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Adjuvant chemotherapy after curative resection for gastric cancer in non-Asian patients: revisiting a meta-analysis of randomised trials.

UNLABELLED: The aim of this study was to assess whether adjuvant chemotherapy after curative resection of gastric cancer increases survival rates. DATA SOURCES: MEDLINE (1966-1999), CancerLit (1983-1999), bibliographies, personal reprint files, and review articles were searched for relevant articles. Studies had to be randomised controlled trials of adjuvant chemotherapy versus observation following curative resection of stomach cancer that took place in non-Asian countries. Two reviewers independently evaluated the trials for eligibility, quality assessment and data abstraction, 13 trials met the eligibility criteria. The odds ratio for death in the treated group was 0.80 (95% confidence interval (CI) 0.66-0.97), corresponding to a relative risk of 0.94 (95% CI 0.89-1.00). Subgroup analyses showed a trend towards a larger magnitude of the effect when analysis was restricted to trials in which at least 2/3 of patients had node-positive disease. Our results suggest that adjuvant chemotherapy may produce a small survival benefit of borderline statistical significance in patients with curatively resected gastric carcinoma. Continued trials to find and confirm an effective adjuvant strategy are warranted.

Chemotherapy, Adjuvant↗

Marine genomics: a clearing-house for genomic and transcriptomic data of marine organisms.

BACKGROUND: The Marine Genomics project is a functional genomics initiative developed to provide a pipeline for the curation of Expressed Sequence Tags (ESTs) and gene expression microarray data for marine organisms. It provides a unique clearing-house for marine specific EST and microarray data and is currently available at http://www.marinegenomics.org. DESCRIPTION: The Marine Genomics pipeline automates the processing, maintenance, storage and analysis of EST and microarray data for an increasing number of marine species. It currently contains 19 species databases (over 46,000 EST sequences) that are maintained by registered users from local and remote locations in Europe and South America in addition to the USA. A collection of analysis tools are implemented. These include a pipeline upload tool for EST FASTA file, sequence trace file and microarray data, an annotative text search, automated sequence trimming, sequence quality control (QA/QC) editing, sequence BLAST capabilities and a tool for interactive submission to GenBank. Another feature of this resource is the integration with a scientific computing analysis environment implemented by MATLAB. CONCLUSION: The conglomeration of multiple marine organisms with integrated analysis tools enables users to focus on the comprehensive descriptions of transcriptomic responses to typical marine stresses. This cross species data comparison and integration enables users to contain their research within a marine-oriented data management and analysis environment.

Animals↗

Automatic rule generation for protein annotation with the C4.5 data mining algorithm applied on SWISS-PROT.

MOTIVATION: The gap between the amount of newly submitted protein data and reliable functional annotation in public databases is growing. Traditional manual annotation by literature curation and sequence analysis tools without the use of automated annotation systems is not able to keep up with the ever increasing quantity of data that is submitted. Automated supplements to manually curated databases such as TrEMBL or GenPept cover raw data but provide only limited annotation. To improve this situation automatic tools are needed that support manual annotation, automatically increase the amount of reliable information and help to detect inconsistencies in manually generated annotations. RESULTS: A standard data mining algorithm was successfully applied to gain knowledge about the Keyword annotation in SWISS-PROT. 11 306 rules were generated, which are provided in a database and can be applied to yet unannotated protein sequences and viewed using a web browser. They rely on the taxonomy of the organism, in which the protein was found and on signature matches of its sequence. The statistical evaluation of the generated rules by cross-validation suggests that by applying them on arbitrary proteins 33% of their keyword annotation can be generated with an error rate of 1.5%. The coverage rate of the keyword annotation can be increased to 60% by tolerating a higher error rate of 5%. AVAILABILITY: The results of the automatic data mining process can be browsed on http://golgi.ebi.ac.uk:8080/Spearmint/ Source code is available upon request. CONTACT: kretsch@ebi.ac.uk.

Algorithms↗

Patterns of failure following curative resection of colorectal liver metastases.

