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Background Endoscopic vacuum therapy (EVT) has become a promising option in the management of anastomotic leakage (AL) after esophagectomy. However, EVT is an effortful approach associated with multiple interventions. In this study, we conduct a comparative cost analysis for methods of management of AL. Methods All patients who experienced AL treated by EVT, stent, or reoperation following Ivor Lewis esophagectomy for esophageal cancer were included. Cases that were managed by more than one modality were excluded. For the remaining cases, in-patient treatment cost was collected for material, personnel, (par)enteral nutrition, intensive care, operating room, and imaging. Results 42 patients were treated as follows: EVT n = 25, stent n = 13, and reoperation n = 4. The mean duration of therapy as well as length of overall hospital stay was significantly shorter in the stent than the EVT group (30 vs. 44d, p = 0.046; 34 vs. 53d, p = 0.02). The total mean cost for stent was €33.685, and the total cost for EVT was €46.136, resulting in a delta increase of 37% for EVT vs. stent cost. 75% (€34.320, EVT), respectively, 80% (€26.900, stent) of total costs were caused by ICU stay. Mean pure costs for endoscopic management were relatively low and comparable between both groups (EVT: €1.900, stent: €1.100, p = 0.28). Conclusion Management of AL represents an effortful approach that results in high overall costs. The expenses directly related to EVT and stent therapy were however comparatively low with more than 75% of costs being attributable to the ICU stay. Reduction of ICU care should be a central part of cost reduction strategies.

Background: Recurrent disease remains a major problem for esophageal cancer. This study was designed to evaluate the impact of localization of lymph node metastasis for tumor recurrence following curative esophageal resection. Methods: 273 patients undergoing esophagectomy for esophageal cancer between 2005 and 2014 at the Department of General, Visceral and Transplant Surgery, University Hospital of Münster were included. Tumor characteristics, treatment details, postoperative course and patients' outcome, including time point and localization of recurrent disease, were analyzed retrospectively. The median follow-up was 46.3 months. Results: Median overall and disease-free survivals were 22.7 and 13 months, respectively. Tumor characteristics including presence and number of lymph node metastasis, and localization of lymph node metastases, paraesophageal, perigastric and intra-abdominal, had significant impact on both tumor recurrence (p

BACKGROUND During the last decade, numerous therapeutic regimes were assessed to improve the outcome of patients with esophageal carcinoma. We analyzed the impact of therapy alterations, including the establishment of a standardized clinical pathway and the introduction of an interdisciplinary tumor conference on the outcome of patients undergoing esophagectomy because of esophageal cancer. METHODS Three hundred one patients were included (204 adenocarcinoma and 97 squamous cell carcinoma) who underwent an esophagectomy between 2006 and 2015. Patients were divided into 3 groups: interval A (2006-2008), interval B (2009-2011) and interval C (2012-2015) and evaluated separately focusing on therapy management and patients' outcome. RESULTS Over the time periods, the incidence of tumor entity of adenocarcinoma increased from 61% to 76.2% (P=0.059). Patients with an initial tumor stage uT1 increased significantly from 4% to 15.9% over the intervals (P=0.002), while positive nodal involvement remained comparable (P=0.237). Patients in the later interval suffered from greater physical impairments preoperatively, represented by a significantly increased American Society Anesthesiologists (ASA) score (P=0.023) and a reduced Karnofsky Index (P

Background Tracheo- or bronchoesophageal fistula (TBF) occurring after esophagectomy represent a rare but devastating complication. Management remains challenging and controversial. Therefore, the purpose of this study was to evaluate the outcome of different treatment approaches and to propose recommendations for the management of TBF. Methods From 2008 to 2018, 15 patients were treated because of TBF and were analyzed with respect to fistula appearance, treatment strategy (stenting, endoscopic vacuum therapy and/or surgical reintervention) and outcome. Results In each case, the fistula was small, located close to the tracheal bifurcation and associated simultaneously (n = 6, 40%) or metachronously (n = 9, 60%) with an anastomotic leakage. Latter was covered by esophageal stents in six patients which in turn resulted in occurrence of TBF at a later time in five patients. Management of TBF included conservative therapy (n = 3), stenting (n = 6), or suturing (n = 6). Ten patients underwent rethoracotomy. Treatment failure was observed in eight patients (53%). In all patients, treatment was accompanied by progressive sepsis. On the contrary, all seven patients with successful defect closure remained in good general condition. Conclusion Fistula appearance was similar in all patients. Implementation of esophageal stents cannot be recommended because of possibility of TBF at a later time point. Surgery is usually required and should preferably be performed when the patient's condition has been optimized at a single-stage repair. Esophageal diversion can only be recommended in patients with persisting mediastinitis. The key element for successful treatment of TBF, however, is control over sepsis; otherwise, outcome of TBF is devastating.

Background With regard to quality of life and organ shortage, follow-up after liver transplantation (LT) should consider risk factors for allograft failure in order to avoid the need for re-LT and to improve the long-term outcome of recipients. Therefore, the aim of this study was to explore potential risk factors for allograft failure after LT. Material and methods A total of 489 consecutive LT recipients who received follow-up care at the University Hospital of Muenster were included in this study. Database research was performed, and patient data were retrospectively reviewed. Risk factors related to donor and recipient characteristics potentially leading to allograft failure were statistically investigated using binary logistic regression analysis. Graft failure was determined as graft cirrhosis, need for re-LT because of graft dysfunction, and/or allograft-associated death. Results The mean age of recipients at the time of LT was 50.3 ± 12.4 years, and 64.0 % were male. The mean age of donors was 48.7 ± 15.5 years. Multivariable statistical analysis revealed male recipient gender (p = 0.04), hepatitis C virus infection (HCV) (p = 0.014), hepatocellular carcinoma (HCC) (p = 0.03), biliary complications after LT (p Conclusion Male recipients, patients who received LT for HCV or HCC, those with pretransplant diabetes mellitus, and LT recipients with biliary complications are at high risk for allograft failure and thus should be monitored closely.

BACKGROUND Passenger lymphocyte syndrome (PLS), a subtype of graft-versus-host disease, is a rare disorder encountered mainly in ABO-mismatched hematopoietic stem cell transplantation and infrequently in all types of ABO-mismatched solid organ transplantation. We here report the fifth case of PLS in small bowel transplantation (SBTx) and the first one describing the successful management of PLS in a cadaveric, isolated SBTx. CASE REPORT A 60-year-old Caucasian female with blood group A D+ suffering from short bowel syndrome received a small bowel transplant from a 32-year-old Caucasian female with blood group O D+ (HLA mismatch 2/6). After onset of massive hemolysis on Postoperative Day 9 the positive direct and indirect antiglobulin tests showing antibodies against A1 and A2 red blood cells (RBCs) led to the diagnosis of PLS. This complication was successfully treated by transfusion of blood group O RBC transfusions, increased immunosuppression, and plasmapheresis. CONCLUSION In the event of severe hemolysis and anemia after ABO-mismatched SBTx, PLS should be considered. In our case successful treatment consisted of transfusion of donor-specific RBCs, increased immunosuppression, and plasmapheresis.

Background Gastrectomy is associated with relevant postoperative morbidity. However, outcome of surgery can be improved by careful selection of patients. The objective of the current study was therefore to identify preoperative risk factors that might impact on patients’ further outcome after surgical resection. Methods Preoperative risk factors having respectively different surgical risk scores for major complex surgery (including Cologne Risk Score, p-/o-POSSUM, and NSQIP risk score) of patients that underwent gastrectomy for AEG II/III tumors and gastric cancer were correlated with complications according to Clavien-Dindo and outcome. Patients who underwent surgery in palliative intention were excluded from further analysis. Results Subtotal gastrectomy was performed in 23%, gastrectomy in 59%, and extended gastrectomy in 18% in a total of 139 patients (mean age: 64 years old). Thirty six percent experienced a minor complication (Dindo I-II) and 24% a major complication (Dindo III-V), which resulted in a prolonged hospital stay (p < 0.001). In-hospital mortality (=Dindo V) was 2.5%. Besides age, type of surgical procedure impacted on complications with extended gastrectomy showing the highest risk (p = 0.005). The o-POSSUM score failed to predict mortality accurately. We observed a highly positive correlation between predicted morbidity respectively mortality and occurrence of complications estimated by p-POSSUM (p = 0.005), Cologne Risk (p = 0.007), and NSQIP scores (p < 0.001). Conclusion The results demonstrate a significant association between different risk scores and occurrence of complications following gastrectomy. The p-POSSUM, Cologne Risk, and NSQIP score exhibited superior performance than the o-POSSUM score. Therefore, these scores might allow identification and selection of high-risk patients and thus might be highly useful for clinical decision making.

