bluuebunny/crossref_metadata_2025_split huggingface dataset:
bcl-2 protein expression in primary cutaneous large B-cell lymphoma is site-related.
Authors: Geelen F A , Vermeer M H , Meijer C J , Van der Putte S C , Kerkhof E , Kluin P M , Willemze R 
Published: February 2017

PURPOSE Primary cutaneous large B-cell lymphoma (PCLBCL) that presents on the leg has recently been recognized as a distinct disease entity. These lymphomas have a reduced disease-free survival and a worse prognosis as compared with the more common, morphologically similar PCLBCL that present on the head or trunk. Studies in noncutaneous diffuse large B-cell lymphomas suggest a relationship between the expression of bcl-2 protein and clinical behavior. In the present study, we investigated whether these two groups of PCLBCL differ in the expression of bcl-2 protein and the presence of t(4;18), known as one of the causes of bcl-2 overexpression. PATIENTS AND METHODS Paraffin sections from pretreatment biopsies of 14 PCLBCLs of the head or trunk and nine PCLBCLs of the legs were investigated for expression of bcl-2 protein using immunohistochemistry, and for the presence of the 14;18 translocation using polymerase chain reaction (PCR) amplification with primers against both the major breakpoint region (mbr) and the minor cluster region (mcr) of bcl-2. For reasons of comparison, nine secondary cutaneous large B-cell lymphomas (SCLBCLs) were also studied. RESULTS Expression of bcl-2 protein was found in all nine PCLBCLs of the leg and in all nine SCLBCLs, but not in any of the 14 PCLBCLs on the head and trunk. The t(14;18) was only detected in two of seven SCLBCLs, but not in the five PCLBCLs of the leg or the eight PCLBCLs on the head or trunk studied. CONCLUSION The striking differences in bcl-2 expression between PCLBCL of the head or trunk and PCLBCL on the leg suggest that bcl-2 expression is site-related and may contribute to the different clinical behavior between these two groups of lymphomas. In addition, they underscore that PCLBCL on the head and trunk and PCLBCL on the leg are distinct disease entities, as recently recognized in the European Organization for Research and Treatment of Cancer (EORTC) classification for primary cutaneous lymphomas.
Unknown primary tumors metastatic to liver.
Authors: Ayoub J P , Hess K R , Abbruzzese M C , Lenzi R , Raber M N , Abbruzzese J L 
Published: February 2017

PURPOSE The objectives of this study were to identify prognostic factors for unknown primary tumor (UPT) patients with hepatic metastases, determine the common primary tumors identified, assess the yield of specific diagnostic studies, and evaluate the impact of therapy on survival. PATIENTS AND METHODS The 1,522 patients analyzed were referred from January 1, 1987 through June 30, 1995. Clinical data from these patients were entered into a computerized database for storage, retrieval, and analysis. Survival was measured from the time of diagnosis; survival distribution was estimated by the product limit method. Multivariate survival analyses were performed by proportional hazards regression. RESULTS Five hundred UPT patients had liver metastases. Primary tumors, usually lung, colorectal, or pancreatic neoplasms, were identified in 135 patients (27%). The remaining 365 unknown primary carcinoma (UPC) patients with liver involvement had a higher death rate than those without liver involvement (hazards ratio, 1.63; P < .0001). Neuroendocrine carcinoma patients had a lower death rate than patients without this histology (hazards ratio, 0.29; (P < .0001). Two hundred sixteen of 365 patients with UPC and liver metastases received chemotherapy. Chemotherapy-treated patients had a lower death rate than those who were not treated with chemotherapy (hazards ratio, 0.52; P < .0001). The effect of chemotherapy was most pronounced in patients with adenocarcinoma. CONCLUSION Hepatic metastases in UPC patients portend a generally poor prognosis. However, subsets of patients with more favorable outcomes can be identified by available clinical and pathologic data. Chemotherapy may be beneficial for the large subset of UPC patients with adenocarcinoma that involves the liver.
Analytical decision model for the cost-effective management of solitary pulmonary nodules.
Authors: Gambhir S S , Shepherd J E , Shah B D , Hart E , Hoh C K , Valk P E , Emi T , Phelps M E 
Published: February 2017

