Twenty Years of Gut Transplantation for Chronic Intestinal Pseudo-obstruction: Technical Innovation, Long-term Outcome, Quality of Life, and Disease Recurrence.

OBJECTIVE: To define long-term outcome, predictors of survival, and risk of disease recurrence after gut transplantation (GT) in patients with chronic intestinal pseudo-obstruction (CIPO). BACKGROUND: GT has been increasingly used to rescue patients with CIPO with end-stage disease and home parenteral nutrition (HPN)-associated complications. However, long-term outcome including quality of life and risk of disease recurrence has yet to be fully defined. METHODS: Fifty-five patients with CIPO, 23 (42%) children and 32 (58%) adults, underwent GT and were prospectively studied. All patients suffered gut failure, received HPN, and experienced life-threatening complications. The 55 patients received 62 allografts; 43 (67%) liver-free and 19 (33%) liver-contained with 7 (13%) retransplants. Hindgut reconstruction was adopted in 1993 and preservation of native spleen was introduced in 1999. Immunosuppression was tacrolimus-based with antilymphocyte recipient pretreatment in 41 (75%). RESULTS: Patient survival was 89% at 1 year and 69% at 5 years with respective graft survival of 87% and 56%. Retransplantation was successful in 86%. Adults experienced better patient (P = 0.23) and graft (P = 0.08) survival with lower incidence of post-transplant lymphoproliferative disorder (P = 0.09) and graft versus host disease (P = 0.002). Antilymphocyte pretreatment improved overall patient (P = 0.005) and graft (P = 0.069) survival. The initially restored nutritional autonomy was sustainable in 23 (70%) of 33 long-term survivors with improved quality of life. The remaining 10 recipients required reinstitution of HPN due to allograft enterectomy (n = 3) or gut dysfunction (n = 7). Disease recurrence was highly suspected in 4 (7%) recipients. CONCLUSIONS: GT is life-saving for patients with end-stage CIPO and HPN-associated complications. Long-term survival is achievable with better quality of life and low risk of disease recurrence.

Modified Antimesenteric Tapering Enteroplasty: An Alternative Technique for the Treatment of Dysfunctional Anastomosis in Patients With Short Bowel.

INTRODUCTION: Several techniques have been described to taper the dilated small bowel to improve intestinal motility and decrease complications related to overdilated small bowel, including longitudinal intestinal lengthening and tapering, serial transverse enteroplasty, and spiral intestinal lengthening and tailoring. We propose an alternative technique designed to optimize bowel function and minimize the effects of recurrent small-bowel bacterial overgrowth in patients with short or ultra-short gut syndrome and dysfunctional anastomosis with maintenance of the actual absorptive surface. TECHNIQUE: The dilated side-to-side anastomosis is identified, and the mesentery leaves from both the proximal and distal small-bowel loops are separated by using blunt dissection. The previous anastomosis is divided longitudinally with a GI stapler. Once the small-bowel transection is completed, 2 separate blind loops of intestine are created, each one with half the circumference of the dilated side-to-side anastomosis. The antimesenteric stapled line is then reinforced with an outer layer of running suture. The blind loops of the tapered small bowel are then trimmed and anastomosed in an end-to-end isoperistaltic fashion in 2 layers. RESULTS: There were no postoperative complications. The length of the tapering ranged from 10 to 23 cm, corresponding to approximately 16% (range, 13%-20%) of the remaining small-bowel length. Three of 4 patients presented significant improvement of their symptoms and were able to have their parenteral support discontinued. CONCLUSIONS: Modified antimesenteric tapering enteroplasty is an alternative technique to improve intestinal motility and treat patients with short-bowel syndrome and dysfunctional side-to-side anastomosis without the need for further small-bowel resection. This bowel-sparing technique represents a valuable option in the armamentarium of the surgeon who manages patients with intestinal failure.

Ileocecal Anastomosis Type Significantly Influences Long-Term Functional Status, Quality of Life, and Healthcare Utilization in Postoperative Crohn's Disease Patients Independent of Inflammation Recurrence.

