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1.
Cancer Commun (Lond) ; 44(1): 127-172, 2024 01.
Article in English | MEDLINE | ID: mdl-38160327

ABSTRACT

The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.


Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Stomach Neoplasms/therapy , Medical Oncology , Immunotherapy , Neoadjuvant Therapy , China
2.
Mol Cancer ; 21(1): 216, 2022 12 12.
Article in English | MEDLINE | ID: mdl-36510184

ABSTRACT

At present, there is no validated marker to identify the subpopulation of patients with advanced gastric cancer (AGC) who might benefit from neoadjuvant chemotherapy (NACT). In view of this clinical challenge, the identification of non-invasive biomarkers for efficacy prediction of NACT in patients with AGC is imperative. Herein, we aimed to develop a non-invasive, liquid-biopsy-based assay by using an exosome-derived RNAs model based on multi-omics characteristics of RNAs. We firstly used a multi-omics strategy to characterize the mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) profiles of circulating exosome enriched fractions in responders to NACT paired with non-responders, using RNA sequencing. Finally, numerous miRNAs, mRNAs and lncRNAs were identified to be associated with the response to NACT in patients with AGC, and it was validated in an independent cohort with promising AUC values. Furthermore, we established a 6-exosome-RNA panel that could robustly identified responders from non-responders treated with fluorouracil-based neoadjuvant chemotherapy.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Stomach Neoplasms , Humans , Neoadjuvant Therapy , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , RNA, Long Noncoding/genetics , MicroRNAs/genetics , RNA, Messenger/genetics , Liquid Biopsy
3.
World J Gastrointest Oncol ; 14(9): 1771-1784, 2022 Sep 15.
Article in English | MEDLINE | ID: mdl-36187403

ABSTRACT

BACKGROUND: There were few studies on the prognosis of tumor patients with sepsis after gastrointestinal surgery and there was no relevant nomogram for predicting the prognosis of these patients. AIM: To establish a nomogram for predicting the prognosis of tumor patients with sepsis after gastrointestinal surgery in the intensive care unit (ICU). METHODS: A total of 303 septic patients after gastrointestinal tumor surgery admitted to the ICU at Peking University Cancer Hospital from January 1, 2013 to December 31, 2020 were analysed retrospectively. The model for predicting the prognosis of septic patients was established by the R software package. RESULTS: The most common infection site of sepsis after gastrointestinal surgery in the ICU was abdominal infection. The 90-d all-cause mortality rate was 10.2% in our study group. In multiple analyses, we found that there were statistically significant differences in tumor type, septic shock, the number of lymphocytes after ICU admission, serum creatinine and total operation times among tumor patients with sepsis after gastrointestinal surgery (P < 0.05). These five variables could be used to establish a nomogram for predicting the prognosis of these septic patients. The nomogram was verified, and the initial C-index was 0.861. After 1000 internal validations of the model, the C-index was 0.876, and the discrimination was good. The correction curve indicated that the actual value was in good agreement with the predicted value. CONCLUSION: The nomogram based on these five factors (tumor type, septic shock, number of lymphocytes, serum creatinine, and total operation times) could accurately predict the prognosis of tumor patients with sepsis after gastrointestinal surgery.

4.
Front Oncol ; 12: 887244, 2022.
Article in English | MEDLINE | ID: mdl-35656510

ABSTRACT

Background: Transcription factors (TFs) play a crucial role in tumorigenesis and anti-tumor immunity. However, the potential role of large-scale transcription factor regulation patterns in the progression in gastric cancer (GC) is unknown. Methods: We comprehensively assessed the relevance of immune-related TF (IRTF) regulation patterns in anti-tumor immunity and immunotherapy in 1,136 gastric cancer (GC) patients, and evaluated the IRTF score based on IRTF regulation patterns using random forests. Results: Two distinct IRTF regulation patterns were identified, which demonstrating the distinct characteristics in clinical phenotypes, tumor immune microenvironment (TIME), immunogenicity and prognosis in GC. Subsequently, the IRTF score was established to quantify the IRTF regulation pattern for each GC patient. Analysis of large conventional therapy cohorts showed low IRTF score was associated with a better prognosis. In addition, analysis of multiple immunotherapy cohorts showed low IRTF score was also linked to enhanced response to immunotherapy. Conclusion: TF regulation patterns were found to play an important role in the complex immune regulatory relationships in GC. Evaluation of the IRTF regulation patterns in patients will enhance our understanding of immune specificities, and thus, provide effective strategies for personalized therapy.

