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BACKGROUND Transplant tolerance would remove the need for maintenance immunosuppression while improving survival and quality of life. METHODS A prospective, randomized pilot study was undertaken to assess the safety and efficacy of donor stem cell infusion (DSCI) in living-related kidney transplant recipients treated with alemtuzumab (C1H) induction and tacrolimus and mycophenolate maintenance with switch to sirolimus and weaning over 2 years. RESULTS Four patients received DSCI; five patients were controls. Graft failure occurred in two patients in the DSCI arm. Recurrence of glomerular disease occurred in two DSCI recipients, leading to graft loss in one. Biopsy-proven acute rejection episodes occurred in three patients (two in the DSCI vs. one in the control). One DSCI patient, with recurrence, subsequently developed antibody-mediated rejection leading to graft failure. In the remaining two DSCI patients, weaning was attempted but was not successful. All (4 of 4) DSCI patients had biopsy-proven chronic allograft injury and/or recurrence. CONCLUSION DSCI with C1H induction and a steroid-free maintenance regimen in a small group of patients failed to induce tolerance, with suboptimal patient and graft survival. The results do not justify extension of this particular trial and underscore the importance of patient selection, specifically avoidance of patients with glomerulopathies whose recurrence may obscure potential benefit.

The impact of machine perfusion (MP) time on kidney transplant outcome is mixed in previous studies using multivariable analyses. In an analysis of 66 pairs of donor-matched adult, first transplant recipients (N = 132) with identical donor characteristics except for pump time, tests of association of shorter versus longer pump time (first versus second kidney removed) by delayed graft function(DGF), slow graft function(SGF), and biopsy proven acute rejection(BPAR) were performed using McNemar's test. Freedom-from-BPAR, graft and patient survival, and renal function were also compared. Mean ± SD pump times for paired recipients with first and second kidneys were 22.7 ± 7.3 h and 31.2 ± 7.9 h, respectively (mean difference: 8.5 ± 4.5 h, P < .000001). There was no significant impact of pump time on DGF or SGF, with discordant pairs favoring less SGF with longer pump time (N.S.). The incidence of BPAR during the first 12 months post-transplant yielded a borderline difference favoring longer pump time (P = .09), and freedom-from-BPAR during the first 12 months was significantly more favorable for longer pump times (95% vs. 84%, P = 0.04). No differences were observed in graft and patient survival, and renal function. While offering significantly favorable protection from BPAR, this analysis of donor-matched recipient pairs corroborates longer MP (pump) times having no unfavorable effect on other clinical outcomes.

Background. Our single-center, open-labeled randomized trial of 150 adult, primary kidney transplant recipients receiving 2 g mycophenolate mofetil (group A, n = 75) versus 1.440 g enteric-coated mycophenolate sodium (group B, n=75), with reduced maintenance tacrolimus dosing, steroid elimination at 1 week, and combined rabbit antithymocyte globulin/daclizumab induction, previously showed at 1 year posttransplant low biopsy-proven acute rejection (BPAR), acceptably high renal function, and no differences in incidence of symptomatic gastrointestinal (GI) side effects between the two groups. This report includes 3 additional years of follow-up with similar endpoints as in the original study. Methods. Rates of developing first BPAR, graft failure (death censored and uncensored), death, and adverse events (GI toxicity, infections requiring hospitalization, and new onset diabetes mellitus after transplantation) during the first 48 months posttransplant were compared between the two groups using an intent-to-treat approach. Results. At 48 months posttransplant, patient/graft survival in groups A and B was 97%/90% vs. 96%/86%, respectively (not significant [NS]). Twenty-seven patients experienced BPAR (including borderline), with actuarial 19% (14/75) vs. 18% (13/75) in groups A and B, respectively (NS). Geometric mean * /standard error serum creatinine level and arithmetic mean calculated glomerular filtration rate (±standard error) at 48 months in groups A and B, respectively, were 1.25*/1.06 and 69.2 ±3.9 vs. 1.20*/1.05 and 71.2±3.2 (NS). Incidence of new onset diabetes mellitus after transplantation (22% vs. 15%), infections requiring hospitalization (31% vs. 39%), and GI side effects (45% vs. 52%) seemed equivalent. Conclusions. This is the first long-term, randomized trial comparing enteric-coated mycophenolate sodium versus mycophenolate mofetil along with reduced maintenance tacrolimus dosing and steroid avoidance, which resulted in similarly low-BPAR rates, acceptably high renal function at 48 months, and an equivalent side effect profile.

