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At least 469 records · Page 26Linked to original sources
PubMed1996

Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors.

OBJECTIVE: The authors reviewed the clinicopathologic characteristics of patients who underwent resection with curative intent for ductal adenocarcinoma of the pancreas between 1983 and 1989. SUMMARY BACKGROUND DATA: Recent studies have demonstrated a reduction in the morbidity and mortality of pancreatic resection and improvement in the actuarial 5-year survival for patients with resected ductal adenocarcinoma. METHODS: Resection with curative intent was performed on 118 of 684 patients (17%) with pancreatic cancer admitted to the authors' institution. Clinical, demographic, treatment, and pathologic variables were analyzed. The original material for all cases was reviewed; nonductal cancers were excluded. RESULTS: The head of the gland was the predominant tumor site (n = 102), followed by the body (n = 9), and tail (n = 7). Seventy-two percent of the patients underwent pancreaticoduodenectomies, 15% underwent total pancreatectomies, 10% underwent distal pancreatectomies, and 3% underwent distal subtotal pancreatectomies. Operative mortality was 3.4%. Median survival was 14.3 months after resection compared with 4.9 months if patients did not undergo resection (p < 0.0001). Twelve patients survived 5 years after surgery (10.2% overall actual 5-year survival rate). Three of the tumors were well differentiated, five were moderately differentiated, and four were poorly differentiated. Extrapancreatic invasion occurred in nine cases (75%), and perineural invasion was present in ten cases (83%). Five tumors exhibited invasion of duodenum, ampulla of Vater, and/or common bile duct, and an additional tumor invaded the portal vein. Lymph node involvement by carcinoma was noted in five cases (42%). Six patients remain alive without evidence of disease at a median follow-up of 101 months (range, 82-133 months). Five patients died of recurrent or metastatic pancreatic cancer at 60, 61, 62, 64, and 64 months, respectively. One patient died at 84 months of metastatic lung cancer without evidence of recurrent pancreatic disease. CONCLUSIONS: This paper emphasizes the grim prognosis of pancreatic ductal adenocarcinoma. Five-year survival cannot be equated to cure. Although pancreatectomy offers the only chance for long-term survival, it should be considered as the best palliative procedure currently available for the majority of patients. This emphasizes the need for the development of novel and effective adjuvant therapies for this disease.

Actuarial Analysis↗
PubMed1999

Response to neoadjuvant chemotherapy best predicts survival after curative resection of gastric cancer.

OBJECTIVE: In Western populations, long-term survival rates after curative resection of gastric cancer remain extremely poor. The lack of effective adjuvant therapy has prompted the evaluation of neoadjuvant approaches. Since 1988, we have conducted three separate phase II trials using neoadjuvant chemotherapy to treat patients with potentially resectable gastric cancer. The present study was conducted to evaluate whether response to neoadjuvant chemotherapy is predictive of survival in patients with resectable gastric cancer. METHODS: Eighty-three patients with pathologically confirmed gastric adenocarcinoma were treated with neoadjuvant chemotherapy before planned surgical resection. Response was assessed by upper gastrointestinal series, endoscopy, computed tomography scan, and pathologic examination. RESULTS: For the three phase II trials, clinical response rates ranged from 24% to 38%. Three patients (4%) had a complete pathologic response. Sixty-one patients (73%) underwent a curative resection. Median follow-up was 26 months. Univariate analysis revealed T stage, number of positive nodes, and response to chemotherapy to be significant predictors of overall survival. However, on multivariate analysis, response to chemotherapy was found to be the only independent prognostic factor. CONCLUSIONS: Response to neoadjuvant chemotherapy is the single most important predictor of overall survival after neoadjuvant chemotherapy for gastric cancer. These findings support further evaluation of neoadjuvant approaches in the treatment of this disease.

Adenocarcinoma↗
PubMed2003

Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients.

