Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer were updated and published online in 2023, and adapted, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with early breast cancer. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with breast cancer representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and KSMO. The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with early breast cancer across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling, as well as the age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

Apparent diffusion coefficient and its standard deviation from diffusion-weighted imaging in preoperative predicting liver invasion by T3-staged resectable gallbladder carcinoma.

AIM: To evaluate apparent diffusion coefficient (ADC) and its standard deviation (SDADC) in preoperative predicting liver invasion by T3-staged gallbladder carcinoma (GBC). MATERIALS AND METHODS: Forty-one consecutive patients with T3-staged resectable GBC were included and divided into two sets with (n=27) and without (n=14) liver invasion. All patients underwent DWI at b-values of 0, 20, 50, 80, 100, 200, 400, 600, 800, and 1,000 s/mm2 with a 3 T magnetic resonance imaging scanner before surgery. ADC and SDADC of tumour-adjacent and tumour-distant liver tissues were measured on DWI, and were compared by Mann-Whitney U-tests. If there was a significant difference in any derived parameter, the area under the receiver operating characteristic curve (AUC) was used to assess performance of this parameter to predict liver invasion. RESULTS: DWI could differentiate between patients with and without liver invasion when b = 0, 1,000 s/mm2 (AUCs of ADC and SDADC were 0.697 and 0.714, respectively). In patients with liver invasion, mean ADC and SDADC of tumour-adjacent liver tissue were lower than of tumour-distant liver tissue when b = 0, 800 s/mm2, and = 0, 1,000 s/mm2 (all p-values <0.05). To differentiate tumour-adjacent from tumour-distant liver tissues in patients with liver invasion, AUCs of ADC were 0.687 (b = 0, 800 s/mm2) and 0.680 (b = 0, 1,000 s/mm2), and AUCs of SDADC were 0.673 (b = 0, 800 s/mm2) and 0.731 (b = 0, 1,000 s/mm2). CONCLUSIONS: DWI could have potential value in preoperative predicting liver invasion by T3-staged GBC.

[Opportunities and prospects for sports medicine in China].

Over the past decades, Chinese sports medicine has made remarkable progress, successfully establishing its status as a discipline and embracing unprecedented development opportunities. In the foreseeable future, "sports for health promotion", in addition to already fast development of "sports injury treatment" and "sports rehabilitation", will become the third vital advancing directions of sports medicine in China. The popularization and application of exercise prescription will become an effective and reliable approach to fulfill sports for health promotion. "Function first, early rehabilitation, return to sports" is the principle of treatment and discipline tenet that will lead the sports injury treatment and rehabilitation to achieve great breakthrough in many fields of sports medicine. With the opportunities and challenges, how to consistently identify and follow the right development path in line with our national circumstances requires the determination, perseverance, courage and wisdom of all Chinese sports medicine practitioners.

Genomic Signature of Mismatch Repair Deficiency in Areca Nut-Related Oral Cancer.

Areca nut (AN) chewing contributes to an increase of oral squamous cell carcinoma (OSCC) cases in South and Southeast Asia; however, genomic events underlying the carcinogenesis process of AN-related OSCC remain unclear. Here, we comprehensively describe the genomic and transcriptome alterations of 113 Chinese OSCC patients (89 AN related and 24 AN negative) by whole-exome sequencing and RNA sequencing, and we compared the genomic differences between AN-related and AN-negative samples by integrating sequencing data of 325 OSCC patients from The Cancer Genome Atlas database and 50 from a published Taiwanese study. We identified 11 significantly mutated genes for OSCC, including 4 novel ones (ATG2A, WEE1, DST, and TSC2), of which WEE1 and ATG2A mutated with significantly higher rates in AN-related samples (P = 0.04 and P = 0.003, respectively). Mutational signature analysis revealed that AN-related OSCCs were specially characterized by the genomic signature of mismatch repair deficiency (dMMR), which could also predict the prognosis status of AN-related OSCC. In addition, an elevated PD-L1 expression was also observed in both AN-related patients (P = 3.71 × 10-11) and those with a high dMMR level (P = 1.99 × 10-4). Further differential expression analysis and in vitro experiments confirmed the role of dMMR in the development of OSCC induced by AN exposure. Taken together, this study first revealed the molecular profiles and highlighted the role of dMMR in AN-related OSCC among the Chinese population and identified that AN-related OSCC may represent a potential cohort for effective anti-PD-1/L1 immunotherapy.

