Conversion chemoradiotherapy combined with nab-paclitaxel plus cisplatin in patients with locally advanced borderline-resectable or unresectable esophageal squamous cell carcinoma: a phase i/ii prospective cohort study.

BACKGROUND: To evaluate the efficacy and safety of nab-paclitaxel plus cisplatin as the regimen of conversional chemoradiotherapy (cCRT) in locally advanced borderline resectable or unresectable esophageal squamous cell carcinoma (ESCC). METHODS: Patients with locally advanced ESCC (cT3­4, Nany, M0­1, M1 was limited to lymph node metastasis in the supraclavicular area) were enrolled. All the patients received the cCRT of nab-paclitaxel plus cisplatin. After the cCRT, those resectable patients received esophagectomy; those unresectable patients continued to receive the definitive chemoradiotherapy (dCRT). The locoregional control (LRC), overall survival (OS), event-free survival (EFS), distant metastasis free survival (DMFS), pathological complete response (pCR), R0 resection rate, adverse events (AEs) and postoperative complications were calculated. RESULTS: 45 patients with ESCC treated from October 2019 to May 2021 were finally included. The median follow-up time was 30.3 months. The LRC, OS, EFS, DMFS at 1 and 2 years were 81.5%, 86.6%, 64.3%, 73.2 and 72.4%, 68.8%, 44.8%, 52.7% respectively. 21 patients (46.7%) received conversional chemoradiotherapy plus surgery (cCRT+S). The pCR rate and R0 resection rate were 47.6 and 84.0%. The LRC rate at 1 and 2 years were 95.0%, 87.1% in cCRT+S patitents and 69.3%, 58.7% in dCRT patients respectively (HR, 5.14; 95%CI, 1.10-23.94; P = 0.021). The toxicities during chemoradiotherapy were tolerated, and the most common grade 3-4 toxicitiy was radiation esophagitis (15.6%). The most common postoperative complication was pleural effusion (38.1%) and no grade ≥ IIIb complications were observed. CONCLUSION: nab-paclitaxel plus cisplatin are safe as the regimen of conversional chemoradiotherapy of ESCC.

Exosomal transfer of HCC-derived miR-17-5p downregulates NK cell function by targeting RUNX1-NKG2D axis.

OBJECTIVE: Natural killer (NK) cells are an integral part of the staunch defense line against malignant tumors within the tumor microenvironment. Existing research indicates that miRNAs can influence the development of NK cells by negatively modulating gene expression. In this study, we aim to explore how the miR-17-5p in Hepatocellular Carcinoma (HCC) exosomes regulates the killing function of NK cells towards HCC cells through the transcription factor RNX1. METHODS: The exosomes were isolated from HCC tissues and cell lines, followed by a second generation sequencing to compare differential miRNAs. Verification was performed using qRT-PCR and Western blot methods. The mutual interactions between miR-17-5p and RUNX1, as well as between RUNX1 and NKG2D, were authenticated using techniques like luciferase reporter gene assays, Western blotting, and Chromatin Immunoprecipitation (ChIP). The cytotoxic activity of NK cells towards HCC cells in vitro was measured using methods such as RTCA and ELISPOT. The zebrafish xenotransplantation was utilized to assess the in vivo killing capacity of NK cells against HCC cells. RESULTS: The level of miR-17-5p in exosomes from HCC tissue increased compared to adjacent tissues. We verified that RUNX1 was a target of miR-17-5p and that RUNX1 enhances the transcription of NKG2D. MiR-17-5p was found to downregulate the expression of RUNX1 and NKG2D, subsequently reducing the in vitro and in vivo cytotoxic capabilities of NK cells against HCC cells. CONCLUSIONS: The miR-17-5p found within HCC exosomes can target RUNX1, subsequently attenuating the cytotoxic activity of NK cells.

A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments.

Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.

Effectiveness and safety of camrelizumab-containing neoadjuvant therapy in patients with esophageal squamous cell carcinoma: a prospective multicenter observational cohort study.