OBJECTIVE: To analyze prognostic factors influencing pancreatic cancer survival following curative resection, using prospectively collected, population-based data. SUMMARY BACKGROUND DATA: Several studies have analyzed the determinants of long-term survival in postresection pancreatic cancer patients, but the majority of these have been single-institutional chart reviews yielding inconsistent results. METHODS: This retrospective cohort study examined 396 Medicare-eligible patients over age 65 who were diagnosed with nonmetastatic pancreatic adenocarcinoma and who underwent surgical resection with curative intent while residing in one of the 11 Survival, Epidemiology, and End Results (SEER) registries between January 1991 and December 1996. Linked Medicare data provided information on treatment and comorbidity, while linked census tract data supplied sociodemographic characteristics. RESULTS: Median survival for the overall study population was 17.6 months, with 1- and 3-year survival rates of 60.1% and 34.3%, respectively. Survival appears to be gradually improving over time, concomitant with a rise in the proportion of patients undergoing surgery in teaching centers. Prognostic variables significantly diminishing survival on univariate analysis included African American race, treatment not in a teaching hospital, lack of adjuvant chemoradiation therapy, as well as histopathologic factors that included tumor size larger than 2 cm in diameter, moderate to poor histologic grade, and positive lymph node metastases. Higher socioeconomic status was associated both with an increased likelihood of receiving adjuvant therapy and improved overall survival. Multivariate analyses indicated the strongest predictors of survival were adjuvant combined chemoradiotherapy, small tumors (<2 cm in diameter), negative lymph nodes, well-differentiated histology, undergoing surgery in a teaching hospital, and high socioeconomic status. CONCLUSIONS: Although biologic characteristics remain important predictors of survival for patients with resected pancreatic cancer, the most powerful determinant is postoperative adjuvant chemoradiation therapy. An interesting finding that warrants further investigation is the effect of socioeconomic status on both the likelihood of receiving adjuvant treatment and subsequent survival, indicating a possible relationship between the quality of care delivered and outcomes.

Adenocarcinoma↗
PubMed2002

Retrospective study on thymidylate synthase as a predictor of outcome and sensitivity to adjuvant chemotherapy in patients with curatively resected colorectal cancer.

We carried out a retrospective evaluation of thymidylate synthase (TS) expression in tumor tissue, and its relation to outcome and response to treatment. The treatment consisted of chemotherapy with tegafur and uracil (UFT). The study group comprised 245 patients with curatively resected Dukes' stage B or C colorectal cancer who were postoperatively enrolled in a controlled study and assigned to receive UFT or no adjuvant chemotherapy. TS expression in tumor tissue was evaluated immunohistochemically with the use of recombinant human TS-specific antibody. Results were as follows. There was no relation between TS expression and the rate of 5-year disease-free survival. Similar results were obtained in both colonic and rectal tumors. The rate of 5-year disease-free survival was significantly higher in the UFT group than in the group receiving no adjuvant chemotherapy ( =0.0055). The difference in survival became more marked among patients whose tumors had diffuse TS expression ( =0.0027). There was no difference in survival between the treatment groups among patients whose tumors had focal TS expression. We conclude that, although unrelated to outcome, TS activity may be useful in predicting the response to adjuvant chemotherapy with UFT in patients with curatively resected Dukes' stage B or C colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Efficacy of adjuvant immunochemotherapy with OK-432 for patients with curatively resected gastric cancer: a meta-analysis of centrally randomized controlled clinical trials.

The benefit of immunochemotherapy employing a streptococcal preparation, OK-432 (Picibanil), in patients with curatively resected gastric cancer was reassessed by meta-analysis of data from 1,522 patients enrolled in six clinical trials with central randomization. All six trials began between 1985 and 1993, and patients were followed-up for at least 3 years after surgery and enrollment of the last patient. In these trials, standard chemotherapy was compared with the same chemotherapy plus OK-432. The endpoint was overall survival and intent-to-treat analysis was done without patient exclusion. Data were analyzed using the Mantel-Haenszel method. The 3-year survival rate for all eligible patients in the six trials was 67.5% in the immunochemotherapy group versus 62.6% in the chemotherapy group. The 3-year overall survival odds ratio was 0.81 (95% confidence interval: 0.65-0.99). The treatment effect was shown to be statistically significant (p = 0.044). The results of this meta-analysis suggest that immunochemotherapy after surgery with OK-432 can improve the survival of patients with curatively resected gastric cancer.

