[Thrombosis prophylaxis in surgery. What is the evidence?]. / Thromboseprophylaxe in der Chirurgie. Was ist wirklich gesichert?

Prevention of venous thromboembolism has become routine in all surgical disciplines and consists of physical and pharmacological measures. The indications and choice of prophylaxis modality depend on the individual patient risk profile which is determined by the combination of exposing and predisposing risk factors. The exposing risk factors are characterized by the type and extent of surgery or trauma, whereas the predisposing risk factors relate to patient-inherent risk factors. This is also taken into consideration for the compilation of guidelines. This review summarizes the recommendations of the German S3 guidelines related to surgery and also discusses the perioperative management of patients receiving long-term anticoagulation with new oral anticoagulants (rivaroxaban, apixaban, dabigatran).

[Preventing venous thromboembolism]. / Prävention venöser Thromboembolien.

Routine antithrombotic prophylaxis today is consistently a part of surgical treatment. The indication and choice of both physical and medical prophylactic measures depend upon the individual thromboembolic risk profile of the patient. This is determined by expositional (procedure, trauma) and dispositional patient-related risk factors. Clinical thromboembolic risk can be differentiated into three risk categories (low, moderate, high) and determines the risk-adapted kind of prophylaxis. Unfractionated heparin and low molecular weight heparins have proven most effective in long-term medical treatment but are still limited in their use by some side effects. The development of new anticoagulant agents may improve antithrombotic prophylaxis and overcome some disadvantages of antithrombotic drugs used till now.

[Optimal recurrence prevention of iodine deficiency related goiter after thyroid gland operation. A prospective clinical study]. / Optimale Rezidivprophylaxe der Jodmangelstruma nach Schilddrüsenoperation. Eine prospektive klinische Studie.

In summary the data of our study show: (1) Sonographically determined thyroid volume of patients with euthyroidism after surgery is found to be significantly lower with a combination therapy (iodide 150 microgram +Levothyroxine 75 microgram) compared to patients with iodide monotherapy (200 microgram). (2) Thyroid volume of patients with hypothyroidism after surgery is found to be significantly lower during a combination therapy (150 microgram iodide + 75 microgram L-thyroxine) compared to patients with a Levothyroxine monotherapy. (3) Patients with hypothyroidism and Levothyroxine monotherapy, however present with a significant increase of thyroid volume after surgery. (4) Urinary iodide excretion in the treatment groups with iodide or combination therapy increases significantly during therapy, however, patients with Levothyroxine monotherapy do not show changes. (5) Thyroid function is well stabilized in all treatment groups with adequate controls and adjustment of Levothyoxine dosage. There data clearly demonstrate that the combination therapy with Levothyoxine and iodide significantly improves prophylaxis of goiter recurrence.

Phagocytosis by emigrated, intra-abdominal neutrophils is depressed during human secondary peritonitis.

The phagocytic function of neutrophils is a crucial element in host defense against invading microorganisms. Patients with diffuse peritonitis depend on adequate reactivity of neutrophils, in particular locally in the peritoneal cavity as well as in the circulation. This study examined phagocytosis as well as numerical expression of Fcgamma I-III (CD16, CD32, CD64) and complement receptors (CD18, CD35) of emigrated, intra-abdominal and circulating neutrophils during human secondary peritonitis using fluorescence-activated cell analysis. Optimally opsonized E. coli bacteria were used independently of the well-known low level of opsonic molecules during peritonitis. Compared with controls (abdominal surgery without peritonitis), the percentage of emigrated neutrophils which engulfed E. coli bacteria was significantly depressed until 48 h after diagnosis of, and surgery for, peritonitis. When patients with complicated peritonitis (septic shock, multiple organ failure) were compared with patients without complications, phagocytosis was even more depressed in patients with complications. Numerical expression of CD64 (Fcgamma RI) and CD35 (CR1) increased significantly on emigrated polymorphonuclear leukocytes (PMNs) during peritonitis when compared to controls. There was no difference in CD18 and CD32 (Fcgamma RII) expression between the two groups. Numerical expression of CD16 (Fcgamma RIII) on emigrated PMNs decreased significantly in peritonitis. This was more pronounced in patients with complicated peritonitis. We conclude that there is a long-lasting depression of phagocytosis by emigrated PMNs during peritonitis, independent of the opsonic activity. Our data suggest that decreased phagocytosis might be correlated to the profound drop in CD16 on these cells.

