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Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.
Subject(s)
Optical Imaging , Parathyroid Glands , Spectroscopy, Near-Infrared , Thyroidectomy , Humans , Parathyroid Glands/surgery , Parathyroid Glands/metabolism , Male , Female , Middle Aged , Optical Imaging/methods , Adult , Spectroscopy, Near-Infrared/methods , Paraffin Embedding/methods , Aged , Thyroid Cancer, Papillary/surgery , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/metabolism , Receptors, Calcium-Sensing/metabolism , Receptors, Calcium-Sensing/analysisABSTRACT
Pancreatic cancer is an aggressive and challenging malignancy with limited treatment options, largely attributed to the dense tumor stroma and intrinsic drug resistance. Here, we introduce a novel iron-containing nanoparticle formulation termed PTFE, loaded with the ferroptosis inducer Erastin, to overcome these obstacles and enhance pancreatic cancer therapy. The PTFE nanoparticles were prepared through a one-step assembly process, consisting of an Erastin-loaded PLGA core stabilized by a MOF shell formed by coordination between Fe3+ and tannic acid. PTFE demonstrated a unique capability to repolarize tumor-associated macrophages (TAMs) into the M1 phenotype, leading to the regulation of dense tumor stroma by modulating the activation of tumor-associated fibroblasts (TAFs) and reducing collagen deposition. This resulted in enhanced nanoparticle accumulation and deep penetration, as confirmed by in vitro multicellular tumor spheroids and in vivo mesenchymal-rich subcutaneous pancreatic tumor models. Moreover, PTFE effectively combated tumor resistance by synergistically employing the Fe3+-induced Fenton reaction and Erastin-induced ferroptosis, thereby disrupting the redox balance. As a result, significant tumor growth inhibition was achieved in mice-bearing tumor model. Comprehensive safety evaluations demonstrated PTFE's favorable biocompatibility, highlighting its potential as a promising therapeutic platform to effectively address the formidable challenges in pancreatic cancer treatment.
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OBJECTIVE: To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the "low-risk" classification for tailored treatment strategies. METHODS: This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis. RESULTS: Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule-capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility. CONCLUSION: This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of "low-risk" categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information.
Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Humans , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Carcinoma, Papillary/surgery , Carcinoma, Papillary/pathology , Neck Dissection , Thyroidectomy , Lymphatic Metastasis/pathology , Retrospective Studies , Lymph Nodes/pathology , Risk FactorsABSTRACT
BACKGROUND: In recent years, computer-assisted intervention and robot-assisted surgery are receiving increasing attention. The need for real-time identification and tracking of surgical tools and tool tips is constantly demanding. A series of researches focusing on surgical tool tracking and identification have been performed. However, the size of dataset, the sensitivity/precision, and the response time of these studies were limited. In this work, we developed and utilized an automated method based on Convolutional Neural Network (CNN) and You Only Look Once (YOLO) v3 algorithm to locate and identify surgical tools and tool tips covering five different surgical scenarios. MATERIALS AND METHODS: An algorithm of object detection was applied to identify and locate the surgical tools and tool tips. DarkNet-19 was used as Backbone Network and YOLOv3 was modified and applied for the detection. We included a series of 181 endoscopy videos covering 5 different surgical scenarios: pancreatic surgery, thyroid surgery, colon surgery, gastric surgery, and external scenes. A total amount of 25,333 images containing 94,463 targets were collected. Training and test sets were divided in a proportion of 2.5:1. The data sets were openly stored at the Kaggle database. RESULTS: Under an Intersection over Union threshold of 0.5, the overall sensitivity and precision rate of the model were 93.02% and 89.61% for tool recognition and 87.05% and 83.57% for tool tip recognition, respectively. The model demonstrated the highest tool and tool tip recognition sensitivity and precision rate under external scenes. Among the four different internal surgical scenes, the network had better performances in pancreatic and colon surgeries and poorer performances in gastric and thyroid surgeries. CONCLUSION: We developed a surgical tool and tool tip recognition model based on CNN and YOLOv3. Validation of our model demonstrated satisfactory precision, accuracy, and robustness across different surgical scenes.
