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Biomedical subjects

P Roy

Publications and source records attributed to P Roy.

At least 91 records · Page 5Linked to original sources
PubMed1999

Tagging sentinel lymph nodes: a study of 100 patients with breast cancer.

The aim of this study was to evaluate in breast cancer patients the feasibility of sentinel lymph node (SLN) identification and the sensitivity of this technique to detect node metastases. Between January and July 1997, SLNs were tracked with Evans Blue dye in 100 patients with breast cancer who then underwent complete level I/II axillary lymph node dissection (ALND). All SLNs were examined by haematoxylin-phloxin-saffron (HPS) staining and immunohistochemistry (IHC) of multiple sections. The findings for the SLNs were compared with results on ANLD. Axillary SLNs were identified in 83 patients (detection rate = 83%; 95% confidence interval (CI) 74-90%). Axillary SLNs were detected in 58/83 cases (70%) at level I only, and in 69/83 (83%) at levels including level I. Histologically positive axillary SLNs were found in 45% (37/83) of patients, including 2 patients with malignancy (micro-metastases) detected by IHC only. The sensitivity of axillary SLN to detect axillary lymph nodes metastases was 37/39 = 95% (95% CI 83-99%). SLNs of the internal mammary chain (IMC) were dissected for 33 tumours of the median or inner quadrants and detected in 26/33 = 79% of cases (95% CI 61-91%). In our experience, the overall sensitivity of SLN identification as a predictor of node (axillary or IMC) metastases was 41/43 = 95% (95% CI 84-99%), confirming the usefulness of the procedure.

Adult↗
PubMed1999

Co-oxidation of acrylonitrile by soybean lipoxygenase and partially purified human lung lipoxygenase.

1. Human lung lipoxygenase (HLLO) was partially purified by concanavalin-A (Con-A) affinity chromatography that provided an easy and rapid one-step procedure for the removal (> or = 96%) of haemoglobin from cytosol. 2. HLLO exhibited dioxygenase activity towards arachidonic acid (AA) and linoleic acid (LA). The dioxygenase activity towards LA varied approximately 12-fold (48-591 nmol/min/mg protein) among different human lung samples examined. 3. Reverse-phase HPLC analysis of AA metabolites indicated the predominance of 15-lipoxygenase in human lung cytosol. 4. HLLO exhibited co-oxidase activity towards benzidine (BZD) and several other model compounds. The co-oxidase activity towards BZD was significantly inhibited by several lipoxygenase inhibitors. 5. HLLO and soybean lipoxygenase (SLO), used as a model enzyme, metabolized acrylonitrile (ACN) to 2-cyanoethylene oxide (CEO) and ultimately to cyanide. 6. HLLO was a approximately 6-fold better catalyst than SLO in converting ACN to cyanide. The generation of cyanide by HLLO was dependent on the concentration of enzyme and the reaction was inhibited by the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) and the anti-oxidant butylated hydroxytoluene (BHT). 7. Under optimal assay conditions, the covalent binding of HLLO-generated reactive intermediate(s) from [14C]ACN to protein and DNA (nmol equivalent bound/15 min/mg HLLO/mg bovine serum albumin or calf thymus DNA) was observed at approximately 1.20+/-0.13 and 2.20+/-0.50 respectively. Both protein and DNA binding were inhibited by NDGA, butylated hydroxyanisole (BHA) and BHT.

Acrylonitrile↗
PubMed1999

Pattern of epithelial cell proliferation in colorectal mucosa of patients with large bowel adenoma or cancer: an ECP case-control study. European cancer prevention.

Proliferative abnormalities of the normal colorectal mucosa have been proposed as a possible marker of enhanced susceptibility to colorectal cancer. A case-control study was conducted to compare the cell kinetics of normal colon mucosa through the different steps of the adenoma-carcinoma sequence. The number and position of labelled epithelial nuclei after in vitro incubation of tritiated thymidine were compared in patients with large bowel cancer (n = 39), large adenoma >1 cm (n = 47), small adenoma (n = 30) and in controls (n = 135). The distribution of tertiles between cases and controls was analysed using odds ratio (OR), comparing the second tertile (OR2) and the third tertile (OR3) to the first one. There was no significant difference in the overall cell proliferation rate when comparing cancer, large adenoma and small adenoma groups to the control group. The ratio number of labelled cells in the upper 40% of the crypt/total number of labelled cells (4h index) was found to be significantly higher only when the cancer group was compared to the control group: OR2 = 5.87 (1.33-25.90), OR3 = 9.48 (2.07-43.38), P for trend = 0.002. The upward shift of the proliferative compartment in the normal mucosa of patients with large bowel cancer suggests that this abnormality is related to cancer risk.