5.
Front Oncol ; 12: 956706, 2022.
Article in English | MEDLINE | ID: mdl-36620591

ABSTRACT

Introduction: To investigate the influences of time interval between multimodality therapies on survival for locally advanced gastric cancer (LAGC) patients, 627 patients were included in a retrospective study, and 350 who received neoadjuvant chemotherapy (NACT) based on SOX (S-1 plus Oxaliplatin)/XELOX (Capecitabine plus Oxaliplatin) treatment, radical surgery, and adjuvant chemotherapy (AC) from 2005.01 to 2018.06 were eligible for analyses. Methods: Three factors were used to assess influences, including time interval from NACT accomplishment to AC initiation (PECTI), time to surgery after NACT accomplishment (TTS), and time to adjuvant chemotherapy after surgery (TAC). Results: Concerning PECTIs, 99 (28.29%) experienced it within 9 weeks, 188 (53.71%) within 9-13 weeks, 63 (18.00%) over 13 weeks. Patients' 5-year overall survival (OS) significantly decreased as trichotomous PECTI increased (78.6% vs 66.7% vs 55.7%, P = .02). Analogously, there was a significant decrease for dichotomous TTS (within vs over 5 weeks) in OS (P = .03) and progression free survival (PFS) (P = .01) but not for dichotomous TAC (within vs over 6 weeks) in OS and PFS (P = .40). Through multivariate Cox analyses, patients with PECTI over 13 weeks had significantly worse OS (P = .03) and PFS (P = .02). Furthermore, extended TTS had significantly worse OS and PFS but insignificantly worse OS and PFS than extended TAC. Therefore, gastric patients receiving perioperative SOX/XELOX chemotherapy and surgery with extended PECTI over 9 weeks or TTS over 5 weeks would have a negative correlation with PFS and OS, and worse when PECTI over 13 weeks. Nomograms (including PECTI, ypT, ypN, Area Under Curve (AUC) = 0.81) could predict patient survival probability and guide intervention with net benefit. Discussion: In control of PECTI, TTS could be extended appropriately, and shortened TAC might make a remedy, and delayed TAC might be allowed when TTS was shortened.

6.
Cancer Commun (Lond) ; 41(8): 747-795, 2021 08.
Article in English | MEDLINE | ID: mdl-34197702

ABSTRACT

There exist differences in the epidemiological characteristics, clinicopathological features, tumor biological characteristics, treatment patterns, and drug selections between gastric cancer patients from the Eastern and Western countries. The Chinese Society of Clinical Oncology (CSCO) has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually. Taking into account regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China. The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis, treatment, follow-up, and screening of gastric cancer. Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines, this updated guideline integrates the results of major clinical studies from China and overseas for the past year, focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations. For the comprehensive treatment of non-metastatic gastric cancer, attentions were paid to neoadjuvant treatment. The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated. For the comprehensive treatment of metastatic gastric cancer, recommendations for immunotherapy were included, and immune checkpoint inhibitors from third-line to the first-line of treatment for different patient groups with detailed notes are provided.


Subject(s)
Stomach Neoplasms , China , Humans , Medical Oncology , Societies, Medical , Stomach Neoplasms/diagnosis , Stomach Neoplasms/drug therapy
7.
Mol Cancer ; 20(1): 99, 2021 07 30.
Article in English | MEDLINE | ID: mdl-34330299

ABSTRACT

Exosomes are a subpopulation of the tumour microenvironment (TME) that transmit various biological molecules to promote intercellular communication. Exosomes are derived from nearly all types of cells and exist in all body fluids. Noncoding RNAs (ncRNAs) are among the most abundant contents in exosomes, and some ncRNAs with biological functions are specifically packaged into exosomes. Recent studies have revealed that exosome-derived ncRNAs play crucial roles in the tumorigenesis, progression and drug resistance of gastric cancer (GC). In addition, regulating the expression levels of exosomal ncRNAs can promote or suppress GC progression. Moreover, the membrane structures of exosomes protect ncRNAs from degradation by enzymes and other chemical substances, significantly increasing the stability of exosomal ncRNAs. Specific hallmarks within exosomes that can be used for exosome identification, and specific contents can be used to determine their origin. Therefore, exosomal ncRNAs are suitable for use as diagnostic and prognostic biomarkers or therapeutic targets. Regulating the biogenesis of exosomes and the expression levels of exosomal ncRNAs may represent a new way to block or eradicate GC. In this review, we summarized the origins and characteristics of exosomes and analysed the association between exosomal ncRNAs and GC development.


