Introduction of a mobile device based tertiary survey application reduces missed injuries: A multi-center prospective study.

BACKGROUND: Missed injuries during the initial assessment are a major cause of morbidity after trauma. The tertiary survey is a head-to-toe exam designed to identify any injuries missed after initial resuscitation. We designed a novel mobile device application (Physician Assist Trauma Software [PATS]) to standardize performance and documentation of the tertiary survey. This study was undertaken to assess the feasibility of introducing PATS into routine clinical practice, as well as its capacity to reduce missed injuries. METHODS: Prior to implementation of PATS, the missed injury rates at a higher-volume and a medium-volume level I trauma center were assessed. The PATS program was implemented simultaneously at both centers. Missed injuries were tracked during the study period. Compliance and tertiary survey completion rates were evaluated as a marker of feasibility. RESULTS: At the higher-volume trauma center, the missed injury rated decreased from 1% to 0% with the introduction of the PATS program (p = 0.04). At the medium-volume trauma center, the missed injury rate decreased from 9% to 1% (p < 0.001). Compliance and documentation increased from 68% to 100%, and from no formal documentation to 60% compliance at the higher- and medium-volume centers respectively. CONCLUSIONS: The implementation of a mobile tertiary survey application significantly reduced missed injuries at both a higher- and medium-volume trauma center. The use of this application resulted in a significant improvement in compliance with documentation of the tertiary survey.

Staging and surgical approaches in gastric cancer: a clinical practice guideline.

BACKGROUND: Resection is the cornerstone of cure for gastric adenocarcinoma; however, several aspects of surgical intervention remain controversial or are suboptimally applied at a population level, including staging, extent of lymphadenectomy (lnd), minimum number of lymph nodes that have to be assessed, gross resection margins, use of minimally invasive surgery, and relationship of surgical volumes with patient outcomes and resection in stage iv gastric cancer. METHODS: Literature searches were conducted in databases including medline (up to 10 June 2016), embase (up to week 24 of 2016), the Cochrane Library and various other practice guideline sites and guideline developer Web sites. A practice guideline was developed. RESULTS: One guideline, seven systematic reviews, and forty-eight primary studies were included in the evidence base for this guidance document. Seven recommendations are presented. CONCLUSIONS: All patients should be discussed at a multidisciplinary team meeting, and computed tomography (ct) imaging of chest and abdomen should always be performed when staging patients. Diagnostic laparoscopy is useful in the determination of M1 disease not visible on ct images. A D2 lnd is preferred for curative-intent resection of gastric cancer. At least 16 lymph nodes should be assessed for adequate staging of curative-resected gastric cancer. Gastric cancer surgery should aim to achieve an R0 resection margin. In the metastatic setting, surgery should be considered only for palliation of symptoms. Patients should be referred to higher-volume centres and those that have adequate support to manage potential complications. Laparoscopic resections should be performed to the same standards as those for open resections, by surgeons who are experienced in both advanced laparoscopic surgery and gastric cancer management.

Invasive mediastinal staging of non-small-cell lung cancer: a clinical practice guideline.

INTRODUCTION: In non-small-cell lung cancer (nsclc), invasive mediastinal staging is typically used to guide treatment decision-making. Here, we present clinical practice guideline recommendations for invasive mediastinal staging in nsclc patients who have been staged T1-4, N0-3, with no distant metastases. METHODS: Draft recommendations were formulated based on the best available evidence gathered by a systematic review and a consensus of expert opinion. The draft recommendations underwent an internal review by clinical and methodology experts, and an external review by clinical practitioners through a survey assessing the clinical relevance and overall quality of the guideline. Feedback from the internal and external reviews was integrated into the clinical practice guideline. RESULTS: In general, most clinical experts agreed with the guideline, approving it for methodologic rigour. More than 80% of the surveyed practitioners gave it a high quality rating. The expert reviewers also provided written comments, with some of the suggested changes being incorporated into the final version of the guideline. CONCLUSIONS: In the clinical practice guideline, invasive mediastinal staging of nsclc is recommended in all cases except those involving patients with normal-sized lymph nodes, negative combine positron-emission tomography and computed tomography, and peripheral clinical stage 1A tumour. When performing mediastinoscopy, 5 nodal stations (2R/L, 4R/L, and 7) should routinely be examined.

Telesurgical evaluation of stable thoracic trauma patients: a feasibility study.

