Sex-specific, non-linear and congener-specific association between mixed exposure to polychlorinated biphenyls (PCBs) and diabetes in U.S. adults.

BACKGROUND: Whether and to what extent the impact of exposure to various polychlorinated biphenyls (PCBs) congeners on diabetes, as well as the important contributors, have remained unclear. OBJECTIVE: We aimed to investigate the association patterns between PCBs mixture and diabetes, identify the critical congeners, and explore the potential modifiers. METHODS: The present study included 5900 U.S. adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016. Weighted logistic regression, restricted cubic spline regression, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were applied to estimate the linear and non-linear associations of single and mixed PCB exposure with diabetes. Subgroup analyses were also conducted to explore potential sex differences. RESULTS: In the weighted logistic regression model, total PCBs were positively associated with diabetes (OR = 1.33, P < 0.025), and significant non-linear associations were observed using RCS analyses. The non-linear positive association between PCBs mixed exposure and diabetes was likewise found in the WQS and BKMR results. PCB180, PCB194, PCB196, and PCB167 were with the highest weights in the WQS, and PCB209 and PCB66 were with the highest posterior inclusion probabilities in the BKMR. Additionally, exposure to total PCBs and most of individual PCB congeners were significantly associated with elevated risk of in females (OR = 1.74; P for trend < 0.001), while fewer significant associations were observed in males. CONCLUSION: The present study highlighted the importance of the long-term surveillance of PCBs and the need to enhance protective measures against them. Notably, these associations were non-linear, congener-specific, and significantly stronger in females than males, especially at relatively high levels of PCBs exposure. Further prospective and mechanistic studies were warranted to ascertain the causal effects between PCBs mixture and diabetes.

Progression of Polypoidal Lesions Associated with Exudative Recurrence in Polypoidal Choroidal Vasculopathy.

PURPOSE: To investigate the characteristics of the branching vascular network (BVN) and polypoidal lesions in polypoidal choroidal vasculopathy (PCV) to determine near-term indicators that may predict exudative recurrence. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with PCV receiving anti-vascular endothelial growth factor (VEGF) monotherapy or anti-VEGF plus photodynamic therapy were followed for at least 1 year using swept-source OCT angiography (SS-OCTA) imaging. METHODS: Patients were divided into 2 groups based on whether exudative recurrence occurred during follow-up. Multiple parameters were collected and compared between the 2 groups, such as age, gender, visual acuity, number of polypoidal lesions, lesion area at the first SS-OCTA visit, and total lesion area change from the first SS-OCTA visit to the last SS-OCTA visit. To evaluate the association between SS-OCTA imaging-based risk factors and the exudative recurrences, imaging features associated with PCV such as BVN growth and polypoidal lesion progression (enlargement, new appearance, and reappearance) at each follow-up visit were analyzed. The time intervals from the nonexudative visit with lesion progression to the corresponding exudative recurrence visit were documented to explore their association with exudative recurrences. Cox regression and logistic regression analyses were used. MAIN OUTCOME MEASURES: Association between BVN growth and polypoidal lesion progression with exudative recurrence. RESULTS: Thirty-one eyes of 31 patients (61% men) were included. Sixteen eyes had no recurrence of exudation, and 15 eyes had recurrence during follow-up. The average follow-up duration was 20.55 ± 6.86 months (range, 12-36 months). Overall, the recurrence group had worse best-corrected visual acuity (P = 0.019) and a greater increase in lesion area (P = 0.010). Logistical regression analysis showed that polypoidal lesion progression, including new appearance, enlargement, and reappearance of polypoidal lesions, was associated with exudative recurrences within 3 months (odds ratio, 26.67, 95% confidence interval, 3.77-188.54, P = 0.001). CONCLUSIONS: Growth of nonexudative BVN and progression of polypoidal lesions were found to be lesion characteristics associated with exudative recurrences, and progression of polypoidal lesions might serve as a stand-alone indicator for the near-term onset of exudation. In PCV, more frequent follow-up visits are recommended when polypoidal lesions show progression.

Residential greenness exposure and decreased prevalence of diabetic retinopathy: A nationwide analysis in China.

