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PubMed2003

Mangafodipir prevents liver injury induced by acetaminophen in the mouse.

BACKGROUND/AIMS: Acute liver failure (ALF), characterized by massive hepatocyte necrosis, is often caused by drug poisoning, particularly with acetaminophen (APAP). Hepatocyte necrosis is consecutive to glutathione depletion by NAPQI, a metabolite of APAP, and to mitochondrial damages caused by reactive oxygen species (ROS) overproduction. Considering the structure of Mangafodipir, a contrast agent currently used in magnetic resonance imaging of the liver, we hypothesized that this molecule could exert an antioxidant activity and be possibly used as a treatment of APAP-induced ALF. METHODS/RESULTS: Mangafodipir is endowed with superoxide dismutase, catalase, and glutathione reductase activities. It can inhibit ROS production by hepatocytes in culture, and protect those cells from oxidative stresses induced by exposure to xanthine oxidase, H(2)O(2), or UV light. Moreover, preventive or curative administration of Mangafodipir to mice with APAP-induced ALF significantly increases survival rates, and abrogates aspartate aminotransferase elevation and histological damage. CONCLUSIONS: Those data point out the potential interest of Mangafodipir in the treatment of toxic ALF in humans.

Acetaminophen↗

PubMed2003

A historical perspective on colorectal liver metastases and peritoneal carcinomatosis: similar results, different treatments.

Similarities between peritoneal carcinomatosis and liver secondaries allow the oncologist to regard the peritoneum as an intraabdominal structure that can, like the liver, be resected with curative intent when disseminated disease has occurred. The possibility for cure of peritoneal carcinomatosis by cytoreductive surgery and IPHC must now be recognized. However, convincing data from controlled studies will be required for rapid general acceptance of this treatment, bringing, as a consequence, a chance of cure to a larger number of patients with a desperate prognosis. This fact, together with a scarcity of patients with peritoneal carcinomatosis eligible for definitive treatment, emphasizes the need for cooperative studies between centers of reference.

Carcinoma↗

PubMed2000

Surgical treatment of hepatocellular carcinoma in cirrhosis.

Hepatocellular carcinoma is one of the most frequent forms of cancer worldwide and its diagnosis and treatment have changed substantially during the last few years. Recent advances in ultrasonography, spiral computed tomography scan and nuclear magnetic resonance have further simplified the diagnostic approach to hepatocellular carcinoma. Ultrasonography is the reference examination, giving a wide variety of information on tumour size, location, relationship with portal and hepatic veins and splanchnic haemodynamics. Surgical resection and liver transplantation can both be defined as curative treatment while other techniques such as percutaneous ethanol injection and chemoembolization must be considered as palliative. Therapeutic strategies for hepatocellular carcinoma are based upon data concerning the characteristics of the tumour the functional status of non-tumoural liver parenchyma and patients' general conditions. Surgery of hepatocellular carcinoma in cirrhotic liver is mainly restricted by lack of functional hepatic reserve and by the limited capacity of hepatic regeneration. The best surgical results are obtained in early tumoural stages which generally need limited resection. Nevertheless, major liver resections have a specific role in selected cases. Recurrence rate after surgical resection is high and is related to a large number of factors. For this reason, liver transplantation, removing at the same time, the tumour and the underlying disease, is considered, theoretically, the best treatment for hepatocellular carcinoma, but its role is still debated and limited by difficult organ sharing. Integration of present therapeutic schemes are under evaluation with promising preliminary results.

Carcinoma, Hepatocellular↗

PubMed2005

Value of chemotherapy before allogeneic hematopoietic stem cell transplantation from an HLA-identical sibling donor for myelodysplastic syndrome.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for myelodysplastic syndrome (MDS). The object of this study was to evaluate the impact of chemotherapy before allo-SCT. We analyzed the data of 283 patients who underwent allo-SCT from an HLA-identical sibling donor for MDS that were reported to the Japan Society for Hematopoietic Cell Transplantation. The cumulative incidence of grade II-IV acute GVHD was 33%. Overall survival (OS) at 5 and 10 years was 48.8 and 42.5%, respectively. Multivariate analyses identified karyotype, FAB classification, and the history of chemotherapy before allo-SCT as significant predictors for OS. OS at 5 years was 57% for patients who underwent allo-SCT as a primary treatment for refractory anemia with excess blasts in transformation (RAEB-t) or secondary acute myeloid leukemia (AML) and 54% for those who underwent allo-SCT in remission after induction chemotherapy (P=0.81). The proportion of patients with a poor karyotype was equivalent between the two groups (P=0.44). Although only a randomized controlled trial will be able to establish a definite conclusion, these results do not support the administration of induction chemotherapy for patients with RAEB-t or secondary AML before allo-SCT.