OBJECTIVES: Anastomotic reconstruction following intestinal resection in Crohn's disease (CD) may employ side-to-side anastomosis (STSA; anti-peristaltic orientation) or end-to-end anastomosis (ETEA). Our aim was to determine the impact of these two anastomotic techniques on long-term clinical status in postoperative CD patients. METHODS: We performed a comparative effectiveness study of prospectively collected observational data from consented CD patients undergoing their first or second ileocolonic bowel resection and re-anastomosis between 2008 and 2012, in order to assess the association between anastomosis type and 2-year postoperative quality of life (QoL), healthcare utilization, disease clinical or endoscopic recurrence, use of medications, and need for repeat resection. RESULTS: One hundred and twenty eight postoperative CD patients (60 STSA and 68 ETEA) were evaluated. At 2 years postoperatively, STSA patients had higher rates of emergency department visits (33.3% vs. 14.7%; P=0.01), hospitalizations (30% vs. 11.8%; P=0.01), and abdominal computed tomography scans (50% vs. 13.2%; P<0.001) with lower QoL (mean short inflammatory bowel disease questionnaire 47.9 vs. 53.4; P=0.007). There was no difference among the two groups in the 30 day surgical complications and 2-year patterns of disease activity, CD medication requirement, endoscopic recurrence, and need for new surgical management (all P > 0.05). CONCLUSIONS: At 2 years postoperatively, CD patients with ETEA demonstrated better QoL and less healthcare utilization compared with STSA, despite having similar patterns of disease recurrence and CD treatment. These findings suggest that surgical reconstruction of the bowel as an intact tube (ETEA) contribute to improved functional and clinical status in patients with CD.

Imaging of Intestinal and Multivisceral Transplantation.

Intestinal transplantation has evolved from its experimental origins in the mid-20th century to its status today as an established treatment option for patients with end-stage intestinal failure who cannot be sustained with total parenteral nutrition. The most common source of intestinal failure in both adults and children is short-bowel syndrome, but a host of other disease processes can lead to this common end-point. The development of intestinal transplantation has presented multiple hurdles for the transplant community, including technical challenges, immunologic pitfalls, and infectious complications. Despite these hurdles, the success rate has climbed over the past decades owing to achievements that include improved surgical techniques, new immunosuppressive regimens, and more effective strategies for posttransplant surveillance and management. Nearly 2800 intestinal transplants have been performed worldwide, and current patient and graft survival rates are now comparable to those of other types of solid organ transplantations. As their population continues to increase, it will be increasingly likely that intestinal-transplant patients will seek imaging at sites other than transplant centers. Therefore, it is important that diagnostic and interventional radiologists be familiar with the procedure, its common variations, and the spectrum of postoperative complications. In this article, the authors provide an overview of intestinal transplantation, including the indications, variations, expected postoperative anatomy, and range of potential complications. ©RSNA, 2018.

Pediatric liver transplantation for hepatocellular cancer and rare liver malignancies: US multicenter and single-center experience (1981-2015).

A tenth of all pediatric liver transplantations (LTs) are performed for unresectable liver malignancies, especially the more common hepatoblastoma (HBL). Less understood are outcomes after LT for the rare hepatocellular carcinoma, nonhepatoblastoma embryonal tumors (EMBs), and slow growing metastatic neuroendocrine tumors of childhood. Pediatric LT is increasingly performed for rare unresectable liver malignancies other than HBL. We performed a retrospective review of outcomes after LT for malignancy in the multicenter US Scientific Registry of Transplant Recipients (SRTR; n = 677; 1987-2015). We then reviewed the Children's Hospital of Pittsburgh (CHP; n = 74; 1981-2014) experience focusing on LT for unresectable hepatocellular cancer (HCC), EMBs, and metastatic liver tumors (METS). HBL was included to provide reference statistics. In the SRTR database, LT for HCC and HBL increased over time (P < 0.001). Compared with other malignancies, the 149 HCC cases received fewer segmental grafts (P < 0.001) and also experienced 10-year patient survival similar to 15,710 adult HCC LT recipients (51.6% versus 49.6%; P = 0.848, not significant [NS], log-rank test). For 22 of 149 cases with incidental HCC, 10-year patient survival was higher than 127 primary HCC cases (85% [95% confidence interval (CI), 70.6%-100%] versus 48.3% [95% CI, 38%-61%]; P = 0.168, NS) and similar to 3392 biliary atresia cases (89.9%; 95% CI, 88.7%-91%). Actuarial 10-year patient survival for 17 EMBs, 10 METS, and 6 leiomyosarcoma patients exceeded 60%. These survival outcomes were similar to those seen for HBL. At CHP, posttransplant recurrence-free and overall survival among 25 HCC, 17 (68%) of whom had preexisting liver disease, was 16/25 or 64%, and 9/25 or 36%, respectively. All 10 patients with incidental HCC and tumor-node-metastasis stage I and II HCC survived recurrence-free. Only vascular invasion predicted poor survival in multivariate analysis (P < 0.0001). A total of 4 of 5 EMB patients (80%) and all patients with METS (neuroendocrine-2, pseudopapillary pancreatic-1) also survived recurrence-free. Among children, LT can be curative for unresectable HCC confined to the liver and without vascular invasion, incidental HCC, embryonal tumors, and metastatic neuroendocrine tumors. Liver Transplantation 23 1577-1588 2017 AASLD.

