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At least 919 records · Page 51Linked to original sources
PubMed2006

Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation registry study.

Relapsed acute myeloid leukemia (AML) in adults has a poor prognosis if treated with chemotherapy alone. Case series have previously supported the role of myeloablation and autologous transplantation as a potentially curative treatment. This study aimed to use the large numbers and extended follow-up data in the British Society of Blood and Marrow Transplantation (BSBMT) registry database to establish long-term outcomes and relate these to biological and procedural factors. The BSBMT registry database was used to retrospectively identify 152 adult patients (age, 16-69 years) with AML in second remission treated with autologous transplantation in 1982-2003. Cytogenetic data were available for 68% of the patients; of these, at diagnosis, 42% had good risk features, 57% had standard risk features, and 1% had poor risk features. Conditioning regimens varied; autologous rescue was provided with bone marrow (BM) (71%), peripheral blood stem cells (PBSCs) (18%), or both (11%), which were harvested during first complete remission (CR1) and/or second CR (CR2). Median follow-up was 84 months (range, 2-200 months). At 10 years, actuarial overall survival (OS) was 32%, progression-free survival (PFS) was 28%, and relapse rate (RR) was 57%. The 100-day nonrelapse mortality (NRM) was 7%, rising to 11% at 1 year and to 14% at 10 years. OS was significantly related to M3 subtype (5-year OS, 66%; P = .005), patient age at diagnosis (P = .005) and transplantation (P = .026), and length of CR1, with greatest significance if the patient was dichotomized at CR1 duration of < 8 months or > or = 8 months (P = .0001). There was no difference in OS between regimens containing total body irradiation (TBI) and chemotherapy alone (P = .7). In relation to the nature of autologous graft material, there was improved OS (P = .025) and PFS (P = .009) with the use of cells harvested entirely in CR1 compared with cells harvested in CR2 or in both CR1 and CR2. Engraftment times were significantly shortened with the use of PBSCs alone or in combination with BM compared with BM alone (P = .0001), but there was no significant long-term impact on OS, PFS, RR, or NRM. This study provides long-term follow-up data in one of the largest series of patients with standard-risk and good-risk AML in CR2 treated with autologous transplantation and supports earlier observations that long-term survival is achievable in about 1/3 of patients overall and in about 2/3 of patients with M3 with a relatively low NRM. Outcomes are better in patients with CR1 > or = 8 months by use of grafts obtained entirely in CR1 and use of PBSCs. TBI conditioning did not confer an advantage. Randomized studies against unrelated donor transplantation are warranted.

Acute Disease↗
PubMed2004

Genetic effects of radiotherapy for childhood cancer: gonadal dose reconstruction.

PURPOSE: To estimate the doses of radiation to organs of interest during treatment of childhood cancer for use in an epidemiologic study of possible heritable diseases, including birth defects, chromosomal abnormalities, cancer, stillbirth, and neonatal and premature death. METHODS AND MATERIALS: The study population was composed of more than 25,000 patients with cancer in Denmark and the United States who were survivors of childhood cancer and subsequently had nearly 6,500 children of their own. Radiation therapy records were sought for the survivors who parented offspring who had adverse pregnancy outcomes (>300 offspring), and for a sample of all survivors in a case-cohort design. The records were imaged and centrally abstracted. Water phantom measurements were made to estimate doses for a wide range of treatments. Mathematical phantoms were used to apply measured results to estimate doses to ovaries, uterus, testes, and pituitary for patients ranging in age from newborn to 25 years. Gonadal shielding, ovarian pinning (oophoropexy), and field blocking were taken into account. RESULTS: Testicular radiation doses ranged from <1 to 700 cGy (median, 7 cGy) and ovarian doses from <1 to >2,500 cGy (median, 13 cGy). Ten percent of the records were incomplete, but sufficient data were available for broad characterizations of gonadal dose. More than 49% of the gonadal doses were >10 cGy and 16% were >100 cGy. CONCLUSIONS: Sufficient radiation therapy data exist as far back as 1943 to enable computation of gonadal doses administered for curative therapy for childhood cancer. The range of gonadal doses is broad, and for many cancer survivors, is high and just below the threshold for infertility. Accordingly, the epidemiologic study has >90% power to detect a 1.3-fold risk of an adverse pregnancy outcome associated with radiation exposure to the gonads. This study should provide important information on the genetic consequences of radiation exposure to humans.

