Hospitalization, frequency of interventions, and quality of life after endoscopic, surgical, or conservative treatment in patients with chronic pancreatitis.

OBJECTIVE: Patients with chronic pancreatitis usually have a long and debilitating history of disease with frequent hospital admissions, episodes of intractable pain and multiple interventions. The sequences of treatment at initial presentation, endoscopy, surgery, or conservative treatment may affect the time course and admissions needed for disease control, thereby determining quality of life and overall outcome. METHODS: A total of 292 patients with initial endoscopic, surgical, or conservative pharmacological treatment were retrospectively analyzed regarding frequency of interventions, days in hospital, symptom-free intervals, morbidity, and mortality. Quality of life (QoL) at the latest follow-up was measured by two standardized quality of life questionnaires (EORTC C30 and PAN26). RESULTS: Endoscopic treatment was initially performed in 150 (51.4%) patients, whereas 99 (33.9%) underwent surgery and 43 (14.7%) patients were treated conservatively at their initial presentation. Patients who underwent surgery had a significantly shorter time in the hospital (25.3 ± 24.6, 34.4 ± 35.1, 61.1 ± 37.9; P < 0.001), fewer subsequent therapies (0.43 ± 1.0, 2.1 ± 2.4, 3.1 ± 3.0; P ≤ 0.001), and a longer relapse-free interval (P = 0.004) compared with endoscopically treated patients. The overall complication rate was 32% both after surgery and endoscopy. Infectious-related complications occurred more often after surgical treatment (P ≤ 0.001), whereas patients after endoscopic intervention developed acute or chronic pancreatitis or pseudocyst formation (P = 0.023). CONCLUSIONS: Patients who undergo surgery as their initial treatment for chronic pancreatitis require less consecutive interventions, a shorter hospital stay, and have a better quality of life compared with any other treatment. Surgery should therefore be considered early for the treatment of chronic pancreatitis, when endoscopic or conservative treatment fails and patients require further intervention.

[Pancreas. Part II: Tumors]. / Pankreas. Teil II: Tumoren.

Adenocarcinoma is the most common malignant pancreatic tumor, affecting the head in 60-70% of cases. By the time of diagnosis, approximately 80% of tumors are unresectable. Helical CT is very effective in detection and staging of adenocarcinoma, with a sensitivity of 76-92% for detection and an accuracy of 80-90% for staging, but it has limitations in the detection of small cancers (< or =2 cm). Multidetector CT (MDCT) has brought substantial improvements with its inherent 3D imaging capability. Mangafodipir-enhanced MRI is a problem-solving tool in the depiction of small cancers following an equivocal CT imaging result. Gadolinium-enhanced 3D gradient-echo MRI is helpful in the assessment of vascular invasion of cancer and in determining the etiology of cystic lesions. Serous cystadenoma is benign, has a lobulated contour and contains innumerable small cysts of 0.1-2 cm in diameter. Mucinous cystic neoplasms are unilocular or multilocular (fewer than six cysts), and the cyst diameter exceeds 2 cm. The presence of solid nodular components should alert the radiologist to suspect cystadenocarcinoma. Neuroendocrine tumors are mostly hypervascular. Diagnosis of insulinoma is a challenge: they are <2 cm in 90% of cases and mostly hypervascular at CT or MRI. A combination of contrast-enhanced MDCT, MRI, endosonography, and/or somatostatin receptor scintigraphy is used to detect these small tumors. This review summarizes the imaging features of the most common pancreatic tumors and discusses the limitations of CT, MRI and endosonography.

[Abdominal dressing -- a new standard in therapy of the open abdomen following secondary peritonitis?]. / Abdominal Dressing -- ein neuer Standard in der Behandlung des offenen Abdomens infolge sekundärer Peritonitis?

