Bilateral negative sentinel nodes accurately predict absence of lymph node metastasis in early cervical cancer: results of the SENTICOL study.

PURPOSE: Sentinel lymph node (SLN) biopsy may be used to target lymph node metastases in patients with early cervical cancer. Whether SLN biopsy only is acceptable in the staging and surgical management of early cervical cancer remains unknown. This prospective multicenter study (SENTICOL [Ganglion Sentinelle dans le Cancer du Col]) assessed the sensitivity and negative predictive value (NPV) of SLN biopsy. PATIENTS AND METHODS: Adults with cervical carcinoma who met the International Federation of Gynecology and Obstetrics criteria for stage IA1 with lymphovascular space invasion to stage IB1 underwent technetium 99 lymphoscintigraphy and Patent Blue injection followed by laparoscopic lymph node mapping, SLN removal, and lymph node dissection. Only surgeons trained in SLN biopsy in cervical carcinoma participated in the study. SLNs and nonsentinel lymph nodes underwent routine staining. Negative SLNs were subjected to ultrastaging. The reference method was pelvic and/or para-aortic lymphadenectomy with histologic examination of all nodes. RESULTS: One hundred forty-five patients were enrolled, and 139 were included in a modified intention-to-diagnose analysis. Intraoperative radioisotope-blue dye mapping detected at least one SLN in 136 patients (97.8%; 95% CI, 93.8% to 99.6%), 23 of whom had true-positive results and two who had false-negative results, yielding 92.0% sensitivity (23 of 25; 95% CI, 74.0% to 99.0%) and 98.2% NPV (111 of 113; 95% CI, 74.0% to 99.0%) for node metastasis detection. No false-negative results were observed in the 104 patients (76.5%) in whom SLN were identified bilaterally. CONCLUSION: Combined labeling for node mapping was associated with high rates of SLN detection and with high sensitivity and NPV for metastasis detection. However, SLN biopsy was fully reliable only when SLNs were detected bilaterally.

Fibrogenic signals in patients with radiation enteritis are associated with increased connective tissue growth factor expression.

PURPOSE: To investigate the expression of a new fibrogenic cytokine the connective tissue growth factor (CTGF) in intestinal radiation fibrosis and to characterize the mesenchymal cell subtypes involved in CTGF synthesis and collagen deposition. METHODS AND MATERIALS: Sixteen patients with radiation enteritis that occurred after radiotherapy for pelvic malignancies and 6 with histologically normal bowel entered the study. Immunohistochemistry, Western blot analysis, and real-time reverse transcriptase-polymerase chain reaction were performed to study CTGF expression, along with other known markers of radiation fibrosis: the pro-fibrogenic cytokine transforming growth factor (TGF)-beta1 and phenotypic markers of the fibroblast differentiation the alpha-sm actin (A), vimentin (V), and desmin (D). Finally, the collagen accumulation was measured by Sirius red staining and colorimetric assay. RESULTS: Radiation enteritis was characterized by increased collagen content within the intestinal wall. CTGF immunoreactivity, protein, and mRNA level were increased in radiation enteritis compared with the healthy bowel. On the contrary, no increase of the TGF-beta1 mRNA level was observed in radiation enteritis compared with healthy bowel, and the level of TGF-beta protein was slightly increased in radiation enteritis. A co-localization of CTGF immunoreactivity and collagen deposition was found in the extracellular matrix and subtypes of activated mesenchymal cells with a fibroblast phenotype (V(+)/D(-)/A(-)) and myofibroblast phenotype (V(+)/D(-/+)/A(+)). CONCLUSION: The increased level of CTGF protein and mRNA associated with the accumulation of fibroblasts/myofibroblasts and collagen deposition were parts of the fibrogenic signals involved in the persistence of late intestinal radiation fibrosis.