2016 Vol.28(6)

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Review Article
Dual effect of WISP-1 in diverse pathological processes
Mengmeng Feng, Shuqin Jia
2016, 28(6): 553-560. doi: 10.21147/j.issn.1000-9604.2016.06.01
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Wnt-1 inducible signaling pathway-1 (WISP-1), also known as CCN-4, belongs to the connective tissue growth factor (CTGF) family. WISP-1 is primarily expressed in embryonic stem cells and is involved in adult organ development. WISP-1 participates in many cellular processes, including proliferation, differentiation, apoptosis and adhesion. In addition, WISP-1 plays an important role in diverse pathophysiological processes, such as embryonic development, inflammation, injury repairs and cancers. Recent studies showed that WISP-1 was highly correlated with tumor progression and malignant transformation, whereas it played an oncogenic role in colorectal cancer, cholangiocarcinoma, hepatocellular carcinoma and breast cancer. However, interestingly, WISP-1 exerts a tumor-suppressing role in lung and prostate cancers. WISP-1 promotes cell proliferation, adhesion, motility, invasion, metastasis and epithelial-to-mesenchymal transition via particular signaling pathways. In this review, we discussed the structure, expression profile, functions, clinical significance and potential mechanisms of WISP-1 in cancer and non-neoplastic diseases.
Original Article
Non-anthracycline-containing docetaxel and cyclophosphamide regimen is associated with sustained worse outcome compared with docetaxel, anthracycline and cyclophosphamide in neoadjuvant treatment of triple negative and HER2-positive breast cancer patients: updated follow-up data from NATT study
Xiaosong Chen, Guolin Ye, Chenfang Zhang, Xinzheng Li, Kunwei Shen
2016, 28(6): 561-569. doi: 10.21147/j.issn.1000-9604.2016.06.02
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ObjectiveA previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide (TC) regimen was inferior to docetaxel, anthracycline and cyclophosphamide (TAC) in neoadjuvant treatment of triple-negative breast cancer (TNBC) and human epidermal growth factor receptor-2-(HER2)-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated.MethodsTNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission (pCR). Secondary endpoints included clinical response rate, event-free survival (EFS), and overall survival (OS).ResultsA cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of 53 (range, 8–76) months, the patients achieving pCR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without pCR (P<0.05). TAC treatment resulted in consistently better EFS than TC treatment: the estimated 5-year EFS was 66.1% vs. 29.8% (P=0.002). Moreover, the estimated 5-year OS was also in favor of TAC: 88.4% vs. 51.6% (P<0.001). Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio (HR), 0.48; 95% confidence interval (95% CI), 0.26–0.90; P=0.021] and OS (HR, 0.20; 95% CI, 0.08–0.60; P=0.003).ConclusionsThe updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.
Prognostic nutritional index is an independent prognostic factor for gastric cancer patients with peritoneal dissemination
Runcong Nie, Shuqiang Yuan, Shi Chen, Xiaojiang Chen, Yongming Chen, Baoyan Zhu, Haibo Qiu, Zhiwei Zhou, Junsheng Peng, Yingbo Chen
2016, 28(6): 570-578. doi: 10.21147/j.issn.1000-9604.2016.06.03
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ObjectiveThe predictive and prognostic role of prognostic nutritional index (PNI) in gastric cancer patients with peritoneal dissemination remains unclear. This study aims to explore the role of the PNI in predicting outcomes of gastric cancer patients with peritoneal dissemination.MethodsA total of 660 patients diagnosed with gastric adenocarcinoma with peritoneal metastasis between January 2000 and April 2014 at Sun Yat-sen University Cancer Center and the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. The clinicopathologic characteristics and clinical outcomes of patients with peritoneal dissemination were analyzed.ResultsCompared with PNI-high group, PNI-low group was correlated with advanced age (P=0.036), worse performance status (P<0.001), higher frequency of ascites (P<0.001) and higher frequency of multisite distant metastasis (P<0.001). Kaplan-Meier survival curves showed that PNI-high group had a significantly longer median overall survival than PNI-low group (13.13 vs. 9.03 months, P<0.001). Multivariate survival analysis revealed that Borrmann type IV (P=0.014), presence of ascites (P=0.017) and lower PNI (P=0.041) were independent poor prognostic factors, and palliative surgery (P<0.001) and first-line chemotherapy (P<0.001) were good prognostic factors. For patients receiving palliative surgery, the postoperative morbidity rates in the PNI-low group and PNI-high group were 9.1% and 9.9%, respectively (P=0.797). The postoperative mortality rate was not significantly different between PNI-low and PNI-high groups (2.3% vs. 0.9%, P=0.362).ConclusionsPNI is a useful and practical tool for evaluating the nutritional status of gastric cancer patients with peritoneal dissemination, and is an independent prognostic factor for these patients.
