BACKGROUND: Prostate cancer (PCa) is one of the most common primary malignancies in humans and the second leading cause of cancer-specific mortality among Western males. Computer-aided detection (CAD) systems have been developed for accurate and automated PCa detection and diagnosis, but the diagnostic accuracy of different CAD systems based on magnetic resonance imaging (MRI) for PCa remains controversial. The aim of this study is to systematically review the published evidence to investigate diagnostic accuracy of different CAD systems based on MRI for PCa.
METHODS: We will conduct the systematic review and meta-analysis according to the Preferred Reporting Items for a systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA) guidelines. Cochrane library, PubMed, EMBASE and Chinese Biomedicine Literature Database will be systematically searched from inception for eligible articles, 2 independent reviewers will select studies on CAD-based MRI diagnosis of PCa and extract the requisite data. The quality of reporting evidence will be assessed using the quality assessment of diagnosis accuracy study (QUADAS-2) tool. Pooled sensitivity, specificity, and the area under the summary receiver operating characteristic (SROC) curves will be calculated to estimate the diagnostic accuracy of CAD system. In addition, we will conduct subgroup analyses according to the type of classifier of CAD systems used and the different prostate zoon.
RESULTS: This study will conduct a meta-analysis of current evidence to investigate the diagnostic accuracy of CAD systems based on MRI for PCa by calculating sensitivity, specificity, and SROC curves.
CONCLUSION: The conclusion of this study will provide evidence to judge whether CAD systems based on MRI have high diagnostic accuracy for PCa.
ETHICS AND DISSEMINATION: Ethics approval is not required for this systematic review as it will involve the collection and analysis of secondary data. The results of the review will be reported in international peer-reviewed journals.
PROSPERO REGISTRATION NUMBER: CRD42019132543.

OBJECTIVE: The aim of this study was to determine the diagnostic accuracy of different computer-aided diagnostic (CAD) systems for thyroid nodules classification.
METHODS: A systematic search of the literature was conducted from inception until March, 2019 using the PubMed, EMBASE, Web of science, and Cochrane library. Literature selection and data extraction were conducted by 2 independent reviewers. Numerical values for sensitivity and specificity were obtained from false negative (FN), false positive (FP), true negative (TN), and true positive (TP) rates, presented alongside graphical representations with boxes marking the values and horizontal lines showing the confidence intervals (CIs). Summary receiver operating characteristic (SROC) curves were applied to assess the performance of diagnostic tests. Data were processed using Review Manager 5.3 and Stata 15. The methodological quality of included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.
TRIAL REGISTRATION NUMBER: PROSPERO CRD42019132540.

Metastasis is considered the latest stage of cancer development; however, metastasis occurs earlier than it can be detected. Metastatic sites are actively remodeled by secretory factors including growth factors, chemokines and cytokines, extracellular matrix (ECM) enzymes, and exosomes produced by the primary cancer tissues. Many of the associated-secretory factors are abundantly induced by inflammation and hypoxia. These secretory factors modify the ECM, immune composition, and blood vessel permeability of the future metastatic sites, a process termed 'metastatic niche formation.' In general, ECM is modified to enhance the attachment of other cell types or cancer cells to establish a growth-factor rich metastatic niche. Immune-suppressive cells such as tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) dominate the metastatic niche to allow metastatic cancer cells to bypass immune surveillance and propagate. Endothelial cell-to-cell junctions of blood vessels are loosened to enhance the penetrance of metastatic cancer cells to the metastatic sites. Different metastatic tissues have unique ECM constituents, resident immune cells, and anatomical positions linked with the circulatory system; therefore, many cancer types have their own metastatic pattern, and they favor metastasis to specific organs. Some of the remodeling events represent the earliest step of metastasis, even preceding the detachment of cancer cells from the primary tumor site. Understanding how the metastatic niche is formed is important for the development of drugs to prevent the earliest step of metastasis and advance our understanding of organotrophic metastasis. This review summarizes the major findings in the field of metastatic niche highlighting the role of hypoxia.

Nasopharyngeal carcinoma is characterised by distinct geographical distribution and is particularly prevalent in east and southeast Asia. Epidemiological trends in the past decade have shown that its incidence has declined gradually but progressively, and mortality has been reduced substantially. These findings probably reflect lifestyle and environmental changes, enhanced understanding of the pathogenesis and risk factors, population screening, advancements in imaging techniques, and individualised comprehensive chemoradiotherapy strategies. In particular, plasma Epstein-Barr virus (EBV) DNA has been used for population screening, prognostication, predicting treatment response for therapeutic adaptation, and disease surveillance. Moreover, the widespread application of intensity-modulated radiotherapy and optimisation of chemotherapy strategies (induction, concurrent, adjuvant) have contributed to improved survival with reduced toxicities. Among the existing developments in novel therapeutics, immune checkpoint therapies have achieved breakthroughs for treating recurrent or metastatic disease and represent a promising future direction in nasopharyngeal carcinoma.

