The heterogeneity and clonal evolution analysis of the advanced prostate cancer with castration resistance.

BACKGROUND: Nowadays, the incidence rate of advanced and metastatic prostate cancer at the first time of diagnosis grows higher in China yearly. At present, androgen deprivation therapy (ADT) is the primary treatment of advanced prostate cancer. However, after several years of ADT, most patients will ultimately progress to castration-resistant prostate cancer (CRPC). Previous studies mainly focus on Caucasian and very few on East Asian patients. METHODS: In this study, the pre- and post-ADT tumor samples were collected from five Chinese patients with advanced prostate cancer. The whole-exome sequencing, tumor heterogeneity, and clonal evolution pattern were analyzed. RESULTS: The results showed that the gene mutation pattern and heterogeneity changed significantly after androgen deprivation therapy. Tumor Mutational Burden (TMB) and Copy Number Alteration (CNA) were substantially reduced in the post-treatment group, but the Mutant-allele tumor heterogeneity (MATH), Socio-Demographic Index (SDI), Intratumor heterogeneity (ITH), and weighted Genome Instability Index (wGII) had no significant difference. According to the clone types and characteristics, the presence of main clones in five pre-and post-treatment samples, the clonal evolution pattern can be further classified into two sub-groups (the Homogeneous origin clonal model or the Heterogeneous origin clonal model). The Progression-free survival (PFS) of the patients with the "Homogeneous origin clonal model" was shorter than the "Heterogeneous origin clonal model". The longer PFS might relate to MUC7 and MUC5B mutations repaired. ZNF91 mutation might be responsible for resistance to ADT resistance. CONCLUSION: Our findings revealed potential genetic regulators to predict the castration resistance and provide insights into the castration resistance processes in advanced prostate cancer. The crosstalk between clonal evolution patterns and tumor microenvironment may also play a role in castration resistance. A multicenter-research including larger populations with different background are needed to confirm our conclusion in the future.

Endoscopic-assisted surgery versus microsurgery for pineal region tumors: a single-center retrospective study.

Pineal region tumors are extremely deep-seated and surgically challenging. The exposure and visualization obtained by microscopic surgery are relatively limiting. The application of high-definition endoscopes has recently provided neurosurgeons with a much more magnified and clearer view of the anatomy in the pineal region. The present study was performed to compare endoscopic-assisted surgery (ES) with microsurgery (MS) for pineal region tumors. We retrospectively analyzed patients admitted to our hospital for treatment of pineal region tumors from January 2016 to June 2019. All patients consented to undergo tumor resection with ES or MS. We compared the extent of resection, postoperative rate of hydrocephalus, complications, and outcomes between the two groups to estimate the safety and efficacy of ES. In total, 41 patients with pineal region tumors were divided into 2 groups: the ES group (n = 20) and MS group (n = 21). The rate of gross total resection was significantly higher in the ES than MS group (90.0% vs. 57.1%, p = 0.04). The rate of postoperative hydrocephalus was significantly lower in the ES than MS group (11.8% vs. 52.9%, p = 0.03). No significant differences were found in complications or the Karnofsky Performance Score between the two groups. ES can be used to safely and effectively achieve complete resection of pineal region tumors. In patients with obstructive hydrocephalus, ES provides a new way to directly open the aqueduct for cerebrospinal fluid recovery following tumor resection.

Intracerebral hemorrhage cadaver model for training in hematoma evacuation under endoscopy.

Neuroendoscopic surgery has been performed as an effective method for intracerebral hemorrhage (ICH). This study describes the know-how of constructing the ICH cadaver model and the training on the main neuroendoscopic procedures for ICH. During the training, operation time of twenty trainees in main stages of craniotomy and corticotomy (stage 2), and hematoma evacuation under endoscopy (stage 3) was recorded. To distinguish factors influencing trainees' surgical proficiency, operation time was calculated according to seniority, experience in neuroendoscopic surgery and training sequence. Questionnaire about validity of model was conducted eventually. Ten ICH cadaver models with bilateral hematoma were constructed. Seven trainees worked with seniority >5 years and eleven had experience in neuroendoscopic surgery. Operation time ranged from 20.6 to 33.4 min in stage 2 and 18.5 to 24.9 min in stage 3. In stage 2, less operation time was needed for trainees with seniority >5 years comparing to trainees with seniority ≦5 years (22.56 ±â€¯1.29 vs 29.25 ±â€¯3.02 min, p < 0.01). In stage 3, significant difference of operation time was found between trainees with experience in neuroendoscopic surgery and trainees without the experience (20.08 ±â€¯1.22 vs 22.02 ±â€¯1.82 min, p = 0.014), and the same between trainees in latter group and in former group (19.75 ±â€¯0.80 vs 22.54 ±â€¯1.45 min, p < 0.01). Questionnaire feedback proved high degree of satisfaction about the training model. Therefore, the ICH cadaver model can assist neurosurgeons with neuroendoscopic treatment learning sessions. Simulation and improvement in neuroendoscopic surgical techniques for ICH treatment were possible with the help of ICH cadaver model.