Oszkár Hahn

Oxidative stress with altered element content and decreased ATP level of erythrocytes in hepatocellular carcinoma and colorectal liver metastases

Our aim was to study the possible alterations of redox status (enzymatic and nonenzymatic parameters and metal elements) in erythrocytes of patients with hepatocellular carcinoma (HCC), colorectal liver metastases (CRLM) and benign liver neoplasms. The function of redox homeostasis is closely connected to the energy level of erythrocytes, therefore, the ATP level was also determined. Antioxidant parameters, enzyme activities of superoxide dismutase and glutathione peroxidase were estimated in the erythrocytes of 11 patients with benign tumour, 23 patients with primary malignant and 37 metastatic liver tumour patients and 30 age-matched and sex-matched healthy controls. Element content with inductively coupled plasma optical emission spectrometer and ATP level by the chemiluminometric method were also determined from the samples. Free radical intensity was significantly increased, whereas erythrocyte glutathione peroxidase and superoxide dismutase activities were significantly decreased in the HCC and CRLM groups versus benign groups and controls. Se, Mn and Zn levels were lowered in HCC and CRLM groups versus benign and control groups. The content of Cu, Mg, Se and Zn changed significantly between HCC and CRLM groups. Similarly, ATP concentration decreased in HCC and CRLM versus controls and benign groups. The lowest levels of ATP and antioxidant enzyme activities were found in the case of CRLM patients. These results reveal an alteration in the ATP level of erythrocytes with concomitant changes in the antioxidant defence system in hepatic cancer patients. Altered redox homeostasis (oxidative damage) may lead to decreased ATP level and consequently may play an important role in primary carcinogenesis and generation of metastases, as well.

The effect of ischemic preconditioning on redox status during liver resections-randomized controlled trial

Portal clamping during liver resection decreases intraoperative blood loss, but causes ischemic‐reperfusion (I‐R) injury. Intermittent portal clamping (IPC) and ischemic preconditioning (IP) decreased I‐R injury in animal models. Most of the human studies about IP excluded cirrhotic patients, whose liver is more vulnerable to I‐R injury. The effect of IP and IPC during extended liver resection was investigated in this randomized controlled trial, with special respect to cirrhotic patients.

Animal Models for Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS): Achievements and Future Perspectives

Background: Since 2012, Associated Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has been standing in the limelight of modern liver surgery and numerous questions have been raised regarding this novel approach. On the one hand, ALPPS has proved to be a valuable method in the treatment of hepatic tumors, while on the other hand, there are many controversies, such as high mortality and morbidity rates. Further surgical research is essential for a better understanding of underlying mechanisms and for enhancing patient safety. Summary: Until recently, only 8 animal models have been created with the purpose to mimic ALPPS-induced liver regeneration. From these 7 are rodent (6 rat and 1 mouse) models, while only 1 is a large animal model, which uses pigs. In case of rodent models, portal flow deprivation of 75-90% is achieved via portal vein ligation leaving only the right (20-25%) or left median (10-15%) lobes portally perfused, while liver splitting in general is carried out positioned according to the falciform ligament. As for the swine model, the left lateral and medial lobes (70-75% of total liver volume) are portally ligated, and the right lateral lobe (accounting for 20-24% of the parenchyma) is partially resected in order to reach critical liver volume. Each model is capable of reproducing the accelerated liver regeneration seen in human cases. However, all species have significantly different liver anatomy compared with the human anatomic situation, making clinical translation somewhat difficult. Key Messages: Unfortunately, there are no perfect animal models available for ALPPS research. Small animal models are inexpensive and well suited for basic research, but may only provide limited translational potential to humans. Clinically large animal models may provide more relevant data, but currently no suitable one exists.

[ALPPS (Associated Liver Partition and Portal vein ligation for Staged hepatectomy) -- faster and greater growth of liver].

CASE REPORT 75 years old female patient was referred with large, multifocal colorectal liver metastasis. Prior to this consultation she received chemotherapies of various protocols and series. Liver metastasis, however, increased at about 3 times of the original size during the 5 months of the oncological treatment. A right extended hepatectomy was planned to remove the tumor, but the residual liver (FLR) was found to be too small. Portal occlusion technique was necessary to induce the hypertrophy of the FLR. Due to rapid tumor progression we decided to perform the first ALPPS (PVL + in situ split) procedure in Hungary. After a very fast (9 days) and significant (94%) hypertrophy of the FLR the planned liver resection was successfully performed.

Single-Port Cholecystectomy Through the Lateral Ring of the Left Inguinal Hernia

Background: Single-port surgery was developed by the evolution of the laparoscopy. The advantage of this new method is mainly cosmetic, but the risk of the hernia—owing to the larger port—increased. Case report: A 71-year-old man was admitted with a left lateral inguinal hernia and gallbladder stones. After preparation of the sac of the hernia, a single-port was inserted into the lateral ring and a cholecystectomy was performed. The operation was completed by the reconstruction of the abdominal wall using a polypropylene mesh. The total operating time was 85 minutes. Conclusion: In the case of the combined operation, the defect of the abdominal wall could be used as a location of the single port, and the trauma of the abdominal wall could be avoided. This is the first publication about single-port cholecystectomy where the ring of the inguinal hernia was used as a placement site of the single port.