Adolescent↗

PubMed2001

A population-based study on management of prostate cancer in four regions of France.

In France, as in other European countries, management of prostate cancer in the population is rather variable. The objective was to analyse diagnosis and treatment modalities of prostate cancer in patients from French cancer registries.A sample of 803 patients with prostate cancer diagnosed in 1995 was drawn at random from cases recorded in four cancer registries in the geographical regions of Bas-Rhin, Calvados, Isère and Tarn. Diagnosis, clinical staging and treatment were analysed by questionnaire. Multivariate analysis by logistic regression was used to describe medical determinants (age, PSA, clinical staging) of the various treatment choices.The mean age of the patients was 71.6 y (range 46-94 y). Clinical staging showed 60% T(1-2) tumours, 15% T(3-4) and 17% N+or metastases. PSA rate (median 18.2 ng/ml) was assessed in 92.4% of patients. Prostate cancer was diagnosed by prostate biopsy in 63% and by transurethral resection of the prostate (TURP) in 32% of patients. The main treatments were radical prostatectomy 22%, radiotherapy 19.4%, hormonal therapy 33%, TURP alone 17.7% and expectant management 6%. The method of treatment was unknown in 5.7% of cases. Adjuvant radiotherapy or hormonal therapy had been used in 31% of cases. Logistic regression analysis showed that radical prostatectomy was most often performed in patients aged <60 y, three times more frequently for T(2) tumour and for PSA between 4 and 20 ng/ml. Radiotherapy was the most frequently applied treatment for patients aged between 65 and 75 y, especially in T(3) tumours.Approximately 75% of the patients in the study underwent a specific treatment for prostate cancer with a curative intention in 40%. This study provides a baseline to clinicians and public health authorities on the management of prostate cancer in France with recent data. This survey will be useful to compare future descriptive analysis and to provide data regarding changing clinical practice.Prostate Cancer and Prostatic Diseases (2001) 4, 154-160.

Journal Article↗

PubMed2004

The importance of chemotherapy dose intensity in lung cancer.

The evidence for the importance of maintaining full dose on schedule chemotherapy for lung cancer varies considerably by histologic type. Several studies have evaluated chemotherapy dose and dose intensity in small cell lung cancer; fewer studies have evaluated the importance of chemotherapy in non-small cell lung cancer. The current guidelines of the National Comprehensive Cancer Network recommend adjuvant chemotherapy in most patients with resectable disease, and there is increasing evidence that chemotherapy benefits elderly patients as much as younger patients. Clinical trials in the setting of palliative treatment of advanced non-small cell lung cancer have focused on testing new regimens rather than evaluating the impact of maintaining the dose and schedule of standard chemotherapy regimens. However, in light of the potential curative role of chemotherapy in the adjuvant setting, the optimal doses and schedules of these regimens may have an important impact on outcomes. In addition, data suggest that responses in the neoadjuvant setting correlate with survival, and this may also be an appropriate setting in which to test the effect of the chemotherapy dose and schedule. Survival is the primary measure of treatment efficacy, but other end points, such as quality of life and disease stability, should also be considered in advanced disease. Because new regimens will shape the choice of treatment in the adjuvant and neoadjuvant settings, it is important to determine the significance of maintaining full dose on schedule with conventional chemotherapy regimens to ensure optimal outcomes in the treatment of lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

[Head and neck cancer surgery in the elderly].

BACKGROUND: The literature on management of advanced head and neck cancer in the elderly is limited. Diagnostic and treatment decisions may be implicated by advanced age itself. METHOD: Treatment outcomes of head and neck cancer in elderly patients were reviewed in the literature. The results should serve as a basis for an individualized treatment strategy. RESULTS: A comparison of data shows that chronologic age alone should not be a contraindication to adequate oncologic surgery. An aggressive approach to head and neck cancer management with curative intention can be also considered in high aged patients with advanced cancer. Surgical therapy of head and neck cancer can be as effective in elderly patients as in younger patients without a significant increase in mortality and complications. CONCLUSIONS: Head and neck cancer patients of all age groups should have a treatment of equal quality regardless of whether the expected outcome is cure or palliation.

Aged↗

PubMed2006

ViTa: prediction of host microRNAs targets on viruses.

