Enhanced Vascular-like Network Formation of Encapsulated HUVECs and ADSCs Coculture in Growth Factors Conjugated GelMA Hydrogels.

Tissue engineering primarily aimed to alleviate the insufficiency of organ donations worldwide. Nonetheless, the survival of the engineered tissue is often compromised due to the complexity of the natural organ architectures, especially the vascular system inside the organ, which allows food-waste transfer. Thus, vascularization within the engineered tissue is of paramount importance. A critical aspect of this endeavor is the ability to replicate the intricacies of the extracellular matrix and promote the formation of functional vascular networks within engineered constructs. In this study, human adipose-derived stem cells (hADSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured in different types of gelatin methacrylate (GelMA). In brief, pro-angiogenic signaling growth factors (GFs), vascular endothelial growth factor (VEGF165) and basic fibroblast growth factor (bFGF), were conjugated onto GelMA via an EDC/NHS coupling reaction. The GelMA hydrogels conjugated with VEGF165 (GelMA@VEGF165) and bFGF (GelMA@bFGF) showed marginal changes in the chemical and physical characteristics of the GelMA hydrogels. Moreover, the conjugation of these growth factors demonstrated improved cell viability and cell proliferation within the hydrogel construct. Additionally, vascular-like network formation was observed predominantly on GelMA@GrowthFactor (GelMA@GF) hydrogels, particularly on GelMA@bFGF. This study suggests that growth factor-conjugated GelMA hydrogels would be a promising biomaterial for 3D vascular tissue engineering.

Image-Guided Thermal Ablation for Hepatic Epithelioid Hemangioendothelioma: A Multicenter Experience.

PURPOSE: To investigate the feasibility, safety, and clinical outcomes of image-guided thermal ablation in patients with hepatic epithelioid hemangioendothelioma (HEHE). MATERIALS AND METHODS: This was a multicenter retrospective investigation of 18 patients (43.9 years [SD ± 14.8]; 6 men) who underwent image-guided thermal ablation for HEHE between January 2013 and February 2023. A total of 31 ablation sessions (24 involving microwave ablation and 7 involving radiofrequency ablation) were evaluated. The rates of technical success, adverse events, and outcomes were assessed. The Kaplan‒Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) rates. The risk factors affecting PFS were investigated using Cox proportional hazard regression analysis. RESULTS: The technical success rate was 93.5% (29/31). No major adverse events occurred. Local tumor progression occurred after 2 sessions (6.5%, 2/31), and intrahepatic distant metastasis occurred after 16 sessions (51.6%, 16/31). During the medium follow-up time of 37.2 months (range, 3-117 months), the OS and PFS rates were 87.6% and 62.2%, respectively, at 1 year; 75.5% and 37.4%, respectively, at 3 years; and 75.5% and 37.4%, respectively, at 5 years. The median OS and PFS were 90.5 months (95% CI: 68.1-112.8) and 23.8 months (95% CI: 15.4-32.2), respectively. According to the multivariate analysis, a larger tumor size (P = .026) was associated with shorter PFS. CONCLUSIONS: Image-guided thermal ablation is a feasible and safe treatment option for patients with HEHE that resulted in local tumor control and a favorable long-term prognosis.

A multicenter case-controlled study on laparoscopic hepatectomy versus microwave ablation as first-line therapy for 3-5 cm hepatocellular carcinoma in patients aged 60 and older.

