Successful Sequential Liver and Isolated Intestine Transplantation for Mitochondrial Neurogastrointestinal Encephalopathy Syndrome: A Case Report.

BACKGROUND Mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE) is an autosomal recessive disease caused by thymidine phosphorylase deficiency leading to progressive gastrointestinal dysmotility, cachexia, ptosis, ophthalmoparesis, peripheral neuropathy and leukoencephalopathy. Although liver transplantation corrects thymidine phosphorylase deficiency, intestinal deficiency of the enzyme persists. Retrospective chart review was carried out to obtain clinical, biochemical, and pathological details. CASE REPORT We present a case of liver and subsequent intestine transplant in a 28-year-old man with MNGIE syndrome with gastrointestinal dysmotility, inability to walk, leukoencephalopathy, ptosis, cachexia, and elevated serum thymidine. To halt progression of neurologic deficit, he first received a left-lobe partial liver transplantation. Although his motor deficit improved, gastrointestinal dysmotility persisted, requiring total parenteral nutrition. After exhaustive intestinal rehabilitation, he was listed for intestine transplantation. Two-and-half years after liver transplantation, he received an intestine transplant. At 4 years after LT and 20 months after the intestine transplant, he remains off parenteral nutrition and is slowly gaining weight. CONCLUSIONS This is the first reported case of mitochondrial neurogastrointestinal encephalomyopathy to undergo successful sequential liver and intestine transplantation.

Deceased Donor Flush Volume Similar for Histidine-Tryptophan-Ketoglutarate and University of Wisconsin at a Single US Organ Procurement Organization: Adult and Pediatric Data.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solutions are the two primary solid-organ preservation solutions used in the United States (>95%), but flush volumes vary markedly by region and center. This study analyzes data from a single organ procurement organization (OPO) to determine the actual clinical flush volumes used for HTK and UW for liver and pancreas grafts. METHODS: All procurements at Indiana Donor Network were analyzed (2016-2020), and data were extracted from the on-site records. Variables included procuring center, solution, volumes, and vessels flushed. Brand and generic versions were considered equivalent. No clinical transplant outcomes were available. RESULTS: Data were analyzed from 875 liver and 192 pancreas procurements by over 70 U.S. centers representing 10 of 11 UNOS regions. The large majority of liver grafts were preserved with HTK (n=810, 93%; UW n=93, 7%). All liver donors received an aortic flush (100%), while portal vein flush was 14% in-situ and 88% back table. For liver grafts, the median volume of infused solution was less for HTK when compared to UW (4225mL vs 5500mL, p=0.04). For pancreas procurement, 100% received aortic flush of the graft, with median HTK and UW volumes being equivalent (3000mL; p=0.85). Pediatric organs were flushed with markedly higher weight-based volumes. CONCLUSIONS: Flush volumes for HTK and UW are similar at one midwestern OPO, with data comprised of procurements performed by centers from across the U.S. These data demonstrate that low-volume HTK flush is commonly used, and this practice may be considered as a cost-saving measure.

Adenovirus-Related Fulminant Liver Failure After Kidney Transplantation.

BACKGROUND Human adenovirus is a well-known pathogen that can potentially lead to severe infection in immunocompromised patients. Adenovirus infections in solid-organ transplant recipients can range from asymptomatic to severe, prolonged, disseminated disease, and have a significant impact on morbidity, mortality, and graft survival. The clinical manifestations vary from asymptomatic and flu-like illness to severe life-threatening viremia with multi-organ failure. Post-transplant adenovirus infection is well described in kidney recipients, but in adult liver transplant recipients the impact of the virus is not well described. In this report, a case of disseminated adenovirus infection with subsequent fatal acute liver failure in a post-kidney transplant patient is presented. CASE REPORT A 51-year-old man underwent a deceased kidney transplantation for focal segmental glomerulosclerosis. Shortly after the kidney transplantation, he received multiple plasmapheresis with additional steroid treatments for cellular rejection and reoccurrence of his primary kidney disease. Three weeks after the kidney transplant, he developed a disseminated adenovirus infection with subsequent acute liver failure. Despite the early diagnosis and aggressive treatment, the patient died. CONCLUSIONS Patients with organ transplantation with autoimmune background etiology are usually over-immunosuppressed to avoid early rejection. In this population, opportunistic infections are not rare. Fever, general malaise, and transplant organ dysfunction are the first signs of bacterial or viral infection. Early infectious diseases work-up, including tissue biopsy, is fundamental to establish a diagnosis. Broad antibiotic and possible antiviral aggressive treatment are mandatory.

Combined liver-kidney transplantation with positive crossmatch: Role of delayed kidney transplantation.