Predicting gastro-oesophageal variceal bleeding in hepatitis B-related cirrhosis by CT radiomics signature.

AIM: To develop liver a computed tomography (CT) radiomics model to predict gastro-oesophageal variceal bleeding (GVB) secondary to hepatitis B-related cirrhosis. MATERIALS AND METHODS: Electronic medical records and image data of liver triple-phase contrast-enhanced CT examinations of 295 patients with hepatitis B-related cirrhosis were collected retrospectively from two hospitals. Two hundred and thirty-six and 59 patients were enrolled randomly into the training and validation cohorts, respectively; and 75 in the training cohort and 16 in the validation cohort endured GVB while the others did not during follow-up period. Radiomics features of the liver were extracted from the portal venous phase images, and clinical features came from medical records. The tree-based method and univariate feature selection were used to select useful features. The radiomics model, clinical model, and integration of radiomics and clinical models were built using the useful image features and/or clinical features. Predicting performance of three models was evaluated with the area under receiver-operating characteristic curve (AUC), accuracy, and F-1 score. RESULTS: Twenty-one useful radiomics features and/or three clinical features were selected to build prediction models that correlated with GVB. AUC of integration of radiomics and clinical models was larger than of clinical or radiomics models for the training cohort (0.83±0.09 versus 0.64±0.08 or 0.82±0.10) and the validation cohort (0.64 versus 0.61 or 0.61). Integration of radiomics and clinical models obtained good performance in predicting GVB for both the training and validation cohorts (accuracy: 0.76±0.07 and 0.73, and F-1 score: 0.77±0.09 and 0.72, respectively). CONCLUSION: Integration of the radiomics and clinical models may be a non-invasive method to predict GVB.

Designing Triple Adult Liver Grafts From an Ideal Deceased Liver.

Splitting deceased donor livers and creating 3 grafts from a whole liver may be feasible and shorten the waiting time for organ donation in patients with high mortality rates. We hypothesized that it might be reasonable to procure 3 grafts for donation from one deceased donor liver by splitting the liver into left (segment II, III, IV), right anterior (segment V, VIII), and right posterior lobes (segment VI, VII) for liver transplantation according to the portal system trifurcated variations. We designed the right anterior branch with the main portal trunk and middle hepatic artery to become inflow of right anterior lobe, the left portal vein and left hepatic artery to become the inflow of left lobe and right posterior branch, and right hepatic artery to become the inflow of right posterior lobe. We retrospectively reviewed the volumetric computed tomography and magnetic resonance cholangiopancreatography of 153 liver donors. The hepatic and portal veins, hepatic artery, and biliary system were reorganized and classified. The volumetric proportions of the liver grafts were measured. Trifurcation of the portal vein variation was found in approximately 13.7% of portal systemic variations. The left lobe accounted for 29.18% of the total liver volume, the right anterior lobe, 35.22%, and the right posterior lobe, 35.6%. We validated this principle by dissecting the explanted liver and identified the triple grafts' weights, percentages, vessels, and biliary ducts system. The splitting of deceased donor livers into 3 split liver grafts for use in liver transplantation surgery can be clinically useful.

Tumour motion of oesophageal squamous cell carcinoma evaluated by cine MRI: associated with tumour location.

AIM: To evaluate the association between oesophageal tumour motion and tumour location using cine magnetic resonance imaging (MRI). MATERIALS AND METHODS: Thirty-three consecutive patients with oesophageal squamous cell carcinoma were enrolled, and underwent cine MRI of oesophageal tumours. The maximum displacements in the anterior-posterior (A-P), superior-inferior (S-I), and left-right (L-R) directions of the tumours were assessed statistically to show their associations with tumour location. RESULTS: Tumour motion in A-P and S-I directions increased from upper to lower oesophagus (r=0.505, p=0.003; and r=0.600, p<0.001, respectively). In A-P and S-I directions, tumours showed larger motion in the lower oesophagus than in the upper or middle oesophagus (all p<0.05). Motion of middle and lower oesophageal tumours in the S-I direction was larger than in L-R or A-P direction (all p<0.05). To provide 95% geometric coverage for the motion of upper oesophageal tumours, statistical analysis showed margins of 3.75 mm in L-R direction, 3.72 mm in A-P direction, and 5.38 mm in S-I direction. For the motion of tumours of the middle oesophagus, 95% coverage required margins of 8.50, 6.62, and 11.96 mm in L-R, A-P, and S-I directions, respectively, and for lower oesophageal tumours, 95% coverage required margins of 9.17, 9.68, and 12.98 mm in L-R, A-P, and S-I direction, respectively. CONCLUSION: Oesophageal tumour motion in different directions can be associated with tumour location as shown on cine MRI, suggesting that the present findings could be helpful for better understanding oesophageal tumour motion and gating individualised radiation delivery strategies.

