Progress of Research on Combination of Intratumoral Immune Injection and Radiotherapy for Tumor / 肿瘤防治研究

With the rapid development of tumor immunotherapy in recent years, therapeutic cancer vaccines are attracting increased attention. Compared with personalized neoantigen vaccines, in situ vaccines could form an antigen reservoir in the tumor itself. Subsequently, antitumor immunity is initiated and the response to immune-checkpoint inhibitors of some patients improve without necessitating these patients to undergo the complicated procedures of detecting personalized antigen and customizing and synthesizing antigen peptide. At this stage, the potential of realizing the clinical translation of in situ vaccination is tremendous. In this review, we primarily introduce the mechanisms of radiotherapy and intratumoral immune injection as in situ vaccination and discuss the current status of preclinical study and clinical application of their combination to attract more attention from researchers and clinicians toward in situ vaccination.

Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC / 医学前沿

Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.

Concordance of HER2 status tested by IHC and FISH in biopsy and surgical resection specimens and comparison with clinicopathological features in gastric carcinoma

Context: HER2-targeted therapy has been shown to benefit HER2-positive gastric cancer. It is very important to determine the HER2 expression level correctly to select the appropriate test and sampling method. Aim: In this study, we investigated the frequency of overexpression of HER2 and intratumoral heterogeneity of HER2-positive cases, comparison of HER2 used immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) performance in biopsy and resection specimens, the correlation of HER2 status between biopsy and resection specimens, and its relationship with clinicopathological findings. Materials and Methods: Formalin-fixed, paraffin-embedded specimens of a total of 40 surgically resected and biopsy specimens of gastric cancer were analyzed. HER2 status was examined using both IHC and FISH techniques, and the findings and their association with different clinicopathological parameters were evaluated. Results: The concordance rate between the results of IHC and FISH in biopsy and resection specimens was 96.6% and 86.6%, respectively. In paired 20 cases, the overall concordance rate of HER2-IHC and HER2-FISH status between biopsy and resection specimens was 90% and 100%, respectively. HER2-IHC analysis revealed that 5/40 cases were IHC 2+ and only 1 of 5 IHC 2+ cases demonstrated HER2-FISH amplification. Conclusion: Our results showed that HER2-IHC was well concordant with FISH in cases with a score of 0/1+ or 3+ and demonstrates strong concordance between biopsy and resection specimens. FISH should be performed when the IHC result is equivocal. In our study, no statistically significant correlation was observed between HER2 positivity and clinicopathological parameters. Overall, both biopsy and resection specimens are appropriate for HER2 testing.

Analysis of microbiota characteristics in tumor tissues sampled under gastroscope / 中华微生物学和免疫学杂志

Objective:To investigate the characteristics of bacterial community in upper gastrointestinal tumors.Methods:The study population was patients with upper gastrointestinal tumors (esophageal cancer and gastric cancer). Gastroscopy was performed on the enrolled patients ( n=17), and the specimens were taken from the tumor sites. At the same time, non-tumor tissues more than 4 cm away from the tumor tissues were taken as the control. After total DNA was extracted and purified, high-throughput 16S DNA gene sequencing was used to detect the microbiota in tumor tissues and control tissues. Bioinformatics analysis was carried out and the differences between groups were compared. Results:16S DNA PCR showed that there was no significant difference in bacterial load between tumor tissues and control tissues. The α-diversity and β-diversity indexes showed that the community composition of the two groups was similar; the samples were discrete and the colony composition was different, but there was no significant difference between the two groups. The results of Venn diagram showed that there were more operational taxonomic units (OTUs) in non-tumor tissues than in tumor tissues (2 068 vs 1 358), indicating that the bacterial species in normal tissues were more abundant than those in tumor tissues. Compared with the control tissues, the percentages of Prevotellaceae ( Prevotella), Lactobacaceae ( Lactobacillus) and Fusobacteriaceae ( Fusobacterium) in tumor tissues were relatively higher (the average percentage was more than twice that of the control). Further paired comparison of the top ten bacteria in the family and genus abundance of the two groups of samples showed that Pseudomonas decreased significantly in tumor tissues at the family ( P=0.041) and genus ( P=0.041) levels, while Prevotella was significantly enriched in tumor tissues at the family ( P=0.031) and genus ( P=0.007) levels. Conclusions:The bacterial community in the tumor microenvironment of the upper gastrointestinal tumor changed, and the species enriched in the tumor site were mainly oral common anaerobic bacteria, such as Prevotellaceae ( Prevotella), Lactobacaceae ( Lactobacillus) and Fusobacteriaceae ( Fusobacterium), especially Prevotellaceae ( Prevotella).