Antineoplastic Agents↗
PubMed2000

Current practice of patient follow-up after potentially curative resection of cutaneous melanoma.

Follow-up care for patients who have undergone potentially curative resection of cutaneous melanoma varies widely among physicians, and the underlying rationale has not been assessed. To quantify current practice patterns and to discern motivation, a custom-designed questionnaire was mailed to U.S. and non-U.S. surgeons, all of whom were members of the American Society of Plastic and Reconstructive Surgeons (ASPRS). Surveys were mailed to 3,032 ASPRS members, chosen randomly from a total of 4,320 members. Of the 1,142 questionnaires that were returned, 395 were evaluable. Nonevaluability was usually due to lack of melanoma patients receiving follow-up in the surgeons' practices. Surveillance of patients after resection of melanoma relies most heavily on office visit, chest x-ray, complete blood count, and liver function tests. There was surprisingly little influence of elective node dissection on follow-up practices. Imaging tests such as computed tomography, magnetic resonance imaging, and position emission tomography scan were rarely employed. Surveillance is motivated by many factors, particularly early detection of recurrence of the index melanoma and second primary melanomas. This survey provides information regarding current follow-up strategies recommended by ASPRS surgeons after potentially curative resection of cutaneous melanoma. There is considerable variation in surveillance intensity and in motivation among practitioners, thus representing a lack of consensus.

Adult↗
PubMed2004

Is there a "curative" role of radiotherapy for clinically localized hormone refractory prostate cancer?

Whether definitive radiotherapy (RT) is still an option for patients with clinically prostate-confined prostate cancer treated with androgen deprivation (AD) alone who develop a rising prostate-specific antigen (PSA) is not clear. In this retrospective series, we report the outcome of 29 such patients treated with "curative" radiotherapy at our institution between 1991 and 2000. At initial diagnosis, all patients had evidence of prostate-confined disease and for several reasons underwent AD alone. Afterward all patients developed rising PSA, but again, without clinical evidence of distant/pelvic node disease. All underwent RT with curative intent up to 70 Gy (66 to 76 Gy). Median follow-up after radiotherapy is 33.1 month (range: 7-134.2 months). For living patients, minimum and median follow-ups are 30.4 and 55.4 months, respectively. Twenty-three patients (79%) developed overt clinical disease, most of which (19/23, 83%) involved distant sites, whereas isolated locoregional failure was observed in only 4 patients (4/23, 17%). The estimates of locoregional control rate (LRC), actuarial incidence of distant metastases, and overall survival at 5 years are 89 +/- 7%, 68 +/- 9%, and 28 +/- 9%, respectively. Although we were unable to find any predictor of LRC at univariate analysis, patients with low Gleason score at diagnosis, lower PSA at RT, lower risk category and advanced age were less likely to develop distant disease. RT has a palliative role, because most patients with still presumed localized hormone refractory prostate cancer will develop distant metastases. A subset of patients, those with more differentiated tumor at diagnosis and with pre-RT PSA less than 20 ng/mL, might be considered for a more aggressive locoregional approach.

Aged↗
PubMed2004

Kidney gene database: a curated and integrated database of genes involved in kidney disease.

