Stefano Di Sandro

First report on a series of HIV patients undergoing rapamycin monotherapy after liver transplantation.

Introduction. Some experimental trials have demonstrated that rapamycin (RAPA) is able to inhibit HIV-1 progression in three different ways: (1) reducing CCR5-gene transcription, (2) blocking interleukin-2 intracellular secondary messenger (mammalian target of rapamycin), and (3) up-regulating the β-chemokine macrophage inflammatory protein (MIP; MIP-1α and MIP-1β). We present the preliminary results of a prospective nonrandomized trial concerning the first HIV patient series receiving RAPA monotherapy after liver transplantation (LT). Methods. Since June 2003, 14 HIV patients have received cadaveric donor LT due to end-stage liver disease (ESLD) associated or not associated with hepatocellular carcinoma, scored by the model for ESLD system. Patients were assessed using the following criteria for HIV characterization: CD4 T-cell count more than 100/mL and HIV-RNA levels less than 50 copies/mL. Primary immunosuppression was based on calcineurin inhibitors (CI), whereas switch to RAPA monotherapy occurred in cases of CI complications or Kaposis sarcoma. Results. Mean overall post-LT follow-up was 14.8 months (range: 0.5–52.6). Six of 14 patients were administered RAPA monotherapy. Mean preswitch period from CI to RAPA was 67 days (range: 10–225 days). Mean postswitch follow-up was 11.9 months (range: 2–31 months). All patients were affected by ESLD, which was associated with hepatocellular carcinoma in seven patients. ESLD occurred due to hepatitis C virus (HCV)-related hepatopathy for nine patients, hepatitis B virus-related hepatopathy for one patient, and hepatitis B virus-HCV hepatopathy for four patients. Significantly better control of HIV and HCV replication was found among patients taking RAPA monotherapy (P=0.0001 and 0.03, respectively). Conclusions. After in vitro and in vivo experimental evidence of RAPA antiviral proprieties, to our knowledge, this is the first clinical report of several significant benefits in long-term immunosuppression maintenance and HIV-1 control among HIV positive patients who underwent LT.

Beyond the Milan criteria: what risks for patients with hepatocellular carcinoma progression before liver transplantation?

Background: To date the selection of the best candidates for liver transplantation (LT) owing to hepatocellular carcinoma (HCC) has been mainly based on tumor morphological characteristics (nodule diameter and number), which have resulted to be independent risk factors for short long-term survival and a high rate of tumor recurrence. Methods: The study cohort included 118 patients among the 166 with HCC transplanted at our unit from January 2000 to December 2007. Patients were classified according to response to locoregional treatments before LT: progressive Group A; complete Group B; partial Group C; stable Group D. Results: The 3-year and 5-year overall survival rates were 65.5% and 48.9% for Group A versus 84.8% and 74.6% for Group BCD (P=0.01). The 3-year and 5-year disease-free survival rates were 74% and 74% for Group A and 95.7% and 93% for Group BCD (P=0.007). HCC progression was the only independent risk factor according to Cox regression P=0.014 − odds ratio 4.4 (1.35−14.3). Conclusion: After aggressive HCC treatment before LT, imaging progression while on the waiting list was a strong predictor of high HCC recurrence rate also in patients who met the Milan criteria. Lack of imaging progression can contribute toward the selection of good transplant candidates for HCC together with the Milan criteria.

Liver Resection for Colorectal Metastases in Older Adults: A Paired Matched Analysis

To assess the safety and long‐term results of hepatic resection of colorectal liver metastases (CLM) in older adults.

Current status and perspectives in split liver transplantation

Growing experience with the liver splitting technique and favorable results equivalent to those of whole liver transplant have led to wider application of split liver transplantation (SLT) for adult and pediatric recipients in the last decade. Conversely, SLT for two adult recipients remains a challenging surgical procedure and outcomes have yet to improve. Differences in organ shortages together with religious and ethical issues related to cadaveric organ donation have had an impact on the worldwide distribution of SLT. Despite technical refinements and a better understanding of the complex liver anatomy, SLT remains a technically and logistically demanding surgical procedure. This article reviews the surgical and clinical advances in this field of liver transplantation focusing on the role of SLT and the issues that may lead a further expansion of this complex surgical procedure.

Successful donation after cardiac death liver transplants with prolonged warm ischemia time using normothermic regional perfusion

The role of donation after cardiac death (DCD) in expanding the donor pool is mainly limited by the incidence of primary nonfunction (PNF) and ischemia‐related complications. Even greater concern exists toward uncontrolled DCD, which represents the largest potential pool of DCD donors. We recently started the first Italian series of DCD liver transplantation, using normothermic regional perfusion (NRP) in 6 uncontrolled donors and in 1 controlled case to deal with the legally required no‐touch period of 20 minutes. We examined our first 7 cases for the incidence of PNF, early graft dysfunction, and biliary complications. Acceptance of the graft was based on the trend of serum transaminase and lactate during NRP, the macroscopic appearance, and the liver biopsy. Hypothermic machine perfusion (HMP) was associated in selected cases to improve cold storage. Most notably, no cases of PNF were observed. Median posttransplant transaminase peak was 1014 IU/L (range, 393‐3268 IU/L). Patient and graft survival were both 100% after a mean follow‐up of 6.1 months (range, 3‐9 months). No cases of ischemic cholangiopathy occurred during the follow‐up. Only 1 anastomotic stricture completely resolved with endoscopic stenting. In conclusion, DCD liver transplantation is feasible in Italy despite the protracted no‐touch period. The use of NRP and HMP seems to earn good graft function and proves safe in these organs. Liver Transplantation 23 166–173 2017 AASLD

Sequential Use of Normothermic Regional Perfusion and Hypothermic Machine Perfusion in Donation After Cardiac Death Liver Transplantation With Extended Warm Ischemia Time.