[Surgery and long-term follow-up of hepatic echinococcosis outside endemic regions]. / Die chirurgische Behandlung der Leberechinokokkose ausserhalb von Endemiegebieten und ihre Spätergebnisse.

UNLABELLED: The aim of the study was to characterize the therapeutic pathways in patients with echinococcal hydatids in an institution outside the endemic areas but with a high frequency of oncological hepatic surgery. PATIENTS AND METHODS: 44 patients with echinococcosis from 1987-1997 were reviewed. To evaluate the long-term results, clinical examination, chest x-ray, serology and liver ultrasound were performed. According to the study protocol 39 patients were evaluable. 89.7 % of the patients suffered from a primary disease, whereas 7.7 had a local recurrence and another 2.5 of patients showed a second site of manifestation after former operation. E. cysticus occurred in 82.5 %, E. alveolaris in 17.5 %. RESULTS: In 66.7 % of all cases a resecting procedure (pericystectomy, atypic resection, regular and extended hemihepatectomy) was performed. One patient underwent an orthotopic liver transplantation and in 10 % the surgical procedure included only an open drainage of the cysts. A simple cystectomy was performed in 23 %. One patient died from multiple organ failure as a consequence of local bleeding complications. The overall complication rate was 38.5 %, including the postoperative death and 7.7 % reoperations. The complication rate following pericystectomy was much higher than after simple cystectomy. At the time of follow-up (median 66 months) no patient showed a recurrent disease. CONCLUSION: Compared to reports from endemic regions the rate of resective procedures was much higher. The therapeutic strategy lead to excellent long-term results. Simple cystectomy should be preferred as pericystectomy showed a higher morbidity.

[Not Available]. / Leitlinien als Instrument der Qualitätssicherung in der Medizin Das Leitlinienprogramm der Arbeitsgemeinschaft Wissenschaftlicher Medizinischer Fachgesellschaften (AWMF) : Das Leitlinienprogramm der Arbeitsgemeinschaft Wissenschaftlicher Medizinischer Fachgesellschaften (AWMF).

The Association of the Scientific Medical Societies in Germany (AWMF) established a national guideline-programme respecting the specific conditions of the German health-care system as well as fulfilling the demands of clinical research. It consists of a three-level concept for guideline development and an implementation system. The three-level concept assumes a continuous process of development and quality improvement of guidelines. At level three, guidelines have to fulfill five criteria of systematic development: consensus (presupposed application of formal techniques and participation of all relevant stakeholders), logical analysis (clinical algorithms), evidence (based on best available evidence derived from comprehensive, systematic reviews and linking all recommendations explicitly to the evidence), decision analysis and outcome analysis (using epidemiologic, effectiveness, pharmacologic, psychometric, economic studies and qualitative methods for identifying the true endpoint). The implementation system is based on four components: definite guideline groups within the scientific societies, conceptualised quality improvement of guidelines, continuous medical education and systematic evaluation. The establishment of this system has induced a change: the process of developing top-level guidelines has become uniform and there is a strong trend towards quality improvement. 75 evidence- and consensus- based guidelines (level two and three) have already been published. The scientific medical societies have indicated their motivation to continue the program by formulating 75 prior conditions for which top-level guidelines shall be developed in the near future.

Effect of fibrin glue occlusion of the hepatobiliary tract on thioacetamide-induced liver failure.

