Pulmonary hypertension as a predictor of postoperative complications and mortality after liver transplantation.

Most transplant centers consider severe pulmonary hypertension (PHT) to be an absolute contraindication for orthotopic liver transplantation (OLT). We retrospectively examined the outcome of 24 patients with PHT (group 1) who underwent OLT compared with 24 matched patients (group 2) without PHT, who also underwent OLT. Based on right cardiac catheterization measurements made after the induction of anesthesia for OLT, PHT was defined as mild or moderate-to-severe if the mean pulmonary arterial pressure exceeded 25 or 35 mm Hg, respectively. The incidence of PHT was 9.8% (24/244); 21/24 PHT patients showed mild and 3/24 moderate PHT. Kaplan-Meier survival analysis did not show a significant difference between the two groups. The incidence of pulmonary infections was significantly greater in group 1 (P < .05). The duration of ventilation and intensive care unit stay was similar in the two groups. Echocardiography detected only the three moderate cases of PHT and not the twenty-one cases of mild PHT. Our analysis suggested that mild PHT was common and did not affect patient outcomes after OLT; moderate or severe PHT was uncommon. The two patients with moderate PHT survived OLT and did not succum to PHT during long-term follow-up.

Use of recombinant factor IX and thromboelastography in a patient with hemophilia B undergoing liver transplantation: a case report.

Hemophilia B is a congenital recessive disorder caused by deficiency of coagulation factor IX (FIX). Surgical procedures can be performed in patients with hemophilia using high-purity and/or recombinant FIX, which has been shown to be safe and effective in surgical hemostasis. Liver transplantation is the only potentially curative treatment available for these patients, providing a long-term phenotypic cure for hemophilia. End-stage liver disease together with hemophilia exposes patients to greater risks of bleeding complications during the perioperative period with consequent difficulties in managing coagulopathy. The limited experiences reported by different investigators and the various strategies for clotting factor replacement make it difficult to define a single approach with respect to the optimal dose and method of administering FIX to achieve perioperative hemostasis. The limits of plasma-based coagulation tests--prothrombin time, activated partial thromboplastin time--have made thromboelastography a valid alternative in this kind of surgery. It has been demonstrated to be a useful tool for real-time analysis of clot formation using a whole-blood assay format. Further, it accurately illustrates the clinical effects of procoagulant or anticoagulant interventions. In this article, we have described the usefulness of thromboelastography to monitor the ability of high-purity FIX supplementation to restore a normal coagulation state and to guide the perioperative administration of blood products in a successful orthotopic liver transplantation in a hemophilic patient with deficiencies of factors IX and X, presenting with hepatitis C virus-related cirrhosis and hepatocellular carcinoma.

Adult-to-adult living donor liver transplantation using left lobes: the importance of surgical modulations on portal graft inflow.

BACKGROUND: Due to the shortage of available cadaveric organs, living donor liver transplantation (LDLT) has been recently applied extensively in adults. The use of the left lobe should be encouraged because of donor safety, but frequently the metabolic requirements of severely cirrhotic patients are great and subsequent graft dysfunction is encountered after transplantation. The importance of increased portal inflow to the graft in previously severely cirrhotic patients and other hemodynamic changes in LDLT using left lobes are still under debate, as are the surgical modulations to correct them. In this study, we have reported an initial series of adult-to-adult LDLT using left lobes, underlining the hemodynamic changes encountered during the transplant and the surgical modulations we applied to correct them. METHODS: Eight adult recipients underwent left lobe liver transplantation from living donors. Portal vein pressure and central venous pressure were measured before and after surgical modulation. RESULTS: We encountered four cases of small-for-size syndrome. Two patients were retransplanted; the other two died. Seventy-five percent of our recipients survived and 50% did not require further surgery. CONCLUSION: Surgical portal inflow modulation should be considered in cases of left lobe liver transplantation between adults.

Intraoperative coagulation evaluation of ischemia-reperfusion injury in small bowel transplantation: a way to explore.

