Safe Use of Erythromycin For Refractory Gastroparesis After Small Bowel Transplantation.

Current therapeutic options with prokinetic agents for posttransplant gastroparesis are limited. Erythromycin is associated with adverse reactions, including corrected QT interval prolongation and cytochrome P450 3A4 isoenzyme inhibition. The use of erythromycin has been avoided in patients undergoing treatment with cyclosporine or tacrolimus because of significant fluctuations in therapeutic immunosuppression levels. We report herein the successful use of erythromycin after visceral transplant to treat delayed gastric emptying. Two patients were managed with oral erythromycin (initial dose of 750 mg/d divided into 3 doses) for gastroparesis after visceral transplant. Patient 1 was a woman aged 42 years with a history of chronic intestinal pseudo-obstruction syndrome who underwent isolated small bowel transplant with dual (gastric and duodenal) proximal allograft anastomosis. Posttransplant gastroparesis was initially managed with oral metoclopramide. The patient also required high doses of tacrolimus (36 mg/d) to maintain adequate immunosuppression levels. The decision was made to change metoclopramide to erythromycin, which significantly decreased the daily tacrolimus dose requirement (from 36 to 9 mg/d), with resolution of nausea and intermittent bloating symptoms. Patient 2 was a woman aged 35 years with ultra-short gut syndrome after extensive enterectomy due to intestinal volvulus who underwent uneventful combined intestinal and colon transplant. Conventional pharmacologic therapy for gastroparesis was initiated after surgery without success. Erythromycin was started 15 days posttransplant, with significant improvement in her symptoms, and discontinued 47 days post-transplant. To maintain therapeutic levels (8-10 mg/dL), daily tacrolimus dose was decreased 75.8% and 36.5% for patients 1 and 2, respectively. No significant side effects associated with erythromycin use were observed in either patient. Our findings here suggest that erythromycin may be safely used for gastroparesis after small bowel transplant. Close monitoring of immunosuppressive drug levels and dose adjustments of other medications affected by inhibition of cytochrome P450 3A4 are advised.

Surgical and medical approach to patients requiring total small bowel resection: Managing the "no gut syndrome".

BACKGROUND: Total resection of the jejunum and ileum, a rarely performed procedure, is indicated after mesenteric vascular events, trauma, or resection of abdominal neoplasms. We describe our recent experience with the operative and medical management of patients with "no gut syndrome." METHODS: We retrospectively reviewed 341 adult patients who were referred to our center between January 2013 and December 2016. RESULTS: Thirteen patients with a mean age of 42.5 years (range 17 to 66 years) underwent near total enterectomy. Indications for small bowel resection were vascular event (n = 5), intraabdominal fibroid/desmoid (n = 4), and trauma (n = 4). Foregut secretions were managed with duodenocolostomy (n = 5), tube decompression (n = 5), and end duodenostomy (n = 2). Duodenal stump was stapled off in 4 cases. One patient underwent a spleen-preserving duodenopancreatectomy combined with total enterectomy. Biliary secretions were managed with choledochocolostomy. All patients were discharged on full total parenteral nutrition infused over a 10- to 16-hour period. Average total parenteral nutrition volume and caloric requirement were 2,800 mL/day (range 2,000 to 4,000) and 1,774 Kcal/day (range 1,443 to 2,290), respectively. Patients who underwent duodenocolonic anastomosis received smaller TPN volume (33.8 vs 49.8 mL/kg). Ten patients (77%) required supplemental intravenous fluid. There were no intraoperative or perioperative deaths. One patient was lost to follow-up 2 months after operation. After a 20-month median follow-up (range 4 to 48 months), 9 patients are still alive (75%). All patients with duodenocolostomy remain alive (median follow-up 36.4 months). Three patients underwent uneventful isolated small bowel transplantation, and another 4 are being evaluated or are already listed for visceral transplantation. CONCLUSION: In summary, resection of the entire small bowel is feasible and can be a lifesaving procedure for a select group of patients. Long-term survival can be achieved in specialized centers. In addition, reestablishment of gastrointestinal tract continuity after total enterectomy appears to be the best option for postoperative fluid and electrolyte management.

Are There Gaps in Current Thoracic Surgery Residency Training Programs?

