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PubMedDate not supplied

Endoscopic mucosal resection for esophageal and gastric mucosal cancers.

Accumulated data from surgically resected specimens reveal that mucosal cancers of the esophagus and stomach pose low risk of lymph node metastasis. The author used endoscopic mucosal resection (EMR) as curative treatment in 142 cases of esophageal cancer and 102 cases of stomach cancer. In absolutely indicated cases there has been no local or distant metastasis during the longest period of follow-up (nine years). One perforation and one post-treatment severe stenosis, which was resistant to dilation therapy in the esophagus, were encountered. Deeper layer resection (including partial proper muscle) occurred in the stomach in three cases where the lesions were positioned to the lesser curvature of the upper part of the stomach. Two cases of gastric mucosal resection leaving residual cancer were successfully treated by laser ablation. No case has required further surgery. Resected specimens were contributed to histological evaluation in all cases. In conclusion, EMR can be considered as the first-line treatment for selected cases of early stage esophageal and stomach cancer.

Carcinoma, Squamous Cell↗
PubMed2002

Re-annotation of genome microbial coding-sequences: finding new genes and inaccurately annotated genes.

BACKGROUND: Analysis of any newly sequenced bacterial genome starts with the identification of protein-coding genes. Despite the accumulation of multiple complete genome sequences, which provide useful comparisons with close relatives among other organisms during the annotation process, accurate gene prediction remains quite difficult. A major reason for this situation is that genes are tightly packed in prokaryotes, resulting in frequent overlap. Thus, detection of translation initiation sites and/or selection of the correct coding regions remain difficult unless appropriate biological knowledge (about the structure of a gene) is imbedded in the approach. RESULTS: We have developed a new program that automatically identifies biologically significant candidate genes in a bacterial genome. Twenty-six complete prokaryotic genomes were analyzed using this tool, and the accuracy of gene finding was assessed by comparison with existing annotations. This analysis revealed that, despite the enormous effort of genome program annotators, a small but not negligible number of genes annotated within the framework of sequencing projects are likely to be partially inaccurate or plainly wrong. Moreover, the analysis of several putative new genes shows that, as expected, many short genes have escaped annotation. In most cases, these new genes revealed frameshifts that could be either artifacts or genuine frameshifts. Some entirely unexpected new genes have also been identified. This allowed us to get a more complete picture of prokaryotic genomes. The results of this procedure are progressively integrated into the SWISS-PROT reference databank. CONCLUSIONS: The results described in the present study show that our procedure is very satisfactory in terms of gene finding accuracy. Except in few cases, discrepancies between our results and annotations provided by individual authors can be accounted for by the nature of each annotation process or by specific characteristics of some genomes. This stresses that close cooperation between scientists, regular update and curation of the findings in databases are clearly required to reduce the level of errors in genome annotation (and hence in reducing the unfortunate spreading of errors through centralized data libraries).

Computational Biology↗
PubMed1997

Definitive radiotherapy for T3 squamous cell carcinoma of the glottic larynx.

PURPOSE: To report the results of radiotherapy alone for stage T3 squamous cell carcinoma of the true vocal cord and compare these data with those obtained with other treatment modalities. METHODS AND MATERIALS: Seventy-five patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated with curative intent with radiotherapy alone (73 patients) or followed by a planned neck dissection (two patients) at the University of Florida between September 1966 and August 1994. No patient received adjuvant chemotherapy. All patients were monitored for at least 2 years and 85% had a minimum follow-up duration of 5 years. No patient was lost to follow-up evaluation. RESULTS: The 5-year local control and ultimate local control rates were 63% and 86%, respectively. The volume of the primary tumor (which was calculated on pretreatment computed tomographic [CT] scans in 38 patients) was inversely related to local control with larynx preservation: < or = 3.5 cm3, 20 of 23 (87%) versus greater than 3.5 cm3, four of 14 (29%) (P = .0005). There was no apparent relationship between local control after radiotherapy as a function of whether the vocal cord regained mobility or remained fixed during or shortly after completion of treatment. The 5-year absolute and cause-specific survival rates were 54% and 78%, respectively. Multivariate analysis showed that pretreatment tracheostomy was significantly related to diminished cause-specific survival (P = .0345). CONCLUSION: Radiotherapy alone results in long-term local-regional control and survival rates that are comparable to those obtained with surgery. It is unclear whether induction or concomitant chemotherapy is associated with improved local-regional control and survival compared with radiotherapy alone.