BACKGROUND AND AIM OF STUDY: The success of intestinal transplantation is affected by the extreme susceptibility of the small bowel to ischemia-reperfusion (I/R) injury. Platelet aggregation decreases after reperfusion in small intestinal ischemia and liver transplantation. Thromboelastography (TEG) is a coagulation test performed whole on blood. The aims of this study were to assess coagulation derangements during bowel transplantation to define appropriate modalities of intraoperative coagulation monitoring. A secondary endpoint was to determine whether measurements of coagulation derangements were useful to estimate small intestinal I/R injury. MATERIALS AND METHODS: We recruited 19 patients who had undergone elective small bowel transplantation for primary short-gut syndrome. We divided our patients into two groups depending on their reperfusion injury as evaluated with a biopsy after reperfusion: group A composed of eight patients who had a reperfusion injury: group B composed of 11 patients who did not experience this problem. We measured five thromboelastogram indicators (r, k, angle, MA, CL30) at defined intervals: dissection phase (T1), vascular anastomoses phase (T2) as well as 30 minutes (T3) and 120 minutes (T4) after reperfusion during the intestinal reconstruction phase. RESULTS: We did not observe any significant difference between intraoperative blood loss, core temperature, or volume of fluid fresh frozen plasma, or platelet administration. Angle and MA were decreased significantly among patients with reperfusion injury. DISCUSSION: Patients showed a hypocoagulation pattern during all the manipulations. This derangement did not depend on the ischemia time. In patients with I/R injury the angle and MA did not change during ischemia, but did change significantly upon reperfusion. Several mechanisms may cause coagulation derangements. During the ischemic period, there may be damage to the vascular bed of the ischemic organ. When arterial blood passes through the damaged vascular bed after reperfusion, platelet activation occurs to varying degrees, resulting in reduced platelet function. CONCLUSION: Further studies are needed to confirm this preliminary work, which was limited by the low number of patients, in order to elucidate relevant mechanisms and develop predictive algorithms.

Twenty-seven consecutive intestinal and multivisceral transplants in adult patients: a 4-year clinical experience.

Adult isolated intestinal and multivisceral transplantation is gaining acceptance as the standard treatment for patients with intestinal failure with life-threatening parenteral nutrition-related complications. We report our 4-year experience with intestinal and multivisceral transplantation. We performed 20 isolated small bowel and seven multivisceral ones, including three with liver. The underlying diseases were mainly short bowel syndrome due to intestinal infarction, chronic intestinal pseudo-obstruction, and Gardner syndrome. Indications for transplant were loss of central venous access in 14 patients, recurrent sepsis in eight patients, and major electrolyte and fluid imbalance in five patients. One-year patient actuarial survival rate was 94% for isolated intestinal transplants and 42% for multivisceral recipients (P = .003), while 1-year graft actuarial survival rate was 88.4% for isolated small bowel patients and 42.8% for multivisceral ones (P = .01). The death rate was 18.5%. Our graftectomy rate was 14.8%. Our immunosuppressive protocols were based on induction agents such as alemtuzumab, daclizumab, and antithymocyte globulins. The majority of our complications were bacterial infections, followed by rejections and relaparotomies; most rejection episodes were treated with steroid boluses and tapering. We believe that our results were due to optimal candidate and donor selection, short ischemia time, and use of induction therapy. Multivisceral transplantation is a more complex procedure with less frequent clinical indications than isolated small bowel transplant, but our data concerning multivisceral transplants include only a small number of patients and require further evaluation.

Liver transplantation for familial amyloid polyneuropathy non-VAL30MET variants: are cardiac complications influenced by prophylactic pacing and immunosuppressive weaning?

