Antibacterial and Anti-inflammatory Effects of Clarithromycin-Loaded Poly(l-Lactide) Membrane in Rabbit Postoperation Model of Chronic Rhinosinusitis.

OBJECTIVE: Macrolide antibiotics are often used to prevent infection and inflammation after functional endoscopic sinus surgery for the treatment of chronic rhinosinusitis (CRS). The purpose of this study was to investigate the anti-inflammatory and antibacterial effects of the clarithromycin-loaded poly(-lactide) (CLA-PLLA) membrane and its mechanism. STUDY DESIGN: Randomized controlled trial. SETTING: Animal Experiment Center. METHODS: We compared the difference between poly(l-lactide) (PLLA) and CLA-PLLA membranes by observing the morphology of fibrous scaffolds, measuring water contact angle, tensile strength, and drug release capacity, and evaluating the antimicrobial activity of CLA-PLLA. Twenty-four rabbits were divided into a PLLA group and a CLA-PLLA group after establishing CRS models. Another 5 normal rabbits comprised the control group. After 3 months, we placed the PLLA membrane in the nasal cavity of the PLLA group and the CLA-PLLA membrane in the CLA-PLLA group. Then, 14 days later, we evaluated the histological and ultrastructural changes in the sinus mucosa, protein, and messenger RNA (mRNA) levels of interleukin (IL)-4, IL-8, tumor necrosis factor-α, transforming growth factor-ß1, α-smooth muscle actin, and type I collagen. RESULTS: The CLA-PLLA membrane showed no significant difference in physical performance to the PLLA membrane, which continuously released 95% of the clarithromycin (CLA) for 2 months. The CLA-PLLA membrane had significant bacteriostatic properties that can improve the morphology of mucosal tissues, and inhibit protein and mRNA expression of inflammatory cytokines. In addition, CLA-PLLA also inhibited the expression of fibrosis-associated marker molecules. CONCLUSION: The CLA-PLLA membrane released CLA slowly and continuously, providing antibacterial, anti-inflammatory, and antifibrotic effects in a rabbit model of postoperative CRS.

Diagnosis and treatment of primary seminoma of the prostate: A case report and review of literature.

BACKGROUND: Primary seminoma of the prostate (PSP) is a rare type of extragonadal germ cell tumour that is easily misdiagnosed, owing to the lack of specific clinical features. It is therefore necessary for clinicians to work toward improving the accuracy of PSP diagnosis. CASE SUMMARY: A 59-year-old male patient presenting with acute urinary retention was admitted to a local hospital. A misdiagnosis of benign prostatic hyperplasia led to an improper prostatectomy. Histopathology revealed PSP invading the bladder neck and bilateral seminal vesicles. Further radiotherapy treatment for the local lesion was performed, and the patient had a disease-free survival period of 96 mo. This case was analysed along with 13 other cases of PSP identified from the literature. Only four of the cases (28.6%) were initially confirmed by prostate biopsy. In these cases, imaging examinations showed an enlarged prostate (range 6-11 cm) involving the bladder neck (13/14). Of the 14 total cases, 11 (78.6%) presented typical pure seminoma cell features, staining strongly positive for placental alkaline phosphatase, CD117, and OCT4. The median age at diagnosis was 51 (range 27-59) years, and patients had a median progression-free survival time of 48 (range 6-156) mo after treatment by cisplatin-based chemotherapy combined with surgery or radiotherapy. The remaining three were cases of mixed embryonal tumours with focal seminoma, which had clinical features similar to those of pure PSP, in addition that they also had elevated serum alpha-fetoprotein, beta-human chorionic gonadotropin, and lactose dehydrogenase. CONCLUSION: PSP should be considered in patients younger than 60 years with an enlarged prostate invading the bladder neck. Further prostate biopsies may aid in proper PSP diagnosis. Cisplatin-based chemotherapy is still the main primary therapy for PSP.

Establishment and Validation of a Novel Prediction Model for Early Natural Biochemical Recurrence After Radical Prostatectomy Based on Post-Operative PSA at Sixth Week.

