Long term outcomes of abdominal wall reconstruction using open component separation and biologic mesh in the liver, kidney, and small bowel transplant population.

PURPOSE: The aim of this study is to critically examine the multidisciplinary approach to abdominal wall reconstruction (AWR) in the solid organ transplant (SOT) population at our institution, MedStar Georgetown University Hospital, using a modified component separation technique (CST). METHODS: A retrospective review of AWR utilizing modified open CST with biologic mesh in SOT patients was performed from January 2010 to June 2018. Patient demographics, comorbidities, operative details, complications, and outcomes were recorded. Descriptive statistics, logistic and linear regression analyses were performed to appraise outcomes. RESULTS: Thirty-five patients were included; mean age was 53 years. Patient demographics and comorbidities were: 82.9% male, 45.7% history of tobacco use, and 28.6% diabetes. Fifty-one percent had undergone prior hernia repair. Transplant types were: kidney (9), liver (16), liver/kidney (1), small bowel (7), multivisceral (2). All were on an immunosuppressive regimen at time of surgery; 22.9% included steroids. Average defect size was 361 cm2. Additional soft tissue procedures were performed in 65.7% (n = 23) of patients. Median time to healing was 29.0 days. Complication rate was 31.4% (n = 11); six patients required reoperation within 90 days. Recurrence rate was 5.7% (n = 2) at mean of follow up of 3.0 years. Additional soft tissue procedures were statistically significant for healing time (p = 0.037). Steroid use was statistically significant for reoperation within 90 days (OR = 12.500; 95% CI 1.694-92.250); however, steroid use was not significant after correction for confounders. CONCLUSION: Modified open CST with biologic mesh is a safe, efficacious approach to complex AWR in the SOT population with recurrence rates comparable to the general population.

Multi-Visceral Transplantation in a 21-Year-Old Man with Prior Pancreatoblastoma.

Organ transplantation in patients with prior malignancy increases the risk of tumor recurrence post-transplantation due to immunosuppression. Only two cases of liver transplantation have so far been reported in children with hepatic metastases from pancreatoblastoma, a rare malignant neoplasm originating from the epithelial exocrine cells of the pancreas. Herein, we describe a case of a successful multi-visceral transplant in a man with intestinal failure after surgical resection of pancreatoblastoma.

Hospital Readmissions After Intestinal and Multivisceral Transplantation.

BACKGROUND: Intestinal transplant recipients require frequent hospital readmission after a successful transplantation, but the reasons for readmission have not been characterized in detail. METHODS: We reviewed our single-center experience to characterize the patterns of readmissions and to identify preventable causes. Among 87 adult patients who received an intestinal or multivisceral transplant, 65 patients (35 males, 30 females; median age, 42 years [range, 19-66]) with a follow-up of at least 1 year were included in this study. Readmissions were defined as any unplanned inpatient hospital stay of 24 hours or longer occurring within 1 year after discharge from the transplantation admission and were classified as early (<1 month) and late (months 2-12) readmissions. RESULTS: Forty-four (68%) patients required early, and 59 (91%) patients required late readmission. A total of 333 readmissions (median, 4 readmissions/patient [0-20]) occurred within the first year post-transplantation; 69 were early (21%) and 264 were late (79%), resulting in a total of 4089 days of hospital stay (median, 7 days/readmission [2-136]). The three most frequent causes of readmission were dehydration, infection, and surgical complications. CONCLUSIONS: These findings suggest that the rate of hospital readmission after intestinal transplantation could potentially be reduced by optimizing fluid balance and hydration status after discharge.

Developing trends in the intestinal transplant waitlist.

The United Network for Organ Sharing database was examined for trends in the intestinal transplant (ITx) waitlist from 1993 to 2012, dividing into listings for isolated ITx versus liver-intestine transplant (L-ITx). Registrants added to the waitlist increased from 59/year in 1993 to 317/year in 2006, then declined to 124/year in 2012; Spline modeling showed a significant change in the trend in 2006, p < 0.001. The largest group of registrants, <1 year of age, determined the trend for the entire population; other pediatric age groups remained stable, adult registrants increased until 2012. The largest proportion of new registrants were for L-ITx, compared to isolated ITx; the change in the trend in 2006 for L-ITx was highly significant, p < 0.001, but not isolated ITx, p = 0.270. New registrants for L-ITx, <1 year of age, had the greatest increase and decrease. New registrants for isolated ITx remained constant in all pediatric age groups. Waitlist mortality increased to a peak around 2002, highest for L-ITx, in patients <1 year of age and adults. Deaths among all pediatric age groups awaiting L-ITx have decreased; adult L-ITx deaths have dropped less dramatically. Improved care of infants with intestinal failure has led to reduced referrals for L-ITx.