BACKGROUND: Cardiothoracic surgery is rapidly evolving to adapt to a changing health care environment and a wider application of innovative techniques. The Society of Thoracic Surgeons Workforce on Thoracic Surgery Resident Issues Transition to Practice Task Force sought to identify new or existing gaps of training in contemporary thoracic surgery residency training programs. METHODS: A voluntary survey consisting of 24 questions was distributed to recent graduates of thoracic surgery residency programs in the United States during the 2014 American Board of Thoracic Surgery oral examination application process. Fifty-five of 132 applicants anonymously participated. RESULTS: The majority of respondents admitted that they needed more instruction or lacked confidence with the following specific cardiothoracic procedures: minimally invasive cardiac operations (25/52, 48%), robotic cardiac operations (29/52, 55.8%), endovascular operations (28/52, 53.8%), robotic pulmonary operations (29/52, 55.8%), minimally invasive esophageal operations (24/52, 46.2%), robotic esophageal operations (32/52, 61.5%), and operations on congenital cardiac conditions (31/52, 59.6%). The respondents further declared either a need for more instruction or lack of confidence in employment contracting (17/21, 81.0%), negotiating terms of employment (17/21, 81.0%), and professional service agreements (16/21, 76.2%). CONCLUSIONS: Further exposure to minimally invasive robotic procedures, operations on congenital conditions, and issues of practice management appear to be needed in contemporary cardiothoracic training in the United States. These identified gaps may assist cardiothoracic surgery residency programs to optimally prepare future graduates for our evolving specialty.

Understanding Why Residents May Inaccurately Log Their Role in Operations: A Look at the 2013 In-Training Examination Survey.

BACKGROUND: With increased time and quality pressures, it may be more difficult for residents in cardiothoracic surgery residency programs to get independent operative experience. That may lead residents to inaccurately report their role as "surgeon" to meet American Board of Thoracic Surgery (ABTS) case requirements. METHODS: The 2013 In-Training Examination surveyed 312 cardiothoracic surgery residents and was used to contrast residents in traditional 2-year and 3-year cardiothoracic surgery residencies (traditional, n = 216) with those in 6-year integrated or 3+4-year programs (integrated, n = 96). RESULTS: Traditional program residents reported a higher percentage of cases that met the ABTS criteria of surgeon than did integrated program residents (p = 0.05) but were less likely to meet requirements if all cases were logged accurately (p = 0.03). The majority of residents in each program believed that their case log accurately reflected their experience as "surgeon." Residents who tended to log cases incorrectly had lower self-reported 2012 In-Training Examination percentiles, were less likely to meet case requirements if logged properly, and felt less prepared for board examinations and eventual practice compared with residents who logged cases correctly (all p < 0.001). Residents who believed they would not meet case requirements if logged correctly cited limited surgical opportunities, poor case diversity, and a compromised training environment but not the 80-hour work week, excessive simulation, or disproportionate number of complex cases as causes. CONCLUSIONS: Overall cardiothoracic surgery residents appear to be satisfied with their training. There were specific subsets of trainees in both traditional and Integrated programs that are misrepresenting their role on cases because they otherwise may not meet the requirements.

Resident Perception of Technical Skills Education and Preparation for Independent Practice.

BACKGROUND: Surgical skills are traditionally taught and practiced in the operating room. However, changes in health care policy and outcome-based evaluation have decreased trainee operative autonomy. We examined cardiothoracic residents' perceptions of operative experience and the role of simulation. METHODS: The In-Training Examination (ITE) is taken each year by all residents. Completion of a 30-question preexamination survey is mandatory, ensuring a 100% response rate. Survey data related to operative experience, career preparedness, and surgical simulation were analyzed. Opinion questions were asked on a 5-point Likert scale. Respondents were grouped into three cohorts by training paradigm (2-year versus 3-year traditional programs and 6-year integrated programs). RESULTS: In all, 314 respondents (122 2-year, 96 3-year, and 96 6-year integrated) completed the survey. Of the three groups, residents in 3-year programs had the highest levels of satisfaction. Advanced training was most common among residents in 6-year integrated programs (66%, versus 49% for 2-year and 26% for 3-year programs; p = 0.63). Desire to specialize drove further training (97%), with 2% stating further training was needed owing to inadequacy and 1% owing to a poor job market. In all assessed categories, the majority of residents believed that simulation did not completely replicate the educational value of an operative case. CONCLUSIONS: Cardiothoracic residents largely feel well prepared for the transition to practice under the current educational paradigm. Although many residents seek advanced training, it seems driven by the desire for specialization. Residents view simulation as an adjunct to traditional intraoperative education, but not as a viable replacement. Further study is necessary to better understand how best to integrate simulation with operative experience.