A kilonova as the electromagnetic counterpart to a gravitational-wave source.

Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

Systemic therapies for recurrent or metastatic nasopharyngeal carcinoma: a systematic review.

BACKGROUND: The majority of published studies in recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) are single-arm trials. Reliable modelling of progression-free survival (PFS) and overall survival (OS) outcomes, therefore, is difficult. This study aim to analyse existent literature to estimate the relative efficacy of available systemic regimens in RM-NPC, as well as provide estimates of aggregate OS and PFS. METHODS: We conducted a systematic search of MEDLINE, EMBASE and the Cochrane Library to March 2015. Clinical trials (in English only) investigating cytotoxic and molecularly targeted agents in adult patients with RM-NPC were included. All relevant studies were assessed for quality using Downs and Blacks (DB) checklist (maximum quality score of 27). Aggregate data analysis and Student's t-test were performed for all identified studies (model A). For studies that published analysable Kaplan-Meier curves, survival data were extracted and marginal proportional hazards models were constructed (model B). RESULTS: A total of 56 studies were identified and included in model A, 26 of which had analysable Kaplan-Meier curves and were included in model B. The 26 studies in model B had significantly higher mean DB scores than the remaining 30 (17.3 vs 13.7, P=0.002). For patients receiving first line chemotherapy, the estimated median OS was 15.7 months by model A (95% CI, 12.3-19.1), and 19.3 months by model B (95% CI, 17.6-21.1). For patients undergoing second line or higher therapies (2nd+), the estimated median OS was 11.5 months by model A (95% CI 10.1-12.9), and 12.5 months by model B (95% CI 11.9-13.4). PFS estimates for patients undergoing first-line chemotherapy by model A was 7.6 months (95% CI, 6.2-9.0), and 8.0 months by model B (95% CI, 7.6-8.8). For patients undergoing therapy in the 2nd+ setting, the estimated PFS by model A was 5.4 months (95% CI, 3.8-7.0), and 5.2 months by model B (95% CI, 4.7-5.6). CONCLUSIONS: We present the first aggregate estimates of OS and PFS for RM-NPC patients receiving first and second-line or higher treatment settings, which could inform the design of future clinical trials in this disease setting.

Semi-quantitative assessment of the presence and Child-Pugh class of hepatitis B related cirrhosis by using liver lobe-based dynamic contrast-enhanced MRI.

AIM: To determine whether liver lobe-based DCE-MRI can be used to detect the presence and Child-Pugh class of hepatitis B-related cirrhosis. MATERIALS AND METHODS: Fifty-six cirrhotic patients with hepatitis B and 20 healthy participants underwent liver DCE-MRI, and the positive enhancement integral (PEI), time to peak (TTP), maximum slope of increase (MSI) and maximum slope of decrease (MSD) of the left lateral liver lobe (LLL), left medial liver lobe (LML), right liver lobe (RL), and caudate lobe (CL) were measured and analysed statistically to evaluate cirrhosis. RESULTS: TTP values of the LLL, LML, RL and CL were positively correlated with the Child-Pugh class of cirrhosis (r=0.452 to 0.55, all p<0.05). PEI values of the LLL, LML, RL and CL, as well as the MSI of the CL and the MSD of the RL, were inversely correlated with the Child-Pugh class (r=-0.349 to -0.72, all p<0.05). PEI values of the LLL and CL, or TTP values of the RL had the most area under receiver operating characteristic curve (AUC) of 0.99 for identifying the presence of liver cirrhosis. The PEI of the RL had the largest AUC of 0.975 and 0.78 for distinguishing the Child-Pugh class A of cirrhosis from class B-C and class A-B of cirrhosis from class C, respectively. CONCLUSION: Liver lobe-based DCE-MRI parameters are associated with the presence and Child-Pugh class of hepatitis B-related cirrhosis.

Impact of mTOR Inhibitors on Cancer Development in Kidney Transplantation Recipients: A Population-Based Study.

