Long-Term Efficacy of Photodynamic Therapy with Fractionated 5-Aminolevulinic Acid 20% versus Conventional Two-Stage Topical Methyl Aminolevulinate for Superficial Basal-Cell Carcinoma.

BACKGROUND: Photodynamic therapy (PDT) is a noninvasive treatment for patients with superficial basal-cell carcinoma (sBCC). The efficacy of PDT may vary with different photosensitizers and treatment schedules. OBJECTIVE: Our objective was to evaluate whether fractionated 5-aminolevulinic acid 20% (ALA)-PDT is superior to conventional two-stage methyl aminolevulinate (MAL)-PDT for sBCC. METHODS: We present the 5 years results of a single-blind, randomized, multicenter trial. 162 patients with a histologically confirmed primary sBCC were randomized to fractionated ALA-PDT or MAL-PDT. RESULTS: The 5-year tumor-free survival rate was 70.7% (95% CI 58.2-80.1%) for ALA-PDT and 76.5% (95% CI 64.4-85.0%) for MAL-PDT. In the first 3 years, there was no significant difference in risk of treatment failure (HR = 1.53, p = 0.283), but in the long-term, the risk of recurrence was significantly lower following MAL-PDT compared to ALA-PDT (HR = 0.125, p = 0.049). As judged by patients, the esthetic result was good-excellent in 96.8% (61/63) and 94.4% (56/59) of patients treated with ALA-PDT and MAL-PDT, respectively (p = 0.631). CONCLUSION: The long-term efficacy is significantly higher for conventional two-stage MAL-PDT than for fractionated ALA-PDT, whereas there was no significant difference in esthetic outcome between the treatments at 5 years after treatment. These results indicate that fractionated ALA-PDT offers no benefit over conventional two-stage MAL-PDT.

[Effect of sorafenib and prophylactic TACE for prevention of postoperative relapse in patients with liver cancer combined with microvascular invasion].

Objective: To study the effect of sorafenib and prophylactic transarterial chemoembolization (TACE) for prevention of postoperative relapse in patients with liver cancer combined with microvascular invasion (MVI) after using radical hepatectomy. Methods: A retrospective analysis was performed on 137 cases that underwent radical hepatectomy at the First Affiliated Hospital of Zhengzhou University from August 2015 to January 2018. Clinical data of liver cancer patients with MVI were diagnosed by postoperative pathology. General data of the three groups were analyzed. Kaplan-Meier was used to calculate the tumor-free survival rate. COX proportional hazards-model was used to analyze the independent risk factors for postoperative recurrence of liver cancer with MVI recurrence. Counting data was compared by x(2) test between groups, and log-rank test was used to compare the tumor-free survival rates. Results: A, B, and C groups had 49, 36, and 52 cases, respectively. General clinicopathological data of the three groups were not statistically significant. The postoperative tumor-free survival rates at 1-, 2-, and 3-years were 71.4%, 51.0%, 38.8%, 86.1%, 75.0%, 66.7%, and 82.7%, 75.0%, and 59.6% respectively in A, B, and C groups. Multivariate Cox proportional-hazards regression model showed that patients' age (HR = 0.622, P = 0.046), maximum tumor diameter (HR = 1.661, P = 0.033), prophylactic TACE (HR = 0.544, P = 0.019), and postoperative use of sorafenib (HR = 0.419, 0.222, 0.791, P = 0.007) were independent risk factors for postoperative recurrence of liver cancer with MVI. Conclusion: Sorafenib or prophylactic TACE use can significantly reduce the recurrence rate within 3 years after radical surgery in patients with liver cancer who were confirmed to have MVI by postoperative pathology.

Prognostic prediction of male recipients selected for liver transplantation: With special attention to neutrophil to lymphocyte ratio.

