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At least 1,027 records · Page 57Linked to original sources
PubMed1995

Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving?

OBJECTIVE: The authors review their recent experience with resected pancreatic ductal adenocarcinoma. SUMMARY BACKGROUND DATA: Ductal adenocarcinoma of the pancreas has traditionally had a 5-year survival rate less than 10% after curative resection. Recently, several groups have reported markedly improved 5-year survival rates (approaching 25%) for patients undergoing curative resection. METHODS: Institutional experience with 186 consecutive patients (1981-1991) with pathologic diagnoses of ductal adenocarcinoma undergoing pancreatic resection was reviewed. Histologic specimens of all 3-year survivors (n = 31) were re-reviewed by two pathologists, one internal and one external; nonductal pancreatic cancers then were excluded. RESULTS: After histologic re-review, 12 patients did not have ductal adenocarcinoma, leaving a total of 174 patients for analysis (102 men, 72 women; mean age 63 years, range 34-82 years). Mean follow-up was 22 months (range 4-109). Classical pancreaticoduodenectomy was performed in 71%, pylorus-preserving resection in 9%, and total pancreatectomy in 20%. Hospital mortality was 3%. Twenty-eight patients (16%) had macroscopically incomplete resections; 98 (56%) had lymph node metastases within the resected specimens, and 21 patients (12%) had extensive perineural invasion. Overall actuarial 5-year survival was 6.8%. Five-year survival was greater for node-negative versus node-positive patients (14% vs. 1%, p < 0.001), and for smaller (< 2 cm) versus larger tumors (20% vs. 1%, p < 0.001). The 5-year survival for the subset of patients with negative nodes and no perineural or duodenal invasion (69 patients) was 23% (p < 0.001). Mean survival of the 12 excluded patients was 53 +/- 7 months compared with 17.5 +/- 1 months in the 174 patients with ductal pancreatic cancer. CONCLUSIONS: Five-year survival for patients undergoing pancreatic resection for lesions deemed to be clinically "curable" intraoperatively and histologically reviewed/confirmed to be ductal adenocarcinoma of the pancreas is approximately 7%. Survival is greater (23%) in the subset of patients with negative nodes and no duodenal or perineural invasions. Pathologic review of all patients with pancreatic ductal cancer adenocarcinoma is mandatory if survival data are to be meaningful.

Adult↗
PubMed1998

PAH Mutation Analysis Consortium Database: 1997. Prototype for relational locus-specific mutation databases.

PAHdb (http://www.mcgill.ca/pahdb ) is a curated relational database (Fig. 1) of nucleotide variation in the human PAH cDNA (GenBank U49897). Among 328 different mutations by state (Fig. 2) the majority are rare mutations causing hyperphenylalaninemia (HPA) (OMIM 261600), the remainder are polymorphic variants without apparent effect on phenotype. PAHdb modules contain mutations, polymorphic haplotypes, genotype-phenotype correlations, expression analysis, sources of information and the reference sequence; the database also contains pages of clinical information and data on three ENU mouse orthologues of human HPA. Only six different mutations account for 60% of human HPA chromosomes worldwide, mutations stratify by population and geographic region, and the Oriental and Caucasian mutation sets are different (Fig. 3). PAHdb provides curated electronic publication and one third of its incoming reports are direct submissions. Each different mutation receives a systematic (nucleotide) name and a unique identifier (UID). Data are accessed both by a Newsletter and a search engine on the website; integrity of the database is ensured by keeping the curated template offline. There have been >6500 online interrogations of the website.

Animals↗
PubMed2000

Thirty-four patients with carcinoma of the cervical esophagus treated with chemoradiation therapy.

