Defining lymphocyte-predominant breast cancer by the proportion of lymphocyte-rich stroma and its significance in routine histopathological diagnosis.

Lymphocyte-predominant breast cancer (LPBC) defined by the density of stromal lymphocytes shows favorable behavior. However, considerable distribution heterogeneity of lymphocytes is a major problem. The present study defined LPBC by the proportion of lymphocyte-rich stroma with the cut-off values of 30, 50, and 75%, and clinicopathologically analyzed mainly LPBC (area > 30%) defined by the cut-off value of 30%. LPBCs (area > 30%), 39 cases in total, were composed mainly of triple-negative and HER2(+) /ER(-) subtypes, without any luminal A-like subtype. LPBCs were composed predominantly of histological grade 3 tumors, without any grade 1 lesions. Multivariate analyses on 477 consecutive tumors revealed that ER-negativity and grade 3 status associated significantly with LPBC. LPBC (area > 30%) showed better disease-free survival than grade-matched controls, and it was a good indicator of complete pathological remission after pre-operative chemotherapy. Patients with LPBC with the cut-off value of 50% and that of 75% showed 100% disease-free survival. These results demonstrated the validity of our definition of LPBC. Our data also suggest that de-differentiated cancers without TILs could be regarded as high-grade cancer without lymphocyte-mediated responses. In conclusion, the definition of LPBC by the proportion of lymphoid stroma is useful for prognostication of high grade breast cancer in routine diagnosis.

Nano-sized fluorescent particles as new tracers for sentinel node detection: experimental model for decision of appropriate size and wavelength.

The concepts of made-to-order and low-invasiveness medicines are becoming widely accepted. A treatment for cancer, with minimum invasive surgery and without lymph nodes dissection based on sentinel lymph node (SN) navigation surgery, would adhere to these concepts. Dyes and/or radioisotopes are employed for SN detection in standard methods, however, each detection method has advantages and disadvantages. To make up for the disadvantages, we aimed at developing a new non-invasive method using fluorescent beads of uniform nano-size that could efficiently visualize SN from outside the body, and conducted experiments to determine the appropriate size and fluorescent wavelength. We examined various bead sizes and fluorescent wavelengths. The sizes were 20, 40, 100 and 200 nm. The fluorescent peak wavelengths of the beads were yellow-green (515 nm), dark red (680 nm), far red (720 nm) and infrared (755 nm). The beads were subcutaneously injected into the foot pad of the hind leg of a rat, and followed by laser scanning of the inguinal area for fluorescence observation. The beads exhibited different times for the fluorescence detection according to their sizes and wavelength. The 40 nm beads were considered to be the most appropriate size for SN detection in rats. The wavelength of near infrared was effective for avoiding attenuation by the tissue. In conclusion, we confirmed that uniformly nano-sized fluorescent beads have the potential to be an alternative to existing tracers in the detection of the SN in animal experiments if we select the appropriate particle size and wavelength.

Motilin regulates interdigestive gastric blood flow in dogs.

BACKGROUND & AIMS: Gastric blood flow exhibits cyclical increases in phase with the interdigestive contractions and secretion of the stomach in dogs. The aim of this study is to clarify the regulatory role of motilin in interdigestive gastric blood flow in dogs. METHODS: Blood flow of the left gastric (LGA) and superior mesenteric (SMA) arteries were measured by ultrasound transit-time blood-flow meters in 5 conscious dogs. Motilin was infused intravenously with or without Phe-cyclo[Lys-Tyr(3-tBu)-betaAla-]. trifluoroacetate (GM-109; motilin antagonist), granisetron (5-HT3 antagonist), atropine, hexamethonium (C6), phenoxybenzamine, propranolol, or cimetidine. RESULTS: Motilin (12.5, 25, 50, and 100 pmol x kg(-1) x h(-1)) induced LGA blood-flow responses, consisting of a sustained increase and a rapid phasic change coupled with a contraction, without affecting the blood pressure, heart rate, and SMA blood flow. GM-109 completely abolished the LGA, motility, and secretory responses to motilin (100 pmol x kg(-1) x h(-1)). Atropine abolished motilin-induced gastric contractions, secretion, and phasic changes of LGA blood flow but failed to affect the sustained flow increase. However, atropine partially inhibited the LGA responses to lower doses of motilin. The LGA flow responses to motilin were not inhibited by granisetron, C6, alpha-adrenergic, beta-adrenergic, or H2 blockers. Motilin induced significantly larger gastric vasodilatation than the equivalent doses of VIP. CONCLUSIONS: Motilin has a potent and selective gastric vasodilator effect, which appears to be mediated by both cholinergic and noncholinergic mechanisms. Motilin plays an important role in the regulation of interdigestive gastric blood flow in dogs.