Proangiogenic potency of MUC18 in arteriosclerotic disease.

AIM: Stenotic peripheral and dilatative arteriosclerotic diseases have different pathomechanism although associations between both diseases are well known. The adhesion molecule MUC18 is a cell membrane glycoprotein also known as the melanoma cell adhesion molecule. As MUC18 has proangiogenic potency in melanoma and prostate cancer this study investigated the role of MUC18 in patients with stenotic or dilatative arteriosclerotic disease as a putative biochemical marker. METHODS: Using qRT-PCR, Western Blot and immunohistochemistry techniques, the expression of MUC18 in arteriosclerotic arteries from major lower limb amputates (AP, N.=15) as well as specimen from femoral endarterectomies (TEA, N.=20) and in dilatative aortic diseases using abdominal aortic aneurysms (AAA, N.=13) was evaluated. Human visceral arteries without macroscopic arteriosclerosis from liver transplants served as controls (AN, N.=19). RESULTS: MUC18 mRNA and protein expression could be found in AN, AP, TEA and AAA tissues. Immunohistochemical analysis showed that a complete and intact intima was the predominant location of MUC18 expression. Although in stenotic arteriosclerotic disease (AP and TEA) the intima was widely calcified, qRT-PCR analysis showed overexpression compared to normal tissue. Interestingly, MUC18 expression was significantly down-regulated in dilatative compared to stenotic arteriosclerotic disease and normal arteries. CONCLUSION: In peripheral stenotic arteriosclerotic disease the proangiogenic potency of MUC18 may play a role in angiogenesis of collaterals, whereas in dilatative aortic diseases the induction of collaterals is typically not evident. The results support the hypothesis of a role in angiogenesis of MUC18 in stenotic arteriosclerotic disease.

[Advance Directives - Not a Lot of Margin for Error - The Surgeon's View of a Complex Medical-Legal Topic]. / Patientenverfügungen - welchen Spielraum erlauben sie? - Chirurgische Sicht auf ein komplexes medizinjuristisches Thema.

Since September 1st, 2009, the most recent version of the German "Betreuungsrechtsänderungsgesetz" has been validated by the legislators. It precisely sets out how physicians and nursing staff have to deal with a written declaration of a patient's will. This new law focuses in a special way on advance directives, describes the precise rules for the authors of an advance directive and shows both its sphere of action and its limitations. This article aims to give an overview on the legal scope of advance directives, and to illustrate potential limitations and conflicts. Furthermore, it shows the commitments and rights of the medical team against the background of an existing advance directive.

Liver injury following blunt abdominal trauma: a new mechanism-driven classification.

PURPOSES: The current classifications for blunt liver trauma focus only on the extent of liver injury. However, these scores are independent from the localization of liver injury and mechanism of trauma. METHODS: The type of liver injury after blunt abdominal trauma was newly classified as type A when it was along the falciform ligament with involvement of segments IVa/b, III, or II, and type B when there was involvement of segments V-VIII. With the use of a prospectively established database, the clinical, perioperative, and outcome data were analyzed regarding the trauma mechanism, as well as the radiological and intraoperative findings. RESULTS: In 64 patients, the type of liver injury following blunt abdominal trauma was clearly linked with the mechanism of trauma: type A injuries (n = 28) were associated with a frontal trauma, whereas type B injuries (n = 36) were found after complex trauma mechanisms. The demographic data, mortality, ICU stay, and hospital stay showed no significant differences between the two groups. Interestingly, all patients with type A ruptures required immediate surgical intervention, whereas six patients (16.7 %) with type B ruptures could be managed conservatively. CONCLUSIONS: This new classification for blunt traumatic hepatic injury is based on the localization of parenchymal disruption and correlates with the mechanism of trauma. The type of liver injury correlated with the necessity for surgical therapy.

[Benchmarking surgical resources--a work sampling analysis at a German university hospital]. / Ärztliche Ressourcennutzung in der Chirurgie auf dem Prüfstand--eine Worksampling-Analyse an einer deutschen Universitätsklinik.