OBJECTIVE: To review the experience of 2 institutions in the management of localized carcinoma of the cervical esophagus with chemoradiation therapy. DESIGN: A series of 34 patients received chemoradiation therapy for a 5-year period. All patients were treated with curative intent. Three different regimens were used, all involving concomitant chemotherapy and high-dose radiation therapy. Data relating to toxic effects, local control of disease, and disease-free and overall survival were prospectively collected. SETTING: Two combined clinics at separate major hospitals where multidisciplinary care is the standard practice for this disease. PATIENTS: Patients with biopsy-proved carcinoma of the cervical esophagus. INTERVENTIONS: Patients received 3 different chemotherapy regimens. Two of the regimens used a combination of cisplatin and fluorouracil. The high-dose cisplatin regimen was a large dose of cisplatin (80 mg/m2) given on days 1 and 22 followed by a 96-hour infusion of fluorouracil (800 mg/m2) from days 2 to 5 and from days 23 to 26. The low-dose cisplatin regimen was cisplatin, 20 mg/m2, from days 1 to 5 and from days 22 to 26 and the same 96-hour infusion of fluorouracil. The third regimen used fluorouracil alone. The mean radiation dose administered was 61.2 Gy in 29.6 fractions during 41.8 days using 4- or 6-mV photons and a shrinking field technique. RESULTS: The results of treatment have shown a high rate of local control, although some patients developed metastases. The local complete response rate following treatment was 91%, and the rate of local control of disease was 88%. The projected actuarial 5-year survival rate was 55%. Death from other causes was common. The acute toxic effects of the treatment were acceptable, with only 5 patients requiring nasogastric feeding or gavage. Two patients died of complications related to strictures. CONCLUSION: Concomitant chemoradiation therapy, should be the treatment of choice for carcinoma of the cervical esophagus.

Adenocarcinoma↗
PubMed1981

Long-term survival in childhood acute lymphocytic leukemia in Italy.

Among 727 children with acute lymphocytic leukemia (ALL) observed at eight pediatric clinics in Italy in the years 1967-1974, 200 (27.5%) survived for more than five years after diagnosis. The proportion of long-term survivors rose significantly during the years 1970-1974 when aggressive therapeutic programs with curative intent were uniformly adopted in Italy (19.8% vs. 29.4%; P less than 0.05). Clinical and laboratory data at diagnosis of the 200 long-term survivors were analyzed and compared with that of the 527 nonsurvivors. We found that, besides a leukocyte count greater than 50,000 cells/mm3, other factors such as early central nervous system CNS leukemia and the presence of mediastinal mass were predictive of a poorer prognosis for long-term survival. Life-table analysis revealed that the chance of long-term survival was significantly higher in those children who have survived for five years without relapse (82.9% vs. 24.1%; P less than 0.01). Although late initial relapse is always possible, if a child with ALL remains in continuous complete remission for at least nine years, it is likely that the patient is cured.

Adolescent↗
PubMedDate not supplied

Splenectomy for treatment of gastric cancer: Japanese experience.

Surgery for gastric cancer in Japan has frequently been combined with resection of the spleen (splenectomy) or of the pancreatic body and tail and spleen (pancreatosplenectomy, PS). Splenectomy in patients with gastric cancer has been performed with two major purposes in mind: (1) curability of the cancer and (2) immunologic reasons. Direct cancerous invasion to the pancreas requires PS, although examination of these cases revealed that in 34.3% of such macroscopic invasions only fibrous adhesion to pancreas existed. Metastases to lymph nodes at the splenic hilus (no. 10) or along the splenic artery (no. 11) also required splenectomy. The incidences of no. 10 or no. 11 lymph node metastasis were as high as 26.7% and 22.2% respectively, for cancers of whole stomach, and 15.5% and 12.1% for cancers of the upper portion of stomach. Concerning the immunologic aspect of splenectomy for gastric cancer, the reports of fundamental research and clinical studies suggest that the spleen plays sometimes acts as a suppressor and at other times as a helper to the tumor activity, according to the number of tumor cells. From these data, we concluded that the spleen should be preserved in stage I, II, and III patients with curative operation; for stage IV patients the spleen should be resected. The immunologic significance of splenectomy should be clarified precisely in the near future.

Humans↗
PubMed1993

Peri-operative heparin: a possible adjuvant to surgery in colo-rectal cancer?

Analysis of data from a randomised trial of adjuvant razoxane involving 603 patients with colo-rectal cancer having curative surgery is reported. The results show that razoxane was ineffective but peri-operative subcutaneous heparin treatment apparently conferred a statistically significant improvement in survival at 5 years, or equivalently a reduction in the risk of death. This beneficial effect is apparent in both razoxane treated and control patients and is not explained by demonstrable differences between heparin and non-heparin treated patients in the distribution of known prognostic factors. Adjustment for these factors slightly increased the apparent magnitude of the beneficial effect.