INTRODUCTION: The management of patients with a laparostoma due to peritonitis is a challenge for every surgeon and intensivist. The goal of this study was to compare the different treatment strategies for the open abdomen: Abdominal Dressing (AD), the classic V.A.C. therapy (CV) and conventional open therapy (CT). METHODS: Between 2001 and 2005 we identified 62 patients in 4 surgical departments in Austria who had to be treated with a laparostoma due to peritonitis. 27 patients were conventionally treated, 16 with the Classic V.A.C. therapy and 19 patients with V.A.C. abdominal dressing. RESULTS: The mortality was 3/16 (14 %) in the AD group vs. 4/12 (21 %) patients in the CV group and 18/9 (59 %) in conventional therapy. There was no significant difference for survivors in the length of ICU stay: 26.6 +/- 23.0 days in the CT group, 34.6 +/- 30.2 days in the CV group and 38.9 +/- 27.2 days in the AD group. Apache II Score and Mannheimer Peritonitis Score showed no difference between the groups. CONCLUSION: We found a reduction of mortality in the V.A.C. Abdominal Dressing group by approximately 40 % (AD: 14 %, CT: 59 %). Although we could identify a difference in age in our retrospective study we believe that V.A.C. Abdominal Dressing is the important factor for the different clinical outcome. These first results indicate the need for further prospective evaluation of the V.A.C. Abdominal Dressing therapy, to prove if a new standard in the therapy of the open abdomen is created.

["Abdominal dressing" - a new method of treatment for open abdomen following secondary peritonitis]. / "Abdominal Dressing" - Eine neue Methode in der Behandlung des offenen Abdomens bei der sekundären Peritonitis.

INTRODUCTION: Treatment of open abdomen following secondary peritonitis is a challenge for surgery and intensive care units (ICU). The aim of this study was to compare three different concurrent treatment strategies. METHODS: Patients suffering an open abdomen following surgery for secondary peritonitis at the Department of General Surgery from 01/01 to 12/03 were investigated. Factor studied: duration of open abdomen, incidence of multi-organ failure, need for surgical revisions, length of stay (LOS) in ICU, nursing requirements (change of dressing/day), survival and integrity of abdominal wall after discharge. Treatment strategies included: open packing (OP), classic vacuum assisted (V.A.C.(R))-therapy with silicone net protection for the intestine (CV) and V.A.C.(R)-therapy with "abdominal dressing" a newly developed meshed polyvinyl wrap (AD). RESULTS: 21 patients were studied: 5 patients were treated with OP, 8 patients with CV and 8 patients with AD. Mean LOS was 65 (OP) vs. 53 (CV) vs. 42 (AD) days (NS), peritonitis related death was 3 (OP) vs. 1 (CV) vs. 0 (AD) (p < 0.05 Chisquare test). Median nursing effort was 4 dressings/day (OP), 0.5 (CV) and 0.5 (AD) (p < 0.005 OP vs CV, AD Kruskal-Wallis test). CONCLUSION: The "abdominal dressing"-therapy seems to be a more efficient treatment option in patients suffering from open abdomen following secondary peritonitis. A trend towards shorter ICU-LOS, lower mortality rates and reduced nursing requirements support our hypothesis.

Oral feeding with glutamine prevents lymphocyte and glutathione depletion of Peyer's patches in endotoxemic mice.

OBJECTIVE: To determine the effect of oral glutamine feeding on lymphocyte subpopulations and glutathione metabolism in Peyer's patches (PPs) of healthy and endotoxemic mice. SUMMARY BACKGROUND DATA: Recent data indicate that nutrients both maintain nitrogen and energy balances and modulate cell and organ function. In particular, glutamine has an impact on gut and immune function. This is of special importance in the perioperative phase. METHODS: Female Balb/c mice were fed a glutamine-enriched diet or a control diet for 10 days. On day 7 25 microg lipopolysaccharide (LPS) or saline was injected. On day 3 after the challenge, mice were killed, total cell yield was determined, and lymphocyte subpopulations (total T cells, CD4+, CD8+ cells, and B cells) were analyzed by flow cytometry. One experimental group was treated with buthionine sulfoximine, a specific inhibitor of glutathione synthesis. The glutathione content in PPs was measured by high-performance liquid chromatography. RESULTS: Glutamine administration led to a significant increase in total cell yield, including T and B cells, in PPs. The LPS-induced reduction of T cells (-45%) and of B cells (-30%) was significantly lower in glutamine-treated mice. Endotoxemia caused a 42% decrease of glutathione in control animals, but not in glutamine-treated animals. As with LPS, buthionine sulfoximine also lowered lymphocyte numbers and glutathione content of the PPs. CONCLUSIONS: Administration of glutamine prevents LPS-stimulated lymphocyte atrophy in PPs, possibly by increasing the glutathione content in the PPs. Therefore, oral glutamine supply seems to be a suitable approach for improving intestinal immunity in immunocompromised patients.