Successful liver allograft inflow reconstruction with the right gastroepiploic vein.

Portal vein thrombosis is a common complication in cirrhotic patients. When portal vein thrombectomy is not a suitable option, a large collateral vessel can be used for allograft venous inflow reconstruction. We describe an unusual case of successful portal revascularization using the right gastroepiploic vein. The patient underwent a cadaveric orthotopic liver transplantation with end-to-end anastomosis of the portal vein to the right gastroepiploic vein. Six months after liver transplantation the patient is well with good liver function. The use of the right gastroepiploic vein for allograft venous reconstruction is feasible and safe, with a great advantage of avoiding the need of venous jump graft.

Autologous Reconstruction and Visceral Transplantation for Management of Patients With Gut Failure After Bariatric Surgery: 20 Years of Experience.

OBJECTIVE: Bariatric surgery (BS) is currently the most effective treatment for severe obesity. However, these weight loss procedures may result in the development of gut failure (GF) with the need for total parenteral nutrition (TPN). This retrospective study is the first to address the anatomic and functional spectrum of BS-associated GF with innovative surgical modalities to restore gut function. METHODS: Over 2 decades, 1500 adults with GF were referred with history of BS in 142 (9%). Of these, 131 (92%) were evaluated and received multidisciplinary care. GF was due to catastrophic gut loss (Type-I, 42%), technical complications (Type-II, 33%), and dysfunctional syndromes (Type-III, 25%). Primary bariatric procedures were malabsorptive (5%), restrictive (19%), and combined (76%). TPN duration ranged from 2 to 252 months. RESULTS: Restorative surgery was performed in 116 (89%) patients with utilization of visceral transplantation as a rescue therapy in 23 (20%). With a total of 317 surgical procedures, 198 (62%) were autologous reconstructions; 88 (44%) foregut, 100 (51%) midgut, and 10 (5%) hindgut. An interposition alimentary conduit was used in 7 (6%) patients. Reversal of BS was indicated in 84 (72%) and intestinal lengthening was required in 10 (9%). Cumulative patient survival was 96% at 1 year, 84% at 5 years, and 72% at 15 years. Nutritional autonomy was restored in 83% of current survivors with persistence or relapse of obesity in 23%. CONCLUSIONS: GF is a rare but serious life-threatening complication after BS. Successful outcome is achievable with comprehensive management, including reconstructive surgery and visceral transplantation.

Pentoxifylline attenuates leukocyte-endothelial interactions in a two-hit model of shock and sepsis.

BACKGROUND: This study investigated the effects of pentoxifylline (PTX) combined with resuscitation fluids on microcirculatory dysfunctions in a two-hit model of shock and sepsis. MATERIALS AND METHODS: Male Wistar rats (250 g) were submitted to hemorrhagic shock and reperfusion followed by sepsis induced by cecal ligation and puncture. For the initial treatment of shock, rats were randomly divided into: sham, no injury, no treatment; hypertonic saline solution (HS) (7.5%, 4 mL/kg); lactated Ringer's solution (LR, 3 × shed blood volume); HS + PTX (4 mL/Kg + 25 mg/kg PTX); and LR + PTX (3 × shed blood volume + 25 mg/kg PTX). After 48 h of being exposed to the double injury, leukocyte-endothelial interactions were assessed by intravital microscopy of the mesentery. Endothelial expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) was evaluated by immunohistochemistry, as well as lung neutrophil infiltration by histology. RESULTS: Lactated Ringer's solution induced marked increases (P < 0.001) in the number of rolling leukocytes per 10 min (two-fold), adherent leukocytes per 100 µm venule length (six-fold), migrated leukocytes per 5000 µm(2) (eight-fold), P-selectin and ICAM-1 expression (four-fold), and lung neutrophil infiltration (three-fold) compared with sham. In contrast, PTX attenuated leukocyte-endothelial interactions, P-selectin and ICAM-1 expression at the mesentery when associated with either LR (P < 0.001) or HS (P < 0.05). Neutrophil migration into the lungs was similarly reduced by PTX (P < 0.05). CONCLUSIONS: Data presented showed that pentoxifylline attenuates microcirculatory disturbances at the mesenteric bed with significant minimization of lung inflammation after a double-injury model of hemorrhagic shock and reperfusion followed by sepsis.

