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OBJECTIVE Salvage endoscopic nasopharyngectomy (ENPG) is a reasonable choice for resectable recurrent nasopharyngeal carcinoma (rNPC). However, in past decades, complete removal of the tumor was not feasible when the recurrent lesion was adjacent to the internal carotid artery (ICA). The present article introduces innovative strategies to ensure sufficient surgical margins while avoiding accidental injury to the ICA. STUDY DESIGN Retrospective study. SETTING Tertiary care center. METHODS We retrospectively reviewed rT2-3 rNPC patients with tumor lesions adjacent to the ICA (

Background Sidedness (right/left) of colorectal cancer (CRC) is essential for treatment. Whether carcinogenesis of tobacco varies by sidedness remains unclear. The present study aims to evaluate the sidedness tendency of cigarette smoking and to explore its impact on prognosis. Methods In the multi-center retrospective study, data on 46 166 Chinese CRC patients were extracted from a big-data platform. Logistic regression analyses were performed to evaluate qualitative and quantitative associations between smoking and tumor sidedness. Survival analyses were conducted in metastatic CRC. Results History of smoking was associated with left-sided CRC (LSCRC; Adjusted odds ratio, 1.25; 95% CI, 1.16 − 1.34; P P for trend P for trend P for trend P = .016). Alcoholism significantly enhanced the association by 7% (P = .027). Furthermore, prognostic advantage of metastatic LSCRC diminished among ever-smokers, with contrary survival impacts of smoking on either side of CRC. Conclusions History of smoking was associated with LSCRC in a positive dose–response relationship, and presented opposite prognostic impacts on right- and left-sided tumors. Smoking potentially plays an instrumental role in the mechanism for sidedness heterogeneity in CRC.

Purpose We aimed to construct a nomogram to predict personalized post‐recurrence survival (PRS) among colorectal cancer liver metastasis (CRLM) patients with post‐hepatectomy recurrence. Methods Colorectal cancer liver metastasis patients who received initial hepatectomy and had subsequent recurrence between 2001 and 2019 in Sun Yat‐sen University Cancer Center from China were included in the study. Patients were randomly assigned to a training cohort and a validation cohort on a ratio of 2:1. Univariable analysis was first employed to select potential predictive factors for PRS. Then, the multivariable Cox regression model was applied to recognize independent prognostic factors. According to the model, a nomogram to predict PRS was established. The nomogram's predictive capacity was further assessed utilizing concordance index (C‐index) values, calibration plots, and Kaplan–Meier curves. Results About 376 patients were finally enrolled, with a 3‐year PRS rate of 37.3% and a 5‐year PRS rate of 24.6%. The following five independent predictors for PRS were determined to construct the nomogram: the largest size of liver metastases at initial hepatectomy, relapse‐free survival, CEA level at recurrence, recurrent sites, and treatment for recurrence. The nomogram displayed fairly good discrimination and calibration. The C‐index value was 0.742 for the training cohort and 0.773 for the validation cohort. Patients were grouped into three risk groups very well by the nomogram, with 5‐year PRS rates of 45.2%, 23.3%, and 9.0%, respectively (p, Independent prognostic factors for post‐recurrence survival were identified in colorectal cancer liver metastasis patients. A prognostic nomogram based on these factors was built and validated, which had relatively good discrimination and calibration ability.

Background Gemcitabine plus cisplatin is regarded as the standard first-line therapy for patients with advanced biliary tract cancer (BTC); however, no standard chemotherapy has yet been recommended after treatment failure. Modified FOLFIRINOX (mFOLFIRINOX) appears to be a better-tolerated regimen, which leads to improved survival in metastatic pancreatic cancer that has histological and molecular similarities with BTC. We assessed the efficacy and safety of mFOLFIRINOX as salvage therapy in advanced BTC patients who were refractory to previous chemotherapy. Methods A total of 15 consecutive patients with documented unresectable locally advanced or metastatic BCT who received the mFOLFIRINOX regimen were included in the study. Patients were intravenously administrated with oxaliplatin (65 mg/m2), leucovorin (400 mg/m2), irinotecan (150 mg/m2), and continuous infusion of fluorouracil (2400 mg/m2) over 46 h. The objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were recorded. Results At least three cycles of mFOLFIRINOX regimen were delivered to 15 patients with a median number of 6.0 cycles (IQR 5.5–11.0). The median duration of treatment was 3.8 months (IQR 2.9–8.5). Four patients (26.7%) achieved an ORR, and 12 patients (80.0%) had a DCR. The median PFS and OS were 6.7 months (95%CI 2.3–11.1) and 13.2 months (95%CI 7.3–19.1), respectively. Five patients (33.3%) had treatment-related grade 3/4 AEs. The most common grade 3/4 AE was neutropenia (n = 3, 20.0%), while there was no occurrence of febrile neutropenia. Conclusion Treatment with mFOLFIRINOX has promising efficacy and favorable tolerance as salvage therapy in patients with refractory advanced BCT.

Chemotherapy-induced neutropenia (CIN) is a potentially fatal and common complication in myelosuppressive chemotherapy. The timing and grade of CIN may play prognostic and predictive roles in cancer therapy. CIN is associated with older age, poor functional and nutritional status, the presence of significant comorbidities, the type of cancer, previous chemotherapy cycles, the stage of the disease, specific chemotherapy regimens, and combined therapies. There are many key points and new challenges in the management of CIN in adults including: (1) Genetic risk factors to evaluate the patient's risk for CIN remain unclear. However, these risk factors urgently need to be identified. (2) Febrile neutropenia (FN) remains one of the most common reasons for oncological emergency. No consensus nomogram for FN risk assessment has been established. (3) Different assessment tools [e.g., Multinational Association for Supportive Care in Cancer (MASCC), the Clinical Index of Stable Febrile Neutropenia (CISNE) score model, and other tools] have been suggested to help stratify the risk of complications in patients with FN. However, current tools have limitations. The CISNE score model is useful to support decision-making, especially for patients with stable FN. (4) There are still some challenges, including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN. In view of the current reports, our group discusses the key points, new challenges, and management of CIN.

Background The prognosis of esophageal squamous cell carcinoma (ESCC) are still poor. Nedaplatin/paclitaxel regimen has shown activity with lower toxicity in metastatic ESCC. Recombinant human endostatin (Rh-endostatin), an inhibitor of angiogenesis, has shown inhibitory effects on ESCC xenograft. We assessed the activity and safety of Rh-endostatin plus paclitaxel/nedaplatin in patients with recurrent or metastatic advanced ESCC. Methods In this single-center, open-label, single-arm, phase II study, patients with recurrent/metastatic or unresectable advanced ESCC were recruited. Eligible patients received the multidrug combination therapy with Rh-endostatin (30 mg/day on days 1–14), paclitaxel (150 mg/m2 on day 4) and nedaplatin (80 mg/m2 on day 4) every 3 weeks. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate, disease control rate, overall survival. Results Between Jan 29, 2015 and Dec 31, 2019, 53 patients were enrolled and received at least one dose of Rh-endostatin. Median progression-free survival was 5.1 months (95% CI: 3.7–6.6), with a 6 month progression-free survival of 41% (95% CI: 25–56). Median overall survival was 13.2 months (95% CI: 8.0-18.4), with a 1-year overall survival of 51% (95% CI: 36–67). 21 (42%, 95% CI: 28–56) of 50 patients had an objective response and 35 (70.00%, 95% CI: 57–83) had a disease control. Treatment-related adverse events of grade 3 or worse were reported in 13 (24.5%) patients. The most common grade 3 or 4 treatment-related adverse events were neutropenia (9 patients [17%]) and anaemia (2 [3.8%]). No treatment-related death occurred. Conclusions Rh-endostatin plus paclitaxel/nedaplatin has anti-tumour activity with acceptable tolerability in patients with recurrent or metastatic advanced ESCC. Randomized controlled trial is needed to confirm the efficacy of this regimen.

Background Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive system. Studies have shown that pseudolaric acid B (PAB) has several pharmacological effects like anti-microtubule, anti-angiogenesis, and antitumor functions, while the effect and mechanism of PAB on esophageal cancer are still unclear. This study was designed to investigate the effects of PAB on ESCC. Methods To study the effects of PAB on the biological function through a series of in vitro and in vivo experiments. Results The results revealed that PAB inhibited the proliferation, invasion, and migration, but promoted the apoptosis of ESCC. Moreover, PAB restrained the growth of cancer cells in vivo and inhibited the angiogenesis of HUVEC in mice with ESCC. CD147 expression was increased in the esophageal squamous cell lines, and interference with CD147 hindered the proliferation, invasion, and migration of ESCC cells, and inhibited the growth and angiogenesis of the esophageal squamous cell line. PAB reduced the expression of CD147 in vivo and in vitro. The expression of MMP2, 3, and 9 was increased after overexpression of CD147, which provided the opportunity to reverse the role of PAB in inhibiting proliferation, invasion, migration, and angiogenesis of ESCC. Discussion The results revealed that PAB inhibited the proliferation, invasion, migration, and angiogenesis of ESCC in vitro and in vivo by CD147. PAB is a promising monomer for therapy of ESCC, providing references for future research on ESCC treatment.