BACKGROUND: An earlier analysis of this phase 3 trial showed that the addition of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor to endocrine therapy provided a greater benefit with regard to progression-free survival than endocrine therapy alone in premenopausal or perimenopausal patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Here we report the results of a protocol-specified interim analysis of the key secondary end point of overall survival.
METHODS: We randomly assigned patients to receive either ribociclib or placebo in addition to endocrine therapy (goserelin and either a nonsteroidal aromatase inhibitor or tamoxifen). Overall survival was evaluated with the use of a stratified log-rank test and summarized with the use of Kaplan-Meier methods.
RESULTS: A total of 672 patients were included in the intention-to-treat population. There were 83 deaths among 335 patients (24.8%) in the ribociclib group and 109 deaths among 337 patients (32.3%) in the placebo group. The addition of ribociclib to endocrine therapy resulted in significantly longer overall survival than endocrine therapy alone. The estimated overall survival at 42 months was 70.2% (95% confidence interval [CI], 63.5 to 76.0) in the ribociclib group and 46.0% (95% CI, 32.0 to 58.9) in the placebo group (hazard ratio for death, 0.71; 95% CI, 0.54 to 0.95; P = 0.00973 by log-rank test). The survival benefit seen in the subgroup of 495 patients who received an aromatase inhibitor was consistent with that in the overall intention-to-treat population (hazard ratio for death, 0.70; 95% CI, 0.50 to 0.98). The percentage of patients who received subsequent antineoplastic therapy was balanced between the groups (68.9% in the ribociclib group and 73.2% in the placebo group). The time from randomization to disease progression during receipt of second-line therapy or to death was also longer in the ribociclib group than in the placebo group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.55 to 0.87).
CONCLUSIONS: This trial showed significantly longer overall survival with a CDK4/6 inhibitor plus endocrine therapy than with endocrine therapy alone among patients with advanced hormone-receptor-positive, HER2-negative breast cancer. No new concerns regarding toxic effects emerged with longer follow-up. (Funded by Novartis; MONALEESA-7 ClinicalTrials.gov number, NCT02278120.).

Organ-specific colonization suggests that specific cell-cell recognition is essential. Yet, very little is known about this particular interaction. Moreover, tumor cell lodgement requires binding under shear stress, but not static, conditions. Here, we successfully isolate the metastatic populations of cancer stem/tumor-initiating cells (M-CSCs). We show that the M-CSCs tether more and roll slower than the non-metastatic (NM)-CSCs, thus resulting in the preferential binding to the peritoneal mesothelium under ascitic fluid shear stress. Mechanistically, this interaction is mediated by P-selectin expressed by the peritoneal mesothelium. Insulin-like growth factor receptor-1 carrying an uncommon non-sulfated sialyl-Lewis

Centrosomes control cell motility, polarity and migration that is thought to be mediated by their microtubule-organizing capacity. Here we demonstrate that WNT signalling drives a distinct form of non-directional cell motility that requires a key centrosome module, but not microtubules or centrosomes. Upon exosome mobilization of PCP-proteins, we show that DVL2 orchestrates recruitment of a CEP192-PLK4/AURKB complex to the cell cortex where PLK4/AURKB act redundantly to drive protrusive activity and cell motility. This is mediated by coordination of formin-dependent actin remodelling through displacement of cortically localized DAAM1 for DAAM2. Furthermore, abnormal expression of PLK4, AURKB and DAAM1 is associated with poor outcomes in breast and bladder cancers. Thus, a centrosomal module plays an atypical function in WNT signalling and actin nucleation that is critical for cancer cell motility and is associated with more aggressive cancers. These studies have broad implications in how contextual signalling controls distinct modes of cell migration.