Current approaches for risk assessment of intestinal transplant patients: A view from the histocompatibility laboratory.

Despite its recent decline in volumes, intestinal transplantation remains an important option for patients with irreversible intestinal failures. The long-term outcome of an intestinal transplant has stagnated. The major cause of graft loss is rejection, resulting from mismatches in human leukocyte antigens (HLA) and the presence of antibodies to mismatched donor-specific HLA antigens (DSA). Literature has reported that DSAs, either preformed before transplantation or developed de novo after transplantation, are harmful to intestinal grafts, especially for those without combined liver grafts. A comprehensive assessment of DSA by the histocompatibility laboratory is critical for successful intestinal transplantation and its long-term survival. This paper briefly reviews the history and current status of different methods for detecting DSA and their clinical applications in intestinal transplantation. The focus is on applying different antibody assays to manage immunologically challenging intestinal transplant patients before and after transplantation. A clinical case is presented to illustrate the complexity of HLA tests and the necessity of multiple assays. The review of risk assessment by the histocompatibility laboratory also highlights the need for close interaction between the laboratory and the intestinal transplant program.

Muscle mass predicts outcomes following liver transplantation.

For patients with end-stage liver disease, commonly used indices of nutritional status (ie, body weight and body mass index) are often inflated because of fluid overload (ie, ascites and peripheral edema), and this results in an underdiagnosis of malnutrition. Because muscle is the largest protein reservoir in the body, an estimate of the muscle mass may be a more reliable and valid estimate of nutritional status. Therefore, we used pretransplant computed tomography data for 338 liver transplantation (LT) candidates to identify muscle and fat mass on the basis of a specific abdominal transverse section commonly used in body composition analyses, and we investigated the contribution of this measure to specific post-LT outcomes. We found that the majority of our patients (68%) could be defined as cachectic. For men, muscle mass predicted many important posttransplant outcomes, including intensive care unit (ICU) stay, total length of stay (LOS), and days of intubation. Muscle mass was a significant predictor of survival and also predicted disposition to home versus another facility. For women, muscle mass predicted ICU stay, total LOS, and days of intubation, but the effect was modest. Muscle mass did not predict survival or disposition for women. In conclusion, because pretransplant muscle mass is associated with many important postoperative outcomes, we discuss these findings in the context of possible pretransplant interventions for either improving or sustaining muscle mass before surgery.

Intestinal and Multivisceral Transplantation: Complications.

Advancements in immunosuppression protocols, surgical techniques, and postoperative care in the last few decades have improved outcomes of intestinal transplant patients. Normal immediate postoperative imaging appearance can simulate pathology. Intestinal transplant recipients are prone for several postoperative complications due to the complex surgical technique, which involves multiple anastomoses, and immunogenic nature of the allograft intestine. Imaging plays a crucial role in detection of several major complications including infectious, immunologic, vascular, gastrointestinal, pancreaticobiliary, genitourinary, and neoplastic complications. The awareness of the posttransplant anatomy and normal imaging appearances helps radiologists anticipate and accurately detect posttransplant complications.

Immunoglobulin G profile in hyperacute rejection after multivisceral xenotransplantation.

