Practical guide to the Idea, Development and Exploration stages of the IDEAL Framework and Recommendations.

BACKGROUND: Evaluation of new surgical procedures is a complex process challenged by evolution of technique, operator learning curves, the possibility of variable procedural quality, and strong treatment preferences among patients and clinicians. Preliminary studies that address these issues are needed to prepare for a successful randomized trial. The IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up) Framework and Recommendations provide an integrated step-by-step evaluation pathway that can help investigators achieve this. METHODS: A practical guide was developed for investigators evaluating new surgical interventions in the earlier phases before a randomized trial (corresponding to stages 1, 2a and 2b of the IDEAL Framework). The examples and practical tips included were chosen and agreed upon by consensus among authors with experience either in designing and conducting IDEAL format studies, or in helping others to design such studies. They address the most common challenges encountered by authors attempting to follow the IDEAL Recommendations. RESULTS: A decision aid has been created to help identify the IDEAL stage of an innovation from literature reports, with advice on how to design and report the IDEAL study formats discussed, along with the ethical and scientific rationale for specific recommendations. CONCLUSION: The guide helps readers and researchers to understand and implement the IDEAL Framework and Recommendations to improve the quality of evidence supporting surgical innovation.

Clinical benefit of neoral dose monitoring with cyclosporine 2-hr post-dose levels compared with trough levels in stable heart transplant patients.

BACKGROUND: Based on the excellent correlation between cyclosporine A 2-hr postdose blood levels (C2) and the area under the concentration versus time curve, we evaluated the clinical benefit of Neoral dose monitoring with C2 compared trough levels (C0) in stable heart transplant patients. METHODS: We studied 114 stable adult patients followed at the heart transplant clinic, who were >1 year after surgery. In May 1996 (period 1, follow-up 10+/-4 months), Neoral dose monitoring was based on C2 (300-600 ng/ml); while in May 1997 (period 2, follow-up 10+/-2 months), it was based on C0 (100-200 ng/ml). Cyclosporine A levels were measured by an enzyme multiplied immunologic technique. Clinical benefit was defined by the absence of acute rejection, no mortality, no fall in left ventricular ejection fraction >10%, and no increase in serum creatinine >10% (compared with baseline). RESULTS: During period 1, Neoral dose, cyclosporine A, C0 and C2, and serum creatinine, decreased by 26, 56, 45, and 2.3%, respectively. At the end of period 2, the same variables increased by 24, 56, 38, and 10%, respectively (P<0.0001). The incidence of acute rejection was similar (period 1: 0.87%, period 2: 0.96%). The left ventricular ejection fraction (initial/final) remained stable (period 1: 57+/-91%/58+/-13%, period 2: 59+/-11d/58+/-10%). Mortality did not differ (period 1: 7.9%, period 2: 9.6%). A clinical benefit was observed in 69.3% of the patients during period 1 vs. 43.3% of the patients during period 2 (P<0.00001). CONCLUSIONS: In stable heart transplant patients, a greater clinical benefit was observed when Neoral dose monitoring was performed according to C2, compared with C0.

Elevation of CA-125 level is due to abdominal distension in liver transplantation candidates.