INTRODUCTION: Work densification caused by lack of young surgeons with increased clinical documentation keeps surgeons busy. It is proven by many studies that surgeons work significantly longer hours per week and deal with a larger amount of medical and non-medical documentation than staff members in conservative disciplines. The aim of the study was to investigate surgeons work distribution in a surgical university department and to evaluate by means of a work sampling analysis whether it can be standardised and slimmed down by systematic use of IT-supported, process-managed work-flow. In addition the data obtained are compared wuith those from other studies on similar topics. METHODS: Based on the results of an independent pilot observational study, 21 surgeons (14 residents, 7 staff surgeons) had to document over a 10-day period in a self-observation once in an hour their actual activity in a two dimensional matrix concerning medical activity (13 items) and patient contact (5 items). After the study, each physician had to estimate his/her own work distribution. Real percentages of the self-observation study were compared to the physicians' estimates of work distribution. IT-supported clinical pathways have been implemented since 2004 in our department. RESULTS: Over a ten-day evaluation period (1830 observation points), surgeons spent 30.2% of their activity in the operating theatre or on direct patient care. During 13.9% they were in meetings and they spent 10.8% of their time on documentation. Time needed for studying medical records (9.2%) and ward rounds (9.0%) ranged in a similar way. There was a significant accordance of estimated and real work distribution concerning the 5 most frequent daily activities. In only 14% there was no direct patient relationship. CONCLUSION: Application of work sampling analysis in surgery is a valid procedure for the evaluation of work flows in the course of personal observations. Surgeons working time in a hospital is limited. To achieve a maximum of direct patient care, clinical documentation has to be optimised by process automatisation within the context of IT-supported clinical pathways. Surgeons are able to estimate very exactly the distribution of their daily activities so that data of working time estimations is valuable.

Hepatic arterial infusion with tumor necrosis factor-α induces early hepatic hyperperfusion.

BACKGROUND: Hepatic arterial infusion (HAI) has been developed for high-dose regional chemotherapy of unresectable liver metastases or primary liver malignancies. While it is well known that high concentrations of tumor necrosis factor (TNF)-α damage tumor blood perfusion, there is no information on whether autochthonous liver perfusion is affected by HAI with TNF-α. Therefore, we investigated the effects of HAI with TNF-α on hepatic macro- and microvascular perfusion. METHODS: Swabian Hall pigs were randomized into three groups. HAI was performed with either 20 or 40 µg/kg body weight TNF-α (n = 6 each group). Saline-treated animals served as controls (n = 6). Analyses during a 2-hour post-HAI observation period included systemic hemodynamics, portal venous and hepatic arterial blood flow, portal venous pressure, and the blood flow in the hepatic microcirculation. RESULTS: HAI with TNF-α caused a slight decrease of mean arterial blood pressure (p < 0.001), which was compensated by a moderate increase of heart rate (p < 0.001). No further systemic side effects of TNF-α were observed. HAI with TNF-α further caused a slight but not significant decrease of portal venous blood flow (p = 0.737) in both experimental groups, paralleled by an increase of hepatic arterial blood flow (p = 0.023, 20 µg/kg; p = 0.034, 40 µg/kg) resulting in an overall hepatic hyperperfusion. The hepatic hyperperfusion after HAI with 20 µg/kg TNF-α was more pronounced and associated with a 40% decrease of the blood flow in the hepatic microcirculation (p = 0.009). HAI with 40 µg/kg TNF-α was only associated with a temporary and moderate total hepatic hyperperfusion and did not affect the blood flow in the hepatic microcirculation. CONCLUSION: HAI with TNF-α causes a decrease of portal venous flow; however, this is overcompensated by an increased hepatic arterial blood flow, resulting in a total hepatic hyperperfusion. Moderate total hepatic hyperperfusion does not affect the blood flow in the hepatic microcirculation, while a persistent and more pronounced hyperperfusion may cause hepatic microcirculatory disturbances.