AIM: Neutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker that has a close relationship with tumor progression and metastasis. In this study, we aimed to investigate the role of NLR in the prognosis of male candidates with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). METHODS: We analyzed the clinical data of 248 male HCC candidates who underwent LT in our Liver Transplantation Center between 2002 and 2012. All risk factors were analyzed by univariate and multivariate Cox analysis and survival rates were calculated by Kaplan-Meier log-rank test. RESULTS: NLR was proved to be an independent risk factor affecting overall survival (OS) (P < 0.001) and tumor-free survival (TFS) (P = 0.003) of male candidates with HCC following LT. Additionally, our study showed that elevated NLR (>4) was associated with early tumor recurrence by Kaplan-Meier analysis. Furthermore, we established Model_OS and Model_TFS to predict prognosis based on multivariate Cox analysis. Our study showed that male candidates with HCC who exceeded the Milan criteria but within Model_OS could achieve similar OS as those within the Milan criteria (P = 0.220). Similarly, male patients who exceeded the Milan criteria but within Model_TFS could achieve similar TFS as those within the Milan criteria (P = 0.197). CONCLUSION: Proper inflammatory response may effectively reduce tumor recurrence after LT. Elevated NLR (>4) within a certain range is associated with early tumor recurrence. NLR-based models are efficient and safe for prognostic prediction among male candidates with HCC for LT.

Thirdhand smoke exposure promotes gastric tumor development in mouse and human.

The pollution of indoor environments and the consequent health risks associated with thirdhand smoke (THS) are increasingly recognized in recent years. However, the carcinogenic potential of THS and its underlying mechanisms have yet to be thoroughly explored. In this study, we examined the effects of short-term THS exposure on the development of gastric cancer (GC) in vitro and in vivo. In a mouse model of spontaneous GC, CC036, we observed a significant increase in gastric tumor incidence and a decrease in tumor-free survival upon THS exposure as compared to control. RNA sequencing of primary gastric epithelial cells derived from CC036 mice showed that THS exposure increased expression of genes related to the extracellular matrix and cytoskeletal protein structure. We then identified a THS exposure-induced 91-gene expression signature in CC036 and a homologous 84-gene signature in human GC patients that predicted the prognosis, with secreted phosphoprotein 1 (SPP1) and tribbles pseudokinase 3 (TRIB3) emerging as potential targets through which THS may promote gastric carcinogenesis. We also treated human GC cell lines in vitro with media containing various concentrations of THS, which, in some exposure dose range, significantly increased their proliferation, invasion, and migration. We showed that THS exposure could activate the epithelial-mesenchymal transition (EMT) pathway at the transcript and protein level. We conclude that short-term exposure to THS is associated with an increased risk of GC and that activation of the EMT program could be one potential mechanism. Increased understanding of the cancer risk associated with THS exposure will help identify new preventive and therapeutic strategies for tobacco-related disease as well as provide scientific evidence and rationale for policy decisions related to THS pollution control to protect vulnerable subpopulations such as children.

Selective COX-2 Inhibitor Is Beneficial in Suppressing Chronic Postsurgical Pain in Esophageal Cancer Patients and May Prolong Patient Survival.

INTRODUCTION: Chronic postsurgical pain (CPSP) is a common complication after surgical procedures. Radical resection of esophageal cancer is a complex procedure, one of the most extensive and traumatic surgical procedures in oncological surgery, and the incidence of postoperative chronic pain is high, seriously affecting patients' postoperative recovery. Therefore, this study aimed to investigate the incidence of CPSP in patients with esophageal cancer and to analyze the risk factors associated with its occurrence in order to provide certain prevention and treatment ideas for clinical prevention and reduction of CPSP. METHODS: Patients with radical esophageal cancer resection were selected as the study subjects, and the clinical data regarding to patients' preoperative comorbidities, ASA grading, surgical method, use of selective COX-2 inhibitors, postoperative analgesic pump use, and patients' postoperative tumor recurrence time were collected. The differences in clinical data between the CPSP group and no-CPSP group were compared to analyze the risk factors for the occurrence of CPSP. RESULTS: A total of 262 patients were included; 57 (21.76%) developed CPSP, and there were statistical differences between the two groups in terms of selective COX-2 inhibitor and postoperative analgesic pump use rates and surgical modality (p < 0.05), and logistic regression analysis showed that age and length of surgery increased the risk of CPSP, perioperative selective COX-2 inhibitor use decreased the risk of CPSP occurrence (p < 0.05), the extent of tumor infiltration and regional lymph node metastasis were risk factors for shortening tumor-free survival (TFS), and age and use of selective COX-2 inhibitor were influential factors for prolonging TFS (p < 0.05). CONCLUSION: Patients with esophageal cancer have a high incidence of postoperative chronic pain, with youth and length of surgery being risk factors for CPSP, and perioperative pain management with selective COX-2 inhibitors can reduce the incidence of CPSP and is associated with prolonged TFS.

