Chinese clinical oncology最新文献

Background: Delayed treatment in symptomatic metastatic epidural spinal cord compression (MESCC) is significantly associated with poorer functional outcomes. In this study, we aim to identify the patterns of treatment delay in patients and factors predictive of postoperative ambulatory function.

Methods: Retrospective review of patients with symptomatic MESCC treated surgically between January 2015 and January 2022. MESCC symptoms were categorized into symptoms suggesting cord compression requiring immediate referral and symptoms suggestive of spinal metastases. Multivariate analysis was performed to identify factors predictive of postoperative ambulatory function. Delays in treatment were identified and categorized into patient delay (onset of symptoms till initial medical consultation), diagnostic delay (medical consultation till radiological diagnosis of MESCC), referral delay (from diagnosis till spine surgeon review) and surgical delay (from spine surgeon review till surgery) and compared between patients.

Results: One hundred and seventy-eight patients were identified. In this cohort 92 (52.0%) patients were able to ambulate independently, and 86 (48.3%) patients were non independent. One hundred and thirty-nine (78.1%) of patients had symptoms of cord compression and 93 (52.3%) had neurological deficits on presentation. On multivariate analysis, pre-operative neurological deficits (P=0.01) and symptoms of cord compression (P=0.01) were significantly associated with post-operative ambulatory function. Mean total delay was 66 days, patient delay was 41 days, diagnostic delay was 16 days, referral delay was 3 days and surgical delay was 6 days. In patients with neurological deficits, there was a significant decrease in all forms of treatment delay (P<0.05). There was no significant decrease in patient delay, diagnostic delay and referral delay in patients with symptoms of cord compression.

Conclusions: Both patients and physicians understand the need for urgent surgical treatment of MESCC with neurological deficits, however there is still a need for increased education and recognition of the symptoms of MESCC.

Background: Whole brain radiotherapy (WBRT) is commonly used as consolidation therapy in primary central nervous system lymphoma (PCNSL). However, high-dose chemotherapy followed by autologous stem cell transplantation (HD-ASCT) has emerged as an alternative approach for PCNSL. This systematic review aims to assess the efficacy and safety of both treatment modalities.

Methods: The systematic review follows PRISMA guidelines. A comprehensive search strategy identified relevant studies from PubMed, Europe PMC, and Cochrane Library. The following search terms were used: "primary central nervous system lymphoma", "Autologous Stem Cell Transplantation", and "whole-brain radiotherapy". We included randomized controlled trials (RCTs) cohort studies evaluating the use of whole-brain radiotherapy and high-dose chemotherapy followed by autologous stem cell transplantation in the treatment of histologically-confirmed PCNSL. Publications included were limited to English language full texts that were published in the past 10 years. Data extraction & manuscript quality assessment was done by two independent reviewers with a third reviewer to resolve any discrepancy. Primary outcomes include overall survival (OS), progression-free survival (PFS) & treatment related toxicity (TRT). Secondary outcomes were clinical neurological function and performance score assessments. Individual studies were assessed using the Jadad Scale and the Newcastle-Ottawa Scale for observational studies.

Results: We identified 5 studies, consisting of 2 RCTs and 3 cohort studies. After all studies considered, analysis revealed that consolidation therapy with HD-ASCT had a better overall PFS and OS compared to whole-brain radiotherapy (P<0.005). Both groups showed similar TRT with mostly haematological toxicity. Holistically clinical cognitive functions are found to be improved in HD-ASCT Patients and poorer results are exhibited by WBRT patients primarily in executive functions. Performance statuses are scored differently across all studies with slightly preferable results shown in patients treated with HDC-ASCT.

Conclusions: Based on the findings of this systematic review, HDC-ASCT might be a preferable choice of consolidative therapy as shown with better OS, PFS with similar TRT. While WBRT are more feasible and cost-efficient, risks of cognitive impairment and reduced performance status after WBRT should be considered for further treatment choices. Further randomized clinical trials with a similar scoring system are needed.

Background: Robotic-assisted radical prostatectomy (RARP) is currently a first-line treatment option for men with localized prostate cancer (PCa), at least 10 years of life expectancy, and candidate for curative treatment. We performed a scoping review to evaluate the role of artificial intelligence (AI) on RARP for PCa.

