A prospective single-center study of sentinel lymph node detection in cervical carcinoma: is there a place in clinical practice?

OBJECTIVE: To establish the accuracy of sentinel lymph node (SLN) detection in early cervical cancer. MATERIALS AND METHODS: Sentinel lymph node detection was performed prospectively over a 6-year period in 86 women undergoing surgery for cervical carcinoma by the combined method (Tc-99m and methylene blue dye). Further ultrastaging was performed on a subgroup of 26 patients who had benign SLNs on initial routine histological examination. RESULTS: The SLN was detected in 84 (97.7%) of 86 women by the combined method. Blue dye uptake was not seen in 8 women (90.7%). Sentinel lymph nodes were detected bilaterally in 63 women (73.3%), and the external iliac region was the most common anatomic location (48.8%). The median SLN count was 3 nodes (range, 1-7). Of the 84 women with sentinel node detection, 65 also underwent bilateral pelvic lymph node dissection, and in none of these cases was a benign SLN associated with a malignant non-SLN (100% negative predictive value). The median non-SLN count for all patients was 19 nodes (range, 8-35). Eighteen patients underwent removal of the SLN without bilateral pelvic lymph node dissection. Nine women (10.5%) had positive lymph nodes on final histology. One patient had bulky pelvic nodes on preoperative imaging and underwent removal of the negative bulky malignant lymph nodes and a benign SLN on the contralateral side. This latter case confirms the unreliability of the SLN method with bulky nodes. The remaining 8 patients had positive SLNs with negative nonsentinel lymph nodes. Fifty-nine SLNs from 26 patients, which were benign on initial routine histology, underwent ultrastaging, but no further disease was identified. Four patients (5%) relapsed after a median follow-up of 28 months (range, 8-80 months). CONCLUSION: Sentinel lymph node detection is an accurate and safe method in the assessment of nodal status in early cervical carcinoma.

A prospective study of sentinel lymph node detection in vulval carcinoma: is it time for a change in clinical practice?

OBJECTIVES: To determine the accuracy of sentinel lymph node (SLN) detection in vulval carcinoma and to report the reliability and safety of this procedure. METHODS/MATERIALS: For a period of 6 years, we recruited women undergoing surgery for vulval carcinoma. All women had a preoperative biopsy confirming the depth of invasion greater than 1 mm. Sentinel lymph node detection was performed using the combined method (Tc-99m and methylene-blue dye). The standard management included complete inguinofemoral lymphadenectomy. When inguinofemoral lymph nodes were found grossly to be enlarged, these nodes were debulked, and the women subsequently treated with radiotherapy with or without chemotherapy. During the last 2 years of the study, a selected group of women had an SLN dissection alone. The SLNs were ultrastaged when they were negative on routine hematoxylin and eosin examination. RESULTS: Among 60 women undergoing SLN detection, SLN was detected in 59 women (98.3%) with combined method. Blue dye did not detect an SLN in 3 women resulting in a 93.3% detection rate. The median SLN count was 2 nodes (range, 1-9). Of the 60 women, 41 had inguinofemoral lymphadenectomy, 4 had only enlarged inguinofemoral nodes debulked, and 15 had the SLN only removed. The non-SLN count was 9 nodes (range, 3-17). There were no false-negative SLNs. Twenty-one women (35%) had positive nodes on final histology. Ultrastaging increased detection of metastases in 6.9% of nodes relative to routine hematoxylin and eosin examination and upstaged 12% of women. The median follow-up was 24 months (range, 2-66 months). CONCLUSIONS: Sentinel lymph node detection is safe and accurate in assessing lymph node status in women with vulval cancer undergoing staging. The combined method using Tc-99m and methylene blue dye injection for SLN detection has the best detection rate. Routine ultrastaging of negative SLN improves the detection of nodal metastases.

Antitumor efficacy and molecular mechanism of TLK58747, a novel DNA-alkylating prodrug.

BACKGROUND: DNA-damaging agents are widely used for the treatment of human malignancies. Agents containing the multifunctional alkylating moiety tetrakis(2-chloroethyl)phosphorodiamidic acid are currently under development as cancer therapeutics. MATERIALS AND METHODS: TLK58747, a phophorodiamidate-based prodrug, was tested in vivo for antitumor efficacy and safety. The in vitro responses of tumor cells to TLK58747 were examined by cytotoxicity assays, cell cycle analysis, immunoblots and microscopy. RESULTS: TLK58747 was efficacious in xenograft models of human breast, pancreas, and prostate cancer, as well as in leukemia and glioma. It caused less bone marrow suppression in rats than did cyclophosphamide. In vitro, TLK58747 inhibited the growth of a wide variety of cancer cells and activated the DNA damage-response pathway, leading to G(2)/M cell cycle arrest and subsequent premature senescence or apoptosis. CONCLUSION: TLK58747 is a promising new alkylating agent with broad antitumor activity and superior safety that warrants further development.

Application of thermal desorption to the development of a gas chromatographic/mass spectrometric method for the determination of toluene, chlorinated aromatic hydrocarbons, and 2,3,7,8-tetrachlorodibenzo-p-dioxin in combustion emissions.

A fast and accurate analytical method, which uses commercially available adsorbents (Tenax TA, Carbotrap B and C, and Carbosieve S-III), was developed for the sampling and determination of aromatic hydrocarbons, chloroaromatic compounds, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. The breakthrough volume data show that Carbotrap C has a good capacity for compounds of high molecular weight, whereas Carbosieve S-III and Tenax TA are efficient for volatile compounds. The organic components are thermally desorbed and transferred to a gas chromatograph/mass spectrometer. Importantly, thermal desorption avoids conventional solvent extraction procedures and also allows reuse of adsorbent tubes. Preliminary results for recovery of analytes from tubes packed with single adsorbent prove that a single-adsorbent bed is not capable of sampling a wide range of compounds. The best method to obtain the desired collection and desorption properties is to use adsorbent tubes containing several different materials. The results of optimization studies are summarized.

Nephrocystin-conserved domains involved in targeting to epithelial cell-cell junctions, interaction with filamins, and establishing cell polarity.

Nephrocystin is the protein product of the gene mutated in juvenile nephronophthisis, an autosomal recessive cystic kidney disease afflicting children and young adults. Because the normal cellular function of nephrocystin is largely unknown, the molecular defects underlying disease pathogenesis remain obscure. Analysis of nephrocystin amino acid sequences from human and other species revealed three distinct conserved domains including Src homology 3 and coil-coil domains in the N-terminal region, as well as a large highly conserved C-terminal region bearing no obvious homology to other proteins and hence referred to as the "nephrocystin homology domain" (NHD). The objective of this study was to gain insight into nephrocystin function by defining functional properties of the conserved domains. We analyzed a series of nephrocystin deletion mutants expressed in Madin-Darby canine kidney and COS-7 cells. This analysis revealed previously unrecognized functional attributes of the NHD, including abilities to promote both self-association and epithelial cell-cell junctional targeting. We further observed that Madin-Darby canine kidney cell lines stably expressing a nephrocystin mutant with a deletion of the Src homology 3 domain have reduced ability to establish tight junctions as measured by transepithelial electrical resistance. Finally, from a two-hybrid screen and coimmunoprecipitation studies we identified members of the filamin family of actin-binding proteins as having the capacity to interact with the NHD. These findings support a functional role for nephrocystin as a docking protein involved in organizing a protein complex to regulate the actin cytoskeleton at sites of epithelial cell-cell adhesion and further suggest that these properties are important for establishing epithelial cell polarity.