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   Table of Contents - Current issue
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 2019
Volume 15 | Issue 2
Page Nos. 265-447

Online since Monday, April 1, 2019

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EDITORIALS  

Computed tomography-guided percutaneous microwave ablation: A new weapon to treat ground-glass opacity–lung adenocarcinoma Highly accessed article p. 265
Yancu Hertzanu, Xin Ye
DOI:10.4103/jcrt.JCRT_65_19  PMID:30964094
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Programmed cell death protein-1 inhibitor for the treatment of hepatocellular carcinoma: “A sharp sword” Highly accessed article p. 267
Xin Li, Ping Liang, Xin Ye
DOI:10.4103/jcrt.JCRT_910_18  PMID:30964095
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REVIEW ARTICLES Top

Translational epidemiology: The powerful tool for precision cancer medicine Highly accessed article p. 269
Zhenming Fu, Rui Zhang, Ping Li, Mingfang Jia
DOI:10.4103/jcrt.JCRT_276_18  PMID:30964096
Although this is an exciting time for translational medicine, systematic approaches and strategies to conduct translational research are sparse. We highlight in this editorial the opportunities to collaborate across disciplines and to forge new interdisciplinary collaborative ventures from the perspective of epidemiology. We specifically outline some feasible research areas, wherein Translational Epidemiology may readily speed up the translation of research for Precision Medicine.
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Targeting the canonical Wnt/β-catenin pathway in cancer radioresistance: Updates on the molecular mechanisms Highly accessed article p. 272
Yu Yang, Huandi Zhou, Ge Zhang, Xiaoying Xue
DOI:10.4103/jcrt.JCRT_421_18  PMID:30964097
Radiation resistance is an important factor that affects the efficacy of radiotherapy; it could even lead to its failure. In recent years, the relationship between the classical Wnt signaling pathway and radiation resistance has gradually attracted attention from scholars. Although most of the findings are comprehensive, they are fragmented and disorganized. This review explores the relationship between classical Wnt signaling pathways and cancer radiation resistance. Previous literature regarding the classical Wnt signaling pathways and cancer radiation resistance from the past decades had been summarized in this article. Moreover, the molecular mechanisms and functions of the canonical Wnt signaling pathway involved in the formation of radioresistance were systemically analyzed and sorted out. Certain rules and internal relationships among different pathways have been further clarified; this is expected to provide valuable clues for further research. The Wnt/β-catenin pathway is closely associated with the formation of cancer radioresistance, which may be a target for improving the effects of radiotherapy.
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Role of miRNA in transformation from normal tissue to colorectal adenoma and cancer p. 278
Guangkuo Liu, Bingqing Li
DOI:10.4103/jcrt.JCRT_135_18  PMID:30964098
Although many modalities can be used to prolong the remission of colorectal cancer (CRC), early diagnosis is essential to improve the therapeutic outcomes. The conventional ways of diagnosing and monitoring the progresses from adenoma to CRC are colonoscopy and fecal occult blood test (FOBT). However, colonoscopy is expensive and invasive; while the FOBT is not sensitive. miRNAs may be a new modality to monitor the transition from adenoma to CRC. We reviewed publications of miRNA profile differences from colorectal normal mucosa (NM) to adenoma, and to CRC and tried to find the roles of miRNA in these transitions. This review also highlighted the possibility of serum miRNAs as markers for monitoring these transitions. The miRNA profiles are different from normal colorectal mucosa to adenoma and to CRC. The miRNAs may have pro- or anti-CRC effects through oncogenes such as c-Met and KRAS. Others may interfere with the immune system. More interestingly, some miRNAs are continuously increased from NM to adenoma and to CRC; others, such as miRNA-30b, are consequently decreased. The literature shows that miRNAs are involved in the whole process of the colorectal carcinogenesis. The miRNAs may be the biomarkers in monitoring the transition from adenoma to CRC.
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ORIGINAL ARTICLES Top

Experimental study in vivo ablation of swine pancreas using high-intensity focused ultrasound p. 286
Guanghui Huang, Xin Ye, Xia Yang, Aimin Zheng, Wenhong Li, Jiao Wang, Xiaoying Han, Zhigang Wei, Min Meng, Yang Ni, Chengkun Qin, Xingbo Fei, Liulin Xiong
DOI:10.4103/jcrt.JCRT_986_17  PMID:30964099
Objective: The objective of this study is to evaluate the feasibility and safety of high-intensity focused ultrasound (HIFU) for ablation of swine pancreas and to detect the pathological variations in pancreas damage. Materials and Methods: (a) Eight swine were involved and randomly divided into two groups (Group A and B). HIFU was applied on swine in both groups for in vivo ablation of pancreas. The animals were anesthetized, and the artificial acoustic window was built. Then, the irradiation of FEP-BY02 type HIFU on pancreas was applied. (b) Swine in Group A were euthanized immediately after treating with HIFU to examine variations in pancreas. The biochemical evidence of pancreatitis was evaluated by blood samples collected from swine in Group B before and after HIFU. Then, the pancreas of swine in Group B was euthanized on day 5 after treatment to examine the pancreas. All specimens were visually inspected for both ultrasonic focal damage region (UFDR) and pathological routine by a skilled pathologist. Results: (a) The vital signs of all animals were stable during HIFU treatment and recovered well after treatment. (b) UFDR were observed in all HIFU irradiation region of the specimens, without significant size difference between the two groups. The coagulation nucleus pyknosis, cytochylema vacuolation, and nucleus membrane disruption were observed after HIFU in both groups. Membranous structure dissolution and inflammatory cell infiltration were also found after HIFU in swine of Group B. (c) There was no significant difference in the levels of blood amylase in swine of Group B before and after HIFU treatment. Conclusions: It was feasible and safe to use HIFU for ablation of the pancreas in swine.
