Chinese clinical oncology最新文献

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: Histopathological examination, a cornerstone in diagnosing cancer, faces challenges due to its time-consuming nature. This review explores the potential of ex-vivo fluorescent confocal microscopy (FCM) in urology, addressing the need for real-time pathological assessment, particularly in prostate cancer. This systematic review aims to assess the applications of FCM in urology, including its role in prostate cancer diagnosis, surgical margin assessment, and other urological fields.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a systematic search of PubMed and SCOPUS was conducted, focusing on English written original articles published after January 1, 2018, discussing the use of FCM in urological practice. The search included keywords related to FCM and urological terms. The risk of bias assessment was performed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.

Results: A total of 17 relevant studies were included in the review that focuses on three main urological issues: prostate cancer (15 articles), bladder cancer (1 article), and renal biopsy (1 article). FCM exhibited significant promise in diagnosing prostate cancer. These studies reported an accuracy range of 85.33% to 95.1% in distinguishing between cancerous and non-cancerous prostate tissues. Moreover, FCM proved valuable for assessing surgical margins in real-time during radical prostatectomy, reducing the need for frozen section analysis. In some investigations, researchers explored the integration of artificial intelligence (AI) with FCM to automate diagnostic processes. Concerning bladder cancer, FCM played a beneficial role in evaluating urethral and ureteral margins during radical cystectomy. Notably, it showed substantial agreement with conventional histopathology and frozen section examination. In the context of renal biopsy, FCM demonstrated the potential to differentiate normal renal parenchyma from cancerous tissue, although the available evidence is limited in this area. The main limitation of the current study is the scarcity of data regarding the topic of interest.

Conclusions: Ex-vivo FCM holds promise in urology, particularly in prostate cancer diagnosis and surgical margin assessment. Its real-time capabilities may reduce diagnostic delays and patient stress. However, most studies remain experimental, requiring further research to validate clinical utility.

Background: Glioblastoma (GBM) is the most malignant brain tumor and ranks among the most lethal of all human cancers, without improvements in survival over the last 30 years. Data obtained in our group suggest that PARP1, a well-known DNA-repairing protein, could also play a key role in the regulation of cell cycle through its interaction with the transcription factor E2F1. Therefore, considering that most oncogenic processes are associated with cell cycle deregulation, we hypothesized that disruption of PARP1-E2F1 interaction would provide a novel therapeutic approach to different types of cancer.

Methods: The identification of novel compounds disrupting PARP1-E2F1 interaction was carried out by combining in silico and in vitro screening, using a rational drug design. The virtual screen was performed using a molecular library of several million compounds at the selected target site, using AtomNet® (Atomwise, San Francisco, CA, USA), the first deep learning neural network for structure-based drug design and discovery. Since there is no complete structural information of the PARP1-E2F1 protein-protein interaction, a homologous structure of the BRCT domain of BRCA1 complex with the phospho-peptide (PDBID: 1T2V) was used to identify the potential binding interface of BRCT domain of PARP-1 (PDBID: 2COK) and the E2F1 protein. Top scoring compounds were clustered and filtered to obtain a final subset of 83 compounds that were incorporated to our in vitro screening, which included both transcriptional E2F1 activity and survival studies. Complete culture medium supplemented with the compounds selected in the in silico screening (10 μM) were added and incubated for 24 hours. E2F1 activity was observed by measuring luminescence. For the viability assay, the fluorescence reading was performed (excitation 544 nm and emission 590 nm).

Results: The in silico and in vitro screening resulted in 12 compounds that inhibited E2F1 transcriptional activity and significantly reduced cell number. The highest inhibition of both E2F1 transcriptional activity and cell growth was observed with compound 3797, which was selected for further studies.

Conclusions: Both in silico and in vitro results indicate that inhibition of PARP1-E2F1 transcriptional activity may provide a new rationale for designing novel therapeutic approaches for the treatment of GBM.

Background: Glioblastoma and brain metastasis are two types of brain tumors that have a significant impact on the global healthcare system, with high rates of morbidity and mortality. These tumors can be challenging to differentiate from each other, as they often present with similar symptoms and features on medical imaging. The purpose of this study was to investigate whether the neutrophil-to-lymphocyte ratio (NLR) could help distinguish between glioblastoma and brain metastasis.

Methods: This is a retrospective cross-sectional analysis that utilized medical records from six hospitals located in Yogyakarta, Indonesia from the period of 2016 to 2021. The study included patients who were diagnosed with glioblastoma and brain metastasis. Laboratory data was collected upon initial admission, and the diagnosis of glioblastoma and brain metastasis was based on a histopathological examination.

Results: This study included a total of 393 subjects, with the glioblastoma group comprising 121 subjects and the brain metastasis group comprising 272 subjects. The group with glioblastoma had a higher NLR (11.12±11.56 vs. 8.75±9.18, P=0.006) than the brain metastasis group. The area under the curve from the receiver operating characteristic analysis was 0.587 (95% confidence Interval: 0.528-0.647, P=0.006). An NLR value greater than 7.14 was found to have 55.4% sensitivity and 62.5% specificity in predicting glioblastoma.