Adolescent↗
PubMed2004

Outcome after simultaneous colorectal and hepatic resection for colorectal cancer with synchronous metastases.

BACKGROUND: Consensus has not been reached concerning the timing of hepatectomy in patients with synchronous colorectal liver metastases, specifically with respect to patient selection criteria for simultaneous resection of the colorectal primary and the liver metastasis. METHODS: Retrospectively obtained clinicopathologic data for 39 consecutive patients with synchronous colorectal cancer metastases to the liver, who underwent curative simultaneous "1-stage" hepatectomy and resection of the colorectal primary at 1 institution, were subjected to univariate and multivariate analysis concerning the safety and success of the combined procedure. RESULTS: Only the volume of the resected liver was selected as a risk factor for postoperative complications (350 g mean resected liver volume in patients with postoperative complications vs 150 g in those without complications; P <.05). Patient age of 70 years or older (P <.05) and poorly differentiated or mucinous adenocarcinoma as the primary lesion (P <.01) predicted decreased overall survival by univariate analysis. Multivariate analysis retained histologic differentiation of the colorectal primary as an independent survival predictor (P <.05). CONCLUSIONS: A 1-stage procedure appears desirable for synchronous colorectal hepatic metastases except for patients requiring resection of more than 1 hepatic section, patients aged 70 years or older, and those with poorly differentiated or mucinous adenocarcinomas as primary lesions.

Adenocarcinoma↗
PubMed1991

The risk of dying of prostate cancer in patients with clinically localized disease.

From 1966 to 1979, 360 patients with clinical stages A2, B and C1 prostate cancer underwent staging pelvic lymphadenectomy, and completed a course of combined interstitial radioactive gold seeds and external beam radiotherapy. All patients had a normal serum prostatic acid phosphatase level and a bone scan negative for metastases. All patients were followed until death or for a mean of 7.3 years (range 1.2 to 18.25 years) for those alive at analysis. To determine the risk of dying of prostate cancer we reviewed the records of the 142 patients (39%) who died. At analysis 21% of the patients had died of prostate cancer and 17% of other known causes. The cause of death could not be determined in 4 patients (1%). Cardiovascular disease accounted for a fifth of all deaths. The actuarial risk of death of prostate cancer for all patients was 8 +/- 3% (+/- 2 standard errors) at 5 years and 30 +/- 7% at 10 years. The risk of death of all causes was 16 +/- 4% at 5 years and 46 +/- 7% at 10 years. An increased risk of cancer death was associated with established risk factors, including advanced local disease, poorly differentiated histology, pelvic nodal metastases and distant recurrence. We also noted a substantial risk of cancer death in patients who had local tumor recurrence. While previous studies have reported a relatively low incidence of cancer deaths (4 to 17%) in patients initially diagnosed with localized disease, our data suggest that prostate cancer is the major cause of mortality in such patients. Aggressive curative therapy, regardless of treatment modality, should be considered for localized prostate cancer in men with a life expectancy of 10 or more years.

Actuarial Analysis↗
PubMed2002

Patterns of failure after primary local therapy for prostate cancer and rationale for secondary therapy.

The timing and type of treatment for patients with biochemical disease recurrence after local therapy for prostate cancer remains controversial. This is because of many unresolved issues surrounding the natural history of disease progression in such patients, including the limited ability of clinical measures to accurately define local versus distant disease recurrence. Clinicians generally rely on clinical tumor characteristics, such as tumor stage, grade, and prostate specific antigen (PSA) kinetics after local therapy, to distinguish local from distant recurrence. This determination is important, because patients with local recurrence may be candidates for a second, potentially curative treatment, whereas those with distant recurrence are generally treated with androgen deprivation therapy (ADT). Data from a national disease registry of patients with prostate cancer, the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), suggest that the use of secondary cancer treatment after local therapy for prostate cancer is common. For patients initially treated with radical prostatectomy, secondary treatment appears to be nearly equally divided between postoperative radiation and ADT, whereas >90% of patients receiving a secondary treatment after radiation are treated with ADT. Serum PSA at diagnosis, Gleason score, and type of initial treatment appear to be predictors of secondary treatment use in this setting. Patient age, lymph node status, and margin status appear to be predictors of secondary treatment with ADT or radiation for patients initially treated with radical prostatectomy.

