Ligation of the middle hepatic vein to increase hypertrophy induction during the ALPPS procedure.

PURPOSE: Here, we analyse the technical modification of the ALPPS procedure, ligating the middle hepatic vein during the first step of the operation to enhance remnant liver hypertrophy. METHODS: In 20 of 37 ALPPS procedures, the middle hepatic vein was ligated during the first step. Hypertrophy of the functional remnant liver volume was assessed in addition to postoperative courses. RESULTS: Volumetric analysis showed a significant volume increase, especially for patients with colorectal metastases. Pre-existing liver parenchyma damage (odds ratio = 0.717, p = 0.017) and preoperative chemotherapy were found to be significant predictors (odds ratio = 0.803, p = 0.045) of higher morbidity and mortality. In addition, a survival benefit for maintenance of middle hepatic vein was shown. CONCLUSION: This technical modification of the ALPPS procedure can accentuate future liver remnant volume hypertrophy. The higher morbidity and mortality observed are most likely associated with pre-existing parenchymal damage within this group.

[Living related liver transplantation]. / Lebertransplantation durch Lebendspende.

Liver transplantation has become established as a standard procedure in the treatment of end-stage liver diseases. Despite intense efforts by all parties involved up to the amendment of the German Transplantation Act, the lack of suitable donor organs was still one of the limiting factors of this therapeutic procedure. One way out of this problem is to make so-called marginal organs usable, e.g. with the help of machine perfusion or by utilizing living liver donation, which are used in some countries for more than 90% of organ donations. In general, there is no difference in the indications for liver transplantation between a (partial) organ obtained by post-mortem or living donation. Before any living donation, a thorough evaluation of the donor is carried out in order to minimize postoperative morbidity as far as possible. Technically the partial liver donation is based on the oncological liver resection, while the partial liver transplantation is a further development of split liver transplantation after post-mortem liver donation. In specialized centers comparable or even better results can nowadays be achieved using living liver donation instead of post-mortem donation.

[Benign liver tumors : Diagnostics and treatment]. / Benigne Lebertumoren : Diagnostik und Behandlung.

Benign liver tumors are often detected during routine ultrasound examinations or as an incidental finding in radiological imaging. Only very few benign liver tumors are at risk of becoming malignant. In the majority of cases the differentiation from malignant tumors is currently carried out using imaging procedures. In a few cases of diagnostic uncertainty, a transcutaneous liver biopsy can lead to clarification. If the suspicion of malignancy is substantiated or this cannot be excluded with absolute certainty, the tumor should be removed by partial liver resection.

Surgical technique for placement of the automated low flow ascites pump (Alfapump).

Approximately 10% of patients with ascites associated with cirrhosis fail to respond to dietary rules and diuretic treatment and therefore present with refractory ascites. In order to avoid iterative large-volume paracentesis in patients with contraindication to TIPS, the automated low flow ascites pump system (Alfapump) was developed to pump ascites from the peritoneal cavity into the urinary bladder, where it is eliminated spontaneously by normal micturition. This manuscript reports the surgical technique for placement of the Alfapump.

[Prerehabilitation in frail patients : Frailty as a risk factor]. / Prärehabilitation gebrechlicher Patienten : "Frailty" als Risikofaktor.

The German population is aging in accordance with the worldwide trend; however, in comparison to most other industrial countries the number of disease-free years of life gained by patients is significantly lower in Germany. Subsequently, the number of hospitalizations and necessary surgical treatment for older and especially frail patients is significantly increasing. Several frailty scoring systems have been published with the aim of improving the assessment of the perioperative risk for these patients; however, these systems for risk assessment have not yet become clinical routine in surgery and therefore this group of frail patients remains underdiagnosed in the field of surgery. Frail patients in particular often need individualized treatment or the adaptation of standard of perioperative care. It has already been clearly shown that frail patients have a markedly higher incidence for certain risk factors (e.g. postoperative delirium, hypovolemia, pharmacological side effects and drug interactions). Additionally, malnutrition is common at the time of hospital admission in up to 70% of this patient group. If not recognized and treated accordingly all these risk factors lead to a compromised rehabilitation, higher complication rates, a prolonged length of hospital stay and a higher mortality. Special preoperative risk assessment scores, which highlight physical, psychological and social evaluation should be widely implemented in surgical departments. A standardized risk assessment embedded in evidence-based prerehabilitation programs and implemented in geriatric surgery centers can help to improve the outcome in this group of fragile patients.