Subject(s)
Neural Networks, Computer , Robotic Surgical Procedures , Humans , Algorithms , Endoscopy , Databases, FactualABSTRACT
Tumour microenvironment has been recognized as a crucial factor influencing disease progression. However, relevant features and functions are insufficiently understood in parathyroid neoplasia. Single-cell RNA sequencing was performed to profile the transcriptome of 27,251 cells from 4 parathyroid adenoma (PA) tissue samples. External transcriptomic datasets and immunofluorescence staining of a tissue microarray were set for expression validation. Eight major cell types and various subpopulations were finely identified in PA. We found that a subcluster of tumour endocrine cells with low copy number variation probably presented as a resting state. Diverse infiltrating immune cell subtypes were identified, constructing an immunosuppressive microenvironment. Tumour-associated macrophages, which indicated an anti-inflammatory phenotype, were significantly increased in PA. Inflammatory tumour-associated fibroblasts (iTAFs) were newly verified and highlighted on the role of stromal-immune crosstalk. Positive correlation between iTAFs and increased CD163+ macrophages was uncovered. Moreover, CXCL12 receptor signalling is important for tumour angiogenesis and immune infiltration. Our findings provide a comprehensive landscape interpreting tumour cell heterogeneity, cell diversity, and immune regulation in parathyroid neoplasia. The valuable resources may promote the understanding of parathyroid tumour microenvironment.
Subject(s)
Parathyroid Neoplasms , Humans , Parathyroid Neoplasms/pathology , Tumor Microenvironment , DNA Copy Number Variations , Macrophages , Signal TransductionABSTRACT
The identification and preservation of parathyroid glands (PGs) during thyroid surgery can be challenging. Many techniques have been developed to help surgeons find PGs. We have developed a novel mitoxantrone hydrochloride injection that can be used for lymphatic targeting. After local application during surgery, mitoxantrone hydrochloride injection for tracing (MHI) helps surgeons better identify and preserve PGs and helps pathologists find more lymph nodes. We conducted an open-label, multicenter, randomized clinical trial (CTR20171137) in six centers in China from 08/2017 to 12/2018. Patients with thyroid carcinoma were randomized to the MHI group or the control group. All patients received total thyroidectomy and bilateral central compartment lymph node dissection. The primary outcomes were the PG resection rate and lymph node staining rate. The full analysis set (FAS) included 461 patients, of which 228 were assigned to the MHI group, and 233 were assigned to the control group. The PG resection rates of the MHI group and the control group were 6.6% (15/228) and 26.6% (62/233), respectively, with a significant difference (P < 0.001). No PGs were stained blue with MHI. The central lymph nodes were stained blue with MHI, and the staining rate was 90.5%±12.0%. More lymph nodes were detected in the MHI group than in the control group (13.0±7.3 vs. 10.1±6.4 nodes/patient, P < 0.001). No adverse events related to MHI were observed. MHI is a safe and effective tracer that may help to preserve PGs and identify more central lymph nodes in patients with thyroid cancer.