The laparoscopic approach to donor nephrectomy is becoming increasingly common. While it is felt that the recovery from laparoscopic nephrectomy is quicker and less painful, a number of complications have been reported. A rarely reported on complication in the literature with significant morbidity is ipsilateral orchalgia. From 1998 to 2008, 257 hand-assisted laparoscopic donor nephrectomies were performed at our institution. Eight of 129 (6.2%) men complained of de novo ipsilateral orchalgia postoperatively. The average duration of pain was 402 days. Patients reported significant morbidity related to this complication. None, however, required further treatment. Three patients reported that they would reconsider organ donation as a result of testicular pain. Our technique originally included dissection and ligation of the gonadal vein en bloc with the ureter at the level of the left common iliac artery. Since recognizing this complication, we have adopted a gonadal vein sparing approach so as not to disturb the vessel below its point of ligation at the renal vein. To date, 50 patients have undergone the modified technique without experiencing orchalgia. In conclusion, ipsilateral testicular pan is a relatively frequent complication of laparoscopic donor nephrectomy and may be a source of significant morbidity. Using a modified surgical technique, this complication can be reduced or eradicated.

Our country faces a shortage of surgeons; hence, we may anticipate the development of new surgery residencies. Therefore, the question of the effect of a new program on operating room times (ORT) is important. Our primary aim was to compare ORT of 3 common procedures done by attendings alone vs ORT of cases with residents.We queried records of 1458 patients from the JFK Medical Center database for laparoscopic cholecystectomy, open inguinal hernia repair, and laparoscopic appendectomy from July 2010 to July 2012. We divided the sample into 2 groups: "attending alone" (2010-2011) and "with residents" (2011-2012). The ORT was calculated by "Cut time" and "Close time," as recorded in the OR. ORT for both groups was calculated using the unpaired t test.Of the total number of patients, 778 underwent laparoscopic cholecystectomy, 407 underwent open inguinal hernia repair, and 273 underwent laparoscopic appendectomy; of these, 620, 315, and 211 procedures, respectively, were done by the attending alone and 158, 92, and 62, respectively, were done with residents. Differences in ORT for the 3 types of surgery were statistically significant (p0.001). There was no statistical significance when comparing the first half with the second half of the academic year for residents' ORT.Resident involvement increases ORT. Cost analysis considering OR time and anesthesia time vs federal funding for Graduate Medical Education is complicated. The benefit of new programs in diminishing the shortage of surgeons cannot be underestimated.

An increasing number of studies have been published since the introduction of robotic technology into general surgery. Gastrointestinal surgery is an area of special interest for the robotic surgeon. Colonic surgery can be challenging depending on the disease and the operative approach. We seek to perform a meta-analysis comparing robotic surgery against laparoscopic surgery in this particular field.We performed a systematic search of MEDLINE database from January 2001 to July 2013 supplemented by manual searches of bibliographies of key relevant articles. Randomized controlled trials and cohort studies were selected for review and for collection of postoperative data (length of stay, time to first flatus and complications).After careful review, nine studies were considered for analysis. Non-pooled data showed a slight trend toward laparoscopy with increased number of events without statistical significance. Pooled data demonstrated a statistical significance for return to bowel function in the right and mixed robotic colectomy arm (WSMD -0.33, 95 % CI -0.5, -0.1; p0.005 and WSMD -0.26, 95 % CI -0.51, 0.0; p = 0.05). Pooled data of length of stay and complications showed no statistical significance between robotic and laparoscopic colonic surgery.Robotic surgery is a comparable option when dealing with colonic disease, either benign or malignant. No difference in complication rate or length of stay was found when comparing the two. Robotic surgery appears to have an advantage over laparoscopy in regards to return of bowel function when dealing with right colectomies.

