Present situation of minimally invasive surgical treatment for early gastric cancer.

Minimally invasive surgery is a kind of surgical operation, which is performed by using professional surgical instruments and equipment to inactivate, resect, repair or reconstruct the pathological changes, deformities and wounds in human body through micro-trauma or micro-approach, in order to achieve the goal of treatment, its surgical effect is equivalent to the traditional open surgery, while avoiding the morbidity of conventional surgical wounds. In addition, it also has the advantages of less trauma, less blood loss during operation, less psychological burden and quick recovery on patients, and these minimally invasive techniques provide unique value for the examination and treatment of gastric cancer patients. Surgical minimally invasive surgical techniques have developed rapidly and offer numerous options for the treatment of early gastric cancer (EGC): endoscopic mucosal resection (EMR), underwater EMR (UEMR), endoscopic submucosal dissection (ESD), endoscopic full-thickness resection (EFTR), endoscopic submucosal excavation (ESE), submucosal tunnel endoscopic resection), laparoscopic and endoscopic cooperative surgery (LECS); Among them, EMR, EFTR and LECS technologies have a wide range of applications and different modifications have been derived from their respective surgical operations, such as band-assisted EMR (BA-EMR), conventional EMR (CEMR), over-the-scope clip-assisted EFTR, no-touch EFTR, the inverted LECS, closed LECS, and so on. These new and improved minimally invasive surgeries are more precise, specific and effective in treating different types of EGC.

Lymph node dissection in small-sized pulmonary metastasectomy: Impact on the long-term survival.

INTRODUCTION: Pulmonary metastasectomy has been clarified in improving long-term survival in most primary malignancies with pulmonary metastasis, while the role of additional lymph node dissection remained controversial. We aimed to investigate the prognosis of lymph node involvement and identify the role of lymph node dissection during pulmonary metastasectomy in a real-world cohort. METHODS: We identified patients diagnosed with pulmonary metastases with ≤3 cm in size and received pulmonary metastasectomy between 2004 and 2017 in the Surveillance, Epidemiology, and End Results database. We compared the survival via Kaplan-Meier analysis and propensity score matching method, and the multivariable analysis was conducted by cox regression analysis. RESULTS: A total of 3452 patients were included, of which 2268(65.7%) received lymph node dissection, and the incidence of node-positive was 11.3%(256/2268). In total, the median overall survival was 62.8 months(interquartile range, 28.6-118.9 months), and the lymph node involvement was referred to an impaired survival compared to node-negative diseases(5-year overall survival rate, 58.0% versus 38.6%), with comparable survival between N1 and N2 diseases(P = 0.774). Lymph node dissection was associated with improved survival(HR = 0.80; 95%CI, 0.71-0.90; P < 0.001), and the survival benefits remained regardless of age, sex, the number of metastases, and surgical procedures, even in those with node-negative diseases. At least eight LNDs might lead to a significant improvement in survival, and additional survival benefits might be limited with additional dissected lymph nodes. CONCLUSIONS: Lymph node involvement was associated with impaired survival, and lymph node dissection during pulmonary metastasectomy could improve long-term survival and more accurate staging.

Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential.

Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract, with the annual incidence and mortality increasing consistently. Oxaliplatin-based chemotherapy is a preferred therapeutic regimen for patients with advanced CRC. However, most patients will inevitably develop resistance to oxaliplatin. Many studies have reported that non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs, and circular RNAs, are extensively involved in cancer progression. Moreover, emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation, and by epigenetic modification. In this review, we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin. Furthermore, we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy. This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.

