Results of local excision of benign and malignant rectal lesions.

Local excision of selected rectal cancers is an acceptable alternative to radical surgery. The results of local excision of various rectal lesions using either the transanal or trans-sacral approach were reviewed over a 10-year period at this institution. A total of 56 procedures were performed on 47 patients (50 transanal/six trans-sacral). The trans-sacral approach was used six times on five patients for lesions averaging a distance of 8 cm from the anal verge. The transanal approach was used 50 times on two patients for lesions occurring at an average distance of 5 cm from the anal verge. Twenty-six malignant lesions were excised (25 transanal/one trans-sacral) with pathologies ranging from poorly to well-differentiated adenocarcinoma. Staging included 12 T1 lesions (46%), 10 T2 lesions (38%), and four T3 lesions (16%). Eighteen malignancies were completely excised and recurrence occurred in four of 18 (22%) with an average follow-up of 2.3 years (range 0-10 years). Local recurrence occurred in two patients (T1 and T2 lesions) and recurrence was in the form of distant metastasis in two patients (two T3 lesions). Three of the recurrences occurred in patients with T3 lesions (three of four; 75%), two occurred in a patient with a T2 lesion (two of 10; 20%), and one occurred in a patient with a T1 lesion (one of 12; 8%). There were no cancer-related deaths during the study period. Twenty-six premalignant lesions (adenomatous polyps) and four benign lesions were excised (25 transanal/five trans-sacral). Local recurrence occurred 10 times with an average follow-up of 1.8 years. In conclusion local excision of certain rectal cancers is an acceptable alternative in the treatment of these malignancies.

CD40-CD154 interactions between macrophages and natural killer cells during sepsis are critical for macrophage activation and are not interferon gamma dependent.

Natural killer (NK) cell interactions with macrophages have been shown to be important during bacterial sepsis in activating macrophages to improve bacterial clearance. The mechanism for this increased activation, however, is unclear. This study determines the relative roles of interferon (IFN)-gamma and CD40/CD154 direct cell interactions on macrophage and NK cell activation in an experimental model of sepsis. Splenic NK cells and peritoneal macrophages were isolated and cultured alone or in coculture, with and without LPS. CD69 expression on NK cells, phagocytosis ability of macrophages, and cell cytokine production was assessed at 24 and 48 h. Coculture of NK cells and macrophages significantly increased activation levels of both cell types, and through experiments culturing NK cells with supernatants from stimulated macrophages and macrophages with supernatants from stimulated NK cells, this activation was determined to be cell-contact-dependent. Similar experiments were conducted using NK cells from IFN-gamma deficient (-/-) mice, as well as anti-IFN-gamma neutralizing antibody. These experiments determined that IFN-gamma is not required for NK or macrophage activation, although it did augment activation levels. Experiments were again repeated using peritoneal macrophages from CD40-/- mice or splenic NK cells from CD154-/- mice. CD40/CD154 interactions were important in the ingestion of bacteria by macrophages, but did not affect NK cell activation at 24 h. There was, however, a protective effect of CD40/CD154 interactions on NK cell activation-induced cell death that occurred at 48 h. CD40/CD154 interactions between macrophages and NK cells are therefore important in macrophage phagocytosis, and are not dependent on IFN-gamma.