Carcinoma, Squamous Cell↗
PubMed2005

The Consortium for Metabonomic Toxicology (COMET): aims, activities and achievements.

The utility of metabonomics in the evaluation of xenobiotic toxicity has been comprehensively assessed by the Consortium for Metabonomic Toxicology (COMET), formed between five major pharmaceutical companies and Imperial College London, UK. The main objectives were to assess methodologies, to generate a metabonomic database using (1)H nuclear magnetic resonance (NMR) spectroscopy of rodent urine and blood serum and to build a predictive expert system for target organ toxicity. The analytic and biologic variation that might arise through the use of metabonomics was evaluated and a high degree of robustness demonstrated. With the completion of 147 studies, the chief deliverables of a curated database of rodent biofluid NMR spectra and computer-based expert systems for the prediction of kidney or liver toxicity in rat and mouse based on the spectral data have been generated, and delivered to the sponsoring companies. The project, with its relatively modest resources, has met and exceeded all of its targets and was judged a resounding success by the sponsoring companies who are, in many cases, already enhancing and making use of the data in their in-house studies.

Animals↗
PubMed2004

Novel combinations using pemetrexed in malignant mesothelioma.

Malignant mesothelioma is an uncommon malignancy that is locally invasive and rapidly fatal. The majority of patients with mesothelioma are not candidates for curative surgical resection. Chemotherapy has yielded only modest results in these patients. Pemetrexed is a multitargeted antifolate that is being evaluated in many tumor types. Recent single-agent data and data in combination with cisplatin have suggested that pemetrexed has therapeutic benefits in patients with malignant mesothelioma. This article summarizes the data regarding pemetrexed in the treatment of malignant mesothelioma and the potential novel combinations involving the drug that may be used in the future for the treatment of the disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

[Dynamics of interdisciplinary around a health care network: simultaneous programme design and evaluation planning].

This article reports on the evaluation experience of a multiple sclerosis care network in the Midi-Pyrénées region (MIPSEP). It shows how an evaluation team composed of public health doctors and sociologists progressively and naturally evolved from having a purely external observation role towards having a collaborative role actively working with the network's members and partners. A qualitative method was chosen for the data collection through interviews with the network's actors, and the frameworks for reference were constituted from official texts which defined the networks and their missions. Coming from a curative and healing culture, the network's actors were concerned primarily about how to organise themselves in order to better respond to the needs expressed by the patients. The various professional backgrounds and cultures, faced with different perspectives from innovation and confronted with the related difficulties, participated in a collective expertise exercise and collaborated in the construction process. This example supports an open, qualitative, evolutionary evaluation approach which is done in close proximity to the field and work on the ground. The study is timely given the current explosion of debate on evaluation methods. With a great deal of exchange and reflection on suitable tools and indicators as well as the respective roles of researchers, care givers and decision-makers, the results of this study advocate to favour multidisciplinary approaches, including opening up this process to funders and planning authorities rather than over-theorising about it, which only serves to enclose and paralyse a process that, on the contrary, should aim to be more inclusive. This could be a useful way to decompartmentalise and break down existing barriers within the health system.

Community Networks↗
PubMedDate not supplied

Nonfunctional parathyroid carcinoma.

Parathyroid carcinoma is a rare entity accounting for 0.5% to 5% of parathyroid neoplasia. Most of these malignancies present as functional hormone-producing masses with elevated serum levels of parathormone and calcium. These tumors may also be nonfunctional. Clinical detection of nonfunctioning parathyroid malignancies preoperatively is primarily based on symptoms of an expanding neck mass. This ominous complaint is typically accompanied with an advanced stage of the disease at initial diagnosis. Because there is a paucity of data in the literature regarding nonfunctioning parathyroid carcinoma, prognosis can not be readily assessed. In both functional and nonfunctional parathyroid carcinoma, early surgery has proven to be the only curative treatment approach whereas both chemotherapy and radiation therapy fail to produce systemic or regional benefit when used alone. Hence, parathyroid cancer should be considered in every patient evaluated for a neck mass regardless of the blood calcium and blood parathormone level.

