Role of Ubiquitin-specific Proteases in Hepatocellular Carcinoma Pathogenesis.

Signaling pathways in hepatocellular carcinoma are primarily mediated by the phosphorylation and ubiquitination of post-translational proteins. In mammalian cells, ubiquitin-specific proteases (USPs) account for the majority of protein deubiquitination activities. In addition to transcriptional and post-translational regulation, ubiquitination plays an important role in the regulation of key proteins. There is a possibility that altered biological processes may lead to serious human diseases, including cancer. Recent studies have revealed the role of USPs in hepatocellular carcinoma tumorigenesis. The purpose of this review is to summarize the involvement of this class of enzymes in the regulation of cell signaling in hepatocellular carcinoma and the therapeutic development of inhibitors that target USPs, which may lead to novel therapies to treat hepatocellular carcinoma.

Acute Porphyromonas gingivalis Subdural Abscess with Brain Abscess in the Left Temporal Lobe: A Case Report and Review of Literature.

Background: Brain abscesses are a rare but serious complication of focal intracerebral infection. Case Description: We present a patient of acute subdural abscess with brain abscess in the left temporal lobe. After craniotomy, combined with the Third Next Generation Sequencing and Gene Diagnosis (TNGS & GD) of abscess, we prescribed sensitive antibiotics; the patient recovers well and the abscess did not recur. Conclusion: For patients with acute subdural abscess, combined craniotomy and the TNGS & GD of abscess could achieve good results.

Guiding ablation strategies for ventricular tachycardia in patients with structural heart disease by analyzing links and conversion patterns of traceable abnormal late potential zone.

BACKGROUND: Substrate-based ablation can treat uninducible or hemodynamically instability scar-related ventricular tachycardia (VT). However, whether a correlation exists between the critical VT isthmus and late activation zone (LAZ) during sinus rhythm (SR) is unknown. OBJECTIVE: To demonstrate the structural and functional properties of abnormal substrates and analyze the link between the VT circuit and abnormal activity during SR. METHODS: Thirty-six patients with scar-related VT (age, 50.0 ± 13.7 years and 86.1% men) who underwent VT ablation were reviewed. The automatic rhythmia ultrahigh resolution mapping system was used for electroanatomic substrate mapping. The clinical characteristics and mapping findings, particularly the LAZ characteristics during SR and VT, were analyzed. To determine the association between the LAZ during the SR and VT circuits, the LAZ was defined as five activation patterns: entrance, exit, core, blind alley, and conduction barrier. RESULTS: Forty-five VTs were induced in 36 patients, 91.1% of which were monomorphic. The LAZ of all patients was mapped during the SR and VT circuits, and the consistency of the anatomical locations of the LAZ and VT circuits was analyzed. Using the ultrahigh resolution mapping system, interconversion patterns, including the bridge, T, puzzle, maze, and multilayer types, were identified. VT ablation enabled precise ablation of abnormal late potential conduction channels. CONCLUSION: Five interconversion patterns of the LAZ during the SR and VT circuits were summarized. These findings may help formulate more precise substrate-based ablation strategies for scar-related VT and shorter procedure times.

Densely populated tiny RuO2 crystallites supported by hierarchically porous carbon for full acidic water splitting.

The exploitation of highly active bifunctional electrocatalysts for the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in acidic media has been a subject receiving immense interest. However, the existing catalysts usually suffer from low catalytic efficiency and poor corrosion resistance under acidic conditions. Herein, we report a facile molten salt method to fabricate ruthenium dioxide nanoparticles supported by hierarchically porous carbon (RuO2/PC) as a bifunctional electrocatalyst for full water splitting under strong acidic conditions. The formation of a densely populated nanocrystalline RuO2/carbon heterostructure helps expose catalytic sites, accelerates the mass transfer rate, and further enhances the acid resistance of RuO2 nanoparticles. The as-synthesized RuO2/PC consequently exhibits superior catalytic performance for the OER with an overpotential of 181 mV upon 10 mA cm-2 compared to that of the commercial RuO2 (343 mV) and a comparable performance to Pt/C for the HER (47.5 mV upon 10 mA cm-2) in 0.5 M H2SO4. The RuO2/PC shows promising stability with little degradation over ∼24 h. Impressively, the water electrolyzer based on RuO2/PC shows an overpotential of 326 mV at 10 mA cm-2, much lower than that of the electrolyzer based on the combination of Pt/C and RuO2 (400 mV), indicating its great potential towards practical application.