A comparative evaluation of ablations produced by high-frequency coagulation-, argon plasma coagulation-, and cryotherapy devices in porcine liver.

INTRODUCTION: Hepatic resection is the only curative treatment option for primary or metastatic malignancies of the liver. Although R1 resections can also lead to prolonged survival, the main surgical goal is complete tumor resection (R0). To achieve this, additional treatment of the resection margin with ablation devices is discussed. Using a porcine in vivo model, we therefore analyzed the effect of different ablation devices on depth and completeness of hepatic parenchymal cell destruction. METHODS: Swabian-Hall strain pigs underwent ablation on the surface of the right, middle, or left liver lobe using seven different types of high-frequency (HF)-, cryotherapy (Cryo)-, or argon plasma coagulation (APC) devices. Penetration depth and volume were analyzed from histological sections. Severity of parenchymal cell destruction was assessed by a histomorphological score. RESULTS: The greatest penetration depth was achieved with Cryo (10.4 ± 1.7 mm), whereas HF and APC exhibited a smaller penetration depth. However, HF and APC compared to Cryo achieved complete destruction of the intralobular architecture and hepatocellular morphology depending on the application time and the adjusted power. CONCLUSION: HF, APC, and Cryo applied to the liver surface induce different parenchymal penetration depth and cell destruction. HF and APC are considered to be standard surgical instruments and therefore recommended as standard treatment, whereas Cryo may be used only if particularly deep penetration is required.

Graft-versus-host disease or toxic epidermal necrolysis: diagnostic dilemma after liver transplantation.

Graft-versus-host disease (GvHD) and toxic epidermal necrolysis (TEN) are rare and severe complications after liver transplantation. While mild acute GvHD is quite different from TEN and easy to distinguish, severe acute GvHD and TEN can be hard to differentiate because of similar clinical symptoms. We herein report a case with rapid progression of critical illness, after liver transplantation, caused by GvHD or TEN, although between those, diagnosis was not possible during the clinical course. Although, based on the timing/progression of the symptoms and the chimerism of >40%, the case seemed much more clinically consistent with GVHD, the combination of clinical symptoms together with skin rashes and the histologic appearance of skin lesions indicated diagnosis of a Stevens-Johnson syndrome/TEN overlap. The true diagnostic dilemma in such cases is discussed in detail, as these cases emphasize the need for more advanced diagnostic techniques.

Octreotide prophylaxis is not beneficial for biochemical activity and clinical severity of postoperative pancreatic fistula after pancreatic surgery.

BACKGROUND: Prospective randomized trials indicate that prophylactic octreotide treatment does not decrease the incidence of postoperative pancreatic fistula (POPF). The aim of this study was to analyze if octreotide prophylaxis could decrease the severity grade of POPFs after pancreatic surgery. METHOD: Seventy-eight of 684 patients undergoing pancreatic resection with POPF were included in the study. Prophylactic octreotide treatment was started immediately after surgery and was performed in 22 patients, whereas 56 patients had no octreotide treatment and served as controls. Lipase activity was measured in the abdominal drainage on postoperative days (POD) 3, 5 and 7. Primary endpoints of the study were clinical severity of the POPF and lipase activity in the drainage. RESULTS: There was no significant difference concerning length of postoperative hospital stay. Lipase activity in the abdominal drainage was not influenced by octreotide prophylaxis at POD 5 or 7 compared to POD 3. Multivariate analysis showed that the risk to develop a type B or C fistula in the octreotide group was independent of the kind of operation and the consistency of the pancreas (RR = 3.4; CI = 1.0-11.7; p = 0.050 and RR = 6.3; CI = 1.4-29.6; p = 0.019). CONCLUSION: Octreotide prophylaxis after pancreatic surgery has no beneficial effect on clinical severity of POPF.

[Closing the abdominal wall - challenges and possible solutions]. / Herausforderung Bauchwandverschluss - Übersicht zur Problematik und Lösungsansätze.

