The contemporary value of pretreatment prostatic acid phosphatase to predict pathological stage and recurrence in radical prostatectomy cases.

PURPOSE: We examine the clinical prognostic value of the currently available simple and inexpensive immunoenzymatic prostatic acid phosphatase (PAP) assay for the staging and prognosis of radical prostatectomy cases. MATERIALS AND METHODS: Between February 1, 1990 and May 3, 1996 pretreatment PAP was measured in 295 patients who underwent radical prostatectomy. From February 1, 1990 to May 17, 1992 the Hybritech Tandem-E assay was used in 75 cases, from May 18, 1992 to February 28, 1993 the Abbott EIA assay was used in 49 and from March 1, 1993 to May 3, 1996 the Abbott IMx assay was used in 171. PAP assays were analyzed individually and the results were combined with pretreatment prostate specific antigen (PSA) values to assess the ability to predict organ confined prostate cancer and serological recurrence after radical prostatectomy. RESULTS: PAP testing was not of value for predicting organ confined disease or positive margins. However, this test was useful for predicting the first serological PSA recurrence in the 3 periods (77 to 85% correct) and overall (82% correct, p < 0.001, odds ratio 6.06). The Kaplan-Meier disease-free survival rate at 4 years was 78.8% for men with PAP less than 3 ng./ml. and 38.8% for those with PAP 3 ng./ml. or greater, which was significant when pretreatment PSA was less than 10 ng./ml. (p = 0.047), 10 ng./ml. or greater (p = 0.012) and overall (p < 0.001). PAP testing added prognostic information to pretreatment PSA values and it was an independent predictor of recurrence. CONCLUSIONS: The widely available and inexpensive PAP assays of the 1990s are predictors of recurrence after radical prostatectomy. They should be included in future studies of prostate cancer recurrence modeling. However, they do not predict pathological stage or margin status.

Fibrin sealant treatment of splenic injury during open and laparoscopic left radical nephrectomy.

PURPOSE: We describe the use of fibrin sealant for rapid and definitive hemostasis of splenic injuries incurred during open and laparoscopic left nephrectomy. MATERIALS AND METHODS: In 2 patients undergoing left nephrectomy for a suspicious renal mass splenic laceration occurred during mobilization of the colonic splenic flexure at open nephrectomy and laparoscopic upper pole dissection, respectively. Fibrin sealant was applied topically in each case. RESULTS: In each patient fibrin sealant achieved immediate hemostasis and each recovered without further splenic bleeding. CONCLUSIONS: The topical application of fibrin sealant safely, rapidly and reliably achieves definitive hemostasis of splenic injuries. It is simple to use in the open and laparoscopic approaches.

Role of the polymorphic residues in HLA-DR molecules in allele-specific binding of peptide ligands.

Analysis of peptide binding to a set of HLA-DR alleles has allowed the proteins to be segregated into functional subsets, depending on the amino acids at positions 57 and 86 of the beta-chain. DR proteins with glycine at 86 beta and aspartic acid at 57 beta bound a simplified peptide with significantly lower IC50 values than alleles that did not have this combination of amino acids. The size of the amino acid at 86 beta seemed to modify the steric requirements for the single most important side chain of the peptide. Within each of the four subgroups, other polymorphic amino acids define allele-specific binding requirements. These were explored by analyzing the ability of eight different DR alleles to bind 13 known T cell determinants. The side chains in the peptides that seemed to be responsible for allele specificity were determined by correlating their common structural features with complementary polymorphic residues in the binding site. The importance of these residues was tested by incorporating them into a polyalanine backbone, and was confirmed by the ability of these residues to transfer allele specificity to these simplified analogues. Even though polymorphic contacts affected peptide affinity, the majority of the free energy of binding in all cases arose from interactions with the peptide backbone and the single hydrophobic amino acid at the third position. These constraints seem to orient all peptides in a similar location, forcing them to adopt a closely related conformation in the binding site. The corresponding side chain in each peptide contacts the same pocket in the binding site, regardless of the allele. This apparent similarity should allow any DR allele to be analyzed by extrapolation from the DR1 crystal structure.