OBJECTIVE: Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness among diabetics. We aimed to explore whether long-term exposure to residential greenness was beneficial to DR. RESEARCH DESIGN AND METHODS: We used data from a large-scale, cross-sectional screening survey conducted in 129 cities of 27 provincial regions of China from 2018 to 2021 among patients with diabetes. We measured residential greenness exposure as the 3-year average of annual maximum Normalized Difference Vegetation Index (NDVI) at a spatial resolution of 250 m. DR was assessed by ophthalmologists based on fundus photographs. The primary outcome was DR, and secondary outcome included DR severity status (i.e., nonproliferative and proliferative), hallmarks of retinal lesions and macular oedema. RESULTS: A total of 484,380 adult participants with diabetes were included in the current analysis, and 15.7% of them were diagnosed with DR. NDVI was inversely and linearly associated with DR prevalence, and an increment of 0.1 NDVI was associated with a 10% (9%-10%) decrease in DR prevalence. Significant and inverse associations were further found for nonproliferative and proliferative DR, hallmarks of lesions and macular oedema. The association between greenness and DR was stronger among participants who were older, obese, lived in the south, had longer duration of diabetes or did not take antidiabetic medications. CONCLUSIONS: This large-scale nationwide study provides the first-hand epidemiological evidence on the associations of residential greenness with DR. Our findings highlight the importance of residential greenness in alleviating DR risk especially in an era of aging and urbanization.

THE REPORTING QUALITY OF NONINFERIORITY TRIALS USING INTRAVITREAL VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS.

PURPOSE: Noninferiority trials (NIFTs) are widely used to study intravitreal vascular endothelial growth factor inhibitors for the treatment of ocular diseases. Thus, this trial design deserves greater attention. We aimed to comprehensively assess the methodological and reporting quality of NIFTs in the field of neovascular ocular diseases. METHODS: We identified NIFTs using antivascular endothelial growth factor agents published before February 2020 from PubMed and Web of Science. Two independent authors extracted and double-checked predefined elements related to the quality of design and reporting. The characteristics and reporting of NIFTs were described with frequencies and percentages. We summarized important factors that were potentially biased the results of NIFTs and provided point-to-point recommendations. RESULTS: In total, 34 studies involving 15,190 subjects and 51 pairs of noninferiority comparisons were identified. Areas of concern that could potentially affect the qualities of NIFTs included the absence of justification for the selection of noninferiority margins (61.8%), the use of unusually wide noninferiority margins (26.5%), the lack of outcome confirmation provided by the intention-to-treat and per-protocol analyses (64.7%), the presence of postrandomization exclusions >10% (52.9%), and not declaring the compensatory benefits (35.3%). Moreover, industry-sponsored NIFTs were more likely to draw positive results (P = 0.036). CONCLUSION: NIFTs of antivascular endothelial growth factor therapies commonly achieved noninferiority of the tested intervention. However, the methodologies and reporting limitations may affect the confidence of the results. Thus, more awareness must be created among investigators for better adherence to guidelines and recommendations while designing, conducting, and reporting on NIFTs.

OUTER RETINAL TUBULATION IN BIETTI CRYSTALLINE DYSTROPHY ASSOCIATED WITH THE RETINAL PIGMENT EPITHELIUM ATROPHY.

PURPOSE: To determine the prognostic value of outer retinal tubulation (ORT) in the eyes of a Chinese cohort with Bietti crystalline dystrophy (BCD). METHODS: This retrospective, multicenter cohort study enrolled 42 patients with clinically and genetically diagnosed BCD. Eighty eyes with good-quality images of spectral domain optical coherence tomography were included. Demographic details and clinical data were collected. The characteristics of ORT, including prevalence, location, and morphologic characteristics were analyzed. RESULTS: Forty-two patients with BCD harbored potentially CYP4V2 disease-causing mutations. The mutation spectrum comprised 17 unique variants, 9 of which were novel. Fifty-two of these 80 eyes demonstrated evidence of ORT. The incidence of ORT is significantly higher in Stage 2 than other stages ( P < 0.001). ORT was mainly bilateral and located at the margin of the atrophic area of retinal pigment epithelium (RPE), and dynamically changed with the progressive RPE atrophy. The process of RPE atrophy was slower in eyes with ORT ( P = 0.017), with significantly longer intact RPE width in Stage 3 ( P = 0.024). Eyes with ORT had slower vision loss than eyes without ORT ( P = 0.044). CONCLUSION: ORT may be a sign of the onset of RPE atrophy in early-stage BCD and may suggest less risk of rapid progression in late-stage BCD.

Changes of serum metabolites levels during neoadjuvant chemoradiation and prediction of the pathological response in locally advanced rectal cancer.