Amine oxidase copper-containing 3 aggravates cardiac remodelling by generating hydrogen peroxide after myocardial infarction.

Amine oxidase copper-containing 3 (AOC3) is a member of the semicarbazide-sensitive amine oxidase enzyme family. It acts as an ectoenzyme catalysing the oxidative deamination of primary amines and generating hydrogen peroxide (H2 O2 ). While AOC3 is implicated in cardiovascular diseases such as atherosclerosis, its role in cardiac remodelling after myocardial infarction (MI) is unclear. In this study, we first confirmed a long-term upregulation of AOC3 in both cardiac myofibroblasts after MI in vivo and angiotensin II (ANGII)-treated cardiac fibroblasts in vitro. AOC3 knockdown not only inhibited the activation of cardiac fibroblasts induced by ANGII but also alleviated cardiac fibrosis in mice after MI. Using sh-AOC3 lentiviruses, exogenous recombinant AOC3 (r-AOC3), semicarbazide (an AOC3 inhibitor), and catalase (a hydrogen peroxide scavenger) treatments, we also demonstrated that AOC3 promoted H2 O2 generation, increased oxidative stress, and enhanced ERK1/2 activation, which were responsible for the activation of cardiac fibroblasts. In particular, AOC3 knockdown also improved cardiac function and hypertrophy after MI. Through a coculture system, we confirmed that AOC3 expressed on cardiac myofibroblasts was able to enhance oxidative stress and induce hypertrophy of cardiomyocytes by promoting H2 O2 generation. Similarly, r-AOC3 promoted H2 O2 generation and resulted in oxidative stress and hypertrophy of cardiomyocytes, which were almost inhibited by both semicarbazide and catalase. In conclusion, AOC3 plays a critical role in cardiac fibrosis and hypertrophy after MI by promoting the generation of H2 O2 . AOC3 is a promising therapeutic target against cardiac remodelling. © 2023 The Pathological Society of Great Britain and Ireland.

Development of Furanopyrimidine-Based Orally Active Third-Generation EGFR Inhibitors for the Treatment of Non-Small Cell Lung Cancer.

The development of orally bioavailable, furanopyrimidine-based double-mutant (L858R/T790M) EGFR inhibitors is described. First, selectivity for mutant EGFR was accomplished by replacing the (S)-2-phenylglycinol moiety of 12 with either an ethanol or an alkyl substituent. Then, the cellular potency and physicochemical properties were optimized through insights from molecular modeling studies by implanting various solubilizing groups in phenyl rings A and B. Optimized lead 52 shows 8-fold selective inhibition of H1975 (EGFRL858R/T790M overexpressing) cancer cells over A431 (EGFRWT overexpressing) cancer cells; western blot analysis further confirmed EGFR mutant-selective target modulation inside the cancer cells by 52. Notably, 52 displayed in vivo antitumor effects in two different mouse xenograft models (BaF3 transfected with mutant EGFR and H1975 tumors) with TGI = 74.9 and 97.5% after oral administration (F = 27%), respectively. With an extraordinary kinome selectivity (S(10) score of 0.017), 52 undergoes detailed preclinical development.

Combined effects of vitamin D and neferine on the progression and metastasis of colorectal cancer.