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Precision dose measurement of 125I seed in solid water through SPECT/CT detecting p. 291
Hongtao Zhang, Yansong Liang, Gang Qiu, Zeyang Wang, Devjoy Dev, Zezhou Liu, Huijuan Li, Huimin Yu, Jingshi Chen, Aixia Sui, Juan Wang, Gaofeng Shi
DOI:10.4103/jcrt.JCRT_522_18  PMID:30964100
Purpose: The aim of the study is to study the feasibility of gamma-ray-detection-based precision dose measurement of 125I seed brachytherapy in solid water. Materials and Methods: Seven group 125I seeds with different activities were put into a hole in the center of solid water individually. Each group had ten seeds, and the seed activity ranged from 1.48 × 107 Bq to 3.7 × 107 Bq. Single-photon emission computed tomography/computed tomography (SPECT/CT) was used to scan the seeds perpendicular to the long axis of the seed, with a slice thickness of 3.75 mm. The radioactive count values (x) of the radioactive concentration around the seeds were collected at a distance of 1–15 mm from the center of the seeds, while the corresponding doses (Y) (Gy) were calculated. SPSS 18.0 was used to analyze the relationship between the count value and the dose. Results: With the same seed activity, the count values became smaller according to the distance from the center of the seeds. The count values at the same point had an increasing trend according to the activity. This is similar to the doses calculated at the same point. There was an exponential relationship between the dose around the 125I seeds, and the radioactive count value detected by SPECT/CT. Correlative curves between the dose and radioactive count value detected by SPECT/CT of different-activity 125I seeds were fitted. The formulas of the dose and radioactive count with different seed activity were in the form of Y = b0 (b1)x. The constant b0 ranged from 1.48 to 3.93, according to the seed activity, while b1 was 1.006 for every seed's activity. Conclusion: The count value around the 125I seed can be detected accurately by SPECT/CT, and then can be quantified. This study provided useful experiment data for the precision measurement of 125I seed implantation. Radiation detection-based dose measurement may become a new noninvasive technology for the dynamic dosimetry verification method after brachytherapy.
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Prospective and prognostic factors for hepatic metastasis of gastric carcinoma: A retrospective analysis p. 298
Jin Cheng Song, Xiao Lei Ding, Yang Zhang, Xian Zhang, Xiu Hua Sun
DOI:10.4103/jcrt.JCRT_576_17  PMID:30964101
Aims: The aim of the study was to prospectively explore the prognostic factor for gastric cancer with liver metastasis (GCLM), since no prognostic factor was reported to be consistently significant across studies. Patients and Methods: One hundred and five patients with GCLM treated at our center between January 1, 2010, and March 31, 2016, were included and their clinical data were retrospectively analyzed. The univariate analyses were first applied for identify the potential independent prognostic and predictive factors for liver metastasis. These factors were further evaluated with Cox proportional-hazard regression model testing. Finally, survival curves were estimated. Results: The Eastern Cooperative Oncology Group (ECOG) score, number of other distant metastases, levels of cancer antigen (CA), and carcinoembryonic antigen (CEA) were independent prognostic factors (adjusted relative risk [RR]: 1.362–2.887; P = 0.000–0.027). The survival of patients who received radical gastrectomy would be associated with the ECOG score, staging (T stage and N stage), CA 19-9, and CEA levels (RR: 2.169–3.787; P = 0.000–0.027). Patients with following indicators 1 month postoperatively were prone to liver metastasis after radical gastrectomy (median, 6.9–12.03 months; P = 0.007–0.042): Venous/lymphatic invasion, pathological Stage IV (especially combined with T4 stage), intestinal Lauren type, and combined elevation of CEA and CA 19-9 levels. Conclusions: The therapy design for patients with GCLM should consider the general conditions and personal clinicopathological characters of patients. After balancing the benefit and risk factors, multidisciplinary treatment and individual treatment should be developed based on evidence-based medicine model for each patient.
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Transcatheter arterial chemoembolization experience for advanced hepatocellular carcinoma with right atrial tumor thrombus p. 305
Linzhong Zhu, Renjie Yang, Xu Zhu
DOI:10.4103/jcrt.JCRT_923_17  PMID:30964102
Background: Hepatocellular carcinoma (HCC) with tumor thrombus extending to the inferior vena cava (IVC) and right atrium (RA) is rare, which is generally associated with serial syndromes and poor prognosis. The results of earlier observations revealed that the median survival was 1–5 months after diagnosis for untreated patients. The prognosis was poor with surgery, radiotherapy, transarterial chemoembolization (TACE), and chemotherapy. Methods: A total of 1850 patients received TACE for advanced HCC at our institution from October 2011 to September 2016. Among them, 18 cases presented tumor thrombus extended from hepatic vein to IVC and RA. TACE was performed to deal with the tumor thrombus inside the RA, and angiography was performed for characterizing. The successful rate, survival, safety, and clinical adverse events were retrospectively studied. Results: A total of 56 interventional procedures were conducted for the 18 cases of tumor thrombus extending to IVC and RA. TACE were successfully performed in all patients without significant complications. One case died of pneumonia, and no severe adverse effect was observed in the other 17 cases. The 1- and 3-year overall survival rates were 50% and 16.7%, respectively. The average survival from diagnosis of right atrial tumor thrombus (RATT) was 15.2 months. The blood supply was rich for all RATT. There were seven cases with single-feeding artery and 11 cases with two or three feeding arteries that originated from intra- or extra-hepatic arteries. The extrahepatic artery played a critical role in the blood supply of RATT, including right inferior phrenic artery (8/18), left inferior phrenic artery (1/18), and the left gastric artery (2/18). Conclusion: For HCC with tumor thrombus in the IVC and RA, TACE could safely improve the prognosis of these patients. Searching for multiple feeding arteries are essential for ensuring efficacy. In addition, careful examination and appropriate embolization technique are essential for safety and efficacy. Lipiodol was a safe and ideal agent for the embolization in RATT.
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Nimotuzumab plus chemotherapy with docetaxel, cisplatin, 5-fluorouracil for locally advanced head and neck squamous cell carcinoma: A clinical study p. 312
Xing Wang, Jianmin Gu, Cuiling Shao, Kun Han, Jian Meng
DOI:10.4103/jcrt.JCRT_889_17  PMID:30964103
Background: A clinical study was conducted to determine the efficacy of nimotuzumab combined with docetaxel, cisplatin, and 5-fluorouracil (TPF) for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) after surgery and conformal radiotherapy. Methods: Thirty-one HNSCC patients received three courses of chemotherapy every 21 days, at a dose of 75 mg/m2 of docetaxel and cisplatin on day 1 and 750 mg/m2 of 5-fluorouracil on days 1–5 followed by 200 mg/m2/week of nimotuzumab on week 1–2 (day 6–21). Results: After sequential therapy, complete and partial responses were observed in 10 (32.3%) and 17 (54.8%) patients, respectively. The overall response rate was 87.1%. A progression-free survival of 71.2% (95% confidence interval [CI] 51.6%–93.7%) and an overall survival of 78.3% (95% CI 58.9%–89.5%) were achieved at 2nd year. The most common Grade 3–4 toxicities during the complete treatment were lymphopenia (25.8%), neutropenia (22.6%), anemia (12.9%), and diarrhea (16%). In addition, no rash and treatment-related death occurred during this study. Conclusions: Nimotuzumab in combination with TPF has been well tolerated as a treatment program for locally advanced HNSCC.