BACKGROUND: Cardiac complications represent a cause of morbidity and mortality after liver transplantation among patients with familial amyloid polyneuropathy (FAP), especially for the non-VAL30MET variant types. METHODS: We retrospectively evaluated 11 recipients from a nonendemic area including 90.9% affected by FAP variants. Preoperative cardiovascular symptoms were present in 81% of patients. An intraoperative pacemaker was placed prophylactically in 90.9% of all recipients. Since tacrolimus has been reported in the international literature to display cardiac toxicity, we evaluated the influence of intraoperative prophylactic pacing and rapid postoperative weaning from tacrolimus, mainly allowed by thymoglobulin on the occurrence of posttransplantation cardiac complications. RESULTS: One patient received a combined heart-liver transplant, another, living donor liver transplantation. We did not observe any significant intraoperative cardiac complications. Postoperatively, the pacemaker was removed from all patients but 1. Five patients received tacrolimus and steroids; a subsequent, second group of 6 patients (54.5%) was treated with thymoglobulin followed by tacrolimus. At discharge the mean tacrolimus level was 10.6 ng/mL, whereas after 1 month it was 7.5 ng/mL. We observed a case of acute cellular rejection before discharge, which was successfully treated with intravenous steroids and OKT3. After a mean follow-up of 17.4 months (range, 1-31), 2 patients had died (18.1%): 1 due to sepsis and another, to MI. Two recipients experienced cardiac complications (18.1%), namely, the patient who died due to an myocardial infarction and a second one with a tachyarrhythmia, which was treated successfully with beta-blockers and amiodarone. CONCLUSION: Prophylactic pacing and rapid weaning from immunosuppression are still associated with a significant rate of postoperative cardiac complications.

[Outcome of isolated small bowel transplantation in adults: experience from a single Italian center]. / Risultati del trapianto di intestino isolato nell'adulto: esperienza di un singolo centro italiano.

AIM: Isolated small bowel transplantation is becoming the treatment of choice for adult patients with serious parenteral nutrition (PN) related complications: we report our three-year experience (December 2000-December 2003) from a single Italian center (Modena-Italy), with one of the larger European series. METHODS: We transplanted 14 patients, with a previous mean PN course of 27 months and a mean 21-month post-transplantation follow-up (range 3-36 months), obtaining a one-year actuarial survival rate of 92.3% with no intraoperative deaths. RESULTS: We lost 1 patient (7.2%), died for post-transplantation overwhelming sepsis following Cytomegalovirus (CMV) enteritis. Thirteen patients are alive, with one-year actuarial graft survival rate of 85.1%: 1 patient underwent graft removal (7.2%) for intractable severe acute rejection. Our immunosuppressive regimen was based on tacrolimus and 3 induction protocols: daclizumab (8 patients) with steroids, alemtuzumab (4 patients) and thymoglobulin (2 patients) without steroids. In 9 cases, we added sirolimus. Nine recipients experienced 22 episodes of acute cellular rejection (ACR), treated successfully in all cases but one. One patient (7.2%) was treated successfully for Post Transplant Lymphoproliferative Disease (PTLD) and is disease-free after 8 months. CONCLUSIONS: Small bowel transplantation can achieve optimal results depending on appropriate immunosuppressive management and candidate selection, added to shorter ischemia time and careful donor and graft selection.

Outcomes after adult isolated small bowel transplantation: experience from a single European centre.

BACKGROUND: Adult isolated small bowel transplantation is considered the standard treatment for patients with life-threatening parenteral nutrition-related complications. Here, we report a 3-year experience in a single European centre between December 2000 and December 2003. AIMS: To evaluate and discuss pre-transplant and post-transplant factors that influenced survival rates in our series. PATIENTS: Fourteen patients, with a mean parenteral nutrition course of 27 months, were transplanted. In eight cases they had not experienced any major complication from parenteral nutrition. METHODS: We described pre-transplant evaluation and inclusion criteria, surgical technique and clinical management after transplant. Immunosuppressive therapy was based on induction drugs and Tacrolimus. We reported survival rates, major complications and rejection events. RESULTS: One-year actuarial survival rate was of 92.3% with a mean 21-month follow-up (range 3-36 months). We had no intraoperative deaths. One patient (7.2%) died of sepsis following cytomegalovirus enteritis. One patient underwent graftectomy (7.2%) for intractable severe acute rejection. One-year actuarial graft survival rate of 85.1%. One patient (7.2%) affected by post-transplant lymphoproliferative disease is alive and disease-free after 8 months. CONCLUSION: We believe candidate selection, induction therapy, donor selection and short ischemia time play an important role in survival after small bowel transplantation.