Adenoma↗
PubMed1999

Faecal neutral sterols and bile acids in patients with adenomas and large bowel cancer: an ECP case-control study. European cancer prevention.

It is unclear whether neutral steroids and bile acids are involved in large bowel carcinogenesis. This study was conducted to compare the concentration of these faecal constituents at the different stages of the adenoma-carcinoma sequence. Neutral sterols and free bile acid concentrations were determined from stool samples collected form patients with large bowel cancer (n = 47), large adenoma > or = 1 cm (n = 42), small adenoma (n = 24), and controls (n = 104). The distribution of tertiles between cases and controls was analysed using odds ratio (OR), with 95% confidence interval (CI), comparing (two-sided tests) the second tertile (OR2) and the third tertile (OR3) to the first one. Persistence of primary bile acids appeared as a protective factor against cancer: (OR = 0.09, 95% CI 0.02-0.54). High values of cholesterol were associated with cancer risk (OR2 = 5.8, 95% CI 1.3-26.6; OR3 6.4, 95% CI 1.3-31.4). High values of cholesterol were more frequently observed in patients with large adenomas than in controls (OR2 = 8.5, 95% CI 1.9-37.5; OR3 = 4.3, 95% CI 0.9-20.9). Neutral sterols, cholesterol especially, may play a role in adenoma growth and adenoma transformation into carcinoma. Persistence of primary bile acids may afford protection.

Adenocarcinoma↗
PubMed1999

Immunochemical evidence that cholesteryl ester transfer protein and bactericidal/permeability-increasing protein share a similar tertiary structure.

Cholesteryl ester transfer protein (CETP) plays an important role in plasma lipoprotein metabolism through its ability to transfer cholesteryl ester, triglyceride, and phospholipid between lipoproteins. CETP is a member of a gene family that also includes bactericidal/permeability-increasing protein (BPI). The crystal structure of BPI shows it to be composed of two domains that share a similar structural fold that includes an apolar ligand-binding pocket. As structurally important residues are conserved between BPI and CETP, it is thought that CETP and BPI may have a similar overall conformation. We have previously proposed a model of CETP structure based on the binding characteristics of anti-CETP monoclonal antibodies (mAbs). We now present a refined epitope map of CETP that has been adapted to a structural model of CETP that uses the atomic coordinates of BPI. Four epitopes composed of CETP residues 215-219, 219-223, 223-227, and 444-450, respectively, are predicted to be situated on the external surface of the central beta-sheet and a fifth epitope (residues 225-258) on an extended linker that connects the two domains of the molecule. Three other epitopes, residues 317-331, 360-366, and 393-410, would form part of the putative carboxy-terminal beta-barrel. The ability of the corresponding mAbs to compete for binding to CETP is consistent with the proximity of the respective epitopes in the model. These results thus provide experimental evidence that is consistent with CETP and BPI having similar surface topologies.

Antibodies, Monoclonal↗
PubMed1999

Expression and functional characterization of bluetongue virus VP2 protein: role in cell entry.

Segment 2 of bluetongue virus (BTV) serotype 10, which encodes the outer capsid protein VP2, was tagged with the S-peptide fragment of RNase A and expressed by a recombinant baculovirus. The recombinant protein was subsequently purified to homogeneity by virtue of the S tag, and the oligomeric nature of the purified protein was determined. The data obtained indicated that the majority of the protein forms a dimer and, to a lesser extent, some trimer. The recombinant protein was used to determine various biological functions of VP2. The purified VP2 was shown to have virus hemagglutinin activity and was antigenically indistinguishable from the VP2 of the virion. Whether VP2 is responsible for BTV entry into permissive cells was subsequently assessed by cell surface attachment and internalization studies with an immunofluorescence assay system. The results demonstrated that VP2 alone is responsible for virus entry into mammalian cells. By competition assay, it appeared that both VP2 and the BTV virion attached to the same cell surface molecule(s). The purified VP2 also had a strong affinity for binding to glycophorin A, a sialoglycoprotein component of erythrocytes, indicating that VP2 may be responsible for BTV transmission by the Culicoides vector to vertebrate hosts during blood feeding. Further, by various enzymatic treatments of BTV-permissive L929 cells, preliminary data have been obtained which indicated that the BTV receptor molecule(s) is likely to be a glycoprotein and that either the protein moiety of the glycoprotein or a second protein molecule could also serve as a coreceptor for BTV infection.

