Expandable metal stents versus laser combined with radiotherapy for palliation of unresectable esophageal cancer: a prospective randomized trial.

BACKGROUND/AIMS: Because of the short life expectancy of patients with esophageal cancer, relief of dysphagia associated with low morbidity and mortality must be the aim of any therapeutic strategy. METHODOLOGY: A total of 39 patients with unresectable esophageal cancer were randomly allocated to either receive combined laser-percutaneous radiotherapy (group 1, n = 21) or to have a self-expanding metal stent placed (group 2, n = 18). Some patients in group 2 required initial laser therapy (group 2a, n = 8). Treatment efficacy was evaluated on the basis of improved dysphagia, restenosis, hospital stay, survival time and costs. RESULTS: Both treatments were able to significantly improve dysphagia. Restenosis occurred in 43% of group 1 and 22% of group 2 patients. In group 1, 2 patients had severe bleeding episodes and 2 patients developed esophago-tracheal fistulas. One group 1 patient died due to uncontrollable bleeding and 1 patient to recurrent aspiration. No treatment-related death was observed in group 2. Hospital stay was 30.0 (mean: 5.4) days in group 1, 18.9 (mean: 4.2) days in group 2a and 7.1 (mean: 3.1) days in group 2b. There was no statistical difference between the 3 groups with regard to survival. Costs were highest in group 1 and lowest in group 2b. CONCLUSIONS: The treatment of unresectable esophageal cancer with self-expanding metal stents appears to be simple, safe, as good as laser combined with radiotherapy and cost efficient.

Influence of hyperinsulinemia on lipoproteins after pancreas transplantation with systemic insulin drainage.

Successful pancreas transplantation with systemic drainage is followed by a normalization of carbohydrate and lipid metabolism with low levels of plasma cholesterol and triglycerides. HDL cholesterol concentration and CETP plasma levels were found to be increased and the composition of lipoproteins altered in that LDL and HDL2/HDL3 were enriched in UC, HDL2 enriched in PL, and LDL depleted in PL. The mechanisms by which hyperinsulinemia may cause the observed changes in surface composition of plasma lipoproteins are unknown, as is their clinical relevance. It remains to be seen whether these changes counterbalance the favorable effects of an increased triglyceride clearance capacity on the cardiovascular risk of diabetic patients.

Dopamine and intestinal mucosal tissue oxygenation in a porcine model of haemorrhage.

Haemorrhage is associated with intestinal mucosal hypoxia and impaired gut barrier function. Dopamine increases oxygen delivery to the intestinal mucosa and may thus counteract haemorrhage-induced mucosal hypoxia. Jejunal mucosal tissue oxygen tension (mucosal PO2) and jejunal oxygen saturation of mucosal microvascular haemoglobin (mucosal HbO2) were measured in 14 anaesthetized pigs. Seven animals served as controls (group C) and seven received continuous infusion of dopamine 16 micrograms kg-1 min-1 (group D) while 45% of blood volume was removed in three equal increments. Resuscitation was performed using shed blood and fluid. Mean arterial pressure and systemic oxygen delivery decreasing significantly during haemorrhage and returned to baseline after resuscitation in both groups. Mucosal PO2 decreased from 4.4 to 1.7 kPa after haemorrhage (P < 0.01) and further to 1.5 kPa after resuscitation (P < 0.01) in group C whereas group D showed an increase from 3.9 to 5.9 kPa after the start of the dopamine infusion (P < 0.05), but no significant difference from baseline after haemorrhage (2.3 kPa) (ns) or resuscitation (3.1 kPa) (ns). Mucosal HbO2 decreased from 52 to 32% after haemorrhage (P < 0.05) and increased to near baseline (37%) (ns) after resuscitation in group C whereas group D showed no significant changes from baseline (54%) throughout the experiment. Comparison between groups showed higher mucosal PO2 and HbO2 values for group D animals after the start of the dopamine infusion (P < 0.05 each), after the first two steps of haemorrhage (P < 0.01 each) and after resuscitation (P < 0.05 each). We conclude that i.v. dopamine 16 micrograms kg-1 min-1 improved tissue oxygenation of the small intestinal mucosa during moderate haemorrhage and subsequent resuscitation.

[Long-term outcome of pancreas segment transplantation--obsolete technique or possible successful alternative?]. / Langzeitergebnisse nach Pankreassegment-Transplantation--obsolete Technik oder erfolgversprechende Alternative?

From January 1987 to August 1995, a total of 89 consecutive segmental pancreas transplants with bladder drainage were performed for end-stage diabetic nephropathy, the majority of them together with a kidney. One-year patient, pancreas, and kidney graft survival was 92%, 82%, and 87%, respectively. Rejection accounted for 64%, and thrombosis for 30% of total graft losses. While there was an increased risk of pancreas graft thrombosis, compared with duodenal pancreas transplantation, we experienced a lower incidence of urinary tract infections. In our series, segmental pancreas transplantation gives excellent long-term results.

MIB1 in colorectal carcinomas: its evaluation by three different methods reveals lack of prognostic significance.

