[Treatment of septic complications od secondary peritonitis]. / Therapie septischer Komplikationen bei der sekundären Peritonitis.

The authors review the current management goals of surgical and antibiotic therapy in secondary peritonitis. Basic therapeutic regimen is the surgical elimination of the infectious source by means of a rational and risk-adapted operative procedure. Other technical procedures (such as intra- and postoperative lavage, drainage of the abdominal cavity, decompression, etc.) are critically reviewed and reduced to the scientific background. A calculated antibiotic therapy should be performed to eliminate the leading pathogens. The golden standard seems to be the short-term application of a third generation cephalosporin in combination with metronidazole. Antibiotic-induced endotoxinemia, bacterial shifting to grampositive species, and escalating antibiotic resistance require the examination of new therapeutic regimens (e.g. with quinolones).

[Adjuvant regional arterial port chemotherapy after resection of colorectal liver metastases]. / Adjuvante regionale arterielle Portchemotherapie nach Resektion colorectaler Lebermetastasen.

Between 1986 and 1995 we performed radical hepatic resections (R0 resections) in 109 patients with hepatic metastases following colorectal carcinoma. In 50 patients a hepatic arterial port device was implanted for adjuvant regional chemotherapy (HAI). Mitomycin C, 5-fluorouracil, and since 1993 folinic acid have been administered during 6 monthly repeated courses. In 9 patients, the treatment had to be withdrawn because of complications. The remaining 59 patients were not treated. In 73% of the patients after port implantation mostly minor complications occurred during chemotherapy. Our results confirmed a markedly increased survival rate during the first 3 postoperative years, followed by a prolongation of median survival time of treated patients compared to untreated patients. Nevertheless, the observed differences of median survival were not statistically different. In contrast, the 5-year survival rates of both groups were not different. The frequency, localization, and resectability of recurrences were not influenced by adjuvant chemotherapy. However, the lengthening of mean survival time in the treated group might reflect a delay in the occurrence of early recurrences. In conclusion, adjuvant hepatic arterial chemotherapy following resection of colorectal hepatic metastases might be able to prolong the time until recurrence, but does not help to avoiding it. Therefore, it did not increase the rate of cure following R0 resections of colorectal hepatic metastases in our series. Taking into account the high rate of local complications of the port systems in our series, angiographic controls are strongly recommended prior to each chemotherapeutic cycle.

Modulation of pro- and antifibrinolytic properties of human peritoneal mesothelial cells by transforming growth factor beta1 (TGF-beta1), tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta).

A decreased fibrinolytic activity of serosal surfaces appears to be a major factor in the development of peritoneal fibrous adhesions. Serosal fibrinolysis is regulated by mesothelial release of tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor types 1 and 2 (PAI-1 and PAI-2). We investigated the influence of tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta1) and interleukin 1beta (IL-1beta) on pro- and antifibrinolytic properties of mesothelial cells (HOMC) using a cell/fibrin clot assay. TGF-beta1, TNF-alpha and IL-1beta induced a dose dependent 2.9, 2.3 and 1.9-fold increase of PAI-1 antigen, respectively, whereas t-PA concentrations decreased to one third of the control values. This modified PAI-1/t-PA secretion pattern leads to a significant delay of fibrinolysis. Analysis of m-RNA levels revealed increased PAI-1 m-RNA concentrations after 12 h and decreased m-RNA concentrations for t-PA after 6 h. Serosal hypofibrinolysis during peritonitis may be explained at least in part by cytokine effects which thus may favor adhesion formation.

The influence of heat shock protein 70 induction on hemodynamic variables in a porcine model of recurrent endotoxemia.