AIMS: Several studies have focused on factors determining recurrence and survival rate after curative resection of colorectal liver metastases (LM). Data are lacking with regard to patterns of failure indicating where and when recurrences arise. METHODS: One-hundred-and-five consecutive patients [F/M: 31/74; mean age 61 years (range 36-80 y)] with primary colorectal liver metastases underwent surgical R0 curative resection between 1990-1999. Patient follow-up was closed in January 2002. The common closing date method was used for survival analysis. Multivariate analysis was performed with the Cox proportional hazard technique. RESULTS: The overall (OS) vs disease free survival (DFS) rates at 1, 2, and 5 years were 88.5 vs 63.3, 73.4 vs 40.2, and 36.8 vs 18.1%, respectively. Elevated serum CEA level was the only factor independently related to recurrent disease. Elevated serum CEA level, maximum diameter of liver metastases (LM), and satellitosis were factors significantly related to poor OS. Recurrent liver metastases developed in 43% and extra-hepatic metastases in 60% of the patients. In about half of the patients cancer recurrence was observed within 18 months, almost equally distributed between hepatic and extra-hepatic sites. CONCLUSION: Despite optimal patient selection and curative resection of colorectal liver metastases, more than a half of the patients developed cancer recurrence within 2 years.

Adult↗

BBP: Brucella genome annotation with literature mining and curation.

BACKGROUND: Brucella species are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and animals. Sequences of four Brucella genomes have been published, and various Brucella gene and genome data and analysis resources exist. A web gateway to integrate these resources will greatly facilitate Brucella research. Brucella genome data in current databases is largely derived from computational analysis without experimental validation typically found in peer-reviewed publications. It is partially due to the lack of a literature mining and curation system able to efficiently incorporate the large amount of literature data into genome annotation. It is further hypothesized that literature-based Brucella gene annotation would increase understanding of complicated Brucella pathogenesis mechanisms. RESULTS: The Brucella Bioinformatics Portal (BBP) is developed to integrate existing Brucella genome data and analysis tools with literature mining and curation. The BBP InterBru database and Brucella Genome Browser allow users to search and analyze genes of 4 currently available Brucella genomes and link to more than 20 existing databases and analysis programs. Brucella literature publications in PubMed are extracted and can be searched by a TextPresso-powered natural language processing method, a MeSH browser, a keywords search, and an automatic literature update service. To efficiently annotate Brucella genes using the large amount of literature publications, a literature mining and curation system coined Limix is developed to integrate computational literature mining methods with a PubSearch-powered manual curation and management system. The Limix system is used to quickly find and confirm 107 Brucella gene mutations including 75 genes shown to be essential for Brucella virulence. The 75 genes are further clustered using COG. In addition, 62 Brucella genetic interactions are extracted from literature publications. These results make possible more comprehensive investigation of Brucella pathogenesis. Other BBP features include publication email alert service, Brucella researchers' contact database, and discussion forum. CONCLUSION: BBP is a gateway for Brucella researchers to search, analyze, and curate Brucella genome data originated from public databases and literature. Brucella gene mutations and genetic interactions are annotated using Limix leading to better understanding of Brucella pathogenesis.

Algorithms↗

Human gene mutation database-a biomedical information and research resource.

Although 20 years have elapsed since the first single basepair substitution underlying an inherited disease in humans was characterised at the DNA level, the initiative has only recently been taken to establish central database resources for pathological genetic variants. Disease-associated gene lesions are currently collected and publicised by the Human Gene Mutation Database (HGMD) in Cardiff, locus-specific mutation databases, and to some extent also by the Genome Database (GDB) and Online Mendelian Inheritance in Man (OMIM). To date, HGMD represents the only comprehensive and publicly available database of gene lesions underlying human inherited disease. By July 1999, HGMD contained over 18,000 different mutations from some 900 human genes, the majority being single basepair substitutions. In addition to its potential as an information resource for clinicians and genetic counsellors, HGMD has allowed molecular geneticists to address a variety of biological questions through meta-analysis of the collated data. HGMD also promises to assist research workers in optimising mutation search strategies for a given gene. A questionnaire sent out to, and answered by, the editors of 20 key journals revealed that human genetics journals are increasingly reluctant to publish mutation reports. Electronic data submission and publication facilities are therefore urgently required. The World Wide Web (WWW) provides an excellent medium within which to combine the centralised management of basic mutation data, including rigorous quality control, with the possibility of publishing additional mutation-related information. In response to these needs, HGMD has both instituted a collaboration with Springer-Verlag GmbH, Heidelberg, to potentiate free online submission and electronic publication of human gene mutation data and developed links with the curators of locus-specific mutation databases.

