Surgical research revisited: clinical trials in the cardiothoracic surgical literature.

OBJECTIVE: Surgeons have been criticised for not undertaking high-quality research. This study examines the quality of randomised controlled trials (RCTs) in the cardiothoracic surgical literature with a view to revisiting the role of RCTs in surgical research. METHODS: All RCTs published in 1998 and 1999 in three major international cardiothoracic journals were analysed for basic components of trial design and presentation. RESULTS: We found 119 papers presented as RCTs. The median size of treatment arms per RCT was 20 (interquartile range 14-40). Of 20 dimensions of trial quality examined, 12 or more were deficient (not described or performed inadequately) in half of the studies. Key information was frequently missing. Additionally, most trials relied on 'soft' endpoints, using surrogate (72, 61%) rather than clinical, and numerical (102, 86%) rather than categorical outcomes suggesting lack of power to detect clinically relevant differences. Although most trials reported positive results (73, 63%), only in 18 (15%) did authors make recommendations for practice change. CONCLUSIONS: Many RCTs in surgery by virtue of their design, sample size, and insufficient power are incapable of answering the questions researchers seek to address. Surgical trials often may not exclude bias because of lack of blinding and variations in surgical technique and performance. It is arguable that for most study questions in clinical surgery, comparative analysis of large case series and databases will provide more robust evidence.     

Surgical therapy for anorectal melanoma

BACKGROUND: Anorectal melanoma is a rare but highly lethal malignancy. Historically, radical resection was considered the "gold standard" for treatment of potentially curable anorectal melanoma. The dismal prognosis of this disease has prompted us to recommend wide local excision as the initial therapeutic approach. The purpose of this study was to review our results in patients who underwent wide local excision or radical surgery (abdominoperineal resection [APR]) for localized anorectal melanoma. STUDY DESIGN: We reviewed the charts of all patients referred for resection of anorectal melanoma between 1988 and 2002. Endpoints included overall survival, disease-free survival, and local, regional, or systemic recurrence. RESULTS: Fifteen patients underwent curative-intent surgery; four underwent APR and 11 underwent wide local excision. Eight patients (53%) are alive; 7 (47%) are disease-free (followup 6 months to 13 years). Of 12 patients who have been followed for more than 2 years, 4 are alive (33%) and 3 are disease-free (25%). Seven patients have been followed for more than 5 years and two are alive and disease-free (29%). All of the longterm survivors underwent local excision as the initial operation. There were no differences in local recurrence, systemic recurrence, disease-free survival, or overall survival between the APR group and the local excision group. Local recurrence occurred in 50% of the APR group and 18% of the local excision group; regional recurrence occurred in 25% versus 27%. Distant metastases were common (75% versus 36%). CONCLUSION: In patients who have undergone resection with curative intent for anorectal melanoma, most recurrences occur systemically regardless of the initial surgical procedure. Local resection does not increase the risk of local or regional recurrence. APR offers no survival advantage over local excision. We advocate wide local excision as primary therapy for anorectal melanoma when technically feasible.     

Surgical therapy of malignant melanoma

148 patients with malignant melanoma are presented. Localization, prognosis and clinical stadium are summarized. The surgical procedure is still three-dimensional excision. The latitude of defects asks for a specialists surgeon.     

