Rectosigmoid Mesorectal-Sparing Resection in Advanced Ovarian Cancer Surgery.

Ovarian cancer is the most lethal of all gynecologic cancers.1 Primary debulking surgery (PDS) with achievement of no residual tumor (RT, 0) still is the recommended treatment, and the one with the greatest prognostic impact.2,3 Given the usual disease spread, several surgical procedures often are needed, and one of the most frequent is rectosigmoid resection.4 Anastomotic leak is the most feared complication. Other common complications are persistent urinary, defecatory, and sexual dysfunction due to autonomic nervous system injuries during surgery.5 Even if mesorectal resection is not deemed part of the treatment paradigm for advanced ovarian cancer (AOC), total mesorectal excision (TME) is the most common surgical technique used. However, for selected cases, with detection of no lymphadenopathies at the origin of the of the inferior mesenteric artery and a favorable ratio between the length of the left colon and the extent of the bowel carcinomatosis, a mesorectal-sparing resection with the preservation of the superior rectal artery and the mesorectal tissue should be pursued. This report presents the case of a 54-year-old woman with a diagnosis of FIGO stage 3C AOC who underwent PDS. The video (video 1) provides a step-by-step description of the surgical technique adopted for colorectal resection with mesorectal-sparing technique. Rectosigmoid mesorectal-sparing resection is feasible and could be a viable option for selected cases of AOC, maximizing the blood supply to colorectal anastomosis while minimizing the risk of both anastomotic leak and pelvic autonomic nervous system dysfunction.6.

Optimizing the number of cycles of neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma: A propensity-score matching analysis.

OBJECTIVE: Neoadjuvant chemotherapy and interval debulking surgery are now widely offered in ovarian cancer patients unsuitable for surgery; the number of preoperative NACT cycles to be given is still an issue. Our aim was to compare survival outcomes of patients with advanced ovarian cancer treated with ≤4 or more NACT cycles. METHODS: A cohort of AEOC patients with stage III-IV epithelial OC who underwent NACT followed by IDS was identified. Patients were classified in group A (≤4 cycles) and group B (>4 cycles). Selection bias from the heterogeneity of demographic and clinical characteristics was avoided using propensity score matching (2:1 ratio). RESULTS: 140 (group A) and 70 (group B) patients were included. After the propensity score matching, there were no imbalances in baseline characteristics. BRCA status was associated to improved OS (HR = 0.41; 95%CI 0.18.0.92, p = 0.032) and residual tumor to decreased OS (HR = 1.93; 95%CI 1.08-3.46, p = 0.026). Statistically significant differences were not observed in OS (2-year OS 82.4% for group A versus 77.1% for group B, p = 0.109) and PFS (2-year PFS 29.7% for group A versus 20.0% for group A, p = 0.875). In group B, the administration of >4 cycles was related to an additional chance of achieving complete (12.9%) and partial (34.3%) responses compared to responses after 3-4 cycles. CONCLUSIONS: Receiving more than 4 cycles of NACT is no detrimental in terms of OS and PFS in advanced ovarian cancer. Response rates can increase following further cycles administration.

Hormone replacement therapy and cervical cancer: a systematic review of the literature.

Gynecological tumor treatment, including cervical cancer (CC) treatment, often leads to iatrogenic premature menopause. This highlights the critical importance of investigating indications for hormone replacement therapy (HRT), as most patients, thanks to the improvement in diagnosis and treatment, have to deal with the sequelae of their cancer treatments for many years. This systematic review aims to provide an overview of the current knowledge regarding the risks of HRT and CC. In particular, we aim to investigate whether the use of HRT can increase CC incidence, and evaluate its risk in CC survivors. A systematic review, in agreement with PRISMA guidelines, of the English literature present in PubMed and SCOPUS has been performed. A total of 2805 articles have been screened, of which 10 were considered eligible. Several studies reported a significantly reduced risk of developing cervical squamous cell carcinoma in postmenopausal women treated with HRT, while a weak increase in the incidence of adenocarcinoma has been shown. No evidence reports a harmful effect of HRT on CC oncological outcome, while several benefits, in terms of reduced metabolic risk and increased quality of life, have been described, thus concluding that HRT should be offered to young CC survivors for the management of early menopause.

Secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer before olaparib maintenance: Still getting any benefit? A case-control study.

OBJECTIVE: The role of secondary cytoreductive surgery (SCS) in platinum-sensitive recurrent ovarian cancer (PSROC) is still controversial. We investigated the role of SCS in PSROC patients with BRCA1/2 mutation (BRCAmut) who received platinum-based chemotherapy followed by olaparib maintenance. METHODS: This is a case-control study. Patients with first PSROC admitted to our Gynecologic Oncology Unit between 2014 and 2018 were identified. Main eligibility criteria: positive BRCA1/2 germline or somatic mutation status and olaparib maintenance at primary recurrence after response to platinum-based chemotherapy. Cases were those who received SCS followed by medical treatment (SCS-CT-OLA, group 1), controls were those who received medical treatment alone (CT-OLA, group 2). RESULTS: Overall, 46 patients were identified; 23 (50%) BRCAmut women undergoing SCS followed by platinum-based chemotherapy and olaparib maintenance were matched with 23 (50%) BRCAmut women who only received medical treatment. Groups were well balanced: no statistical differences were found with regard of age, mutational status, treatment's approach at diagnosis, timing and patterns of disease presentation at recurrence. Median time to first subsequent therapy (TFST) was significantly longer in the SCS-CT-OLA than in the CT-OLA group (42 months vs 16 months; p = 0.05). Also, SCS-CT-OLA patients had the best post-recurrence survival (PRS), with a 3-year PRS of 79% in SCS-CT-OLA group versus 42% in CT-OLA group (p = 0.02). CONCLUSIONS: SCS increases TFST and PRS in PSROC patients with BRCAmut candidate for olaparib maintenance after platinum-based chemotherapy. Prospective studies are needed. In the era of personalized medicine, indication to SCS should be individualized.

Robotic Single-Port Platform in General, Urologic, and Gynecologic Surgeries: A Systematic Review of the Literature and Meta-analysis.

BACKGROUND: Robotic platforms have recently acquired progressive importance in different surgical fields, such as urology, gynecology, and general surgery. Through the years, new surgical robots have become available as single-port robotic platform. The study is aimed to value the single-port robotic platform characteristics in different surgical specialties. METHODS: The terms "LESS" OR "single port" OR "single site" AND "robot" OR "robotic" were systematically used to search the PubMed and Scopus databases. A total of 57 studies were considered eligible for the present review. The articles included were divided according to the surgical field in which the study was conducted: General surgery (29 articles), Gynecology (18 articles), Urology (10 articles). RESULTS: Most part of the articles showed the feasibility of robotic single-port surgical procedures and described advantages in terms of cosmetic, hospital stay, and in some series even cost reduction. A meta-analysis was conducted, showing a significant increment of complications using RSP if compared with SLPS and a trend (P = 0.008) when RSP was compared with LESS. The comparison of different techniques in terms of conversion to laparotomy did not show any significant difference. CONCLUSION: Robotic single port potentially furnishes an important surgical and post-operatory improvement; however, some limits still prolong the surgical time and complication rate.

Total laparoscopic hysterectomy for enlarged uteri: factors associated with the rate of conversion to open surgery.

