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Extreme drought events are becoming frequent globally, resulting in widespread plant mortality and forest dieback. Although savanna vegetation cover ~20% of the earth’s land area, their responses to extreme drought have been less studied than that of forests. Herein, we quantified branch dieback, individual mortality and the associated physiological responses of four evergreen shrubs (Tarenna depauperate Hutch., Maytenus esquirolii (H. Lév.) C.Y. Cheng, Murraya exotica L., Jasminum nudiflorum Lindl.) in a savanna ecosystem in Southwest China to an incidence of extreme drought during 2019 and 2020. We found that 80–100% of the individuals of these species exhibited branch dieback, whereas individual mortality was only found in T. depauperate (4.5%). All species showed high resistance to stem embolism (P50, water potential at 50% loss of hydraulic conductivity ranged from −5.62 to −8.6 MPa), whereas the stem minimum water potentials reached −7.6 to ca −10.0 MPa during the drought. The low water potential caused high native embolism levels (percentage loss of hydraulic conductivity (PLC) 23–65%) in terminal branches, and the remaining stems maintained 15–35% PLC at the end of the drought. Large within-individual variations in stem vulnerability to embolism were detected, and shedding of vulnerable branches could be a mechanism for shrubs to reduce water and carbon consumption. Overall, the content of total nonstructural carbohydrates (NSC) and their components in the stem were generally comparable to or higher than those in the rainy season in three of the four species. Because the leaves were turgor-less for most time during the drought, high NSC levels during the drought could be due to recycling of NSC from dead branches or translocation from roots. Our results suggest high tolerance of savanna shrub species to extreme drought, which could be facilitated by high embolism resistance in some stems and shedding of vulnerable branches to maintain individual water and carbon balance.

Background Compared with single‐drug TACE, our previous phase III study demonstrated that triple‐drug transarterial chemoembolization (TACE) prolonged overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). The aim of this study was to find which patients can benefit from the triple drugs TACE compared with single‐drug TACE. Methods Patients in the triple‐drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin, 50 mg lobaplatin, 6 mg mitomycin C, and lipiodol, while patients in the single‐drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin and lipiodol. From July 2007 to November 2009, 244 patients (224 men and 20 women; age ranged from 21 to 75 years) from our phase III study formed the initial cohort. From January 2010 to June 2015, external validation cohort was composed of 449 patients (411 men and 38 women; age ranged from 18 to 75 years) from another institution. The validation cohort after propensity score matching (PSM) (n = 374) was analyzed. Cox proportional hazard model was used to evaluate the interaction term between treatments for each subgroup. This retrospective study was approved by the institutional review board at each center. Results No difference was observed in the baseline characteristic of three cohorts. This exploratory analysis showed that triple‐drug TACE brought a survival benefit in the initial cohort, validation cohort (before PSM), and validation cohort (after PSM) compared with single‐drug TACE. The outcomes of three cohorts all showed that a significantly greater OS triple‐drug chemotherapy benefit versus single‐drug chemotherapy was seen in patients with large tumors (larger than 10 cm) while no survival difference was seen in patients with small tumors (10 cm or smaller). Conclusions Triple‐drug TACE seems to benefit patients with HCC larger than 10 cm in particular compared with single‐drug TACE.

Hydraulic failure caused by severe drought contributes to aboveground dieback and whole-plant death. The extent to which dieback or whole-plant death can be predicted by plant hydraulic traits has rarely been tested among species with different leaf habits and/or growth forms. We investigated 19 hydraulic traits in 40 woody species in a tropical savanna and their potential correlations with drought response during an extreme drought event during the El Niño–Southern Oscillation in 2015. Plant hydraulic trait variation was partitioned substantially by leaf habit but not growth form along a trade-off axis between traits that support drought tolerance versus avoidance. Semi-deciduous species and shrubs had the highest branch dieback and top-kill (complete aboveground death) among the leaf habits or growth forms. Dieback and top-kill were well explained by combining hydraulic traits with leaf habit and growth form, suggesting integrating life history traits with hydraulic traits will yield better predictions.

ObjectiveData regarding direct comparison of contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) and Computed Tomography/Magnetic Resonance Imaging (CT/MR) LI-RADS in diagnosis of non-hepatocelluar carcinoma (non-HCC) malignancies remain limited. Our study aimed to compare the diagnostic performance of the CEUS LI-RADS version 2017 and CT/MRI LI-RADS v2018 for diagnosing non-HCC malignancies in patients with risks for HCC.Materials and MethodsIn this retrospective study, 94 liver nodules pathologically-confirmed as non-HCC malignancies in 92 patients at risks for HCC from January 2009 to December 2018 were enrolled. The imaging features and the LI-RADS categories on corresponding CEUS and CT/MRI within 1 month were retrospectively analyzed according to the ACR CEUS LI-RADS v2017 and ACR CT/MRI LI-RADS v2018 by two radiologists in consensus for each algorithm. The sensitivity of LR-M category, inter-reader agreement and inter-modality agreement was compared between these two standardized algorithms.ResultsNinety-four nodules in 92 patients (mean age, 54 years ± 10 [standard deviation] with 65 men [54 years ± 11] and 27 women [54 years ± 8]), including 56 intrahepatic cholangiocarcinomas, 34 combined hepatocellular cholangiocarcinomas, two adenosquamous carcinomas of the liver, one primary hepatic neuroendocrine carcinoma and one hepatic undifferentiated sarcoma were included. On CEUS, numbers of lesions classified as LR-3, LR-4, LR-5 and LR-M were 0, 1, 10 and 83, and on CT/MRI, the corresponding numbers were 3, 0, 14 and 77. There was no significant difference in the sensitivity of LR-M between these two standardized algorithms (88.3% of CEUS vs 81.9% of CT/MRI, p = 0.210). Seventy-seven lesions (81.9%) were classified as the same LI-RADS categories by both standardized algorithms (five for LR-5 and 72 for LR-M, kappa value = 0.307). In the subgroup analysis for ICC and CHC, no significant differences were found in the sensitivity of LR-M category between these two standardized algorithms (for ICC, 94.6% of CEUS vs 89.3% of CT/MRI, p = 0.375; for CHC, 76.5% of CEUS vs 70.6% of CT/MRI, p = 0. 649).ConclusionCEUS LI-RADS v2017 and CT/MRI LI-RADS v2018 showed similar value for diagnosing non-HCC primary hepatic malignancies in patients with risks.

