Consensus priority research questions in gastrointestinal and endoscopic surgery in the year 2020: results of a SAGES Delphi study.

INTRODUCTION: The objectives of this study were to identify consensus priority research questions according to members of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), and to explore differences in priorities according to specific membership subgroups. METHODS: A modified Delphi study was conducted including active members of SAGES. An initial list of research questions was compiled by members of 26 SAGES Committees and Task Forces, and was further refined by the SAGES Delphi Task Force. The questions were divided into five research categories: (1) Surgical Outcomes; (2) Education, Training, and Simulation; (3) Health Services Research; (4) New Technology; and (5) Artificial Intelligence. Delphi respondents were asked to rank each question with regards to its importance in the field of gastrointestinal and endoscopic surgery (1-low; 5-high). "Priority" was defined as a single-round mean score of ≥ 3.5, and "consensus" as a single-round standard deviation < 1.0. Subgroup analyses were performed according to a priori selected respondent characteristics. RESULTS: The total number of respondents for each round was: Round 1 (n = 407); Round 2 (n = 569); Round 3 (n = 273). In each round, the majority of respondents were male (Round 1: 77.4%; Round 2: 77.1%; Round 3: 76.7%), self-identified as academic (vs. community) surgeons (Round 1: 57.1%; Round 2: 61.1%; Round 3: 60.2%), and practiced in North America (Round 1: 71.8%; Round 2: 70.8%; Round 3: 75.9%). A total of 29 out of 122 research questions met criteria for both "priority" and "consensus"-Surgical Outcomes, n = 6; Education, Training, and Simulation, n = 9; Health Services Research, n = 5; New Technology, n = 5; and Artificial Intelligence, n = 4. CONCLUSIONS: Consensus priority research questions in gastrointestinal and endoscopic surgery were identified across five different research categories. These results can provide direction and areas of interest for funding and investigation for future studies.

Update regarding the society of American Gastrointestinal and Endoscopic Surgeons (SAGES) grant distribution and impact on recipient's academic career.

BACKGROUND: Small seed grants strongly impact academic careers, result in future funding, and lead to increased involvement in surgical societies. We hypothesize that, in accordance with the SAGES Research and Career Development committee mission, there has been a shift in grant support from senior faculty to residents and junior faculty. We hypothesize that these junior physician-researchers are subsequently remaining involved with SAGES and advancing within their academic institutions. METHODS: All current and previous SAGES grant recipients were surveyed through Survey Monkey™. Questions included current academic status and status at time of grant, ensuing funding, publication and presentation of grant, and impact on career. Results were verified through a Medline query. SAGES database was examined for involvement within the society. Respondent data were compared to 2009 data. RESULTS: One hundred and ninety four grants were awarded to 167 recipients. Of those, 75 investigators responded for a response rate 44.9%. 32% were trainees, 43% assistant professors, 16% associate professors, 3% full professors, 3% professors with tenure, and 3% in private practice. This is a shift from 2009 data with a considerable increase in funding of trainees by 19% and assistant professors by 10% and a decrease in funding of associate professors by 5% and professors by 10%. 41% of responders who were awarded the grant as assistant or associate professors had advanced to full professor and 99% were currently in academic medicine. Eighty-two percent indicated that they had completed their project and 93% believed that the award helped their career. All responders remained active in SAGES. CONCLUSION: SAGES has chosen to reallocate an increased percentage of grant money to more junior faculty members and residents. It appears that these grants may play a role in keeping recipients interested in the academic surgical realm and involved in the society while simultaneously helping them advance in faculty rank.

Comprehensive evaluation of endoscopic fundoplication using the EsophyX™ device.

