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PubMed2000

Curative property of Withania somnifera Dunal root in the context of carbendazim-induced histopathological changes in the liver and kidney of rat.

The liver and kidney of rat underwent severe histopathological lesions when treated with a single bolus dose of carbendazim, a fungicide, particularly affecting the hepatocytes and the renal corpuscles, respectively. The effects appear to be manifestations of the microtubule-disrupting activity of carbendazim. Treatment of carbendazim-treated rats with the powder of tuberous root of Withania somnifera (Ashwagandha) for 48 days resulted in complete cure of these organs. The results indicate that Withania somnifera would be an effective curative for carbendazim-induced histopathological changes in the liver and kidney.

Animals↗

PubMed1997

Medical treatment for idiopathic male infertility: is it curative or palliative?

Medical treatment of disorders of sperm production and function remains an important goal despite major advances in assisted reproductive technology. Effective treatments exist for genital tract obstruction, gonadotrophin deficiency, sperm autoimmunity, coital disorders and some impairments caused by toxins or illness. However, the majority of men seen for reduced sperm production or function do not have these conditions and the empirical treatments used in the past are probably ineffective. New therapeutic approaches derived from research on the causes and mechanisms of testicular dysfunction are needed and their curative effects must be established by well-designed controlled clinical trials.

Clinical Trials as Topic↗

PubMed2001

Implantation metastasis caused by fine needle aspiration biopsy following curative resection of stage IB non-small cell lung cancer.

Fine needle aspiration is a useful procedure in the diagnosis of lung cancer, however controversy still remains as to whether it should be employed particularly in patients with operable lung cancer. We report herein a case of metastatic tumor at the site of transthoracic needle biopsy following a curative resection in a patient with stage IB bronchogenic carcinoma. The patient was managed with aggressive chest wall resection and subsequent musculocutaneus flap transposition, however he died 11 months after the initial operation. The tumor implantation risk and the related complications should be considered in patients with operable bronchogenic carcinoma undergoing a tranthoracic needle aspiration biopsy.

Aged↗

PubMed2000

Integrating radiation therapy in the curative management of ovarian cancer: current issues and future directions.

Although important advances in surgery, chemotherapy (CT), and radiation therapy (RT) have been made, overall survival for patients with ovarian cancer (OC) has not changed significantly. Despite its long history in the treatment of OC and its proven curative role in patients with microscopic or minimal residual disease, the proper role of RT in the management of OC is not clearly established. Although the use of primary adjuvant RT (whole abdominal irradiation) has declined in the last 15 years, there has been a resurgence of interest in RT as part of a combined modality approach and as salvage therapy for patients with small-volume persistent disease after primary cytoreductive surgery and platinum-based CT. This article reviews the evidence supporting the use of RT alone or combined with chemotherapy as primary adjuvant therapy or in the salvage setting. Current issues in the radiotherapeutic management are discussed along with ideas for future clinical research directions.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

[Non-metastatic advanced non-small cell lung carcinoma: systemic high-dose brachytherapy following curative external radiotherapy].

PURPOSE: To analyse retrospectively the local control, overall survival and immediate and long-term tolerance after a radiotherapy delivered with a curative intent systematically including a high-dose rate brachytherapy. PATIENTS AND METHODS: From January 1993 to January 1995, 50 patients (45 males-five females, median age: 61) with non-small cell lung cancers, inoperable for tumour reasons, non-metastatic, were included in the protocol. Following external radiotherapy (55-65 Gy conventional fractionation), all the patients received high-dose rate brachytherapy delivering 14 to 24 Gy using fractions of 7 Gy. RESULTS: Immediate tolerance was good. Two months after the end of the treatment, five patients suffered from massive haemorrhages and three others experienced a mucosal necrosis (two tracheal sites). Tumour response was observed endoscopically in 88% of the cases (38/50) and was complete in 38%. Median survival of complete responders was 15 months. In the mean follow-up period of 24 months, five patients were still alive with no evidence of disease (median survival: 30 months). Most of the patients died from distant metastases (33/50: 66%). CONCLUSION: Systematic use of endoluminal high-dose rate brachytherapy in addition to external radiotherapy did not improve survival. The gain in the local control rate was counteracted by an increase in haemorrhages and mucosal necroses. Improving techniques and dosimetry, and combining different methods which have proved their efficiency, should result in improvements in survival. Quality of life would be part of the analysed parameters in any future study.

Adult↗

PubMed1999

Neurocysticercosis case with a single cyst in the brain showing dramatic drop in specific antibody titers within 1 year after curative surgical resection.