Subject(s)
Biomarkers, Tumor , Exosomes/metabolism , RNA, Untranslated/genetics , Stomach Neoplasms/etiology , Stomach Neoplasms/metabolism , Animals , Disease Progression , Disease Susceptibility , Drug Resistance, Neoplasm/genetics , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Helicobacter Infections/complications , Helicobacter Infections/microbiology , Humans , Molecular Targeted Therapy , Neoplasm Metastasis , Neoplasm Staging , Prognosis , RNA, Untranslated/metabolism , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Tumor Escape/genetics , Tumor Escape/immunology , Tumor Microenvironment
8.
World J Gastrointest Surg ; 13(3): 256-266, 2021 Mar 27.
Article in English | MEDLINE | ID: mdl-33796214

ABSTRACT

BACKGROUND: There have been different reports on mortality of sepsis; however, few focus on the prognosis of patients with sepsis after surgery. AIM: To study the clinical features and prognostic predictors in patients with sepsis after gastrointestinal tumor surgery in intensive care unit (ICU). METHODS: We retrospectively screened patients who underwent gastrointestinal tumor surgery at Peking University Cancer Hospital from January 2015 to December 2019. Among them, 181 patients who were diagnosed with sepsis in ICU were included in our study. Survival was analysed by the Kaplan-Meier method. Univariate and multivariate adjusted analyses were performed to identify predictors of prognosis. RESULTS: The 90-d all-cause mortality rate was 11.1% in our study. Univariate analysis showed that body mass index (BMI), shock within 48 h after ICU admission, leukocyte count, lymphocyte to neutrophil ratio, international normalized ratio, creatinine, procalcitonin, lactic acid, oxygenation index, and sequential organ failure assessment (SOFA) score within 24 h after ICU admission might be all significantly associated with the prognosis of sepsis after gastrointestinal tumor surgery. In multiple analysis, we found that BMI ≤ 20 kg/m2, lactic acid after ICU admission, and SOFA score within 24 h after ICU admission might be independent risk predictors of the prognosis of sepsis after gastrointestinal tumor surgery. Compared with SOFA score, SOFA score combined with BMI and lactic acid might have higher predictive ability (area under the receiver operating characteristic curve, 0.859; 95% confidence interval, 0.789-0.929). CONCLUSION: Lactic acid and SOFA score within 24 h after ICU admission are independent risk predictors of the prognosis of sepsis after gastrointestinal tumor surgery. SOFA score combined with BMI and lactic acid might have good predictive value.

9.
Cancer Commun (Lond) ; 41(3): 258-272, 2021 03.
Article in English | MEDLINE | ID: mdl-33570246

ABSTRACT

BACKGROUND: Insulin gene enhancer protein 1, (ISL1), a LIM-homeodomain transcription factor, is involved in multiple tumors and is associated with insulin secretion and metabolic phenotypes. However, the role of ISL1 in stimulating glycolysis to promote tumorigenesis in gastric cancer (GC) is unclear. In this study, we aimed to characterize the expression pattern of ISL1 in GC patients and explore its molecular biological mechanism in glycolysis and tumorigenesis. METHODS: We analyzed the expression and clinical significance of ISL1 in GC using immunohistochemistry and real-time polymerase chain reaction (PCR). Flow cytometry and IncuCyte assays were used to measure cell proliferation after ISL1 knockdown. RNA-sequencing was performed to identify differentially expressed genes, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) to reveal key signaling pathways likely regulated by ISL1 in GC. Alteration of the glycolytic ability of GC cells with ISL1 knockdown was validated by measuring the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) and by detecting glucose consumption and lactate production. The expression of glucose transporter 4 (GLUT4) and ISL1 was assessed by Western blotting, immunohistochemistry, and immunofluorescent microscopy. The luciferase reporter activity and chromatin immunoprecipitation assays were performed to determine the transcriptional regulation of ISL1 on GLUT4. RESULTS: High levels of ISL1 and GLUT4 expression was associated with short survival of GC patients. ISL1 knockdown inhibited cell proliferation both in vitro and in vivo. KEGG analysis and GSEA for RNA-sequencing data indicated impairment of the glycolysis pathway in GC cells with ISL1 knockdown, which was validated by reduced glucose uptake and lactate production, decreased ECAR, and increased OCR. Mechanistic investigation indicated that ISL1 transcriptionally regulated GLUT4 through binding to its promoter. CONCLUSION: ISL1 facilitates glycolysis and tumorigenesis in GC via the transcriptional regulation of GLUT4.