Objective: Based on post-operative PSA at 6th week (PSA6w) after radical prostatectomy to establish an optimal model for predicting natural biochemical recurrence (BCR). Methods: A total of 742 patients with post-operative PSA6w from PC-follow database, between January 2003 and October 2022, were included. All the patients had not received any hormone therapy and radiotherapy before operation and BCR. Of these patients, 588 cases operated by one surgeon were enrolled for modelling and another 154 cases operated by other surgeons were for external validation. After screened by Cox regression, the post-operative PSA6w, pathological stage, Gleason Grade and positive surgical margins were adopted for modelling. The R software was used to plot the nomogram of the prediction model for BCR. C-index and calibration curve were calculated to evaluate the new model. Finally, integrated discrimination improvement was adopted to evaluate the prediction performances of the new nomogram model and the classical Kattan nomogram. Results: The C-index of the new model was 0.871 (95% CI: 0.830-0.912). The calibration curve of the new model demonstrated superior consistency between the predicted and actual value. The C-index of the external validation group was 0.850 (95% CI: 0.742-0.958), which demonstrated perfect universality. The integrated discrimination improvement showed a 12.61% improvement in prediction performance over that of the classical Kattan nomogram (P < 0.01). Based on the new nomogram, patients were divided to high and low BCR group with a 3 year BCR-free cutoff probability as 74.72%. Low-risk patients, accounting for 77.89% of the patients, have no need to follow up frequently with a false-negative rate only 5.24%, which will save medical resources to a large extent. Conclusion: Post-operative PSA6w is a sensitive risk biomarker for early natural BCR. The new nomogram model could predict BCR probability with a higher accuracy and will further simplify the clinical follow-up strategies.

Clinicopathological and immunological profiles of prostate adenocarcinoma and neuroendocrine prostate cancer.

BACKGROUND: Biomarkers of DNA damage repair deficiency provide opportunities for personalized treatment with immunotherapy. However, there is limited research on the immune microenvironment of adeno-neuroendocrine prostate cancer (NEPC). In this study, we aimed to assess and describe the comprehensive clinicopathological manifestations of NEPC to improve diagnosis and predict prognosis. METHODS: A retrospective medical record review of 66 patients with prostate cancer (PCa) was performed. PCa samples from the 66 patients were analyzed using immunohistochemical staining for the detection of chromogranin, neural cell adhesion molecule 1, and synaptophysin. For tumor-associated immune microenvironment analysis, PD-L1, CD3, and CD8 were labeled in tissue slides. The effect of clinicopathological factors on the survival of patients with Adeno-NEPC was analyzed. RESULTS: Twenty patients presented with adeno-NEPC, whereas 46 presented with adeno-PCa. The median age of patients at PCa diagnosis was 67.86 ± 7.05 years (68.65 ± 7.23 years, adeno-NEPC; 67.52 ± 7.02 years, adeno-PCa). Eleven patients with adeno-NEPC underwent prostatectomy, whereas nine received primary androgen deprivation therapy (ADT). Additionally, 30 patients with adeno-PCa underwent prostatectomy, whereas 16 (34.8%) received primary ADT. There was a significant difference in overall survival between patients with adeno-NEPC and those with adeno-PCa (46.0 months vs. 65.0 months). There was also a significant difference in time from prostatectomy to biochemical recurrence between the groups of patients who underwent prostatectomy. Prostatectomy and normal lactate dehydrogenase levels were clinical factors that were significantly associated with better outcomes in patients with adeno-NEPC. Metastatic adeno-NEPC was associated with a higher programmed death ligand 1 (PD-L1) score (2-4) than localized PCa. The data showed that PD-L1 expression in adeno-NEPC may be negatively associated with that in CD8+ T cells. CONCLUSIONS: Our study revealed clinicopathological manifestations of adeno-NEPC and some possible predictive factors significantly associated with better outcomes in patients with adeno-NEPC. These findings might be beneficial in the development of diagnostic strategies and customized treatment plans.

[Clinical and genetic analysis of seven Chinese pedigrees affected with multiple endocrine neoplasia type 2A with cutaneous lichen amyloidosis].

