Maximilian von Heesen

Parenchyma-preserving hepatic resection for colorectal liver metastases

BackgroundHepatic resection of colorectal liver metastases is the only curative treatment option. As clinical and experimental data indicate that the extent of liver resection correlates with growth of residual metastases, the present study analyzes the potential benefit of a parenchyma-preserving liver surgery approach.MethodsData from a prospectively maintained database of patients undergoing liver resection for colorectal metastases were reviewed. Evaluation of outcome was performed using the Kaplan–Meier method. Correlations were calculated between clinical–pathological variables.ResultsOne hundred sixty-three patients underwent 198 liver resections for colorectal metastases: 26 major hepatectomies, 65 minor anatomical resections, 78 non-anatomical resections, as well as 29 combinations of minor anatomical and non-anatomical procedures. Overall 1-, 3-, and 5-year survival was 93%, 62%, and 40%, respectively. Patients with repeated liver resections had a 5-year survival of 27%. Interestingly, large dissection areas were associated with a significant reduction of the 5-year survival rate (33%). Five-year survival after major hepatectomy was not significantly reduced.ConclusionFor colorectal liver metastases, minor resections offer a prolonged survival compared to major hepatectomies. As patients with stage IV colorectal disease are candidates for repeat resections, preservation of hepatic parenchyma is of increasing importance in the setting of multi-modal and repeated therapy approaches.

Multidrug donor preconditioning protects steatotic liver grafts against ischemia-reperfusion injury

BACKGROUND Graft dysfunction of steatotic livers (SL) still remains a major challenge in liver transplantation. Different mechanisms are thought to be involved in the impaired tolerance of SL to ischemia-reperfusion injury. Thus, different pharmacologic strategies may need to be combined to effectively protect SL and to reduce graft dysfunction after transplantation. Therefore, we analyzed the effectiveness of a multidrug donor preconditioning (MDDP) procedure to protect SL from cold ischemia-reperfusion injury. METHODS Liver steatosis was induced by a high-carbohydrate, fat-free diet. A total of 24 Sprague-Dawley rats were divided into 3 groups (n = 8 each), including a control group with nonsteatotic livers (Con), a vehicle-treated SL group (SL-Con), and a SL group undergoing MDDP (SL-MDDP), including pentoxyphylline, glycine, deferoxamine, N-acetylcysteine, erythropoietin, melatonin, and simvastatin. MDDP was applied before liver perfusion with 4°C histidine-tryptophan-ketoglutarate (HTK) solution and organ harvest. After 24 hours of cold storage in HTK, postischemic reperfusion was performed in an isolated liver reperfusion model using 37°C Krebs-Henseleit bicarbonate buffer. RESULTS After 60 minutes of reperfusion, SL showed a significant reduction of bile flow as well as a marked increase of liver enzyme levels and apoptotic cell death compared with Con. This was associated with an increased malondialdehyde formation, interleukin-1 production, and leukocytic tissue infiltration. MDDP completely abolished the inflammatory response and was capable of significantly reducing parenchymal dysfunction and injury. CONCLUSIONS MDDP decreases SL injury after cold storage and reperfusion. The concept of MDDP as a simple and safe preoperative regime, thus may be of interest in clinical use, expanding the donor pool from marginal donors.

Split-Liver Procedure and Inflammatory Response: Improvement by Pharmacological Preconditioning

BACKGROUND Final outcome of split-liver (SL) transplantation is impaired due to an increased rate of vascular complications and primary non-function. Herein, we hypothesized that an in situ split-liver procedure induces an inflammatory response and a deterioration of graft quality. We further studied whether graft quality can be improved by pharmacologic preconditioning. MATERIAL AND METHODS SL-procedure was performed in rats. One group (SL-HPP; n = 8) was pretreated according to a defined protocol [Homburg preconditioning protocol (HPP)], including pentoxyphylline, glycine, deferoxamine, N-acetylcysteine, erythropoietin, melatonin, and simvastatin. A second SL group (SL-Con; n = 8) received NaCl. Untreated non-SL served as controls (Sham; n = 8). Cytokines release, leukocyte invasion, endothelial activation and liver morphology were studied directly after liver harvest and after 8 h cold storage. Lung tissue was studied to determine remote injury. RESULTS The SL-procedure induced an increase of TNF-α concentration, intercellular-adhesion-molecule 1 (ICAM-1) expression, leukocytic-tissue infiltration and vacuolization. This was associated with an increased number of apoptotic hepatocytes. HPP reduced TNF-α release, ICAM-1 expression, the number of infiltrated leukocytes, as well as hepatocellular vacuolization and apoptosis. In lung tissue, the SL-procedure caused an increased IL-1 and IL-6 concentration and leukocyte infiltration. CONCLUSIONS HPP was capable of abrogating cytokine-mediated leukocytic response. Pharmacologic preconditioning of liver donors prevents the SL procedure-mediated inflammatory response, resulting in an improved graft quality.