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Receptors for advanced glycation end products is associated with autophagy in the clear cell renal cell carcinoma p. 317
Yong Guo, Hai-Cong Zhang, Sheng Xue, Jun-Hua Zheng
DOI:10.4103/jcrt.JCRT_180_18  PMID:30964104
Background: The receptor for advanced glycation end-product (RAGE) was one of the signal transduction receptors. RAGE interacted with various signaling molecules which were involved in human disease processes including tumorigenesis. Previous reports have indicated that RAGE/high-mobility group box 1 (HMGB1) could regulate autophagy in different carcinomas. However, the functional role of RAGE/ HMGB1 in the regulation of clear cell renal cell carcinoma (ccRCC) autophagy remained unrevealed. Methods: Western blot, quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence were used in the present study. Results: In this study, we demonstrated that the levels of RAGE/HMGB1 and autophagic protein LC3, Beclin-1, PI3K were much higher in ccRCC samples than those of in adjacent normal tissues. RAGE and autophagic protein expression was regulated with RAGE/HMGB1 in human RCC cell lines. Conclusion: Our results implicated that RAGE and autophagy played important roles in ccRCC, and RAGE/HMGB1 might serve as a novel therapeutic target for future ccRCC treatment.
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Chyle test is not a valuable laboratory index in identifying chylothorax after pulmonary resection and lymph node dissection for primary non-small cell lung cancer p. 324
Hui Wang, Jinping Gao, Renfeng Zhang, Hounai Xie, Zhongmin Peng
DOI:10.4103/jcrt.JCRT_249_18  PMID:30964105
Objective: Chyle test is widely used to identify chylothorax after pulmonary resection and lymph node dissection for primary non-small cell lung cancer (NSCLC). Low accuracy of chyle test in identifying chylothorax is rarely reported. This observational study was designed to identify the diagnostic value of chyle test. Patients and Methods: From September 2016 to March 2017, 185 consecutive patients either suspected or histologically documented lung cancer were screened for this observational study. Except exclusion, 108 patients were eligible for further analysis. Daily chest-tube output as well as the postoperative day of chest tube removal was documented. Chyle test was analyzed with 108 cases, and the results were blinded to the thoracic surgeons. Chest tube was timely removed regardless of the results of chyle test. A high-output pleural effusion and an associated change in quality of the pleural fluid, from serous to milky yellowish after normal diet, led to the diagnosis of chylothorax. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of chyle test in identifying chylothorax were calculated. Results: Of 108 patients, 4 (3.7%) were observed with chylothorax after pulmonary resection and lymph node dissection for primary NSCLC. Postoperative chylothorax was conservatively managed in three patients and chest tubes were removed 12 days (from 10 to 16) after surgery. Failed in conservative treatment, one patient underwent thoracic duct ligation performed by video-assisted thoracic surgery. For patients without chylothorax, the median day of chest tube removal was postoperative day 4. Among the 108 patients, 75.9% (82/108) was found with a positive chyle test result, of which 95.1% (78/82) was false positive in identifying chylothorax. The sensitivity and specificity of chyle test in identifying chylothorax were 100% and 25%, respectively. The positive predictive value, negative predictive value, and accuracy of chyle test for chylothorax diagnosis were 4.9%, 100%, and 27.8%, respectively. Conclusions: It was suggested that the specificity and accuracy of chyle test in identifying chylothorax were relatively low. Chyle test is not a good laboratory index in identifying chylothorax. With highly positive result, chyle test should not preclude the removal of chest tube in patients after pulmonary resection and lymph node dissection for primary NSCLC.
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The effects of microRNA-1224-5p on hepatocellular carcinoma tumor endothelial cells p. 329
Chao Hu, Xi Cheng, Qi MingYu, Xin Bao Wang, Shi Qiang Shen
DOI:10.4103/jcrt.JCRT_40_18  PMID:30964106
Aim: The aim of this study was to investigate the effect of microRNA-1224-5p (miR-1224-5p) on tumor endothelial cells (TECs) of human hepatocellular carcinoma (HCC). Subjects and Methods: Oligonucleotides were chemically synthesized and transfected into TECs using Lipofectamine 2000. TECs were divided into three groups, namely a control (CON) group without transfection, a negative control (NC) group transfected with negative control oligonucleotides and green fluorescent protein (GFP), and a micro-up (MU) group transfected with miR-1224-5p mimic and GFP. The expression of miR-1224-5p was quantified via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The proliferation of TECs was detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the optical density value at 490 nm was measured after every 24 h. Apoptosis was detected via flow cytometry using a 7-aminoactinomycin/APC Annexin V kit. The migration and invasion of TECs were detected using transwell assay. The tube formation ability was evaluated using the tube formation assay. Results: Oligonucleotides were successfully transduced into TECs, and the expression of miR-1224-5p was specifically upregulated. The results of qRT-PCR analysis showed that the expression of miR-1224-5p was significantly upregulated in the MU group (2ΔΔCt = 3.27 ± 0.15) than in the CON group (2ΔΔCt = 1) and NC group (2ΔΔCt = 1.08 ± 0.11) (P < 0.01). The results of MTT assay showed that the cell proliferation was significantly inhibited in the MU group at four time points than in the CON and NC groups (P < 0.01). Flow cytometry analysis revealed the significant increase in apoptosis of cells from the MU group (19.29% ± 0.95%) than those from the CON (8.73% ± 0.64%) and NC (9.51% ± 0.56%) (P < 0.01) groups. The migration ability was significantly inhibited in MU group (51.0 ± 3.6) as compared with CON (77.7 ± 2.5) and NC (79.2 ± 3.5) groups (P < 0.01). The invasion ability of TECs was significantly inhibited in MU group (9.8 ± 1.3) than in CON (15.8 ± 0.8) and NC (15.4 ± 0.9) groups (P < 0.01). The ability of tube formation of TECs was completely inhibited in MU group but remained unaffected in CON and NC groups. Conclusions: miR-1224-5p may serve as a potential tumor suppressor in HCC. Upregulation in miR-1224-5p expression may decrease proliferation, induce apoptosis, inhibit migration and invasion, and suppress tube formation in TECs of human HCC.
