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At least 451 records · Page 25Linked to original sources
PubMed1993

Mesorectal excision for rectal cancer.

Concern about world wide local recurrence rates for rectal cancer of 20-45%, together with anxiety at the recent proliferation of adjuvant therapies, led us to review the efficacy of total mesorectal excision (TME) with which no adjuvant therapy had been combined. Precise, sharp dissection is undertaken around the integral mesentery of the hind gut, which envelopes the entire mid rectum. This procedure adds to operative time and complications but has been claimed to eliminate virtually all locally recurrent disease after "curative" surgery. Independent analysis (J. K. M.) of prospective follow-up data extended over a 13-year interval (1978-91; mean 7.5 years). The actuarial local recurrence rate after curative anterior resection at 5 years is 4% (95% Cl 0-7.5%) and the overall recurrence rate is 18% (10-25%). 10-year figures are 4% (0-11%) and 19% (7-32%). In view of the high-risk classification used for the North Central Cancer Treatment Group (NCCTG), which has led to a trend to chemoradiotherapy, a similar group of high-risk Basingstoke cases was constructed for comparison purposes. This group included 135 consecutive Dukes' B (B2) and Dukes' C cancer operations, both anterior resection and abdominal-perineal excision, for tumours below 12 cm from the anal verge. Results from TME alone are substantially superior to the best reported (NCCTG) from conventional surgery plus radiotherapy or combination chemoradiotherapy: 5% local recurrence at 5 years compared with 25% and 13.5%, respectively; and 22% overall recurrence compared with 62.7% and 41.5%, respectively (Dukes' B cases [B2], 15%; Dukes' C cases, 32%). Meticulous TME, which encompasses the whole field of tumour spread, can improve cure rates and reduce the variability of outcomes between surgeons. Far more genuine "cures" of rectal cancer are possible by surgery alone than have generally been believed or are currently accepted. Better surgical results are an essential background for the more selective use of adjuvant therapy in the future.

Aged↗
PubMedDate not supplied

[Rectal cancer: locoregional recurrence in relation to surgical and complementary treatment].

Much recent data have been published on the risk of local recurrence (LR) following curative surgery for rectal cancer and the impact of adjuvant therapy. On the other hand, improvements in surgical techniques, as the total mesorectal excision, have apparently reduced the risk of LR. Furthermore, in selected cases, neoadjuvant therapy seems to reduce much more the incidence of LR. A list of prognostic factors which affect the onset of LR, other than the different procedures, was considered. To investigate such evidences a retrospective analysis was undertaken in our series, focusing on examination of the employed techniques as potential predictors of local recurrence. Thus, in a 18-yr-period (1986-2003), two hundred and ninety-five patients who had undergone elective curative surgical resection of rectal cancer were included in the study. The demographic, operative and follow-up data were collected retrospectively. All patients underwent total mesorectal excision, whereas neoadjuvant therapy was performed in a selected series of patients, according to defined entry criteria patterns. Results evidenced LR in 7.1% of patients and occurred between 6 months to 8 year following surgery. Comparisons were made between patients who had different surgical procedures; indeed sphyncter saving procedures correlated with a higher incidence of LR rather than abdomino-perineal resection. Pelvic recurrences were observed more frequently compared to the anastomotic ones. A limited number of patients with LR underwent surgery due to the associated condition of metastatic lesions; the follow-up related to such series evidenced a mortality rate of 57% within 3 year from reoperation. A low local recurrence rate can be achieved after total mesorectal excision (TME) without preoperative radiotherapy. Our results suggest that preoperative radiotherapy may be employed only for those patients who are at a higher risk for local recurrence.

Combined Modality Therapy↗
PubMed2002

Reirradiation: a potentially curative approach to locally or regionally recurrent head and neck cancer.

The treatment options for patients with recurrent head and neck malignancies arising in a previously irradiated field are limited. Surgical salvage is feasible in a minority of patients. The majority are referred for palliative chemotherapy with no realistic chance for cure. Data are accumulating to support reirradiation as a potentially curative approach for patients with locally or regionally recurrent head and neck cancer. This article provides a rationale for management and reviews recent results of reirradiation.