Aneuploidy of chromosome 8 in circulating tumor cells correlates with prognosis in patients with advanced gastric cancer
Yilin Li, Xiaotian Zhang, Jifang Gong, Qiyue Zhang, Jing Gao, Yanshuo Cao, Daisy Dandan Wang, Peter Ping Lin, Lin Shen
2016, 28(6): 579-588. doi: 10.21147/j.issn.1000-9604.2016.06.04
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ObjectivePrevious work indicated that aneuploidy of chromosome 8 in circulating tumor cells (CTCs) correlated with therapeutic efficacy for advanced gastric cancer (AGC) patients. In this follow-up study performed on the same population of AGC patients, we investigated whether and how aneuploidy of chromosome 8 in CTCs correlates with patients’ clinical prognosis.MethodsThe prospective study was performed on 31 patients with newly diagnosed AGC. Previously established integrated subtraction enrichment (SE) and immunostaining-fluorescence in situ hybridization (iFISH) platform was applied to identify, enumerate and characterize CTCs. Quantification of CTCs and analysis of their aneuploidy of chromosome 8 were performed on patients before and after therapy.ResultsCTCs were measured in 93.5% of AGC patients, and two CTC subtypes with diverse threshold values were identified, multiploid CTCs with the threshold of ≥2 per 7.5 mL and multiploid plus triploid CTCs with the threshold of ≥4, which were found to significantly correlate with poor progression-free survival (PFS) and overall survival (OS). In particular, patients with ≥10% increased multiploid CTCs after an initial 6 weeks of therapy had poor PFS and OS, whereas improved PFS and OS were observed on those who had ≥10% decreased multiploid CTCs. After adjusting for clinically significant factors, ≥10% increased post-therapy multiploid CTCs was the only independent predictor of PFS and OS.ConclusionsAneuploidy of CTCs correlates with prognosis of AGC patients. Quantitative comparison monitoring multiploid CTCs before and after therapy may help predict improved or inferior prognosis and chemoresistance.
CapOX as neoadjuvant chemotherapy for locally advanced operable colon cancer patients: a prospective single-arm phase II trial
Fangqi Liu, Li Yang, Yuchen Wu, Cong Li, Jiang Zhao, Adili Keranmu, Hongtu Zheng, Dan Huang, Lei Wang, Tong Tong, Junyan Xu, Ji Zhu, Sanjun Cai, Ye Xu
2016, 28(6): 589-597. doi: 10.21147/j.issn.1000-9604.2016.06.05
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ObjectiveThe aim of this prospective, single-arm phase II trial was to confirm the safety and efficacy of neoadjuvant chemotherapy (NAC) using oxaliplatin plus capecitabine (CapOX) for patients with operable locally advanced colon cancer (CC).MethodsPatients with computed tomography-defined T4 or lymph node-positive CCs were enrolled. After radiological staging, patients were treated with at least 2 cycles of NAC consisting of 130 mg/m2 oxaliplatin on d 1, plus 1,000 mg/m2 capecitabine twice daily for 14 d every 3 weeks, followed by surgery, and then with the rest cycles of adjuvant chemotherapy. Radiological response was evaluated after 2 cycles of NAC. Tumor response, treatment toxicity, and surgical complications were recorded. The pathological response to therapy was evaluated according to the tumor regression grade (TRG) score. The primary endpoint was pathologic tumor response. This trial is registered in ClinicalTrials.gov (No: NCT02415829).ResultsForty-seven patients were enrolled in the study. Forty-two patients completed the planned treatments. The total radiological response rate was 68% (32/47), including complete and partial response rates of 2% (1/47) and 66% (31/47), respectively. Stable disease was observed in 32% (15/47) and progressive disease was observed in none. Complete pathologic response, major regression, and at least moderate regression were achieved in 1 (2%), 2 (4%), and 29 (62%) patients, respectively. Four patients developed grade 3 treatment toxicities. One patient with wound infection occurred after operation (1/47, 2%). There was no treatment-related death.ConclusionsOur results suggest that NAC with CapOX is an effective and safe treatment option for patients with locally advanced CCs.