Background and study aims Endoscopic vacuum therapy (EVT) is a promising new approach for the treatment of anastomotic leakage in the gastrointestinal tract. Here, we present the first case series demonstrating successful use of EVT for the treatment of post-esophagectomy anastomotic ischemia prior to development of leakage. Patients and methods Between 2012 and 2015, intraluminal EVT was performed in eight patients with anastomotic ischemia following esophagectomy. The primary outcome measure was successful mucosal recovery. Secondary outcome measures were duration of treatment, number of sponge changes, septic course, and associated complications. Results Complete mucosal recovery was achieved in six patients (75 %) with different degrees of anastomotic ischemia. In two patients (25 %), small anastomotic leaks developed, which resolved by continuing the EVT treatment. Median duration of EVT treatment until mucosal recovery was 16 days (range 6 – 35), with a median of 5 sponge changes per patient (range 2 – 11). No EVT-associated complications were noted. Three patients developed anastomotic stenoses, which were treated by endoscopic dilation therapy. Conclusion This is the first case series to demonstrate that the early use of EVT potentially modulates clinical outcomes and infection parameters in patients with anastomotic ischemia following esophagectomy. Further studies are needed to define the indications and patients who are most likely to benefit from early EVT.

Secondary lymphedema accompanied with strong restrictions in quality of life is still major side effects in cancer therapy. Therefore, dedicated diagnostic tools and further investigation of the lymphatic system are crucial to improve lymphedema therapy. In this pilot study, a method for quantitative analysis of the lymphatic system in a rat model by laser ablation (LA) with inductively coupled plasma mass spectrometry imaging (ICP-MSI) is presented. As a possible lymph marker, thulium(III)(1R,4R,7R,10R)-α,α′,α′′,α′′′-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (Tm-DOTMA) is introduced and compared to the clinically used magnetic resonance imaging contrast agent gadolinium(III)2,2′,2′′-(10-((2R,3S)-1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate (Gd-DO3A-butrol). Gadobutrol functioned as standard contrast media in MRI lymphangiography to detect lymphatic flow qualitatively. Thus, Tm-DOTMA was investigated as lymphatic marker to detect lymphatic flow quantitatively. Both contrast agents were successfully used to visualize the lymphatic flow in successive lymph nodes in LA-ICP-MS due to lower limits of detection compared to MRI. Furthermore, the distribution of contrast agents by multicolored imaging showed accumulation in specific areas (sectors) of the lymph nodes after application of contrast agents in different areas.

Perforations and anastomotic leakages of the upper gastrointestinal (GI) tract cause a high morbidity and mortality rate. Only limited data exist for endoscopic vacuum therapy (EVT) in the upper GI tract. Fifty-two patients (37 men and 15 women, ages 41–94 years) were treated (12/2011–12/2015) with EVT for anastomotic insufficiency secondary to esophagectomy or gastrectomy (n = 39), iatrogenic esophageal perforation (n = 9) and Boerhaave syndrome (n = 4). After diagnosis, polyurethane sponges were endoscopically positioned with a total of 390 interventions and continuous negative pressure of 125 mm of mercury (mmHg) was applied to the EVT-system. Sponges were changed endoscopically twice per week. Clinical and therapy-related data and mortality were analyzed. After 1–25 changes of the sponge at intervals of 3–5 days with a mean of 6 sponge changes and a mean duration of therapy of 22 days, the defects were healed in 94.2 % of all patients without revision surgery. In three patients (6 %), EVT failed. Two of these patients died due to hemorrhage related to EVT. Four postinterventional strictures were observed during the follow-up of up to 4 years. Esophageal wall defects of different etiology in the upper gastrointestinal tract can be treated successfully with EVT, considering that indication for EVT should be weighed carefully. EVT can be regarded as a novel life-saving therapeutic tool.

BackgroundGiven the gap between patients in need of a renal transplantation (RTx) and organs available, transplantation centers increasingly accept organs of suboptimal quality, e.g. from donors with acute kidney injury (AKI).MethodsTo determine the outcome of kidney transplants from deceased donors with AKI (defined as ≥ AKIN stage 1), all 107 patients who received a RTx from donors with AKI between August 2004 and July 2014 at our center were compared to their respective consecutively transplanted patients receiving kidneys from donors without AKI. 5-year patient and graft survival, frequencies of delayed graft function (DGF), acute rejections and glomerular filtration rate (eGFR, CKD-EPI) were assessed.ResultsPatient survival was similar in both groups, whereas death-censored and overall graft survival were decreased in AKI kidney recipients. AKI kidney recipients showed higher frequencies of DGF and had a reduced eGFR at 7 days, three months and one and three years after RTx. However, mortality was noticeably lower compared to waiting list candidates. Rejection-free survival was similar between groups.ConclusionsIn our cohort, both short-term and long-term renal function was inferior in recipients of AKI kidneys, while patient survival was similar. Our data indicates that recipients of donor AKI kidneys should be carefully selected and additional factors impairing short- and long-term outcome should be minimized to prevent further deterioration of graft function.

Accumulating evidence indicates that anastomotic leakages and perforations of the upper gastrointestinal tract (uGIT) can be treated successfully with endoscopic vacuum therapy (EVT). So far, no data is available regarding the long-term quality of life (QoL) after successful EVT of defects in the uGIT. We present a prospective survey on long-term Qol of 52 patients treated by EVT for defects of the uGIT. Results are compared with 63 of 221 patients treated by esophagectomy without anastomotic insufficiency (w/o EVT) between 12/2011 and 12/2015. The Gastrointestinal Quality of Life-Index (GIQLI) score was determined by a 36-item questionnaire of 25 respondents with EVT and 50 respondents w/o EVT. The response rate was 78.95% (75/95) including 25 survey respondents who were treated with EVT for anastomotic insufficiency secondary to esophagectomy or gastrectomy (n = 19), iatrogenic esophageal perforation (n = 4), and Boerhaave syndrome (n = 2) and 50 respondents with complication-free esophagectomy w/o EVT. The median follow-up was 19 months for EVT patients and 21 months for patients w/o EVT. Except for “social function” (p = 0.009) in favor for patients w/o EVT, the median GIQLI score did not differ significantly between both study groups concerning the categories ‘symptoms’, ‘emotions’, ‘physical functions’, and ‘medical treatment’ resulting in a total median GIQLI score of 83 in EVT versus 96.5 in patients w/o EVT (p = 0.185). Spearman Rho analysis revealed that a high GIQLI score correlated with a low ASA score (p

Background/Aims: Surgery for esophageal cancer is associated with a high morbidity and mortality. With this study, we investigated if a validated preoperative risk score correlates with overall morbidity, mortality, anastomotic insufficiency, respiratory complications and with the severity of complications after open Ivor-Lewis esophagectomy. Methods: A total of 94 patients undergoing esophageal resection for adenocarcinoma between 2005 and 2009 were included. Patients were assigned using the preoperative risk score according to Schröder et al. [Langenbecks Arch Surg 2006;391:455-460] and the Dindo classification regarding the severity of complications. Results: Of all the patients, 12% had a ‘normal', 54% a ‘moderateʼ and 34% a ‘high' preoperative risk score. Postoperative complications occurred in 79%. Furthermore, 36 or 21 or 14 or 7% of patients experienced complications of category I/II or III or IV or V, respectively. There was a significant association between preoperative risk score and overall morbidity (p = 0.010), mortality (p = 0.035) and anastomotic insufficiency (p = 0.023). Furthermore, higher preoperative risk score was significant related to increasing severity of postoperative complications (grade IV according to the Dindo classification: p = 0.018, Dindo grade V: p = 0.035). Neoadjuvant therapy consisting of cisplatin and 5-fluorouracil had no influence. Conclusion: As we demonstrated, a significant association between preoperative risk score and occurrence and severity of postoperative complications after open Ivor-Lewis esophagectomy, standardized, organ-specific pre- and postoperative categorizations might be useful for individual clinical decision making in this group of patients.