A new therapeutic approach for bone metastasis in colorectal cancer: intratumoral melittin

Background: Melittin has shown antiproliferative effects on tumor cells. Therefore, it comprises a valuable compound for studies on cancer treatment. To the best of our knowledge, no studies have reported melittin effects on bone metastasis. Herein, we propose an approach based on intrametastatic melittin injection to treat bone metastases in colorectal cancer. Methods: Following the characterization of melittin and antiproliferative tests in vitro, a single dose was injected through intrametastatic route into the mouse bone metastasis model. Following treatment, metastasis growth was evaluated. Results: A single dose of melittin was able to inhibit metastasis growth. Histological analysis showed necrosis and inflammatory processes in melittin-treated metastasis. Except by mild weight loss, no other systemic effects were observed. Conclusion: Our data suggest that melittin might be a promising agent for the future development of treatment strategies aiming to reduce the bone metastasis skeletal-related impact in colorectal cancer patients with bone metastasis.(AU)

A new therapeutic approach for bone metastasis in colorectal cancer: intratumoral melittin

Abstract Background: Melittin has shown antiproliferative effects on tumor cells. Therefore, it comprises a valuable compound for studies on cancer treatment. To the best of our knowledge, no studies have reported melittin effects on bone metastasis. Herein, we propose an approach based on intrametastatic melittin injection to treat bone metastases in colorectal cancer. Methods: Following the characterization of melittin and antiproliferative tests in vitro, a single dose was injected through intrametastatic route into the mouse bone metastasis model. Following treatment, metastasis growth was evaluated. Results: A single dose of melittin was able to inhibit metastasis growth. Histological analysis showed necrosis and inflammatory processes in melittin-treated metastasis. Except by mild weight loss, no other systemic effects were observed. Conclusion: Our data suggest that melittin might be a promising agent for the future development of treatment strategies aiming to reduce the bone metastasis skeletal-related impact in colorectal cancer patients with bone metastasis.

La infiltración linfocitaria (tils) como factor pronóstico en pacientes con cáncer de mama Triple Negativo que realizan quimioterapia neoadyuvante / Intratumoral lymphocyte infiltration (tils) as prognostic factor in patients with Triple Negative breast cancer who underwent neoadjuvant chemotherapies

Introducción Los cánceres de mama Triple Negativo representan entre el 12 y el 17% de todos los carcinomas mamarios. Son un grupo heterogéneo con diferentes subgrupos. La reacción inflamatoria que produce el huésped como respuesta a la enfermedad puede cuantificarse a través de la infiltración linfocitaria intratumoral (tils). Objetivos Evaluar la infiltración linfocitaria intratumoral (tils) como factor pronóstico independiente en las core biopsias de las pacientes con cáncer de mama Triple Negativo que fueron sometidas a quimioterapias neoadyuvantes. Relacionarla con la respuesta patológica obtenida luego de la cirugía. Material y método Se seleccionaron retrospectivamente pacientes con carcinoma de mama Triple Negativo que realizaron quimioterapia neoadyuvante en la Unidadde Mastología de la Clínica Breast y en el Hospital Italiano de la Ciudad de La Plata entre los años 2014 y 2017. Se obtuvo una muestra de 36 pacientes. Resultados Sobre un total de 36 pacientes, 24 mostraron tils estromales menores al 50% y 12 mayores o iguales al 50%. El 16,7% de los tumores con tils menores al 50% y la mitad de los tumores con tils mayores o iguales al 50% presentaron una Respuesta Patológica Completa (rpc) post tratamiento quimioterápico neoadyuvante. En relación con los tils intratumorales, 6 tumores de 32 con tils menores al 50% (18,8%) y 4 de 4 (100%) con tils > o iguales al 50% presentaron una Respuesta Patológica Completa (rpc) post tratamiento quimioterápico neoadyuvante. Conclusiones En nuestra serie de casos, observamos que existe relación entre el porcentaje de tils y la respuesta patológica obtenida luego de la realización del tratamiento con quimioterapia neoadyuvante, siendo un factor pronóstico en las pacientes con cáncer de mama Triple Negativo