BACKGROUND: There is currently a lack of convincing evidence for microwave ablation (MWA) and laparoscopic liver resection (LLR) for patients ≥60 years old with 3-5 cm hepatocellular carcinoma. MATERIALS AND METHODS: Patients were divided into three cohorts based on restricted cubic spline analysis: 60-64, 65-72, and ≥73 years. Propensity score matching (PSM) was performed to balance the baseline variables in a 1:1 ratio. Overall survival (OS) and disease-free survival (DFS) were assessed, followed by a comparison of complications, hospitalization, and cost. RESULTS: Among 672 patients, the median age was 66 (IQR 62-71) years. After PSM, two groups of 210 patients each were selected. During the 36.0 (20.4-52.4) month follow-up period, the 1-year, 3-year, and 5-year OS rates in the MWA group were 97.6, 80.9, and 65.3% and 95.5, 78.7, and 60.4% in the LLR group (HR 0.98, P =0.900). The corresponding DFS rates were 78.6, 49.6, and 37.5% and 82.8, 67.8, and 52.9% (HR 1.52, P =0.007). The 60-64 age cohort involved 176 patients, with no a significant difference in OS between the MWA and LLR groups (HR 1.25, P =0.370), MWA was associated with a higher recurrence rate (HR 1.94, P =0.004). A total of 146 patients were matched in the 65-72 age cohort, with no significant differences in OS and DFS between the two groups (OS (HR 1.04, P =0.900), DFS (HR 1.56, P =0.110)). In 76 patients aged ≥73 years after PSM, MWA provided better OS for patients (HR 0.27, P =0.015), and there were no significant differences in DFS between the two groups (HR 1.41, P =0.380). Taken together, for patients older than 65 years, the recurrence rate of MWA was comparable with LLR. Safety analysis indicated that LLR was associated with more postoperative bleeding ( P =0.032) and hypoproteinemia ( P =0.024). CONCLUSIONS: MWA was comparable to LLR in patients aged 65 years and older. MWA could be an alternative for the oldest old or the ill patients who cannot afford LLR, while LLR is still the first option of treatments for early-stage 3-5 cm hepatocellular carcinoma in capable elderly's.

Hippocampal volume and resting-state functional connectivity on magnetic resonance imaging in patients with Parkinson and depression.

Background: Recent structural and functional imaging studies of depression in Parkinson disease (DPD) have failed to reveal the relevant mechanism, and relatively few studies have been conducted on limbic systems such as the hippocampus. This study thus aimed to gain new insights into the pathogenesis of DPD by detecting the changes in the hippocampal structure and the resting-state functional connectivity (FC) of patients with DPD. Methods: This study included 30 patients with DPD (DPD group), 30 patients with nondepressed Parkinson disease (NDPD; NDPD group), and 30 normal controls (NCs; NC group) with no significant age or gender differences with the DPD group. The Hamilton Depression Rating Scale (HAMD) and three-dimensional T1-weighted imaging and blood oxygen level-dependent imaging data of all patients were collected. The hippocampal volumes were measured using MATLAB software (MathWorks). The correlation between hippocampal volume and the HAMD score in the DPD group was analyzed with Pearson correlation coefficient. The bilateral hippocampi were used as the regions of interest and as the seed points for FC. FC analysis was performed between the preprocessed functional data of the whole brain and the two seed points with Data Processing Assistant for Resting-State and Statistical Parametric Mapping 8 software, respectively. The correlation between FC and HAMD scores in the patients with DPD was determined using partial correlation analysis. Results: Compared with those in the NC group and the NDPD group, the bilateral hippocampal volumes in the DPD group were significantly decreased (P<0.05). There was a negative correlation between the bilateral hippocampal volume and the HAMD score in the DPD group (P<0.05). Compared with that of the NDPD group, the FC of the right hippocampus with the right occipital lobe and left precuneus was reduced in the DPD group. In the DPD group, the FC values of the right hippocampus, right occipital lobe, and left anterior cuneiform lobe were negatively correlated with HAMD scores. Conclusions: The volume of bilateral hippocampi in patients with DPD is significantly decreased and negatively correlated with the severity of depressive disorder. The weakened FC of the right hippocampus to the right occipital lobe and the left precuneus may play an important role in the neurological basis of DPD.

Surgical timing and long-term outcomes in patients with severe haemorrhagic spinal cord cavernous malformations.

BACKGROUND: Surgical resection of the lesions remains the main treatment method for most symptomatic spinal cord cavernous malformations (SCCMs) to eliminate the occupation and associated subsequent lifelong haemorrhagic risk. However, the timing of surgical intervention remains controversial, especially for patients in the acute stage after severe haemorrhage. METHODS: Patients diagnosed with SCCMs who were surgically treated between January 2002 and December 2021 were selected and retrospectively reviewed. The Modified McCormick Scale (MMS) was used to evaluate neurological and disability status. All medical information was reviewed, and all patients were followed up for at least 6 months. RESULTS: A total of 279 patients were ultimately included. With regard to long-term outcomes, 110 (39.4%) patients improved, 159 (57.0%) remained unchanged and 10 (3.6%) worsened. For patients with an MMS score of 2-5 on admission, in univariate and multivariate analyses, a ≤6 weeks period between onset and surgery (adjusted OR 3.211, 95% CI 1.504 to 6.856, p=0.003) was a significant predictor of improved MMS. Among 69 patients who first presented with severe haemorrhage, undergoing surgery within 6 weeks of the onset of severe haemorrhage (adjusted OR 4.901, 95% CI 1.126 to 21.325, p=0.034) was significantly associated with improvement of MMS score. CONCLUSION: Surgical timing can influence the long-term outcome of SCCMs. For patients with symptomatic SCCMs, especially those with severe haemorrhage, early surgical intervention within 6 weeks can provide more benefit.