Positron emission tomography combined with computed tomography (PET/CT) is increasingly being used in the staging of esophageal cancer, and some recent studies suggested the maximal standardized uptake value (SUVmax) as a prognostic factor for prediction of survival of these patients. However, data on correlations between SUVmax and other established prognostic markers is rare, and the impact of neoadjuvant treatment on SUVmax ability to predict outcome is not clear. The aim of the present study was therefore to evaluate the prognostic significance of the SUVmax in patients with or without neoadjuvant therapy (NAT) by comparing SUVmax to different established prognostic factors and survival.Esophageal cancer patients receiving either neoadjuvant therapy or no pretreatment before surgery were included in our study, and correlations between SUVmax and prognostic factors such as tumour/nodal stage, grading, tumour length or survival were investigated.Between January 2004 and December 2011, a total of 114 patients was included (mean age 63 years, 96 men, 36 SCC, 78 adenocarcinoma). A number of 74 patients underwent neoadjuvant therapy. The median follow-up was 52 months. The SUVmax was significantly correlated to initial tumour stage (p = 0.000) and tumour length (p ≤ 0.010). Survival was significantly better in patients undergoing primary surgery if SUVmax was6 compared to SUVmax6 (p = 0.008), whereas neither neoadjuvant-treated patients in general (p = 0.950) nor the different subgroups of responders showed a comparable correlation between survival and SUVmax (complete responder p = 0.808, partial responder p = 0.409, nonresponder p = 0.529).The SUVmax highly correlates with well-known prognostic factors and survival of esophageal cancer patients after surgery but only in case of primary surgery and not if patients received neoadjuvant therapy.

We present a rare case of a big oesophageal liposarcoma causing dysphagia and weight loss in a 75-year-old patient. Endoscopically, a pedunculated lesion with subtotal obstruction of the oesophageal lumen had been detected and thoracoabdominal oesophageal resection with gastric sleeve reconstruction was performed. Surprisingly, a liposarcoma of the oesophagus was revealed on histopathological analysis, showing MDM2 overexpression. Oncological follow-up has been uneventful and the patient remains in good clinical shape at 15 months after surgery.

As esophagectomy is associated with a considerable complication rate, the aim of this study was to assess the impact of postoperative complications and neoadjuvant treatment on long-term outcome of adenocarcinoma (EAC) and squamous cell carcinoma (SCC) patients. Altogether, 134 patients undergoing transthoracic esophagectomy between 2005 and 2010 with intrathoracic stapler anastomosis were included in the study. Postoperative complications were allocated into three main categories: overall complications, acute anastomotic insufficiency, and pulmonary complications. Data were collected prospectively and reviewed retrospectively for the purpose of this study. SCC patients suffered significantly more often from overall and pulmonary complications (SCC vs. EAC: overall complications 67 vs. 45 %, p = 0.044; pulmonary complications 56 vs. 34 %, p = 0.049). The anastomotic insufficiency rates did not differ significantly (SCC 11%, EAC 15%, p = 0.69). Long-term survival of EAC and SCC patients was not affected by perioperative (overall/pulmonary) complications or by the occurrence of anastomotic insufficiency. Also, neoadjuvant treatment did not influence the incidence of complications or long-term survival. This is the first time the patient population of a center experienced with esophageal cancer surgery was assessed for the occurrence of general and esophageal cancer surgery-specific perioperative complications. Our results indicated that these complications did not affect long-term survival of EAC and SCC patients. Our data support the hypothesis that neoadjuvant treatment might not affect the incidence of perioperative complications or long-term survival after treatment of these tumor subtypes.

Secondary lymphedema is still a worldwide problem. Symptomatic approaches to lymphedema therapy have been mainly used, with complete decongestive therapy as the cornerstone. Due to a lack of regenerative therapy, researchers have established various animal models to obtain insights into pathomechanisms and to reveal the best therapeutic option. Since the first reproducible and reliable animal model of lymphedema was reported in dogs, the technique of circumferential excision of lymphatic tissue has been translated mainly to rodents to induce secondary lymphedema. In these models, various promising pharmacological and surgical approaches have been investigated to improve secondary lymphedema therapy. Imaging modalities are crucial to detect the extent of lymphatic dysfunction and decide the best therapy. The gold standard of lymphoscintigraphy is currently limited by poor spatial resolution and lack of quantification. Animal models could help to bridge a gap in improving morphological correlation and quantifying lymphatic functionality. This review summarizes the animal models used in lymphatic research and focuses on new therapeutic options and requirements for imaging modalities to visualize the lymphatic system.

Fistulas between the upper intestinal tract and the airway following esophagectomy are a rare and severe complication with significant mortality. Treatment and therapy are difficult and require a multidisciplinary approach. The objective of this retrospective study was to identify risk factors for these fistulas following esophagetcomy, and to assess their impact on the further clinical course and outcome. 211 patients undergoing Ivor-Lewis esophagectomy for esophageal cancer between 2005 and 2012 were included. The preoperative risk factors including the risk score according to Schroder et al. and the O-Physiological and Operative Severity Score (POSSUM) score, operative and postoperative parameters and the outcome were evaluated. 65% of all patients developed postoperative complications, including 12 patients that developed fistulas between the upper intestinal tract and the airway (airway fistulas [AF]; 5.6%). Neither patient related risk factors nor esophagus-specific risk scores correlated with occurrence of AF. Furthermore, surgical treatment and neoadjuvant treatment did not show any effect on development of AF in our patients. However, we could demonstrate that AF significantly impacted on length of hospital stay (AF 52 days vs. No-AF group 16 days, P

We present our current clinical approach for the treatment of postoperatively infected wounds of the abdominal wall healing by secondary intention that may help in the design of a randomized controlled trial to develop a standardized wound treatment pathway. Patients with postoperatively infected abdominal wounds treated with either Advanced Wound Care (AWC) dressings or vacuum-assisted closure (VAC) therapy were enrolled in the study. Follow-up was carried out prospectively for wound healing and incidence of incisional hernia at the earliest 3 years after surgery. Sixty-two patients were included and wounds were initially treated antiseptically for 5.19 ± 2.91 days. Prior to VAC therapy, AWC dressings were applied for 8.75 ± 2.93 days to reduce reinfection. Greater wound size (>12 × 6 × 6cm) and extensive secretion (>200 ml/day) argued for the VAC system. Overall incidence of incisional hernia was 20.4 %, with 18.4 % occurring in AWC-treated patients and 27.3 % in VAC-treated patients. Based on these results, a wound treatment pathway was established in our department. The established wound treatment pathway has helped to increase both workflow efficacy and outcome in the treatment of abdominal wounds. Wound size, amount of secretion, and status of infection were the parameters we used for the determination of appropriate treatment. The observational data gathered during the initiation of our pathway lay the basis for future randomized controlled trials that will determine the most appropriate treatment options in the setting of a standardized wound treatment pathway.

Background Renal allograft outcome in heart–kidney transplantation (HKTx) might be affected by hemodynamic instability and high levels of calcineurin inhibitor-dependent immunosuppression. Methods From November 1999 to March 2008, 13 patients who received HKTx were compared with a matched control group of 13 kidney transplantation (KTx) recipients with similar cardiovascular risk factors. Graft function, rejection periods, and patient survival were analyzed. Results Renal allograft rejection was noted in three patients (23%) after HKTx and in four patients (31%) after KTx. Serum creatinine levels were comparable at 1 week, 1 month, 1, 2, and 3 years after transplantation. Patient survival rates at 1, 2, and 3 years were 100% for HKTx recipients and 100, 92, and 92% for isolated KTx patients. Graft survival was 92% at 1, 2, and 3 years after HKTx and 100% at 1 year and 92% at 2 and 3 years after isolated KTx. Conclusions Our results with excellent long-term graft function and survival after combined HKTx indicate that this procedure is a valuable option for a growing number of patients suffering from coexistent cardiac and renal failure.

