-fluorouracil associated with oxaliplatin or CPT-11 have shown promising activity. The aim of the present study was to analyze the tolerability and activity of chemotherapy with 5-fluorouracil plus oxaliplatin or CPT-11 in elderly patients with advanced colorectal cancer. Methods Patients aged 70 years or older with advanced colorectal cancer were treated with 5-fluorouracil (400 mg/m2 in bolus and 600 mg/m2 in a 22-hr continuous infusion on days 1-2) plus folinic acid (100 mg/m2) associated to oxaliplatin (85 mg/m2 on day 1, FOLFOX regimen) or CPT-11 (180 mg/m2 on day 1, FOLFIRI regimen), every 14 days. Results Twenty-nine patients with a median age of 76 years (range, 70-82) were treated with FOLFOX or FOLFIRI as first-line chemotherapy for metastatic disease. We observed a partial response in 8/29 (27.6%), stable disease in 11/29 (37.9%) and progressive disease in 10/29 (34.5%). Median survival was 21 months; 1-year survival probability was 89.8%. Grade III leukopenia was observed in 2/29 (7%) patients and grade III diarrhea in 1/29 patients. No other grade III-IV toxicity was observed. Conclusions FOLFOX and FOLFIRI appear to be active and well tolerated regimens for elderly patients with advanced colorectal cancer.
Low-Molecular-Weight Heparin and Calcium Heparin in Thrombosis Prophylaxis in Patients with Percutaneous Arterial and Venous Ports for Colorectal Liver Metastases
Authors: Zanon Claudio , Bortolini Massimiliano , Chiappino Isabella 
Published: July 2019

Study Objective The evaluation of low-molecular-weight heparin use to prevent arterial and venous thrombosis in patients with indwelling arterial Port-a-Cath implants. Methods From 1996 to March 2003 we placed 370 indwelling hepatic arterial catheters with a minimally invasive approach. The left distal subclavian artery was approached from beneath the left clavicle, then an angiographic study of the tumoral vascular district was performed and the gastroduodenal artery was occluded by an embolus. A polyurethane catheter was introduced distally into the hepatic artery and connected to a reservoir through a 3-4 cm long subcutaneous tunnel. In 90 patients a venous Port-a-Cath was placed for concurrent systemic chemotherapy. All 370 patients received regional chemotherapy and were treated with calcium heparin at a dose of 5000 IU twice a day and with low-molecular-weight heparin at prophylactic doses (dalteparin 2500 IU or nadroparin 3000 IU) during catheter permanence to prevent hepatic artery thrombosis. Intra-arterial trans-port radionuclide scans using technetium-99m-labeled micro-aggregated albumin were performed monthly to check the infusion distribution and hepatic artery patency. In the presence of anomalous patterns, thrombosis, pulmonary embolism or other complications, angiography and/or other diagnostic studies were performed to determine the cause of the vascular event and the local or systemic symptoms. The mean arterial and venous Port-a-Cath permanence times were 6 and 8 months, respectively. Results We observed episodes of hepatic artery thrombosis in 4.3% of patients. Three of these 17 patients were successfully treated by intra-arterial thrombolysis using urokinase. No venous thrombosis occurred as a consequence of regional and/or systemic chemotherapy, no episodes of arterial thrombosis were registered during arterial catheter permanence, nor did any hemorrhagic complications related to anti-coagulant therapy occur. Five patients treated with low-molecular-weight heparin required treatment suspension due to a platelet count of <40,000/dL. Conclusion Our experience suggests that low-molecular-weight heparin and/or calcium heparin at prophylactic doses could be useful in the prevention of arterial and venous thrombosis in patients with indwelling arterial catheters or venous Port-a-Cath treated with regional or systemic chemotherapy for hepatic metastases from colorectal cancer. The homogeneity of the patient group and the use of analogous chemotherapeutic drugs (fluoropyrimidines) avoided statistical contamination related to differences between kinds of cancer and between the chemotherapeutic agents used.
Liver Resection for Intrahepatic Cholangiocarcinoma
Authors: Giuliante Felice , Gauzolino Riccardo , Vellone Maria , Ardito Francesco , Murazio Marino , Nuzzo Gennaro 
Published: July 2019

