Adjuvant chemotherapy in pathological node-negative non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is associated with a poor survival rate, even for patients with early-stage cancer. Identifying patients with pathological N0 NSCLC who may benefit from adjuvant chemotherapy treatment after surgery is essential. We conducted a retrospective cohort study used data from the Surveillance, Epidemiology, and End Results database and included 26,380 patients with pathological N0 NSCLC after surgery between January 2018, and December 2019. Among 26,380 patients, 24,273 patients received surgery alone and the other 2107 patients received surgery plus adjuvant chemotherapy. After 1:1 propensity score matching, both groups contained 2107 patients. Adjuvant chemotherapy did not show significantly better 24-month survival in T2aN0 NSCLC patients (83.41% vs. 82.91%, p = 0.067), although it did for T2bN0 patients (86.36% vs. 81.70%, p = 0.028). Poorly-differentiated NSCLC remained a high-risk factor for pT2N0, and adjuvant chemotherapy provided better 24-month survival after matching (86.36% vs. 81.70%, p = 0.029). In conclusion, when treating pN0 NSCLC, adjuvant chemotherapy had a beneficial effect when the tumor size was larger than 4 cm. The effect when the tumor size was between 3 and 4 cm was not remarkable. Poorly-differentiated NSCLC was a high-risk factor in the pT2N0 stage.

Prediction of Surgical Outcome by Tumor Volume Doubling Time via Stereo Imaging Software in Early Non-Small Cell Lung Cancer.

BACKGROUND: Volume doubling time (VDT) has been proven to be a powerful predictor of lung cancer progression. In non-small cell lung cancer patients receiving sublobar resection, the discussion of correlation between VDT and surgery was absent. We proposed to investigate the surgical outcomes according to VDT. METHODS: We retrospectively studied 96 cases post sublobar resection from 2012 to 2018, collecting two chest CT scans preoperatively of each case and calculating the VDT. The receiver operating characteristic curve was constructed to identify the optimal cut-off point of VDTs as 133 days. We divided patients into two groups: VDT < 133 days and VDT ≥ 133 days. Univariable and multivariable analyses were performed for comparative purposes. RESULTS: Univariable and multivariable analyses revealed that the consolidation and tumor diameter ratio was the factor of overall survival (OS), and VDT was the only factor of disease-free survival (DFS). The five year OS rates of patients with VDTs ≥ 133 days and VDTs < 133 days, respectively, were 89.9% and 71.9%, and the five year DFS rates were 95.9% and 61.5%. CONCLUSION: As VDT serves as a powerful prognostic predictor and provides an essential role in planning surgical procedures, the evaluation of VDT preoperatively is highly suggested.

Comparing Outcomes of Single-Incision Laparoscopic Herniorrhaphy in Newborns and Infants.

BACKGROUND: As surgical techniques progress, laparoscopic herniorrhaphy is now performed more often in premature babies. The aim of this study was to analyze the outcomes of newborns and infants who underwent single-incision laparoscopic herniorrhaphy (SILH) at our center. METHODS: We retrospectively reviewed patients younger than 12 months old who received SILH at our department from 2016 to 2020. SILH involved a 5 mm 30-degree scope and 3 mm instruments with a 3-0 Silk purse-string intracorporeal suture for closure of the internal ring. At the time of surgery, Group 1 newborns, whose corrected age was 2 months and below, were compared to the Group 2 infants, whose age was above 2 months. We assessed the patients' characteristics, anesthesia, surgical data, and complications. RESULTS: A total of 197 patients were included (114 newborns in Group 1 and 83 infants in Group 2). The mean age and body weight in Group 1 were 1.2 months and 3.8 kg, respectively, whereas in Group 2, they were 3.2 months and 6.7 kg, respectively. There were no significant differences in operative time (Group 1 = 34.1 min vs. Group 2 = 32.3 min, p = 0.26), anesthetic time (Group 1 = 80.0 min vs. Group 2 = 76.3 min, p = 0.07), length of hospitalization (Group 1 = 2.3 days vs. Group 2 = 2.4 days, p = 0.88), postoperative complications including omphalitis (Group 1 = 5.3% vs. Group 2 = 1.2%, p = 0.13), wound infection (Group 1 = 0.9% vs. Group 2 = 1.2%, p = 0.81), and hydrocele (Group 1 = 0.35% vs. Group 2 = 8.4%, p = 0.14). No recurrence, testicular ascent or atrophy, or mortality was observed in either group during the 2-year follow-up period. CONCLUSIONS: Single-incision laparoscopic herniorrhaphy is a safe and effective operation for inguinal hernia repair in infants, even those with prematurity, lower body weight at the time of surgery, or cardiac and/or pulmonary comorbidities. Comparable results revealed no significant differences in perioperative complications despite younger ages and lower body weights.