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Embolization of hepatic arterioportal shunt with ethanol-soaked gelatin sponge p. 336
Jing Li, Xinxin Kang, Leiming Guo, Jincheng Xiao, Jingliang Cheng
DOI:10.4103/jcrt.JCRT_825_17  PMID:30964107
Objective: The objective of this study is to investigate the effect of ethanol-soaked gelatin sponge (ESG) in the treatment of hepatic arterioportal shunt (APS). Methods: Hepatocellular carcinoma (HCC) patients with APS were divided into experimental group (Group E) and control group (Group C). Patients in Group E were treated with ESG for APS embolization, whereas patients in Group C were treated with polyvinyl alcohol particles for APS embolization, with other treatment unchanged. APS and the Eastern Cooperative Oncology Group (ECOG) physical status scores of patients before and after the first treatment and further consultation in the 6th week and the survival rate in follow-up visit were recorded. The changes of liver function during treatment were monitored. Results: Before the first treatment, there was no statistical significant difference in APS between two groups. After that, APS in Groups E (P = 2.49 × 10−7) and C (P = 2.10 × 10−4) was improved. In further consultation, APS in Groups E (P = 2.73 × 10−13) and C (P = 2.90 × 10−8) was further improved after examinations and corresponding treatment. After the first treatment and further consultation, APS score was lower in Group E than in Group C, and there were still five patients whose APS score was 2 in Group C. Quality of life in two groups was effectively controlled without getting worse and the ECOG score reduced. Liver function in the two groups did not worsen with the use of liver protective drugs. No deaths occurred in Group E, whereas two patients died in Group C during treatment and follow-up visit. Conclusion: The results show that ESG can effectively reduce APS score and improve the survival rate of HCC patients.
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Transauricular arterial access for hepatic artery embolization in rabbit VX2 liver tumor p. 341
Bo Hu, Peng Du, Chao Yang, Yun-Liang Wang, Cai-Fang Ni, Zhi Li
DOI:10.4103/jcrt.JCRT_58_18  PMID:30964108
Purpose: The purpose of this study is to evaluate the feasibility of percutaneous transauricular artery access for hepatic artery catheterization using a peripherally inserted central catheter (PICC) device and hepatic artery catheterization through auricular approach. Methods: Ten New Zealand White rabbits were used to establish a VX2 liver tumor model. Hepatic artery angiography and embolization were performed 3 weeks after inoculation. The rabbits were restrained in supine position under anesthesia. Intra-arterial access was accomplished with percutaneous Seldinger technique through the auricular artery using a PICC device. The hepatic artery catheterization was performed with a microcatheter and guide wire. The rate of technical success and procedure time was investigated. Results: Two rabbits failed initial percutaneous transauricular arterial access, with success in a contralateral attempt. Thus, percutaneous transauricular arterial access was achieved in 10 of 12 auricular arteries, with a technical success rate of 83.3%. The time needed to obtain intra-auricular access was 7.2 ± 3.1 min. Hepatic artery catheterization, angiography, and embolization were accomplished through the auricular approach in all 10 rabbits. Conclusion: Arterial access in rabbits can be achieved through the auricular artery. Hepatic artery catheterization, angiography, and embolization can be performed through auricular arterial access.
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Clinical characteristics and prognosis of cancer patients with venous thromboembolism p. 344
Hui Wang, Xiaomao Xu, Chun Pu, Lin Li
DOI:10.4103/jcrt.JCRT_121_18  PMID:30964109
Aims: The aim of this study is to analyze the clinical features and prognosis of cancer patients with venous thromboembolism (VTE). Subjects and Methods: This was a retrospective observational study that selected cancer patients with a new VTE event from January 2003 to 2013 using the hospital information system in Beijing Hospital. The patients were divided into three groups according to the site of thrombosis as follows: pulmonary thromboembolism (PTE), deep venous thrombosis (DVT), or PTE plus DVT. The clinical manifestations and prognosis among the three groups were compared. Results: Among the 18,531 patients diagnosed with a malignant tumor, 280 (1.51%) patients presented with VTE at first diagnosis or during the disease course; of these, 26 had incidental pulmonary embolism (IPE). Dyspnea was the most common symptom in the PTE group (51.65%), and lower limb swelling was found mostly in the DVT group (65.27%). Approximately 53.92% and 63.21% of patients had VTE events within the first 3 and 6 months after cancer diagnosis, respectively. The median survival time of all VTE patients was 24.0 ± 7.85 months, with the DVT group having the longest survival time among the three groups (P < 0.05). About 29.23% of the 130 patient deaths occurred within the first 30 days after VTE diagnosis, and 46.92% occurred within the first 3 months. Conclusions: The incidence of IPE in cancer patients was not rare. Most VTE events occurred within the first 6 months after the cancer diagnosis, and nearly half of the deaths occurred within the first 3 months of VTE diagnosis in cancer patients.
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Chromatin remodeling factor lymphoid-specific helicase links with Epstein-Barr virus associated the follicular germinal center B cell lymphomas p. 350
Chunhui Ouyang, Zhenghao Deng, Jianhua Zhou, Chunyan Fu, Shuang Liu, Yongguang Tao, Desheng Xiao
DOI:10.4103/jcrt.JCRT_243_18  PMID:30964110
Background: We assessed the frequency of epigenetic lesions, including lymphoid-specific helicase (LSH), 5-hydroxymethylcytosine (5-hmC) and E2F1, and the possible correlations among molecular findings, phenotype, clinical features, and outcome. Methods: We investigated 181 paraffin-embedded B-cell lymphoma samples using immunohistochemistry and in situ hybridization. Results: The levels of Ki67, LSH, 5-hmC, and E2F1 were all increased in germinal center B-cell lymphomas when compared with those in normal lymph nodes, and LSH was highly expressed in diffuse large B-cell lymphomas (DLBCLs) and Burkitt lymphomas (BLs) that were positive for Epstein-Barr virus (EBV) infection, indicating that LSH is linked to EBV infection in DLBCL and BL. Interestingly, LSH was mainly localized in the germinal centers of lymph nodes whereas 5-hmC staining localized to areas surrounding the germinal centers. Conclusions: These findings indicate a critical role for LSH as a biomarker and therapeutic target in follicular germinal center B-cell lymphoma.