Postoperative glycyl-glutamine infusion reduces immunosuppression: partial prevention of the surgery induced decrease in HLA-DR expression on monocytes.

BACKGROUND AND AIMS: Surgery, trauma and inflammation reduce HLA-DR expression on monocytes, which is associated with an increased susceptibility to infection and sepsis. Furthermore, surgery decreases plasma glutamine (GLN) levels. The expression of HLA-DR on human monocytes in vitro is dependent on the concentration of GLN in the culture medium. We therefore hypothesized that postoperative infusions of glutamine-dipeptides would prevent the decreased HLA-DR expression on monocytes. METHODS: Thirty patients undergoing major abdominal surgery were randomly allocated to receive either 1500 ml Vamin (control) or an isonitrogenic formulation containing Vamin and 500 ml glycyl-glutamine (35 g GLN; 0.5g/kg BW) (GLY-GLN), or Vamin and 500 ml alanyl-glutamine (35 g GLN; 0.5 g/kg BW) (ALA-GLN) as a continuous infusion over 48 h post-operatively. Immediately and 48 h after surgery blood samples were collected to determine HLA-DR expression on monocytes by flow cytometry. RESULTS: The groups were comparable with respect to age, gender distribution and operation time. In patients receiving GLY-GLN mean HLA-DR expression on monocytes at 48 h was significantly better preserved than in controls (65.0 %+/-7 % vs 42.5 %+/-4 %;P<0.05), whereas HLA-DR expression on monocytes in patients receiving ALA-GLN was not significantly different. CONCLUSION: This is the first study comparing the dipeptides GLY-GLN and ALA-GLN in the postoperative setting. The GLY-GLN induced preservation of HLA-DR on monocytes following surgery may prevent infectious complications in these patients.

Severe acute pancreatitis causes alterations in HLA-DR and CD14 expression on peripheral blood monocytes independently of surgical treatment.

OBJECTIVE: To find out if the severity of acute pancreatitis or the surgical treatment of severe acute pancreatitis influences HLA-DR and CD14 expression on peripheral blood monocytes. DESIGN: Prospective open study. SETTING: University hospital, Austria. SUBJECTS: 9 consecutive patients with severe acute pancreatitis in need of operative treatment, 5 patients with mild acute pancreatitis, and 7 healthy volunteers. INTERVENTIONS: Samples of 5 ml blood were taken daily into endotoxin free tubes at same time points. Surgical treatment for severe acute pancreatitis consisted of blunt necrosectomy, operative lavage, laparostomy, and open drainage. MAIN OUTCOME MEASURES: Correlation between HLA-DR and CD14 expression on peripheral blood monocytes on the one hand and the severity of acute pancreatitis and operative treatment of severe acute pancreatitis, on the other. RESULTS: In patients with severe acute pancreatitis expression of HLA-DR and CD14 was significantly downregulated both before and after operation (p < 0.0001; ANOVA), compared with patients with mild acute pancreatitis or healthy controls. However the expression of the two cell surface markers was not affected either by the first operation, or by the reoperations. CONCLUSION: These findings suggest that in acute pancreatitis the expression of cell surface markers on peripheral blood monocytes is related to the severity of disease but is not influenced by operative treatment.

Catecholamines up-regulate lipopolysaccharide-induced IL-6 production in human microvascular endothelial cells.

