How Much Is the Inevitable Loss of Different Coagulation Factors During Blood Product-Free Liver Transplantations?

BACKGROUND: Bloodless liver transplantations (LT) have already been reported, but special characteristics of hemostatic changes remain less defined. The aim of this study was to evaluate the "inevitable" loss of coagulation factors (CF) in blood product-free LT. METHODS: Blood product and CF concentrate-free LT patient data were analyzed in terms of the first 2 days of perioperative hemostasis kinetics (N = 59). CF levels (FI, II, V, VII, X, and XIII), platelet (PLT) levels, and hemoglobin levels were measured before LT (T1), on arrival at the intensive care unit (T2), and 12, 24, and 48 hours after LT (T3, T4, and T5, respectively). Thromboelastographic (TEG) parameters were determined before and at the end of LT (T1-T2). RESULTS: Fibrinogen levels decreased by 1.2 ± 0.6 g/L, prothrombin levels by 26% ± 14%, factor V levels by 40% ± 23%, VII levels by 29% ± 19%, and X levels by 39% ± 22% (P < .001). From T2 to T4 fibrinogen increased by 0.9 ± 0.6g/L for 24 hours (P < .001). Factor II, V, and VII levels increased by 20% ± 16%, 31% ± 32%, and 12% ± 27%, respectively, between T3 and T5 (P < .001). However, factor X reached only half of the T1 level (T3-T5, P < .001). Platelet count increased in 34 (58%) patients at T2 (P < .001). The TEG parameters remained in the normal range during LT (T1-T2). CONCLUSION: The major findings of this study advocate that "inevitable" levels of CF decrease during LT by an average of 1.2 g/L in terms of fibrinogen and 23% to 40% regarding factors II, V, VII, and X. The authors suggest that knowing the "magic numbers" and comparing them against baseline laboratory results might predict the possibility of blood product-free transplant, providing confidence and safety to the surgeon and the anesthetist.

Abdominal Compartment Syndrome After Liver Transplant in Drug-Induced Acute Liver Failure: A Case Report.

The incidence of drug-induced acute liver failure (ALF) has been increasing in recent years. Despite the complex intensive treatment, liver transplant should be performed in progressive cases. A systemic inflammatory response syndrome and the burden of surgical intervention promote abdominal compartment syndrome (ACS); observed preoperatively, they are significant negative prognostic factors. THE CASE: We demonstrate a young woman with liver transplant after ALF and a consecutive ACS. We presumed drug toxicity in the background of the rapidly progressive ALF, based on the preoperative hematologic examination and the histology of the removed liver. An ACS has occurred in the postoperative period that must have been resolved with mesh, and later, anatomic segment 2-3 resection had to be performed to further decrease the pressure. The patient left the hospital after 62 days with good graft function. DISCUSSION: A complex intensive care is mandatory in the case of orthotopic liver transplant for ALF. Outcomes are good after orthotopic liver transplant. An ACS might occur after surgery. In these rare cases a delayed abdominal closure or even a liver resection can be the only solution and sometimes an urgent need to resolve the life-threatening problem.

Management of Portal Hypertension After Liver Transplantation.

INTRODUCTION: Post-transplantation portal hypertension has severe complications, such as esophageal varix bleeding, therapy refractory ascites, extreme splenomegaly, and graft dysfunction. The aim of our study was to analyze the effectiveness of the therapeutic strategies and how to visualize the procedure. METHODS: A retrospective study involving liver transplantation patients from the Semmelweis University Department of Transplantation and Surgery was performed between 2005 and 2015. The prevalence, etiology, and leading complications of the condition were determined. The applied interventions' effects on the patients' ascites volume, splenic volume, and the occurrence of variceal bleeding were determined. Mean portal blood flow velocity and congestion index values were calculated using Doppler ultrasonography. RESULTS: The prevalence of post-transplantation portal hypertension requiring intervention was 2.8%. The most common etiology of the disease was portal anastomotic stenosis. The most common complications were esophageal varix bleeding and therapy refractory ascites. The patients' ascites volume decreased significantly (2923.3 ± 1893.2 mL vs. 423.3 ± 634.3 mL; P < .05), their splenic volume decreased markedly. After the interventions, only one case of recurrent variceal bleeding was reported. The calculated Doppler parameters were altered in the opposite direction in cases of pre-hepatic versus intra- or post-hepatic portal hypertension. After the interventions, these parameters shifted towards the physiologic ranges. CONCLUSION: The interventions performed in our clinic were effective in most cases. The patients' ascites volume, splenic volume, and the prevalence of variceal bleeding decreased after the treatment. Doppler ultrasonography has proved to be a valuable imaging modality in the diagnosis and the follow-up of post-transplantation portal hypertension.