The most common complications after abdominal surgery - wound infections and the development of incisional hernia - are associated with the opening and closing of the abdominal wall. Depending on the selection of patients, wound infection rates of up to 19 % and hernia rates of up to 38 % are reported. Based on a summary of the actual literature, the abdominal wall should be closed with continuous slowly absorbable sutures with a suture length to wound length ratio of over 4 using small stitches. While antiseptic suture material may help to reduce wound infections after abdominal incision, preventing the development of incisional hernia is still a unsolved problem. As there is still no standard surgical technique for abdominal wall closure, surgeons should pay greater attention to the standardisation and documentation of techniques and wound care.

[Antibiotic prophylaxis and endoluminal tubes]. / Antibiotikaprophylaxe und endoluminäre Sonden.

Surgical site infections are one of the most common complications after surgical procedures. The use of perioperative antibiotic prophylaxis can successfully reduce the number of wound infections. The indications, timing and choice of antibiotics are discussed critically. Taken together antibiotic prophylaxis should be evaluated depending on wound contamination, the type of operation and patient-specific risk factors. In the second part of this work the current literature on the effectiveness of endoluminal tubes in abdominal surgery is analyzed. While many surgeons use these tubes regularly in elective abdominal surgery, only few data are available on this topic. The use of nasogastric tubes in elective surgery should be avoided.

[Increasing efficiency and patient satisfaction by structured clinical processes in presurgical visits]. / Steigerung von Effizienz und Patientenzufriedenheit durch strukturierte Prozesse am Beispiel der Prämedikationsambulanz.

BACKGROUND: In clinical routine the process of presurgical visit and signed informed consent is imperfectly realized in surgical patients. MATERIAL AND METHODS: A total of 450 consecutive patients were interviewed after a presurgical visit for informed consent using a questionnaire. The aim of the study was to investigate the amount of knowledge gained by informed consent. Patient satisfaction with medical treatment and logistic workflow was correlated with real waiting times and process times. RESULTS: Mean information duration was 36.1±0.8 min. In patients with no appointed time, waiting times and overall stay was shorter. Patient's satisfaction with medical treatment and time process was significantly higher in the elderly. Longer conversation with the surgeon was associated with a higher assessment of surgeons' medical experience irrespective of his specialist's state. Real waiting times did not affect patient's satisfaction. CONCLUSION: A walk-in clinic for presurgical visit and signed informed consent can improve patient satisfaction. It allows an excellent patients information in an appropriate time-frame. Clinical pathways can improve patient satisfaction and information concerning the lining up operation and disease pattern.

[Multimodal approach in coincidence of covered ruptured abdominal aortic aneurysm and aortocaval fistula]. / Multimodales Vorgehen bei einem gedeckt rupturierten Bauchaortenaneurysma mit aortocavaler Fistel.

HISTORY AND ADMISSION FINDINGS: A 71-year-old patient had been referred to our hospital with the diagnosis, made by angio-computed tomography (CTA), of a covered ruptured abdominal aortic aneurysm (AAA) resulting in an aortocaval fistula (ACF). INVESTIGATIONS: The physical examination revealed macrohematuria and high-output heart failure with increasing circulatory insufficiency. DIAGNOSIS, TREATMENT AND COURSE: An open endovascular procedure was not possible because the AAA had extended into both internal iliac arteries. A bifurcated prosthesis connecting to both femoral arteries was then successfully implanted and the infrahepatic aortocaval fistula closed by a patch through the AAA. Ischemic colitis, diagnosed on postoperative day 2 (POD 2), was successfully treated with antibiotics. CTA, done on POD 5, revealed a small residual ACF, filling retrogradely from the right external iliac artery via the surgically closed aneurysmal sack. Closure of the residual ACF was achieved with an Amplatz occluder inserted into the right external iliac artery, introduced percutaneously via the right femoral artery. The postoperative course was uneventful and the patient discharged on POD 13. CONCLUSION: The coincidence of AAA and ACF is rare. However, the morbidity and mortality are high and require early diagnosis and immediate treatment.

Tumour growth following portal branch ligation in an experimental model of liver metastases.