Correct diagnosis, surgical treatment, and perioperative management of patients with esophageal carcinoma remain crucial for prognosis within multimodal treatment procedures. This study aims to achieve a consensus regarding current management strategies in esophageal cancer by questioning a panel of experts from the German Advanced Surgical Treatment Study (GAST) group, comprised of 9 centers specialized in esophageal surgery, with a combined total of >220 esophagectomies per year. The Delphi method, a systematic and interactive, evidence-based approach, was used to obtain consensus statements from the GAST group regarding ambiguities and disparities in diagnosis, patient selection, surgical technique, and perioperative management of patients with esophageal carcinoma. After four rounds of surveys, agreement was measured by Likert scales and defined as full (100% agreement), near (≥66.6% agreement), or no consensus (

Background: The regeneration capacity of cirrhotic livers might be affected by angiotensin-1 (AT1) receptors located on hepatic stellate cells (HSC). The effect of AT1 receptor blockade on microcirculation, fibrosis and liver regeneration was investigated. Materials and methods: In 112 Lewis rats, cirrhosis was induced by repetitive intraperitoneal injections of CCl4. Six hours, 3, 7 and 14 days after partial hepatectomy or sham operation, rats were sacrificed for analysis. Animals were treated with either vehicle or 5 mg/kg body weight losartan pre-operatively and once daily after surgery by gavage. Microcirculation and portal vein flow were investigated at 6 h. The degree of cirrhosis was assessed by Azan Heidenhein staining, activation of HSC by desmin staining, apoptosis by ssDNA detection and liver regeneration by Ki-67 staining. Changes in expression of various genes important for liver regeneration and fibrosis were analysed at 6 h and 3 days. Haemodynamic parameters and liver enzymes were monitored. Results: Losartan treatment increased sinusoidal diameter, sinusoidal blood flow and portal vein flow after partial hepatectomy (P

The predictive value of positron emission tomography-computed tomography (PET-CT) in primary staging and response control in patients with esophageal carcinoma (EC) is under discussion. In the present study initial staging and metabolic response of PET-CT was correlated with tumor regression and survival in patients with multimodal treatment of EC.The authors conducted a retrospective analysis on a prospective database for 83 patients with EC (42 squamous cell, 39 adenocarcinoma, 2 anaplastic carcinoma) undergoing PET-CT for primary staging. Twenty-four of the patients underwent primary esophagectomy, 9 had palliative treatment, and 50 neoadjuvant radiochemotherapy (cisplatin, 5-fluorouracil; 50.4 Gy). The PET-CT study was repeated 6 weeks after induction of chemotherapy and compared with endoscopic ultrasound (EUS). For response control, the metabolic response (tumor standardized uptake value [SUV] reduction) was correlated with histopathologic (ypT0-4) and histomorphologic response (tumor regression) and survival.At primary staging 81 of 83 EC (97.5%) showed an increased SUV uptake correlating with the EUS tumor stage. Suspicious lymph nodes were detected in 51 (61.4%) patients by PET-CT and 66 (79.5%) were detected by EUS. Fifteen patients had additional findings on PET-CT examination leading to a change in therapy in 9 patients (10.3%). Of 50 patients receiving a second PET-CT study, a SUV reduction50% correlated with major histomorphologic response (tumor regression grade 4,10% vital tumor cells) and histopathologic response (ypT0 ypN0). Furthermore, these patients showed a significantly increased survival (33.1 ± 3.5 months) compared to non-responders (21.7 ± 3.3 months; p = 0.02) and patients after primary surgery (29 ± 3.2 months; p = 0.05).The present study shows that PET-CT is a valuable tool for primary staging and response control in multimodal treatment of patients with EC.

The management of an asymptomatic failed renal graft remains controversial. The aim of our study was to explore the effect of failed allograft nephrectomy on kidney retransplantation by comparing the outcome of recipients who underwent graft nephrectomy prior to retransplantation with those who did not. Retrospective comparison of patients undergoing kidney retransplantation with (group A, n = 121) and without (group B, n = 45) preliminary nephrectomy was performed, including subgroup analysis with reference to patients with multiple (≥2) retransplantations and patients of the European Senior Program (ESP). Nephrectomy leads to increased panel reactive antibody (PRA) levels prior to retransplantation and is associated with significantly increased rates of primary nonfunction (PNF; P = 0.05) and acute rejection (P = 0.04). Overall graft survival after retransplantation was significantly worse in group A compared with group B (P = 0.03). Among the subgroups especially ESP patients showed a shorter graft survival after previous allograft nephrectomy. On the multivariate analysis, pretransplant graft nephrectomy and PRA >70% were independent and significant risk factors associated with graft loss after kidney retransplantation. Nephrectomy of the failed allograft was not beneficial for retransplant outcome in our series. Patients with failed graft nephrectomy tended to have a higher risk of PNF and acute rejection after retransplantation. The possibility that the graft nephrectomy has a negative impact on graft function and survival after retransplantation is worth studying further.

AIM: Children undergoing laparoscopic herniorrhaphy may benefit from a minimally invasive access and the possible exploration of the contralateral groin. In this prospective feasibility study, the experiences and results after introduction of this method in a tertiary referral medical center are reported. METHODS: 50 laparoscopic herniorrhaphies were performed in 44 children (32 boys and 12 girls, range: 17 months-11 years) with open inner inguinal rings between January 2001 and March 2007. In 6 children (13.6 %) an additional contralateral open inner inguinal ring was detected. Laparoscopic access was obtained with a 5-mm laparoscope which was inserted transumbilically and two 2-mm needle holders were inserted through the inferolateral abdominal wall. The open inner inguinal rings were closed in 8 children using a resorbable Z-suture and in 36 children using a monofilamentous non-absorbable suture. Follow-up examinations included records of intra- and postoperative complications, recurrence rate and economic aspects. RESULTS: No intra- or perioperative complications occurred. Median operation time was 19 minutes. 43 / 44 operations were carried on an outpatient basis. Average material costs were about 20 Euro without any difference from the open access. During 36 months the follow-up rate was 91 %. Two children who had previously received an absorbable suture suffered from a recurring groin hernia within the first 6 months. CONCLUSION: Laparoscopic herniorrhaphy in children represents a safe and effective surgical method that can be recommended for tertiary referral medical centers with training facilities and experience in minimally invasive surgery.

Background Because of its immunomodulatory action, the protease bromelain represents a novel strategy for the treatment of hepatic ischemia/reperfusion (I/R) injury. A dose-response study was performed to investigate the effect of bromelain on liver function, microcirculation, and leukocyte-endothelium interactions in hepatic I/R injury. Materials and methods One hundred forty rats were randomized to 8 short-term or 12 long-term groups ( n = 7 each). A 30 min normothermic hepatic ischemia was induced by Pringle maneuver with a portocaval shunt. Animals were treated 60 min prior to ischemia with either no therapy, 0.1, 1.0, or 10 mg/kg b.w. bromelain i.v. In the short-term experiments, microcirculation was investigated 30 min after sham operation or ischemia using intravital microscopy. In the long-term experiments AST, ALT, and bradykinin levels were determined for 14 d after central venous catheter (CVC) placement only, sham operation, or ischemia. Additionally, apoptosis rate, Kupffer cell activation, endothelial cell damage, and eNOS expression were analyzed. Results In sham-operated animals, treatment with 10 mg/kg b.w. bromelain led to a disturbed microcirculation with increased leukocyte adherence, apoptosis rate, Kupffer cell activation, and endothelial cell damage. Six h after CVC placement and administration of 10 mg/kg b.w. bromelain, AST and ALT levels were significantly increased. After I/R, rats treated with 0.1 mg/kg b.w. bromelain showed an improved microcirculation, reduction in leukocyte adhesion, apoptosis rates, Kupffer cell activation and endothelial cell damage, increased eNOS expression, and significantly lower AST levels compared with untreated animals. Conclusion Bromelain represents a novel approach to the treatment of hepatic I/R injury with a limited therapeutic window.

Controversy still exists about the need for pyloric drainage procedures (pyloroplasty or pyloromyotomy) after esophagectomy with esophagogastrostomy and vagotomy. Although pyloric drainage may prevent postoperative delayed gastric emptying, it may also promote bile reflux into the oesophagus. We analysed pyloric drainage methods for their potential effect on gastric outlet obstruction and bile reflux in patients undergoing esophagectomy. One hundred and ninety-eight patients with esophageal carcinoma were treated by transthoracal esophagectomy with gastric conduit reconstruction either with pyloromyotomy (group II, n = 118), pyloroplasty (group III, n = 34) or without pyloric drainage (group I, n = 46) between January 2000 and December 2004. The postoperative gastrointestinal passage by radiological investigation, anastomotic leakage rate, mortality and incidence of gastroesophageal reflux by endoscopy within the first postoperative year were retrospectively analysed. Patient demographics and the types of surgical procedures did not differ between the three groups. There was no difference in hospital mortality, anastomotic leakage rate, gastrointestinal passage and postoperative hospital stay between the three groups. However, more patients with pyloric drainage showed bile reflux (I = 0% vs II+III=14.9%, p = 0.069) and reflux esophagitis (I = 10.3% vs II+III = 34.5%, p