Biomarkers, Tumor↗
PubMed1993

[Infectious diseases transmitted by animal bites].

The animal population, and most of all pets, entail a high risk of bites, some of them severe, which may lead to complications among which infection is a major one. Epidemiological data about the germs liable to grow (Pasteurellae, pyogenic germs, anareobes...) are helpful to guide curative, and even more, prophylactic approaches to treatment.

Animals↗
PubMed2001

Muscle-invasive transitional cell carcinoma of the urinary bladder: a population-based study of patterns of care and prognostic factors.

PURPOSE: Population-based cancer registries can permit the study of the survivorship of all patients with a particular diagnosis regardless of patterns of referral and practice within a specific geographic distribution. The purpose of this study is to describe the patterns of care, outcome, and prognostic factors for bladder cancer in the northern region of the province of Alberta, Canada, between 1984 and 1993. METHODS AND MATERIALS: Between 1984 and 1993, 184 patients from northern Alberta were identified from the Alberta Cancer Registry as having undergone curative treatment for biopsy-proven muscle-invasive transitional cell carcinoma of the bladder. Data were obtained, by retrospective chart review, regarding the staging, pathology, treatment, and outcome of patients treated in the northern Alberta cities of Edmonton, Grande Prairie, and Red Deer, regardless of the responsible treating institution. The prognostic significance of patient-, tumor-, and treatment-related variables were tested using univariate and multivariate analysis using the Cox proportional-hazard model. RESULTS: As the primary treatment modality, 74 patients (40%) received radical radiotherapy (RT) without surgery; surgery was used alone in 81 patients (44%), and was combined with preoperative or postoperative radiotherapy in 29 patients (16%). Seventy-three (40%) patients also received concurrent, neoadjuvant, or adjuvant chemotherapy. The Kaplan-Meier estimate of median survival was 2.2 years, and the 5-year overall survival was 30%. Univariate analysis demonstrated the prognostic significance of T classification (p < 0.001), lymph node involvement (p < 0.001), complete response to RT (p = 0.001), hydronephrosis (p = 0.017), and vascular/lymphatic involvement (p = 0.035). Multivariate analysis revealed the following to have a significant association with survival: T classification (p = 0.001), lymph node involvement (p = 0.004), complete response to RT (p = 0.054), hydronephrosis (p = 0.019), and use of chemotherapy in the treatment regimen (p = 0.025). CONCLUSION: The strongest prognostic factors in this study were tumor related, and no significant differences in survival were detected between patients treated with primary surgery vs. organ-preservation approaches. A survival advantage associated with the incorporation of chemotherapy into the management schema was detected on multivariate, but not univariate, analysis. Stratification of patients based on tumor characteristics is imperative in clinical trials for invasive bladder cancer. Novel treatment approaches are required to improve survival further in patients with apparently localized disease.

Adult↗
PubMed2005

Screening for pancreatic neoplasia in high-risk individuals: who, what, when, how?

Pancreatic cancer (PC) is a highly lethal disease. Most symptomatic, clinically detected PCs are advanced and not curable. Indeed, the estimated 5-year survival rate is 4%, which is attributable to late diagnosis and low resection rate. Screening of high-risk individuals and early detection of small PCs and precursor lesions might improve the outcome if curative therapy could be offered in the presymptomatic stage. This article summarizes the available published data and preliminary results and discusses the different approaches to screening for pancreatic neoplasia at 2 university-based programs in the United States.

Humans↗
PubMed2001

Evaluation of the 5th edition of the TNM classification for gastric cancer: improved prognostic value.