[Benign liver tumors : Diagnostics and treatment]. / Benigne Lebertumoren : Diagnostik und Behandlung.

Benign liver tumors are often detected during routine ultrasound examinations or as an incidental finding in radiological imaging. Only very few benign liver tumors are at risk of becoming malignant. In the majority of cases the differentiation from malignant tumors is currently carried out using imaging procedures. In a few cases of diagnostic uncertainty, a transcutaneous liver biopsy can lead to clarification. If the suspicion of malignancy is substantiated or this cannot be excluded with absolute certainty, the tumor should be removed by partial liver resection.

[Preoperative conditioning in ageing patients-gerontosurgery]. / Präoperative Konditionierung im Alter ­ Gerontochirurgie.

Adapting the daily hospital routine to changes in the aging structure of society and the patients will be one of the main challenges for surgeons in the coming years. Important factors regarding the outcome of aging patients will be preoperative conditioning, specific age-adapted surgical strategies and the organization of the hospital infrastructure. Nutritional protocols and liquid intake schedules should be taken into account as well as cognitive assessment tools and strategies to protect aging patients from postoperative delirium. The importance of changes in metabolism and the concomitant comorbidities are very similar in most specialty disciplines. The lack of a clear and widely accepted definition of biological age and the missing adaptations of, e. g. complication scores, currently exacerbate the compilation of a resilient survey. In the absence of a reimbursement-system for geriatric medicine it will be very difficult to achieve the necessary structural changes in the treatment regimens for older patients. The establishment of the necessary surgical treatment adapted to the needs of older patients therefore remains a challenging task.

Randomized clinical trial comparing liver resection with and without perioperative assessment of liver function.

BACKGROUND: Liver function tests may help to predict outcomes after liver surgery. The aim of this study was to evaluate the clinical impact on postoperative outcome and patient management of perioperative liver function testing using the LiMAx® test. METHODS: A multicentre RCT was conducted in six academic liver centres. Patients with intrahepatic tumours scheduled for open liver resection of at least one segment were eligible. Patients were randomized to undergo additional perioperative liver function tests (LiMAx® group) or standard care (control group). Patients in the intervention arm received two perioperative LiMAx® tests, one before the operation for surgical planning and another after surgery for postoperative management. The primary endpoint was the proportion of patients transferred directly to a general ward. Secondary endpoints were severe complications, length of hospital stay (LOS) and length of intermediate care/ICU (LOI) stay. RESULTS: Some 148 patients were randomized. Thirty-six of 58 patients (62 per cent) in the LiMAx® group were transferred directly to a general ward, compared with one of 60 (2 per cent) in the control group (P < 0·001). The rate of severe complications was significantly lower in the LiMAx® group (14 per cent versus 28 per cent in the control group; P = 0·022). LOS and LOI were significantly shorter in the LiMAx® group (LOS: 10·6 versus 13·3 days respectively, P = 0·012; LOI: 0·8 versus 3·0 days, P < 0·001). CONCLUSION: Perioperative use of the LiMAx® test improves postoperative management and reduces the incidence of severe complications after liver surgery. Registration number: NCT01785082 ( https://clinicaltrials.gov).

[Precancerous and early stage cancer of the bile duct system]. / Präkanzerosen und Frühkarzinome des Gallengangsystems.

Early stage cancer of the bile duct system is still difficult to diagnose. In cases of suspect lesions a stepwise diagnostic procedure consisting of computed tomography (CT), magnetic resonance imaging (MRI) with MR cholangiography (MRC) and possibly endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology should immediately be carried out. If there is a sufficient suspicion for premalignancy or early stage cancer the indications for surgical intervention should clearly be defined. Only resection can lead to a decrease in the recurrence rate and a better long-term outcome. If the patient is in a functionally nonresectable condition the possibility of liver transplantation should be considered.

[Puberty is a major factor in pilonidal sinus disease : Gender-specific investigations of case number development in Germany from 2007 until 2015]. / Die Pubertät ist ein wichtiger Faktor bei der Pilonidalsinuserkrankung : Geschlechtsspezifische Untersuchung der Fallzahlentwicklung in Deutschland 2007 bis 2015.