Background Surgical access for retropharyngeal lymph node (RPLN) dissection is difficult. We aimed to examine the efficacy of transcervical endoscopic RPLN dissection (TSE-RPLND) for recurrent RPLN in nasopharyngeal carcinoma (NPC). Methods From April 2013 to February 2019, a total of 31 patients with NPC diagnosed with RPLN recurrence underwent TSE-RPLND. The clinical characteristics, complications, and survival outcomes were retrospectively analyzed. Results The mean duration of surgery, quantity of bleeding and postoperative hospitalization stay were 347.9 minutes, 107.7 mL, and 8.7 days, respectively. After a median follow-up of 31.0 months, the 2-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival rates were 63.9%, 95.2%, 59.9%, and 83.3%, respectively. The long-term incidences of swallowing problems, permanent nutrient tube, tongue atrophy, and shoulder problems were 6 (19.4%), 3 (9.7%), 3 (9.7%), and 3 (9.7%), respectively. Conclusions TSE-RPLND is an effective method to treat RPLN recurrence in NPC, but nerve injury-related complications should not be ignored.

Background Several programmed cell death ligand 1 (PD‐L1)/programmed cell death protein 1 (PD‐1) antibodies have been approved for cancer treatment worldwide. Their pharmacokinetic and pharmacodynamic characteristics have been reported mainly in western countries, but related data in Chinese patients are limited. This study was conducted to investigate the safety, efficacy, pharmacokinetics, and pharmacodynamics of an anti‐PD‐1 antibody, toripalimab, in Chinese patients. Methods A single‐center phase I study was conducted in Sun Yat‐sen University Cancer Center. Eligible patients were adults with histologically confirmed, treatment‐refractory, advanced, solitary malignant tumors. Toripalimab was intravenously infused every 2 weeks in dose‐escalating cohorts at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg. The study followed standard 3 + 3 design. Results Between 15th March 2016 and 27th September 2016, 25 patients were enrolled, of whom 3 (12.0%), 7 (28.0%), 6 (24.0%), 6 (24.0%), 3 (12.0%) received 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg toripalimab, respectively. After a median follow‐up time of 5.0 months (range: 1.5‐19.8 months), we observed that the commonest treatment‐related adverse events (TRAEs) were fatigue (64.0%) and rash (24.0%). No grade 3 or higher TRAEs were observed. No dose‐limiting toxicity, treatment‐related serious adverse events (SAEs), or treatment‐related death occurred. Objective response rate was 12.5%. The half‐life of toripalimab was 150‐222 h after a single dose infusion. Most patients, including those from the 0.3 mg/kg group, maintained complete PD‐1 receptor occupancy (> 80%) on activated T cells since receiving the first dose of toripalimab. Conclusions Toripalimab is a promising anti‐PD‐1 antibody, which was well tolerated and demonstrated anti‐tumor activity in treatment‐refractory advanced solitary malignant tumors. Further exploration in various tumors and combination therapies is warranted.

Purpose To identify how Epstein‐Barr virus (EBV) status combined with molecular profiling predicts the prognosis of gastric cancer patients and their associated clinical actionable biomarkers. Experimental Design A next‐generation sequencing assay targeting 295 cancer‐related genes was performed in 73 EBV‐associated gastric cancer (EBVaGC) and 75 EBV‐negative gastric cancer (EBVnGC) specimens and these results were compared with overall survival (OS). Results PIK3CA, ARID1A, SMAD4, and PIK3R1 mutated significantly more frequently in EBVaGC compared with their corresponding mutation rate in EBVnGC. As the most frequently mutated gene in EBVnGC (62.7%), TP53 also displayed a mutation rate of 15.1% in EBVaGC. PIK3R1 was revealed as a novel mutated gene (11.0%) associated almost exclusively with EBVaGC. PIK3CA, SMAD4, PIK3R1, and BCOR were revealed to be unique driver genes in EBVaGC. ARID1A displayed a significantly large proportion of inactivated variants in EBVaGC. A notable finding was that integrating the EBV status with tumor mutation burden (TMB) and large genomic instability (LGI) categorized the tumors into four distinct molecular subtypes and optimally predicted patient prognosis. The corresponding median OSs for the EBV+/TMB‐high, EBV+/TMB‐low, EBV‐/LGI‐, and EBV‐/LGI+ subtypes were 96.2, 75.3, 44.4, and 20.2 months, respectively. The different subtypes were significantly segregated according to distinct mutational profiles and pathways. Conclusions Novel mutations in PIK3R1 and TP53 genes, driver genes such as PIK3CA, SMAD4, PIK3R1, BCOR, and ARID1A, and distinguished genomic profiles from EBVnGC were identified in EBVaGC tumors. The classification of gastric cancer by EBV, TMB, and LGI could be a good prognostic indicator, and provides distinguishing, targetable markers for treatment.

Background Monosialotetrahexosylganglioside (GM1) is a neuroprotective glycosphingolipid that repairs nerves. Oxaliplatin‐based chemotherapy is neurotoxic. This study assessed the efficacy of GM1 for preventing oxaliplatin‐induced peripheral neurotoxicity (OIPN) in colorectal cancer (CRC) patients receiving oxaliplatin‐based chemotherapy. Methods In total, 196 patients with stage II/III CRC undergoing adjuvant chemotherapy with mFOLFOX6 were randomly assigned to intravenous GM1 or a placebo. The primary endpoint was the rate of grade 2 or worse cumulative neurotoxicity (NCI‐CTCAE). The secondary endpoints were chronic cumulative neurotoxicity (EORTC QLQ‐CIPN20), time to grade 2 neurotoxicity (NCI‐CTCAE or the oxaliplatin‐specific neuropathy scale), acute neurotoxicity (analog scale), rates of dose reduction or withdrawal due to OIPN, 3‐year disease‐free survival (DFS) and adverse events. Results There were no significant differences between the arms in the rate of NCI‐CTCAE grade 2 or worse neurotoxicity (GM1: 33.7% vs placebo: 31.6%; P = .76) or neuropathy measured by the EORTC QLQ‐CIPN20 or time to grade 2 neurotoxicity using NCI‐CTCAE and the oxaliplatin‐specific neuropathy scale. GM1 substantially decreased participant‐reported acute neurotoxicity (sensitivity to cold items [P, Neuropathy is the most prominent dose‐limiting toxicity of oxaliplatin. Patients receiving Monosialotetrahexosylganglioside (GM1) were less troubled by the symptoms of acute neuropathy. However, we do not support the use of GM1 to prevent cumulative neurotoxicity.

Background Oxaliplatin, irinotecan, 5-fluorouracil, and l-leucovorin (FOLFIRINOX) has become one of the first-line treatment options for advanced pancreatic cancer (PC). However, the relatively high rate of grade 3 or 4 adverse events associated with the standard dosage of FOLFIRINOX limits its widespread use in clinical practice. In this study, we were to evaluate the efficacy and safety of a modified FOLFIRINOX regimen as a first-line chemotherapy for Chinese patients with metastatic PC. Methods Patients with histologically confirmed primary metastatic pancreatic adenocarcinoma with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0–2 were recruited to receive the modified FOLFIRINOX regimen (intravenous infusion of oxaliplatin, 65 mg/m2; irinotecan, 150 mg/m2; l-leucovorin, 200 mg/m2; and 5-fluorouracil, 2400 mg/m2, repeated every 2 weeks). The treatment was continued for 12 cycles unless the patient had progressive disease (PD), stable disease (SD) with symptom deterioration, unacceptable adverse events, or requested to terminate the treatment prematurely. The primary endpoint was objective response rate (ORR). Results Sixty-five patients were enrolled from July 2012 to April 2017 in three institutions, and they all received at least one cycle of chemotherapy, with a median of 8 cycles (range 1–12 cycles). No complete response was observed. Twenty-one (32.3%) patients had partial responses, and 27 (41.5%) had SD. The ORR and disease control rate of the study cohort was 32.3% and 73.8%. The estimated median overall survival and progression-free survival were 11.60 (95% confidence interval [CI] 8.76–14.44) and 5.77 (95% CI 5.00–6.54) months. Major grade 3 or 4 adverse events included neutropenia (12.3%) and diarrhea (6.2%). No treatment-related death was observed. Conclusions Modified FOLFIRINOX was well-tolerated and might be a promising option as first-line therapy for Chinese patients with metastatic PC. Trial registration ClinicalTrials.gov, NCT02028806. Registered 7 January 2014, https://clinicaltrials.gov/ct2/show/NCT02028806