MicroRNAs (miRNAs) are involved in various biological processes by suppressing gene expression. A recent work has indicated that host miRNAs are also capable of regulating viral gene expression by targeting the virus genomes. To investigate regulatory relationships between host miRNAs and related viruses, we present a novel database, namely ViTa, to curate the known virus miRNA genes and the known/putative target sites of human, mice, rat and chicken miRNAs. Known miRNAs are obtained from miRBase. Virus data are collected and referred from ICTVdB, VBRC and VirGen. Experimentally validated miRNA targets on viruses were derived from literatures. Then, miRanda and TargetScan are utilized to predict miRNA targets within virus genomes. ViTa also provides the virus annotations, virus-infected tissues and tissue specificity of host miRNAs. This work also facilitates the comparisons between subtypes of viruses, such as influenza viruses, human liver viruses and the conserved regions between viruses. Both textual and graphical web interfaces are provided to facilitate the data retrieves in the ViTa database. The database is now freely available at http://vita.mbc.nctu.edu.tw/.

Animals↗

PubMed1991

Diarrhoea mortality in rural Bangladeshi children.

Diarrhoeal mortality and hospital admissions for diarrhoea are described among children under the age of 5 years in a large rural Bangladeshi community during 1986-87. Acute watery (dehydrating) diarrhoea was associated with 11 per cent of all deaths among infants aged 1-11 months and 5 per cent among children aged 1-4 years. Acute non-watery diarrhoea, including bloody dysentery and diarrhoea with mucoid stools, was associated with 16 per cent of all deaths among children aged 1-4 years. In this age group, persistent diarrhoea, particularly when accompanied by recent and/or severe wasting, was associated with 63 per cent of all diarrhoeal deaths and 34 per cent of all deaths. These data suggest that exclusive emphasis on ORT will have little impact on diarrhoea mortality among children in rural Bangladesh. A broader strategy, both preventive and curative, including measles immunization, nutrition education, dietary management of diarrhoea, and the treatment of dysentery in the community, carries a greater potential.

Bangladesh↗

PubMed2002

Preoperative radiotherapy improves survival for patients undergoing total mesorectal excision for stage T3 low rectal cancers.

OBJECTIVE: To examine the effect of preoperative radiotherapy (PRT) on patients who undergo rectal resection with total mesorectal excision (TME) for stage T3 low rectal cancers. SUMMARY BACKGROUND DATA: Evidence for the value of PRT before rectal cancer surgery is weakened by variability in the use of TME. Many surgeons have concluded that PRT is unnecessary for small rectal tumors if TME is performed, but there are no prospective data to support this opinion. METHODS: Since 1980, 2,200 patients with rectal cancer have been enrolled in a prospective database. Of these, 259 underwent curative anterior or abdominoperineal resection with TME for pathologically confirmed T3 lesions within 8 cm of the anal verge. Patients were grouped by receiving PRT (n = 92) or not receiving PRT (n = 167). Five-year overall survival and 5-year local recurrence rates were evaluated. RESULTS: Overall survival was increased from 52% in patients not receiving PRT to 63% in those receiving PRT. PRT increased overall survival for node-negative patients from 58% to 82%, with no benefit for node-positive patients. There was no significant difference in local recurrence rates. When categorized by tumor size, there was no difference in overall survival or local recurrence for 0- to 2-cm tumors or those larger than 5 cm, but PRT increased overall survival from 50% to 72% for patients with 2- to 5-cm tumors. Similar results were observed for patients with tumors staged as T3 on preoperative endoluminal ultrasound. CONCLUSIONS: Patients with pT3 low rectal cancers undergoing resection with TME have an improved survival with PRT. The effect is most beneficial for patients with node-negative and 2- to 5-cm tumors, although this group may include larger and node-positive tumors that have been downstaged by PRT. PRT should be advocated for all patients with T3 rectal cancers less than 8 cm from the anal verge, even if the surgery includes a properly performed TME.

Adenocarcinoma↗

PubMed1984

Therapy in stage I non-seminomatous testicular tumor. A critical review of current strategies.

Currently administered forms of treatment after orchiectomy of non-seminomatous testicular tumor include unilateral (modified) or bilateral (radical) retroperitoneal lymph node dissection (RLND), adjuvant chemotherapy with or without RLND, radiotherapy, and a watch policy with close follow-up ('wait and see'). As diagnostic techniques and therapy concepts improve and new results become accessible, an up-to-date appraisal of these strategies in view of accuracy of staging procedures, of risk of progression, and of morbidity of treatment is being attempted. Our own results of modified and radical RLND are presented. 4 of 55 patients (9.5%) relapsed within 2 years after modified RLND. 1 of 26 patients (Urological Clinic, Bonn) and 13 of 106 patients (Bonn Register of Testicular Tumor) relapsed within 2 years after radical RLND. Relapse rates are 4 and 13.4%, respectively. Correlation between pT stage and rate of progression was found to be significant (95 cases; alpha = 0.01). From data published in the literature and our own data, we conclude that modified RLND with close follow-up is still preferable to other strategy, for reasons of exact staging, low morbidity, and curativity for all patients in clinical stage I. Expected results from current trials on a 'wait and see' approach for patients with low risk of progression may alter this conclusion. The therapeutic advantage of adjuvant chemotherapy for patients with high risk of progression has yet to be demonstrated.