Agglutination Tests↗
PubMed1999

Quantitation of nucleolar organizer regions by image analysis in glottic squamous cell carcinoma.

OBJECTIVE: To apply computer image analysis as a quantitative method for analyzing interphase nucleolar organizer regions (NORs) to determine whether this proliferative marker provides useful prognostic information in glottic squamous cell carcinoma. DESIGN: Retrospective testing of biopsy samples and resected tissue. SETTING: Nova Scotia Regional Cancer Centre and regional hospitals in Nova Scotia and Prince Edward Island, Canada. PATIENTS: Patients with primary glottic cancer presenting to the cancer centre between 1984 and 1991. INTERVENTIONS: Semiautomated image analysis was used to measure the nuclear area and the NOR area in formalin-fixed paraffin-embedded tumour samples. OUTCOME MEASURES: Mean nuclear area, mean NOR area and NOR percentage of nuclear area, calculated as the mean NOR area divided by the mean nuclear area, expressed as a percentage. RESULTS: Of 154 cases, 90 samples were received; however, 8 paraffin blocks were exhausted and 29 samples stained poorly due to extent of fixation. Analysis of the remaining 53 cases, all primary squamous cell carcinomas, showed no statistically significant association between, on one hand, mean NOR area or NOR percentage of nuclear area and, on the other hand, tumour grade, tumour stage, tumour recurrence or disease-related death. CONCLUSIONS: This study does not demonstrate a prognostic value of NOR measurement as a proliferative marker in primary glottic squamous carcinoma. However, given the small number of cases in this study, further research should be conducted using a larger number of cases from one centre and comparing NOR measures with other markers of cell proliferation.

Biomarkers, Tumor↗
PubMed1999

Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles.

The contributions of specific human liver cytochrome P-450 (CYP) enzymes to the activation, via 4-hydroxylation, of the oxazaphosphorine anticancer prodrugs cyclophosphamide (CPA) and ifosfamide (IFA) were investigated. Analysis of a panel of 15 human P-450 cDNAs expressed in human lymphoblasts and/or baculovirus-infected insect cells (Supersomes) demonstrated that CYPs 2A6, 2B6, 3A4, 3A5, and three CYP2C enzymes (2C9, 2C18, 2C19) exhibited significant oxazaphosphorine 4-hydroxylase activity, with 2B6 and 3A4 displaying the highest activity toward CPA and IFA, respectively. CYP2B6 metabolized CPA at a approximately 16-fold higher in vitro intrinsic clearance (apparent Vmax/Km) than IFA, whereas 3A4 demonstrated approximately 2-fold higher Vmax/Km toward IFA. A relative substrate-activity factor (RSF)-based method was developed to calculate the contributions of individual P-450s to total human liver microsomal metabolism based on cDNA-expressed P-450 activity data and measurements of the liver microsomal activity of each P-450 form. Using this method, excellent correlations were obtained when comparing measured versus predicted (calculated) microsomal 4-hydroxylase activities for both CPA (r = 0. 96, p <.001) and IFA (r = 0.90, p <.001) in a panel of 17 livers. The RSF method identified CYP2B6 as a major CPA 4-hydroxylase and CYP3A4 as the dominant IFA 4-hydroxylase in the majority of livers, with CYPs 2C9 and 2A6 making more minor contributions. These predicted P-450 enzyme contributions were verified using an inhibitory monoclonal antibody for 2B6 and the P-450 form-specific chemical inhibitors troleandomycin for 3A4 and sulfaphenazole for 2C9, thus validating the RSF approach. Finally, Western blot analysis using anti-2B6 monoclonal antibody demonstrated the presence of 2B6 protein at a readily detectable level in all but one of 17 livers. These data further establish the significance of human liver CYP2B6 for the activation of the clinically important cancer chemotherapeutic prodrug CPA.

Antibodies, Monoclonal↗
PubMed1999

Stereoselective metabolism of ifosfamide by human P-450s 3A4 and 2B6. Favorable metabolic properties of R-enantiomer.