A Decade of Change: Training and Career Paths of Cardiothoracic Surgery Residents 2003 to 2014.

BACKGROUND: During the past decade, cardiothoracic surgery (CTS) education has undergone tremendous change with the advent of new technologies and the implementation of integrated programs, to name a few. The goal of this study was to assess how residents' career paths, training, and perceptions changed during this period. METHODS: The 2006 to 2014 surveys accompanying the Thoracic Surgery Residents Association/Thoracic Surgery Directors' Association in-training examination taken by CTS residents were analyzed, along with a 2003 survey of graduating CTS residents. Of 2,563 residents surveyed, 2,434 (95%) responded. RESULTS: During the decade, fewer residents were interested in mixed adult cardiac/thoracic practice (20% in 2014 vs 52% in 2003, p = 0.004), more planned on additional training (10% in 2003 vs 41% to 47% from 2011 to 2014), and the frequent use of simulation increased from 1% in 2009 to 24% in 2012 (p < 0.001). More residents recommended CTS to potential trainees (79% in 2014 vs 65% in 2010, p = 0.007). Job offers increased from a low of 12% in 2008 with three or more offers to 34% in 2014. Debt increased from 0% with more than $200,000 in 2003 to 40% in 2013 (p < 0.001). Compared with residents in traditional programs, more integrated residents in 2014 were interested in adult cardiac surgery (53% vs 31%) and congenital surgery (22% vs 7%), fewer were interested in general thoracic surgery (5% vs 31%, p < 0.001), and more planned on additional training (66% vs 36%, p < 0.001). CONCLUSIONS: With the evolution in CTS over the last decade, residents' training and career paths have changed substantially, with increased specialization and simulation accompanied by increased resident satisfaction and an improved job market.

Predictors of Career Choice Among Cardiothoracic Surgery Trainees.

BACKGROUND: The impact of factors influencing career choice by cardiothoracic surgery (CTS) trainees remains poorly defined in the modern era. We sought to examine the associations between CTS trainee characteristics and future career aspirations. METHODS: The 2012 Thoracic Surgery In-Training Examination survey results were used to categorize responders according to career interest: congenital, adult cardiac, mixed cardiac/thoracic, and general thoracic surgery. Univariate and multivariable analyses were used to identify and analyze characteristics associated with career interest categories. RESULTS: With a 100% response rate, 300 responses from trainees in programs accredited by the Accreditation Council for Graduate Medical Education were included in the analysis. Multinomial logistic regression identified three factors associated with career choice in CTS: level of training (p < 0.001), type of training pathway (p < 0.001), and primary motivating factor to pursue CTS (p = 0.002). Trainees interested in general thoracic surgery were more likely to commit to CTS during their senior years of general surgery training and were more likely to enroll in 2-year or 3-year traditional fellowships, whereas individuals pursuing adult or congenital cardiac surgery were more likely to commit earlier during training and were more commonly interested in 6-year integrated or joint training pathways. Moreover, trainees interested in general thoracic surgery were predominantly influenced by early mentorship (p = 0.025 vs adult cardiac), and trainees interested in adult cardiac surgery were more likely to be influenced by types of operations (p = 0.047 vs general thoracic). CONCLUSIONS: Career choice in CTS appears strongly associated with level of training, exposure to mentors, and training paradigm. These results demonstrate the importance of maintaining all four currently approved training pathways to retain balance and diversity in future CTS practices.

Resident Perceptions of 2-Year Versus 3-Year Cardiothoracic Training Programs.