Purpose Previous studies reported an association between an increased risk of tongue cancer and radiation treatment for nasopharyngeal carcinoma (NPC). This study compared the clinicopathologic characteristics and outcomes of tongue squamous cell carcinoma (TSCC) in patients with and without a history of radiotherapy for NPC. Materials and methods From 1965 to 2009, a total of 73 patients were diagnosed with TSCC with a history of radiotherapy for NPC. The patients were matched in a 1:3 ratio with patients with sporadic TSCC according to age, sex, and year of the TSCC diagnosis. The primary endpoint was the overall survival. Results The median interval from NPC to TSCC was 82 months. The NPC survivors were more likely to be diagnosed with a more advanced T classification, less likely to have lymph node involvement, and more likely to have the tumor located in the dorsum of the tongue than sporadic TSCC. Regarding the histologic characteristics, the NPC survivors were more likely to have a weak lymphocytic host response, low tumor budding, and low risk of a worse pattern of invasion. The sporadic TSCC patients had a better overall survival (hazard ratio, 0.690; p=0.033) than the NPC survivors. In competing risks analysis, the cumulative incidence functions for the competing event (documented non-tongue cancer death) were significantly higher in the NPC survivors (Gray's test, p=0.001). Conclusion TSCC patients with a history of radiotherapy for NPC appear to have particular clinicopathologic features, a poorer survival, and are more likely to die from non-tongue cancer causes than those with sporadic TSCC.

We used the status of microvascular invasion (MVI) at primary resection to help treatment selection for hepatitis B virus-positive (HBV+) recurrent hepatocellular carcinoma (rHCC) patients in Barcelona Clinic Liver Cancer (BCLC) stage B-C.From 2009 to 2017, we enrolled 221 consecutive HBV+ rHCC patients at BCLC stage B-C who underwent re-resection (RR), radiofrequency ablation (RFA), or transarterial chemoembolization (TACE). Post recurrence survival (PRS) and overall survival (OS) were compared between RR/RFA and TACE according to MVI status. A one-to-one propensity score matching analysis was performed.For MVI(-) patients, the median PRS was 62.3 months for the RR/RFA group and 21.1 months for the TACE group (p = 0.039). The corresponding OS was 71.4 months and 26.6 months, respectively (p = 0.010). For MVI(+) patients, the median PRS in the RR/RFA group and TACE group was 14.7 months and 10.1 months (p = 0.115). The corresponding OS was 23.4 months and 16.4 months, respectively (p = 0.067). After matching, the dominance of RR/RFA over TACE remained in MVI(-) patients for both PRS (62.3 months vs 15.3 months, p = 0.019) and OS (98.1 months vs 33.4 months, p = 0.046). No significant difference was found in MVI(+) patients for either PRS (14.7 months vs 11.8 months, p = 0.593) or OS (23.4 months vs 28.1 months, p = 0.662).MVI status definitely helps select treatment options in HBV+ rHCC patients. For MVI(-) patients, RR/RFA provided better survival than TACE while for MVI(+) patients, TACE shared similar survival outcomes.• This study aimed at the determination of the optimal treatment options (ablation /resection vs TACE) in case of recurrent HBV-related HCC. • It showed that MVI status, established at primary resection of HCC, was a powerful marker for selecting the best treatment option in these patients. • In MVI(-) patients, RR/RFA achieved a better survival than TACE. In MVI(+) patients, TACE shared similar survival.