Databases, Factual↗

Incidence and patterns of recurrence after resection for cure of colonic cancer in a well defined population.

BACKGROUND: The aim of this study was to determine the incidence and patterns of failure following potentially curative surgery of colonic cancer. METHODS: Data were obtained from the cancer registry of the Côte-d'Or (France). Data on 2657 patients who had resection for cure of colonic cancer between 1976 and 2000 were analysed. Local and distant failure rates were calculated using the actuarial method and multivariable analysis was performed using a Cox model. RESULTS: The 5-year cumulative rate was 12.8 percent for local recurrence and 25.6 percent for distant metastases. Five-year cumulative local recurrence rates were 4.9 percent for stage I, 11.0 percent for stage II and 23.5 percent for stage III tumours (P<0.001). The corresponding rates for distant metastases were 6.4, 21.4 and 48.0 percent (P<0.001). The 5-year cumulative rates for distant metastases were 31.7 percent for the period 1976-1980 and 21.1 percent for 1996-2000, and the local recurrence rates were 17.6 and 9.0 percent respectively. The decreases in rates of local recurrence and distant metastases were significant in multivariable analysis. Cancer extension and presenting features were related to patterns of failure. Tumour location was significantly associated with risk of local recurrence, whereas age and gross features were associated with risk of distant metastasis. CONCLUSION: Recurrence following resection of colonic cancer remains a substantial problem. Follow-up is of particular importance in the 3 years after surgery.

Aged↗

Prognostic factors associated with differentiated thyroid cancer.

A multivariate analysis was conducted on the survival data of 180 patients who underwent curative resection for differentiated thyroid cancer between 1966 and 1987, and the 10- and 20-year survival rates were found to be 80.6% and 73.1%, respectively. A survival analysis was also performed, testing the following factors: the patient's age at the time of diagnosis, tumor size, extraglandular extension, nodal status, distant metastases, operative procedure, sex, and histology. A univariate analysis found the initial six factors to be significant prognostic variables, but the latter two to be of no significance. On the other hand, the multivariate analysis showed that distant metastases, age, and tumor size were the most significant prognosticators. Thus, the age of the patient should be taken into consideration during the follow-up of treatment for differentiated thyroid cancer.

Adenocarcinoma, Follicular↗

Prevention of local recurrence by extended lymphadenectomy for rectal cancer.

This study was undertaken to determine if the degree of lymphadenectomy correlates with the prevention of local recurrence. The authors retrospectively reviewed the clinical data of 269 patients who underwent curative surgery for rectal cancer. The study was divided into three periods based on the method of lymphadenectomy as follows: period I (1963-1979) when extended lymphadenectomy was not performed; period II (1980-1985) when this was partially done with no attempt to dissect the obturator and proximal middle rectal lymph nodes; and period III (1986-1990) when this was completely performed for patients with appropriate indications. The local recurrence rates were 21%, 10%, and 8% for Periods I, II, and III, respectively (P < 0.05). The incidence of local recurrence tended to be greater in period I versus periods II and III according to type of operation, location, and stage of the primary tumors. The local recurrence rates arising from lateral node metastases were 11%, 4%, and 2% for periods I, II, and III, respectively (P < 0.05), while the incidence related to an insufficient surgical margin was approximately 5% throughout the three periods. We thus conclude that the degree of lymphadenectomy is a major determinant of local recurrence following a curative operation for rectal cancer.