Size Measurement and Segmentectomy Resection Margin of Early-Stage Lung Adenocarcinoma Manifesting on Virtual 3D Imagery and Pathology: A Pilot Correlation Study.

BACKGROUND: The objective of our study was to assess if 3D reconstructed images could be extrapolated to reflect pathologies, as evaluated by early-stage lung adenocarcinoma tumor size and simulated segmentectomy resection margin. METHODS: Retrospectively selected patients (n = 18) who underwent segmentectomy at Changhua Christian Hospital between 2012 and 2018 and then had pulmonary 3D reconstruction using Ziostation2 were included in our study. Tumor size and simulated segmentectomy resection distance on a 3D model were measure and compared to pathology. RESULTS: Both tumor size and segmentectomy resection margin showed positive correlations between 3D image measurements and pathological measurements. The resection margin showed a stronger correlation and was beneficial in pre-operative planning. CONCLUSIONS: A 3D reconstructed model aided understanding of pulmonary anatomy, prompting confidence in surgical approaches and ensured segmentectomy outcome success. Regardless of age and pulmonary function, 3D simulation can accurately mimic segmentectomy, making it a simple, effective and feasible pre-operative planning tool.

Using 3D Microscope for Hepatic Artery Reconstruction in Living Donor Liver Transplant.

INTRODUCTION: This study compares the intraoperative process of hepatic artery anastomosis using conventional microscope and novel 3D digital microscope and discusses our technique and operative set-up. METHOD: A retrospective comparative cohort study with 46 hepatic artery reconstructions in living donor liver transplant patients. Either an operational microscope (control group) or a 3D digital microscope Mitaka Kestrel View II (study group) was used for hepatic artery anastomosis. We then discuss and share our institution's experience of improving surgical training. RESULTS: Both operation instruments provide effective and comparable results. There was no statistical difference regarding operational objective results between conventional microscope and exoscope. Both instruments have no hepatic artery size limit, and both resulted in complete vessel patency rate. CONCLUSIONS: There was no statistical differences regarding hepatic artery anastomosis between microscope and exoscope cohorts. Microsurgeons should perform hepatic artery anastomosis efficiently with the instruments they are most proficient with. Yet, exoscope provided better ergonomics in the operation room and lessened musculoskeletal strain, allowing surgeons to work in a more neutral and comfortable posture while allowing the first assistant to learn and assist more effectively. Using exoscope with micro-forceps and modified tie technique make artery reconstruction easier.

Artery Reconstruction in Right Lobe Living Donor Liver Transplantation: Donor-Recipient Vessel Ratio Is Key to Choosing Recipient Artery.

BACKGROUND: The aims of this study were to investigate if recipient artery choice in right lobe living donor liver transplant affects postoperative complications and discuss solutions accordingly. METHODS: Three hundred fourteen right lobe living donor liver transplantation patients were divided into 2 groups: 163 patients using right hepatic artery as the recipient vessel and 151 patients using left hepatic artery as the recipient vessel. Cases involving 2 recipient blood vessels or the use of other blood vessels as recipient vessels were excluded. RESULTS: Overall vascular embolism rate in both groups was 1.3%, and our complication rate was lower than those in previous studies. There was no significant difference in complication rate between the groups, but a significant difference in recipient/donor artery size ratio was noted. CONCLUSIONS: Although left hepatic artery's anatomical position makes it less affected by bile duct anastomosis and thus fewer postoperative complications, we believe that the ratio of the donor-recipient blood vessel size and the length of the anastomosis vessel stumps are the key factors that affect the outcome of the vascular anastomosis.

Minimal Access (Endoscopic and Robotic) Breast Surgery in the Surgical Treatment of Early Breast Cancer-Trend and Clinical Outcome From a Single-Surgeon Experience Over 10 Years.