OBJECTIVE: To explore the pathological characteristics and significance of RET proto-oncogene screening in multiple endocrine neoplasia type 2A (MEN2A) with cutaneous lichen amyloidosis (CLA). METHODS: Clinical data of 51 members from 7 unrelated pedigrees of MEN2A-CLA were collected. Systemic clinical investigations including biochemical testing, imaging examination, germline RET variant screening and histopathological examination were carried out. RESULTS: RET gene variants were detected in 28 patients with MEN2A (C634G/F/R/S/W and C611Y) including 12 males and 16 females, with the mean age of diagnosis being (41.1 ± 18.3) years old, which were consistent with their clinical manifestations. The incidence of medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), hyperparathyroidism (HPTH) and CLA among 28 MEN2A patients were 89.3%, 28.6%, 7.1% and 28.6%, respectively. Comparison of the incidence of MTC/PHEO/HPTH and CLA between C611Y and C634G/F/R/S/W, only PHEO and CLA in C611Y were lower than those in C634G/F/R/S/W (P < 0.05; P < 0.05). Among 8 patients with CLA, the male to female ratio was 2 : 6. The clinical features included pruritus in the interscapular region and presence of dry, thickened, scaly, brown pigment, clustered or desquamate-like plaques. The mean onset age of CLA [(18.4 ± 4.6) years] versus the mean age at diagnosis of CLA or MEN2A were significantly different (P < 0.001; P < 0.001). CONCLUSION: MEN2A-CLA may be the early clinical manifestation of MEN2A and most frequently occurred along with RET-C634 variant. To facilitate the recognition of MEN2A-CLA, to combine family investigation and screening of RET variant are helpful for early diagnosis and standardized treatment, which can improve the long-term outcome of MEN2A-specific tumors.

Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer.

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer, with a 10% five-year survival rate. However, little is known about its origin and the mechanisms governing its emergence. Our study characterized ADPC and NEPC in prostate tumors from 7 patients using scRNA-seq. First, we identified two NEPC gene expression signatures representing different phases of trans-differentiation. New marker genes we identified may be used for clinical diagnosis. Second, integrative analyses combining expression and subclonal architecture revealed different paths by which NEPC diverges from the original ADPC, either directly from treatment-naïve tumor cells or from specific intermediate states of treatment-resistance. Third, we inferred a hierarchical transcription factor (TF) network underlying the progression, which involves constitutive regulation by ASCL1, FOXA2, and selective regulation by NKX2-2, POU3F2, and SOX2. Together, these results defined the complex expression profiles and advanced our understanding of the genetic and transcriptomic mechanisms leading to NEPC differentiation.

Clinical Benefit of Niraparib to TKI/mTORi-Resistance Metastatic ccRCC With BAP1-Frame Shift Mutation: Case Report and Literature Review.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. The top four mutant genes affecting the occurrence and progression of ccRCC are VHL, PBRM1, BAP1, and SETD2, respectively. Tyrosine kinase/mammalian target of rapamycin inhibitors (TKI/mTORis) with or without immunotherapy are the standard and effective therapy to metastatic ccRCC. Once TKI/mTORis fail to ccRCC, there is still a lack of other effective therapies. In this study, we reported a case in which a metastatic ccRCC patient (T2aN1M1) presented resistance after a 28-month treatment by sorafenib-axitinib-everolimus (TKI-TKI-mTORi). Subsequently, a frame shift pathogenic mutation, c.799_800del (p.Q267fs) in the exon10 of BAP1 in ccRCC, was revealed by targeted sequencing. Oral administration of nilapanib (PARP inhibitor) was further given, which may provide a new therapy for TKI/mTORi-resistance metastatic ccRCC. Fortunately, a partial response has been achieved and lasted for 5 months. Since the frequency of BAP1 mutations in ccRCC patients was approximately 10%-20%, as reported previously, we also tried to explore the potential mechanisms benefitting from the nilapanib. Moreover, the literature concerning BAP1 mutation and associated cancers including ccRCC is reviewed.

Simultaneous bilateral laparoscopic cortical-sparing adrenalectomy for bilateral pheochromocytomas in multiple endocrine neoplasia type 2.