BACKGROUND: Resident perceptions of 2-year (2Y) vs 3-year (3Y) programs have never been characterized. The objective was to use the mandatory Thoracic Surgery Residents Association and Thoracic Surgery Directors Association In-Training Examination survey to compare perceptions of residents graduating from 2Y vs 3Y cardiothoracic programs. METHODS: Each year Accreditation Council for Graduate Medical Education cardiothoracic residents are required to take a 30-question survey designed by the Thoracic Surgery Residents Association and the Thoracic Surgery Directors Association accompanying the In-Training Examination with a 100% response rate. The 2013 and 2014 survey responses of residents graduating from 2Y vs 3Y training programs were compared. The Wilcoxon signed rank test was used to analyze ordinal and interval data. RESULTS: Graduating residents completed 167 surveys, including 96 from 2Y (56%) and 71 from 3Y (43%) programs. There was no difference in the perception of being prepared for the American Board of Thoracic Surgery examinations or amount of debt between 2Y and 3Y respondents. There was no difference in intended academic vs private practice. Graduating 3Y residents felt more prepared to meet case requirements and better trained, were more likely to pass their written American Board of Thoracic Surgery examinations, and were less likely to pursue additional training beyond their cardiothoracic residency. CONCLUSIONS: There was no difference in field of interest, practice type, and amount of debt between graduating 2Y vs 3Y residents. Respondents from 2Y programs expressed more difficulty in meeting case requirements, whereas residents from 3Y programs felt more prepared for independent practice and had higher American Board of Thoracic Surgery written pass rates.

Ventricular arrhythmia after cardiac surgery: incidence, predictors, and outcomes.

OBJECTIVES: This study sought to investigate the prevalence, predictors, and outcomes of patients with post-operative ventricular arrhythmia (POVA) in a large cohort of patients. BACKGROUND: New-onset POVA after cardiac surgery (CS) is uncommon and has controversial prognostic value. METHODS: A total of 14,720 consecutive patients undergoing CS at Emory University between January 2004 and July 2010 were included in the study. Data on all-cause mortality were obtained from Social Security Administration death records. Multivariable regression models were constructed to determine the risk factors for POVA and to estimate the independent impact of POVA on long-term survival after adjusting for 40 different covariates. RESULTS: POVA occurred in 248 patients (1.7%). Patients with POVA were older (63.5 vs. 61.6 years), had lower left ventricular ejection fraction (EF) (43.7 vs. 51.3), and had greater comorbidities (Society of Thoracic Surgeons mortality risk score of 7.2% vs. 3.1%, p < 0.001). Multivariable analysis showed that older age (odds ratio [OR]: 1.018 per 1-year increase, p < 0.001), emergent surgery (OR: 1.77, p = 0.019), and the presence of PVD (OR: 1.41, p = 0.049) were associated with a higher incidence of POVA, whereas higher left ventricular EF (OR: 0.97 per 1% increase, p < 0.001), mild chronic obstructive pulmonary disease (OR: 0.37, p < 0.001), and off-pump surgery (OR: O.41, p < 0.001) were associated with a lower incidence of POVA. POVA was associated with substantially increased adjusted long-term mortality (hazard rate: 2.53, p < 0.001) over 3.5 years of follow-up. CONCLUSIONS: POVA is associated with increased long-term mortality after CS. Older age, PVD, lower EF, and emergent surgery are associated with a higher risk of POVA, whereas off-pump surgery seems to be protective.

Modified "liver-sparing" multivisceral transplant with preserved native spleen, pancreas, and duodenum: technique and long-term outcome.

BACKGROUND: Modification of the originally described multivisceral transplant operation was introduced at our institution 17 years ago. Donor liver was spared, and native spleen along with pancreaticoduodenal complex was preserved. METHODS: Thirty-six modified multivisceral grafts that include stomach, duodenum, pancreas, and intestine were given to 30 adults and six children. Leading causes of intestinal failure were pseudo-obstruction and Gardner's syndrome. Native spleen was preserved in 24 (67%) recipients along with pancreaticoduodenal complex in 18 (50%). Immunosuppression was tacrolimus-based, and recipient preconditioning was utilized in 80% of patients. RESULTS: Patient survival was 94% at 1 year and 75% at 5 years with graft survival of 91% and 51%; respectively. With mean follow-up of 51 ± 35 months, full nutritional autonomy was achieved in 89% of current survivors with no single example of disease recurrence. Preservation of native spleen was associated with increased survival and reduced risk of PTLD, life-threatening infections, and GVHD with no significant impact on graft loss due to rejection. Concomitant preservation of pancreaticoduodenal complex eliminated risks of biliary complications and glucose intolerance. CONCLUSION: Modified multivisceral transplantation with and without preservation of native spleen, pancreas, and duodenum is a valid therapeutic option for patients with diffuse gastrointestinal disorders and preserved hepatic functions.