PURPOSE: To investigate the synergistic effect of vitamin D and neferine on the growth and metastasis of colorectal cancer (CRC). METHODS: The synergistic effect of biologically active form of vitamin D, VD3 and neferine on the treatment of CRC was investigated by bliss analysis. Colony formation and wound healing ability, migration and invasion ability, and epithelial mesenchymal transition of HCT-116 cells, as a response to the combination treatment with VD3 and neferine were evaluated. RESULTS: VD3 and neferine showed a synergistic effect on CRC cell growth at a relatively low dose. The wound healing and colony formation capacity, cell migration and invasion abilities were all decreased by combination use of VD3 and neferine, compared to the VD3 or neferine treated single group. Furthermore, VD3 and neferine significantly decreased the expressions of N-cadherin, vimentin, snail, and slug in HCT-116 cells. CONCLUSION: These data suggest that neferine enhances the anticancer capability of VD3 and reduces the dose dependency of VD3. The combination of vitamin D with neferine appears to be a potential therapeutic strategy for CRC.

Early committed polarization of intracellular tension in response to cell shape determines the osteogenic differentiation of mesenchymal stromal cells.

Within the heterogeneous tissue architecture, a comprehensive understanding of how cell shapes regulate cytoskeletal mechanics by adjusting focal adhesions (FAs) signals to correlate with the lineage commitment of mesenchymal stromal cells (MSCs) remains obscure. Here, via engineered extracellular matrices, we observed that the development of mature FAs, coupled with a symmetrical pattern of radial fiber bundles, appeared at the right-angle vertices in cells with square shape. While circular cells aligned the transverse fibers parallel to the cell edge, and moved them centripetally in a counter-clockwise direction, symmetrical bundles of radial fibers at the vertices of square cells disrupted the counter-clockwise swirling and bridged the transverse fibers to move centripetally. In square cells, the contractile force, generated by the myosin IIA-enriched transverse fibers, were concentrated and transmitted outwards along the symmetrical bundles of radial fibers, to the extracellular matrix through FAs, and thereby driving FA organization and maturation. The symmetrical radial fiber bundles concentrated the transverse fibers contractility inward to the linkage between the actin cytoskeleton and the nuclear envelope. The tauter cytoskeletal network adjusted the nuclear-actomyosin force balance to cause nuclear deformability and to increase nuclear translocation of the transcription co-activator YAP, which in turn modulated the switch in MSC commitment. Thus, FAs dynamically respond to geometric cues and remodel actin cytoskeletal network to re-distribute intracelluar tension towards the cell nucleus, and thereby controlling YAP mechanotransduction signaling in regulating MSC fate decision. STATEMENT OF SIGNIFICANCE: We decipher how cellular mechanics is self-organized depending on extracellular geometric features to correlate with mesenchymal stromal cell lineage commitment. In response to geometry constrains on cell morphology, symmetrical radial fiber bundles are assembled and clustered depending on the maturation state of focal adhesions and bridge with the transverse fibers, and thereby establishing the dynamic cytoskeletal network. Contractile force, generated by the myosin-IIA-enriched transverse fibers, is transmitted and dynamically drives the retrograde movement of the actin cytoskeletal network, which appropriately adjusts the nuclear-actomyosin force balance and deforms the cell nucleus for YAP mechano-transduction signaling in regulating mesenchymal stromal cell fate decision.

Trimethylamine-N-oxide (TMAO) promotes balloon injury-induced neointimal hyperplasia via upregulating Beclin1 and impairing autophagic flux.

BACKGROUND AND AIMS: TMAO is a microbiota-dependent metabolite associated with increased risk of various cardiovascular diseases. However, the relationship between TMAO and vascular injury-related neointimal hyperplasia is unclear. This study aimed to explore whether TMAO promotes neointimal hyperplasia after balloon injury and elucidate the underlying mechanism. METHODS AND RESULTS: Through hematoxylin and eosin staining and immunohistochemistry staining, we found that supplementary TMAO promoted balloon injury-induced neointimal hyperplasia, while reducing TMAO by antibiotic administration produced the opposite result. TMAO showed limited effect on rat aortic vascular smooth muscle cells (RAOSMCs) proliferation and migration. However, TMAO notably induced dysfunction of rat aortic vascular endothelial cells (RAOECs) in vitro and attenuated reendothelialization of carotid arteries after balloon injury in vivo. Autophagic flux was measured by fluorescent mRFP-GFP-LC3, transmission electron microscopy, and western blot. TMAO impaired autophagic flux, as evidenced by the accumulation of p62 and LC3II and high autophagosome to autolysosome ratios. Furthermore, we confirmed that Beclin1 level increased in TMAO-treated RAOECs and carotid arteries. Knocking down Beclin1 alleviated TMAO-induced autophagic flux impairment and neointimal hyperplasia. CONCLUSIONS: TMAO promoted neointimal hyperplasia through Beclin1-induced autophagic flux blockage, suggesting that TMAO is a potential target for improvement of vascular remodeling after injury.