PURPOSE AND METHODS Multiple strategies are currently being used to manage patients who present with indeterminate solitary pulmonary nodules (SPN). We have used decision-analysis models to assess the cost-effectiveness of various strategies for the diagnosis and management of SPN. Four decision strategies were compared: a wait and watch strategy, a surgery strategy, a computed tomography (CT)-based strategy, and a CT-plus-positron emission tomography (PET) strategy. An incremental cost-effectiveness ratio (ICER) was used to compare all strategies to the wait and watch strategy. RESULTS A CT-plus-PET strategy was the most cost-effective over a large pretest likelihood (probability of having a malignant nodule), with a range of 0.12 to 0.69. Furthermore, within this likelihood range, the potential cost savings of using the CT-plus-PET strategy over the CT strategy ranged from $91 to $2,200 per patient. This translates to a yearly national savings of approximately $62.7 million. CONCLUSION Decision-analysis modeling indicates the potential cost-effectiveness of [18F]2-fluoro-2-deoxy-D-glucose (FDG)-PET in the management of SPN. Furthermore, the decision trees developed can be used to model various features of the management of SPN, including modeling the cost-effectiveness of other newly emerging technologies.
Tumor lysis syndrome: an uncommon complication of fludarabine therapy of chronic lymphocytic leukemia.
Authors: Cheson B D , Frame J N , Vena D , Quashu N , Sorensen J M 
Published: February 2017

PURPOSE To quantify the incidence and severity of tumor lysis syndrome (TLS) as a consequence of fludarabine therapy in patients with advanced chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS A retrospective review and questionnaire follow-up of clinical and laboratory data were performed on patients with intermediate or high-risk CLL on the National Cancer Institute Group C protocol or special exception mechanisms, or phase II trials of fludarabine, for whom adverse drug reports of TLS were available. Fludarabine was administered at a dose of 20 to 40 mg/m2 per day for 5 days at monthly intervals. RESULTS Among the 6,137 patients, TLS was suspected in 26 (0.42%), with clinical and laboratory features consistent with TLS present in 20 (0.33%). Prophylaxis against TLS had been administered to 60% of these patients. Clinical or laboratory features were similar to patients who did not develop TLS. Of the patients with TLS, 90% had high-risk CLL, 60 months of prior disease duration, with a median pretreatment WBC of 109 x 10(9)/L, two prior regimens, lymphadenopathy in 89%, splenomegaly and/or hepatomegaly in 90%. TLS developed on approximately day 7 and lasted a median of 9.5 days. Dialysis was required in 30% during the TLS episode; 20% of patients died during cycle one of fludarabine therapy with renal failure, and another 20% died of infection or congestive heart failure. Six patients were retreated with fludarabine without recurrent TLS. CONCLUSION TLS after fludarabine therapy is extremely uncommon, but may be associated with significant morbidity and mortality.
Costs of blood transfusion: a process-flow analysis.
Authors: Cantor S B , Hudson D V , Lichtiger B , Rubenstein E B 
Published: February 2017

PURPOSE To determine the cost of transfusing 2 units (U) of packed RBCs at a comprehensive cancer center. METHODS We performed a process-flow analysis to identify all costs of transfusing 2 U of allogeneic packed RBCs on an outpatient basis to patients with either (1) solid tumor who did not undergo bone marrow transplantation (BMT), (2) solid tumor who underwent BMT, (3) hematologic malignancy who did not undergo BMT, (4) hematologic malignancy who underwent allogeneic BMT, or (5) hematologic malignancy who underwent autologous BMT. We conducted structured interviews to determine the personnel time used and physical resources necessary at all steps of the transfusion process. RESULTS The mean cost of a 2-U transfusion of allogeneic packed RBCs was $548, $565, $569, $569, and $566 for patients with non-BMT solid tumor, BMT solid tumor, non-BMT hematologic malignancy, allogeneic BMT hematologic malignancy, and autologous BMT hematologic malignancy, respectively. Sensitivity analysis showed that total transfusion costs were sensitive to variations in the amount of clinician compensation and overhead costs, but were relatively insensitive to reasonable variations in the direct costs of blood tests and the blood itself, or the probability or extent of transfusion reaction. CONCLUSION The costs of the transfusion of packed RBCs are greater than previously analyzed, particularly in the cancer care setting.
Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk.
Authors: Frank T S , Manley S A , Olopade O I , Cummings S , Garber J E , Bernhardt B , Antman K , Russo D , Wood M E , Mullineau L , Isaacs C , Peshkin B , Buys S , Venne V , Rowley P T , Loader S , Offit K , Robson M , Hampel H , Brener D , Winer E P , Clark S , Weber B , Strong L C , Thomas A 
Published: February 2017