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Chemokine (C-C motif) ligand 18 is highly expressed in glioma tissues and promotes invasion of glioblastoma cells p. 358
Lixin Ma, Hui Wang, Zhenzhu Li, Xin Geng, Meng Li
DOI:10.4103/jcrt.JCRT_360_17  PMID:30964111
Objective: The objective of the study is to evaluate levels of chemokine (C-C motif) ligand 18 (CCL18) in human glioma tissues and effects of CCL18 on U251 glioma cells. Materials and Methods: By using the real-time reverse transcription polymerase chain reaction and immunochemically histological staining, we determined the mRNA and protein levels of CCL18 in tissues of 60 patients with World Health Organization (WHO) Grades II, III and IV glioma and the normal brain. Cultured U251 glioma cells were incubated with CCL18 and then subjected to transwell. The scratch wound-healing and cell count kit (CCK-8) assays were performed to detect the possible effects of CCL18 on the cell invasion, migration, and proliferation. Results: In the tissues of the normal brain (n = 10), glioma Grade II (n = 26), III (n = 18), and IV (n = 16), CCL18 mRNA expression levels were 1.00 ± 0.09, 6.02 ± 1.26, 26.35 ± 3.98, and 112.21 ± 13.25 fold, respectively (P < 0.01); the percentage of CCL18-positive glioma cells was 0%, 58.8%, 70.0%, and 100% in the normal brain, glioma WHO Grade II, III, and IV, respectively (P < 0.01). Different concentrations of CCL18 (0, 5, and 10 ng/ml) enhanced the of U251 glioma cell invasion in 24 h transwell assays [from 43.5 ± 8.3 to 202.0 ± 18.5 and 279.7 ± 18.6 cells (P < 0.01)], increased the cell migration quantified by comparing the areas of the scratch (pixel) [at 12 h, 498.4 ± 75.3, 381.3 ± 21.4, and 347.7 ± 14.2; at 24 h, 299.5 ± 15.3, 284.6 ± 7.8, and 237.3 ± 20.6 (P < 0.05)], and significantly increased the cell growth in CCK-8 assay [from 1.000 ± 0.019–1.260 ± 0.094 and 2.070 ± 0.138 fold in CCL18, respectively (n = 20/each group) (P < 0.01)]. Conclusion: We have found that CCL18 is highly expressed in glioma tissues and enhances the invasion, migration, and proliferation of U251 glioma cells. Therefore, CCL18 may be a potential biomarker for detecting and grading human glioma.
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Evaluation of efficacy and safety of apatinib treatment in advanced gastric cancer p. 365
Yang Yang, Xiuwei Wu, Fanfan Li, Nianfei Wang, Mingjun Zhang, Tong Sun, Zhendong Chen
DOI:10.4103/jcrt.JCRT_297_18  PMID:30964112
Aim: We aimed to evaluate the efficacy and safety of apatinib treatment and its impact on the quality of life (QOL) of patients with advanced gastric cancer (GC) who experienced failure with at least two chemotherapeutic regimens. Materials and Methods: All patients received apatinib at a daily dose of 500 mg for 4 weeks per cycle until it was stopped due to disease progression, intolerable toxicity. Response Evaluation Criteria in Solid Tumors version 1.1 and Common Terminology Criteria for Adverse events 4.0 were used to assess tumor responses and toxicities, respectively. The European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-STO22 were used to assess the impact on patient's QOL. Results: Twenty-five patients were enrolled, but only 24 were evaluated for therapeutic effects. After apatinib treatment, none of the patients achieved complete response (CR), one achieved partial response (PR), and eight had stable disease (SD), resulting in a disease control rate of 37.5% (CR + PR + SD). Responses to questions regarding abdominal pain, nausea/vomiting, insomnia, constipation, and diarrhea in QLQ-C30 and abdominal pain and reflux in QLQ-STO22 were changed over the course of treatment (P < 0.05). The QOL score was elevated after three treatment cycles, but it was not considered statistically significant (P > 0.05). Conclusion: Results indicated that apatinib was effective in heavily pretreated patients with advanced GC who experienced failure with two or more line chemotherapies. The toxicities were tolerable or could be clinically controlled. Apatinib treatment alleviated some of the clinical symptoms but did not improve QOL significantly.
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Computed tomography-guided percutaneous cryoablation for lung ground-glass opacity: A pilot study p. 370
Shupeng Liu, Xinhai Zhu, Zilin Qin, Jiongyuan Xu, Jianying Zeng, Jibing Chen, Lizhi Niu, Meng Xu
DOI:10.4103/jcrt.JCRT_299_18  PMID:30964113
Context: Ground-glass opacity (GGO) is a nonspecific imaging parameter for early-stage pulmonary cancer. In these cases, a definite diagnosis and prompt surgery usually yield satisfactory outcomes. Aims: This study aimed to assess the safety and feasibility of cryoablation treatment for lung GGO. Subjects and Methods: We reviewed the clinical data of 14 patients (19 lung tumors) with lung GGO and evaluated the adverse events, lung function, and treatment efficacy after cryoablation. Statistical Analysis Used: Statistical analyses were performed using the Statistical Package for the Social Sciences software (version 13.0; SPSS Inc., Chicago, IL, USA). Results: None of the patients exhibited serious complications, and lung function recovered to >95% after 1 month. During a follow-up, computed tomography scan at 24 months, the GGO appeared to have been successfully ablated in all patients. Conclusion: Cryoablation may serve as a safe and feasible option for the treatment of GGO.