The main change in the 5th edition (1997) of the TNM classification for gastric cancer compared to the 4th edition (1987) is the use of the number of involved nodes instead of the location of positive nodes. As a result stage grouping is also altered. A second change is the requirement for the examination of at least 15 nodes to justify the N0 status. Patients with fewer examined negative nodes are unclassifiable (Nx). Data were retrieved from a randomized trial database comparing D1 and D2 dissection and 633 curatively operated patients were included. According to the criteria of the 5th edition, 39% of the node-positive patients had another N stage compared to the 4th: 21% had a lower and 18% had a higher stage. 5-year survival rates according to the 4th edition N0, N1 and N2 groups were respectively 72%, 34% and 27%. According to the 5th edition these percentages were for the N0, N1, N2, N3 and Nx groups respectively 75%, 38%, 19%, 8% and 65%. The former 1987 N1 and N2 group were significantly split into three new N 1997 groups (P = 0.006, respectively P< 0.0005). The Cox's regression analysis showed the N 1997 classification to be the most important prognostic variable, with a higher prognostic value than N 1987. In addition, the new TNM stage was also a better prognosticator. The requirement for examining at least 15 nodes, however, could not be fulfilled in 38% of all node-negative patients and we found that a minimum of 5 consecutive negative lymph nodes is a reliable number for staging purposes. We conclude that the 5th edition of the TNM classification provides a better estimation of prognosis, however, examination of at least 15 negative regional lymph nodes is too high a threshold and 5 gives similar prognostic value.

Humans↗
PubMed2004

Gene therapy for thyroid cancer: current status and future prospects.

Despite multimodality treatment for thyroid cancer, including surgical resection, radioiodine therapy, thyrotropin (TSH)-suppressive thyroxine treatment, and chemotherapy/radiotherapy, survival rates have not improved over the last decades. Therefore, development and evaluation of novel treatment strategies, including gene therapy, are urgently needed. A variety of gene therapy approaches have been evaluated for the treatment of follicular cell-derived and medullary thyroid cancer, including corrective gene therapy (p53 restoration, expression of a dominant negative RET mutant), cytoreductive gene therapy (suicide gene/prodrug strategy herpes simplex virus-thymidine kinase [HSV-tk]/ganciclovir, antiangiogenic therapy with endostatin) and immunomodulatory gene therapy (expression of interleukin (IL)-2 and IL-12). Furthermore, cloning of the sodium iodide symporter (NIS) gene has paved the way for the development of a novel cytoreductive gene therapy strategy based on NIS gene transfer followed by the application of radioiodine therapy ((131)I). NIS gene delivery into medullary and follicular cell-derived thyroid cancer cells has been shown to be capable of establishing or restoring radioiodine accumulation and might therefore represent an effective therapy for medullary and dedifferentiated thyroid tumors that lack iodide accumulating activity. The data summarized in this review article clearly demonstrate that the currently available strategies represent potentially curative novel therapeutic approaches for future gene therapy of thyroid cancer. The combination of different therapeutic genes has been demonstrated to be very useful to enhance therapeutic efficacy and seems to have a promising role at least as part of a multimodality approach for advanced thyroid cancer.

Endocrinology↗
PubMed2006

ParameciumDB: a community resource that integrates the Paramecium tetraurelia genome sequence with genetic data.

ParameciumDB (http://paramecium.cgm.cnrs-gif.fr) is a new model organism database associated with the genome sequencing project of the unicellular eukaryote Paramecium tetraurelia. Built with the core components of the Generic Model Organism Database (GMOD) project, ParameciumDB currently contains the genome sequence and annotations, linked to available genetic data including the Gif Paramecium stock collection. It is thus possible to navigate between sequences and stocks via the genes and alleles. Phenotypes, of mutant strains and of knockdowns obtained by RNA interference, are captured using controlled vocabularies according to the Entity-Attribute-Value model. ParameciumDB currently supports browsing of phenotypes, alleles and stocks as well as querying of sequence features (genes, UniProt matches, InterPro domains, Gene Ontology terms) and of genetic data (phenotypes, stocks, RNA interference experiments). Forms allow submission of RNA interference data and some bioinformatics services are available. Future ParameciumDB development plans include coordination of human curation of the near 40 000 gene models by members of the research community.

Alleles↗
PubMed1988

Effects of age and nutritional status on surgical outcomes in head and neck cancer.

Older and younger malnourished and well-nourished head and neck cancer patients scheduled for surgery were studied. More of the young (75%) compared with the old (58%) underwent curative surgery, and only the old with lower clinical states of cancer were selected. When data on those undergoing surgery were analyzed in regard to older and younger malnourished and well-nourished men, the malnourished old had the poorest surgical outcomes of any group, with significantly more complications and morbidity rates. The well-nourished old had outcomes that did not differ from younger patients. On further examination, 60% of the young malnourished and only 20% of the old malnourished received preoperative enteral or parenteral nutritional support. Findings suggest that more attention to the needs of the older malnourished patients could improve surgical outcomes.