BACKGROUND: Pilonidal sinus disease is an acute abscess-forming or chronic subacute inflammation, characterized by a fistula system with typical ostia. Treatment is primarily surgical. OBJECTIVE: This study aimed to investigate and evaluate the evolution of pilonidal sinus disease in Germany on the basis of data provided by the Federal Statistical Office in Germany (Statistisches Bundesamt). MATERIAL AND METHODS: From the diagnosis data of hospital inpatients generated by the Federal Statistical Office in Germany the data on the International Classification of Diseases (ICD) code L05 for pilonidal sinus from 2007 to 2015 were extracted and processed. RESULTS AND DISCUSSION: The number of cases increased from 25,835 cases in 2007 to 31,033 cases in 2011, followed by a decrease to 30,235 cases in 2015. Considering the number of patients under 20 years of age, there was also an increase from 40 cases per 100,000 population in 2007 to 50 cases per 100,000 population in 2013. Ever since, the case numbers have remained relatively constant and have reached a plateau. The maximum number of case numbers was in the age group of 20-24 years. The female age group 10-14 years old is the only group among all investigated age groups with more cases than the respective male age group. The investigated data did not permit any epidemiological conclusions for pilonidal sinus disease because outpatient cases have not been included. The higher incidence in the female age group 10-14 years old could be explained by the earlier onset of adolescence. Thus, adolescence appears to have a major impact on the development of pilonidal sinus disease.

Pulmonary metastasectomy for metastasized hepatocellular carcinoma after liver resection and liver transplantation: a single center experience.

BACKGROUND: The role of surgery in the treatment of metastasized hepatocellular carcinoma (HCC) remains uncertain. We here report our single centre experience with pulmonary metastasectomy (PM) for metachronous HCC metastases to the lung following curative liver resection (LR) and liver transplantation (LT), respectively. METHODS: Of 270 patients with HCC being treated by LR or LT at the University Hospital of Leipzig between January 1996 and July 2014, PM was performed in the follow up of 10 patients because of metachronous pulmonary HCC metastases. We retrospectively analyzed demographic and clinicopathological factors as well as the outcome after primary and secondary tumor treatment in these patients. RESULTS: Following LR/LT and metastasectomy, respectively, mean overall survival was 4.58 ± 0.84 years and 2.4 ±â€Š0.69 years. Postoperative morbidity after primary and secondary tumor treatment was 30 % and 20 %, respectively. Perioperative 30-day mortality was 0 %. Univariate analysis suggest tumor grading (p < 0.05), and a disease free-intervall > 1 year (p = 0.02) as significant prognostic parameters for survival in our collective. CONCLUSION: PM can be performed safely with a reasonable morbidity even in immunosuppressed patients after LT. Further studies are needed to evaluate whether PM can increase long-term survival in selected patients with resectable metastases and represents an alternative or additive treatment modality to the protein kinase inhibitor sorafenib.

Mouse white adipose tissue-derived mesenchymal stem cells gain pericentral and periportal hepatocyte features after differentiation in vitro, which are preserved in vivo after hepatic transplantation.

AIM: Mesenchymal stem cells may differentiate into hepatocyte-like cells in vitro and in vivo. Therefore, they are considered a novel cell resource for the treatment of various liver diseases. Here, the aim was to demonstrate that mesenchymal stem cells may adopt both perivenous and periportal hepatocyte-specific functions in vitro and in vivo. METHODS: Adipose tissue-derived mesenchymal stem cells were isolated from immunodeficient C57BL/6 (B6.129S6-Rag2(tm1Fwa) Prf1(tm1Clrk) ) mice and differentiated into the hepatocytic phenotype by applying a simple protocol. Their physiological and metabolic functions were analysed in vitro and after hepatic transplantation in vivo. RESULTS: Mesenchymal stem cells changed their morphology from a fibroblastoid into shapes of osteocytes, chondrocytes, adipocytes and hepatocytes. Typical for mesenchymal stem cells, hematopoietic marker genes were not expressed. CD90, which is not expressed on mature hepatocytes, decreased significantly after hepatocytic differentiation. Markers indicative for liver development like hepatic nuclear factor 4 alpha, or for perivenous hepatocyte specification like cytochrome P450 subtype 3a11, and CD26 were significantly elevated. Periportal hepatocyte-specific markers like carbamoylphosphate synthetase 1, the entry enzyme of the urea cycle, were up-regulated. Consequently, cytochrome P450 enzyme activity and urea synthesis increased significantly to values comparable to cultured primary hepatocytes. Both perivenous and periportal qualities were preserved after hepatic transplantation and integration into the host parenchyma. CONCLUSIONS: Adult mesenchymal stem cells from adipose tissue differentiated into hepatocyte-like cells featuring both periportal and perivenous functions. Hence, they are promising candidates for the treatment of region-specific liver cell damage and may support organ regeneration in acute and chronic liver diseases.