Background: Camrelizumab has been demonstrated to be a feasible treatment option for locally advanced esophageal squamous cell carcinoma (ESCC) when combined with neoadjuvant chemotherapy. This trial was conducted to investigate the effectiveness and safety of camrelizumab-containing neoadjuvant therapy in patients with ESCC in daily practice. Methods: This prospective multicenter observational cohort study was conducted at 13 tertiary hospitals in Southeast China. Patients with histologically or cytologically confirmed ESCC [clinical tumor-node-metastasis (cTNM) stage I-IVA] who had received at least one dose of camrelizumab-containing neoadjuvant therapy were eligible for inclusion. Results: Between June 1, 2020 and July 13, 2022, 255 patients were enrolled and included. The median age was 64 (range, 27 to 82) years. Most participants were male (82.0%) and had clinical stage III-IVA diseases (82.4%). A total of 169 (66.3%) participants underwent surgical resection; 146 (86.4%) achieved R0 resection, and 36 (21.3%) achieved pathological complete response (pCR). Grades 3-5 adverse events (AEs) were experienced by 14.5% of participants. Reactive cutaneous capillary endothelial proliferation occurred in 100 (39.2%) of participants and all were grade 1 or 2. Conclusions: Camrelizumab-containing neoadjuvant therapy has acceptable effectiveness and safety profiles in real-life ESCC patients.

Is laparoscope surgery feasible for upper gastrointestinal cancer patients with a history of abdominal surgery?

Objective: To investigate the feasibility of laparoscopic abdominal mobilization in patients with cancers of the esophagus or gastroesophageal junction who have a history of abdominal surgery. Methods: A total of 132 patients who underwent resection for cancers of the esophagus or gastroesophageal junction from August 2018 to March 2022 in the Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, were selected (66 patients with a history of abdominal surgery (observation group) and 66 patients without a history of abdominal surgery (control group)). All patients were treated with preoperative neoadjuvant therapy, based on the clinical stage. Thoracoscopic and laparoscopic resection was performed under general anesthesia. The intraoperative and postoperative conditions and surgical complications were compared between the two groups. Results: No significant differences were found in baseline data between the observation group and the control group (p > 0.05). Laparoscopic abdominal mobilization was completed in both groups, and there were no significant differences between the two groups in the total operation time [(272.50 ± 86.45) min vs. (257.55 ± 67.96) min], abdominal mobilization time [(25.03 ± 9.82) min vs. (22.53 ± 3.88) min], blood loss [(119.09 ± 72.17) ml vs. (104.39 ± 43.82) ml], and postoperative time to first flatus [(3.44 ± 0.73) d vs. (3.29 ± 0.60) d] (p > 0.05). The abdominal mobilization time was longer in observation group than that in control group (p = 0.057). After excluding the patients (31/66) with a history of simple appendectomy from the observation group, the abdominal mobilization time was significantly longer in observation group than that in control group [(27.97 ± 12.16) min vs. (22.53 ± 3.88) min] (p < 0.05). There were significantly fewer dissected abdominal lymph nodes in the observation group than in the control group [(18.44 ± 10.87) vs. (23.09 ± 10.95), p < 0.05]. After excluding the patients (15/66) with a history of abdominal tumor surgery from the observation group, there was no significant difference in the number of dissected abdominal lymph nodes between the two groups [(20.62 ± 10.81) vs. (23.09 ± 10.95)] (p > 0.05).In addition, no postoperative complications, such as intestinal obstruction, abdominal infection and bleeding, occurred in either group. Conclusion: Patients with cancers of the esophagus or gastroesophageal junction who have a history of abdominal surgery are suitable for minimally invasive laparoscopic mobilization.

Explainable survival analysis with uncertainty using convolution-involved vision transformer.

Image-based precision medicine research is able to help doctors make better decisions on treatments. Among all kinds of medical images, a special form is called Whole Slide Image (WSI), which is used for diagnosing patients with cancer, aiming to enable more accurate survival prediction with its high resolution. However, One unique challenge of the WSI-based prediction models is processing the gigabyte-size or even terabyte-size WSIs, which would make most models computationally infeasible. Although existing models mostly use a pre-selected subset of key patches or patch clusters as input, they might discard some important morphology information, making the prediction inferior. Another challenge is improving the prediction models' explainability, which is crucial to help doctors understand the predictions given by the models and make faithful decisions with high confidence. To address the above two challenges, in this work, we propose a novel explainable survival prediction model based on Vision Transformer. Specifically, we adopt dual-channel convolutional layers to utilize the complete WSIs for more accurate predictions. We also introduce the aleatoric uncertainty into our model to understand its limitation and avoid overconfidence in using the prediction results. Additionally, we present a post-hoc explainable method to identify the most salient patches and distinct morphology features as supporting evidence for predictions. Evaluations of two large cancer datasets show that our proposed model is able to make survival predictions more effectively and has better explainability for cancer diagnosis.