Adult↗
PubMed2000

Detection of hematogenic tumor cell dissemination in patients undergoing resection of liver metastases of colorectal cancer.

OBJECTIVE: To determine the extent of pre- and intraoperative hematogenic tumor cell dissemination in patients undergoing liver resection for metastatic colorectal cancer. SUMMARY BACKGROUND DATA: For patients with hepatic metastases of colorectal cancer, liver resection is the only potentially curative therapy. However, 38% to 53% of patients develop extrahepatic tumor recurrence, probably caused by tumor cells disseminated before or during surgery not detected by current staging systems. METHODS: Blood samples harvested before, during, and after surgery from 41 patients and bone marrow samples from 30 patients undergoing resection of liver metastases of colorectal cancer were analyzed for disseminated tumor cells using cytokeratin 20 reverse transcriptase-polymerase chain reaction. RESULTS: Tumor cells were detected in the blood samples of 26 of the 41 patients (63.4%) and in the bone marrow samples of 8 of the 30 patients (26.7%). Tumor cells were detected significantly more often during surgery than before or after surgery. Intraoperative tumor cell dissemination was detected in 41.7% of patients undergoing resection of two or more liver segments but only 14.3% of patients undergoing resection of one liver segment. Compared with resection of primary colorectal cancer, major liver resection carries an increased risk for intraoperative tumor cell dissemination. CONCLUSIONS: Detection of disseminated tumor cells in patients undergoing liver resection for metastases of colorectal cancer using cytokeratin 20 reverse transcriptase-polymerase chain reaction might help to identify patients at high risk for tumor recurrence who may benefit from adjuvant therapy. Major liver resection of metastases leads to frequent intraoperative tumor cell shedding, possibly preventable by alternative surgical strategies.

Adult↗
PubMed2003

The Gene Ontology Annotation (GOA) project: implementation of GO in SWISS-PROT, TrEMBL, and InterPro.

Gene Ontology Annotation (GOA) is a project run by the European Bioinformatics Institute (EBI) that aims to provide assignments of terms from the Gene Ontology (GO) resource to gene products in a number of its databases (http://www.ebi.ac.uk/GOA). In the first stage of this project, GO assignments have been applied to a data set representing the complete human proteome by a combination of electronic mappings and manual curation. This vocabulary has also been applied to the nonredundant proteome sets for all other completely sequenced organisms as well as to proteins from a wide range of organisms where the proteome is not yet complete.

Computational Biology↗
PubMed1999

Number of nodes examined and staging accuracy in colorectal carcinoma.

PURPOSE: The objective of this study was to determine the number of nodes that need to be examined to accurately reflect the histology of the regional lymphatics in colorectal carcinoma. PATIENTS AND METHODS: Patients undergoing curative resection for T2 and T3 colorectal cancer between 1992 and 1996 were reviewed. Pathologic data from these patients were entered into a computerized database for storage, retrieval, and analysis. The major outcome measured was the number of nodes that need to be examined to achieve a node-positive rate consistent with that reported in the National Cancer Data Base (NCDB) report. RESULTS: The number of nodes examined ranged from 0 to 78 (mean, 17 nodes). Node-negative patients had fewer nodes examined (mean, 14 nodes) than node-positive patients (mean, 20 nodes; P =.003). The entire sample had a node-positive rate of 38.8% (95% confidence interval [CI], 32% to 45.5%), not statistically different from that in the NCDB report. When at least 14 nodes were examined, the percent of patients with at least one positive node was 33.3% (95% CI, 24.6% to 42.3%), not statistically different from the NCDB report. CONCLUSION: In a sample of patients statistically similar to the sample in the NCDB report, the examination of at least 14 nodes after resection of T2 or T3 carcinoma of the colon and rectum will accurately stage the lymphatic basin.

Colonic Neoplasms↗
PubMed1991

Radiotherapy or surgery for prostate cancer? Ten and fifteen-year results of external beam therapy.