BACKGROUND: There are limited studies that evaluate the efficacy of endoscopic fundoplication (EF) for gastroesophageal reflux disease (GERD) with the EsophyX™ device, especially with the most recent procedural iteration (TIF-2). This study was a prospective evaluation of our early experience with this device and procedure. METHODS: Data were collected prospectively on 23 consecutive patients undergoing EF (March 2009 to August 2010). All patients completed a symptom questionnaire assessing frequency and severity of gastrointestinal and respiratory symptoms, 24-h pH, and manometry studies preoperatively and were encouraged to repeat these at 6 months. RESULTS: All patients had abnormal pH studies and were on proton-pump inhibitor (PPI) therapy prior to EF. Median age was 47 years (19-62 years), and six (23%) were male. Nine (41%) patients had Body Mass Index (BMI) ≥ 30 kg/m(2), and three (14%) had a small hiatal hernia (≤ 2 cm). The procedure was aborted in two patients for retained food. Three patients underwent subsequent laparoscopic Nissen fundoplication for persistent or recurrent symptoms. Median hospitalization was 1 day, and there were no major perioperative complications. At 6 month follow-up, 19 (86%) patients completed a symptom questionnaire, and 14 (64%) and 11 (50%) patients underwent pH and manometry studies, respectively. There was a significant reduction in heartburn (P = 0.02), total percentage acid contact time (P = 0.002), DeMeester score (P = 0.002), and PPI use (P = 0.003). Overall, 8 out of 14 (57%) patients had abnormal pH studies and 11 out of 19 (58%) remained on PPI therapy at 6 months. CONCLUSION: EF with EsophyX™ is associated with significant reduction in heartburn and abnormal acid exposure at 6 months, although the majority of patients did not experience normalization of their pH studies and remained on PPI therapy. The procedure has an acceptable safety profile, but the question remains as to whether it is effective enough to warrant a place in the armamentarium for the treatment of GERD.

The safety of biologic mesh for laparoscopic repair of large, complicated hiatal hernia.

BACKGROUND: Biologic mesh is widely used for repair of large, complicated hiatal hernias. Recently, there have been reports of complications after its implantation. We studied the course of a large group of patients who had undergone hiatal hernia repair with use of biologic mesh to determine the rate of immediate and late complications related to its use. METHODS: All patients who had biologic mesh placed at the hiatus and who had been followed for at least 1 year were included. Perioperative data were reviewed, and a questionnaire was administered, designed to identify symptoms of gastroesophageal reflux, other symptoms such as dysphagia, and all other operative or endoscopic interventions that occurred after mesh implantation. In addition, postoperative radiologic and endoscopic studies were reviewed to assess signs of complications related to use of mesh. RESULTS: There were 126 patients eligible for the study. We were able to contact 73 of these patients, at median follow-up of 45 months. No mesh-related complications were found. The frequency and severity of heartburn, regurgitation, and dysphagia improved significantly compared with preoperative values, and 89% of the patients reported good to excellent results in terms of overall satisfaction. Six patients recorded worsening of dysphagia postoperatively, but after careful work-up and review of each individual case, no case seemed to be directly related to the mesh. No erosions, strictures, or other complications directly related to use of mesh were found. One patient required reoperation due to hiatal hernia recurrence with gastroesophageal reflux disease (GERD) symptoms. CONCLUSIONS: Use of biologic mesh for laparoscopic repair of large, complicated hiatal hernias appears safe. There were no major complications related to the mesh, and overall satisfaction with the operation was very good.

Laser Doppler flowmetry assessment of peristernal perfusion after cardiac surgery: beneficial effect of negative pressure therapy.

Negative pressure therapy has been successfully applied to clean, closed incisions in patients at high-risk for wound complications. Using laser Doppler flowmetry, we evaluated peristernal perfusion after cardiac surgery via median sternotomy, assessing the influence of mammary artery harvesting and the impact of negative pressure therapy. Twenty adult patients underwent median sternotomy for cardiac surgery followed by routine closure. Negative pressure was applied at 125 mm Hg for 4 days postoperatively in patients with increased risk for wound complications (n = 10, negative pressure group); standard dressings were applied to control incisions postoperatively (n = 10). Presternal perfusion was determined at baseline and daily for 4 days postoperatively using laser Doppler flowmetry. Results within and between groups were compared with analysis of variance. No wound complications were encountered in either group. Perfusion increased among the patients who underwent negative pressure therapy and decreased among the controls (P = 0.004). Mammary artery harvesting reduced peristernal perfusion by 25.7% in the controls, but negative pressure increased perfusion by 100% after mammary harvesting (P = 0.04). Negative pressure therapy increased perfusion relative to controls and compensated for reduced perfusion rendered by mammary artery harvesting, providing additional support for 'well wound therapy' in high-risk patients.

Emergency Restructuring of a General Surgery Residency Program During the Coronavirus Disease 2019 Pandemic: The University of Washington Experience.