Carcinoma↗
PubMed2004

[Long-term result of low anterior resection with stapling devices for rectal cancer].

BACKGROUND & OBJECTIVE: Currently, to preserve the anal function and improve the patients' quality of life, low anterior resection has become the preferred option in curative rectal cancer surgery. As the use of stapling instruments provides more reliable anastomoses in low anterior resection for rectal cancer, it enlarges the indication of this procedure. The aim of this study was to review the operation results and their outcomes of 449 rectal cancer patients who recieved of curative low anterior resections with stapling devices, and intent to find some measures that can reduce complications and improve long-term effects of this procedure. METHODS: The study included 449 patients who had a potentially curative anterior resection with stapled anastomosis in rectal cancer between Jan.1990 and Sept. 2002 at Sun Yat-sen University Cancer Center. All patients had complete follow-up data. All data were analyzed by SPSS8.0 software, risk factors for anastomotic leakage and recurrence were analyzed by Logistic regression, survival was analyzed by life table, and prognostic factors were screened by multivariate COX model. RESULTS: There were 11 cases of anastomotic leakage and 23 cases of anastomotic recurrence after operation. The 5-year survival rate was 78.4%. Age of >/= 65 years, and tumor involvement of more than half circumference were risk factors for anastomotic leakage, blood transfusion during operation was the risk factor for anastomotic recurrence. The independent factors for poor survival were stage of disease and tumor differentiation. CONCLUSIONS: Stapling devices can improve the anal reservation rate in low rectal cancer surgery, and stapled anastomoses is safe and feasible. Adequate preparation of bowel ends, a tension-free anastomosis with excellent blood supply and skilled stapled anastomoses were key measures to reduce anastomotic leakage, While TME, multidisciplinary therapy and the principle of avoiding medical spread, were key measures to improve treatment effect of rectal cancer.

Adenocarcinoma↗
PubMed2005

Current roles for allogeneic hematopoietic cell transplantation following nonmyeloablative or reduced-intensity conditioning.

Nonmyeloablative and reduced-intensity conditioning regimens followed by allogeneic hematopoietic cell transplantation (HCT) have been evaluated in patients with hematologic malignancies who were not considered candidates for conventional HCT because of age or medical comorbidities and in selected patients with metastatic renal cell carcinoma. The regimens have relied more on graft-versus-tumor effects than on chemoradiation therapy to facilitate engraftment and eradicate malignant cells. While nonmyeloablative HCT has been associated with reduced regimen-related toxicities and has been curative for a number of patients with hematologic malignancies, challenges have remained in regard to graft-versus-host disease, infections, and disease progression. In this article, we review data from a number of published phase I and II studies that describe the results of allogeneic HCT after nonmyeloablative conditioning.

Graft vs Host Disease↗
PubMed2006

A descriptive study comparing health attitudes of urban and rural oncology patients.