BACKGROUND The indication for anti-reflux-surgery in patients with gastroesophageal reflux disease (GERD) who are totally symptom-free under conservative treatment with proton pump inhibitors (PPI) is still seen controversially. Arguments for PPI-treatment include the missing trauma and few side-effects, arguments against include the life-time-long drug intake. We prospectively observed the indication of anti-reflux-surgery in symptom-free patients in comparison to patients with remaining symptoms under treatment with PPI. PATIENTS AND METHODS Between January 1999 and December 2001, 317 patients with GERD were treated by laparoscopic hemifundoplication and grouped in patients with adequate response to PPI (n = 103) and patients with residual discomfort in spite of or by PPI (n = 214). Preoperative diagnostic included endoscopy, ph-testing, manometry and quality of life scoring by a standardized questionnaire. Peri- and postoperative morbidity as well as quality of life were analyzed and compared with healthy individuals (n = 50). RESULTS Patient demographics and surgical procedures did not differ between the two groups. After a median follow-up of 49 months and a follow-up rate of 89.9 %, the recurrence rate was 2.5 % and perioperative complication rate was 6.3 % without any significant differences between the groups. Patients with GERD and adequate response to PPI showed preoperatively during PPI omission a significant lower incidence of esophagitis (3.9 % vs. 18.2 %) and higher quality of life score (93.7 +/- 11.3 vs. 75.3 +/- 12.6), which significantly decreased in comparison to healthy individuals (132.9 +/- 10.5). After anti-reflux surgery the quality of life has been increased in both groups (130.5 +/- 11.4 vs. 121.8 +/- 13.2). However, only patients with adequate response to PPI reached the quality of life score of healthy individuals. CONCLUSION Patients with preoperatively adequate response to PPI profit of anti-reflux surgery in terms of postoperative quality of life. Concerning the indication for anti-reflux surgery in these patients, one has to balance between the individual inconvenience due to the long-lasting drug intake on the one hand and the operative risk, morbidity and outcome of a specialized surgical department on the other hand.

Laparoscopic inguinal hernia repair requires the use of prosthetic material. This prospective, single-center study was intended to investigate the impact of the amount of polypropylene (PP) mesh used in hernia repair on functional results and quality of life. For this series, 672 consecutive patients with primary inguinal hernia undergoing transabdominal preperitoneal hernia repair (TAPP) using a heavyweight PP mesh (Prolene 10 × 15 cm, 1.5 g, group I, n = 232), a mixed PP- and Polyglactin mesh (Vypro II, 10 × 15 cm, 0.53 g, group II, n = 217), or a light-weight titanized PP mesh (Ti-Mesh, 10 × 15 cm, 0.24 g, group III, n = 223) were compared in terms of postoperative complications (seroma, wound healing disorders), quality of life score (pain development, physical condition, urologic disorders), and hernia recurrence. During a 12-month follow-up there were no significant differences in the recurrence rate (1.3%-1.7%). Patients with a pure PP mesh (group I) showed significantly more postoperative seromas (12.1% versus 4.1%/1.8%), foreign body sensations (9.1% versus 5.5%/3.5%), and sensitivity to weather changes (5.6% versus 3.2%/2.2%) compared to groups II and III. In all groups, the quality of life score was improved postoperatively. However, among those patients in our series with few preoperative complaints, the postoperative quality of life was worsened when heavy-weight PP meshes (group I+II) were used but significantly improved when light-weight titanized PP meshes were used. Comparable functional results, fewer postoperative complications, and improved quality of life can be achieved by reducing the amount of PP in meshes used for laparoscopic hernia repair by TAPP procedure.

According to anatomical investigations the whole esophagus plays a crucial role as reflux barrier in the pathogenesis of gastroesophageal reflux disease (GERD). Morphologically, the spirally arranged muscle fibres present a tension-dependent "stretch closure" and in the event of any reduction of tension, as for example caused by an axial hiatus hernia, the organ may become inefficient. The aim of this study was to evaluate quality of life as the main success criterion after anti-reflux surgery based strictly on the restoration of functional morphology.Between January 1999 and December 2000, 185 patients with GERD were treated by surgery in accordance with functional-morphological principles. After dissecting the mediastinum, the gastroesophageal junction was displaced into the abdomen with consecutive retensioning the esophagus. The esophageal hiatus was reconstructed with non-absorbable single knot sutures and strengthened with alloplastic material. The application of a 180 degrees fundus cuff around the posterior esophageal circumference served as a "spacer" and also restored the angle of His. Preoperatively, all patients underwent endoscopy, pH metry and manometry. During postoperative follow-up, recurrence rate and quality of life were evaluated via a disease-specific scale.Preoperatively, 85% of the patients had an elevated DeMeester Score with a median of 81.4; 64% had reflux esophagitis and 37% had reduced lower esophageal sphincter pressure. All 185 operations were performed without conversion in a median operating time of 74 min. In one patient a lesion of the esophagus was treated during the operation; two patients had lesions of the splenic capsule which were also dealt with during the operation. Postoperatively, pleural effusions occurred in 15 patients and puncture was deemed necessary in one subject. Ninety-three percent were followed up for a median of 45 months and the recurrence rate was 2.3%. The quality of life index was 81.6+/-12.4 points preoperatively, and had significantly improved to 125.2+/-12.7 points in the follow-up.Through the functional-morphological concept of anti-reflux surgery comprising the restoration of the tension-dependent "stretch closure" of the esophagus, significant long-term improvement in quality of life with a low recurrence rate and perioperative morbidity can be achieved.

Liver resection exposes the remaining sinusoids to an over-proportional blood flow. This mechanism may aggravate ischaemia/reperfusion damage and rejection in partial liver transplants. We studied the potential relevance of this mechanism for the pathogenesis of partial liver transplant dysfunction. Eighty-four isogeneic Lewis rats were divided into four groups: (I) sham operation; (II) partial liver resection (30% residual liver volume); (III) orthotopic transplantation of a full-size liver; (IV) transplantation of a reduced-size liver (30% transplant volume). Microcirculation was determined by intravital microscopy 90 min after surgery. Survival rates, liver function and morphology were monitored over a period of 14 days. Lowest survival rates and impaired liver function were observed after partial liver transplantation (group IV). These transplants displayed the lowest perfusion rate and an increased rate of leukocyte-endothelium interactions in the presence of a significantly increased sinusoidal blood flow velocity compared with those in groups I and III. Sinusoidal overperfusion in groups II and IV resulted in widespread endothelium lesions. Sinusoidal overperfusion seems to be a significant factor impairing liver function after liver resection. In addition to other adverse factors, such as ischaemia/reperfusion injury, it can contribute to the pathogenesis of postoperative dysfunction of partial liver transplants.

BACKGROUND: Although in hospitals focussing on minimal invasive surgery laparoscopic appendectomy (LA) is widely practiced as method of choice in patients with acute appendicitis, the decision for the laparoscopic or the conventional technique (OA) is usually ensued by individual viewpoints. Aim of this prospective observation study was to analyse the decision algorithm for both procedures in patients with the presumptive diagnosis "appendicitis". PATIENTS AND METHODS: Between January 1996 and July 2001 512 patients with the presumptive diagnosis "acute appendicitis" underwent surgery and, assigned by intention-to-treat, were subdivided in a laparoscopic (I) and a conventional group (II). The choice of surgical procedure was analysed with regard to patient characteristics (age, gender, comorbidity), severity of appendicitis (clinical manifestation, preoperative inflammation signs), surgeon (clinical experience) and daytime (during the day, in the evening, at night). Furthermore, the outcome of either method was related to postoperative diagnosis, perioperative morbidity, analgesia, length of hospital stay and cosmetic results. RESULTS: In group I 265 patients and in group II 247 patients underwent surgery. Conversion from LA to OA was necessary in 6.4 %. Group I consisted of significantly more female (67.9 % vs. 45.7 %) and younger patients (21 yrs. vs. 30 yrs.) with less medical history as well as minor severity of tissue inflammation and significantly lower preoperative serum inflammation parameters (leukocytes (1000/ml): 10.6 +/- 4.3 vs. 13.5 +/- 4.9; CRP (mg/l): 2.3 +/- 3.3 vs. 5.6 +/- 7.5, I vs. II: p < 0.001). In group I more patients underwent surgery during day-time as well as by more laparoscopic-experienced surgeons. In the postoperative histopathologic evaluation there were significantly fewer cases with complicated appendicitis (33.2 % vs. 52.2 %, p < 0.001). Additionally, patients after LA revealed a lower postoperative complication rate (9.3 % vs. 18.3 %), length of hospital stay (median 3 vs. 4 days) and duration of analgesia (2.1 +/- 1.8 vs. 4.1 +/- 7.1 days). CONCLUSIONS: Important factors for decision algorithm between a laparoscopic or an open appendectomy include severity of appendicitis, gender, day-time as well as the surgeon's individual laparoscopic experience. With appropriate indication for each technique, both procedures are of equal value in the treatment of acute appendicitis. Furthermore the positive patient selection for laparoscopic appendectomy contributed to a better postoperative outcome in this study.