The manipulation of stress gene expression by heavy metals provides protection against the lethal effects of endotoxemia in murine models of septic shock. These findings suggest that the increased resistance to endotoxin in vivo after stress protein induction could be explained by an attenuation of hemodynamic alterations and an altered pattern of inflammatory mediator release. Therefore, we measured main hemodynamic variables such as systemic and pulmonary artery pressure, cardiac output, heart rate, central venous pressure, and pulmonary artery wedge pressure, as well as the time-course of thromboxane-B2, 6-keto-PGF1 alpha, and interleukin 6 formation with and without induction of the stress response in an established porcine model of recurrent endotoxemia (Circ Shock 35:237-244, 1991). Induction of the stress response was carried out by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenaspartate) = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced an increased heat shock protein 70 (HSP70) expression in the lungs, liver, and kidneys and significantly increased plasma levels of interleukin 6, 6-keto-PGF1 alpha, and thromboxane-B2, compared with untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators compared with the untreated group. Hemodynamic data presented significantly decreased peak pulmonary artery pressure and pulmonary vascular resistance index values, significantly increased systemic artery pressure and systemic vascular resistance index values, and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of HSP70 by Zn2+ attenuates the liberation of inflammatory mediators, as well as the course of hemodynamic variables due to LPS.

Induction of heat shock protein 70 by zinc-bis-(DL-hydrogenaspartate) reduces cytokine liberation, apoptosis, and mortality rate in a rat model of LD100 endotoxemia.

A prospective, randomized model of LD100/24 h endotoxemia was performed in male Wistar rats (n = 26; 250-300 g). The animals were divided into four groups: Group I (n = 5; saline treatment only), Group II (n = 5; Zn2+ treatment only), Group III (n = 8; saline pretreatment, lipopolysaccharide (LPS) treatment), and Group IV (n = 8; Zn2+ pretreatment, LPS treatment). Zn2+ pretreatment was carried out by intraperitoneal injection of 50 mg/kg zinc-bis-(DL-hydrogenaspartate) (10 mg/kg Zn2+). LD100/24 h endotoxemia was induced by intraperitoneal administration of 20 mg/kg LPS of the Escherichia coli strain WO111:B4. Tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 were detected by enzyme-linked immunosorbent assay (ELISA). HSP70 expression in the lungs, the liver, and the kidneys was determined by immunohistochemistry, Western blotting, and an HSP70 ELISA. Apoptosis was also detected by an in situ apoptosis detection kit (TUNEL) and a cell death detection ELISA, respectively. This rat model of endotoxemia proves the close relationship between HSP70 expression, cytokine liberation, and development of apoptosis. The data demonstrate that: 1) Zn2+ is a potent inducer of HSP70 expression; 2) the application of Zn2+ leads to slightly increased cytokine plasma levels; and 3) the manipulation of the heat shock response by Zn2+ significantly increases the survival rate after LD100 endotoxemia. Enhanced survival rate in animals pretreated with Zn2+ may be explained by increased tissue levels of HSP70, a subsequent significantly decreased liberation of the proinflammatory cytokines after LPS challenge, and a significantly decreased rate of apoptosis.

[Stage-oriented antibiotic therapy of peritonitis. Prospective study]. / Stadienorientierte Antibiotikatherapie der Peritonitis. Prospektive Studie.

PATIENTS AND METHODS: In a prospective protocol 25 consecutive patients with diffuse peritonitis were treated in the Surgical Clinic of the RWT-University in Aachen, Germany, from January to December 1995. According to the "Mannheim Peritonitis Score" three different stages were treated with different surgical procedures and a selective antibiotic regimen. Group-A patients with prognostically favorable peritonitis (MPS 0-20) were treated with the so-called standard procedure, group-B patients (MPS: 21-29) with closed postoperative lavage. The antibiotic regimen was cefotaxime (2 x 2 g) and metronidazole (2 x 500 mg) for both group-A and group-B patients. Severe group-C cases (MPS > 29) were treated with the so-called Etappenlavage (multiple reexplorations and intra-operative lavage) and received a combination of three antibiotics (2 x 2 g cefotaxime; 2 x 500 mg metronidazole and 2 x 200 mg ofloxacin). RESULTS: Eight patients belonged to group A, 10 to group B, and 7 to group C. The mortality was 0% (group A), 20% (group B), and 29% (group C), respectively. The actual overall mortality of the whole group was 16% (4/25). The statistically expected mortality was 36%, according to the APACHE-II-Score (P = 0.0982).

Repeat resection of recurrent hepatic metastases--improvement in prognosis?