6021 Background: Camrelizumab is a fully humanized, monoclonal antibody against PD-1. We aimed to assess the efficacy and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor targeting VEGFR2, in patients with advanced cervical cancer. Methods: In this open-label, single-arm, phase 2 study done at four centres in China, eligible patients were aged 18–70 years, had an ECOG performance status of 0 or 1, progressed after at least one line of systemic chemotherapy for metastatic, recurrent or persistent cervical cancer, and had measurable disease. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once daily. Treatment continued until disease progression, unacceptable toxicity, and withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by RECIST version 1.1. An optimal Simon two-stage design was employed to test the null hypothesis of a 17% ORR versus 35% alternative (1-sided alpha 0.10, 80% power), if > 3 responses out of the first 16 patients were observed, then the study would continue to enroll a total of 44 patients. Results: Between Jan 21st, 2019, and Aug 1st, 2019, 45 patients were enrolled and received study treatment (safety population). The median age was 51 (range, 33–67) years. Median previous treatment lines were 2 (range, 1–4). As of Jan 22, 2020, median follow-up was 9.2 months (range, 2.4–12.2). 25 (59.5%; 95%: CI 44.7–74.4) of 42 patients who had at least one post-baseline tumor assessment (efficacy evaluable population) achieved an objective response, including two (4.8%) complete response, and 23 (54.8%) partial response. Median duration of response was not reached. The disease control rate was 88.1% (37/42). Median progression-free survival (PFS) was 7.6 months (95% CI: 5.8–not reached). 31 (68.9%) patients had grade ≥ 3 treatment-related adverse events (TRAEs). Grade ≥ 3 TRAEs occurring in ≥ 5% of patients were hypertension (24.4%), anemia (20.0%), fatigue (15.6%), γ-glutamyltransferase increased (13.3%), neutropenia (6.7%), and thrombocytopenia (6.7%). In post-hoc analyses, objective response was noted in 20 (69%) of 29 patients with PD-L1-positive tumors, and in 5 (50.0%) of 10 patients with PD-L1-negative tumors (Chi-square test, P = 0.281). PFS was longer in patients with PD-L1-positive tumors than patients with PD-L1-negative tumors (median PFS: 9.6 versus 5.3 months; log-rank test, P = 0.017). Conclusions: Camrelizumab plus apatinib showed promising antitumor activity and tolerable toxicities in patients with advanced cervical cancer. Clinical trial information: NCT03816553.

Summary Background Anti-angiogenic therapy combined with chemotherapy could improve the outcomes of patients with platinum-resistant ovarian cancer. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits VEGF receptor 2. We assessed the efficacy and safety of the combination therapy of apatinib and oral etoposide, considering the potential advantage of home administration without hospital admission, in patients with platinum-resistant or platinum-refractory ovarian cancer. Methods In this phase 2, single-arm, prospective study, we recruited patients aged 18–70 years with platinum-resistant or platinum-refractory ovarian cancer at the Sun Yat-sen University Cancer Center (China). The treatment consisted of apatinib at an initial dose of 500 mg once daily on a continuous basis, and oral etoposide at a dose of 50 mg once daily on days 1–14 of a 21-day cycle. Oral etoposide was administered for a maximum of six cycles. Treatment was continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoint was the proportion of patients achieving an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1. We used Simon's two-stage design, and analysed efficacy in the intention-to-treat and per-protocol populations. Safety analyses included enrolled patients who had received at least one dose of study medication, but excluded those without any safety data. This study is registered with ClinicalTrials.gov , number NCT02867956 . Findings Between Aug 10, 2016, and Nov 9, 2017, we screened 38 and enrolled 35 patients. At the data cutoff date (Dec 31, 2017), 20 (57%) patients had discontinued the study, and 15 (43%) patients remained on treatment. Objective responses were achieved in 19 (54%; 95% CI 36·6–71·2) of 35 patients in the intention-to-treat population and in 19 (61%; 42·2–78·2) of 31 patients in the per-protocol population. The most common grade 3 or 4 adverse events were neutropenia (17 [50%]), fatigue (11 [32%]), anaemia (ten [29%]), and mucositis (eight [24%]). Serious adverse events were reported in two patients who were admitted to hospital (one patient had anaemia and anorexia; the other patient had increased ascites due to disease progression). No treatment-related deaths were recorded. Interpretation The combination of apatinib with oral etoposide shows promising efficacy and manageable toxicities in patients with platinum-resistant or platinum-refractory ovarian cancer, and further study in phase 3 trials is warranted. Funding None.

To evaluate the outcomes of preoperative transarterial chemoembolization (TACE) for resectable hepatocellular carcinoma (HCC) with portal vein invasion. From February 2006 to July 2011, 320 patients initially diagnosed with resectable HCC and portal vein invasion were prospectively non-randomized into two arms. In the immediate resection arm (Arm 1, n = 205) patients received immediate surgical resection. 115 patients were included in the preoperative TACE arm (Arm 2), and eventually 85 patients underwent TACE followed by surgical resection. The 1-, 3- and 5-year overall survival rates were 48.3 %, 18.7 % and 13.9 % for Arm 1 and 61.2 %, 31.7 % and 25.3 % for Arm 2 (P = 0.001), respectively. In the subgroup analysis of types I and II portal vein tumour thrombus (PVTT), the preoperative TACE arm demonstrated significantly better survival rates than the immediate resection arm (P I = 0.001, P II = 0.036). However, no significant difference was found for patients with type III PVTT (P III = 0.684). No significant difference was found between the two arms in terms of complications and mortality. Preoperative TACE seems to confer a survival benefit for resectable HCC with PVTT, especially for types I and II PVTT, and preoperative TACE should therefore be recommended as a routine procedure. • Preoperative TACE improves the clinical outcomes for patients with PVTT • Preoperative TACE could significantly improve the rate of en bloc thrombectomy • Preoperative TACE does not increase the related adverse events

Background and purpose Genetic single nucleotide polymorphisms (SNP) play a critical role in the development of esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the associations between insulin-like growth factor binding protein-3 ( IGFBP-3 ) gene polymorphisms and ESCC patients risk and survival after definitive chemoradiotherapy (CRT). Materials and methods We undertook a case-control study to analyze two IGFBP-3 polymorphisms (rs2854744 A > C and rs2854746 G > C) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 110 ESCC patients treated with CRT and 128 control participants, and performed IGFBP-3 genotyping using DNA sequencing. Results The obtained results indicated that overall, no statistically significant association was observed in rs2854746 G > C. However, rs2854744 A > C genotype was at increased risk of ESCCs ( P = 0.032; odds ratio (OR) = 1.201, CI 95%:1.014–1.423). Moreover, rs2854744 A > C genotype ESCCs were more significantly common in patients with tumor size of >6 cm than A allele ESCC and in cases of lower T stage. Furthermore, ESCC patients with rs2854744CC genotype have the poorer CRT response and shorter survival time than GG + GC genotype ESCC. Conclusions In conclusion, polymorphism in IGFBP-3 rs2854744 A > C might be a potential predictor of ESCC risk and patient survival. Nevertheless, further investigation with a larger sample size is needed to support our results.