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The efficacy of endoscopic stenting combined with laparoscopy in the treatment of left colon cancer with obstruction p. 375
Wenming Li, Xin Jin, Guogang Liang
DOI:10.4103/jcrt.JCRT_111_18  PMID:30964114
Context: Endoscopic self-expandable metal stents (SEMSs) are the bridge of obstructive colorectal cancer surgery. The debate is still open on whether the procedure and effects can be the same between the SEMS combined obstructive colon cancer resection and nonobstructive colon cancer resection, both of which were under laparoscopic. Aims: This retrospective study was designed to compare whether the same effects could be achieved in both resections. Settings and Design: The retrospective analysis was from September 2016 to November 2017. In the observation group (OG), 20 patients hospitalized for obstruction of the left colon cancer were included, who received obstructive colon cancer laparoscopic resection (LR) combined with SEMS insertion. In control group (CG), 20 patients were randomly selected, who underwent nonobstructive colon cancer LR during this period. Subjects and Methods: The differences between the two groups were compared, including operation time, intraoperative blood loss, the number of removed lymph nodes, postoperative anal exhaust time, and hospital stay. Results: Both groups were comparable in the age, gender, weight, the distribution of tumor, lymph node metastasis, tumor, node, and metastasis staging, operation time, intraoperative blood loss, the number of removed lymph nodes, and postoperative anal exhaust time. The hospital stay was 15.2 ± 1.3 days and 14.2 ± 1.5 days in OG and CG, respectively, and it was longer in OG than that of in CG (P = 0.032). Conclusions: Obstructive colon cancer LR combined with SEMS insertion was a safe and feasible radical treatment strategy. The same level of procedure and effects could be achieved, compared to that of nonobstructive colon cancer LR.
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Evaluation of 24-core coaxial needle saturation biopsy of the prostate by the transperineal approach in detecting prostate cancer in patients without previous biopsy history: A single-center report p. 380
Fengbo Zhang, Qiang Shao, Yuan Du, Ye Tian
DOI:10.4103/jcrt.JCRT_384_18  PMID:30964115
Background: The value of saturation prostate biopsy (SPBx) in patients without biopsy history remains controversial. Materials and Methods: A total of 644 consecutive suspected prostate cancer (PCa) cases without biopsy history were retrospectively grouped as 24-core transperineal SPBx (n = 368) guided by coaxial needle and prostate transperineal biopsy (PBx) (systematic 14-core scheme, n = 276). PCa detection rates were compared based on prostate-specific antigen (PSA) levels, PSA density (PSAD), and Gleason scores. Complications associated with those procedures were assessed. Results: Coaxial SPBx was superior to the 14-core scheme for overall PCa detection rates (39.67% vs. 24.64%), at PSA levels of 4.1–10.0 ng/ml (37.37% vs. 23.48%) or 10.1–20.0 ng/ml (43.31% vs. 27.21%), and PSAD <0.15 (47.80% vs. 29.23%) or 0.15–0.24 (34.07% vs. 20.93%) (all P < 0.05). In patients with positive biopsy, the rates of nonclinically significant PCa were comparable between the two biopsy groups. Conclusions: Transperineal coaxial needle SPBx as the initial scheme improves PCa detection compared with initial systematic 14-core PBx, without increasing complications and overdiagnosis.
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Efficacy and safety of a combination of hydrodissection and radiofrequency ablation therapy for benign thyroid nodules larger than 2 cm: A retrospective study p. 386
Dan Cui, Min Ding, Xiaoyin Tang, Jiachang Chi, Yaoping Shi, Tao Wang, Bo Zhai, Ping Li
DOI:10.4103/jcrt.JCRT_419_18  PMID:30964116
Background: Radiofrequency ablation (RFA) is a safe, highly effective, and novel method used to treat benign thyroid nodules. This study aimed to evaluate the efficacy and safety of a combination of RFA and hydrodissection for treating benign thyroid nodules larger than 2 cm. Materials and Methods: The data of 137 patients with at least one thyroid nodule ≥2 cm who underwent RFA combined with hydrodissection at our medical center from November 2014 to October 2016 were analyzed. Ultrasound-guided RFA was applied to 532 nodules, including 139 nodules ≥2 cm and 393 nodes <2 cm. Results: The volumes of thyroid nodules, complications, and changes in thyroid function were analyzed. Ablation treatments were successfully performed without intraoperative skin burns, serious bleeding, or serious thyroid storm. A positive correlation was observed between ablation time and nodule size (R2 = 0.674). Only one patient (0.7%) experienced laryngeal nerve injury after operation. Moreover, the results of thyroid function tests (free triiodothyronine, free thyroxine, and thyroid-stimulating hormone) remained within normal ranges both before and after ablation. The complete ablation rate was 99.06%. The volumes of both nodules ≥2 cm and <2 cm significantly decreased after ablation. Six months after ablation, the average volume of nodules ≥2 cm had decreased to 1.02 ± 2.42 mL, and the volume reduction ratio was 83.11%. Conclusion: The combination of ultrasound-guided RFA with hydrodissection very effectively treats benign thyroid nodules while reducing damage to the surrounding tissues. This method is safe and effective for treating benign thyroid nodules.
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Magnetic resonance imaging-guided transperineal prostate biopsy p. 394
Jie Chen, Zhengyu Lin, Jin Chen, Qingfeng Lin, Jian Chen, Yuan Yan
DOI:10.4103/jcrt.JCRT_725_18  PMID:30964117
Purpose: The purpose of the study is to assess the clinical value of magnetic resonance imaging (MRI)-guided transperineal prostate biopsy in the diagnosis of prostate disease. Materials and Methods: The institutional ethics committee approved this study. MRI-guided transperineal prostate biopsy was performed on 78 patients who had presented to our hospital with a prostate-specific antigen level >4 ng/mL or with MRI scans suggesting prostate cancer between January 2015 and August 2017. Written informed consent was obtained from all patients. Results: Of the 78 patients, pathological diagnosis could not be carried out in one because insufficient prostate tissue was obtained during biopsy. Prostate adenocarcinoma was confirmed in 34 patients, small-cell neuroendocrine carcinoma in 1 patient, prostatic tuberculosis in 1 patient, and benign prostatic hyperplasia in 41 patients. These diagnoses were confirmed by surgical pathology in 31 patients, and all results were consistent with the biopsy pathology, with no false positives. Postoperative urinary tract infection occurred in one patient, and mild postoperative hemorrhage around the prostate gland was seen in 65 patients, without the need for further clinical treatment. Conclusion: MRI-guided transperineal prostate biopsy is helpful in the diagnosis and treatment of prostatic disease.