OBJECTIVE: To find out if resection of recurrent hepatic metastases improves survival. DESIGN: Retrospective study. SETTING: University hospital, Germany. SUBJECTS: 25 patients who had recurrent metastases after radical resection of hepatic metastases from colorectal and other primary carcinomas. INTERVENTIONS: Repeat liver resection with the intention to cure. Limited hepatic resections were preferred if they could be done without loss of radicality. MAIN OUTCOME MEASURES: Operative morbidity and mortality, survival time after second hepatic resection, analysis of possible prognostic factors. RESULTS: Hemihepatectomy was done for 4 patients, and infiltration of the diaphragm led to extended resections in a further 4. Locoregional recurrence of rectal carcinoma together with a solitary pulmonary metastases in another patient were removed simultaneously. The remainder were limited resections. Seventeen procedures were regarded as radical. There were no operative deaths, and five patients developed minor complications. Actuarial survival rates after radical repeat liver resections were 94% after one year, 53% after two years, and 24% after three years. Radicality was the main prognostic factor of survival. CONCLUSIONS: Repeat hepatic resections seem to improve prognosis and are recommended in patients with recurrent metastases confined to the liver.

[Differentiated surgical therapy of diffuse peritonitis--a prospective study]. / Die differenzierte chirurgische Therapie der diffusen Peritonitis--eine prospektive Studie.

PATIENTS AND METHODS: In a prospective protocol 86 consecutive patients with a diffuse peritonitis were treated in the Surgical Clinic of the RWT-University in Aachen (FRG) from January 1992 to June, 1994. According to the "Mannheim Peritonitis-Score" three different stages were treated with different procedures. Stage-I-peritonitis (mild forms, MPS 0-20) was treated with the so-called standard procedure, Stage-II-cases (MPS: 21-29) with the closed postoperative lavage and severe stage-III-cases (MPS > 29) with the so-called "Etappenlavage" (multiple reexplorations and intraoperative lavage). RESULTS: 36 patients showed stage-I-, 29 stage-II-, and 21 stage-III-peritonitis. Mortality was 3% (1/36) in stage-I-, 24% (7/29) in stage-II-, and 33% (7/21) in stage-III-groups. The overall mortality of the whole group was 17% (15/86). The statistically expected mortality was 38% according to the MPS and 33% related to the APACHE-II-Score.

[Surgical treatment of intra-abdominal abscesses]. / Die chirurgische Behandlung intraabdomineller Abszesse.

To define the role of operative treatment of intraabdominal abscesses, we retrospectively reviewed 106 patients, who were operated for intraabdominal abscesses between January 1988 and October 1994. 49 patients had had a primary abscess, 57 patients had an anteceding operation. In both groups appendix and bilio-pancreatic tract were the mostly involved organs. 81 (76,4%) abscesses were single, whereas 17 patients had 2 and 8 patients had 3 synchronous abscesses. All abscesses fulfilled the criteria of complicated abscesses. Successful drainage was achieved in 83%, 17% of cases had to be reoperated or percutaneously drained for recurrence of abscess or abscess related complications. The procedure related morbidity was 37,7% (40/106), half of these were minor complications. 5 patients died, conferring to a mortality of 4,7%. We conclude, that operative drainage plays an important role in the therapeutic regimes of intraabdominal complicated abscesses and can be performed with low morbidity and mortality.

[Benefits and risk of resection of liver metastases in elderly patients]. / Nutzen und Risiko der Resektion von Lebermetastasen beim alten Menschen.

Between 1986 und 1995 we performed 60 hepatic resections in 52 patients aged over 70 years for liver metastases of different primary tumours. The results were comparable regarding morbidity, mortality and long-term prognosis to the group of 176 patients under the age of 70 undergoing a total of 210 hepatic resections for metastases during the same time period. Thus liver resections for metastases can be performed with tolerable risks even in aged patients; postoperative mortality is independent of the patients' age and is due to the extent of resection; the survival rate is mainly influenced by radical resection.

Prevention of postoperative adhesions by single intraperitoneal medication.