The Asian Prostate Cancer (A-CaP) Study is an Asia-wide prospective registry study for surveying the treatment outcome of prostate cancer patients who have received a histopathological diagnosis. The study aims to clarify the clinical situation for prostate cancer in Asia and use the outcomes for the purposes of international comparison. Following the first meeting in Tokyo on December 2015, the second meeting in Seoul, Korea 2016, the third meeting in Chiang Mai, Thailand, on October 2017, the fourth meeting was held in Seoul, again on August 2018 with the participation of members and collaborators from 13 countries and regions. In the meeting, participating countries and regions presented the current status of data collection and the A-CaP office presented a preliminary analysis of the registered cases received from each country and region. Participants discussed ongoing challenges relating to data cleaning and data up-dating which is the next step of the A-CaP study following the data collection phase between 2016 and 2018. There was specific difference in term of the patient characteristics, and initial treatment pattern among East Asia, Southeast Asia and Turkey, and Jordan. Finally, a close relationship between prevalence of PSA test and disease stage of the patients at diagnosis in Japan and Malaysia was discussed.

BACKGROUND: Colorectal cancer (CRC) screening, such as fecal occult blood test (FOBT), is an effective way to prevent CRC, one of the most common cancers worldwide. However, studies found that South Asian ethnic minorities tend not to utilize CRC screening, whose importance on CRC prevention shall be educated among those from ethnic minorities, especially older adults. The purpose of this study is to develop and implement a family-based, multimedia intervention to augment the knowledge of CRC prevention among older South Asian adults in Hong Kong and enhance their motivation for undergoing FOBT. The acceptability and effectiveness of the intervention will be assessed using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework.
METHODS: A cluster randomized controlled trial will be carried out. Three hundred and twenty South Asian dyads, comprising an older adult aged between 50 and 75 and a younger family member aged between 18 and 49, will be recruited in ten districts in Hong Kong through community organizations that provide support services for South Asians in local communities. Dyads will be randomly allocated to either the intervention or wait-list control group. Intervention dyads will receive intervention, whose contents are based on the health belief model, via multiple forms of media including PowerPoint presentation, video clip and health information booklet. Control dyads will receive intervention after post-intervention data are collected. For dyads in both groups, an appointment with a family doctor will be arranged for those willing to undergo FOBT. Outcomes will be assessed at baseline and post-intervention. Data will be analysed using the Generalised Linear Models Procedure in an intention-to-treat manner.
DISCUSSION: Findings of this study will provide evidence of the benefits of utilizing multimedia and family-based approaches in intervention development to enhance the effectiveness of health promotion interventions for ethnic minorities. Further, the findings would provide reference to the potential incorporation of the intervention in the existing support services for South Asian ethnic minorities in local communities.
TRIAL REGISTRATION: This trial is registered at the ISRCTN Registry ( ISRCTN72829325 ) on 19th July 2018.

A balance of Bcl-2 family proteins dictates cell survival or death, as the interactions between these proteins regulate mitochondrial apoptotic signaling pathways. However, cancer cells frequently show upregulation of pro-survival Bcl-2 proteins and sequester activated pro-apoptotic BH3-only proteins driven by diverse cytotoxic stresses, resulting in tumor progression and chemoresistance. Synthetic molecules from either structure-based design or screening procedures to engage and inactivate pro-survival Bcl-2 proteins and restore apoptotic process represent a chemical biological means of selectively killing malignant cells. 17 years ago, one of us reviewed on the discovery of novel Bcl-2 targeted agents [1]. Here we revisit this area and examine the progress and current status of small molecule Bcl-2 inhibitor development, demonstrating the Bcl-2 family as a valid target for cancer therapy and providing successful examples for the discovery of inhibitors that target protein-protein interactions.

The International Academy of Cytology (IAC) gathered together a group of cytopathologists expert in breast cytology who, working with clinicians expert in breast diagnostics and management, have developed the IAC Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy (FNAB) Cytology. The project was initiated with the first cytopathology group meeting in Yokohama at the 2016 International Congress of Cytology. This IAC Yokohama System defines five categories for reporting breast cytology, each with a clear descriptive term for the category, a definition, a risk of malignancy (ROM) and a suggested management algorithm. The key diagnostic cytopathology features of each of the lesions within each category will be presented more fully in a subsequent atlas. The System emphasizes that the crucial requirements for diagnostic breast FNAB cytology are a high standard for the performance of the FNAB and for the making of direct smears, and well-trained experienced cytopathologists to interpret the material. The performance indicators of breast FNAB, including specificity and sensitivity, negative predictive value, positive predictive value and ROM stated in this article have been derived from the recent literature. The current practice of breast FNAB has evolved with the increasing use of ultrasound guidance and rapid on-site evaluation. Two recent publications have shown a range of ROM for the insufficient/inadequate category of 2.6-4.8%, benign 1.4-2.3%, atypical 13-15.7%, suspicious of malignancy 84.6-97.1%, and malignant 99.0-100%. The management algorithm in the System provides options because there are variations in the management of breast lesions using FNAB and core-needle biopsy in those countries utilizing the "triple test" of clinical, imaging, and FNAB assessment, and also variations in the availability of CNB and imaging in low- and middle-income countries. The System will stimulate further discussion and research, particularly in the cytological diagnostic features of specific lesions within each category and in management recommendations. This will lead to continuing improvements in the care of patients with breast lesions and possible modifications to the IAC Yokohama System.