BACKGROUND: CA (cancer antigen) 125 is a serologic marker used in the monitoring of ovarian cancer. Elevated levels are also reported in cirrhosis. We evaluated the range of serum CA 125 levels seen before and after liver transplantation, and examined possible factors associated with CA 125 elevation. METHODS: We examined prospectively 57 consecutive patients with cirrhosis who underwent liver transplantation. CA 125 levels were also measured in two patients with polycystic liver disease. RESULTS: The mean serum CA 125 level before transplantation was 352+/-549 u/ml, compared with 46+/-49 u/ml after transplantation (P<0.001). Multivariate analysis identified the degree of ascites as the only significant predictive variable of preoperative CA 125 level. In five patients who underwent abdominal paracentesis, the mean ascites CA 125 level (951+/-322 u/ml) was higher than that of the serum (619+/-290 u/ml) (P<0.003). In 16 hepatectomy specimens, the grade of staining for CA 125 was 0.8+/-1.4 for the mesothelium of patients with a normal serum CA 125 level, compared with 1.5+/-1.1 in patients with elevated serum levels (P=0.37). Two patients with severe abdominal distension due to polycystic liver disease but without ascites had elevated serum CA 125 levels. DISCUSSION: CA 125 concentration is elevated in the majority of patients with cirrhosis and normalizes after liver transplantation. It is a reflection of the abdominal distention seen in these patients. Therefore, an elevation in CA 125 should not be considered a contraindication to liver transplantation in the absence of evidence of malignancy.

Comparison of neoral dose monitoring with cyclosporine through levels versus 2-hr postdose levels in stable liver transplant patients.

BACKGROUND: We reported that cyclosporine 2-hr postdose levels (C2) correlate better with the AUC0-4 hr than trough levels (C0) in heart transplant patients receiving Neoral. METHODS: We compared Neoral dose adjustment with C0 (group 1: 100-200 ng/ml) vs. C2 (group 2: 700-1000 ng/ml; group 3: 300-600 ng/ml) in 35 stable adult patients >1 year after liver transplantation. The AUC0-4hr was calculated, and simultaneous blood samples were obtained to measure calcineurin inhibition. Clinical benefit was defined as the absence of rejection and no increase in serum creatinine at the 7-month follow-up. RESULTS: C2 correlated better with the AUC0-4 hr than C0 (r=0.92 vs. r=0.40). Neoral dose increased by 17% and 39% in groups 1 and 2, and decreased by 18% in group 3 (P=0.002 vs. group 1 and P=0.0004 vs. group 2). Serum creatinine increased by 2.1% and 16% in groups 1 and 2, and decreased by 5.1% in group 3 (P=0.006 vs. group 2). A clinical benefit was observed in 37.5%, 23%, and 82% of patients in groups 1, 2, and 3 (P=0.03 vs. group 1 and P=0.01 vs. group 2). Calcineurin inhibition was similar in all groups at 2-hr (44+/-17%, 39+/-30%, and 44+/-35%), in spite of different Neoral doses (2.9+/-0.9, 4.0+/-1.8, and 2.6+/-1.3 mg/kg/day) and C2 (857+/-226, 922+/-274, and 588+/-274 ng/ml). CONCLUSIONS: C2 correlated better with the AUC0-4 hr than C0. Neoral dose monitoring with a C2 range of 300-600 ng/ml resulted in a lower dose and greater clinical benefit compared to C0 or a higher C2 in stable liver transplant patients. The correlation between calcineurin inhibition and clinical events deserves further research.

Laparoscopic fundoplication: a model for assessing new technology in surgical procedures.

BACKGROUND: Surgical success has traditionally been judged from the surgeon's perspective. A more complete evaluation of outcome incorporates the patient's, surgeon's, and payor's perspectives. Because gastroesophageal reflux disease (GERD) is primarily a quality-of-life (QOL) problem, the evaluation of laparoscopic fundoplication (LF) is a useful model for evaluating outcomes from these 3 perspectives. METHODS: Between 1995 and 2000, 74 patients underwent primary LF for GERD. In addition to undergoing physiologic testing, 63 patients (85%) were evaluated with use of a disease-specific health-related QOL scale (GERD-HRQL), scored from 0 (no symptoms) to 45 (incapacitating symptoms). Thirty-three patients also completed a generic QOL questionnaire (SF-12), in which patient satisfaction was scored from 1 (very satisfied) to 5 (very dissatisfied). Preoperative and postoperative data were compared with use of the Wilcoxon signed rank test or the paired t test. RESULTS: The median GERD-HRQL score improved from 18 to 0 at 2 years postoperation (P <.01). The median satisfaction score improved from 5 to 1 (P <.01). The SF-12 summary scores also improved after 6 weeks postoperatively (P <.05). The mean +/- SD lower esophageal sphincter pressure rose from 7.3 +/- 4 mm Hg preoperatively to 17.5 +/- 6 postoperatively (P <.01), and the mean percentage of time that the esophagus was exposed to a pH of less than 4 declined from 14.7% +/- 12% to 1.1% +/- 2% (P <.01). The median operative time was 110 minutes, which declined with experience with the procedure (P <.01). Median postoperative stay was 2 days. CONCLUSIONS: In evaluating the outcomes of a new procedure, 3 overlapping points of view were addressed: the patient's (QOL, satisfaction), the surgeon's (physiologic changes), and the payor's (operating room time, hospital stay). With use of this framework, we found that LF for GERD improves QOL, corrects the physiologic abnormalities, and is associated with short hospitalization and operating time that declines with experience with the procedure.