BACKGROUND: We evaluated a robotic telesurgical platform in managing thoracic trauma in an animal model. STUDY DESIGN: The da Vinci(®) robot was used to evaluate and treat a random number of blinded injuries in ten porcine thoraces. RESULTS: Ninety-five percent of injuries were correctly identified. The median survey time was 20.5 min (range 16-63 min). The mean time to repair lung lacerations was 19.8 min (range 14-27.5 min) and to evacuate the hemothoraces, it was 5.3 min (range 4.5-6.5 min). Diaphragmatic lacerations required repositioning of the ports and the robot. Only two out of five lacerations were successfully repaired (mean time 38.8 min, range 32.5-45 min). All aortic injuries were correctly identified. One subject died of a pre-existing pneumonia. CONCLUSIONS: A robotic telesurgical approach to the evaluation of stable thoracic trauma patients is safe and feasible in a porcine model. Diaphragmatic injuries can be repaired but require repositioning of the robot.

What are the factors that predict outcome at relapse after previous esophagectomy and adjuvant therapy in high-risk esophageal cancer?

OBJECTIVES: The present study investigated factors affecting outcome at relapse after previous surgery and adjuvant chemoradiation (crt) in high-risk esophageal cancer patients. PATIENTS AND METHODS: From 1989 to 1999, we followed high-risk resected esophageal cancer patients who had completed postoperative crt therapy. Patients who relapsed with a disease-free interval of less than 3 months were treated with palliative crt when appropriate. Patients with a disease-free interval of 3 months or more were treated with best supportive care. Post-recurrence survival was estimated using the Kaplan-Meier technique, and statistical comparisons were made using log-rank chi-square tests and Cox regression. RESULTS: Of the 69 patients treated with adjuvant crt after esophagectomy, 46 experienced recurrence. Median time to relapse was 28 months (range: 0.1-40 months). Among the 46 relapsed patients, median age was 61 years (range: 37-82 years), and 42 were men. At the initial staging, 44 of 46 were node-positive; 31 of 46 had adenocarcinoma. In 33 of 46, post-esophagectomy resection margins were clear. Median follow-up after recurrence was 30.5 months (range: 1.3-100 months). Median overall survival after recurrence was 5.8 months, and the 12-month, 24-month, and 36-month survival rates were 20%, 10%, and 5% respectively. Of the prognostic factors analyzed, only resection margin status and interval to recurrence were statistically significant for patient outcome in univariate and multivariate analysis. Patients who had positive resection margins and who relapsed 12 or fewer months after surgery and adjuvant crt had a median post-recurrence overall survival of 0.85 months as compared with 6.0 months in other patients (more than 12 months to relapse, or negative resection margins, or both; log-rank p = 0.003). CONCLUSIONS: Resection margin status and interval to disease relapse are significant independent prognostic factors for patient outcome after adjuvant crt therapy.

Preoperative or postoperative therapy for resectable oesophageal cancer: an updated practice guideline.

AIMS: Oesophageal cancer is an aggressive disease and the optimal therapy for patients with resectable tumours remains unclear. A systematic review and companion practice guideline were published in 2004; however, new evidence has become available since the publication of the original report. An update of the literature search and a revision of the recommendations were undertaken to incorporate the new data. The following research question was addressed: should patients with resectable oesophageal cancer receive preoperative or postoperative therapy together with surgery? The outcomes of interest were survival, adverse effects and quality of life. MATERIALS AND METHODS: The literature search of the original systematic review was updated to April 2007. MEDLINE, EMBASE, Cochrane Library and abstracts from the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were searched for reports of randomised controlled trials and meta-analyses comparing preoperative or postoperative therapy with surgery alone or other preoperative or postoperative therapy. After the completion of the draft systematic review and practice guideline, the report was distributed through a mailed survey to 133 health care providers in Ontario for review and feedback. RESULTS: The updated literature search yielded eight new randomised controlled trial reports and seven new meta-analysis reports for consideration, together with the evidence reviewed in the original review publication. Of the 31 practitioners who responded to the mailed survey, 80% agreed with the draft recommendations as stated, 83% agreed that the report should be approved as a practice guideline and 86% indicated that they would probably use the guideline in their own practice. CONCLUSIONS: Preoperative cisplatin-based chemotherapy plus radiotherapy is recommended as the preferred modality for the management of surgically resectable patients with oesophageal cancer. Preoperative cisplatin-based chemotherapy alone is an alternative choice for the management of these patients.

New tactile sensing system for minimally invasive surgical tumour localization.

