Higher procoagulatory potential but lower DIC score in COVID-19 ARDS patients compared to non-COVID-19 ARDS patients.

BACKGROUND: COVID-19 is a novel viral disease. Severe courses may present as ARDS. Several publications report a high incidence of coagulation abnormalities in these patients. We aimed to compare coagulation and inflammation parameters in patients with ARDS due to SARS-CoV-2 infection versus patients with ARDS due to other causes. METHODS: This retrospective study included intubated patients admitted with the diagnosis of ARDS to the ICU at Munich university hospital. 22 patients had confirmed SARS-CoV2-infection (COVID-19 group), 14 patients had bacterial or other viral pneumonia (control group). Demographic, clinical parameters and laboratory tests including coagulation parameters and thromboelastometry were analysed. RESULTS: No differences were found in gender ratios, BMI, Horovitz quotients and haemoglobin values. The median SOFA score, serum lactate levels, renal function parameters (creatinine, urea) and all inflammation markers (IL-6, PCT, CRP) were lower in the COVID-19 group (all: p < 0.05). INR (p < 0.001) and antithrombin (p < 0.001) were higher in COVID-19 patients. D-dimer levels (p = 0.004) and consecutively the DIC score (p = 0.003) were lower in this group. In ExTEM®, Time-to-Twenty (TT20) was shorter in the COVID-19 group (p = 0.047), these patients also had higher FibTEM® MCF (p = 0.005). Further, these patients presented with elevated antigen and activity levels of von-Willebrand-Factor (VWF). CONCLUSION: COVID-19 patients presented with higher coagulatory potential (shortened global clotting tests, increased viscoelastic and VWF parameters), while DIC scores were lower. An intensified anticoagulation regimen based on an individual risk assessment is advisable to avoid thromboembolic complications.

Sclerosing mesenteritis as a rare cause of upper abdominal pain and digestive disorders.

Sclerosing mesenteritis is a rare inflammatory disease of the bowel mesentery of unknown etiology, which can be mistaken for malignancy. We report a case of a 60-year-old male patient with sclerosing mesenteritis as a rare cause of upper abdominal pain and digestive disorders, and present the corresponding magnetic resonance imaging (MRI) findings indicative of the underlying disease.

[Metastatic lesions to the pancreas. When is resection reasonable?]. / Metastasen im Pankreas. Wann ist eine Resektion sinnvoll?

BACKGROUND: The significance of pancreatic resection for pancreatic metastatic lesions has not yet been sufficiently investigated. A retrospective analysis of patients undergoing pancreatic resections for pancreatic metastases was conducted. MATERIAL AND METHODS: Twenty patients were resected due to metastatic lesions to the pancreas. Histopathological findings were: renal cell carcinoma (n=9), colon carcinoma (n=1), malignant schwannoma (n=2), leiomyosarcoma (n=2), teratocarcinoma (n=1), adenocarcinoma of the oesophagus (n=1), gallbladder carcinoma (n=1), malignant melanoma (n=1), gastrointestinal stromal tumor (n=1), and spindle cell tumor (n=1). Operative procedures were standard pancreaticoduodenectomy (n=6), pylorus-preserving pancreaticoduodenectomy (n=6), and distal pancreatectomy (n=8). RESULT: The overall 5-year survival rate was 61%, for patients with renal cell carcinoma 100%. CONCLUSION: Pancreatic metastasectomy is a reasonable therapeutic option in suited patients. Patients with pancreatic metastases of renal cell carcinoma achieved excellent prognoses after radical resection.

Nitric oxide production in host-versus-graft and graft-versus-host reactions in the rat.