Examinations of Factors Influencing Survival of Liver Transplantation for Hepatocellular Carcinoma: A Single-Center Experience From Budapest.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Orthotopic liver transplantation (OLT) is the best therapy of choice for early, unresectable HCC. The Hungarian Liver Transplantation Program was launched in 1995 at the Department of Transplantation and Surgery, Semmelweis University, Budapest. From that time more than 60 patients underwent OLT for hepatic tumors, which in most cases were HCC. Our clinical examination was undertaken to analyze the possible influential factors of outcomes for our series of patients who received OLT for HCC. METHODS: We performed a review of all patients who underwent OLT for HCC at our department from 1996 to October 1, 2013. Disease extent was determined by preoperative computed tomography or magnetic resonance images. All explants were examined and categorized based on tumor number, size, distribution, HCC histologic grade, and vascular invasion. Patients with HCC were classified as having tumors either meeting Milan criteria, beyond Milan criteria but within UCSF criteria, or exceeding UCSF criteria. OLT was performed using standard techniques including orthotopic implantation with cross-clamp technique or with the piggyback technique. Postoperative immunosuppression included a triple drug regimen of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and prednisone. mTOR inhibitors have been available since 2004. RESULTS: HCC most commonly occurs in the presence of cirrhosis as a result of longstanding chronic liver disease. Most of our patients who underwent OLT for HCC are 56 to 60 years old, and most also had underlying HCV cirrhosis. As of October 1, 2013, 21 of 49 (42.85%) patients had died after OLT for HCC. The main cause was the recurrence of the HCC in 38%, followed by sepsis in 33%, and HCV recurrence in 19%. One death each (4.7% of the total number of deaths) was caused by primary nonfunction of the graft, acute myocardial infarct, and de novo malignancy, respectively. Overall survival for the entire group at 1, 3, and 5 years after transplantation was 73.48%, 65.2%, and 50.08%, respectively. Using pretransplant imaging, 34 tumors (69.3%) were within Milan criteria, 8 (16.3%) were beyond Milan but within UCSF criteria, and 7 (14.3%) exceeded UCSF criteria. Based on explant pathology, 30 tumors (61.2%) were within Milan criteria, 7 (14,3%) were beyond Milan but within UCSF criteria, and 12 (24.3%) exceeded UCSF criteria. New onset, non-HCC malignant tumor developed in 2 cases (4%). There was no significant difference between the surgical techniques or the immunosuppressive strategies. Using the Cox analysis in our series, it can be seen that mortality was higher with tumors exceeding Milan criteria but within UCSF criteria compared with tumors within Milan criteria (Coef. = 0.5749 in Setting 1 and 0.1226 in Setting 2), and even higher with tumors beyond UCSF criteria compared with tumors within Milan criteria (Coef. = 0.7228 in Setting 1 and 0.1456 in Setting 2). Recurrence of the tumor causes higher mortality (Coef. = 1.709 in Setting 1 and 1.0256 in Setting 2). It seems that using an mTOR inhibitor has a beneficial impact on mortality (Coef. = -1.409 in Setting 1). Vascular invasion was associated with higher mortality (Coef. = 0.6581in Setting 1). Higher AFP levels correlated with higher mortality but not significantly (Coef. = 0.0002 in Setting 2). In our series, survival after OLT for HCC was best with tumors within Milan criteria comparing those exceeded Milan criteria (odds ratio = 4.000). CONCLUSION: According to our findings, the Milan criteria are still the safest criteria system; however, slightly expanded criteria do not have significantly worse results. Preoperative imaging methods sometimes show fewer or smaller tumors, and the explant histology reports the exact staging of HCC at the time of OLT. Histological examination especially of the lymphovascular invasion is mandatory to assess the estimated prognosis. Extremely high levels of AFP mean higher risk. HCC recurrence is an important factor on the outcome; therefore, continuous oncologic screening is mandatory. Immunosuppressant agents are chiefly responsible not just for higher risk of recurrence but for higher risk to develop de novo malignancies. Viral serology must be done periodically to catch HCV recurrence in time and begin adequate antiviral therapy. Potentially, mTOR inhibitors could be potent immunosuppressive agents after OLT for HCC due to this antiproliferative effect.