INTRODUCTION: Previous studies have explored prediction value of serum metabolites in neoadjuvant chemoradiation therapy (NCRT) response for rectal cancer. To date, limited literature is available for serum metabolome changes dynamically through NCRT. OBJECTIVES: This study aimed to explore temporal change pattern of serum metabolites during NCRT, and potential metabolic biomarkers to predict the pathological response to NCRT in locally advanced rectal cancer (LARC) patients. METHODS: Based on dynamic UHPLC-QTOF-MS untargeted metabolomics design, this study included 106 LARC patients treated with NCRT. Biological samples of the enrolled patients were collected in five consecutive time-points. Untargeted metabolomics was used to profile serum metabolic signatures from LARC patients. Then, we used fuzzy C-means clustering (FCM) to explore temporal change patterns in metabolites cluster and identify monotonously changing metabolites during NCRT. Repeated measure analysis of variance (RM-ANOVA) and multilevel partial least-squares discriminant analysis (ML-PLS-DA) were performed to select metabolic biomarkers. Finally, a panel of dynamic differential metabolites was used to build logistic regression prediction models. RESULTS: Metabolite profiles showed a clearly tendency of separation between different follow-up panels. We identified two clusters of 155 serum metabolites with monotonously changing patterns during NCRT (74 decreased metabolites and 81 increased metabolites). Using RM-ANOVA and ML-PLS-DA, 8 metabolites (L-Norleucine, Betaine, Hypoxanthine, Acetylcholine, 1-Hexadecanoyl-sn-glycero-3-phosphocholine, Glycerophosphocholine, Alpha-ketoisovaleric acid, N-Acetyl-L-alanine) were further identified as dynamic differential biomarkers for predicting NCRT sensitivity. The area under the ROC curve (AUC) of prediction model combined with the baseline measurement was 0.54 (95%CI = 0.43 ~ 0.65). By incorporating the variability indexes of 8 dynamic differential metabolites, the prediction model showed better discrimination performance than baseline measurement, with AUC = 0.67 (95%CI 0.57 ~ 0.77), 0.64 (0.53 ~ 0.75), 0.60 (0.50 ~ 0.71), and 0.56 (0.45 ~ 0.67) for the variability index of difference, linear slope, ratio, and standard deviation, respectively. CONCLUSION: This study identified eight metabolites as dynamic differential biomarkers to discriminate NCRT-sensitive and resistant patients. The changes of metabolite level during NCRT show better performance in predicting NCRT sensitivity. These findings highlight the clinical significance of metabolites variabilities in metabolomics analysis.

Who really benefits from intraperitoneal chemotherapy for advanced ovarian cancer? A treatment-free survival analysis of the AICE trial.

OBJECTIVE: To investigate whether peritoneal disease extent can predict the survival benefit of intraperitoneal/intravenous (IP/IV) chemotherapy in ovarian cancer. DESIGN: A treatment-free survival (TFS) analysis. SETTING: Five-centre trial. POPULATION: An extended follow-up of the Additional Intraperitoneal Cisplatin and Etoposide in ovarian cancer (AICE) trial (NCT01669226), with data cut-off on 27 August 2020. Patients were categorised into subgroups with high tumour burden (HTB) and low tumour burden (LTB). METHODS: Overall survival (OS) was divided into time on protocol treatment exposure (T), time free of subsequent treatment or death (TFS) and time after the first subsequent therapy (REL). TFS analyses and quality-adjusted OS were calculated by multiplying the mean time in each health state by its assigned utility: quality-adjusted OS = ut  × T + TFS + urel  × REL. MAIN OUTCOME MEASURES: The area under each Kaplan-Meier curve was estimated using the 96-month restricted mean time, with threshold utility analyses used to illustrate quality-adjusted OS comparisons. RESULTS: In the HTB subgroup, the restricted mean TFS was 33.9 months and 18.7 months in the IP/IV and IV groups, respectively (p = 0.005), with a significant quality-adjusted OS gain (13.2-16.0 months). In the LTB subgroup, IP/IV therapy yielded no survival benefit in either TFS (p = 0.268) or quality-adjusted OS (range: 1.4-6.3 months). CONCLUSIONS: Both TFS and quality-adjusted OS was longer across all utility weight values with IP/IV than with standard IV therapy in the HTB subgroup, whereas patients in the LTB subgroup did not benefit from the therapy. The tumour burden of ovarian cancer should be assessed before deciding on IP/IV versus IV treatment.

Status of visual impairment among children with special needs in rural China.

Introduction Previous studies have reported a high prevalence of visual defects in children with special needs. However, routine ocular examinations for these children in rural areas of China are lacking. This study aimed to evaluate the status of visual impairment (VI) in children at special education schools in rural China. Methods A total of 316 students from two special schools in Zunyi city, Guizhou province, were enrolled. Full ophthalmic examinations were performed, and gene-sequencing services were offered to potential patients. Results The mean age of the 316 participants was 12.27±3.49 years, and 75 showed abnormal ophthalmic manifestations on slit-lamp examination. Visual acuity (VA) was assessed in 232 eyes, and the mean VA (logarithm of the minimum angle of resolution, logMAR) was 0.27±0.34. Whole-exome sequencing (WES) identified 19 mutations in these children, which might explain their visual complaints. Children with Down syndrome had a significantly higher prevalence of ocular disorders than those without. Conclusion VI is common among children at special education schools in rural areas; however, routine screening and effective interventions have not been consistently implemented. Efforts should be made to address this issue in these already disadvantaged children.

Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: The benefits of secondary cytoreduction for platinum-sensitive relapsed ovarian cancer are still widely debated. We aimed to assess the efficacy of secondary cytoreduction plus chemotherapy versus chemotherapy alone in this patient population. METHODS: This multicentre, open-label, randomised, controlled, phase 3 trial (SOC-1), was done in four primarily academic centres in China (two in Shanghai, one in Hangzhou, and one in Guangzhou). Eligible patients were women aged 18 years and older with platinum-sensitive relapsed epithelial ovarian cancer with a platinum-free interval of at least 6 months after the end of first-line platinum-based chemotherapy and were predicted to have potentially resectable disease according to the international model (iMODEL) score and PET-CT imaging. iMODEL score was calculated using six variables: International Federation of Gynecology and Obstetrics stage, residual disease after primary surgery, platinum-free interval, Eastern Cooperative Oncology Group performance status, serum level of cancer antigen 125 at recurrence, and presence of ascites at recurrence. An iMODEL score of 4·7 or lower predicted a potentially complete resection. As per a protocol amendment, patients with an iMODEL score of more than 4·7 could only be included if the serum level of cancer antigen 125 was more than 105 U/mL, but the principal investigators assessed the disease to be resectable by PET-CT. Eligible participants were randomly assigned (1:1) via a permuted block design (block size of six) and stratified by study centre, iMODEL score, residual disease at primary surgery, and enrolment in the Shanghai Gynecologic Oncology Group SUNNY trial, to undergo secondary cytoreductive surgery followed by intravenous chemotherapy (six 3-weekly cycles of intravenous paclitaxel [175 mg/m2] or docetaxel [75 mg/m2] combined with intravenous carboplatin [area under the curve of 5 mg/mL per min]; surgery group) or intravenous chemotherapy alone (no surgery group). Primary endpoints were progression-free survival and overall survival, analysed in all participants randomly assigned to treatment, regardless of treatment received (intention-to-treat [ITT] population). Here, we report the final analysis of progression-free survival and the prespecified interim analysis of overall survival. Safety was assessed in all participants who received their assigned treatment and had available adverse event data. This study is registered with ClinicalTrials.gov, NCT01611766, and is ongoing but closed to accrual. FINDINGS: Between July 19, 2012, and June 3, 2019, 357 patients were recruited and randomly assigned to the surgery group (182) or the no surgery group (175; ITT population). Median follow-up was 36·0 months (IQR 18·1-58·3). In the no surgery group, 11 (6%) of 175 participants had secondary cytoreduction during second-line therapy while 48 (37%) of 130 participants who had disease progression crossed-over and had surgery at a subsequent recurrence. Median progression-free survival was 17·4 months (95% CI 15·0-19·8) in the surgery group and 11·9 months (10·0-13·8) in the no surgery group (hazard ratio [HR] 0·58; 95% CI 0·45-0·74; p<0·0001). At the interim overall survival analysis, median overall survival was 58·1 months (95% CI not estimable to not estimable) in the surgery group and 53·9 months (42·2-65·5) in the no surgery group (HR 0·82, 95% CI 0·57-1·19). In the safety population, nine (5%) of 172 patients in the surgery group had grade 3-4 surgical morbidity at 30 days, and no patients in either group had died at 60 days after receiving assigned treatment. The most common grade 3-4 adverse events during chemotherapy were neutropenia (29 [17%] of 166 patients in the surgery group vs 19 [12%] of 156 patients in the no surgery group), leucopenia (14 [8%] vs eight [5%]), and anaemia (ten [6%] vs nine [6%]). Four serious adverse events occurred, all in the surgery group. No treatment-related deaths occurred in either group. INTERPRETATION: Secondary cytoreduction followed by chemotherapy was associated with significantly longer progression-free survival than was chemotherapy alone in patients with platinum-sensitive relapsed ovarian cancer, and patients should be counselled about the option of secondary cytoreduction in specialised centres. Long-term survival outcomes will be assessed using mature data on overall survival. FUNDING: Zhongshan Development Program. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Second Primary Malignancies in Patients with Colorectal Cancer: A Population-Based Analysis.