Purpose: This study aimed to assess the feasibility of synchronous bilateral laparoscopic or open cortical-sparing adrenalectomy (SB-LCSA or SB-OCSA) for bilateral pheochromocytomas (bPHEOs) in multiple endocrine neoplasia type 2 (MEN2). Methods: Altogether, 31 patients (54.8% were women) were diagnosed with MEN2-related bPHEOs, and 29 of them underwent varying specific adrenalectomies. We systematically analyzed and evaluated their clinical profiles, mutation types, tumor histopathological features, and follow-up records. Results: All 31 patients with bPHEOs presented with RET-C634 (90.3%) and RET-M918T (9.7%) mutations, and the median age at initial presentation was 38 years (range, 23-78). bPHEOs were synchronous in 27 patients and metachronous in 4 (12.9%) patients. In total, 29 patients underwent initial cortical-sparing adrenalectomy (CSA) including 23 (79.3%) undergoing synchronous bilateral CSA (18 SB-LCSA and 5 SB-OCSA) and 6 (20.7%) undergoing metachronous CSA. SB-LCSA and synchronous surgery were associated with less bleeding volume and shorter length of hospital stay than SB-OCSA and metachronous surgery (all P's < 0.05). Corticosteroid replacement treatment was necessary for 14 patients (45.2%) after bilateral CSA. During a median follow-up period of 7 years (range, 1.8-23), three of these patients (10.3%) had a recurrent disease that required reoperation. Conclusion: SB-LCSA is feasible for treating synchronous bPHEOs and should be recommended as a prioritized surgical approach.

Case Report: Systemic Treatment and Serial Genomic Sequencing of Metastatic Prostate Adenocarcinoma Progressing to Small Cell Carcinoma.

Small cell carcinoma (SCC)/neuroendocrine prostate cancer (NEPC) is a rare and highly aggressive subtype of prostate cancer associated with an AR(androgen receptor)-null phenotype and visceral metastases. This study presents a 44-year-old man originally diagnosed with metastatic hormone-sensitive prostatic adenocarcinoma. After 6-month androgen deprivation therapy (ADT) combined with docetaxel, the patient developed paraplegia. Laminectomy was performed, and a thoracic vertebral biopsy revealed neuroendocrine differentiation and mixed adenocarcinoma. The patient developed liver metastases and experienced stable disease for 4 months following etoposide combined with cisplatin and pembrolizumab. Seminal vesicle biopsy after chemotherapy revealed small-cell cancer. The prostate biopsy specimen also indicated pure SCC. We witnessed the dynamic evolution from pure adenocarcinoma to fully differentiated SCC, leading to obstruction and death. In addition, whole-exome sequencing was performed on both biopsy specimens of the thoracic vertebra at the beginning of castration resistance and that of seminal vesicle after multiple lines of treatment failure. Utilizing phylogenetic reconstruction, we observed that both samples shared a common ancestor clone harboring aberrations in the TP53, RB1, and NF2 genes. We also discovered that driver events in the private subclones of both samples, such as alterations in CDC27 and RUNX1, might have played a significant role in tumor progression or even neuroendocrine differentiation. Tumor biopsy and IHC assessment must be repeated at different stages of progression, because of intrapatient spatial and temporal heterogeneity of adenocarcinoma versus SCC/NEPC. Although, typical treatments including ADT, docetaxel, etoposide, cisplatin, and pembrolizumab provided temporary response, the patient still had a poor prognosis.

Transperineal Parallel Biopsy of the Prostate: A New Approach of Tissue Sampling for Precision Medicine.

PURPOSE: Through an observational study to present a new approach for obtaining high-quality samples for the targeted therapy of prostate cancer. PATIENTS AND METHODS: Parallel biopsy, which was defined as collecting the tissue from the same site by two biopsies, was performed on patients with elevated PSA. Each tissue was stained by ink to identify the pathological characteristics, including Gleason score and tumor tissue ratio. Kendall tau-b test and intraclass correlation coefficient test were used to compare the consistency between each paired sample. Then, based on the pathology of the biopsies, high-quality tissues would be selected for sequencing, and PyClone model was used to track the clonal evolution. RESULTS: In total, 252 pairs of biopsies were collected. The consistency of Gleason score between each paired biopsy is 0.777 (p<0.01), and the consistency of tumor tissue ratio is 0.853 (p<0.01). With the application of parallel biopsy, on average five nonsynonymous mutations could be identified in patients with castration-resistant prostate cancer. Six out of eight had at least one biology-relevant alteration in patients, guiding further treatment. Meanwhile, clonal evolution was constructed to investigate the progress of tumor. CONCLUSION: Parallel biopsy is a reliable approach to collect high-quality tissue and shows potential application in precision medicine.

Spectrum of Germline RET variants identified by targeted sequencing and associated Multiple Endocrine Neoplasia type 2 susceptibility in China.