BACKGROUND: Expression and activation of hepatocyte growth factor (HGF) is stimulated by a complex system of interacting proteins, with thrombin playing an initial role in this process. The impact of temporary occlusion of the hepatobiliary tract with fibrin glue (major component thrombin) on the HGF system in acute and chronic liver damage in a rat model was investigated. METHODS: Chronic liver damage was induced in 40 rats by daily intraperitoneal application of thioacetamide (100 mg/kg) for 14 days. After 7 days half of them received an injection of 0.2 mL fibrin glue into the hepatobiliary system. Daily intraperitoneal administration of thioacetamide continued for 7 consecutive days. The rats were then sacrificed for blood and tissue analysis. Acute liver failure was induced in 12 rats by intraperitoneal administration of a lethal dose of thioacetamide (500 mg/kg per day for 3 days) after an injection with 0.2 mL fibrin glue into their hepatobiliary tract. Survival rates and histological outcome were investigated and compared with control animals. RESULTS: Fibrin glue occluded rats showed significantly lower liver enzyme activities and serum levels of bilirubin, creatinine and urea nitrogen. Immunohistochemistry revealed a significant increase in c-met-, HGFalpha- and especially HGFbeta-positive cells. Rats subjected to a lethal dose of thioacetamide survived when fibrin glue was applied 24 hours prior to the toxic challenge. These animals showed normal liver structure and no clinical abnormalities. CONCLUSION: Fibrin glue occlusion of the hepatobiliary tract induces therapeutic and prophylactic effects on chronic and acute liver failure by stimulating the HGF system. Therefore, fibrin glue occlusion might be useful in treating toxic liver failure.

Anticoagulation: the present and future.

Thrombin is a central bioregulator of coagulation and is therefore a key target in the therapeutic prevention and treatment of thromboembolic disorders, including deep vein thrombosis and pulmonary embolism. The current mainstays of anticoagulation treatment are heparins, which are indirect thrombin inhibitors, and coumarins, such as warfarin, which modulate the synthesis of vitamin K-dependent proteins. Although efficacious and widely used, heparins and coumarins have limitations because their pharmacokinetics and anticoagulant effects are unpredictable, with the risk of bleeding and other complications resulting in the need for close monitoring with their use. Low-molecular-weight heparins (LMWHs) provide a more predictable anticoagulant response, but their use is limited by the need for subcutaneous administration. In addition, discontinuation of heparin treatment can result in a thrombotic rebound due to the inability of these compounds to inhibit clot-bound thrombin. Direct thrombin inhibitors (DTI) are able to target both free and clot-bound thrombin. The first to be used was hirudin, but DTIs with lower molecular weights, such as DuP 714, PPACK, and efegatran, have subsequently been developed, and these agents are better able to inhibit clot-bound thrombin and the thrombotic processes that take place at sites of arterial damage. Such compounds inhibit thrombin by covalently binding to it, but this can result in toxicity and nonspecific binding. The development of reversible noncovalent DTIs, such as inogatran and melagatran, has resulted in safer, more specific and predictable anticoagulant treatment. Oral DTIs, such as ximelagatran, are set to provide a further breakthrough in the prophylaxis and treatment of thrombosis.

Granulocyte-colony stimulating factor in the prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). Protocol of a controlled clinical trial developed by consensus of an international study group. Part three: individual patient, complication algorithm and quality manage.

GENERAL DESIGN: Presentation of a new type of a study protocol for evaluation of the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and of sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). A randomised, placebo controlled, double-blinded, single-centre study is performed at an University Hospital (n = 40 patients for each group). This part presents the course of the individual patient and a complication algorithm for the management of anastomotic leakage and quality management. OBJECTIVE: In part three of the protocol, the three major sections include: The course of the individual patient using a comprehensive graphic display, including the perioperative period, hospital stay and post discharge outcome. A center based clinical practice guideline for the management of the most important postoperative complication--anastomotic leakage--including evidence based support for each step of the algorithm. Data management, ethics and organisational structure. CONCLUSIONS: Future studies with immune modifiers will also fail if not better structured (reduction of variance) to achieve uniform patient management in a complex clinical scenario. This new type of a single-centre trial aims to reduce the gap between animal experiments and clinical trials or--if it fails--at least demonstrates new ways for explaining the failures.

[Robot-assisted laparoscopic cholecystectomy and fundoplication--initial experiences with the Da Vinci system]. / Roboterassistierte laparoskopische Cholecystektomie und Fundoplicatio--erste Erfahrungen mit dem Da-Vinci-System.