Laparoscopic versus open inguinal herniorrhaphy: preliminary results of a randomized controlled trial.

BACKGROUND: Benefits of laparoscopic herniorrhaphy (LH) over open hernia repair (OH) remain unproved. METHODS: Interim analysis of a prospective randomized controlled trial compared OH with LH where study outcomes were measured by third-party evaluators through patient interviews. RESULTS: Both groups were well matched for all baseline parameters, although LH patients anticipated a quicker postoperative recovery than OH (p = 0.014). No significant difference was noted in operating time or surgeon operative satisfaction. The median duration of hospital stay was 1 day in both groups; LH patients made use of significantly less postoperative narcotics than OH (p = 0.02). No difference was observed in the durations of convalescence (LH, 9.6 +/- 7.6 days; OH, 10.9 +/- 7.4 days). Greater improvements in quality of life were exhibited in LH patients than OH patients 1 month after operation (p = 0.035), with one of the two measures used. A greater percentage of LH patients seemed "very satisfied with their operation" (p = 0.07). Complication rates were similar, and a single recurrence, in a patient in the OH group, has been observed after a median follow-up of 14 months. CONCLUSIONS: Direct cost measurements showed LH to be 40% more expensive than OH in the context of a Canadian-type health care system. To date, benefits in postoperative pain and possibly quality of life have been detected in the LH group.

Evolving management of mild-to-moderate gallstone pancreatitis.

The objective of this study was to describe recent trends in the management of mild-to-moderate gallstone pancreatitis and assess patient outcomes. Acute gallstone pancreatitis has traditionally been managed with open cholecystectomy and intraoperative cholangiography during the initial hospitalization. The popularization of endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic cholecystectomy has made a reassessment necessary. Two consecutive time periods were retrospectively analyzed: prior to laparoscopic cholecystectomy (prelaparoscopic era [PLE]) and after the diffusion of laparoscopic cholecystectomy (laparoscopic cholectomy era [LCE]). There were 35 patients in the PLE group and 58 in the LCE group. LCE patients waited 37.1 +/- 63 days from admission until cholecystectomy, compared to 9.8 +/- 14.8 days in the PLE group (P = 0.04). Biliary-pancreatic complications occurred in 24% of LCE patients and only 6% of PLE patients (P = 0.05), nearly always while they were awaiting cholecystectomy (P = 0.009). Patients in either time period who underwent cholecystectomy with intraoperative cholangiography developed less pancreatic-biliary complications than those who underwent ERCP prior to cholecystectomy, with or without sphincterotomy. Delaying the interval from pancreatitis to laparoscopic cholecystectomy beyond historical values is associated with a greater risk of recurrent biliary-pancreatic complications, which are not prevented by the use of ERCP. Early cholecys tectomy with intraoperative ductal evaluation is still the approach of choice.

Short-term outcomes in open vs. laparoscopic herniorrhaphy: confounding impact of worker's compensation on convalescence.