We report on one Japanese case subject with neurocysticercosis (NCC) who had a single cyst in the brain and had undergone curative surgical resection. Pathological examination revealed that it was a cysticercus of Taenia solium. Serological examination of the pair serum samples just before and 1 year after surgery revealed that antibody responses against the glycoproteins, highly specific to NCC and detected in the serum sample just before surgery by both immunoblot and ELISA became negative within 1 year after the surgery. It is, therefore, strongly suggested that this case had a single cysticercus in his whole body and the presence of a single cysticercus was sufficient to evoke antibody responses against it.

Animals↗

PubMed2004

Design and synthesis of a fluoroindolocarbazole series as selective topoisomerase I active agents. Discovery of water-soluble 3,9-difluoro-12,13-dihydro-13-[6-amino-beta-D-glucopyranosyl]-5H,13H-benzo[b]- thienyl[2,3-a]pyrrolo[3,4-c]carbazole- 5,7(6H)-dione (BMS-251873) with curative antitumor activity against prostate carcinoma xenograft tumor model.

A series of fluoroindolocarbazoles were studied with respect to their topoisomerase I activity, cytotoxicity, selectivity, and in vivo antitumor activity. Emerging from this series was BMS-251873, a potential clinical candidate possessing a robust pharmacological profile including curative antitumor activity against prostate carcinoma.

Animals↗

PubMed1997

Prognostic indicators for survival after curative resection for patients with carcinoma of the stomach.

This study aims to determine prognostic indicators among patient-, tumor-, and treatment-related factors of gastric cancer patients. A total of 510 patients who underwent curative gastric resection were studied. Univariate analysis of patient-related factors showed a significantly lower survival in patients with a history of obstruction, hypoalbuminemia, and anemia. Tumor-related factors including gross appearance, location, and size of tumor; depth of cancer invasion; level, number, and frequency of lymph node metastasis; stromal reaction and tumor growth pattern; and histological classification all significantly affected survival. Surgical treatment related factors such as total or distal subtotal gastrectomy, extent of lymphadenectomy, and combined resection of adjacent organ(s) showed a statistically significant adverse influence on survival. Multivariate analysis identified only four tumor-related factors-number of metastatic lymph nodes, depth of cancer invasion, stromal reaction, and gross appearance of the tumor-as independently affecting survival. These findings suggest that only four tumor-related factors were prognostic indicators in patients with gastric cancer.

Adenocarcinoma↗

PubMed1991

Death due to recurrence following curative resection of early gastric cancer depends on age of the patient.

This study was done to define the relationship between age at the time of surgery and the prognosis after curative resection for patients with an early gastric cancer. Three hundred and eighty-two patients were identified and 25 patients died of tumour recurrence. Overall, the cumulative survival rate was 94.9% at 5 years and 92.4% at 10 years. Patients with a recurrence of the gastric cancer tended to be older, were more likely to have large differentiated type of tumour and lymph node metastases were often present. Stratified into age-classified groups, the survival rate decreased with increase of age (for patients under age 34 years, 35 to 44, 45 to 54, 55 to 64, 65 to 74, over age 75 years, the 5-year survival rates were 100.0, 97.7, 97.6, 94.2, 94.1 and 84.4 (%]. Of the 25 patients with a tumour recurrence and who died, the survival time of 18 patients over age 55 years was significantly shorter than that of seven patients under age 54 years (median, 1.7 vs 5.6 years, P less than 0.05). The multivariate analysis showed that, over and above the differentiated type of tumour (P less than 0.01) and the presence of lymph node metastases (P less than 0.01), age was one of the prognostic factors (P less than 0.05). We conclude that age at the time of primary surgery is a significant factor in patients with an early gastric cancer.

Adult↗

PubMed1997

The Rhesus D-negative phenotype is an independent predictor of poor prognosis in curatively (RO) resected gastric cancer patients.

Among gastric cancer patients, the Rhesus D-negative phenotype correlated with increased tumour recurrence [all patients, n = 83, P = 0.026; curatively (R0) resected patients, n = 51, P = 0.093] and reduced overall survival time (all patients, log-rank P = 0.0028; R0 patients, log-rank P = 0.0003) and was identified in multivariate analysis as the most important independent prognostic marker in the R0 patient group (relative risk 9.1, P = 0.0013).

Aged↗

PubMed2002

Expression of multidrug resistance-associated protein1,P-glycoprotein, and thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection.

