Mario Spaggiari

Pancreatic metastases from renal cell carcinoma：The state of the art

Pancreatic metastases are rare, with a reported incidence varying from 1.6% to 11% in autopsy studies of patients with advanced malignancy. In clinical series, the frequency of pancreatic metastases ranges from 2% to 5% of all pancreatic malignant tumors. However, the pancreas is an elective site for metastases from carcinoma of the kidney and this peculiarity has been reported by several studies. The epidemiology, clinical presentation, and treatment of pancreatic metastases from renal cell carcinoma are known from single-institution case reports and literature reviews. There is currently very limited experience with the surgical resection of isolated pancreatic metastasis, and the role of surgery in the management of these patients has not been clearly defined. In fact, for many years pancreatic resections were associated with high rates of morbidity and mortality, and metastatic disease to the pancreas was considered to be a terminal-stage condition. More recently, a significant reduction in the operative risk following major pancreatic surgery has been demonstrated, thus extending the indication for these operations to patients with metastatic disease.

Minimally Invasive Robotic Kidney Transplantation for Obese Patients Previously Denied Access to Transplantation

Epidemiological data indicate that 20-50% of patients on dialysis for end-stage renal disease (ESRD) are obese (body mass index [BMI] ≥30 kg/m2) (1). Obese patients with chronic renal failure have longer wait times until kidney transplantation (2) and inferior patient outcomes (3-7). In the US, for example, patients with a BMI 40 kg/m2 (2). Higher BMIs in kidney transplant recipients are associated with excess risk of surgical site infections (SSIs), which negatively impact graft survival (8). Obesity is also associated with comorbidities such as diabetes, although data on whether obesity increases mortality in kidney transplanted patients remains unclear (8,9). Provider perceptions of these risks accompanied by the expectation of some centers to give obese patients time to lose weight are the main reasons why a number of transplant centers are reluctant to list obese patients for transplantation (2,10). Unfortunately, many of these obese patients have diabetes and hypertension likely secondary to their obesity (11) and such patients who remain on dialysis have a very high mortality rate. The 5-year mortality rate for diabetic and hypertensive dialysis patients is 75 and 70%, respectively (1). A recent study demonstrated that obese patients who did not present with any SSIs had the same kidney transplant success rate as patients with a normal BMI (8). If surgical procedures could be developed that prevent SSIs and demonstrate successful outcomes, transplant centers may become less reluctant to list obese patients for kidney transplantation. Although any benefit would still have to be weighed against potential increased risks from obesity-related comorbidities. The prevalence of obesity and ESRD is higher among racial and ethnic minority populations, including African-Americans and Hispanics, compared to Non-Hispanic whites (12-15). These observations suggest developing kidney transplantation options for obese patients with ESRD may also help to reduce health disparities in racial and ethnic minorities. We therefore developed a new, minimally invasive, robotic-assisted kidney transplantation method using a short epigastric incision. This method avoids any incision in the infection prone lower quadrants of the abdomen. We hypothesized a priori that the robotic approach would reduce SSIs and improve outcomes in obese kidney transplant patients. Herein, we present our experience and outcomes of the patients undergoing minimal invasive, robotic kidney transplantation at a single institution compared to patients who underwent the conventional open procedure.

Robot‐assisted right lobe donor hepatectomy

Recent advances in robotic surgical technology have enabled application to complex surgical procedures. Following extensive institutional experience with major robotic liver resections, we determined that it was safe to apply this technology to right lobe donor hepatectomy (RLDH). The procedure was performed using the Da Vinci Robotic Surgical System, in an entirely minimally invasive fashion, during which the liver graft was safely extracted through a limited lower abdominal incision. Both donor and recipient recovered well, without acute complications. To our knowledge, this is the first case reported in the literature. The technical feasibility of this minimally invasive approach is demonstrated, exemplifying the novel exciting opportunities offered by robotic technology.

Long-term follow-up and outcome of liver transplantation from anti-hepatitis C virus-positive donors: a European multicentric case-control study.

Background. The growing prevalence of hepatitis C virus (HCV) infection in the general population has resulted in an increased frequency of potential organ donors that carry the virus. Given the significant disparity between organ supply and demand for transplantation, it becomes essential to consider whether livers from anti-HCV-positive donors may be considered suitable for transplantation. Methods. Based on a multicenter European database, 694 patients with HCV-related cirrhosis underwent liver transplantation and 11% of them received the graft from anti-HCV-positive donors. Of this group, we selected 63 patients (study group) and, after a 1:1 case-control approach, compared them with 63 patients that received an anti-HCV-negative donor graft (control group). Only grafts with preperfusion liver biopsy results with a fibrosis score of not more than 1 were used for transplantation. Results. Patients who received anti-HCV-positive grafts had a cumulative survival rate of 83.6% and 61.7% at 1 and 5 years, respectively, vs. 95.1% and 68.2% for the control group. In comparing overall patient and graft survival, there was no statistically significant difference between the two groups (P=0.22 and 0.11). Recurrence of hepatitis C tended to be more rapid in the group of patients who received anti-HCV-positive grafts, although it did not reach statistical significance (P=0.07). Conclusions. We do not recommend the indiscriminate use of anti-HCV-positive donors, especially if HCV-RNA positive, as the use of this kind of graft could be linked to an advanced stage of fibrosis, the main risk factor we observed for earlier hepatitis C recurrence.

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.

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.