Introduction Triple Negative breast cancers account for between 12 and 17% of all breast carcinomas. They are a heterogeneous group with different subgroups. The inflammatory reaction produced by the host in response to the disease can be quantified through intratumoral lymphocyte infiltration (tils). Objectives To evaluate intratumoral lymphocyte infiltration (tils), as an independent prognostic factor, in the core biopsies of patients with Triple Negative breast cancer who underwent neoadjuvant chemotherapies. To relate it to the pathological response obtained after surgery. Materials and method Patients with Triple Negative breast carcinoma who underwent neoadjuvant chemotherapy in the Mastology Unit of the Breast Clinic and the Italian Hospital of La Plata were retrospectively selected between the years 2014 and 2017. A sample of 36 patients was obtained. Results Out of a total of 36 patients, 24 showed stromal tils less than 50% and 12 greater than or equal to 50%. 16.7% of tumours with tils less than 50% and half of tumours with tils greater than or equal to 50% presented a complete pathological response after neoadjuvant chemotherapy treatment. In relation to intratumoral tils, 6 tumors of 32 with tils less than 50% (18.8%) and 4 of 4 (100%) with tils > or equal to 50% presented a complete pathological response after neoadjuvant chemotherapy treatment. Conclusions In our series of cases, we observe that there is a relationship between the percentage of tils and the pathological response obtained after treatment with neoadjuvant chemotherapy, being a prognostic factor in patients with triple negative breast cancer

Radiomics in Oncological PET/CT: a Methodological Overview / 대한핵의학회잡지

Radiomics is a medical imaging analysis approach based on computer-vision. Metabolic radiomics in particular analyses the spatial distribution patterns of molecular metabolism on PET images. Measuring intratumoral heterogeneity via image is one of the main targets of radiomics research, and it aims to build a image-based model for better patient management. The workflow of radiomics using texture analysis follows these steps: 1) imaging (image acquisition and reconstruction); 2) preprocessing (segmentation & quantization); 3) quantification (texture matrix design & texture feature extraction); and 4) analysis (statistics and/or machine learning). The parameters or conditions at each of these steps are effect on the results. In statistical testing or modeling, problems such as multiple comparisons, dependence on other variables, and high dimensionality of small sample size data should be considered. Standardization of methodology and harmonization of image quality are one of the most important challenges with radiomics methodology. Even though there are current issues in radiomics methodology, it is expected that radiomics will be clinically useful in personalized medicine for oncology.

PTEN loss in Gleason grade 7 prostate tumors exhibits intratumoral heterogeneity and is associated with unfavorable pathological features

Background: PTEN loss is observed in 20­30% of prostate cancers and is associated with a poor outcome, but clinical details of the impact of this biomarker are unclear for intermediate grade tumors. Methods: We investigated 43 radical prostatectomy-derived grade 7 prostate tumors from the Clinics Hospital of Ribeirão Preto. Tissue microarray (TMA) blocks were constructed and PTEN copy number status was determined for all patients through fluorescence in situ hybridization (FISH). To determine the presence of PTEN protein loss in our study cohort, we performed immunohistochemistry (IHC) in TMA sections. We then developed an automated algorithm in HALO™ to identify regions of PTEN protein loss in whole prostate scanned sections from ten patients with known PTEN deletion status by FISH. Clinical analyses were conducted to determine the associations between PTEN loss and patient outcome. All statistical analyses were conducted in R v3.4.3 with P-values below 0.05 being considered statistically significant. Results: In this study of 43 grade 7 tumors, we found PTEN deletions by FISH in 18.9% of tumors, and PTEN protein loss by IHC in 16.3% of tumors. Both techniques were highly concordant and complementary. Clinical analysis demonstrated that PTEN deletion by FISH was significantly associated with positive margin invasion (P = 0.04) and Gleason score upgrade (P = 0.001). Digital image analysis of ten representative tumors demonstrated distinct intratumoral heterogeneity for PTEN protein loss in four tumors. Conclusions: This study shows that PTEN loss in Gleason grade 7 tumors can be heterogeneous and that a systematic analysis of this biomarker using a combination of FISH, IHC, and digital imaging may identify patients with a greater risk of poor outcome (AU)