Isolated peritoneal donor-related plasmacytoma 3 years after liver transplantation: a case report.

Organ transplantation carries a risk of disease transmission from donor to recipient, primarily infection or malignancy. Although donors are thoroughly screened, donor-related malignancies are reported to occur in 0.01% of solid organ transplants. Plasma cell neoplasm, to the best of our knowledge, has not been reported as a donor-transmitted malignancy in liver transplantation. We describe a liver transplant from a donor with unrecognized plasmacytoma requiring retransplantation. Three years after the first transplant a single peritoneal mass was detected on surveillance imaging and radically excised; HLA phenotyping confirmed the mass to be an isolated extra-medullary plasmacytoma of chimeric donor and recipient origin.

Computed tomography (CT) colonography with CT arteriography and venography for the workup of intestinal transplant candidates.

Prior to intestinal transplantation, prospective candidates must undergo a series of radiologic examinations to address a variety of clinical issues. To date, little literature exists to guide physicians in this preoperative assessment. Multiple imaging studies can provide overlapping information. We have developed a simple two- or three-test protocol to streamline the workup. Sixteen adult patients presented as potential intestinal transplant candidates to Georgetown University Hospital. All but two patients underwent the full protocol of a biphasic IV contrast-enhanced computed tomography (CT) scan of the chest, abdomen, and pelvis with rectal carbon dioxide, an upper gastrointestinal study with small bowel follow through, and fistulogram when appropriate. Three-dimensional (3-D) reconstructions of the vascular anatomy as well as the colon were also generated. A telephone survey to other transplant centers was additionally conducted to compare radiographic evaluations. Overall, 15 of the 16 scans were diagnostic. One patient required a barium enema. Mean examinations per patient was 2.4. Only one of seven other centers was performing CT colonography in prospective intestinal transplant candidates. Our protocol provided all the necessary anatomic information needed to evaluate prospective transplant candidates. CT colonography with angiography is a suitable alternative to more time-consuming radiological studies.

Successful isolated intestinal transplantation in sensitized recipients with the use of virtual crossmatching.

We evaluated virtual crossmatching (VXM) for organ allocation and immunologic risk reduction in sensitized isolated intestinal transplantation recipients. All isolated intestine transplants performed at our institution from 2008 to 2011 were included in this study. Allograft allocation in sensitized recipients was based on the results of a VXM, in which the donor-specific antibody (DSA) was prospectively evaluated with the use of single-antigen assays. A total of 42 isolated intestine transplants (13 pediatric and 29 adult) were performed during this time period, with a median follow-up of 20 months (6-40 months). A sensitized (PRA ≥ 20%) group (n = 15) was compared to a control (PRA < 20%) group (n = 27) to evaluate the efficacy of VXM. With the use of VXM, 80% (12/15) of the sensitized patients were transplanted with a negative or weakly positive flow-cytometry crossmatch and 86.7% (13/15) with zero or only low-titer (≤ 1:16) DSA. Outcomes were comparable between sensitized and control recipients, including 1-year freedom from rejection (53.3% and 66.7% respectively, p = 0.367), 1-year patient survival (73.3% and 88.9% respectively, p = 0.197) and 1-year graft survival (66.7% and 85.2% respectively, p = 0.167). In conclusion, a VXM strategy to optimize organ allocation enables sensitized patients to successfully undergo isolated intestinal transplantation with acceptable short-term outcomes.

Metabolomics of human intestinal transplant rejection.

Surveillance endoscopy with biopsy is the standard method to monitor intestinal transplant recipients but it is invasive, costly and prone to sampling error. Early noninvasive biomarkers of intestinal rejection are needed. In this pilot study we applied metabolomics to characterize the metabolomic profile of intestinal allograft rejection. Fifty-six samples of ileostomy fluid or stool from 11 rejection and 45 nonrejection episodes were analyzed by ultraperformance liquid chromatography in conjunction with Quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS). The data were acquired in duplicate for each sample in positive ionization mode and preprocessed using XCMS (Scripps) followed by multivariate data analysis. We detected a total of 2541 metabolites in the positive ionization mode (mass 50-850 Daltons). A significant interclass separation was found between rejection and nonrejection. The proinflammatory mediator leukotriene E4 was the metabolite with the highest fold change in the rejection group compared to nonrejection. Water-soluble vitamins B2, B5, B6, and taurocholate were also detected with high fold change in rejection. The metabolomic profile of rejection was more heterogeneous than nonrejection. Although larger studies are needed, metabolomics appears to be a promising tool to characterize the pathophysiologic mechanisms involved in intestinal allograft rejection and potentially to identify noninvasive biomarkers.