BACKGROUND: Minimally invasive surgery (MIS) suffers from the inability to directly palpate organs for tumour localization. A tactile sensing system (TSS), consisting of a probe and a visualization interface, was developed to present an active pressure map of the contact surface to locate tumours during MIS. METHODS: The TSS performance was compared to MIS graspers to locate occult 10 mm phantom tumours in ex vivo bovine liver and ex vivo porcine lung. Performance assessment included applied pressure, localization distance and accuracy. RESULTS: The TSS realized a relative 71% reduction in maximum applied pressure and a 31% increase in detection accuracy in liver tissue (when compared to MIS graspers) and demonstrated no significant differences in performance when palpating lung tissue. CONCLUSIONS: The TSS may help surgeons to identify occult tumours during surgery by restoring some of the haptic information lost during MIS.

Postoperative extended-volume external-beam radiation therapy in high-risk esophageal cancer patients: a prospective experience.

BACKGROUND AND PURPOSE: Extended-volume external-beam radiation therapy (RT) following esophagectomy is controversial. The present prospective study evaluates the feasibility of extended-volume RT treatment in high-risk esophagectomy patients with a cervical anastomosis receiving postoperative combined chemoradiation therapy. PATIENTS AND METHODS: From 2001 to 2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study to evaluate the adverse effects of extended-volume RT. Postoperative management was carried out at London Regional Cancer Program. Eligibility criteria were pathology-proven esophageal malignancy (T3-4, N0-1), disease amenable to surgical resection, and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous RT were excluded. All 15 study patients received 4 cycles of 5-fluorouracil-based chemotherapy. External-beam RT was conducted using conformal computed tomography planning, with multi-field arrangement tailored to the pathology findings, with coverage of a clinical target volume encompassing the primary tumour bed and the anastomotic site in the neck. The radiation therapy dose was 50.40 Gy at 1.8 Gy per fraction. The RT was delivered concurrently with the third cycle of chemotherapy. The study outcomes-disease-free survival (DFS) and overall survival (OS)-were calculated by the Kaplan-Meier method. Treatment-related toxicities were assessed using the U.S. National Cancer Institute's Common Toxicity Criteria. RESULTS: The study accrued 10 men and 5 women of median age 64 years (range: 48-80 years) and TNM stages T3N0 (n = 1), T2N1 (n = 2), T3N1 (n = 11), and T4N1 (n = 1). Histopathology included 5 adenocarcinomas and 10 squamous-cell carcinomas. Resection margins were clear in 10 patients. The median follow-up time was 19 months (range: 3.5-53.4 months). Before radiation therapy commenced, delay in chemotherapy occurred in 20% of patients, and dose reduction was required in 13.3%. During the concurrent chemoradiation therapy phase, 20% of the patients experienced chemotherapy delay, and 6.6% experienced dose reduction. No patient experienced treatment-related acute and chronic esophagitis above grade 2. Disease recurred in 40% of the patients (6/15), and median time to relapse was 24 months. No tumour recurred at the anastomotic site. The median DFS was 23 months, and the median OS was 21 months. CONCLUSIONS: Extended-volume external-beam RT encompassing the tumour bed and the anastomotic site is feasible and safe for high-risk T3-4, N0-1 esophageal cancer patients after esophagectomy.

Electromagnetic navigation improves minimally invasive robot-assisted lung brachytherapy.

OBJECTIVE: Recent advances in minimally invasive thoracic surgery have renewed an interest in the role of interstitial brachytherapy for lung cancer. Our previous work has demonstrated that a minimally invasive robot-assisted (MIRA) lung brachytherapy system produced results that were equal to or better than those obtained with standard video-assisted thoracic surgery (VATS) and comparable to results with open surgery. The purpose of this project was to evaluate the performance of an integrated system for MIRA lung brachytherapy that incorporated modified electromagnetic navigation and ultrasound image guidance with robotic assistance. METHODS: The experimental test-bed consisted of a VATS box, ZEUS and AESOP surgical robotic arms, a seed injector, an ultrasound machine, video monitors, a computer, and an endoscope. Our previous custom-designed electromagnetic navigational software and the robotic controller were modified and incorporated into the MIRA III system to become the next-generation MIRA IV. Inactive brachytherapy seeds were injected as close as possible to a small metal ball target embedded in an opaque agar cube. The completion time, the number of attempts, and the accuracy of seed deployment were compared for manual placement, standard VATS, MIRA III, and the new MIRA IV system. RESULTS: The MIRA IV system significantly reduced the median procedure time by 61% (104 s to 41 s), tissue trauma by 75% (4 attempts to 1 attempt), and mean seed placement error by 64% (2.5 mm to 0.9 mm) when compared to a standard VATS. MIRA IV also reduced the mean procedure time by 48% (85 s to 44 s) and the seed placement error by 68% (2.8 mm to 0.9 mm) compared to the MIRA III system. CONCLUSIONS: A modified integrated system for performing minimally invasive robot-assisted lung brachytherapy was developed that incorporated electromagnetic navigation and an improved robotic controller. The MIRA IV system performed significantly better than standard VATS and better than MIRA III.

