No abstract

The applicability of circulating tumor DNA (ctDNA) genotyping to inform enrollment of patients with cancer in clinical trials has not been established. We conducted a phase 2 trial to evaluate the efficacy of pertuzumab plus trastuzumab for metastatic colorectal cancer (mCRC), with human epidermal growth factor receptor 2 (HER2) amplification prospectively confirmed by tumor tissue or ctDNA analysis (UMIN000027887). HER2 amplification was confirmed in tissue and/or ctDNA in 30 patients with mCRC. The study met the primary endpoint with a confirmed objective response rate of 30% in 27 tissue-positive patients and 28% in 25 ctDNA-positive patients, as compared to an objective response rate of 0% in a matched real-world reference population treated with standard-of-care salvage therapy. Post hoc exploratory analyses revealed that baseline ctDNA genotyping of HER2 copy number and concurrent oncogenic alterations adjusted for tumor fraction stratified patients according to efficacy with similar accuracy to tissue genotyping. Decreased ctDNA fraction 3 weeks after treatment initiation associated with therapeutic response. Pertuzumab plus trastuzumab showed similar efficacy in patients with mCRC with HER2 amplification in tissue or ctDNA, showing that ctDNA genotyping can identify patients who benefit from dual-HER2 blockade as well as monitor treatment response. These findings warrant further use of ctDNA genotyping in clinical trials for HER2-amplified mCRC, which might especially benefit patients in first-line treatment.

We have shown that using Interceed in laparoscopic colorectal surgery is valid and technically safe.

Rats were sensitized with ovalbumin (OVA) with a molecular weight of 45 kd, challenged with OVA orally, followed by orally administered beta-lactoglobulin (BLG) as an intestinal permeability marker. BLG is a macro-molecular protein with a molecular weight of 18 kd. Blood BLG concentrations were measured (by ELISA) serially over 4 hours following BLG administration, which in turn was given 1 hour after OVA challenges. The maximum BLG concentration was at 2 hours. BLG was then administered orally 1, 3, 6, 12 and 24 hours after oral OVA challenge, and the serum BLG concentration at 2 hours after BLG administration was compared among the five groups. BLG appeared in the circulation of the animals 1, 6 and 24 hours after allergen challenge, but not after 3 and 12 hours. The serum BLG concentration was not significantly different at 1, 6 and 24 hours. Histopathological examinations of the intestines showed mast cell infiltration of the intestinal mucosa at 1 hour, remarkable edema of villi at 3 hours, eosinophil infiltration at 6 hours, an increase of goblet cells at 12 hours and villous atrophy and lymphocyte infiltration at 24 hours. The appearance in the serum of three BLG peaks of comparable heights suggested that the intestinal absorption of BLG may be related to a late and delayed phase as well as the immediate IgE-dependent phase response.

We studied the l-type isoproterenol inhalation therapy for patients with severe asthmatic attacks who were admitted at the Department of Allergy of National Children’s Hospital from 1981 to 1991. One hour after l-type isoproterenol inhalation therapy, statistically significant effects were noted with regard to the asthmatic status. Moreover, no side effect was found amoung the subjects. From these data, l-type isoproterenol inhalation therapy is thought to be effective for severe asthmatic attacks.