Combination therapy of irreversible electroporation and cytokine-induced killer cells for treating mice bearing panc02 pancreatic-cancer xenografts.

The current study aimed to investigate the antitumor effects and potent mechanism of cytokine-induced killer (CIK) cells combined with irreversible electroporation (IRE) via Panc02 cell-bearing mouse model in vivo. CIK cells were isolated from the spleens of Panc02 pancreatic-cancer (PC) subcutaneous-xenograft model and the proportion of different lymphocytes was also determined. The antitumor effect of the combination of IRE and CIK cells in a PC subcutaneous-xenograft model was also investigated. The proportion of cells that were positive for CD3+CD8+ and the proportion of CD3+CD56+ cells were both significantly increased after 21 days of in vitro culture. Combined treatment of IRE and CIK cell significantly inhibited tumor growth and increased the survival rate of Panc02 cell-bearing mice. Furthermore, infiltration of lymphocytes into tumor tissue was significantly increased by this combination therapy compared with the untreated group or monotherapy group. In addition, IRE significantly enhanced the expression of chemokine receptors elicited by CIK cells. In conclusion, IRE combined with CIK cells showed superior antitumor efficacy in a PC xenograft model, which we attributed to the promotion of lymphocytic infiltration, as well as to upregulation of chemokine receptor expression and the regulators of CIK cell proliferation.

Major complications after ultrasound-guided liver biopsy: An annual audit of a Chinese tertiary-care teaching hospital.

BACKGROUND: As ultrasound-guided percutaneous liver biopsy (PLB) has become a standard and important method in the management of liver disease in our country, a periodical audit of the major complications is needed. AIM: To determine the annual incidence of major complications following ultrasound-guided PLB and to identify variables that are significantly associated with an increased risk of major complications. METHODS: A total of 1857 consecutive cases of PLB were included in our hospital from January 2021 to December 2021. The major complication rate and all-cause 30-d mortality rate were determined. Multivariate analyses were performed by logistic regression to investigate the risk factors associated with major complications and all-cause 30-d mortality following ultrasound-guided PLB. RESULTS: In this audit of 1857 liver biopsies, 10 cases (0.53%) of major complications occurred following ultrasound-guided PLB. The overall all-cause mortality rate at 30 d after PLB was 0.27% (5 cases). Two cases (0.11%) were attributed to major hemorrhage within 7 d after liver biopsy. Fibrinogen less than 2 g/L [odds ratio (OR): 17.226; 95% confidence interval (CI): 2.647-112.102; P = 0.003], post-biopsy hemoglobin level (OR: 0.963; 95%CI: 0.942-0.985; P = 0.001), obstructive jaundice (OR: 6.698; 95%CI: 1.133-39.596; P = 0.036), application of anticoagulants/antiplatelet medications (OR: 24.078; 95%CI: 1.678-345.495; P = 0.019) and age (OR: 1.096; 95%CI: 1.012-1.187; P = 0.025) were statistically associated with the incidence of major complications after PLB. CONCLUSION: In conclusion, the results of this annual audit confirmed that ultrasound-guided PLB can be performed safely, with a major complication rate within the accepted range. Strict patient selection and peri-biopsy laboratory assessment are more important than procedural factors for optimizing the safety outcomes of this procedure.

Ultrasound identification of hepatic echinococcosis using a deep convolutional neural network model in China: a retrospective, large-scale, multicentre, diagnostic accuracy study.