Background: The benefit of palliative gastrectomy for patients with metastatic gastric cancer (mGC) is controversial, and suitable candidates for surgery and treatment strategies remain unclear. The present study aimed to investigate the efficacy of palliative gastrectomy plus chemotherapy among patients with mGC and to identify the potential patients for such treatment using real-world data. Methods: A dataset of 236 patients with mGC diagnosed at the Sun Yat-Sen University Cancer Center from January 1, 2006 to December 31, 2012 were analyzed retrospectively. The cohort comprised 80 patients who had palliative gastrectomy plus chemotherapy (SC) and 156 patients who had chemotherapy only (CO). Propensity score matching (PSM) was employed to minimize the influence of confounders. Results: The median overall survival of the SC group was significantly better than that of the CO group (Before PSM: 17.0 months vs 12.0 months, P=0.038; after PSM: 17.0 months vs 13.0 months, P=0.017). In the multivariate analysis, SC (Before PSM: hazard ratio (HR) =0.68, P=0.023; after PSM: HR =0.64, P=0.021) was favored for better survival after adjustment for sex, age, year of diagnosis, primary tumor location, and tumor grade. Total gastrectomy (P=0.026) was associated with worse survival for the SC group. The significant survival advantage of SC over CO was retained in patients with single organ metastasis (P=0.016), peritoneal seedings (P=0.039), and those receiving taxane-based chemotherapy (P=0.011). Conclusion: SC could improve the overall survival of patients with mGC as compared with CO. The chemotherapy regimen and type of resection were proven to influence efficacy. Patients who received taxane-based regimens might be suitable for palliative gastrectomy.

BACKGROUND: To evaluate whether fat-free mass index (FFMI) could be predictive of prolonged air leak (PAL) complicating video-assisted thoracoscopic (VATS) lobectomy for non-small-cell lung cancer (NSCLC). METHODS: A retrospective study was conducted on the prospectively-maintained database in our institution between January 2015 and July 2017. The gender-specific median values of FFMI for males and females were applied as their respective cutoffs to stratify patients into low-FFMI group and high-FFMI group in initial univariable analyses. An effective multivariable logistic-regression analysis was then performed to demonstrate the predictive value of dichotomized FFMI. RESULTS: There were 1,091 surgical patients with NSCLC included (616 males and 475 females), with a PAL incidence of 14.6%. The median FFMI values among males and females were 17.3 and 14.6 kg/m(2), respectively. PAL cases in both male (16.9±1.5 vs. 17.4±1.5 kg/m(2); P=0.002) and female (14.0±0.9 vs. 14.6±1.1 kg/m(2); P

An increasing amount of evidence suggests that high‐density lipoprotein cholesterol (HDL‐C) is related to a positive prognosis in various cancers. However, the correlation between HDL‐C and the immune signature and the prognostic role of HDL‐C in stage II/III colorectal cancer (CRC) has not been previously reported. A total of 667 CRC patients were enrolled and divided into two groups based on the lower limit of normal HDL‐C values (0.78 mmol/L). We used Kaplan‐Meier curves and the Cox regression model to analyze the prognostic role of HDL in both disease‐free survival (DFS) and overall survival (OS). Fifty‐five pairs of tumor tissues were selected according to the variation in HDL‐C levels (high or low) and the matched characterizes (ages, T stage, and N stage). Using immunohistochemistry, tumor tissues were stained with antibodies against CD3, CD8, CD163, iNOS, Forkhead box P3 (FOXP3), and CD33. We calculated the density of positively‐stained infiltrating cells in the tumor center (TC) and invasive margin (IM). We then used Spearman rank correlation to further investigate the relationship between HDL‐C levels and the immune signatures. Our results revealed that compared to patients with high HDL‐C levels, patients with low HDL‐C levels had poor 3‐year DFS (68.9% vs 83.1%, P = 0.032) and 5‐year OS rates (66.6% vs 85.3%, P = 0.002). We also identified a positive correlation between HDL‐C and CD3+, CD8+ and iNOS+ cells and a negative correlation between HDL‐C and CD163+ cells in both the TC and IM. This study reveals that a low HDL‐C level in stage II/III CRC patients predicts poor prognosis. The correlation between the HDL‐C level and immune signature in tissue specimens suggested that HDL‐C is likely to play an inhibitory role in tumor development via affecting immune responses.

Background: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) antibody that has shown preclinical and clinical anticancer activity in cerebral glioblastoma multiforme (GBM). We conducted a phase II, single-arm, multicenter clinical trial to evaluate the benefit of adding nimotuzumab to current standard chemo-radiotherapy for patients with GBM with positive EGFR expression. Methods: Newly diagnosed patients with histologically proven single supratentorial GBM and epidermal growth factor receptor (EGFR) positive expressions were recruited. All patients were treated with nimotuzumab, administered once a week intravenously for 6 weeks in addition to radiotherapy with concomitant and adjuvant temozolomide after surgery. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary objectives included objective response rate (ORR) and toxicity. Results: A total of 39 patients were enrolled and 36 patients were evaluated for efficacy. The ORR at the end of RT was 72.2%. Median OS and PFS were 24.5 and 11.9 months. The 1-year OS and PFS rates were 83.3% and 49.3%. The 2-year OS and PFS rates were 51.1% and 29.0%. O (6)-methylquanine DNA methyl-tranferase (MGMT) expression is known to affect the efficacy of chemotherapy and status of its expression is examined. No significant correlation between treatment outcomes and MGMT status was found. Most frequent treatment-related toxicities were mild to moderate and included constipation, anorexia, fatigue, nausea, vomiting, and leucopenia. Conclusions: Our study show that nimotuzumab in addition to standard treatment is well tolerable and has increased survival in newly diagnosed GBM patients with EGFR positive expression.

BACKGROUND: Increasing evidence suggests that the immune score is significantly associated with cancer prognosis. However, the prognostic role of primary tumor immune score in colorectal cancer liver metastases (CRLM) after hepatectomy in Chinese patients has not been reported. The present study is designed to investigate whether the immune score of primary tumor can predict the postoperative survival of liver metastases in Chinese patients. METHODS: A total of 131 patients diagnosed with CRLM were included, and the corresponding primary tumor and liver metastasis specimens were acquired. An immune score ranging from 0 to 4 was established based on the counts and densities of CD3(+) and CD8(+) T cells in the core tumor (CT) and the invasive margin (IM). Relapse-free survival (RFS) and overall survival (OS) were analyzed by Kaplan-Meier curves to assess the prognostic role of primary tumor immune score. Furthermore, we conducted a comprehensive search of the Gene Expression Omnibus (GEO) and selected stage IV colorectal cancer (CRC) patients with liver metastasis to compare the tumor-infiltrating T cell profiles of the primary tumor and liver metastases by CIBERSORT. RESULTS: Patients with high immune scores in the primary tumor has no significantly better RFS and OS after hepatectomy than those with low immune scores [median RFS (95% CI): 19.13 (10.07–28.20) vs. 27.13 (15.97–38.29) months, P=0.604; median OS (95% CI): 64.37 (35.96–92.78) vs. 40.07 (32.54–47.59) months, P=0.652]. Data collected from the GEO indicates that the proportion of CD8(+) T cells and total T cells in the primary tumor and liver metastatic lesion are also not significantly correlated (CD8(+) T cells: r(2) =0.030, P=0.468; total T cells: r(2) =0.165, P=0.076). CONCLUSIONS: The immune score of the primary tumor fails to predict the prognosis of CRLM after hepatectomy in Chinese patients.

Background. The molecular mechanism of nonobstructive azoospermia (NOA) remains unclear. The aim of this study was to identify gene expression changes in NOA patients and to explore potential biomarkers and therapeutic targets. Methods. The gene expression profiles of GSE45885 and GSE145467 were collected from the Gene Expression Omnibus (GEO) database, and the differences between NOA and normal spermatogenesis were analyzed. Enrichment analysis was performed to explore biological functions for common differentially expressed genes (DEGs) in GSE45885 and GSE145467. Coexpression analysis of DEGs in GSE45885 was performed, and two modules with the highest correlation with NOA were screened. Key genes were then screened from the intersection genes of the two modules and common DEGs and PPI network. The expression of key genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR) experiments. Finally, through miRTarBase, miRDB, and RAID, the miRNAs were predicted to regulate key genes, respectively. Results. A total of 345 common DEGs were identified and they were mainly related to spermatogenesis, insulin signaling pathway. Coexpression analysis of DEGs in GSE45885 yielded eight modules; MEblack and MEturquoise had the highest correlation with NOA. Six genes in MEturquoise and RNF141 in MEblack were identified as key genes. qRT-PCR experiments validated the differential expression of key genes between NOA and control. Furthermore, RNF141 was regulated by the largest number of miRNAs. Conclusion. Our findings suggest that the significant change expression of key genes may be potential markers and therapeutic targets of NOA and may have some impact on the development of NOA.