Background and purpose: There is increasing evidence that the presence of an inflammation-based prognostic score (modified Glasgow prognostic score, mGPS) is associated with survival in patients with advanced cancer. This study aimed to assess whether the mGPS has prognostic value in patients with thoracic esophageal squamous cell carcinoma undergoing chemoradiotherapy. Materials and methods: A total of 212 patients undergoing chemoradiotherapy for newly-diagnosed esophageal squamous cell carcinoma between October, 2006 and December, 2011 were retrospectively analyzed. Serum C-reactive protein (CRP) and albumin were measured before initiation of treatment. The relationships between the mGPS and other relevant variables including white blood cell count, neutrophilic granulocyte count, platelet count, hemoglobin, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were analyzed. Overall survival (OS) and progression-free survival (PFS) were calculated. Significant prognostic factors were identified using univariate and multivariate analyses. Results: Three-year OS for all patients was 24.6%; 3-year PFS was 21.3%. Patients with a mGPS of 0, 1 and 2 were 90, 78, 44, respectively. Higher mGPS was related to higher white blood cell, neutrophilic granulocyte and platelet counts, and lower total bilirubin. T stage, M stage and mGPS were independent prognostic indicators for OS; T stage, M stage, mGPS and platelet count were independent prognostic indicators for PFS. Conclusions: Pretreatment mGPS is an easily measurable significant prognostic factor and can be used in combination with conventional TNM staging to predict survival in patients with squamous cell carcinoma undergoing chemoradiotherapy.

Background: In patients with a large, unresectable hepatocellular carcinoma (HCC), the primary recommendation is for transarterial chemoembolization (TACE) but used alone TACE is not typically curative. Combinations of TACE followed in a delayed fashion by single-applicator thermal ablation have also been suboptimal. As an alternative, we investigated the combination of TACE followed within 1–3 days by multi-antenna microwave ablation (MWA) in patients with a large HCC, to determine the feasibility, safety, local control, and short-term survival rates of this approach. Methods: We retrospectively studied 43 patients with a large HCC (mean diameter, 8.8 cm; SD, 2.8 cm) treated between July 2015 and July 2018, who underwent TACE followed within 3 days by multi-antenna simultaneous MWA. We measured the liver and renal function before and after treatment, recorded complications, used three-dimensional software and imaging to calculate tumor necrosis rates at 1 month after therapy, and calculated overall survival (OS) and progression-free survival (PFS) using the Kaplan–Meier method. Results: Mean follow up was 12.2 (range, 3.5–35.6) months. All patients completed the treatment protocol. At 1 month after combined therapy, tumor necrosis was complete in 16 (37.2%), nearly complete in 19 (44.2%), and partial in 8 (18.6%) patients. The 1- and 2-year OS rates were 64.0% and 46.8%, respectively, with a median OS of 23.0 months; and the 1- and 2-year PFS rates were 19.9% and 4.4%, respectively, with a median PFS of 4.2 months. A transient change in liver function occurred 3 days after MWA but resolved within 1 month. Only two patients had major complications, which were treatable and resolved. Conclusion: Multi-antenna MWA-oriented combined therapy is feasible and well tolerated, and it results in satisfactory initial local control and short-term survival in some but not all patients with a large HCC.

Insulin-like growth factor binding protein-3 (IGFBP-3) plays an essential role in radiosensitivity of esophageal squamous cell carcinoma (ESCC). However, the underlying mechanism is not completely understood. Here, we observed that IGFBP-3 had favorable impact on the tumorigenicity of ESCC cells in nude mice by using an in vivo imaging system (IVIS) to monitor tumor growth treated with ionizing radiation (IR). Downregulation of IGFBP-3 expression enhanced tumor growth, inhibited anti-proliferative and apoptotic activity and result in IR resistance in vivo. Cell cycle antibody array suggested that silencing IGFBP-3 promoted transition from G0/G1 to S phase, perhaps though influencing Smad3 dephosphorylation and retinoblastoma protein (Rb) phosphorylation. Downregulation of P21 and P27 and upregulation of p-P27 (phospho-Thr187), cyclin-dependent kinase 2 (CDK2) and cyclin E1 might contribute to the G0/G1 to S phase transition promoted by IGFBP-3. Our results suggest that Smad3-P27/P21-cyclin E1/CDK2-phosphorylated retinoblastoma protein pathways might be involved in this IGFBP-3 mediated radiosensitivity transition in ESCC.