The catecholamine-mediated modulation of the cytokine network has primarily been demonstrated for leukocytes. Whereas catecholamines decrease the LPS-induced production of IL-6 by leukocytes, serum levels of IL-6 are dramatically increased by the catecholamine epinephrine in animal endotoxemia models. We now demonstrate that epinephrine as well as norepinephrine can induce IL-6 in an endothelial cell line (HMEC-1). Furthermore, these catecholamines could even potentiate the LPS-induced IL-6 protein production. The synergistic effect of catecholamines and LPS could be reproduced in primary human skin microvascular endothelial cells. The catecholamine-induced IL-6 stimulation is based on increased IL-6 mRNA levels. RNA stability assays revealed that this regulation is not a result of enhanced RNA stability and therefore is most likely due to an increased transcription. Treatment with cycloheximide indicated that new protein synthesis is not necessary for this transcriptional up-regulation of IL-6 mRNA. Preincubation with alpha and beta receptor antagonists showed that the effect is mediated by beta(1)- and beta(2)-adrenergic receptors. Thus, endothelial cells might be a possible source of increased IL-6 production observed in situations such as stress or septic shock, in which catecholamines are elevated due to endogenous production or exogenous application.

Attenuation of catecholamine-induced immunosuppression in whole blood from patients with sepsis.

Studies performed on healthy volunteers have revealed that catecholamines down-regulate the lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF)alpha, interleukin (IL)-6, and IL-1beta. We extended this observation and show that this effect is based on changes in the mRNA concentration of these cytokines. Catecholamines are increased in severe sepsis due to endogenous production and have to be administered exogenously when the disease has proceeded to the state of prolonged hypotension. We here investigated whether the immunomodulating effect of catecholamines could also be demonstrated in the blood of patients with prolonged severe sepsis and of those in prolonged septic shock. Blood was stimulated ex vivo with LPS in the presence and absence of epinephrine and the cytokine protein concentration was determined. In blood of healthy volunteers, epinephrine reduced the LPS-stimulated synthesis of TNFalpha by 62.5% (P< 0.0001), of IL-6 by 39% (P< 0.0001), and of IL-1beta by 40% (P= 0.015), and increased the LPS-stimulated IL-10 production by 77.8% (P < 0.0001). Correspondingly, in blood of patients with prolonged severe sepsis, TNFalpha was reduced by 67.2% (P < 0.0001) and IL-6 was reduced by 32.9% (P < 0.0001); IL-1beta and IL-10 were not modulated by catecholamines in these patients. In blood samples of patients in prolonged septic shock, epinephrine did not modulate cytokine levels of IL-6 and IL-10, and decreased TNFalpha only by 36.4% (P < 0.0001). Interestingly, epinephrine suppressed the IL-1beta production by 73% (P < 0.0001) in blood of patients in prolonged septic shock, which was twice as much as in blood samples of healthy volunteers. The altered response of septic blood to catecholamines might be due to an altered reactivity of leukocytes in the prolonged disease although an additional role of preexisting catecholamines cannot be completely excluded.

Outcomes of surgical, percutaneous endoscopic, and percutaneous radiologic gastrostomies.

OBJECTIVES: To evaluate and compare outcomes and complications in patients having undergone gastrostomy by surgical (SG), percutaneous endoscopic (PEG), or percutaneous radiological (PRG) procedure. DESIGN: Retrospective analysis. SETTING: University-based tertiary care center. PATIENTS: Of 82 patients who met inclusion criteria, 14 patients (median age, 40 years) received a surgical tube placement (SG), in 24 patients (median age, 55 years) a PEG procedure was performed, and in 44 patients (median age, 57 years) the tube was placed under fluoroscopic guidance (PRG). Indications for gastrostomy were similar in all groups, representing mainly cancer of the oropharyngeal, head and neck region (51 [61%]) as well as the upper gastrointestinal tract (6 [8%]), neurological disorders (15 [18%]), and others (10 [13%]). MAIN OUTCOME MEASURES: Catheter function rates, major and minor procedure-related complications, and survival. RESULTS: Median follow-up was 17.2 months. Ten patients (71%) died in the SG group 7 to 855 days (median, 67 days) after the procedure, 7 patients (29%) died 5 to 263 days (median, 103 days) after PEG placement, and 30 patients (68%) died within 3 to 621 days (median, 112 days) after PRG, of their underlying disease or disease-related complications; 1 procedure-related death occurred 6 days after radiological tube placement. We observed a rate of minor complications of 43% (6 patients), 33% (8), and 36% (16) and a major complication rate of 14% (2 patients), 17% (4), and 11% (5) in the SG, PEG, and PRG groups, respectively. Tube function rates at 1 year were 67% (9 patients) and 68% (20) in the SG and PEG groups, respectively, and 10% lower (39) in the PRG group, although the difference was not statistically significant. CONCLUSIONS: There is no major difference between SG, PEG, and PRG concerning procedure-related complications. Tube function tends to be inferior after radiological tube placement.