Chemotherapy, Adjuvant↗
PubMed2003

Does anastomotic leakage affect functional outcome after rectal resection for cancer?

BACKGROUND: Anastomotic leakage is the most threatening early complication in sphincter-preserving rectal cancer surgery. While the oncological consequences have been well examined, only few data exist about the functional outcome. PATIENTS AND METHODS: We investigated continence function in 150 patients after curative sphincter-preserving rectal cancer surgery. Functional results were compared in 22 patients with a clinically relevant anastomotic leakage, confirmed radiologically or endoscopically, and 128 patients with uneventful recovery. Evaluation of continence function was based on the Cleveland Clinic Continence Score and was examined in all patients with anastomotic leakage and in 111 patients without complications 107+/-46 weeks postoperatively. Additionally, 14 patients with anastomotic leakage and 58 patients with uneventful recovery underwent anorectal manometry 26+/-15 weeks postoperatively. RESULTS: The continence score in patients after anastomotic leakage did not differ significantly from that in patients without complications. Sphincter function was similar. Maximum tolerable volume and rectal compliance were slightly but not significantly worse after leakage. CONCLUSIONS: Continence function remained undisturbed after anastomotic leakage due to rectal resection

Anastomosis, Surgical↗
PubMed2004

Risk factors associated with requiring a stoma for the management of anal cancer.

PURPOSE: Combination chemotherapy and radiation therapy has become the standard of care for epidermoid carcinoma of the anus. This treatment modality has allowed for preservation of the anus in most patients, sparing them the morbidity of a stoma. Some patients will ultimately require a stoma as a result of salvage surgery or to manage complications of chemoradiotherapy. We hypothesized that tumor characteristics and radiation dose had an impact on the requirement for stoma formation. METHODS: Data on all patients with epidermoid carcinoma of the anal canal who were treated with chemoradiation with curative intent at Ochsner Clinic Foundation were entered into a prospective registry. We excluded four patients who were lost to follow-up and one patient who died during chemoradiation therapy. RESULTS: Fifty-one patients were followed for an average of 5.6 years. Primary tumor size average was 3.9 cm. Six patients had Stage I disease, 33 patients had Stage II disease, and 12 patients had Stage III disease (N+ disease). The average radiation dose was 57 +/- 17 Gy. Univariate analysis revealed pretreatment tumor size to be the only significant factor associated with the need for a stoma ( P = 0.01). Radiation dose was not an important factor ( P = 0.38). An additional finding was that the pretreatment tumor size and N+ disease were significant predictors of mortality; however, logistic-regression analysis revealed that N+ disease was the only independent predictor of mortality ( P = 0.02). CONCLUSIONS: Patients who have large tumors on presentation should be made aware of the possibility of requiring salvage surgery to treat persistent or recurrent disease. Toxicities from chemoradiotherapy do arise, but patients are not at increased risk for requiring a stoma.

Adult↗
PubMed2003

Surgical technique and survival in patients having a curative resection for colon cancer.