Antineoplastic Agents↗
PubMed1999

[Hormone substitution after carcinoma].

OBJECTIVE: The colorectal carcinoma is one of the most frequent malignomas in western countries. Therefore the gynecologist often will be confronted with the question whether a hormone replacement with sexual steroids is allowed after a curative operation. MATERIAL AND METHODS: Basing on the data of several international publications we have substituted in an own study from 1989 to 1997 42 women with colon and 10 with rectal cancer after successful operation with a combined preparation. RESULTS: In the meantime it could be proved that in the cells of colorectal carcinomas estrogen and progesterone receptors are absent or only existing in a low concentration. Thus analogous to the receptor positive breast cancer the hormone replacement therapy also after curative treatment of a colorectal cancer should be justified. Therefore the benefit of the individual hormone replacement therapy shouldn't be withheld from these women without worsening the prognosis. CONCLUSIONS: After palliative therapy and in the case of a relapse a combined hormone replacement can be an act for diminishing the disease and should be recommended after a corresponding clearing-up and weighing the risk.

Aged↗
PubMed1994

[The indications for the curative radiotherapy of non-small-cell bronchial carcinoma. Reflections from a clinical viewpoint].

PURPOSE: To find out the indications for treatment and selection criteria of patients who will profit from curative radiotherapy. PATIENTS AND METHODS: A literature review and own data concerning the lymphogenous metastatic pathways and incidence of involvement of loco-regional lymph nodes are used to define the biological treatment volume of a curative irradiation. A retrospective analysis of 266 patients with non-small-cell lung cancer (NSCLC) was performed. The metastatic pathway of the lymphogenous spread was analysed based on pretherapy CT scan as well as clinical examination. RESULTS: Only carefully selected patients under similar selection criteria as for curative surgery are suitable to undergo a curative radiotherapy. The biological treatment volume for curative irradiation has to include the primary with a margin, the ipsilateral hilar nodes as well as the whole mediastinum including the subcarinal lymph nodes, but not the contralateral hilar and supraclavicular lymph nodes. The survival rate of patients with N3 nodal stage are 0%. A 3-step concept for curative radiotherapy until 70 Gy is proposed. CONCLUSIONS: A limited number of patients with NSCLC, carefully selected as for surgery, are suitable to undergo a curative radiotherapy with 70 Gy. This will enable to demonstrate a curative value of radiotherapy.

Carcinoma, Bronchogenic↗
PubMed2005

GANA--a genetic algorithm for NMR backbone resonance assignment.

NMR data from different experiments often contain errors; thus, automated backbone resonance assignment is a very challenging issue. In this paper, we present a method called GANA that uses a genetic algorithm to automatically perform backbone resonance assignment with a high degree of precision and recall. Precision is the number of correctly assigned residues divided by the number of assigned residues, and recall is the number of correctly assigned residues divided by the number of residues with known human curated answers. GANA takes spin systems as input data and uses two data structures, candidate lists and adjacency lists, to assign the spin systems to each amino acid of a target protein. Using GANA, almost all spin systems can be mapped correctly onto a target protein, even if the data are noisy. We use the BioMagResBank (BMRB) dataset (901 proteins) to test the performance of GANA. To evaluate the robustness of GANA, we generate four additional datasets from the BMRB dataset to simulate data errors of false positives, false negatives and linking errors. We also use a combination of these three error types to examine the fault tolerance of our method. The average precision rates of GANA on BMRB and the four simulated test cases are 99.61, 99.55, 99.34, 99.35 and 98.60%, respectively. The average recall rates of GANA on BMRB and the four simulated test cases are 99.26, 99.19, 98.85, 98.87 and 97.78%, respectively. We also test GANA on two real wet-lab datasets, hbSBD and hbLBD. The precision and recall rates of GANA on hbSBD are 95.12 and 92.86%, respectively, and those of hbLBD are 100 and 97.40%, respectively.

Algorithms↗
PubMed2004

Gastric cancer: establishing predictors of biologic behavior with use of population-based data.