Objectives Nasopharyngeal carcinoma (NPC) patients with retropharyngeal lymph node (RPLN) recurrence typically undergo reirradiation and experience severe radiotoxicity. Salvage open surgery is challenging because gaining access to the retropharyngeal space is complex and risky. Thus, only several centers can perform this procedure, and complications are common. We applied transoral robotic surgery RPLN dissection (TORS-RPLND) to NPC patients with RPLN recurrence to address the problem with open surgery. Materials and methods From March 2017 to October 2020, 10 NPC patients with RPLN recurrence underwent TORS-RPLND using the da Vinci Si/Xi Surgical System. We applied the balloon occlusion test to protect the internal carotid artery, induction chemotherapy to shrink large tumors preoperatively, and ultrasound positioning to effectively locate unrecognizable RPLNs during surgery. Clinical characteristics, complications, and survival outcome data were retrospectively collected. Results Of 10 patients, 8 underwent en bloc resection via TORS-RPLND, and the remaining 2 patients were converted to open surgery because we failed to identify the RPLN during TORS. After introducing intraoperative ultrasound positioning, no such failure occurred. The mean operative time and intraoperative blood loss were 297 ± 120 min and 40 ± 43 ml, respectively. All surgical margins were negative. TORS-related complications were mild, and the most severe one was grade 3 dysphagia in one patient who underwent conversion to open surgery (10%). With a median follow-up of 19 months, only 1 (10%) patient developed cervical recurrence. Conclusions TORS-RPLND is feasible, safe, and effective in the treatment of NPC patients with RPLN recurrence, especially with the help of intraoperative ultrasound positioning. Level of evidence 4 Laryngoscope, 131:E1895-E1902, 2021.

Background:BRAFV600E mutation is associated with poor prognosis of colorectal cancer (CRC) patients, but the comparison of clinic-pathologic features between V600E and non-V600E mutation was not well-known in CRC patients. The aim of this study is to evaluate the clinical and pathological features, prognostic value of BRAF mutations in CRC.Methods: We conducted a retrospective study to characterize the clinical and pathological features and survival of patients with BRAF mutated CRC. Patients were classified according to BRAF status as BRAFV600E mutation and non-V600E mutations. Difference of characteristics and survival between the two groups was analyzed.Results: There was no significant difference in gender, family history, location of primary tumor, metastatic sites between patients with BRAF-V600E mutation and non-V600E mutations. Patients with V600E mutation were younger than those with non-V600E mutations (p = 0.002). Patients with BRAFV600E mutation showed a poorer outcome than those with non-V600E mutations (23.1 vs. 49.9 months, respectively, p = 0.0024). Lack of CDX2 expression was associated with worse prognosis (mOS: 9.4 m vs. not reached, respectively, p = 0.016). Status of V600E mutation did not affect the mPFS and ORR of first-line or second-line treatment.Conclusion:BRAFV600E mutation defines a distinct subgroup of CRC with worse prognosis. Lack of CDX2 expression is associated with poor OS. Status of V600E mutation did not affect the mPFS of first-line or second-line treatment.

Background and Aims. Cancer-specific survival (CSS) of rectal cancer (RC) is associated with several factors. We aimed to build an efficient competing-risk nomogram based on log odds of positive lymph nodes (LODDS) to predict RC survival. Methods. Medical records of 8754 patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database, of 4895 patients from SEER during 2011–2014 and of 478 patients from an Eastern center as a development cohort, validation cohort, and test cohort, respectively. Univariate and multivariate competing-risk analyses were performed to build competing-risk nomogram for predicting the CSS of RC patients. Prediction efficacy was evaluated and compared with reference to the 8th TNM classification using the factor areas under the receiver operating characteristic curve (AUC) and Brier score. Results. The competing-risk nomogram was based on 6 variables: size, M stage, LODDS, T stage, grade, and age. The competing-risk nomogram showed a higher AUC value in predicting the 5-year death rate due to RC than the 8th TNM stage in the development cohort (0.81 vs. 0.76), validation cohort (0.85 vs. 0.82), and test cohort (0.71 vs. 0.66). The competing-risk nomogram also showed a higher Brier score in predicting the 5-year death rate due to RC than the 8th TNM stage in the development cohort (0.120 vs. 0.127), validation cohort (0.123 vs. 0.128), and test cohort (0.202 vs. 0.226). Conclusion. We developed and validated a competing-risk nomogram for RC death, which could provide the probability of survival averting competing risk to facilitate clinical decision-making.

The present study is the first phase II clinical trial aimed to evaluate the efficacy and safety of S-1 plus nanoparticle albumin-bound paclitaxel (Nab-PTX) as first-line chemotherapy for advanced gastric cancer (AGC). Previously untreated patients with metastatic gastric adenocarcinoma received S-1 in oral doses of 40 mg (BSA

Rationale: Patients with gastrointestinal stromal tumors (GISTs) are often found to have liver metastases at their 1st presentation. Most patients need preoperative treatment to reduce the size of the liver metastases to increase the possibility of surgical resection. Currently, imatinib mesylate is the drug of 1st choice for preoperative treatment and sunitinib malate (SM) is seldom used. Here we report a case of GIST with liver metastases where SM was used as a preoperative treatment. Patient concerns: A 56-year-old worker presented with intermittent abdominal pain and eating difficulties. Diagnoses: An enhanced computed tomography scan showed a 15 × 15 × 10 cm malignant mass in the upper abdomen, and 2 metastases (15.1 × 13.1 cm and 14.8 × 8.8 cm) in the liver. The postcaval and middle hepatic veins were compressed by the liver metastases, making radical resection very difficult. Interventions: First the primary tumor in the jejunum was resected, and then SM was used as a preoperative treatment to reduce the size of the liver metastases to improve the possibility of surgical resection. Outcomes: Both liver metastases regressed considerably in size and it was then possible to perform a radical resection. Lessons: The SM has the potential to be used as preoperative therapy for GIST with large liver metastases. This method provides a new option for the preoperative treatment of GIST with liver metastases.

Background The Asia-Pacific Colorectal Screening (APCS) score is effective to screen high-risk groups of advanced colorectal neoplasia (ACN) patients but needs revising and can be combined with the fecal immunochemical test (FIT). This paper aimed to improve the APCS score and evaluate its use with the FIT in stratifying the risk of ACN. Methods This prospective and multicenter study enrolled 955 and 1201 asymptomatic Chinese participants to form the derivation and validation set, respectively. Participants received the risk factor questionnaire, colonoscopy and FIT. Multiple logistic regression was applied, and C-statistic, sensitivity and negative predictive values (NPVs) were used to compare the screening efficiency. Results A modified model was developed incorporating age, body mass index (BMI), family history, diabetes, smoking and drinking as risk factors, stratifying subjects into average risk (AR) or high risk (HR). In the validation set, the HR tier group had a 3.4-fold (95% CI 1.8–6.4) increased risk for ACN. The C-statistic for the modified score was 0.69 ± 0.04, and 0.67 ± 0.04 for the original score. The sensitivity of the modified APCS score combined with FIT for screening ACN high-risk cohorts was 76.7% compared with 36.7% of FIT alone and 70.0% of the modified APCS score alone. The NPVs of the modified score combined with FIT for ACN were 98.0% compared with 97.0% of FIT alone and 97.9% of the modified APCS score alone. Conclusions The modified score and its use with the FIT are efficient in selecting the HR group from a Chinese asymptomatic population.

Anastomotic leakage, fibrous stricture and gastro-oesophageal reflux are three major complications of gastro-oesophageal anastomosis, particularly in cervical anastomosis. Our aim was to evaluate the safety and efficacy of a novel cervical anastomosis technique (NA) by comparing it to traditional side-to-side anastomosis (SS) and end-to-side anastomosis using a circular stapler (CS) in terms of postoperative leakage, stricture and reflux.A total of 390 patients with thoracic oesophageal cancer underwent minimally invasive oesophagectomy with cervical anastomosis (192 with NA, 34 with SS and 164 with CS) in our institute from January 2013 and May 2016. A detailed description of the surgical procedure is provided, and the major postoperative complications, including postoperative leakage, stricture and reflux, were compared using a three-armed controlled study.The anastomotic method was an independent risk factor for anastomotic leakage, as well as stricture and reflux. The rate of anastomotic leakage of the NA group (1.0%) was significantly lower than that in the SS group (8.8%, P = 0.025) and in the CS group (8.5%, P = 0.001). The rate of anastomotic stricture in the NA group was not significantly different than that in the SS group (1.5% vs. 2.9%, P = 0.368) but was significantly lower than that in the CS group (1.5% vs. 18.9%, P 0.001). The incidence of gastro-oesophageal reflux in the NA group was significantly lower than that in the SS group and the CS group (5.7% vs. 23.5% and 18.3%, P = 0.003 and 0.001, respectively).Jiang's anastomosis technique remarkably reduces the incidence of gastro-oesophageal anastomotic leakage, stricture and reflux, and it is a safe and effective technique for minimally invasive oesophagectomy.