Subject(s)
Insulins , Stomach Neoplasms , Carcinogenesis , Cell Line, Tumor , Glucose Transport Proteins, Facilitative , Glycolysis/genetics , Humans , Stomach Neoplasms/genetics
10.
World J Gastrointest Oncol ; 13(12): 2161-2179, 2021 Dec 15.
Article in English | MEDLINE | ID: mdl-35070049

ABSTRACT

BACKGROUND: Current tumor regression grade (TRG) evaluations are based on various systems which brings confusion for oncologists and pathologists when interpreting results. The recent six-tier system (JGCA2017-TRG) recommended by the Japanese Gastric Cancer Association (JGCA) is worth investigating, as four-tier TRG systems are favored in various parts of the world. AIM: To compare the predictive accuracies of five published TRG systems. METHODS: Data were retrospectively collected from patients with locally advanced gastric cancer (LAGC) who underwent neoadjuvant chemotherapy followed by D2 Lymphadenectomy between January 2005 and January 2014 at our institution. Outcomes were overall survival (OS) and disease-free survival (DFS), which were evaluated separately using the following TRG systems: JGCA2017, JGCA, Becker, AJCC/CAP, and Mandard. RESULTS: All five published TRG systems were independent predictors for OS and DFS. Concordance indices of the JGCA2017, JGCA, Becker, AJCC/CAP-TRG, and Mandard systems were 0.651/0.648 0.652/0.649, 0.693/0.695, 0.688/0.685, and 0.674/0.675 for OS and DFS, respectively. The four-tier Becker system showed the highest c-index, which was significantly greater than that of the six-tier JGCA2017 and five-tier JGCA systems (P < 0.05 in OS and DFS). When residual tumor percentages were reset as: "no residual tumor", < 10%, < 100%, and "no response", the rearranged cutoff values achieved a maximum c-index with 0.728 for OS and 0.737 for DFS, which was superior to the other five systems. CONCLUSION: The newly introduced six-tier JGCA-TRG system cannot increase prognostic stratification. The four-tier Becker system is more suitable for LAGC patients. A population-based study is warranted to define the optimal criterion for TRG in LAGC patients.

11.
Gastric Cancer ; 24(1): 245-257, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32712769

ABSTRACT

BACKGROUND: For patients with locally advanced proximal gastric cancer (LAPGC), the individualized selection of patients with highly suspected splenic hilar (No. 10) lymph node (LN) metastasis to undergo splenic hilar lymphadenectomy, is a clinical dilemma. This study aimed to re-evaluate the feasibility and safety of laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) and to identify the population who would benefit from it. METHODS: A total of 1068 patients (D2 group = 409; D2 + No. 10 group = 659) who underwent laparoscopic total gastrectomy from four prospective trials between January 2015 and July 2019 were analyzed. RESULTS: No significant difference in the incidence (16.9% vs. 16.4%; P = 0.837) of postoperative complications were found between the two groups. The metastasis rate of No. 10 LN among patients in the D2 + No. 10 group was 10.3% (68/659). Based on the decision tree, patients with LAPGC with tumor invading the greater curvature (Gre), patients with non-Gre-invading LAPGC with a tumor size > 5 cm and clinical positive locoregional LNs were defined as the high-priority No. 10 dissection group. The metastasis rate of No. 10 LNs in the high-priority group was 19.4% (41/211). In high-priority group, the 3-year overall survival of the D2 + No. 10 group was better than that of the D2 group (74.4% vs. 42.1%; P = 0.005), and the therapeutic index of No. 10 was higher than the indices of most suprapancreatic stations. CONCLUSIONS: LSPSHL for LAPGC is safe and feasible when performed by experienced surgeons. LSPSHL could be recommended for the high-priority group patients even without invasion of the Gre.