Conclusions: According to this study, the NLR value of patients suffering from glioblastoma was significantly higher when compared to those with brain metastasis. This indicates that there is a higher degree of systemic inflammation in glioblastoma as compared to brain metastasis. Therefore, the NLR value can be a useful diagnostic tool to distinguish between glioblastoma and brain metastasis.

Background: Existing international data has shown that glioma patients suffer from poorer health-related quality of life (HRQoL). The European Organization for Research and Treatment of Cancer (EORTC) brain cancer-specific Quality of Life Questionnaire (QLQ-BN20) was developed to be together with EORTC Core Quality of Life Questionnaire (QLQ-C30) for cancer patients, highlighting issues particularly relevant to brain tumor patients. It has since been translated and validated across numerous cohorts. However, its psychometric properties have yet to be examined in Singapore. This study aimed to validate the use of QLQ-BN20 in a nationally representative sample of glioma patients in Singapore.

Methods: Eighty-seven patients who had undergone neurosurgery for glioma from six hospitals in Singapore completed three self-reported measures of HRQoL (the EuroQol EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ-BN20). Descriptive statistics summarized their characteristics and scores on the questionnaires. Psychometric properties of QLQ-BN20 examined included convergent and discriminant validity, internal consistency (Cronbach's alpha), and construct validity (Spearman's correlation). Clinical validity of QLQ-BN20 was determined based on whether QLQ-BN20 scores could differentiate patients with good and poor functional status as measured by Karnofsky Performance Scale and Barthel's Index.

Results: The QLQ-BN20 was demonstrated to have good convergent validity (item-own scale correlation >0.70) and discriminant validity (item-own scale correlation higher than item-other scale correlation). There is high internal consistency, both overall (α=0.88) and within multi-item subscales (α=0.74-0.88). Conceptually similar subscales between different tools were more strongly correlated. For instance, the QLQ-C30 physical functioning subscale and the QLQ-BN20 motor dysfunction subscale (r=-0.65, P<0.001), and the QLQ-C30 cognitive functioning subscale and the QLQ-BN20 cognitive deficits subscale (r=-0.51, P<0.001). QLQ-BN20 was also able to distinguish between functional statuses of patients (P<0.05).

Conclusions: This study supports the validity and reliability of the EORTC QLQ-BN20 among patients with glioma in Singapore. There is good convergent and discriminant validity, internal consistency, construct validity, and clinical validity. The QLQ-BN20 is a valuable supplement to the QLQ-C30. Hence, we recommend expanding its use for all glioma patients and possibly brain cancer patients in Singapore.

Background: Due to their location, sellar region tumors can affect a patient's quality of life by mass compression effect and disrupting pituitary function. The treatment choice is determined by some factors, including the presence of mass effect and whether the tumor is secreting or non-secreting. This study assessed the preoperative and postoperative clinical manifestation, hormonal, and head magnetic resonance imaging (MRI) profile of sellar region tumor in Dr. Saiful Anwar General Hospital, East Java.

Methods: This study used a descriptive, cross-sectional design. Data were taken from sellar region tumor registry of Dr. Saiful Anwar General Hospital from March 2023 to April 2024.

Results: Twenty-five patients were included in the study, with 18 (72%) women and 22 patients (88%) aged 41-60 years old. The most frequent neurological symptom was blurred vision (23 patients; 92%). Hormones checked were thyroid hormones [free T4 (FT4), T3, thyroid-stimulating hormone (TSH)], prolactin, cortisol, growth hormone, and gonadotropic hormone [testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH)], but not all patients were checked for all these hormones. Patients were further classified into having low, normal, or high level of the respective hormones, and patients mostly had normal levels. Pituitary macroadenoma was the frequently suspected tumor from head MRIs (11 patients; 44%). Eleven patients underwent tumor excision. Ten patients showed pituitary adenoma and one patient showed pituicytoma on histopathological examination. Mean levels of FT4, T3, and prolactin were decreased after surgery, but TSH and cortisol levels were increased. On postoperative head MRI, four patients showed reduced mass size and one patient showed no residual lesion.

Conclusions: While pituitary macroadenoma was suspected in most head MRIs in this study, most of them were likely non-secreting. Therefore, surgical approach remained the mainstay of treatment. The need for medical management for hormonal disturbances was minimal. While postoperative data were incomplete, some findings from our patients showed that surgical approach could indeed reduce mass effect by improving bitemporal hemianopsia and pituitary deficit.

Background: Giant bilateral intraventricle ependymoma in pediatric patient is indeed a rare type of brain tumor that primarily affects children, accounting for about 5-10% of all brain tumors in children. It arises from ependymal cells, which line the ventricles of the brain and the spinal cord. Essential tremors in the tumor brain have been related to several brain areas, including the thalamus, cortex, globus pallidus, and cerebellum.