Methods: A comprehensive literature search was performed using EMBASE, PubMed, and Scopus. Only English papers were accepted. The PICOS (Patient Intervention Comparison Outcome Study type) model was used; P: adult men with PCa undergoing RARP; I: use of AI; C: none; O: preoperative planning improvement and postoperative outcomes; S: prospective and retrospective studies.

Results: Seventeen papers were included, dealing with prediction of positive surgical margins/extraprostatic extension, biochemical recurrence, patient's outcomes, intraoperative superimposition of magnetic resonance images to identify and locate lesions for nerve-sparing surgery, identification and labeling of surgical steps, and quality of surgery. All studies found improving outcomes in procedures employing AI.

Conclusions: The integration of AI in RARP represents a transformative advancement in surgical practice, augmenting surgical precision, enhancing decision-making processes and facilitating personalized patient care. This holds immense potential to improve surgical outcomes and teaching, and mitigate complications. This should be balanced against the current costs of implementation of robotic platforms with such a technology.

Background: Temozolomide (TMZ) resistance in glioblastoma (GBM) remains a challenge in clinical treatment and the mechanism is largely unknown. Emerging evidence shows that epigenetic modifications including DNA methylation and non-coding RNA were involved in diverse biological processes, including therapeutic resistance. However, the underlying mechanisms by which DNA methylation-mediated non-coding RNA regulates TMZ resistance remain poorly characterized.

Methods: RNA microarray and DNA methylation chips of TMZ-resistant and parental GBM cells were performed for the gain of unreported long non-coding RNA HSD52. Quantitative reverse transcription polymerase chain reaction (PCR) and fluorescence in situ hybridization assays were used to detect HSD52 levels in GBM cells and tissues. The investigation into HSD52's impact on TMZ resistance was conducted utilizing both in vitro assays and intracranial xenograft mouse models. The mechanism of HSD52 expression and its relationships with paraspeckle proteins, non-POU domain-containing octamer-binding protein (NONO) and splicing factor proline/glutamine rich (SFPQ), as well as alpha-thalassemia mental retardation X-linked (ATRX) mRNA were determined by pyrosequencing assay, chromatin immunoprecipitation, chromatin isolation by RNA purification, RNA immunoprecipitation, RNA pulldown, immunofluorescence, and western blot assays.

Results: HSD52 was highly expressed in high-grade glioma and TMZ-resistant GBM cells. Phosphorylated p38 mitogen-activated protein kinase (p38 MAPK)/ubiquitin specific peptidase 7 (USP7) axis mediates H3 ubiquitination, impairs the interaction between H3K23ub and DNA methyltransferase 1 (DNMT1) and the recruitment of DNMT1 at the HSD52 promoter to attenuate DNA methylation, which makes the transcription factor 12 (TCF12) more accessible to the promoter region to regulate HSD52 expression. Further analysis showed that HSD52 can serve as a scaffold to promote the interaction between NONO and SFPQ, and then increase the paraspeckle assembly and activate the paraspeckle/ataxia telangiectasia mutated (ATM) kinase pathway in GBM cells. In addition, HSD52 forms an RNA-RNA duplex with ATRX mRNA, and facilitates the association of heteromer of SFPQ and NONO with RNA duplex, thus leading to the increase of ATRX mRNA stability and level. In clinical patients, HSD52 is required for TMZ resistance and GBM recurrence.

Conclusions: Our results reveal that HSD52 in GBM could serve as a therapeutic target to overcome TMZ resistance, enhancing the clinical benefits of TMZ chemotherapy.

Background: Anaplastic astrocytoma [AA; World Health Organization (WHO) grade III] is a diffusely infiltrative astrocytic brain tumor with anaplasia and represents 3.3% of primary brain tumors. Overall, 5-year median survival can range from 22% to 50%, depending on various prognostic features, including the patient's age, tumor location and genetics, resection, etc. Given the higher grade and increased likelihood of transformation to WHO-grade IV tumors (glioblastomas), these tumors are generally treated aggressively upfront. Headache and seizures are the most common symptoms, occurring in about 50% of the cases. Other symptoms, including memory loss, motor weakness, language deficit, and cognitive and personality changes, occur in 20% of cases. Standard treatment involves surgical resection, radiotherapy, and chemotherapy, but treatment options are greatly limited for progression and recurrence. This paper highlights the case of a 48-year-old male who presents with chronic progressive cephalgia and a new-onset seizure. We review the diagnostic and therapeutic challenges associated with the treatment of AA.