PURPOSE: We have created a curated and integrated database, the Kidney Gene Database (KGDB) (http://www.urogene.org/kgdb) that contains current information about genes or genomic loci involved in human kidney disease. MATERIALS AND METHODS: Genes that undergo molecular, genetic or epigenetic events that affect kidney function are identified through a biomedical literature search and catalogued in the database. RESULTS: Events that are currently screened for are gene amplification, mutation, deletion, polymorphism, loss of heterozygosity, DNA methylation and DNA hypomethylation. In addition, genes that are uniquely expressed in the kidney, as determined by analyzing the expressed sequence tags database and the Serial Analysis of Gene Expression database, are also included in KGDB. For each gene KGDB provides basic information about the gene product, a tissue type gene expression profile, links to protein, mRNA and genomic DNA sequence information, relevant literature citations and cross-references to other databases. CONCLUSIONS: We present KGDB, which is to our knowledge the first curated and integrated database of genes involved in human kidney disease. KGDB is free, widely accessible and easy to use, and it provides a wealth of relevant information. In addition, KGDB will be continuously updated every 6 months to include new information published in the biomedical literature or in gene expression databases. We envision that KGDB will serve as a valuable resource for scientists and clinicians.

Databases, Genetic↗
PubMed2004

A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases.

OBJECTIVE: To assess outcome after a 2-stage hepatectomy procedure (TSHP) combined with portal vein embolization (PVE) in the treatment of patients with unresectable multiple and bilobar colorectal liver metastases (MBCLM). BACKGROUND: Patients with MBCLM are often considered for palliative chemotherapy only, due to too small future remnant liver (FRL). Recently, right hepatectomy with simultaneous left liver wedge resections after previous right PVE has been reported in a curative intent. However, the growth of metastatic nodules in FRL after PVE can be more rapid than that of the nontumoral remnant hepatic parenchyma. Therefore, metastases located in the FRL should be ideally resected before PVE. Then, a right (or extended right) hepatectomy can be safely performed during a second-stage hepatectomy. Therefore, we analyzed our experience with the use of TSHP combined with PVE in treatment of MBCLM. PATIENTS AND METHODS: Between December 1996 and April 2003, 33 patients with unresectable MBCLM were selected for a TSHP. A right or an extended right hepatectomy was planned after treatment of left FRL metastases to achieve a curative resection. The first-stage hepatectomy consisted in a clearance of the left hemiliver by resection or radiofrequency destruction of metastases of the left FRL. Subsequently, a right PVE was performed to induce atrophy of the right hemiliver and hypertrophy of the left hemiliver. Finally, a second-stage hepatectomy was planned to resect the right liver metastases. RESULTS: There was no operative mortality. Post-PVE morbidity was 18.1%; postoperative morbidity was 15.1% and 56.0% after first- and second-stage hepatectomy, respectively. TSHP could be achieved in 25 of 33 patients (75.7%). The 1- and 3-year survival rates were 70.0% and 54.4%, respectively, in the 25 patients in whom the TSHP was completed. CONCLUSIONS: In selected patients with initially unresectable MBCLM, a TSHP combined with PVE can be achieved safely with long-term survival similar to that observed in patients with initially resectable liver metastases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Prognostic significance of p53 and ras gene abnormalities in lung adenocarcinoma patients with stage I disease after curative resection.

We investigated the prognostic significance of p53 gene abnormalities and ras gene mutations in patients with curatively resected stage I lung adenocarcinoma. Formalin-fixed and paraffin-embedded tissues were obtained from 30 patients who had undergone curative resection for stage I lung adenocarcinoma. Abnormalities of the p53 gene were detected using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis and immunohistochemistry and ras mutations were detected using PCR-restriction fragment length polymorphism (RFLP) analysis. Both univariate and multivariate analyses were performed to assess the relationship between the presence of abnormalities of these genes and the patients' disease-free survival. Eleven tumors (37%) had mutated p53 sequences and 11 (37%) showed p53 overexpression. A total of 15 tumors (50%) had p53 gene abnormalities and the concordance rate was 73%. Seven tumors (23%) showed mutated ras sequences. The univariate analysis revealed that the disease-free survival of patients with any p53 abnormality was shorter than that of those without abnormalities (P = 0.02, generalized Wilcoxon test), and survival of those with p53 protein overexpression was more significantly shorter (P = 0.003, generalized Wilcoxon test). Multivariate analysis using the Cox proportional hazards model indicated that the presence of p53 abnormalities was a significantly (P = 0.01) unfavorable prognostic factor. There was no significant correlation between the presence of ras mutation and survival. These results suggest that analysis of the p53 gene may be helpful for the selection of high-risk patients for clinical trials of adjuvant therapy for stage I lung adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Effect of heavy alcohol intake on long-term results after curative resection of hepatitis C virus-related hepatocellular carcinoma.