BACKGROUND: Ultrasonography is the most widely used technique to diagnose echinococcosis; however, challenges in using this technique and the demand on medical resources, especially in low-income or remote areas, can delay diagnosis. We aimed to develop a deep convolutional neural network (DCNN) model based on ultrasonography to identify echinococcosis and its types, especially alveolar echinococcosis. METHODS: This retrospective, large-scale, multicentre study used ultrasound images from patients assessed at 84 hospitals in China, obtained between Jan 1, 2002, and Dec 31, 2021. Patients with a diagnosis of cystic echinococcosis, alveolar echinococcosis, or seven other types of focal liver lesions were included. We tested ResNet-50, ResNext-50, and VGG-16 as the backbone network architecture for a classification DCNN model and input the perinodular information from the ultrasound images. We trained and validated the DCNN model to diagnose and classify echinococcosis using still greyscale ultrasound images of focal liver lesions in four stages: differentiating between echinococcosis and other focal liver lesions (stage one); differentiating cystic echinococcosis, alveolar echinococcosis, and other focal liver lesions (stage two); differentiating cystic echinococcosis, alveolar echinococcosis, benign other focal liver lesions, and malignant focal liver lesions (stage three); and differentiating between active and transitional cystic echinococcosis and inactive cystic echinococcosis (stage four). We then tested the algorithm on internal, external, and prospective test datasets. The performance of DCNN was also compared with that of 12 radiologists recruited between Jan 15, 2022, and Jan 28, 2022, from Qinghai, Xinjiang, Anhui, Henan, Xizang, and Beijing, China, with different levels of diagnostic experience for echinococcosis and other focal liver lesions in a subset of ultrasound data that were randomly chosen from the prospective test dataset. The study is registered at ClinicalTrials.gov (NCT03871140). FINDINGS: The study took place between Jan 1, 2002, and Dec 31, 2021. In total, to train and test the DCNN model, we used 9631 liver ultrasound images from 6784 patients (2819 [41·7%] female patients and 3943 [58·3%] male patients) from 87 Chinese hospitals. The DCNN model was trained with 6328 images, internally validated with 984 images, and tested with 2319 images. The ResNet-50 network architecture outperformed VGG-16 and ResNext-50 and was generalisable, with areas under the receiver operating characteristic curve (AUCs) of 0·982 (95% CI 0·960-0·994), 0·984 (0·972-0·992), and 0·913 (0·886-0·935) in distinguishing echinococcosis from other focal liver lesions; 0·986 (0·966-0·996), 0·962 (0·946-0·975), and 0·900 (0·872-0·924) in distinguishing alveolar echinococcosis from cystic echinococcosis and other focal liver lesions; and 0·974 (0·818-1·000), 0·956 (0·875-0·991), and 0·944 (0·844-0·988) in distinguishing active and transitional cystic echinococcosis from inactive echinococcosis in the three test datasets. Specifically, in patients with the hepatitis B or hepatitis C virus, the model could distinguish alveolar echinococcosis from hepatocellular carcinoma with an AUC of 0·892 (0·812-0·946). In identifying echinococcosis, the model showed significantly better performance compared with senior radiologists from a high-endemicity area (AUC 0·942 [0·904-0·967] vs 0·844 [0·820-0·866]; p=0·027) and improved the diagnostic ability of junior, attending, and senior radiologists before and after assistance with AI with comparison of AUCs of 0·743 (0·714-0·770) versus 0·850 (0·826-0·871); p<0·0001, 0·808 (0·782-0·832) versus 0·886 (0·864-0·905); p<0·0001, and 0·844 (0·820-0·866) versus 0·870 (0·847-0·890); p=0·092, respectively. INTERPRETATION: The DCNN model was shown to be accurate and robust, and could improve the ultrasound diagnostic ability of radiologists for echinococcosis and its types for highly endemic and remote regions. FUNDING: National Natural Science Foundation of China and National Key Research & Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

A mixed-methods assessment of off-duty police shootings in a media-curated database.