Increasing living donor kidney transplantation numbers in Budapest.

Living related kidney donations (LRD) have had a significant impact on therapy of kidney diseases. Due to their ease of scheduling in the general surgery program and better half-life of about 21.6 versus 13.8 years for deceased donor kidneys, this approach has revolutionized nephrology and transplantation medicine. Since the first Hungarian LRD which was performed in 1974 in Budapest, Hungary, donations have expanded especially in the last 3 years. This has been followed in 2000 by living unrelated kidney donations (LURD). Since 2000 LURD can be also performed in Hungary. From the 251 LRD in our country in the last 3 years, 79 living donations have accounted for nearly one-third of the cases. In comparison of 2008, and 2011 the absolute numbers of LRD as well as LURD have more than doubled from 9 to 20 and 6 to 14 respectively. Based on international ranking data from the global observatory on donation and transplantation Budapest has improved from 1.20 in 2000 to 6.20 LRD per million persons (p.m.p.) in 2010. The increase in LURD has also led to some side effects: an increase in recipient age from 26 years in 2000 to 46 in 2011 and greater HLA mismatches. In 2010, Budapest ranked higher than Croatia or Portugal but still behind Germany (8.13 LRD p.m.p.) and the leading countries: the Netherlands (28.49 LRD p.m.p.) and Norway (16.94 LRD p.m.p.). Because of the tremendous progress in LRD, the gap between today's leading countries and Budapest is closing.

Successful treatment of renal failure caused by multiple myeloma with HLA-identical living kidney and bone marrow transplantation: a case report.

Here we have described a successful HLA-identical living allogeneic kidney transplantation after bone marrow transplantation in a patient with end-stag liver disease caused by multiple myeloma (MM). Our case is unique, because this combined transplantation is rarely possible and because of our unique immunosuppressive and management strategies. A 45-year-old man with ESRD MM and κ light-chain nephropathy was diagnosed. Cytostatic treatment resulted in partial remission, so autologous peripheral stem cell transplantation (SCT) was performed leading to a complete remission; however the patient remained anuric. The patient's HLA-identical brother offered to be a donor of peripheral stem cells for collection and cryopreservation. Kidney transplantation was performed with a combination of tacrolimus sirolimuns, and methylprednisolone. With a well-functioning kidney graft, allogeneic SCT was performed in the incipient relapse phase of MM, after total body irradiation. Severe oropharyngeal infections, diarrhea, sepsis, and renal failure. Fearing acute renal rejection, we administered steroid bolus. He experienced therapy with gradual restoration of kidney function. Then, steroid-responsive acute graft-versus-host disease (grade II, predominantly bowel) was diagnosed on the background of diarrhea, which returned once. Later he experienced a left subclavian vein thrombosis at the site of a central venous catheter and sepsis. Having recovered from these events, the patient enjoys good health, with stable kidney function and normal protein excretion. After the steroid was stopped, a bone marrow biopsy revealed full-donor type normocellular hemopoiesis. Because of the chimerism, we gradually discontinued the immunosuppression including, sirolimus and finally tacrolimus, since with minimal trough levels there were no complications. Bone marrow biopsy showed a complete remission. In MM with ESRD HLA-identical combined kidney and bone marrow transplantation from a living donor may offer not only complete remission and good renal function, but also good health without immunosuppression.

Examination of carbohydrate metabolism parameters after simultaneous pancreas-kidney transplantation.