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BACKGROUND: Parathyroid carcinoma (PC) is a rare endocrine malignancy with poor outcomes. Over 60% of PC patients experience repeated disease recurrence or metastasis. The significance of cervical lymph node dissection (LND) for PC remains inconclusive. METHODS: PC patients diagnosed at Peking Union Medical College Hospital between 1992 and 2021 were reviewed retrospectively. Clinical data, initial tumor histological staging, parafibromin histochemical staining results, Ki67 index, CDC73 gene mutation status and outcome information were collected systemically. The risk factors for recurrence and lymph node or distant metastasis were explored. RESULTS: Sixty-eight PC patients receiving LND were enrolled. Cervical lymph node metastasis was identified in 19.4% of patients at initial surgery and 25.0% of patients including reoperations for recurrences. The independent risk factor for PC recurrence was a Ki67 index ≥ 5% (HR4.41, 95% confidence interval (CI)1.30-14.95, p = 0.017). Distant metastasis was an independent prognostic factor for PC patient overall survival (HR 5.44, 95% CI 1.66-17.82, p = 0.005). High-risk Schulte staging (p = 0.021) and CDC73 abnormalities (p = 0.012) were risk factors for cervical lymph node metastasis. CONCLUSION: Most PCs were slow-growing, but lymph node metastasis was not rare. For patients planning to undergo remedial surgery after previous local resection of PC, central LND is suggested for tumors with high-risk Schulte staging or CDC73 abnormalities.
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Background: Laparoscopic surgery has been in great demand over the past decades; it has also brought several obstacles, such as increasing difficulty in maintaining hemostasis, changes in surgical approach, and reduced field of vision. Locating the bleeding point can help surgeons to control bleeding quickly, however, to date, there have been no tools designed for automatic bleeding tracking in laparoscopic operations. Herein, we have proposed a spatiotemporal hybrid model based on a faster region-based convolutional neural network (RCNN) for bleeding point detection in laparoscopic surgery videos. Methods: Laparoscopic videos performed at our hospital were retrieved and images containing bleeding events were extracted. Spatiotemporal features were extracted by using red-green-blue (RGB) frames and optical flow maps and a spatiotemporal hybrid model was developed based on the faster RCNN. The proposed model contributed to (I) providing real-time bleeding point detection which directly assist surgeons, (II) showing the blood's optical flow which improved bleeding point detection, and (III) detecting both arterial and venous bleeding. Results: In this study, 12 different bleeding videos were included for deep learning model training. Compared with models containing a single RGB or a single optical flow map, our model combining RGB and optical flow achieved great detection results (precision rate of 0.8373, recall rate of 0.8034, and average precision of 0.6818). Conclusions: Our approach performs well in bleeding point location and recognition, indicating its potential value in helping to maintain and re-establish hemostasis during operations.
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Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Radical resection is currently the only potential curative treatment. However, over 80% of patients present with unresectable tumor at the time of diagnosis. It is recommended that patients with unresectable pancreatic cancers be offered neoadjuvant treatment. A combination of gemcitabine and S-1 (GS-1) has been reported to be an effective regimen for unresectable pancreatic cancers, however, there have been no reports of pathological complete response up until now. Case Description: Herein, we present a 67-year-old male who presented with a 4-month history of upper abdominal and back pain, as well as unintentional weight loss. Abdominal computed tomography (CT) confirmed a hypovascular mass in the pancreas neck consistent with unresectable pancreatic cancer. Positron emission tomography (PET)/CT also revealed a high fludeoxyglucose (FDG)-avid lesion in the pancreas neck without evidence of distant metastasis. Pancreatic adenocarcinoma was confirmed with ultrasound-guided fine-needle aspiration cytology. The patient was recommended to undergo treatment with gemcitabine and S-1. After 5 cycles of neoadjuvant chemotherapy, CT and PET/CT both revealed the disappearance of the lesion and a pancreaticoduodenectomy was offered as a potentially curative treatment. Histological assessment revealed no evidence of residual adenocarcinoma [ypT0N0 (0/38)]. The tumor marker cancer antigen (CA)125 increased one month after the surgery, resulting in two additional cycles of GS-1. This patient remained disease-free for 21 months after surgery. Conclusions: This report is the first to present a case of a pathological complete response in a patient with locally advanced pancreatic cancer following GS-1 treatment, suggesting radical resection after GS-1 chemotherapy might be a potential curative treatment strategy for unresectable PDAC.