Feasibility of locating tumours in lung via kinaesthetic feedback.

BACKGROUND: Localizing lung tumours during minimally invasive surgery is difficult, since restricted access precludes manual palpation and pre-operative imaging cannot map directly to the intra-operative lung. This study analyses the force-sensing performance that would allow an instrumented kinaesthetic probe to localize tumours based on stiffness variations of the lung parenchyma. METHODS: Agar injected into ex vivo porcine lungs produced a model approximating commonly encountered tumours. Force-deformation data were collected from multiple sites at various palpation depths and velocities, before and after the tumours were injected. RESULTS: Analysis showed an increase in force after the tumours were injected, in the range 0.07-0.16 N at 7 mm (p < 10(-4)). A 2 mm/s palpation velocity minimized exponential stress decay at constant depths, facilitating easier comparisons between measurements. CONCLUSION: A sensing range of 0-2 N, with 0.01 N resolution, should allow a kinaesthetic palpation probe to resolve local tissue stiffness changes that suggest an underlying tumour.

Development and validation of a disease-specific quality of life questionnaire (EQOL) for potentially curable patients with carcinoma of the esophagus.

The objective was to develop, pretest and validate a disease-specific quality of life questionnaire for potentially curable patients with esophageal carcinoma, for use with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in order to assess the quality of life associated with the various treatment modalities available for this disease. Questionnaire development phase Patients were enrolled in three centres. Literature reviews, patients, family members, and health care professionals generated 195 items: symptoms (55); emotions (53); physical functioning (17); activities of daily living (ADL) (48); and leisure/social (22). Thirty-eight patients identified items of importance and assigned importance ratings on a 5-point Likert scale. Impact scores were calculated as frequency times mean item importance. Item impact scores<20/100 were excluded. Pearson's correlation co-efficients compared domains with the Medical Outcomes Study SF-20 (MOS SF-20). Fifteen items remained. Questionnaire validation phase EORTC QLQ-C30, Esophageal Quality of Life Questionnaire (EQOL), MOS SF-36 and a Global Rating of Change Questionnaire were completed at baseline, 1 week after baseline but prior to any treatment, 1 month, 3 months, and 6 months after treatment began. Reliability was assessed using paired samples correlations. Responsiveness was assessed between mean scores of changed and unchanged patients, and a responsiveness index was calculated. The MOS SF-36 was used for criterion validity. Construct validity included four a priori predictions. Sixty-five patients were enrolled in four centres in the validation phase. Paired samples correlations were high for all domains (0.749-0.889) indicating good reliability. Symptom, physical function and social domains were responsive to change at all time intervals (P<0.05). Emotional function was responsive at 1 and 3 months, activities of daily living (ADLs) at 1 and 6 months. Magnitude of change was significant when direction of change was stated. Between better and worse, magnitude of change was significant in all domains except at 6 months in symptoms, emotional and physical domains. The minimal clinically important difference was consistently around 0.5 for all domains. Minimal, moderate and large effect ranges were established. Only 2/16 time intervals had poor correlations with the SF-36, establishing criterion validity. Of the four a priori predictions for construct validity, only the second part of one prediction, in the emotional function domain, was not confirmed. We have developed a 15-item questionnaire (EQOL) which has good reliability, responsiveness and validity and is now in use in studies in Canadian centres with the EORTC QLQ-C30.

Robot-assisted minimally invasive lung brachytherapy.