Management of urologic complications in renal transplantation: a single-center experience.

INTRODUCTION: Ureterovesical complications subsequent to renal transplantation are associated with a high morbidity leading to graft loss or even death. In the present study, the management of these complications by using interventional and surgical procedures (native pyeloureterostomy [NPUS]/ureteroureterostomy [NUU] vs ureteroneocystostomy [UNC]) was evaluated retrospectively. PATIENTS AND METHODS: Between 1994 and 2012, a total of 780 kidney transplantations (690 deceased and 90 living donors) were performed at our institution. Demographic, clinical, and laboratory data from patients with urologic complications were analyzed and compared. RESULTS: Fifty patients (6.4%) exhibited ureterovesical complications, and 18 patients (36%) were operated on immediately. In 32 (64%) of 50 patients, an interventional procedure was initially performed, with 21 patients (66%) undergoing operation due to therapy failure. NPUS/NUU and UNC were performed in 26 (66.6%) and 13 (33.3%) patients, respectively. Indications for an operation were ureteral stenosis in 12 patients (30.8%), ureteral necrosis and urine leakage in 19 patients (48.7%), and symptomatic vesicoureteral reflux in 8 patients (20.5%). Long-term results were comparable between all groups. CONCLUSIONS: Surgical revision of ureteral complications should be the standard therapy. NPUS/NUU, UNC, and the successful interventional procedures did not differ significantly in terms of long-term results.

[Early results after peripheral vascular replacement with biosynthetic collagen prosthesis in cases of graft infection]. / Frühergebnisse nach peripherem Gefäßersatz mit einer biosynthetischen Kollagenprothese bei Protheseninfektionen.

INTRODUCTION: Vascular graft infection in peripheral bypass surgery represents a highly significant risk with regard to limb loss and morbidity. In the absence of autologous superficial veins, finding a suitable replacement material can be difficult. Silver-coated polyester grafts, homografts, or use of deep veins can pose additional risks. Use of a biosynthetic collagen prosthesis on a Dacron matrix ("Omniflow-II®") was investigated as an alternative method, and the cost-effectiveness was evaluated. MATERIALS AND METHODS: From December 2010 to December 2011, eight patients with clinical symptoms of vascular graft infection, confirmed by imaging, were treated. Graft function or acute graft failure due to the infection was necessary for enrollment in the study. Infected material was removed, microbiological specimens taken and, in the absence of superficial veins, an "Omniflow-II®" prosthesis was implanted in an orthotopic position. Patients were followed up to evaluate their outcome, and the cost-effectiveness of the procedure was also analysed. RESULTS: The technical feasibility of the procedure was assessed in all cases. Pathogens were detected in five of eight cases. After a mean follow-up of 8 months, seven of eight patients showed that they were clinically cured of infection. Primary patency was 63%, secondary patency was 75%, and prevalence of limb salvage was 88%. One patient had to undergo limb amputation to avoid sepsis, and another unsuccessfully underwent thrombectomy after 12 months. Four PET-CT follow-up studies showed a reduction of uptake in the affected area. To generate adequate revenue by using this technique, specialised knowledge of the diagnosis-related group system is necessary. DISCUSSION: Treatment of vascular graft infections in peripheral bypass surgery in the absence of endogenous material necessitates the use of infection-resistant materials. The present study showed promising results using a collagen-biosynthetic prosthesis. Due to a lack of long-term results, the graft should be used only after detailed informed consent is obtained from the patient. The expenses incurred by using the biosynthetic graft should be covered adequately by revenues from these patients.