Immunohistochemically detected MIB1 has been determined in a series of 106 colorectal carcinomas with three different evaluation methods (semiquantitative estimation, evaluation by image analysis, and cell count). Although the semiquantitative estimation correlated significantly with results obtained by image analysis (R = 0.8), both methods were only poorly associated with MIB1 counts (R = 0.5). Additionally, all three methods revealed no statistical correlation of MIB1 with the clinical outcome of the respective patients. Our results indicate a pronounced heterogeneity of MIB1 in colorectal adenocarcinoma, thus leading, irrespectively of the evaluation method used, to non-representative results with lack of clinical relevance.

Effects of short-term endotoxemia and dopamine on mucosal oxygenation in porcine jejunum.

Effects of Escherichia coli lipopolysaccharide (2 micrograms.kg-1.20 min-1; LPS), given systemically (S) or via superior mesenteric artery (M), and consecutive dopamine infusion (16 micrograms.kg-1.20 min-1) on jejunal mucosal tissue O2 tension (PO2muc) and serosal tissue O2 tension (PO2ser; Clark-type surface electrodes) and jejunal mucosal microvascular hemoglobin O2 saturation (HbO2muc; tissue reflectance spectrophotometry) were investigated in a hemodynamically stable pig model. Twenty-one pigs were anesthetized, paralyzed, and mechanically ventilated. After laparotomy, a mesenteric venous catheter was inserted and a jejunal antimesenteric enterotomy performed. LPS-infused animals developed similar degrees of pulmonary hypertension. No differences in cardiac output and mean arterial blood pressure between groups were found. PO2muc and HbO2muc were significantly lower in M animals compared with control (C) [210 min; PO2muc: 7.12 +/- 1.81 (M), 19.01 +/- 3.12 mmHg (C); HbO2muc: 28.78 +/- 3.36 (M), 49.09 +/- 3.84% (C)], whereas S animals ranged in between (PO2muc: 13.36 +/- 2.2 mmHg; HbO2muc: 40.68 +/- 4.43%). Of measured PO2muc values, 12.6 (C), 20.6 (S), and 46.3% (M) ranged from 0 to 5 mmHg. PO2ser was lower in LPS animals compared with control [59.43 +/- 5.4 (C), 45.00 +/- 6.12 (S), 47.33 +/- 4.34 (M) mmHg]. Dopamine increased PO2muc and HbO2muc to similar absolute values and significantly decreased frequency of PO2muc (0-5 mmHg) in M animals. We conclude that LPS impairs mucosal tissue oxygenation independently of systemic hemodynamics. Mucosal microvascular dysfunction depends on regional LPS concentrations. Under conditions of compromised tissue oxygenation, dopamine significantly improves PO2muc and HbO2muc.

Long-term outcome after switch from cyclosporine-based triple-drug immunosuppression to double therapy at three months.

Cyclosporin A (CyA) together with steroids and azathioprine (Aza) has been successfully used for prophylactic immunosuppression in numerous recipients of kidney allografts. The aim of this study was to evaluate the long-term effect of reducing this initial triple-drug therapy to double-drug therapy at 3 months. One hundred consecutive recipients of a cadaveric renal allograft with stable and good graft function were randomly allocated to continue with CyA and steroids (group 1) or CyA and Aza (group 2). Both groups were comparable with regard to all relevant patient characteristics. After a mean observation period of 55 (26-76) months no significant difference was observed in the incidence of acute rejection episodes after conversion (4 in group 1 and 5 in group 2), or in the incidence of graft loss (4 in group 1 and 5 in group 2); all graft rejection episodes were easily reversed with steroid pulses and patients switched back to triple-drug therapy. Patient survival was 94% in group 1 and 100% in group 2 at 55 months. In group 1, however, a higher number of viral infections and steroid-related side effects was noted. From these data it is concluded that initial triple-drug therapy can safety be reduced to a CyA-based double-drug combination after 3 months in renal allograft recipients with stable function. The combination with Aza is recommended because of its fewer side effects.

The effect of nephrectomy on the outcome of renal transplantation in patients with polycystic kidney disease.

Although various forms of polycystic kidney disease (PKD) account for up to 10% of patients requiring renal replacement therapy and severe complications may arise from these kidneys, no clear indications for pretransplant nephrectomy have been defined so far. A total of 104 renal transplants in three pediatric and 96 adult patients suffering from PKD were analysed retrospectively with regard to patient and graft survival in relation to pretransplant or posttransplant nephrectomy and no nephrectomy. Of these 99 patients, 25 had had either unilateral (19) or bilateral (6) nephrectomy sometime before transplantation and 10 patients between 3 and 81 months after transplantation. All patients received Cyclosporine-based immunosuppression. One-year patient and graft survivals for recipients of a first cadaveric renal graft (n = 91) were 94% and 92%, for recipients of second or third graft (n = 13) 89% and 78%. One- and five-year patient survival rates for patients with or without pretransplant nephrectomy were 100% and 100% vs 92% and 84%, respectively. One- and five-year graft survival rates were 100% and 93% for pretransplant nephrectomy patients vs 89% and 74% for the non-nephrectomy group (p < 0.05). Patients not undergoing nephrectomy sometime after transplantation had the same patient but better five-year graft survival when compared to the posttransplant nephrectomy group (89% vs 52%). In patients with early posttransplant urinary tract infection, which is considered in this analysis as a cyst-related complication, graft survival at one year was 77% but 97% in patients without this complication. From these data it is recommended that polycystic kidneys should be removed before transplantation if cyst-related complications occur repeatedly. Posttransplant nephrectomy can be performed with no mortality and should be carried out whenever clinically indicated.