Aims and Background Intrahepatic cholangiocarcinoma (IHCC) is the second most common primary liver cancer, representing 10% of all primary liver malignancies. Despite the increase in its incidence, this tumor remains extremely rare in Western countries and few reports detailing experience with surgical resection have been published. The aim of this study was to analyze the experience with resection of IHCC in our center. Methods From 1987 to 2003 we observed 35 patients with IHCC; 15 of them (42.8%) were submitted to hepatic resection. IHCCs accounted for 13% of all liver resections for primary liver tumors carried out at our center during this period. According to the classification of the Liver Cancer Study Group of Japan, the tumors were classified as “mass-forming” in 14 cases and as “periductal” in one case. Major resections were performed in ten cases and minor resections in five cases. In the patient with a periductal tumor a major resection was performed along with excision of the main biliary confluence. In 14 cases (93.3%) tumor-free resection margins were obtained. Results The intraoperative mortality was nil and the postoperative mortality 6.6%. The postoperative morbidity rate was 21.4%. The mean overall survival was 38.4 months, with 86% and 49% one- and three-year survival rates, respectively. Patients with mass-forming tumors and curative resections (R0) (mean survival 40.8 months; one- and three-year survival rates 92.3% and 52.7%), and those with TNM stage I-II tumors (mean survival 43.7 months; one- and three-year survival rates 100% and 66.7%) had a longer survival. The patient with the periductal tumor and R1 resection died after seven months. Conclusions These results support a surgical approach based on accurate selection of patients with IHCC and aimed at radical resection whenever possible. The good survival rates observed in R0 resections emphasize the role of radical surgery as the only chance of cure for patients with this tumor.
Fusion Hybrid of Dendritic Cells and Engineered Tumor Cells Expressing Interleukin-12 Induces Type 1 Immune Responses against Tumor
Authors: Shi Meiqing , Su Liping , Hao Sigou , Guo Xulin , Xiang Jim 
Published: July 2019

Aims and Background Dendritic cell (DC)-tumor fusion hybrid vaccinees that facilitate antigen presentation represent a novel powerful strategy in cancer immunotherapy. Preclinical studies have demonstrated that IL-12 promotes specific antitumor immunity mediated by T cells in several types of tumors. In the present study, we investigated the antitumor immunity derived from vaccination of fusion hybrids between DCs and engineered J558/IL-12 myeloma cells secreting Th1 cytokine IL-12. Methods The expression vector pcDNA-IL-12 was generated and transfected into J558 myeloma cells and then bone marrow-derived DCs were fused with engineered J558/IL-12 cells. The antitumor immunity derived from vaccination of the fusion hybrid DC/J558/IL-12 was evaluated in vitro and in vivo. Results DC/J558/IL-12 cells secreted recombinant IL-12 (1.6 ng/mL), and inoculation of BALB/c mice with DC/J558/IL-12 hybrid induced a Th1 dominant immune response and resulted in tumor regression. Immunization of mice with engineered DC/J558/IL-12 hybrid elicited stronger J558 tumor-specific cytotoxic T lymphocyte (CTL) responses in vitro as well as more potent protective immunity against J558 tumor challenge in vivo than immunization with the mixture of DCs and J558/IL-12, J558/IL-12 and J558, respectively. Furthermore, the antitumor immunity mediated by DC/J558/1L-12 tumor cell vaccination in vivo appeared to be dependent on CD8+ CTL. Conclusions These results demonstrate that the engineered fusion hybrid vaccines that combine Th1 cytokine gene-modified tumor cells with DCs may be an attractive strategy for cancer immunotherapy.
Upregulation and Overexpression of DVL1, the Human Counterpart of the Drosophila Dishevelled Gene, in Prostate Cancer
Authors: Mizutani Kazunori , Miyamoto Shizuyo , Nagahata Takemitsu , Konishi Noboru , Emi Mitsuru , Onda Masamitsu 
Published: July 2019