End-stage renal failure, a frequent complication of type 1 diabetes mellitus, requires renal replacement therapy. Our team examined the laboratory parameters of carbohydrate metabolism in 18 patients with type 1 diabetes at 10 to 89 months after simultaneous pancreas-kidney transplantation. We compared these results with those of 17 patients with type 1 diabetes who had formerly received kidney-alone transplantations, and were undergoing insulin treatment, as well as with those of 16 metabolically healthy controls. The hemoglobin A1c (HbA1c) and blood glucose levels of the pancreas-kidney transplant recipients were within the normal ranges, not differing significantly from those of the healthy controls. In contrast, the HbA1c and glucose levels were significantly elevated among kidney transplanted diabetic subjects. However, fasting and 2-hour insulin levels of pancreas-kidney transplant patients were significantly higher than those of the controls, indicating insulin resistance. According to these results, the insulin secretion by the pancreas graft sufficiently compensated for insulin resistance. Thus 10 to 89 months after successful pancreas-kidney transplantation, carbohydrate metabolism by type 1 diabetic patients was well controlled without antidiabetic therapy.

Deviceless low-pressure operation; a cost-effective way to reduce CO2-induced barotrauma during hand-assisted laparoscopic donor nephrectomy.

Between March 2008 and March 2011, hand-assisted laparoscopic donor nephrectomles were performed on 70 patients. Following the first 26 cases undertaken based on guidelines in the literature, we modified the procedure to avoid barotrauma to the kidney caused by the usual 12-13 mm Hg CO(2) pneumoperitoneum or pneumoretroperitoneum. The perirenal CO(2) pressure, therefore, was decreased to 8 mm Hg from the beginning of the surgery; the operation was performed without using a handport. Our early experience with the modified technique suggested that the safety and duration of the procedure were not affected but the incidence of delayed graft function due to barotrauma was decreased, a cost-effective improvement.

Role of early systemic inflammatory response in simultaneous pancreas-kidney transplantation.

Pancreas grafts are susceptible to surgical complications mostly related to exocrine secretions and the low microcirculatory blood flow through the gland. During simultaneous kidney-pancreas transplantation, the systemic response depends on reperfusion of two organs acute graft pancreatitis, immunotherapy, coagulopathy, bleeding, and other factors. We performed a retrospective review of 10 adult simultaneous pancreas-kidney transplant patients to evaluate progression of early postoperative inflammation in the absence of infection. All patients were treated with four-drug therapy. We performed analyses of procalcitonin (PCT), C-reactive protein, serum creatinine, amylase, and lipase levels over the first 5 postoperative days. Relatively high peak PCT levels (maximum 130 ng/mL) were reached within 24 to 48 hours postoperatively followed by a moderate decrease. Consistent with this observation, the serum creatinine, amylase, and lipase levels decreased continuously to normal concentrations within the first week. The increased PCT levels seemed depend upon the surgical procedure and intraoperative events. PCT was superior to C-reactive protein to discriminate infection from inflammation in this setting. The dynamics of PCT levels, rather than absolute values, seemed to be important. Lack of a decrease in PCT levels after the peak, suggested an infectious complication or the development of sepsis. Monitoring and assessment of PCT levels may help in early recognition of infection and institution of therapy.

The significance of the circumaortic left renal vein and other venous variations in laparoscopic living donor nephrectomies.

Among the several vascular variation those concerning the venous system of the kidneys show the most significant variability. They often play an important role when it comes to choosing the kidney to be removed for transplantation. Based on our prior studies, we have surveyed these variations. When performing a laparoscopic living donor nephrectomy owing to the limited field of vision and the restricted possibilities for preparation, preoperative radiologic planning is of utmost importance. We evaluated 55 donors who underwent laparoscopic nephrectomies using the 16-section multidetector-row computed tomography angiography. Among the donors who underwent surgeries we observed circumaortic veins (CAV) in three cases, retroaortic veins in 6 cases, multiple renal veins in 10 cases, and a lumbar vein draining into the left renal vein (RV) in 30 cases. In the 2 cases wherein CAVs were discovered, the team decided to use the other kidney. In 1 case, due to a short right RV, we chose the left kidney. The complex development of the CAV that is sometimes difficult to reconstruct in 3D poses a challenge for both the radiologist and the surgeon.