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Rapamycin may inhibit murine S180 sarcoma growth by regulating the pathways associated with autophagy and cancer stem cells p. 398
Hubo Shi, Lulu Zhang, Chengke Zhang, Yingtao Hao, Xiaogang Zhao
DOI:10.4103/jcrt.JCRT_639_18  PMID:30964118
Objective: The objective of this study was to investigate the molecular mechanisms involved in rapamycin-induced inhibition of tumor growth. Materials and Methods: Murine S180 sarcoma cells were subcutaneously injected into mice, and the tumor-bearing mice were randomly divided into three groups (vehicle control, 2 mg/kg rapamycin, and 4 mg/kg rapamycin). The effect of rapamycin on tumor growth was determined by measuring tumor volume. Mammalian target of rapamycin (mTOR), Beclin1, ULK1, LC3, Notch1, CD133, and CD90 expressions was confirmed using confocal microscopy and Western blotting. Results: The tumor growth inhibition rates induced by high-dose and low-dose rapamycin were 48.8% and 30.1%, respectively. Beclin1 and ULK1 expressions and the LC3-II/LC3-I ratio in tumor tissues were altered by rapamycin, whereas mTOR, Notch1, CD133, and CD90 expressions were significantly inhibited by rapamycin in immunofluorescence assays. Western blotting also showed similar results. Conclusion: Tumor growth delay induced by rapamycin may be associated with the suppression of the cancer stem cell phenotype (Notch1, CD133, and CD90) and promotion of autophagy (mTOR, Beclin1, ULK1, and LC3-II/LC3-I ratio) in the murine S180 sarcoma model.
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Local tumor control of thoracoabdominal wall seeding tumor from hepatocellular carcinoma with ultrasound-guided interventional treatment: A summarized study p. 404
Chao An, Xin Li, Ping Liang, Jie Yu, Zhigang Cheng, Zhiyu Han, Mengjuan Mu
DOI:10.4103/jcrt.JCRT_784_18  PMID:30964119
Objective: The aim of the study is to evaluate the effectiveness of ultrasound (US)-guided interventional treatments in local tumor control (LTC) for thoracoabdominal wall seeding tumor (TAWST) from hepatocellular carcinoma (HCC), and explore the survival outcomes of the patients underwent surgical resection (SR) and microwave ablation (MWA) for intrahepatic tumor. Materials and Methods: A total of 40 patients with 47 TAWST from HCC were recruited from April 2007 to May 2018. LTC was evaluated by contrast-enchanced image. Long-time survival outcomes were compared. Overall survival (OS), disease-free survival (DFS), and local seeding progress-free survival (LSPFS) were analyzed. Results: One-year LTC rate was 65.2% in all patients; 72%, 0%, 50%, and 0% in the patients who underwent MWA, high-intensity focused US, iodine-125 (125I) brachytherapy and MWA combined with 125I brachytherapy, respectively. The 3-year OS, DFS rates and LSPFS rates were 51.8% and 28.6%, 12.0% and 23.8%, and 10.0% and 10.0% after MWA and SR, respectively. Univariate analysis results showed that age (P = 0.049), Karnofsky performance scale (KPS) (P = 0.002), and chemoradiation (P = 0.032); and multivariate analysis results showed that age (P = 0.045) and KPS (P = 0.010) might be predictors for LCT. While univariate analysis results showed that KPS (P = 0.032), intrahepatic tumor size (P = 0.006), chemoradiation (P = 0.003), preoperative alpha-fetoprotein level (P = 0.007), metastasis (P = 0.049), and albumin-bilirubin grade (P = 0.002), and multivariate analysis results showed that comorbidities (P = 0.004), KPS (P = 0.007), and metastasis (P = 0.009) might be predictors for OS. The pain degree of patients was improved obviously after treatments. Conclusions: US-guided interventional treatments were an effective option in LTC for TAWST from HCC, and MWA could achieve comparable long-time survival outcomes with SR for HCC patients with TAWST.
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Endoscopic ultrasonography-guided poly (lactic acid-co-glycolic acid)-poly (ethylene glycol)-poly (lactic acid-co-glycolic acid) thermogel tunnel creation for natural orifice transluminal endoscopic surgery in porcine model p. 415
Xiaotian Sun, Lin Yu, Jianbin Zhu, Shengzhou Zu, Jiandong Ding, Yan Liu
DOI:10.4103/jcrt.JCRT_400_18  PMID:30964120
Background: Natural orifice transluminal endoscopic surgery (NOTES) is a minimal invasive treatment. However, tissue dissection under endoscopy is still challenging due to the flexibility of endoscopy body and there is still no effective method for establishing a tunnel towards the targeted area. We previously showed that a new kind of thermogel could be submucosallly injected and served as a cushion for endoscopic dissection. Thus, in this study we investigated the feasibility and safety of tunnel creation using poly (lactic acid-co-glycolic acid)-poly (ethylene glycol)-poly (lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) thermogel for NOTES in a porcine model. Methods: We prepared an injectable thermogel composed of PLGA-PEG-PLGA triblock copolymers which exhibited a low-viscous sol at room temperature and spontaneously transformed into a no-flowing gel at body temperature. This thermogel was used in NOTES in pigs. The success rate and adverse events were observed. Results: The PLGA-PEG-PLGA thermogels were successfully injected to the targeted areas under the guide of endoscopic ultrasonography and the tunnels were created by sucking the gel during NOTES as the endoscopy went forwards in all the three animals. The necropsy of the pigs showed no evidence of iatrogenic injury. No serious bleeding and perforation was observed. The results demonstrated that thermogel injection and tunnel creation by suction during NOTES were feasible, which simplified the procedure of tissue dissection and developed a new method of identifying the targeted area for surgical interventions without causing severe tissue damage. Conclusion: The application of thermogel for tunnel creation in NOTES could optimize current procedures and may have a promising prospect in clinical application.