El infiltrado tumoral del carcinoma ductal infiltrante en Holguín, Cuba / Ductal infiltrating carcinoma´s inflammatory tumor infiltrates in Holguín, Cuba

Introducción: el carcinoma ductal infiltrante es la neoplasia maligna mamaria más frecuente. Entre sus características anatomopatológicas se presenta el grado histológico de malignidad, como su factor pronóstico. Existen otras alteraciones histopatológicas, como la presencia e intensidad del infiltrado inflamatorio intratumoral y peritumoral, sobre lo cual es necesario profundizar. Objetivos: determinar la intensidad del infiltrado inflamatorio intraperitumoral y peritumoral, e identificar su relación con el grado histológico de malignidad. Métodos: el estudio de una serie de casos de 392 biopsias, diagnosticadas con carcinoma ductal infiltrante de mama, en el Departamento de Anatomía Patológica del Hospital Lenin, de Holguín, Cuba, desde el año 2011 al 2015. Se determinó la presencia e intensidad del infiltrado inflamatorio intratumoral y peritumoral, y su grado histológico de malignidad. Resultados: se logró diferenciar el 68,1% de los tumores de mama. Predominaron los infiltrados inflamatorios intratumoral y peritumoral ligeros, con 44,9% y 55,4% respectivamente. El 84,6% de los tumores bien diferenciados, mostraron un infiltrado inflamatorio intratumoral ligero. En el 47,2% de los tumores moderadamente diferenciados, y en el 41,7% de los tumores poco diferenciados, con un infiltrado inflamatorio severo; se realizaron infiltrados moderados. En los tumores bien diferenciados se observó un predominio del infiltrado inflamatorio peritumoral ligero, de hasta el 92,3%; mientras que el 48,3% de los tumores con poca diferenciación, mostraron una correlación positiva con el infiltrado inflamatorio severo. Conclusiones: en el infiltrado inflamatorio intratumoral y peritumoral, predominó la intensidad ligera, y apareció un factor pronóstico potencial: la correlación entre la intensidad del infiltrado inflamatorio y el grado histológico de malignidad.

Introduction: among most frequent malignant breast tumors, ductal carcinoma has prevailed. Its malignancy histological level has become the prognosis factor. However, histopathological abnormalities like intra and peritumoral inflammatory infiltrates intensity, still require serious studies. Objectives: to determine intra and peritumoral inflammatory infiltrates intensity, and to identify their relation to malignancy histological levels. Methods: a case series study with 392 infiltrating ductal carcinoma diagnosed biopsies, at Lenin Hospital Pathological Anatomy Department, from 2011 to 2015; in which presence and intensity of intratumoral, and peritumoral inflammatory infiltrates, and malignancy histological level, were found. Results: breast tumors were differentiated up to 68.1%. Intra and peritumoral lights inflammatory infiltrate prevailed, with 44.9% and 55.4% each. Well differentiated lights inflammatory infiltrated tumors reached 84.6%. Moderate differentiated tumors were moderate infiltrated, up to 47.2%; and poor diferentiated with severe inflamatory infíltrate, presented 41.7%. Among well differentiated tumors, peritumoral light inflamatory infiltrate revealed 92.3%. Those poor differentiated were only 48.3% positively related. Conclusions: intra and peritumoral light intensity inflammatory infiltrate was the most frequent, considered as the potential prognosis factor, because of its directly proportional relationship with malignancy histological level.

Intratumoral Bleeding in a Vestibular Schwannoma

Vestibular schwannomas (VSs) account for 70% of all tumors of the cerebellopontine angle (CPA). Their clinical presentation is often insidious, with progressive hearing loss and involvement of other cranial nerves. Spontaneous hemorrhage in those tumors is very unusual, and generally presents with acute clinical features such as nausea, vomiting, headache and altered consciousness, usually with marked dysfunction of the cranial nerve involved, and with new deficits of neighboring cranial nerves. Asymptomatic patients are extremely rare. We present a case report of an incidental VS with asymptomatic bleeding, which evolved to death after surgery.