OBJECTIVE: Endoscopic assisted breast surgery (EABS) or robotic assisted breast surgery (RABS) performed through minimal axillary and/or peri-areolar incisions has become the representative of minimal access breast surgery (MABS). We report the trend and clinical outcome of MABS for treatment of breast cancer. METHODS: Information on patients who underwent breast cancer operation by the principal investigator during the period of 2011 to 2020 was collected from a single institute for analysis. The clinical outcome, trend, and cost of MABS were analyzed and compared with conventional breast surgery (CBS). RESULTS: A total of 824 breast cancer patients operated by a single surgeon were enrolled in this study: 254 received CBS and 570 received MABS, namely, 476 EABS and 94 RABS. From 2011 to 2020, the number of MABS performed annually has shown an increasing trend. Compared with CBS, MABS such as breast conserving surgery and nipple sparing mastectomy (NSM) have effectively reduced wound scar length. Since the sequential uprise from conventional NSM (C-NSM), dual-axillary-areolar-incision two dimensional (2D) endoscopic assisted NSM (E-NSM), single-axillary-incision E-NSM, robotic assisted NSM (R-NSM), and single-port 3D E-NSM, the development of minimal access mastectomies increasingly paralleled with NSM. The operation time of various MABS decreased significantly and showed no statistical difference compared with CBS. R-NSM was associated with highest cost, followed by 3D E-NSM, E-NSM, and C-NSM. The positive surgical margin rate and local recurrence rate of MABS and CBS were not statistically different. CONCLUSION: MABS showed comparable clinical outcome and preliminary oncologic safety as CBS and has been increasingly performed as the surgical treatment of breast cancer, especially minimal access NSM.

An uncommon spontaneous right distal tubal pregnancy post bilateral laparoscopic sterilization: A case report.

RATIONALE: Tubal sterilization as a contraception method has a high success rate; however, it also carries a low risk of incidental pregnancy. A majority of these pregnancies are ectopic. In this study, we report a rare case of spontaneous right distal tubal pregnancy after bilateral laparoscopic tubal sterilization. PATIENT CONCERNS: A 36-year-old woman who had undergone bilateral laparoscopic tubal sterilization presented with abdominal pain and a positive test for pregnancy. DIAGNOSIS: Ectopic pregnancy was suspected based on absence of gestational sac in the uterine cavity on ultrasound and elevated beta-human chorionic gonadotropin (ß-hCG) level. INTERVENTION: Since the patient had unstable vitals, emergency laparoscopic surgery was performed, which revealed a right distal fallopian tube pregnancy. We performed a complete bilateral residual tubal stump excision. OUTCOMES: The patient recovered well after surgery, with a reduction in ß-hCG level, and was discharged after 3 days. LESSONS: To ensure complete sterilization, the gap at the excised end needs to be adequately widened and enhanced with electro-destruction to prevent formation of a fistula.

The inhibitory effect of 7,7″-dimethoxyagastisflavone on the metastasis of melanoma cells via the suppression of F-actin polymerization.

7,7″-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from Taxus × media cv. Hicksii, induces apoptotic and autophagic cell death. However, whether DMGF suppresses tumor metastasis is unclear. The aim of this study was to investigate the anti-metastatic activities of DMGF on the metastatic processes of melanoma cells in vivo and in vitro. A transwell assay showed that DMGF could effectively attenuate the motility of B16F10 cells, and the results of real-time PCR revealed that DMGF also suppressed the expressions of matrix metalloproteinase-2 (MMP-2). Moreover, DMGF did not influence tube formation but inhibited the migration of endothelial cells. Furthermore, animal models were used to monitor the effects of DMGF on tumor metastasis, and all models showed that DMGF significantly suppressed the metastatic behaviors of B16F10 cells, including intravasation, colonization, and invasion of the lymphatic duct. In addition, DMGF could also reduce the densities of the blood vessels in the tumor area in vivo. Further investigation of the molecular mechanisms of anti-metastatic activity revealed that DMGF can down-regulate the levels of key modulators of the Cdc42/Rac1 pathway to interfere in F-actin polymerization and suppress the formation of lamellipodia by reducing the phosphorylation of CREB. These data suggested that DMGF presents anti-metastatic activities in B16F10 melanoma cells. Here, we demonstrated that DMGF can inhibit the metastasis of highly invasive melanoma cancer cells through the down-regulation of F-actin polymerization. Considering these findings, DMGF may be further developed to serve as a chemoprevention drug for patients with metastatic melanoma.

miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions.

MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively regulating gene expression to control many cellular mechanisms. The miRTarBase database (http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and comprehensive information of experimentally validated miRNA-target interactions. The database was launched in 2010 with data sources for >100 published studies in the identification of miRNA targets, molecular networks of miRNA targets and systems biology, and the current release (2013, version 4) includes significant expansions and enhancements over the initial release (2010, version 1). This article reports the current status of and recent improvements to the database, including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv) miRNA target-associated diseases and (v) additional utilities including an upgrade reminder and an error reporting/user feedback system.

Inhibitory effects of chloroform extracts derived from Corbicula fluminea on the release of pro-inflammatory cytokines.

Corbicula fluminea, the primary freshwater bivalve cultivated in Taiwan, was formerly used as a remedy for hepatitis. Recent reports indicate that C. fluminea has many bioactivities, but it remains unknown whether C. fluminea affects inflammation. This study explored the anti-inflammatory activity of C. fluminea. C. fluminea was first treated with chloroform to obtain clam chloroform extracts (CCEs). On the basis of the assay for the release of pro-inflammatory cytokines in vitro and in vivo, the results show that the CCEs significantly lowered the release of lipopolysaccharide (LPS)-induced pro-inflammatory cytokines. Additionally, the CCEs reduced LPS-induced organ damage. Real-time polymerase chain reaction analysis suggested that CCEs inhibit the LPS-induced mRNA expression of interleukin-1ß and tumor necrosis factor-α. Western blot analysis indicated that the CCEs increased expression of IκB and attenuated the phosphorylation of IκB. Gas chromatography-mass spectrometry suggests that phytosterols and fatty acids are responsible for the anti-inflammatory properties of CCEs. Taken together, CCEs have the potential to be developed as an anti-inflammatory functional food.

Liposome-based polymer complex as a novel adjuvant: enhancement of specific antibody production and isotype switch.

The aim of vaccination is to induce appropriate immunity against pathogens. Antibody-mediated immunity is critical for protection against many virus diseases, although it is becoming more evident that coordinated, multifunctional immune responses lead to the most effective defense. Specific antibody (Ab) isotypes are more efficient at protecting against pathogen invasion in different locations in the body. For example, compared to other Ab isotypes, immunoglobulin (Ig) A provides more protection at mucosal areas. In this study, we developed a cationic lipopolymer (liposome-polyethylene glycol-polyethyleneimine complex [LPPC]) adjuvant that strongly adsorbs antigens or immunomodulators onto its surface to enhance or switch immune responses. The results demonstrate that LPPC enhances uptake ability, surface marker expression, proinflammatory cytokine release, and antigen presentation in mouse phagocytes. In contrast to Freund's adjuvant, LPPC preferentially activates Th1-immunity against antigens in vivo. With lipopolysaccharides or CpG oligodeoxynucleotides, LPPC dramatically enhances the IgA or IgG2A proportion of total Ig, even in hosts that have developed Th2 immunities and high IgG1 serum titers. Taken together, the results demonstrate that the LPPC adjuvant not only increases the immunogenicity of antigens but also modulates host immunity to produce an appropriate Ab isotype by combining with immunomodulators.

A Lipo-PEG-PEI complex for encapsulating curcumin that enhances its antitumor effects on curcumin-sensitive and curcumin-resistance cells.

A cationic liposome-PEG-PEI complex (LPPC) was used as a carrier for the encapsulation of hydrophobic curcumin to give curcumin/LPPC. Curcumin/LPPC had an average size less than 270 nm and a zeta potential of approximately 40 mV. The LPPC encapsulation efficiency for curcumin was about 45%. The authors found it surprising that the cytotoxic activity of the curcumin/LPPC was fivefold higher than curcumin when tested on curcumin-sensitive cells and 20-fold more active against curcumin-resistant cells. Curcumin/LPPC treatment caused a cell cycle arrest at G2/M phase, which rapidly resulted in apoptosis. The increased cytotoxic activity of curcumin/LPPC is likely attributable to its rapid accumulation in the cell. In vivo, administration of curcumin/LPPC inhibited about 60 - 90% of tumor growth in mice bearing CT-26 or B16F10 cells. These results demonstrate LPPC encapsulation technology is able to enhance the effects of antitumor drugs. Use of this technology may provide a new tool for cancer therapy, especially for drug-resistant cancer. From the Clinical Editor: This team of investigators used a cationic liposome-PEG-PEI complex (LPPC) to encapsulate curcumin. The different delivery method resulted in the five-fold increase of cytotoxic activity against curcumin-sensitive cells and twenty-fold against curcumin-resistant cells.