Local metabolic response of Escherichia coli to the module genetic perturbations in l-methionine biosynthetic pathway.

l-Methionine biosynthesis is through multilevel regulated and multibranched biosynthetic pathway (MRMBP). Because of the complex regulatory mechanism and the imbalanced metabolic flux between branched pathways, microbial production of l-methionine has not been commercialized. In this study, local metabolic response in MRMBP of l-methionine was investigated and various crucial genes in branched pathways were determined. In l-serine pathway, the crucial gene was serABC. In O-succinyl homoserine (OSH) pathway, which was the C4 backbone of l-methionine, metB and metL controlled the metabolic flux jointly. In l-cysteine pathway, the crucial gene cysEfbr could disturb the flux distribution of local network in l-methionine biosynthesis. However, no crucial gene for l-methionine production in 5-methyl tetrahydrofolate (CH3-THF) pathway was found. The relation between these pathways was also researched. l-Serine pathway, as the upstream pathway of l-cysteine and CH3-THF, played a crucial role in l-methionine biosynthesis. l-Cysteine pathway showed the strongest controlling force of the metabolic flux, and OSH pathway was second to l-cysteine pathway. In contrast, CH3-THF pathway was the weakest, which was probably the mainly limited steps at present and had great potential in further research. In addition, constructed W3110 IJAHFEBC/pA∗HAmL was able to produce 2.62 g/L l-methionine in flask. This study is instructive for l-methionine biosynthesis and provides a new research method of biosynthesizing other metabolic products in MRMBPs.

Is video-assisted thoracoscopic surgery comparable with thoracotomy in perioperative and long-term survival outcomes for non-small-cell lung cancer after neoadjuvant treatment?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'Is video-assisted thoracoscopic surgery comparable with thoracotomy in perioperative and long-term survival outcomes for patients with non-small cell lung cancer following neoadjuvant therapy intended for anatomical lung resection?'. Altogether 655 papers were found using the reported search, of which 12 studies represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type and relevant outcomes and results of these papers are tabulated. Almost all of the enrolled cohort studies reported that video-assisted thoracoscopic surgery (VATS) was comparable with thoracotomy in negative surgical margin rate, postoperative mortality, complication rate, overall survival and disease-free survival. Moreover, 7 studies found patients in the VATS group had a significantly shorter hospital stay. Furthermore, in these well-matched cohort studies (6 studies), it still held true that VATS was comparable with thoracotomy in long-term prognosis with enhanced recovery. However, the issue regarding surgical radicality and intraoperative conversion to thoracotomy still should be noted carefully among these patients receiving VATS surgery because all the current available evidence was retrospective based on relatively small sample sizes. Nevertheless, thoracic surgeons should not consider VATS inferior to thoracotomy for patients after neoadjuvant treatment. VATS surgery could be an alternative for selected patients with locally advanced but relatively small, peripheral, fewer positive N2 lymph nodes and non-squamous NSCLC intended for anatomic lung resection.

Does the division of the inferior pulmonary ligament in upper lobectomy result in improved short-term clinical outcomes and long-term survival?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'Does the division of the inferior pulmonary ligament (IPL) in upper lobectomy result in improved short-term clinical outcomes and long-term survival?'. Altogether 43 papers were found using the reported search, of which 6 studies represented the best evidence to answer the clinical question, including a previous best evidence topic study, a meta-analysis and 4 retrospective cohort studies. The author, journal, date and country of publication, patient group studied, study type and relevant outcomes and results of these papers are tabulated. Most of the enrolled studies reported that there is no significant difference between the division groups and the preservation groups in terms of drainage time, drainage volume, postoperative dead space and complications. While 3 cohort studies revealed unfavoured postoperative pulmonary function in the division groups, including lung volume, forced vital capacity and forced expiratory volume in 1 s. The previous meta-analysis and a recent cohort study also found that the division of IPL might lead to increased bronchus angle change or torsion. Moreover, 2 cohort studies found that the division of IPL could not improve the long-term survival of patients undergoing upper lobectomy. Current evidence showed that dividing the IPL could not result in clinical benefits but might lead to decreased pulmonary function instead. Therefore, we recommended not dissecting the IPL routinely during upper lobectomy.

LobE-Specific lymph node diSsectiON for clinical early-stage non-small cell lung cancer: protocol for a randomised controlled trial (the LESSON trial).