We studied the effect of heavy alcohol intake (ethanol intake > or = 80 g/day for > or = 5 yr) on long-term results in 53 patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) who had undergone curative hepatic resection. Cell proliferative activity in the tumor and non-tumorous liver was also assessed by counting argyrophilic nucleolar organizer region-associated proteins (Ag-NOR) in the resected specimens. Twenty patients (20 males, 0 females) were positive for heavy alcohol intake [AI(+)] and 33 (28 males, 5 females) were not [AI(-)]. All patients were positive for HCV antibody and negative for hepatitis B surface antigen. Carcinoma recurred within 3 to 51 postoperative months in 42 (79.2%) of the 53 patients. The median disease-free survival time was 12.6 mo in the AI(+) group and 25.4 mo in the AI(-) group (P < 0.01). The AI(+) group also had significantly poorer survival than the AI(-) group (P < 0.05, 3-year survival rate: 66.7% vs. 93.5%). HCC tumor in the AI(+) group showed significantly increased proliferative activity compared with that in the AI(-) group (P < 0.05, Ag-NOR number: 2.3 +/- 0.8 vs. 1.9 +/- 0.4). However, there was no significant difference between the numbers of Ag-NORs in non-tumorous liver from these two groups (1.5 +/- 0.2 vs. 1.5 +/- 0.2). Patients with heavy alcohol intake should be followed particularly closely, even if they have received curative surgery, since heavy alcohol intake is closely related to a poor postoperative prognosis.

Carcinoma, Hepatocellular↗
PubMed1993

Prospective study of the need for long-term antisecretory therapy in patients with Zollinger-Ellison syndrome following successful curative gastrinoma resection.

A long-term cure is now possible in more than 30% of selected patients with Zollinger-Ellison syndrome who undergo gastrinoma resection. The need, however, for continued gastric acid antisecretory therapy in these patients remains controversial. The current study was designed to determine whether post-operative antisecretory therapy is needed in patients who have undergone successful gastrinoma resection and, if so, to attempt to define criteria with which to identify patients who require therapy. Twenty-eight consecutive patients who had previously undergone curative gastrinoma resection were prospectively studied. When antisecretory therapy was discontinued, 43% (12/28) of these patients developed gastro-oesophageal reflux, diarrhoea, acid-peptic symptoms or endoscopic evidence of acid-peptic disease within 2 weeks and were deemed to have failed a trial of antisecretory drug withdrawal. The remaining 57% (16/28) of patients who successfully discontinued antisecretory therapy were followed for a mean time of 31 months after withdrawal of therapy. Analysis of acid output studies pre-operatively, as well as at the time of drug withdrawal, demonstrated that patients who were unable to discontinue antisecretory therapy exhibited higher pre-operative maximal acid output values and higher basal acid output values at the time of attempted drug withdrawal than patients who were able to discontinue therapy. Despite these findings, there was significant overlap in acid output values between groups so that it was not possible to define specific acid output criteria for successful drug withdrawal. Pre-operative clinical characteristics, such as the presence or absence of gastro-esophageal reflux or acid-peptic disease, or post-operative laboratory values, such as the fasting serum gastrin level, did not correlate with the ability to discontinue antisecretory therapy. We conclude that following successful curative gastrinoma resection, 40% of patients still require antisecretory therapy and that both symptom evaluation as well as upper endoscopy should be used to guide attempted drug withdrawal. Although patients who are not able to discontinue therapy have significantly higher acid output measurements than those who are able to discontinue therapy, neither acid output criteria nor any other laboratory or clinical characteristics are able to predict the need for continued antisecretory therapy in these patients.

