Comparison of Sirolimus Combined With Tacrolimus and Mycophenolate Mofetil Combined With Tacrolimus in Kidney Transplantation Recipients: A Meta-Analysis.

PURPOSE: The study was designed to compare the outcomes of sirolimus (SRL) combined with tacrolimus (TAC) and mycophenolate mofetil (MMF) combined with TAC in kidney transplantation recipients. METHODS: A literature search of PubMed, Embase, and Web of Science was performed to identify relevant studies, and the last update was on February 1, 2018. All studies with appropriate data comparing the SRL group with the MMF group were included. SRL and MMF were used in sufficient doses. Relevant information was recorded and analyzed. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the effects of SRL and MMF. Relevant outcomes, including delayed graft function, acute rejection, graft survival, seroma, anemia, lymphocele, and hyperlipidemia, were compared. RESULTS: Ten studies with a total of 2357 patients (n = 1256 receiving SRL vs n = 1101 receiving MMF) were ultimately included. Our results indicated that the SRL group experienced a higher rate of hyperlipidemia (OR: 1.864; 95% CI, 1.494-2.325) and lymphocele (OR: 2.58; 95% CI, 1.49-4.47). However, no significant differences were detected regarding the rates of delayed graft function, acute rejection, graft survival, infectious complications, anemia, or seroma. CONCLUSIONS: This meta-analysis suggested that SRL combined with TAC and MMF combined with TAC were equally safe and effective for the kidney transplantation recipients. However, the MMF group exhibited a marginally significant advantage of lower incidence of hyperlipidemia and lymphocele.

A reproducible in-vivo model of lymphatic malformation in rats.

The aim of this study was to develop a reproducible rat model of lymphatic malformation. Different types of adjuvant, with and without vascular endothelial growth factor (VEGF)-C, was injected into the neck and floor of the mouth of rats. The rats were killed 2 months after the injection. Injected rats developed cystic lesions in the neck and floor of the mouth. Immunohistochemical examination revealed that the cysts were lined by endothelium, which expressed the lymphatic endothelial markers LYVE-1 and VEGF receptor-3. Raman spectra of the liquid contents of the cysts were similar in all injected rats. Transmission electron microscopy revealed that the endothelial cells had no basement membrane or surrounding pericytes. The cystic lesions were consistent with human lymphatic malformation. This animal model could be used to investigate pathogenesis of lymphatic malformation and its responses to candidate therapies.

Impact of mycophenolate mofetil on wound complications and lymphoceles after kidney transplantation.

BACKGROUND/AIMS: Despite improved efficacy, modern immunosuppressive agents may show unanticipated side effects. In this study we investigated the possible interactions of mycophenolate mofetil (MMF) with wound healing and lymphocele formation. METHODS: We conducted a retrospective single-center analysis in 144 patients receiving a cyclosporine A-based immunosuppression with prednisolone and either MMF (n = 77) or azathioprine (AZA, n = 77). Endpoints were incidences of lymphocele formation and non-primary wound healing during 6 months' follow-up. RESULTS: AZA-treated patients had more rejection episodes and consecutively more steroid pulses, both being potential risk factors for endpoints. No graft was lost in any group and graft function was comparable. AZA patients demonstrated a trend for more frequent wound infections. Fluid accumulation around the graft, however, was more frequent in the MMF group (OR = 2.6; p = 0.03). Consequently, more drainage maneuvers (17 vs. 5 interventions) and sclerotherapies (8 vs. 0 interventions) were undertaken in MMF patients. Pre-assigned risk factors for lymphoceles reported before did not differ between both cohorts; patients experiencing acute rejection episodes had even less symptomatic lymphoceles (n = 23). CONCLUSION: We found a possible relationship between the administration of MMF and lymphocele formation. To avoid the hazard of reinterventions, the prolongation of hospitalization and impairment of graft function, it requires awareness and attention in patients treated with this immunosuppressant.

[Side effects of proliferation signal inhibitors and their management]. / Effets secondaires des inhibiteurs du signal de prolifération et leur gestion.