ALPPS (Associated Liver Partition and Portal vein ligation for Staged hepatectomy) – gyorsabb, nagyobb májhypertrophia

CASE REPORT 75 years old female patient was referred with large, multifocal colorectal liver metastasis. Prior to this consultation she received chemotherapies of various protocols and series. Liver metastasis, however, increased at about 3 times of the original size during the 5 months of the oncological treatment. A right extended hepatectomy was planned to remove the tumor, but the residual liver (FLR) was found to be too small. Portal occlusion technique was necessary to induce the hypertrophy of the FLR. Due to rapid tumor progression we decided to perform the first ALPPS (PVL + in situ split) procedure in Hungary. After a very fast (9 days) and significant (94%) hypertrophy of the FLR the planned liver resection was successfully performed.

Laparoscopic surgery of benign liver tumours

273 patients underwent elective surgical treatment for benign liver lesions at the 1st Surgical Department of Semmelweis University, Budapest, Hungary between 2004 and 2014. Laparoscopic (LAP) interventions were performed in 83 cases. Cyst fenestration in 52, and hepatic resection in 31 cases. LAP liver resections were set against to open surgery of paired group of patients with comparable demographic and clinical parameters. Data revealed that the operative time in LAP group (113.7 min) was significantly longer than that in the open surgery group (89.5 min). The average postoperative length of hospital stay was shorter after LAP surgery (5.8 vs 9.1 days). There was no postoperative complication in the LAP group, two wound infections and one biliary collection were treated by ultrasonic drainage in the open group. Three patients were given blood transfusion in the LAP, four in the open group. Operative mortality was zero, and no reoperation required. The surgical technique which is described in detail in the text enables safe resection of segments 7-8 which are difficult to approach. Our data support the safety and feasibility of laparoscopic liver resection after adequate preoperative investigations.

In depth evaluation of the prognostic and predictive utility of PTEN immunohistochemistry in colorectal carcinomas: performance of three antibodies with emphasis on intracellular and intratumoral heterogeneity

BackgroundPhosphatase and tensin homolog deleted in chromosome 10 (PTEN) loss of function is frequently detected in advanced colorectal cancer. Its detection is thought to have prognostic significance and it is being considered to predict responsiveness to anti-EGFR therapy. Unfortunately, while immunohistochemical assessment of PTEN expression is widespread, it lacks standardization and the results are hardly comparable across the available publications.MethodsRetrospectively collected, formalin-fixed and paraffin-embedded colorectal tumor tissue samples from 55 patients were combined into tissue microarray (TMA) blocks. We used three different PTEN antibodies to determine the frequency, intensity and intracellular pattern of PTEN immunohistochemical labeling: Neomarkers, Dako and CellSignaling. We evaluated the aforementioned parameters in selected regions of colorectal cancers and in their lymph node metastases by using three scoring methods that take into consideration both staining frequency and intensity (H1-H3-score). We also evaluated intracellular localization.ResultsThe Dako and CellSignaling antibodies stained predominantly cytoplasms, while the Neomarkers antibody specifically stained cell nuclei. PTEN H-scores were significantly lower in all tumor areas as compared to the normal colonic mucosa based on staining with the DAKO and CellSignaling antibodies. Intratumoral regional differences or differences between matching tumors and metastases were not detected with any of the antibodies. Neither Dako, neither CellSignaling, nor the Neomarkers antibodies revealed a significant correlation between PTEN expression and pT, Dukes/MAC and clinical stage. KRAS status, histological grade correlated with PTEN H-scores based on staining with the Neomarkers antibody. PTEN H-scores did not correlate with MMR status. PTEN H-scores did not show any correlation with relapse-free survival based on staining with either antibody.ConclusionsWhile PTEN expression decreased in colorectal cancer according to two antibodies, neither of the three applied PTEN antibodies could justify significant correlation with clinicopathological data, nor had prognostic value. Thus, we might conclude that immunohistochemical PTEN investigation remains a challenge requiring more standardized evaluation on larger number of cases to clarify its utility as a prognostic and predictive tool in CRC. The standardization of immunohistochemical method is key in the evaluation process, which is further discussed.

The importance of postoperative circulatory alterations in hepatic surgery

There are two afferent (hepatic artery, portal vein) and one efferent (hepatic veins) systems responsible for the unique circulation of the liver. Given this special form of vasculature, acute, isolated (i.e. involving selectively one particular vessel) vascular occlusions may lead to different, however still life threatening conditions. Hence, it is essential to recognize these anomalies in order to preserve the healthy state of both the liver and the patients lives. Acute circulatory failures are dominantly associated with liver surgery. Adequate therapy can only be provided promptly, if the clinician is well aware of the peculiarities of these conditions. The aim of this study is to overview the etiology and symptoms of these clinical conditions; furthermore to offer technical proposals for the required diagnostic and therapeutical steps via case reports. Furthermore, hepatic injury, caused by ischemia-reperfusion secondary to total vascular occlusion (Pringle maneuver) used in hepatic surgery is outlined.

ALPPS (AssociatedLiverPartition andPortal vein ligation forStaged hepatectomy) – gyorsabb, nagyobb májhypertrophia

CASE REPORT 75 years old female patient was referred with large, multifocal colorectal liver metastasis. Prior to this consultation she received chemotherapies of various protocols and series. Liver metastasis, however, increased at about 3 times of the original size during the 5 months of the oncological treatment. A right extended hepatectomy was planned to remove the tumor, but the residual liver (FLR) was found to be too small. Portal occlusion technique was necessary to induce the hypertrophy of the FLR. Due to rapid tumor progression we decided to perform the first ALPPS (PVL + in situ split) procedure in Hungary. After a very fast (9 days) and significant (94%) hypertrophy of the FLR the planned liver resection was successfully performed.