INTRODUCTION: Lung cancer was the most common malignancy and the leading cause of cancer-related death in China or worldwide, and surgery is still the preferred treatment for early-stage non-small cell lung cancer (NSCLC). The pattern of lymph node metastasis was found potentially lobe specific, and thus, lobe-specific lymph node dissection (L-SLND) was proposed to be an alternative to systematic lymph node dissection (SLND) for the treatment of early-stage NSCLC. METHODS AND ANALYSIS: The LobE-Specific lymph node diSsectiON trial is a single-institutional, randomised, double-blind and parallel controlled trial to investigate the feasibility of L-SLND in clinically diagnosed stage IA1-2 NSCLC with ground-glass opacity components (≥50%). The intraoperative frozen section examination of surgical tissues confirms the histological type of NSCLC. We hypothesise that L-SLND (experimental group) is not inferior to SLND (control group) and intend to include 672 participants for the experimental group and 672 participants for the control group with a follow-up duration of 60 months. The primary outcomes are 5-year disease-free survival and 5-year overall survival. The secondary outcomes are metastatic lymph node ratio, postoperative complication incidence and mortality, duration of operation, duration of anaesthesia (min), the volume of bleeding (mL) and drainage volume. The intention-to-treat analysis would be performed in the trial. ETHICS AND DISSEMINATION: This trial was approved by the ethics committee on biomedical research, West China Hospital of Sichuan University (2021-332). Informed consent would be obtained from all participants, and dissemination activities would include academic conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: This trial was registered in the Chinese Clinical Trial Registry, ChiCTR2100048415.

Correlation between circulating endothelial cell level and acute respiratory distress syndrome in postoperative patients.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is injury of alveolar epithelial cells and capillary endothelial cells caused by various factors, including endogenous and exogenous lung factors, leading to diffuse pulmonary interstitial and alveolar edema, and acute respiratory failure. ARDS involves alveolar epithelial cells and pulmonary interstitial capillary endothelial cells. Circulating endothelial cells (CECs) are the only marker that directly reflects vascular endothelial injury in vivo. There have been few studies on the correlation between peripheral blood CECs and ARDS at home and abroad. The lungs are the organs with the highest capillary density and the most endothelial cells, thus, it is speculated that when ARDS occurs, CECs are stimulated and damaged, and released into the circulatory system. AIM: To explore the correlation between CEC level and severity of ARDS in patients postoperatively. METHODS: Blood samples were collected from all patients on day 2 (d2) and day 5 (d5) after surgery. The control group comprised 32 healthy volunteers. Number of CECs was measured by flow cytometry, and operation time was recorded. Changes in various indexes of patients were monitored, and diagnosis of ARDS was determined based on ARDS Berlin definition. We comprised d2 CECs in different groups, correlation between operation time and d2 CECs, ARDS of different severity by d2 CECs, and predictive value of d2 CECs for ARDS in postoperative patients. RESULTS: The number of d2 CECs in the ARDS group was significantly higher than that in the healthy control group (P < 0.001). The number of d2 CECs in the ARDS group was significantly higher than that in the non-ARDS group (P < 0.001). The number of d2 CECs in the non-ARDS group was significantly higher than that in the healthy control group (P < 0.001). Operation time was positively correlated with number of CECs on d2 (rs = 0.302, P = 0.001). The number of d2 CECs in the deceased group was significantly higher than that in the improved group (P < 0.001). There was no significant difference in number of d2 CECs between patients with mild and moderate ARDS. The number of d2 CECs in patients with severe ARDS was significantly higher than that in patients with mild and moderate ARDS (P = 0.041, P = 0.037). There was no significant difference in number of d5 and d2 CECs in the non-ARDS group after admission to intensive care. The number of d5 CECs was higher than the number of d2 CECs in the ARDS improved group (P < 0.001). The number of d5 CECs was higher than the number of d2 CECs in the ARDS deceased group (P = 0.002). If the number of CECs was > 1351/mL, sensitivity and specificity of predicting ARDS were 80.8% and 78.1%, respectively. CONCLUSION: Changes in number of CECs might predict occurrence and adverse outcome of ARDS after surgery, and higher numbers of CECs indicate worse prognosis of ARDS.