Background & aims At present, increasing reports have shown that pretreatment platelet count was associated with the prognosis of many types of cancer. We performed rounded analysis to comprehensively analyze and evaluate the prognostic significance of pretreatment thrombocytosis for patients with gastric cancer. Methods We identified relevant studies by searching database including PubMed, Embase, Cochrane Library and Web of Science. The relative risk (RR) with its 95% confidence interval (CI) was used to assess the correlation between thrombocytosis and overall survival (OS) of gastric cancer patients. We also conducted subgroup analysis and sensitivity analysis for the prognostic effect of thrombocytosis on OS. The analysis was performed and assessed using Review Manager 5.2. Results A total of nine studies including 7158 participants were included in this systematic review. Analysis results showed that pretreatment thrombocytosis had a close relationship with 1, 3 and 5 years survival of gastric cancer, with the pooled RRs being 0.80 (95% CI 0.71–0.90; P = 0.0004), 0.65 (95% CI 0.45–0.92; P = 0.02) and 0.64 (95% CI 0.47–0.87; P = 0.004) respectively. Conclusions The present rounded analysis suggests that pretreatment thrombocytosis may have significant association with poor survival of patients with gastric cancer.

Shuangjiang Li,1,* Zhiqiang Wang,2,* Kun Zhou,1,* Yan Wang,1 Yanming Wu,1 Pengfei Li,1 Guowei Che1 1Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 2Department of Thoracic Surgery, Chongqing University Cancer Hospital, Chongqing Cancer Institute, Chongqing Cancer Hospital, Chongqing University, Chongqing China *These authors contributed equally to this work Background: To evaluate the clinical significance of degree of pulmonary fissure completeness (PFC) on major in-hospital outcomes following video-assisted thoracoscopic (VATS) lobectomy for non-small-cell lung cancer (NSCLC). Materials and methods: We carried out a single-center retrospective analysis on the prospectively maintained database at our unit between August 2014 and October 2015. Patients were divided into two groups based on their fissure sum average (FSA). Patients with FSA >1 (1< FSA ≤3) were considered to have incomplete pulmonary fissures (group A), while patients with FSA of 0–1 were considered to have complete pulmonary fissures (group B). Demographic differences in perioperative characteristics and surgical outcomes between these two groups were initially assessed. Then, a multivariate logistic-regression analysis was further conducted to identify the independent predictors for major in-hospital outcomes. Results: A total of 563 patients undergoing VATS lobectomy for NSCLC were enrolled. There were 190 patients in group A and 373 patients in group B. The overall morbidity and mortality rates of our cohort were 30.6% and 0.5%, respectively. Group A patients had a significantly higher overall morbidity rate than group B patients (42.1% vs 24.7%,P

BACKGROUND The anterolateral thigh (ALT) free flap has been an extremely versatile flap. The purpose of this study was to propose comprehensive functional assessments of the donor site. METHODS A total of 33 ALT flaps were enrolled prospectively. Objective assessments included isokinetic testing of the knee, and electromyographic examination of the lateral femoral cutaneous nerve (LFCN). The Patient and Observer Scar Assessment Scale (POSAS) was used to subjectively assess the donor-site scar. RESULTS On the donor side, a significant decrease in most isokinetic muscle strength values was obvious 1 year postoperatively (P

Background: The purpose of our cohort study was to investigate the effects of pleural adhesions on perioperative outcomes in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for non-small-cell lung cancer (NSCLC). Methods: We performed a single-center retrospective analysis on the prospectively-maintained dataset at our unit from February 2014 to November 2015. Patients were divided into two groups (Group A: presence of pleural adhesions; Group B: absence of pleural adhesions) according to our grading system of pleural adhesions when entering the chest cavity. Demographic differences in perioperative outcomes between these two groups were initially estimated. A multivariate logistic-regression analysis was then performed to confirm the predictive value of the presence of pleural adhesions. Results: A total of 593 NSCLC patients undergoing VATS lobectomy were enrolled. The conversion and postoperative morbidity rates were 3.2% and 29.2%, respectively. There were 154 patients with pleural adhesions (Group A) and 439 patients without pleural adhesions (Group B). Group A patients had significantly higher rates of conversion to thoracotomy (9.1% vs . 1.1%; P vs . 14.4%; P=0.006) than those of Group B patients. No significant difference was found in the overall morbidity and cardiopulmonary complication rates between these two groups. The presence of pleural adhesions was also significantly associated with the prolonged length of chest tube drainage (logrank P Conclusions: Presence of pleural adhesions can predict conversion to thoracotomy and postoperative surgical complications in patients undergoing VATS lobectomy for NSCLC. Our study calls for an internationally accepted grading system for the presence of pleural adhesions to stratify the surgical risk.

Yuan Ding,1,* Wei Cui,2,* Dan Sun,1 Gui-Ling Wang,1 Yu Hei,1 Shuai Meng,1 Jian-Hua Chen,3 Ying Xie,1 Zhi-Qiang Wang4 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, 2School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 3School of Medicine, Jianghan University, Wuhan, People’s Republic of China; 4Department of Chemistry and Biochemistry, Kent State University Geauga, Burton, OH, USA *These authors contributed equally to this work Abstract: In vivo evaluation of drug delivery vectors is essential for clinical translation. In BALB/c nude mice bearing human breast cancer tumors, we investigated the biocompatibility, pharmacokinetics, and pharmacodynamics of doxorubicin (DOX)-loaded novel cell-penetrating peptide (CPP)-modified pH-sensitive liposomes (CPPL) (referred to as CPPL(DOX)) with an optimal CPP density of 4%. In CPPL, a polyethylene glycol (PEG) derivative formed by conjugating PEG with stearate via acid-degradable hydrazone bond (PEG2000-Hz-stearate) was inserted into the surface of liposomes, and CPP was directly attached to liposome surfaces via coupling with stearate to simultaneously achieve long circulation time in blood and improve the selectivity and efficacy of CPP for tumor targeting. Compared to PEGylated liposomes, CPPL enhanced DOX accumulation in tumors up to 1.9-fold (p

Trastuzumab has substantial antitumor activity in metastatic gastric cancer. One such mechanism by which it exerts its antitumor activity is antibody-dependent cell-mediated cytotoxicity, which has been reported to be influenced by FcγRIIA and IIIA polymorphisms. This study is the first to assess their impact on trastuzumab efficacy in patients with metastatic gastric cancer. We retrospectively examined 42 Her-2-positive patients receiving fluorouracil and platinum-based chemotherapy and trastuzumab, and 68 Her-2-negative patients receiving fluorouracil and platinum-based chemotherapy only as the first-line treatment. FcγRIIA and IIIA polymorphisms were assessed, and their associations with efficacy in both settings were analyzed. In patients treated with trastuzumab, the FcγRIIA H/H genotype was associated with significantly superior progression-free survival (PFS) (hazard ratio [HR] [95% CI]: 0.36 [0.16-0.82], adjusted HR [95% CI]: 0.18 [0.07-0.48], P=0.001). When combining FcγRIIA and IIIA polymorphisms, the FcγRIIA H/H or FcγRIIIA V/V genotype was associated with a significantly improved disease control rate (P=0.04) and PFS (HR [95% CI]: 0.29 [0.13-0.67], adjusted HR [95% CI]: 0.17 [0.07-0.45], P