PURPOSE: This study was performed to determine whether the adoption of a standardized technique for resection of colon cancer, based on mobilization along anatomic planes, resulted in improved survival after adjustment for other known prognostic factors. METHODS: Patients undergoing a potentially curative, elective colonic resection at Concord Hospital from 1971 to 1995 were included. None received adjuvant therapy. Data were recorded prospectively. Overall survival and colon-cancer-specific survival were examined by the Kaplan-Meier method and proportional-hazards regression in relation to patient and tumor characteristics and the introduction of a standardized surgical technique in 1980. RESULTS: Overall five-year survival rose from 48.1 percent before 1980 to 63.7 percent after 1980 (P < 0.0001); cancer-specific survival rose from 66.4 percent to 76.6 percent (P = 0.002). Factors that did not change significantly before and after 1980 were patient age and gender, tumor site, stage, grade, serosal surface involvement, and apical node metastases. The proportion of tumors > or =5 cm in diameter decreased after 1980 (61.9 to 49.2 percent, P = 0.001) but survival was unrelated to size. Venous invasion rose after 1980 (9 to 15.8 percent, P = 0.014). Multiple regression with adjustment for age, stage, grade, venous invasion, serosal surface involvement, and apical node metastases showed significantly shorter overall survival before the introduction of the standardized technique (hazard ratio, 1.5; 95 percent confidence interval, 1.2-1.8) and significantly shorter colon-cancer-specific survival (hazard ratio, 1.7; 95 percent confidence interval, 1.3-2.2). The proportion of patients having a noncurative operation because of residual tumor in a line of resection (excluded from the survival analyses) fell from 10.6 percent (confidence interval, 7-15.3 percent) before 1980 to 3.2 percent (confidence interval, 2-4.9 percent) after 1980. CONCLUSION: As in rectal cancer surgery, mobilization of the colon along anatomic planes is an important principle that influences outcome and needs to be emphasized.

Aged↗
PubMed1983

Recurrence of sebaceous carcinoma of the eyelid after radiation therapy.

Sebaceous carcinoma originating in the meibomian gland recurred in six patients (four women, 61, 68, 71, and 88 years old, and two men, 52 and 65 years old) who had undergone radiation therapy. The patients had received radiation dosages ranging from 3,300 to 11,900 rads. The tumors recurred two months to two years after treatment. All six patients then underwent surgical excision of the tumors and have remained tumor-free for follow-up periods of as long as 42 months. These data indicated that radiation therapy of sebaceous carcinoma of the eyelid should be considered palliative rather than curative.

Adenocarcinoma↗
PubMed1993

Exclusive radiation therapy in endometrial carcinoma.

PURPOSE: From 1967 to 1986, 250 patients with endometrial carcinoma were treated with exclusive radiation therapy: 178 with a minimal follow-up of 5 years and 146 with a minimal follow-up of 10 years. The mean age was 68 years, ranging from 53 to 82 years, and the median follow-up duration was 8.5 years (minimum of 5 years and maximum of 23 years). METHODS AND MATERIALS: All the patients received an external beam radiation treatment (45 Gy in 4.5 to 5 weeks to the whole pelvis) followed by a utero-vaginal brachytherapy. RESULTS: At 5 years, the overall survival rate was 58.4% and the disease-free survival rate 55%. At 10 years the overall survival rate was 46.5% and the disease-free survival rate was 45.2%. Without considering deaths from intercurrent disease, the overall survival rate was 76.5% and the disease-free survival rate was 65.8% after 5 years, and 68% and 66%, respectively, after 10 years. The causes of failure were: isolated metastasis: 7.3%, local failure: 24.1% (4.5% with and 19.6% without concomittent distant metastasis). The rates of local control and of survival are related to the tumor stage and the tumor grade. CONCLUSION: The results are discussed according to the literature data and show the ability of exclusive radiation treatment to achieve acceptable results and to be a curative alternative for treating endometrial cancer providing that a correct external beam radiation therapy and a suitable brachytherapy are fulfilled.

Adenocarcinoma↗
PubMed1990

Cancer of the pancreas. Pylorus-preserving resection of the pancreas.

Pylorus-preserving pancreaticoduodenectomy represents an important advance in the history of pancreatic surgery. The operation can be performed with a low operative mortality and morbidity, is technically easier than the standard Whipple resection, and it minimizes the long-term physiological disturbance to the patient. Clinical and experimental evidence has substantiated the view that preservation of the pylorus reduces the incidence of marginal anastomotic ulceration following pancreatectomy. Although gastric emptying may be prolonged transiently in the immediate postoperative period, this complication is easily managed, and is hardly a frequent long-term problem. PPPD is associated with a lower incidence of enterogastric reflux, dumping and diarrhoea than the classical Whipple operation, and patients who have had PPPD are more likely to regain their preoperative and preillness weight. Initial concerns about the use of PPPD in malignant disease have not been borne out, and should now be considered for curative or palliative resections of lesions in the periampullary region including the head of the pancreas. Present data suggest that PPPD does not compromise the long-term survival in patients with periampullary cancers. There is little doubt that the excellent results reported with this procedure as with other forms of major pancreatic surgery, are not simply related to improvements in surgical technique but to establishment of specialist pancreatic surgery.