Subject(s)
Gastrectomy/methods , Laparoscopy/methods , Lymph Node Excision/methods , Spleen/surgery , Stomach Neoplasms/surgery , Clinical Trials as Topic , Feasibility Studies , Female , Gastrectomy/adverse effects , Humans , Incidence , Intention to Treat Analysis , Laparoscopy/adverse effects , Lymph Node Excision/adverse effects , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Organ Sparing Treatments/adverse effects , Organ Sparing Treatments/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Propensity Score , Prospective Studies , Stomach Neoplasms/pathology
12.
Mol Ther Nucleic Acids ; 22: 1129-1141, 2020 Dec 04.
Article in English | MEDLINE | ID: mdl-33294297

ABSTRACT

Long non-coding RNAs (lncRNAs) are characterized as key layers of the genome in various cancers. TSPEAR-AS2 was highlighted to be a candidate lncRNA potentially involved in gastric cancer (GC) progression. However, the clinical significance and mechanism of TSPEAR-AS2 in GC required clarification. The clinical significance of TSPEAR-AS2 was elucidated through Kaplan-Meier Plotter. The mechanism of TSPEAR-AS2 in GC was clarified in vitro and in vivo using luciferase reporter, chromatin immunoprecipitation, RNA immunoprecipitation assays, and animal models. TSPEAR-AS2 elevation was closely correlated with overall survival of GC patients. A basic transcription element-binding protein 2 (BTEB2)-activated TSPEAR-AS2 model was first explored in this study. TSPEAR-AS2 silencing substantially reduced tumorigenic capacities of GC cells, while TSPEAR-AS2 elevation had the opposite effect. Mechanistically, TSPEAR-AS2 bound with both polycomb repressive complex 2 (PRC2) and argonaute 2 (Ago2). TSPEAR-AS2 knockdown significantly decreased H3K27me3 levels at promoter regions of gap junction protein alpha 1 (GJA1). Ago2 was recruited by TSPEAR-AS2, which was defined to sponge miR-1207-5p, contributing to the repression of claudin 4 (CLDN4) translation. The axis of EZH2/GJA1 and miR-1207-5p/CLDN4 mediated by BTEB2-activated-TSPEAR-AS2 plays an important role in GC progression, suggesting a new therapeutic direction in GC treatment.

13.
J Gastrointest Oncol ; 11(5): 894-898, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33209485

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate the health economics of patients with sepsis after gastrointestinal tumor operation in ICU. METHODS: This case-control study used 1:1 propensity-score (PS) matched method and patients were matched according to tumor type, age and gender. The study group was composed of 181 patients with sepsis after operation of gastrointestinal tumor in ICU, while the control group was composed of 181 patients without sepsis after operation of gastrointestinal tumor. The medical expenses and length of stay in the hospital of these patients were analyzed. RESULTS: The median of the total hospitalization cost for the study group was $26,038, which was 1.7 times of the control group (P<0.001). The costs of drugs, laboratory test, examination, treatment, operation, anesthesia, materials, ward and other costs in the study group were higher than those in the control group (P<0.001). The median length of stay in the hospital in the study group was 26 days, which were 12 days longer than that of the control group (P<0.001). However, there was no significant difference in daily average cost between the two groups (P=0.103). CONCLUSIONS: In ICU, patients with sepsis after operation of gastrointestinal tumor increased the cost of hospitalization and prolonged the length of stay in the hospital than those without sepsis.

14.
Gastroenterol Rep (Oxf) ; 8(3): 167-174, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32661490

ABSTRACT

Novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing public-health pandemic worldwide. Although SARS-CoV-2 has been known to spread primarily through respiratory droplets, recent evidence also supports fecal/oral as an additional route of transmission, raising concerns over gastrointestinal (GI) transmission of the infection. Herein, we, as the front-line Chinese GI surgeons, would like to share our experience and lessons in the combat against COVID-19. It is essential to create science-based, rational, and practical strategies during the outbreak of COVID-19. Here, we provide multi-institutional consensus on minimizing disease transmission while continuing to provide care from all aspects for patients in GI surgery, including outpatient clinics, inpatient units, gastrointestinal endoscopy centers, and adjustments in perioperative care. Our experiences and recommendations are worth sharing and may help to establish specific infection-control and outcome measures.