PURPOSE Previous studies of mutations in BRCA1 or BRCA2 have used detection methods that may underestimate the actual frequency of mutations and have analyzed women using heterogeneous criteria for risk of hereditary cancer. PATIENTS AND METHODS A total of 238 women with breast cancer before age 50 or ovarian cancer at any age and at least one first- or second-degree relative with either diagnosis underwent sequence analysis of BRCA1 followed by analysis of BRCA2 (except for 27 women who declined analysis of BRCA2 after a deleterious mutation was discovered in BRCA1). Results were correlated with personal and family history of malignancy. RESULTS Deleterious mutations were identified in 94 (39%) women, including 59 of 117 (50%) from families with ovarian cancer and 35 of 121 (29%) from families without ovarian cancer. Mutations were identified in 14 of 70 (20%) women with just one other relative who developed breast cancer before age 50. In women with breast cancer, mutations in BRCA1 and BRCA2 were associated with a 10-fold increased risk of subsequent ovarian carcinoma (P = .005). CONCLUSION Because mutations in BRCA1 and BRCA2 in women with breast cancer are associated with an increased risk of ovarian cancer, analysis of these genes should be considered for women diagnosed with breast cancer who have a high probability of carrying a mutation according to the statistical model developed with these data.
Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor.
Authors: Loehrer P J , Gonin R , Nichols C R , Weathers T , Einhorn L H 
Published: February 2017

PURPOSE This study was designed to assess the effectiveness of vinblastine, ifosfamide, and cisplatin (VeIP) as second-line therapy in patients with recurrent germ cell tumors with previous treatment with cisplatin plus etoposide, usually in combination with bleomycin. PATIENTS AND METHODS From July 1984 through December 1989, 135 patients with progressive, disseminated germ cell tumors after cisplatin-etoposide-based combination therapy induction chemotherapy were treated with VeIP. Patients who progressed within 3 weeks of previous cisplatin therapy were not eligible. Progression was documented by biopsy or increasing serum markers. No exclusion was made on the basis of metastatic site or performance status. The dosages were vinblastine 0.11 mg/kg/d (days 1 and 2), ifosfamide 1.2 gm/m2/d (days 1 through 5), and cisplatin 20 mg/m2/d (days 1 through 5), with courses repeated every 21 days for four cycles. RESULTS Sixty-seven (49.6%) patients achieved a disease-free status after chemotherapy with or without surgical resection of residual carcinoma or teratoma. Overall, 42 (32%) patients are alive and 32 (23.7%) are continuously free of disease. None of the 32 patients with nonseminomatous extragonadal tumors are disease-free compared with 30 of 100 patients with gonadal primaries. Two of three extragonadal seminomas are continuously disease-free. CONCLUSION VeIP is capable of producing durable complete remissions in patients with disseminated germ cell cancer who relapse after cisplatin-etoposide-based induction therapy. Long-term disease-free survival is not seen in those patients with extragonadal nonseminomatous germ cell tumors.
Positron emission tomography with 5-hydroxytryprophan in neuroendocrine tumors.
Authors: Orlefors H , Sundin A , Ahlström H , Bjurling P , Bergström M , Lilja A , Långström B , Oberg K , Eriksson B 
Published: February 2017