The present study was designed to determine whether .N = O produced in vivo during the rejection of histoincompatible tissues might permit serum NO2-/NO3- levels to serve as markers of a rejection reaction. Rat syngeneic and allogeneic liver, heart, bone marrow/spleen cell, small bowel, skin, and sponge matrix grafts were performed and the stable end-products of .N = O, NO2-/NO3-, were serially assayed in the serum of the grafted animals. A significant rise of serum NO2-/NO3- levels in the allografted animals preceded the onset of clinical signs of rejection or graft-versus-host disease, with the exception of the skin and sponge matrix graft models, where elevated serum NO2-/NO3- levels were never observed. In all transplant models, normal serum NO2-/NO3- levels were observed at all times in animals that received syngeneic grafts. Furthermore, treatment of allograft recipients with the immunosuppressive agents FK 506 or cyclosporine A inhibited .N = O production. Determination of serum creatinine levels demonstrated that the elevated serum NO2-/NO3- levels were not caused by kidney dysfunction. Serum NO2-/NO3- levels might be useful early serum markers of the initiation of a rejection reaction or graft-versus-host disease when functional markers of graft dysfunction are not apparent.

Adult living donor liver transplantation: living donation of the right liver lobe.

BACKGROUND: Adult living donor liver transplantation (LDLT) has become a routine treatment option for patients waiting for liver transplantation. In European and North American countries, LDLT for adult recipients is mainly performed with right lobe grafts. Indications, when compared to deceased donor liver transplantation, are controversial. MATERIALS AND METHODS: In our institution, patients suffering from hepatocellular carcinoma in cirrhosis, non-resectable hilar cholangiocarcinoma, viral hepatitis associated cirrhosis, as well as cholestatic liver and biliary disease are considered good candidates for LDLT. RESULTS: In this overview, donor evaluation, graft selection, and the donor operation with special regard to operative techniques and strategies are discussed. For visualization, a 5-min video sequence of the standard donor operation as performed in our institution is attached. CONCLUSION: Given the ongoing shortage of donor organs, adult LDLT has become a routine treatment option for patients waiting for liver transplantation. The associated inevitable risk for the healthy donor, however, remains ethically controversial.

Assessment of local control after laser-induced thermotherapy of liver metastases from colorectal cancer: contribution of FDG-PET in patients with clinical suspicion of progressive disease.

BACKGROUND: Management of patients after locally ablative treatment of liver metastases requires exact information about local control and systemic disease status. To fulfill these requirements, whole-body imaging using positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) is a promising alternative to morphologic imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). PURPOSE: To evaluate FDG-PET for the assessment of local control and systemic disease in patients with clinical suspicion of tumor progression after laser-induced thermotherapy (LITT) of colorectal liver metastases. MATERIAL AND METHODS: In 21 patients with suspicion of progressive disease after LITT, whole-body FDG-PET was performed. The presence of viable tumor within treated lesions, new liver metastases, and extrahepatic disease was evaluated visually and semiquantitatively (maximal standard uptake value [SUV(max)], tumor-to-normal ratio [T/N]). The standard of reference was histopathology (n = 25 lesions) and/or clinical follow-up (>12 months) including contrast-enhanced MRI of the liver. RESULTS: Among 54 metastases treated with LITT, 29 had residual tumor. Receiver operating characteristic (ROC) analysis of SUV(max) (area under the curve (AUC) 0.990) and T/N (AUC 0.968) showed a significant discrimination level of negative or positive lesion status with an equal accuracy of 94% (51/54). The overall accuracy of visual FDG-PET was 96% (52/54), with one false-negative lesion among six examined within 3 days after LITT, and one false-positive lesion examined 54 days after LITT. In the detection of new intra- and extrahepatic lesions, FDG-PET resulted in correct alteration of treatment strategy in 43% of patients (P = 0.007). CONCLUSION: FDG-PET is a promising tool for the assessment of local control and whole-body restaging in patients with clinical suspicion of tumor progression after locally ablative treatment of colorectal liver metastases with LITT.

Fast tracking in liver transplantation: which patient benefits from this approach?