BACKGROUND: Tumor thickness and nodal status are important predictors of survival following curative resection for gastric cancer. Lymphovascular invasion (LVI) is a potential predictor of biological behavior. The relationship between LVI and tumor thickness (T status) has not been established in population-based studies. METHODS: Clinicopathological and survival data of 577 patients at nine centers, from between 1991 and 1997, was collected from patient records and a Provincial Cancer Registry. The primary endpoint of the study was death. A secondary analysis of a node-negative subgroup examined the significance of LVI with respect to T status. RESULTS: The population disease-specific survival was 28%. In a multivariate analysis, T, N, M, esophageal margin, tumor morphology, and residual tumor category were independent predictors of survival. LVI was documented in 58% of resected tumors. LVI correlated with advancing T and N status but was not significant in a multivariate population model. Subgroup analysis of node-negative gastric cancer found T status and LVI to be independent predictors of survival. LVI was associated with a 5-year survival of 8%, versus 43% among patients in whom it was absent (P <.001). CONCLUSIONS: T status and N status were the most important independent predictors of survival in a population-based study of gastric cancer. LVI correlated with advancing N and T status. Multivariate analysis of node-negative patients showed LVI and T status are independent predictors of survival.

Adenocarcinoma↗
PubMed1990

Socioeconomic and health programme effects upon the behavioral management of diarrhoeal disease in northeast Thailand.

This study investigates the effects of socioeconomic and health programme factors on preventive and curative health behaviors and assesses the impact of preventive health behaviors on the incidence of diarrhoea among children under five years of age. Methodological approaches included focus groups to uncover local definitions of diarrhoeal disease, a baseline survey which collected data on maternal preventive health behaviors for 1,364 children, and a monitoring system which collected data on the incidence of diarrhoea and on maternal curative behaviors among the same group of children. Results indicate that socioeconomic status and exposure to health programmes showed significant relationships with selected maternal preventive behaviors. Children whose mothers washed their hands before breastfeeding, gave their child food immediately after cooking and warmed foods each time before meals had significantly lower proportions with diarrhoea than children of mothers who did not practice these behaviors, and 70 percent of the children with diarrhoea were exposed to high risk of severe dehydration and related health complications. Implications of these findings for health programmes are discussed.

Child, Preschool↗
PubMed1996

A clinicopathological study of asymptomatic gastric cancer.

The clinicopathological profiles of 419 patients with asymptomatic gastric cancer (AGC) first detected by gastric screening, were reviewed and compared with those of the 1727 patients with symptomatic gastric cancer (SGC). The incidence of AGC increased gradually and has amounted to 30% of the total resected cases in recent years. About 75% of AGC cases were of early cancer and 84% were negative for lymph node metastases. In contrast, only 33% of SGC cases were of early cancer and 57% were node positive. Curative resection was done in 97% of AGC and 75% of SGC. The cumulative 5 and 10 year survival rates of patients with curatively resected AGC were 85.2% and 72.2%, respectively, while those for patients with SGC were 66.8% and 55.4%. These data demonstrated that most patients with asymptomatic gastric cancers could expect a curative resection, i.e. have a better clinical outcome, than those with symptomatic cancer.

Adult↗
PubMed1997

The Bamako Initiative in Benin and Guinea: improving the effectiveness of primary health care.

The objective of the health system revitalization undergone in Benin and Guinea since 1986 is to improve the effectiveness of primary health care at the periphery. Second in a series of five, this article presents the results of an analysis of data from the health centres involved in the Bamako Initiative in Benin and Guinea since 1988. Data for the expanded programme of immunization, antenatal care and curative care, form the core of the analysis which confirms the improved effectiveness of primary health care at the peripheral level over a period of six years. The last available national data show a DPT3 immunization coverage of 80% in 1996 in Benin and 73% in 1995 in Guinea. In the Bamako Initiative health centres included in our analysis, the average immunization coverage, as measured by the adequate coverage indicator, increased from 19% to 58% in Benin and from less than 5% to 63% in Guinea between 1989 to 1993. Average antenatal care coverage has increased from 5% in Benin and 3% in Guinea to 43% in Benin and 51% Guinea. Utilization of coverage with curative care has increased from less than 0.05 visit per capita per year to 0.34 in Guinea and from 0.09 visit per capita per year to 0.24 in Benin. Further analysis attempts to uncover the reasons which underlie the different levels of effectiveness obtained in individual health centres. Monitoring and microplanning through a problem-solving approach permit a dynamic process of adaptation of strategies leading to a step by step increase of coverage over time. However, the geographical location of centres represents a constraint in that certain districts in both countries face accessibility problems. Outreach activities are shown to play an especially positive role in Guinea, in improving both immunization and antenatal care coverage.