The anticancer prodrug ifosfamide (IFA) contains a chiral phosphorous atom and is administered clinically as a racemic mixture of R and S enantiomers. Animal model studies and clinical data indicate enantioselective differences in cytochrome P-450 (CYP) metabolism, pharmacokinetics, and therapeutic efficacy between the two enantiomers; however, the metabolism of individual IFA enantiomers has not been fully characterized. The role of CYP enzymes in the stereoselective metabolism of R-IFA and S-IFA was investigated by monitoring the formation of both 4-hydroxy (activated) and N-dechloroethyl (DCl) (inactive, neurotoxic) metabolites. In the 4-hydroxylation reaction, cDNA-expressed CYPs 3A4 and 3A5 preferentially metabolized R-IFA, whereas CYP2B6 was more active toward S-IFA. Enantioselective IFA 4-hydroxylation (R > S) was observed with six of eight human liver samples. In the N-dechloroethylation reaction, CYPs 3A4 and 2B6 both catalyzed a significantly higher intrinsic metabolic clearance (V(max)/K(m)) of S-IFA compared with R-IFA. Striking P-450 form specificity in the formation of individual DCl metabolites was evident. CYPs 3A4 and 3A5 preferentially produced (R)N2-DCl-IFA and (R)N3-DCl-IFA (derived from R-IFA and S-IFA, respectively), whereas CYP2B6 correspondingly formed (S)N3-DCl-IFA and (S)N2-DCl-IFA. In human liver microsomes, the CYP3A-specific inhibitor troleandomycin suppressed (R)N2- and (R)N3-DCl-IFA formation by >/=80%, whereas (S)N2- and (S)N3-DCl-IFA formation were selectively inhibited (>/=85%) by a CYP2B6-specific monoclonal antibody. The overall extent of IFA N-dechloroethylation varied with the CYP3A4 and CYP2B6 content of each liver, but was significantly lower for R-IFA (32 +/- 13%) than for S-IFA (62 +/- 17%, n = 8; p <.001) in all livers examined. R-IFA thus has more favorable liver metabolic properties than S-IFA with respect to less extensive N-dechloroethylation and more rapid 4-hydroxylation, indicating that R-IFA may have a distinct clinical advantage over racemic IFA.

Antineoplastic Agents, Alkylating↗
PubMed1998

Recombinant glutathione S-transferase/CD36 fusion proteins define an oxidized low density lipoprotein-binding domain.

CD36 is a multifunctional cell-surface receptor that binds adhesion molecules such as thrombospondin-1 and collagen and modified lipids and/or lipoproteins. It participates in cellular uptake of photoreceptor outer segments and scavenging of apoptotic cells and oxidized low density lipoprotein (Ox-LDL). Recognition and internalization of Ox-LDL by mononuclear phagocytes may play an important role in the development of atherosclerotic lesions. We have utilized a series of recombinant bacterial glutathione S-transferase/CD36 fusion proteins that span nearly all of the CD36 molecule to characterize the structural domain on CD36 that recognizes Ox-LDL. We found that the Ox-LDL-binding domain is different from the thrombospondin-1-binding domain located at amino acids 93-120. A fusion protein containing the region extending from amino acids 5 to 143 formed specific, saturable, and reversible complexes with Ox-LDL. As with intact CD36, binding was blocked by excess unlabeled Ox-LDL and antibodies to CD36. The stoichiometry and affinity of the fusion protein for Ox-LDL were similar to those of the intact protein. We also demonstrated that this fusion protein competitively inhibited binding of Ox-LDL to purified platelet CD36 and to CD36 expressed on peripheral blood monocytes and CD36 cDNA-transfected melanoma cells. The use of smaller peptides and fusion proteins including those spanning amino acids 28-93 and 5-93 has further narrowed the binding site to a region from amino acids 28 to 93, although participation of a sequence in the noncontiguous region 120-155 cannot be excluded. This study, for the first time, demonstrates unique regions of the scavenger receptor CD36 that bind the Ox-LDL ligand. Our structural analysis of the receptor provides information as to potential control of the trafficking of modified lipoproteins into the blood vessel wall.

Binding Sites↗
PubMed1998

Interaction of the antitumor antibiotic chromomycin A3 with glutathione, a sulfhydryl agent, and the effect upon its DNA binding properties.