OBJECTIVE: The aim of this study was to examine rates of killings perpetrated by off-duty police and news coverage of those killings, by victim race and gender, and to qualitatively evaluate the contexts in which those killings occur. DATA SOURCES AND STUDY SETTING: We used the Mapping Police Violence database to curate a dataset of killings perpetrated by off-duty police (2013-2021, N = 242). We obtained data from Media Cloud to assess news coverage of each off-duty police-perpetrated killing. STUDY DESIGN: Our study used a convergent mixed-methods design. We examined off-duty police-perpetrated killings by victim race and gender, comparing absolute rates and rates relative to total police-perpetrated killings. [Correction added on 26 June 2023, after first online publication: 'policy-perpetrated' has been changed to 'police-perpetrated' in the preceding sentence.] We also conducted race-gender comparisons of the frequency of news media reporting of these killings, and whether reporting identified the perpetrator as an off-duty officer. We conducted thematic analysis of the narrative free-text field that accompanied quantitative data using grounded theory. PRINCIPAL FINDINGS: Black men were the most frequent victims killed by off-duty police (39.3%) followed by white men (25.2%), Hispanic men (11.2%), white women (9.1%), men of unknown race (9.1%), and Black women (4.1%). Black women had the highest rate of off-duty/total police-perpetrated killings relative to white men (rate = 12.82%, RR = 8.32, 95% CI: 4.43-15.63). There were threefold higher odds of news reporting of a police-perpetrated killing and the off-duty status of the officer for incidents with Black and Hispanic victims. Qualitative analysis revealed that off-duty officers intervened violently within their own social networks; their presence escalated situations; they intentionally obscured information about their lethal violence; they intervened while impaired; their victims were often in crisis; and their intervention posed harm and potential secondary traumatization to witnesses. CONCLUSIONS: Police perpetrate lethal violence while off duty, compromising public health and safety. Additionally, off-duty police-perpetrated killings are reported differentially by the news media depending on the race of the victim.

Simultaneous Delivery of Dual Inhibitors of DNA Damage Repair Sensitizes Pancreatic Cancer Response to Irreversible Electroporation.

Pancreatic ductal adenocarcinoma (PDAC) is an abysmal disease refractory to most standard therapies. Irreversible electroporation (IRE) is a local ablative technique for the clinical treatment of solid tumors, including locally advanced and unresectable PDAC, by intratumorally delivering high-intensity electric pulses to permanently disrupt cell membranes and induce cell death. But the distribution of electric field is uneven within the tumor, and in some regions, tumor cells only experience temporary perturbation to their cell membrane, a phenomenon denoted as reversible electroporation (RE). These tumor cells may survive and therefore are the main culprit of tumor relapse after IRE. We herein showed that RE, although not killing tumor cells, induced DNA double-strand breaks and activated DNA damage repair (DDR) responses. Using reactive oxygen species-sensitive polymeric micelles coloaded with Olaparib, an inhibitor of poly(ADP-ribose) polymerase (PARP), and AZD0156, an inhibitor of ataxia telangiectasia mutated (ATM), the resultant nanoformulation (M-TK-OA) disrupted both homologous recombination and nonhomologous end joining signaling of the DDR response and impaired colony formation in pancreatic cancer cells after RE. The combination of IRE and M-TK-OA significantly prolonged animal survival in both subcutaneous and orthotopic murine PDAC models and elicited CD8+ T cell-mediated antitumor immunity with a sustained antitumor memory. The efficacy of combined IRE and M-TK-OA treatments was partially attributed to the activation of cyclic GMP-AMP synthase-stimulator of interferon genes innate immune responses. Our study suggests that dual inhibition of PARP and ATM with nanomedicine is a promising strategy to enhance the pancreatic cancer response to IRE.

Safety and efficacy of microwave ablation for the treatment of low-risk papillary thyroid microcarcinoma: a prospective multicenter study.

OBJECTIVES: To assess the safety and efficacy of ultrasound-guided thermal ablation for low-risk papillary thyroid microcarcinoma (PTMC) via a prospective multicenter study. METHODS: From January 2017 through June 2021, low-risk PTMC patients were screened. The management details of active surveillance (AS), surgery, and thermal ablation were discussed. Among patients who accepted thermal ablation, microwave ablation (MWA) was performed. The main outcome was disease-free survival (DFS). The secondary outcomes were tumor size and volume changes, local tumor progression (LTP), lymph node metastasis (LNM), and complication rate. RESULTS: A total of 1278 patients were included in the study. The operation time of ablation was 30.21 ± 5.14 min with local anesthesia. The mean follow-up time was 34.57 ± 28.98 months. Six patients exhibited LTP at 36 months, of whom 5 patients underwent a second ablation, and 1 patient received surgery. The central LNM rate was 0.39% at 6 months, 0.63% at 12 months, and 0.78% at 36 months. Of the 10 patients with central LNM at 36 months, 5 patients chose ablation, 3 patients chose surgery and the other 2 patients chose AS. The overall complication rate was 1.41%, and 1.10% of patients developed hoarseness of the voice. All of the patients recovered within 6 months. CONCLUSIONS: Thermal ablation of low-risk PTMC was observed to be safe and efficacious with few minor complications. This technique may help to bridge the gap between surgery and AS as treatment options for patients wishing to have their PTMC managed in a minimally invasive manner. CLINICAL RELEVANCE STATEMENT: This study proved that microwave ablation is a safe and effective treatment method for papillary thyroid microcarcinoma. KEY POINTS: Percutaneous US-guided microwave ablation of papillary thyroid microcarcinoma is a very minimally invasive treatment under local anesthesia during a short time period. The local tumor progression and complication rate of microwave ablation in the treatment of papillary thyroid microcarcinoma are very low.

