Early effect of hepatic artery TNF-alpha infusion on systemic hemodynamics and inflammation: a dose-response study in pigs.

PURPOSE: Therapy of unresectable hepatic metastases may include tumor necrosis factor (TNF)-alpha treatment. Because of its serious systemic side effects, TNF-alpha is only used in isolated hepatic perfusion. This, however, is a technically demanding procedure with a substantial mortality rate. The infusion of TNF-alpha via the hepatic artery without hepatic isolation would be less invasive. Systemic side effects, however, have not been studied yet. Therefore, we evaluated in pigs the effects of TNF-alpha hepatic artery infusion (HAI) on systemic hemodynamics, inflammation, and organ injury. METHODS: Animals were randomized in three groups. In group 1, HAI was performed with 0.9% NaCl (n = 6). In group 2, 20 microg/kg TNF-alpha (n = 6), and in group 3, 40 microg/kg TNF-alpha (n = 6) were added. HAI was performed over 15 min, followed by 120 min of observation. Finally, 250 ml hydroxyethylstarch (HAES; 6%) was administered for resuscitation and hemodynamics were analyzed for another 30 min. RESULTS: Hepatic artery TNF-alpha infusion did not cause complications such as bleeding, cardiac depression, pulmonary dysfunction, or SIRS. TNF-alpha induced a 30% decrease of MAP and systemic vascular resistance, as well as a rise in heart rate and endexspiratory pCO(2). TNF-alpha also moderately (10-20%) lowered the cardiac preload and induced a metabolic acidosis, which, however, could easily be controlled. TNF-alpha HAI did not induce liver toxicity, and all hemodynamic changes normalized either spontaneously within the 120-min observation period, or, at least, after HAES resuscitation. CONCLUSIONS: TNF-alpha-based HAI, which may represent a minimally invasive alternative to isolated hepatic perfusion, can be performed without early systemic hemodynamic complications.

Prostheto-ureteral fistula: a rare complication after aortic graft surgery.

Prostheto-ureteral fistula after aortic graft surgery is a potentially life-threatening, rare pathology. We report the successful treatment of a prostheto-ureteral fistula that caused hematuria with hemorrhagic shock in two patients by explantation of aortic prosthetic grafts and implantation of a silver-bonded prosthetic graft (Intergard S, Intervascular). These cases show that this surgical procedure is effective, and that straightforward diagnostic procedures are necessary to initiate correct therapeutic approach without delay. Various different possible risk factors for the formation of a prostheto-ureteral fistula are also discussed.

Hirudin-based anticoagulant strategy during isolated limb perfusion in a patient with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy. The administration of heparin in patients with HIT causes platelet aggregation, thromboembolism and thrombocytopenia. Therefore, an alternative anticoagulant is recommended in these patients. We describe the use of recombinant hirudin (r-hirudin; Refludan, Pharmion Germany GmbH, Hamburg, Germany) as an anticoagulant in a patient with HIT requiring isolated limb perfusion (ILP) for in-transit metastases of malignant melanoma of the leg; r-hirudin was used in both the extracorporeal and systemic circuits. The coagulation monitoring included the activated partial thromboplastin time (aPTT) and ecarin clotting time (ECT). There were no thrombotic or bleeding complications. The dosage regimen and the strategy of monitoring of the anticoagulant activity are described. It can be concluded that ILP in patients with suspected or confirmed HIT can be safely performed with the use of r-hirudin in both the extracorporeal and systemic circuits. Monitoring of the anticoagulation effect is necessary and should preferably be performed using ECT.

Low toxic neoadjuvant cisplatin, 5-fluorouracil and folinic acid in locally advanced gastric cancer yields high R-0 resection rate.

PURPOSE: Neoadjuvant chemotherapy in locally advanced gastric cancer is effective, but is often associated with severe side effects, including fatal outcome. This study evaluates a combination of cisplatin, folinic acid and 5-fluorouracil (PLF) in terms of efficacy (R-0 resection rate) and toxicity. METHODS: Twenty-five patients with locally advanced gastric cancer who after extensive staging were deemed not suitable for curative resection underwent neoadjuvant chemotherapy. Three or four cycles of cisplatin (50 mg/m(2) days 1 and 15), folinic acid (200 mg/m(2) days 1, 8, 15 and 22), and 5-fluorouracil (2,000 mg/m(2 ) days 1, 8, 15 and 22) were administered. Cases with progressive disease were taken off the study. Two weeks after finishing chemotherapy resection was performed and all patients were enrolled in a structured follow-up. RESULTS: Of the patients, 22/25 finished chemotherapy and 20 of those underwent laparotomy. In 13/25 patients (52%) a R-0 resection and in three cases a R-1 resection were achieved. Four patients stayed irresectable. During 76 completed cycles of chemotherapy we observed five cases of WHO grade-III toxicity and no grade-IV toxicity. CONCLUSIONS: The presented PLF protocol yields R-0 resection rates comparable to protocols like EAP (etoposide, adriamycin, platinum), but with a better safety profile allowing administration in an outpatient setting. Our study supports PLF as a reference neoadjuvant treatment for gastric cancer even outside of clinical studies.