Ex vivo tumor dissection followed by kidney autotransplantation in bilateral wilms tumor.

Introduction: Successful management of bilateral Wilm's tumor (BWT) involves a radical resection while preserving enough normal kidney tissue. Nephron-sparing surgery often results in an R1/R2 resection with a high recurrence rate in children with huge or multiple tumors, or tumors proximity to the renal hilum. In contrast, kidney autotransplantation can completely resect the tumor while maintaining homeostasis and preserving the patient's healthy kidney tissues. Methods: We summarized the clinical data of 8 synchronous BWT patients who underwent kidney autotransplantation at the First Affiliated Hospital of Sun Yat-sen University from 2018 to 2020. Ex vivo tumor resection and kidney autotransplantions were performed on 11 kidneys. The baseline characteristics, perioperative management, and survival status were reported. Results: Nephron-sparing surgeries were performed on 5 kidneys in vivo. Among all the 8 patients, six of them (75%) received staged operation and the other 2 patients (25%) received single-stage operation. No residual tumors were found on the postoperative imaging in all the 8 patients. In total, 6 (75%) patients occurred complications after the autotransplantation, among which, 2 (33.3%) patients had complication of Clavien-Dindo grade IIIa, and 4 (66.7%) patients had complication of grade < 3. During the 38 months of follow-up, 87.5% (7/8) of patients were tumor-free survival with normal renal function. One patient died from renal failure without tumor recurrence. Discussion: Therefore, our study indicated that autologous kidney transplantation can be an option for patients with complex BWT if the hospital's surgical technique and perioperative management conditions are feasible.

The Prognostic Long-Term Impact of Chronic Obstructive Pulmonary Disease and Postoperative Mucostasis in Patients with Curatively Resected Non-Small Cell Lung Cancer.

Chronic obstructive pulmonary disease (COPD) serves as risk factor for the development of lung cancer and seems to have a prognostic impact after surgery for non-small cell lung cancer (NSCLC). The aim was to investigate the impact of COPD and postoperative mucostasis on the long-term survival after resected NSCLC. We retrospectively reviewed the data from 342 patients with curatively resected NSCLC. The prognostic long-term impact of COPD and postoperative mucostasis on overall survival (OS), recurrence free survival (RFS) and cancer specific survival (CSS) was calculated using univariable and multivariable Cox regression analyses. We found that 52.3% suffered from COPD and 25.4% had postoperative mucostasis. COPD was significantly more common among smokers (59.9%) compared with non-smokers (21.3%), (p < 0.001). There was a significant relationship between COPD and postoperative mucostasis (p = 0.006) and between smoking and mucostasis (p = 0.023). Patients with postoperative mucostasis had a significantly worse OS (p < 0.001), RFS (p = 0.009) and CSS (p = 0.008). The present analysis demonstrated that postoperative mucostasis, but not COPD, was associated with both worse short- and long-term outcomes for OS, RFS and CSS in curatively resected NSCLC.

Thirdhand tobacco smoke exposure increases the genetic background-dependent risk of pan-tumor development in Collaborative Cross mice.

Increasing evidence has shown that thirdhand smoke (THS) exposure is likely to induce adverse health effects. An important knowledge gap remains in our understanding of THS exposure related to cancer risk in the human population. Population-based animal models are useful and powerful in investigating the interplay between host genetics and THS exposure on cancer risk. Here, we used the Collaborative Cross (CC) mouse population-based model system, which recapitulates the genetic and phenotypic diversity observed in the human population, to assess cancer risk after a short period of exposure, between 4 and 9 weeks of age. Eight CC strains (CC001, CC019, CC026, CC036, CC037, CC041, CC042 and CC051) were included in our study. We quantified pan-tumor incidence, tumor burden per mouse, organ tumor spectrum and tumor-free survival until 18 months of age. At the population level, we observed a significantly increased pan-tumor incidence and tumor burden per mouse in THS-treated mice as compared to the control (p = 3.04E-06). Lung and liver tissues exhibited the largest risk of undergoing tumorigenesis after THS exposure. Tumor-free survival was significantly reduced in THS-treated mice compared to control (p = 0.044). At the individual strain level, we observed a large variation in tumor incidence across the 8 CC strains. CC036 and CC041 exhibited a significant increase in pan-tumor incidence (p = 0.0084 and p = 0.000066, respectively) after THS exposure compared to control. We conclude that early-life THS exposure increases tumor development in CC mice and that host genetic background plays an important role in individual susceptibility to THS-induced tumorigenesis. Genetic background is an important factor that should be taken into account when determining human cancer risk of THS exposure.