Two Cases Report of Intrathecal Tigecycline Therapy for Intracranial Infection with Acinetobacter baumannii and Review of Literatures.

OBJECTIVE: To explore the treatment scheme for intracranial infection with Acinetobacter baumannii. METHODS: We retrospective analyzed two cases of patients of intracranial infection with Acinetobacter baumannii. RESULTS: The intracranial infection was controlled effectively by the scheme to intravenous"tigecycline + cefperazone-sulbactam"combined with intrathecal tigecycline injection, the two patients recover well with 21 months' follow-up. CONCLUSIONS: Tigecycline-based drug scheme combined with intrathecal tigecycline injection can achieve the effect of controlling intracranial infection. Lumbar cisterna drainage tube plays a major role in controlling intracranial infection.

Elabela ameliorates doxorubicin-induced cardiotoxicity by promoting autophagic flux through TFEB pathway.

Doxorubicin (DOX) is a widely used and effective antineoplastic drug; however, its clinical application is limited by cardiotoxicity. A safe and effective strategy to prevent from doxorubicin-induced cardiotoxicity (DIC) is still beyond reach. Elabela (ELA), a new APJ ligand, has exerted cardioprotective effect against multiple cardiovascular diseases. Here, we asked whether ELA alleviates DIC. Mice were injected with DOX to established acute DIC. In vivo studies were assessed with echocardiography, serum cTnT and CK-MB, HW/BW ratio and WGA staining. Cell death and atrophy were measured by AM/PI staining and phalloidin staining respectively in vitro. Autophagic flux was monitored with Transmission electron microscopy in vivo, as well as LysoSensor and mRFP-GFP-LC3 puncta in vitro. Our results showed that ELA improved cardiac dysfunction in DIC mice. ELA administration also attenuated cell death and atrophy in DOX-challenged neonatal rat cardiomyocytes (NRCs). Additionally, we found that ELA restored DOX-induced autophagic flux blockage, which was evidenced by the reverse of p62 and LC3II, improvement of lysosome function and accelerated degradation of accumulated autolysosomes. Chloroquine, a classical autophagic flux inhibitor, blunted the improvement of ELA on cardiac dysfunction. At last, we revealed that ELA reversed DOX-induced downregulation of transcription factor EB (TFEB), and silencing TFEB by siRNA abrogated the effects of ELA on autophagic flux as well as cell death and atrophy in NRCs. In conclusion, this study indicated that ELA ameliorated DIC through enhancing autophagic flux via activating TFEB. ELA may become a potential target against DIC.

Effect of Body Mass Index in Coronary CT Angiography Performed on a 256-Slice Multi-Detector CT Scanner.

We aimed to investigate the effect of a patient's body mass index (BMI) on radiation dose and image quality in prospectively ECG-triggered coronary CT angiography (CCTA) performed on a 256-slice multi-detector CT scanner. In total, 87 consecutive patients receiving CCTA examinations acquired with tube current modulation (TCM) and iterative reconstruction (IR) were enrolled in this study. The dose report recorded from the CT scanner console was used to derive the effective dose for patients. Subjective image quality scoring and objective noise measurements were conducted to quantify the impact of BMI on the image quality of CCTA. Because of the TCM technique, we expected tube current and radiation dose to increase as BMI increased. However, using TCM did not always guarantee sufficient radiation exposure to achieve consistent image quality for overweight or obese patients since the maximum X-ray tube output in milliamperes and kilovoltage peak was reached. The impact of photon starvation noise on image quality was not significant until BMI ≥ 27 kg/m2; this result could be due to IR's noise reduction capability. Our results also suggest that using TCM with a noise index of 25 HU can reduce radiation dose without compromising image quality compared to images obtained based on the manufacturer's default settings.