Both 5-fluorouracil and doxorubicin are commonly used agents in chemotherapy of gastric cancer in adjuvant setting as well as metastatic disease. In a variety of malignancies, high expression of multidrug resistance-associated protein1 and P-glycoprotein has been associated with resistance to doxorubicin, whereas 5-fluorouracil resistance has correlated with the level of thymidylate synthase expression. We evaluated the expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase using immunohistochemistry in 103 locally advanced gastric cancer patients (stage IB-IV) who underwent 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection and investigated the association between their expression and clinicopathologic characteristics including prognosis of the patients. While high expression (> or =5% of tumour cells positive) of multidrug resistance-associated protein1 and P-glycoprotein was observed in 70 patients (68%) and 42 patients (41%), respectively, 65 patients (63%) had primary tumours with high expression (> or =25% of tumour cells positive) of thymidylate synthase. There was a significant association between multidrug resistance-associated protein1 and P-glycoprotein expression (P<0.0001) as well as P-glycoprotein and thymidylate synthase expression (P<0.0001). High multidrug resistance-associated protein1 and P-glycoprotein expressions were associated with well and moderately differentiated histology (P<0.0001 and P=0.03, respectively) and intestinal type (P<0.0001 and P=0.009, respectively). High multidrug resistance-associated protein1 expression correlated with lymph node metastasis (P=0.037), advanced stage (P=0.015), and older age (P=0.021). Five-year disease-free survival and overall survival of total patients were 55.2% and 56.2%, respectively, with a median follow-up of 68 months. There were no significant differences in disease-free survival and overall survival according to the expression of multidrug resistance-associated protein1 (P=0.902 and P=0.975, respectively), P-glycoprotein (P=0.987 and P=0.955, respectively), and thymidylate synthase (P=0.604 and P=0.802, respectively). Concurrent high expression of these proteins (high multidrug resistance-associated protein1/P-glycoprotein, high multidrug resistance-associated protein1/thymidylate synthase, high P-glycoprotein/thymidylate synthase) did not correlate with disease-free survival or overall survival. Even high expression of all three proteins was not associated with poor disease-free survival (P=0.919) and overall survival (P=0.852). In conclusion, high expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase did not predict poor prognosis of gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy. A larger study including patients treated with surgical resection alone would be necessary.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Follow-up of patients with Hodgkin's disease following curative treatment: the routine CT scan is of little value.

A total of 10-40% of patients with Hodgkin's disease relapse following initial curative therapy. Intensive follow-up is resource intensive and may identify false relapses. We performed a retrospective review of all patients with Hodgkin's disease treated at our centre between 1990 and 1999 to evaluate the utility of the components of follow-up. A total of 107 patients met the inclusion and exclusion criteria. The median age was 33 years and the median duration of follow-up 38 months. The total number of follow-up visits was 1209 and total number of CT scans 283. There were 109 suspected relapses of which 22 proved to be true relapses. Of the latter, 14 were identified clinically, six radiologically and two via lab testing. The routine CT scan detected only two relapses (9%), yet accounted for 29% of the total follow-up costs. Based on data from our centre, the cost per true relapse was $6000 US, 49% incurred by radiological tests. The majority of the cost of follow-up was incurred by routine follow-up (84%) as opposed to the investigation of suspected relapses (16%). We conclude that most true relapses are clinically symptomatic and that the routine CT is an expensive and inefficient mode of routine follow-up.

Adolescent↗

PubMed2003

The effect of deprivation and the systemic inflammatory response on outcome following curative resection for colorectal cancer.

The presence of a systemic inflammatory response predicted cancer-specific (HR 2.55, 95% CI 1.22-5.32, P<0.05) and overall survival (HR 2.12, 95% CI 1.17-3.87, P<0.05), independent of Dukes stage, in patients who had undergone apparently curative surgery for colorectal cancer (n=158). Deprivation predicted overall survival (HR 1.26, 95% CI 1.04-1.51, P<0.05) independent of Dukes stage.

Aged↗

PubMed2003

The relationship between T-lymphocyte infiltration, stage, tumour grade and survival in patients undergoing curative surgery for renal cell cancer.

The present study examined the relationship between tumour stage, grade, T-lymphocyte subset infiltration and survival in patients who had undergone potentially curative surgery for renal clear-cell cancer (n=73). Intratumoural CD4+ T-lymphocyte infiltrate was associated with poor cancer-specific survival, independent of grade, in this cohort.