INTRODUCTION: Rural patients have poor outcomes in cancer management. Previous studies have shown different health beliefs and values in rural populations with high levels of stoicism and fatalism, leading to later presentation and diagnosis, with subsequent poorer prognosis and survival. This study explores the relationship between urban or rural background and health attitudes of newly diagnosed oncology patients, attending one oncology unit in north Queensland, during a 5 month period. This study is a forerunner to a planned larger project to explore the research question: do oncology patients from rural backgrounds differ in their health attitudes and hope levels compared with those from urban backgrounds? The aim of this study was to determine the utility of the selected validated instruments, newly diagnosed patients' willingness and ability to complete the composite survey instrument, and to identify likely issues for inclusion and/or greater focus in the larger project. As pilot studies are also used to develop or refine research questions and hypotheses, this article also considers some research questions for the planned large scale study. METHODS: Self-administered questionnaire survey of 47 patients newly referred to the Medical Oncology Department in The Townsville Cancer Centre. Scales used were: the EORTC QLQ-C30 to assess symptom burden and quality of life; the Duke UNS Functional Social Support Questionnaire to assess social support; the Herth Hope Index to assess hope; and the Multi-Dimensional Health Locus of Control to assess health beliefs. Data were collated and transformed according to the various scales' scoring manuals. Rurality was ascertained using the RRMA classification and patient self-assessment. Uni-variate analyses were conducted as small numbers precluded multi-variate analysis. Non-parametric Mann-Whitney U and Kruskal-Wallis tests were used where data were skewed, or categorical. Monte-Carlo estimations of p-values were generated. RESULTS: In all, 28 of 47 patients classified as rural, 27 were suitable for curative treatment, and 31 were male. Median age was 56 years. Some respondents (17%) identified as 'rural', although they had an urban residence, and vice versa. Health attitude scores were not affected by global health scores or by intent of treatment (palliative/curative). Males scored significantly higher for belief in chance. Rural patients scored significantly higher for internal belief and belief in chance. No statistically significant differences were evident between rural/urban patients by gender, nor social support scores. Hope levels were generally high with no significant difference between urban and rural patients, regardless of treatment intent. DISCUSSION: The study does reveal differences in health attitudes between urban and rural populations; however, there are several confounding factors which may contribute to this, especially gender. In this study women were under-represented. People with fatalistic beliefs (high belief in chance) tend to have poor initiative in health matters which may cause delay in seeking treatment, or poor compliance with treatment. Analysis is limited by small numbers of patients. This study is a pilot to a larger project to investigate health attitudes and decisions by oncology patients in northern Queensland. The questionnaire was well received by patients, but the need for a dedicated recruitment person was evident. There is a need to determine how patients identify in terms of rurality over and above their actual place of residence.

Adult↗
PubMed1996

[Survival in colorectal adenocarcinoma in Cantabria. A population-based study (1989)].

PURPOSE: To analyse a population-based study of postoperative mortality and five-year survival in patients with colorectal adenocarcinoma and to compare the results to those of a previous survival study of 1970-1978 period. METHODS: Using the Register of Colorectal Cancer of Cantabria, with a population of 531.654 inhabitants according to the 1989 census, we studied 187 patients with primary colorectal adenocarcinoma. Patients with recurrence after previous excision and who were not residents of Cantabria were excluded. Postoperative mortality included 30-days postoperative period. Survival was calculated using the Kaplan-Meier method and the log-rank test was used to compare curves of probability. RESULTS: Postoperative mortality was 7.7%. Overall five-year survival was 42.4%. Specific-cancer survival was 46%. Type of surgical procedure (curative or palliative) and TNM classification showed significant differences (p < 0.05). CONCLUSION: In Cantabria the five-years survival rate in patients with colorectal adenocarcinoma is similar to published data from other population-based studies but the survival rate did not change over the last decade.

Adenocarcinoma↗
PubMed1998

Adjuvant chemotherapy in non-small cell lung cancer.

Surgery is the main curative treatment of patients with non-small cell lung cancer (NSCLC), but half of all patients will experience local or distant failure after complete resection. An individual data-based meta-analysis has suggested a 13% reduction in the risk of death and an absolute benefit of 5% at 5 years with adjuvant cisplatin-containing chemotherapy in patients with resected NSCLC. These data led several national and international groups to initiate a new generation of adjuvant trials in resected NSCLC, and more than 2,500 patients have already been included in these randomized studies. Chemotherapy can also be proposed preoperatively. Two randomized studies, which included 60 patients each, strongly suggested a benefit from neoadjuvant chemotherapy in patients with stage III NSCLC. A large French randomized study that included 375 patients with early stage NSCLC who did or did not receive preoperative chemotherapy has recently been completed. This study should help clarify the role of neoadjuvant chemotherapy in operable NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2026

PanelAppRex aggregates disease gene panels and facilitates sophisticated search.