Non-invasive deep-tissue three-dimensional optical imaging of live mammals with high spatiotemporal resolution is challenging owing to light scattering. We developed near-infrared II (1,000-1,700 nm) light-sheet microscopy with excitation and emission of up to approximately 1,320 nm and 1,700 nm, respectively, for optical sectioning at a penetration depth of approximately 750 μm through live tissues without invasive surgery and at a depth of approximately 2 mm in glycerol-cleared brain tissues. Near-infrared II light-sheet microscopy in normal and oblique configurations enabled in vivo imaging of live mice through intact tissue, revealing abnormal blood flow and T-cell motion in tumor microcirculation and mapping out programmed-death ligand 1 and programmed cell death protein 1 in tumors with cellular resolution. Three-dimensional imaging through the intact mouse head resolved vascular channels between the skull and brain cortex, and allowed monitoring of recruitment of macrophages and microglia to the traumatic brain injury site.

The use of targeted therapy in the management of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer is an important milestone in the management of advanced lung cancer. There are several generations of EGFR tyrosine kinase inhibitors available for clinical use. Dacomitinib is a second-generation irreversible EGFR tyrosine kinase inhibitor with early-phase clinical studies showing efficacy in non-small-cell lung cancer. In the recently published ARCHER 1050 phase III study, dacomitinib given at 45 mg/day orally was superior to gefitinib, a first-generation reversible EGFR tyrosine kinase inhibitor, in improving both progression-free survival and overall survival when given as first-line therapy. There is no prospective evidence to support the use of dacomitinib as subsequent therapy in patients previously treated with chemotherapy or a first-generation EGFR tyrosine kinase inhibitor such as gefitinib and erlotinib. Dacomitinib has not demonstrated any benefit in unselected patients with non-small-cell lung cancer, and its use should be limited to those with known EGFR-sensitizing mutations. Dacomitinib is associated with increased toxicities of diarrhea, rash, stomatitis, and paronychia compared with first-generation EGFR inhibitors. Global quality of life was maintained when assessed in phase III studies. Overall, dacomitinib is an important first- line agent in EGFR-mutated non-small-cell lung cancer in otherwise fit patients whose toxicities can be well managed.

BACKGROUND: Quality of life (QOL) assessments with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-HCC18, C30 and HCC18 index scores have been shown to be prognostic factors for overall survival (OS) in patients with hepatocellular carcinoma (HCC), independent of disease stage and liver function. Liver function parameters (including bilirubin, albumin, international normalized ratio [INR], Child-Pugh class, ALBI grade, MELD, alkaline phosphatase [ALP]-to-platelet ratio, albumin-to-ALP ratio) have also been found to be independent prognostic factors for OS in HCC patients. There has been scanty data on whether QOL and baseline liver function per se are correlated in HCC patients. This study investigates the correlations between baseline QOL data and liver function variables in HCC patients.
METHODS: From 2007 to 2011, 517 patients were enrolled. Baseline QOL was assessed at diagnosis using the EORTC QLQ-C30 and QLQ-HCC18; thereafter C30 and HCC18 index scores were derived. Clinical and laboratory data were collected. For liver function assessment, Child-Pugh class, ALBI grade, MELD, ALP-to-platelet ratio and albumin-to-ALP ratio were derived. Correlation analyses were performed between QOL and liver function data.
RESULTS: Complete QOL data were available in 472 HCC patients. After adjusting for clinical variables, significant correlations were found between QOL (QLQ-C30 and QLQ-HCC18) and dichotomized liver function variables (including Child-Pugh class, ALBI grade and the presence of ascites). It was demonstrated that QOL had significant and potentially clinically important correlations with continuous liver function variables (albumin, bilirubin, ALP and albumin-to-ALP ratio), with the highest Spearman's rank correlation coefficient (rho) exceeding 0.4. HCC18 and C30 index scores were also significantly correlated with these liver function variables. HCC18 index score, which had rho up to 0.37, generally performed better than C30 index score, which had rho up to 0.33.
CONCLUSIONS: In HCC patients, baseline QOL assessment (using EORTC QLQ-C30, QLQ-HCC18, C30 index-score or HCC18 index-score) is significantly correlated with liver function. Based on the findings of this study, future trials are warranted to assess whether treatment to enhance liver function could improve HCC patients' QOL.