Molecular Profiling Provides Clinical Insights Into Targeted and Immunotherapies as Well as Colorectal Cancer Prognosis.

BACKGROUND & AIMS: Tumor genetic testing is indispensable in the management of primary and metastatic colorectal cancer (CRC), yet the indications for genomics-guided precision medicine and immunotherapy must be better understood and defined. METHODS: We prospectively sequenced tumors from 869 Chinese patients with CRC by a large panel and evaluated the clinical significance of single-gene somatic mutations and co-occurring events in metastatic CRC, as well as their functional effects and tumorigenic mechanisms. We systematically assessed the heterogeneity of the tumor immune microenvironment in different genomic contexts through the combined analysis of Immunoscore, multiplex immunostaining, whole-exome sequencing, transcriptome, and single-cell sequencing. RESULTS: Single-gene somatic mutations in BRAF or RBM10 were associated with shorter progression-free survival in patients with metastatic CRC. Functional studies suggested RBM10 acts as a tumor suppressor in CRC development. Co-mutations of KRAS/AMER1 or KRAS/APC were enriched in the metastatic cohort, which had poor progression-free survival and did not benefit from bevacizumab due to accelerated drug metabolism. Forty patients (4.6%) carried pathogenic or likely pathogenic germline alterations in the DNA damage repair pathway and 37.5% of these tumors had secondary-hit events with loss of heterozygosity or biallelic alterations. A high tumor insertion or deletion burden with high microsatellite instability suggested immunogenicity with numerous activated tumor-infiltrating lymphocytes, whereas polymerase epsilon exonuclease mutation with ultrahigh tumor mutation burden indicated a relatively quiescent immunophenotype. The heterogeneous genomic-immunologic interactions were reflected in the divergent neoantigen presentation and depletion, immune checkpoint expression, PD-1/PD-L1 interaction, and T-cell responsiveness to pembrolizumab. CONCLUSIONS: Our integrated analysis provides insights into CRC prognostic stratification, drug response, and personalized genomics-guided targeted and immunotherapies.

Somatic variants of MAP3K3 are sufficient to cause cerebral and spinal cord cavernous malformations.

Cerebral cavernous malformations (CCMs) and spinal cord cavernous malformations (SCCMs) are common vascular abnormalities of the CNS that can lead to seizure, haemorrhage and other neurological deficits. Approximately 85% of patients present with sporadic (versus congenital) CCMs. Somatic mutations in MAP3K3 and PIK3CA were recently reported in patients with sporadic CCM, yet it remains unknown whether MAP3K3 mutation is sufficient to induce CCMs. Here we analysed whole-exome sequencing data for patients with CCM and found that ∼40% of them have a single, specific MAP3K3 mutation [c.1323C>G (p.Ile441Met)] but not any other known mutations in CCM-related genes. We developed a mouse model of CCM with MAP3K3I441M uniquely expressed in the endothelium of the CNS. We detected pathological phenotypes similar to those found in patients with MAP3K3I441M. The combination of in vivo imaging and genetic labelling revealed that CCMs were initiated with endothelial expansion followed by disruption of the blood-brain barrier. Experiments with our MAP3K3I441M mouse model demonstrated that CCM can be alleviated by treatment with rapamycin, the mTOR inhibitor. CCM pathogenesis has usually been attributed to acquisition of two or three distinct genetic mutations involving the genes CCM1/2/3 and/or PIK3CA. However, our results demonstrate that a single genetic hit is sufficient to cause CCMs.

Radical Resection Combined With Intestinal Autotransplantation for Locally Advanced Pancreatic Cancer After Neoadjuvant Therapy: A Report of 36 Consecutive Cases.

