Efficacy and Safety of Complete Mesocolic Excision in Patients With Colon Cancer: Three-year Results From a Prospective, Nonrandomized, Double-blind, Controlled Trial.

OBJECTIVE: The aim of the study was to evaluate the oncological outcomes of complete mesocolic excision (CME) in colon cancer patients. SUMMARY BACKGROUND DATA: CME is considered a standard procedure for colon cancer patients. However, previous evidence regarding the effect of CME on prognosis has fundamental limitations that prevent it from being fully accepted. METHODS: Patients who underwent radical resection for colon cancer were enrolled between November 2012 and March 2016. According to the principles of CME, patients were stratified into 2 groups based on intraoperative surgical fields and specimen photographs. The primary outcome was local recurrence-free survival (LRFS). The clinicopathological data and follow-up information were collected and recorded. The final follow-up date was April 2016. The trial was registered in ClinicalTrials.gov (identifier: NCT01724775). RESULTS: There were 220 patients in the CME group and 110 patients in the noncomplete mesocolic excision (NCME) group. Baseline characteristics were well balanced. Compared with NCME, CME was associated with a greater number of total lymph nodes (24 vs 20, P = 0.002). Postoperative complications did not differ between the 2 groups. CME had a positive effect on LRFS compared with NCME (100.0% vs 90.2%, log-rank P < 0.001). Mesocolic dissection (100.0% vs 87.9%, log-rank P < 0.001) and nontumor deposits (97.2% vs 91.6%, log-rank P < 0.022) were also associated with improved LRFS. CONCLUSIONS: Our findings demonstrate that, compared with NCME, CME improves 3-year LRFS without increasing surgical risks.

Tumor-associated macrophages regulate gastric cancer cell invasion and metastasis through TGFß2/NF-κB/Kindlin-2 axis.

OBJECTIVE: Recent studies have shown that tumor-associated macrophages (TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis of gastric cancer (GC) cells through the Kindlin-2 pathway. However, the mechanism needs to be clarified. METHODS: THP-1 monocytes were induced by PMA/interleukin (IL)-4/IL-13 to establish an efficient TAM model in vitro and M2 macrophages were isolated via flow cytometry. A dual luciferase reporter system and chromatin immunoprecipitation (ChIP) assay were used to investigate the mechanism of transforming growth factor ß2 (TGFß2) regulating Kindlin-2 expression. Immunohistochemistry was used to study the relationships among TAM infiltration in human GC tissues, Kindlin-2 protein expression, clinicopathological parameters and prognosis in human GC tissues. A nude mouse oncogenesis model was used to verify the invasion and metastasis mechanisms in vivo. RESULTS: We found that Kindlin-2 expression was upregulated at both mRNA and protein levels in GC cells cocultured with TAMs, associated with higher invasion rate. Kindlin-2 knockdown reduced the invasion rate of GC cells under coculture condition. TGFß2 secreted by TAMs regulated the expression of Kindlin-2 through the transcription factor NF-кB. TAMs thus participated in the progression of GC through the TGFß2/NF-κB/Kindlin-2 axis. Kindlin-2 expression and TAM infiltration were significantly positively correlated with TNM stage, and patients with high Kindlin-2 expression had significantly poorer overall survival than patients with low Kindlin-2 expression. Furthermore, Kindlin-2 promoted the invasion of GC cells in vivo. CONCLUSIONS: This study elucidates the mechanism of TAMs participating in GC cell invasion and metastasis through the TGFß2/NF-κB/Kindlin-2 axis, providing a possibility for new treatment options and approaches.

A wideband high-power microwave radiation source based on gyromagnetic nonlinear transmission line and Vlasov antenna.

The gyromagnetic nonlinear transmission line (GNLTL) is a special kind of coaxial transmission line partially loaded with the ferrite material. A GNLTL system can modulate the input high-power pulses into wideband high-power microwaves without relying on the electron beam and confining magnetic field. The unique working mechanism gives the GNLTL system the potential to be a small portable wideband high-power microwave radiation source. In this study, a wideband high-power microwave radiation source based on a GNLTL system is designed and constructed. In order to effectively radiate the wideband microwaves into the air, a high-power wideband Vlasov antenna and a special absorption high-pass filter are developed. The designs of key subsystems and high-power radiation experiments have been introduced and discussed in detail. In the test experiments, a radiated pulse with a peak electric field strength of 23 kV/m was measured at 20 m away from the transmitting antenna and the effective potential of radiation is 460 kV/m. The pulse width of the radiation pulse is about 4 ns, the center frequency is about 2.25 GHz, and the highest repetition rate can reach 25 Hz.