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PURPOSE: To describe the genetic landscape and clinical characteristics of Chinese patients diagnosed with papillary thyroid cancer (PTC) and to determine which high-risk genetic characteristics suggest a likelihood of lymph node metastasis (LNM) and lateral lymph node metastasis (LLNM). PATIENTS AND METHODS: Data from previously untreated patients with PTC collected between May 2018 and December 2020 from 14 hospitals in China were analyzed retrospectively. High-risk pathologic characteristics were defined as T3/T4, N(+), and N1b(+) stages. All patients were tested for 57 genes by second-generation sequencing. The t-test, chi-square test, and Fisher's exact test were performed for statistical analysis. RESULTS: Overall, 395 patients were enrolled in this study. The prevalence of BRAF mutation was 78.53%. BRAF mutant allele frequency (MAF) >16.93% was associated with a significantly higher risk of LNM, LLNM, and T3 + T4 stage compared with a low-risk group, defined by a MAF <2.54% (odd ratios [ORs] for each risk=3.38, 3.46, and 8.54, respectively), and an intermediate-risk group, defined by a MAF of 2.54% to 16.93% (ORs=2.04, 2.07, and 4.07, respectively). The population with RET fusion had higher T, N, and N1b stages (ORs for each stage=10.40, 7.60, and 8.77, respectively) compared with a RET-negative population. Similar conclusions about T, N, and N1b stages were observed in relation to multiple driver gene mutations (ORs for each stage=7.48, 2.80, and 7.04, respectively) compared with population without multiple driver mutations. These genetic characteristics may be suggestive of high clinical risk. However, regardless of genetic profiles, patients younger than age 45 years had greater rates of LNM and LLNM. CONCLUSION: The main driver gene in this study, BRAF, differs significantly between the United States (79% vs 51%) and other countries. The Chinese population in this study that experienced more aggressive tumor biology had a BRAF MAF greater than 16.93%, exhibited RET fusion events, and had multiple driver gene mutations; thus, these traits may be considered high-risk genetic characteristics in PTC that could warrant aggressive treatment in such population.
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ABSTRACT: A 68-year-old woman with melanoma in the left heel underwent sentinel node lymphoscintigraphy and radioguided biopsy. The sentinel node lymphoscintigraphy with SPECT/CT detected 3 foci of increased activity in the popliteal fossa and inguinal region. When coregistered to CT, the sentinel node was localized in the inguinal region, and the popliteal foci were considered tracer retention in lymphatic vessel. In another patient with melanoma in the foot, sentinel node lymphoscintigraphy detected 3 foci of increased activity in the popliteal fossa and inguinal region, which were all identified to be nodal uptake in SPECT/CT. The sentinel node was finally localized in popliteal fossa in this patient.
Subject(s)
Melanoma , Sentinel Lymph Node , Skin Neoplasms , Aged , Female , Humans , Lymph Nodes/diagnostic imaging , Lymphoscintigraphy , Melanoma/diagnostic imaging , Melanoma/surgery , Sentinel Lymph Node/diagnostic imaging , Sentinel Lymph Node Biopsy , Single Photon Emission Computed Tomography Computed Tomography , Skin Neoplasms/diagnostic imagingABSTRACT
BACKGROUND: Photodynamic therapy (PDT) is a clinically implemented modality to combat malignant tumor, while its efficacy is largely limited by several resistance factors from tumor microenvironment (TME), such as hypoxia, anti-oxidant systems, and ATP-dependent tumor adaptive resistances. The aim of this work is to construct a multifunctional nanoplatform to remodel multiple resistant TME for enhanced PDT. RESULTS: Here, a targeting nano-reactor was facilely constructed to reverse the multiple resistances of PDT by incorporating glucose oxidase (GOx) and chlorin e6 (Ce6) into poly (D, L-lactic-co-glycolic acid) (PLGA)/ metal-organic framework (MOF) core-shell nanoassembly, with surface deposition of hyaluronic acid (HA) stabilized MnO2. The nano-reactor could selectively target tumor cells by virtue of surface HA modification, and once internalization, a few reactions were initiated to modulate TME. Glucose was consumed by GOx to inhibit ATP generation, and the produced H2O2 was catalyzed by MnO2 to generate O2 for tumor hypoxia alleviation and photodynamic sensitization, and glutathione (GSH) was also effectively depleted by MnO2 to suppress the tumor antioxidant defense. Consequently, the nano-reactor achieved robust PDT with amplified tumor therapy via intravenous injection. CONCLUSIONS: This nano-reactor offers a multifunctional nanoplatform to sensitize TME-limited tumor treatment means via reversing multiple resistances.