Seattle, Washington, is an epicenter of the coronavirus disease 2019 epidemic in the United States. In response, the Division of General Surgery at the University of Washington Department of Surgery in Seattle has designed and implemented an emergency restructuring of the facility's general surgery resident care teams in an attempt to optimize workforce well-being, comply with physical distancing requirements, and continue excellent patient care. This article introduces a unique approach to general surgery resident allocation by dividing patient care into separate inpatient care, operating care, and clinic care teams. Separate teams made up of all resident levels will work in each setting for a 1-week period. By creating this emergency structure, we have limited the number of surgery residents with direct patient contact and have created teams working in isolation from one another to optimize physical distancing while still performing required work. This also provides a resident reserve without exposure to the virus, theoretically flattening the curve among our general surgery resident cohort. Surgical resident team restructuring is critical during a pandemic to optimize patient care and ensure the well-being and vitality of the resident workforce while ensuring the entire workforce is not compromised.

Isolated limb infusion for in-transit malignant melanoma of the extremity: a well-tolerated but less effective alternative to hyperthermic isolated limb perfusion.

BACKGROUND: Isolated limb infusion (ILI) is a recently described minimally invasive technique developed in Australia for delivering regional chemotherapy. This study examined the efficacy and toxicity of ILI, compared to hyperthermic isolated limb perfusion (HILP), in treating extremity in-transit melanoma. METHODS: Variables from a prospective single institution database of 120 regionally treated melanoma patients (1995-2007) were compared using chi-square analysis. This included 61 consecutive ILI treatments in 58 patients and 59 HILP treatments in 54 patients. Response was defined at 3 months using the response evaluation criteria in solid tumors (RECIST). ILI was performed using melphalan (LPAM) and dactinomycin for 30 min after limb temperature reached 37 degrees C. HILP was performed using LPAM for 60 min after limb temperature reached 38.5 degrees C. RESULTS: For ILI (n = 61), the complete response (CR) rate was 30%, the partial response (PR) rate was 14%, and there was no response (NR) in 56% of patients. The median duration of CR was 12 months and 18% of patients experienced (grade >or=3) toxicity. HILP (n = 59) was associated with a better (P < 0.001) response rate (CR 57%, PR 31%, and NR 12%) however, more patients (32%) experienced grade >or=3 toxicity (P = 0.037). The dose of LPAM was corrected for ideal body weight (IBW) in 40 out of 61 ILI procedures, and 13 of 59 HILP procedures. This dosing modification was associated with decreased toxicity (P = 0.024) without diminishing response. CONCLUSION: ILI was found to be a well-tolerated alternative to HILP. While ILI does not appear to be as effective as HILP, it does seem to be associated with less morbidity.

Marginal cardiac allografts do not have increased primary graft dysfunction in alternate list transplantation.

BACKGROUND: Clinical success with modern heart transplantation (HT) has led to the development of an alternate list (AL) HT strategy, matching marginal cardiac allografts with recipients who do not meet standard criteria for HT. Marginal allografts may be at an increased risk for primary graft dysfunction (PGD), the leading cause of early mortality after HT.(1) The incidence of PGD in AL HT relative to standard list (SL) HT has not been evaluated, and may contribute to the greater mortality associated with AL HT.(2) The objective of this study was to determine the incidence of and predictors for PGD. METHODS AND RESULTS: A retrospective analysis was performed on 260 consecutive adult patients undergoing either SL HT (n=207) or AL HT (n=53) at our institution from 1/2000 to 1/2005. PGD was defined by requirement for mechanical circulatory support immediately post-HT or more broadly as the need for either mechanical support or high-dose inotrope (epinephrine > or = 0.07 microg/kg/min). Donor hearts allocated to AL recipients were turned down for SL HT for reasons that included coronary disease, left ventricular dysfunction or hypertrophy, and high-dose inotropic requirement. AL HT recipients were significantly older, with a higher proportion of diabetes mellitus and ischemic cardiomyopathy. Both groups experienced a similar incidence of significant rejection, but overall mortality was higher in the AL HT group. (2) The incidence of PGD did not differ between AL and SL HT recipients. Pre-transplant VAD and prolonged total ischemic times (> or = 4.5 hours) were independent predictors of PGD. CONCLUSIONS: Select marginal donor hearts used in AL HT do not have an increased incidence of PGD. Pre-transplant VAD and prolonged ischemic times are more important determinants of PGD. These data support continued aggressive utilization of marginal donor hearts in AL HT.