INTRODUCTION: Xenotransplantation is a potential solution for the high mortality of patients on the waiting list for multivisceral transplantation; nevertheless, hyperacute rejection (HAR) hampers this practice and motivates innovative research. In this report, we describe a model of multivisceral xenotransplantation in which we observed immunoglobulin G (IgG) involvement in HAR. METHODS: We recovered en bloc multivisceral grafts (distal esophagus, stomach, small intestine, colon, liver, pancreas, and kidneys) from rabbits (n = 20) and implanted them in the swine (n = 15) or rabbits (n = 5, control). Three hours after graft reperfusion, we collected samples from all graft organs for histological study and to assess IgG fixation by immunofluorescence. Histopathologic findings were graded according to previously described methods. RESULTS: No histopathological features of rejection were seen in the rabbit allografts. In the swine-to-rabbit grafts, features of HAR were moderate in the liver and severe in esophagus, stomach, intestines, spleen, pancreas, and kidney. Xenograft vessels were the central target of HAR. The main lesions included edema, hemorrhage, thrombosis, myosites, fibrinoid degeneration, and necrosis. IgG deposition was intense on cell membranes, mainly in the vascular endothelium. CONCLUSIONS: Rabbit-to-swine multivisceral xenotransplants undergo moderate HAR in the liver and severe HAR in the other organs. Moderate HAR in the liver suggests a degree of resistance to the humoral immune response in this organ. Strong IgG fixation in cell membranes, including vascular endothelium, confirms HAR characterized by a primary humoral immune response. This model allows appraisal of HAR in multiple organs and investigation of the liver's relative resistance to this immune response.

Safe Use of Erythromycin For Refractory Gastroparesis After Small Bowel Transplantation.

Current therapeutic options with prokinetic agents for posttransplant gastroparesis are limited. Erythromycin is associated with adverse reactions, including corrected QT interval prolongation and cytochrome P450 3A4 isoenzyme inhibition. The use of erythromycin has been avoided in patients undergoing treatment with cyclosporine or tacrolimus because of significant fluctuations in therapeutic immunosuppression levels. We report herein the successful use of erythromycin after visceral transplant to treat delayed gastric emptying. Two patients were managed with oral erythromycin (initial dose of 750 mg/d divided into 3 doses) for gastroparesis after visceral transplant. Patient 1 was a woman aged 42 years with a history of chronic intestinal pseudo-obstruction syndrome who underwent isolated small bowel transplant with dual (gastric and duodenal) proximal allograft anastomosis. Posttransplant gastroparesis was initially managed with oral metoclopramide. The patient also required high doses of tacrolimus (36 mg/d) to maintain adequate immunosuppression levels. The decision was made to change metoclopramide to erythromycin, which significantly decreased the daily tacrolimus dose requirement (from 36 to 9 mg/d), with resolution of nausea and intermittent bloating symptoms. Patient 2 was a woman aged 35 years with ultra-short gut syndrome after extensive enterectomy due to intestinal volvulus who underwent uneventful combined intestinal and colon transplant. Conventional pharmacologic therapy for gastroparesis was initiated after surgery without success. Erythromycin was started 15 days posttransplant, with significant improvement in her symptoms, and discontinued 47 days post-transplant. To maintain therapeutic levels (8-10 mg/dL), daily tacrolimus dose was decreased 75.8% and 36.5% for patients 1 and 2, respectively. No significant side effects associated with erythromycin use were observed in either patient. Our findings here suggest that erythromycin may be safely used for gastroparesis after small bowel transplant. Close monitoring of immunosuppressive drug levels and dose adjustments of other medications affected by inhibition of cytochrome P450 3A4 are advised.

Effects of ethyl pyruvate and other α-keto carboxylic acid derivatives in a rat model of multivisceral ischemia and reperfusion.

BACKGROUND: Ethyl pyruvate (EP) has been shown to ameliorate hepatic, renal, and intestinal mucosal injury and down-regulate expression of several pro-inflammatory mediators in a wide variety of preclinical models of critical illnesses, such as sepsis, burn injury, acute pancreatitis, stroke, and hemorrhagic shock. The molecular mechanisms responsible for the therapeutic effects of EP remain poorly understood, but might be related to the compound's structure as the ester of an α-keto carboxylic acid. Herein, we tested the hypothesis that EP and other α-keto carboxylic acid derivatives can modulate organ injury after lower torso ischemia/reperfusion (I/R). METHODS: Rats were subjected to 50 min of supraceliac aortic occlusion. Over a 20-min period, starting 2 min before the release of the aortic clamp, the animals received 2 µL/g of Ringer's lactate solution (RL, n = 5) or an equivalent volume of a solution containing EP (n = 5), benzoyl formate (BF, n = 5), parahydroxyphenyl pyruvate (PHPP, n = 5) or sodium pyruvate (NaPyr, n = 5). The total dose of each compound was 0.86 mMol/kg. After 1h of reperfusion, we measured ileal mucosal permeability to fluorescein-labeled dextran (mw 4000 Da), liver malondialdehyde (MDA) content, and plasma levels of alanine aminotransferase (ALT) and TNF. Rats in the control group (CT, n = 4) were subjected to laparotomy and surgical isolation of the supraceliac aorta, but not visceral I/R. RESULTS: Ileal mucosal permeability, plasma levels of ALT and TNF, and hepatic MDA content increased significantly in the RL group relative to the CT group. Both EP and BF significantly ameliorated the development of systemic arterial hypotension, mucosal hyperpermeability, and significantly decreased plasma levels of TNF. MDA content was significantly decreased by EP, PHPP, BF, and NaPyr. CONCLUSIONS: In general, EP is more efficacious in this model than is NaPyr. Although more remains to be learned about the pharmacologic differences between EP and pyruvate, one important factor may the greater lipophilicity of the former compound. This insight may permit the development of even more effective cytoprotective and anti-inflammatory agents based on the pyruvoyl moiety.