Postoperative adhesions account for a significant morbidity after abdominal, gynecological, or cardiac surgery. A large number of compounds have been suggested to prevent such adhesions, but none is generally accepted. We have compared eight different substances that could be beneficial for the prevention of postoperative adhesions in a new standardized rabbit model with measurement of the areas of adhesion. In 10 groups of 20 rabbits an area of abrasion of the serosa of the ileum, the appendix, and the abdominal wall measuring 10,000 mm2 was created by an emery piston during celiotomy. The controls received no medication. The treatment groups received a single intraperitoneal administration of 1 ml per 100 g body wt of normal saline (NaCl), 5 mg taurolidine (T), 0.5 U plasmin/300 U DNase (PD), 2000 IU streptokinase/500 IU streptodornase (SS), 7 mg phosphatidylcholine (PC), 4 mg hyaluronic acid (HA), 7 mg sphingolipid (SL), 7 mg galactolipid (GL), or 0.5 ml tetrachlorodecaoxide (TCDO), respectively. Ten days later the extent of adhesions was quantified by morphometry. The total area of adhesions (+/- SEM) was found to be 1998 +/- 124 mm2 in controls. The application of NaCl reduced the adhesions to 1368 +/- 58 mm2, of T to 1012 +/- 48 mm2, of PD to 673 +/- 33 mm2, of SS to 360 +/- 44 mm2, of PC to 335 +/- 84 mm2, of HA to 328 +/- 76 mm2, of SL to 278 +/- 80 mm2, of GL to 261 +/- 67 mm2, and of TCDO to 240 +/- 45 mm2. The effects of PD, SS, PC, HA, SL, GL, and TCDO were significant in comparison to controls and NaCl. Our experimental data suggest that the two new lipid substances, SL and GL, are the most likely candidates for routine clinical use in the prevention of postsurgical adhesions.

[Prevention and therapy of intra-abdominal adhesions. A survey of 1,200 clinics in Germany]. / Prophylaxe und Therapie intraabdomineller Adhäsionen. Eine Umfrage an 1200 Kliniken in Deutschland.

A survey of 1200 hospitals in Germany was undertaken to estimate the current standards of prevention and treatment of postoperative peritoneal adhesions. The 751 (62.2%) evaluated questionnaires showed a representative distribution according to postal zones and annual laparotomies. The rate of coeliotomies for adhesional bowel obstruction is 2.6%. Starch-powdered gloves are used in 54.2% and washed before operating in 69.3%. Dry swabs and towels are used in 60.7 and 22.5%, respectively. Most of the surgeons suture the peritoneum. Adhesions are divided in patients with respective symptoms but without intestinal obstruction by 32.6% and during laparotomies for non-adhesion-related diseases by 20.4%. Long intestinal tubes and plication procedures are applied by 43.9 and 33.7%, respectively. Medication is administered for routine prophylaxis of adhesion by 6%, for prevention of recurrencies by 17.2%. Although it has been revealed that adjuvant measures for prevention of adhesions are needed, as of today, no regimen has proofed its efficacy and gotten accepted for clinical usage.

[Endoscopic emergency therapy and early elective operation of at risk bleeding types in gastroduodenal ulcer hemorrhage--a prospective study]. / Endoskopische Notfalltherapie und frühelektive Operation risikogefährdeter Blutungstypen bei der gastroduodenalen Ulkusblutung--eine prospektive Studie.

253 consecutive patients with bleeding gastroduodenal ulcers were treated in a prospective protocol from Jan/1986 to Dec/1993. All underwent emergency endoscopy and injection therapy. In ulcers with a high risk of rebleeding (Forrest Ia, Ib, and IIvisible vessel) we performed an early elective operation (n = 126). Operative mortality was 9% (11/126). No patient died after endoscopic treatment, therefore the over-all mortality was 4% (11/253).

[Anastomotic ulcers after duodenopancreatectomy for carcinoma of the head of the pancreas]. / Anastomosenulzera nach Duodenopankreatektomie wegen Pankreaskopfkarzinoms.