The compensatory mechanism and clinical significance of hydrocephalus after cranioplasty.

Objective: Cranioplasty (CP) and ventriculoperitoneal shunt (VPS) are procedures required after decompression of the flap (DC) to protect the cranial frame and prevent hydrocephalus. This study evaluated the safety and efficacy of different surgical sequences of CP and VPS after DC and identified risk factors for necessary permanent VPS. Methods: From January 2017 to December 2021, valid follow-up data were collected in 192 cases. The observation group preferred CP, and then evaluated whether to receive VPS according to the progress of hydrocephalus. the control group was prioritized for VPS and continued with CP after 1 week. The improvement of hydrocephalus symptoms, follow-up outcomes, and post-operative complications before and after surgery were compared between the two groups, and univariate analysis was used to determine the risk factors for necessary permanent risk factors for VPS. Results: There were 86 cases (44.8%) in the observation group, who received CP first, while 106 cases (55.2%) in the control group received VPS and CP, respectively. There was no significant difference between the two groups according to Barthel index, FMAS, Mrs, GCS, and Evans index, and there was no statistical difference in complications between the two groups. However, in the observation group, hydrocephalus disappeared after CP operation in 29 cases (33.7%), and finally avoided VPS. Univariate analysis showed that the main etiology was related to the size of the skull defect, the distance of the talus margin relative to the flap to the midline, and lumbar puncture pressure was a predictor of the need for permanent VPS. Conclusion: This study provides detailed information on the efficacy and complications of different sequences of preferential CP or VPS after DC surgery. We found that priority CP reduced the incidence of VPS surgery without affecting surgical outcomes and complications.

Fine Mapping of the MHC Region Identifies Novel Variants Associated with HBV-Related Hepatocellular Carcinoma in Han Chinese.

INTRODUCTION: Genome-wide association studies identified susceptibility loci in the major histocompatibility complex region for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, the causal variants underlying HBV-related HCC pathogenesis remain elusive. METHODS: With a total of 1,161 HBV-related HCC cases and 1,353 chronic HBV carriers without HCC, we imputed human leukocyte antigen (HLA) variants based on a Chinese HLA reference panel and evaluated the associations of these variants with the risk of HBV-related HCC. Conditional analyses were used to identify independent signals associated with the risk of HBV-related HCC (P false-discovery rate (FDR) <0.20). A total of 14,930 variants within the MHC region were genotyped or imputed. RESULTS: We identified two variants, rs114401688 (P = 1.05 × 10-6, PFDR = 2.43 × 10-3) and rs115126566 (P = 9.04 × 10-5, PFDR = 1.77 × 10-1), that are independently associated with the risk of HBV-related HCC. Single nucleotide polymorphism (SNP) rs114401688 is in linkage disequilibrium with a previously reported SNP rs9275319. In the current study, we found that its association with HCC could be explained by HLA-DQB1*04 and HLA-DRB1*04. SNP rs115126566 is a novel risk variant and may function by regulating transcriptions of HLA-DPA1/DPB1 through enhancer-mediated mechanisms. HLA zygosity analysis showed that homozygosity at HLA-DQB1 gene is suggestively associated with a higher risk of HCC (P = 0.10) and the risk was more pronounced in the older age group (age ≥50, P = 0.03). DISCUSSION: Our findings further the understanding of the genetic basis for HBV-related HCC predisposition in chronic HBV carriers.

Nkx2-3 induces autophagy inhibiting proliferation and migration of vascular smooth muscle cells via AMPK/mTOR signaling pathway.