Wound Morbidity in Minimally Invasive Anterior Component Separation Compared to Transversus Abdominis Release.

BACKGROUND: Transversus abdominis release is a novel approach for myofascial advancement in ventral hernia repair and has been hypothesized to have lower rates of wound complication than anterior component separation. METHODS: Patients who had a ventral hernia repair with either transversus abdominis release or minimally invasive anterior component separation from January of 2010 to January of 2016 were enrolled in this retrospective cohort study. Patient characteristics were collected through chart review. Primary outcomes were operative time and wound complications. Multiple linear/Poisson regression and Fisher's exact test were used to determine statistical significance. RESULTS: Of 142 patients analyzed, 75 subjects underwent Butler minimally invasive anterior component separation and 67 underwent transversus abdominis release. There were no differences in baseline characteristics between groups, except that the anterior component separation group had more immunosuppressed patients (35 percent versus 19 percent). Median operative time for anterior component separation was 6.3 hours versus 6.1 hours for transversus abdominis release (p = 0.6). Overall wound complications did not differ between the groups (p = 0.5). Compared with anterior component separation, transversus abdominis release had a similar incidence of seroma/hematoma (relative risk, 0.9; 95 percent CI, 0.5 to 1.7), wound infection (relative risk, 1.1; 95 percent CI, 0.5 to 2.2), and mesh infection (relative risk, 0.7; 95 percent CI, 0.2 to 3.4). Hernia recurrence was 12 percent for anterior component separation and 6 percent for transversus abdominis release (relative risk, 0.6; 95 percent CI, 0.2 to 1.7). Reoperation was required in 19 percent of anterior component separation and 12 percent of transversus abdominis release subjects (relative risk, 0.5; 95 percent CI, 0.2 to 1.2). CONCLUSIONS: Transversus abdominis release patients had similar operative times, wound complications, reoperations, and hernia recurrences compared with Butler minimally invasive anterior component separation patients. This contemporary comparison helps inform operative decisions for reconstructive surgeons. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Effects of decreased preoperative endotoxin core antibody levels on long-term mortality after coronary artery bypass graft surgery.

HYPOTHESIS: Decreased preoperative levels of antiendotoxin core antibody (EndoCAb) in patients undergoing cardiac surgery with cardiopulmonary bypass are associated with increased long-term mortality. DESIGN: Observational study. SETTING: Academic medical center. PATIENTS: A total of 474 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. INTERVENTIONS: Preoperative serum IgM EndoCAb levels were determined, and established preoperative risk factors were assessed. Patients were assigned a risk score using a validated method. MAIN OUTCOME MEASURES: The primary end point was mortality. Statistical analysis used the Cox proportional hazards regression model with log EndoCAb as the predictor of interest and Parsonnet additive risk score as a covariate. Kaplan-Meier survival curves were generated to visually compare groups with high vs low EndoCAb levels. RESULTS: Forty-six deaths occurred in 5 years. Annual follow-up rates during the 5 years were 100%, 94%, 93%, 98%, and 98% for the 1-, 2-, 3-, 4-, and 5-year periods, respectively. Parsonnet additive risk score (hazard ratio, 1.07; 95% confidence interval [CI], 1.04-1.11; P < .001) and log EndoCAb (hazard ratio, 0.73; 95% CI, 0.53-0.99; P = .04) were independent predictors of long-term mortality in the final model. Kaplan-Meier analysis revealed that the preoperative EndoCAb level was significantly associated with mortality up to 5 years (P = .01 by log-rank test). CONCLUSION: Lower preoperative serum EndoCAb level is a significant predictor of long-term mortality independent of other known risk factors.

Laparoscopic paraesophageal hernia repair: defining long-term clinical and anatomic outcomes.