A hysterectomy for enlarged uteri is considered a challenge for gynaecologic surgeons, due to the limit of exposure to surgical spaces. Our objective is to investigate the different variables that may have an impact on the risk of conversion to open surgery. This is a retrospective cohort study consisting of 133 women who were submitted to surgery for uterine fibroids and who underwent total hysterectomy by laparoscopic approach attempt. The median uterus weight was 622 grams (range 301-3882) and the median maximum diameter of the bigger fibroid was 74 mm (range 33-148). We registered 13 (9.8%) cases of conversion to laparotomy. Minor and major post-operative complications were recorded in 4 (3%) and in 4 (3%) cases, respectively. After multivariable analysis, the surgeon's experience (OR: 0.24; 95% CI: 0.06-0.94, p = .027) and a maximum diameter of the biggest fibroid ≥10 cm (4.7; 1.39-15.87; p = .046), but not the uterus weight were associated with the risk of conversion to open surgery. IMPACT STATEMENT What is already known on this subject? Laparoscopic procedures for enlarged uteri are well described in literature; however, the only parameters that have been studied for the success of a laparoscopic procedure have been the uterus weight and the surgeon's experience. What do the results of this study add? This study aimed to value all the possible variables related to the successful of laparoscopic procedures; in fact, we investigated not only the uterine weight, but in our multivariate analysis, the position of the fibroids, the trocar's setting, etc. were analysed. What are the implications of these findings for clinical practice and/or further research? This study reported novel data about the feasibility of laparoscopic hysterectomy for enlarged uteri. In opposition to the literature, the uterine weight is not a predictive value for laparotomic conversion. Moreover, we discussed the possible reasons of our novel findings. It opens new perspective to create a predictive value of laparoscopic feasibility for the different types of enlarged uteri.

A Copernican revolution of multigenic analysis: A retrospective study on clinical exome sequencing in unclear genetic disorders.

Despite the inevitable shift in medical practice towards a deeper understanding of disease etiology and progression through multigenic analysis, the profound historical impact of Mendelian diseases cannot be overlooked. These diseases, such as cystic fibrosis and thalassemia, are characterized by a single variant in a single gene leading to clinical conditions, and have significantly shaped our medical knowledge and treatments. In this respect, the monogenic approach inevitably results in the underutilization of Next-Generation Sequencing (NGS) data. Herein, a retrospective study was performed to assess the diagnostic value of the clinical exome in 32 probands with specific phenotypic characteristics (patients with autoinflammation and immunological dysregulation, N = 20; patients diagnosed with Hemolytic uremic syndrome N = 9; and patients with Waldenström macroglobulinemia, N = 3). A gene enrichment analysis was performed using the *. VCF file generated by SOPHiA-DDM-v4. This analysis selected a subset of genes containing pathogenic or likely pathogenic variants with autosomal dominant (AD) inheritance. In addition, all variants of uncertain significance (VUS) were included, filtered by AD inheritance mode, the presence of compound heterozygotes, and a minor allele frequency (MAF) cutoff of 0.05 %. The aim of the pipeline described here is based on a perspective shift that focuses on analyzing patients' gene assets, offering new light on the complex interplay between genetics and disease presentation. Integrating this approach into clinical practices could significantly enhance the management of patients with rare genetic disorders.

Robotic platforms in gynaecological surgery: past, present, and future.

Background: More than two decades ago, the advent of robotic laparoscopic surgery marked a significant milestone, featuring the introduction of the AESOP robotic endoscope control system and the ZEUS robotic surgery system. The latter, equipped with distinct arms for the laparoscope and surgical instruments, was designed to accommodate remote connections, enabling the practice of remote telesurgery as early as 2001. Subsequent technological progress has given rise to a range of options in today's market, encompassing multi-port and single-port systems, both rigid and flexible, across various price points, with further growth anticipated. Objective: This article serves as an indispensable guide for gynaecological surgeons with an interest in embracing robotic surgery. Materials and methods: Drawing insights from the experience of the Strasbourg training centre for minimally invasive surgery (IRCAD), this article offers a comprehensive overview of existing robotic platforms in the market, as well as those in development. Results: Robotic surgical systems not only streamline established operative methods but also broaden the scope of procedures, including intra- and transluminal surgeries. As integral components of the digital surgery ecosystem, these robotic systems actively contribute to the increasing integration and adoption of advanced technologies, such as artificial intelligence-based data analysis and support systems. Conclusion: Robotic surgery is increasingly being adopted in clinical practice. With the growing number of systems available on the marketplace, the primary challenge lies in identifying the optimal platform for each specific procedure and patient. The seamless integration of robotic systems with artificial intelligence, image-guided surgery, and telesurgery presents undeniable advantages, enhancing the precision and effectiveness of surgical interventions. What is new?: This article provides a guide to the robotic platforms available on the market and those in development for gynaecologists interested in robotic surgery.

Primary flap closure of perineal defects to avoid empty pelvis syndrome after pelvic exenteration in gynecologic malignancies: An old question to explore a new answer.