OBJECTIVE: To evaluate the effect of haemostatic sealant compared with bipolar coagulation on ovarian reserve after laparoscopic cystectomy for ovarian endometriomas.
DESIGN: Patient-blinded, randomised controlled trial.
SETTING: University-affiliated tertiary hospital.
POPULATION: Women aged 18-40 years with 3-8 cm unilateral or bilateral endometriomas.
METHODS: Ninety-four patients were randomised to receive haemostasis by the application of haemostatic sealant (n = 47) or standard care (n = 47).
MAIN OUTCOME MEASURES: Primary outcome was the effect on the antral follicular count 3 months after the operation as it captures the effect on the ovary subjected to treatment. Secondary outcomes included the change in anti-Mullerian hormone, follicular-stimulating hormone and peri-operative outcomes including haemostasis, complications, pain, and satisfaction scores.
RESULTS: A total of 94 patients aged 32.36 ± 4.92 years underwent laparoscopic cystectomy for ovarian endometriomas. The average diameter of the endometrioma was 4.21 ± 1.38 cm. The increase in antral follicle count of the affected ovaries at 3 months in the intervention group (+2.36 ± 0.37) was significantly (P = 0.013) higher than that in the control group (+1.08 ± 0.36). Repeated measures analysis of variance revealed significant effect with time (P < 0.001) and of interaction of group × time (P = 0.029) for affected ovary antral follicle count. No significant difference was noted between the two groups with regard to follicular-stimulating hormone, anti-Mullerian hormone, and other secondary outcomes.
CONCLUSIONS: Applying haemostatic sealant after laparoscopic cystectomy of ovarian endometriomas produced a greater increase in antral follicle count 3 months after surgery compared with the control group.
TWEETABLE ABSTRACT: RCT: Haemostatic sealant in laparoscopic cystectomy of endometriomas increase in the antral follicle count after surgery.

DNA ligase III (LIG3) has been implicated in the etiology of cancer. However, few studies have accessed the association of LIG3 single nucleotide polymorphisms (SNPs) with gastric cancer risk, especially in Chinese population. The current study was undertaken to investigate contribution of LIG3 gene polymorphisms to gastric cancer risk. We first applied TaqMan assay to genotype three LIG3 gene SNPs (rs1052536 C > T, rs3744356 C > T, rs4796030 A > C) in 1142 patients with gastric cancer and 1173 healthy controls. And then, we adopted unconditional multivariate logistic regression analysis to estimate the association between LIG3 SNP genotypes and gastric cancer risk. In all, no positive association was found between the three LIG3 SNPs and gastric cancer risk in single locus analysis or combined risk genotypes analysis. However, compared with participants with rs4796030 AA genotype, participants with the AC/CC had a decreased risk of developing tumors from cardia at an adjusted OR of 0.68 (95% CI = 0.48-0.96, P = 0.026). In addition, we found that participants harboring 2-3 risk genotypes were at a significantly increased risk of developing tumor from cardia (adjusted OR = 1.63, 95% CI = 1.16-2.28, P = 0.005). These results suggest that genetic variations in LIG3 gene may play a weak role in modifying the risk of gastric cancer. Future functional studies should be performed to elucidate the biological role of LIG3 polymorphisms in gastric cancer carcinogenesis.

BACKGROUND: Circular RNAs are a class of regulatory RNA transcripts, which are ubiquitously expressed in eukaryotes. In the current study, we evaluate the function of a novel circRNA derived from the β-catenin gene locus, circβ-catenin.
RESULTS: Circβ-catenin is predominantly localized in the cytoplasm and displays resistance to RNase-R treatment. We find that circβ-catenin is highly expressed in liver cancer tissues when compared to adjacent normal tissues. Silencing of circβ-catenin significantly suppresses malignant phenotypes in vitro and in vivo, and knockdown of this circRNA reduces the protein level of β-catenin without affecting its mRNA level. We show that circβ-catenin affects a wide spectrum of Wnt pathway-related genes, and furthermore, circβ-catenin produces a novel 370-amino acid β-catenin isoform that uses the start codon as the linear β-catenin mRNA transcript and translation is terminated at a new stop codon created by circularization. We find that this novel isoform can stabilize full-length β-catenin by antagonizing GSK3β-induced β-catenin phosphorylation and degradation, leading to activation of the Wnt pathway.
CONCLUSIONS: Our findings illustrate a non-canonical function of circRNA in modulating liver cancer cell growth through the Wnt pathway, which can provide novel mechanistic insights into the underlying mechanisms of hepatocellular carcinoma.