In liver transplantation, "fast tracking" means postoperative extubation in the operating theater immediately after surgery. This procedure was performed in a series of 837 adult liver transplant recipients between January 1997 and April 2005, proving to be safe and feasible in almost 80% of patients without increasing the incidence of reintubation. This patient population experienced a significantly higher survival compared to patients who were extubated in the intensive care unit. Consequently, fast tracking should become the standard procedure after orthotopic liver transplantation. However, special attention is required for recipients with acute liver failure, retransplantation, Child C status, or complicated surgery in terms of increased transfusion of red blood cells. These patients do not participate in fast-tracking protocols, as demonstrated by a uni- and multivariate logistic regression analysis. Moreover, ROC analysis revealed that only intraoperative transfusion of

Complication rate of pancreas retransplantation after simultaneous pancreas-kidney transplantation compared with pancreas after kidney transplantation.

Simultaneous pancreas kidney transplantation is currently the state of the art therapy for patients with type 1 diabetes mellitus and diabetic nephropathy. Up to 30% of patients loose the pancreas with a kidney graft that continues to function. Under those conditions, isolated pancreas retransplantation can be indicated. We compared the outcome of these patients with the outcome of patients undergoing primary pancreas after kidney transplantation. From 1998 to 2005, we performed 205 pancreas transplantations. Three patients were considered for isolated pancreas retransplantation; to date, two have received a new organ. One was retransplanted twice. In two cases, the reasons for the initial graft loss in the retransplantation group were pancreatitis with hemorrhagic bleeding and in the third case severe rejection. After retransplantation two of three patients lost their graft owing to bleeding and venous thrombosis. One of three organs was successfully transplanted and the patient does not require insulin. During the same time, three pancreas after kidney transplantations were performed; all are doing well und are free of insulin. The study despite the small number of cases shows a high complication rate after pancreas retransplantation. Nevertheless, pancreatic retransplantation should be considered in selected patients.

[A method for reassessment of cost-intensive cases in visceral surgery. Results of project by the German Society for Visceral Surgery]. / Methode zur Abbildung kostenintensiver Fälle in der Viszeralchirurgie. Ergebnisse des DRG-Projekts der Deutschen Gesellschaft für Viszeralchirurgie.

Since the introduction of diagnosis-related groups (DRGs) many surgical departments report inappropriate reimbursement for complex cases and a shift in costly cases. To evaluate this situation, the German Society for Visceral Surgery inaugurated the present cost calculation project. In three university hospitals for 50 cases each, we depicted possible cost separators and utilized the complete cost calculation data (so-called Paragraph 21 data set) to test these separators. We identified "admission from another hospital", "severe surgically relevant concomitant disease", and "reoperation during the same hospital admission". The last was considered the economically most significant and medically most valid factor and was submitted as a possible modification to the german DRG system. The proposed cost separator "reoperation during the same hospital admission" was introduced into the DRG system after validation and leads to better allocation of reimbursements to complex and costly cases.

Evaluation of patients with liver metastases from colorectal cancer for locally ablative treatment with laser induced thermotherapy. Impact of PET with 18F-fluorodeoxyglucose on therapeutic decisions.

PURPOSE: Before locally ablative treatment of colorectal liver metastases, patients have to be carefully evaluated to decide whether this is the adequate therapy. In this study we determined the value of FDG-PET in comparison to conventional staging procedures. PATIENTS, METHODS: In 68 consecutive patients referred for laser induced thermotherapy (LITT) of liver metastases from colorectal cancer, pretherapeutic staging with conventional imaging (thoracic and abdominal CT, liver MRI, chest X-ray) and FDG-PET was performed. The examinations were analysed separately and blinded. Based on the staging information, therapeutic decisions were made by an interdisciplinary review board according to a standardized algorithm. The results were compared between conventional imaging and FDG-PET, and were validated by clinical follow up data and histopathology, respectively. RESULTS: On FDG-PET 210 lesions were interpreted as tumour manifestations. 48 of these were not seen on conventional imaging (true positive, n = 46). In contrast, 24 lesions were visualized by conventional imaging only (true positive, n = 12). Compared to conventional imaging, discrepant findings on FDG-PET led to treatment modifications in 25 patients (37%); these were correct in 20/25 patients. According to the actual treatment course, the inadequate treatment modifications in the remaining 5 patients were avoided by further diagnostic procedures (i.e. biopsies). CONCLUSION: In the evaluation of patients with known liver metastases from colorectal cancer before LITT, FDG-PET depicts relevant findings subsidiary to conventional imaging and thus is of high value for therapeutic decision making.