Age independent survival benefit for patients with small hepatocellular carcinoma undergoing percutaneous cryoablation: A propensity scores matching study.

Background: Hepatocellular carcinoma (HCC) is the major cause of malignancy-related deaths worldwide, and its incidence is likely to increase in the future as life expectancy increases. Therefore, the management of elderly patients with HCC has become a global issue. Aim of this study was to assess whether elderly patients with small HCC could obtain survival benefit from cryoablation (CRYO) in a real-world. Materials and methods: From July 2007 to June 2013, 185 patients with small HCC who underwent curative-intent percutaneous CRYO. All patients were divided into three groups according to age distribution. Overall survival (OS) and tumor-free survival (TFS) were compared between among of groups before and after the 1:1 propensity score matching, respectively. Univariate and multivariate Cox analyses were performed to determine the potential relationships between variables and prognostic outcomes. Results: One hundred and eighty-five patients (144 men, 41 women) received CRYO for small HCC, including 59 patients with age <50 years, 105 patients with age between 50 and 65 years, and 21 patients with age >65 years. The three age groups showed significant differences in the terms of underlying chronic liver disease and the number of patients with minor postoperative complications. After propensity score matching, the younger and elderly groups showed significant differences in mean OS (P=0.008) and tumor progression (P=0.050). However, no significant differences were shown in mean progression-free survival (PFS) (P=0.303). The Cox multivariate analysis showed that the Child-Pugh grade (HR=3.1, P<0.001), albumin (HR=0.85, P=0.004) and total of bilirubin (HR=1, P=0.024) were the independent prognostic factor for mean OS. Conclusion: Our propensity-score-matched study suggested that elderly patients with small HCC can achieve acceptable prognostic outcomes with PFS similar to those of younger patients with small HCC after treatment with CRYO, while Child-Pugh grade, bilirubin and serum albumin levels were associated with the prognosis of small HCCs.

Case Report: Stage IIIc primary malignant mixed Müllerian tumor of the fallopian tube: A case of 5-year disease-free survival after cytoreductive surgery combined with peritoneal resection and adjuvant chemotherapy with paclitaxel plus carboplatin.

Malignant mixed Müllerian tumor (MMMT) of the fallopian tube is rare and has a poor prognosis. For the patient with fallopian tube MMMT, complete resection of the tumor invading the viscera and the peritoneum is a prerequisite for long-term survival. We report a case of stage IIIc MMMT of the fallopian tube treated by cytoreductive surgery (CRS), peritoneal resection, and adjuvant chemotherapy (paclitaxel plus carboplatin), with 5-year tumor-free survival. Postoperative chemotherapy combining platinum and paclitaxel is the most potent adjuvant therapy.

Circulating Tumor Cells Undergoing the Epithelial-Mesenchymal Transition: Influence on Prognosis in Cytokeratin 19-Positive Hepatocellular Carcinoma.

PURPOSE: The purpose of this study was to elucidate the relationship between cytokeratin 19 (CK19) expression and levels of circulating tumor cells (CTCs) in preoperative peripheral blood of patients with hepatocellular carcinoma (HCC), and the potential influence of that relationship on prognosis. PATIENTS AND METHODS: CanPatrol™ CTC-enrichment technique and in situ hybridization (ISH) were used to enrich and classify CTCs undergoing the epithelial-mesenchymal transition (EMT) from blood samples of 105 HCC patients. CK19 immunohistochemistry staining was performed on HCC tissues and compared with demographic and clinical data. RESULTS: In total, 27 of 105 (25.7%) HCC patients were CK19-positive. CK19-positive patients had significantly lower median tumor-free survival (TFS) than CK19-negative patients (5 vs 10 months, P = 0.047). In total, 98 (93.3%) patients showed pre-surgery peripheral blood CTCs (range: 0-76, median: 6), and 57 of 105 (54.3%) patients displayed CTC counts ≥6. Furthermore, CK19-positive patients with CTC count ≥6 showed significantly higher percentage than CK19-negative ones (77.8% vs 46.2%, P = 0.004). CK19-positive patients showed a significantly higher proportion of mesenchymal CTCs among CTCs undergoing EMT than CK19-negative patients (mean rank: 62.28 vs 49.79, P = 0.046). We also found that CK19-positive patients with high CTC count showed significantly shorter median tumor-free survival than CK19-negative patients with low CTC count (5 vs 16 months, P = 0.039). CONCLUSION: High CTC count and high percentage of mesenchymal CTCs are closely related to the expression of CK19, which is associated with poor prognosis in HCC patients.