We report on our first five robot-assisted laparoscopic cholecystectomies and one fundoplication (Da Vinci system). No postoperative complications were observed. For the cholecystectomies (three elective and two acute cases) mean operation time was 1 h 35 min, and mean hospital stay was 5 days; for fundoplication the operation time was 2 h 15 min. The main advantages seem to be improved visualization by using a stereo camera und ease of precise dissection by micromechanical instruments directed by masterslaves from a distant console. The main disadvantage is the high cost. To fully evaluate the benefit for the patient, prospective clinical trials are warranted.

Impact of cyclosporine and low-dose steroid therapy on insulin sensitivity and beta-cell function in patients with long-term liver grafts.

To examine whether factors controlling glucose tolerance, i.e., insulin sensitivity (SI) and first-(phi1) and second-phase insulin secretion (phi2), are impaired in after orthotopic liver transplantation (OLT), they were assesssed in patients that had undergone OLT for cirrhosis (n = 10) with cyclosporin A and low-dose steroid therapy (5 mg prednisone per day) and were compared with those of healthy matched control subjects (n = 10). These factors were determined by means of computer-based analysis of frequently sampled intravenous glucose tolerance tests (FSIGTT). Glucose and insulin profiles (posthepatic insulin) did not differ between both groups, whereas C-peptide levels (prehepatic insulin) were elevated in the transplant group after the FSIGTT, indicating an increased hepatic insulin degradation. SI and (phi1 did not differ between both groups. phi2, however, was significantly enhanced (23.94 +/- 2.63 vs 13.88 +/- 1.25 min(-1), P < 0.05). These results indicate that cyclosporine and low-dose steroid therapy do not impair SI and phi1. However, enhanced phi2 compensates the increased hepatic insulin clearance.

Oxygen radical generation by emigrated, intra-abdominal, and circulating PMNLs during human secondary peritonitis.

The purpose of the study was to characterize oxygen radical generation by emigrated, intraabdominal and circulating polymorphonuclear leukocytes (ePMNLs and cPMNLs) during peritonitis, as well as to assess any differences between oxygen radical production in patients with low Mannheim peritonitis index (MPI < 26, group 1) or high Mannheim peritonitis index (MPI > or = 26, group 2). Lucigenin-enhanced chemiluminescence was used to determine spontaneous and stimulated (FMLP, PMA, and A23 187) oxygen radical generation by ePMNLs and cPMNLs. In group 1 spontaneous and stimulated oxygen radical generation by emigrated PMNLs was markedly enhanced compared to circulating PMNLs (e.g., spontaneous oxygen radical generation: 30.3 +/- 11.8 cpm/cPMNLs versus 107 +/- 46 cpm/ePMNLs, P < 0.05) . In group 2 oxygen radical generation by cPMNLs markedly increased within 48 h after diagnosis of peritonitis and surgery, contrary to radical generation by ePMNLs (e.g., A23 187-stimulated oxygen radical generation 993.7 +/- 350 cpm/cPMNLs versus 285.6 +/- 77 cpm/ePMNLs, P < 0.05. In conclusion, cPMNLs and ePMNLs exhibit marked polymorphism in their capacity to generate oxygen radicals in response to secondary peritonitis. Severe peritonitis (MPI - 26) was associated with a strong increase in oxygen radical generation by cPMNLs without a parallel activity being manifest by ePMNLs.

[Insular carcinoma of the thyroid: a differentiated thyroid carcinoma with poor prognosis]. / Das insuläre Schilddrüsencarcinom--ein differenziertes Schilddrüsencarcinom mit schlechter Prognose.