Portal Hyperperfusion after Extended Hepatectomy Does Not Induce a Hepatic Arterial Buffer Response (HABR) but Impairs Mitochondrial Redox State and Hepatocellular Oxygenation

Background & Aims Portal hyperperfusion after extended hepatectomy or small-for-size liver transplantation may induce organ dysfunction and failure. The underlying mechanisms, however, are still not completely understood. Herein, we analysed whether hepatectomy-associated portal hyperperfusion induces a hepatic arterial buffer response, i.e., an adaptive hepatic arterial constriction, which may cause hepatocellular hypoxia and organ dysfunction. Methods Sprague-Dawley rats underwent 30%, 70% and 90% hepatectomy. Baseline measurements before hepatectomy served as controls. Hepatic arterial and portal venous flows were analysed by ultrasonic flow measurement. Microvascular blood flow and mitochondrial redox state were determined by intravital fluorescence microscopy. Hepatic tissue pO2 was analysed by polarographic techniques. Hepatic function and integrity were studied by bromosulfophthalein bile excretion and liver histology. Results Portal blood flow was 2- to 4-fold increased after 70% and 90% hepatectomy. This, however, did not provoke a hepatic arterial buffer response. Nonetheless, portal hyperperfusion and constant hepatic arterial blood flow were associated with a reduced mitochondrial redox state and a decreased hepatic tissue pO2 after 70% and 90% hepatectomy. Microvascular blood flow increased significantly after hepatectomy and functional sinusoidal density was found only slightly reduced. Major hepatectomy further induced a 2- to 3-fold increase of bile flow. This was associated with a 2-fold increase of bromosulfophthalein excretion. Conclusions Portal hyperperfusion after extended hepatectomy does not induce a hepatic arterial buffer response but reduces mitochondrial redox state and hepatocellular oxygenation. This is not due to a deterioration of microvascular perfusion, but rather due to a relative hypermetabolism of the remnant liver after major resection.

Cilostazol improves hepatic blood perfusion, microcirculation, and liver regeneration after major hepatectomy in rats

Major hepatectomy or small‐for‐size liver transplantation may result in postoperative liver failure. So far, no treatment is available to improve liver regeneration. Herein, we studied whether cilostazol, a selective phosphodiesterase III inhibitor, is capable of improving liver regeneration after major hepatectomy. Sprague‐Dawley rats (n = 74) were treated with cilostazol (5 mg/kg daily) or a glucose solution and underwent either 70% liver resection or a sham operation. Before and after surgery, hepatic arterial and portal venous blood flow and hepatic microvascular perfusion were analyzed. Liver morphology, function, and regeneration were studied with histology, immunohistochemistry, western blotting, and bile excretion analysis. Cilostazol significantly increased hepatic blood flow and microcirculation before and after hepatectomy in comparison with sham‐operated controls. This was associated with an elevation of hepatic vascular endothelial growth factor expression, an increase of hepatocellular proliferation, and an acceleration of liver regeneration. Furthermore, cilostazol protected the tissue of the remnant liver as indicated by an attenuation of hepatocellular disintegration. In conclusion, cilostazol increases hepatic blood perfusion, microcirculation, and liver regeneration after a major hepatectomy. Thus, cilostazol may represent a novel strategy to reduce the rate of liver failure after both extended hepatectomy and small‐for‐size liver transplantation. Liver Transpl 21:792–800, 2015.

Endoscopic Resection Techniques

Cancers at an early stage of disease with a low risk of lymph node metastases or distant spread can be managed endoscopically. Different endoscopic techniques can be applied in the gastrointestinal tract. Furthermore, endoscopic and laparoscopic surgery can be combined in specific indications today. Most of all, resection-related complications can also be solved endoscopically.

Isoflurane does not Protect from Brain Death-Associated Aggravation of Cold Hepatic Ischemia-Reperfusion Injury

BACKGROUND Previous studies have shown that brain death aggravates cold ischemia-reperfusion injury in liver transplantation. Isoflurane, a volatile anesthetic, has been indicated to reduce warm hepatic ischemia-reperfusion injury. Herein, we studied in Sprague-Dawley rats whether isoflurane is capable of ameliorating brain death-associated aggravation of cold hepatic ischemia-reperfusion injury. MATERIAL AND METHODS Brain-dead animals were treated for 30 min with isoflurane (MAC 1.5%; n=8). Animals without isoflurane treatment served as controls (n=8). Another 13 animals without induction of brain death served as sham controls. After a 4-h period portal venous blood perfusion, hepatic microcirculation and bile flow were determined. Livers were recovered and stored for 24 h in 4°C cold HTK solution, followed by reperfusion with 37°C Krebs-Henseleit-buffer for 60 min. Liver enzymes in the effluent and bile flow were analyzed. Hepatocellular morphology was determined by histology and immunohistochemistry. RESULTS Brain death reduced portal venous blood perfusion and bile flow, induced heme oxygenase-1 (HO-1), and resulted in hepatocellular damage. Isoflurane treatment did not prevent the reduction of portal venous blood perfusion or bile flow or the induction of HO-1. Accordingly, isoflurane was not capable of reducing the hepatocellular injury. CONCLUSIONS Isoflurane does not protect from brain death-associated aggravation of cold hepatic ischemia-reperfusion injury.

Successful Management of Postoperative Necrotizing Pancreatitis After Infrarenal Abdominal Aortic Aneurysm Repair

We present a case of severe necrotizing pancreatitis that developed after elective repair of an abdominal aortic aneurysm. Surgeons are confronted in cases of postoperative acute pancreatitis with the dilemma of potential intraabdominal infection and the high risk of a subsequent infection of the retroperitoneal synthetic material. The therapeutic options range from a restrictive regime to radical necrosectomy and multivisceral resection.