The Association of Single-Nucleotide Polymorphism rs13181 in ERCC2 with Risk and Prognosis of Nasopharyngeal Carcinoma in an Endemic Chinese Population.

OBJECTIVE: We examined whether the single-nucleotide polymorphism (SNP) rs13181 in the gene encoding excision repair cross complementation group 2 (ERCC2) is associated with the risk and prognosis of nasopharyngeal carcinoma (NPC). METHODS: SNPs at rs13181 were genotyped in 439 NPC patients (NPC group) and 431 age- and gender-matched cancer-free controls (control group) from a region of China where NPC is endemic, and frequencies of GG, GT and TT genotypes were compared between the two groups in the case-control study. In a subset of 365 NPC cases, SNPs were examined for potential correlation with tumor-free survival time (TFS) and overall survival (OS). RESULTS: Relative to NPC risk with a TT genotype, NPC risk was similar with GT + GG genotypes (OR 1.052, 95% CI 0.656-1.688), after adjusting for gender, age, smoking history, and immunoglobin A against Epstein-Barr virus capsid antigen (EBV-VCA-IgA) status. Univariate analysis showed that the GG or GT genotype was associated with significantly worse TFS (p<0.001) and OS (p=0.010) than the TT genotype. Prognosis was significantly worse for men than for women (TFS, p=0.045; OS, p=0.031), for T3-T4 classification than for T1-T2 (TFS, p=0.009; OS, p=0.007), for N3 than for N0+N1+N2 (TFS, p<0.001; OS, p<0.001). Based on multivariate analysis, independent risk factors for poor TFS were GG or GT genotype (HR 2.629, 95% CI 1.625-4.254, p<0.001), T3-T4 classification (HR 2.146, 95% CI 1.244-3.701, p=0.006) and N3 (HR 2.527, 95% CI 1.574-4.059, p<0.001). GG or GT genotype (HR 2.217, 95% CI 1.283-3.832, p=0.004), gender (HR 1.989, 95% CI 1.046-3.785, p=0.036), T3-T4 (HR 2.431, 95% CI 1.306-4.526, p=0.005) and N3 (HR 2.693, 95% CI 1.637-4.432, p<0.001) were independent risk factors for poor OS. CONCLUSION: The rs13181 SNP in ERCC2 does not appear to be associated with NPC risk, but it may serve as an independent prognostic factor for NPC recurrence and death.

S100P as a novel biomarker of microvascular invasion and portal vein tumor thrombus in hepatocellular carcinoma.

BACKGROUND: Portal vein tumor thrombus (PVTT) and microvascular invasion (MVI) are types of intrahepatic vascular metastasis of hepatocellular carcinoma (HCC) and are highly correlated with poor prognosis. However, the underlying biomarkers of PVTT and MVI are unclear. METHODS: We identified a PVTT/MVI-associated gene S100P by cDNA microarray analysis, and assess the potential value of serum S100P measurement in the differential diagnosis of HCC and prediction of MVI status with large retrospective and perspective cohort studies. RESULTS: The mRNA and protein of S100P was increased in HCCs with PVTT or MVI. High S100P immunostaining in tumors was correlated with inferior tumor-free survival. Serum S100P values discriminated patients with HCCs from those with benign liver tumors, and it showed predictive potential of MVI status in both retrospective and perspective cohorts. S100P may regulate HCC tumorigenicity and invasive ability; S100P also was associated with up-regulation of CD44, which may mediate HCC cell adhesion to form PVTT/MVI. CONCLUSIONS: Serum S100P may be a novel differential diagnostic marker for HCC and a potential predictor of MVI status pre-surgery for HCC patients. S100P overexpression in HCC is highly correlated with the formation of PVTT and MVI, which may make S100P as a potential therapeutic target for HCC metastasis.