BACKGROUND: This paper presents a novel alternative for the treatment of lung cancer. The method consists of accessing the lung through small incisions in a minimally invasive manner in order to insert radioactive seeds directly into the lung using a robotic surgical system. METHODS: An experimental test-bed to evaluate the feasibility of this approach has been developed. It consists of two surgical robotic systems, a device specifically designed to robotically implant radioactive seeds, needle tracking software, ultrasound imaging, electromagnetic tracking, and a surgical box that mimics a patient's thorax. A detailed comparison has been performed between currently available access options and robot-assisted minimally invasive access. RESULTS: The results show insignificant differences in accuracy between the methods, with the exception of a significant improvement when electromagnetic (EM) guidance was added to the non-robotic techniques. The navigation system reduced the number of attempts for all seed delivery methods. Significant reductions in time were achieved in the minimally invasive procedures by the addition of EM guidance. CONCLUSIONS: The performance achieved when using robotic systems and image guidance for minimally-invasive brachytherapy is clinically comparable to that achieved in an open surgery procedure, while reducing the invasiveness of the procedure, improving ergonomic conditions for the clinician and reducing radiation exposure.

3D thoracoscopic ultrasound volume measurement validation in an ex vivo and in vivo porcine model of lung tumours.

The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial "tumours" were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the "tumours" were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the ultrasound images and a manual-radial segmentation technique and these were compared with the known volumes of the agar. In vitro measurements had average accuracy and precision of 4.76% and 1.77%, respectively; in vivo measurements had average accuracy and precision of 8.18% and 1.75%, respectively. The 3D thoracoscopic ultrasound can be used to accurately and reproducibly measure "tumour" volumes both in vivo and ex vivo.

Cyclosporin versus tacrolimus for liver transplanted patients.

BACKGROUND: Most liver transplant recipients receive either cyclosporin or tacrolimus to prevent rejection. Both drugs inhibit calcineurin phosphatase which is thought to be the mechanism of their anti-rejection effect and principle toxicities. The drugs have different pharmacokinetic profiles and potencies. Several randomised clinical trials have compared cyclosporin and tacrolimus in liver transplant recipients, but it remains unclear which is superior. OBJECTIVES: To evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded, and conference proceedings were searched (August 2005) to identify relevant randomised clinical trials. Our search included scanning of reference lists in relevant articles and correspondence with investigators and pharmaceutical companies. SELECTION CRITERIA: All randomised clinical trials where tacrolimus was compared with cyclosporin for the initial treatment of first-time liver transplant recipients. We included randomised trials irrespective of blinding, language, and publication status. DATA COLLECTION AND ANALYSIS: The primary outcome measure was all-cause mortality. Data were synthesised (fixed-effect model) and results expressed as relative risk (RR), values less than 1.0 favouring tacrolimus, with 95% confidence intervals (CI). Two authors assessed trials for eligibility, quality, and extracted data independently. MAIN RESULTS: We included 16 randomised trials. The number of deaths was 254 in the tacrolimus group (1899 patients) and 302 in the cyclosporin group (1914 patients). At one year, mortality (RR 0.85, 95% CI 0.73 to 0.99) and graft loss (RR 0.73, 95% CI 0.61 to 0.86) were significantly reduced in tacrolimus-treated recipients. Tacrolimus reduced the number of recipients with acute rejection (RR 0.81, 95% CI 0.75 to 0.88), and steroid-resistant rejection (RR 0.54, 95% CI 0.47 to 0.74) in the first year. Differences were not seen with respect to lymphoproliferative disorder or de-novo dialysis rates, but more de-novo insulin-requiring diabetes mellitus (RR 1.38, 95% CI 1.01 to 1.86) occurred in the tacrolimus group. More patients were withdrawn from cyclosporin therapy than from tacrolimus (RR 0.57, 95% CI 0.49 to 0.66). AUTHORS' CONCLUSIONS: Tacrolimus is superior to cyclosporin in improving survival (patient and graft) and preventing acute rejection after liver transplantation, but it increases the risk of post-transplant diabetes. Treating 100 recipients with tacrolimus instead of cyclosporin would avoid acute rejection and steroid-resistant rejection in nine and seven patients, respectively, and graft loss and death in five and two patients, respectively, but four additional patients would develop diabetes after liver transplantation.

Stapled versus conventional surgery for hemorrhoids.