Catalytic Asymmetric Conjugate Addition/Hydroalkoxylation Sequence: Expeditious Access to Enantioenriched Eight-Membered Cyclic Ether Derivatives.

A sequential enantioselective conjugate addition/hydroalkoxylation between in situ generated ortho-quinomethanes and ynones by combining bifunctional squaramide and DBU catalysis has been developed. A variety of eight-membered cyclic ethers with two contiguous tertiary stereocenters were obtained in high yields with excellent stereoselectivities. This reaction not only provides a new strategy for constructing enantioenriched eight-membered cyclic ethers but also demonstrates the practicability of ynones as C4-syntons for the synthesis of chiral medium-membered rings.

Near-infrared AIEgens as transformers to enhance tumor treatment efficacy with controllable self-assembled redox-responsive carrier-free nanodrug.

Nanosized drug delivery systems (nDDS) have been extensively exploited to achieve improved therapeutic performance of chemotherapeutic drugs in cancer treatment. Carrier-free nanodrugs have recently emerged as a promising generation of nDDS. In this work, a carrier-free theranostic nanodrug was fabricated by incorporating near-infrared (NIR) emission AIEgens (NPAPF) with redox responsive camptothecin-gemcitabine amphiphilic prodrug (CPT-ss-GEM) to form self-assembled nanoparticles (NCssG NPs). The introducing of AIEgens is designed to not only endow the nDDS with NIR imaging ability but also to act as transformers to modulate the geometry of the self-assembled nanostructures from nanowires to spherical nanoparticles. Interestingly, this unique geometric effect is further demonstrated to be very crucial to the anticancer performance of the nDDS in vitro and in vivo. The AIEgens-doped spherical nanoparticles NCssG NPs showed much higher cellular uptake efficiency and tumor penetration ability, therefor achieving much stronger anticancer efficacy than free CPT/GEM mixture and CPT-ss-GEM nanowires (CssG NWs). The theranostic features of NCssG NPs were fully utilized to evaluate the redox-triggered drug release process, in vivo biodistribution and tumor targeted accumulation of NCssG NPs. This work provides a novel strategy and some useful information for the optimization of the design of theranostic nDDS to benefit for the clinic application of nanodrugs in the future.

Ultrasensitive Tyrosinase-Activated Turn-On Near-Infrared Fluorescent Probe with a Rationally Designed Urea Bond for Selective Imaging and Photodamage to Melanoma Cells.

Melanoma is a highly aggressive malignancy and early monitoring and diagnosis are challenging at present. Tyrosinase is overexpressed in melanoma and regarded as an important biological marker for diagnosis and treatment. Thus, the selective and sensitive detection of tyrosinase is of great significance. To date, a few fluorescent probes have been reported for the detection of tyrosinase in vitro or in vivo. However, a highly sensitive near-infrared probe for tyrosinase monitoring is still missing. In this study, the Gibbs free energy change of different urea bonds during spontaneous hydrolysis is analyzed with the aid of chemical thermodynamic computation. On the basis of this analysis, we modified the dye methylene blue with a rationally designed urea bond to specifically create a probe, called MB1, for rapid detection of tyrosinase. Our experimental results demonstrated that MB1 can serve as a highly sensitive near-infrared responsive fluorescent probe for the monitoring and bioimaging of tyrosinase. In addition, the activated MB1 probe can effectively kill melanoma cells by photodynamic therapy. Thus, the near-infrared probe has great potential for monitoring and treating melanoma.

Carrier-free, self-assembled pure drug nanorods composed of 10-hydroxycamptothecin and chlorin e6 for combinatorial chemo-photodynamic antitumor therapy in vivo.