BACKGROUND Given our previous experience using dual-induction therapy with antithymocyte globulin (ATG)/daclizumab (Dac) (each with fewer doses than if used alone), we chose to compare two distinct dual-induction strategies. METHODS Single-center, open-label randomized trial of 200 primary kidney transplant recipients was performed: (group I, n=100) ATG/Dac (3 ATG, 2 Dac doses) versus (group II, n=100) ATG/alemtuzumab (1 dose each), with maintenance consisting of reduced tacrolimus dosing (rTd), enteric-coated mycophenolate sodium (EC-MPS), and early corticosteroid withdrawal. One half of standard EC-MPS dosing was targeted in group II to avoid severe leukopenia previously seen with alemtuzumab. The goal in both arms was to achieve rapid and effective lymphocyte depletion while simultaneously allowing reduced maintenance immunosuppression. Primary endpoint was the incidence of biopsy-proven acute rejection (BPAR). RESULTS With median follow-up of 38 months, there were no differences in BPAR rates: 14 of 100 vs. 13 of 100 (including borderline) and 10 of 100 vs. 9 of 100 (excluding borderline) in groups I and II, respectively (nonsignificant). Actuarial patient/graft survival at 48 months was 96%/91% in group I vs. 92%/83% in group II (N.S.). Mean estimated glomerular filtration rate (±standard error) at 36 months was 72.1±3.3 vs. 67.5±3.3 in groups I and II (N.S.). Greater incidence of leukopenia occurred in group II at month 1 only (P=0.002). Percentages having EC-MPS withheld/discontinued due to leukopenia, gastrointestinal symptoms, and infection were 12 of 100, 7 of 100, and 0 of 100 in group I vs. 19 of 100, 0 of 100, and 2 of 100 in group II, respectively (P=0.01). Rates of new onset diabetes mellitus after transplantation and infections were equally low in both groups (no lymphoproliferative disorders were observed). CONCLUSIONS These two distinct dual-induction therapies with rTd, EC-MPS, and planned early corticosteroid withdrawal resulted in favorable rates of BPAR and all secondary outcomes.

The impact of machine perfusion (MP) time on kidney transplant outcome is mixed in previous studies using multivariable analyses. In an analysis of 66 pairs of donor-matched adult, first transplant recipients (N = 132) with identical donor characteristics except for pump time, tests of association of shorter versus longer pump time (first versus second kidney removed) by delayed graft function(DGF), slow graft function(SGF), and biopsy proven acute rejection(BPAR) were performed using McNemar's test. Freedom-from-BPAR, graft and patient survival, and renal function were also compared. Mean ± SD pump times for paired recipients with first and second kidneys were 22.7 ± 7.3 h and 31.2 ± 7.9 h, respectively (mean difference: 8.5 ± 4.5 h, P.000001). There was no significant impact of pump time on DGF or SGF, with discordant pairs favoring less SGF with longer pump time (N.S.). The incidence of BPAR during the first 12 months post-transplant yielded a borderline difference favoring longer pump time (P = .09), and freedom-from-BPAR during the first 12 months was significantly more favorable for longer pump times (95% vs. 84%, P = 0.04). No differences were observed in graft and patient survival, and renal function. While offering significantly favorable protection from BPAR, this analysis of donor-matched recipient pairs corroborates longer MP (pump) times having no unfavorable effect on other clinical outcomes.

The optimal long-term regimen for immunosuppression for kidney transplant recipients is unknown. We conducted a randomized trial involving 150 kidney transplant recipients to compare tacrolimus/sirolimus, tacrolimus/mycophenolate mofetil (MMF), and cyclosporine/sirolimus. All patients received daclizumab induction and maintenance corticosteroids. Median follow-up was 8 yr post-transplant. Acute rejection (AR) occurred significantly less often among those treated with tacrolimus/MMF (12%) than among those treated with tacrolimus/sirolimus (30%) or cyclosporine/sirolimus (28%). Mean estimated GFR was consistently higher in the tacrolimus/MMF arm, especially after controlling for donor age in a multivariable model during the first 36 mo (P ≤ 0.008). The rate of dying with a functioning graft was significantly higher among those treated with tacrolimus/sirolimus (26%) than among those treated with tacrolimus/MMF (12%) or cyclosporine/sirolimus (4%). We did not observe significant differences in actuarial graft survival at 8 yr post-transplant between the groups. Patient noncompliance seemed responsible for 45% (13/29) of observed graft failures, with 11 of these occurring after 36 mo. Significantly more viral infections, protocol violations, and need for antilipid therapy occurred among patients receiving sirolimus, but we did not observe differences between the groups with regard to infections requiring hospitalization or new-onset diabetes. Taken together, these results suggest that maintenance therapy with tacrolimus/MMF is more favorable than either tacrolimus/sirolimus or cyclosporine/sirolimus.

Although antibody induction has gained in popularity, two agents are rarely combined. We retrospectively analyzed peripheral lymphocyte phenotypes of renal transplant recipients who received induction therapy with a different antibody/combination: alemtuzumab(C1H), Thymoglobulin(rATG), daclizumab(Dac), rATG + C1H, and rATG + Dac. CD4+ T-cells were suppressed by C1H and rATG + C1H, as well as by rATG and rATG + Dac but to a lesser extent. The effect lasted for 3 years at around 40% of baseline values. CD8+ T-cells showed a similar trend but had a more rapid recovery to baseline. CD19+ B-cells were effectively suppressed for 2 months by C1H and rATG + C1H, and abruptly returned to baseline afterwards; suppression by rATG(7 doses) was modest but lasted longer. A higher proportion of CD56 + CD16+ Natural Killer cells in C1H treated patients suggested a relatively spared effect of C1H on this cell type. Low CD25+ T-cells by 5-dose Dac returned to baseline around 6 months, whereas rATG + C1H and rATG + Dac showed persistent effect. CD4 + CD25hi T-cells were suppressed by both rATG + C1H and rATG + Dac, but the initial proportion of CD4 + CD25hi T-cells among CD4+ T-cells and CD4 + CD25hi/CD4 + CD25lo ratio were significantly higher in rATG + C1H. Overall, with extensive and persistent lymphocyte suppression by a simple administration of agents, single-dose rATG + C1H induction can be an alternative in renal transplantation.

