The prognostic value of lymph node ratio and updated TNM classification in rectal cancer patients with adequate versus inadequate lymph node dissection.

BACKGROUND: The aim of this study was to clarify whether the lymph node ratio (LNR) is superior to the updated TNM classification regarding the prognosis of stage III rectal cancer patients who have not undergone neoadjuvant therapy. The TNM system is based on the absolute number of lymph nodes involved, and the LNR takes into account involved and examined nodes. METHODS: In 237 patients with stage III rectal cancer, we evaluated prognostic factors for 5-year overall survival (OS), disease-free survival (DFS), and risk of distant metastases (DM) using the Kaplan-Meier method, with patients divided based on adequate versus inadequate lymph node dissection (≥12 vs. <12 lymph nodes examined). The updated TNM divides patients into four groups (1, 2-3, 4-6, and ≥7 involved nodes), while LNR divides patients into quartiles. Multivariate Cox regression analyses were performed. RESULTS: Among patients with adequate lymph node dissection, the distributions within the two systems were in agreement in 141/178 (79.2 %, kappa 0.721), and the predictive values for OS, DFS, and DM were similar. In patients with inadequate lymph node dissection, the classifications of both systems were concordant in only 13/59 (22 %, kappa 0.021). The pN system significantly under-staged patients, while the LNR classification was a better predictor of OS, DFS, and DM. CONCLUSIONS: In patients with adequate lymph node dissection, LNR staging does not add substantial information to the predictions of updated TNM lymph node staging. However, in patients with inadequate lymph node harvesting, the LNR compensates for the under-staging of the TNM classification and provides a better estimation of prognosis than the updated TNM system.

Shift of C3 deposition from localization in the glomerulus into the tubulo-interstitial compartment in the absence of secreted IgM in immune complex glomerulonephritis.

The role of secretory IgM in protecting kidney tissue from immune complex glomerulonephritis induced by 4 mg horse spleen apoferritin and 0.05 mg lipopolysaccharide has been investigated in mutant mice in which B cells do not secrete IgM, but are capable of expressing surface IgM and IgD and secreting other Ig isotypes. Glomerular size, number of glomeruli per cross-section, glomerular cellularity and urine content of protein and creatinine was comparable in treated secreted IgM (sIgM)-deficient and wild-type mice. Assessment of urinary proteins by sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed a 30 kDa low molecular weight protein in treated sIgM-deficient animals only, reflecting dysfunction of proximal tubules. A shift of bound C3 from glomeruli to the tubulo-interstitial compartment in sIgM-deficient mice also suggests tubulo-interstitial damage. In contrast, local C3 synthesis within the kidney tissue did not differ between the two treated groups. Apoptosis physiologically present to maintain kidney cell homeostasis was increased slightly in treated wild-type mice. These results indicate that secretory IgM can protect the tubulo-interstitial compartment from immune complex-induced damage without having an effect on the glomerulus.

STRO-1+ mesenchymal precursor cells located in synovial surface projections of patients with osteoarthritis.

OBJECTIVE: To investigate the presence of mesenchymal precursor cells (MPCs) in synovial surface projections of patients with osteoarthritis (OA), to characterize their phenotype and to show their localization. METHODS: Progenitor cells in synovial surface projections were identified by immunohistochemistry, morphometric analysis and confocal laser scanning microscopy using the following phenotypic markers: STRO-1, CD34, and alpha smooth muscle actin (alpha-SMA). RESULTS: In the synovial tissue of all 21 patients with OA MPCs were detected. Immunohistochemistry and subsequent morphometric analysis showed that approximately twice as many STRO-1+ cells/mm2 were observed in synovial tissue of patients with OA as compared to healthy organ donors and that number of STRO-1+ cells/mm2 correlated with total cell number/mm2. Interestingly, in the synovial tissue of patients with OA, twice as many STRO-1+ cells/mm2 were found in synovial surface projections as compared to the sublining area without villi. Using confocal laser scanning microscopy two populations of STRO-1+ MPCs could be detected in synovial surface projections. Single STRO-1+ cells that co-expressed alpha-SMA resemble a population of pericyte precursors required to stabilize the immature vasculature. The second STRO-1+ cell population that was found lacked alpha-SMA but co-expressed CD34 on their surface with low intensity. CONCLUSION: Here we can show that in the synovial tissue of patients with OA twice as many STRO-1+ MPCs can be found in synovial surface projections as compared to the sublining area. These cells are preferentially located at the basis and in the protruding end of the synovial surface projection.