Evaluation of histopathological response to neoadjuvant therapy in rectal cancer using slide-free, stain-free multimodal multiphoton microscopy.

Neoadjuvant therapy has become a standard treatment for patients with locally advanced rectal cancer to achieve better prognostic outcomes. The response to treatment has been shown to correlate closely with the prognosis. However, current evaluation systems only provide coarse assessment on limited information, due to the lack of accurate and reproducible approach for quantitation of different types of responses. In this study, a novel stain-free, slide-free multimodal multiphoton microscopy imaging technique was applied to image rectal cancer tissues after neoadjuvant therapies with high resolution and contrast. Qualitative and quantitative evaluation of tumor, stromal, and inflammatory responses were demonstrated which are consistent with current tumor regression grading system using American Joint Committee on Cancer criteria, showing the great potential of such approach to build a more informative grading system for accurate and standardizable assessment of neoadjuvant therapy in rectal cancer.

Operation analysis of the wideband high-power microwave sources based on the gyromagnetic nonlinear transmission lines.

The wideband High-Power Microwave (HPM) sources, which combine the advantages of narrowband and ultrawideband sources, have drawn much attention. As a kind of wideband source, the gyromagnetic nonlinear transmission lines (GNLTLs) can directly modulate the incident pulses into radio frequency pulses without relying on the interaction between e-beam and microwaves. Due to the special working mechanism of gyromagnetic precession, the center frequency of the GNLTL can also be adjusted in a certain range. Based on classical magnetism and a simplified model of the GNLTL, this paper semi-quantitatively and theoretically analyzed the generation mechanism of HPM and illustrated the influences of the variations of parameters on the output microwaves. Then, a simple simulation based on 1-dimensional transmission line modeling method was carried out to study the performance of the GNLTL quantitatively, with the coupling of 1D telegraphist equations and the 3D Landau-Lifshitz-Gilbert equation. Simulation results preliminarily verified the conclusions derived from the theoretical analysis, and some working characteristics of the GNLTL were also obtained. This paper may help to understand the special working mechanism of the GNLTL and provide certain guidance for related simulations and experiments.

Current Trends and Research Topics Regarding Intestinal Organoids: An Overview Based on Bibliometrics.

Currently, research on intestinal diseases is mainly based on animal models and cell lines in monolayers. However, these models have drawbacks that limit scientific advances in this field. Three-dimensional (3D) culture systems named organoids are emerging as a reliable research tool for recapitulating the human intestinal epithelium and represent a unique platform for patient-specific drug testing. Intestinal organoids (IOs) are crypt-villus structures that can be derived from adult intestinal stem cells (ISCs), embryonic stem cells (ESCs), or induced pluripotent stem cells (iPSCs) and have the potential to serve as a platform for individualized medicine and research. However, this emerging field has not been bibliometric summarized to date. Here, we performed a bibliometric analysis of the Web of Science Core Collection (WoSCC) database to evaluate 5,379 publications concerning the use of organoids; the studies were divided into four clusters associated with the current situation and future directions for the application of IOs. Based on the results of our bibliometric analysis of IO applications, we systematically summarized the latest advances and analyzed the limitations and prospects.

Gastric cancer complicated with hemophagocytic lymphohistiocytosis: case report and a brief review.

Hemophagocytic lymphohistiocytosis (HLH) comprises a group of severe immune function disorders that can lead to immune-mediated organ damage. There are two subtypes of HLH: primary and secondary. Secondary HLH is associated with infectious, oncologic, chemotherapeutic, and other underlying causes, and studies on HLH triggered by tumors have mainly focused on hematological malignancies. Secondary HLH in patients with solid tumors is rare. Here, we present two cases of gastric cancer complicated with HLH. The patient 1 was diagnosed as gastric cancer at stage I and got intractable fever after a distal subtotal gastrectomy without any evidence of infections or other complications. The patient 2 suffered from unresectable gastric adenocarcinoma and got fever, hemorrhagic rashes, and petechiae in mouth after six cycles of neoadjuvant chemotherapy. After detailed and comprehensive examinations, HLH was diagnosed in the two patients according to 2004 HLH diagnostic criteria, and the patients received treatment including immunosuppressive agents immediately. After therapy, the two patients showed partial remission, but both eventually died due to HLH relapse or progression of the primary tumor. The treatment regimen for HLH is intricate, and only a few relevant studies have focused on the treatment of cancer patients with HLH. The high mortality associated with this disease calls for more attention and additional research to improve the prognosis for these patients.