BACKGROUND: The mammalian target of rapamycin (mTOR) inhibitor is an immunosuppressive drug used in kidney transplantation. Whether the mTOR inhibitor is associated with reduced risk of cancer development and mortality after kidney transplantation is controversial. METHODS: We conducted a nationwide population-based study. Patients who did not have malignancy history and received kidney transplantation between 2010 and 2013 were enrolled. Recipients who had mTOR inhibitors (n = 430) for more than 30 days comprised the study group; 1720 recipients who did not have mTOR inhibitors comprised the control group. The primary outcome is the development of cancer after kidney transplantation. These patients were followed until the first-time admission with diagnosis of cancer, death, or the end of 2014. A Cox proportional-hazard model was used to determine the risk of cancer development and all-cause mortality. RESULTS: During the 35-month median duration of observation, there were 16 and 61 patients with cancer development in the study group and the control group, respectively. The cancer incidence was 12.8 and 12.4 per 1000 person-years. There were 10 and 135 mortality cases, with the incidence rate of 7.8 and 26.9 per 1000 person-years. After multivariable adjustment, the mTOR inhibitors users were not associated with reduced risk of new cancer development as compared with control (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.46-1.60; P = .63), nor risk of all-cause mortality (HR, 0.70; 95% CI, 0.33-1.46; P = .34). CONCLUSIONS: The use of mTOR inhibitors was not associated with a reduction in the risk of cancer development and all-cause mortality in kidney transplantation recipients.

How to Improve the Positive Predictive Value of Urinary Decoy Cell Surveillance for Polyomavirus BK-Associated Nephropathy in Kidney Transplant Patients.

BACKGROUND: Polyomavirus BK-associated nephropathy (BKVN) has been a serious problem after kidney transplantation. Detection of urinary decoy cells (UDCs) and assessment of polyomavirus BK nucleic acids by polymerase chain reactions (PCRs) are currently used, noninvasive tests. PCRs have better positive predictive value (PPV) but higher cost and lower accessibility. This study investigated ways to improve the PPV of UDCs for BKVN prediction. METHODS: From 2000 to 2013, kidney transplant recipients with sustained UDCs for more than half a month and who had received allograft biopsies were enrolled. We analyzed the PPV of UDCs for BKVN with 2 variables: (i) the percentage changes in serum creatinine (SCr) levels and (ii) the duration of sustained UDCs by receiver operating characteristic (ROC) curve analysis; we predicted the percentage changes in SCr levels with the corresponding PPV using a linear regression model. RESULTS: BKVN was diagnosed in 26 of 68 enrolled patients. The percentage changes in SCr levels significantly deteriorated in the BKVN group during 1-2 months of UDC positivity. According to ROC curve analysis, percentage changes in SCr levels had a significant discriminating power for BKVN during 1-1.5 month, and if the percentage changes in SCr levels were >19%, the PPV of UDCs for BKVN was 50%. CONCLUSIONS: An UDC surveillance program is a judicious strategy to predict BKVN in kidney transplant patients, particularly when graft renal function shows deterioration after 1 month of UDC positivity.

Levels of F2-isoprostanes, F4-neuroprostanes, and total nitrate/nitrite in plasma and cerebrospinal fluid of patients with traumatic brain injury.

Several events occurring during the secondary damage of traumatic brain injury (TBI) can cause oxidative stress. F(2)-isoprostanes (F(2)-IsoPs) and F(4)-neuroprostanes (F(4)-NPs) are specific lipid peroxidation markers generated from arachidonic acid and docosahexaenoic acid, respectively. In this study, we evaluated oxidative stress in patients with moderate and severe TBI. Since sedatives are routinely used to treat TBI patients and propofol has been considered an antioxidant, TBI patients were randomly treated with propofol or midazolam for 72 h postoperation. We postoperatively collected cerebrospinal fluid (CSF) and plasma from 15 TBI patients for 6-10 d and a single specimen of CSF or plasma from 11 controls. Compared with the controls, the TBI patients exhibited elevated levels of F(2)-IsoPs and F(4)-NPs in CSF throughout the postsurgery period regardless of the sedative used. Compared with the group of patients who received midazolam, those who received propofol exhibited markedly augmented levels of plasma F(2)-IsoPs, which were associated with higher F(4)-NPs levels and lower total nitrate/nitrite levels in CSF early in the postsurgery period. Furthermore, the higher CSF F(2)-IsoPs levels correlated with 6-month and 12-month worse outcomes, which were graded according to the Glasgow Outcome Scale. The results demonstrate enhanced oxidative damage in the brain of TBI patients and the association of higher CSF levels of F(2)-IsoPs with a poor outcome. Moreover, propofol treatment might promote lipid peroxidation in the circulation, despite possibly suppressing nitric oxide or peroxynitrite levels in CSF, because of the increased loading of the lipid components from the propofol infusion.