Adult↗

Tumor size as a simple prognostic indicator for gastric carcinoma.

BACKGROUND: Tumor size can be measured easily before or during operation with no special tools, but its prognostic use in patients with gastric carcinoma is still unclear. METHODS: Clinicopathologic data of 479 patients who underwent curative operation for gastric carcinoma were studies. The relationship between tumor size and survival of patients was investigated. RESULTS: The patients were divided into three groups: 182 with tumors measuring < 4 cm (group I), 252 with tumors of 4-10 cm (group II), and 45 with tumors of > or = 10 cm (group III). The 10-year survival rates for group I, II, and III patients were 92%, 66% and 33%, respectively (p < 0.01), and the three groups were significantly different with regard to depth of invasion (p < 0.01), number and level of lymph node metastasis (p < 0.01), and stage of disease (p < 0.01). Multivariate analysis indicated that tumor size independently influenced the survival of patients. CONCLUSIONS: Tumor size clinically serves as a simple predictor of tumor progression and survival of patients in gastric carcinoma.

Adenocarcinoma↗

Reconstruction of the lower urinary tract using autologous muscle transfer and cell seeding: current status and future perspectives.

Functioning free-muscle transfer has established itself for the treatment of skeletal muscle deficiency over the last two decades. The capability of skeletal muscle to empty a spherical reservoir has been shown to be lessened if the muscle has contracted due to dissection. Currently there is no established curative treatment for bladder acontractility. Experimental data and preliminary clinical results have shown that innervated free latissimus dorsi muscle (LD) may serve as a substitute for a dysfunctional detrusor. In a clinical protocol, latissimus dorsi detrusor myoplasty (LDDM) was applied in 11 patients (age 9-68 years) with bladder acontractility due to spinal cord injury (seven patients), congenital malformations (two patients), detrusor myopathy (one patient), and idiopathic causes (one patient) who had required catheterization for bladder emptying for a minimum of 2 years. In all, 10 of 11 patients were capable of voiding volitionally, with eight of them no longer requiring catheterization, throughout the follow-up period of 12-46 months. Transplanted LD activity was confirmed by ultrasonography and flow-mode computerized tomography. It can thus be concluded that emptying of the bladder can be induced through the contractility of reinnervated free LD that has been wrapped around the bladder. An innervated free-LD flap does not undergo the severe muscle fibrosis, contracture, and atrophy that occur after transfer of completely or partially denervated pedicled muscle. Apart from the restoration of deficient detrusor function, microneurovascular transfer of a free-LD flap may be combined with tissue engineering to serve as a basis for bladder augmentation and substitution.

Adolescent↗

Unproven methods in cancer: a worldwide problem.

Questionable or unproven methods are used by cancer patients throughout the world. Treatments include drugs, vitamins, herbs, diets, healing, "psychological" treatments, folk medicines, and homeopathy. The exact frequency of questionable methods in cancer is difficult to evaluate because of the variety of methods, some being used as complementary treatments to conventional ones (and often not mentioned by patients) and others, as curative treatment (alternative treatment). In Europe, data are available for the Nordic countries, Switzerland, Germany, Austria, United Kingdom, The Netherlands, France and Italy. High frequencies of use are observed in German-speaking countries (52-65%). In North America, many publications give frequencies of between 7% and 54%. In Mexico, the frequency is 50%, higher than in Argentina (17%). In Australia, 22% have used complementary medicines. In Asia, some data are available from India, Taiwan and Japan. In Tunisia (northern Africa), the results of 59 interviews also show the use of questionable methods among Arabic patients. There is a lack of data from countries in Africa and in Asia. While some products are used all over the world (e.g. mistletoe, vitamins), others are country specific (Moerman diet in The Netherlands). Some traditional medicines are also country specific (e.g., Chinese medicine, Ayurvedic medicine in India). Both alternative and complementary unproven methods are prescribed either according to classical concepts of cancer treatment or according to a new concept of the world and of life.