A pilot phase II study of neoadjuvant triplet chemotherapy regimen in patients with locally advanced resectable colon cancer
Haitao Zhou, Yan Song, Jun Jiang, Haitao Niu, Hong Zhao, Jianwei Liang, Hao Su, Zheng Wang, Zhixiang Zhou, Jing Huang
2016, 28(6): 598-605. doi: 10.21147/j.issn.1000-9604.2016.06.06
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ObjectiveThis study aims to investigate the feasibility, safety and efficacy of triplet regimen of neoadjuvant chemotherapy in patients with locally advanced resectable colon cancer.MethodsPatients with clinical stage IIIb colon cancer received a perioperative triple chemotherapy regimen (oxaliplatin 85 mg/m2 and irinotecan 150 mg/m2, combined with folinic acid 200 mg, 5-fluorouracil 500 mg bolus and then 2,400 mg/m2 by 44 h infusion or capecitabine 1 g/m2 or S-1 40–60 mg b.i.d orally d 1–10, repeated at 2-week intervals) for 4 cycles. Complete mesocolic excision was scheduled 2–6 weeks after completion of neoadjuvant treatment and followed by a further 6 cycles of FOLFOXIRI or XELOX. Primary outcome measures of this stage II trial were feasibility, safety, tolerance and efficacy of neoadjuvant treatment.ResultsAll 23 patients received neoadjuvant chemotherapy and underwent surgery. Twenty-one patients (91.3%) had reductions in tumor volume after neoadjuvant treatment, and 13 patients (56.5%) had grade 3–4 toxicity. No patients had severe complications from surgery. Preoperative therapy resulted in significant down-staging of T-stage and N-stage compared with the baseline clinical stage including one pathological complete response.ConclusionsNeoadjuvant triple chemotherapy has high activity and acceptable toxicity and perioperative morbidity, and is feasible, tolerable and effective for locally advanced resectable colon cancer.
ALK gene expression status in pleural effusion predicts tumor responsiveness to crizotinib in Chinese patients with lung adenocarcinoma
Zheng Wang, Xiaonan Wu, Xiaohong Han, Gang Cheng, Xinlin Mu, Yuhui Zhang, Di Cui, Chang Liu, Dongge Liu, Yuankai Shi
2016, 28(6): 606-616. doi: 10.21147/j.issn.1000-9604.2016.06.07
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ObjectiveThe relationship between anaplastic lymphoma kinase (ALK) expression in malignant pleural effusion (MPE) samples detected only by Ventana immunohistochemistry (IHC) ALK (D5F3) and the efficacy of ALK-tyrosine kinase inhibitor therapy is uncertain.MethodsVentana anti-ALK (D5F3) rabbit monoclonal primary antibody testing was performed on 313 cell blocks of MPE samples from Chinese patients with advanced lung adenocarcinoma, and fluorescence in situ hybridization (FISH) was used to verify the ALK gene status in Ventana IHC ALK (D5F3)-positive samples. The follow-up clinical data on patients who received crizotinib treatment were recorded.ResultsOf the 313 MPE samples, 27 (8.6%) were confirmed as ALK expression-positive, and the Ventana IHC ALK (D5F3)-positive rate was 17.3% (27/156) in wild-type epidermal growth factor receptor (EGFR) MPE samples. Twenty-three of the 27 IHC ALK (D5F3)-positive samples were positive by FISH. Of the 11 Ventana IHC ALK (D5F3)-positive patients who received crizotinib therapy, 2 patients had complete response (CR), 5 had partial response (PR) and 3 had stable disease (SD).ConclusionsThe ALK gene expression status detected by the Ventana IHC ALK (D5F3) platform in MPE samples may predict tumor responsiveness to crizotinib in Chinese patients with advanced lung adenocarcinoma.