Insular carcinoma of the thyroid is a low differentiated type constituting about 5% of all thyroid cancers. Higher aggressiveness has been suggested as an important clinical feature. The value of preoperative fine-needle aspiration biopsy is not clearly proven for insular carcinoma. The criteria for histological diagnosis have been outlined by Carcangiu et al. Because of its aggressiveness, radical treatment at primary surgery appears advisable. Its clear distinction from undifferentiated (anaplastic) and medullary (C cell) cancers is important, as thyroglobulin is regularly synthesized by cancer cells. Enrichment of radioactive iodine makes such treatment feasible postoperatively and at relapse. Follow-up should be performed as in highly differentiated papillary and follicular thyroid cancer. A patient series of eight cases is presented. While all cancers were advanced at the initial diagnosis, the observed disease courses were in agreement with the assumption that insular carcinoma is a more aggressive form of differentiated thyroid cancer.

Regional chemotherapy in the treatment of advanced pancreatic cancer--is it relevant?

The treatment of pancreatic cancer is still problematic for physicians. Only 15% of patients present with resectable tumours, and systemic chemotherapy is of limited effectiveness. In order to achieve higher local drug concentrations in the tumour without causing the side-effects of a comparable level of systemic treatment, regional chemotherapy has been introduced as an alternative treatment. Several techniques have been developed over recent years, these include: celiac axis infusion (CAI), CAI with microspheres or haemofiltration, aortic stop flow (ASF) and isolated hypoxic perfusion (IHP). Whilst several authors have reported improved response rates and a prolongation of median survival time, these results have not been confirmed by others. In addition, the incidence of side-effects and the rate of technical complications have been reported to be high during regional chemotherapy. Except for a single trial containing 14 patients, no randomised trial comparing systemic and regional chemotherapy has been conducted. For these reasons, none of the reported treatment regimens can be considered to be standard treatment and in order to evaluate, if regional chemotherapy is indeed superior to systemic chemotherapy, randomised trials must be conducted.

Mycophenolate mofetil decreases endothelial prostaglandin E2 in response to allogeneic T cells or cytokines.

BACKGROUND: Prostaglandin E2 (PGE2) is a powerful endogenous immune suppressant and interferes with various T-cell functions. However, it is not known in detail whether immunosuppressive drugs influence the PGE2-driven immune response in transplant patients. Therefore, we investigated the effect of several immunosuppressive compounds, in particular the novel drug mycophenolate mofetil (MMF), on endothelial PGE2 release. METHODS: Endothelial cells (HUVEC) were activated by either allogeneic CD4+ or CD8+ T cells, or by the cytokines interleukin-1 or gamma-interferon. Using an enzyme-linked immunosorbent assay, we analyzed PGE2 release of the activated HWEC in the presence of MMF, cyclosporine, or tacrolimus. As verapamil and mibefradil also possess immunosuppressive properties, they were included in the study as well. RESULTS: Activation of HUVEC with interleukin-1 or T cells resulted in a drastic accumulation of PGE2 in the supernatant. Cyclosporine or tacrolimus had no effect on PGE2 release. However, Ca2+ channel blockers, when applied at higher dosages, caused a significant increase in PGE2. Interestingly, MMF strongly diminished the PGE2 level in the cell culture supernatant in a concentration-dependent manner. CONCLUSION: The results demonstrate an inhibitory effect of MMF on PGE2 production, which may lower the benefits of the PGE2-triggered immune response after organ transplantation.

[Diagnosis and therapy of abnormal bleeding in surgery]. / Diagnostik und Therapie abnormer Blutungen in der Chirurgie.

Abnormal surgical bleeding may be caused by congenital or acquired plasmatic and/or thrombocytic coagulation disorders. They may be known at the time of operation, or they may occur during the perioperative course for the first time. A detailed identification of haemostatic defects can be performed by a diagnostic spectrum of multiple tests. However, in clinical practice global screening tests are used first. In diagnostic routine three groups of patients have to be considered: (1) patients with no personal or family history of bleeding and no operative bleeding risk; (2) patients with no history, but increased bleeding risk by the planned procedure; (3) patients with a known haemorrhagic diathesis in their own history. In all difficult situations a specialist in haemostasiology should be consulted, because only rational diagnosis and therapeutic monitoring achieve an optimal and cost-effective operative result. The surgeon should always be aware that surgical bleeding from an operative cause must be considered in the differential diagnosis.