// Han-Yu Deng 1, 2, * , Zi-Hang Chen 3, * , Zhi-Qiang Wang 1, * , Yun-Cang Wang 1 , En-Min Li 4 , Li-Yan Xu 5 , Yi-Dan Lin 1 and Long-Qi Chen 1 1 Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China 2 Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China 3 Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China 4 The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area and Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041, China 5 The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area and Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong 515041, China * These authors contributed equally to this work and share co-first authors Correspondence to: Long-Qi Chen, email: drchenlq@scu.edu.cn Keywords: esophagus, small cell carcinoma, Ki-67, prognosis Received: February 13, 2017 Accepted: July 12, 2017 Published: July 21, 2017 ABSTRACT Background: The prognostic value of Ki-67 expression in small cell carcinoma of the esophagus (SCCE) has not been explored in any previous studies. Therefore, we conducted this retrospective study to investigate the prognostic role of Ki-67 in SCCE for the first time. Results: A total of 44 patients were included for analysis. The baseline clinicopathological data of these SCCE patients shared similar characteristics with previous studies. Ten patients were at stage I, 17 at stage II, and the remaining 17 were at stage III. Postoperatively, 23 patients received adjuvant therapy. Twenty-eight patients were found to have a high expression of Ki-67 (> 50%). After a median follow-up time of 54.8 months, the median survival time of those patients was 22.1 months. Early TNM stage, application of adjuvant therapy, and high expression of Ki-67 (Hazard Ratio = 0.314, 95% CI: 0.127–0.774; P = 0.012) were found to be favorable prognostic factors of patients with SCCE. In subgroup analysis, adjuvant therapy could only bring significant survival benefit for patients with high expression of Ki-67 ( P = 0.008). Materials and Methods: Patients undergoing esophagectomy with lymphadenectomy for SCCE from January 2009 to January 2015 in our department were retrospectively analyzed. Data for analysis included demographic data, pathologic findings, tumor stage, adjuvant therapy, and survival time as well as Ki-67 index. Conclusions: This study suggested that high expression of Ki-67 may not only serve as a favorable prognostic factor of SCCE but also an indication of providing adjuvant therapy for SCCE patients with surgical resection.

// Razan Sheta 1, 2 , Zhi-Qiang Wang 1, 2 , Magdalena Bachvarova 2 , Marie Plante 2, 3 , Jean Gregoire 2, 3 , Marie-Claude Renaud 2, 3 , Alexandra Sebastianelli 2, 3 , Stephane Gobeil 1, 4 , Chantale Morin 2 , Elizabeth Macdonald 5 , Barbara Vanderhyden 5 and Dimcho Bachvarov 1, 2 1 Department of Molecular Medicine, Universite Laval, Quebec, Quebec, Canada 2 Centre de recherche du CHU de Quebec, L’Hotel-Dieu de Quebec, Quebec, Quebec, Canada 3 Department of Obstetrics and Gynecology, Universite Laval, Quebec, Quebec, Canada 4 Centre de recherche du CHU de Quebec, CHUL, Quebec, Quebec, Canada 5 Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada Correspondence to: Dimcho Bachvarov, email: dimtcho.batchvarov@crhdq.ulaval.ca Keywords: Hic-5, TGFB1I1, epithelial ovarian cancer, epithelial-to-mesenchymal transition, RhoA/ROCK Received: May 12, 2017 Accepted: June 17, 2017 Published: July 31, 2017 ABSTRACT The molecular basis of epithelial ovarian cancer (EOC) dissemination is still poorly understood. We have previously identified the hydrogen peroxide-inducible clone-5 (Hic-5) gene as hypomethylated in high-grade (HG) serous EOC tumors, compared to normal ovarian tissues. Hic-5 is a focal adhesion scaffold protein and has been primarily studied for its role as a key mediator of TGF-β–induced epithelial-to-mesenchymal transition (EMT) in epithelial cells of both normal and malignant origin; however, its role in EOC has been never investigated. Here we demonstrate that Hic-5 is overexpressed in advanced EOC, and that Hic-5 is upregulated upon TGFβ1 treatment in the EOC cell line with epithelial morphology (A2780s), associated with EMT induction. However, ectopic expression of Hic-5 in A2780s cells induces EMT independently of TGFβ1, accompanied with enhancement of cellular proliferation rate and migratory/invasive capacity and increased resistance to chemotherapeutic drugs. Moreover, Hic-5 knockdown in the EOC cells with mesenchymal morphology (SKOV3) was accompanied by induction of mesenchymal-to-epithelial transition (MET), followed by a reduction of their proliferative, migratory/invasive capacity, and increased drugs sensitivity in vitro , as well as enhanced tumor cell colonization and metastatic growth in vivo . The modulation of Hic-5 expression in EOC cells resulted in altered regulation of numerous EMT-related canonical pathways and was indicative for a possible role of Hic-5 in controlling EMT through a RhoA/ROCK mediated mechanism. To our knowledge, this is the first report examining the role of Hic-5 in EOC, and its role in maintaining the mesenchymal phenotype of EOC cells independently of exogenous TGFβ1 treatment.

Purpose PD-L1 is thought to play an important role in the antitumor immune response. In this study, we investigated the expression of PD-L1 within breast tumor subsets to better define its prognostic significance. Methods Immunohistochemistry was performed to determine PD-L1 tumor cell expression and to enumerate CD8, CD4 and CD68 tumor-infiltrating leucocytes (TIL) in a cohort of 443 breast cancers categorized by molecular subtype. Results Across the entire cohort, PD-L1 tumor cell expression was observed in 73/443 (16.5%) cases and associated with known indicators of poor prognosis, including low patient age, high tumor grade, ER/PR negative status, but not with outcome. However, in the Triple Negative breast cancer subset PD-L1 was associated with better recurrence free survival (RFS) especially within the Basal-like subset (Hazard ratio = 0.39, 95% CI = 0.22 - 0.86, p = 0.018). Combined PD-L1/epithelial CD8 positive status was also strongly associated with better RFS and OS (Hazard ratio = 0.12, 95% CI = 0.10 - 0.71, p = 0.010 and Hazard ratio = 0.11, 95% CI = 0.11 - 0.68, p = 0.006 respectively) in the Basal-like subgroup. Conclusions PD-L1 expression is associated with better patient survival in Basal-like breast cancer.

Purpose: To investigate the prognosis of esophageal squamous cell carcinoma with a microscopically incomplete (R1) resection margin following an esophagectomy, as well as the impact of adjuvant treatment on survival. Methods: Data obtained from 124 patients with R1-resected ESCC were reviewed. The impact of clinicopathological factors and adjuvant treatment on the overall survival, locoregional recurrence, and distant recurrence were explored. Results: For a median follow-up time of 16.8 months, the median overall survival of 124 patients was 25.6 months. The 1, 3, and 5-year overall survival rates were 75.6%±4.0%, 35.9%±5.1%, and 23.2%±5.0%, respectively. Adjuvant therapy was administered in 78 patients. In the univariate analyses, patients with a pN0 stage (log rank, p=0.028) and adjuvant chemotherapy (log rank, p=0.032) exhibited more favorable overall survival. In the multivariate analyses, the pN stage (HR=2.192, p=0.004) and adjuvant chemotherapy (HR=0.032, p=0.004) were independent prognostic factors for overall survival. Locoregional recurrence was the main failure pattern after R1 resection. The pN stage (HR=2.567, p=0.009) and adjuvant radiotherapy (HR=0.278, p=0.000) were independent prognostic factors for locoregional recurrence. Conclusion: In R1-resected esophageal squamous cell carcinoma, adjuvant radiotherapy reduced locoregional recurrence; however, it did not improve overall survival. Adjuvant chemotherapy demonstrated benefits for overall survival. The pN stage was an independent prognostic factor for locoregional recurrence and overall survival.

Purpose: CD103 is expressed in several immune cell types but in the context of the intratumoral immune response may be most important as a marker of antigen-activated CD8 T cells. Methods: We have examined the prognostic significance of CD103 TILs in breast cancer by IHC in a cohort of 424 breast cancer patients. Results: CD103 TILs were present in all subtypes but were more abundant in ER-negative tumors where CD103 TILs were preferentially localized to the intraepithelial compartment. CD103 was associated with tumor size, tumor grade, and ER/PR status (P < 0.05). CD103 TIL density and the epithelial to stromal ratio was highest in the basal-like tumors. Intraepithelial CD103 but not intrastromal CD103 was associated with better relapse-free and overall survival in basal-like subtype tumors [HR = 0.28; 95% confidence interval (CI), 0.17–0.72; P = 0.0047 and HR = 0.25; 95% CI, 0.17–0.66; P = 0.0017, respectively). CD8 status showed similar but less significant associations, but the combination of dual CD103+CD8+ TIL status was the most strongly prognostic combination for relapse-free and overall survival (HR = 0.10; 95% CI, 0.07–0.62; P = 0.006 and HR = 0.09; 95% CI, 0.07–0.57; P = 0.003, respectively). Conclusions: CD103 TILs are indicative of a good prognosis specifically within the basal-like subtype of breast cancer. Clin Cancer Res; 22(24); 6290–7. ©2016 AACR.