Vascular remodeling and restenosis are common complications after percutaneous coronary intervention. Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in intimal hyperplasia-induced vascular restenosis. NK2 Homeobox 3 (Nkx2-3), a critical member of Nkx family, is involved in tissue differentiation and organ development. However, the role of Nkx2-3 in VSMCs proliferation and migration remains unknown. In this study, we used carotid balloon injury model and platelet-derived growth factor-BB (PDGF)-treated VSMCs as in vivo and in vitro experimental models. EdU assay and CCK-8 assay were used to detect cell proliferation. Migration was measured by scratch test. Hematoxylin and eosin staining and immunohistochemistry staining were used to evaluate the intimal hyperplasia. The autophagy level was detected by fluorescent mRFP-GFP-LC3 in vitro and by transmission electron microscopy in vivo. It was shown that Nkx2-3 was upregulated both in balloon injured carotid arteries and PDGF-stimulated VSMCs. Adenovirus-mediated Nkx2-3 overexpression inhibited intimal hyperplasia after balloon injury, and suppressed VSMCs proliferation and migration induced by PDGF. Conversely, silencing of Nkx2-3 by small interfering RNA exaggerated proliferation and migration of VSMCs. Furthermore, we found that Nkx2-3 enhanced autophagy level, while the autophagy inhibitor 3-MA eliminated the inhibitory effect of Nkx2-3 on VSMCs proliferation and migration both in vivo and in vitro. Moreover, Nkx2-3 promoted autophagy in VSMCs by activating the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. These results demonstrated for the first time that Nkx2-3 inhibited VSMCs proliferation and migration through AMPK/mTOR-mediated autophagy.

Comparisons of cancer detection rate and complications between transrectal and transperineal prostate biopsy approaches - a single center preliminary study.

BACKGROUND: Prostate biopsy remains the gold standard approach to verify prostate cancer diagnosis. Transrectal (TR) biopsy is a regular modality, while transperineal (TP) biopsy is an alternative for the patients who display persistently high levels of prostate-specific antigen (PSA) and thus have to undergo repeat biopsy. This study aimed to compare the cancer detection rates between TR and TP approaches and assess the post-bioptic complications of the two procedures. Besides, the feasibility of performing TP biopsies under local anesthesia was also evaluated. METHODS: A total of 238 outpatient visits meeting the criteria for prostate cancer biopsy were enrolled for this study. They were divided into two groups: the TP group (n = 130) consists of patients destined to undergo local anesthetic TP biopsy; and the TR group (n = 108) contained those who received TR biopsy as comparison. Age, PSA level, digital rectal exam (DRE) finding, prostate volume, and biopsy core number were used as the parameters of the multivariable analyses. The comparable items included cancer detection rate, complication rate, admission rate and visual analog scale (VAS) score. RESULTS: The cancer detection rates between TP and TR groups were quite comparable (45% v.s. 49%) (p = 0.492). However, the TP group, as compared to the TR group, had significantly lower incidence of infection-related complications (except epididymitis and prostatitis) that commonly occur after biopsies. None of the patients in the TP group were hospitalized due to the post-bioptic complications, whereas there was still a minor portion of those in the TR group (7.4%) requiring hospitalization after biopsy. Medians (25-75% quartiles) of visual analog scale (VAS) were 3 [3, 4] and 4 [3-5] respectively for the TP and TR procedures under local anesthesia, but no statistical significance existed between them (p = 0.085). CONCLUSIONS: Patients receiving TP biopsy are less likely to manifest infection-related complications. Therefore, TP biopsy is a more feasible local anesthetic approach for prostate cancer detection if there are concerns for infectious complications and/or the risk of general anesthesia.

Clinical features and operative technique of transinfundibular craniopharyngioma.