15.
Gastric Cancer ; 23(6): 1041-1050, 2020 11.
Article in English | MEDLINE | ID: mdl-32500456

ABSTRACT

BACKGROUND: Early diagnosis of Peritoneal metastasis (PM) is clinically significant regarding optimal treatment selection and avoidance of unnecessary surgical procedures. Cytopathology plays an important role in early screening of PM. We aimed to develop a deep learning (DL) system to achieve intelligent cytopathology interpretation, especially in ascites cytopathology. METHODS: The original ascites cytopathology image dataset consists of 139 patients' original hematoxylin-eosin (HE) and Papanicolaou (PAP) Staining images. DL system was developed using transfer learning (TL) to achieve cell detection and classification. Pre-trained alexnet, vgg16, goolenet, resnet18 and resnet50 models were studied. Cell detection dataset consists of 176 cropped images with 6573 annotated cell bounding boxes. Cell classification data set consists of 487 cropped images with 18,558 and 6089 annotated malignant and benign cells in total, respectively. RESULTS: We established a novel ascites cytopathology image dataset and achieved automatically cell detection and classification. DetectionNet based on Faster R-CNN using pre-trained resnet18 achieved cell detection with 87.22% of cells' Intersection of Union (IoU) bigger than the threshold of 0.5. The mean average precision (mAP) was 0.8316. The ClassificationNet based on resnet50 achieved the greatest performance in cell classification with AUC = 0.8851, Precision = 96.80%, FNR = 4.73%. The DL system integrating the separately trained DetectionNet and Classificationnet showed great performance in the cytopathology image interpretation. CONCLUSIONS: We demonstrate that the integration of DL can improve the efficiency of healthcare. The DL system we developed using TL techniques achieved accurate cytopathology interpretation, and had great potential to be integrated into clinician workflow.


Subject(s)
Ascites/diagnosis , Deep Learning , Early Detection of Cancer/methods , Image Interpretation, Computer-Assisted/methods , Peritoneal Neoplasms/diagnosis , Area Under Curve , Ascites/classification , Datasets as Topic , Humans , Neoplasm Metastasis/diagnosis , Neural Networks, Computer , Peritoneal Neoplasms/classification , Reproducibility of Results
16.
Sci Transl Med ; 12(549)2020 06 24.
Article in English | MEDLINE | ID: mdl-32581131

ABSTRACT

Several patient-derived tumor models emerged recently as robust preclinical drug-testing platforms. However, their potential to guide clinical therapy remained unclear. Here, we report a model called patient-derived tumor-like cell clusters (PTCs). PTCs result from the self-assembly and proliferation of primary epithelial, fibroblast, and immune cells, which structurally and functionally recapitulate original tumors. PTCs enabled us to accomplish personalized drug testing within 2 weeks after obtaining the tumor samples. The defined culture conditions and drug concentrations in the PTC model facilitate its clinical application in precision oncology. PTC tests of 59 patients with gastric, colorectal, or breast cancers revealed an overall accuracy of 93% in predicting their clinical outcomes. We implemented PTC to guide chemotherapy selection for a patient with mucinous rectal adenocarcinoma who experienced recurrence with metastases after conventional therapy. After three cycles of a nonconventional therapy identified by the PTC, the patient showed a positive response. These findings need to be validated in larger clinical trials, but they suggest that the PTC model could be prospectively implemented in clinical decision-making for therapy selection.


Subject(s)
Breast Neoplasms , Pharmaceutical Preparations , Thyroid Neoplasms , Breast Neoplasms/drug therapy , Female , Humans , Neoplasm Recurrence, Local , Precision Medicine
17.
Eur J Radiol ; 128: 108974, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32416553