Pelvic exenteration (PE) is a radical oncological surgical procedure proposed in patients with recurrent or persistent gynecological cancers. The radical alteration of pelvic anatomy and of pelvic floor integrity can cause major postoperative complications. Fortunately, PE can be combined with reconstructive procedures to decrease complications and functional and support problems of pelvic floor, reducing morbility and mortality and increasing quality of life. Many options for reconstructive surgery have been described, especially a wide spectrum of surgical flaps. Different selection criteria have been proposed to select patients for primary perineal defect flap closure without achieving any strict indication of the best option. The aim of this review is to focus on technical aspects and the advantages and disadvantages of each technique, providing an overview of those most frequently used for the treatment of pelvic floor defects after PE. Flaps based on the deep inferior epigastric artery, especially vertical rectus abdominis musculocutaneous (VRAM) flaps, and gracilis flaps, based on the gracilis muscle, are the most common reconstructive techniques used for pelvic floor and vaginal reconstruction. In our opinion, reconstructive surgery may be considered in case of total PE or type II/III PE and in patients submitted to prior pelvic irradiation. VRAM could be used to close extended defects at the time of PE, while gracilis flaps can be used in case of VRAM complications. Fortunately, numerous choices for reconstructive surgery have been devised. As these techniques continue to evolve, it is advisable to adopt an integrated, multi-disciplinary approach within a tertiary medical center.

Is the sarcomatous component (homologous vs heterologous) the prognostic "driving force" in early-stage uterine carcinosarcomas? A retrospective multicenter study.

PURPOSE: Uterine carcinosarcomas (UCSs) are aggressive biphasic malignancies, with a carcinomatous/epithelial component and a sarcomatous/mesenchymal counterpart. The aim of this study was to evaluate the impact of the sarcomatous component (homologous vs heterologous) on the overall survival (OS) and progression-free survival (PFS). METHODS: This is a multicenter observational retrospective study conducted in patients with stage I and II UCSs. RESULTS: Ninety-five women with histological diagnosis of early-stage UCSs were retrieved: 60 (63.2%) had tumors with homologous sarcomatous components, and 35 (36.8%) with heterologous. At univariate analysis, a stromal invasion ≥ 50%, the presence of clear cell, serous or undifferentiated carcinomatous component, the heterologous sarcomatous component and FIGO stage IB and II were shown to be variables with a statistically significant negative impact on PFS. Similarly, a depth of invasion ≥ 50%, the heterologous sarcomatous component and FIGO stage IB and II were statistically negative prognostic factors also concerning OS. At multivariate analysis, only the heterologous sarcomatous component was confirmed to be a statistically significant negative prognostic factor both on PFS (HR 2.362, 95% CI 1.207-4.623, p value = 0.012) and on OS (HR 1.950, 95% CI 1.032-3.684, p = 0.040). CONCLUSION: Carcinomatous and sarcomatous components both played a role in tumor progression and patients' survival. However, only the sarcomatous component retained a statistical significance at the multivariable model suggesting its preeminent prognostic role in early-stage UCSs.

Surgical and functional impact of nerve-sparing radical hysterectomy for parametrial deep endometriosis: a single centre experience.

Background: Deep endometriosis (DE) usually creates a distortion of the retroperitoneal anatomy and may infiltrate the parametria with an oncomimetic pathway similar to cervical cancer. The condition represents a severe manifestation of endometriosis that may result in a functional impairment of the inferior hypogastric plexus. An extensive surgical resection may be required with an associated risk of increased neurogenic postoperative pelvic organ dysfunction. Objectives: To evaluate the post-operative function and complications following hysterectomy with posterolateral parametrial resection for DE. Materials and Methods: In total, 23 patients underwent radical hysterectomy for DE with the parametria involved. The severity of pain was assessed by the Visual Analogue Scale (VAS) score. The KESS, GQLI, BFLUTS and FSFI were used to examine the gastrointestinal, urinary and sexual functions respectively. Intra and post-operative complications were recorded. Main outcome measures: The main outcomes were gastrointestinal, urinary and sexual function and intra and post-operative complications. Results: Dyschezia, dyspareunia and chronic pelvic pain were significantly reduced following hysterectomy. Furthermore, an improvement of gastrointestinal function was observed, while sexual functions, examined by FSFI and urinary symptoms, examined by BFLUTS, was not shown to be significant. Conclusion: The modified nerve-sparing radical hysterectomy for DE results in an improvement of symptoms. Nevertheless, despite the nerve-sparing approach, this procedure may be associated with a not-negligible risk of post-operative bladder voiding deficit. What is new?: This is the first study that focuses on parametrial endometriosis using validated questionnaires to assess functional outcomes following radical hysterectomy for DE.