Early effects of catecholamine therapy on mucosal integrity, intestinal blood flow, and oxygen metabolism in porcine endotoxin shock.

OBJECTIVE: To determine the early effects of therapy of endotoxin (ET) shock with epinephrine, norepinephrine, or dopexamine on splanchnic circulation, oxygen metabolism, sigmoid mucosal pHi, bacterial translocation, and morphologic integrity of the ileal, colonic, and sigmoid mucosa. SUMMARY BACKGROUND DATA: Conflicting concepts exist concerning the catecholamine therapy of septic shock, but little is known about the effects of catecholamine treatment on splanchnic circulation and mucosal integrity. METHODS: ET shock was induced in pigs by ET infusion over 30 minutes, and animals were studied for 4 hours. All animals were resuscitated with fluid. To mimic the treatment of septic shock in humans, mean arterial pressure was maintained in two groups at >70 mm Hg with the administration of epinephrine or norepinephrine. A third group of animals received dopexamine at 7 microg/kg per minute. Systemic and splanchnic blood flow and oxygen metabolism were studied, sigmoid colon mucosal pHi was obtained tonometrically, and bacterial translocation was determined by culture of portal venous blood, mesenteric lymph nodes, liver, spleen, and lung specimens. Histologic sections of ileal, colonic, and sigmoid mucosa were morphometrically examined for therapy effects. RESULTS: All investigated catecholamines increased cardiac output and systemic oxygen delivery, whereas intestinal blood flow and oxygen delivery remained unchanged. Sigmoid mucosal pHi decreased in all study animals, but the decrease was most pronounced in the epinephrine group. Pigs receiving epinephrine also showed >40% damage of the mucosa of the ileum and colon, whereas animals receiving ET alone, norepinephrine, or dopexamine showed only moderate lesions with signs of restitution. No animal showed bacterial translocation. CONCLUSIONS: Systemic hemodynamics and oxygen metabolism data do not reflect intestinal perfusion. Norepinephrine or dopexamine administration in ET shock causes no additional impairment of intestinal integrity. Epinephrine therapy, in contrast, is associated with a significant reduction of mucosal pHi and considerable early mucosal damage. Its application in septic shock is hazardous.

Receptor and non-receptor mediated formation of superoxide anion and hydrogen peroxide in neutrophils of intensive care patients.

Generation of reactive oxygen intermediates (ROI) has been implicated in tissue damage in a variety of disease states including sepsis and trauma. On the other hand, generation of ROI in polymorphonuclear granulocytes (PMN) presents a crucial element in the defence of the host against invading microorganisms. In the present study we investigated the generation of superoxide anions (O2-) and hydrogen peroxide (H2O2) by neutrophils (PMN)5 of 17 critically ill patients treated at a intensive care unit (ICU) after polytrauma (n = 6), heart operation (n = 6) or during septic shock (n = 5) using flow cytometry. O2- production of PMN from ICU patients was significantly lower (p < 0.01) than that in healthy volunteers (HV) during non-receptor mediated stimulation with phorbol-myristate-acetate (PMA) but higher (p < 0.001) during receptor mediated stimulation with formylmethionine-leucine-phenylalanine (FMLP). H2O2 generation of PMN from ICU patients was increased after stimulation with FMLP (p < 0.01) and remained unchanged after stimulation with PMA. Patients in septic shock had lower O2(-)-generation of PMN than did injured patients and patients after heart operations. We conclude that receptor mediated formation of O2- and H2O2 is stimulated in ICU patients. However, in patients in septic shock O2(-)-generation decreases, which potentially might contribute to the immunoparalysis present in septic shock.