Carrier-free nanodrugs formulated from the supramolecular self-assembly of pure drug molecules have emerged as an innovative and promising strategy for tumor therapy. We report herein a new and simple method to directly assemble a small hydrophobic anticancer drug, 10-hydroxycamptothecin (HCPT), with a photosensitizer chlorin e6 (Ce6) to form stable, discrete nanorods (NRs), which not only circumvent the extreme hydrophobicity of HCPT but also incorporate two different modalities into one delivery system for combination therapy. Different ratios of HCPT to Ce6 were evaluated to afford the optimal nanoformulation. The as-prepared HCPT/Ce6 NRs were fully characterized, indicating a relatively uniform size of about 360 nm in length and 135 nm in width, and a surface charge of about -33 mV. Efficient internalization of the NRs by cancer cells was observed by using a confocal microscope and the generation of singlet oxygen species arising from the NRs under 655 nm laser irradiation was detected by DCFH-DA. As a result, very potent in vitro efficacy against several kinds of cancer cell lines was achieved through chemo-photodynamic dual therapy. The in vivo tumor suppression effect of HCPT/Ce6 NRs was verified on a subcutaneous xenograft mouse model, achieving almost complete inhibition of the tumor growth, which may benefit from the superiority of nanomedicine and combination therapy. The rationale of this facile and green strategy for carrier-free nanodrug formulation via the self-assembly approach might provide new opportunities for the development of combinatorial therapeutics for tumors.

Nanoparticle-based drug delivery systems: What can they really do in vivo?

In the past few decades, there has been explosive growth in the construction of nanoparticle-based drug delivery systems (NDDSs), namely nanomedicines, owing to their unique properties compared with traditional drug formulations. However, because of a variety of challenges, few nanomedicines are on sale in the market or undergoing clinical trial at present. Thus, it is essential to look back and re-evaluate what these NDDSs can really do in vivo, why nanomedicines are regarded as potential candidates for next-generation drugs, and what the future of nanomedicine is. Here, we focus mainly on the properties of NDDSs that extend blood circulation, enhance penetration into deep tumor tissue, enable controllable release of the payload into the cytoplasm, and overcome multi-drug resistance. We further discuss how to promote the translation of nanomedicines into reality. This review may help to identify the functions of NDDSs that are really necessary before they are designed and to reduce the gap between basic research and clinical application.

Successful vaginal delivery at term after vaginal reconstruction with labium minus flaps in a patient with vaginal atresia: A rare case report.

We report a case of successful vaginal delivery after vaginal reconstruction with labium minus flaps in a 23-year-old patient with congenital vaginal atresia. The patient primarily presented with amenorrhea and cyclic abdominal pain; transabdominal ultrasonography revealed an enlarged uterus due to hematometra and absence of the lower segment of the vagina. Eight years ago, she had undergone an unsuccessful attempt at canalization at a local hospital. Upon referral to our hospital, she underwent vaginal reconstruction with labium minus flaps. Four months after this procedure, she became pregnant and, subsequently, successfully and safely vaginally delivered a healthy female baby weighing 3250 g at 38+1 weeks' gestation. The delivery did not involve perineal laceration by lateral episiotomy. To the best of our knowledge, this is the first reported case of successful vaginal delivery at term after vaginal reconstruction with labium minus flaps in a patient with vaginal atresia.

Toxicities of different first-line chemotherapy regimens in the treatment of advanced ovarian cancer: A network meta-analysis.