Timing of bone marrow cell delivery has minimal effects on cell viability and cardiac recovery after myocardial infarction.

BACKGROUND: Despite ongoing clinical trials, the optimal time for delivery of bone marrow mononuclear cells (BMCs) after myocardial infarction is unclear. We compared the viability and effects of transplanted BMCs on cardiac function in the acute and subacute inflammatory phases of myocardial infarction. METHODS AND RESULTS: The time course of acute inflammatory cell infiltration was quantified by FACS analysis of enzymatically digested hearts of FVB mice (n=12) after left anterior descending artery ligation. Mac-1(+)Gr-1(high) neutrophil infiltration peaked at day 4. BMCs were harvested from transgenic FVB mice expressing firefly luciferase (Fluc) and green fluorescent protein (GFP). Afterward, 2.5x10(6) BMCs were injected into the left ventricle of wild-type FVB mice either immediately (acute BMC) or 7 days (subacute BMC) after myocardial infarction, or after a sham procedure (n=8 per group). In vivo bioluminescence imaging showed an early signal increase in both BMC groups at day 7, followed by a nonsignificant trend (P=0.203) toward improved BMC survival in the subacute BMC group that persisted until the bioluminescence imaging signal reached BACKGROUND: <0.01) and 6 weeks (both BMC groups versus saline; P<0.05) but no significant differences between the 2 BMC groups. FACS analysis of BMC-injected hearts at day 7 revealed that GFP(+) BMCs expressed hematopoietic (CD45, Mac-1, Gr-1), minimal progenitor (Sca-1, c-kit), and no endothelial (CD133, Flk-1) or cardiac (Trop-T) cell markers. CONCLUSIONS: Timing of BMC delivery has minimal effects on intramyocardial retention and preservation of cardiac function. In general, there is poor long-term engraftment and BMCs tend to adopt inflammatory cell phenotypes.

Poor functional recovery after transplantation of diabetic bone marrow stem cells in ischemic myocardium.

BACKGROUND: Autologous bone marrow mononuclear cell (BMMC) therapy has shown promise for improving cardiac function after myocardial infarction. The efficiency of such therapy for diabetic patients remains unknown. METHODS: BMMCs were harvested from type 2 diabetic male BKS.Cg-m+/+Lepr(db)/J mice or C57BLKS/J (non-diabetic control) mice and were isolated using Ficoll-based separation. Cell characterization was performed by flow cytometry. Cell viability was determined by apoptosis and proliferation assays. Female BKS.Cg-m+/+Lepr(db)/J mice underwent left anterior descending artery ligation and were randomized into 3 groups receiving 2.5 x 10(6) diabetic BMMCs (n = 8), 2.5 x 10(6) control BMMCs (n = 8), or phosphate-buffered saline (n = 6). At Week 5, cardiac function was assessed with echocardiography and invasive hemodynamic measurements. Post-mortem cell survival was quantified by TaqMan real-time transcription polymerase chain reaction (RT-PCR) for the male Sry gene. RESULTS: BKS.Cg-m+/+Lepr(db)/J BMMCs showed a significantly lower mononuclear fraction and a significantly lower proliferation rate compared with C57BLKS/J BMMCs. Fractional shorting (40.1% +/- 1.2% vs 30.3% +/- 1.9%; p = 0.001) and cardiac output (4,166 +/- 393 vs 2,246 +/- 462 microl/min; p = 0.016) significantly improved for mice treated with control BMMCs injection compared with those treated with diabetic BMMCs, respectively. This difference could not be attributed to difference in cell engraftment because TaqMan RT-PCR showed no significant difference in cell survival in infarcted hearts between the 2 groups. CONCLUSIONS: Diabetic BMMCs are significantly impaired in their ability to improve cardiac function after myocardial infarction compared with control BMMCs. These findings could have significant clinical implication regarding autologous BMMC therapy in diabetic patients.