PURPOSE: This study aimed to profile the characteristics of patients with colorectal cancer (CRC) with a second primary malignancy (SPM) and to identify patients with CRC at high risk of developing SPMs. METHODS: We retrospectively reviewed data on patients with CRC aged 20-79 years from the Surveillance, Epidemiology, and End Results (SEER) database. Eligible patients were categorized into only one primary malignancy and SPM cohorts. A competing-risk model was used to quantify associations between SPM occurrence and the multiple traits of patients. Finally, a decision curve analysis (DCA) was used to evaluate the clinical usefulness of the model by calculating net benefit. RESULTS: A total of 179,884 patients were identified, 18,285 (10.2%) of whom developed SPMs during a maximum follow-up of approximately 18 years. The median survival time after the second diagnosis was less than 4 years. The 3-year, 5-year, and 10-year cumulative risks of developing an SPM were 3.9%, 5.9%, and 10.0%, respectively. According to the multivariable competing-risk model, male colon cancer survivors, older in age, with a well-differentiated tumor and localized disease, who were treated with surgery were susceptible to SPMs. The DCA yielded a wide range of risk thresholds at which the net benefits would be obtained from our proposed model. CONCLUSION: CRC survivors remain at high risk of developing SPMs. Patients with a second diagnosis of cancer showed not only significantly worse survival but also higher cancer-specific mortality. A web-based individualized predictive tool was also provided to assist clinicians in identifying patients at high risk of developing SPMs and planning their future care management. IMPLICATIONS FOR PRACTICE: Colorectal cancer survivors remain at high risk of developing a second primary malignancy (SPM). This study aimed to profile the characteristics of patients with colorectal cancer with second primary malignancies and to further explore the risk factors related to the development of second primary malignancies, using a large population-based cohort. A clinically useful competing-risk nomogram was developed to predict the risk of SPMs based on individual clinical factors. According to the findings, older age, male sex, white or black race, localized disease, and treatment with surgery among patients with colon cancer were associated with an increased risk of developing an SPM. These findings and the proposed tool could be useful to clinicians and caregivers in the clinical counseling of patients with colorectal cancer and the development of long-term care management.

Survival benefits of dose-dense early postoperative intraperitoneal chemotherapy in front-line therapy for advanced ovarian cancer: a randomised controlled study.

Dose-dense early postoperative intraperitoneal chemotherapy (DD-EPIC) significantly increased non-progression rate in advanced ovarian cancer (OC) patients. We report final overall survival (OS) results to further strengthen the efficacy of DD-EPIC in the front-line therapy. In this phase 2 trial, 218 patients with FIGO IIIC-IV OC were randomly allocated to receive DD-EPIC followed by intravenous (IV) chemotherapy (DD-EPIC group), or IV chemotherapy alone (IV group). The study was prespecified to detect differences in progression-free survival (PFS) and OS. At a median follow-up period of 69.1 months, the median OS was 67.5 and 46.3 months in the DD-EPIC and IV group, respectively. The probability rate of OS at 5 years was 61.0% with DD-EPIC, and 38.2% with IV (hazard ratio [HR] for death from OC, 0.70; 95% confidence interval [CI], 0.49-1.00). DD-EPIC was associated with a prolonged PFS compared with the IV group (the estimated rate of PFS at 5 years, 26.0% vs. 8.5%; HR for disease progression, 0.64; 95% CI, 0.47-0.86). DD-EPIC was associated with a longer OS than IV chemotherapy alone. It may be considered as a valuable option of the front-line therapy for advanced ovarian cancer.Trial registration: ClinicalTrials.gov, NCT01669226 (date of registration: August 20, 2012).

Nomogram-based parameters to predict overall survival in a real-world advanced cancer population undergoing palliative care.

BACKGROUND: Although palliative care has been accepted throughout the cancer trajectory, accurate survival prediction for advanced cancer patients is still a challenge. The aim of this study is to identify pre-palliative care predictors and develop a prognostic nomogram for overall survival (OS) in mixed advanced cancer patients. METHODS: A total of 378 consecutive advanced cancer patients were retrospectively recruited from July 2013 to October 2015 in one palliative care unit in China. Twenty-three clinical and laboratory characters were collected for analysis. Prognostic factors were identified to construct a nomogram in a training cohort (n = 247) and validated in a testing cohort (n = 131) from the setting. RESULTS: The median survival time was 48.0 (95% CI: 38.1-57.9) days for the training cohort and 52.0 (95% CI: 34.6-69.3) days for the validation cohort. Among pre-palliative care factors, sex, age, tumor stage, Karnofsky performance status, neutrophil count, hemoglobin, lactate dehydrogenase, albumin, uric acid, and cystatin-C were identified as independent prognostic factors for OS. Based on the 10 factors, an easily obtained nomogram predicting 90-day probability of mortality was developed. The predictive nomogram had good discrimination and calibration, with a high C-index of 0.76 (95% CI: 0.73-0.80) in the development set. The strong discriminative ability was externally conformed in the validation cohort with a C-index of 0.75. CONCLUSIONS: A validated prognostic nomogram has been developed to quantify the risk of mortality for advanced cancer patients undergoing palliative care. This tool may be useful in optimizing therapeutic approaches and preparing for clinical courses individually.

Addition of intraperitoneal cisplatin and etoposide to first-line chemotherapy for advanced ovarian cancer: a randomised, phase 2 trial.