BACKGROUND: Positive crossmatch (XM+) combined liver-kidney transplantation due to preformed donor-specific human leukocyte antigen antibodies has produced mixed results. We sought to understand the role of delayed kidney transplant approach in XM+ combined liver-kidney transplantations. METHODS: XM+ combined liver-kidney transplantations were retrospectively reviewed. T- and B-cell XM, complement-dependent cytotoxic crossmatch, and flow cytometric crossmatch were performed prospectively. RESULTS: Of 183 combined liver-kidney transplantations performed (2002-2019), 114 (62%) were with "delayed" kidney transplant approach and 19 (19 of 183, 10%) were XM+. Of 19 XM+ combined liver-kidney transplantations, kidney transplant was "delayed" in 14 by an average of 47 hours (range 24-64 hours) from liver transplant. There was a significant reduction in both class I (mean pre-liver transplant mean fluorescence intensity (MFI) 26,230 versus mean post-liver transplant and pre-delayed kidney transplant MFI 3,272, P = .01) and total MFI (mean pre-liver transplant MFI 27,233 vs mean post liver transplant and predelayed kidney transplant MFI 11,469, P = .01). However, there was no significant change in the MFI of class II donor-specific antibodies (mean pre-liver transplant MFI 17,899 versus post-liver transplant and pre-delayed kidney transplant MFI 14,341, P = .19). None of XM+ delayed kidney transplants had delayed graft function, and there was no antibody-mediated rejection. One-year patient survival for the XM+ combined liver-kidney transplantation with delayed kidney transplant approach was 92.9%, which is comparable to patient survival of XM- combined liver-kidney transplantation. Whereas patient survival in recipients before "delayed" approach ("simultaneous"; n = 5) was 40% when liver-kidney transplants were performed simultaneously (P = .06). CONCLUSION: In sensitized combined liver-kidney transplantation recipients, the "delayed" kidney transplant approach is associated with a significant reduction in total and class I donor-specific antibodies after liver transplant before kidney transplant, enabling therapeutic interventions such as plasmapheresis, if needed, providing optimal outcomes similar to crossmatch recipients.

Oncologic indications of liver transplantation and deceased donor liver allocation in the United States.

PURPOSE OF REVIEW: Liver transplantation is a standard therapy for certain liver cancers. The majority of liver transplantation in the United States is through deceased donor liver transplantation (DDLT). A significant disparity between the demand of livers and patients awaiting liver transplantation still remains, relying on United Network for Organ Sharing (UNOS) to make policies to determine priority amongst recipients, including for patients with liver cancer. We review the scope of liver transplantation in patients with liver cancer with a focus on hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and unresectable colorectal liver metastases (CRLM) with respect to current liver allocation policy. RECENT FINDINGS: Recently, liver allocation changed in the United States. Under the current allocation policy, select patients with HCC and hilar CCA (hCCA) receive priority with an exception score of median MELD score at transplant (MMAT)-3. There is scope for other liver cancers, such as iCCA and CRLM to be considered, as reasonable outcomes have been achieved in these patients outside of the United States through DDLT and living donor liver transplantation (LDLT). SUMMARY: With the growing experience of liver transplantation for nonconventional oncologic indications, the current policy for prioritization of liver cancer within deceased donor liver allocation may need to be re-evaluated.

Tracheostomy Post Liver Transplant: Predictors, Complications, and Outcomes.

BACKGROUND Liver transplant (LT) patients have an increased risk of postoperative respiratory failure requiring tracheostomy. This study sought to characterize objective clinical predictors of tracheostomy. MATERIAL AND METHODS The records for 2017 LT patients at a single institution were reviewed. Patients requiring tracheostomy were first compared with all other patients. A case-control subgroup analysis was conducted in which 98 tracheostomy patients were matched with 98 non-tracheostomy LT patients. For the case-control study, muscle mass was assessed using preoperative computed tomography scans. RESULTS Among 2017 LT patients, 98 required tracheostomy (5%), with a 19% complication rate. Tracheostomy patients were older and had a higher model for end-stage liver disease score, a lower body mass index (BMI), and a greater smoking history. Tracheostomy patients had a longer hospital stay (45 vs. 10 days, P<0.001) and worse 1-year survival (65% vs. 91%, P<0.001). Ten-year Cox regression patient survival for tracheostomy patients was significantly worse (32% vs. 68%, P<0.001). In the case-control analysis, respiratory failure patients were older (P<0.01) and had a lower BMI (P=0.05). They also had a muscle mass deficit of -39% compared with matched LT controls (P<0.001). No significant differences were seen with pre-LT total protein or albumin or with forced expiratory volume in 1 s divided by forced vital capacity (FEV1/FVC) values. CONCLUSIONS Predictors for respiratory failure requiring post-LT tracheostomy include higher model for end-stage liver disease score, older age, lower BMI, greater smoking history, and worse sarcopenia. Patients requiring tracheostomy have dramatically longer hospital stays and worse survival.