Schwannomas vestibulares (SVs) são responsáveis por cerca de 70% de todos os tumores do ângulo pontocerebelar. Sua apresentação costuma ser insidiosa, com perda auditiva progressiva e envolvimento de outros nervos cranianos. Hemorragia espontânea nesses tumores é incomum, e geralmente apresenta-se agudamente, com náusea, vômitos, cefaleia e alterações de consciência, normalmente com disfunção importante dos nervos cranianos envolvidos e com novos déficits dos nervos próximos. Pacientes assintomáticos são extremamente raros. Apresentamos um relato de caso de um SV incidental com sangramento assintomático que evoluiu para o óbito após cirurgia.

The predictive values of intratumoral arteries and tumoralmorphological classification on microvascular invasion in patients with hepatocellular carcinoma / 中华肝胆外科杂志

Objective To investigate the predictive values of preoperative radiological features-intratumoral arteries and tumoral morphological classification on microvascular invasion (MVI) and on prognosis in patients with hepatocellular carcinoma (HCC).Methods A total of 220 consecutive HCC patients who underwent curative hepatectomy at Nanjing Drum Tower Hospital from January 2008 to December 2014 were retrospectively analyzed.The predictive values of preoperative radiological features and clinical data on MVI were analyzed by the univariate analysis and multivariate logistic regression methods.The prognosis of HCC patients was analyzed by the Kaplan-Meier survival analysis and the Cox proportional hazards models.Results Univariate analysis and multivariate logistic regression showed intratumoral arteries and tumoral morphological classification using preoperative CT[called the radiological predictorsof microvascular invasion (RPMVI)] to be independent predictors of MVI.The AUROC for RPMVI inpredicting MVI was O.830 (95％ CI,O.769 ～ 0.891,P ＜0.05).The Cox multivariate analysis identified Child-Pugh grading,tumor size ＞ 5 cm,RPMVI,MVI and non-anatomical liver resection to be independent risk factorsof overall survival (OS),while tumor size ＞ 5 cm,RPMVI,MVI and non-anatomical liver resection to be independent risk factor sofre currence-free survival (RFS).The 1-,3-,and 5-year OS rates were 83.3％,61.7％,and 40.1％ in patients with RPMVI and 97.1％,76.5％,and 69.6％ in patients without RPMVI (P ＜0.05),respectively.The 1-,3-,and 5-year RFS rates were 61.9％,36.9％,and 28.4％ in patients with RPMVI and 81.6％,61.9％,and 52.2％ in patients without RPMVI (P ＜ 0.05),respectively.Conclusions RPMVI is a novel radiological marker that accurately predicted histological MVI in HCC patients preoperatively.Similar to MVI,RPMVI was found to be an independent risk factor for prognosisin HCC patients,and it may provide the important information for surgical treatment planning in HCC patients.

A correlation study between intravoxel incoherent motion MRI and histopathology in a hepatocellular carcinoma tumor model / 中华放射学杂志

Objective To explore the correlations between intravoxel incoherent motion (IVIM) parameters measured at different time points and histopathological markers in an orthotopic xenograft hepatocellular carcinoma (HCC) nude mice model. Methods A total of 40 HCC orthotopic bearing mouse models were established. When they grew to 21 days, 10 HCC-bearing mice were randomly selected as the baseline group (Group A) by a numeric table method. Then the rest mice were randomly selected on the 28th day, 35th day, and 42nd day of the growth by using the same method, 10 each for B, C, and D groups, respectively. All mice underwent MR IVIM study and apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion fraction (f) were measured. After the MRI scanning, the tumors were removed for pathological examination. The necrosis score (NF), tumor size and microvessel density (MVD) were calculated. The IVIM parameters were compared among these 4 groups by Kruskal-Wallis H test and the correlations between these IVIM parameters and histological features were studied with Spearman rank correlation test. Results One tumor in each of C and D groups was excluded because f values of IVIM were close to zero. There were significant differences found in ADC and D among all the 4 groups (P＜0.05). However, no difference was found in D*and f (P＞0.05). Compared with the baseline (group A), ADC decreased significantly at 7 and 14 days, whilst D decreased significantly at 7 days. The differences in tumor size, MVD and NF between the 4 groups were statistically significant. Compared with the baseline, the tumor size and NF significantly increased at 7, 14 and 21 days, and MVD increased at 14 and 21 days. Significantly positive correlations were demonstrated between ADC and MVD, NF (r=0.461 and 0.442, P＜0.05), between D and MVD, NF (r=0.568 and 0.519, P＜0.05) after exclusion of the data from the baseline. The parameter f from all the time points including the baseline was positively correlated with histological MVD and NF (r=0.590 and 0.458, P＜0.05). Conclusion IVIM parameters may reflect the intratumoral vascularity, tumor cell proliferation and necrosis of HCC, and they are correlated with the pathological indicators.