Preemptive kidney transplantation in systemic lupus erythematosus.

Preemptive kidney transplantation is associated with superior outcomes. Patients who have kidney failure due to systemic lupus erythematosus (SLE) may not receive a preemptive kidney transplant because of the concern for risk of disease recurrence with shortened graft and patient survival. We identified 8001 patients in the United Network for Organ Sharing dataset who underwent kidney transplantation between October 1987 and February 2009 with kidney failure due to SLE. Seven hundred thirty patients received a preemptive kidney transplant with 7271 patients who were on dialysis before transplantation; their mean ages were 40.0±11.6 years and 36.9±11.7 years, respectively, (P<.01). Women constituted 82.5% of preemptive and 81.4% of non-preemptive groups (P=.47). Preemptive transplant recipients were more likely to receive a living donor kidney transplant (odds ratio [OR]=3.6; 95% confidence interval [CI]=3.3-4.5; P<.01). In unadjusted analyses, preemptive transplantation was associated with lower risk of recipient death (hazard ratio [HR]=0.52; 95% CI=0.38-0.70; P<.01). The difference remained significant after adjustment fr covariates (HR=0.55; 95% CI=0.36-0.84; P<.01). Graft survival was also superior among preemptive kidney transplant recipients in both unadjusted (HR=0.56; 95% CI=0.49-0.68; P<.01), and adjustment analyses (HR=0.69; 95% CI=0.55-0.86; P<.01). We concluded that preemptive kidney transplantation among patients with SLE was associated with superior patient and graft outcomes and should be considered when feasible.

Complex arterial reconstruction in multivisceral transplantation.

We report the case of a successful multivisceral transplant in which both donor and recipient presented aberrant anatomy of the celiac-mesenteric axis requiring five separate arterial anastomoses to reconstruct the blood inflow to the graft.

Calculation of the local optical density of states in absorbing and gain media.

The local optical density of states plays a key role in a wide range of phenomena. Near to structures displaying optical absorption or gain, the definition of the photonic local density of states needs to be revised. In this case two operative different definitions can be adopted to characterize photonic structures. The first (ρ(A)(r, ω)) describes the light intensity at a point r when the material system is illuminated isotropically and corresponds to what can be measured by a near-field microscope. The second (ρ(B)(r, ω)) gives a measure of vacuum fluctuations and coincides with ρ(A)(r, ω) in systems with real susceptibility. Scattering calculations in the presence of dielectric and metallic nanostructures show that these two definitions can give rather different results, the difference being proportional to the thermal emission power of the photonic structure. We present a detailed derivation of this result and numerical calculations for nanostructures displaying optical gain. In the presence of amplifying media, ρ(B)(r, ω) displays regions with negative photon densities, thus failing in describing a power signal. In contrast, ρ(A)(r, ω), positive definite, properly describes the near-field optical properties of these structures.

Monocyte infiltration and kidney allograft dysfunction during acute rejection.

Multiple cell types infiltrate acutely rejecting renal allografts. Typically, monocytes and T cells predominate. Although T cells are known to be required for acute rejection, the degree to which monocytes influence this process remains incompletely defined. Specifically, it has not been established to what degree monocytes impact the clinical phenotype of rejection or how their influence compares to that of T cells. We therefore investigated the relative impact of T cells and monocytes by correlating their presence as measured by immunohistochemical staining with the magnitude of the acute change in renal function at the time of biopsy in 78 consecutive patients with histological acute rejection. We found that functional impairment was strongly associated with the degree of overall cellular infiltration as scored using Banff criteria. However, when cell types were considered, monocyte infiltration was quantitatively associated with renal dysfunction while T-cell infiltration was not. Similarly, renal tubular stress, as indicated by HLA-DR expression, increased with monocyte but not T-cell infiltration. These data suggest that acute allograft dysfunction is most closely related to monocyte infiltration and that isolated T-cell infiltration has less acute functional impact. This relationship may be useful in assigning acute clinical relevance to biopsy findings.

Segmental liver transplantation from non-heart beating donors--an early experience with implications for the future.