OBJECTIVE: We recently reported in a multi-institutional, randomized study of laparoscopic paraesophageal hernia repair (LPEHR) that the anatomic recurrence rate at a median of approximately 5 years was >50%. This study focuses exclusively on the symptomatic response to LPEHR and its relationship with the development of a recurrent hernia. METHODS: During 2002 to 2005, 108 patients underwent LPHER with or without biologic mesh. A standardized symptom severity questionnaire, SF-36 health survey, and upper gastrointestinal series were performed at baseline, 6 months, and during 2008-2009. RESULTS: Of 108 patients, 72 (average age of 68 ± 10 years) underwent clinical assessment, and 60 of them also had radiologic studies at a median follow-up of 58 (40-78) months. Radiographic recurrence (≥ 20 mm) was 14% at 6 months and 57% at the time of follow-up, and the average recurrence size was 40 ± 10 mm. All symptoms were significantly improved at long-term follow-up and, with the exception of heartburn, were unaffected by the presence or size of the recurrence. Two patients (3%) with recurrent symptoms related to their hernia underwent reoperation. CONCLUSION: Despite frequent radiologic recurrences after LPEHR, symptoms remain well controlled, patient satisfaction is high, and the need for reoperation is low.

Does method of sternal repair influence long-term outcome of postoperative mediastinitis?

BACKGROUND: Post-sternotomy mediastinitis reduces survival after cardiac surgery, potentially further affected by details of mediastinal vascularized flap reconstruction. The aim of this study was to evaluate survival after different methods for sternal reconstruction in mediastinitis. METHODS: Two hundred twenty-two adult cardiac surgery patients with post-sternotomy mediastinitis were reviewed. After controlling infection, often augmented by negative pressure therapy, muscle flap, omental flap, or secondary closure was performed. Outcomes were reviewed and survival analysis was performed. RESULTS: Baseline characteristics were similar. In-hospital mortality (15.7%) did not differ between groups. Secondary closure was correlated with negative pressure therapy and reduced length hospital of stay. Recurrent wound complications were more common with muscle flap repair. Survival was unaffected by sternal repair technique. By multivariate analysis, heart failure, sepsis, age, and vascular disease independently predicted mortality, while negative pressure therapy was associated with survival. CONCLUSIONS: Choice of sternal repair was unrelated to survival, but mediastinal treatment with negative pressure therapy promotes favorable early and late outcomes.

Revisional surgery after Heller myotomy for esophageal achalasia.

Revisional surgery for persistent or recurrent dysphagia following Heller myotomy is rare and should become even more rare if an extended myotomy has been carried out. It is important to work-up patients who experience persistent or recurrent dysphagia in a systematic fashion that includes the determination of the diagnosis of achalasia, the type of operation performed, the results obtained with the primary operation, and to further classify the type of recurrence. Use of adjunctive studies, including upper gastrointestinal study, endoscopy, manometry, and pH monitoring is critical to guiding clinical decision making. This article will review the differential diagnosis, diagnostic workup, and available treatment options for patients with achalasia who present with persistent or recurrent dysphagia following Heller myotomy.

Modified ultrafiltration attenuates pulmonary-derived inflammatory mediators in response to cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) stimulates systemic and pulmonary inflammation. Modified ultrafiltration (MUF) mitigates deleterious CPB effects by unclear mechanisms. We evaluated pulmonary inflammation in piglets undergoing CPB followed by MUF. Twenty-four piglets underwent 60 min of hypothermic CPB. MUF subjects (n=12) underwent hemoconcentration postCPB to the target hematocrit. Pulmonary vascular resistance (PVR), proinflammatory cytokine concentrations, and transpulmonary thromboxane gradients were determined at baseline, following CPB, and at end of the study (EOS) in MUF and control (n=12) groups. PVR significantly increased postCPB in both groups but decreased after MUF. MUF and control groups were similar in regards to systemic cytokine concentrations. Bronchoalveolar lavage concentrations of IL-6 and IL-8 significantly increased in controls throughout the study. Alveolar IL-6 and IL-8 were unchanged at EOS in MUF subjects, and IL-6 concentrations were significantly less than controls at EOS (P=0.015). Similarly, transpulmonary thromboxane gradient was significantly less at EOS in MUF subjects compared with controls (P=0.04). MUF removed circulating inflammatory mediators, lessened pulmonary hypertension, and reduced pulmonary-derived inflammatory markers, providing further evidence that MUF ameliorates pulmonary-based inflammation. These findings lend insight into mechanisms behind salutary clinical benefits of MUF after CPB.

Impact of oropharyngeal dysphagia on long-term outcomes of lung transplantation.