BACKGROUND: We assessed the efficacy of adding intraperitoneal (IP) chemotherapy to standard first-line intravenous (IV) chemotherapy in epithelial ovarian cancer (EOC) patients. METHODS: Patients with stage IIIC-IV EOC who underwent optimal debulking surgery were randomly assigned to four cycles of weekly IP chemotherapy with cisplatin (50 mg/m2) and etoposide (100 mg/m2) followed by six cycles of IV chemotherapy every 3 weeks (IP/IV arm), or were administered IV chemotherapy alone (IV arm). The primary endpoint for this study was the 12-month non-progression rate (NPR). RESULTS: Between 4/2009 and 9/2015, 218 patients were randomised, of whom 215 initiated treatment. In the IP/IV arm, 90.6% of patients completed 4 cycles of IP chemotherapy. The 12-month NPRs were 81.9% and 64.2% in the IP/IV and IV groups, respectively (HR 0.48 (95% CI 0.27-0.82)). The median progression-free survival (PFS) was increased in the IP/IV arm compared with that in the IV arm (22.4 vs. 16.8 months; HR 0.66 (0.48-0.91)) and in a subgroup with no gross cytoreduction (31.1 vs. 16.8 months; HR 0.46 (0.26-0.82)). Similar findings were detected with regard to time to first subsequent anticancer therapy (TFST) (25.9 vs. 18.0 months; P = 0.009) and time to second subsequent anticancer therapy (TSST) (40.8 vs. 30.1 months; P = 0.042). Grade 3/4 leukopenia, anaemia and gastrointestinal events were more common in the IP/IV arm, but the treatment burden was considered acceptable. CONCLUSIONS: IP chemotherapy prior to IV chemotherapy was associated with an increased 12-month NPR and a longer TSST than IV alone in patients with EOC, albeit with acceptable toxic effects. Long-term follow-up is warranted to identify the effects of IP therapy on overall survival.

Extended Right Thoracic Approach Compared With Limited Left Thoracic Approach for Patients With Middle and Lower Esophageal Squamous Cell Carcinoma: Three-year Survival of a Prospective, Randomized, Open-label Trial.

OBJECTIVE: To investigate whether survival is improved by using the right thoracic approach (extended lymphadenectomy) compared with the left thoracic approach (limited lymphadenectomy) for esophageal cancer. BACKGROUND: The optimal surgical technique for esophageal cancer remains unclear. METHODS: Between May 2010 and July 2012, 300 patients with middle and lower thoracic esophageal carcinoma were randomized to receive esophagectomy through either the right or left thoracic approach. Of these, 286 patients with squamous cell carcinoma determined by postoperative pathology were included in this analysis. Disease-free survival (DFS) and overall survival (OS) were compared between the right (n = 146) and left thoracic groups (n = 140). RESULTS: The median follow-up was 55.9 months [95% confidence interval (CI): 53.1-58.6]. The 3-year DFS rates were 62% and 52% in the right and left thoracic arms, respectively [hazard ratio (HR) 0.709; 95% CI, 0.506-0.995; P = 0.047, log-rank test]. The 3-year OS rates were 74% and 60%, respectively (HR, 0.663; 95% CI, 0.457-0.961; P = 0.029). Subgroup analyses revealed longer DFS in the right thoracic arm (vs left thoracic arm) in patients with lymph node involvement (HR, 0.632; 95% CI, 0.412-0.969, P = 0.034), but not in patients without lymph node involvement (HR, 0.757; 95% CI, 0.434-1.320, P = 0.325), and in patients with R1-2 resection margins (HR, 0.495; 95% CI, 0.290-0.848, P = 0.009), but not R0 margins (HR, 0.944; 95% CI, 0.603-1.477, P = 0.801). CONCLUSIONS: Compared with the left thoracic approach, the right thoracic approach associated with increased DFS and OS in esophageal squamous cell carcinoma patients, particularly in those with lymph node involvement and/or R1-2 resection margins.

Diffusion kurtosis imaging in the characterisation of rectal cancer: utilizing the most repeatable region-of-interest strategy for diffusion parameters on a 3T scanner.