The aim of this study was to develop and establish a new system of laparoscopic fluorometry for the purpose of investigating the intestinal microcirculation. In 25 pigs (German Landrace, 16-25 kg body weight), ischemia was established in two segments (A, irreversible; B, reversible ischemia; C, internal control) of the small intestine by a laparoscopic technique. Microcirculation in the segments was assessed by laparoscopy at a second-look operation 24 h later by means of the fluorescence system Endoscan. The fluorescence of the three bowel segments was measured by arbitrary dye fluorescence units (DFU) 15 min after starting reperfusion, before and after injection of sodium fluorescein (NaFlu, 0.25 mg/kg body weight). The dividing line between viable and nonviable bowel tissue was established from the inflow and outflow rates of NaFlu with the aid of ROC (receiver operating characteristic) curves. The specificity and sensitivity of the new method were evaluated by correlating the results with the viability of each intestinal segment as predicted by three laparoscopically experienced surgeons and by histological examination. By means of the calculated separation sharpness (fluorescence index at 2 min0.5, outflow factor of NaFlu at 10 min20%), the overall predictions of intestinal viability in all 25 animals achieved a sensitivity of 93.5% and a specificity of 94.1% by laparoscopic fluorometry, versus a sensitivity of 70.8% and a specificity of 87.5% for the prediction of bowel viability by ordinary laparoscopic technique. Used as an adjunct to conventional laparoscopy, laparoscopic fluorometry brought significant gains in sensitivity and specificity in the distinction between reversible and irreversible intestinal ischemia.

Blood samples taken directly from the hepatic veins are often required for evaluation of liver function or ischemia/reperfusion injury and for direct determination of metabolic products of the liver. In the rat, blood samples are usually obtained by direct puncture of the hepatic veins. Successful catheterization of these small vessels is only possible under direct vision because great dexterity is needed to persuade the catheter to enter the hepatic vein. In this report a procedure for hepatic vein catheterization under direct vision is described in the rat. After performing a median laparotomy, a flexible catheter (Buchbinder, 3.0 F/1 mm, as used in cardiology) with a bent end is inserted into the infrahepatic vena cava. Under direct vision through the thin walls of the inferior vena cava the bent end of the catheter is slowly pushed up until the tip slides into a hepatic vein, which opens into the inferior vena cava at a right angle. Selective catheterization of the desired hepatic vein is possible by rotating the catheter and changing the position of its tip. This is a reliable new technique of hepatic vein catheterization in rats, by which blood samples can be collected directly from the hepatic veins.

This study investigates the impact of rat strain on the development of nonalcoholic fatty liver disease (NAFLD) focusing on morphological features and microcirculation. Male rats of Lewis, Wistar, and Sprague Dawley (n = 6 per strain and group) were randomized into a high-fat group which was fed with a special high-fat nutrition for a 3-week period and a control group which received standard nutrition. Intravital microscopy was used for the evaluation of microcirculation and correlated to morphological changes using a fatty liver scoring system. All three strains receiving a high-fat diet developed a grade 3 steatosis (>66% liver cell steatosis). Whereas Lewis showed a solely microvesicular steatosis, Wistar developed a mixed form and Sprague Dawley showed a pure macrovesicular steatosis and the highest degree of fibrosis and hepatocyte damage. Microcirculatory results revealed that sinusoidal density was already affected by a microvesicular steatosis and decreased with increasing macrovesicular proportion (Lewis: 18%, Wistar: 31%, Sprague Dawley: 23%). The degree of steatosis correlates with reduced blood flow velocity in central veins as well as in sinusoids (Lewis: 28%, Wistar: 39%, Sprague Dawley 44%). The densities of hepatocytes and hepatic stellate cells were only impaired once macrovesicular cell steatosis (Wistar and Sprague Dawley) was present. The development of NAFLD in the rat revealed strain-specific morphological features correlating with microcirculatory changes that should be considered in further studies using these models.

Background. Access-related problems are one of the major causes of morbidity in elderly patients with chronic kidney disease. The aim of this study was to assess potential risks and benefits in elderly patients comparing forearm arteriovenous fistula (AVF) and perforating vein AVF below the elbow for primary vascular access. Methods. A retrospective comparison of elderly patients (65.7 6 9.3 years, 70.4% male patients, 36.2% late referral) undergoing primary vascular access surgery using forearm AVF (n ¼ 50) and perforating vein AVF (n ¼ 55) was performed over a 2-year period, including a multivariate analysis of potential risk factors and benefits of primary patency (PP ¼ intervention-free access survival) and secondary patency (SP ¼ access survival until abandonment). Results. Patency rates after 24 months were significantly higher in patients with perforating vein AVF (PP 1 SP: 78.2%) compared to forearm AVF (PP: 62%, SP: 56%, P ¼ 0.04). Presence of diabetes mellitus in patients with forearm AVF was associated with a decreased PP [odds ratio (OR): 3.6, 95% confidence interval (CI): 0.9–13.8] and SP (OR: 4.8, 95% CI: 1.3–17.9), and arterial hypertension was associated with a lower PP (OR: 6.7, 95% CI: 0.8–53.9), whereas the presence of hyperparathyroidism was associated with higher PP and SP (OR: 0.2, 95% CI: 0.1–0.7). In contrast, PP and SP in patients with perforating vein AVF were not influenced by comorbidities. Conclusions. Perforating vein AVF is superior to forearm AVF in elderly patients with diabetes and arterial hypertension due to the proximal fistula location, probably caused by an improved artery distensibility during fistula maturation.

Background Renal dysfunction, primarily related to long-term use of calcineurin inhibitor–based immunosuppression, is the most common complication after liver transplantation. Objective To evaluate whether liver transplant recipients with impaired kidney function at transplantation can benefit from early conversion to mammalian target of rapamycin inhibitor therapy (mTORi) compared with patients with late induction of mTORi-based therapy. Materials and Methods Between 2003 and 2008, therapy was changed to an mTORi-based regimen in 57 patients. Patients were divided into 4 groups: group 1, early conversion (≤3 months after orthotopic liver transplantation) to mTORi therapy, and with impaired perioperative renal function; group 2, early conversion to mTORi therapy, and with normal perioperative renal function; group 3, late conversion to mTORi therapy, and with impaired perioperative renal function; and group 4, late conversion to mTORi therapy, and with normal perioperative renal function. Results One month after conversion, the mean (SD) increase in calculated glomerular filtration rate in groups 1 (early conversion) and 3 (late conversion) was comparable: 8 (9) mL/min vs 7 (10) mL/min. At month 3, the increase in calculated glomerular filtration rate between groups 1 and 3 was significant (15 [11] mL/min vs 9 [15] mL/min; P = .04), an effect that persisted at month 6 (16 [12] mL/min vs 10 [12] mL/min; P = .05) and month 12 (22 [14] mL/min vs 12 [15] mL/min; P = .04). Conclusion In liver transplant recipients with perioperatively impaired renal function, early conversion to mTORi therapy should be performed because this approach seems to be more effective in improving long-term renal function.