Boerhaave's syndrome: primary repair vs. esophageal resection--case reports and meta-analysis of the literature.

Boerhaave's syndrome is a life-threatening disease with a high mortality. With regard to the heterogeneity of treatment strategies, no comparative studies exist and recommendations remain controversial. Seventeen cases of Boerhaave's syndrome operated on between 1989 and 2000 at our hospital were reviewed retrospectively to compare the time period between perforation and diagnosis, and the morbidity and mortality among the different treatment options. In addition, we conducted a meta-analysis of the literature including all series containing five or more patients and compared the findings with our own data. Our patients with a perforation history of less than 12 hours showed significantly fewer signs of sepsis compared to patients with a history of more than 12 hours. In a comparison of patients with primary repair vs. patients treated with esophageal resection or an exclusion operation, no differences were found. In the literature, patients with a long period of perforation (more than 24 hours) were treated more often with an esophageal resection than patients with primary repair. In cases of Boerhaave's syndrome, primary suturing of the esophageal perforation should be reserved only for those patients presenting within 12 hours after perforation. In all other cases, depending on the extent of the tissue damage, a two-stage esophageal resection with cervical esophagostomy and gastrostomy is recommended as the safest treatment.

Thoracotomy procedures effect cytokine levels after thoracoabdominal esophagectomy.

Pulmonary complications together with surgical complications are the most frequent causes for morbidity and mortality after thoracoabdominal esophagectomy. The con-tinuous improvement of surgical techniques has led to a decrease in surgical complications, whereas up to 30% of the patients develop postoperative pulmonary complications such as acute lung injury (ALI) or even the more severe acute respiratory distress syndrome (ARDS), which are characterized by an acute inflammation in the lung parenchyma and the airspace. Evidence from several studies indicates that a complex network of inflammatory cytokines and mediators play a key role in mediation, amplification, and perpetuation of the process of lung injury and that the thoracotomy itself is a risk factor for developing ALI or ARDS. In this trial, the cytokine levels of IL6, IL8 and IL10 were measured and compared in 30 patients who had undergone an extended radical thoracoabdominal esophagectomy for esophageal cancer, via anterolateral thoracotomy (n=17) or posterolateral thoracotomy (n=13). Patients of both groups were similar in terms of age, sex and preoperative pulmonary function as well as in the anesthetic procedures they have undergone. All patients displayed significantly increased serum levels of IL6 and IL8 after thoracoabdominal esophagectomy. However, patients who were subjected to an anterolateral thoracotomy were reported with significantly higher serum levels of IL6 and IL8 compared to patients who had received a posterolateral thoracotomy. Thus, the choice of the thoracotomy method during the thoracoabdominal esophagectomy and the resultant cytokine levels may contribute to the occurrence of postoperative pulmonary complications and may have an impact on the extent and severity of the surgical stress.

Transureteroureterostomy allows renal sparing radical resection of advanced malignancies with rectosigmoid invasion.

BACKGROUND: In case of advanced colorectal cancer or other malignancies with pelvic involvement, tumor invasion of the ureter may afford partial ureteral resection for curative multivisceral resection. One preferable approach for the primary reconstruction of the urinary tract to preserve the ipsilateral kidney and maintain normal urinary function is transureteroureterostomy, i.e. termino-lateral anastomosis of both ureters. MATERIALS AND METHODS: Between June 2001 and August 2004, 15 multivisceral en bloc resections including a distal tumor-infiltrated ureteral segment were performed. Reconstruction was achieved by transureteroureterostomy with or without additional insertion of double J stents. Clinical outcome and especially complications of the urinary tract were monitored within the follow-up-period until August 2005. RESULTS: Post-operative course was uncomplicated in 12 cases and double J stents were removed after ultrasound control on the 14th post-operative day. Percutaneous nephrostomy was post-operatively necessary in three patients who were initially operated without insertion of double J catheters: two suffered from leakage of the transureteroureterostomy and one patient had bilateral hydronephrosis due to stenosis of the transureteroureterostomy. After 6 weeks, percutaneous nephrostomy could be removed and urine flow was uncomplicated in all three patients. CONCLUSION: For patients with advanced colorectal cancer or other pelvic malignancy, transureteroureterostomy is a favourable technique for definitive reconstruction of the urinary tract whenever tumor resection affords partial ureteral resection. Intra-operative insertion of double J stents into both ureters is highly recommended to prevent leakage or stenosis of the anastomosis.