Anastomosis, Surgical↗
PubMed2003

Domains, motifs and clusters in the protein universe.

The rapid growth of bio-sequence information has resulted in an increasing demand for reliable methods that group proteins. A few databases with curated alignments of protein families have demonstrated that expert-driven repositories can keep up with the data deluge in the genome era. These original resources implicitly identify domain-like modules in proteins. An increasing number of automatic methods have sprouted over the past few years that cluster the protein universe. Many of these implicitly dissect proteins into structural domain-like fragments. In a very coarse-grained evaluation, some of the automatic methods appear to be on par with expert-driven approaches. However, neither automatic nor manual methods are currently entirely up to the challenges of tasks such as target selection in structural genomics. Thus, we urgently need refined and sustained automatic clustering tools.

Amino Acid Motifs↗
PubMed1996

p53 mutation and locoregional treatment failure in head and neck squamous cell carcinoma.

BACKGROUND: The p53 gene (also known as TP53) may be the most common genetic target involved in the malignant transformation of human cells. Direct sequence analysis has demonstrated that alteration of this gene occurs in approximately 45% of head and neck squamous cell carcinomas. The consequences of p53 mutations in these cancers with respect to tumor behavior and patient survival have not been rigorously determined. PURPOSE: We evaluated the implications of p53 mutations in relation to the control of locoregional disease and overall survival following radiation therapy. METHODS: Data from 110 consecutive patients with invasive disease who were treated with primary radiation therapy (given with curative intent) or with adjuvant radiation therapy (following complete surgical extirpation of gross disease) were included in the analysis. A 1.8-kilobase fragment of the p53 gene encompassing exons 5-9 was amplified from the DNA of stored (frozen) tumor specimens; the amplified DNA was cloned and sequenced by use of standard techniques. Overall survival and locoregional disease-free survival after the completion of radiation therapy were estimated by the Kaplan-Meier method; survival comparisons were made by use of the logrank test or proportional hazards regression models. Reported P values are two-sided. RESULTS: Fortyeight (44%) of the 110 tumors had cells bearing p53 mutations. The risk of locoregional recurrence following either primary or adjuvant radiation therapy was significantly greater (i.e., the time to recurrence was shorter) for patients whose tumors contained mutant p53 genes (univariate model hazard ratio [HR] for p53 mutation versus wild-type = 2.2; 95% confidence interval [CI] = 1.2-4.1; P = .02). The presence of regional lymph node metastases (presence versus absence, HR = 2.0; 95% CI = 1.0-4.2; P = .05) and treatment type (primary radiation therapy versus surgery plus adjuvant radiation therapy, HR = 2.3; 95% CI = 1.2-4.3; P = .01) were also associated with greater risks of locoregional failure. The presence of p53 mutations and lymph node metastases and treatment with primary, as opposed to adjuvant, radiation therapy remained significant risk factors in multivariate regression analysis. No relationship was demonstrated between p53 status and overall survival (mutant versus wild-type, HR = 1.1; 95% CI = 0.6-2.1; P = .66); however, a relationship was shown for tumor stage and overall survival (stages III and IV [more advanced] versus stages I and II [less advanced], HR = 3.3; 95% CI = 1.0-10.8; P = .05). Mutation of the p53 gene was not associated with patient age, sex, tumor stage, primary tumor site, regional lymph node status, degree of tumor cell differentiation, or treatment method. CONCLUSIONS: Mutation of the p53 gene is associated with an increased risk of locoregional failure in patients with invasive head and neck squamous cell carcinoma who are treated with radiation therapy.

Carcinoma, Squamous Cell↗
PubMed2004

IntAct: an open source molecular interaction database.

IntAct provides an open source database and toolkit for the storage, presentation and analysis of protein interactions. The web interface provides both textual and graphical representations of protein interactions, and allows exploring interaction networks in the context of the GO annotations of the interacting proteins. A web service allows direct computational access to retrieve interaction networks in XML format. IntAct currently contains approximately 2200 binary and complex interactions imported from the literature and curated in collaboration with the Swiss-Prot team, making intensive use of controlled vocabularies to ensure data consistency. All IntAct software, data and controlled vocabularies are available at http://www.ebi.ac.uk/intact.