Background & aims The discontinuation rules of transarterial chemoembolization (TACE) for patients who were assessed as progressive disease (PD) but stage progression-free (SP-free: still belongs to Barcelona Clinic Liver Cancer B) after TACE are unclear. We aimed to evaluate the impact of the PD-pattern on the survival of these patients retreated with TACE. Methods In total, 115 consecutive patients who were assessed as PD but SP-free after TACE and then underwent at least one subsequent TACE session were included. Sixty patients were assessed as PD with target lesion progression (TP), and 55 patients were assessed as PD with target lesion non-progression (TNP). Survival and treatment-related adverse events were compared between the two groups. Additional external validation was performed using a data set (n = 103) from another institution. Results Patients with TNP had significantly longer median post-progression survival (PPS) than those with TP (21.0 vs. 11.9 months, P = 0.004). After TACE retreatment, the incidence of liver dysfunction was significantly higher for patients with TP than for patients with TNP (45% vs. 20%, P = 0.031). In the multivariate analysis, the target lesion response was one of the most significant prognostic factors for PPS (HR = 2.01; 95% confidence interval: 1.23-3.27; P = 0.005). The findings were supported by an independent external cohort. Conclusions Compared to patients with TNP, patients with TP might exhibit no improvement in survival and even present damaged liver function after retreatment with TACE. Target lesion response is useful as a clinical decision for repeated TACE in these patients.

Purpose To compare the stability of stable and unstable water-in-oil emulsions and the efficacy and safety of these emulsions in a single-center, prospective double-blind trial of transarterial chemoembolization for hepatocellular carcinoma (HCC). Materials and Methods A total of 812 patients with inoperable HCC were randomized (stable emulsion, n = 402; unstable emulsion, n = 410). The 2 emulsions were prepared by using the same protocol except that different solvents were used for chemotherapy agents, including epirubicin, lobaplatin, and mitomycin C. The solvent in the stable emulsion arm was contrast medium and distilled water, and the solvent in the unstable emulsion arm was distilled water. The primary endpoint was overall survival (OS), and secondary endpoints were time to progression (TTP), tumor response, adverse events (AEs), and plasma epirubicin concentrations. Results In vitro, stable emulsions did not occur until 1 day, and unstable emulsions, with a lower peak plasma concentration (P = .001) in vivo, exhibited rapid separation of the oil and aqueous phases after 10 minutes. Median OS times in the stable and unstable emulsion arms were 17.7 and 19.2 months, respectively (P = .81). No differences were found in TTP, tumor response, and AEs except for myelosuppression (anemia, 3.5% vs 7.6%; thrombocytopenia, 11.5% vs 17.7%), which was significantly more severe and frequent in the unstable emulsion arm (P = .013). Conclusions Chemoembolization is equally effective with the use of stable and unstable emulsions, but the use of a stable emulsion has the advantage of less myelosuppression and a favorable pharmacokinetic profile.

Background Insulin-like growth factor-binding protein-3 (IGFBP-3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma (ESCC). The present study was designed to investigate the clinical and prognostic effects of IGFBP-3 on ESCC. Methods IGFBP-3 was detected by immunohistochemistry in paraffin-embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non-malignant esophageal specimens. Receiver operating characteristic (ROC) analysis was used to determine cut-off scores for tumor positivity and to evaluate patient survival status. The χ2 test was performed to analyze the association of IGFBP-3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP-3 expression were investigated using Kaplan–Meier analysis and the Cox proportional hazards model. Results The threshold for IGFBP-3 positivity was set to greater than 65% [area under the ROC curve (AUC) = 0.690, P

The prognostic value of the primary lesion pretreatment apparent diffusion coefficient (ADC), which is obtained by diffusion-weighted magnetic resonance imaging (MR-DWI), remains unknown in nasopharyngeal carcinoma (NPC). Thus, to investigate whether the pretreatment ADC value as measured from the primary site on MR-DWI is an independent prognostic factor in NPC, we retrospectively reviewed a cohort of 541 patients with histologically-proven stage I-IVB NPC. All patients underwent MRI using a 3-Tesla system (Trio Tim; Siemens, Erlangen Germany). To calculate ADC, the primary lesion was designated on the ADC map at the level of the largest tumor diameter to cover most of the lesion, avoiding cystic or necrotic components. Median and mean (±SD) pretreatment ADC were 0.713 and 0.716 ± 0.079 × 10−3 mm2/s, respectively. Univariate and multivariate analysis confirmed high pretreatment ADC was a good prognostic factor for poor local relapse-free survival and disease-free survival. Furthermore, the area under the ROC curve for prediction of local failure significantly increased when pretreatment ADC was combined with T classification (P = 0.004). Thus, pretreatment ADC might provide useful information for predicting outcome and selecting high-risk patients appropriate for more aggressive therapy. Further studies are warranted to investigate the biological basis of this observation.

Background The prognostic factors of thoracic esophageal squamous carcinoma with cervical lymph nodal metastasis (CLNM) have not been specifically investigated. This study was performed to analyze the efficacy and prognostic factors of chemoradiotherapy for thoracic esophageal carcinoma with CLNM alone. Methods From 2002 to 2011, 139 patients with inoperable esophageal cancer who underwent chemoradiotherapy at the Sun Yat-Sen University were retrospectively analyzed. Median radiation doses were 60 Gy (range: 50–68 Gy). Univariate and multivariate analyses were performed to compare overall survival (OS) and progression-free survival (PFS). Results The 1- and 3-year OS rates were 68.2% and 27.9%, respectively. The 1- and 3-year PFS rates were 51.9% and 20.1%, respectively. The multivariate analysis demonstrated that response to treatment, T stage, pathological grade, and laterality of cervical lymph nodal metastases were independent prognostic factors for thoracic esophageal carcinoma with CLNM. Conclusions Concurrent chemoradiotherapy is an important and hopeful treatment option for patients with esophageal cancer with CLNM alone. Our study has revealed that response to treatment, T stage, pathological grade and laterality of cervical lymph nodal metastases are significant prognostic factors for long-term survival.