BACKGROUND: Germline RET mutations and variants are involved in development of multiple endocrine neoplasia type 2 (MEN2). The present study investigated a spectrum of RET variants, analyzed genotype-phenotype relationships, and evaluated their effect on the MEN2 phenotype in Han Chinese patients. METHODS: Targeted sequencing detected germline RET variants in 697 individuals, including 245 MEN2, 120 sporadic medullary thyroid cancer (MTC), and 15 pheochromocytoma (PHEO) patients and their 493 relatives. In silico analyses and classifications following ACMG-2015 were performed. Demographic, clinical variant types, and endocrine neoplasia molecular diagnosis records were also analyzed. RESULTS: Nineteen different RET mutations (18 point and 1 del/ins mutations) in 214 patients with MEN2A (97.7%) or MEN2B (2.3%) were found, of which exon 11/10 mutations accounted for 79% (169/214). Nineteen compound mutations were found in 31 patients with MEN2A. Twenty-three variants (18 single and 5 double base substitution/compound variants) non-classification were also found. Of these, 17 (3 of pathogenic, 10 of uncertain significance, 2 of likely benign and 2 as benign) were found in 31 patients with MTC/PHEO. The remaining 6 variants (4 of uncertain significance and 2 of likely benign) found in 8 carriers had no evidence of MEN2. The entire cohort showed MEN2A-related PHEO, all occurring in exons 11/10, particularly at C634. Kaplan-Meier curves showed age-dependent penetration rates of MTC and PHEO, and occurrence rates of PHEO in patients with exon 11 mutations were all higher than those within exon 10; these bilateral PHEO were always associated with exon 11 mutations (all P < 0.05). While patient offspring had PHEO, parents with MEN2A had none, the frequency was approximately 10%. Interestingly, at least 6.8% of families were adoptive. Also, 3 non-hotspot RET variants (R114H, T278N, and D489N) appeared with high frequency. Conversely, polymorphism S836S was absent. CONCLUSIONS: These data are largely consistent with current evidence-based recommendations in the clinical practice guidelines. Diversity of RET variants or carriers may involve a different natural disease course. Further large-scale targeted sequencing studies will serve as an accurate and cost-effective approach to investigating MEN2 genotype-phenotype correlations for discovery of rare or unknown variants of RET.

Sustainable functional urethral reconstruction: Maximizing early continence recovery in robotic-assisted radical prostatectomy.

OBJECTIVE: To evaluate the safety profile and short-term functional outcome of sustainable functional urethral reconstruction (SFUR) in robotic-assisted radical prostatectomy (RARP). METHODS: One hundred and sixty-two consecutive prostate cancer patients who underwent RARP were retrospectively analyzed, in which 53 had undergone SFUR while the other 109 had undergone conventional RARP procedures. Immediate, 2-week, 1-month and 3-month continence recovery and other perioperative data were compared to evaluate short-term surgical and functional outcome. RESULTS: The median age was 68 and 67 years in the experimental group and control group, respectively (p=0.206), with a median prostate-specific antigen (PSA) of 13.6 ng/mL (interquartile range [IQR], 8.46-27.32 ng/mL) in the experimental group and 13.84 ng/mL (IQR, 9.12-26.80 ng/mL) in control group (p=0.846). Immediate, 2-week, 1-month and 3-month continence recovery rates between the groups were 34.0% vs. 3.7%, 50.9% vs. 14.7%, 62.3% vs. 27.5%, and 79.2% vs. 63.3% (all p<0.05). The morphological changes made by the new reconstruction technique were maintained on magnetic resonance imaging (MRI) 3 months postoperatively. Nerve-sparing procedures and adoption of the new reconstruction technique were significantly relevant to continence recovery on logistics regression model (p<0.001). CONCLUSIONS: SFUR is a safe and easy-to-handle modification that may contribute to early continence return for RARP. Long-term follow-up and prospective studies are required to further evaluate its value in postoperative quality-of-life improvement.

Postoperative placement of an anti-fibrotic poly L-lactide electrospun fibrous membrane after sinus surgery.