Does reoperation for abdominal sepsis enhance the inflammatory host response?

OBJECTIVE: To determine the effect of reoperation for severe abdominal sepsis on the course of proinflammatory mediators and hemodynamic factors. DESIGN: Inception cohort. SETTING: A university hospital and a secondary care hospital. PATIENTS AND METHODS: Fifteen patients suffering from severe peritonitis due to intestinal perforation or infected necrotizing pancreatitis were studied following 19 subsequent operations. Plasma samples were obtained immediately before and after reoperation, as well as at 1, 3, 6, 12, and 24 hours after operation to determine endotoxin, tumor necrosis factor alpha, and interleukin-6 levels. Clinical factors and therapeutic support were recorded at the corresponding times. MAIN OUTCOME MEASURES: Postoperative hemodynamic instability as defined by changes of the mean arterial pressure, pulmonary capillary wedge pressure, and vasopressor support. Courses of proinflammatory mediators were correlated to the hemodynamic findings. RESULTS: Mean arterial pressure decreased from 94 mm Hg postoperatively to 80 mm Hg at 3 hours (P = .006) and 81 mm Hg at 6 hours postoperatively (P = .005). Pulmonary capillary wedge pressure dropped from 14 mm Hg postoperatively to 12 mm Hg at 1 hour (P = .05). Vasopressor support significantly increased from 1 to 6 hours postoperatively (P = .02). Neither endotoxin nor tumor necrosis factor alpha levels showed significant changes in the postoperative course. Interleukin-6 levels continously increased from 586 pg/mL preoperatively to 910 pg/mL at 1 hour (P = .02) and 931 pg/mL at 3 hours postoperatively (P = .04). Overall interleukin-6 levels (R = -0.38, P = .003) and especially early postoperative interleukin-6 levels inversely correlated with postoperative mean arterial pressure. CONCLUSIONS: Reoperation for abdominal sepsis frequently causes substantial hypotension, and is, thus, potentially harmful to the patient. Reoperative trauma may induce an early postoperative increase in interleukin-6 levels. Because this increase occurs before the development of hypotension, a relationship between the kinetics of this cytokine and the observed hemodynamic instability may be present.

[Revision of diffuse peritonitis: planned versus on demand]. / Revision bei diffuser Peritonitis: geplant v. on-demand.

Planned and "on-demand' reoperations are well-established concepts in the management of severe diffuse peritonitis. Both concepts were applied at our surgical department and reviewed with regard to specific complications and lethality. In the period between 1 January 1989 and 31 May 1994, 62 patients with the diagnosis of diffuse peritonitis underwent operative treatment at our surgical department. The mean age of the 29 female and 33 male patients was 58.2 years (range 17-93 years). The origin of peritonitis was the stomach in 8.1%, duodenum in 16.1%, small intestine in 12.9%, large intestine in 41.9% and the pancreas in 16.1%. Among these 62 patients, 15 were reoperated upon according to plan and 47 were reoperated upon on demand. The intraoperatively gained Mannheim peritonitis index and the Apache II score were similar in both groups. The average number of reoperations was five in the group of planned revisions and three in the group of on-demand revisions. Also lethality was similar in both groups. Regarding lethality, only the age of the patient (P < 0.03) and the preoperative Apache II score (P < 0.01) reached statistical significance. As expected, eradication of the infectious source was the precondition of survival regardless of the type of reoperation. Regarding our results, we conclude that planned or on-demand reoperations lead to similar results in the treatment of diffuse peritonitis. The crucial point for success is that elimination of the infection source take place as soon as possible.

Necrosectomy and laparostomy--a combined therapeutic concept in acute necrotising pancreatitis.