Case description: We describe a patient who presented with chronic progressive cephalgia, gradual right-sided weakness, an asymmetrical face, slurred speech, and a new-onset focal-to-bilateral seizure. A cranial magnetic resonance imaging revealed a mass in the left frontoparietal region, causing herniation of the cerebri to the right. The patient had a maximal tumor resection, and the histopathology showed tissue sections containing tumors that were infiltrative in the stroma, forming a diffuse pattern consisting of proliferation of oval, round, polygonal, spindle, pleomorphic oval nucleated cells, hyperchromatic, some nucleoli appearing prominent, and cytoplasmaeosinophilic. There were areas of stromal necrosis and mitosis [3/10 high power field (HPF)]. The pathology result was reported with AA. The patient underwent concomitant chemoradiation and followed oral chemotherapy with temozolomid. Subsequent imaging revealed a significant decrease in the tumor's size and a resolution of the compression of the brain parenchyma underneath. The Response Assessment in Neuro-Oncology (RANO) evaluation showed partial responses with good clinical improvement.

Conclusions: The case presented an AA that was responsive to radiotherapy and temozolomid chemotherapy. Despite being rare, knowledge of this malignant tumor type and a multidisciplinary approach to case management are essential to optimizing treatment results.

Background: Inhibitors of programmed cell death ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) are commonly used in the clinic, but they are beneficial for only a minority of glioblastoma multiforme (GBM) patients. GBM has significant immunosuppressive properties, and there are many immunosuppressive cells and dysfunctional effector T-cell in the tumor microenvironment (TME), which is one of the important reasons for the failure of clinical treatment of GBM. P21-activated kinase 4 (PAK4) is a threonine protein kinase, and as a pivotal immune suppressor in the TME. PAK4 knockdown attenuates vascular abnormalities and promotes T-cell infiltration.

Methods: Using RNA sequencing (RNA-seq) technology, western blotting, and immunofluorescence, we identified changes in genes expression following VEGFR2 knockdown. The impact of anti-PD-L1 and anti-VEGFR2 on GBM cells apoptosis was assessed using coculture assays, western blotting, and flow cytometry. Additionally, the therapeutic efficacy of anti-PD-L1 and anti-VEGFR2 therapy was evaluated through in vivo experiments, immunohistochemistry, and immunofluorescence.

Results: Our studies revealed that VEGFR2 binds and phosphorylates signal transducer and activator of transcription 3 (p-STAT3), thereby regulating the expression of PAK4. Anti-PD-L1 and anti-VEGFR2 therapy can increase the secretion of interferon-gamma (IFN-γ), granzyme B, and perforin by immune cells and promoting the cytotoxic effects of cytotoxic cluster of differentiation 8 (CD8)+ T cells, and overexpression of PAK4 could reverse this effect. We also demonstrated that combination therapy with anti-PD-L1 and anti-VEGFR2 agents prevents tumor growth in an intracranial tumor model.

Conclusions: Our results support that anti-VEGFR2 therapy can downregulate PAK4, reprogram the TME by increasing CD8+ T cells infiltration and activation, and enhance the therapeutic effect of anti-PD-L1 therapy on GBM cells.

Background: The cerebellopontine angle (CPA) is a multifaceted triangular region bordered by the brainstem medially, the cerebellum superiorly and posteriorly, and the temporal bone laterally. Tumors located in the CPA comprise 5% to 10% of all intracranial neoplasms, with vestibular schwannomas being the most prevalent, followed by meningiomas and epidermoid tumors. Various surgical approaches exist for removing these lesions, which consistently present challenges for neurosurgeons in effectively managing them. This study presents a case of a CPA tumor successfully treated via the retrosigmoid approach, followed by an assessment of the approach's efficacy and surgical outcomes.

Methods: A comprehensive literature search was conducted using electronic databases, including PubMed, ScienceDirect, and Google Scholar, to gather studies on surgically managed CPA tumors. In addition to reviewing the literature, we present a case study of a patient with CPA tumor who underwent surgery using the retrosigmoid approach.

Results: The literature review revealed that the retrosigmoid approach emerged as a commonly utilized technique, particularly for tumors in the CPA region. Analysis of the collected data indicated that the retrosigmoid approach offers several advantages, including excellent exposure of the CPA, minimal brain retraction, and reduced risk of injury to critical neurovascular structures. Moreover, studies consistently reported favorable surgical outcomes, with low rates of morbidity and mortality associated with this approach. In our case study, we successfully employed the retrosigmoid approach to resect a CPA tumor in a patient presenting with typical symptoms of spasticity in all four extremities and progressive hearing loss.