BACKGROUND: Hemorrhoids are one of the most common anorectal disorders. The Milligan­Morgan open hemorrhoidectomy is the most widely practiced surgical technique used for the management of hemorrhoids and is considered the current "gold standard". Circular stapled hemorrhoidopexy was first described by Longo in 1998 as alternative to conventional excisional hemorrhoidectomy. Early, small randomized­controlled trials comparing stapled hemorrhoidopexy with traditional excisional surgery have shown it to be less painful and that it is associated with quicker recovery. The reports also suggest a better patient acceptance and a higher compliance with day­case procedures potentially making it more economical. A previous Cochrane Review of stapled hemorrhoidopexy and conventional excisional surgery has shown that the stapled technique is associated with a higher risk of recurrent hemorrhoids and some symptoms in long term follow­up. Since this initial review, several more randomized controlled trials have been published that may shed more light on the differences between the novel stapled approach and conventional excisional techniques. OBJECTIVES: This review compares the use of circular stapling devices and conventional excisional techniques in the surgical treatment of hemorrhoids. Its goal is to ascertain whether there is any difference in the outcomes of the two techniques in patients with symptomatic hemorrhoids. SEARCH STRATEGY: We searched all the major electronic databases (MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from 1998 to December 2009. SELECTION CRITERIA: All randomized controlled trials comparing stapled hemorrhoidopexy to conventional excisional hemorrhoidal surgeries with a minimum follow­up period of 6 months were included. DATA COLLECTION AND ANALYSIS: Data were collected on a data sheet. When appropriate, an Odds Ratio was generated using a random effects model. MAIN RESULTS: Patients with SH were significantly more likely to have recurrent hemorrhoids in long term follow up at all time points than those with CH (12 trials, 955 patients, OR 3.22, CI 1.59­6.51, p=0.001). There were 37 recurrences out of 479 patients in the stapled group versus only 9 out of 476 patients in the conventional group. Similarly, in trials where there was follow up of one year or more, SH was associated with a greater proportion of patients with hemorrhoid recurrence (5 trials, 417 patients, OR 3.60, CI 1.24­10.49, p=0.02). Furthermore, a significantly higher proportion of patients with SH complained of the symptom of prolapse at all time points (13 studies, 1191 patients, OR 2.65, CI 1.45­4.85, p=0.002). In studies with follow up of greater than one year, the same significant outcome was found (7 studies, 668 patients, OR 3.14, CI 1.20­8.22, p=0.02). Patients undergoing SH were more likely to require an additional operative procedure compared to those who underwent CH (8 papers, 553 patients, OR 2.75, CI 1.31­5.77, p=0.008). When all symptoms were considered, patients undergoing CH surgery were more likely to be asymptomatic (12 trials, 1097 patients, OR 0.59, CI 0.40­0.88). Non significant trends in favor of SH were seen in pain, pruritis ani, and fecal urgency. All other clinical parameters showed trends favoring CH.

Preoperative chemotherapy for resectable thoracic esophageal cancer.

BACKGROUND: Surgery has been the treatment of choice for localized esophageal cancer. A number of studies have investigated whether preoperative chemotherapy followed by surgery leads to an improvement in cure rates but the individual reports have been conflicting. An explicit systematic update of the role of preoperative chemotherapy in the treatment of resectable thoracic esophageal cancer is, therefore, warranted. OBJECTIVES: The objective of this review is to determine the role of preoperative chemotherapy on patients with resectable thoracic esophageal carcinomas. SEARCH STRATEGY: Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2006), EMBASE (1988 to 2006) and CANCERLIT (1993 to 2002). There were no language restrictions. SELECTION CRITERIA: All trials of patients with potentially resectable carcinomas of the esophagus (of any histologic type) who were randomised to having either chemotherapy or no chemotherapy before surgery. DATA COLLECTION AND ANALYSIS: The primary outcome was survival, which was assessed using hazard ratios. This is an amendment to the original review which used relative risks to assess survival at yearly intervals. Hazard ratios (HR) have now been introduced to summarise the complete survival experience in a single analysis. The risk ratio (relative risk; RR) was used to compare rates of resections, tumour recurrences and treatment morbidity and mortality. MAIN RESULTS: There were eleven randomised trials involving 2019 patients. Eight trials (1729 patients) reported sufficient detail on survival to be included in a meta-analysis for the primary outcome. There was some evidence to suggest that preoperative chemotherapy improves survival, but this was inconclusive (HR 0.88; 95% CI 0.75 to 1.04). There was no evidence to suggest that the overall rate of resections (RR 0.96, 95% CI 0.92 to 1.01) or the rate of complete resections (R0) (RR 1.05; 95% CI 0.97 to 1.15) differ between the preoperative chemotherapy arm and surgery alone. There is no evidence that tumour recurrence (RR 0.81, 95% CI 0.54 to 1.22) or non-fatal complication rates (RR 0.90; 95% CI 0.76 to 1.06) differ for preoperative chemotherapy compared to surgery alone. Trials reported risks of toxicity with chemotherapy that ranged from 11% to 90%. AUTHORS' CONCLUSIONS: In summary, preoperative chemotherapy plus surgery may offer a survival advantage compared to surgery alone for resectable thoracic esophageal cancer, but the evidence is inconclusive. There is some evidence of toxicity and preoperative mortality associated with chemotherapy.