OBJECTIVE: To present our experience with laparostomy and necrosectomy in the treatment of acute necrotising pancreatitis, and to show how refinements in our treatment regimen improved mortality over the years despite no reduction in the severity of the disease. DESIGN: Retrospective study. SETTING: University hospital, Austria. SUBJECTS: 125 patients treated by laparostomy/necrosectomy with repeated revisions during the period January 1983 to December 1991. INTERVENTIONS: Laparostomy, blunt necrosectomy, operative lavage, and open drainage. MAIN OUTCOME MEASURES: Mortality and morbidity. RESULTS: The severity of disease was assessed by the APACHE II score (median 15, range 4-30). In 106 of the 125 patients (85%) the necrotic pancreatic tissue was infected. Patients were operated on if they deteriorated clinically or if organ failure was suspected. A change in the protocol from revisions on demand (1983/4) to planned re-exploration at 48 hour intervals (1985/8) was associated with a reduction in mortality from 53% (16/30) to 28% (20/72). This was further reduced in 1989/91 to 17% (4/23) when a protocol of revisions planned for individual patients was introduced (p = 0.02). The incidence of gastrointestinal fistulas during the three periods was 6/30 (20%); 24/72 (33%); and 1/23 (4%); (p = 0.022), whereas that of intraabdominal bleeding remained much the same (7/23, 23%; 13/72, 18%; and 4/23, 17%; p = 0.56). The median (range) APACHE II scores for the three periods were 12 (4-27), 15 (5-30), and 14 (4-25). CONCLUSION: By continual revision of our protocol, together with accompanying improvements in intensive care, our mortality decreased significantly during the nine year period.

Tumour necrosis factor-alpha and interleukin-6: early indicators of bacterial infection after human orthotopic liver transplantation.

OBJECTIVE: To see if it was possible to predict the development of infection after liver transplantation from concentrations of endotoxin, tumour necrosis factor-alpha (TNF-alpha), or interleukin-6 (IL-6) in plasma. DESIGN: Prospective open study. SETTING: University hospital, Austria. SUBJECTS: 46 Consecutive patients who underwent liver transplantation for end stage liver disease, 1989-90. INTERVENTIONS: Samples of 4 ml blood were taken in endotoxin free tubes, and of 10 ml into heparinised tubes at the beginning of the operation, during hepatectomy, at the beginning and end of the anhepatic phase, 10 minutes after reperfusion, and at the end of the operation. MAIN OUTCOME MEASURES: Correlation between development of infections postoperatively and operative release of endotoxin, TNF-alpha, and IL-6. RESULTS: There was no correlation between development of postoperative infections and operative concentrations of endotoxin, and of TNF-alpha and IL-6 up to the end of the anhepatic phase. There was, however, a sixfold increase in TNF-alpha and IL-6 concentrations between the end of the anhepatic phase and the end of the operation in patients who subsequently developed infections (p = 0.01). CONCLUSION: The increase in the concentrations of these two cytokines in the blood after reperfusion of the transplanted liver seems to predict the development of subsequent bacterial infection.

The value of obturator canal bypass. A review.

OBJECTIVE: To review the value of obturator canal bypass with respect to long-term results. DESIGN: Case series and literature review. SETTING: University of Vienna Medical School in Austria. PATIENTS/METHODS: Personal experience with 34 consecutive patients and 125 cases published since 1982 with respect to patient data, patency, and survival are compared and jointly analyzed retrospectively. INTERVENTIONS: Patients received obturator canal bypass for lesions of the pelvic or common femoral vessels precluding orthotopic reconstruction. MAIN OUTCOME MEASURES: The rates of patient survival, limb salvage, and graft patency were analyzed. RESULTS: The postoperative mortality rate in the present series was 14.7%. The limb salvage rate after 5 years was 76.5%. One- and 5-year secondary patency rates were 75.3% and 54.9%, respectively. All grafts in patients without atherosclerosis were patent at a median of 34 months. For 57 cases documented in the literature, 1- and 5-year patency rates were 70.8% and 59.7%, respectively. Combined analysis of 90 obturator canal bypasses revealed rates of 72.7% and 56.9% of patent grafts at 1- and 5-years, respectively. CONCLUSIONS: The use of obturator canal bypass is recommended in deep groin infections and especially in patients with lesions of the pelvic vessels due to other occlusive vascular disease.