Acute renal failure after liver transplantation: incidence, etiology, therapy, and outcome.

Acute renal failure (ARF) was a frequent complication after orthotopic liver transplantation (OLT) when ARF was defined by a calculated glomerular filtration rate decrease of >50% or by a doubled serum creatinine above 2.5 mg/dL within the first week after OLT. We analyzed 1352 liver transplant recipients in retrospective fashion with regard to the incidence, etiology, therapy, and outcome of ARF; 162 patients developed ARF within the first week after OLT (12%), among whom 157 patients (97%) were recompensated by postoperative day 28. Altogether 52 patients (32%) received an average of 6 hemodialysis treatments, excluding the 5 patients (3%) who developed end-stage renal failure. Risk factors for this complication included hepatorenal syndrome type II, a glomerular filtration rate of <50 mL/min, and a diagnosis of hepatitis C.

[Carcinomas of the distal bile duct]. / Extrahepatische distale Gallenwegskarzinome.

Malignancies of the biliary tree are classified into three groups according to location: intrahepatic, central (perihilar), and distal. Of all cholangiocarcinomas, 25% are located distally and can be subdivided into middle and lower bile duct carcinomas. Surgical approaches for achieving tumor-free resection margins (R0) are directly associated with the origin of the tumor. Intrahepatic and central cancers usually must be treated by liver surgery, whereas the majority of distal cholangiocarcinomas require pancreaticoduodenectomy. In case of a small, middle bile duct carcinoma, exclusive extrahepatic bile duct resection without pancreatic resection can be adequate. Five-year survival after radical resection is about 25%. Cancer of the distal bile duct has to be distinguished from ductal adenocarcinoma of the pancreas and carcinoma of the ampulla of Vater. Curative surgery is possible if the tumor is diagnosed early and radical resection is feasible. In this context, the role of an extended lymph node dissection remains unclear. To improve survival, future studies are needed to evaluate the role of novel adjuvant strategies (i.e., gemcitabine, capecitabine).

Primary immunosuppression with tacrolimus after liver transplantation: 12-years follow-up.

The early safety and efficacy of tacrolimus after liver transplantation has been shown in two multicenter trials. Herein, we report our single-center long-term follow-up of a randomized controlled trial. As part of a European multicenter trial, 121 patients entered the study at our institution and were randomly assigned to receive either tacrolimus and steroids (n=61) or a quadruple protocol (n=60) using ciclosporin A, steroids, azathioprine, and antithymocyte globulin (ATG). Twelve-year figures of patient survival were 74% in the tacrolimus group and 66% in the cyclosporine-based group. Graft survival after 12 years was 69% in the tacrolimus group compared to 56% in the cyclosporin-based group (not significant, p=0.15). The total rate of graft loss and retransplantation decreased significantly in the tacrolimus arm (p<0.05). De novo malignancies increased significantly in the ciclosporin-based group and dominated as single cause of death beyond 5 years posttransplant. The use of tacrolimus after liver transplantation resulted in a decreased rate of graft loss over the long-term. An increased number of de novo malignancies in the ciclosporin-based group may be attributable to the use of ATG as induction therapy.

Anti-TNF-alpha therapy for acute rejection in intestinal transplantation.

INTRODUCTION: We present our experience with infliximab rescue therapy for steroid- and OKT3-resistant rejection after intestinal transplantation (ITx). METHODS: Twelve ITx and one multivisceral transplant recipients were immunosuppressed with tacrolimus, rapamycin, daclizumab, steroids (n = 10) or tacrolimus, campath, and steroids (n = 3). RESULTS: In two patients, severe acute rejection did not resolve despite steroid bolus therapy plus 5 to 10 days of OKT3 treatment. Signs of moderate rejection persisted in the distal portions of the grafts. Treatment with infliximab, a chimeric anti-TNF-alpha antibody (four infusions of 3 mg/kg body weight), induced a complete remission of histological and clinical signs of rejection. Two further patients with steroid-resistant rejection received two courses of infliximab (3 mg/kg body weight) as antirejection therapy. All rejection episodes resolved completely. CONCLUSIONS: Infliximab effectively treats steroid and OKT3 resistant acute rejection episodes of intestinal transplantations.