Three-year experience in clinical intestinal transplantation.

BACKGROUND: The purpose of this study was to evaluate the outcome of 19 patients who underwent intestinal transplantation (ITx) for intestinal failure. METHODS: The 19 patients who underwent primary ITx between December 2000 and May 2003 were prescribed three different immunosuppressive protocols that included daclizumab, alemtuzumab, and antithymocyte globulin induction, respectively. A mucosal surveillance protocol for early detection of rejection consisted of zoom video endoscopy and serial biopsies associated with orthogonal polarization spectral imaging. Retrospective review of the clinical records was performed to assess the impact of new modalities of immunosuppression and intestinal mucosal monitoring on patient outcomes. RESULTS: All patients were adults (mean age 35.8 years). Etiology of intestinal failure included chronic intestinal pseudo-obstruction (n = 6), intestinal angiomatosis (n = 1), Gardner syndrome (n = 2), intestinal infarction (n = 8), radiation enteritis (n = 1), and intestinal atresia (n = 1). All patients experienced complications from total parenteral nutrition (TPN). Thirteen patients (68.4%) received isolated small bowel, whereas six (31.6%) received multivisceral grafts with or without the liver. Thirteen of 19 patients experienced at least one episode of rejection (68.4%). Most ACR episodes were treated with steroid boluses and resolved completely within 5 days. The overall 1-year patient survival was 82%. All living patients are in good health with functioning grafts having been weaned off TPN after a mean of 23.7 days post-ITx. DISCUSSION: Advances in immunosuppressive therapy with early detection and prompt treatment of rejection episodes make ITx a valuable treatment option for patients with intestinal failure and TPN-related life-threatening complications.

Hepatic resections for hepatocellular carcinoma (HCC): short and long-term results on 106 cirrhotic patients.

To evaluate the short and long term outcome of liver resections for hepatocellular carcinoma in cirrhotic patients. A retrospective analysis was performed on 106 consecutive cirrhotic patients with hepatocellular carcinoma resected between June 1974 and September 2002 at the Department of Surgery "Pietro Valdoni" - University of Rome "La Sapienza" and at the Liver and Multivisceral Transplant Unit of the University of Modena. Univariate and multivariate analyses were performed on several clinicopathological variables to analyze factors affecting the long-term outcome and intrahepatic recurrence. Overall mortality and morbidity were 10.7% and 26% respectively. These rates significantly decreased in the last years: from 1997 to 2002 no hospital mortality has been recorded. After a median follow-up of 19 months (interquartile range: 10-36), tumour recurrence appeared in 25 patients (23,5%). The 1-, 3-, and 5-year overall survival rates were 86,6%, 70,3%, and 60,6%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 86,3%, 58,1%, and 40,7%. On univariate analysis, viral ethiology of cirrhosis (p=0.03), presence of multiple nodules (p=0.02) and vascular invasion (p=0.05) were found to be related to a worse long-term survival. At the multivariate analysis only the viral ethiology of cirrhosis and the presence of multiple nodules were confirmed as indipendent prognostic factors. Early results after hepatic resection for HCC can be improved by using a limited surgical approach. The viral ethiology of cirrhosis, the presence of multiple nodules and vascular invasion negatively affected recurrence rate and long-term survival.

Intraoperative effects of combined versus general anesthesia during major liver surgery.