Background and purpose The benefit of concurrent chemoradiotherapy (CCRT) in elderly patients with inoperable esophageal squamous cell carcinoma (SCC) is controversial. This study aimed to assess the efficiency and safety of CCRT in elderly thoracic esophageal cancer patients. Methods and materials Between January 2002 and December 2011, 128 patients aged 65 years or older treated with CCRT or radiotherapy (RT) alone for inoperable thoracic esophageal SCC were analyzed retrospectively (RT alone, n = 55; CCRT, n = 73). Results No treatment-related deaths occurred and no patients experienced any acute grade 4 non-hematologic toxicities. Patients treated with CCRT developed more severe acute toxicities than patients who received RT alone. The 3-year overall survival (OS) rate was 36.1% for CCRT compared with 28.5% following RT alone (p = 0.008). Multivariate analysis identified T stage and treatment modality as independent prognostic factors for survival. Further analysis revealed that survival was significantly better in the CCRT group than in the RT alone group for patients ≤ 72 years. Nevertheless, the CCRT group had a similar OS to the RT group for patients > 72 years. Conclusion Our results suggest that elderly patients with inoperable thoracic esophageal SCC could benefit from CCRT, without major toxicities. However, for patients older than 72 years, CCRT is not superior to RT alone in terms of survival benefit.

Background Epidermal growth factor receptor (EGFR) is suggested to predict the radiosensitivity and/or prognosis of human esophageal squamous cell carcinoma (ESCC). The objective of this study was to investigate the efficacy of Nimotuzumab (an anti-EGFR monoclonal antibody) on ESCC radiotherapy (RT) and underlying mechanisms. Methods Nimotuzumab was administrated to 2 ESCC cell lines KYSE30 and TE-1 treated with RT. Cell growth, colony formation and apoptosis were used to measure anti-proliferation effects. The method of RNA interference was used to investigate the role of insulin-like growth factor binding protein-3 (IGFBP-3) in ESCC cells radiosensitivity treated with Nimotuzumab. In vivo effect of Nimotuzumab on ESCC radiotherapy was done using a mouse xenograft model. Results Nimotuzumab enhanced radiation response of KYSE30 cells (with high EGFR expression) in vitro, as evidenced by increased radiation-inhibited cell growth and colony formation and radiation-mediated apoptosis. Mechanism study revealed that Nimotuzumab inhibited phosphorylated EGFR (p-EGFR) induced by EGF in KYSE30 cells. In addition, knockdown of IGFBP-3 by short hairpin RNA significantly reduced KYSE30 cells radiosensitivity (PP>0.05). In KYSE30 cell xenografts, Nimotuzumab combined with radiation led to significant tumor growth delay, compared with that of radiation alone (P=0.029), and also with IGFBP-3 up-regulation in tumor tissue. Conclusions Nimotuzumab could enhance the RT effect of ESCC cells with a functional active EGFR pathway. In particular, the increased ESCC radiosensitivity by Nimotuzumab might be dependent on the up-regulation of IGFBP-3 through EGFR-dependent pathway.

It is difficult to discriminate progressive gastric cancer and gastric lymphoma by CT imaging, because incrassate gastric wall, lump in gastric cavity, confined gastric cavity, intumescent lymph node, and distant metastasis can be displayed in both of them. This study was to compare the CT findings between gastric cancer and gastric lymphoma to improve diagnosis of gastric tumors, especially for gastric lymphoma.CT images of 27 patients with pathologically proved progressive gastric cancer and 25 patients with pathologically proved gastric lymphoma were reviewed. Tumor location, appearance, scope of involvement, gastric wall thickness, mucous membrane, mucosal fold, serosa membrane, necrosis, enhancement degree and uniformity, involvement of other organs, and abdominal lymph nodes were observed.White line sign was observed in 23 cases (85.2%) of gastric cancer, but not in the 25 cases of gastric lymphoma. The extent of white line sign in gastric cancers was larger in portal vein phase than in arterial phase. Enhancement degree outside the white line was higher in portal vein phase than in arterial phase in 13 cases (48.1%) of gastric cancer. The extent of involved gastric wall was smaller than 50% of the whole gastric wall in all the 27 cases of gastric cancer, while it was larger than 75% in 23 cases (85.2%) of gastric lymphoma. Gastric mucous membrane ulcer was found in all of the 27 cases (100%) of gastric cancer, while it was found in only 1 case (4.0%) of gastric lymphoma. Intumescent lymph nodes in two or more areas were found in 11 cases (40.0%) of gastric lymphoma, but not in gastric cancer. Intumescent lymph nodes in the retroperitoneal space below renal hilum were found in 8 cases (32%) of gastric lymphoma, but not in gastric cancer.There are some different CT features between gastric cancer and gastric lymphoma, such as white line sign, gastric mucous membrane ulcer, extent of involved gastric wall, location of intumescent lymph nodes surrounding the stomach and in retroperitoneal space below renal hilum, and so on, which could be helpful in differential diagnosis of these two diseases.

