Plasma endothelin and nitric oxide levels in patients with acute pancreatitis

Objective: To explore the changes of plasma endothelin(ET) and nitric oxide (NO) levels in patients with a-cute pancreatitis.Methods: The level of plasma ET was measured by ra-dioactive-immunoassay, and NO by spectrophotometry.Results: The levels of ET, NO and the ET/NO ratioin patients with severe acute pancreatitis(SAP) within24 hours in hospital were all significantly higher thanthose in other groups of patients [(176±8)pg/ml,(97±11) μmol/L, and 1.83±0.12, P<0.01]. Com-pared to healthy controls(N), the levels of ET and NOin patients without pancreatitis acute abdomen (NAP)and patients with mild acute pancreatitis (MAP) in-creased significantly (P<0.01). After appropriate treat-ment, the levels of ET and NO in the MAP groupwere lower (P<0.01). Compared with those beforetreatment, the levels of ET and NO in the SAP groupon the 3rd and 7th day in hospital dropped signifi-cantly(P<0.01).The ET/NO ratio on the 7th daywas also lower than that on admission (P<0.01).Conclusions: The malfunction of endothelial cells andthe increased ET/NO ratio may be related to the mecha-nism of pancreatic microcirculatory disturbance in pa-tients with SAP; early dynamic determination of theseparameters may help predict the prognosis of SAP.

Regional location of lymph node metastases predicts survival in patients with de novo metastatic prostate cancer

To report the regional locations of metastases and to estimate the prognostic value of the pattern of regional metastases inmen with metastatic hormone-sensitive prostate cancer (mHSPC), we retrospectively analyzed 870 mHSPC patients betweenNovember 28, 2009, and February 4, 2021, from West China Hospital in Chengdu, China. The patients were initially classifiedinto 5 subgroups according to metastatic patterns as follows: simple bone metastases (G1), concomitant bone and regional lymphnode (LN) metastases (G2), concomitant bone and nonregional LN (NRLN) metastases (G3), lung metastases (G4), and livermetastases (G5). In addition, patients in the G3 group were subclassified as G3a and G3b based on the LN metastatic plane(below or above the diaphragm, respectively). The associations of different metastatic patterns with castration-resistant prostatecancer-free survival (CFS) and overall survival (OS) were analyzed by univariate and multivariate analyses. The results showedthat patients in G1 and G2 had relatively favorable clinical outcomes, patients in G3a and G4 had intermediate prognoses, andpatients in G3b and G5 had the worst survival outcomes. We observed that patients in G3b had outcomes comparable to those inG5 but had a significantly worse prognosis than patients in G3a (median CFS: 8.2 months vs 14.3 months, P = 0.015;medianOS: 38.1 months vs 45.8 months, P = 0.038). In conclusion, metastatic site can predict the prognosis of patients with mHSPC,and the presence of concomitant bone and NRLN metastases is a valuable prognostic factor. Furthermore, our findings indicatethat the farther the NRLNs are located, the more aggressive the disease is.

The safety of radium-223 combined with new-generation hormonal agents in bone metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis

Patients with bone metastatic castration-resistant prostate cancer (mCRPC) might benefit from radium-223 (^(223)Ra) combined withnew-generation hormonal agents (NHAs) in terms of survival and quality of life (QoL). However, the safety of combination therapiesremains unclear. Therefore, we aimed to perform a network meta-analysis by reviewing the literature about the combination of^(223)Ra with abiraterone acetate plus prednisone (AAP) or enzalutamide and to evaluate the safety of combination therapy in bonemCRPC patients. Ultimately, ten studies (2835 patients) were selected, including four randomized controlled trials (RCTs), fiveretrospective cohort studies, and one single-arm study. Overall, there was no difference in the incidence of fracture between the^(223)Ra+NHA combination group and the ^(223)Ra monotherapy group (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.91–2.34,P = 0.66), but the incidences in both the ^(223)Ra+NHA combination group (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01) and the ^(223)Ramonotherapy group (OR: 2.24, 95% CI: 1.23–4.08, P < 0.01) were higher than that in the NHA monotherapy group. However, inthe meta-analysis involving only RCTs, there was no difference between the ^(223)Ra monotherapy group and the NHA monotherapygroup (OR: 1.14, 95% CI: 0.22–5.95, P = 0.88), while the difference between the ^(223)Ra+NHA combination group and the NHAmonotherapy group remained significant (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01). Symptomatic skeletal events (SSEs), SSE-freesurvival (SSE-FS), all grades of common adverse events (AEs), and ≥grade 3 AEs among all groups did not show any significantdifference. Our results indicate that the combination of ^(223)Ra with NHAs was well tolerated in bone mCRPC patients compared to ^(223)Ra monotherapy, even though the incidence of fracture was higher in patients who received ^(223)Ra than that among those whoreceived NHA monotherapy. More evidence is needed to explore the safety and efficiency of ^(223)Ra combination therapies.