Antibodies against Helicobacter pylori heat shock protein 60 aggravate HSP60-mediated proinflammatory responses.

Anti-Helicobacter pylori heat shock protein 60 (HpHSP60) antibodies are usually found in H. pylori-infected patients and are known to be associated with the progression of gastric diseases. However, the effects of these antibodies on the functions of HpHSP60 have not been identified. This study aims to investigate the effects of the interaction between anti-HSP60 antibodies and HpHSP60 on inflammatory responses. Anti-HpHSP60 polyclonal sera and monoclonal antibodies (mAbs) were produced to evaluate their effects on HpHSP60-induced IL-8 and TNF-α activity. The results indicated that anti-HpHSP60 polyclonal sera collected from patients infected with H. pylori or from rabbit and mice immunized with HpHSP60 could significantly enhance HpHSP60-mediated IL-8 and TNF-α secretion from monocytic THP-1 cells. Similar effects were also found with anti-HpHSP60 mAbs. Further analysis revealed that this phenomenon was only carried out by anti-HpHSP60 antibody but not by other non-specific mAbs. Moreover, the non-specific mAbs decreased the synergism of HpHSP60 and anti-HpHSP60 mAbs in proinflammatory cytokine induction. Herein, we have examined the role of anti-HpHSP60 antibody in host immune responses for the first time. This study demonstrated that H. pylori HSP60/mAbs could modulate helicobacterial pathogenesis by increasing IL-8 and TNF-α production. The pathogen-specific antibodies may execute potential immune functions rather than recognize or neutralize microbes.

A unique and potent protein binding nature of liposome containing polyethylenimine and polyethylene glycol: a nondisplaceable property.

Most of the currently available targeting vectors are produced via the linkage of targeting molecules. However, the coupling process is complicated, and the covalent linkage may attenuate the activity of certain targeting molecules. In this study, we have developed a cationic liposome complexed with polyethylenimine and polyethylene glycol polymers (LPPC) that can capture various proteins without covalent conjugation. Characterizations of prepared LPPC revealed that the maximal-binding capacity was about 170 µg of bovine serum albumin to 40 µg of sphere-shaped LPPC (180 nm). The proteins were essentially located at or near the surface when analyzed by atomic force or transmission electron microscopy. We demonstrate that polyethylenimine was an essential component to bind the proteins. Upon the saturation of captured proteins, a given protein could not be displaced by other additional proteins and still retained its biological activity. Using a variety of functional proteins, we show some typical examples of the utility of incorporated beta-glucuronidase and antibodies onto the LPPC. The beta-glucuronidase can be used for the study of antigen-antibody interactions, whereas in studies with the antibody complex, we used anti-CD3 as an agonist to stimulate the proliferation of peripheral blood mononuclear cells via a receptor-mediated mechanism and anti-VEGFR for cell staining. In conclusion, the prepared LPPC can provide a platform to capture biologically and biochemically functional proteins on its surface for various applications, such as cell signaling, cell profiling, noncovalent enzyme-linked immunoassays, and others not mentioned.

Utilization of IκB-EGFP Chimeric Gene as an Indicator to Identify Microbial Metabolites with NF-κB Inhibitor Activity.

NF-κB regulates several important expressions, such as cytokine release, anti-apoptosis, adhesion molecule expression, and cell cycle processing. Several NF-κB inhibitors have been discovered as an anti-tumor or anti-inflammatory drug. The activity of NF-κB transcription factor is negatively regulated by IκB binding. In this study, IκB assay system was established and IκB-EGFP fusion protein was used as an indicator to monitor the effects of substances on the IκB degradation. The results indicated that the chosen hydroquinone could inhibit the IκB degradation and cause the cell de-attachment from the bottom of culture plate. In addition, this system could also monitor the IκB degradation of microbial metabolite of natural mixtures of propolis. Thus, the IκB assay system may be a good system for drug discovery related to microbial metabolite.