BACKGROUND: Endoscopic sinus surgery (ESS) is used to treat chronic rhinosinusitis. However, nasal adhesions often develop postoperatively, triggered by chronic inflammation and local fibrosis. A poly L-lactide (PLLA) electrospun microfibrous membrane is a functional biodegradable material that can be placed on the wound surface to protect the wound and prevent adhesions. METHODS: We divided 24 rabbits randomly into 2 groups, a control operation group (group A) and an operation+PLLA placement group (group B). We investigated the anti-fibrotic effects of the topical biomaterial after sinus surgery. We placed PLLA fibrous membranes in the sinus cavity of group B rabbits after sinus surgery, and then evaluated changes in the mucosa and in the levels of collagen fibers, interleukin 4 (IL-4), IL-8, tumor necrosis factor α (TNF-α), transforming growth factor ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), and collagen I (Col I), using morphological and molecular biological methods. RESULTS: PLLA fibrous membranes did not inhibit the synthesis of messenger RNAs (mRNAs) encoding IL-4, IL-8, or TNF-α, or the protein levels, indicating that the membrane did not have an anti-inflammatory effect. However, the membrane inhibited the synthesis of mRNAs encoding TGF-ß1, α-SMA, and Col I, and reduced collagen production. Thus, the nanostructured membrane inhibited fibroblast proliferation. CONCLUSION: The PLLA membrane had anti-fibrotic effects, and may be used to prevent fibrosis and adhesions after ESS in human patients.

A genomic and epigenomic atlas of prostate cancer in Asian populations.

Prostate cancer is the second most common cancer in men worldwide1. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients2,3. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.

Experience of one single surgeon with the first 500 robot-assisted laparoscopic prostatectomy cases in mainland China.

OBJECTIVES: To summarize the experience of the first 500 robot-assisted laparoscopic radical prostatectomy (RALP) cases by one surgeon and analyze the influencing factors of functional and oncological outcomes. METHODS: Between April 2012 and October 2017, 500 patients who underwent RALP were included and divided sequentially into five equal groups. Patients' preoperative, perioperative and postoperative outcomes were analyzed and evaluated, and the Kruskal-Wallis test was used to analyze and compare the effect of surgeon experience by case. RESULTS: There is a statistically significant reduction in operative time, intraoperative estimated blood loss and postoperative hospital stay time (all p<0.001) with the increased experience. The results show that experience was the most important influencing factor in both operative time and blood loss. Pelvic lymph node dissection (PLND) might increase the operative time. The total positive surgical margin (PSM) rate was 21.8%. The PSM rate in pT3 tumors was significantly higher than that in pT2 tumors (12.0% vs. 37.1%, p<0.001). The 5-year biochemical recurrence (BCR)-free rate was 70.8%. The results of Cox regression showed that preoperative prostate-specific antigen (PSA), postoperative Gleason score (GS), and pathologic T stage were independent risk factors for BCR. CONCLUSION: After approximately 200 cases, the surgeon reached a plateau for RALP, but the outcomes could still improve after more cases. The surgeon's experience was the most important influencing factor for both operative time and blood loss. PSM rate was mainly determined by tumor stage rather than by operation experience.

Short-term therapeutic outcomes of robotic-assisted laparoscopic radical prostatectomy for oligometastatic prostate cancer: a propensity score matching study.

BACKGROUND: The role of local treatment in oligometastatic prostate cancer (PCa) is gaining interest with the oligometastases hypothesis proposed and the improvement of various surgical methods and techniques. This study aimed to compare the short-term therapeutic outcomes of robotic-assisted laparoscopic radical prostatectomy (RALP) for oligometastatic prostate cancer (OPC) vs. localized PCa using propensity score matching. METHODS: Totally 508 consecutive patients underwent RALP as a first-line treatment. The patients were divided into two groups according to oligometastatic state: the OPC group (n = 41) or the localized PCa group (n = 467). Oligometastatic disease was defined as the presence of two or fewer suspicious lesions. The association between the oligometastatic state and therapeutic outcomes of RALP was evaluated, including biochemical recurrence (BCR) and overall survival (OS). A Cox proportional hazards model was used to assess the possible risk factors for BCR. RESULTS: Totally 41 pairs of patients were matched. The median operative time, the median blood loss, the overall positive surgical margin rate, the median post-operative hospital stays, and the post-operative urinary continence recovery rate between the two groups showed no statistical significance. The 4-year BCR survival rates of the OPC group and localized PCa group were 56.7% and 60.8%, respectively, without a significant difference (P = 0.804). The 5-year OS rates were 96.3% and 100%, respectively (P = 0.326). Additionally, the results of Cox regression showed that oligometastatic state was not an independent risk factor for BCR (P = 0.682). CONCLUSIONS: Our findings supported the safety and effectiveness of RALP in OPC. Additionally, oligometastatic state and sites did not have an adverse effect on BCR independently.