Over a 28-month period, 123 patients with a unilateral inguinal hernia were recruited into a randomized controlled trial comparing open herniorrhaphy (OH) to laparoscopic inguinal herniorrhaphy (LH). The primary end point was duration of convalescence. Sixty-five patients underwent OH and 58 underwent LH. Both groups were well matched for all baseline parameters, although LH patients anticipated a shorter convalescence than OH patients (14.3 +/- 9.4 days vs. 18.5 +/- 10.8 days; P = 0.021). The median duration of hospital stay was one day in both groups. No difference was observed in the duration of convalescence (LH 9.8 +/- 7.4 days; OH 11.6 +/- 7. 7 days) across groups. However, when the data were analyzed after removing patients receiving disability ("worker's") compensation (21 patients), patients undergoing LH recovered on average 3 days faster (LH 7.8 +/- 5.6 days; OH 10.9 +/- 7.5 days; P = 0.02). Patients not receiving worker's compensation appear to have a shorter convalescence after LH compared to OH. Disability compensation is a major confounding variable in determining convalescence and needs to be controlled for in any future trial design.

Laparoscopic versus open cholecystectomy: the Canadian experience. The McGill Gallstone Treatment Group.

Numerous uncontrolled trials have suggested that laparoscopic cholecystectomy (LC) is a major improvement over open cholecystectomy (OC). In an effort to objectively document the benefits of LC, two Canadian studies are reviewed. The first is a matched time series based on prospective data from a single surgeon's practice in which patients are closely matched for baseline characteristics. The groups consist of 121 patients from each of 3 time periods: 1989, prior to the introduction of LC; 1990, when LC was being introduced; and 1991, when LC had become the preferred method of cholecystectomy. The second study is a randomized trial, in which LC is compared with mini-cholecystectomy. In both studies, the superior efficacy of LC is demonstrated with respect to the duration of hospitalization and the duration of postoperative convalescence. The incidence of complications as well as their severity is also less in LC patients. Although quality of life improves after any type of cholecystectomy, LC patients improve faster and seem to accept the operation better. These studies support the widespread dispersion of LC in Canada, although comparative efficacy with nonsurgical alternatives has not been addressed.

Factors determining conversion to laparotomy in patients undergoing laparoscopic cholecystectomy.

Laparoscopic cholecystectomy (LC) has been performed increasingly in an outpatient setting. Conversion from LC to open cholecystectomy (OC) is sometimes required. To predict conversion to OC, a single institutional study of 1,676 consecutive patients in whom LC was attempted was performed. Factors evaluated were age, sex, history of acute cholecystitis, pancreatitis, or jaundice, previous abdominal surgery, abnormalities of liver function tests, thickened gallbladder wall identified by preoperative ultrasound, obesity or morbid obesity, and cumulative institutional experience in LC. Conversion to OC was required in 90 of 1,676 (5.4%) patients. Significant preoperative predictors of conversion were acute cholecystitis, increasing age, male sex, obesity, and thickened gallbladder wall found by ultrasound. Nonobese women younger than age 65 years with symptoms of biliary colic and normal gallbladder wall thickness found by preoperative ultrasound required conversion only 1.9% of the time. These predictors may be useful in planning a program of ambulatory or short stay surgical units for patients undergoing LC and for comparing data between series.

Development of a model for training and evaluation of laparoscopic skills.