MOTIVATION: Gene panel data are essential for variant interpretation and genomic diagnostics, but existing resources are fragmented, inconsistently annotated, and not easily accessible for programmatic use. We developed PanelAppRex, a harmonised dataset and interactive search tool that integrates over 58&#x202f;000 curated gene-disease panel associations. It supports natural language-style queries by gene, phenotype, disease group, and mode of inheritance, with results returned in machine-readable export formats. RESULTS: The resulting dataset includes standardised gene identifiers, disease annotations, mode of inheritance, and literature support, enabling seamless integration into bioinformatic pipelines. We benchmarked 15 case studies spanning immunology, neurology, and additional disease areas. Under the recommended usage, in which the union of returned panels is considered, the causal gene was recovered in every case. Across all returned panels, the causal gene was present in 85.6% of panels. For manual interface interpretation, the causal gene was present in the user-selected best-fit panel(s) in all 15 benchmarked cases. AVAILABILITY: The platform data is openly available at Zenodo https://doi.org/10.5281/zenodo.15736689, with source code at https://github.com/DylanLawless/PanelAppRex, and demonstration page at https://panelapprex.github.io/landing_page. The dataset is maintained for a minimum of two years following publication.

Journal Article↗
PubMed1991

Influence of major histocompatibility complex class I and II antigens on survival in colorectal carcinoma.

HLA-A,B,C and HLA-D molecules present antigenic peptides to the antigen-specific receptor of autologous T-lymphocytes. T-cell-mediated host-versus-tumor response might therefore depend on the presence of these molecules on tumor cells, although the absence of HLA-A,B,C determinants on a cell has been shown to increase its susceptibility to lysis by natural killer cells. To investigate whether the presence or absence of HLA-A,B,C and/or HLA-DR in colorectal carcinoma influences relapse rate and time of tumor-related death, 152 patients who underwent putatively curative surgical treatment were surveyed for a maximum of 65 months (mean, 48 months). As determined by immunohistochemistry, aberrant reduction or loss of HLA-A,B,C/beta 2-microglobulin molecules was more frequent in tumors of the proximal colon than of the rectosigmoid (P = 0.032) and in mucinous carcinomas than in nonmucinous ones (P = 0.022). An abnormal induction of the HLA-D-associated invariant chain (Ii) was more frequent in Dukes' A and B than in stage C (P = 0.046). Reduction/loss of HLA-A,B,C/beta 2-microglobulin was correlated with the absence of HLA-DR (P = 0.024) and Ii (P = 0.005). In contrast to the prognostic role of tumor stage and grade, the presence versus the absence of HLA-A,B,C/beta 2-microglobulin and HLA-DR/Ii molecules was not correlated with recurrence rate or survival. We conclude that in spite of an increasing amount of experimental data suggesting the contrary, the status of HLA-A,B,C and HLA-DR expression in colorectal carcinoma seems to be irrelevant in vivo, regarding survival and growth of residual tumor cells after putatively curative resection of the initial tumor burden.

Aged↗
PubMed2004

ORFcurator: molecular curation of genes and gene clusters in prokaryotic organisms.

UNLABELLED: The ability to detect clusters of functionally related genes in multiple microbial genomes has enormous potential for enhancing studies on gene function and microbial evolution. The staggering amount of new genome sequence data presents a largely untapped resource for gene cluster discovery. To date, gene cluster analysis has not been fully automated, and one must rely on manual, tedious and time-consuming manipulation of sequences. To facilitate accurate and rapid identification of conserved gene clusters, we developed a database-driven web application, called ORFcurator. We used ORFcurator to find clusters containing any genes similar to those of the 14-gene Widespread Colonization Island of Actinobacillus actinomycetemcomitans. From 126 genomes, ORFcurator identified all 73 clusters previously determined by manual searching. AVAILABILITY: ORFcurator and all associated scripts are freely available as supplementary information. SUPPLEMENTARY INFORMATION: http://www.genomecurator.org/ORFcurator/

Algorithms↗
PubMed2002

Prognostic histologic indicators of curatively resected hepatocellular carcinomas: a multi-institutional analysis of 425 patients with definition of a histologic prognostic index.