Proliferation signal inhibitors (PSI) could help to lower the calcineurine inhibitors level to minimize their toxicity and improve long-term graft survival. Side effects of this drugs are specific and must been known. Hyperlipidemia and cutaneous side-effects are the most frequent, angioedema and interstital pneumonitis the most serious. In majority of cases, early and adapted management could limit the impact of these side effects.

Management of side effects of sirolimus therapy.

Sirolimus (SRL) has been shown to improve long-term graft survival in several calcineurin inhibitor avoidance/minimization protocols. Although SRL has been suggested to reduce the progression of chronic renal graft damage and to prevent the development of neoplasia, two of the most prominent challenges in the field of transplantation, its use is significantly limited by an extremely high incidence of side effects. Some of the side effects are directly linked to the antiproliferative action of SRL, whereas the mechanisms underlying most of the undesired effects of the drug are still far from being clarified. Nevertheless, there is an increasing body of evidence linking most these drug-associated events to SRL dose. In addition, it is now possible to identify well-defined risk factors for most of these effects. Thus, to limit SRL-related side effects the two golden rules are (1) accurate selection of patients to be treated and (2) avoidance of high SRL doses.

Sealants after axillary lymph node dissection for breast cancer: good intentions but bad results.

BACKGROUND: This study was conducted to evaluate the effect of 2 surgical sealants on postsurgical drainage and lymphocele formation after axillary surgery for breast cancer. METHODS: This was a prospective, randomized study. Seventy-seven consecutive patients with breast cancer were included and randomized into a control group (18F vacuum drain) and 2 study groups (18F vacuum drain plus COSEAL or BioGlue). RESULTS: The 3 groups were matched. Neither postsurgical drainage nor time to drain removal was affected by the use of either of the 2 sealants. Although no statistically significant difference in lymphocele formation and wound infection was noted, complications caused by intense foreign-body reaction that led to surgical intervention occurred in both study groups. COMMENTS: The use of surgical sealants is not recommended after axillary lymph node dissection for breast cancer. Complications of their use may lead to reoperation.

A systematic approach to minimizing wound problems for de novo sirolimus-treated kidney transplant recipients.

BACKGROUND: Wound healing problems and lymphoceles have been reported with greater frequency in kidney recipients given de novo sirolimus. This problem has led to increased patient morbidity and cost; and has been an impediment to the completion of randomized controlled trials in which wound problems have necessitated premature discontinuation of mammalian target of rapamycin inhibitors. METHODS: We developed a systematic program to reduce these problems based on patient selection (body mass index [BMI] <32 kg/m2), the use of closed suction drains, modifications of surgical technique, and avoidance of a loading dose of sirolimus. Consecutive series of adult kidney-only recipients given antibody induction followed by de novo sirolimus, mycophenolate mofetil, and steroids were compared; group 1: 204 patients transplanted with few restrictions and group 2: 103 patients transplanted using the above program. RESULTS: This approach resulted in a significant reduction (group 2 vs. group 1) in cumulative wound complications (7.8% vs. 19.6%, P=0.007), and nonoperative wound complications (2.9% vs. 14.2%, P=0.001). In addition, the incidence of lymphoceles detected (22.3% vs. 47.1%, P<0.0001), treated (4.8% vs. 24.5%, P<0.0001), or needing surgical intervention (1.9% vs. 14.2%, P=0.001) was significantly reduced. Multivariate analysis demonstrated that a BMI more than 30 to 32 kg/m2 was the most significant variable related to delayed wound healing (odds ratio [OR] 3.01, 0.02) or surgical repair (OR 8.05, P=0.0001), whereas BMI (OR 1.54, P=0.038) and acute rejections (OR 1.34, P=0.03) were most associated with lymphocele treatment. CONCLUSIONS: A systematic program of wound care using de novo sirolimus can produce wound healing complications comparable with that reported with other agents.