Subject(s)
Photochemotherapy/methods , Animals , Cell Line, Tumor , Chlorophyllides , Drug Resistance, Neoplasm , Female , Glutathione , Humans , Hydrogen Peroxide , Manganese Compounds , Metal-Organic Frameworks , Mice , Mice, Inbred BALB C , Nanoparticles , Oxides/pharmacology , Particle Size , Porphyrins , Tumor Hypoxia , Tumor Microenvironment/drug effectsABSTRACT
Purpose: Hyperparathyroidism is the third most common endocrine disease. Parathyroid adenoma (PA) accounts for approximately 85% of cases of primary hyperparathyroidism, but the molecular mechanism is not fully understood. Herein, we aimed to investigate the genetic and transcriptomic profiles of sporadic PA. Methods: Whole-exome sequencing (WES) and transcriptome sequencing (RNA-seq) of 41 patients with PA and RNA-seq of 5 normal parathyroid tissues were performed. Gene mutations and characterized expression changes were identified. To elucidate the molecular mechanism underlying PA, unsupervised consensus clustering of RNA-seq data was performed. The correlations between the sequencing data and clinicopathological features of these patients were analyzed. Results: Previously reported PA driver gene mutations, such as MEN1 (9/41), mTOR (4/41), ZFX (3/41), CASR (3/41), EZH2 (2/41) and FAT1 (2/41), were also identified in our cohort. Furthermore, somatic mutation of EZH1, which had not been reported in PA, was found in 4 samples. RNA-seq showed that the expression levels of 84 genes were upregulated and 646 were downregulated in PA samples compared with normal samples. Unsupervised clustering analysis of RNA-seq data clustered these patients into 10 subgroups related to mutation or abnormal expression of a group of potential pathogenic genes. Conclusion: MEN1, EZH2, CASR, EZH1, ZFX, mTOR and FAT1 mutations in PA were revealed. According to the RNA-seq data clustering analysis, cyclin D1, ß-catenin, VDR, CASR and GCM2 may be important factors contributing to the PA gene expression profile.