A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors.

BACKGROUND: There are limited data about the quality of immune-related adverse event (irAE) reporting in immune checkpoint inhibitor (ICI) clinical trial publications. METHODS: A systematic search of citations from Medline, EMBASE and Cochrane databases identified prospective clinical trials involving ICIs in advanced solid tumors from 2003 to 2013. A 21-point quality score (QS) was adapted from the CONSORT harms extension statement. Linear regression was used to identify factors associated with quality reporting. RESULTS: After a review of 2628 articles, 50 trial reports were included, with ICIs as either monotherapy (54%) or part of a combination regimen (46%). The mean QS was 11.21 points (range 3.50-17.50 points). The median grade 3/4 AE rate reported was 21% (range 0%-66%) and 29/50 (58%) trials concluded that irAEs were tolerable. Multivariate regression analysis revealed that year of publication (within last 5 years, P = 0.01) and journal impact factor >15 (P = 0.004) were associated with higher QS. Complete reporting of specific characteristics of irAEs including onset, management and reversibility were reported by 14%, 8% and 6% of studies, respectively. The incidence of grade 3/4 adverse events was higher for inhibitors against CTLA-4 compared with other immune checkpoints (P < 0.001). CONCLUSIONS: The reporting of irAEs is suboptimal. A standardized reporting method of irAEs that accounts for tolerability, management and reversibility is needed and would enable a more precise evaluation of the therapeutic risk benefit ratio of ICIs.

Advanced age is not a contraindication for liver resection in cases of large hepatocellular carcinoma.

BACKGROUND: The role of surgery in the management of large hepatocellular carcinomas (HCCs) is controversial. Advanced age and comorbidities are taken into account when major surgery is considered. PURPOSE: To compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) for resectable HCC in patients aged 70 years or older. PATIENTS AND MATERIALS: This study included 70 patients aged 70 years or older treated for large HCCs (≥5 cm) between January 2007 and December 2012: 37 underwent LR and 33 underwent TACE. The outcomes of these patients were retrospectively analyzed. Univariate and multivariate Cox proportional hazard models were established. Kaplan-Meier survival curves were generated, and survival data were compared using the log-rank test. RESULTS: Hospital stay was significantly longer in the LR group than in the TACE group (10 days vs 8.5 days; P = 0.003). Treatment-related complications were more frequent in the TACE group, but this difference was not statistically significant. LR was associated with a better disease-free survival rate, median survival rate and cumulative overall survival rate. CONCLUSION: Our results showed that LR could be a safe and effective treatment option for HCC tumors ≥5 cm in patiets aged 70 years or older.

Slowly fading super-luminous supernovae that are not pair-instability explosions.

Super-luminous supernovae that radiate more than 10(44) ergs per second at their peak luminosity have recently been discovered in faint galaxies at redshifts of 0.1-4. Some evolve slowly, resembling models of 'pair-instability' supernovae. Such models involve stars with original masses 140-260 times that of the Sun that now have carbon-oxygen cores of 65-130 solar masses. In these stars, the photons that prevent gravitational collapse are converted to electron-positron pairs, causing rapid contraction and thermonuclear explosions. Many solar masses of (56)Ni are synthesized; this isotope decays to (56)Fe via (56)Co, powering bright light curves. Such massive progenitors are expected to have formed from metal-poor gas in the early Universe. Recently, supernova 2007bi in a galaxy at redshift 0.127 (about 12 billion years after the Big Bang) with a metallicity one-third that of the Sun was observed to look like a fading pair-instability supernova. Here we report observations of two slow-to-fade super-luminous supernovae that show relatively fast rise times and blue colours, which are incompatible with pair-instability models. Their late-time light-curve and spectral similarities to supernova 2007bi call the nature of that event into question. Our early spectra closely resemble typical fast-declining super-luminous supernovae, which are not powered by radioactivity. Modelling our observations with 10-16 solar masses of magnetar-energized ejecta demonstrates the possibility of a common explosion mechanism. The lack of unambiguous nearby pair-instability events suggests that their local rate of occurrence is less than 6 × 10(-6) times that of the core-collapse rate.