Ten and 15-year outcome results are reviewed that demonstrate the role of radiation therapy in the management of prostate cancer. Patients with favorable T2a (B1) cancers of unknown nodal status are shown to have equal 15-year survival whether treated with external beam radiation therapy or radical prostatectomy. Patients of unknown nodal status treated for T2b (stage B2) cancer with external beam radiation therapy show superior survival and disease-free survival when compared to results with radical prostatectomy. The role of radical prostatectomy in these patients is unproven. Patients with lymph node dissection negative clinical stages T1b (A2) and T2 (B) treated with external beam radiation therapy exceed their expected survival at 10 years (65% vs 60%), and 70% are free of any failure at 10 years with the majority of failures due to metastasis, not local disease. Similar results are obtained in selected surgical centers with radical prostatectomy in highly selected patients. Patients with stage T3, 4 (stage C) prostate cancer show 10 and 15-year survivals that offer curative therapy and hope to patients with these locally advanced cancers. No long-term data support a role for radical prostatectomy in these patients.

Humans↗
PubMed2001

K-ras mutational analysis of polyclonal colorectal cancers identifies uniclonal circulating tumor cells.

The clonal development of colorectal carcinoma resulting from specific mutations in certain oncogenes and/or tumor suppressor genes is a well-accepted model. It is increasingly recognized that a majority of colorectal cancers are polyclonal on the basis of molecular analysis that demonstrates cells with different mutations within a given oncogene or tumor suppressor gene in the same tumor. This polyclonal pattern may occur as a result of either clonal convergence or divergence during the many steps of oncogenesis. Further complicating this picture is the fact that metastatic lesions may arise from only one of the clonal populations within a tumor and thereby present only a partial molecular make-up of the whole tumor. There are few data available that define clonal selection or specificity of circulating tumor cells in patients undergoing curative resection of colorectal carcinoma. The purpose of this paper is to describe the clonal distribution of circulating tumor cells in four patients with multiple K-ras mutations present in the primary lesion. Patients were selected who were known to have polyclonal primary colorectal cancers resected for cure. All patients had multiple mutations present in exon one, codon 12 and/or 13, of the K-ras gene. Blood samples were drawn immediately before surgery and at 2-week to 6-month intervals postoperatively. Epithelial cells were isolated from peripheral blood mononuclear cells using Dynal Immunobeads coated with antiepithelial antibodies. DNA was extracted from these cells and analyzed for all K-ras mutations present in codons 12 and 13 of the patient's primary tumor using allele-specific polymerase chain reaction followed by Microwell Array Diagonal Gel Electrophoresis. Circulating tumor cells were identified in all four patients. However, in each case of positive circulating cells the only mutation identified was an aspartic acid mutation at codon 13. Once positive the circulating tumor cells persisted in subsequent multiple blood samples. These results provide further strength for the theory of polyclonal progression in primary colorectal cancers, although there may be specific mutational patterns that confer the ability to metastasize. The significance of this persistence of the glycine-to-aspartic acid mutation at codon 13 remains to be defined given that none of these patients has clinical evidence of recurrent cancer at the time of this report.

Aspartic Acid↗
PubMed2003

[Treatment of acute ruptured aneurysm with Guglielmi detachable coil embolization].

OBJECTIVE: To investigate the curative effect of Guglielmi detachable coil (GDC) on acute ruptured intracranial aneurysms. METHODS: The clinical data of 34 patients with acute rupture of intracranial aneurysms treated with early GDC embolization within 6 days after the rupture, 6 being of grade I, 23 of grade II, 4 of grade III and 1 of grade IV according to Hunt-Hess grading, were analyzed retrospectively. Fourteen patients were treated within 3 days, and 20 patients were treated in the 4th to 6th days after the rupture. Two cases of wide-neck aneurysm were embolized with Medtronic AVE stent supported GDC. Angiography was used to observe the effects. RESULTS: Angiography showed complete occlusion in 28 cases and 90% occlusion in 4 cases. One aneurysm was ruptured during the procedure. The caudal tip of GDC protruded to the parent vessel in 2 cases. Two cases failed to be embolized due to severe cerebrovascular spasm. There were no mortality and complications. No re-rupture occurred in the follow-up. CONCLUSION: Less invasive and with less risk and complication, early GDC embolization is one of the ideal therapeutic methods to manage acute ruptured aneurysms.

Adult↗