Hepatocyte growth factor or vascular endothelial growth factor gene transfer maximizes mesenchymal stem cell-based myocardial salvage after acute myocardial infarction.

BACKGROUND: Mesenchymal stem cell (MSC)-based regenerative strategies were investigated to treat acute myocardial infarction and improve left ventricular function. METHODS AND RESULTS: Murine AMI was induced by coronary ligation with subsequent injection of MSCs, hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), or MSCs +HGF/VEGF into the border zone. Left ventricular ejection fraction was calculated using micro-computed tomography imaging after 6 months. HGF and VEGF protein injection (with or without concomitant MSC injection) significantly and similarly improved the left ventricular ejection fraction and reduced scar size compared with the MSC group, suggesting that myocardial recovery was due to the cytokines rather than myocardial regeneration. To provide sustained paracrine effects, HGF or VEGF overexpressing MSCs were generated (MSC-HGF, MSC-VEGF). MSC-HGF and MSC-VEGF showed significantly increased in vitro proliferation and increased in vivo proliferation within the border zone. Cytokine production correlated with MSC survival. MSC-HGF- and MSC-VEGF-treated animals showed smaller scar sizes, increased peri-infarct vessel densities, and better preserved left ventricular function when compared with MSCs transfected with empty vector. Murine cardiomyocytes were exposed to hypoxic in vitro conditions. The LDH release was reduced, fewer cardiomyocytes were apoptotic, and Akt activity was increased if cardiomyocytes were maintained in conditioned medium obtained from MSC-HGF or MSC-VEGF cultures. CONCLUSIONS: This study showed that (1) elevating the tissue levels of HGF and VEGF after acute myocardial infarction seems to be a promising reparative therapeutic approach, (2) HGF and VEGF are cardioprotective by increasing the tolerance of cardiomyocytes to ischemia, reducing cardiomyocyte apoptosis and increasing prosurvival Akt activation, and (3) MSC-HGF and MSC-VEGF are a valuable source for increased cytokine production and maximize the beneficial effect of MSC-based repair strategies.

Imaging gene expression in human mesenchymal stem cells: from small to large animals.

PURPOSE: To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning. MATERIALS AND METHODS: Animal protocols were approved by the Institutional Administrative Panel on Laboratory Animal Care. Transduction of human MSCs by using different doses of adenovirus that contained a cytomegalovirus (CMV) promoter driving the mutant herpes simplex virus type 1 thymidine kinase reporter gene (Ad-CMV-HSV1-sr39tk) was characterized in a cell culture. A total of 2.25 x 10(6) transduced (n = 5) and control nontransduced (n = 5) human MSCs were injected into the myocardium of 10 rats, and reporter gene expression in human MSCs was visualized with micro-PET by using the radiotracer 9-(4-[fluorine 18]-fluoro-3-hydroxymethylbutyl)-guanine (FHBG). Different numbers of transduced human MSCs suspended in either phosphate-buffered saline (PBS) (n = 4) or matrigel (n = 5) were injected into the myocardium of nine swine, and gene expression was visualized with a clinical PET-CT. For analysis of cell culture experiments, linear regression analyses combined with a t test were performed. To test differences in radiotracer uptake between injected and remote myocardium in both rats and swine, one-sided paired Wilcoxon tests were performed. In swine experiments, a linear regression of radiotracer uptake ratio on the number of injected transduced human MSCs was performed. RESULTS: In cell culture, there was a viral dose-dependent increase of gene expression and FHBG accumulation in human MSCs. Human MSC viability was 96.7% (multiplicity of infection, 250). Cardiac FHBG uptake in rats was significantly elevated (P < .0001) after human MSC injection (0.0054% injected dose [ID]/g +/- 0.0007 [standard deviation]) compared with that in the remote myocardium (0.0003% ID/g +/- 0.0001). In swine, myocardial radiotracer uptake was not elevated after injection of up to 100 x 10(6) human MSCs (PBS group). In the matrigel group, signal-to-background ratio increased to 1.87 after injection of 100 x 10(6) human MSCs and positively correlated (R(2) = 0.97, P < .001) with the number of administered human MSCs. CONCLUSION: Reporter gene imaging in human MSCs can be translated to large animals. The study highlights the importance of co-administering a "scaffold" for increasing intramyocardial retention of human MSCs.