BACKGROUND: Portal branch ligation (PBL) is being used increasingly before hepatectomy for colorectal metastases. This study evaluated the effect of PBL on angiogenesis, growth factor expression and tumour growth in a mouse model of hepatic colorectal metastases. METHODS: CT26.WT cells were implanted into the left liver lobe of BALB/c mice. Animals underwent PBL of the left liver lobe or sham treatment. Angiogenesis, microcirculation, growth factor expression, cell proliferation and tumour growth were studied over 14 and 21 days by intravital multifluorescence microscopy, laser Doppler flowmetry, immunohistochemistry and western blotting. RESULTS: Left hilar blood flow and tumour microcirculation were significantly diminished during the first 7 days after PBL. This resulted in tumour volume being 20 per cent less than in sham controls by day 14. Subsequently, PBL-treated animals demonstrated recovery of left hilar blood flow and increased expression of hepatocyte growth factor and transforming growth factor alpha, associated with increased cell proliferation and acceleration of growth by day 21. CONCLUSION: PBL initially reduced vascular perfusion and tumour growth, but this was followed by increased growth factor expression and cell proliferation. This resulted in delayed acceleration of tumour growth, which might explain the stimulated tumour growth observed occasionally after PBL.

Laser Doppler flowmetry of hepatic microcirculation during Pringle's maneuver: determination of spatial and temporal liver tissue perfusion heterogeneity.

BACKGROUND: Laser Doppler flowmetry (LDF) is frequently used for non-invasive microvascular perfusion measurements. The aim of the present study was to analyze liver blood flow heterogeneity in detail using LDF devices under normal and low-flow conditions. MATERIALS AND METHODS: In 5 anesthetized and laparotomized Suabian-Hall strain pigs, systemic hemodynamics and hepatic arterial/portal venous blood flow were constantly recorded. Hepatic microcirculation was assessed by 2 different LDF devices, analyzing microvascular flow and velocity before, during and after inducing a Pringle's maneuver for hepatic inflow occlusion. Offline data analysis comprised differentiation between the two LDF devices used as well as calculation of temporal and spatial heterogeneity of liver perfusion. RESULTS: Pringle's maneuver induced complete inflow occlusion, confirmed by hepatic arterial/portal venous blood flow measurement. Laser Doppler signals showed a significant decrease during Pringle's maneuver. Spatial heterogeneity of flow and velocity increased more than temporal heterogeneity during Pringle's maneuver. CONCLUSION: Both LDF devices proved suitable for assessing hepatic microvascular perfusion during normal perfusion and low-flow conditions. Reduced microvascular perfusion induces a significant increase in temporal and spatial perfusion heterogeneity. In particular, the pronounced spatial heterogeneity requires measurements at different places when assessing hepatic microcirculation by LDF during impaired perfusion conditions.

[A totally implantable venous access device. Implantation in general or local anaesthesia? A retrospective cost analysis]. / Venöses Portsystem. Implantation in Vollnarkose oder Lokalanästhesie? Eine retrospektive Aufwandsanalyse.

BACKGROUND: Implantation of venous access port systems can be performed in local or general anesthesia. In spite of the increasing rate of interventionally implanted systems, the surgical cut-down represents a safe alternative. Thus, the question arises whether--in context to the increasing health-economic pressure--open implantation in general anesthesia is still a feasible alternative to implantation in local anesthesia regarding OR efficiency and costs. PATIENTS AND METHODS: In a retrospective analysis, 993 patients receiving a totally implantable venous access device between 2001 and 2007 were evaluated regarding OR utilization, turnover times, intraoperative data and costs. Implantations in local (LA) and general anesthesia (GA) were compared. RESULTS: GA was performed in 762 cases (76.6 %), LA was performed in 231 patients (23.3 %). Mean operation time was similar in both groups (LA 47.27 +/- 1.40 min vs. GA 45.41 +/- 0.75 min, p = 0.244). Patients receiving local anesthesia had a significantly shorter stay in the OR unit (LA 95.9 +/- 1.78 min vs. GA 105.92 +/- 0.92 min; p < 0.001). Specifically, the time from arrival in the operating room to surgical cut (LA 39.57 +/- 0.69 min vs. GA 50.46 +/- 0.52 min; p < 0.001) was shorter in the LA group. Personnel and material costs were significantly lower in the LA group compared with the GA group (LA: 400.72 +/- 8.25 euro vs. GA: 482.86 +/- 6.23 euro; p < 0.001) Blood loss as well as duration and dose of radiation were similar in both groups. CONCLUSIONS: Our study shows that implantation of totally implantable venous access port systems in local anesthesia is superior in comparison to the implantation under general anesthesia regarding procedural times in the OR unit and costs. With the same operation duration, but less personnel and material expenditure, implantation in local anesthesia offers a potential economic advantage by permitting faster changing times. Implantation in GA only should be performed at a special request by the patient or in difficult venous conditions.