Renal cell carcinoma of the native kidney: a frequent tumor after kidney transplantation with favorable prognosis in case of early diagnosis.

INTRODUCTION: The frequency of malignant tumors as a cause of death is increasing among kidney transplant patients. The aim of our study was to characterize kidney tumors occurring in the native kidneys of renal transplanted patients, and to determine their impact on recipient survival. METHODS: We retrospectively analyzed the 43/3003 (1.43%) renal cell carcinomas (RCC) in the native kidneys of patients transplanted between 1973 and 2010. RESULTS: During this period we diagnosed 293 posttransplant tumors, 14.6% of which were RCC. The male/female ratio was 2.1:1. The mean age of recipients at the time of tumor detection was 52.4 ± 12.1 years. The mean time from transplantation to diagnosis was 72.4 ± 61.6 months. RCC occurred on both sides in similar numbers. Tumors were multifocal in 8 cases. According to TNM staging, RCC was stage I in 38 cases. The histologic type was clear cell (n=27), papillary (n=13), chromophobe (n=2) or sarcomatoid (n=1). Radical nephrectomy was performed in 41 cases. Immunosuppressive management was converted to proliferation signal inhibitors in 27 patients (sirolimus n=19 or everolimus n=8). Fifteeen patients died at a mean survival time of 38.9 ± 62.4 months with 28 patients still alive at a mean follow-up 43.8 ± 35.6 months. Cumulative survival according to the Kaplan-Meier method was 79.2% at 1 year, 66.1% at 5 years, and 59.0% at 10 years. The patient survival rate was better among papillary than clear cell RCC (P=.038). CONCLUSION: RCC was the second most frequent tumor among kidney transplanted patients at our center. The diagnosis established at an early stage in the majority of cases, leading to favorable patient survivals. A regular yearly abdominal ultrasound screening is suggested for early tumor diagnosis.

The impact of Milan criteria on liver transplantation for hepatocellular carcinoma: first 15 years' experience of the Hungarian Liver Transplant Program.

In addition to hepatitis C, hepatocellular carcinoma. is a leading indication for orthotopic liver transplantation (OLT). The indications for OLT in HCC remains a topic of debate. The successful Milan criteria are still accepted as the gold standard to select candidates with a good chance for long-term survival. The Hungarian Liver Transplant Program launched in 1995 reached 45 OLT/year in 2010. Among 412 first OLTs, there were 49 cases of a malignant tumor, including 41 among which the indication was the tumor. Of the 412 patients, 154 (37.4%) were hepatitic C virus (HCV) positive, including 29 with HCC and 23 cases in which HCC was the indication itself. Half of the HCC patients were within the Milan criteria; 50% exceeded the criteria. We observed a solitary HCC in 36% of cases: 2 foci in 18%; 3 in 7%, 4 in 14%, and ≥5 in 25%. Only 12 patients underwent a "down-staging" treatment before OLT: 8 radiofrequency ablation (RFA) and 4 transarterial chemoembolization (TACE). Cumulative 1-, 3-, and 5-year patient survivals were 62%, 54%, and 43%, respectively in HCC/HCV-positive patients and they were 74%, 67%, and 61% among non-HCC HCV-positive subjects. The cumulative HCC patient survival rates of 64%, 64%, and 53% among Milan criteria were superior to those of 57%, 40%, and 27% among subjects exceeding the Milan criteria (P=.01). Pre-OLT "down-staging" treatment increased the 1-year patient survival from 64% to 70%; however, it did not affect the long-term results. Among items of the Milan criteria tumor size had less impact on outcomes then number of foci. The majority of cases who exceeded the Milan criteria had been transplanted before 2003. Our results suggested that the Milan criteria should be applied for the selection of candidates in order to promise good survival after OLT for HCC.

Incisional hernia after simultaneous pancreas kidney tranplantation: a single-center experience from Budapest.