OBJECTIVE: Transinfundibular craniopharyngioma (TC) is one of the 4 subtypes of suprasellar craniopharyngioma. In this study, the authors analyzed the clinical features of and operative technique for TC. METHODS: A total of 95 consecutive cases of suprasellar craniopharyngioma that had been resected via the endoscopic expanded endonasal approach were retrospectively reviewed. Patients were divided into 2 groups: 34 in the TC group and 61 in the nontransinfundibular craniopharyngioma (NC) group. Clinical and radiographic features, intraoperative findings, histopathological and genetic findings, and surgical outcomes were analyzed and compared between groups. RESULTS: Compared with NC, TC was mostly seen in adult patients (97.1%); it was rare in children (2.9%). Clinical presentations tended toward headache, hydrocephalus, and diabetes insipidus. The relatively smaller volume, midline location (consistent with the stalk position), unidentifiable stalk, no shift of the third ventricle, and greater likelihood to involve the third ventricle and cause hydrocephalus were the characteristic features of TC in the preoperative MRI study. According to the degree of vertical extension of the tumor, the 34 TCs could be classified into 3 subtypes: type 1, entity was limited to stalk (n = 2, 5.9%); type 2, tumor extended up to the third ventricle (type 2a) or down to the subdiaphragmatic cavity (type 2b) (n = 23, 67.6%); and type 3, tumor extended in both directions (n = 9, 26.5%). For TC resection, the chiasm-pituitary corridor, lamina terminalis corridor, and pituitary corridor could be used separately or jointly. Most of the TCs originated from the infundibulum-tuber cinereum, grew within and along the long axis of the infundibulum, and the pituitary stalk was not usually preserved in TCs (20.6%), whereas the rate of preservation was higher (80.3%) in NCs. Bilateral hypothalamic injury was found in nearly all TCs if radical resection was performed, whereas the relationship between NCs and hypothalamus was either compression (32.8%) or unilateral invasion (67.2%). Meanwhile, the postoperative endocrine and neuropsychological function outcomes in patients with TC were worse than in patients with NC. The genetic analysis with whole-exome sequencing studies showed no differential mutations of CTNNB1 (ß-catenin) and BRAF (V600E) between TC and NC subtypes, but there was a difference between adamantinomatous craniopharyngioma and papillary craniopharyngioma. CONCLUSIONS: TC is a special subtype of suprasellar craniopharyngioma, which is remarkably different from NC. Identification of this type of tumor preoperatively is essential for the planning of appropriate surgical approach and degree of excision.

Does preoperative percutaneous nephrostomy insertion worsen upper-tract urothelial cancer oncological outcome? A retrospective single center study.

BACKGROUND: Physicians doubt percutaneous nephrostomy (PCN) insertion on cancer related hydronephrosis patients causes tumor seeding and worse cancer control. In this article, we attempted to determine if preoperative PCN alters cancer control in upper tract urothelial cancer (UTUC) patients. METHODS: Retrospective analysis of UTUC patients in a single center from 2005 to 2015. Exclusion criteria included lymph node metastasis, and patients underwent perioperative adjuvant chemotherapy or radiotherapy. There were 664 patients in this analysis, with clinico-pathological data being collected retrospectively for Cox-regression statistical analysis. Outcomes were measured by local recurrence, distant metastasis and cancer-specific death with Kaplan-Meier curves. RESULTS: There were respectively 25 and 639 UTUC cancers in the preoperative PCN and non-PCN insertion groups with mean follow-up duration of 37.9 and 48.6 months, respectively. The preoperative PCN group consisted of 17 patients (68%) with tumor located in the ureter, while the PCN-negative group included 236 patients (36%) with tumor located in the ureter being statistically significant. These two groups were comparable in gender, age, follow-up duration, tumor stage, and pathological features of the UTUC. As for the cancer control in the PCN group, 4(16%), 1(4%) and 1(4%) had local recurrence, distant metastasis and cancer-specific death respectively; in the non-PCN group, 101(15.8%), 96(15%) and 72(11.2%) exhibited local recurrence, distant metastasis and cancer-specific death respectively. Statistical analysis showed no difference in oncologic outcomes between these two groups.(p = 0.804, 0.201 and 0.254). CONCLUSIONS: Preoperative percutaneous nephrostomy on upper-tract urothelial cancer poses little risk on tumor seeding and could be considered as part of treatment strategy if renal function preservation is needed.