BACKGROUND: Interest in the training and evaluation of laparoscopic skills is extending beyond the realm of the operating room to the use of laparoscopic simulators. The purpose of this study was to develop a series of structured tasks to objectively measure laparoscopic skills. This model was then used to test for the effects of level of training and practice on performance. METHODS: Forty-two subjects (6 each of surgical residents PGY1 to PGY5, 6 surgeons who practice laparoscopy and 6 who do not) were evaluated. Each subject viewed a 20-minute introductory video, then was tested performing 7 laparoscopic tasks (peg transfers, pattern cutting, clip and divide, endolooping, mesh placement and fixation, suturing with intracorporeal or extracorporeal knots). Performance was measured using a scoring system rewarding precision and speed. Each candidate repeated all 7 tasks and was rescored. Data were analyzed by linear regression to assess the relationship of performance with level of residency training for each task, and by ANOVA with repeated measures to test for effects of level of training, of repetition, and of the interaction between level of training and repetition on overall performance. Student's t test was used to evaluate differences between laparoscopic and nonlaparoscopic surgeons and between each of these groups and the PGY 5 level of surgical residents. RESULTS: Significant predictors of overall performance were (a) level of training (P = 0.002), (b) repetition (P < 0.0001), and (c) interaction between level of training and practice (P = 0.001). There was also a significant interaction between level of training and the specific task on performance scores (P = 0.006). When each task was evaluated individually for the 30 residents, 4 of the 7 tasks (tasks 1, 2, 6, 7) showed significant correlation between PGY level and score. A significant difference in performance scores between laparoscopic and nonlaparoscopic surgeons was seen for tasks 1, 2, and 6. CONCLUSIONS: A model was developed to evaluate laparoscopic skills. Construct validity was demonstrated by measuring significant improvement in performance with increasing residency training, and with practice. Further validation will require correlation of performance in the model with skill in vivo.

The impact of thymoglobulin on renal function and calcineurin inhibitor initiation in recipients of orthotopic liver transplant: a retrospective analysis of 298 consecutive patients.

BACKGROUND: Renal dysfunction remains the Achilles' heel of calcineurin inhibitor (CI)use. The purpose of this study was to assess our institutional, renal-sparing strategy using thymoglobulin (TMG) in recipients of orthotopic liver transplants. METHODS: We performed a retrospective analysis of data from 298 adult recipients who were transplanted between 1991 and 2002. The patients were divided into two groups: those induced with TMG (group 1) and those that were not treated with this agent (group 2). A subgroup analysis was performed of patients with baseline serum creatinine values above 1.5 mg/dL (group 1A received TMG; group 2A did not). All patients received tacrolimus or cyclosporine (CyA) maintenance immunosuppression. RESULTS: Indications and demographics were similar between the two groups. Although there was no difference in patient and graft survivals, there was a statistically significant benefit in the rejection-free graft survival at 1 year for group 1 (51% vs 39%; P =.02). Furthermore, serum creatinine at 6 months was lower for group 1, despite a similar baseline creatinine. Subgroup analysis for patients with baseline abnormal serum creatinines showed that group 1A displayed an improved rejection-free graft survival at 1 month but not at 1 year. CONCLUSIONS: Thymoglobulin induction therapy may allow a delay in the initiation of CI therapy without compromising patient and graft survival, while preventing early rejection, even among patients with baseline renal dysfunction.

Leukoreduction and acute rejection in liver transplantation: an interim analysis.

BACKGROUND: Little is known about the effect of blood transfusions and leukoreduction on acute rejection in liver transplantation. The purpose of this study was to assess the impact of leukoreduction on the occurrence of early rejection episodes in liver transplantation. METHODS: In 1999, mandatory leukoreduction was implemented in our program. Data from 339 consecutive liver transplant recipients were analyzed with attention to the time period as a proxy for leukoreduction, the number of transfusions, the wait list status, the hepatitis B or C status, the recipient age, and the type of immunosuppression. RESULTS: Using an early (6-month) rejection-free graft survival model, we observed that introduction of leukoreduction was independently associated with fewer rejection episodes (P =.001). Despite the lower rejection rate, due to a regimen of tacrolimus and antithymocyte globulin, the effect of implementation of leukoreduction remained significant (P =.021). CONCLUSION: The use of leukoreduction is associated with fewer early rejections, irrespective of the type of immunosuppression. These data support an exploration of the immunomodulatory effect of leukoreduction.

