Aim The need or otherwise for lateral pelvic node dissection (LPND) in rectal cancer patients with clinical lateral pelvic node metastasis (LPNM) after neoadjuvant chemoradiotherapy (nCRT) is controversial. This study was designed to explore the predictive factors for pathological LPNM in rectal cancer patients with clinical LPNM after nCRT.Method From January 2010 to February 2018, a consecutive series of patients with rectal cancer and clinical LPNM after nCRT who underwent total mesorectal excision and LPND were reviewed. Patient demographics, operative and pathological outcomes were collected and analysed.Results A total of 76 consecutive cases were included in this study: 53 (69.7%) patients underwent unilateral LPND and 23 (30.3%) bilateral LPND. The pathological results showed that LPNM was found in 13 (17.1%) patients. Multivariate logistic regression analysis showed that the post-nCRT lateral pelvic node size ≥ 5 mm (OR = 7.67, 95% CI = 1.45-40.63, P = 0.017) and mucinous/signet-ring adenocarcinoma (OR = 4.60, 95% CI = 1.11-19.08, P = 0.035) were independent risk factors for pathological LPNM.Conclusion Post-nCRT lateral pelvic node size ≥ 5 mm and mucinous/signet-ring adenocarcinoma were independent predictive factors of pathological LPNM for rectal cancer patients with clinical LPNM after nCRT, and patients with these characteristics may benefit from LPND.What does this paper add to the literature? The aim of this paper was to determine the optimal indication for lateral pelvic node dissection after neoadjuvant chemoradiotherapy for mid/low rectal cancer, so as to avoid the occurrence of overtreatment in clinical work.
In this small-sample study, 1-hour infusion of rhANP produced beneficial hemodynamic effects in CHF patients compared with standard therapy, and it was well tolerated. 0·1 μg/kg/min may be the optimum dose for short-term rhANP infusion to treat CHF for the further large sample trial before clinical application.
Background:The blastic phase (BP) with B‐acute lymphoblastic leukemia (B‐ALL) of chronic myelogenous leukemia (CML) are generally refractory to treatment with a survival ranging from weeks to months. Although allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is curative, it is important to eliminate the blast of ALL and achieve chronic phase (CP) before HSCT.Aims:To explore the effectiveness and advantages of FasT CD19 CAR‐T therapy, we report a case of B‐ALL (BP‐CML) treated with FasT CD19 CAR‐T.Methods:A 39‐year‐old woman had received irregular treatments for her CP‐CML, which led to B‐ALL (BP‐CML). The classic chemotherapy regimens were ineffective. The patient had T315I/V299L mutation and was resistant to the available TKIs in China. After combination chemotherapy, hematological remission was achieved. However, bone marrow examination showed lymphoblasts and the prolymphocytes was up 4.5%. PCR showed BCR‐ABL p210/ABL 99.1%, and flow cytometry showed abnormal B lymphoblasts was up to 0.5% in total karyocytes. In order to eliminate the minimal residual disease (MRD) of the blasts of B‐ALL prior to HSCT, we employed FasT CD19 CAR‐T therapy. Three days after FC preconditioning (fludarabine 50 mg d1–3, cyclophosphamide 300 mg d1–3), a low dose of FasT CAR‐T cells (5 × 104/kg) was infused. The vein‐to‐vein time of the FasT CAR‐T is 10 days, in which the manufacturing time is only 1 day.Results:Ten days after CAR‐T infusion, the patient's body temperature went up to 39 °C and returned to normal within one day. Flow cytometry showed the number of CAR‐T cells were 9.0 cells /uL blood and 42.37 cells /uL blood on Day 11 and Day 13, respectively. From Day 1–7, few CD19+ B cells detected in peripheral blood by FACS, and the CAR DNA copy could not be detected by Q‐PCR. Between Day 8 and Day 28, CD19+ B cells could not be detected in the blood, and the CAR copy number reached the highest on Day 13 (4670.2 copies/ug DNA) and dropped to 15.4 copies/ug DNA on Day 28. On Day 18, FCM and reexamination of the bone marrow showed CP‐CML, and the patient underwent allo‐HSCT on Day 39.Summary/Conclusion:Low dose FasT CD19 CAR‐T therapy showed an excellent therapeutic effect to eliminate the MRD without serious cytokines release symptom (CRS) and neurotoxicity. The infusion time was 7–10 days earlier than the conventional CD19 CAR‐T cells. The peak CAR‐T cell number and CAR copy number were detected later than the conventional CD19 CAR‐T. The expansion procedure of the novel FasT CD19 CAR‐T cells in vivo instead of in vitro may explain the later CRS and better tumor‐killing activity. Low dose FasT CD19 CAR‐T infusion gives us a new efficient approach for leukemia MRD clearance. There are still many questions that remains answered in clinic. Based on the preclinical experiment, FasT CD19 CAR‐T cells express higher level CARs and cytokines (IL‐2 and IFNγ), which may lead to more efficiency in killing than the conventional CAR‐T cells. The clinical trial (ChiCTR‐OOC‐16008448) is launched to explore new indications, proper dosages and side‐effects. At present, we have successfully treated three r/r B‐ALL patients with FasT CD19 CAR‐T therapy.image
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