Comparison of neoadjuvant nab-paclitaxel plus immunotherapy versus paclitaxel plus immunotherapy for esophageal squamous cell carcinoma.

BACKGROUND: This study aimed to compare the feasibility of nab-paclitaxel plus platinum-based chemotherapy (nabTP) versus paclitaxel plus platinum-based chemotherapy (TP) with immune checkpoint inhibitors (ICIs) as a neoadjuvant modality for locally resectable esophageal squamous cell carcinoma (ESCC). METHODS: Between April 2019 and March 2022, we identified ESCC patients who received neoadjuvant immunotherapy with both nabTP (n = 213) and TP (n = 98) at our institution and Henan Cancer Hospital. The patients in the ICIs-nabTP and ICIs-TP groups were pair-matched (1:1) for tumor location, sex, smoking, drinking, clinical T and N stage. The primary endpoint was the hazard of 30-day major postoperative complications. Second, logistic models were applied to estimate the risk factors for pathological complete response (pCR) rate. RESULTS: All patients underwent esophagectomy with R0 resection. A statistically significant increase in the risk of developing major pulmonary (odds ratio [OR], 1.182; 95% confidence interval [CI]: 0.530-2.635; p = 0.683), anastomotic (OR, 1.881; 95% CI: 0.607-5.830; p = 0.267), cardiac (OR, 1.000; 95% CI: 0.426-2.349; p = 1.000) complications after neoadjuvant immunotherapy plus nabTP was not observed. The median interval to surgery was 39 days in the ICIs-nabTP group versus 44 days in the ICIs-TP group (p = 0.119). There was no 30-day mortality in each group. However, there was a slight difference in the 30-day readmission rate (p = 0.043) and the incidence of hydropneumothorax (p = 0.027) between the two groups. The pCR rates of the ICIs-nabTP and ICIs-TP group were 36.7 and 21.4%, respectively (p = 0.018). CONCLUSIONS: It appears to be feasible to add immunotherapy to nabTP regimen for locally advanced ESCC. Compared with TP, nabTP plus ICIs can achieve a better pCR rate in ESCC.

High-Precision Intelligent Cancer Diagnosis Method: 2D Raman Figures Combined with Deep Learning.

Raman spectroscopy, as a label-free detection technology, has been widely used in tumor diagnosis. However, most tumor diagnosis procedures utilize multivariate statistical analysis methods for classification, which poses a major bottleneck toward achieving high accuracy. Here, we propose a concept called the two-dimensional (2D) Raman figure combined with convolutional neural network (CNN) to improve the accuracy. Two-dimensional Raman figures can be obtained from four transformation methods: spectral recurrence plot (SRP), spectral Gramian angular field (SGAF), spectral short-time Fourier transform (SSTFT), and spectral Markov transition field (SMTF). Two-dimensional CNN models all yield more than 95% accuracy, which is higher than the PCA-LDA method and the Raman-spectrum-CNN method, indicating that 2D Raman figure inputs combined with CNN may be one reason for gaining excellent performances. Among 2D-CNN models, the main difference is the conversion, where SRP is based on the structure of wavenumber series with the best performances (98.9% accuracy, 99.5% sensitivity, 98.3% specificity), followed by SGAF on the wavenumber series, SSTFT on wavenumber and intensity information, and SMTF on wavenumber position information. The inclusion of external information in the conversion may be another reason for improvement in the accuracy. The excellent capability shows huge potential for tumor diagnosis via 2D Raman figures and may be applied in other spectroscopy analytical fields.

Comparative genomic analysis of esophageal squamous cell carcinoma among different geographic regions.

Introduction: Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence, survival, and risk factors. Although the genomic characteristics of ESCC have been extensively characterized, the genomic differences between different geographic regions remain unclear. Methods: In this study, we sequenced 111 patients with ESCC from northern (NC) and southern (SC) China, combined their data with those of 1081 cases from previous reports, and performed a comparative analysis among different regions. In total, 644 ESCC cases were collected from six geographic regions (NC, SC, Xinjiang, China [XJC], Japan [JP], Vietnam [VN], and Europe & America [EA]) as the discovery cohort. Validation cohort 1 included 437 patients with ESCC from the NC region. Validation cohort 2 included 54 and 57 patients from the NC and SC regions, respectively. Results: Patients with ESCC in different regions had different genomic characteristics, including DNA signatures, tumor mutation burdens, significantly mutated genes (SMGs), altered signaling pathways, and genes associated with clinical features. Based on both the DNA mutation signature and the mutation profile of the most common genes, the NC and SC groups were clustered close together, followed by the JP, XJC, EA, and VN groups. Compared to patients with ESCC from SC, SMGs, including KMT2D, FAT1, and NOTCH1 were more frequently identified in patients with ESCC from NC. Furthermore, some genes (TDG and DNAH8) correlated with overall survival in completely opposite ways in patients with ESCC from different geographical regions. Conclusions: Our study provides insights into genomic differences in ESCC among different regions. These differences may be related to differences in environmental carcinogens, incidence, and survival.