Prognostic Significance of Preoperative Gamma-Glutamyltransferase to Alkaline Phosphatase Ratio in Hepatocellular Carcinoma Patients with Curative Liver Resection: A Retrospective Cohort Study.

PURPOSE: Gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) were involved in the development and progression of cancers. This study aimed to evaluate the prognostic value of a preoperative GGT:ALP ratio (GAR) in hepatocellular carcinoma (HCC) patients with curative liver resection. PATIENTS AND METHODS: A total of 380 HCC patients underwent curative liver resection before December 2017 and from January to December 2018 were included and stratified into training set and validation set, respectively. Prediction accuracy was evaluated by the area under the receiver operating characteristic curve (AUC). Factors determined to be significant for overall survival (OS) and tumor-free survival (TFS) by using Cox regression analysis. The Kaplan-Meier method and Log rank test were utilized for survival analysis. RESULTS: The AUC of GAR was 0.70 (P < 0.001). An optimal cut-off value of 0.91 yielded a sensitivity of 78.1% and a specificity of 60.4% for GAR (P < 0.001), which stratified the HCC patients into high-risk (>0.91) and low-risk (≤ 0.91) groups. Time-dependent ROC revealed that the AUCs for 1-, 3-, and 5-year OS predictions for GAR were 0.60, 0.69 and 0.62, respectively. In addition, GAR was identified as an independent risk factor for OS and TFS both in training and validation cohort by univariate and multivariate Cox regression analysis, as well as a good prognostic indicator for patients with Barcelona Clinic Liver Cancer stage C or without vascular invasion. Notably, the AUC of the GAR for survival was better than several potential prognostic indices (P < 0.05). CONCLUSION: We identified the GAR as a prognostic indicator in two independent cohorts of HCC patients with curative liver resection. The patients with decreased GAR score were significantly associated with better OS and TFS.

The impact of HER2 and C-reactive protein/albumin ratio on the long-term survival of gastric cancer patients after surgery / 中国医师杂志

Objective:To investigate the impact of human epidermal growth factor receptor 2 (HER2) and C-reactive protein/albumin ratio (CAR) on the long-term survival of gastric cancer patients after surgery.Methods:A retrospective analysis was conducted on 136 gastric cancer patients admitted to Lishui Central Hospital from January 2015 to December 2017, who underwent radical surgery and were followed up for 5 years. Patients were divided into HER2 positive and HER2 negative groups based on HER2 immunohistochemical results, and into high CAR and low CAR groups based on the CAR mean value. The relationship between HER2 and CAR with clinicopathological characteristics of gastric cancer patients was analyzed. The postoperative tumor-free survival rate and overall survival rate were compared between the two groups of patients (HER2 positive group and HER2 negative group, as well as high CAR group and low CAR group). Cox regression analysis was used to identify independent prognostic factors for postoperative tumor recurrence, metastasis, and death in gastric cancer patients.Results:The proportion of HER2 positive patients with large tumor size, low differentiation, T 3-4 tumor invasion depth, lymph node metastasis, and vascular invasion was significantly higher than that of HER2 negative patients (all P<0.05). The proportion of high CAR patients with large tumor size, low differentiation, T 3-4 tumor invasion depth, lymph node metastasis, and vascular invasion was significantly higher than that of low CAR patients (all P<0.05). Kaplan-Meier survival analysis showed that HER2 negative patients had significantly higher 1-year, 3-year, and 5-year cumulative tumor-free survival rate and overall survival rate than HER2 positive patients, while low CAR patients had significantly higher 1-year, 3-year, and 5-year cumulative tumor-free survival rate and overall survival rate than high CAR patients (all P<0.05). Multivariate Cox regression analysis identified T 3-4 tumor invasion depth, lymph node metastasis, HER2 positivity, and high CAR expression as independent prognostic factors for postoperative tumor recurrence, metastasis, and death in gastric cancer patients (all P<0.05). HER2 positive gastric cancer patients had a 1.895-fold higher risk of postoperative tumor recurrence and metastasis than HER2 negative patients ( HR: 1.895, 95% CI: 1.245-4.229, P=0.034), while high CAR gastric cancer patients had a 1.769-fold higher risk of postoperative tumor recurrence and metastasis than low CAR patients ( HR: 1.769, 95% CI: 1.433-3.959, P=0.039). HER2 positive gastric cancer patients had a 2.145-fold higher risk of postoperative death than HER2 negative patients ( HR: 2.145, 95% CI: 1.378-4.589, P=0.028), while high CAR gastric cancer patients had a 1.926-fold higher risk of postoperative death than low CAR patients ( HR: 1.926, 95% CI: 1.564-3.853, P=0.025). Conclusions:HER2 and CAR are independent prognostic factors for postoperative tumor recurrence, metastasis, and death in gastric cancer patients. Gastric cancer patients with HER2 positivity and high CAR have a higher risk of postoperative tumor recurrence, metastasis, and death. This study has some limitations due to its small sample size and single-center design, which may introduce some bias. Future multicenter and large-scale studies are needed to confirm the results of this study.