Adult↗
PubMed1986

Curative local excision of rectal adenocarcinoma.

The records of all 28 patients with rectal adenocarcinoma treated by potentially curative local excision by one surgeon (A.M.C.) between 1970 and 1984 were reviewed. Patient age, sex, tumour size, site, degree of differentiation and level of invasion are reported. The procedure was associated with no mortality and minimal morbidity. Twenty-two patients, followed for an average of 51 months, have either died of other causes or remain free of recurrent or disseminated malignancy. Six patients have required further surgery for local recurrence. Of these, one patient has had a repeat local excision while the remaining five patients have had an abdominoperineal excision of the rectum. All six patients, followed since the second operation for an average of 50 months, are free of further recurrent or disseminated disease. The results reported in this review suggest that in a selected group of patients with rectal adenocarcinoma curative local excision may offer a safe alternative to more radical forms of surgery.

Adenocarcinoma↗
PubMed1999

Intraoperative radiofrequency ablation of chronic atrial fibrillation: a left atrial curative approach by elimination of anatomic "anchor" reentrant circuits.

INTRODUCTION: The percutaneous approach to radiofrequency (RF) catheter ablation for curative treatment of atrial fibrillation (AF) is an investigational technique, and the optimal composition of lesion lines is unknown. We tested an intraoperative RF ablation concept with elimination of left atrial anatomic "anchor" reentrant circuits. METHODS AND RESULTS: In 12 patients with an indication for valve surgery and chronic AF, a right atrial-transseptal approach was chosen for access to the left atrium. AF had been present for 4.3 +/- 3.9 years; the left atria measured 56 +/- 7 mm. Under direct vision, contiguous lesion lines were placed endocardially with temperature-guided RF energy applications for treatment of AF with a specially designed probe. The lesion lines were placed between the mitral annulus and the left lower pulmonary vein, further to the left upper pulmonary vein, from there to the right upper pulmonary vein, and finally to the right lower pulmonary vein. The antiarrhythmic ablation procedure lasted 19 +/- 4 minutes. One patient died postoperatively of low cardiac output. During follow-up of 11 +/- 6 months, chronic AF was ablated successfully in 9 of 11 patients (82%). Six patients were in stable sinus rhythm or intermittent pacemaker rhythm, and three patients were in sinus rhythm with intermittent atypical atrial flutter. CONCLUSIONS: Intraoperative RF energy application for induction of contiguous lesion lines is feasible. Elimination of anatomically defined "anchor" reentrant circuits within the left atrium prevented chronic AF in > 80% of the patients treated. Intraoperative validation of lesion line concepts for curative treatment of AF may be transferred to percutaneous ablation techniques.

Aged↗
PubMed2000

The influence of perioperative blood transfusion on intrahepatic recurrence after curative resection of hepatocellular carcinoma.

OBJECTIVE: This study retrospectively evaluated the association between perioperative blood transfusion and intrahepatic recurrence in patients with hepatocellular carcinoma (HCC) who had undergone curative hepatic resections. METHODS: Hepatic resection was performed with curative intent in 195 patients with primary HCC between 1985 and 1996. Patients who had received perioperative blood transfusion (transfused group: n = 117) and those who had no perioperative blood transfusion (nontransfused group: n = 78) were compared in terms of conventional prognostic variables and cancer-free survival by the univariate and multivariate analyses. RESULTS: The 1-, 3-, and 5-yr cancer-free survival rates in the nontransfused and transfused groups were 83.4% and 67.9%, 43.0% and 36.7%, and 23.1% and 24.6%, respectively (p = 0.175). Multivariate analysis of prognostic factors in all patients revealed that vascular invasion, tumor size (> or =5 cm), and Child's class were independent factors for intrahepatic recurrence. Further analyses in various stratified groups showed that perioperative blood transfusion was an independent predictor of prognosis in HCC patients with portal vein invasion (RR: 2.8, p = 0.0038). The 1-, 3-, and 5-yr survival rates in the nontransfused and transfused groups with portal vein invasion were 71.9% and 41.6%, 54.5% and 10.9%, and 26% and 0%, respectively (p = 0.0003). CONCLUSIONS: We conclude that perioperative blood transfusions enhance the risk of intrahepatic recurrence of HCC in patients with portal vein invasion. As well, the more difficult surgery and the increased manipulation of the liver that occur in these cases create a greater possibility of tumor dissemination.