Complementary Therapies↗

KID, a Kinase Inhibitor Database project.

The Kinase Inhibitor Database is a small specialized database dedicated to the gathering of information on protein kinase inhibitors. The database is accessible through the World Wide Web system and gives access to structural and bibliographic information on protein kinase inhibitors. The data in the database will be collected and submitted by researchers working in the kinase inhibitor field. The submitted data will be checked by the curator of the database before entry.

Databases as Topic↗

Haemopoietic stem cell transplantation for advanced polycythaemia vera or essential thrombocythaemia.

Ten patients with polycythaemia vera (PV) and nine with essential thrombocythaemia (ET) received a haemopoietic stem cell transplant (HSCT) at the Fred Hutchinson Cancer Research Center between May 1988 and March 2000. HSCT was performed because of progression to the spent phase of the disease with myelofibrosis and splenomegaly in 10 patients and evolution into a myelodysplastic syndrome (MDS) or acute myelogenous leukaemia (AML) in nine patients. Patients were 18-59 years old (median 43). The interval from diagnosis to HSCT was 77-300 months (median 170). Seven patients were splenectomized before transplantation, and all but five had been treated with cytotoxic agents. Eleven patients received a transplant from a related, and eight from an unrelated, donor following conditioning with chemotherapy only or chemotherapy plus total body irradiation regimens. All evaluable patients achieved sustained engraftment. Twelve patients are surviving 5-116 months (median 41) after transplant, 10 in continued complete remission, one in haematological remission with residual marrow fibrosis and one with mixed haemopoietic chimaerism currently receiving therapy with interferon. Seven patients (six with AML/MDS and one with myelofibrosis) died of transplant-related complications. These data show that HSCT can provide curative therapy for patients with PV and ET with advanced disease.

Adult↗

Pre-operative serum vascular endothelial growth factor can select patients for adjuvant treatment after curative resection in colorectal cancer.

We aim to determine the clinical usefulness of pre-operative serum vascular endothelial growth factor (VEGF) as a predictor of outcome in patients undergoing curative resection for colorectal cancer. Serum VEGF was assayed by quantitative ELISA in 81 patients prior to curative resection for node-negative (n = 53) and node-positive (n = 28) disease. Median follow-up for patients without cancer death was 27 months (range 21-37). Pre-operative serum VEGF was significantly higher in patients who went on to develop metastases than those who did not (median, 713 pg ml-1 vs. 314 pg ml-1, P < 0.0001). Using multivariate Cox regression analysis, pre-operative serum VEGF was the most important prognostic factor independent of nodal status and adjuvant chemotherapy, and was superior to nodal status in predicting outcome (P < 0.00001). At 575 pg ml-1, pre-operative serum VEGF was 64% sensitive and 89% specific in predicting the development of metastases in curative resections, with a positive predictive value of 73% and a negative predictive value of 85%. Pre-operative serum VEGF is a powerful predictor of outcome following curative surgery for colorectal cancer. These data support the measurement of pre-operative serum VEGF as a method for selecting patients who require adjuvant therapy.

Aged↗

Strategies in the surgical treatment of gastric carcinoma.

Surgical therapy still represents the treatment of choice for patients with primary gastric adenocarcinoma, but surgery may have reached its limits concerning the rate of resectability, postoperative mortality and survival rates. Resectability is as high as 80%, mortality after resection ranges between 3% and 5% and the best survival data can be achieved if potentially curative tumor-free (R0-) resection including systematic lymphadenectomy can be performed. Significant prognostic benefits are to be expected in tumor stages II and IIIA. Most gastric carcinomas, however, are diagnosed in far advanced tumor stages (i.e., stage IIIB and IV) and the survival rates in these patients remain disappointing. Multimodality treatment, consisting of preoperative chemotherapy and surgery, may be an encouraging alternative strategy. By endoscopic ultrasonography and staging laparoscopy it may be possible to identify patients with locally advanced tumors, so that these patients should be subjected to multimodal therapy to improve their prognosis. Primary surgical treatment should be exclusively performed in patients with tumor stages up to IIIA and those who are not eligable for aggressive chemotherapeutic regimens, while the concept of multimodality therapy needs to be investigated in the other cases within controlled prospective clinical trials.