Aims and Background The Wnt/beta-catenin signaling pathway is one of the main carcinogenic mechanisms in human malignancies including prostate cancer. Recently, the DVL1 gene was identified as a middle molecule of the Wnt/beta-catenin signaling pathway. In addition, alterations of the DVL1 gene have been reported in breast and cervical cancer. The abnormality of beta-catenin in prostate cancer has been well studied, so the examination of the DVL1 gene in prostate cancer is appealing. Methods We investigated DVL1 messenger RNA alterations by semiquantitative PCR (SQ-PCR) in 20 primary prostate cancers and assessed the protein expression by immunohistochemical analysis in the same samples. In addition, DVL1 and beta-catenin protein expression was evaluated with a new validated set of 20 prostate cancers. Results SQ-PCR revealed significant overexpression of DVL1 in prostate cancer (65%). Upregulation of the DVL1 gene product in prostate cancer was confirmed by immunostaining. With SQ-PCR and immunostaining, none of the cases showed underexpression or downregulation of DVL1. In addition, the data showed correlations between DVL1 mRNA and protein expression. Interestingly, the expression level of DVL1 increased with worsening histological grade. In addition, a correlation between DVL1 expression and beta-catenin expression was confirmed. Conclusions DVL1 was overexpressed in prostate cancer and its overexpression might be related to prostate cancer progression through the Wnt/beta-catenin pathway.
Splenic Metastases from Mucinous Neoplasms of the Appendix and Colon
Authors: Cabanas Jacobo , da Silva Rodrigo Gomes , Zappa Luis , Esquivel Jesus , Cerruto Carlos , Goldstein Paulo , Sugarbaker Paul H 
Published: July 2019

Aims and Background Splenic metastases associated with mucinous intraabdominal tumors have been an enigma in the radiologic and oncology literature. These focal parenchymal defects from a non-metastasizing malignancy within an organ that rarely develops metastatic foci, even with high-grade cancer, were studied. Methods Information on 9 patients who underwent splenectomy with intraparenchymal splenic masses associated with appendiceal or colorectal mucinous tumors with peritoneal dissemination was collected. The CT scan, the histopathology and the clinical parameters of these patients were studied. A literature review searching for prior reports of this subject was performed. Results Eight of these patients had mucinous appendiceal tumors and 1 a mucinous sigmoid colon cancer. All patients had mucinous carcinomatosis at some time in their clinical course. These splenic tumor masses had a CT image compatible with metastases and not compatible with mucinous tumor layered out of the splenic capsule. None of the patients had evidence of metastases to other sites such as liver or lymph nodes. All patients had a mucinous histopathology. Splenectomy may be associated with prolonged survival. Conclusions From our review of the clinical information available on these 9 patients, these splenic lesions were thought to be an entrapment of mucinous tumor within splenic surface trabeculae, which expand into the splenic parenchyma resembling metastatic disease. These CT findings may be more accurately referred to as splenic pseudometastases.
Lymphatic Mapping and Sentinel Lymph Node Biopsy in the Management of Primary Cutaneous Melanoma: Report of a Single-centre Experience
Authors: Cecchi Roberto , De Gaudio Cataldo , Buralli Lauro , Innocenti Stefania 
Published: July 2019