BACKGROUND: Lung transplantation, definitive therapy for end-stage lung disease, is limited long-term by allograft dysfunction including bronchiolitis obliterans syndrome (BOS). Few modifiable risk factors for pulmonary transplant-related mortality are recognized. However, oropharyngeal dysphagia frequently occurs after thoracic surgical procedures, including lung transplantation, and increases morbidity. We evaluated the impact of oropharyngeal dysphagia on survival and BOS after lung transplantation. METHODS: A total of 263 consecutive lung transplant patients were reviewed. Each underwent clinical swallowing evaluation early after surgery; 149 patients underwent additional fiberoptic or videofluoroscopic swallowing evaluation (SE). Results of SE were correlated with BOS, defined by accepted criteria, and mortality using Kaplan-Meier survival curves. Cox proportional hazard modeling assessed preoperative and postoperative variables associated with development of BOS and mortality. RESULTS: Mean follow-up was 920 ± 560 days. The SE identified tracheal aspiration and (or) laryngeal penetration in 70.5%. Preoperative tobacco abuse, gastroesophageal reflux, and cardiopulmonary bypass independently predicted oropharyngeal dysphagia. Peak FEV(1) (forced expiratory volume in the first second of expiration) alone independently predicted BOS (hazard ratio 0.98; confidence interval 0.975 to 0.992, p < 0.0001); oropharyngeal dysphagia was not associated with BOS. Independent predictors of mortality by multivariable analysis were ventilator dependence (p = 0.038) and peak FEV(1) (p < 0.0001); normal SE was associated with improved survival (hazard ratio 0.13; confidence interval 0.03 to 0.54, p = 0.03). CONCLUSIONS: Oropharyngeal dysphagia, often overlooked on clinical examination, is common after lung transplantation. Normal deglutition may improve survival after lung transplantation, but oropharyngeal dysphagia does not independently affect BOS. Institution of protocols aimed at identifying previously unrecognized dysphagia may improve results of pulmonary transplantation.

Thoracoscopic lobectomy is associated with lower morbidity compared with thoracotomy.

OBJECTIVES: Advantages of thoracoscopic lobectomy include less postoperative pain, shorter hospitalization, and improved delivery of adjuvant chemotherapy. The incidence of postoperative complications has not been thoroughly assessed. This study analyzes morbidity after lobectomy to compare the thoracoscopic approach and thoracotomy. METHODS: By using a prospective database, the outcomes of patients who underwent lobectomy from 1999-2009 were analyzed with respect to postoperative complications. Propensity-matched groups were analyzed based on preoperative variables and stage. RESULTS: Of the 1079 patients in the study, 697 underwent thoracoscopic lobectomy, and 382 underwent lobectomy by means of thoracotomy. In the overall analysis thoracoscopic lobectomy was associated with a lower incidence of atrial fibrillation (P = .01), atelectasis (P = .0001), prolonged air leak (P = .0004), transfusion (P = .0001), pneumonia (P = .001), sepsis (P = .008), renal failure (P = .003), and death (P = .003). In the propensity-matched analysis based on preoperative variables, when comparing 284 patients in each group, 196 (69%) patients who underwent thoracoscopic lobectomy had no complications versus 144 (51%) patients who underwent thoracotomy (P = .0001). In addition, thoracoscopic lobectomy was associated with a lower incidence of atrial fibrillation (13% vs 21%, P = .01), less atelectasis (5% vs 12%, P = .006), fewer prolonged air leaks (13% vs 19%, P = .05), fewer transfusions (4% vs 13%, P = .002), less pneumonia (5% vs 10%, P = .05), less renal failure (1.4% vs 5%, P = .02), shorter chest tube duration (median of 3 vs 4 days, P < .0001), and shorter length of hospital stay (median of 4 vs 5 days, P < .0001). CONCLUSIONS: Thoracoscopic lobectomy is associated with a lower incidence of major complications, including atrial fibrillation, compared with lobectomy by means of thoracotomy. The underlying factors responsible for this advantage should be analyzed to improve the safety and outcomes of other thoracic procedures.

Prognostic factors for recurrence after pulmonary resection of colorectal cancer metastases.