Extended endoscopic endonasal approach for recurrent or residual symptomatic craniopharyngiomas.

OBJECTIVES: Removal of recurrent or residual symptomatic craniopharyngiomas is more challenging than the primary surgery. The extended endoscopic endonasal (EEE) approach has been proposed an alternative surgical route for removal of various suprasellar tumors including craniopharyngiomas currently. In this study, we summarized the operative experience and described the feasibility and advantages of this technique in recurrent or residual symptomatic craniopharyngiomas. PATIENTS AND METHODS: A retrospective review of 15 patients (9 males and 6 females) whom underwent EEE approach between April 2012 and February 2017, were included in this study. The lesions included 8 purely suprasellar craniopharyngiomas (2 extraventricular, 6 intraextraventricular), 3 both intra- and suprasellar craniopharyngiomas, and 4 intrasellar craniopharyngiomas. The mean preoperative (that is, EEE approach) tumor volume was 10.54 cm3. The mean follow-up period was 23.1 months (range, 8-54). All patients were analyzed in terms of the treatment effect, complictions and follow-up results. RESULTS: Total removal of tumors was achieved in 12 patients (80.0%) and subtotal removal in 3 cases (20.0%). The pituitary stalks were identified in 11 patients during operations and secured in 8 patients. Postoperative visual acuity was improved in 10 cases, and normalization of the impairment was achieved in 3 patients. There were no significant differences between pre and postoperative endocrine function, except in one patient with normal preoperative pituitary hormone function who suffered postoperative hypopituitarism. Postoperative diabetes insipidus (DI) occurred in 14 patients including 6 patients who had long-term DI and others reporting transient postoperative DI. No cerebrospinal fluid (CSF) leak was identified. There were no deaths or major complications. Obesity developed in 2 patients, with no deaths and recurrent cases during follow-up period. CONCLUSION: The pure EEE approach is a safe, effective alternative for treatment of recurrent or residual symptomatic craniopharyngiomas owing to its advantages including wide-angle view, close observation and elimination of brain retraction. Larger studies with further follow-up is needed to assess the long-term efficacy of this minimal access approach.

Endoscopic Endonasal Clipping of Anterior Circulation Aneurysm: Surgical Techniques and Results.

BACKGROUND: Endoscopic endonasal clipping of intracranial aneurysms may use microsurgical techniques as an alternative to the transcranial approach. Here we report a series of patients who underwent microsurgical clipping of anterior circulation aneurysms via an endoscopic endonasal approach (EEA). METHODS: This retrospective chart review included all the patients who underwent standard binostril EEA for aneurysm clipping. Surgical outcomes and complications are noted. The rationality and limitations of this procedure are discussed. RESULTS: Seven patients with 12 aneurysms of the anterior circulation underwent EEA for clipping. These 12 aneurysms consisted of 5 anterior communicating artery (AComA) aneurysms, 4 paraclinoid aneurysms, 1 ophthalmic artery aneurysm, and 2 aneurysm located in the cavernous segment of internal carotid artery (ICA). Nine of the 12 aneurysms were successfully clipped. One giant paraclinoid aneurysm could not be clipped during operation and was coiled in second endovascular stage. The 2 aneurysms located in the cavernous segment of ICA were not clipped intentionally in a single-stage procedure, after weighing the surgical benefit against the difficulty of surgical exposure and feasibility. The proximal control of ICA was achieved in all cases. There was no death, no cerebrospinal fluid leak, or other complications. All patients recovered completely. CONCLUSIONS: EEA can provide direct access for microsurgical clipping of strictly selected anterior circulation aneurysms. All the principles of cerebrovascular surgery must be followed. These procedures require a long learning curve. Only teams with adequate experience in microvascular and endoscopic skull base surgeries should attempt this approach for treating aneurysms.