Benin↗
PubMed2006

Transterm--extended search facilities and improved integration with other databases.

Transterm has now been publicly available for >10 years. Major changes have been made since its last description in this database issue in 2002. The current database provides data for key regions of mRNA sequences, a curated database of mRNA motifs and tools to allow users to investigate their own motifs or mRNA sequences. The key mRNA regions database is derived computationally from Genbank. It contains 3' and 5' flanking regions, the initiation and termination signal context and coding sequence for annotated CDS features from Genbank and RefSeq. The database is non-redundant, enabling summary files and statistics to be prepared for each species. Advances include providing extended search facilities, the database may now be searched by BLAST in addition to regular expressions (patterns) allowing users to search for motifs such as known miRNA sequences, and the inclusion of RefSeq data. The database contains >40 motifs or structural patterns important for translational control. In this release, patterns from UTRsite and Rfam are also incorporated with cross-referencing. Users may search their sequence data with Transterm or user-defined patterns. The system is accessible at http://uther.otago.ac.nz/Transterm.html.

Databases, Nucleic Acid↗
PubMed2026

CholeraSeq: a comprehensive genomic pipeline for cholera surveillance and near real-time outbreak investigation.

SUMMARY: Next Generation Sequencing is widely deployed in cholera-endemic regions, yet an end-to-end reproducible pipeline that unifies read QC, filtering, reference mapping, variant calling/annotation, recombination screening, and extraction of parsimony informative sites/variant codons, phylogenetic inference for downstream phylodynamic and epidemiological analyses have been lacking, slowing outbreak investigation and public health response. CholeraSeq is a high-throughput genomics pipeline for cholera genomic surveillance. It ingests consensus genomes, short read sequence data, draft assemblies, and scales seamlessly from local to cloud environments. To accelerate epidemiological context placement of new outbreak strains, we provide a curated ready-to-use core genome alignment compiled from public data, enabling flexible, fast, integration of new samples for outbreak investigations. AVAILABILITY AND IMPLEMENTATION: CholeraSeq is freely available on the GitHub platform https://github.com/CERI-KRISP/CholeraSeq. CholeraSeq is implemented in Nextflow with a modular design building upon the nf-core community standards.

Cholera↗
PubMed1991

Curative resection: the major determinant of survival in patients with large bowel cancer.

Data collected prospectively from 578 patients with colorectal cancer managed by 12 Manchester surgeons were analysed to evaluate the effects on survival of prognostic, clinical and pathological factors. Available preoperative and perioperative factors were included in a stepwise regression analysis and curative resection was found to be most strongly associated with patient survival. Other variables ranked according to their relative importance were performance status, weight loss and sex. The finding of the study supports the need to establish an early diagnosis if long-term survival results are to improve.

Activities of Daily Living↗
PubMedDate not supplied

Selective use of adjuvant radiation therapy in resectable colorectal adenocarcinoma.