Animals↗
PubMed2005

UTRdb and UTRsite: a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs.

The 5' and 3' untranslated regions of eukaryotic mRNAs play crucial roles in the post-transcriptional regulation of gene expression through the modulation of nucleo-cytoplasmic mRNA transport, translation efficiency, subcellular localization and message stability. UTRdb is a curated database of 5' and 3' untranslated sequences of eukaryotic mRNAs, derived from several sources of primary data. Experimentally validated functional motifs are annotated (and also collated as the UTRsite database) and cross-links to genomic and protein data are provided. The integration of UTRdb with genomic and protein data has allowed the implementation of a powerful retrieval resource for the selection and extraction of UTR subsets based on their genomic coordinates and/or features of the protein encoded by the relevant mRNA (e.g. GO term, PFAM domain, etc.). All internet resources implemented for retrieval and functional analysis of 5' and 3' untranslated regions of eukaryotic mRNAs are accessible at http://www.ba.itb.cnr.it/UTR/.

3' Untranslated Regions↗
PubMed1997

An audit of occupational health care for employees with low-back pain.

Guidelines for occupational rehabilitation of workers with low-back pain were developed as part of a larger study. We have formulated criteria for good practice of occupational rehabilitation on the basis of these guidelines. To assess the quality of occupational rehabilitation in the Netherlands, these criteria were subsequently used in an audit of medical records. The number of patients who received care consistent with the guidelines was compared to the number of patients eligible to receive that kind of care (performance rate). Six performance rates were calculated from the medical files of 40 workers with 48 new episodes of low-back pain. Two performance rates proved to be below 25% and two almost 50%. The highest performance rate, that for curative policy was 90%. These results are discussed in the light of the reliability of the original data. We recommend construction of guidelines as well as reliable registration of the occupational rehabilitation process to increase the possibilities of auditing and to raise the quality of occupational health care.

Absenteeism↗
PubMed2004

Efficacy of infliximab for disc herniation-induced sciatica: one-year follow-up.

STUDY DESIGN: An open-label trial. OBJECTIVES: To test the long-term efficacy of infliximab, a monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha), in disc herniation-induced sciatica. SUMMARY OF BACKGROUND DATA: Our recent trial indicated that a single infusion of 3 mg/weight-kg of infliximab produced a rapid curative effect in disc herniation-induced sciatica. Here, we describe the 1-year effect of a 3 mg/kg of infliximab in these 10 patients and our experience with a lower dose of 1 mg/kg of infliximab for the same indication in 2 additional patients. METHODS: Patients with severe sciatica were treated with a single infusion of infliximab, 3 mg/weight-kg in 10 patients and 1 mg/kg in 2 patients, intravenously over 2 hours. The outcomes (leg and back pain on a 100-mm visual scale, Oswestry disability, clinical signs) were assessed at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 1 year after the infusion. The outcomes with 3 mg/kg of infliximab were compared to 62 patients who received periradicular saline for sciatica in a previous trial. The resorption rate of disc herniations from baseline to 1 year was compared between infliximab and control groups. RESULTS: The response to 1 mg/kg of infliximab for leg pain was good only in 1 of the 2 patients treated, whereas the response to 3 mg/kg of infliximab for leg pain was sustained in most patients over the 1-year follow-up. The 1-year response significantly favored 3 mg/kg of infliximab over periradicular saline in leg pain (P = 0.005) and disability (P = 0.003). Neurologic abnormalities normalized more comprehensively in the infliximab group (P = 0.001). Reduction in disc herniation volume did not differ between the infliximab-treated patients and controls. CONCLUSIONS: The results showed that the beneficial effect of a single infusion of 3 mg/kg of infliximab for herniation-induced sciatica is sustained in most patients over a 1-year follow-up period. Furthermore, infliximab does not seem to interfere with the spontaneous resorption of disc herniations.

Antibodies, Monoclonal↗