PurposeThe impact of previous abdominal surgery (PAS) on surgical outcomes from laparoscopic and robot surgeries is inconclusive. This study aimed to investigate the impact of PAS on perioperative outcomes from laparoscopic and robotic colorectal surgeries.MethodsFrom March 2007 to February 2014, a total of 612 and 238 patients underwent laparoscopic and robotic surgeries, respectively. Patients were divided into 3 groups: those who did not have a PAS (NPAS), those who had a major PAS, and those who had a minor PAS. We further divided the patients so that our final groups for analysis were: patients with NPAS (n = 478), major PAS (n = 19), and minor PAS (n = 115) in the laparoscopy group, and patients with NPAS (n = 202) and minor PAS (n = 36) in the robotic surgery group.ResultsIn the laparoscopy group, no differences in the conversion rates between the 3 groups were noted (NPAS = 1.0% vs. major PAS = 0% vs. minor PAS = 1.7%, P = 0.701). In the robotic surgery group, the conversion rate did not differ between the NPAS group and the minor PAS group (1.0% vs. 2.8%, P = 0.390). Among the groups, neither the operation time, blood loss, days to soft diet, length of hospital stay, nor complication rate were affected by PAS.ConclusionPAS did not jeopardize the perioperative outcomes for either laparoscopic or robotic colorectal surgeries. Therefore, PAS should not be regarded as an absolute contraindication for minimally invasive colorectal surgeries.
Trastuzumab resistance in HER2-positive breast cancer is associated with a poorer prognosis. HSP90 is thought to play a major role in such resistance, but N-terminal inhibitors of this target have had little success. We sought to investigate the utility of NCT-547, a novel, rationally-designed C-terminal HSP90 inhibitor in the context of overcoming trastuzumab resistance. NCT-547 treatment significantly induced apoptosis without triggering the heat shock response (HSR), accompanied by caspase-3/− 7 activation in both trastuzumab-sensitive and -resistant cells. NCT-547 effectively promoted the degradation of full-length HER2 and truncated p95HER2, while also attenuating hetero-dimerization of HER2 family members. The impairment of cancer stem-like traits was observed with reductions in ALDH1 activity, the CD24low/CD44high subpopulation, and mammosphere formation in vitro and in vivo. NCT-547 was an effective inhibitor of tumor growth and angiogenesis, and no toxic outcomes were found in initial hepatic and renal analysis. Our findings suggest that NCT-547 may have applications in addressing trastuzumab resistance in HER2-positive breast cancer.
Introduction Tumor-infiltrating lymphocytes (TILs) might be associated with host-cell mediated immunity, which could be partly reflected by peripheral blood cell counts. In addition, lymphocyte-predominant breast cancer (LPBC), which was defined as tumors having high TIL levels, showed a favorable prognosis among triple-negative breast cancer or HER2-positive breast cancer. We aimed to investigate whether peripheral blood cell counts are associated with LPBC. Methods We evaluated the percentage of stromal TILs in breast cancer patients who underwent primary surgery, using the standardized methodology proposed by the international TIL Working Group. Lymphocyte-predominant breast cancer (LPBC) was defined as tumors having high TIL levels (≥50%). Peripheral blood cell counts including absolute neutrophil counts (ANC), absolute lymphocyte counts (ALC) and neutrophil-to-lymphocyte ratio (NLR) was obtained from pretreatment laboratory data. Result Of the 810 patients, 132 (16.3%) had LPBC, and 678 (83.7%) had non-LBPC. In a comparison of 3 markers of peripheral blood counts, LPBC had a significantly lower mean ANC than non-LPBC (3,304 vs. 3,564; P = 0.023), but the other means were not different. In multivariable analysis, each 1K increment in ANC corresponded to an odds ratio of 0.790 (95% CI, 0.642 to 0.971) for LPBC. In the ER-negative and high-Ki67 subgroups identified by interaction tests, significant inverse correlations between continuous ANC and TILs were noted. Conclusion Low peripheral ANC could be linked with LPBC, supporting the hypothesis that systemic immune cell counts might be associated with the tumor-immune microenvironment.
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