Randomized clinical trial of efficacy and costs of three dissection devices in liver resection.

BACKGROUND: In recent decades a variety of instruments for liver dissection has become available. This randomized controlled trial analysed the efficacy and costs of three different liver dissection devices. METHODS: Ninety-six patients without cirrhosis undergoing liver resection were randomized to either ultrasonic dissection, waterjet dissection or dissecting sealer (32 in each group). Patients were unaware of the device used. The primary endpoint was dissection speed. Secondary endpoints were intraoperative blood loss, morbidity and mortality, and costs of dissection devices, staplers and haemostatic agents. RESULTS: Dissection was slower with the dissecting sealer (P = 0.004 versus waterjet dissector). The difference was more pronounced for extended resections (mean(s.e.m.) 1.62(0.36) cm(2)/min versus 3.42(0.53) and 3.63(0.51) cm(2)/min for ultrasonic and water dissectors respectively; P = 0.037). Costs were significantly higher for the dissecting sealer when atypical or segmental resections were performed. Four patients died after extended resections; postoperative complications did not differ between groups. CONCLUSION: The dissecting sealer is slower than the ultrasonic dissector or water dissector. The three devices are equally safe in terms of blood loss, transfusions and postoperative complications. Ultrasonic and water dissectors might be more favourable economically than the dissecting sealer. REGISTRATION NUMBER: ISRCTN52294555 (http://www.controlled-trials.com).

[Anatomic and atypical resections of the gallbladder bed in patients with gallbladder carcinoma]. / Anatomische und atypische Resektionen des Gallenblasenbetts beim Gallenblasenkarzinom.

BACKGROUND: At present, atypical as well as anatomic liver resections are recommended as the surgical therapy for gallbladder cancer (GC) at stages > or = T 2. The aim of this study was to compare atypical with anatomic resections (mostly resections of segments IV b / V with selective vascular occlusion using the round ligament approach). PATIENTS AND METHODS: Between November 1994 and January 2007, n = 56 patients were treated for GC. The staging, operative and histological results and the postoperative course were recorded. In addition, the survivals at a mean follow-up of 13 (range: 3-54) months were estimated and compared between the two study groups. RESULTS: We performed 28 liver resections for GC (n = 14 atypical and n = 14 anatomic resections). In the anatomic resection group, there was one extended right hepatectomy as well as thirteen segment IV b / V resections. The volume of the resected liver specimen, the frequency of the Pringle manoeuvre, the transfusion requirements, and the duration of the operation did not differ between the two study groups. However, in only 64 % of the atypical resections, the recommended resection margin of at least 3 cm could be achieved. One patient died after extended hepatectomy. There were no other major complications. The mean follow-up was 16 +/- 5 months in the anatomic and 22 +/- 7 months in the atypical resection group. Survival was not statistically different between the two study groups. CONCLUSION: Segment IV b / V resections are attractive procedures to treat GC due to their lower invasiveness in spite oncological adequacy. However, we could not demonstrate any superiority in terms of survival for the segment IV b / V liver resections. Nevertheless, extended liver resections are rarely necessary in the operative treatment of GC.