ABSTRACT

PURPOSE: To assess the efficacy of diffusion kurtosis imaging (DKI) in the prediction of the treatment response to neoadjuvant chemotherapy in patients with locally advanced gastric cancer (LAGC). METHODS: A total of 31 LAGC patients were enrolled in this prospective study. All patients underwent diffusion-weighted MRI examination (with b = 01, 2001, 5001, 8002, 10004, 15004, 20006 s/mm2, the subscript denotes the number of signal averages) before and after chemotherapy. DKI and mono-exponential (b = 0, 800 s/mm2) models were built. Apparent diffusion coefficient (ADC), mean diffusivity (MD) and mean kurtosis (MK) of the LAGC tumors were measured. The absolute change values (ΔX) and percentage change values (%ΔX) of the above parameters post neoadjuvant chemotherapy (NACT) were calculated. The response was evaluated according to the pathological tumor regression grade scores (effective response group: TRG 0-2, poor response group: TRG 3). Mann-Whitney U test and receiver operating characteristic (ROC) curves were applicated for statistical analysis. RESULTS: There were 17 patients in the effective response group (ERG), and 14 patients in the poor response group (PRG). The MKpre and MKpost values in PRG were significantly higher than those in ERG [(0.671 ±â€¯0.026) and (0.641 ±â€¯0.019) vs. (0.584 ±â€¯0.023) and (0.519 ±â€¯0.018), p < 0.001]. ADCpost and MDpost in PRG were significantly lower than those in ERG (p = 0.005, p =0.001). Significant differences were also observed for % ΔMK, ΔMD and ΔMK between the two groups (p < 0.05). The area under the curve (AUC) for the prediction of PRG was highest for MKpost (AUC = 0.958, cutoff value = 0.614). The MKpre and MKpost had the highest sensitivity (91.70 %) and specificity (93.80 %) in the prediction of PRG, respectively. CONCLUSION: Both DKI and ADC values show potential for the prediction of the PRG in LAGC patients. The DKI parameters, especially MKpost displayed the best performance.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Image Interpretation, Computer-Assisted/methods , Neoadjuvant Therapy/methods , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/drug therapy , Aged , Area Under Curve , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , ROC Curve , Reproducibility of Results , Sensitivity and Specificity , Statistics, Nonparametric , Treatment Outcome
18.
J Laparoendosc Adv Surg Tech A ; 30(7): 713-722, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32471317

ABSTRACT

Background: With the rapid aging of global population, the number of elderly patients with gastric cancer is increasing. This study aimed to evaluate short- and long-term outcomes after laparoscopic gastrectomy (LG) versus open gastrectomy (OG) in elderly gastric cancer patients. Materials and Methods: We searched PubMed, EMBASE, and the Cochrane library databases from January 1994 to May 2019. Surgical safety, postoperative complications, number of harvested lymph nodes, and overall survival rate were included and analyzed. The qualities of the included studies were evaluated by Newcastle-Ottawa Quality Assessment Scale. The evidence of outcomes was evaluated using the GRADE approach. The Review Manager® 5.3 (Cochrane, London, UK) and Stata® 14.0 (StataCorp., College Station, Texas) were used to analyze the outcomes. Results: Thirteen studies containing 4768 elderly patients with gastric cancer were included in this meta-analysis. LG was more favorable than OG in terms of overall postoperative morbidity (odds ratio [OR]: 0.56; 95% confidence interval [CI]: 0.44 to 0.70; P < .00001), the postoperative stay (standardized mean difference [SMD]: -0.56; 95% CI: -0.76 to (-0.37); P < .00001), and the number of harvested lymph nodes (SMD: 0.19; 95% CI: 0.09 to 0.29; P = .0003). No significant difference was found in anastomotic leakage rate (OR: 0.82; 95% CI: 0.59 to 1.12; P = .21), mental disease (OR: 0.79; 95% CI: 0.44 to 1.44; P = .44), or overall survival rate (P = .62) between two groups. However, in the subgroup with a cutoff age of 80 years, the anastomotic leakage rate was higher in LG (OR: 10.27; 95% CI: 1.31 to 80.35; P = .03). Conclusions: LG was more favorable than OG in the elderly patients <80 years old with gastric cancer.