Adult liver transplantation using liver grafts from donors over 70 years of age.

UNLABELLED: The increasing organ shortage calls for widening the selection criteria for liver transplant donors. However, concern exists about the use of grafts from donors older than 70 years. We report our clinical experience with graft-age related outcomes, presenting data on 41 patients transplanted with grafts from older donors. PATIENTS/METHODS: Between January 1995 and October 2003, 41 liver grafts were transplanted from donors older than 70 years. We analyzed patient and graft survival, incidence of retransplantation, initial nonfunction (INF), rejection, intra- and postoperative requirement for red blood cells. We also recorded cholestasis, protein synthesis and urinary retention. RESULTS: The mean donor age was 73.4 +/- 0.37 years. After one year, the patient survival was 91% and the graft survival 86%. The retransplantation rate was 9.75%; only one graft was lost due to INF. We observed an incidence of 11 rejection episodes. Of these, five patients needed OKT3 therapy for steroid-resistent rejection. The intra- and postoperative requirement for red blood cells was 4.0 +/- 0.65 and 1.4 +/- 0.25 units. Cholestasis, protein synthesis, and urinary retention parameters were within normal limits. CONCLUSIONS: Among donors of mean age 73.4 years, patient and graft survivals were excellent. One organ was lost due to INF. The intra- and postoperative need for red blood cells was within acceptable ranges. Liver function tests, cholestasis, and retention parameters were normal after 1 year follow up. Thus, we recommend to accept liver grafts from donors older than 70 years to expand the organ pool.

Liver transplantation for hepatocellular carcinoma in cirrhosis: prognostic parameters.

Selection of patients suffering from hepatocellular carcinoma (HCC) in cirrhosis for liver transplantation is based upon the number and diameter of tumor nodules but not with vascular invasion. From 1989 to 2003, 1619 liver transplantations were performed in 1471 patients, including 163 patients with an HCC in cirrhosis. Selection criteria were a maximal diameter of up to 5 cm when the tumor appeared to be uninodular, or up to 3 cm in the case of two or three nodules and no vascular invasion prior to transplantation. The postoperative mortality rate was 1.7%. One-, 5- and 10-year survivals were 88%, 62%, and 51%, respectively. Among 1307 transplantations without HCC, the rates were 90%, 84%, and 76%, respectively (P < .0001). Multivariate analysis identified histopathological grading and vascular invasion to predict survival. A subgroup analysis showed 5-year survivals of 67% and 57% for well versus moderately differentiated tumors with vascular invasion. Liver transplantation is a safe and effective long-term treatment for small HCC in cirrhosis. Exeptions from the morphometric rules may be justified for patients with HCC in cirrhosis who show well or moderately differentiated tumors with vascular invasion.

Liver transplantation for primary biliary cirrhosis: influence of primary immunosuppression on survival.

INTRODUCTION: Liver transplantation is the only established curative therapy for end-stage primary biliary cirrhosis (PBC). However, the influence of primary immunosuppression on long-term patient and graft survival is still controversial. PATIENTS AND METHODS: Among 1372 patients who underwent liver transplantation from April 1989 to January 2001, 95 (6.9%) suffered from PBC. The primary immunosuppression consisted of cyclosporine (CyA; n = 56) and tacrolimus (FK; n = 39). RESULTS: The median survival of all PBC patients at 5 years was 92% and at 10 years, 90%. There was no difference between the two primary immunosuppression agents. Seven patients died, including five in the cyclosporine group (median = 25 months) and two in the tacrolimus cohort (median = 37 months). One CyA patient group died due to PBC recurrence. Seven patients underwent retransplantation without any difference in primary immunosuppression (CyA 7%; FK 10%). Fifty patients developed an acute rejection episode (CyA 57%; FK 46%); 2 patients, chronic rejection (CyA 2%; FK 4%). Fifty-five patients developed AMA titers after liver transplantation (CyA 66%; FK 46%). Patients presented cyclosporine-based regimens showed significantly (P = .001) more side effects. CONCLUSION: Long-term follow-up after liver transplantation for PBC shows excellent organ and patient survival. The choice of the primary immunsuppressant had no significant influence on patient survival, PBC-related graft loss, or development of acute or chronic rejection episodes.