INTRODUCTION: The occurrence of postoperative incisional hernia is more frequent after simultaneous pancreas-kidney transplantation compared with other transplanted parenchymal organs. These complications are especially dangerous in this patient population, because they can compromise the survival of the transplanted organ. METHODS: We performed a retrospective review of a series of adult patients with incisional herniae after 23 consecutive simultaneous pancreas-kidney transplantations between January 2004 and June 2010 seeking to identify risk factors. All 23 patients had a body mass index (BMI) of <25. All surgeons used a similar technique, including a median incision with an intraperitoneal approach, and systemic venous and enteric drainage methods and a layered fascial closure. All combined pancreas-kidney transplant recipients received induction with thymoglobulin and maintenance therapy with sirolimus, reduced-dose cyclosporine and corticosteroids. RESULTS: An incisional hernia repair was performed in 8/23 patients (34.8%). Four reoperations were required in this group (50%), due to hemoperitoneum (n=2), intra-abdominal abscess (n=1), and venous thrombosis (n=1). The mean elapsed time between transplantation and hernioplasty was 24.5 months (range, 8-51). There was no significant difference in age, gender, BMI, dialysis modality, or operative time among affected compared with the other members of the group. CONCLUSION: Despite lack of obesity we observed a relatively higher rate of postoperative herniase, possibly owing to the side effects of a thymoglobulin-sirolimus combination.

Outcome of liver transplantation based on donor graft quality and recipient status.

BACKGROUND: Availability of suitable donor organs has always limited the number of liver transplantations performed. Use of marginal donor organs is an alternative to overcome organ shortage. OBJECTIVE: To analyze the effect of various combinations of donor organ quality and recipient status on the outcome of liver transplantation. MATERIALS AND METHODS: Data from 260 whole-liver transplantations performed between January 2003 and September 2009 were analyzed retrospectively. Study groups were established according to donor organ quality (marginal score 0-1 vs 2-5) and recipient status (Model for End-Stage Liver Disease [MELD] score <17 or >17). In patients at low risk, 102 received optimal grafts (good-to-good group [G/G], and 75 received marginal grafts (bad-to-good group [B/G]. In patients at high risk, 46 received optimal grafts (good-to-bad group [G/B], and 37 received marginal grafts (bad-to-bad group [B/B]. RESULTS: No differences were observed in cumulative patient and graft survival rates; however, total survival differed in the early period after transplantation, that is, within 1 year. There was a higher rate of overall postoperative complications including initial poor graft function, bleeding, infection, and kidney failure in group B/B compared with group G/B (25 of 37 patients [67.5%] vs 27 of 46 patients [59.0%]), group B/G (25 of 37 patients [68%] vs 39 of 75 patients [52%], and group G/G (25 of 37 patients [68%] vs 43 of 102 patients [42%]) (P = .04). Patients with a high MELD score (G/B and B/B) demonstrated increased risk of postoperative complications. Use of donor organs with marginal score of 2 or higher in patients with high MELD scores increased early patient mortality. CONCLUSION: In summary, patients with a high MELD score (G/B and B/B) are at an increased risk of post-OLT complications. In contrast, use of marginal grafts (B/G and B/B) increased the rate of hepatitis C virus recurrence and decreased the response rate to antiviral therapy. The combination of impaired donor grafts and recipients at high risk should be avoided.

Significance and imaging of lumbar veins and early-branching arteries in planning living-donor laparoscopic nephrectomy: two case reports from 21 months' experience.

A key aspect in planning laparoscopic living-donor nephrectomy is mapping of vascular variations. Lumbar veins and early-branching renal arteries are of utmost importance. To date, 43 candidates including 18 men and 25 women aged 25 to 67 years have been examined at our clinic using 16-section multidetector-row computed tomography angiography. Each examination was double-checked by an experienced radiologist. Of the 43 patients, 31 underwent surgery. In 29 of 31 patients (93.5%), the anatomy observed during surgery was identical to that demonstrated on the preoperative computed tomography scan. In 1 of 2 patients, 2 separate arteries were found at surgery, rather than the prognosticated early-branching arteries. In this patient, conversion to open surgery was necessary. In the other patient, a lumbar vein running into a retroaortic renal vein was discovered. In this patient, a 6-mm length of the joint stem contained the wall of the aorta and the periaortic tissue; thus, technically they were of separate origins. Careful mapping of the anatomy helps to prevent unexpected operative complications that are difficult to manage. Correct interpretation of the data must always be based on agreement between the radiologist and the surgeon.