BACKGROUND: This study was undertaken to review a large series of resections of colorectal pulmonary metastases in the era of modern chemotherapy. METHODS: A retrospective chart review of prospectively maintained thoracic surgery databases identified 378 patients who underwent pulmonary resection for colorectal cancer metastases with curative intent from 1998 to 2007. RESULTS: The primary site of disease was rectum (52%), left colon (26%), right colon (16%), and unknown (6%). Before thoracic recurrence, 166 patients (44%) had previously undergone resection of extrathoracic metastases. Median disease-free interval (DFI) was 24 months from the time of the primary operation. The number of metastatic deposits resected was one in 60%, two in 20%, three in 10%, and four or more in 10%. Chemotherapy was administered to 87 patients (23%) before resection and to 169 patients (45%) after resection. Three-year recurrence-free survival was 28%, and 3-year overall survival was 78%. Multivariable analysis revealed age younger than 65 years, female sex, DFI less than 1 year, and number of metastases greater than three as independent predictors of recurrence. Of 44 patients with three or more lesions and less than 1 year DFI, none was cured by operation. By contrast, recurrence-free survival was 49% at 3 years for those with one lesion and DFI greater than 1 year. CONCLUSIONS: Age younger than 65 years, female sex, DFI less than 1 year, and number of metastases greater than three predict recurrence. Medical management alone should be considered standard for patients who have both three or more pulmonary metastases and less than 1 year DFI.

A multi-institutional experience of isolated limb infusion: defining response and toxicity in the US.

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive approach for treating in-transit extremity melanoma, with only two US single-center studies reported. Establishing response and toxicity to ILI as compared with hyperthermic isolated limb perfusion is important for optimizing future regional chemotherapeutic strategies in melanoma. STUDY DESIGN: Patient characteristics and procedural variables were collected retrospectively from 162 ILIs performed at 8 institutions (2001 to 2008) and compared using chi-square and Student's t-test. ILIs were performed for 30 minutes in patients with in-transit melanoma. Melphalan dose was corrected for ideal body weight (IBW) in 42% (n = 68) of procedures. Response was determined at 3 months by Response Evaluation Criteria in Solid Tumors; toxicity was assessed using the Wieberdink Limb Toxicity Scale. RESULTS: In 128 evaluable patients, complete response rate was 31%, partial response rate was 33%, and there was no response in 36% of patients. For all patients (n = 162), 36% had Wieberdink toxicity grade >or=3 with one toxicity-related amputation. On multivariate analysis, smaller limb volumes were associated with better overall response (p = 0.021). Use of papaverine in the circuit to achieve cutaneous vasodilation was associated with better response (p < 0.001) but higher risk of grade >or=3 toxicity (p = 0.001). Correction of melphalan dose for ideal body weight did not alter complete response (p = 0.345), but did lead to marked reduction in toxicity (p < 0.001). CONCLUSIONS: In the first multi-institutional analysis of ILI, a complete response rate of 31% was achieved with acceptable toxicity demonstrating this procedure to be a reasonable alternative to hyperthermic isolated limb perfusion in the management of advanced extremity melanoma.

Infectious complications in extended criteria heart transplantation.

BACKGROUND: We have previously shown that extended criteria heart transplant recipient mortality is higher than standard list mortality, but this is not associated with an increased incidence of either primary graft dysfunction or acute rejection. We hypothesized that other adverse outcomes, principally determined by recipient characteristics, occur at a higher rate in extended criteria recipients. METHODS: A retrospective review of adult heart transplant recipients was conducted at Duke University Medical Center between January 2000 and July 2007. Infectious complications considered risk factors for recipient mortality were identified. In addition, the incidence of these complications was compared between standard and alternate list recipients. RESULTS: Infectious complications, including pneumonia, bacteremia and sepsis, were significant predictors of overall mortality (pneumonia hazard ratio 4.2 [95% CI 2.5 to 7.0], bacteremia hazard ratio 3.0 [95% CI 1.9 to 4.9], sepsis hazard ratio 6.0 [95% CI 3.6 to 10.2]). In addition, pneumonia occurred at a significantly higher rate in extended criteria (EC) than in standard list (SL) patients (27% vs 13%, p = 0.005), and bacteremia and sepsis demonstrated a trend toward higher occurrence in EC patients (36% vs 25%, p = 0.076, and 15% vs 8%, p = 0.114, respectively). In contrast, severe acute cellular rejection (ISHLT Grade >/=3A) was not a predictor of mortality, and had a similar incidence in both groups. Finally, although overall survival among patients in the SL group was not influenced by the occurrence of a major infectious complication, survival in the extended criteria group was significantly impacted by major infectious complications (p < 0.001). CONCLUSIONS: Infectious complications may account for decreased survival in extended criteria heart transplant recipients.