PURPOSE Carcinoid tumors, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP). We have evaluated the usefulness of positron emission tomography (PET) with carbon-11-labeled 5-HTP in the diagnosis and treatment follow-up evaluation of patients with neuroendocrine tumors. PATIENTS AND METHODS PET using 11C-labeled 5-HTP was compared with computed tomography (CT) in 18 patients (14 midgut, one foregut, one hindgut carcinoid, and two endocrine pancreatic tumors [EPT]). In addition, 10 of 18 patients were monitored with PET examinations during treatment. RESULTS All 18 patients, including two with normal urinary 5-hydroxyindole acetic acid (U-5-HIAA), had increased uptake of 11C-labeled 5-HTP in tumorous tissue as compared with normal tissue. Liver metastases, as well as lymph node, pleural, and skeletal metastases, showed enhanced 5-HTP uptake and PET could detect more lesions than CT in 10 patients and equal numbers in the others. Tumor visibility was better for PET than for CT due to the high and selective uptake of 5-HTP with a high tumor-to-background ratio. Binding studies indicated an irreversible trapping of 5-HTP in the tumors. Linear regression analyses showed a clear correlation (r = .907) between changes in U-5-HIAA and changes in the transport rate constant for 5-HTP during treatment. CONCLUSION PET with 11C-labeled 5-HTP demonstrated high uptake in neuroendocrine gastrointestinal tumors and thereby allowed improved visualization compared with CT. The in vivo data on regional tumor metabolism, as expressed in 11C-5-HTP uptake and transport rate, provided additional information over conventional radiologic techniques. The close correlation between the changes in 11C-5-HTP transport rate and U-HIAA during medical treatment indicates the potential of 11C-5-HTP-PET as a means to monitor therapy.
BAX protein expression and clinical outcome in epithelial ovarian cancer.
Authors: Tai Y T , Lee S , Niloff E , Weisman C , Strobel T , Cannistra S A 
Published: February 2017

PURPOSE Expression of the pro-apoptotic protein BAX sensitizes ovarian cancer cell lines to paclitaxel in vitro by enhancing the pathway of programmed cell death. The present study was performed to determine the relationship between BAX expression and clinical outcome in 45 patients with newly diagnosed ovarian cancer. METHODS BAX protein expression was analyzed by immunohistochemistry, and its relationship with clinical outcome was determined. Assessment of BAX mRNA transcript levels and mutational analysis of the BAX coding region were also performed. RESULTS BAX protein was expressed at high levels (defined as > or = 50% of tumor cells positive) in tumor tissue from 60% of newly diagnosed patients. All patients whose tumors expressed high levels of BAX achieved a complete response (CR) to first-line chemotherapy that contained paclitaxel plus a platinum analogue, compared with 57% of patients in the low-BAX group (P = .036). After a median follow-up of 1.9 years, the median disease-free survival (DFS) of patients in the high-BAX group has not been reached, compared with a median DFS of 1.1 years for low-BAX expressors (P = .0061). BAX retained independent prognostic significance in multivariate analysis when corrected for stage and histology. BAX mRNA transcripts were easily detected in samples with low BAX protein expression, and no BAX mutations were identified. CONCLUSION The correlation between high BAX levels and improved clinical outcome suggests that an intact apoptotic pathway is an important determinant of chemoresponsiveness in ovarian cancer patients who receive paclitaxel.
Clinical significance of alpha-catenin, collagen IV, and Ki-67 expression in epithelial ovarian cancer.
Authors: Anttila M , Kosma V M , Ji H , Wei-Ling X , Puolakka J , Juhola M , Saarikoski S , Syrjänen K 
Published: February 2017

PURPOSE To analyze alpha-catenin and collagen IV expression in epithelial ovarian cancer with special reference to their prognostic significance and correlations with clinical and pathologic characteristics, as well as cell proliferation marker Ki-67. PATIENTS AND METHODS Alpha-catenin, collagen IV, and Ki-67 expression was immunohistochemically analyzed in paraffin-embedded specimens of 316 patients with epithelial ovarian cancer. RESULTS Alpha-catenin and collagen IV expression was not interrelated or related to International Federation of Gynecology and Obstetrics (FIGO) stage or proliferation marker Ki-67. Alpha-catenin expression was reduced (< 100%) in 50% of primary tumors. Reduced alpha-catenin and collagen IV expression was directly related to high histologic grade (P < .001). In both univariate and multivariate analyses, Ki-67 proliferation significantly predicted overall survival. In the subset of 86 patients with stage I tumor, a reduced (< 100%) alpha-catenin expression approached statistical significance as a negative prognostic factor (P = .035) and retained its statistical significance in the multivariate analysis (P = .025). The low (< 30%) expression of alpha-catenin (n = 10) was a sign of inferior survival as compared with normal expression in both the univariate (P = .0107) and multivariate analyses (P = .0105). CONCLUSION Alpha-catenin expression seems to be a useful marker of those FIGO stage I tumors likely to run a less favorable course. The high cell proliferative activity was associated with poor survival. In the future, alpha-catenin and Ki-67 expression should be studied in a large prospective cohort that includes early-stage cancers to select the more aggressive tumors for intense early chemotherapy.
Human papillomavirus genotype as a major determinant of the course of cervical cancer.
Authors: Lombard I , Vincent-Salomon A , Validire P , Zafrani B , de la Rochefordière A , Clough K , Favre M , Pouillart P , Sastre-Garau X 
Published: February 2017