Clinical Benefit of Sorafenib Combined with Paclitaxel and Carboplatin to a Patient with Metastatic Chemotherapy-Refractory Testicular Tumors.

Testicular cancer is one of the few tumor types that have not yet benefited from targeted therapy. Still no new active agents for treating this cancer have been identified over the past 15 years. Once patients are refractory to cisplatin-based chemotherapy, they will be expected to die from testicular cancer. This report describes a 21-year-old man who was refractory to chemotherapy and immunotherapy. Whole exome sequencing and low-depth whole genome sequencing confirmed the KRAS gene amplification, which may lead to the tumor cells' progression and proliferation. After discussion at the molecular tumor board, the patient was offered paclitaxel, carboplatin, and sorafenib (CPS) based on a phase III clinical trial of melanoma with KRAS gene copy gains. After treatment with CPS, the patient achieved excellent curative effects. Because of a nearly 50% frequency of KRAS amplification in chemotherapy-refractory testicular germ cells, CPS regimen may provide a new therapy, but it still warrants further validation in clinical studies. KEY POINTS: Chemotherapy-refractory testicular cancer has a very poor prognosis resulting in a lack of effective targeted therapies. KRAS gene amplification occurs in nearly 20% of testicular cancer and 50% of chemotherapy-refractory testicular cancer. KRAS amplification may activate the MAPK signaling pathway, and inhibition of MAPK by sorafenib combined with paclitaxel and carboplatin could be a viable option based on a phase III clinical trial of melanoma.To the authors' knowledge, this is the first report of response to sorafenib-based combination targeted therapy in a patient with chemotherapy-refractory testicular cancer.Clinical genomic profiling can confirm copy number variation of testicular cancer and provide insights on therapeutic options.

Palliative Transurethral Resection of the Prostate in Patients with Metastatic Prostate Cancer: A Prospective Study of 188 Patients.

Purpose: Palliative transurethral resection of the prostate (pTURP) in metastatic prostate cancer (mPCa) is reported to be rarely applied in clinics. We prospectively evaluated the ability of pTURP to achieve tumor control in patients with mPCa. Patients and Methods: A prospective study of patients with mPCa from 2011 to 2018 was conducted. The patients were divided into two groups: a pTURP + androgen deprivation therapy (ADT) group and an ADT group. Castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival (CSS) were analyzed as research endpoints between the groups using a Kaplan-Meier estimator. Results: A total of 188 patients with mPCa were enrolled in the study from our center, of which 110 patients were in the pTURP + ADT group, and 78 patients were in the ADT group. The basic clinical characteristics were comparable between the groups. There were no reoperations or severe complications in the pTURP + ADT group. The median follow-up was 29 months. The median CRPC-free survival was significantly increased when the 7-month prostate-specific antigen (PSA) was <4 ng/mL (34 vs 6, p < 0.01) and bone metastasis was ≤5 (25 vs 10, p < 0.01) but not in the pTURP + ADT group (16 vs 12, p = 0.267). The 3-year CSS was higher in the pTURP + ADT group than that in the ADT group (95.9% vs 64.9%, p = 0.004), as well as when the 7-month PSA was <4 ng/mL compared to ≥4 ng/mL (90.7% vs 36.6%, p < 0.01) and when bone metastasis was ≤5 compared to >5 (82.2% vs 63.2%, p < 0.01). In subgroup analysis, pTURP + ADT could significantly improve patients' CSS when PSA ≥65 ng/mL, Gleason Score (GS) ≥8, and bone metastasis ≤5. Conclusions: We used our center-based cancer database to analyze survival in patients with mPCa undergoing pTURP. In the study population, pTURP + ADT was indicated to benefit CSS and shown to be safe. Moreover, we suggest that mPCa patients with PSA ≥65 ng/mL, GS ≥8, and bone metastasis ≤5 may perform pTURP before ADT.