Adult↗
PubMed1984

The relationship between curative factors perceived by patients in their psychotherapy and treatment outcome: an exploratory study.

Researchers are becoming increasingly interested in those aspects of the curative process that are not specific to any treatment approach. Two hypotheses were tested in this study: (1) that patients would, among those factors they suggest as helpful in their treatment, develop a list of consistently suggested curative factors; (2) that some of the consistently suggested factors will have a direct positive relationship to outcome. Twenty-four out-patients were interviewed. Both hypotheses were supported. Two factors emerged as having a significant influence on outcome: they were advice and the understanding of the therapist.

Humans↗
PubMed1977

Comparison of the curative antimalarial activities and toxicities of primaquine and its d and l isomers.

This investigation was undertaken to determine whether either d-primaquine or l-primaquine has sufficient advantage over primaquine to warrant evaluation for curative activity in human volunteers infected with Plasmodium vivax. It was found: (i) that the capacities of the isomers and the racemate to cure infections with Plasmodium cynomolgi in rhesus monkeys were essentially identical; (ii) that the subacute toxicities of the isomers and racemate for this monkey were qualitatively the same, but that l-primaquine was three to five times as toxic as d-primaquine and at least twice as toxic as primaquine; and (iii) that the acute single-dose toxicities of the isomers for mice were not only qualitatively different, but that the d isomer was at least four times as toxic as l-primaquine. Since previous appraisals of curative activity and tolerability of 8-aminoquinolines in rhesus monkeys have correlated well with appraisals in human volunteers, attention was focused on results acquired with these test subjects. The relevant evaluations showed that d-primaquine had a therapeutic index at least twice that of primaquine. If this advantage carries over to man, problems that now complicate routine use of primaquine might be obviated. Therefore, a critical comparison of d-primaquine and primaquine in human volunteers seems indicated.

Animals↗
PubMed2002

Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials.

OBJECTIVE: To review the evidence from clinical trials of follow up of patients after curative resection for colorectal cancer. DESIGN: Systematic review and meta-analysis of randomised controlled trials of intensive compared with control follow up. MAIN OUTCOME MEASURES: All cause mortality at five years (primary outcome). Rates of recurrence of intraluminal, local, and metastatic disease and metachronous (second colorectal primary) cancers (secondary outcomes). RESULTS: Five trials, which included 1342 patients, met the inclusion criteria. Intensive follow up was associated with a reduction in all cause mortality (combined risk ratio 0.81, 95% confidence interval 0.70 to 0.94, P=0.007). The effect was most pronounced in the four extramural detection trials that used computed tomography and frequent measurements of serum carcinoembryonic antigen (risk ratio 0.73, 0.60 to 0.89, P=0.002). Intensive follow up was associated with significantly earlier detection of all recurrences (difference in means 8.5 months, 7.6 to 9.4 months, P<0.001) and an increased detection rate for isolated local recurrences (risk ratio 1.61, 1.12 to 2.32, P=0.011). CONCLUSIONS: Intensive follow up after curative resection for colorectal cancer improves survival. Large trials are required to identify which components of intensive follow up are most beneficial.

Colorectal Neoplasms↗