ABSTRACT
Objective:The real-world clinical data of patients with newly diagnosed ovarian cancer (including fallopian tube cancer and primary peritoneal cancer) who received first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi) were retrospectively analyzed, and the prognostic factors were preliminarily explored.Methods:(1) The clinicopathological data and follow-up data of ovarian cancer patients treated with PARPi first-line maintenance therapy from August 2018 (PARPi was launched in China) to December 31, 2021 in Sichuan Cancer Hospital were collected (real-world clinical data). (2) According to the different types of PARPi, real-world clinical data were divided into olaparib group and niraparib group, which were respectively compared with the inclusion and exclusion criteria of representative domestic and foreign phase Ⅲ randomized controlled trials (RCT), including olaparib as first-line maintenance therapy for advanced ovarian cancer patients with BRCA1/2 gene mutation (SOLO-1 study), niraparib as first-line maintenance therapy (PRIMA study), and niraparib as first-line maintenance therapy for Chinese advanced ovarian cancer patients (PRIME study). (3) The prognosis of the two groups and the prognostic factors were analyzed.Results:(1) A total of 83 patients were included in this study, with a median age of 51 years (47-57 years), including 75 cases of ovarian cancer, 5 cases of fallopian tube cancer, and 3 cases of primary peritoneal cancer; 5 cases of stage Ⅰ, 9 cases of stage Ⅱ, 55 cases of stage Ⅲ, 12 cases of stage Ⅳ, and 2 cases of unknown stage; neoadjuvant chemotherapy (NACT) was performed in 40 cases and non-NACT in 43 cases; 62 cases had no visible residual lesion after surgery (R0), 9 cases had residual disease lesions <1 cm (R1), 8 cases had residual disease lesions ≥1 cm (R2), and 4 cases with unknown postoperative residual disease. Thirty-two cases had PARPi treatment interruption, 40 cases had PARPi reduction, and 1 case terminated treatment due to acute leukemia. Of the 83 patients, 35 were in the olaparib group and 48 were in the niraparib group. The proportion of patients with high-grade serous carcinoma (100% and 75%, respectively) and the proportion of BRCA mutant patients (91% and 10%, respectively) in the olaparib group were higher than those in the niraparib group (all P<0.01). (2) Compared with the inclusion and exclusion criteria of the SOLO-1 study, the olaparib group had only 60% (21/35) coincidence rate; compared with the inclusion and exclusion criteria of PRIMA and PRIME studies, the coincidence rates of niraparib group were only 31% (15/48) and 69% (33/48). The most common reasons for non-compliance were number of chemotherapy courses, histopathological type, and surgical pathological stage. (3) Of the 83 cases received first-line maintenance therapy with PARPi, the median follow-up was 15.9 months (11.3-22.9 months), the median progression-free survival (PFS) was 29.7 months (95% CI: 25.9-33.6 months), and the median overall survival was 49.8 months (95% CI: 47.4-52.2 months). Univariate analysis showed that unilateral or bilateral ovarian cancer, efficacy after platinum-containing chemotherapy, presence or absence of measurable lesions at the end of chemotherapy, and total number of chemotherapy courses were significantly associated with PFS (all P<0.05). Multivariate analysis showed that unilateral or bilateral ovarian cancer, total number of chemotherapy courses, and efficacy after platinum-containing chemotherapy were independent factors affecting PFS in stage Ⅱ-Ⅳ patients with PARPi first-line maintenance therapy (all P<0.05). Conclusions:Unilateral ovarian cancer, the total number of chemotherapy courses no more than 9, and achieving complete response after platinum-containing chemotherapy before maintenance therapy are independent influencing factors of PFS benefit in patients with PARPi first-line maintenance therapy. Due to the large differences between the patients in real clinical practice and the research subjects of phase Ⅲ RCT, the results of representative retrospective studies still have important clinical reference significance.
ABSTRACT
Objective:To introduce the technical essentials of cytoreduction surgery (CRS) with extensive peritonectomy （“rolling carpet” surgery） in stage Ⅲc epithelial ovarian cancer (EOC) and evaluate the feasibility and safety of the operation by analyzing the incidence of surgical complications and perioperative mortality.Methods:From December 2017 to December 2019, 30 patients with stage IIIc EOC who underwent “rolled carpet” CRS and 30 patients who underwent traditional CRS at the same period in Sichuan Cancer Hospital were collected. To summarize the key points of “rolled carpet” CRS operation technology, i.e. the extraperitoneal space was the cut path of ovarian cancer operation, and the tumor in the pelvic cavity was dissociated from the extraperitoneal space of the pelvic cavity. The tumor in the pelvic cavity and all the implants or potential metastases on the parietal peritoneum were removed completely. The clinical and pathological characteristics between the two groups were analyzed retrospectively, and the feasibility and safety of “rolling carpet” CRS were evaluated by comparing the operation related indexes and the occurrence of surgical complications between the two groups.Results:(1) Clinicopathological features: the age of patients in “rolling carpet” CRS group and traditional CRS group were respectively (55.4±9.6) and (54.6±9.5) years, and the median peritoneal cancer index (PCI) was 12 (range, 4-24) and 10 (range, 5-18), respectively. There were no statistical significance between the two groups (all P>0.05). (2) Operation related indexes: in the “rolled carpet” CRS group, all patients （100%, 30/30） were performed optimal CRS, reaching completeness of cytoreduction score （CC score）, named CC-0 score, and there was no visible residual lesion after operation. While, in the traditional CRS group, 23 patients （77%, 23/30） reached CC-0 score, 5 cases （17%, 6/30） reached CC-1 score, 2 cases （7%, 2/30） reached CC-2 score, and there were statistical significance between the two groups ( P=0.011). The median surgical time was 315 minutes (range, 252-446 minutes) vs 268 minutes (range, 215-372 minutes), the median intraoperative blood loss was 589 ml (range, 300-900 ml) vs 450 ml (range, 250-800 ml), the median ICU hospital stay time was 2 days (range, 1-7 days) vs 1 day (range, 0-5 days), the median total hospital stay time was 14 days (range, 9-17 days) vs 12 days (range, 7-15 days). There were no statistical significance between the two groups (all P>0.05). (3) Surgical complications: there were respectively 5 cases (17%, 5/30) and 3 cases (10%, 3/30) complications with Clavien-Dindo grading Ⅰ-Ⅱ, which was significant no difference between the “rolled carpet” CRS group and the traditional CRS groups ( P>0.05). No re-operations were needed and the operative mortality was 0. Conclusion:It is safe and feasible to perform “rolled carpet” CRS in patients with advanced stage Ⅲc EOC with peritoneum implantation and metastasis, which could achieve optimal CRS, and has an acceptable incidence of perioperative complications, no perioperative death.