Despite growing information on the clinical behavior of hepatocellular carcinoma, the histologic features associated with survival are not well characterized. Clinical and pathologic data on 425 patients who underwent complete resection for hepatocellular carcinoma were reviewed. Six microscopic features, namely, microvascular invasion, nuclear pleomorphism, mitosis, tumor architecture, growth interface, and tumor necrosis, were examined. Independent predictors of survival were identified and combined into a simple prognostic index. By univariate analysis, microvascular invasion, seen in 51.3% of patients (p <0.001), nuclear grade 3, present in 42% of the cases (p <0.001), and mitosis (p <0.008) were significant predictors of poor survival. Hepatocellular carcinoma with a compact growth pattern had a better prognosis as compared with macrotrabecular (p = 0.014) and acinar (p = 0.051) patterns. By multiple regression analysis, only microvascular invasion (p <0.001) and nuclear grade 3 (p = 0.008) were independent predictors of poor survival. The predictive values of microvascular invasion and nuclear grade allowed the construction of a hepatocellular prognostic index (HPI) whereby HPI = (microvascular invasion status x 0.459) + (nuclear grade x 0.287), with microvascular invasion either absent (0) or present (1) and nuclear grade scored as 1, 2, or 3. Using a cut-off of 0.746 (corresponding to at least nuclear grade 2 with microvascular invasion), two groups could be segregated: fair prognosis (HPI < or = 0.746), with a 50% survival of 5.06 years, and poor prognosis (HPI >0.746) with a 50% survival of 2.71 years (p <0.001). HPI was more discriminating than Edmondson grade, with Edmondson II hepatocellular carcinomas dispersed in both fair and poor prognosis groups. Microvascular invasion and nuclear grade 3 emerge as strong prognostic indicators, and their combination provides adequate prognostic stratification. Practically, hepatocellular carcinoma can be stratified in two groups with regard to prognosis: 1) fair prognosis group (nuclear grade 1 with or without microvascular invasion and nuclear grade 2 without microvascular invasion), and 2) poor prognosis (nuclear grade 2 with microvascular invasion and nuclear grade 3 with or without microvascular invasion). The combination of these histologic parameters provides adequate prognostic stratification.

Adolescent↗
PubMed1998

Evidence of survival benefit of extended (D2) lymphadenectomy in western patients with gastric cancer based on a new concept: a prospective long-term follow-up study.

BACKGROUND: The use of extended (D2) lymph node dissection in gastric cancer achieves better locoregional tumor control than limited (D1) lymphadenectomy, but its influence on survival is controversial. The value of D2 resection is unproven in randomized trials. However, a survival benefit in favor of D2 resection has been shown in reports from some specialized centers. This study was undertaken to assess whether D2 resection improves survival. We evaluated the efficacy of D2 resection on the basis of a new concept that eliminates the stage migration phenomenon. METHODS: D2 resection achieved with a standardized technique in this prospective study included dissection of the perigastric lymph nodes (stations 1 through 6, D1 resection), as well as those at the celiac axis (stations 7 through 11) and at hepatoduodenal ligament (station 12, N2 level). We evaluated survival data of patients with involved nodes at stations 7 through 12 (N2 disease) because these nodes are left behind in a D1 resection. RESULTS: D2 resection resulted in a resection of cure in 31 patients with N2 disease, a 25% (31 of 125) increase of the curative resection compared with a supposed D1 resection. The 5-year survival rate for N2 patients was 17%, which demonstrates the therapeutic benefit of the D2 resection. In patients with pN0 and pN1 disease, the 5-year survival rates were 71% and 53%, respectively. Overall hospital mortality and morbidity were 1.3% (2 of 146) and 33.4% (40 of 146), respectively. CONCLUSIONS: D2 resection can be performed safely and is of therapeutic value in patients with advanced lymph node metastases. Furthermore, the survival data suggest indirectly a possible beneficial effect for patients with node-negative disease (N0) or early node metastases (N1).

Adult↗