Antineoplastic Agents↗

Resected pancreatic cancer treated with adjuvant radiotherapy with or without 5-fluorouracil: treatment results and patterns of failure.

There are relatively little data regarding patterns of recurrence after curative resection and postoperative radiotherapy with or without 5-fluorouracil (5-FU) for patients with adenocarcinonima of the pancreas. Between 1978 and 1997, 41 patients underwent postoperative radiotherapy (RT) at Loyola-Hines Department of Radiotherapy. Of the 38 evaluable patients, 30 had RT + 5-FU and 8 had RT alone. Twenty-nine patients (76.3%) had a Whipple's resection, seven (18.4%) had distal pancreatectomy, and two (5.2%) had total pancreatectomy. Thirty-three (86.8%) of the 38 patients received > or =4,500 cGy to the tumor bed. Median survival for all patients was 21 months. The median survivals for patients who received RT + 5-FU and RT alone were 26 months and 5.5 months (p = 0.004). The most common site of failure was the liver, as seen in 79.2% of all recurrences. The peritoneum, other distant sites (lungs, bone, distant lymph nodes), and locoregional tumor bed were components of failure in 33.3%, 29.2%, and 25.0%, respectively. Locoregional failure alone was found in only one patient. Our median survival with postoperative RT + 5-FU is consistent with results reported by the Gastrointestinal Tumor Study Group and Mayo Clinic. Although patients who had RT + 5-FU had a better median survival than those who received RT alone, our RT-alone group had an inferior survival outcome compared to other published reports and may represent patient selection bias. Efforts in controlling this disease should be directed to prevention of intraabdominal relapse.

Adenocarcinoma↗

Pelvic resection of recurrent rectal cancer.

OBJECTIVE: The authors describe their experience with pelvic resection of recurrent rectal cancer with emphasis on patient selection for curative intent based on known tumor risk factors. SUMMARY BACKGROUND DATA: Pelvic recurrence is a formidable problem in 30% of patients who have undergone a curative resection of primary rectal cancer. Although radiation can reduce the development of local recurrence and can provide palliation to many patients with localized disease, it is not curative. The authors and others have used the technique of abdominal sacral resection (ABSR) with or without pelvic exenteration to resect pelvic recurrence and its musculoskeletal extensions in selected patients with satisfactory long-term survival. METHODS: The technique of ABSR with or without pelvic exenteration or resection of pelvic viscera, which the authors have described previously, was used in 53 patients with recurrent rectal cancer--47 patients for curative intent and 6 for palliation. Previous surgeries were abdominal perineal resections (APRs) in 26 patients, anterior resections in 19 patients, and other procedures in 2 patients; original primary Dukes' stage was B in 52% and C in 48%. Almost all patients had been irradiated previously, generally in the 4000 to 5900 cGy range. Preoperative carcinoembryonic antigen (CEA) levels (before ABSR) were elevated (> 5 ng/mL) in 54%. RESULTS: Postoperative morbidity was encountered in most patients. Mortality was 8.5% in the curative group. Long-term survival for 4 years was achieved in 14 of 43 patients (33%), and 10 patients were alive with an acceptable quality of life after 5 years. Patients who had previous anterior resections or whose preoperative CEA levels were less than 10 ng/mL had a survival rate of approximately 45%, whereas patients with previous APRs and preoperative CEA levels greater than 10 ng/mL had a survival rate of only 15% to 18%. Patients with bone marrow invasion, positive margins, or pelvic node metastases had a median survival of only 10 months. CONCLUSIONS: Pelvic recurrence of rectal cancer can be resected safely with expectation of long-term survival of 33%. Patient selection based on known risk factors can identify patients most likely to benefit from resection and eliminate those who should be treated for palliation only.

Carcinoembryonic Antigen↗