A multicentre controlled study of the InLine radiofrequency ablation device for liver transection.

BACKGROUND: Surgical resection is the most effective therapy for liver cancer. Intraoperative blood loss during liver resection remains a major concern due to association with higher postoperative complications. The InLine radiofrequency ablation device (ILRFA) has achieved promising results in liver surgery with minimal blood loss and no increase of postoperative complications. In this multicentre controlled study, 108 patients undergoing liver resection were investigated. PATIENTS AND METHODS: A total of 108 patients underwent liver resections in 4 medical centres; the prospective sequential cohort study consisted of 54 ILRFA and 54 ultrasonic surgical aspirator transections as the control group. RESULTS: The type of liver resection performed was very similar in both groups. The median number of RFA deployments was 3 (range 1-12) with a median coagulation time of 9 (range 3-36) min. Median blood loss was 165+/-20 ml (range 5-675) in the ILRFA and 654+/-83 ml (range 80-3600) in the control group (p<0.001). The median transection time was 27 (2-219) min in the ILRFA group and 35 (5-62) min in controls. CONCLUSIONS: Our study indicates that ILRFA device for liver transection is effective in reducing blood loss and is safe. Precoagulation before parenchymal transection appears to be a valid concept in liver surgery. The avoidance of vascular inflow occlusion during parenchymal transection could also be of value.

One-stage sigmoid colon resection for perforated sigmoid diverticulitis (Hinchey stages III and IV).

INTRODUCTION: Guidelines for the treatment of complicated sigmoid diverticulitis recommend Hartmann's procedure or anastomosis with protective colostomy for Hinchey stage III diverticulitis and Hartmann's procedure only for Hinchey stage IV diverticulitis. We evaluated the outcome of patients with perforated sigmoid diverticulitis Hinchey III/IV undergoing one-stage colon resection and primary anastomosis without protective colostomy. METHODS: After implementation of a protocol to treat Hinchey III/IV diverticulitis with primary anastomosis without protective ileocolostomy, the patients' data were recorded prospectively between August 2001 and August 2003 and analyzed retrospectively from a computer-related database. RESULTS: Of 41 patients, 34 (81%) underwent one-stage sigmoid resection and primary anastomosis, 3 of 41 patients (7%) underwent primary anatomosis with protective ileostomy, and 5 of 41 patients (12%) had a Hartmann's procedure. The mortality was 11% in patients undergoing primary anastomosis and 60% in patients with Hartmann's procedure. The relative risk of co-morbidity factors for lethal outcome after sigmoid resection was 6.94 for preceding operations, 3.75 for renal failure or renal transplantation, and 3.25 for immunosuppression. CONCLUSIONS: One-stage sigmoid resection and primary anastomosis can be performed safely in nearly 90% of all patients with perforated sigmoid diverticulitis (Hinchey III/IV) by surgeons of different training levels. Patients with immunosuppression, chronic renal failure, liver cirrhosis, or previous organ transplantation or complex cardiovascular reconstructive procedures have a significantly increased risk of dying after sigmoid resection for perforated diverticulitis.

Serological immune response to cancer testis antigens in patients with pancreatic cancer.

Serological screening approaches have allowed for the identification of a large number of potentially relevant tumor antigens in cancer patients. Within this group, cancer testis antigens represent promising targets for cancer immunotherapy, since they are widely expressed in a variety of human cancer entities. In pancreatic cancer, however, there are only few data available about the expression pattern and serological response to cancer testis antigens and other serological-defined tumor antigens. Therefore, we investigated the IgG antibody response against 11 cancer testis antigens (SCP-1, GAGE, LAGE-1a,-1b, CT-7, NY-ESO-1, SSX-1-5) recombinantly expressed on yeast surface (RAYS) in patients with pancreatic cancer (n = 96), chronic pancreatitis (n = 18) and healthy donors (n = 48). We found in 14% of all patients antibody responses to SCP-1, but not to other cancer testis antigens (GAGE, LAGE-1a,-1b, CT-7, NY-ESO-1, SSX-1-5). Antibody response correlated with the expression of SCP-1 in the primary tumor of the respective patient as shown by RT-PCR, immunohistochemistry and Western blot. In contrast, no serological response to cancer testis antigens was observed in healthy donors. The humoral immune response against SCP-1 was associated with the size of tumor, but not with other clinico-pathological parameters such as histology, stage, presence of lymph node metastases, grading, age, gender or gemcitabine treatment. In conclusion, antibody response to cancer testis antigen SCP-1 is found in a proportion of pancreatic carcinoma patients. These results indicate that identification of additional tumor antigens by serological screening of tumor cDNA expression libraries by RAYS is a promising goal in pancreatic cancer.