Case description: We presented an 8-year-old boy with diagnosed ependymoma with essential tremor, double vision, and dyspnea as symptoms. The magnetic resonance imaging (MRI) with contrast showed the mass appears to be isointense with clear boundaries and regular edges; the impression comes from the bilateral ventricle lateral, which is welded to the bilateral thalamus. A surgical resection was performed in this case. The indication for surgery in this case was due to symptoms of shortness of breath and tremors that unstopped since 1 month ago. The surgery was performed with bilateral occipital craniectomies with the aim of facilitating access to the tumor and a bilateral occipital transcortical approach. Histopathological examination revealed support for an ependymoma.

Conclusions: Ependymoma, especially in children, has various symptoms based on the size, location, and extent of the tumor. MRI with contrast is the main modality for the diagnosis of ependymomas, followed by histopathological examination to confirm. Ependymoma should be considered, and these tumors must be monitored routinely because they can recur. It should be conducted in a multidisciplinary manner to ensure excellent outcomes and avoid fatal complications.

Background: Potential barriers to epilepsy surgery can be divided into two broad groups: reluctance of patients/caregivers and deficient knowledge of neurologists. Pakistan, in particular, faces an epilepsy surgery treatment gap of 70-94%. This study aimed to assess the knowledge and practice of neurologists and the knowledge of the patients diagnosed with epilepsy to identify the barriers to adequate provision of this modality in Pakistan.

Methods: We conducted a cross-sectional study comprising two surveys. Records of patients diagnosed with epilepsy at our hospital during 2.5 years were retrieved from the Neurophysiology database. The second form was designed for neurologists working in Pakistan. The questionnaires were disseminated via email to neurologists and phone calls to patients.

Results: In the patients' survey, we obtained 194 responses from caregivers. The median age of patients was 10 years [interquartile range (IQR): 6-14 years]. We found that 74.2% (n=144) of patients were unaware of surgical options in medically refractory epilepsy (MRE). Therefore, most did not comment on it due to the limited information. Forty-eight patients (24.8%) reported more than 1 seizure per month, and 29 (60.4%) were unaware of the surgical treatment. Seizures were disabling in 88% (n=171) of patients. Patients taking more AEDs were significantly more likely to be aware of surgical options (P=0.001). In the survey from neurologists, only 6.6% (n=4) always discussed epilepsy surgery with MRE patients. Around half of the neurologists, 44.3% (n=27), had never referred a patient for epilepsy surgery. However, 95.1% (n=58) were aware of the under-utilization of epilepsy surgery, and 67.2% (n=41) believed that epilepsy surgery is under-recommended. Almost all neurologists (n=60; 98.4%) believe that comprehensive epilepsy treatment centers are required in the country.

Conclusions: In our survey, we found a lack of awareness in both patients and neurologists to be a major barrier. This contrasts the literature from developed or high-income countries, where physician awareness seems adequate, and stigmas associated with surgery seem to be the major barrier. Multifaceted approaches catered to local concerns are necessary to address these hindrances.

Background: Traditional preclinical experiments on brainstem gliomas mainly rely on patient-derived primary cell lines, but there are problems such as low success rate in establishment and inability to preserve tumor heterogeneity, which limit the clinical transformation. As a new type of in vitro tumor model, organoids have similar structure and function to the original tumor, requiring less tissue for cultivation, with short cycle and high success rate, which is particularly suitable for brainstem glioma biopsy. There is currently no precedent for the successful construction of brainstem glioma organoid models. This new established organoid provides us a more robust preclinical tool for comprehending the pathogenesis and conducting drug screening for this kind of disease.

Methods: Cultivate patient-derived brainstem glioma organoids in vitro, verify the genetic fidelity and consistency of the organoids through morphological experiments as well as sequencing technology. Then explore the evolutionary direction of multiple types of brainstem gliomas through pseudo-time series analysis. Complete drug screening, natural killer (NK) cell co-culture, oncolytic virus therapy, and other treatments based on organoids in vitro, and evaluate the efficacy. Complete co-culture of organoids and Institute of Cancer Research (ICR) mouse brain slices in vitro. Establish patient-derived organoid xenograft (PDOX) mouse models derived from organoids in vivo.

Results: The establishment of organoids of all types of brainstem gliomas was completed for the first time in the world, with a total of 41/48 organoid models derived from patients, with a success rate of 85.4%, covering all segments and pathological types. The results of morphological experiments and sequencing showed that the genetic characteristics of organoids were highly consistent with those of tumor tissues. Drug screening tests for temozolomide and panobinostat were completed in vitro, and NK cell co-culture and oncolytic virus therapy testing were achieved. Co-culture of brainstem glioma organoids and mouse brain slices was achieved in vitro. Furthermore, a PDOX model of brainstem glioma was established.

Conclusions: Brainstem glioma organoids can be established maturely, stably, and reliably, and can be used for preclinical drug testing for patients. Animal models derived from brainstem glioma organoids have broad preclinical experimental value.

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.