Transhepatic metabolism of TNF-alpha, IL-6, and endotoxin in the early hepatic reperfusion period after human liver transplantation.

Several studies have shown that the postoperative course of cytokines such as TNF-alpha or IL-6 is predictive of rejection and infection after human orthotopic liver transplantation (OLT). The aim of this prospective clinical trial was to evaluate the impact of transhepatic metabolism of endotoxin (ET), tumor necrosis-factor-alpha (TNF-alpha), and interleukin-6 (IL-6) after hepatic ischemia/reperfusion on the postoperative graft function. In 13 consecutive elective adult OLT patients with primary grafts, we determined concentrations of ET, TNF-alpha, and IL-6 in the radial artery, portal vein, and right hepatic vein at 1, 4, 7, 10, and 13 min after reperfusion. Of the 13 patients, four had ET levels below the detection limit (< 10 ng/L), and one patient had extremely high ET concentrations (151 ng/L in the hepatic vein). In the remaining patients the mean ET levels were 26 +/- 14, 26 +/- 15, and 24 +/- 14 ng/L in the portal vein, hepatic vein, and in the radial artery, respectively. These values indicate that in patients with a moderately elevated ET level, no transhepatic concentration differences of ET exist. However, in the patient with severe endotoxemia, the liver was apparently an ET-producing organ (HV-P: 29 +/- 13 ng/L). TNF-alpha levels were not measurable in four patients, and varied between 15 and 72 pg/ml (portal vein) in the remaining patients. The transhepatic concentration differences (HV-P and HV-A, respectively) of patients with PNF or dysfunction were higher than in those with "good" or "excellent" graft function (HV-P: 160 +/- 122 pg/ml vs. 7.3 +/- 9.7 pg/ml; P < 0.01 and HV-A: 137 +/- 101 pg/ml vs. 3.9 +/- 12 pg/ml; P < 0.01, respectively). Arterial IL-6 levels were below 88 pg/ml (mean value: 31 +/- 20 pg/ml) at the beginning of the operation, and increased considerably in three patients during the anhepatic phase and after reperfusion. No clinical correlation was found with the transhepatic concentration differences of IL-6. We conclude that in OLT patients without infection no transhepatic ET exchange was documented. However, a stimulated hepatic TNF-alpha release seems to be predictive of the beginning of liver dysfunction.

Adjuvant intraperitoneal cisplatin chemotherapy does not improve long-term survival after surgery for advanced gastric cancer.

PURPOSE: The long-term survival probability of patients who undergo surgery for stage 3 and 4 gastric cancer is poor, predominantly due to metastatic spread of the tumor. Depending on the type of tumor histology, the pathway of metastases is mainly peritoneal or hepatic dissemination. Interruption of this mechanism may be possible by intraperitoneal chemotherapy (IPT). PATIENTS AND METHODS: In a prospective randomized trial of 67 patients undergoing surgery for stage 3 and 4 gastric cancer, 33 patients underwent adjuvant postoperative IPT with cisplatin, while 34 control subjects remained untreated. RESULTS: Patients in the treatment group received a median of four IPT perfusions. Apart from frequent nausea, no adverse reactions or complications were noted. The median disease-free survival durations were 12.7 months and 9.7 months in treated patients and controls, respectively (P = .8). After a median follow-up duration of 72 months, 54 patients (80%) had died of primary disease or related complications. The median survival duration for IPT patients was 17.3 months as compared with 16.0 months for controls (P = .6). Autopsies were performed on 12 (18%) of 54 patients who died, and showed tumor spread to the peritoneal cavity and/or to the liver, irrespective of the application of IPT. CONCLUSION: IPT with cisplatin monotherapy does not improve survival probability after surgery for stage 3 and 4 gastric cancer. The reasons for ineffectiveness of IPT may be the choice of an unsuitable chemotherapeutic agent, an inefficient modus of application, or a lack of sufficient drug penetration into the serosa or peritoneal metastasis.