Clinical study of CT-guided radiofrequency ablation plus intratumoral chemotherapy for patients with stage Ⅲ non-small cell lung cancer / 国际肿瘤学杂志

Objective To explore the clinical efficacy and safety of CT-guided radiofrequency ablation plus intratumoral chemotherapy in patients with stage Ⅲ non-small cell lung cancer (NSCLC).Methods From February 2014 to May 2015,38 patients with stage Ⅲ NSCLC who did not receive systematic chemotherapy due to advanced age were selected in our hospital.The patients were divided into experimental group (n =19) and control group (n =19) by stratified random method.The patients in experimental group received CT-guided radiofrequency ablation plus Lobaplatin intratumoral chemotherapy,and the patients in control group only received CT-guided radiofrequency ablation.The adverse events,Karnofsky performance system (KPS) scores,1-year overall survival rates and short-term curative effects of patients in the two groups were observed.Results All 38 patients completed the course of therapy successfully.The 3-month response rates and 6-month response rates in experimental group and control group were 89.5％ vs.63.2％ and 78.9％ vs.52.6％,with no significant differences (P =0.124;P =0.170).The KPS score improvement rates were 42.1％ (8/19) and 31.6％ (6/19) in experimental group and control group,the KPS score stable rates were 52.6％ (10/19) and 52.6％ (10/19) in the two groups,and the KPS score deterioration rates were 5.3％ (1/19) and 15.8％ (3/19) in the two groups,with no significant differences (P =0.737;P =1.000;P =0.290).The 1-year survival rate of patients in experimental group was higher than that in control group (89.5％ vs.73.7％),with a significant difference (x2 =5.573,P =0.034).The rates of less than or equal to grade 3 pain (31.6％ vs.42.1％),low fever (21.1％ vs.26.3％),aerothorax (31.6％ vs.42.1％),gastrointestinal reaction (15.8％ vs.31.6％) and bone marrow depression (5.3％ vs.15.8％) in experimental group were lower than those in control group,but the differences were not statistically significant (P =0.501;P =0.703;P =0.501;P =0.252;P =0.290).Conclusion CT-gnided radiofrequency ablation plus intratumoral chemotherapy for stage Ⅲ NSCLC can improve short-term survival rate,and it does not increase the adverse reaction.While,the long-term overall survival rate has yet to be followed up.

Chinese medicine ligustrazine combined with percutaneous transhepatic tumor intramuscular injection of lipiodol pirarubicin combined with transhepatic arterial chemotherapy in advanced liver cancer and safety observation / 中国生化药物杂志

Objective Observing the clinical effect of Ligustrazine Phosphate Tablets combined with percutaneous intratumoral injection of lipiodol THP on advanced hepa-tocellular carcinoma.Methods83 patients with advanced hepatocellular carcinoma from January 2012 to September 2014 were analyzed.Double-blind, randomized method All patients were divided into the control group 41 cases and observation group 42 cases.The control group were treatedwith percutaneous transhepatic intratumoral injection of lipiodol THP, the observation groupwere given Ligustrazine Phosphate Tablets combined with percutaneous intratumoral injection of lipiodol THP to treat.After treatment, the two groups of patients with treatment efficacy, adverse reactions and Karnofsky and prothrombin time were analyzed.ResultsAftertreatment, the efficacy of the two groups of patients were compared, the results showed that patients in the observation group total effective rate of the control group (χ2=4.034),the difference was statistically significant (P<0.05);two groups adverse reactions in patients after treatment were compared, liver pain, blood toxicity, fever, gastrointestinal reactions similar proportion of patients, the difference was not statistically significant;Theproportion of patients in the observation group AFP<8.1ng/mL was significantly higher (χ2=4.338), the difference was statistically significant (P<0.05);patients were observed after treatment Karnofsky score was significantly higher, the difference was statistically significant (t=7.141, P<0.05);after two groups of patients were compared prothrombin time, the difference was not statistically significant.ConclusionHepatic arterial chemoembolization and percutaneous intratumoral injection of THP lipiodol emulsion on the basis of the combination of Ligustrazine Phosphate Tablets can effectively improve the efficacy of treatment, and has good security, which is a safe and effective methods of treatment should be to promote and use in clinical.