Repeated steroid pulse therapies in HCV-positive liver recipients: significant risk factor for HCV-related graft loss.

BACKGROUND: The optimal immunosuppressive regimen for HCV-positive liver transplant recipients has not been established. Treatment for acute cellular rejection (ACR) with steroids is associated with increased viral replication and graft hepatitis. We retrospectively analyzed 232 patients after orthotopic liver transplantation (OLT) for HCV cirrhosis to determine the influence of methylprednisolone pulse therapy on long-term outcome after OLT. METHODS: Two hundred thirty-two liver transplants were performed in HCV-positive recipients between 1989 and 2001. Median follow-up was 4.4 years and median age of patients was 53 years (range 15 to 72 years). Immunosuppression consisted of tacrolimus (Tac) or cyclosporine (CyA) in different protocols. All rejection episodes were histologically proven. RESULTS: Twenty-eight of 232 (12.06%) graft losses were due to severe hepatitis C reinfection. Of 232 patients, 105 showed a minimum of one episode of ACR (45.25%). Of 232 patients, 71 (30.6%) received methylprednisolone pulse therapy once and 15 of 232 required OKT3 treatment for steroid-resistant rejection (6.4%). Of 232 patients, 19 (8.1%) required repeated steroid pulse therapy due to more than one episode of ACR. In patients with more than one episode of ACR, the risk of HCV-related graft loss was significantly enhanced (6/19, P < .05). The primary immunosuppression had no influence on the outcome in our data. CONCLUSION: Our data show that outcome of HCV-positive patients who require repeated steroid pulse therapy (RSPT) for ACR is significant worse than that in patients with a single pulse therapy. Therefore RSPT should be avoided in HCV-positive transplant recipients. New strategies to manage acute rejection are required for these patients.

Cobalt-protoporphyrin induced heme oxygenase overexpression and its impact on liver regeneration.

Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect from ischemia-reperfusion injury, which remains a major source of graft loss after liver transplantation. The impact of HO-1 on liver regeneration, especially in reduced-size grafts, has not yet been evaluated. Using an experimental model, we investigated HO-1 induction by CoPP treatment on postoperative recovery of ischemically injured livers following partial (70%) hepatectomy. Wistar rats underwent partial hepatectomy under temporary inflow occlusion (30 minutes). One group of animals received CoPP (5 mg/kg body weight i.p.) 24 hours prior to surgery to induce high levels of HO-1 at the time of surgery, and the second group served as nontreated controls. At postoperative days 1, 4, 7, and 10, animals were exsanguinated, and blood and liver samples were stored for enzymatic (serum AST and ALT levels) and histologic (mitotic index) analyses (n = 5 each day). Additionally, postoperative body weight and weight of the remnant liver were measured. Although serum AST and ALT levels as well as remnant liver weight were comparable between both groups, CoPP-treated animals recovered from surgery more quickly as indicated by postoperative body weight. Moreover, the number of mitotic cells was significantly increased in this group at day 1 (33 +/- 5 versus 20 +/- 5 per 2000 hepatocytes) as compared with nontreated animals. Liver regeneration of ischemically injured livers following partial hepatectomy was improved by HO-1 overexpression following preoperative CoPP administration. Thus, it is conceivable that prevention of ischemia-reperfusion injury by HO-1 overexpression also might be beneficial for reduced-size liver grafts without affecting their proliferative capacity.