A compact solid-state high voltage pulse generator.

In this paper, a compact solid-state high voltage pulse generator, composed of a pulse transformer and a magnetic pulse compressor, is investigated numerically and experimentally. The generator can achieve pulses with a peak voltage over several tens of kilovolts and a rise-time in the microsecond level, which can be widely used in plasma physics research, high power microwave generation, and material treatment. Specifically, PSpice software is used to analyze the performance of the generator. Then, the generator was constructed in our laboratory. The experimental results illustrate that when the charging voltage of the generator was changing from 10 kV to 14 kV, typical pulses with a peak voltage ranging from 67 kV to 95 kV and rise-time between 10 µs and 12 µs were obtained on a dummy load. The generator can continually work over 10 min with a repetitive rate of 20 Hz, and until now, it has been successfully achieving over 1 × 106 high voltage pulses. Experiments show reasonable agreement with numerical analysis.

Numerical simulation and experiment of pulsed switching of a ferromagnetic core.

Ferromagnetic core based magnetic switches are widely used in various pulsed power facilities. The dynamic characteristics of high-power magnetic switches, which have important impacts on the pulse modulation process, are analyzed via an improved numerical model in this paper. The model is established by simultaneously solving the circuit equations and the magnetic field diffusion equations. An implicit finite difference method is used in solving the diffusion equations, which has no numerical convergence problems, and the Jiles-Atherton model is used to obtain an accurate hysteresis loop of the core. The improved model predicts the performance of the magnetic switch quite well. It is then used to analyze the detailed dynamic saturation process of a core, and the core's saturation time predicted by the model is consistent with the experimental data, the error being less than 5%. Furthermore, the interlamination electric field is calculated and analyzed, and it is predicted that breakdown is most likely to occur at the inner side of the core and at the edge of the lamination.

Experiments of a 100 kV-level pulse generator based on metal-oxide varistor.

This paper introduces the development and experiments of a 100 kV-level pulse generator based on a metal-oxide varistor (MOV). MOV has a high energy handling capacity and nonlinear voltage-current (V-I) characteristics, which makes it useful for high voltage pulse shaping. Circuit simulations based on the measured voltage-current characteristics of MOV verified the shaping concept and showed that a circuit containing a two-section pulse forming network (PFN) will result in better defined square pulse than a simple L-C discharging circuit. A reduced-scale experiment was carried out and the result agreed well with simulation prediction. Then a 100 kV-level pulse generator with multiple MOVs in a stack and a two-section pulse forming network (PFN) was experimented. A pulse with a voltage amplitude of 90 kV, rise time of about 50 ns, pulse width of 500 ns, and flat top of about 400 ns was obtained with a water dummy load of 50 Ω. The results reveal that the combination of PFN and MOV is a practical way to generate high voltage pulses with better flat top waveforms, and the load voltage is stable even if the load's impedance varies. Such pulse generator can be applied in many fields such as surface treatment, corona plasma generation, industrial dedusting, and medical disinfection.

Extramural vascular invasion detected by contrast-enhanced multiple-row detectors computed tomography (ceMDCT) as a predictor of synchronous metastases in colon cancer.

BACKGROUND: Extramural Vascular Invasion (EMVI) is histologically defined as the presence of tumor cells beyond the muscularis propria in vessels resulting in disease metastases. OBJECTIVE: To determine whether EMVI, detected by contrast-enhanced multiple-row detectors computed tomography (MDCT), has closely association with synchronous metastases in colon cancer. METHODS: Patients with pathology proven colon cancer were included in this retrospective study. Preoperative imaging status, including Extramural tumor depth, Lymph nodes, tumor location, and ctEMVI status, were defined on MDCT. Postoperative pathological tumor stage, lymph node stage, and tumor differentiation, were defined in accordance with the American Joint Committee on Cancer (AJCC) 7th Edition. Synchronous metastases were detected on follow-up MDCT 3 months after initial diagnosis or by surgery, if available. Associations between ctEMVI and other preoperative and postoperative factors were analyzed using Chi-squared tests. Logistic regression analyses were performed to analyze the preoperative and postoperative factors of synchronous metastases in colon cancer. RESULTS: ctEMVI was observed in 96 patients (96/241, 39.8%). The presence of ctEMVI varied significantly depending on ctEMD (χ2 = 66.557, P<0.001), lymph nodes status on MDCT (χ2 =24.533, P=0.001), pathological tumor status (χ2 = 36.267, P <0.001) and pathological lymph nodes status analyses (χ2 =32.103, P <0.001). Synchronous metastases were seen in 36 patients (36/96, 37.5%) with ctEMVI and 11 (11/145, 7.6%) patients without ctEMVI. The incidence of synchronous metastases was significantly higher in the cohort of positive ctEMVI with odds ratio (OR) of 7.309 (95% CI 3.485∼15.330, P<0.001). Positive ctEMVI (Odds ratio 4.654, 95%CI: 1.987∼10.898, P <0.001) and ctEMD larger than 5 mm (Odds ratio 2.654, 95%CI: 1.116∼6.309, P =0.027) were demonstrated to be significant preoperative factors in predicting synchronous metastases. CONCLUSION: MDCT-detected EMVI could be used as a preoperative factor to predict synchronous metastases in colon cancer.