OBJECTIVE: To achieve radical resection of locally advanced pancreatic ductal adenocarcinoma (PDAC), and tested the safety and benefits of intestinal autotransplantation in pancreatic surgery. BACKGROUND: PDAC has an extremely dismal prognosis. Radical resection was proved to improve the prognosis of patients with PDAC; however, the locally advanced disease had a very low resection rate currently. We explored and evaluated whether the combination of modern advances in systemic treatment and this macroinvasive surgery was feasible in clinical practice. METHODS: Patients diagnosed as PDAC with superior mesenteric artery involvement and with or without celiac trunk involvement were included. Patients were treated with modified-FOLFIRINOX chemotherapy with or without anti-PD-1 antibodies and were applied to tumor resection combined with intestinal autotransplantation. Data on operative parameters, pathologic results, mortality, morbidity, and survival were analyzed. RESULTS: A total of 36 consecutive cases were applied to this strategy and underwent radical resection combined with intestinal autotransplantation. Among these patients, 24 of them received the Whipple procedure, 11 patients received total pancreatectomy, and the other 1 patient received distal pancreatectomy. The median operation time was 539 minutes. Postoperative pathology showed an R0 resection rate of 94.4%, and tumor invasion of a superior mesenteric artery or superior mesenteric vein was confirmed in 32 patients. The median number of dissected lymph nodes was 43, and 25 patients were positive for lymph node metastasis. The median time of intensive care unit stay was 4 days. Two patients died within 30 days after surgery due to multiorgan failure. The severe postoperative adverse events (equal to or higher than grade 3) were observed in 12 out of 36 patients, and diarrhea, gastroparesis, and abdominal infection were the most frequent adverse events. Postoperative hospital stay was averagely of 34 days. The recurrence-free survival is 13.6 months. The median overall survival of patients after diagnosis and after surgery was 21.4 months and 14.5 months, respectively. CONCLUSIONS: Our attempt suggests the safety of this modality and may be clinically beneficial for highly selected patients with PDAC. However, the experience in multidisciplinary pancreatic cancer care and intestinal transplantation is warranted.

Diagnostic Value of Qualitative and Quantitative Contrast-Enhanced Ultrasound for Pathological Subtypes of Small Solid Renal Masses.

OBJECTIVES: To assess the diagnostic value of qualitative and quantitative contrast-enhanced ultrasound (CEUS) for pathological subtypes of small solid renal masses (sSRMs). METHODS: Patients with sSRMs confirmed by surgical pathology from January 2019 to November 2021 were retrospectively identified. All patients were divided into 3 groups: clear cell renal cell carcinoma (ccRCC) group, none-ccRCC group (renal cell carcinoma other than ccRCC), and angiomyolipoma (AML) group. The mass position, size, echogenicity and blood flow signals were compared. The speed of wash-in, wash-out, the degree of peak enhancement and the homogeneity at peak enhancement, the presence of pseudocapsule sign in CEUS imaging were qualitatively evaluated. Peak enhancement, wash-in area under the curve (WiAUC), rise time, time to peak, wash-in rate (WiR), wash-in perfusion index (WiPI) and tumor-to-cortex enhancement ratio of the above parameters in CEUS imaging were quantitatively evaluated. RESULTS: Of 105 patients, 105 sSRMs (66 ccRCC, 18 none-ccRCC, 21 AML) were enrolled in this study. No significant differences were found on location, size and echogenicity among 3 groups (all P > .05). The proportion of fast-washout and hypo-enhancement were highest in none-ccRCC group. Heterogeneous enhancement was detected in 87.88% in ccRCC group which is significantly higher than other 2 groups. Hundred percent of the AML showed no pseudocapsule sign, which is the highest among the 3 groups. Peak enhancement, WiAUC, WiR, WiPI of ccRCC group were the highest among the 3 groups. CONCLUSIONS: Qualitative and quantitative CEUS not only has the diagnostic value in distinguishing AML from malignant sSRMs, but also helps to differentiate the pathological subtypes of sSRMs.

Percutaneous ultrasound and endoscopic ultrasound-guided biopsy of solid pancreatic lesions: An analysis of 1074 lesions.