Ischemia leads to profound endothelin- (ET) related constriction of hepatic microvessels, causing disturbances in blood and oxygen supply. The aim of the study was to modulate hepatic microvascular diameters by blocking ET receptors to find the optimal therapeutic vessel width for reduction of ischemia-reperfusion injury. In an in vivo model (84 female Wistar rats, 250-300 g) with portal decompression by means of a splenocaval shunt, normothermic hepatic ischemia was induced for 30 min by crossclamping of the hepatoduodenal ligament. The ET receptor antagonist (ERA) bosentan was administered before induction of ischemia in different dosages [0.1, 1.0 and 10.0 mg/kg body weight (BW) i.v. and 10 mg/kg BW intraportally (i.p.)]. The effect on microcirculation was assessed by in vivo microscopy and influence on hepatocellular function by measurement of aspartate aminotransferase (AST) levels. Sinusoidal diameters were reduced as a result of ischemia to 76.3 +/- 7.4% compared with values received from sham-operated animals. After application of 0.1 mg/kg of bosentan, sinusoids remained constricted (89.7 +/- 9.9%, AST 255.0 +/- 12.8 U/l). Blocking ET receptors with 1 mg/kg bosentan avoided sinusoidal constriction (99.0 +/- 8.8%, p0.05) and led to the most effective reduction of AST level peak after 6 h of reperfusion (244.0 +/- 34.2 U/l vs 422.9 +/- 163.3 U/l in untreated ischemia). Bosentan (10 mg/kg i.v.) caused an increase in sinusoidal diameter to 109.1 +/- 6.4% (AST 311.7 +/- 33.6 U/l) and 10 mg/kg i.p. to 136.8 +/- 19.3% and even increase AST levels (618.90 +/- 209.32 U/l). After intravenous application of 1 and 10 mg/kg BW bosentan the perfusion rate was significantly increased and sticking of leukocytes in sinusoids and venules reduced (p0.05). In our model, diameters of sinusoids and postsinusoidal venules could be regulated gradually. We conclude that the avoidance of constriction, but not an excessive vasodilation leads to increased perfusion rate and hence improved hepatocellular function.

Background There is controversy about the effectiveness of intraperitoneal local anaesthesia (LA) in laparoscopic surgery. The aim of the present randomized clinical trial was to compare the analgesic effect of pre-emptive (preoperative) versus postoperative intraperitoneal LA in two different types of laparoscopic surgery. Methods Between July 2004 and January 2005, 133 consecutive patients scheduled to undergo laparoscopic fundoplication or hernia repair were randomly assigned to one of three treatments: placebo solution (50 ml 0·9 per cent saline) or LA (50 ml 0·5 per cent lidocaine) administered immediately after creation of the pneumoperitoneum, or LA (50 ml 0·5 per cent lidocaine) at the end of the operation. Analgesic requirements were analysed, and pain was assessed using a visual analogue scale (VAS) from 0 to 100 at 6, 12, 24 and 48 h after surgery. Results The duration of pneumoperitoneum (median 66 versus 46 min respectively; P < 0·001) and overall pain intensity (median VAS score 46·7 versus 6·5; P < 0·001) were higher for laparoscopic fundoplication than for hernia repair. Preoperative application of LA reduced abdominal pain (median 28·6 versus 74·9; P < 0·005), shoulder pain (median 24·3 versus 43·8; P = 0·004) and analgesic consumption (mean(s.d.) 11·1(5·0) versus 18·5(5·4) mg piritramide per 48 h; P = 0·002) after fundoplication, but had no analgesic effects after hernia repair. Conclusion Pre-emptive application of LA reduced postoperative pain and analgesic requirements after laparoscopic fundoplication.

Anastomotic insufficiency in patients with colorectal anastomosis is a major complication with high morbidity and mortality. Local treatment with transrectal lavage and drainage can be considered in patient without peritonitis. In order to prevent prolonged wound closure and secondary complications during conservative treatment we investigated the vacuum assisted closure (VAC) in this setting. Ten patients with anastomotic insufficiency after colorectal resections, who did not require transabdominal interventions, were treated with an Endo-vacuum assisted closure dressing (Group A; n = 5) or by transrectal lavage (Group B; n = 5). Time for wound healing, duration of hospitalization and pain assessment were compared in both groups. The Endo-vacuum assisted closure treatment was performed for a median time of 27 days without any vacuum assisted closure associated complications. Wound healing was significantly accelerated in Group A compared to Group B. Time in hospital was slightly shortened in patients with Endo-vacuum assisted closure. Pain assessment in both groups did not show any significant differences. Endo-vacuum assisted closure therapy is a novel approach that can be considered in diverted patients with failed colorectal anastomoses. Larger randomized trials that include complete cost-benefit analyses are needed to establish its role in this setting.

Background Preservation injury is a main factor leading to graft failure in liver transplantation. The aim of the study was to minimize preservation injury by modifications of the histidine-tryptophan-ketoglutarate (HTK) solution (incorporation of N-acetyl-histidine, aspartate, glycine, alanine, and arginine). Materials and methods The study was carried out in rats and subdivided into four parts. (1) Systemic toxicity of the modified HTK solution in comparison to the standard HTK solution was tested. (2) Hemodynamic and microcirculatory parameters were analyzed after i.v. injection of the respective solution. (3) Preservation injury after cold storage for different periods of time was assessed microscopically. (4) Reperfusion injury was analyzed in the isolated perfused liver by enzyme release and bile production. Results Blood values, hemodynamic and microcirculatory parameters after i.v. and i.p. application did not significantly differ from control. The modified HTK solution led to an attenuated preservation injury after cold preservation for 24 h compared with standard HTK solution. There was a significantly decreased lactate dehydrogenase release after ischemia for 72 h and reperfusion using the modified solution. After 24 h cold storage and reperfusion the apoptosis index was reduced and bile production significantly increased. Conclusion Optimizing the HTK solution may be a promising therapeutic strategy for attenuation of cold storage injury.

During the education of the next generation of scientists in experimental research, careful instruction in surgical techniques is of major importance. This applies in particular to complicated microsurgical models, which require a structured teaching concept with clearly laid-down working steps and adequate didactic resources. Transplantations in rats are undoubtedly among the most difficult models in experimental surgery. Because completely sutured orthotopic liver transplantation and kidney transplantation have been practiced for many years in our Surgical Research Unit, techniques must be transmitted to future generations. A microsurgical training program has been set up with the aim of being efficient, transparent, and motivating. Simply learning-by-doing in the sense of “laissez-faire” is ineffective and costly. Our training program is based on “three-phase didactics,” in which the learning targets are presented in sequence and are clearly defined. This report is intended to give a brief overview of the principal transplantation models and to serve as a guide for teaching these models. © 2005 Wiley-Liss, Inc. Microsurgery 25:614–623, 2005.

The impact of 3 different reperfusion sequences following orthotopic liver transplantation (OLT) in pigs were evaluated. The reperfusion technique commonly performed is primary portal in order to shorten warm ischemic times (WITs). Experimental and clinical data, usually comparing 2 out of 3 possible reperfusion sequences, provide controversial results. OLT was performed in 24 pigs randomized into 3 groups: primary arterial (A), simultaneous (SIM), and primary portal (P) reperfusion. Hemodynamics were continuously monitored and reperfusion injury and primary graft function were assessed by standard serum parameters, histopathological findings, immunohistochemistry for heme oxygenase 1 (HO-1), and heat shock protein 70 (HSP 70). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and gamma-glutamyl transpeptidase (gammaGT) following reperfusion were significantly increased for group A when compared to groups SIM and P. Hemodynamics showed significant differences after reperfusion compared to physiological data; differences in group comparisons were not significant. The bile production/100 g liver/hr was significantly higher for group SIM (1.15 mL) compared to group P (0.66 mL) and group A (0.62 mL). Histology and immunohistochemistry significantly correlated with functional results and outcome. Histological score was best for group SIM and worst for group A. HSP 70, being visualized mainly in the hepatocytes, showed higher expression for groups SIM and P. Inversely, HO-1, found in perisinusoidal cells, showed highest expression after primary arterial reperfusion. In conclusion, although associated with a 10-minute longer warm ischemic time, simultaneous reperfusion causes the least reperfusion injury with superior primary transplant function. Primary arterial reperfusion showed the worst overall outcome and highest degree of HO-1 expression.

Background Bradykinin is both a potent vasodilatator and a central inflammatory mediator. Similar to findings in myocardial reperfusion injury, bradykinin might mediate the protective effects of angiotensin-converting enzyme (ACE) inhibition after liver ischemia via increased bradykinin-2-receptor (B-2) stimulation. On the other hand, B-2-inhibtion has been shown to reduce liver reperfusion injury. This study was designed to investigate the role of Bradykinin in hepatic reperfusion injury. Materials and methods Twenty eight rats were allocated randomly to Sham procedure (Sham), 30-min normothermic ischemia (ischemia), ischemia with Ramiprilat (ACE-I), or ischemia with Ramiprilat and B-2-inhibitor HOE 140 (ACE-I+B-2-I). Liver microcirculation and leukocyte adherence were investigated using intravital microscopy 30 min after reperfusion (n = 7 per group). In addition, serum activities of AST and ALT were measured for 7 days (n = 28). Results Ischemia was associated with a loss of perfused sinusoids, sinusoidal vasoconstriction, and a reduction in microvascular blood flow. Permanent leukocyte adherence increased both in sinusoids and in postsinusoidal venoles. ACE-I restored sinusoidal perfusion, normalized vasoregulation, maintained sinusoidal blood flow, and inhibited leukocyte adhesion. ACE-I+B-2-I abolished the protective effects linked to ACE-I. Ischemia-induced liver cell injury after 5 h of reperfusion was ameliorated by ACE-I. In the ACE-I+B-2-I group, reduction in liver cell injury was reversed. Conclusion After hepatic ischemia, ACE-I reduced reperfusion injury in a B-2-dependent manner. These results suggest a pivotal role for bradykinin in the treatment of reperfusion injury by Ramiprilat, mediating sinusoidal dilation and blunting hepatic inflammation.