Most parotid tumors grow slowly. It is difficult to evaluate their malignancy. This study was to analyze the CT features of parotid tumors.CT images of 133 patients with 157 lesions of parotid tumors, confirmed by histopathology, were reviewed. The location, contour, margin, enhancing type, necrosis and liquefaction, and adjacent structure involvement were analyzed.Among the 157 lesions, 110 (70.1%) were benign tumors, 18 (11.5%) were borderline tumors, and 29 (18.5%) were malignant tumors; 80 (72.7%) benign lesions and 14 (77.8%) borderline lesions located in the superficial lobe, whereas 7 (24.1%) malignant lesions located in the deep lobe and 10 (34.5%) in both the superficial lobe and the deep lobe; 99 (90.0%) benign lesions had sharp margins, 8 (44.4%) borderline lesions had sharp margins and 10 (55.6%) had partly unsharp margins, 10 (34.5%) malignant lesions had partly unsharp margins and 11 (37.9%) had unsharp margins. Most benign lesions were round (68/110, 61.8%) or oval (23/110, 20.9%), while malignant lesions were often irregular (14/29, 48.3%). Eleven lesions, including 2 borderline tumors and 9 malignant tumors, involved the adjacent subcutaneous fat. All the lesions which involved the bed of parotid gland were malignant. No benign tumor involved adjacent structures.On CT images, a parotid tumor located in the superficial lobe, with a round or oval contour and sharp margin, is more likely to be a benign tumor; otherwise, it might be a malignant tumor.

BACKGROUND: The peripheral enhancement of small hepatocellular carcinoma (SHCC) is a rare appearance in dual phase images by helical computed tomography (CT). This study discusses this phenomenon and its correlative histopathology. METHODS: The helical CT dual phase appearance of peripheral enhancement in SHCC was analyzed in 21 cases (22 lesions). All lesions were confirmed as SHCC by histopathological examination. RESULTS: In these 22 lesions, enhanced peripheral ring in 20 lesions was incomplete, the thickness of enhanced peripheral ring varied and mural node could be found in hepatic arterial phase; only 2 lesions had complete peripheral ring enhancement and ring of uniform thickness in hepatic arterial phase. The enhancement of some peripheral rings and mural nodes dropped to very low density in portal venous phase. The tumour cells were grade I in 3 lesions, II in 16, III in 2 and IV in 1. The vascular supply was more abundant at the border than in the centre of 15 lesions and the vascular supply was deficient in both centre and border of the remaining 7 lesions. In 3 lesions, the pseudocapsule showed in the border of the lesion. In 12 lesions, flecks of necrosis were found in the border and/or centre of the lesion. CONCLUSIONS: The characteristic peripheral enhancement in helical CT dual phase images of small hepatocellular carcinoma correlates with different vascular supplies, fibrous capsule and necrosis of the lesion.

Malignant epithelial parotid tumors have various histopathologic types. Computed tomography (CT) has been widely used to detect parotid masses. This study was to analyze CT features of malignant epithelial parotid tumors to evaluate the diagnostic value of CT in the characterization of malignant epithelial parotid tumors.CT reports of 29 patients with malignant epithelial parotid tumors (8 at low grade and 21 at intermediate or high grade), confirmed by histopathology in Cancer Center of Sun Yat-sen University, were reviewed. The localization, contour, margin, enhancing type, homogeneity, infiltration into the adjacent structures, and lymph node metastasis detected by CT scan were compared with relevant pathologic results.Of the 8 cases at low grade, 4 were well-differentiated mucoepidermoid carcinoma, 3 were acinic cell carcinoma, and 1 was epithelial-myoepithelial carcinoma; 3 had sharp margin, 3 had partly unsharp margin, and 2 had unsharp margin; 5 had regular contour, and 3 had irregular contour; all were enhanced obviously; 2 showed homogeneous appearance, and 6 showed inhomogeneous appearance with low-density areas; none had adjacent infiltration; 3 had lymph node metastasis. Of the 21 cases at intermediate or high grade, 5 were poorly-differentiated squamous cell carcinoma, 8 were malignant pleomorphic adenoma, 2 were adenocarcinoma, 1 was lymph-epithelial carcinoma, 4 were mucoepidermoid carcinoma, and 1 was adenoidcystic carcinoma; 5 had sharp margin, 7 had partly unsharp margin, and 9 had unsharp margin; 10 had regular contour, and 11 had irregular contour; 17 were enhanced obviously, and the 4 cases of malignant pleomorphic adenoma were enhanced slightly; 9 showed homogeneous appearance, and 12 showed inhomogeneous appearance with low-density areas; 8 had adjacent infiltration (the fat space between tumor and the parotid bed disappeared); 6 had lymph node metastasis.To some extent, CT features of malignant epithelial parotid tumors are correlated to the differentiation of tumor cells. Moreover, tumor size and histologic subtype should be considered to make a more accurate imaging diagnosis.

Thymic epithelial tumors have a broad spectrum of biologic and morphologic features. This study was to assess the CT features of various subtypes of thymic epithelial tumors on the basis of the 1999 World Health Organization (WHO) classification.CT features of thymic epithelial tumors in 94 patients were retrospectively analyzed. All cases were confirmed histologically according to the 1999 WHO classification, including 7 cases of type A, 24 cases of type AB, 16 cases of type B1, 13 cases of type B2, 16 cases of type B3, and 18 cases of type C.In the 94 cases, the long- and short-axis diameters of type A and type AB tumors were significantly shorter than those of type C tumors (P0.05). All type A tumors had smooth contours, type A, AB, and B1 tumors were likely to have smooth contours (P0.05), while type B3 and C tumors were likely to have irregular contours (P0.05). Type A tumors had less necrotic areas than any other types (P0.05). Multiple calcifications were more frequently seen in type B2, B3, and C tumors than in type A, AB, and B1 tumors (P0.05). Homogeneous enhancement was more frequently seen in type A, AB, B1, and B2 tumors than in type B3 and C tumors (P0.001). Type B3 and C tumors significantly preferred to infiltrate into mediastinal fat than any other types (P0.05).Though CT features of different subtypes of thymic epithelial tumors according to WHO classification are overlapped, short diameter, smooth contour, round shape, homogeneous density, and homogeneous enhancement are most suggestive for type A tumor; large diameter, irregular contour, necrosis and multiple calcifications in the lesion, heterogeneous enhancement, mediastinal fat infiltration, and great vessel infiltration are most suggestive for type B3 and C tumors.