Background The first one-arm phase II trial aimed to evaluate and predict efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach. Patients and methods A total of 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), while the secondary endpoints were progression-free survival (PFS), time to failure (TTF), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Peripheral blood was sampled prospectively for baseline expression of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS), CYP2A6 gene polymorphisms, and 5-FU pharmacokinetics. Results The ORR and DCR were 41.0 and 76.9%. The median PFS, TTF, and OS were 4.13, 3.70, and 11.40 months. Grade 3–4 AEs occurred in only 13 patients, and grade 4 AEs occurred in only 1 of them. High OPRT/TS and peritoneal metastasis (vs. liver metastasis) independently predicted responding. High OPRT/DPD independently predicted grade 3–4 AEs. High AUC0–24h of 5-FU and metastatic/recurrent sites ≤2 (vs. >3) independently predicted prolonged PFS. Low baseline plasmic DPD independently predicted prolonged OS. Conclusions Two-week, oral S-1/LV regimen demonstrated promising efficacy and safety as first-line chemotherapy for AGC. ClinicalTrials.gov identifier NCT02090153

Backgrounds: The diagnosis of pulmonary embolism (PE) still remains difficult in clinical practice. MicroRNAs (miRNAs) have been widely investigated as biomarkers for various diseases. However, the diagnostic biomarker value of miRNAs in the diagnosis of PE is unclear. Therefore, we conducted this meta-analysis to establish the diagnostic power of miRNAs for PE diagnosis. Methods: A systematic literature search in PubMed and Embase was conducted to identify relevant studies dated up to July 22, 2016. Data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were pooled from those included studies. Summary receiver operating characteristic (SROC) curves were used to summarize overall diagnostic power of miRNAs for PE diagnosis. Results: A total of three studies with five types of miRNAs covering 254 participants were included in our meta-analysis. The overall pooled results for sensitivity, specificity, PLR, NLR, and DOR of miRNAs for PE diagnosis were 0.83 [95% confidence intervals (CI): 0.67–0.92], 0.85 (95% CI: 0.72–0.92), 5.4 (95% CI: 2.7–10.9), 0.20 (95% CI: 0.10–0.44), and 26.00 (95% CI: 7.00–101.00), respectively. The area under the SROC curve was 0.90 (95% CI: 0.87–0.92). Even though heterogeneity was observed in the analysis of sensitivity, there was no evidence of publication bias. Conclusions: MiRNAs could serve as novel non-invasive diagnostic biomarkers of PE with a relatively high diagnostic power. More researches, however, are needed to explore the diagnostic as well as therapeutic values of miRNAs for PE.

Background: The prognostic value of the right upper mediastinal lymph node dissection (RUMLND) for patients with middle or lower thoracic esophageal squamous cell carcinoma (ESCC-MLT) is still not well established yet. Our objective is to evaluate the prognostic role of the Sweet procedure plus right upper mediastinal lymph node dissection (MS) by comparing with the Sweet procedure with standard lymph node dissection (SS) in terms of long-term survival. Methods: Totally 1,477 ESCC-MLT patients underwent radical intent surgery (186 with MS, 1,291 with SS) at our department between January 2007 and September 2013. After propensity score matching (PSM), 186 patients from each group were matched and analyzed. The 5-year survival rates in two groups were compared by detailed stratifications in terms of clinical characteristics. Results: As for the prognostic role of RUMLND, patients treated with MS tended to obtain higher 5-year survival rate than patients treated with SS in univariate analysis (48.1% vs . 37.4%). Moreover, in multivariate analysis, MS yielded significant higher 5-year survival rate compared with SS (P=0.041). In addition, subgroup analyses of the survival between the MS and SS patients by detailed stratifications demonstrated the survival superiority in the MS group with age Conclusions: The RUMLND in Sweet procedure is an independent prognostic factor for ESCC-MLT patients, especially for those with thoracic middle segment-located tumor, stage III or younger.

We report the case of a 74-year-old man with suspected recurrent prostate carcinoma who underwent F-PSMA-1007 PET/CT for restaging the disease. PET/CT imaging presented an incidentaloma with intense F-PSMA-1007 uptake in the right thyroid lobe. Biopsy and genomic sequencing test confirmed the diagnosis of Hürthle cell thyroid adenoma. Therefore, it is important to raise awareness of this benign lesion in the differential diagnosis of incidental thyroid nodules with high F-PSMA-1007 activity.

In the original version of [this article][1] ([1][2]), the immunostaining of Ki-67 (si#ME1 group of PDX#2 and PDX#3) in Fig. 5G was inadvertently duplicated during data arrangement. The image has been replaced with the intended image for Fig. 5G. The error does not affect the conclusion and has been

Shuangjiang Li,1,* Zhiqiang Wang,2,* Wenbiao Zhang,1Jue Li,1 Kun Zhou,1 Guowei Che11Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Thoracic Surgery, Chongqing University Cancer Hospital, Chongqing Cancer Institute, Chongqing Cancer Hospital, Chongqing University, Chongqing 400030, People’s Republic of China*These authors contributed equally to this work Objectives: To evaluate whether the systemic inflammation score (SIS) could predict postoperative outcomes for patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for early-stage non-small-cell lung cancer (NSCLC).Methods: This retrospective study was conducted on the prospectively maintained database in our institution between January 2016 and December 2017. Preoperative SIS comprising serum albumin (sALB) and lymphocyte-to-monocyte ratio (LMR) was graded into 0, 1 and 2, and then utilized to distinguish patients at high surgical risks. Multivariable logistic-regression analysis was conducted to determine independent risk factors for postoperative outcomes.Results: There were 1,025 patients with TNM-stage I-II NSCLC included, with an overall morbidity rate of 31.1% and mortality rate of 0.3%. We applied the sALB at 40 g/L and the median LMR of our series at 4.42 as dichotomized cutoffs for modified SIS scoring criteria. Both minor and major morbidity rates in patients with SIS=2 were significantly higher than those in patients with SIS=0 and with SIS=1 (P

Background Preclinical studies suggest synergistic effectiveness of ascorbic acid (AA, vitamin C) and cytotoxic agents in gastrointestinal malignancies. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AA combined with mFOLFOX6 or FOLFIRI regimens in patients with metastatic colorectal cancer (mCRC) or gastric cancer (mGC). Methods In the dose-escalation phase, patients received AA (0.2–1.5 g/kg, 3-h infusion, once daily, days 1–3) with mFOLFOX6 or FOLFIRI in a 14-day cycle until the MTD was reached. In the speed-expansion phase, AA was administered at the MTD or at 1.5 g/kg if the MTD was not reached at a fixed rate of 0.6, 0.8 or 1 g/min. Pharmacokinetics and preliminary efficacy were also assessed. Results Thirty-six patients were enrolled. The MTD was not reached. The RP2D was established as AA at 1.5 g/kg/day, days 1–3, with mFOLFOX6 or FOLFIRI. No dose-limiting toxicity (DLT) was detected during dose escalation. The most common treatment-emergent adverse events (TRAEs) were sensory neuropathy (50%), nausea (38.9%), vomiting (36.1%) and neutropenia (27.8%). Grade 3–4 TRAEs were neutropenia (13.9%), sensory neuropathy (2.8%), vomiting (2.8%), diarrhea (2.8%) and leukopenia (2.8%). AA exposure was dose-proportional. The objective response rate was 58.3%, and the disease control rate was 95.8%. No difference in efficacy was found between mCRC patients with wild-type RAS/BRAF and mutant RAS or BRAF. Conclusions The favorable safety profile and preliminary efficacy of AA plus mFOLFOX6/FOLFIRI support further evaluation of this combination in mCRC or mGC. Trial registration ClinicalTrial.gov Identifier: NCT02969681. Electronic supplementary material The online version of this article (10.1186/s12885-019-5696-z) contains supplementary material, which is available to authorized users.

Background Initial 3-year results from our clinical trial in locoregionally advanced nasopharyngeal carcinoma (NPC) patients showed that induction chemotherapy (IC) with cisplatin and fluorouracil resulted in improved disease-free survival (DFS) with a marginally significant effect on distant metastasis-free survival (DMFS), but the effect of IC on locoregional relapse-free survival and overall survival (OS) did not differ significantly. Here, we present 5-year follow-up results. Patients and methods Our trial was a randomised, open-label phase III trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. The IC followed by CCRT group received cisplatin (80 mg/m2 d1) and fluorouracil (800 mg/m2 d1-5) every 3 weeks for two cycles before CCRT. Both groups were treated with 80 mg/m2 cisplatin every 3 weeks concurrently with radiotherapy. The primary end-points were DFS and DMFS. We did efficacy analyses in the 476 randomised patients (intention-to-treat population). Results After a median follow-up of 82.6 months, the 5-year DFS rate was 73.4% (95% confidence interval [CI] 67.7–79.1) in the IC followed by CCRT group and 63.1% (95% CI 56.8–69.4) in the CCRT alone group (p = 0.007). The 5-year DMFS rate was also significantly higher in the IC followed by CCRT group (82.8%, 95% CI 77.9–87.7) than in the CCRT alone group (73.1%, 95% CI 67.2–79.0, p = 0.014). Our updated analysis revealed an OS benefit of IC: the 5-year OS rate was 80.8% in the IC followed by CCRT group versus 76.8% in the CCRT alone group (p = 0.040). The proportion of patients with eye damage was significantly higher in the CCRT alone group than the IC followed by CCRT group (16.4% [39/238] versus 9.7% [23/238], p = 0.029). Conclusion IC followed by CCRT provides long-term DFS, DMFS and OS benefits compared with CCRT alone in locoregionally advanced NPC and, therefore, can be recommended for these patients.