Small-for-size (SFS) liver graft injury is probably related to microcirculatory disorders due to an imbalance of vasoconstricting, e.g. endothelin (ET)-1, and vasorelaxing mediators, e.g. nitric oxide (NO). We studied the role of ET-1/NO balance and the effect of an endothelin A receptor (ETAR) antagonist on SFS injury after liver resection and reduced-size liver transplantation (RSLT). One hundred twenty-six Lewis rats were divided into five groups: (I) 70% liver resection, (II) 70% liver resection treated with the ETAR antagonist LU 135252 (1 mg/kg b.w. i.v.), (III) RSLT (30% residual liver volume), (IV) RSLT treated with the ETAR antagonist, (V) sham operation. Liver microcirculation was measured by intravital microscopy. ET-1, ETAR, endothelial NO-synthase (eNOS), activation of Kupffer cells (KCs) and parenchymal injury were studied by immunohistology. Survival and liver function were followed up to 14 days. RSLT led to increased ET-1, ETAR and decreased eNOS protein expression, accompanied by activation of KC, reduced perfusion rate, vasoconstriction and elevated sinusoidal blood flow, as well as hepatocellular damage, impaired liver function and impaired survival. ETAR blockade (groups II + IV) improved the ET-1/NO balance, attenuated microcirculatory disorders and improved hepatocellular apoptosis and liver function. Microcirculatory disorders related to an ET-1/NO imbalance may contribute to SFS liver injury. Maintenance of ET-1/NO balance by blocking ETAR reduces SFS injury by protecting liver microcirculation, thus reducing hepatocellular damage.

Background. The living-donor and dual kidney trans- plantation programmes were initiated in the transplan- tation centre of Munster (TCM) as two approaches to compensate for the declining numbers of cadaver donor kidney transplants after the implementation of the new Eurotransplant Kidney Allocation System (ETKAS). We analysed the outcome of cadaver, living- donor and dual kidney transplantation and their effects on the waiting list in the TCM. Methods. Between January 1990 and December 2000, 1184 kidney transplants were performed in the TCM. They were subdivided into cadaver, living-donor and dual kidney transplants and retrospectively analysed in terms of the number of kidney transplants performed, waiting time and waiting coefficient. In addition four representative groups were formed to reflect donor origin (I: cadaver kidney transplants allocated by the old ETKAS, n ¼ 180; II: cadaver kidney transplants allocated by the new ETKAS, n ¼ 139; III: living- donor kidney transplantation, n ¼ 59; IV: dual kidney transplantation, n ¼ 31) and compared according to graft function (initial diuresis, creatinine, 3-year graft function), patient survival and median waiting time. Results. After the implementation of the new ETKAS, the number of cadaver donor kidney transplants at the TCM almost halved, but the proportion of living- donor kidney transplantations increased significantly by 12.8% and of dual kidney transplantations by 8.5%. Patients who had received kidneys from cadaver donors allocated by the new ETKAS (group II) had a better survival rate, short- and long-term function but a longer waiting time than in group I (old ETKAS). Patients with dual kidney transplants (group IV) showed the lowest survival and short-term function rate, but had long-term function equivalent to that of cadaver kidney transplants (groups I and II). Patients who had received kidneys from living donors (group III) had the best survival, and short- and long-term function rate as well as the shortest mean waiting time. Conclusions. Living-donor and dual kidney transplan- tation proved to be functionally equivalent alternatives and successful strategies for compensating the declin- ing numbers of cadaver donor kidney transplants.

Owing to its powers of regeneration, the liver is capable of in vivo "tissue engineering" which enables complete restoration of liver architecture and re-establishment of the specific functions of the liver after various types of liver injury. Our current understanding of liver regeneration forms the basis of modern liver surgery and is now taken into consideration in the treatment of many liver diseases, in liver transplantation and hepatic tissue engineering. These advances have been achieved primarily by studies of liver regeneration in animal models after partial hepatectomy, attention being focused on the general mechanisms of cell proliferation. In recent years, however, toxin-induced models of liver regeneration have assumed growing importance, and by studying the interaction between cell damage and cell regeneration have made possible an investigation of liver regeneration of greater clinical relevance. However, the mechanisms of liver regeneration in patients with pre-existing chronic liver damage such as liver cirrhosis are still largely unexplored. This review examines and critically appraises the various approaches to the study of liver regeneration in animal models, including both surgical and pharmacological approaches.

Because of the risk of life-threatening complications, the discovery of a complete intrathoracic stomach demands urgent surgery with the aim of repositioning the stomach and gastropexy, and secondarily, to improve life quality. In this study the feasibility of surgical technique and postoperative quality of life after laparoscopic treatment of complete intrathoracic stomach has been evaluated. From June 1999 to December 2001 16 patients with an intrathoracic stomach (hiatus hernia Types IIB and III) were treated by laparoscopic techniques, including the repositioning of the stomach, hemi-fundoplication and anterior gastropexy. During the postoperative follow-up the recurrence rate and quality of life (Eypasch index) were evaluated. All operations were performed laparoscopically without conversion, with a mean operating time of 155 min. Pleural injuries occurred in 31% of patients and pleural effusions in 38%, which required puncture in three cases. Complete follow-up showed no recurrences at a median of 14 months. The median quality of life index was 84.6 preoperatively and had significantly improved to 117.8 after the operation. Laparoscopic access for the treatment of intrathoracic stomach represents a minimally invasive and safe treatment option for complete intrathoracic stomach, with a low level of perioperative morbidity and significant improvement in quality of life.

We would like to thank Prof. Bonavina for his interest and comments on our paper. Our paper deals with the effect of pyloric drainage procedures on gastric passage and bile reflux after esophagectomy with gastric conduit reconstruction. Omitting pyloric drainage is not only safe after esophagectomy, it also avoids bile reflux and esophagitis in the long term as gastric outlet obstruction due to pyloric spasm only represents a transient phenomena that either spontaneously disappears or can be successfully treated by endoscopic intervention [1, 2]. Alternatively, additional intraoperative mechanical dilatation of the pylorus has been shown to be as effective and safe [3]. However, until now, the pathomechanism of the spontaneously declining pylorospasm has not been completely understood. We agree that the size of the gastric conduit might contribute to a faster passage due to an increased wall stress, e.g., by inducing peristaltic waves, which possibly reduce pylorus spasm respectively lead to a reflectory opening of the pylorus. Therefore, in our institution, we always create a 4to 5-cm wide tubularized stomach, and the anastomosis is placed above the arch of the azygos vein to reduce reflux esophagitis. It is interesting to observe that by laparoscopic conditioning of the stomach, the incidence of clinically significant gastric outlet obstruction seems to be further reduced (3.6 vs 6.1% [4]). On the other hand, it is also surprising that anastomotic leakage rate seems to be not reduced by ischemic conditioning of the stomach. Theoretically, after partial devascularization, the gastric conduit should recover, and gastric tissue perfusion should be improved prior to pull-up and anastomosis to the esophagus resulting in better prerequisites for anastomotic healing. Perhaps, the size of the leakage and severity of symptoms can be reduced by ischemic conditioning as all patients with leakages of the esophagogastrostomy (6.1%) had only minor clinical symptoms, and endoscopy showed very well-vascularized resection lines of the esophagus and stomach [4]. However, information whether ischemic conditioning of the stomach before esophagectomy affects local tumor recurrence, and therefore, long-term survival would be desirable. Further controlled randomized studies on these topics are necessary and worthwhile for patients with esophageal carcinoma, as normal gastrointestinal function after esophagectomy is still rare and improving the quality of life represents one of the main goals in these patients [5]. Langenbecks Arch Surg (2008) 393:119–120 DOI 10.1007/s00423-007-0241-y