Highly accurate diagnosis of lung adenocarcinoma and squamous cell carcinoma tissues by deep learning.

Intraoperative detection of the marginal tissues is the last and most important step to complete the resection of adenocarcinoma and squamous cell carcinoma. However, the current intraoperative diagnosis is time-consuming and requires numerous steps including staining. In this paper, we present the use of Raman spectroscopy with deep learning to achieve accurate diagnosis with stain-free process. To make the spectrum more suitable for deep learning, we utilize an unusual way of thinking which regards Raman spectral signal as a sequence and then converts it into two-dimensional Raman spectrogram by short-time Fourier transform as input. The normal-adenocarcinoma deep learning model and normal-squamous carcinoma deep learning model both achieve more than 96% accuracy, 95% sensitivity and 98% specificity when test, which higher than the conventional principal components analysis-linear discriminant analysis method with normal-adenocarcinoma model (0.896 accuracy, 0.867 sensitivity, 0.926 specificity) and normal-squamous carcinoma model (0.821 accuracy, 0.776 sensitivity, 1.000 specificity). The high performance of deep learning models provides a reliable way for intraoperative detection of marginal tissue, and is expected to reduce the detection time and save human lives.

Phase Ib trial of camrelizumab combined with chemotherapy and apatinib for neoadjuvant treatment of locally advanced thoracic esophageal squamous cell carcinoma.

Objective: This is a prospective, single-arm, phase Ib study to evaluate the safety and efficacy of camrelizumab combined with chemotherapy and apatinib as neoadjuvant therapy for locally advanced thoracic esophageal squamous cell carcinoma (ESCC). Methods: The regimen encompassed 2-4 cycles of neoadjuvant camrelizumab, nab-paclitaxel, nedaplatin, and apatinib to treatment-naive patients with resectable locally advanced ESCC. The treatment was repeated every 14 days. Initially, six patients were planned to receive two cycles of neoadjuvant therapy as safety assessment, and then 24 patients received four cycles of neoadjuvant therapy, followed by esophagectomy after 4-8 weeks. The primary endpoint was safety. The key secondary endpoints were pathologic complete response (pCR) and major pathologic response (MPR). Results: This study enrolled 30 patients, among whom, five patients received two cycles of neoadjuvant therapy, and one patient missed the second cycle of therapy due to grade 3 elevated alanine transaminase (ALT) level. The remaining 24 patients received four planned cycles of neoadjuvant therapy. Eleven patients (36.7%) developed grade 3 neoadjuvant treatment-related adverse events (TRAEs). No patient developed grade 4 or 5 TRAEs. Neutropenia (23.3%) was the most common grade 3 TRAE. Twenty-nine patients underwent esophagectomy after neoadjuvant therapy. Among them, 15 patients (51.7%) achieved MPR, including seven patients with pCR (24.1%). Radiographic analyses established a significant correlation between maximal standardized uptake value (SUVmax) reduction and pathologic regression (P = 0.00095). Conclusions: Neoadjuvant camrelizumab combined with chemotherapy plus apatinib demonstrated a manageable safety profile for patients with locally advanced ESCC, and an encouraging efficacy was observed in most of the treated patients. A decrease in SUVmax of the primary tumor may be a predictor of pathologic response to neoadjuvant camrelizumab combined with chemotherapy plus apatinib in ESCC.

Accurate diagnosis of lung tissues for 2D Raman spectrogram by deep learning based on short-time Fourier transform.