Colorectal cancer recurs within the operative field in 10-20 per cent of patients undergoing potentially curative surgery. In certain subgroups, the recurrence rate is 20-50 per cent. There are some data to suggest either preoperative or postoperative radiation therapy as an adjuvant to potentially curative surgery can reduce the local operative failure rate. However, since radiation therapy has significant side effects, patient selection to maximize the therapeutic ratio is important. This report defines the criteria at the Massachusetts General Hospital for selection of patients with colorectal cancer for adjuvant radiation therapy, defines radiation therapy-surgery sequencing alternatives used, and describes techniques to reduce radiation side effects. Over a period of three and a half years, 196 patients received adjuvant radiation therapy: 51 patients received either moderate or low dose preoperative radiation therapy to rectal or rectosigmoid cancers, and 161 patients received postoperative radiation therapy to the pelvis or extrapelvic colonic tumor-lymph node beds. Some patients who received low-dose preoperative radiation therapy also received moderate-dose postoperative radiation therapy. We prefer moderate-dose postoperative radiation therapy as the approach most likely to decrease the local recurrence rate with minimal interference with surgical procedures and late small-bowel complications. Patients who received postoperative radiation therapy were those without distant metastases, whose primary tumor pathology revealed macroscopic or extensive microscopic transmural tumor penetration into extraperitoneal tissues. Careful case selection, multiple field techniques, the use of reperitonealization, omental flaps, and retroversion of the uterus into the pelvis were combined with postoperative small-bowel x-rays, bladder distention, and lateral portals to minimize radiation damage to normal structures.

Adenocarcinoma↗
PubMed2006

Mathematical modelling of survival of glioblastoma patients suggests a role for radiotherapy dose escalation and predicts poorer outcome after delay to start treatment.

AIMS: The outcome of patients with glioblastoma (GBM) remains extremely poor. We have developed a mathematical model, using pathological and radiation biology concepts, to assess the detrimental effect of delay to start radiotherapy, the possible benefit from dose escalation, and to extract biological data from clinical data. MATERIALS AND METHODS: Survival data were available for 154 adult patients with GBM treated in our centre with curative intent to a dose of 60 Gy in 30 fractions between 1996 and 2002. Survival data for 129 patients from the 60 Gy arm of the MRC BR02 randomised trial of radiotherapy dose were obtained for comparison. The model generates the equivalent of individual patients with a brain tumour, and produces an explicit outcome, either death or survival. The tumour, assumed to be growing exponentially, causes normal cell damage in the brain, and death occurs when the number of normal brain cells falls below a critical level. The outcome for an individual patient is determined by values of the variables assigned by the model. Parameters for the single patient include tumour doubling time, surviving fraction of tumour cells after each fraction of radiotherapy, and a waiting time from presentation to the start of radiotherapy. A surrogate for performance status is implemented, using a rule that rejects patients whose tumours are too advanced at presentation to be suitable for radical radiotherapy. Values for the parameters that determine individual patient outcome are randomly assigned from a set of probability distributions, using Monte Carlo simulation. The simulation constructs survival results for a population, typically 2000 individuals. The descriptors of the probability distributions that are used to determine the parameters that define the patient characteristics are adjusted to optimise the fit of the modelled population to real clinical data, using a combination of folding polygon and simulated annealing techniques. RESULTS: The model fits the clinical data well. The results suggest that the surviving fraction of tumour cells after a radiation dose of 2 Gy (SF2) does influence patient outcome. The mean in vivo SF2 for the Addenbrooke's data is 0.80, implying that hypoxia is a serious problem in radiotherapy for GBM. The Addenbrooke's data suggest a mean tumour doubling time of 24 days, so that a delay to start radiotherapy would be expected to have an adverse effect. Considering patients by treatment intent, median survival plummets as delay increases, and almost no patients survive long term after a 70-day delay. Radiotherapy dose escalation has an important predicted effect on survival. Assuming that the treatment could be delivered safely, a dose of 74 Gy, given at 2 Gy/fraction, would extend the survival of all patients. The proportion of long-term survivors would increase, from 2.4% with 60 Gy, to 6.4% with 74 Gy. The model can be used to derive gamma50, which has a value of 0.42, lower than the typical value of 1-2. CONCLUSION: Using the model, we have extracted biological information from clinical data. The model could be used to assess the potential benefit, or lack of benefit, from a proposed radiotherapy trial, and to estimate the necessary size. It shows that a single modality is unlikely to achieve a major improvement in long-term survival, although radiotherapy dose escalation should have a role, provided it can be given safely. The model could be extended to include chemotherapy, bio-reductive drugs, or gene therapy.

Brain Neoplasms↗
PubMed2003

ArrayExpress--a public repository for microarray gene expression data at the EBI.