Chromomycin A3 (CHR), an anticancer antibiotic, blocks macromolecular synthesis via reversible interaction with DNA only in the presence of divalent cations like Mg2+. In the absence of DNA, the antibiotic forms a dimer: Mg2+ complex [(CHR)2Mg2+]. It is the DNA-binding ligand. The antibiotic has potential reactive centers that could interact with GSH, the most abundant non-protein thiol in eukaryotic cells and a putative cofactor involved in the activation of many antibiotics in vivo. To understand the mode of action of CHR in vivo, we studied the interactions of CHR and the (CHR)2Mg2+ complex with GSH and the association of the resultant complexes with DNA by means of absorption, fluorescence, and circular dichroism spectroscopy. The novel finding was that GSH interacts non-covalently with CHR without a chemical modification of the antibiotic. The interaction was reversible in nature. The results are reported in two parts: the interaction of CHR with GSH in the absence and presence of Mg2+, and the effect of this interaction on the DNA-binding properties of the antibiotic. CHR forms a single type of complex with GSH. In contrast, (CHR)2Mg2+ forms two different types of complexes with GSH: a low GSH complex at approximately 12 mM GSH and a high GSH complex at > or = 16 mM GSH. Binding and thermodynamic parameters for the reversible association of the complexes with DNA demonstrated that they bind differently to the same DNA. The thermodynamic parameters indicate that the presence of GSH alters the mode of binding of the (CHR)2Mg2+ complex with DNA. The (CHR)2Mg2+ complex binds to DNA via an entropy-driven process, whereas in the presence of GSH the association is enthalpy-driven. The significance of these results in the understanding of the molecular basis of action of the antibiotic is discussed.

Antibiotics, Antineoplastic↗
PubMed1998

Capping and methylation of mRNA by purified recombinant VP4 protein of bluetongue virus.

The core of bluetongue virus (BTV) is a multienzyme complex composed of two major proteins (VP7 and VP3) and three minor proteins (VP1, VP4, and VP6) in addition to the viral genome. The core is transcriptionally active and produces capped mRNA from which all BTV proteins are translated, but the relative role of each core component in the overall reaction process remains unclear. Previously we showed that the 76-kDa VP4 protein possesses guanylyltransferase activity, a necessary part of the RNA capping reaction. Here, through the use of highly purified (>95%) VP4 and synthetic core-like particles containing VP4, we have investigated the extent to which this protein is also responsible for other activities associated with cap formation. We show that VP4 catalyzes the conversion of unmethylated GpppG or in vitro-produced uncapped BTV RNA transcripts to m7GpppGm in the presence of S-adenosyl-L-methionine. Analysis of the methylated products of the reaction by HPLC identified both methyltransferase type 1 and type 2 activities associated with VP4, demonstrating that the complete BTV capping reaction is associated with this one protein.

Bluetongue virus↗
PubMed1998

Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes.

Dendritic cells, but not macrophages, efficiently phagocytose apoptotic cells and cross-present viral, tumor, and self-antigens to CD8(+) T cells. This in vitro pathway corresponds to the in vivo phenomena of cross-priming and cross-tolerance. Here, we demonstrate that phagocytosis of apoptotic cells is restricted to the immature stage of dendritic cell (DC) development, and that this process is accompanied by the expression of a unique profile of receptors, in particular the alphavbeta5 integrin and CD36. Upon maturation, these receptors and, in turn, the phagocytic capacity of DCs, are downmodulated. Macrophages engulf apoptotic cells more efficiently than DCs, and although they express many receptors that mediate this uptake, they lack the alphavbeta5 integrin. Furthermore, in contrast to DCs, macrophages fail to cross-present antigenic material contained within the engulfed apoptotic cells. Thus, DCs use unique pathways for the phagocytosis, processing, and presentation of antigen derived from apoptotic cells on class I major histocompatibility complex. We suggest that the alphavbeta5 integrin plays a critical role in the trafficking of exogenous antigen by immature DCs in this cross-priming pathway.

Antigen Presentation↗
PubMed1998

Guanylyltransferase and RNA 5'-triphosphatase activities of the purified expressed VP4 protein of bluetongue virus.