BACKGROUNDS: Percutaneous ultrasound (US) and endoscopic ultrasound (EUS)-guided pancreatic biopsies are widely accepted in the diagnosis of pancreatic diseases. Studies comparing the diagnostic performance of US- and EUS-guided pancreatic biopsies are lacking. This study aimed to evaluate and compare the diagnostic yields of US- and EUS-guided pancreatic biopsies and identify the risk factors for inconclusive biopsies. METHODS: Of the 1074 solid pancreatic lesions diagnosed from January 2017 to February 2021 in our center, 275 underwent EUS-guided fine needle aspiration (EUS-FNA), and 799 underwent US-guided core needle biopsy (US-CNB/FNA). The outcomes were inconclusive pathological biopsy, diagnostic accuracy and the need for repeat biopsy. All of the included factors and diagnostic performances of both US-CNB/FNA and EUS-FNA were compared, and the independent predictors for the study outcomes were identified. RESULTS: The diagnostic accuracy was 89.8% for EUS-FNA and 95.2% for US-CNB/FNA (P = 0.001). Biopsy under EUS guidance [odds ratio (OR) = 1.808, 95% confidence interval (CI): 1.083-3.019; P = 0.024], lesion size < 2 cm (OR = 2.069, 95% CI: 1.145-3.737; P = 0.016), hypoechoic appearance (OR = 0.274, 95% CI: 0.097-0.775; P = 0.015) and non-pancreatic ductal adenocarcinoma carcinoma (PDAC) diagnosis (OR = 2.637, 95% CI: 1.563-4.449; P < 0.001) were identified as factors associated with inconclusive pathological biopsy. Hypoechoic appearance (OR = 0.236, 95% CI: 0.064-0.869; P = 0.030), lesions in the uncinate process of the pancreas (OR = 3.506, 95% CI: 1.831-6.713; P < 0.001) and non-PDAC diagnosis (OR = 2.622, 95% CI: 1.278-5.377; P = 0.009) were independent predictors for repeat biopsy. Biopsy under EUS guidance (OR = 2.024, 95% CI: 1.195-3.429; P = 0.009), lesions in the uncinate process of the pancreas (OR = 1.776, 95% CI: 1.014-3.108; P = 0.044) and hypoechoic appearance (OR = 0.127, 95% CI: 0.047-0.347; P < 0.001) were associated with diagnostic accuracy. CONCLUSIONS: In conclusion, both percutaneous US- and EUS-guided biopsies of solid pancreatic lesions are safe and effective; though the diagnostic accuracy of EUS-FNA is inferior to US-CNB/FNA. A tailored pancreatic biopsy should be considered a part of the management algorithm for the diagnosis of solid pancreatic disease.

Deep learning radiomics of ultrasonography for comprehensively predicting tumor and axillary lymph node status after neoadjuvant chemotherapy in breast cancer patients: A multicenter study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) can downstage tumors and axillary lymph nodes in breast cancer (BC) patients. However, tumors and axillary response to NAC are not parallel and vary among patients. This study aims to explore the feasibility of deep learning radiomics nomogram (DLRN) for independently predicting the status of tumors and lymph node metastasis (LNM) after NAC. METHODS: In total, 484 BC patients who completed NAC from two hospitals (H1: 297 patients in the training cohort and 99 patients in the validation cohort; H2: 88 patients in the test cohort) were retrospectively enrolled. The authors developed two deep learning radiomics (DLR) models for personalized prediction of the tumor pathologic complete response (PCR) to NAC (DLR-PCR) and the LNM status (DLR-LNM) after NAC based on pre-NAC and after-NAC ultrasonography images. Furthermore, they proposed two DLRNs (DLRN-PCR and DLRN-LNM) for two different tasks based on the clinical characteristics and DLR scores, which were generated from both DLR-PCR and DLR-LNM. RESULTS: In the validation and test cohorts, DLRN-PCR exhibited areas under the receiver operating characteristic curves (AUCs) of 0.903 and 0.896 with sensitivities of 91.2% and 75.0%, respectively. DLRN-LNM achieved AUCs of 0.853 and 0.863, specificities of 82.0% and 81.8%, and negative predictive values of 81.3% and 87.2% in the validation and test cohorts, respectively. The two DLRN models achieved satisfactory predictive performance based on different BC subtypes. CONCLUSIONS: The proposed DLRN models have the potential to accurately predict the tumor PCR and LNM status after NAC. PLAIN LANGUAGE SUMMARY: In this study, we proposed two deep learning radiomics nomogram models based on pre-neoadjuvant chemotherapy (NAC) and preoperative ultrasonography images for independently predicting the status of tumor and axillary lymph node (ALN) after NAC. A more comprehensive assessment of the patient's condition after NAC can be achieved by predicting the status of the tumor and ALN separately. Our model can potentially provide a noninvasive and personalized method to offer decision support for organ preservation and avoidance of excessive surgery.