Conclusions: In conclusion, the retrosigmoid approach remains a valuable surgical technique for the management of CPA tumors. This approach enhances the exposure of the CPA and increases the surgical angle of maneuverability. In most literature, the retrosigmoid approach provides adequate access that is safe and effective, with a low rate of postoperative complications. However, further prospective studies and comparative analyses are warranted to validate these findings and refine surgical techniques for optimizing patient outcomes.

Background and objective: The landscape of surgical training is undergoing transformative changes, especially in the realm of robot-assisted procedures like radical prostatectomy (RARP). This narrative review explores the evolving methodologies and innovations in RARP training, emphasizing the shift from traditional training approaches, such as the Halsted method, to more scientific methods like proficiency-based progression (PBP). The rationale for the review stems from the increased adoption of robot-assisted surgery and the resulting increase in associated adverse events reported in the United States. The Patient Safety in Robotic Surgery (SAFROS) project initiated by the European Commission of the World Health Organization emphasized the importance of structured training programs for robotic surgeons. However, the review points out the limited availability of standardized curricula for RARP training, leading to non-homogeneous training worldwide.

Methods: PubMed was searched primarily for the following topics: training AND robotic AND prostatectomy; robotic training AND prostatectomy AND learning; simulator AND robotic AND prostatectomy. Literature was selected based on historical significance and landmark studies as well as publications published after 2000. References from select studies were additionally included.

Key content and findings: The advent of robotic surgery, especially in RARP, demands unique skills necessitating specialized training. The review delves into the diverse stages of robotic surgery training, starting with e-learning and progressing through virtual reality simulators, dry and wet laboratories, culminating in modular console training. Each training stage plays a critical role, addressing the challenges posed by new technologies and tools.

Conclusions: The ever-evolving landscape of surgical training underscores the critical need for globally standardized, effective, and accessible programs. PBP emerges as a promising methodology, and technological advancements open new possibilities for telementoring via platforms like 5G. This review emphasizes the imperative to equip surgeons with the requisite skills for intricate procedures like RARP, addressing current challenges while anticipating the future developments in this dynamic field.

Background: Intraoperative functional mapping for glioma resection often necessitates awake craniotomies, requiring active patient participation. This procedure presents challenges for both the surgical team and the patient. Thus, minimizing mapping time becomes crucial. Passive mapping utilizing electrocorticography (ECoG) presents a promising approach to reduce intraoperative mapping efforts via direct electrical stimulation. This study aims to identify an efficient mapping protocol for hand movement by optimizing mapping duration and localization accuracy.

Methods: Three glioma patients (two males, one female) underwent awake craniotomy for tumor resection at Asahikawa Medical University Hospital and Kindai University in Osaka. Patients were maintained at a bispectral index (BIS) level above 90 to ensure wakefulness during mapping. Data were collected using a DC-coupled g.HIamp biosignal amplifier, digitized with 24-bit resolution at a minimum sampling rate of 1,200 Hz. Each session comprised ten runs, each lasting 250 seconds, consisting of a 12-second rest phase (baseline) followed by a 12-second grasping period containing ten grasping movements. High-gamma activity (HGA, 60-170 Hz) was recorded from ECoG locations on the pre- and postcentral gyrus. Locations exhibiting significant grasping-related HGA, with stronger responses during early trials within a run, were classified as "attenuated".

Results: Among 37 electrodes on the sensorimotor cortex, 16 exhibited significant HGA during grasping. Three locations demonstrated significant attenuation after three runs, with one location showing attenuation after the first three trials within a run.

Conclusions: The observed attenuation effect of short-term repeated movements during intraoperative monitoring is relatively modest initially. However, as the number of repeated grasping blocks increases, the number of attenuated locations also rises. Consequently, minimizing overall mapping time, rather than reducing the number of tasks per block, is paramount. For statistical analysis, a minimum of 20 grasping trials (two runs of ten movements) or 48 seconds of motor mapping is recommended. Alternatively, a mapping protocol involving a third run or 30 grasping trials (72 seconds) may enhance data robustness. These preliminary findings, though based on a limited patient cohort, warrant confirmation and further investigation, particularly in epilepsy patients.