Relationships of body composition and adipocytokines with outcomes in metastatic castration-resistant prostate cancer patients receiving docetaxel chemotherapy

We evaluated the relationships of body composition and serum adipocytokine levels with progression-free survival(PFS)and overall survival(OS)in metastatic castration-resistant prostate cancer(mCRPC)patients receiving docetaxel.The medical records of mCRPC patients who received docetaxel between January 2011 and December 2015 at Fudan University Shanghai Cancer Center(Shanghai,China)were reviewed.The following body composition parameters were calculated using computed tomography:skeletal muscle index(SMI),visceral adipose tissue index(VATI),and subcutaneous adipose tissue index(SATI).Pretreatment serum adipocytokine levels,including interleukin 6,insulin,leptin,monocyte chemoattractant protein-1,adiponectin,and resistin,were measured using the multiplex bead-based immunoassays.Cox regression and Kaplan–Meier methods were used for survival analyses.Of the 453 mCRPC patients initially identified,105 were included in the analysis.High VATI group patients had longer PFS(median,10 months vs 7 months,P=0.008)and OS(median,24 months vs 15 months,P=0.017),compared with low VATI group patients.SMI and SATI were not significantly associated with PFS or OS.Of the six detected adipocytokines,only leptin was associated with mCRPC prognosis.High leptin group patients had shorter PFS(median,7 months vs 12 months,P=0.0018)and OS(median,17 months vs 22 months,P=0.042),compared with low leptin group patients.Multivariate analysis showed that a high VATI was an independent protective factor for PFS and OS,while a high leptin level was an independent risk factor for PFS and OS.Therefore,VATI and serum leptin levels could provide important information concerning mCRPC prognosis.

Prior switching to a second-line nonsteroidal antiandrogen does not impact the therapeutic efficacy of abiraterone acetate in patients with metastatic castration-resistant prostate cancer： a real-world retrospective study

Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen （NSAA） is still widely used in treating metastatic castration-resistant prostate cancer （mCRPC）, especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate （Abi） remains uncertain, in the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA （from bicalutamide to flutamide） before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan-Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival （PSA-PFS, 5.5 vs 5.6 months, P = 0.967）, radiographic progression-free survival （rPFS, 12.8 vs 13.4 months, P = 0.508）, overall survival （OS, not reached vs 30.6 months, P = 0.606）, or PSA-response rate （71.4% [15121] vs 60.6% [40166], P = 0.370）. This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors＇ decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.

Predictive efficacy of the 2014 International Society of Urological Pathology Gleason grading system in initially diagnosed metastatic prostate cancer

We compared the predictive ability of the 2014 and 2005 Gleason grading systems in 568 patients initially diagnosed with metastatic prostate cancer （PCa）. Outcomes included the duration of castration-resistant prostate cancer-free survival （CFS） and overall survival （OS）. Univariate analyses and log-rank tests were used to identify prognosis indicators and assess univariable differences in CFS and OS in Gleason score （GS） groups. Cox proportional hazards and area under the curves of receiver operator characteristics methods were used to evaluate the predictive efficacy of the 2005 and 2014 ISUP grading systems. Univariate analyses showed that the 2005 and 2014 grading systems were prognosticators for CFS and OS; both systems could distinguish the clinical outcome of patients with GS 6, GS 7, and GS 8-10. Using the 2014 criteria, no statistical differences in patient survival were observed between GS 3 ＋ 4 and GS 4 ＋ 3 or GS 8 and GS 9-10. The predictive ability of the 2014 and 2005 grading systems was comparable for CFS and OS （P = 0.321）. However, the 2014 grading system did not exhibit superior predictive efficacy in patients initially diagnosed with PCa and bone metastasis; trials using larger cohorts are required to confirm its predictive value. To the best of our knowledge, ours is the first study to compare the 2005 and 2014 grading systems in initially diagnosed PCa with bone metastasis. At present, we recommend that both systems should be used to predict the prognosis of patients with metastatic PCa.

Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer(mCRPC).Here,we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate(AA).We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018.All cases received AA plus prednisone as first-line therapy during mCRPC.Primary end points were biochemical progression-free survival(bPFS)and overall survival(OS).The risk groups were defined based on multivariate analysis.A total of 42(41.6%)and 25(24.8%)patients achieved 30%and 50%decline in prostate-specific antigen(PSA),respectively,after corticosteroid switching.The median bPFS and median OS on AA plus dexamethasone were 4.9(95%confidence interval[CI]:3.7–6.0)months and 18.8(95%CI:16.2–30.2)months,respectively.Aldo-keto reductase family 1 member C3(AKR1C3)expression(hazard ratio[HR]:2.15,95%Cl:1.22–3.80,P=0.008)and baseline serum alkaline phosphatase(ALP;HR:4.95,95%Cl:2.40–10.19,P<0.001)were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS.Only baseline serum ALP>160 IU l−1(HR:3.41,95%Cl:1.57–7.38,P=0.002)together with PSA level at switch≥50 ng ml−1(HR:2.59,95%Cl:1.22–5.47,P=0.013)independently predicted poorer OS.Based on the predictive factors in multivariate analysis,we developed two risk stratification tools to select candidates for corticosteroid switching.Detection of serum ALP level,PSA level,and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.