Cyclosporin versus tacrolimus as primary immunosuppressant after liver transplantation: a meta-analysis.

A systematic review of randomized clinical trials (RCT) was undertaken to evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. MEDLINE, EMBASE, Cochrane Central and Hepato-Biliary Group Controlled Trials Registers were searched. Using fixed and random effects model, relative risk (RR), values <1 favoring tacrolimus, with 95% confidence intervals (CI) were calculated. Of 717 potentially relevant references, 16 RCTs were eligible for inclusion. Mortality and graft loss at 1 year were significantly reduced in tacrolimus-treated recipients (Death: RR 0.85, 95% CI 0.73-0.99; graft loss: RR 0.73, 95% CI 0.61-0.86). Tacrolimus reduced the number of recipients with acute rejection (RR 0.81, 95% CI 0.75-0.88) and steroid-resistant rejection (RR 0.54, 95% CI 0.47-0.74) in the first year. Lymphoproliferative disorder or dialysis rates were not different but more de novo diabetes (RR 1.38, 95% CI 1.01-1.86) occurred with tacrolimus. More patients stopped cyclosporin than tacrolimus (RR 0.57, 95% CI 0.49-0.66). Treating 100 recipients with tacrolimus instead of cyclosporin would avoid rejection and steroid-resistant rejection in nine and seven patients respectively, graft loss and death in five and two patients respectively, but four additional patients would develop diabetes after liver transplantation.

Combined chemotherapy and radiotherapy (without surgery) compared with radiotherapy alone in localized carcinoma of the esophagus.

BACKGROUND: Esophageal carcinoma can be managed primarily with either a surgical or non-surgical radiotherapeutic approach. Combination chemotherapy (CT) and radiotherapy (RT) has been incorporated into clinical practice and applied increasingly, especially in North America. OBJECTIVES: To evaluate combined CT and RT (CTRT) versus RT alone in patients with localized esophageal carcinoma. Outcomes included overall survival, cause-specific survival, local recurrence, dysphagia relief, quality of life, acute and chronic toxicities. SEARCH STRATEGY: The Cochrane strategy for identifying randomized trials was combined with relevant MeSH headings. The Cochrane Library, MEDLINE, CancerLIT and EMBASE were last searched in April 2005. References from relevant articles and personal files were included. SELECTION CRITERIA: Randomized controlled trials in patients with localized esophageal cancer comparing RT alone with combined CTRT were included. Studies comparing non-chemotherapy agents such as pure radiotherapy sensitisers, immunostimulants, planned esophagectomy, were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data independently. Trial quality was assessed using the Jadad scale and Detsky checklist. Sensitivity analyses were planned to examine the effect of concomitant versus sequential treatment, study quality, radiotherapy dose, and whether the drug regimen contained cisplatin or 5-fluorouracil were performed. MAIN RESULTS: Nineteen randomized trials were included, with eleven concomitant and eight sequential RTCT studies. Concomitant RTCT provided significant reduction in mortality with a harms ratio (HR) of 0.73 (95% confidence interval (CI) 0.64 to 0.84). Using an estimated mortality rate for the control group of 62% at year one and 83% at year two, the absolute survival benefit for RTCT was 9% (95% CI 5 to 12%) and 4% (95% CI 3 to 6%]) respectively. There was an absolute reduction of local recurrence rate of 12% (95% CI 3 to 22%), number needed to treat (NNT) of 9, when the local recurrence rate for the RT alone arm was 68%. This was associated with a significant risk of severe and life-threatening toxicities (number needed to harm (NNH)of 6). Sensitivity analyses did not identify any factors that interacted with the results. The results from sequential RTCT studies showed no significant benefit in survival or local control but significant toxicities. AUTHORS' CONCLUSIONS: Based on the available data, when a non-operative approach is selected then concomitant RTCT is superior to RT alone for patients with localized esophageal cancer but with significant toxicities. In patients who are in good general condition, and the risk benefit has been thoroughly discussed with the patient, concomitant RTCT should be considered for the management of esophageal cancer compared with radiotherapy alone.