Castration↗

PubMed2006

Oncologic results of laparoscopic versus conventional open surgery for stage II or III left-sided colon cancers: a randomized controlled trial.

INTRODUCTION: Minimal invasive surgical approach can achieve quick functional recovery. However, the oncologic outcome for cancer is still a concern. This study aims to compare the oncologic outcome between laparoscopic and open methods in the curative resection of Stage II or III left-sided colon cancers. METHODS: In consideration of statistical power up to 90%, 286 eligible patients with curable left-sided colon cancer (Tumor-Node-Metastasis Stage II and Stage III disease) requiring the takedown of colonic splenic flexure to facilitate a curative left hemicolectomy were recruited randomly and equally allocated to the laparoscopic and open group. The primary endpoint was time-to-recurrence of tumor. Data was analyzed according to intention-to-treat principle. RESULTS: Postrandomization exclusion occurred because of metastatic disease detected intraoperatively occurred in 13 patients and because of patient withdrawal from trial in 4. Therefore, 135 and 134 patients actually comprised the laparoscopic and open group, respectively. The median follow-up of patient was 40 months (range: 18-72 months). The oncologic results were similar (P = 0.362, one-sided log-rank test) in laparoscopic and open group of patients, with the estimated cumulative recurrence rate of 13.2% (9/68) versus 17.2% (11/64) in Stage II disease and 20.9% (14/67) versus 25.7% (18/70) in Stage III disease, respectively. The recurrence patterns were similar between the two groups. Both open and laparoscopic groups were comparable in the number of dissected lymph node (15.6 +/- 3.0 vs. 16.0 +/- 6.0, P = 0.489), various demographic and clinicopathologic parameters. CONCLUSIONS: The estimated cumulative recurrence rate for the surgery of Stage II or III left-sided colon cancers was the same between laparoscopic and open methods.

Colectomy↗

PubMed2006

[Treatment of childhood adrenocortical tumor].

Adrenocortical tumors (ACT) in children are uncommon. However, the incidence of these tumors in Paraná is 15 times higher than that worldwide. A germline mutation, R337H TP53, present in more than 95% of our patients, is probably the reason for the higher incidence in our state. A hundred twenty-five patients were treated in the period of 1966 to 2003. Surgery is the only curative treatment. In our experience, disease stage I, absence of spillage during surgery and absence of intravenous thrombus are associated with better survival rates. Preliminary data with the combination of etoposide, doxorubicin, cisplatin, and mitotane have shown that in some patients a complete remission is observed both of the tumor and metastasis. Side effects due to these drugs are common and adrenal insufficiency may occur. Glucocorticoid and mineralocorticoid reposition should be done with 2 to 3 times the physiological doses.

Adrenal Cortex Neoplasms↗

PubMed2005

The benefit of post-operative adjuvant chemotherapy using oral fluoropyrimidines in rectal cancer.

Recent meta-analysis has shown that oral fluoropyrimidenes is effective as post-operative adjuvant therapy in stage II or III colorectal cancer. However, because the efficacy of oral fluoropyrimidines was expected to be mild, it is important to know patients who respond to this mild chemotherapy for reasonable adjuvant therapy for rectal cancer. To clarify the benefit and problems of the post-operative adjuvant chemotherapy using oral fluoropyrimidines, the clinicopathological data of 169 rectal cancer patients treated with or without the post-operative chemotherapy were analyzed retrospectively. Patients in chemotherapy group (n = 100) underwent curative resection with lymphadenectomy were followed by administration of oral fluoropyrimidine. Other 69 patients underwent surgery alone. The disease-free survival rates were compared between the two groups. The disease-free survival rate in the chemotherapy group was significantly higher than that in the surgery alone. However, no significant difference in disease-free survival rate was found for those with tumor which was associated with metastasis of mesenteric lymph node or node belonging to the internal iliac artery, and tumor with lymphatic invasion or venous invasion. Post-operative adjuvant chemotherapy using oral fluoropyrimidines such as UFT and 5'-DFUR might not reduce the risk of recurrence in rectal cancer with metastasis of mesenteric lymph node or node belonging to the internal iliac artery, and with lymphatic permeation and venous invasion.