4K versus 3D total laparoscopic hysterectomy by resident in training: a prospective randomised trial.

Background: The introduction of ultra-high-definition laparoscopic cameras (4K), by providing stronger monocular depth perception, could challenge the existing 3D technology. There are few available studies on this topic, especially in gynaecological setting. Objectives: Prospective, single institution, randomised clinical trial (NCT04209036). Materials and Methods: The two laparoscopes utilised were the 0°ULTRA Telescopes with 4K technology and the 0°3D-HD by Olympus. The surgeons were all trainees and in their last year of residency and who had obtained the certificate of first or second level of the Gynaecological Endoscopic Surgical Education and Assessment program - GESEA program. Twenty-nine patients with benign uterine pathology were enrolled. Main outcome measures: To compare if the use three-dimensional (3D) versus ultra-high-definition laparoscopic vision system (4K) for total laparoscopic hysterectomy performed by trainees was associated with a shorter operative time. Results: The 3D vision system did not prove to be superior to the 4K vision system. Operators reported significantly more vision-related side effects when using 3D than 4K. Completing the GESEA training program was the only factor with a positive and statistically significant impact on the overall time of the procedure, especially when greater dexterity and tissue handling were required. Conclusions: Neither technology used proved superior to the other, although operators showed a preference for 4K over 3D due to the lower number of visual side effects. Attendance at courses on laparoscopic simulators and training programs allowed trainees to demonstrate excellent surgical skills.

[Nuchal translucency and combined test: what are the implications in clinical practice?]. / La translucenza nucale e il test combinato: quali risvolti nella pratica clinica?

AIM: The aim of this study was to evaluate the performance of the combined test (nuchal translucency, NT) and maternal serum free-beta human chorionic gonadotropin (free beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), compared to the NT measurement alone, in fetal aneuploidy screening in the general population and in pregnant women aged 35 years and over. In addition, the association between increased NT and presence of cardiac defects in fetuses with normal karyotype was evaluated. METHODS: Screening at 11-14 weeks of gestation by NT measurement and combined test was carried out in 1521 pregnant women. The estimated risk for trisomy 21 and trisomy 13+18 was calculated (risk cut-off 1/300 and 1/750 respectively) and the outcomes was evaluated. RESULTS: Ten cases of trisomies (21 and 18) occurred, seven of which among the older group of pregnant women. The detection rate (DR) for the combined test was 80% in the general population and 85.7% in older pregnant women, which resulted higher rate than NT measurements alone. Detection rate of cardiac defects using NT measurements was 66.6%. CONCLUSION: The combined test is an effective screening for aneuploidies and reduces at 14% the need of invasive testing in the older obstetric population, detecting all the trisomies occurred in this group. The association between increased NT and cardiac defects is confirmed but it seems too weak to consider NT as a single screening strategy for these abnormalities.

Renal involvement in systemic amyloidosis: an Italian collaborative study on survival and renal outcome.