The Use of Bortezomib as a Rescue Treatment for Acute Antibody-Mediated Rejection: Report of Three Cases and Review of Literature

Antibody-mediated rejection (AMR) typically occurs early after transplantation in approximately 5%-7% of recipients. The literature reports suggest that 12%-37% of kidney transplant recipients with acute AMR do not respond to treatment and eventually lose their grafts. The proteasome inhibitor bortezomib is currently approved by the Food and Drug Administration for the treatment of multiple myeloma. It has been demonstrated both in vitro and in vivo to possess apoptotic properties against mature plasma cells. Herein we have described a series of 3 patients with positive cross-matches who developed early AMR after kidney transplantation. Bortezomib rescue treatment was administered after the patients failed to respond to plasmapheresis/intravenous immunoglobulin and splenectomy. All 3 patients responded with full, durable recovery of renal function. In conclusion, bortezomib is useful to treat refractory AMR after kidney transplantation.

Effects of Everolimus Monotherapy on Hematological Parameters and Iron Homeostasis in De Novo Liver Transplant Recipients: Preliminary Results

INTRODUCTION Anemia after orthotopic liver transplantation (OLT) is a common complication due to several reasons. Immunosuppressive drugs play an important role in anemia occurring at 1 month or more after OLT. Several studies describe myelosuppression immunosuppressants such as the mammalian target of rapamycin inhibitors. METHODS We performed a single-center, prospective trial consisting of a short 30-day course of cyclosporine (CsA) associated with everolimus (EVL) from postoperative day 10 (Group EVL) versus a CsA immunosuppressive regimen (Group CsA) in de novo OLT patients. We explored the influence of immunosuppressive drugs on hematological parameters comparing EVL versus CsA. RESULTS Twenty-eight patients were enrolled in the EVL and 12 in the CsA Groups. After OLT, hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell (WBC), platelets (PLT), transferrin saturation (TSAT), iron, ferritin, and transferrin did not differ significantly between the 2 groups at any time point. Among the patients who reached 6-months of follow-up, 5 (41.7%) EVL and 4 (80%) CsA subjects were anemic (P=not significant [NS]). Only anemia in patients enrolled in Group EVL showed a trend toward the features of microcytic, hypochromic anemia. DISCUSSION Our results demonstrated that de novo anemia in OLT patients treated with EVL monotherapy showed the same incidence as in patients treated with CsA. Hb values remained similar during the entire follow-up. Moreover, overall myelosuppression in the EVL Group was not significantly different from patients in the CsA Group.

Multiple Ways to Manage Portal Thrombosis During Liver Transplantation: Surgical Techniques and Outcomes

BACKGROUND Portal vein thrombosis (PVT) is a well-recognized complication of chronic liver disease with a prevalence ranging from 1% to 16%. MATERIALS AND METHODS We performed a retrospective review of 447 consecutive patients who underwent liver transplantation (OLT) between October 2000 and December 2011 comparing 51 recipients with PVT (study group) with 399 without PVT (control group). The aim of this study was to determine the impact of pre-existent PVT on the surgical procedure, to identify specific preventable perioperative complications, and based on our studies and other works, to determine whether this group of patients are acceptable candidates for OLT. RESULTS Among the 51 patients with PVT, 44 showed partial and 7 complete thrombosis. In 47 cases, we performed a thromboendovenectomy. There were six anastomoses at the confluence of the superior mesenteric vein (SMV) and one, with a venous graft interposition. In four complete thrombosis recipients we performed an extra-anatomic by pass between the main trunk of the SMV and the donor portal vein. Compared with the control group, regarding preoperative characteristics, PVT patients were older at the time of transplantation (P = .001) and had a higher use of TIPS (P = .02). The operative characteristics showed a longer warm ischemia time in the PVT group (46.9 ± 22.5 vs 39.3 ± 15 min; P = .004). There were significant differences in postoperative evaluations, nor in the complication rates. Overall survivals at 10 years were similar: 61.7% versus 65.3%; (P = .9). CONCLUSION Although PVT was associated with greater operative complexity, it had no influence on postoperative complications or overall survival.

Cell population in spleens during antibody-mediated rejection: Pathologic and clinical findings

Background In the treatment of refractory antibody-mediated rejection (AMR), splenectomy has been associated with surprisingly rapid recovery of renal function. The mechanism is still unclear. Methods We review 11 recipients, who underwent rescue splenectomy (RS) as a treatment of AMR within 3 months after kidney transplantation. At transplantation, all patients had undergone desensitization for initially positive crossmatch to their prospective donors. The cellular populations of the spleen were analyzed by immunohistochemistry. For comparison, we obtained spleen specimens from eight controls who were nontransplantation patients. Results Rejection occurred in all the patients early after transplantation (mean [SD], 7.1 [5.7] days). One graft was lost 4 weeks after kidney transplantation. A significantly higher number of plasma cells (PCs) (P=0.049) and lower number of T and B lymphocytes (P=0.02 and P=0.005, respectively) were detected in the RS group compared with the control group. By analyzing the PC variations in the RS group, significantly lower numbers of PCs were detected in the spleens of patients who received rituximab before splenectomy (P=0.0004). In contrast, a higher number of PCs were found in patients (n=3) who did not respond to splenectomy and subsequently underwent bortezomib treatment and recovered their renal function (P=0.02). Conclusions Splenectomy may reverse AMR by debulking PCs. Our analysis suggests that patients with a very high load of PCs may not be rescued by splenectomy alone and may need additional treatments.