Administration, Oral↗

PubMed1999

Recurrence and survival after potentially curative surgery for colorectal cancer.

AIMS: To measure long-term outcomes in an unselected consecutive series of patients undergoing potentially curative surgery for colorectal cancer at Dunedin Hospital and identify risk factors for disease recurrence and mortality. METHOD: A retrospective study of 241 patients operated on between January 1990 and December 1992, and followed up to January 1996. RESULTS: Overall five-year actuarial survival was 55 percent, and 66, 56 and 43 percent respectively for Dukes' stage A, B and C disease. Factors associated with increased overall mortality were advanced Dukes' stage, perioperative blood transfusion and smoking, whereas factors associated with disease recurrence were advanced Dukes' stage, large tumour size and presentation with obstruction. CONCLUSIONS: Mortality following potentially curative surgery for colorectal cancer in Dunedin has not changed significantly since the previous study 15 years earlier and is similar to more recently published data from other New Zealand centres.

Aged↗

PubMedDate not supplied

Diuretics and dopamine for the prevention and treatment of acute renal failure: a critical reappraisal.

The efficacy of diuretics and dopamine in preventing and treating acute renal failure (ARF) is still debated, although these drugs are widely used in clinical practice. The present review addresses this debate providing an update on available data. There are very few well controlled and sufficiently large trials testing these agents in different ARF clinical settings, with either a preventive or a curative goal. Unfortunately, most findings rule out any favourable effects of diuretics, mannitol, atrial natriuretic peptides, and dopamine. In fact, at least in some clinical conditions, they can even worsen the risk of ARF or aggravate its course.

Acute Kidney Injury↗

PubMed2003

[Methodology of economic assessment: example in oncology].

The increasing costs of care make it important to identify those strategies of greatest value from both an effectiveness and cost perspective. Economic analysis is characterized by a simultaneous consideration of alternatives costs and outcomes, and can provide useful data for managerial decision making. In this paper, methods of economic evaluations in general and in cancer in particular is reviewed. In cancer treatment, preventive, curative or palliative strategies can be concerned. Economic evaluation have become increasingly important in oncology because of the proliferation of expensive new treatments. Furthermore, considering quality of life effects is particularly important in oncology, where many treatments obtain modest improvements in response or survival. Quality of life measurements are also reviewed.

Cost-Benefit Analysis↗

PubMed2004

[Surgical treatment of epilepsy: outcome of various surgical procedures in adults and children].

Surgical treatment of drug-resistant epilepsy is being performed in a growing number of adults and children. The objective of this report is to review and evaluate the published literature related to the outcome of epilepsy surgery. Surgical procedures were classified as "curative", which included temporal and extratemporal resections, as well as hemispherotomy and stereotactic radiosurgery, and as "palliative", which mainly included callosotomy and multiple subpial transections. Data obtained from the literature suggest that after temporal lobe surgery, 68 percent of the adult patients, on average, are seizure-free. This result may vary, according to the authors, from 50 to 93 percent. One randomized controlled study concludes that 58 percent of patients treated surgically become seizure-free, compared to only 8 percent in the group of patients who do not receive surgery. This suggests that temporal lobe surgery is an efficient treatment of drug-refractory temporal lobe surgery. Seizure outcome is similar in the pediatric population. Studies of frontal lobe surgery report that an average of 60 percent of patients are seizure-free after surgery, in adults as well as in children. These results may vary considerably, depending on how the seizure outcome is defined. Too few studies are available to allow for an evaluation of parietal or occipital lobe surgery. Hemispherotomy is mostly performed in the pediatric population. Studies of this procedure report that 60 percent of patients become seizure free after surgery, whereas 80 percent are improved in terms of seizure outcome and in terms of behavior. Stereotactic radiosurgery may be performed in case of hypothalamic hamartoma, and in some cases of temporal lobe epilepsy. In this later case, the reported results are similar to those obtained with temporal resections. Seizure outcome after corpus callosotomy is difficult to summarize, because of the many variations, according to the authors, of the definition of a good or poor seizure outcome. However, it can be stated that 65 to 85 percent of patients achieve a significant reduction in overall seizure frequency. The best reduction in seizure frequency is achieved in patients with atonic. Reported percentages of patients who benefit from multiple subpial transection, varies between 50 and 70 percent. In conclusion, our report shows that temporal resection is an efficient and scientifically validated treatment of drug-resistant temporal lobe epilepsy. Extra-temporal resections, hemispherotomy, and palliative surgery often allow cure of epilepsy, or a decrease of seizure frequency, however, prospective studies of these surgical procedures are needed.

Adult↗