Utility of percutaneous radiofrequency ablation alone or combined with transarterial chemoembolization for early hepatocellular carcinoma.

Percutaneous radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) is an effective, standard therapy against small hepatocellular carcinoma (HCC). However, there is debate regarding the effectiveness of RFA combined with TACE (RFA/TACE) compared with RFA alone. These two approaches were compared for the treatment of early HCC. The present study examined 83 HCC tumors in 83 patients treated with RFA between April 2007 and August 2014 at three medical institutions. All HCCs were single hypervascular tumors, with a median diameter of 16 mm (range, 6-30 mm). The overall survival (OS) rate of all patients (n=83) was 97.5% at 1 year, 82.8% at 3 years and 48.6% at 5 years, and the local recurrence rate of all patients was 14.3% at 1 year, 32.3% at 3 years and 36.5% at 5 years. The tumor-free survival (TFS) rate of all patients was 95.1% at 1 year, 56.3% at 3 years and 23.4% at 5 years. Compared with RFA alone, RFA/TACE significantly improved OS (P<0.001), intrahepatic distant recurrence (IDR; P=0.038) and TFS (P=0.010). A univariate analysis of prognostic indicators revealed that age <70 years (P=0.008), aspartate transaminase <40 IU/l (P=0.003), alanine aminotransferase <40 IU/l (P=0.006) and platelet count >10×104/µl (P=0.05) were associated with a high survival rate. Multivariate analysis identified RFA/TACE [hazard ratio (HR), 0.108; P=0.001] as an independent prognostic indicator. RFA/TACE was identified as the only independent indicator of IDR (HR: 0.467; P=0.042) and TFS (HR: 0.452; P=0.012). RFA/TACE improved OS rate, IDR and TFS compared with RFA alone. The data suggested that RFA/TACE should be considered for the treatment of single hypervascular HCC.

The combination of systemic chemotherapy and local treatment may improve the survival of patients with unresectable metastatic colorectal cancer.

With the development of systemic chemotherapy, the survival time of patients with advanced colorectal cancer (CRC) has increased. In addition, local treatments, such as microwave ablation and radioactive seed implantation, have been shown to be effective. However, the number of studies reporting on the effect of systemic chemotherapy combined with local treatments is limited. The present study was conducted to determine the effect of local treatment combined with systemic chemotherapy in patients with initial unresectable metastatic CRC (mCRC). Clinicopathological and follow-up data from 273 patients with initial unresectable mCRC between April, 2007 and October, 2013 were retrospectively analyzed. A total of 51 patients received minimally invasive treatments combined with systemic chemotherapy and 39 patients achieved tumor-free survival (TFS). The median TFS time was 9 months (range, 2-45 months); the median overall survival (OS) time was 40 months (range, 12-108 months). In patients who did not achieve TFS, the OS was 37 months. Thus, patients who achieved TFS exhibited a significantly longer OS compared with those who did not achieve TFS (P=0.049). The results of the univariate analysis demonstrated that certain characteristics, such as the number of lesions and maximum tumor diameter, were associated with the achievement of TFS. The patients assessed herein achieved TFS in response to local treatments combined with systemic chemotherapy. Furthermore, the achieved TFS provided an OS benefit.