We have examined the RNA-capping enzyme activities of bluetongue virus (BTV) minor core protein, VP4. Recombinant BTV VP4 protein was purified to homogeneity from insect cell culture infected with a baculovirus VP4 of BTV serotype 10. We demonstrate that the purified protein, and VP4 encapsidated in core-like particles, react with GTP and covalently bind GMP via a phosphoamide linkage, a characteristic feature of guanylyltransferase enzyme. VP4 also catalyses a GTP-PPi exchange reaction indicating that the protein is the guanylyltransferase of the virus. In addition, VP4 possesses an RNA 5'-triphosphatase activity which catalyses the first step in the RNA-capping sequence. Further, an inorganic pyrophosphatase activity was identified which may aid the transcription activity within the virus by removing inorganic pyrophosphate which is an inhibitor of the polymerization reaction. Finally, the direct evidence of VP4 capping activity has been obtained by demonstrating in vitro transfer of GMP to the 5' end of in vitro synthesized BTV ssRNA transcripts to form a cap structure.

Acid Anhydride Hydrolases↗
PubMed1998

Using relative risk models for estimating synergy between two risk factors.

The synergy between two risk factors measures the extent to which each of them is more harmful in combination with the other than when acting alone. Relative risk models which describe interaction between risk factors with a few parameters are well adapted to the quantification of synergy. A simple measure of synergy and a method for its estimation with the help of relative risk models are proposed. This concept of synergy provides a simple interpretation of the non-linear parameter of several classical relative risk models. The discussion is illustrated with examples taken from cancer epidemiology of the upper aerodigestive tract.

Alcohol Drinking↗
PubMed1998

Genetic polymorphisms in the tumor necrosis factor locus influence non-Hodgkin's lymphoma outcome.

Systemic release of tumor necrosis factor (TNF) and lymphotoxin-alpha (LTalpha) has been found to contribute to the severity of non-Hodgkin's lymphoma (NHL). We investigated whether genetic polymorphisms in the TNF locus, previously shown to influence TNF and LTalpha genes expression, might contribute to these cytokines production and to the clinical course of NHL. Genomic DNA from 273 lymphoma patients was typed for TNF (-308) polymorphism using an allele-specific polymerase chain reaction (PCR) and for LTalpha (+252) polymorphism with a PCR-based restriction fragment length polymorphism. The presence of the TNF allele involved in increased TNF gene transcription was associated with higher plasma levels of this cytokine at the time of lymphoma diagnosis (chi2 test, P = .013). An extended haplotype analysis showed that the presence of at least two TNF or LTalpha high-producer alleles constituted a risk factor for first-line treatment failure (chi2 test, P = .021), shorter progression-free survival (log-rank test, P = .0007), and overall survival (log-rank test, P = .012). In the subgroup of 126 patients with diffuse large-cell lymphoma, the presence of two or more TNF/LTalpha high producing alleles contributed significantly to a higher rate of relapse and progression (log-rank test, P = .045 and P = .027). In multivariate Cox regression models including the variables of the International Prognostic Index, the TNF/LTalpha haplotype status was found to be an independent risk factor for progression-free survival (relative risk 2.33, 95% confidence interval [1.17 to 4.64], P = . 0053) and overall survival (relative risk 1.92, 95% confidence interval [0.63 to 5.80], P = .081) of large-cell lymphoma patients. These results indicate that genetic polymorphism leading to increased TNF production influences the outcome of NHL and suggest a pathophysiological role for the genetic control of the immune response in lymphoid malignancies.

Adult↗
PubMed1998

Outcome of treatment of upper third vaginal recurrences of cervical and endometrial carcinomas with interstitial brachytherapy.

PURPOSE: To describe an original brachytherapy technique using a dedicated intravaginal template for the treatment of vaginal vault recurrences and to evaluate the results of such a treatment. METHODS AND MATERIALS: Between 1978 and 1993, 78 patients with isolated recurrence of cervical or endometrial carcinoma located in the vaginal vault have been treated in Lyon. Initial treatment was surgery alone in 49 cases and irradiation with surgery in 37 cases. Treatment of the vaginal recurrence was performed with interstitial Iridium 192 brachytherapy combined with pelvic external beam radiation therapy in 34 patients. The tumor was implanted with a dedicated intravaginal plastic template. Six parallel metallic needles were implanted in the vaginal vault and afterloaded with Iridium 192 wires of 4 to 6 cm long. The mucosa of the upper half of the vagina received the same dose as the one encompassing the tumor on the 85% isodose of the Paris system. RESULTS: At 5 years the local control rate was 70% and the overall survival rate 56%. Grade 3 complications occurred in 10% of the cases and only in patients who had received irradiation during the initial treatment of the primary tumor. CONCLUSIONS: This brachytherapy technique makes it possible to perform Iridium 192 implants in a difficult situation with a favorable long-term control rate and an acceptable rate of complications.

Adult↗