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Expression of polymeric immunoglobulin receptor and its biological function in endometrial adenocarcinoma p. 420
Mingshu Zhou, Chongdong Liu, Guangming Cao, Huiqiao Gao, Zhenyu Zhang
DOI:10.4103/jcrt.JCRT_536_18  PMID:30964121
Aim: To investigate the expression of polymeric immunoglobulin receptor (pIgR) in endometrial adenocarcinoma and the relationship between pIgR and the clinicopathological features of endometrial adenocarcinoma. To investigate the role of pIgR in the biological behavior of endometrial adenocarcinoma cell lines. Methods: First, the paraffin-embedded endometrial adenocarcinoma samples and clinicopathological data from the Chao-Yang Hospital were collected. Next, immunohistochemistry was conducted to test the expression of pIgR in endometrial adenocarcinoma; the correlations between pIgR and clinicopathological features were detected. Then, the expression of pIgR in the Ishikawa cells was interfered with short-interfering RNA (siRNA). Finally, the migration and proliferation abilities of Ishikawa cells were detected by transwell and CCK8 assays before and after interference. Results: pIgR had a high expression level and higher H-score in endometrial adenocarcinoma (P = 0.013) than in noncancerous tissues. There was no correlation between pIgR and the histopathological features of endometrial adenocarcinoma (P ≥ 0.418). The migration ability of Ishikawa cells was increased after interference with pIgR (P = 0.023). The proliferation of Ishikawa cells was not different between the untreated and siRNA215-treated groups (P = 0.967). Conclusion: PIgR may be a predictive biomarker of endometrial adenocarcinoma and a potential target protein for immunotherapy of endometrial adenocarcinoma.
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Prognostic value of the Epstein–Barr virus and tumor suppressor gene p53 gene in nasopharyngeal squamous cell carcinoma p. 426
Junjie Liu, Ying Liu, Zhenyu Zhang, Hongwei Sun, Xiaofei Ji, Boqing Li, Xiuzhi Zhou, Pengzhou Gai
DOI:10.4103/jcrt.JCRT_750_18  PMID:30964122
Aims and Methods: Retrospectively, this paper compared the differences of the Epstein–Barr virus (EBV)-encoded small RNAs (EBERs), protein expression and gene mutations of tumor suppressor gene p53 (TP53) in keratinized nasopharyngeal squamous cell carcinoma (KNSCC) and nonKNSCC, and the relationships between pathological features and the prognosis of patients were analyzed. Results: The positive rate of EBERs hybridization and TP53 expressions was 76.3% and 52.2%, respectively, while the mutation rate of TP53 gene was 39.6%. Logistic regression analysis showed direct relationships between the subtypes of nasopharyngeal squamous cell carcinoma (NPSCC) and EBERs-positive, or frequent consumption of pickled food. Overall survival rates of patients with positive TP53 expression, the TP53 gene mutations, vascular invasions, organ metastases, lymph node metastasis, and clinical recurrence were significantly lower than those of patients without those symptoms. The poorer prognosis was related to regularly drinking and the advanced age. According to the Cox regression analysis, we found that the main prognostic factors of NPSCC patients were the aging, recurrence, TP53 gene mutations, especially exon 7 or 8 mutations. Conclusions: We concluded that there were the correlations between NPSCC subtypes with EBV infection and frequent intaking of pickled food, while aging, clinical recurrence, and TP53 gene mutations were independent predictors for the poor prognosis of nasopharyngeal carcinoma.
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Usefulness of large-section cytokeratin 20 in the detection of intestinal wall infiltration and mesangial metastasis in patients with middle and lower rectal cancer p. 437
Ke-Shu Shan, Xiao-Peng Zhang, Jin-Shen Wang, Xiao-Bo Guo, Liang Shang, Feng Tian, Chang-Qing Jing, Le-Ping Li, De-Sen Wan, Chen-Sheng Li
DOI:10.4103/jcrt.JCRT_405_18  PMID:30964123
Objective: The objective of the study was to evaluate the usefulness of large-section cytokeratin 20 (CK20) staining technique in the detection of infiltration on the distal wall and mesangial metastasis in patients with middle and lower rectal cancer. Materials and Methods: A total of 62 patients with rectal cancer in the middle and lower segment were studied on large slices stained with CK20. Logistic regression was used to analyze the clinicopathologic factors related to distal low and middle rectal cancer metastasis to the mesorectum and rectal wall. Results: Two types of distal metastasis of the tumor were observed in the rectal wall in 18% (11/62) of the patients: submucosal invasion and muscularis propria invasion. The extent of distal metastasis to the rectal wall was around 0.5–1.0 cm. Four types of distal metastasis occurred in the mesorectum: lymph node invasion, blood and lymphatic vessel invasion, perineural invasion, and isolated neoplastic microfoci. Distal metastasis to the mesorectum was observed in 24% (15/62) of the patients. The extent of metastasis to the mesorectum was around 0.5–4.0 cm. Another three patients with microcapillary invasion in the distal mesorectum were observed by immunohistochemistry, as it was difficult to determine the spread by conventional hematoxylin and eosin staining. Conclusion: The large-section CK20 staining technique is useful for the detection of infiltration on the distal wall and mesangial metastasis in patients with middle and lower rectal cancer.
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CORRESPONDENCE Top

Apatinib and S-1 combination therapy for the treatment of advanced head and neck neoplasms: Three case reports p. 442
Min Meng, Xin Ye, Xia Yang, Guanghui Huang, Zhigang Wei, Yang Ni, Wenhong Li, Xiaoying Han, Jiao Wang
DOI:10.4103/jcrt.JCRT_894_18  PMID:30964124
Apatinib, one of the novel oral antiangiogenic agents, shows survival benefits in treating advanced or metastatic gastric adenocarcinoma. However, its efficacy in treating advanced head and neck neoplasms has not been reported. Herein, three elderly men with advanced head and neck neoplasms were treated with apatinib and S-1. Their initial diagnoses were hypopharyngeal carcinoma, metastatic squamous cell carcinoma of head and neck, and squamous cell carcinoma of the pyriform sinus. All patients underwent repeated chemotherapy but developed disease progression. As they refused radiotherapy due to its serious adverse reaction, apatinib was administered at a dose of 425 mg daily and S-1 at 60 mg twice daily. Thirty days after apatinib administration, the patients achieved partial response according to the Response Evaluation Criteria in Solid Tumors 1.1 standard. Mild toxicity or drug-related side effect was observed during the treatment. Therefore, apatinib and S-1 could be the new treatment option for advanced head and neck neoplasms. However, clinical trials are required to confirm their efficacy and safety.
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ERRATUM Top

Erratum: Comparison of the short-term clinical outcome between open and minimally invasive esophagectomy by Comprehensive Complication Index p. 447

DOI:10.4103/2277-9175.241836  PMID:30310777
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