BACKGROUND: Previous neurocognitive assessments in non-central nervous system cancers highlight the high incidence of neurocognitive dysfunction in this study population. However, there have been few studies exploring neurocognitive dysfunction induced by chemotherapy in gynecological cancer patients. This prospective longitudinal study was conducted to assess neurocognitive functioning and functional brain networks in Chinese gynecological cancer patients pre- and post-chemotherapy, while additionally including age-matched healthy subjects as the control group.
METHODS: All research participants were evaluated using a resting-state functional magnetic resonance imaging and neurocognition assessment. Behavioral data were conducted using SPSS for descriptive statistics, correlation and comparison analyses. Preprocessing of MRI (Magnetic Resonance Imaging) data and network analyses were performed using GRETNA (Graph Theoretical Network Analysis).
RESULTS: A total of 40 subjects joined this study, with 20 subjects in each group. With the exception of the mean of psychomotor speed, there was no significant difference pre-chemotherapy between patients and healthy controls in neurocognitive test mean scores (Ps > 0.05). During the post-chemotherapy assessment, there were significant differences in the mean scores of neurocognitive tests (including Digit Span tests, verbal memory, immediate recall, delayed recall, and information processing speed tests) (all Ps < 0 .05). Longitudinal graph analysis revealed statistically significant differences in the patient group, with significant decreases in both local efficiency (P < 0.01) and global efficiency (P = 0.04). Lower raw TMT-A scores were significantly associated with lower local efficiency (r = 0.37, P = 0.03). Lower verbal memory scores were statistically significant and associated with lower global efficiency (r = 0.54, P = 0.02) in the patient group, but not in the healthy control group.
CONCLUSIONS: This study found that the risk of brain function and neurocognitive changes following chemotherapy could potentially guide patients in making appropriate treatment decisions, and this study may identify a cohort that could be suited for study of an intervention.

BACKGROUND: Over the last 10 years, there has been a major treatment revolution for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We aimed to explore the outcome of different neoadjuvant chemotherapy in a tertiary breast cancer centre with early HER2-positive breast cancer as well as factors associated with pathological complete response (pCR) and recurrence-free survival (RFS). The pattern of recurrence was also studied.
METHODS: This retrospective study analysed the outcome of neoadjuvant chemotherapy during the period 2005 to 2016 in a tertiary referral centre in Hong Kong. Patients were divided into three groups according to the neoadjuvant chemotherapy they received: chemotherapy only (Chemo), chemotherapy plus trastuzumab (Chemo-H) and chemotherapy plus double anti-HER2 therapy (Chemo-DH).
RESULTS: There were 226 cases analysed during the study period. The rate of pCR was 5%, 26% and 60% in Chemo, Chemo-H and Chemo-DH groups, respectively (Chemo vs pooled Chemo-H/DH: p<0.0001; Chemo-H vs Chemo-DH: p<0.0001). This was accompanied by a trend of increased rate of breast conservation therapy in Chemo-DH cohort (p=0.046). Use of double anti-HER2 therapy, older age (>50 years) and hormone receptor negativity were associated with more pCR. pCR was associated with better RFS. Among those with recurrence, the proportion of patients with brain as the only site of recurrence increased remarkably with more efficacious anti-HER2 treatment (0% in Chemo, 8% in Chemo-H, 67% in Chemo-DH).
CONCLUSION: pCR remains an important predictive factor for improved RFS. In the era of dual anti-HER2 neoadjuvant therapy, brain-only recurrence poses a challenge to disease surveillance and treatment.

Natural products, explicitly medicinal plants, are an important source of inspiration of antitumor drugs, because they contain astounding amounts of small molecules that possess diversifying chemical entities. For instance,

BACKGROUND: Despite decades of research and intervention programs, the epidemic of esophageal squamous cell carcinoma (ESCC) in the Taihang Mountain area of north China has not seen convincing explanation by any risk factor yet and the incidence has not seen a substantial decrease. Based on recently disclosed association of aridity and wheat consumption with esophageal cancer, we revisited the hypothesis of biogenic silica in esophageal cancer development.
METHODS: From the archives of the Pathology Department of Heping Hospital, Changzhi Medical College, we selected three pairs of formalin-fixed samples, tumor tissues and distant normal tissues, of three patients operated for ESCC who had no history of workplace exposure to silica dust. Two pairs of dried tissue samples were used for phytolith (silica body) analysis and another pair for microanalysis with Transmission Electron Microscope (TEM).
RESULTS: One of the phytoliths in ESCC tumor tissue was similar to the prickle hair on the surface of wheat bract. In the mineral particles detected in the tumor tissue the predominant elements were Si, Ca, and P, whereas Si signals were not obvious in the distant normal tissue.
CONCLUSIONS: The preliminary findings on the detection of phytoliths and the higher than normal Si concentration in ESCC tumor tissue warrants further testing the role of biogenic silica in esophageal cancer.