Oxidative stress is detrimental to animals and can depress the growth performance and regulate the gene expression of animals. However, it remains unclear how oxidative stress regulates the expression of long noncoding RNAs (lncRNAs) and mRNAs. Therefore, the purpose of this article was to explore the profiles of lncRNAs and mRNAs in the liver of piglets under oxidative stress. Here, we constructed a piglet oxidative stress model induced by diquat and evaluated the effects of oxidative stress on the growth performance and antioxidant enzyme activity of piglets. We also used RNA-Seq to examine the global expression of lncRNAs and mRNAs in piglets under oxidative stress. The targets of lncRNAs and mRNAs were enriched in gene ontology (GO) terms and signaling pathways. The results show that the growth performance and activities of antioxidant enzymes were decreased in piglets under oxidative stress. Moreover, eight lncRNAs (6 upregulated and 2 downregulated) and 30 mRNAs (8 upregulated and 22 downregulated) were differentially expressed in the oxidative stress group of piglets compared to the negative control group. According to biological processes in enriched GO terms, the oxoacid metabolic process, intramolecular oxidoreductase activity, and oxidation-reduction process play important roles in oxidative stress. Pathway analysis showed that the signaling pathways involved in insulin and glucose metabolism had a close relationship with oxidative stress. Furtherin vitroexperiments showed that the expression of the upregulated geneGNMTwas significantly increased in primary porcine hepatocytes after diquat stimulation. In contrast, the level of the downregulated geneGCKwas significantly decreased at 12 h in primary porcine hepatocytes after diquat stimulation. Our results expand our knowledge of the lncRNAs and mRNAs transcribed in the livers of piglets under oxidative stress and provide a basis for future research on the molecular mechanisms mediating oxidative stress and tissue damage.

Introduction The current metastatic category (M) of nasopharyngeal carcinoma (NPC) is a “catch-all” category, we previously successfully established a M1 subdivision system based on prognostic metastatic characteristics in epidemic areas. We aimed to figure out metastatic characteristics associated with survival outcomes of NPC in non-epidemic areas. Methods A total of 428 newly diagnosed de novo metastatic NPC patients from 2010 to 2016 were analyzed from the population-based Surveillance, Epidemiology, and End Results program. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival. Results The most frequently involved metastatic locations were the bones (53.04%), the lungs (36.68%), the livers (29.21%) and the distant lymph nodes (24.07%). Univariate analysis indicated that bone involvement (HR = 1.39, 95% CI = 1.09–1.77), liver involvement (HR = 1.44, 95% CI = 1.12–1.85) and multiple metastatic locations (HR = 1.32, 95% CI = 1.04–1.67) were negative prognostic factors of overall survival (OS) for patients with synchronous metastasis. We established a new M1 subdivision system based on metastatic characteristics: M1a, without bone and liver involvement; M1b, single bone or liver involvement; M1c, multiple metastatic locations including bone and/or liver. Multivariate analysis confirmed that our new subcategories were associated with significantly different OS (M1b vs M1a: HR = 1.54, 95% CI = 1.11–2.16; M1c vs M1a: HR = 2.03, 95% CI = 1.47–2.78). Conclusions Synchronous metastatic NPC patients with multiple metastatic locations involved bone and/or liver were prone to suffer from dismal OS and might need more attentions for selection of treatment modality.

Nasopharyngeal carcinoma (NPC) is highly radiosensitive, and radiotherapy is recommended for newly diagnosed NPC. Because of the poor visual surgical field, narrow operating space, difficulty protecting the internal carotid artery (ICA) and poor wound healing, the development of NPC surgery has been severely limited. For recurrent NPC, some open surgical approaches, such as the maxillary swing, successfully solve the above major problems. However, these operations are traumatic and lead to many postoperative complications. With the development of minimally invasive surgery, two concepts, the “third-hand technique” and “dumpling making technique”, have been proposed, combining with the intraoperative navigation systems and multiple anatomical landmarks for identifying ICA. Endoscopic nasopharyngectomy (ENPG) can also break through the above restrictions and has become a first-line treatment for locally recurrent NPC. Moreover, a new surgical staging system for recurrent NPC was devised to aid clinicians in choosing the most suitable treatment for these patients. A current study on ENPG alone for newly diagnosed stage I NPC shows that the long-term survival outcomes after ENPG are similar to those after IMRT. ENPG was associated with low medical costs and satisfactory QOL and might be an alternative strategy for treating newly diagnosed localized stage I NPC patients who refuse radiotherapy.

Background: Esophagectomy via left thoracotomy (the Sweet procedure) has long been the conventional route for resection of esophageal carcinoma, especially in China. However, this procedure is being increasingly critiqued, mainly regarding the lymphadenectomy. The objective of this study was to compare the Sweet procedure with the right upper mediastinal lymph node resection (MS) and Ivor-Lewis (IL) procedure in the treatment of middle or lower thoracic esophageal squamous cell carcinoma (OSCC-MLT) in terms of lymphadenectomy, postoperative complications, and long-term survival. Methods: A total of 336 OSCC-MLT patients underwent radical intent surgery (188 with MS and 148 with IL procedure) between January 2007 and September 2013 in our hospital. After propensity score matching, 129 patients from each procedure were included. The efficacy of lymph node dissection at each station was estimated by the index of estimated benefit from lymph node dissection (IEBLD). Results: IEBLD is relatively high in stations 2L, 2R, 8, 16 and 17. The metastasis rates and ratios were similar between the MS and IL procedures at each station. The MS procedure significantly outperformed the IL procedure with a shorter operating time (212 vs . 317 min), shorter in-hospital stay (10.7 vs . 15.3 days), and fewer postoperative complications (30.2% vs . 43.4%). However, the 5-year survival rates were not significantly different between the two procedures (46.9% vs . 44.0%). Conclusions: The MS procedure of esophagectomy is not inferior to the IL procedure in efficiency, moreover the MS procedure is safer.

Background The free fibula flap has become popular for mandibular reconstruction. The purpose of this study was to propose comprehensive functional assessments of the donor site. Methods Thirty free fibula flaps for mandible reconstruction were prospectively enrolled in the study. Objective assessments included isokinetic testing of the ankle joint, electromyographic examination of the superficial peroneal nerve (SPN), and preoperative and postoperative foot scans. The Patient and Observer Scar Assessment Scale (POSAS) was used to subjectively assess the donor site. Results The isokinetic values of the donor side showed a significant decrease 1 year postoperatively. The results of the electromyographic test of the SPN were categorized as 3 types. The plantar center pressure shifted to the heel on the donor side 6 months postoperatively. The aesthetic outcome was satisfactory. Conclusion The functional parameters of the donor site indeed declined in our assessments. Further refinements in the surgical technique are needed to improve the donor site status. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Salvage treatment for locoregionally recurrent nasopharyngeal carcinoma remains a significant challenge. The present study was conducted to evaluate the efficacy, toxicity and prognostic factors of a triplet chemotherapy regimen involving cisplatin, fluorouracil and paclitaxel (TPF) for locoregionally recurrent nasopharyngeal carcinoma (NPC) cases contraindicated for re-irradiation/surgery.Patients with locoregionally recurrent NPC unsuitable for re-irradiation/surgery were treated with TPF therapy. The chemotherapy drugs were administered as follows: 135 mg/m(2) paclitaxel on day 1, 25 mg/m(2)/day cisplatin on days 1-3, followed by continuously infused intravenous fluorouracil for 120 h at a variable dosage from 600 to 800 mg/m(2)/day, depending on prior radiation.Twenty-seven patients were enrolled. The overall response was 66.7%. The median progression-free survival (PFS) and overall survival (OS) were 8.5 and 27.2 months, respectively. Toxicity was mild to moderate. Neutropenia and leukopenia were the primary grade 3-4 chemotherapy toxicities. 6 patients who regained the potential for re-radiotherapy or surgery showed significantly better outcomes than those treated with chemotherapy alone (median PFS: 20.8 vs. 7.1 months, P = 0.005; median OS: 54.2 vs. 20.6 months, P = 0.021).TPF triplet chemotherapy showed a high response rate for locoregionally recurrent NPC with an acceptable toxicity profile.