Evolution of the immunosuppressive strategies for the intestinal and multivisceral recipients with special reference to allograft immunity and achievement of partial tolerance.

Introduction of new innovative immunosuppressive strategies has been the milestone of the recent evolution of intestinal and multivisceral transplantation. With new insights into the mechanisms of organ engraftment and acquired tolerance, the Pittsburgh tolerogenic protocol was recently introduced and consisted of two main therapeutic principles: recipient pretreatment with lymphoid ablating antibodies and minimal post-transplant immunosuppression with tacrolimus monotherapy. The reported herein improved survival and the striking ability to wean immunosuppression among the intestinal and multivisceral recipients pretreated with a single-dose of Thymoglobulin (rATG) or Campath-1H (alemtuzumab) supports our working hypothesis with successful induction of variable tolerance. It is important, however, that careful monitoring of subtle histologic changes in serial endoscopic-guided mucosal biopsies be carried out for early diagnosis of allograft immune activation with prompt restoration of the baseline immunosuppressive therapy. Future scientific discoveries with better understanding of the mechanisms of immune tolerance and clinical introduction of reliable assays will increase the chance and safety of achieving complete tolerance among the intestinal and other solid organ recipients. This review will focus on the historic evolution of the immunosuppressive and other management strategies utilized for the intestinal and multivisceral recipients at the University of Pittsburgh with special reference to allograft immunity and the successful achievement of partial tolerance.

Right atrial mass after primary repair of an atrial septal defect: thrombus masquerading as a myxoma.

Atrial septal defects are among the most common congenital anomalies requiring surgical repair. Thrombus formation after patch-based repair is a recognized complication, usually manifested by an embolic event. However, thromboembolic complications after primary repair of atrial septal defects are exceedingly rare. We present a 38-year-old woman found to have a right atrial mass diagnosed as a myxoma by echocardiography and magnetic resonance imaging 3 years after primary atrial septal defect repair. However, final pathology revealed an organized thrombus. A review of the literature and clinical management of postoperative atrial thrombi are discussed.

High-resolution fluorodeoxyglucose positron emission tomography with compression ("positron emission mammography") is highly accurate in depicting primary breast cancer.

We sought to prospectively assess the diagnostic performance of a high-resolution positron emission tomography (PET) scanner using mild breast compression (positron emission mammography [PEM]). Data were collected on concomitant medical conditions to assess potential confounding factors. At four centers, 94 consecutive women with known breast cancer or suspicious breast lesions received 18F-fluorodeoxyglucose (FDG) intravenously, followed by PEM scans. Readers were provided clinical histories and x-ray mammograms (when available). After excluding inevaluable cases and two cases of lymphoma, PEM readings were correlated with histopathology for 92 lesions in 77 women: 77 index lesions (42 malignant), 3 ipsilateral lesions (3 malignant), and 12 contralateral lesions (3 malignant). Of 48 cancers, 16 (33%) were clinically evident; 11 (23%) were ductal carcinoma in situ (DCIS), and 37 (77%) were invasive (30 ductal, 4 lobular, and 3 mixed; median size 21 mm). PEM depicted 10 of 11 (91%) DCIS and 33 of 37 (89%) invasive cancers. PEM was positive in 1 of 2 T1a tumors, 4 of 6 T1b tumors, 7 of 7 T1c tumors, and 4 of 4 cases where tumor size was not available (e.g., no surgical follow-up). PEM sensitivity for detecting cancer was 90%, specificity 86%, positive predictive value (PPV) 88%, negative predictive value (NPV) 88%, accuracy 88%, and area under the receiver-operating characteristic curve (Az) 0.918. In three patients, cancer foci were identified only on PEM, significantly changing patient management. Excluding eight diabetic subjects and eight subjects whose lesions were characterized as clearly benign with conventional imaging, PEM sensitivity was 91%, specificity 93%, PPV 95%, NPV 88%, accuracy 92%, and Az 0.949 when interpreted with mammographic and clinical findings. FDG PEM has high diagnostic accuracy for breast lesions, including DCIS.