BACKGROUND: Ovarian cancer (OC) is the 5th leading cause of cancer-related deaths around the world, and several chemotherapy regimens have been applied in the treatment of OC. We aim to compare toxicities of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) using network meta-analysis. METHODS: Literature research in Cochrane Library, PubMed, and EMBASE was performed up to November 2015. Eligible randomized controlled trials (RCTs) of different chemotherapy regimens were included. Network meta-analysis combined direct and indirect evidence to assess pooled odds ratios (ORs) and draw the surface under the cumulative ranking (SUCRA) curves. RESULTS: Thirteen eligible RCTs were included in this network meta-analysis, including 8 chemotherapy regimens (paclitaxel + carboplatin [PC], pegylated liposomal doxorubicin [PLD] + carboplatin, carboplatin, gemcitabine + carboplatin, paclitaxel, PC + epirubicin, PC + topotecan, docetaxel + carboplatin). Gemcitabine + carboplatin regimen exerted higher incidence of anemia when compared with carboplatin and paclitaxel regimens. The incidence of febrile neutropenia of gemcitabine + carboplatin regimen was higher than that of PC, PLD + carboplatin, carboplatin, and PC + topotecan regimens. Topotecan PC + epirubicin regimen had a higher toxicity, comparing with PC, PLD + carboplatin, and PC + topotecan regimens. As for thrombocytopenia, gemcitabine + carboplatin chemotherapy regimen produced an obviously higher toxicity than PC and carboplatin. As for nausea, PLD + carboplatin chemotherapy regimen had a significantly higher toxicity than that of carboplatin chemotherapy regimen. Moreover, when compared with PC and carboplatin chemotherapy regimens, the toxicity of PC + epirubicin was greatly higher to patients with AOC. CONCLUSION: The nonhematologic toxicity of PLD + carboplatin regimen was higher than other regimens, which was clinically significant for the treatment of AOC.

Self-assembling nanowires of an amphiphilic camptothecin prodrug derived from homologous derivative conjugation.

A novel amphiphilic camptothecin prodrug, CPT-ss-Ir, consisting of CPT, Ir and a disulfide bond linker, was synthesized, and it could self-assemble into nanowires in aqueous solution. Upon intracellular triggering, active CPT and Ir species were released to exert a considerable anticancer effect.

Multi-stable fluorescent silica nanoparticles obtained from in situ doping with aggregation-induced emission molecules.

Microenvironment in biology is diverse and complex which has been a great challenge for in vivo imaging materials, and so materials with environmental tolerance and photostability need to be explored. For aggregation-induced emission (AIE) molecules, the fluorescence is closely related to the restricted structure which is directly affected by the microenvironment. Inorganic silica nanoparticles can provide a rigid microenvironment which can stabilize AIE molecules to obtain fluorescent materials with environmental tolerance. Here, stable fluorescent SiO2 nanoparticles (CWQ-11@SiO2 NPs) have been prepared by doping with typical AIE molecules named CWQ-11. CWQ-11@SiO2 NPs have narrow size distribution and spherical morphology with a size of around 50 nm. The fluorescence intensity of CWQ-11@SiO2 NPs is nearly 45.4 times higher than that of free CWQ-11. CWQ-11@SiO2 NPs maintain excellent fluorescence stabilities under various conditions, such as in solutions with different pH values, different viscosities, or continuous irradiation, and even in simulated gastric fluid (SGF). Cellular imaging research represents efficient imaging ability of CWQ-11@SiO2 NPs in two different tumor cells including MCF-7S and HepG-2. All these results demonstrate that the CWQ-11@SiO2 NPs have been successfully prepared and remain stable under different harsh conditions, and have promising potential in imaging, tracing for drugs or diagnosis in complicated biological systems.

[Application of video endoscopic inguinal lymphadenectomy in radical vulvectomy for carcinoma].

OBJECTIVE: To evaluate the feasibility and safety of applying video endoscopic inguinal lymphadenectomy via hypogastric subcutaneous approach (VEIL-H) in the treatment of vulvar carcinoma. METHODS: From September 2009 to December 2012, 15 patients with vulvar carcinoma underwent VEIL-H plus radical vulvectomy at many participating hospitals. RESULTS: All were treated surgically. Two of them underwent laparoscopic pelvic lymphadenectomy (LPL) upon the positive results of parotid operations with frozen section. The mean operative duration of VEIL-H (bilateral groin) were (80.8 ± 2.9) minutes. The mean total volume of blood loss in VEIL was (5.5 ± 0.4) ml, the mean drainage duration (6 ± 2) days and the average postoperative hospitalization (11 ± 4) days. The mean follow-up period was 13.0 months. One patient suffered local recurrence at Month 2 postoperation. CONCLUSION: VEIL-H is both feasible and safe in inguinal lymphadenectomy.