Mediastinal lymph node staging in non-small cell lung cancer (NSCLC) is important to choose standard treatment plan and estimating prognosis. This study was to evaluate the clinical value of spiral CT in staging mediastinal lymph node in NSCLC through comparing spiral CT findings with corresponding pathology.A total of 89 patients with pathologically proven NSCLC received spiral CT and mediastinoscopic biopsy. The spiral CT findings and corresponding pathologic findings in staging mediastinal lymph node were compared. The sensitivity, specificity, and accuracy of diagnosing mediastinal lymph node metastasis were calculated.Compared with corresponding pathologic results, the overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of mediastinal lymph node staging with spiral CT were 58.9%, 70.0%, 60.5%, 68.6%, and 65.2%, respectively. The accuracy and specificity of spiral CT was relatively low in staging 4R, 5, 6, 7 lymph node groups; the false negative and false positive rates were relatively high in staging 4R, 7 lymph node groups.Spiral CT is a non-invasive clinical examination which may be used in staging mediastinal lymph node in NSCLC; however, there exists false negative and false positive rates. It should be combined with other investigations, such as mediastinoscopy, to assess a more accurate mediastinal lymph node staging.

Purpose To analyze the clinicopathological characteristics, treatment modalities, and potential prognostic factors of radiation-related second malignant neoplasms (SMNs) in a large group of nasopharyngeal carcinoma (NPC) cases. Methods and Materials Institutional electronic medical records of 39,118 patients with NPC treated by definitive radiotherapy between February 1964 and December 2003 were reviewed. A total of 247 patients with confirmed SMN attributable to radiotherapy were included. Results Median latency between radiotherapy for NPC and the diagnosis of SMN was 9.5 years (range, 3.1–36.8 years). Squamous cell carcinoma was the most common histologic type, followed by fibrosarcoma and adenocarcinoma. Median progression-free survival and overall survival (OS) of the 235 patients who underwent treatment were 17.3 months and 28.5 months, respectively. The 5-year OS rates were 42.9%, 23.7%, and 0% for the surgery, radiotherapy, and chemotherapy groups, respectively. The independent prognostic factors associated with survival were sex, histologic type, and treatment modality in both the early stage subgroup and the advanced stage subgroup of SMN. Conclusions Sex, histologic type, and treatment modality were the significant prognostic factors for SMN. Complete resection offers the best chance for long-term survival. In select patients with locally advanced and unresectable SMN, reirradiation should be strongly considered as a curative option.

AIM: To discuss the safety, feasibility and regularity of destruction to porcine spleen in vivo with congestion and tumescence by microwave ablation (MWA). METHODS: Ligation of the splenic vein was used to induce congestion and tumescence in vivo in five porcine spleens, and microwave ablation was performed 2-4 h later. A total of 56 ablation points were ablated and the ablation powers were 30-100 W. The ablation time (1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 min) was performed at a power of 60 W. After ablation, the ablation size was measured in pigs A, C, D and E and spleen resection. In pig B, the ablation size was measured and 2 ablation points were sent for pathology analysis and all tissues were sutured following ablation. Pig B was killed 1 wk later and the ablation points were sent for pathology analysis. Bleeding, tissue carbonization surrounding electrodes, and pathological changes were observed, and the effect on destruction volume relative to different ablation powers, times and positions was analyzed. RESULTS: The incidence of bleeding (only small am-ounts, < 20 mL) in the course of ablation was 5.4% (3/56) and was attributed to tissue carbonization surrounding electrodes, which also exhibited an incidence of 5.4% (3/56). The destruction volume was influenced by different ablation powers, times and points. It showed that the ablation lesion size increased with increased ablation time, from 1 to 10 min, when the ablation power was 60 W. Also, the ablation lesion size increased with the increase of ablation power, ranging from 30 to 100 W when the ablation time was set to 3 min. A direct correlation was seen between the destruction volume and ablation time by the power of 60 W (r = 0.97542, P < 0.0001, and also between the destruction volume and ablation powers at an ablation time of 3 min (r = 0.98258, P < 0.0001). The destruction volume of zone II (the extra-2/3 part of the spleen, relative to the first or second class vascular branches), which was near the hilum of the spleen, was noteably larger than the destruction volume of zoneI(the intra-1/3 part of the spleen) which was distal from the hilum of the spleen (P = 0.0015). Pathological changes of ablation occurring immediately and 1 wk after MWA showed large areas of coagulation. Immediately following ablation, intact spleen tissues were observed in the areas of coagulation necrosis, mainly around arterioles, and there were no obvious signs of hydropsia and inflammation, while 1 wk following the ablation, the coagulation necrosis was well distributed and complete, as many nuclear fragmentations were detected, and there were obvious signs of hydropsia and inflammation. CONCLUSION: In vivo treatment of congestion and tumescence in the spleen using microwave ablation of water-cooled antenna is a safe and feasible method that is minimally invasive.