ArrayExpress is a new public database of microarray gene expression data at the EBI, which is a generic gene expression database designed to hold data from all microarray platforms. ArrayExpress uses the annotation standard Minimum Information About a Microarray Experiment (MIAME) and the associated XML data exchange format Microarray Gene Expression Markup Language (MAGE-ML) and it is designed to store well annotated data in a structured way. The ArrayExpress infrastructure consists of the database itself, data submissions in MAGE-ML format or via an online submission tool MIAMExpress, online database query interface, and the Expression Profiler online analysis tool. ArrayExpress accepts three types of submission, arrays, experiments and protocols, each of these is assigned an accession number. Help on data submission and annotation is provided by the curation team. The database can be queried on parameters such as author, laboratory, organism, experiment or array types. With an increasing number of organisations adopting MAGE-ML standard, the volume of submissions to ArrayExpress is increasing rapidly. The database can be accessed at http://www.ebi.ac.uk/arrayexpress.

Animals↗
PubMed1994

High dose external beam radiation therapy with or without concomitant chemotherapy for esophageal carcinoma.

Esophageal cancer patients treated with radiotherapy (RTx) are most often those with malignancies too extensive for surgery or those who deemed medically unsuitable for an aggressive surgical approach. Summarizing RTx series, the 2-year survival rate is in the range of 10% and at 5 years about 5%. Although not randomly compared, these results are not significantly worse than those achieved with surgery in more advanced tumors. In stage I/II tumors, more recent trials reported of 5-year survival rates varying between 12% and 20%. These data indicate that irradiation may be administered with curative intention but usually only for patients who are also candidates for primary surgery. On the other hand, modern RTx (doses > 60 Gy) +/- endoluminal after-loading may provide good palliation (relief of dysphagia) for patients with good prognostic factors such as weight loss of less than 10% body weight, good performance status, younger age, and location of the tumor. In the perioperative setting, RTx reduced the frequency of the local recurrences but did not increase the overall resection and R0 resection rates and did not improve survival due to more patients relapsing at distant sites. Combined chemoradiotherapy has shown to be superior to RTx alone with respect to local control, disease free survival and overall survival and in a marked reduction of distant failures. These data support the use of chemoradiotherapy as standard treatment of locally advanced and nonresectable esophageal cancer. They also provide a basis for randomized trials comparing chemoradiotherapy alone versus preoperative treatment modalities.

Antineoplastic Agents↗
PubMed1992

Significance of multidisciplinary therapy for hepatocellular carcinoma.

The effect of multidisciplinary therapy for hepatocellular carcinoma (HCC) was evaluated in 121 resected cases. The 5-year survival was 100% for absolute curative resection (12 cases), 59.1% for relative curative resection (n = 37) and 10.9% for relative non-curative resection (n = 59). However, none of the patients survived for more than 3 years after absolute non-curative resection (n = 13). The non-recurrence in the preoperative TAE groups was different from that in non-TAE groups undergoing absolute and relative curative resection. The 1- and 3-year non-recurrence rates for relative non-curative resection were 92.3% and 53.8%, respectively, for the preoperative TAE group and 56.1% and 28.1%, respectively for the non-TAE group. These data show that preoperative TAE is effective in relative non-curative resection. Functional disturbances of the coagulation-fibrinolysis system in cirrhotic patients were improved after PSE. All patients undergoing hepatectomy after PSE had an uneventful postoperative course, including well-maintained function of the coagulation-fibrinolysis system and a decrease in splenic volume. At 1 year after hepatectomy, cirrhotic patients with critical liver function and poor coagulation-fibrinolysis showed appreciable hepatic regeneration. One patient died of hepatic failure 1 year after the operation. In recurrent HCC, the 1-, 2- and 3-year survival values after reresection were 100%, 75.0% and 25.0%, respectively. The respective values following TAE were 79.0%, 42.0% and 9.0%. Three cases of recurrent HCC were effectively treated, i.e., two patients achieved a partial response and one showed no change, by continuous intra-arterial infusion of 5-FU and lentinan with intermittent one-shot injections of epirubicin using a subcutaneous infusion pump. These three patients are alive at 1 year and 7 months, 1 year and 4 months and 6 months after the treatment, respectively.

Adult↗