PURPOSE To determine whether the prognosis of invasive cancers of the uterine cervix is related to the type of human papillomavirus (HPV) associated with the tumor. PATIENTS AND METHODS Two hundred ninety-seven patients with invasive cervical cancer were prospectively registered from 1986 to 1994. HPV typing was performed on DNA extracted from frozen tumor specimens by means of Southern blot hybridization (SBH) and polymerase chain reaction (PCR) techniques. The median follow-up was 38 months. RESULTS HPV sequences were detected in 246 patients (83%): 150 patients had HPV16, 31 patients had HPV18, and 14 patients had one of the intermediate-oncogenic-risk HPV types (HPV31, 33, 35, 52, 58). In 51 patients, HPV type remained undetermined, and in 51 patients, no viral sequences were found. No significant associations were observed between virologic data and tumor stage or node status. The 5-year disease-free survival (DFS) rate was 100% for patients with intermediate-risk HPV-associated tumors, 58% for patients with HPV16-positive tumors, and 38% for patients with HPV18-positive tumors (P = .02). In multivariate analysis, patients with HPV18-associated tumors had a relative risk (RR) of death 2.4 times greater (95% confidence interval [CI], 1.29-4.59) than that for patients with HPV16, and 4.4 times greater (95% CI, 3.48-5.32) than that for patients with a tumor associated with a viral type different from HPV16/18. CONCLUSION The prognosis for invasive cancers of the uterine cervix is dependent on the oncogenic potential of the associated HPV type. HPV typing may provide a prognostic indicator for individual patients and is of potential use in defining specific therapies against HPV-harboring tumor cells.
Limitations of specific reverse-transcriptase polymerase chain reaction markers in the detection of metastases in the lymph nodes and blood of breast cancer patients.
Authors: Bostick P J , Chatterjee S , Chi D D , Huynh K T , Giuliano A E , Cote R , Hoon D S 
Published: February 2017

PURPOSE This study was performed to evaluate the potential of specific mRNA markers to detect micrometastases by reverse-transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis of sentinel lymph nodes (SNs) and blood from patients with breast cancer. PATIENTS AND METHODS We assessed the specificity of carcinoembryonic antigen (CEA), cytokeratin-19 (CK-19), CK-20, gastrointestinal tumor-associated antigen-733.2 (GA733.2), and mucin-1 (MUC-1) in the blood of healthy donors (n = 13) and lymph nodes from patients without cancer (n = 3) by RT-PCR assay. The sensitivity of the RT-PCR assay for the target mRNA markers was assessed in breast cancer cell lines (n = 4), primary breast tumors (n = 8), and the frozen sections of SNs (n = 22) from 22 patients with American Joint Committee on Cancer (AJCC) stages I to IIIA breast cancer. RESULTS CK-20 was the only mRNA marker not detected in lymph nodes or blood from patients without cancer. Both the blood and lymph nodes from patients without cancer expressed CEA, CK-19, GA733.2, and MUC-1 mRNA. All four breast cancer cell lines and six of eight primary breast tumors expressed all five mRNA markers. Expression of mRNA by the RT-PCR assay in the frozen-section SNs (n = 12) without metastases by conventional histopathology ranged from 8% (CK-20) to 92% (GA733.2). Detection of RT-PCR cDNA products in frozen-section SNs was increased with Southern blot analysis compared with ethidium bromide gel electrophoresis (EtBr) for all mRNA markers except CK-19. CONCLUSION CEA, CK-19, GA733.2, and MUC-1 show no diagnostic value as mRNA markers for the detection of micrometastases by the RT-PCR assay because they are expressed in the blood and lymph nodes of patients without cancer. Further studies are needed to assess the sensitivity of CK-20 to detect micrometastases by the RT-PCR assay in the blood and frozen-section SNs of patients with breast cancer.