Anastomotic ulceration following partial pancreatoduodenectomy carries a substantial risk of complications. More than 50% of patients have episodes of bleeding and up to 20% die as a direct consequence of peptic complications. In a retrospective study of 88 patients, frequency of ulcer was analysed comparing Whipple-Child reconstruction and partial pancreatoduodenectomy with a Roux-Y gastrojejunostomy. Indication was ductal carcinoma of the pancreas in 80 cases and periampullary carcinoma in eight patients. Roux-Y gastrojejunostomy was performed in 53 cases, Billroth-II anastomosis with enteroanastomosis in 35 patients. Perioperative mortality was 7% (n = 6). Nine cases of anastomotic ulceration were verified after Roux-Y gastrojejunostomy (18%). Three out of five Roux patients with a periampullary carcinoma developed ulcers. After Billroth-II reconstruction anastomotic ulceration was found in only one out of 33 cases (3%). Six ulcers presented with bleeding, anastomotic stenosis occurred in two cases. Three ulcer patients with curatively resected periampullary carcinoma were reoperated. After resection of the Roux limb and truncal vagotomy no recurrence was seen during a follow-up period of 19 to 46 months. Roux-Y gastrojejunostomy carries an increased risk of anastomotic ulceration. The lack of inactivation of pepsin by bile acids has to be discussed as an underlying mechanism.

[Surgical therapy of liver metastases. Therapeutic procedures, results and prognostic factors]. / Chirurgische Therapie von Lebermetastasen. Therapieverfahren, Ergebnisse und Prognosefaktoren.

In a period of 7 years, 151 patients were treated by resection and/or regional chemotherapy after liver metastases from various primary tumours. The subgroup of patients with colorectal liver metastases was evaluated separately from the heterogeneous group with any other primaries. Radical resection of colorectal liver metastases was followed by a 5-year survival of 17%. The time from resection of the primary to development of the metastatic lesions was shown by univariate and multivariate analysis to be the most important prognostic factor. Adjuvant regional chemotherapy failed to improve outcome after curative resection of liver metastases. Neither palliative regional chemotherapy in cases of diffuse hepatic metastases nor the combination of palliative resection with regional or systemic chemotherapy significantly prolonged survival.

[Surgical therapy of myasthenia gravis and thymoma]. / Chirurgische Therapie bei Myasthenia gravis und Thymom.

Between 1986 and 1992 eighteen patients underwent transsternal radical thymectomy at the Department of Surgery of the RWTH Aachen. Operation was indicated for myasthenia gravis (n = 14) or suspect of thymoma (n = 4). Patients with myasthenia were preoperatively classified according to Osserman and postoperatively with respect to their clinical status and drug dosages. Patients with thymoma were classified according to Masaoka. After a mean follow-up period of 43.6 months 76.9% of the patients with myasthenia demonstrated a significant improvement. All patients with thymoma were free of recurrence.

Protection of intestinal anastomoses by biodegradable intraluminal bypass tubes under the condition of general peritonitis: an experimental study on the CLP model in rats.

The purpose of this experimental study was to affirm the protective effect of biodegradable tubes for the intraluminal bypass procedure under the adverse condition of general peritonitis. General peritonitis was induced by means of the cecal ligation and puncture (CLP) model in the rat. The leakage rate in the control group (n = 20) without anastomotic protection was 70 percent (14/20). In three therapeutic groups, each consisting of 20 animals, the intestinal anastomoses were protected by an intraluminal bypass tube of different biodegradable biomaterials (collagen-II, BCL-002, and BCL-004). The best results were noted in the collagen-II and BCL-002 groups, where the leakage rates could be reduced to 10 percent. These highly significant results (P = 0.0001) prove the feasibility of biodegradable biomaterials for the intraluminal bypass procedure in the rat, even in cases with underlying peritonitis.

[Pneumatosis cystoides intestinii]. / Pneumatosis cystoides intestinii.

Pneumatosis cystoides intestinalis (PCI), a condition involving submucosal or subserosal gas-containing cysts of the wall of the gastrointestinal tract, is a rare entity. It is mostly diagnosed between the third and fifth decades of life without a clear sexual predominance. Different aetiopathogenetic factors are under discussion, the most probable being a bacteriologic cause (Clostridium perfringens) in combination with minimal leaks in the mucosal barrier. There are no pathognomonic symptoms; the clinical picture ranges from incidental findings to haematochezia. Diagnosis is based on plain abdominal film and X-ray following barium enema. Methods of treatment in symptomatic cases are oxygen and antibiotic (metronidazole) therapies and, in severe cases, resection of the diseased part of the intestine.