We could demonstrate selleck ARQ197 that the ratio of CD8+ lymphocytes to tumor buds (CD8+/tumor budding index) out-performed both tumor budding or CD8+ lymphocytes alone as independent prognostic factors in two independent cohorts[103]. Using double immunostaining for CD8+ antibody and pan-cytokeratin, a ratio of 3:1 for CD8+ lymphocytes to tumor buds was a highly favourable phenotypic constellation associated with earlier pT stage, lymph node negativity, low tumor grade and absence of vascular and lymphatic invasion in addition to conferring a prolonged clinical outcome in both stage II and stage III colorectal cancer (Figure (Figure1E1E and andF).F).

Although we cannot allude to the direct functional interaction between CD8+ lymphocytes and tumor buds themselves, the strong circumstantial relationship between the ratio of tumor budding and CD8+ lymphocytes in the microenvironment of budding cells appears, nonetheless, to be a reproducible and independent prognostic factor in colorectal cancer. DISCUSSION The invasive front of colorectal cancer represents a dynamic interface between pro- and anti-tumor factors, which can be visualized as a balance between ��attackers�� (pro-tumor) and ��defenders�� (anti-tumor). On the one hand, the infiltrating tumor border configuration and its ��cavalry�� tumor budding promote progression and dissemination of tumor cells by penetrating the vascular and lymphatic vessels. On the other, the host attempts to fend off this attack by mounting an immune response using its ��infantry��, in particular cytotoxic T lymphocytes, to protect vascular and lymphatic channels from invasion by tumor buds.

Although evidence shows that both pro- and anti-tumor factors contribute prognostic information in a TNM-independent manner, the ratio of attackers and defenders may better capture the interaction at the invasive front which could translate into more powerful prognostic indicators. Whereas standard pathology reporting of breast and prostate cancer involves additional prognostic features, such as the BRE and Gleason scores, the ratio of attackers/defenders could be a promising approach for the future development of a prognostic score for patients with colorectal cancer which could complement TNM stage to improve the clinical management of patients with this disease. Footnotes Peer reviewer: Dr.

Marek Bebenek, MD, PhD, Department of Surgical Oncology, Regional Comprehensive Cancer Center, pl. Hirszfelda AV-951 12, 53-413 Wroclaw, Poland S- Editor Wang YR L- Editor O��Neill M E- Editor Ma WH
Annular pancreas is a rare congenital anomaly, which consists of a ring of pancreatic tissue, confluent with the head of the pancreas, and partially or completely encircling the second segment of the duodenum. It was first described by Tiedemann in 1818[1] and first named ��pancreas anulare �� by Ecker in 1862[2].