BACKGROUND: Neutropenia is associated with an increased risk of mortality and hospitalisation. Strategies, including the prescribing of colony-stimulating growth factors (CSFs), are adopted when a high risk (> 20%) of neutropenic complications are seen in the clinical trial setting. With a diverse treatment population that may differ from the patient groups recruited to studies, appropriate prescribing decisions by clinicians are essential. At present, results are conflicting from studies evaluating the risks of certain patient attributes on neutropenic events; we aimed to aggregate these associations to guide future management.
DESIGN: A systematic review with a meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Studies were identified through a literature search using MEDLINE, EMBASE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to December 1, 2017. Studies were included into a meta-analysis if they adjusted for confounders; analyses were conducted in STATA v 15.1 SE.
RESULTS: A total of 4415 articles were retrieved by the search with 37 meeting the inclusion criteria and 12 eligible for meta-analysis. Meta-analysis was conducted for increasing age and yielded a pooled odds ratio of 1.39 (1.11, 1.76, I
CONCLUSIONS: Results can enhance current guidance in prescribing primary prophylaxis for treatments that either fall marginally under the internationally recognised 20% neutropenia risk.

BACKGROUND: Suturing the proximal pancreatic stump and performing pancreaticoenterostomy for the distal pancreatic stump following central pancreatectomy is a conventional procedure. This reconstruction after resection of the pathological pancreatic lesion brings changes in anatomy and physiology. In this study, an innovative one-stage robotic end-to-end pancreatic anastomosis was reported to replace the conventional pancreaticoenterostomy following central pancreatectomy.
MATERIALS AND METHODS: The clinical data of 11 consecutive patients who underwent robotic central pancreatectomy with end-to-end pancreatic anastomosis between August 2017 and December 2017 were analyzed retrospectively.
RESULTS: All operations were completed successfully without any conversion to open surgery. Nine patients had benign tumors, one had a mass-forming chronic pancreatitis, and one had an isolated pancreatic metastasis from a renal cancer. The mean gap left after central pancreatectomy was 4.3 ± 1.0 cm. The median operative time was 121 (range, 105 to 199) min. The median blood loss was 50 (range, 20 to 100) ml. Seven (63.6%) patients developed complications which included Clavien-Dindo Grade I complications in five patients, a Grade II complication in one patient, and a Grade IIIa complication in one patient. Seven patients developed a Grade B postoperative pancreatic fistula, and two patients a biochemical leak. There was no Grade C or worse pancreatic fistula. Magnetic resonance cholangiopancreatography at postoperative 6 months showed no stricture in any of the main pancreatic ducts. Three patients had an asymptomatic and small pancreatic pseudocyst.
CONCLUSION: Robotic central pancreatectomy with end-to-end pancreatic anastomosis was safe and feasible. It restores the normal anatomy of the pancreas. With its good short-and long-term outcomes, it could be an alternative reconstructive method to pancreaticoenterostomy following central pancreatectomy.

Esophageal squamous cell carcinoma (ESCC) ranks fourth among cancer-related deaths in China due to the lack of actionable molecules. We performed whole-exome and T-cell receptor (TCR) repertoire sequencing on multi-regional tumors, normal tissues and blood samples from 39 ESCC patients. The data revealed 12.8% of ERBB4 mutations at patient level and functional study supported its oncogenic role. 18% of patients with early BRCA1/2 variants were associated with high-level contribution of signature 3, which was validated in an independent large cohort (n = 508). Furthermore, knockdown of BRCA1/2 dramatically increased sensitivity to cisplatin in ESCC cells. 5% of patients harbored focal high-level amplification of CD274 that led to massive expression of PD-L1, and might be more sensitive to immune checkpoint blockade. Finally, we found a tight correlation between genomic and TCR repertoire intra-tumor heterogeneity (ITH). Collectively, we reveal high-level ITH in ESCC, identify several potential actionable targets and may provide novel insight into ESCC treatment.