OBJECTIVES: Our goal was to investigate the correlation between histopathology and diffusion parameters by utilising the most repeatable region-of-interest (ROI) strategy for diffusion parameters in rectal cancer on a 3T scanner. METHODS: 113 patients underwent DKI-MR and 66 of these patients received surgery without neoadjuvant chemoradiotherapy. Two readers independently measured the parameters using three slice protocols including single slice, three slices and whole-tumour slice (WTS), combined with one of two ROIs, including outline and round ROI. ANOVA, Kruskal-Wallis, a paired sample t-test, interclass correlation coefficient (ICC), Bland-Altman, Student's t-tests, receiver operating characteristic curves and z statistic were used for statistical analysis. RESULTS: There were no significant differences among the three slice protocols in ADC values (p = 0.822, 0.987), K values (p = 0.842, 0.859) and D values (p = 0.917, 0.988) using round and outline ROI, respectively. The ADC and D values derived from outline ROIs were higher than those from round ROIs (all p < 0.001 for ADC, all p < 0.001 for D), while K values derived from outline ROIs were lower than those from round ROIs (p < 0.001, p = 0.001, p < 0.001) using three slice protocols, respectively. The WTS-outline ROI resulted in the best intra- and inter-observer ICC. Utilising the WTS-outline ROI method, the AUC for assessment of well-differentiated tumours was 0.871 by K and 0.809 by ADC; and the AUC for T2 was 0.768 by K. CONCLUSIONS: The most repeatable strategy was the WTS-outline ROI method. In addition to DWI, DKI also have diagnostic value for rectal cancer histopathological characteristics utilising the WTS-outline ROI on a 3T scanner. KEY POINTS: • DKI using a 3T scanner is feasible for assessing rectal cancer. • ROI and slice protocol show considerable influence on DKI parameters. • DKI parameters exhibit excellent repeatability using whole-tumour slice-outline ROI on 3T scanner. • DKI has considerable diagnostic value for the estimation of rectal cancer characteristics.

Prognostic Impact of Hypochloremia in Patients With Stage I to III Colorectal Cancer After Radical Resection.

BACKGROUND: Recent studies have suggested that electrolyte disorders might be a negative prognostic factor for some diseases. OBJECTIVE: The purpose of this study was to systematically evaluate the prognostic role of electrolyte disorders in patients with stage I to III colorectal cancer who received radical surgical resection. DESIGN: This study was retrospectively performed. SETTINGS: The study was conducted at a single tertiary care center. PATIENTS: Patients with colorectal cancer who underwent radical resection in between April 2007 and April 2014 were included. MAIN OUTCOME MEASURES: The Kaplan-Meier method was adopted to estimate the overall and disease-free survival with and without propensity score matching. RESULTS: In total, our study recruited 5089 eligible patients. In prematching analysis, patients with hypochloremia showed both shorter overall survival (HR = 0.943 (95% CI, 0.908-0.980); p = 0.003) and disease-free survival (HR = 0.957 (95% CI, 0.933-0.981); p < 0.001) than those with normal serum chloride levels. In postmatching analysis, 770 patients from each group were compared, and the results further confirmed that hypochloremia was significantly associated with worse overall survival (HR = 0.646 (95% CI, 0.489-0.855); p = 0.002) and disease-free survival (HR = 0.782 (95% CI, 0.647-0.944); p = 0.01), with the hypochloremia group as a reference. LIMITATIONS: The study was limited by its retrospective nature. CONCLUSIONS: Hypochloremia diagnosed before treatment can independently prognosticate the overall and disease-free survival for patients with stage I to Ш colorectal cancer after radical resection. Intensive surveillance and management might improve the survival outcome for patients with hypochloremia. See Video Abstract at http://links.lww.com/DCR/A727.

Assessing the adequacy of lymph node yield for different tumor stages of colon cancer by nodal staging scores.

BACKGROUND: According to the current official guidelines, at least 12 lymph nodes (LNs) are qualified as an adequate sampling for colon cancer patients. However, patients evaluated with less nodes were still common in the United States, and the prevalence of positive nodal disease may be under-estimated because of the false-negative assessment. In this study, we present a statistical model that allows preoperative determination of the minimum number of lymph nodes needed to confirm a node-negative disease with certain confidence. METHODS: Adenocarcinoma colon cancer patients with stage T1-T3, diagnosed between 2004 and 2013, who did not receive neoadjuvant therapies and had at least one lymph node pathologically examined, were extracted from the Surveillance, Epidemiology and End Results (SEER) database. A beta binomial distribution was used to estimate the probability of an occult nodal disease is truly node-negative as a function of total number of LNs examined and T stage. RESULTS: A total of 125,306 patients met study criteria; and 47,788 of those were node-positive. The probability of falsely identifying a patient as node-negative decreased with an increasing number of nodes examined for each stage, and was estimated to be 72% for T1 and T2 patients with a single node examined and 57% for T3 patients with a single node examined. To confirm an occult nodal disease with 90% confidence, 3, 8, and 24 nodes need to be examined for patients from stage T1, T2, and T3, respectively. CONCLUSIONS: The false-negative rate of diagnosed node negative, together with the minimum number of examined nodes for adequate staging, depend preoperatively on the clinical T stage. Predictive tools can recommend a threshold on the minimum number of examined nodes regarding to the favored level of confidence for each T stage.

Lymphocyte count or percentage: which can better predict the prognosis of advanced cancer patients following palliative care?