Aims and Background Lymphatic mapping and sentinel lymph node biopsy provide important prognostic data in patients with early stage melanoma and are crucial in guiding the management of the tumor. We report our experience with lymphatic mapping and sentinel lymph node biopsy in a group of patients with primary cutaneous melanoma and discuss recent concepts and controversies on its use. Patients and Methods A total of 111 patients with stage I-II AJCC primary cutaneous melanoma underwent lymphatic mapping and sentinel lymph node biopsy from December 1999 through December 2004 using a standardized technique of preoperative lymphoscintigraphy and biopsy guided by blue dye injection in addition to a hand-held gamma probe. After removal, sentinel lymph nodes were submitted to serial sectioning and permanent preparations for histological and immunohistochemical examination. Complete lymph node dissection was performed only in patients with tumor-positive sentinel lymph nodes. Results Sentinel lymph nodes were identified and removed in all patients (detection rate of 100%), and metastases were found in 17 cases (15.3%). The incidence of metastasis in sentinel lymph nodes was 2.1%, 15.9%, 35.2%, and 41.6% for melanomas < or 1.0, 1.01-2.0, 2.01-4.0, and > 4.0 mm in thickness, respectively. Complete lymph node dissection was performed in 15 of 17 patients with positive sentinel lymph nodes, and metastases in non-sentinel lymph nodes were detected in only 2 cases (11.7%). Recurrences were more frequently observed in patients with a positive than in those with negative sentinel lymph node (41.1% vs 5.3% at a median follow-up of 31.5 months, P<0.001). The false-negative rate was 2.1%. Conclusions Our study confirms that lymphatic mapping and sentinel lymph node biopsy allow accurate staging and yield relevant prognostic information in patients with early stage melanoma.
Ct Image Fusion as a Tool for Measuring in 3D the Setup Errors during Conformal Radiotherapy for Prostate Cancer
Authors: Cambria Raffaella , Cattani Federica , Ciocca Mario , Garibaldi Cristina , Tosi Giampiero , Orecchia Roberto 
Published: July 2019

Aims and Background The importance of optimal daily patient positioning has been stressed in order to ensure treatment reproducibility and gain in accuracy and precision. We report our data on the 3D setup uncertainty during radiation therapy for prostate cancer using the CT image fusion technique. Methods Ten consecutive patients scheduled for radiation therapy for prostate cancer underwent 5 prone position CT scans using an individualized immobilization cast. These different setups were analyzed using the image fusion module of the ERGO 3D-Line Medical System (Milan, Italy) treatment planning system. The isocenter and the body marker displacements were measured. Results The 3D isocenter dislocations were quantified: systematic error was Σ3D = 3.9 mm, whereas random error was σ3D = 1 mm. The mean of the minimum displacements was 0.2 ± 1 mm showing that the immobilization device used allows an accurate setup to be obtained. Single direction errors were also measured showing systematic errors, ΣAP = 2.6 mm, ΣLL = 0.6 mm, ΣSI = 3 mm in the anterior-posterior, latero-lateral, superior-inferior direction, respectively. Related random errors were σAP = 1 mm, σLL = 0.6 mm, σSI = 1.2 mm. In terms of accuracy, our uncertainties are similar to those reported in the literature. Conclusions By applying the CT image fusion technique, a 3D study on setup accuracy was performed. We demonstrated that the use of an individualized immobilization system for prostate treatment is adequate to obtain good setup accuracy, as long as a high-quality positioning control method, such as the stereoscopic X-ray-based positioning system, is used.
Association of Cyclooxygenase-2 Immunoreactivity with Tumor Recurrence and Disease Progression in Superficial Urothelial Bladder Cancer
Authors: Mokos Ivica , Jakić-Razumović Jasminka , Mareković Zvonimir , Pasini Josip 
Published: July 2019

Aims and Background The main characteristic of urothelial bladder cancer is a clear predisposition to recurrence and disease progression. The aim of this study was to assess the possible relationship between cyclooxygenase-2 (COX-2) immunoreactivity in superficial urothelial bladder carcinoma and tumor grade, stage, number of recurrences and clinical disease progression. Methods In this prospective study 70 consecutive patients who underwent transurethral resection for superficial urothelial bladder cancer were included. Tumor slides were immuno-histochemically stained for COX-2, and COX-2 immunoreactivity in tumor and inflammatory stromal cells was categorized as negative or mildly, moderately or strongly positive. Patients were followed up for 2 years, and during this period the possible association of COX-2 immunoreactivity with tumor stage and grade, number of recurrences and progression of disease was evaluated. Results COX-2 immunoreactivity in tumor cells was found in 57 (81.4%) patients and did not correlate with tumor grade, stage of disease, number of recurrences, and progression of disease. COX-2 immunoreactivity in inflammatory cells was found in 16 of the 57 patients with COX-2 positive tumors, and was significantly related to the number of recurrences, time to appearance of the first recurrence, and disease progression. Conclusions COX-2 immunoreactivity in inflammatory stromal cells adjacent to the COX-2-positive tumor might be useful in clinical practice for selection of patients with a high risk of tumor recurrence and disease progression.
Clinical Significance of Serum p53 Antibodies in Oral Cancer
Authors: Sainger Rachana Narendra Singh , Shah Manisha Hasmukhray , Desai Amisha Anil , Shukla Shilin Nandubhai , Shah Pankaj Manubhai , Telang Shaila Dattatraya , Patel Prabhudas Shankerbhai 
Published: July 2019