The great potential of donation after cardiac death (DCD) in expanding the liver donor pool is limited by the inferior results due to the ischemic injury.1 Normothermic regional perfusion (NRP) and hypothermic machine perfusion (HMP) can improve the transplantation outcome.2,3 These technologies may

Cystic Pancreatic Neuroendocrine Neoplasms with Uncertain Malignant Potential : Report of Two Cases

Neuroendocrine tumors of the pancreas (NETP) represent only 1%–2% of all pancreatic neoplasms. They can be classified as functioning or non-functioning, respectively, according to the presence or absence of paraneoplastic syndrome. Case 1 concerned a 70-year-old woman with a cystic lesion of the pancreatic head and body. All tumor markers were negative. The patient underwent a distal pancreatectomy. The histology revealed a well-differentiated endocrine tumor with uncertain malignant potential. Case 2 was a 61-year-old man with chronic polyserositis. The serum tumor markers were negative, while he was strongly positive for intracystic tumor markers carcinoembryonic antigen, carbohydrate antigen (CA) 19–9, and CA 125. The patient underwent a cephalo-pancreatic duodenectomy. The preoperative differential diagnosis of cystic NETP is still a challenge due to the high rate of the nonfunctional variant. Although cystic NETPs are well differentiated, they are still tumors with a malignant potential, and therefore an early diagnosis and radical surgical resection could be associated with a better long-term survival.

Donor safety in living donor liver donation: An Italian multicenter survey

Major concerns about donor morbidity and mortality still limit the use of living donor liver transplantation (LDLT) to overcome the organ shortage. The present study assessed donor safety in LDLT in Italy reporting donor postoperative outcomes in 246 living donation procedures performed by 7 transplant centers. Outcomes were evaluated over 2 time periods using the validated Clavien 5‐tier grading system, and several clinical variables were analyzed to determine the risk factors for donor morbidity. Different grafts were obtained from the 246 donor procedures (220 right lobe, 10 left lobe, and 16 left lateral segments). The median follow‐up after donation was 112 months. There was no donor mortality. One or more complications occurred in 82 (33.3%) donors, and 3 of them had intraoperative complications (1.2%). Regardless of graft type, the rate of major complications (grade ≥ 3) was 12.6% (31/246). The overall donor morbidity and the rate of major complications did not differ significantly over time: 26 (10.6%) donors required hospital readmission throughout the follow‐up period, whereas 5 (2.0%) donors required reoperation. Prolonged operative time (>400 minutes), intraoperative hypotension (systolic < 100 mm Hg), vascular abnormalities, and intraoperative blood loss (>300 mL) were multivariate risk factors for postoperative donor complications. In conclusion, from the standpoint of living donor surgery, a meticulous and well‐standardized technique that reduces operative time and prevents blood loss and intraoperative hypotension may reduce the incidence of donor complications. Transparency in reporting results after LDLT is mandatory, and we should continue to strive for zero donor mortality. Liver Transplantation 23 184–193 2017 AASLD

Evolution of robotic nephrectomy for living donation: From hand-assisted to totally robotic technique

The application of robotic‐assisted surgery offers EndoWrist instruments and 3‐D visualization of the operative field, which are improvements over traditional laparoscopy. The results of the few studies published so far have shown that living donor nephrectomy using the robot‐assisted technique is safe, feasible, and offers advantages to patients.

Sirolimus monotherapy effectiveness in liver transplant recipients with renal dysfunction due to calcineurin inhibitors.

Introduction Among the adverse effects of different calcineurin inhibitors (CIs), nephrotoxicity is the most common (incidence: 18.1% at 13 y from liver transplantation) and depends on a variable degree of tubular-interstitial injury accompanied by focal glomerular sclerosis. A new immunosuppressive drug was introduced in solid organ transplant management, Sirolimus (SRL). It is a non-nephrotoxic immunosuppressor. Methods Twenty-six patients who developed nephrotoxicity owing to CIs, showing an increment of serum creatinine levels (>1.8 mg/dL) were switched to SRL monotherapy, initially at a dosage between 3 and 5 mg/d, and subsequently adapted to achieve trough level between 8 to 10 ng/mL. Results Patients were followed-up for a mean period of 40.3 months (range, 8.4 to 76.7) from liver transplantation. Mean follow-up after switch was 27.5 months (range, 2 to 71.2). Immunosuppression therapy was converted after a mean period of 12.8 months (range, 0.2 to 43.4). Serum creatinine, urea, and estimated glomerular filtration rate were significantly improved. Discussion Patients developing renal dysfunction after liver transplantation may be successfully treated by conversion from CI to SRL. Hypertriglyceridemia and hypercholesterolemia represent the principal side effects from SRL, but are treatable. Furthermore, SRL can significantly improve glucose tolerance.