Clinical analysis of treatment of airway stenosis caused by advanced central lung cancer with bronchoscopic endobronchial ultrasound guided intratumoral injection of Cisplatin (10 cases) / 中国内镜杂志

Objective To explore the clinical application value of bronchoscopic endobronchial ultrasound (EBUS) guided intratumoral injection of Cisplatin in treatment of airway stenosis caused by advanced central lung cancer. Methods The clinical data of 10 cases of airway stenosis caused by advanced central lung cancer between Nov 2015 and Jan 2017 were analyzed retrospectively. Results 10 cases airway stenosis caused by advanced central lung cancer received EBUS guided intratumoral injection of Cisplatin treatment. Assessed by bronchoscopic, there were 8 cases of patients showed favorable effects after the treatment; Assessed by CT scan, 6 cases showed effects;And 8 cases relieved dyspnea. Conclusion EBUS guided intratumoral injection of Cisplatin in treatment of airway stenosis caused by advanced central lung cancer have some effect.

Application of susceptibility weighted and perfusion weighted imaging techniques in diagnosis and grading of clear cell renal cell carcinomas / 第二军医大学学报

Objective To investigate whether the degree of intratumoral susceptibility signal intensity (ITSS) of susceptibility weighted imaging" (SWI) correlates with the transfer constant (Ktrans) of perfusion weighted imaging (PWI), and to assess their values in diagnosis and grading of clear cell renal cell carcinoma (ccRCC). Methods Thirty-six patients with pathologically confirmed ccRCC and Fuhrman grades (I W) underwent both 2D multi-breath-hold SWI and renal PWI examination. The degree of ITSS and the mean value of Ktrans were evaluated. Kruskal-Wallis test and one-way analysis of variance (ANOVA) were applied to compare the differences among the three groups (Fuhrman I, TJ and [TJ). Spearman correlation coefficient was used to determine the correlation between degree of ITSS and mean value of Ktrans. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy. Results The degrees of ITSS of Fuhrman grade I (8 patients), grade TJ (16 patients) and grade III (12 patients) were (1. 25 ± 0. 43), (1. 75 ± 0. 83) and (2. 20 ± 0. 75), with the Ktrans values being (0. 24 ± 0. 07)min-1, (0. 31 ± 0. 08)min-1 and (0. 34 ± 0. 07) min-1, respectively, statistical significances were found for both degrees of ITSS and Ktrans values among the three Fuhrman groups (χ2 = 6. 089, P< 0. 05, F=4. 116, P<0. 05). A positive correlation was found between the degree of ITSS and value of Ktrans (r = 0. 536, P< 0. 01). ITSS and value of KtransROC curve analysis was used to distinguish Fuhrman UJ vs T - II ccRCC, the optimal area under curves (AUCs), sensitivity and specificity were 0. 737, 80. 0%, 37. 5% and 0. 737, 90. 0%. 68. 8%, respectively. Conclusion Both the degree of ITSS and mean value of Ktrans can provide more pre-operative information of ccRCC, helping to make surgical plans and to predict the prognosis.

Prognostic value of preoperative intratumoral FDG uptake heterogeneity in early stage uterine cervical cancer / 부인종양