AIM: The study compares the intraoperative effects of combined versus general anesthesia during major liver surgery. METHODS: In this prospective randomized study, 70 patients were divided into 2 group of 35 subjects. Group A received general anesthesia (thiopentone, fentanyl, vecuronium, sevoflurane in a closed circuit) 15 minutes after placement of an epidural catheter (D9-D10) and induction of epidural anesthesia (6 ml 2% naropine). Continuous epidural infusion was initiated before surgical incision and continued with 0.2% naropine (7 ml/h) until the end of the operation. Group B received combined intraoperative anesthesia wit fentanyl doses according to hemodynamic parameters and 0.1 mg/kg morphine 30-4 minutes before cutaneous suture. Hemodynamic values were measured at base line (T0), and then at 15, 30, 60, 120 and 180 minutes after induction of general anesthesia (T1, T2, T3, T4 and T5, respectively). On recovery, patients were assessed for pain at rest and on movement reported on a visual analog scale; degree of motor blockade according to the Bromage scale; appearance of side effects; use af analgesic. RESULTS: A statistically significant decrease in the mean arterial blood pressure (ABP) and heart rate (HR) was noted within each group at 15 minutes after induction of general anesthesia. Significant differences in ABP were found between the 2 groups at T1 to T5, whereas HR values were substantially similar. The mean intraoperative use of fentanyl was significantly higher in Group B than in Group A, as was that of vecuronium. Pain intensity on recovery in patients who received epidural anesthesia was lower both at rest and on movement; only the patients in Group B required additional analgesics. No motor blockade was observed in either group. Nausea and vomiting were more frequent in Group B; hypotension was more frequent in Group A. CONCLUSION: The study confirms the safety of locoregional anesthesia in liver surgery, with good hemodynamic stability and absence of major side effects. The lower intraoperative use of opioids and muscle relaxants in patients who received epidural anesthesia confirms the neurovegetative protection this method provides. The data support the hypothesis that greater intraoperative use of opioids may be responsible for the higher incidence of side effects. Therefore, the intraoperative use of combined low-concentration anesthetic agents alone appears to offer a reasonable treatment option that provides adequate pain control at recovery from general anesthesia, with only minor side effects typically associated with analgesic (motor blockade) and opioids (nausea and vomiting). Given the complications associated with the technique, it should be performed by an expert anesthetist.

Patient position for a synchronous cervicothoracoabdominal two-team esophagectomy.

Cervicothoracoabdominal and cervicoabdominal approach are routinely adopted for total or subtotal esophagectomy. We propose a modification of the Nanson's patient position to optimize sequential or simultaneous left cervicotomy, laparotomy, and eventual right thoracotomy with one or two surgical teams. This technique permits better control of the operative field for each phase of the procedure with coordinated operating of two surgical teams on the neck, abdomen, and chest.

Piggy-back versus conventional technique in liver transplantation: report of a randomized trial.

Liver transplantation with preservation of the recipient vena cava (the "piggy-back" technique) has been proposed as an alternative to the traditional method. We performed a randomized study on 39 cirrhotic patients, 20 who underwent the piggy-back technique (group 1) and 19 the traditional method using venovenous bypass (group 2) to evaluate the feasibility and true advantages of the piggy-back technique compared to the traditional method. Two patients were switched to the conventional technique due to the presence of a caudate lobe embracing the vena cava in one patient and a caval lesion in the other. Statistically significant differences between the two groups were only found for the warm ischemia time (48.5 +/- 13 min for piggy-back vs 60 +/- 12 min for the conventional method) and for renal failure (zero cases in group 1 vs four cases in group 2). We therefore believe that liver transplantation with the piggy-back technique can easily be performed in almost all cases, and that only a few, specific situations, such as a very enlarged caudate lobe, do not justify its routine use.

[Myasthenia and muscle relaxants]. / Miastenia e miorilassanti.

Eighteen myasthenic patients have been operated on under general anaesthesia; 14 subjected to thymectomy and 2 to emergency procedures (caesarean section and laparotomy because of intestinal obstruction). Atracurium (0.3 mg/kg) and vecuronium (0.06 mg/kg) exhibited a long duration of action only in the two cases affected by the more severe signs and symptoms of the disease.