Immunohistochemically detectable bcl-2 expression in colorectal carcinoma: correlation with tumour stage and patient survival.

The bcl-2 gene encodes for a mitochondrial membrane proto-oncoprotein, the expression of which is known to suppress programmed cell death (apoptosis). In the present study the prognostic value of bcl-2 proto-oncoprotein was immunohistochemically investigated in a series of 104 colorectal carcinomas. The bcl-2 staining patterns were semiquantitatively assessed and correlated with the pTNM stage, Dukes' classification, lymphocytic infiltration (Jass classification) and tumour grade as well as parameters not associated with prognosis (gender, age, tumour site, histological tumour type). Statistical analysis was carried out using the Kaplan-Meier method, the log-rank test, hazard ratios and their confidence intervals. Fifty-five out of 104 cases completely lacked immunohistochemical bcl-2 expression. Fewer than 5% of bcl-2-positive cells were found in 25, 5-50% in 17 and more than 50% in five cases. The extent of bcl-2 expression by tumour cells decreased significantly with respect to increasing tumour size (P < 0.05), decreasing lymphocytic infiltration (P < 0.05) and chance of poor clinical outcome (P < 0.05), but not with worsening of Dukes stages. In multivariate analysis (Cox regression model) bcl-2 expression remained as an independent prognostic parameter with Dukes' classification as stratification factor (P < 0.001). Although the biological functions of bcl-2 protein are not yet well understood, our results provide further evidence that bcl-2 oncoprotein appears to be associated with favourable clinical outcome. Thus immunohistochemical bcl-2 phenotyping of colorectal carcinoma may contribute in future to the clinical management of these patients.

Standardized staining and analysis of argyrophilic nucleolar organizer region associated proteins (AgNORs) in radically resected colorectal adenocarcinoma--correlation with tumour stage and long-term survival.

Quantification of silver-stained nucleolar organizer region associated proteins (AgNORs) was introduced in histopathology as a marker of cellular and nucleolar activity. However, due to the poor staining quality obtained on routinely processed archival material, the method yielded controversial and sometimes non-reproducible results. The recent introduction of wet autoclave pretreatment has reliably improved AgNOR staining quality on routinely formalin-fixed and paraffin-embedded tissues. In the present study, 92 routinely processed colorectal carcinomas were investigated, applying this novel staining technique. Subsequent standardized morphometric analysis revealed, irrespective of common tumour staging or grading classifications, a statistically highly significant correlation between AgNOR parameters and clinical course. The usefulness of standardized AgNOR parameters for the independent prediction of patient survival was proven by uni- and multivariate analysis.

Immunohistochemically detectable p53 and mdm-2 oncoprotein expression in colorectal carcinoma: prognostic significance.

Aims-To investigate the correlation between the expression of the p53 and mdm-2 oncoproteins and to assess their prognostic value in colorectal cancer.Methods-Using a polyclonal (CM1) and a monoclonal antibody directed against p53 and mdm-2, respectively, these oncoproteins were stained immunohistochemically in 109 colorectal adenocarcinomas.Results-p53 was detected in less than 10% of tumour cells in 11 of 109 adenocarcinomas, in 10-50% of tumour cells, in 17 of 109 adenocarcinomas, and in more than 50% of tumour cells in 32 of 109 adenocarcinomas. Expression of mdm-2 was detected in 22 of 109 (20%) cases investigated, of which 19 showed concomitant p53 expression. In most cases mdm-2 immunoreactivity was strongly associated with a small proportion of p53 positive tumour cells. Both p53 and mdm-2 expression lacked statistical significance when correlated with common staging and grading parameters.Conclusions-Detection of p53 and mdm-2 oncoprotein expression, detected using immunohistochemistry, is of no prognostic value in colorectal cancer. However, the close correlation between mdm-2 immunoreactivity and the proportion of p53 positive cells provides further evidence that the mdm-2 gene product interacts with p53 protein.

Pentoxifylline as an adjunct to cyclosporine-based immunosuppression does not improve the outcome of renal transplantation.

The adjunct of PTX to the therapeutic regimen after renal transplantation had no effect on the incidence of ATN, immunologic or infectious complications, or CyA toxicity. Also, patient and graft survival was not affected. The four deaths in the study group can probably not be attributed to PTX therapy. From these data it is concluded that PTX is not able to improve the outcome of renal transplantation.