ABSTRACT
Objective To investigate the effects of S-allylcysteine ( SAC ) , on nitric oxide ( NO ) production and antioxidant enzyme activities in hyperlipidemic rats. Methods Male Wistar rats were randomly divided into seven groups. Five groups including normal control group ( normal diet) , model control group ( high-fat diet, HFD) and SAC low,medium,high treated group (high-fat diet +25,50,100 mg·kg-1 SAC) were sacrificed after 4 weeks dosing,while the other two groups including L-arginine group (normal diet+ 20 mg·kg-1 L-arginine) and SAC+L-arginine group (50 mg·kg-1 SAC+20 mg·kg-1 L-arginine) were sacrificed at 4 h after dosing. The serum, livers and kidneys were collected. The levels of NO, the activities of nitric oxide synthase ( NOS ) , antioxidant enzymes in vivo and L-arginine contents in serum were determined. Results Comparing with model control group, the activities of total NOS in serum and liver were significantly reduced in SAC-treated groups (P<0. 05). The level of L-arginine in SAC-treated groups was (8. 25 ± 1. 15), (7. 76 ± 1. 24) and (7. 22 ± 1. 64)μg·mL-1 , respectively. Compared with model control group, the level of L-arginine were significantly reduced in SAC-treated groups (P<0. 05). Comparing with L-arginine group, the activities of total NOS (T-NOS) and iNOS were reduced in SAC+L-arginine group. SAC treatment (100 mg·kg-1) significantly increased the activities of superoxide dismutase (SOD) (P<0. 01) and the level of glutathione (GSH) (P<0.01), and decreased the level of malondialdehyde (MDA) in serum and liver of hyperlipidemic rats. Conclusion These data suggest that SAC inhibits the NO production by reducing iNOS activity, arginine concentration and exhibited antioxidant activity, which may play a pharmacologically important role in protection from oxidative injury and pathogenesis of atherosclerosis.
ABSTRACT
Objective To evaluate the incidence and significance of perineural invasion (PNI) in cervical cancer. Methods Retrospective chart review of patients with cervical cancer (stages Ⅰa2-Ⅱb) who underwent radical hysterectomy and pelvic lymphadenectomy from 2007 to 2012. To evaluate the incidence and significance of PNI in cervical and uterine tissues by microscopic examination. Results A total of 238 patients were included, 9.2% (22/238) patients with PNI in the cervical stroma. Patients with PNI were more likely to have adverse histopathologic features, including lymphoma vascular space invasion, parametrical invasion, depth of invasion, tomor size and lymph nodes metastases (all P0.05). Patients with PNI had shorter disease-free and overall survival (P=0.002 and P=0.008, respectively). On multivariate analysis, risk factors for recurrence and death included parametrical invasion and depth of invasion (P0.05). Conclusions PNI exists in early cervical cancer. PNI is associated with tumor size, depth of invasion, parametrical invasion, lymphoma vascular space invasion and lymph nodes metastases. PNI represente a decreasing disease-free and overall survival in patients with early-stage cervical cancer, and is independently associated with multiple high-risk factors, which be informed management decisions regarding adjuvant therapy.
ABSTRACT
AIM To investigate if inhibiting neutrophil infiltration and adhesion molecules expression is a part of the mechanisms of ginsenoside Rg1 protecting from cerebral injury after cerebral ischemia-reperfusion. METHODS Rats were pretreated with ginsenoside Rg1 25, 50 and 100 mg·kg-1·d-1, ig, for 7 d, respectively, then subjected to cerebral ischemia (middle cerebral artery occlusion) for 2 h and reperfusion for 22 h. The infarct volume and the neurological deficit were determined by TTC staining and Longa's scoring, respectively. The infiltration of neutrophils was evaluated by measuring the activity of myeloperoxidase (MPO). The expressions of intercellular adhesion molecule-1 (ICAM-1) and E-selectin were analyzed by Western blot. The permeability of the blood-brain barrier was evaluated by measurement of Evans blue content in brain tissue with spectrophotometer at 4 h after reperfusion. RESULTSCompared with vehicle-treated group, ginsenoside Rg1 (50 and 100 mg·kg-1·d-1) treatment significantly reduced infarct volume and elevated permeability of blood-brain barrier, alleviated the neurological deficit, and inhibited protein expressions of ICAM-1 and E-selectin in brain tissue. CONCLUSION Ginsenoside Rg1 has protective effects on cerebral injury induced by ischemia-reperfusion through inhibiting neutrophil infiltration and expression of the adhesion molecules.