OBJECTIVE: We investigated the prognostic value of intratumoral [18F]fluorodeoxyglucose (FDG) uptake heterogeneity (IFH) derived from positron emission tomography/computed tomography (PET/CT) in patients with cervical cancer. METHODS: Patients with uterine cervical cancer of the International Federation of Obstetrics and Gynecology (FIGO) stage IB to IIA were imaged with [18F]FDG PET/CT before radical surgery. PET/CT parameters such as maximum and average standardized uptake values (SUV(max) and SUV(avg)), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and IFH were assessed. Regression analyses were used to identify clinicopathological and imaging variables associated with progression-free survival (PFS). RESULTS: We retrospectively reviewed clinical data of 85 eligible patients. Median PFS was 32 months (range, 6 to 83 months), with recurrence observed in 14 patients (16.5%). IFH at an SUV of 2.0 was correlated with primary tumor size (p<0.001), SUV(tumor) (p<0.001), MTV(tumor) (p<0.001), TLG(tumor) (p<0.001), depth of cervical invasion (p<0.001), and negatively correlated with age (p=0.036). Tumor recurrence was significantly associated with TLG(tumor) (p<0.001), MTV(tumor) (p=0.001), SUV(LN) (p=0.004), IFH (p=0.005), SUV(tumor) (p=0.015), and FIGO stage (p=0.015). Multivariate analysis identified that IFH (p=0.028; hazard ratio, 756.997; 95% CI, 2.047 to 279,923.191) was the only independent risk factor for recurrence. The Kaplan-Meier survival graphs showed that PFS significantly differed in groups categorized based on IFH (p=0.013, log-rank test). CONCLUSION: Preoperative IFH was significantly associated with cervical cancer recurrence. [18F]FDG based heterogeneity may be a useful and potential predicator of patient recurrence before treatment.

Formula Screening and in vitro Drug Release of Tegafur Thermo-sensitive Gel for Intratumor Injection / 中国药师

Objective:To screen the best formula of tegafur temperature-sensitive gel for intratumor injection and investigate the in vitro drug release behavior. Methods:The drug dose was determined by cytotoxicity experiment. The thermo-sensitive gel was prepared with PLGA-PEG-PLGA and HPMC as the matrix. With the in vitro release as the index, the effects of PLGA-PEG-PLGA and HPMC at different concentrations on gel were investigated. The gelation temperature, viscosity and pH were detected. Results:The best formula was as follows:25% PLGA-PEG-PLGA, 1% HPMC, and tegafur dose of 1 mg·ml-1 . The average gelation temperature was 36. 7℃, the average viscosity was 7550 mPa·s, and the average pH was 7. 2. Conclusion:Tegafur thermo-sensitive gel for intratumor in-jection shows temperature sensitivity and obvious sustained-release property, which provides experimental basis for the further clinical research.

Effect and apoptosis of percutaneous intratumoral injection with 188Re labeled stannic sulfur colloid on VX2 liver tumor in rabbits / 中华肝胆外科杂志

Objective To evaluate the efficacy and safety of rabbit VX2 liver tumor model by percutaneous intratumoral injection with 188Re labeled stannic sulfur colloid.Methods The VX2 liver tumor model was established in 45 rabbits,which were randomly assigned to 3 groups (n =15) according to material used in intratumoral injections,as follows:0.1 ml normal saline (Group A,control group),absolute ethanol 1ml (Group B),37MBq (1mCi) 188Re labeled stannic sulfur colloid 0.1 ml (Group C).Five rabbits from each group were killed at intervals of 1,4 and 7d after injection and the volume of tumors were measured.Meanwhile,the histopathological changes and extent of cell apoptosis were evaluated.ALT and urea levels before the operation and at intervals of 1,4,7d post injection were also detected.Results In the first day after the injection,there was no significant statistical heterogeneity of the tumor volumes between each group.At 4th day post injection,tumor volumes of group A [(1 873.1 ± 77.3) mm3] showed significant statistical heterogeneity with group B [(905.7 ± 113.3) mm3] and C [(860.2 ± 59.6) mm3] (P ＜0.01),while there were no obvious statistical significance between group B and group C (P =0.421).At 7th day post injection,there were marked statistical significance of tumor volumes between A,B and C groups[respectively,(4093.1 ± 126.5)mm3,[(2569.5 ±64.6)mm3 and (2 169.6 ± 141.9)mm3](P＜0.01).At any time after injection,the apoptosis index (AI) of peritumoral tissue in group B and C was higher than control group with statistical significance (P ＜ 0.001).At 4th day post injection,AI of group C remained higher than group B (P ＜ 0.05).At 7th day,AI of group C progressively decreased,and there were no statistical difference between group B and group C (P ＞ 0.05).Conclusion Percutaneous intratumoral injection of 188Re labeled stannic sulfur colloid is a safety and effective approach to the treatment of VX2 liver tumor in rabbits.