Background. Hypothermic machine perfusion (MP) preservation is used for all deceased donor kidney transplants at our center. Kidneys are placed in cold storage at retrieval, then transferred to MP on arrival. Because a lack of consensus regarding optimal use of MP still exists, we evaluated the overall impact of using MP at our center and the prognostic value of MP (Pump) time. Methods. We retrospectively analyzed 339 adult, primary deceased donor kidney transplant recipients who were pooled across three prospective, randomized immunosuppression trials (since 2000) at our center. In addition to providing overall results for delayed graft function (DGF) (requirement for dialysis in the first week), slow graft function (SGF), first biopsy-proven acute rejection (BPAR), and graft failure, stepwise logistic and Cox regression analyses were used to determine the prognostic value of pump time, particularly after controlling for other significant prognosticators. Results. Mean cold storage and pump times were 6.6 and 26.7 hr, consistent across immunosuppression protocols. Overall DGF and SGF rates were 4.4% (15/339) and 12.1% (41/339). DGF was equally low for pump time less than 24 vs. more than or equal to 24 hr, 5.2% (6/116) vs. 4.0% (9/223) (P=0.63), with similar results after adjusting for known DGF predictors. A significantly lower first BPAR rate was observed for longer pump time (as a continuous variable) among more immunologically active recipients (those having more risk factors: DGF, age

Background We performed a randomized trial evaluating Alemtuzumab, a humanized anti-CD52 monoclonal antibody, in living donor (LD) kidney transplantation. Methods Thirty-eight LD first renal transplant recipients were randomized into three single-agent antibody induction groups: thymoglobulin (group A); alemtuzumab (group B); and daclizumab (group C). In groups A and C, target tacrolimus trough levels were 6 to 8 ng/mL, with 1 gm mycophenolate mofetil (MMF) administered twice daily, and maintenance methylprednisolone. In group B, the target tacrolimus trough level was 4 to 6 ng/mL, with 500 mg MMF administered twice daily, without methylprednisolone. Results With 29/38 patients now followed beyond 36 months posttransplantation, we observed no graft failures and only one death with a functioning graft (in group B). Acute rejection episodes were low: 0/13, 1/13, and 1/12 patients in groups A, B, and C. Biopsy-proven chronic allograft injury was higher among group B (3/13) versus groups A (0/13) or C (0/12; P = .01). Poorer renal function was observed in group B; the mean calculated creatinine clearance at 3 months posttransplantation was significantly poorer: 63.3 ± 3.0 versus 85.4 ± 7.2 and 82.2 ± 8.2 in groups A and C (P = .01). No differences in the incidence of adverse events were observed.

This retrospective study was designed to evaluate the efficacy of low-molecular-weight heparin (enoxeparin) as a prophylaxis for venous thromboembolism and deep venous thrombosis (DVT) in the management of large-volume liposuction, added body-contouring procedures, or both. The author present an 18-month experience with the use of this therapy for 291 consecutive patients. All the patients fell into the categories of high risk and highest risk for the development of deep vein thrombosis, embolism, or both. Three patients experienced transient DVT-like symptoms and underwent a thorough workup by an independent highly specialized critical care medical team. The results were found ultimately to be inconclusive for DVT and pulmonary embolism. However, all the patients experienced a complete recovery. The results show a 0% incidence of DVT and pulmonary embolism among patients who received enoxeparin as prophylaxis. The medication did not precipitate major bleeding when administered 1 h after surgery. This study offers the first report that describes the use of enoxeparin in aesthetic surgery for high-risk patients. The authors feel the need to inform their colleagues of the benefits obtained over the past 18 months by incorporating this therapy in large-volume liposuction and extensive body-contouring procedures performed during the same operative session. This study was conducted by a highly experienced surgical team in a fully accredited outpatient facility with established protocols for handling these types of procedures on a daily basis. The authors are optimistic about the results, and the use of enoxeparin is now part of their postoperative regimen in high-risk aesthetic surgery cases.