Radical cystectomy with extended lymphadenectomy: evaluating separate package versus en bloc submission for node positive bladder cancer.

PURPOSE: To provide future mapping analysis of lymph node positive disease we modified our lymphadenectomy at radical cystectomy for bladder cancer from an en bloc packet to 13 separate nodal packets. We evaluated the clinical and pathological findings resulting from this modification. MATERIALS AND METHODS: A total of 1,359 patients underwent en bloc radical cystectomy and extended lymphadenectomy for bladder cancer. They were compared to 262 patients who underwent radical cystectomy and extended lymphadenectomy with lymph nodes submitted in 13 distinct nodal packets. Overall 317 patients (23%) of the en bloc group (group 1) and 66 of the 262 (25%) in the separately packaged group (group 2) had node positive disease. Clinical and pathological findings were analyzed to compare these 2 groups of patients. RESULTS: Although the incidence of lymph node positivity was not different, the median number of total lymph nodes removed in group 2 was significantly higher than that in group 1 (68, range 14 to 132 vs 31, range 1 to 96, p<0.001). A trend toward more lymph nodes involved was observed in group 2 compared to group 1 (3, range 1 to 91 vs 2, range 1 to 63, p=0.062). These findings significantly lowered median lymph node density in group 2 compared to that in group 1 (6% vs 9%, p=0.006). CONCLUSIONS: Although the overall incidence of lymph node positive disease was not different, the submission of 13 separate nodal packets at radical cystectomy significantly increased the total number of lymph nodes removed/analyzed and identified a slightly higher number of positive lymph nodes compared to en bloc submission.

Fully human, HLA-DR-specific monoclonal antibodies efficiently induce programmed death of malignant lymphoid cells.

The Human Combinatorial Antibody Library (HuCAL) was screened for antibodies specific to human leukocyte antigen-DR (HLA-DR) that induce programmed death of lymphoma/leukemia cells expressing the target antigen. The active Fab fragments were affinity-matured, and engineered to IgG(4) antibodies of sub-nanomolar affinity. The antibodies exhibited potent in vitro tumoricidal activity on several lymphoma and leukemia cell lines and on chronic lymphocytic leukemia patient samples. They were also active in vivo in xenograft models of non-Hodgkin lymphoma. Cell death occurred rapidly, without the need for exogenous immunological effector mechanisms, and was selective to activated/tumor-transformed cells. Although the expression of HLA-DR on normal hematopoietic cells is a potential safety concern, the antibodies caused no long-lasting hematological toxicity in primates, in vivo. Such monoclonal antibodies offer the potential for a novel therapeutic approach to lymphoid malignancies.