Multivariate statistical analysis methods have an important role in spectrochemical analyses to rapidly identify and diagnose cancer and the subtype. However, utilizing these methods to analyze lager amount spectral data is challenging, and poses a major bottleneck toward achieving high accuracy. Here, a new convolutional neural networks (CNN) method based on short-time Fourier transform (STFT) to diagnose lung tissues via Raman spectra readily is proposed. The models yield that the accuracies of the new method are higher than the conventional methods (principal components analysis -linear discriminant analysis and support vector machine) for validation group (95.2% vs 85.5%, 94.4%) and test group (96.5% vs 90.4%, 93.9%) after cross-validation. The results illustrate that the new method which converts one-dimensional Raman data into two-dimensional Raman spectrograms improve the discriminatory ability of lung tissues and can achieve automatically accurate diagnosis of lung tissues.

Association between microRNA-146a, -499a and -196a-2 SNPs and non-small cell lung cancer: a case-control study involving 2249 subjects.

MicroRNA (miR) acts as a negative regulator of gene expression. Many literatures have suggested that miRs may be involved in the process of cell proliferation, inflammation, oxidative stress, energy metabolism and epithelial-mesenchymal transition. Thus, miRs may be implicated in the occurrence of non-small cell lung cancer (NSCLC). In the current investigation, we included 2249 subjects (1193 NSCLC patients and 1056 controls) and designed a study to identify the relationship of miR-146a rs2910164 C/G, -499a rs3746444 A/G and -196a-2 rs11614913 T/C with the risk of NSCLC. The risk factors (e.g., body mass index (BMI), sex, smoking, drinking and age) was used to adjust the odds ratios (ORs) and 95% confidence intervals (CIs). After conducting a power value assessment, we did not confirm that the miR-single nucleotide polymorphisms (SNPs) genotypic distributions were different in NSCLC cases and controls. However, the association of miR-196a-2 rs11614913 with a decreased risk of NSCLC was identified in the female subgroup (adjusted P=0.005, power = 0.809 for TC vs. TT, and adjusted P=0.004, power = 0.849 for CC/TC vs. TT). In addition, gene-gene interaction analysis showed that rs11614913 TC/3746444 AA and rs11614913 CC/rs3746444 AA could also reduce the susceptibility to NSCLC (rs11614913 TC/rs3746444 AA vs. rs11614913 TT/rs3746444 AA, P=0.001, power = 0.912 and rs11614913 CC/rs3746444 AA vs. rs11614913 TT/rs3746444 AA, P=0.003, power = 0.836). In conclusion, in overall comparisons, we did not confirm that the rs2910164, rs3746444, and rs11614913 SNPs genotypic distributions were different in NSCLC cases and controls. However, this case-control study demonstrates that miR-196a-2 rs11614913 may be a protective factor for the development of NSCLC among female patients.

Assessing the Survival Benefit of Surgery and Various Types of Radiation Therapy for Treatment of Hepatocellular Carcinoma: Evidence from the Surveillance, Epidemiology, and End Results Registries.

OBJECTIVE: To evaluate the survival benefit of surgery and radiation for hepatocellular carcinoma (HCC) after adjusting for patient-specific and tumor-specific factors. METHODS: This study analyzed HCC patients who enrolled in the Surveillance, Epidemiology, and End Results (SEER) registry between January 2004 and December 2013. Of the 5552 HCC patients, 4597 received surgery and 955 received radiation. Patients who received radiation were further divided into 3 subgroups: 541 who received beam radiation (BR), 197 who received radioactive implants (RI), and 217 who received radioisotopes (RIT). Propensity score weighting analysis derived from generalized boosted models (GBMs) was performed to ensure well-balanced characteristics in all comparison groups. RESULTS: Overall survival rates and HCC-specific survival rates were higher in those receiving surgery compared with those receiving radiotherapy. This was confirmed by Cox proportional hazard regression both before and after inverse probability of treatment weighting (IPTW). Before IPTW, the RIT group had a better outcome than the BR group in terms of overall and HCC-specific survival rates, but there was no significant difference between the RI and BR groups. After IPTW, Cox proportional hazard regression demonstrated that both the RIT and RI groups had higher survival rates than the BR group. CONCLUSION: In HCC patients, surgery was associated with higher survival rates compared with radiotherapy while adjusting for other factors. Among those who received radiotherapy, RIT and RI granted survival benefits.

CircRNA_102179 promotes the proliferation, migration and invasion in non-small cell lung cancer cells by regulating miR-330-5p/HMGB3 axis.