BACKGROUND: The lymphocytes played an important role in the natural history of cancer. The aim of this study was to explore the prognostic value of lymphocyte count and percentage for survival in advanced cancer patients receiving palliative care. METHODS: A retrospective review of clinicopathological data from 378 consecutive advanced cancer patients and 106 extended follow-up patients treated with palliative care was conducted. Kaplan-Meier curves and multivariate cox regression analyses were used to evaluate the relationships of peripheral lymphocyte count (LC) and lymphocyte to white blood cell ratio (LWR) with overall survival (OS). RESULTS: The median values for pretreatment LC and LWR were 1.1 (IQR, 0.8 ~ 1.5 × 109/L) and 0.138 (IQR, 0.086 ~ 0.208). The median survival times across LWR quartiles were 19, 47, 79, and 101 days (P < 0.001). Multivariate analysis indicated that patients in the highest quartiles of LC and LWR had an HR of 1.082 (95% CI 0.777 ~ 1.506, P = 0.642) and 0.466 (95% CI 0.328 ~ 0.661, P < 0.001), respectively, compared with patients in the lowest quartiles. Furthermore, only the dynamic changes of LWR were confirmed as an independent prognostic factor for overall survival during the follow-up (HR = 0.396, 95% CI 0.243 ~ 0.668; P = 0.001), as were primary tumor site and ECOG. No effect was observed for the dynamic changes of LC. CONCLUSIONS: Our findings demonstrate that measurement of the dynamic changes of LWR prior to treatment and during follow-up may represent a simple and new powerful prognostic factor for patients with advanced cancer, unlike measurement of LC. As a bedside marker of immune status, the prognostic role of LWR should be further evaluated in prospective studies.

Survival prediction of anxious emotion in advanced cancer patients receiving palliative care.

BACKGROUND: This study was carried out to investigate the prognostic value of baseline and dynamic changes in anxious emotion in advanced cancer patients undergoing palliative care. METHODS: The association between anxious emotion and survival was investigated in a retrospective sample of 377 consecutive advanced cancer patients receiving palliative care from August 2013 to October 2015 and in an extended follow-up study of 106 of those patients. RESULTS: The prevalence of anxious emotion was 24.93% (94/377) overall, 22.48% (47/209) in men and 27.97% (47/168) in women. Significant associations between baseline anxious emotion and overall survival (OS) were not found in the whole sample or in women. However, univariate and multivariate analyses showed that anxious emotion was an independent prognostic indicator of OS in men (hazard ratio [HR]: 1.811, P = .003). Moreover, findings showed that newly developed anxious emotion was significantly associated with poor OS in all readmitted patients (HR: 5.568, P < .001), in men (HR: 5.104, P = .006) and women (HR: 5.820, P = .004). CONCLUSIONS: Our study suggests that anxious emotion, especially dynamic changes in anxious emotion, needs to be monitored in advanced cancer patients; whether targeted interventions would prolong survival requires further studies.

Nomograms for predicting prognostic value of inflammatory biomarkers in colorectal cancer patients after radical resection.

Increasing evidence indicates that inflammation plays a vital role in tumorigenesis and progression. However, the prognostic value of inflammatory biomarkers in colorectal cancer (CRC) has not been established. In this study, a retrospective analysis was conducted in patients with CRC in Fudan University Shanghai Cancer Center (FUSCC) between April 1, 2007 and April 30, 2014, and 5,336 patients were identified eligible. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and albumin/globulin ratio (AGR) were analyzed. Kaplan-Meier analysis was used to calculate the 5-year overall survival (OS) and disease-free survival (DFS). Cox regression analysis was performed to assess the prognostic factors. Nomograms were established to predict OS and DFS, and Harrell's concordance index (c-index) was adopted to evaluate prediction accuracy. As results, the 5-year OS was 79.2% and the 5-year DFS was 56.0% in the cohort. Patients were stratified into 2 groups by NLR (≤2.72 and >2.72), PLR (≤219.00 and >219.00), LMR (≤2.83 and >2.83) and AGR (<1.50 and ≥1.50). Patients with NLR > 2.72, PLR > 219.00, LMR ≤ 2.83 and AGR < 1.50 were significantly associated with decreased OS and DFS (p < 0.001). Multivariate analysis indicated that NLR, LMR and AGR were independent factors of OS (p = 0.047, p = 0.008 and p < 0.001, respectively) and DFS (p = 0.009, p < 0.001 and p = 0.008, respectively). In addition, nomograms on OS and DFS were established according to all significant factors, and c-indexes were 0.765 (95% CI: 0.744-0.785) and 0.735 (95% CI: 0.721-0.749), respectively. Nomograms based on OS and DFS can be recommended as practical models to evaluate prognosis for CRC patients.