Surgical treatment of malignant melanoma

The surgical management of melanoma has evolved over the last 100 years. when early concepts of lymphatic permeation of the tumors and metastases led surgeons to perform radical operative procedures. Wide excision of primary melanoma is now performed with 1- to 2-cm radial margins, significantly reducing the need for complex plastic closures, skin grafts. and hospital admissions. Although elective lymph node dissection remains controversial as a therapeutic procedure, the development of SL has improved the staging of the regional lymph nodes and diminished the morbidity of lymph node dissection. The role of SL for routine care of melanoma patients remains unknown. Metastasectomy, which is the surgical resection of distant metastases with tumor-free surgical margins, has not been popular for AJCC stage IV patients with multiple metastases, because surgery is considered a local therapy and therefore of little value for management of disseminated disease. Nevertheless, the many reports of long-term survival after resection of distant melanoma metastases to diverse soft tissue and organ sites clearly indicate that this form of cytoreductive surgery can be extremely successful in carefully selected patients. Unlike chemotherapy, complete surgical metastasectomy can rapidly render a patient disease-free with only a short period of postoperative morbidity. Most patients fully recover from the surgical procedure within 6 weeks, returning to most or all activities. The ability to select patients for surgery is based on the development of more sophisticated imaging techniques, which allow better preoperative differentiation of patients with single versus multiple metastases and improve the surgeon's ability to identify and resect multiple metastatic sites. The overall data suggest that patients whose metastases can be completely resected will experience improved overall survival and occasional long-term cure regardless of the metastatic organ site and number of metastases. We believe that increased understanding of the biology of the primary and metastases, dramatic improvement in the accuracy of staging metastatic disease, and better techniques of surgical resection provide the best chance for long-term palliation or cure of melanoma. Cytoreductive surgery should be considered a form of immunotherapy. The long-term clinical benefit of this therapy depends on the patient's immune response to, the surgical reduction in tumor burden: an immune response that controls subclinical micrometastases should optimize postoperative survival.     

Statistics in clinical trials

This article describes the role of statistics in clinical trials, covering study design, directionality, variables, randomization and blinding, error reduction, probability and ethics as applied to trial design.     

Ethics in clinical trials

Although one of the first pieces of legislation to address ethical issues in clinical trials was drawn up following the findings from the Nuremberg Trials, only in the more recent clinical research have the principles of beneficence, non-maleficence, autonomy and justice been considered and informed consent plays a major role. In the UK, the National Research Ethics Service and the Medicines and Healthcare Products Regulatory Agency require compliance with Good Clinical Practice. Patients are unlikely to participate in, or clinicians consent their patients to, trials where they do not feel safe or protected - data and safety monitoring assess for loss of clinical equipoise thus ensuring the most efficacious treatment is always available. Honesty and trust are crucial and place an obligation on investigators to disseminate even less favourable trial results, with the ultimate aim being partnerships between patients, their families, and those delivering the research which are mutually beneficial and respectful.     

Ethics in clinical trials

Although one of the first pieces of legislation to address ethical issues in clinical trials was drawn up following the findings from the Nuremberg Trials, only in the most recent clinical research have the principles of beneficence, non-maleficence, autonomy and justice been considered and informed consent plays a major role. In the UK, the National Research Ethics Service and the Medicines and Healthcare Products Regulatory Agency require compliance with Good Clinical Practice. Patients are unlikely to participate in, or clinicians consent their patients to, trials where they do not feel safe or protected – data and safety monitoring assess for loss of clinical equipoise thus ensuring the most efficacious treatment is always available. Honesty and trust are crucial and place an obligation on investigators to disseminate even less favourable trial results, with the ultimate aim being partnerships between patients, their families, and those delivering the research which are mutually beneficial and respectful.     

Surgical versus conservative treatment for first patellofemoral dislocations: a meta-analysis of clinical trials

European Journal of Orthopaedic Surgery & Traumatology - The first approach for acute patellar dislocation is still a debated topic. The purpose of the present study was to perform a...     

Review of breast cancer clinical trials conducted by the National Surgical Adjuvant Breast Project

The National Surgical Adjuvant Breast Project (NSABP) is a clinical trials cooperative group funded by the National Cancer Institute that has been responsible for the majority of prospective, randomized studies that have defined standards of breast cancer care in the United States during the past 4 decades. This article summarizes the design of and findings from a selection of their landmark studies. Results from their many successfully completed trials have been reported as subset analyses, pooled analyses, and retrospective studies. This article focuses on presenting the study designs, aims, and primary endpoint results of these studies.