Isolation and hepatocyte differentiation of mesenchymal stem cells from porcine bone marrow--"surgical waste" as a novel MSC source.

Mesenchymal stem cells (MSC) isolated from bone marrow and differentiated into hepatocyte-like cells have increasingly gained attention for clinical cell therapy of liver diseases because of their high regenerative capacity. They are available from bone marrow aspirates of the os coxae after puncture of the crista iliaca or from bone marrow "surgical waste" gained from amputations or knee and hip operations. Thus, the aim of the study was to demonstrate whether these pBM-MSC (porcine bone marrow-derived mesenchymal stem cells) displayed mesenchymal features and hepatocyte differentiation potential. MSC were isolated either from crista iliaca punctures or after sampling and collagenase digestion of bone marrow from the os femoris. Mesenchymal features were assessed by flow cytometry for specific surface antigens and their ability to differentiate into at least 3 lineages. Functional properties, such as urea or glycogen synthesis and cytochrome P450 activity, as well as the cell morphology were examined during hepatocyte differentiation. pBM-MSC from both sources lacked the hematopoietic markers CD14 and CD45 but expressed the typical mesenchymal markers CD44, CD29, CD90, and CD105. Both cell types could differentiate into adipocyte, osteocyte, and hepatocyte lineages. After hepatocyte differentiation, CD105 expression decreased significantly and cells changed morphology from fibroblastoid into polygonal, displaying significantly increased glycogen storage, urea synthesis, and cytochrome activity. pBM-MSC from various sources were identical in respect to their mesenchymal features and their hepatocyte differentiation potential. Hence, long bones might be a particularly useful resource to isolate bone marrow mesenchymal stem cells for transplantation.

Liver resection for hepatocellular carcinoma in patients without cirrhosis.

BACKGROUND: Data on liver resection for hepatocellular carcinoma (HCC) without cirrhosis are sparse. The present study was conducted to evaluate the indications and results of liver resection for HCC with regard to safety and efficacy. METHODS: Data for patients who had liver resection for HCC without cirrhosis between January 1996 and March 2011 were retrieved retrospectively using a prospective database containing information on all patients who underwent hepatectomy for HCC. Patient and tumour characteristics were analysed for influence on overall and disease-free survival to identify prognostic factors by univariable and multivariable analysis. RESULTS: The 1-, 3- and 5-year overall survival rates after resection with curative intent for HCC without cirrhosis were 84, 66 and 50 per cent respectively. Disease-free survival rates were 69, 53 and 42 per cent respectively. The 90-day mortality rate was 4·5 per cent (5 of 110 patients). Surgical radicality and growth pattern of the tumour were independent prognostic factors for overall survival. Disease-free survival after resection with curative intent was independently affected by growth pattern and by the number and size of tumour nodules. CONCLUSION: Liver resection for HCC without cirrhosis carries a low perioperative risk and excellent long-term outcome if radical resection is achieved.

Kidney transplant from the same donor without maintenance immunosuppression after previous hematopoietic stem cell transplant.

In January 2005, an 18-year-old male patient with acute myeloid leukemia (AML) received a haploidentical hematopoietic stem cell transplantation (HSCT) from his father. He developed hemolytic uremic syndrome and end-stage renal disease (ESRD) requiring hemodialysis on day 357 after HSCT. On day 1020 after HSCT, a living kidney donation from the stem cell donor was carried out. The creatinine before kidney transplantation (KT) was ≈450 µmol/L, 268 µmol/L on day 2 after KT, 88 µM on day 38 and 89 µmol/L on day 960 (day 1980 after HSCT). Immunosuppression was gradually discontinued: cortisone on day 28, tacrolimus on day 32 and MMF on day 100 after KT (day 1120 after HSCT). As of June 2010, 66 months after HSCT and 32 months after KT, the patient has had neither rejection episodes nor clinical manifestations of transplantation-related complications. The patient reached 100% hematopoietic donor chimerism prekidney transplant and retained this state postkidney transplant. This unique case is the first report of a successful kidney transplant without immunosuppression after HSCT from the same haploidentical donor.