Complex Abdominal Wound Healing After Multivisceral Retransplant: A Case Report on the Importance of Nutrition.

BACKGROUND: Intestinal transplantation (ITx) is performed as an isolated ITx or as a part of multivisceral transplantation for intestinal failure secondary to short gut syndrome, inflammatory bowel disease, trauma, and sequelae of chronic parenteral nutrition dependence. Wound complications after ITx are very common, and abdominal wound closure cannot be immediately achieved in half of cases. CASE PRESENTATION: A 25-year-old man sustained an abdominal crush injury causing complete loss of his small intestine, requiring an isolated ITx in March 2016. He lost his graft because of early exfoliative rejection in November 2016. Five months after enterectomy and the immunosuppression-free period, he underwent multivisceral retransplantation in April 2017. His post-transplant course was complicated by wound healing problems that improved with treatment of his malnutrition, quantified by increasing albumin, total protein, prealbumin, weight, body mass index, and total psoas muscle area over a period of 19 months after retransplant. CONCLUSION: To our knowledge, this is the first case described of long-term wound follow-up after a multivisceral (re)transplantation, with corresponding nutrition information and images of the wound.

Recurrence of Hyperoxaluria and Kidney Disease after Combined Intestine-Kidney Transplantation for Enteric Hyperoxaluria.

BACKGROUND: Enteric hyperoxaluria (EH) occurs with a rate of 5-24% in patients with inflammatory bowel disease, ileal resection and modern bariatric surgery. The excessive absorption of calcium oxalate causes chronic kidney disease (CKD) in patients with EH. In the literature, a single experience was reported in combined intestine-kidney transplantation (CIKTx) in patients with CKD due to EH. METHODS: After a report of 2 successful cases of CIKTx in patients with EH and CKD, one was performed at our center in a 59-year-old Caucasian female who developed intestinal failure with total parenteral nutrition (TPN) dependence after a complication post-bariatric surgery. Before CIKTx, she underwent kidney transplantation alone (KTA) twice, which failed due to oxalate nephropathy. RESULTS: In July 2014, the patient underwent CIKTx and bilateral allograft nephrectomy to avoid EH and oxalate stone burden. The postoperative course was complicated with acute tubular necrosis due to the use of high pressors related to perioperative bleeding. The patient was discharged 79 days after CIKTx with a serum creatinine (sCr) of 1.2 mg/dl and free of TPN. Her sCr increased at 7 months and a renal biopsy showed oxalate nephropathy. SLC26A6 (oxalate transporter) staining was significantly diminished in native duodenum/rectum as well as in intestinal allograft compared to control. CONCLUSIONS: KTA in patients with CKD secondary to EH should not be recommended due to high risk of recurrence. Although other centers showed good long-term outcomes in CIKTx, our patient experienced recurrence of EH due to oxalate transporter defect, early kidney allograft dysfunction and prolonged antibiotic use.

Survival after Liver Transplant: Influence of Progression of Disease and of Restoration of the "Milan" Criteria in Patients with Hepato-cellular Carcinoma undergoing Down-staging Procedures.

BACKGROUND/AIMS: Selection of patients with hepa- to-cellular carcinoma for liver transplantation is gen- erally performed according to the so-called Milan cri- teria. The aim of this study was to learn whether, after down-staging loco-regional therapies, patients origi- nally non-fulfilling the MC (Milan-OUT) meet these criteria (Milan-IN). METHODOLOGY: Between January 2000 and December 2008, 172 patients with HCC re- ceived LT at our Department. Of these, 142 were sub- jected to DS before LT. RESULTS: Of the 142 patients who received DS, 115 (81%) were Milan-IN and 27 (19%) were Milan-OUT at the time of their enrollment in the waiting list for LT. After a median follow-up of 50 months, overall 1-, 3-, and 5-year survival and dis- ease recurrence-free survival were not significantly different. CONCLUSIONS: Patients with Milan-OUT HCC can be successfully subjected to LT when they fulfill the MC after being subjected to DS. Imaging progres- sion while on the waiting list is a strong predictor of high rates of HCC recurrence even in patients meet- ing the MC. Lack of imaging progression seems to be a strong predictor of positive LT outcome and should be added to the eligibility criteria for the assessment of LT candidates with HCC.