BACKGROUND: Prognoses of most adult Hodgkin lymphoma (HL) patients are excellent; most of them can achieve permanent remission that can be considered cured. However, many are under-treated or over-treated by standard modern therapies. An accurate determination of prognosis may allow clinicians to design personalised treatment according to individual risk of disease progression and survival. Lymphocyte monocyte ratio (LMR) at diagnosis has been investigated as a prognostic biomarker in patients with HL. Our objective with this meta-analysis was to explore the prognostic value of the LMR at diagnosis in adult HL, by investigating the association between LMR and survival outcomes.
METHODS: PUBMED and EMBASE were searched for relevant articles. Survival outcomes that we investigated included overall survival (OS), progression-free survival (PFS), event-free survival (EFS), lymphoma-specific survival (LSS), and time to progression (TTP). No restriction to the language, date, study country, or sample size was applied. Final search of databases was performed on 2 April 2018. We performed random-effects meta-analysis to aggregate and summarise the results from included studies, where four or more studies on a particular outcome were available.
RESULTS: A total of eight studies (all retrospective cohort studies) involving 3319 HL patients were selected for analysis. All studies except one reported the effect of LMR on OS; five reported on PFS, three reported on TTP and LSS, respectively, and one reported on EFS. The pooled estimates showed low LMR was associated with poor OS (hazard ratio [HR] 2.67, 95% CI 1.67, 4.26) and PFS (HR 2.19, 95% CI 1.46, 3.29). Subgroup analyses of OS stratified by LMR cut-off values and sample sizes both indicated that low baseline LMR was associated with poorer prognosis.
CONCLUSIONS: Low LMR at diagnosis was associated with poor OS and PFS in HL. LMR is easy and cheap to determine and has a potential role in daily clinical management. More studies are needed to validate this biomarker and explore its interaction with known prognostic factors.

The current study aimed to provide a comprehensive bibliometric overview of the literature on curcumin, complementing the previous reviews and meta-analyses on its potential health benefits. Bibliometric data for the current analysis were extracted from the Web of Science Core Collection database, using the search string TOPIC=("curcumin*"), and analyzed by the VOSviewer software. The search yielded 18,036 manuscripts. The ratio of original articles to reviews was 10.4:1. More than half of the papers have been published since 2014. The major contributing countries were the United States, China, India, Japan, and South Korea. These publications were mainly published in journals representing the following scientific disciplines: biochemistry, chemistry, oncology, and pharmacology. There was a significant positive correlation between the total publication count and averaged citations per manuscript for affiliations, but not for countries/regions and journals. Chemicals that were frequently mentioned in the keywords of evaluated curcumin publications included curcuminoids, resveratrol, chitosan, flavonoids, quercetin, and polyphenols. The literature mainly focused on curcumin's effects against cancer, inflammation, and oxidative stress. Cancer types most frequently investigated were breast, colon, colorectal, pancreatic, and prostate cancers.

Emerging evidence shows that palmitic acid (PA), a common fatty acid in the human diet, serves as a signaling molecule regulating the progression and development of many diseases at the molecular level. In this review, we focus on its regulatory roles in the development of five pathological conditions, namely, metabolic syndrome, cardiovascular diseases, cancer, neurodegenerative diseases, and inflammation. We summarize the clinical and epidemiological studies; and also the mechanistic studies which have identified the molecular targets for PA in these pathological conditions. Activation or inactivation of these molecular targets by PA controls disease development. Therefore, identifying the specific targets and signaling pathways that are regulated by PA can give us a better understanding of how these diseases develop for the design of effective targeted therapeutics.

BACKGROUND: First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater.
METHODS: This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894.
FINDINGS: From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively.
INTERPRETATION: The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS.
FUNDING: Merck Sharp & Dohme.

Colorectal cancer (CRC) is a leading cancer globally; therefore, early diagnosis and surveillance of this cancer are of paramount importance. Current methods of CRC diagnosis rely heavily on endoscopy or radiological imaging. Noninvasive tests including serum detection of the carcinoembryonic antigen (CEA) and faecal occult blood testing (FOBT) are associated with low sensitivity and specificity, especially at early stages. DNA methylation biomarkers have recently been found to have higher accuracy in CRC detection and enhanced prediction of prognosis and chemotherapy response. The most widely studied biomarker in CRC is methylated septin 9 (SEPT9), which is the only FDA-approved methylation-based biomarker for CRC. Apart from SEPT9, other methylated biomarkers including tachykinin-1 (TAC1), somatostatin (SST), and runt-related transcription factor 3 (RUNX3) have been shown to effectively detect CRC in a multitude of sample types. This review will discuss the performances of various methylated biomarkers used for CRC diagnosis and monitoring, when used alone or in combination.