Clinical value of contrast-enhanced ultrasound in improving diagnostic accuracy rate of transthoracic biopsy of anterior-medial mediastinal lesions
Jingjing Fu, Wei Yang, Song Wang, Jing Bai, Hao Wu, Haiyue Wang, Kun Yan, Minhua Chen
2016, 28(6): 617-625. doi: 10.21147/j.issn.1000-9604.2016.06.08
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ObjectiveTo evaluate the clinical value of contrast-enhanced ultrasound (CEUS) in transthoracic biopsy of anterior-medial mediastinal lesions.MethodsA total of 123 patients with anterior or middle mediastinum lesions required ultrasound guided transthoracic biopsy for pathological diagnosis. Among them, 72 patients received CEUS examinations before biopsy. After CEUS, 8 patients were excluded from biopsy and the rest 64 patients underwent biopsy (CEUS group). During the same period, 51 patients received biopsy without CEUS examination (US group). The ultrasonography characteristics, the number of biopsy puncture attempts, diagnostic accuracy rate and the incidence of complications were recorded and compared between the two groups.ResultsA large portion of necrosis area or superficial large vessels was found in 8 patients, so the biopsy was cancelled. The internal necrosis was demonstrated in 43.8% of the lesions in CEUS group and in 11.8% of US group (P>0.001). For thymic carcinoma, CEUS increased the detection rate of internal necrosis and pericardial effusion than conventional ultrasound (62.5% vs. 18.8%, P=0.012; 56.3% vs. 12.5%, P=0.023). The average number of punctures in CEUS group and US group was 2.36±0.70 and 2.21±0.51 times, respectively (P>0.05). The diagnostic accuracy rate of biopsy in CEUS group (96.9%, 62/64) was significantly higher than that in US group (84.3%, 43/51) (P=0.022). In US group, 2 patients suffered from mediastinal bleeding (3.9%), while no major complications occurred in CEUS group.ConclusionsCEUS examination provided important information before transthoracic mediastinum biopsy and improved diagnostic accuracy rate in biopsy of anterior and middle mediastinum lesions than conventional ultrasound.
Comprehensive evaluation of nutritional status before and after hematopoietic stem cell transplantation in 170 patients with hematological diseases
Peng Liu, Boshi Wang, Xia Yan, Jingjing Cai, Yu Wang
2016, 28(6): 626-633. doi: 10.21147/j.issn.1000-9604.2016.06.09
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ObjectiveTo investigate the nutritional status of patients before and after hematopoietic stem cell transplantation (HSCT), and explore optimal methods for assessing nutritional status in patients with hematological diseases.MethodsThis cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People's Hospital between May 2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002 (NRS-2002), Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA) and Malnutrition Universal Screening Tools (MUST), in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms.ResultsAfter HSCT, patients had significant reduction in weight, hip circumference, waist-hip ratio, calf circumference, mid-upper arm circumference, and suprailiac skinfold thickness compared with pre-HSCT measurements. Before HSCT, NRS-2002 identified that 21.2% of patients were at nutritional risks, compared with 100% after HSCT. MUST indicated that before HSCT, 11.77% of patients were at high nutritional risk, compared with 59.63% after HSCT. MNA assessed that 0.06% of patients were malnourished before HSCT, compared with 19.27% after HSCT. SGA identified that before HSCT, 1.76% of patients had mild to severe malnutrition, which increased to 83.3% after HSCT. There is a significant increase in the nutritional risk and malnutrition in patients who received HSCT.ConclusionsBefore HSCT, some patients already had nutritional risk or nutritional deficiencies, and prompt and close nutritional screening or assessment should be performed. The nutritional status of patients after HSCT was generally deteriorated compared with that before transplantation. Body measurements should be taken more frequently during the subsequent treatment window in the laminar air flow rooms. After HSCT, it is recommended to combine MNA and SGA to fully evaluate the nutritional status, and thus provide timely and reasonable nutritional support.
Case Report
Boron neutron capture therapy for malignant melanoma: first clinical case report in China
Zhong Yong, Zewen Song, Yongmao Zhou, Tong Liu, Zizhu Zhang, Yanzhong Zhao, Yang Chen, Congjun Jin, Xiang Chen, Jianyun Lu, Rui Han, Pengzhou Li, Xulong Sun, Guohui Wang, Guangqing Shi, Shaihong Zhu
2016, 28(6): 634-640. doi: 10.21147/j.issn.1000-9604.2016.06.10
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A phase I/II clinical trial for treating malignant melanoma by boron neutron capture therapy (BNCT) was designed to evaluate whether the world’s first in-hospital neutron irradiator (IHNI) was qualified for BNCT. In this clinical trial planning to enroll 30 patients, the first case was treated on August 19, 2014. We present the protocol of this clinical trial, the treating procedure, and the clinical outcome of this first case. Only grade 2 acute radiation injury was observed during the first four weeks after BNCT and the injury healed after treatment. No late radiation injury was found during the 24-month follow-up. Based on positron emission tomography-computed tomography (PET/CT) scan, pathological analysis and gross examination, the patient showed a complete response to BNCT, indicating that BNCT is a potent therapy against malignant melanoma and IHNI has the potential to enable the delivery of BNCT in hospitals.