We report our experience of pediatric liver transplantation with partial grafts from non-heart beating donors (NHBD). Controlled donors less than 40 years of age with a warm ischemia time (WI) of less than 30 min were considered for pediatric recipients. Death was declared 5 min after asystole. A super-rapid recovery technique with aortic and portal perfusion was utilized. Mean donor age was 29 years and WI 14.6 min (range 11-18). Seven children, mean age 4.9 years (0.7-11), median weight 20 kg (8.4-53) received NHBD segmental liver grafts. Diagnoses included seronegative hepatitis, neonatal sclerosing cholangitis, familial intrahepatic cholestasis, hepatoblastoma, primary hyperoxaluria and factor VII deficiency (n=2). The grafts included four reduced and one split left lateral segments, one left lobe and one right auxiliary graft. Mean cold ischemia was 7.3 h (6.2-8.8). Complications included one pleural effusion and one biliary collection drained percutaneously. At 20 months (10-36) follow-up all children are alive and well with functioning grafts. Donation after cardiac death is a significant source of liver grafts for adults and children with careful donor selection and short cold ischemic times.

Long-term outcome of immunosuppression withdrawal after liver transplantation.

Eighteen liver transplant recipients were followed up for 10 years after a trial of immunosuppression withdrawal. Three groups were identified according to the early outcome of complete (group A, n = 5), partial (group B, n = 9), and unsuccessful (group C, n = 4) withdrawal of immunosuppression. The indications for liver transplantation (LT) (August 1983-December 1988) were as follows: primary biliary cirrhosis (n = 3), primary sclerosing cholangitis (n = 3), Budd-Chiari syndrome (n = 3), acute liver failure (n = 3), hepatitis C virus (HCV) cirrhosis (n = 1), HCV and autoimmune hepatitis (n = 1), HCV and alcohol-related cirrhosis (n = 1), HCV and hepatocellular carcinoma (HCC) (n = 1), cystic fibrosis (n = 1), and liver metastases from testicular teratoma (n = 1). Immunosuppression was based on cyclosporine. All patients experienced 1 or more complications of prolonged immunosuppression (median, 7 years; range, 5-11). Thirteen patients (72%) are alive at a median interval of 17 years (range, 16-21) after LT. Of the 5 patients in group A, 2 currently have normal graft function with no rejection episodes, and 3 have restarted immunosuppression following late low-grade acute rejection (n = 1), retransplantation for chronic rejection (n = 1), and kidney transplantation (n = 1). Of the 9 patients in group B, 5 died. The deaths were due to ruptured arterial pseudoaneurysm following retransplantation, HCC recurrence, cardiac failure, renal failure, and posttransplant lymphoma at 5, 7, 7, 14, and 17 years after LT, respectively. All 4 patients in group C are alive on a full immunosuppressive regimen. Long-term follow-up of 18 LT recipients withdrawn from immunosuppression has shown that at a median of 17 years 10% of patients remain off all immunosuppression.

Immunosuppression withdrawal after auxiliary liver transplantation for acute liver failure.

BACKGROUND: The potential for immunosuppression withdrawal is the rationale for auxiliary liver transplantation (AUX) in patients with acute liver failure (ALF). PATIENTS AND METHODS: Forty-four AUX were performed in 28 adults and 16 children with ALF secondary to seronegative hepatitis (n = 20; 45%), paracetamol hepatotoxicity (n = 14; 32%), acute viral hepatitis (hepatitis B virus [HBV] n = 3, Epstein-Barr virus n = 1; 9%), drug-induced hepatitis (n = 3; 7%), autoimmune hepatitis (n = 2; 5%), and mushroom poisoning (n = 1; 2%). All patients fulfilled the King's College Hospital transplant criteria for ALF. After partial hepatectomy, 38 patients received a segmental auxiliary graft and six, a whole auxiliary graft. Immunosuppression was based on calcineurin inhibitors and steroids. RESULTS: Thirty-four patients (77%) are alive after a median follow-up of 30 months (range 4 to 124). Eight adults and two children died of sepsis (n = 6; 14%) at a median interval of 30 days (range 2 to 66), intraoperative cardiac failure (n = 1), brain edema on postoperative day 8 (n = 1), sudden death on day 35 (n = 1), and multiple organ failure associated with HBV recurrence 4 years after transplantation (n = 1). Three patients underwent retransplantation for small-for-size graft syndrome with sepsis on postoperative day 15 (n = 1) and for ductopenic rejection 4 and 15 months after AUX (n = 2). In 10/31 (32%) survivors (6/18 adults and 4/13 children) immunosuppression was completely withdrawn after a median of 19 months. CONCLUSION: Complete immunosuppression withdrawal can be achieved in a significant proportion of patients after AUX for ALF.