Subject(s)
Adenoma/genetics , Adenoma/metabolism , Exome , Parathyroid Neoplasms/genetics , Parathyroid Neoplasms/metabolism , Transcriptome , Adult , Aged , Cadherins/genetics , Cadherins/metabolism , Cluster Analysis , Enhancer of Zeste Homolog 2 Protein/genetics , Enhancer of Zeste Homolog 2 Protein/metabolism , Female , Gene Expression Regulation , Genomics , Humans , Hyperparathyroidism/genetics , Hyperparathyroidism/metabolism , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , Male , Middle Aged , Mutation , Polycomb Repressive Complex 2/genetics , Polycomb Repressive Complex 2/metabolism , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , RNA-Seq , Receptors, Calcium-Sensing/genetics , Receptors, Calcium-Sensing/metabolism , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Tissue BanksABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory human malignancies. F-box only proteins (FBXO) are the core components of SKP1-cullin 1-F-box E3 ubiquitin ligase, which have been reported to play crucial roles in tumor initiation and progression via ubiquitination-mediated proteasomal degradation. However, the clinical implications and biological functions of FBXOs in PDAC have not been fully clarified. Herein we perform a comprehensive analysis for the clinical values and functional roles of FBXOs in PDAC using different public databases. We found that FBXO1 (CCNF), FBXO20 (LMO7), FBXO22, FBXO28, FBXO32, and FBXO45 (designated six-FBXOs) were robustly upregulated in PDAC tissues, which predicted an adverse prognosis of PDAC patients. There was a significant correlation between the expression levels of six-FBXOs and the clinicopathological features in PDAC. The transcriptional levels of six-FBXOs were subjected to the influence of promoter methylation levels. There were more than 40% genetic alterations and mutations of six-FBXOs, which affected the clinical outcome of PDAC patients. Furthermore, the expression of six-FBXOs was associated with immune infiltrations and activated status, including B cells, CD8+ T cells, CD4+ T cells, NK cells, macrophages, and dendritic cells. The functional prediction revealed that the six-FBXOs were involved in ubiquitination-related pathways and other vital signaling pathways, such as p53, PI3K/Akt, and Hippo pathway. Therefore, six-FBXOs are the promising prognostic biomarkers or potential targets for PDAC diagnosis and treatment.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Pancreatic Ductal/pathology , F-Box Proteins/metabolism , Pancreatic Neoplasms/pathology , Tumor Microenvironment/immunology , Biomarkers, Tumor/analysis , Carcinoma, Pancreatic Ductal/immunology , F-Box Proteins/analysis , Humans , Pancreatic Neoplasms/immunology , Prognosis , UbiquitinationABSTRACT
Pancreatic cancer is one of the most lethal tumors across the world with an overall 5-year survival rate of 9%, and great efforts have been devoted in early diagnosis and treatment in the past decades. Competing endogenous RNAs are novel and specific regulatory mechanisms of gene expression, and researches have indicated its important roles in tumor regulation. In this study, we explored the circ-0050102 expression in pancreatic cancer and its impacts on tumor malignant phenotypes and further investigated the correlations among circ-0050102, miR-1182 and NPSR1. Results of real-time quantitative PCR showed that circ-0050102 expressed higher in pancreatic cancers compared with that in adjacent normal tissues. In cell functional experiment, downregulation of circ-0050102 could suppress cell proliferation, migration and invasion ability, boost cell apoptosis and arrest cell cycle in both PANC-1 and CFPAC-1 cells. Furthermore, allogeneic transplantation in nude mice was performed and results showed that the inhibition of circ-0050102 could slow down tumor formation in vivo. Mechanism research suggested that circ-0050102 could downregulate miR-1182, while miR-1182 could not influence the expression of circ-0050102, and miR-1182 could directly target at NPSR1 and suppress it. Moreover, circ-0050102 could reverse the effects of si-NPSR1 on pancreatic cancer cells. In conclusion, we identified that circ-0050102 played an important role in promoting pancreatic cancer by regulating the miR-1182/NPSR1 pathway.
Subject(s)
Carcinoma, Pancreatic Ductal/genetics , MicroRNAs/metabolism , Pancreatic Neoplasms/genetics , RNA, Circular/metabolism , Receptors, G-Protein-Coupled/genetics , Animals , Carcinoma, Pancreatic Ductal/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Male , Mice , MicroRNAs/agonists , MicroRNAs/antagonists & inhibitors , Pancreas/pathology , Pancreatic Neoplasms/pathology , RNA, Circular/antagonists & inhibitors , RNA, Circular/genetics , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: The safety of total laparoscopic pancreaticoduodenectomy still remains controversial. Laparoscopic assisted pancreaticoduodenectomy (LAPD) may be an alternative selection. The purpose of the present study is to compare a consecutive cohort of LAPD and open pancreaticoduodenectomy (OPD) from a single surgeon. METHODS: A comparison was conducted between LAPD and OPD from January 2013 to December 2018. Perioperative outcomes and short-term oncological results were compared. Univariate and multivariable analyses were performed to determine associations among variables. RESULTS: 133 patients were enrolled, 36 patients (27.1%) underwent LAPD and 97 (72.9%) underwent OPD. No 30-day and 90-day mortality occurred. LAPD was associated with decreased intraoperative estimated blood loss (300 versus 500 ml; P = 0.002), longer operative time (372 versus 305 min; P < 0.001) compared with OPD. LAPD had a conversion rate of 16.7%, and wasn't associated with an increased grade B/C pancreatic fistula rate, major surgical complications, intraoperative blood transfusion, reoperation rate or length of hospital stay after surgery. In the subset of 58 pancreatic ductal adenocarcinomas, R0 resection rate, median total harvested lymph node or lymph nodes ≥12 did not differ between the two groups. CONCLUSION: LAPD could be performed with non-inferior short-term perioperative and oncologic outcomes achieved by OPD in selected patients.