Subject(s)
Gastrectomy/methods , Laparoscopy , Stomach Neoplasms/surgery , Age Factors , Aged , Aged, 80 and over , Humans , Neoplasm Staging , Stomach Neoplasms/pathology , Treatment Outcome
19.
Ann Surg Oncol ; 27(4): 1103-1109, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31965376

ABSTRACT

BACKGROUND: Preoperative diagnosis of peritoneal metastasis with gastric cancer remains challenging. This study explored the abnormal computed tomography (CT) signs of occult peritoneal metastasis (OPM) and evaluated it by region-to-region comparison using staging laparoscopy, from which a 4-point CT score system was developed. METHODS: Patients with advanced gastric cancer (stage cT ≥ 2M0) diagnosed by CT were enrolled in the study. Occult peritoneal metastasis detected during staging laparoscopy was compared with preoperative CT to investigate the presence of abnormal signs by a region-to-region comparison. A 4-point CT score system was developed to define the radiologic characteristics. Subsequently, the diagnostic efficacy of the CT score system was prospectively verified. RESULTS: In this study, 57 OPM regions were detected by staging laparoscopy in 33 of the 385 enrolled patients. The greater omentum was the most frequent site of OPM (38.60%, 22/57), which usually exhibited a smudge-like ground-glass opacity (S-GGO) (90.91%, 20/22) with a mean CT score of 2.14. The parietal and perihepatic peritoneum was the second most common site (22.81%, 13/57). A 4-point CT score system was developed based on the results. A cutoff CT score of 2 or higher was associated with a false-negative rate of 2% (2/99). This CT score system had a sensitivity of 87.5% and a specificity of 76.4% for an OPM-positive diagnosis (area under the curve, 0.848). The agreement between two radiologists on the assigned final score was 76.2% (kappa, 0.5). CONCLUSIONS: Patients with OPM mostly exhibited S-GGO on CT, which should be interpreted cautiously. The 4-point CT score system may improve the pretreatment evaluation of occult peritoneal metastasis, and staging laparoscopy might not be necessary for patients with a score lower than 2.


Subject(s)
Peritoneal Neoplasms/diagnostic imaging , Radiometry/methods , Stomach Neoplasms/diagnostic imaging , Tomography, X-Ray Computed , Humans , Laparoscopy , Neoplasm Metastasis , Neoplasm Staging , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/secondary , Prospective Studies , ROC Curve , Sensitivity and Specificity , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology
20.
Surg Endosc ; 34(3): 1191-1199, 2020 03.
Article in English | MEDLINE | ID: mdl-31236721

ABSTRACT

OBJECTIVES: Healing of gastric endoscopic submucosal dissection (ESD)-induced ulcer is critical for patient recovery. During ESD treatment, submucosal incisions are made with an electrosurgical knife to accomplish en bloc resections of superficial lesions. Nevertheless, excess electrocoagulation may decrease the blood supply of ESD-induced ulcer and delay the ulcer healing. The aim of this retrospective study was to evaluate the effectiveness of conservative electrocoagulation followed by porcine fibrin sealant (FS) as a wound microvessels-protective hemostatic technique in promoting the healing of ESD-induced ulcer. METHODS: A total of 332 patients with early gastric cancer (EGCs), or gastric precancerous lesion and gastric adenoma were retrospectively analyzed. Propensity score matching was used to compensate for the differences in age, gender, tumor location, resected specimen area, and pathology. One-month ulcer healing rates and delayed bleeding were compared between two matched groups (combined hemostats group and electrocautery group). RESULTS: A total of 115 matched pairs were created after propensity score matching. There was no difference in tumor location, specimen surface area, tumor differentiation and invasion depth between groups. The completed healing rate 1 month after ESD was 44.3% in combined hemostats group and 30.4% in electrocautery group (P = 0.004). There was no difference in delayed massive bleeding rate between two groups (P = 0.300). In addition, based on the multivariate regression analysis for ulcer healing rate, the use of FS (OR, 0.348, 95% CI 0.196 - 0.617, P = 0.000) and larger specimen size (OR, 2.640, 95% CI 2.015-3.458, P = 0.000) were associated with nonhealing ulcer 1 month after ESD. CONCLUSION: Applying conservative electrocoagulation followed by porcine FS as a wound microvessels-protective hemostatic technique can promote ESD-induced ulcer healing without increasing delayed bleeding.


Subject(s)
Electrocoagulation , Endoscopic Mucosal Resection/adverse effects , Fibrin Tissue Adhesive , Postoperative Complications/therapy , Stomach Neoplasms/surgery , Stomach Ulcer/therapy , Adenoma/surgery , Aged , Combined Modality Therapy , Female , Hemostatic Techniques , Humans , Male , Middle Aged , Precancerous Conditions/surgery , Propensity Score , Retrospective Studies , Stomach Ulcer/etiology , Treatment Outcome
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