A case of bronchopulmonary carcinoid tumor: the role of octreotide scanning in localization of an ectopic source of ACTH.

BACKGROUND: Bronchopulmonary carcinoids are neuroendocrine tumors. They can present with Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion. Curative resection is possible only after adequate localization of the ectopic source. OBJECTIVE: To describe a case that illustrates the role of octreotide scanning in the management of a bronchopulmonary carcinoid. RESULTS: The use of preoperative and postoperative octreotide scanning aided in performing a limited resection, thereby preserving the lung parenchyma. CONCLUSIONS: We propose that octreotide scanning can be a very important and informative test in the management of carcinoid tumors. In situations when conventional imaging is not conclusive, octreotide scanning may be of help in determining the source of ectopic ACTH syndrome.

Preoperative chemotherapy for resectable thoracic esophageal cancer.

BACKGROUND: Surgery has been the treatment of choice for localized esophageal cancer. A number of studies have investigated whether preoperative chemotherapy followed by surgery leads to an improvement in cure rates, but the individual reports have been conflicting. An explicit systematic update of the role of preoperative chemotherapy in the treatment of resectable thoracic esophageal cancer is therefore warranted. OBJECTIVES: The objective of this review is to determine the role of preoperative chemotherapy on patients with resectable thoracic esophageal carcinomas. SEARCH STRATEGY: Trials were identified by searching the Cochrane Controlled Trials Register, MEDLINE (1966 - 2003), EMBASE (1988 - 2003) and CancerLit (1993 - 2003). There were no language restrictions. SELECTION CRITERIA: Types of studies. Studies that randomised patients with potentially resectable carcinomas of the esophagus (of any histologic type) to chemotherapy or no chemotherapy before surgeries were included in this review. Types of participants. The participants consisted of patients with localized potentially resectable thoracic esophageal carcinomas. Trials involving patients with carcinomas of the cervical esophagus were excluded. Types of interventions. Trials that compared chemotherapy before surgery (esophagectomy) with surgical resections alone (esophagectomy) were included. Types of outcome measures. The primary outcome was overall survival at yearly intervals after randomisation. Secondary outcomes of interest included rates of resections, response to chemotherapy, rates of local and distant recurrences, quality-of-life, and treatment morbidity and mortality. DATA COLLECTION AND ANALYSIS: All analyses were carried out on intention-to-treat. Survival at 1, 2, 3, 4 and five years were used as endpoints of clinical relevance along with the median survival. The risk ratio (relative risk; RR) was the primary measure of effect for survival, rates of resections, and tumour recurrences. The risk difference (RD) was used to describe differences in response to chemotherapy, treatment morbidity and mortality. MAIN RESULTS: There were 11 randomised trials involving 2051 patients. At 1- year and 2-year the risk ratios showed no difference in survival between preoperative chemotherapy and surgery alone. The 3-year risk ratios found a 21% increase in survival (RR = 1.21; 95% CI 0.88 to 1.68; p = 0.25) and a 24% increase in survival with preoperative chemotherapy at 4 years (RR = 1.24; 95% CI 0.92 to 1.68; p = 0.15) but they did not reach statistical significance. Only at 5 years did the results become significant (RR = 1.44; 95% CI 1.05 to 1.97; p = 0.02). The overall rate of resections and the rate of complete resections (R0) did not differ between the preoperative chemotherapy arm and surgery alone. The pooled clinical response to chemotherapy was about 36% (RD = 0.36; 95% CI 0.26 to 0.47) but the complete pathologic response was a disappointing 3% (RD = 0.03; 95% CI 0.01 to 0.04). No single agent or combination of chemotherapeutic agents was found to be superior to the others. There was a 19% reduction in local recurrence with preoperative chemotherapy, but this was not significant (RR = 0.81; 95% CI 0.54 to 1.22; p = 0.3). Preoperative chemotherapy was somewhat more harmful to patients than surgery alone. REVIEWER'S CONCLUSIONS: In summary, preoperative chemotherapy plus surgery appears to offer a survival advantage at 3, 4, and 5 years, which reached significance only at 5 years compared to surgery alone for resectable thoracic esophageal cancer of any histologic type. The number needed to treat for one extra survivor at five years is eleven patients. The results are tempered by the increased toxicity and mortality associated with chemotherapy. The most beneficial chemotherapy combination appears to be cisplatin and 5-flurouracil based, however, the dosing is unclear.