Aim and Background The incidence and mortality due to oral cancer have increased worldwide. In India, the use of tobacco has been found to be the major etiological factor for the development of oral cancers. Various studies on serum p53 antibodies have suggested their clinical importance as prognostic markers in cancer. However, there is a dearth of data on serum p53 antibodies in oral cancer patients in India. The present study was carried to evaluate the clinical significance of serum p53 antibodies in oral cancer. Materials and Methods The serum p53 antibody status was analyzed by means of ELISA in 55 healthy individuals, 60 patients with oral precancerous conditions, 75 untreated oral cancer patients, and 86 follow-up blood samples of the oral cancer patients. Results We found serum p53 antibodies in 23% of cancer patients. The frequency of p53 antibody positivity was higher in patients with lymph node metastasis, advanced disease and well-differentiated tumors. Furthermore, p53 antibody positivity strongly correlated with poor treatment outcome in cancer patients. Kaplan-Meier survival analysis showed significantly poorer disease-free survival in patients with serum p53 antibodies. Conclusion The results of this study suggest the usefulness of serum p53 antibodies in the prognostication of oral cancer patients.
Matrix Metalloproteinase-9 (MMP-9) Elevated in Serum but not in Bronchial Lavage Fluid in Patients with Lung Cancer
Authors: Koç Melike , Ediger Dane , Budak Ferah , Karadağ Mehmet , Oral Haluk Barbaros , Uzaslan Esra , Ege Ercüment , Gözü Ramazan Oktay 
Published: July 2019

Aims and Background Matrix metalloproteinase (MMP) family member MMP-9 degrades type IV collagen, which is one of the main constituents of the basement membrane. MMP-9 is closely associated with the invasive and metastatic potential of most types of lung cancer. In this study we investigated the levels of MMP-9 in serum and bronchial lavage fluid from lung cancer patients and compared them with the levels in patients with nonmalignant lung disease. We also attempted to clarify the possible relationship between serum and bronchial lavage fluid MMP-9 levels and histopathology, staging and metastasis of lung cancer. Study Design The study group consisted of 34 patients with lung cancer. The control group comprised 21 patients with nonmalignant lung disease. MMP-9 levels in serum and bronchial lavage fluid were evaluated by ELISA. Results MMP-9 levels in serum samples from the group with malignant disease were significantly higher than those from the control group (P <0.05). Bronchial lavage MMP-9 levels did not differ significantly between the two groups (P >0.05). Serum MMP-9 levels were two-fold higher than those in bronchial lavage, but there was no correlation between bronchial lavage and serum levels in both groups (r = 0.18, P >0.05). In the group with malignant disease, MMP-9 levels in serum and bronchial lavage fluid did not show any relationship with histopathological type and tumor stage. There was a statistically significant correlation between serum MMP-9 levels and local tumor stage in smoking nonsmall cell lung cancer (NSCLC) patients (r = 0.33, P <0.05). Karnofsky scores of lung cancer patients were inversely correlated with MMP-9 levels of serum (r = -0.39, P <0.05) but not of bronchial lavage fluid. Conclusion From our data it can be concluded that MMP-9 levels of serum but not of bronchial lavage fluid can be helpful in differentiating between malignant and benign lung diseases, and are related to the local stage in NSCLC patients and general clinical status of lung cancer patients.