Subject(s)
Carcinoma, Pancreatic Ductal/surgery , Laparoscopy/methods , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/methods , Adolescent , Adult , Aged , Blood Loss, Surgical , Blood Transfusion , Cohort Studies , Female , Humans , Length of Stay , Male , Middle Aged , Operative Time , Pancreatic Fistula/epidemiology , Postoperative Complications/epidemiology , Retrospective Studies , Young AdultABSTRACT
Objective: Parathyroid carcinoma (PC) is a rare endocrine malignancy with a poor prognosis. The optimal surgical procedure and prognostic factors for PC remain controversial. Methods: Clinical information and parafibromin staining results from 53 patients with PC were reviewed retrospectively from 1997 to 2018. Immunohistochemical staining for parafibromin was performed on formalin-fixed, paraffin-embedded tissue samples. The influence of clinical parameters, surgical procedure, and parafibromin staining of tumor tissues on prognosis were evaluated. Results: A total of 53 patients with PC were enrolled in this study. The male to female ratio was 1.94:1. En bloc resection was performed as initial surgery for 18 patients (34.0%), and 35 patients (66.0%) underwent local resection. Parafibromin staining was negative in the tumor tissues of 24 PC patients (45.3%). Thirty-three patients suffered from local recurrence or distant metastasis, and overall mortality was 16/53 at a median follow-up time of 80 months (range, 7 to 282 months). Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio [HR], 4.13; 95% confidence interval [CI], 1.73 to 9.87; P = .001) was related to recurrence or metastasis and that age >50 years (HR, 5.66; 95% CI, 1.58 to 20.31; P = .008) was related to mortality. The extent of resection was not related to recurrence or overall survival. Conclusion: The majority of PC patients have a relatively long survival with multiple recurrences. Absence of parafibromin staining was a factor that influenced PC recurrence. The main factor influencing PC outcomes may be the biological characteristics rather than surgical extent. Abbreviations: CI = confidence interval; DFS = disease-free survival; HR = hazard ratio; OS = overall survival; PC = parathyroid carcinoma; WHO = World Health Organization.
Subject(s)
Parathyroid Neoplasms , Female , Humans , Male , Neoplasm Recurrence, Local , Prognosis , Retrospective Studies , Staining and Labeling , Tumor Suppressor ProteinsABSTRACT
Cells can secrete extracellular vesicles (EVs) to communicate with neighboring or distant cells by EVs which are composed of a lipid bilayer containing transmembrane proteins and enclosing cytosolic proteins, lipids, and nucleic acids. Breast Cancer is the most frequently diagnosed malignancy with more than 1 million new cases each year and ranks the leading cause of cancer mortality in women worldwide. In this review, we will discuss recent progresses of the roles and mechanisms of cancer-derived EVs in metastatic breast cancer, with a special attention on tumor microenvironment construction, progression, and chemo/radiotherapy responses. This review also covers EV roles as biomarker and therapeutic target in clinical application.