Do biliary endoprostheses decrease biliary complications after liver transplantation?

AIM: Most technical complications after orthotopic liver transplantation (OLT) are related to the biliary tree. This report reviews the role of routine intraoperative placement of stents to reduce biliary complications. METHODS: We retrospectively analyzed 396 consecutive OLTs. We reviewed rates of biliary complications after hepaticojejunostomy (HJA) as well as following choledochocholedochostomy (CCA) groups: "experimental" group (routine intraoperative biliary stenting, last 10 months), "recent" control group (nonstented, previous 10 months), "historical" control group (prior to that period of time). RESULTS: All groups were matched for donor/recipient characteristics and for graft cold/warm ischemia time. The overall prevalence of biliary complications was 30.7% after CCA versus 35% after HJA. In the experimental group 21 patients had a 4.8% biliary complication rate compared to the recent control and historical groups, where biliary complication rates were 30% and 32.6%, respectively (P <.05). CONCLUSIONS: The intraoperative use of biliary stents is feasible and appears to decrease the rate of biliary complications. These results support the need for a prospective randomized trial.

Randomised clinical trial: MRCP-first vs. ERCP-first approach in patients with suspected biliary obstruction due to bile duct stones.

BACKGROUND: The preferred initial investigation with either magnetic resonance (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) in patients with suspected biliary obstruction remains controversial in many clinical settings. AIM: To assess the effectiveness of an initial MRCP vs. ERCP in the work-up of patients at moderate likelihood of a suspected biliary obstruction. METHODS: Patients with an unconfirmed benign biliary obstruction, based on laboratory and ultrasound findings, were randomised to an ERCP-first or MRCP-first strategy, stratified by level of obstruction. The primary outcome was the occurrence of a disease or procedure-related bilio-pancreatic adverse events within the next 12 months. Secondary outcomes were the number of subsequent bilio-pancreatic procedures, duration of hospitalisation, days away from activities of daily living (ADL), quality of life (SF-36) and mortality. RESULTS: We randomised 126 patients to ERCP-first and 131 to MRCP-first (age 54 ± 18 years, 62% female, 39% post-cholecystectomy). In follow-up, 18/126 (14.3%) ERCP-first and 25/131 (19.1%) MRCP-first patients experienced a procedure- or disease-related complication (P = 0.30) (disease-related in 13 and 18 patients, and procedure-related in 5 and 7 patients respectively). A cause of biliary obstruction was found in 39.7% vs. 49.6% of patients (P = 0.11). Sixty-six (50%) patients in the MRCP-first group ended up avoiding an ERCP in follow-up. ERCP-first and MRCP-first patients were away from usual activities for 3.4 ± 7.7 days and 2.0 ± 4.8 days respectively (P < 0.001). CONCLUSION: A strategy of MRCP-first decreased the need for subsequent MRCPs, but not complications. Further study is required to define factors influencing the eventual use of MRCP vs. ERCP in appropriately selected patients (ClinicalTrial.gov: NCT01424657).

Liver transplantation for metastases from a bile duct carcinoid.

BACKGROUND: A 29-year-old woman who presented with fatigue and jaundice was found to have an obstructing mass at the bifurcation of the bile duct. The patient underwent a successful left hepatectomy with resection of the bile duct bifurcation and a reconstruction with a right hepaticojejunostomy. Pathology revealed an atypical carcinoid tumour of the left extrahepatic bile duct, with perineural and lymphatic invasion. The patient subsequently developed multiple metastases in the remaining liver. METHODS: In the absence of extrahepatic disease, the patient underwent a successful liver transplant. RESULTS: Two years later she remains disease-free. DISCUSSION: To our knowledge this is the first report of a biliary carcinoid treated with hepatectomy and finally with liver transplantation, with excellent results. The biological behaviour of these rare tumours mandates aggressive surgical management.