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

BACKGROUND: 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. MATERIALS AND METHODS: Since November 2009, 16 patients have undergone robotic-assisted living donor nephrectomy at our Institute. Patients were divided into two groups according to the surgical technique adopted for the procedure: Group A, hand-assisted robotic nephrectomy (eight patients); Group B, totally robotic nephrectomy (eight patients). RESULTS: Intra-operative bleeding was similar in the two groups (90 vs 100 mL for Group A and B, respectively). Median warm ischemia time was significantly shorter in Group A (2.3 vs 5.1 min for Group A and B, respectively, P-value = 0.05). Switching to the open procedure was never required. Median operative time was not significantly longer in Group A than Group B (275 min vs 250 min, respectively). CONCLUSION: Robotic assisted living kidney recovery is a safe and effective procedure. Considering the overall technical, clinical, and feasibility aspects of living kidney donation, we believe that the robotic assisted technique is the method of choice for surgeon's comfort and donors' safety.

Liver transplantation for hepatocellular carcinoma recurrence after liver resection: why deny this chance of cure?

INTRODUCTION: Liver transplantation (LT) after liver resection (LR) for hepatocellular carcinoma (HCC) recurrence may be associated with poor patient long-term results and higher perioperative patient morbidity and mortality. This study focused on short-term and long-term outcomes of LT recipients due to HCC recurrence after LR in a single-institution cohort, and in highly comparable case-matched subgroups. METHODS: Between 2000 and 2009, 570 consecutive patients with documented HCC underwent LR (n=355, 62.2%) or LT (n=215, 37.8%) at our Institute. The case-matched analysis was between 2 groups: group A1, LT recipients who had already undergone LR (n=26); group B1, LT recipients who had not already undergone LR (n=26). RESULTS: Patient morbidity was higher in the A1 group in terms of packed red blood cell units transfused, fresh frozen plasma units transfused, median operative time, postoperative bleeding, and postoperative reoperations. No differences were detected in terms of patient mortality, patient survival, and patient recurrence-free survival at the univariate and multivariate analysis. CONCLUSIONS: Although LT among patients who have already undergone LR is associated with higher risk of patient morbidity, patient long-term survival and recurrence-free survival is not impaired. Therefore, there do not seem to be any valid reasons to deny the chance of LT to patients who have already undergone LR.

Living donor liver transplantation for hepatocellular carcinoma: the impact of neo-adjuvant treatments on the long term results.

BACKGROUND/AIMS: LDLT may represent a valid therapeutic option allowing several advantages for patients affected by HCC and waiting for liver transplantation (LT). However, some reports show a worse long term survival and disease free survival among patients treated by LDLT for HCC than deceased donor liver transplantation (DDLT) recipients. METHODOLOGY: Among 1145 LT patients, 63 received LDLT. From January 2000 to December 2008, 179 patients underwent LT due to HCC, 30 (16.7%) received LDLT and 154 (86.0%) received DDLT. Patients were selected based on the Milan criteria. TACE, radiofrequency ablation, percutaneous alcoholization, or liver resection were applied as downstaging procedures, while on the waiting list. RESULTS: Overall 3- and 5-year survival rate was 77.3% and 68.7% vs. 82.8% and 76.7%, respectively for LDLT and DDLT recipient with not significant differences. Moreover, 3- and 5- years of recurrence free survival rate was 95.5% (LDLT) vs. 90.5% and 89.4% (DDLT) and resulted not significantly different. CONCLUSIONS: LDLT guarantees same long term results than DDLT if the selection criteria of candidates are analogues. Milan criteria remains a valid candidate selection tool to obtain optimal long term results in LDLT. An aggressive downstaging policy seems to improve the long-term results in LDLT, thus LRT may be considered useful to prevent tumor progression waiting for transplantation as well as a neoadjuvant therapy for HCC. A literature detailed meta-analysis could definitely clarify if LDLT is an independent risk factor for HCC recurrence.

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.

Atypical presentation of pioderma gangrenosum complicating ulcerative colitis: rapid disappearance with methylprednisolone.

Pioderma gangrenosum (PG) is an uncommon ulcerative cutaneous dermatosis associated with a variety of systemic diseases, including inflammatory bowel disease (IBD), arthritis, leukaemia, hepatitis, and primary biliary cirrhosis. Other cutaneous ulceration resembling PG had been described in literature. There has been neither laboratory finding nor histological feature diagnostic of PG, and diagnosis of PG is mainly made based on the exclusion criteria. We present here a patient, with ulcerative colitis (UC) who was referred to the emergency section with a large and rapidly evolving cutaneous ulceration. Laboratory and microbiological investigation associated with histological findings of the ulcer specimen allowed us to exclude autoimmune and systemic diseases as well as immuno-proliferative disorders. An atypical presentation of PG with UC was diagnosed. Pulse boluses of i.v. methyl-prednisolone were started, and after tapering steroids, complete resolution of the skin lesion was achieved in 3 wk. The unusual rapid healing of the skin ulceration with steroid mono-therapy and the atypical cutaneous presentation in this patient as well as the risk of misdiagnosis of PG in the clinical practice were discussed.