Hepatosplanchnic vasoregulation and oxygen consumption during selective aortic blood flow reduction and reperfusion.

BACKGROUND: Several studies have shown that the distribution of cardiac output to the intra-abdominal organs may vary during low-flow states. In this study, we developed an experimental model to selectively reduce the abdominal aortic blood flow in order to assess the initial impact of selective hepatosplanchnic hypoperfusion on regional blood flow redistribution. METHODS: Eight anesthetized and mechanically ventilated mongrel dogs were subjected to aortic blood flow reduction with an occluder in a stepwise manner by 50% and 100% for 45 min. After the ischemic period, the occluder was released, and animals were observed for an additional 45 min. Systemic hemodynamics were evaluated through a Swan-Ganz and arterial catheters, and gastrointestinal tract perfusion was evaluated by portal vein and hepatic arterial blood flows measurements (ultrasonic flowprobe). Intestinal O2-derived variables, intestinal mucosal (tonometric)-arterial and tonometric-(end-tidal-carbon-dioxide) gradients (Dt-apCO2 and Dt-EtpCO2) were also calculated. RESULTS: No significant changes in systemic and regional oxygen consumption were observed during the 50% reduction of aortic blood flow. On the other hand, both microregional pCO2 gradients (Dt-apCO2 e Dt-EtpCO2) showed a significant increase during this period. Aortic occlusion was associated with a marked reduction of systemic and regional oxygen delivery and consumption. During the reperfusion, no significant improvement in the tonometry-based pCO2 gradients was observed, in spite of the partial reestablishment of blood flow to the hepatosplanchnic territory. CONCLUSION: During selective intra-abdominal low-flow, a proportional reduction in the splanchnic and hepatic blood flows occurs. A selective reduction of approximately 50% in splanchnic oxygen delivery was not associated with significant changes in macroregional markers of hypoperfusion. In this situation, tonometry-based pCO2 gradients can be used for the assessment of hepatosplanchnic perfusion and histologic changes.

Short-term effects of hydroxyethylstarch resuscitation on systemic and regional hemodynamics and metabolism in a brain-dead canine model.

BACKGROUND: Hydroxyethylstarch (HES) is a synthetic polymer of glucose that has been suggested for therapeutic use in long-term plasma expansion. The aim of this study was to test the hypothesis that the infusion of a small volume of HES may provide benefits in systemic and regional hemodynamics and metabolism in a brain-dead canine model compared with large volume crystalloid resuscitation. METHODS: Fourteen mongrel dogs were subjected to a brain-death protocol by consecutive insufflations of a balloon catheter in the epidural space. One hour after induction of brain-death, the animals were randomly assigned to two groups: NS (0.9% NaCl, 33 mL/kg), and HES (6%HES 450/0.7, 17 mL/Kg). Systemic and regional hemodynamics were evaluated using Swan-Ganz, ultrasonic flowprobes, and arterial catheters. Serial blood samples were collected for blood gas, electrolyte, and serum chemistry analysis. Systemic, hepatic, and splanchnic O(2)-derived variables were also calculated. RESULTS: Epidural balloon insufflations induced a significant increase in mean arterial pressure, cardiac output (MAP and CO, respectively), regional blood flow, and systemic vascular resistance. Following the hyperdynamic phase, severe hypotension with normalization of systemic and regional blood flow was observed. Fluid resuscitation induced a prompt increase in MAP, CO, and portal vein blood flow, and a significant reduction in systemic and pulmonary vascular resistance. There were no differences between groups in metabolic indices, liver function tests (LFTs), or renal function tests. HES was more effective than NS in restoring cardiac performance in the first 2h after fluid resuscitation (P < 0.05). Both tested solutions partially and temporarily restored systemic and regional oxygen delivery. CONCLUSION: Small volumes of 6% HES 450/0.7 improved cardiovascular performance and provided the same regional hemodynamic and metabolic benefits of large volumes of isotonic crystalloid solutions.