Hormonal receptors and vascular endothelial growth factor in juvenile nasopharyngeal angiofibroma: immunohistochemical and tissue microarray analysis.

CONCLUSION: This work demonstrated that juvenile nasopharyngeal angiofibromas (JNAs) express high levels of hormone receptors and vascular endothelial growth factor (VEGF) compared with normal nasal mucosa. The interaction between hormone receptors and VEGF may be involved in the initiation and growth of JNA. OBJECTIVES: JNA is a rare benign tumor that occurs almost exclusively in male adolescents. Although generally regarded as a hormone-dependent tumor, this has not been proven in previous studies. The aim of this study was to investigate the role of hormone receptors in JNA and the relationship with clinical characteristics. METHODS: Standard immunohistochemical microarray analysis was performed on 70 JNA samples and 10 turbinate tissue samples. Specific antibodies for androgen receptor (AR), estrogen receptor-α (ER-α), estrogen receptor-ß (ER-ß), progesterone receptor (PR), and VEGF were examined, and the relationships of receptor expression with age, tumor stage, and bleeding were evaluated. RESULTS: RESULTS showed that JNA expressed ER-α (92.9%), ER-ß (91.4%), AR (65.7%), PR (12.8%), and VEGF (95.7%) at different levels. High level of VEGF was linked to elevated ER-α and ER-ß. There was no significant relationship between hormonal receptors and age at diagnosis, tumor stage or bleeding. However, overexpression of ER-α was found to be an indicator of poor prognosis (p = 0.031).

Relationship between expression level of 15-PGDH and clinical prognosis of liver transplantation for hepatocellular carcinoma / 器官移植

Objective To investigate the relationship between the expression level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and clinical prognosis of liver transplantation for hepatocellular carcinoma. Methods The clinical data of 94 recipients undergoing liver transplantation for hepatocellular carcinoma were retrospectively analyzed. The expression of 15-PGDH in the pathological tissues of all recipients was detected by immunohistochemical staining. The relationship between the expression level of 15-PGDH protein and clinical parameters of hepatocellular carcinoma patients was analyzed. The 5-year tumor-free survival and overall survival rates of liver transplant recipients were calculated. The possible independent risk factors of the clinical prognosis of liver transplant recipients were analyzed. Results The expression level of 15-PGDH was significantly correlated with age, Child-Pugh grade and preoperative level of alpha-fetoprotein (AFP) of the recipients (all P < 0.05). The tumor-free survival and overall survival rates of the recipients with low expression of 15-PGDH were significantly lower than those in their counterparts with high expression of 15-PGDH (both P < 0.05). The expression level of 15-PGDH, degree of tumor differentiation and American Joint Committee on Cancer (AJCC) staging were the independent risk factors of clinical prognosis of liver transplantation for hepatocellular carcinoma (all P < 0.05). Conclusions The expression level of 15-PGDH is an independent risk factor of clinical prognosis of liver transplantation for hepatocellular carcinoma.

A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy.

The last several years have witnessed exciting progress in the development of immunotherapy for the treatment of cancer. This has been due in great part to the development of so-called checkpoint blockade. That is, antibodies that block inhibitory receptors such as CTLA-4 and PD-1 and thus unleash antigen-specific immune responses against tumors. It is clear that tumors evade the immune response by usurping pathways that play a role in negatively regulating normal immune responses. In this regard, adenosine in the immune microenvironment leading to the activation of the A2a receptor has been shown to represent one such negative feedback loop. Indeed, the tumor microenvironment has relatively high concentrations of adenosine. To this end, blocking A2a receptor activation has the potential to markedly enhance anti-tumor immunity in mouse models. This review will present data demonstrating the ability of A2a receptor blockade to enhance tumor vaccines, checkpoint blockade and adoptive T cell therapy. Also, as several recent studies have demonstrated that under certain conditions A2a receptor blockade can enhance tumor progression, we will also explore the complexities of adenosine signaling in the immune response. Despite important nuances to the A2a receptor pathway that require further elucidation, studies to date strongly support the development of A2a receptor antagonists (some of which have already been tested in phase III clinical trials for Parkinson Disease) as novel modalities in the immunotherapy armamentarium.