Bucrylate treatment of bleeding gastric varices: 12 years' experience.

BACKGROUND AND STUDY AIMS: For several years now there has been an increasingly widespread use of a tissue adhesive in the treatment of bleeding gastric varices to achieve rapid, safe control of hemostasis and prevent rebleeding. In this study we report on our experience with the use of Bucrylate (Hystoacryl) for the treatment of gastric varices over a period of more than a decade. PATIENTS AND METHODS: Since 1988, 174 cirrhotic patients with actively bleeding gastric varices have been admitted to our department, where they received emergency treatment with injections of Bucrylate. Any associated nonbleeding esophageal varices were subjected to traditional sclerotherapy in combination with the Bucrylate treatment. The gastric varices were subdivided into four distinct groups according to the method advocated by Sarin in 1989. The patients underwent weekly sclerotherapy sessions until their varices were eradicated, and the follow-up with a mean of 36 months (range 9-90 months) consisted of endoscopy at 3, 6, and 12 months during the first year and then yearly checks to confirm obliteration of the varices. RESULTS: The hemostasis (97.1%), early rebleeding (15.5%), and hospital mortality (19.5%) rates of the patients with bleeding gastric varices, treated with the tissue adhesive, were very similar to those of patients treated for esophageal varices over the same period (98.1%, 13.0%, and 16.4%, respectively). The most frequent cause of death at 30 days was liver failure (76% of cases), followed by hemorrhagic shock (8.8%), and other less frequent causes. Sclerotherapy achieved obliteration rate for gastric varices (70-75%) similar to that for esophageal varices in those patients with portal hypertension due to intrahepatic block (alcoholic and posthepatitis cirrhosis), but a rate of only 32% in the group of patients with prehepatic block (splenoportomesenteric thrombosis), where surgery proved more effective (69%). The medium- and long-term survival rates depended on the stability of the patients' liver conditions, on rapid, effective control of variceal hemostasis, and on complete, lasting obliteration of the gastric varices. CONCLUSIONS: The use of Bucrylate in emergency sclerotherapy achieved results in bleeding gastric varices on a par with those obtained in esophageal varices in cases of alcoholic and posthepatitis cirrhosis. The group of patients with portal hypertension due to prehepatic block (splenoportal thrombosis) showed no benefit from sclerotherapy in terms of obliteration of gastric varices, but benefited from elective surgery. The choice of the obliterating treatment indicated may be facilitated by classifying gastric varices into distinct groups on the basis of anatomicotopographic criteria.

TIPS allowing for an endoscopic mucosal resection of early gastric cancer in a cirrhotic patient with severe hypertensive gastropathy: report of a case.

This report describes the use of a transjugular intrahepatic portosystemic shunt (TIPS) in a cirrhotic patient with early gastric cancer, presenting with gastroesophageal varices and severe hypertensive gastropathy, in order to perform an endoscopic mucosal resection. The patient first underwent a TIPS to reduce the hypertensive gastropathy and thereafter was successfully treated by an endoscopic mucosal resection. Owing to the high operative risk, the treatment of gastric cancer in cirrhotic patients needs to be individualized. New procedures such as TIPS and an endoscopic mucosal resection may be useful in selected high-risk patients.

Solitary fibrous tumor of the liver with CD 34 positivity and hypoglycemia.

We report a new case of solitary fibrous tumor (SFT) of the liver, an extremely rare neoplasm. Including the present case no more than ten cases are reported in the English-language literature. To date there is no definite proof of the origin of this tumor. Both mesothelial and fibroblas-tic genesis has been postulated. The monoclonal antibody CD 34 has recently been used for the characterization of SFT. SFT would appear to be histogenetically related to a CD 34 - positive fibroblastic stem cell. A 61-year-old woman was admitted to our department with epigastric and right hypochondriac pain, weight loss, and hypoglycemia. Ultrasonography and computed tomography demonstrated a large heterogeneous mass in the right hepatic lobe. A right hepatectomy was performed. The tumor weighed 2850 g and microscopic section revealed a peculiar random pattern, the so-called patternless pattern of spindle tumor cells separated by abundant thick collagen bands. The tumor presented a number of highly cellular areas composed of plump spindle cell with hyperchromatic nuclei and rare mitotic figures. Ninety percent of the neoplastic cells displayed strong immunoreactivity for CD 34/My 10. The postoperative course was uneventful and the patient is alive and well without recurrence 6 years after surgery.