Prognostic significance of computed tomography-detected extramural vascular invasion in colon cancer.

AIM: To compare disease-free survival (DFS) between extramural vascular invasion (EMVI)-positive and -negative colon cancer patients evaluated by computed tomography (CT). METHODS: Colon cancer patients (n = 194) undergoing curative surgery between January 2009 and December 2013 were included. Each patient's demographics, cancer characteristics, EMVI status, pathological status and survival outcomes were recorded. All included patients had been routinely monitored until December 2015. EMVI was defined as tumor tissue within adjacent vessels beyond the colon wall as seen on enhanced CT. Disease recurrence was defined as metachronous metastases, local recurrence, or death due to colon cancer. Kaplan-Meier analyses were used to compare DFS between the EMVI-positive and -negative groups. Cox's proportional hazards models were used to measure the impact of confounding variables on survival rates. RESULTS: EMVI was observed on CT (ctEMVI) in 60 patients (30.9%, 60/194). One year after surgery, there was no statistically significant difference regarding the rates of progressive events between EMVI-positive and -negative patients [11.7% (7/60) and 6.7% (9/134), respectively; P = 0.266]. At the study endpoint, the EMVI-positive patients had significantly more progressive events than the EMVI-negative patients [43.3% (26/60) and 14.9% (20/134), respectively; odds ratio = 4.4, P < 0.001]. Based on the Kaplan-Meier method, the cumulative 1-year DFS rates were 86.7% (95%CI: 82.3-91.1) and 92.4% (95%CI: 90.1-94.7) for EMVI-positive and EMVI-negative patients, respectively. The cumulative 3-year DFS rates were 49.5% (95%CI: 42.1-56.9) and 85.8% (95%CI: 82.6-89.0), respectively. Cox proportional hazards regression analysis revealed that ctEMVI was an independent predictor of DFS with a hazard ratio of 2.15 (95%CI: 1.12-4.14, P = 0.023). CONCLUSION: ctEMVI may be helpful when evaluating disease progression in colon cancer patients.

[Animal experimental study of biodegradable magnesium alloy stapler for gastrointestinal anastomosis].

OBJECTIVE: To explore the safety and feasibility of biodegradable magnesium alloy stapler based on the result of animal experimental study for gastrointestinal anastomosis. METHODS: Sixteen beagle dogs were equally and randomly divided into experimental (magnesium alloy) group and control (titanium alloy) group. A gastrojejunal and a colonic anastomosis were performed in each beagle dog. The anastomosis time, postoperative complications, body weight, blasting pressure of anastomosis and serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, creatinine, blood urea nitrogen, and serum magnesium were compared between the two groups. The healing of anastomosis and degradation of magnesium alloy were observed. The histopathological features of heart, liver, spleen and kidney were examined in the two groups. RESULTS: There were no significant differences in anastomosis time, body weight, postoperative complications, anastomotic bursting pressure between the two groups. The anastomosis was healed well, and no dramatic inflammatory cell infiltration was observed. Magnesium alloy could be degraded completely in the animal body within 90 days. There were no significant differences in serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, creatinine, blood urea nitrogen and serum magnesium between the two groups. Histopathological examination showed that the degradation of magnesium alloy did not harm the important organs (liver, kidney, heart, brain and spleen). CONCLUSIONS: Magnesium alloy stapler is safe and feasible for gastrointestinal anastomosis in beagle dogs. The degradation of magnesium alloy does not harm the healing of anastomosis and other important organs. Magnesium alloy stapler may be a candidate of biodegradable and safe material of stapler for gastrointestinal anastomosis in human.