BACKGROUND: Few data are available from large population-based studies on survival and renal outcome of patients with renal involvement and different types of systemic amyloidosis. METHODS: Two hundred and ninety of over 373 patients affected from systemic amyloidosis with renal involvement diagnosed in Italy between January 1995 and December 2000 were followed from diagnosis to death or until the last available clinical control. Eighty-three patients were excluded from analysis either because the amyloid type remained undetermined or they were lost at follow-up. Clinical and laboratory information was collected according to the different types of amyloidosis using a specific form which included renal function with 24 h proteinuria at diagnosis and at the end of follow-up, the type and the date of onset of dialysis and the kind of treatment they underwent. RESULTS: The median time of follow-up was 24 months in primary (AL) amyloidosis (range: 1-88 months), 16 months in AL with associated multiple myeloma (MM + AL: range 1-76 months), 30 months in reactive (AA) amyloidosis (range: 1-99 months) and 52 months in patients with familial forms (AF: range 14-82 months). Patients with AL showed a significantly shorter survival than AA. Despite no significant differences of renal outcome or survival on dialysis being observed between the two groups, a lower renal survival with a higher number of patients who progressed to end-stage renal disease (ESRD) was observed in patients with AA. Overall survival was markedly improved in patients with AL who underwent a specific therapy (conventional chemotherapy or autologous stem cell transplantation (ASCT)) even in the absence of a positive kidney response. Multivariate analysis showed cardiac involvement and specific therapy to significantly influence survival in AL whereas age, serum creatinine (sCr) and heart involvement significantly affected survival in AA. In both groups, sCr and heart involvement were the most relevant predictors for renal outcome, together with urinary protein excretion, in patients with AA. CONCLUSIONS: Our results show a worse survival in AL due to the higher prevalence of heart involvement in this group and emphasize that a specific therapy significantly prolongs survival and slows the progression of renal disease in patients with AL. We suggest that a late nephrological referral is likely the cause of the higher sCr found at presentation in patients with AA and probably accounts for the lower renal survival observed in the short term in these patients. At the time being, renal transplantation and ASCT are still rare therapeutic options for renal patients affected from systemic amyloidosis.

Perinatal infections and cerebral palsy.

Cerebral palsy (CP) is a complex disease characterized by the aberrant control of movement or posture that appears in early life and affect about 2 per 1000 live-born children. CP represents the most common physical disability in childhood. An association between clinical chorioamnionitis and cerebral palsy has been recognised. Very low-birthweight infants constitute more than 1/4 of all new cases of cerebral palsy. The use of antimicrobial treatment of pregnant women with bacterial vaginosis, a complete course of antenatal steroids and magnesium sulphate are the most important strategies to prevent cerebral palsy.

The social cost of chronic kidney disease in Italy.

This study aims to estimate the mean annual social cost per patient with chronic kidney disease (CKD) by stages 4 and 5 pre-dialyses and cost components in Italy. The multicenter cross-sectional study included all adult outpatients in charge of the 14 main Nephrology Centers of Tuscany Region during 7 weeks from 2012 to 2013. Direct medical costs have been estimated using tariffs for laboratory tests, diagnostic exams, visits, hospitalization and prices for drugs. Non-medical costs included expenses of low-protein special foods, travel, and formal and informal care. Patients' and caregivers' losses of productivity have been estimated as indirect costs using the human capital approach. Costs have been expressed in Euros (2016). Totals of 279 patients in stage 4 and 205 patients in stage 5 have been enrolled. The estimated mean annual social cost of a patient with CKD were €7422 (±€6255) for stage 4 and €8971 (±€6503) for stage 5 (p < 0.05). Direct medical costs were higher in stage 5 as compared to stage 4; direct non-medical costs and indirect costs accounted, respectively, for 41 and 5 % of the total social cost of CKD stage 4 and for 33 and 9 % of CKD stage 5. In Italy, the overall annual social cost of CKD was €1,809,552,398 representing 0.11 % of the Gross Domestic Product. Direct non-medical costs and indirect costs were weighted on the social cost of CKD almost as much as the direct medical cost. Patients, their families and the productivity system sustain the burden of the disease almost as much as the healthcare system.

Low 1-year cyclosporine microemulsion doses are associated with better 5-year renal graft function: an insight from MOST, a multinational observational study.

BACKGROUND: In earlier registry analyses, cyclosporine at doses of < 3 mg/kg/d at 1 year post-renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study-Neoral MOST. RESULTS: Glomerular filtration rate (GFR) at year 1 was 63 +/- 20 mL/min and 59 +/- 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age > 60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (<65 mL/min) included donor or recipient age >60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose <3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point. CONCLUSIONS: Compared to higher doses, CsA-ME <3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.