Hepatitis C recurrence is not adversely affected by the use of donation after cardiac death liver allografts.

Many factors can worsen a recurrent hepatitis C virus (HCV) infection after liver transplantation (LT). We sought to determine whether the use of donation after cardiac death (DCD) livers affects HCV recurrence. From January 2000 to June 2008, 37 HCV patients underwent LT with DCD allografts. The outcomes and severity of HCV recurrence were analyzed along with those for 74 matched control patients with HCV who received donation after brain death (DBD) livers. The 2 groups had similar donor and recipient characteristics, immunosuppression regimens, rates of acute cellular rejection (ACR), and HCV profiles. DCD patients had a higher incidence of primary nonfunction (19% versus 3%, P = 0.006) and significantly higher peak aspartate aminotransferase levels in comparison with DBD subjects, suggesting a greater degree of ischemia/reperfusion injury. Although the survival rates were not significantly different, DCD recipients had lower 1- and 5-year patient survival rates (83% and 69% versus 84% and 78%, respectively, P = 0.75) and graft survival rates (70% and 61% versus 82% and 74%, respectively, P = 0.24). Three hundred fourteen protocol and clinically indicated liver biopsy procedures were performed within 6 years after transplantation, and mixed modeling analysis showed that fibrosis progression rates were similar for the 2 groups (0.6 fibrosis units/year according to the Ishak modified staging system). The rates of severe HCV recurrence (retransplantation or death due to recurrent hepatitis C and/or the development of stage 4/6 fibrosis or worse within 2 years) were similar [3 DCD patients (8%) versus 11 DBD patients (15%), P = 0.38], and cytomegalovirus infection (hazard ratio = 7.9, P = 0.002, 95% confidence interval = 2.1-28.9) and ACR (hazard ratio = 6.2, P = 0.002, 95% confidence interval = 2.0-19.7) were the only independent risk factors for severe recurrence. In summary, although there was a trend of poorer overall outcomes in DCD patients, the use of DCD livers did not appear to adversely affect HCV recurrence after LT.

Regional blood flow distribution and oxygen metabolism during mesenteric ischemia and congestion.

BACKGROUND: Acute mesenteric ischemia is a potentially fatal vascular emergency with mortality rates ranging between 60% and 80%. Several studies have extensively examined the hemodynamic and metabolic effects of superior mesenteric artery occlusion. On the other hand, the cardiocirculatory derangement and the tissue damage induced by intestinal outflow obstruction have not been investigated systematically. For these reasons we decided to assess the initial impact of venous mesenteric occlusion on intestinal blood flow distribution, and correlate these findings with other systemic and regional perfusion markers. METHODS: Fourteen mongrel dogs were subjected to 45 min of superior mesenteric artery (SMAO) or vein occlusion (SMVO), and observed for 120 min after reperfusion. Systemic hemodynamics were evaluated using Swan-Ganz and arterial catheters. Regional blood flow (ultrasonic flow probes), intestinal O(2)-derived variables, and mesenteric-arterial and tonometric-arterial pCO(2) gradients (D(mv-a)pCO(2) and D(t-a)pCO(2)) were also calculated. RESULTS: SMVO was associated with hypotension and low cardiac output. A significant increase in the regional pCO(2) gradients was also observed in both groups during the ischemic period. After reperfusion, a progressive reduction in D(mv-a)pCO(2) occurred in the SMVO group; however, no improvement in D(t-a)pCO(2) was observed. The histopathologic injury scores were 2.7 +/- 0.5 and 4.8 +/- 0.2 for SMAO and SMVO, respectively. CONCLUSIONS: SMV occlusion promoted early and significant hemodynamic and metabolic derangement at systemic and regional levels. Additionally, systemic pCO(2) gradient is not a reliable parameter to evaluate the local intestinal oxygenation. Finally, the D(t-a)pCO(2) correlates with histologic changes during intestinal congestion or ischemia. However, minor histologic changes cannot be detected using this methodology.