Non-small cell lung cancer (NSCLC) accounting for 85 % of all lung cancer was one of the main causes of death worldwide. In this study, we investigated the role of circRNA_102179 in NSCLC development. The levels of circRNA_102179 in NSCLC tissues and cell lines were determined by quantitative real-time PCR assay (qRT-PCR). CCK8 and colony formation assays were applied to explore the effect of circRNA_102179 on the growth of NSCLC cells in vitro. Transwell assay was utilized to analyze the impact of circRNA_102179 on the migration and invasion of NSCLC cells. Target prediction and luciferase reporter assay were used to identify the interacting miRNA of circRNA_102179. The interaction among circRNA_102179/ miR-330-5p/HMGB3 was further validated by colony formation and Transwell invasion assays. Finally, the mouse xenograft NSCLC model was used to explore the role of circRNA_102179 in the tumor growth of NSCLC cells in vivo. CircRNA_102179 was overexpressed in NSCLC tissues and cells compared with normal lung tissues and human bronchial epithelial cells (HBEs). The down-regulation of circRNA_102179 markedly reduced the proliferation, migration, and invasion of NSCLC cells. Moreover, down-expression of circRNA_102179 significantly increased the level of miR-330-5p/HMGB3 in NSCLC cells. Further functional experiments indicated that over-expression of miR-330-5p reversed the inhibitory effect of circRNA_102179 on NSCLC cells growth, migration, and invasion. Our results reveal that circRNA_102179 facilitates the proliferation, migration, and invasion of NSCLC cell via modulating miR-330-5p/ HMGB3 axis in NSCLC cells.

Raman spectroscopy as a potential diagnostic tool to analyse biochemical alterations in lung cancer.

Patient survival remains poor even after diagnosis in lung cancer cases, and the molecular events resulting from lung cancer progression remain unclear. Raman spectroscopy could be used to noninvasively and accurately reveal the biochemical properties of biological tissues on the basis of their pathological status. This study aimed at probing biomolecular changes in lung cancer, using Raman spectroscopy as a potential diagnostic tool. Herein, biochemical alterations were evident in the Raman spectra (region of 600-1800 cm-1) in normal and cancerous lung tissues. The levels of saturated and unsaturated lipids and the protein-to-lipid, nucleic acid-to-lipid, and protein-to-nucleic acid ratios were significantly altered among malignant tissues compared to normal lung tissues. These biochemical alterations in tissues during neoplastic transformation have profound implications in not only the biochemical landscape of lung cancer progression but also cytopathological classification. Based on this spectroscopic approach, classification methods including k-nearest neighbour (kNN) and support vector machine (SVM) were successfully applied to cytopathologically diagnose lung cancer with an accuracy approaching 99%. The present results indicate that Raman spectroscopy is an excellent tool to biochemically interrogate and diagnose lung cancer.

Neutral diagnosis: An innovative concept for medical device clinical trials.

Study design and statistical analysis are crucial in pivotal clinical trials to evaluate the effectiveness and safety of new medical devices under investigation. In recent years, innovative intraoperative in vivo breast tumor diagnostic devices have been proposed to improve the accuracy and surgical outcomes of breast tumor patients undergoing resection. Although such technologies are promising, investigators need to obtain statistical evidence for the effectiveness and safety of these devices by conducting valid clinical trials. However, the study design and statistical analysis for these clinical trials are complicated. While these trials are designed to provide real-time intraoperative diagnosis of cancerous tissue, they also have clear therapeutic objectives to lower the reoperation rate of breast cancer surgery. This research article introduces the new concept of neutral diagnosis (ND), and the ND clinical trial design as an innovative study design to evaluate the effectiveness and safety of diagnostic devices with direct therapeutic purposes. A joint modeling approach is adopted to make inferences on the effectiveness and safety of these devices for non-neutral diagnosis (non-ND) clinical trials. Simulation studies were conducted to show the efficiency of the ND trials and strength of the joint modeling approach in the non-ND clinical trials. An example on a diagnostic medical device that provides real-time, intraoperative diagnosis of breast cancer tumor tissues during breast cancer surgeries is comprehensively discussed and analyzed.

Patterns and rates of abdominal lymphatic metastasis following esophageal carcinoma.