[Lymphocele and kidney transplantation]. / Lymphokele és vesetranszplantáció

INTRODUCTION: Lymphocele is a special complication following kidney transplantation. The authors examined the factors associated with an increased occurrence of clinically significant perinephric fluid collections and/or lymphoceles among sirolimus-treated renal transplant recipients. AIM: From the point of view of the lymphocele a comparison was made for the risks and benefits of the conventional and a newer immunosuppressive combination. METHODS: At the University of Texas in Houston in a retrospective study the incidence, predisposing factors, and consequences of these fluid collections among patients treated with sirolimus-cyclosporine-prednisone ( n = 354, Group I) versus cyclosporine-prednisone-azathioprine ( n = 136, Group II) were compared. RESULTS: More Group I patients (135/354; 38.1%) displayed perinephric fluid collections than Group II patients (24/136; 17.6%; p < 0.001). In both subgroups the serum creatinine levels were elevated at the time of diagnosis from a nadir of 179.5 +/- 141.7 to 359.9 +/- 259.6 mmol/l (Group III, sirolimus treated) and from 222.6 +/- 205.9 to 383.7 +/- 255.2 mmol/l (Group IV, sirolimus free). A significantly greater number of patients required treatment for lymphoceles among Group I (15.8%; 56/354) versus Group II recipients (4.4%; 6/136; p < 0.001). Single or repeated percutaneous drainage procedures successfully treated 35 Group I patients versus all 6 Group IV patients ( p = 0.033). No patients in Group II versus 21 patients in Group I underwent surgical procedures ( p < 0.001). A significantly higher rate and higher histologic grade of acute rejection episodes, particularly proximate to the onset of the lymphocele, occurred among Group IV patients, namely 54.2% (13/24) versus 21.4% (29/135) Group III patients ( p < 0.001). Additionally we report the case of a 29-year-old patient who underwent a lymphocele fenestration with omentoplasty 8 years after his transplantation. Despite an Influenza A + Chlamydia pneumonia and acute rejection which was followed by a GI bleeding and stomach resection he fully recovered and is doing well with an excellent kidney function a year after. CONCLUSIONS: Addition of sirolimus to a cyclosporine-prednisone regimen resulted in both a higher incidence and a requirement for more aggressive treatment of perinephric fluid collections and/or lymphoceles with a much lower acute rejection frequency.

Low molecular weight heparin prophylaxis increases the incidence of lymphocele after kidney transplantation.

Lymphocele formation after kidney transplantation has become more frequent at our department after the introduction of routine thromboembolic prophylaxis with low molecular weight heparin (LMWH). A consecutive series of 130 kidney transplant recipients were included in a retrospective study. Fifty-eight patients received prophylaxis and 72 did not. Other background data between the two patient groups was comparable. Lymphocele was diagnosed by ultrasound. Lymphocele formation was significantly more common (p<0.01) among patients who received LMWH prophylaxis (43%) than patients who did not (20%). There was no increase in bleeding-related complications in the prophylaxis group. An interesting finding was that, in the prophylaxis group, fewer grafts were lost due to vascular complications or early rejection, leading us to conclude that the use of LMWH increases the incidence of lymphocele formation after kidney transplantation, but may also reduce early graft loss due to thrombosis and vascular rejection.

Is heparin contraindicated in pelvic lymphadenectomy and radical prostatectomy?

PURPOSE: We initiated a prospective study to verify or refute the complications of lymphocele formation and excessive blood loss associated with heparin prophylaxis in pelvic lymphadenectomy and radical prostatectomy. MATERIALS AND METHODS: A prospective study was completed on 579 men undergoing pelvic lymphadenectomy usually in association with radical prostatectomy. Patients were assigned to group 1 (given preoperative and postoperative subcutaneous heparin) and group 2 (no heparin). All patients were evaluated 2 to 3 weeks after surgery with ultrasound for pelvic lymphocele. RESULTS: There was no statistically significant difference in the number or size of pelvic lymphoceles or blood loss in group 1 versus group 2. CONCLUSIONS: The use of heparin prophylaxis to prevent thromboembolic complications in conjunction with pelvic lymphadenectomy and radical prostatectomy is not associated with increased blood loss or increased rate of lymphocele formation.