Aged↗

PubMed2004

High curative resection rate with weekly cisplatin, 5-fluorouracil, epidoxorubicin, 6S-leucovorin, glutathione, and filgastrim in patients with locally advanced, unresectable gastric cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

The aim of the present study was to evaluate the role of a weekly preoperative chemotherapy in locally advanced, unresectable gastric cancer. In all, 82 patients with an Eastern Oncology Cooperative Group PS <or=2 and normal cardiac function were enrolled onto the study. Surgical unresectability was confirmed in 52 patients (63%) at laparotomy, and in 30 (27%) cases by CT scan of the abdomen and endoscopic ultrasonography. Chemotherapy treatment was: cisplatin 40 mg x m(-2); 5-fluorouracil 500 mg x m(-2); epidoxorubicin 35 mg x m(-2); 6S-leucovorin 250 mg x m(-2) and glutathione 1.5 g x m(-2) (PELF). One cycle consisted of 8 weekly treatments. Response to chemotherapy was observed in 40 of 82 patients (49%): six (7%) complete and 34 (41%) partial responses, and in four (5%) cases a complete pathological response was confirmed. Of the 40 responding patients, 37 (45%) had potentially curative surgery. Grade 3/4 leucopenia and thrombocytopenia occurred in three and two patients. At a median follow-up of 48 months, 25 of the 37 resected patients (68%) were alive and 24 (65%) were disease free. The median and 4-year survival for the whole group was 17 months and 31%, respectively. The median survival was 12 months for inoperable patients and it was not reached in resected patients.

Adult↗

PubMed2004

Evaluation of a cumulative prognostic score based on the systemic inflammatory response in patients undergoing potentially curative surgery for colorectal cancer.

The value of combining Dukes' stage and C-reactive protein to form a cumulative prognostic score was assessed in 147 patients undergoing potentially curative resection for colorectal cancer. The cancer-specific survival rates at 3 years for patients with a cumulative prognostic score of 0, 1 and 2 were 100, 77 and 40%, respectively (HR 4.76, 2.78-8.15, P<0.001).

Adult↗

PubMed2005

The relationship between tumour T-lymphocyte infiltration, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer.

There is increasing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of common solid tumours. The aim of the present study was to examine the relationship between tumour T-lymphocyte subset infiltration, the systemic inflammatory response and cancer-specific survival in patients with colorectal cancer. In all, 147 patients undergoing potentially curative resection for colorectal cancer were studied. Circulating concentrations of C-reactive protein were measured prior to surgery. CD4+ and CD8+ T-lymphocyte infiltration of the tumour was assessed using immunohistochemistry and a point counting technique. When patients were grouped according to the percentage tumour volume of CD4+ T-lymphocytes, there was no difference in terms of age, sex, tumour site, stage and tumour characteristics. However, there was an inverse relationship between percentage tumour CD4+ T-lymphocytes and C-reactive protein (P<0.01). On univariate analysis, both C-reactive protein concentrations (P<0.001) and percentage tumour volume of CD4+ (P<0.05) T-lymphocytes were associated with cancer-specific survival. The results of the present study show that low tumour CD4+ T-lymphocyte infiltration is associated with elevated C-reactive protein concentrations and both predict poor cancer-specific survival.

Aged↗

PubMed2003

Meta-analysis: evaluation of adjuvant therapy after curative liver resection for hepatocellular carcinoma.

AIM: To evaluate adjuvant modalities after curative resection for hepatocellular carcinoma using a meta-analysis of randomized and non-randomized controlled trials. METHODS: In a first step, a meta-analysis of randomized controlled trials was carried out. Sensitivity analyses after inclusion of non-randomized controlled trials were performed. Four therapeutic modalities were evaluated: pre-operative transarterial chemotherapy, post-operative transarterial chemotherapy, systemic chemotherapy and a combination of systemic and transarterial chemotherapy. RESULTS: Only post-operative transarterial chemotherapy improved survival significantly at 2 years [difference, 22.8%; confidence interval (CI), 8.6-36.9%; P = 0.002] and 3 years (difference, 27.6%; CI, 8.2-47.1%; P = 0.005), and decreased the probability of no recurrence at 1 year (difference, 28.8%; CI, 16.7-40.8%; P < 0.001), 2 years (difference, 27.6%; CI, 8.2-47.1%; P = 0.005) and 3 years (difference, 28%; CI, 8.2-47.9%; P = 0.006). In a sensitivity analysis after inclusion of non-randomized controlled trials, post-operative transarterial chemotherapy still improved survival at 1 year (difference, 9.6%; CI, 0.8-18.3%; P = 0.03), 2 years (difference, 13.5%; CI, 0.9-26%, P = 0.04) and 3 years (difference, 18%; CI, 7-28.9%; P < 0.001), and decreased the probability of no recurrence at 1 year (difference, 20.3%; CI, 7.7-33%; P = 0.002), 2 years (difference, 35%; CI, 21.4-46.3%; P < 0.001) and 3 years (difference, 34.5%; CI, 18.7-50.3%; P < 0.001). CONCLUSION: Post-operative transarterial chemotherapy improved survival and decreased the cumulative probability of no recurrence. New randomized controlled trials evaluating this modality are required.

Antineoplastic Agents↗