AIM: To determine the rate of abdominal lymph node metastasis after radical surgery for esophageal cancer and define the radiotherapy target area. METHODS: Of the 1593 patients who underwent R0 radical esophagectomy for thoracic esophageal squamous cell carcinoma (TE-SCC), 148 developed abdominal lymph node (LN) metastases within three years of surgery. During that time interval, patients were examined by various imaging methods (enhanced computer tomography, magnetic resonance imaging, and positron emission tomography-CT) at set time points. The emerging recurrence pattern, preferred sites for abdominal metastasis, and correlation with added clinical factors were carefully recorded, to permit for delineation of a target area for radiotherapy. RESULTS: We found postoperative metastatic abdominal LNs in 9.3% of the patients treated for esophageal cancer. Lesions in the upper, middle, and lower esophageal segments metastasized to abdominal LNs at 2.3%, 7.8%, and 26.6% (P < 0.0001), respectively. Of all cases, 4.8% had fewer than two affected LNs, while 20.1% had more than three metastatic LNs (P< 0.0001). The metastasis rates of negative and positive celiac LNs were 4.6% and 22.7%, respectively. Abdominal LN metastasis rates for the following LNs: 16a2 and 16a1 of para-aortic, celiac artery, posterior surface of the pancreatic head and common hepatic artery were 64.9%, 41.2%, 37.8%, 32.4%, and 20.9%, respectively. The overall rate of metastasis to these groups of LNs was 91.9%. CONCLUSION: This study determined that stations 16a1 and 16a2 of the para-aortic, truncus coeliacus, posterior surface of the pancreatic head, and arteria hepatica communis lymph nodes were the preferred sites for abdominal LN metastasis, thus defining target areas for postoperative radiotherapy.

Nanoscale Metal-Organic Frameworks Decorated with Graphene Oxide for Magnetic Resonance Imaging Guided Photothermal Therapy.

Imaging-guided photothermal therapy (PTT) provides an attractive way to treat cancer. A composite material of a nanoscale metal-organic framework (NMOF) and graphene oxide (GO) has been prepared for potential use in tumor-guided PTT with magnetic resonance imaging (MRI). The NMOFs containing Fe3+ were prefabricated with an octahedral morphology through a solvothermal reaction to offer a strong T2 -weighted contrast in MRI. Then the NMOFs were decorated with GO nanosheets, which had good photothermal properties. After decoration, zeta-potential characterization shows that the aqueous stability of the composite material is enhanced, UV/Vis and near-infrared (NIR) spectra confirm that NIR absorption is also increased, and photothermal experiments reveal that the composite materials express higher photothermal conversion effects and conversion stability. The fabricated NMOF/GO shows low cytotoxicity, effective T2 -weighted contrast of MRI, and positive PTT behavior for a tumor model in vitro. The performance of the composite NMOF/GO for MRI and PTT was also tested upon injection into A549 tumor-bearing mice. The studies in vivo revealed that the fabricated NMOF/GO was efficient in T2 -weighted imaging and ablation of the A549 tumor with low cytotoxicity, which implied that the prepared composite contrast agent was a potential multifunctional nanotheranostic agent.

Nodal Skip Metastasis in Esophageal Squamous Cell Carcinoma Patients Undergoing Three-Field Lymphadenectomy.

BACKGROUND: The clinical and prognostic implications of nodal skip metastasis (NSM) remain unclear in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Patients with pathologically confirmed node metastasis who underwent three-field lymphadenectomy from January 1999 to December 2008 were retrospectively enrolled. The node station is determined based on the classification of the Japanese Society for Esophageal Diseases. NSM is defined as the occurrence of metastases in nodes distant from the primary tumor (station 2 or 3) without the involvement of the adjacent nodes (station 1). To balance the baseline characteristics, a matched cohort was generated by propensity score matching analysis with covariates of age, sex, pathologic status, and treatment. The prognostic implication of NSM was assessed using log-rank tests and Cox regression analyses. RESULTS: In the entire cohort, the NSM rate was 64.0% (657 of 1026); NSM was substantially associated with clinicopathologic variables, including an increased likelihood of middle thoracic tumor location and limited nodal status. Univariate analysis showed similar outcomes between patients with and without NSM (unadjusted hazard ratio [HR] 1.018, 95% confidence interval [CI]: 0.855 to 1.213, p = 0.838). A similar result was obtained in the matched cohort (unadjusted HR 1.057, 95% CI: 0.870 to 1.285, p = 0.578). Although in patients with solitary node metastasis, patients with NSM presented a worse prognosis than patients without (p = 0.043 in log-rank test). CONCLUSIONS: NSM is a common phenomenon in ESCC. Among ESCC patients who underwent three-field lymphadenectomy, NSM is associated with a relatively poor prognosis in individuals with solitary node metastasis.