[Effect of postoperative adjuvant chemotherapy on prognosis of patients with intrahepatic cholangiocarcinoma:a multicenter retrospective study].

Objectives: To examine the influence of adjuvant chemotherapy after radical resection on the survival of patients with intrahepatic cholangiocarcinoma(ICC) and to identify patients who may benefit from it. Methods: The clinical and pathological data of 654 patients with ICC diagnosed by postoperative pathology from December 2011 to December 2017 at 13 hospitals in China were collected retrospectively. According to the inclusion and exclusion criteria,455 patients were included in this study,including 69 patients (15.2%) who received adjuvant chemotherapy and 386 patients (84.8%) who did not receive adjuvant chemotherapy. There were 278 males and 177 females,with age of 59 (16) years (M(IQR))(range:23 to 88 years). Propensity score matching (PSM) method was used to balance the difference between adjuvant chemotherapy group and non-adjuvant chemotherapy group. Kaplan-Meier method was used to plot the survival curve,the Log-rank test was used to compare the difference of overall survival(OS) and recurrence free survival(RFS)between the two groups. Univariate analysis was used to determine prognostic factors for OS. Multivariate Cox proportional hazards models were then performed for prognostic factors with P<0.10 to identify potential independent risk factors. The study population were stratified by included study variables and the AJCC staging system,and a subgroup analysis was performed using the Kaplan-Meier method to explore the potential benefit subgroup population of adjuvant chemotherapy. Results: After 1∶1 PSM matching,69 patients were obtained in each group. There was no significant difference in baseline data between the two groups (all P>0.05). After PSM,Cox multivariate analysis showed that lymph node metastasis (HR=3.06,95%CI:1.52 to 6.16,P=0.039),width of resection margin (HR=0.56,95%CI:0.32 to 0.99,P=0.044) and adjuvant chemotherapy (HR=0.51,95%CI:0.29 to 0.91,P=0.022) were independent prognostic factors for OS. Kaplan-Meier analysis showed that the median OS time of adjuvant chemotherapy group was significantly longer than that of non-adjuvant chemotherapy group (P<0.05). There was no significant difference in RFS time between the adjuvant chemotherapy group and the non-adjuvant chemotherapy group (P>0.05). Subgroup analysis showed that,the OS of female patients,without HBV infection,carcinoembryonic antigen<9.6 µg/L,CA19-9≥200 U/ml,intraoperative bleeding<400 ml,tumor diameter>5 cm,microvascular invasion negative,without lymph node metastasis,and AJCC stage Ⅲ patients could benefit from adjuvant chemotherapy (all P<0.05). Conclusion: Adjuvant chemotherapy can prolong the OS of patients with ICC after radical resection,and patients with tumor diameter>5 cm,without lymph node metastasis,AJCC stage Ⅲ,and microvascular invasion negative are more likely to benefit from adjuvant chemotherapy.

[Analysis of the relationship between the number of lymph nodes examined and prognosis for curatively resected gallbladder carcinoma: a multi-institutional study].

Objective: To examine the role of the number of lymph nodes examined(NLNE) on the prognosis of patients with curatively resected gallbladder carcinoma(GBC). Methods: The clinicopathological data and prognosis of 401 patients with GBC who underwent radical surgery from six institutions of China from January 2013 to December 2017 were analyzed retrospectively. There were 153 males(38.2%) and 248 females(61.8%), with age of (62.0±10.5) years (range: 30-88 years). Fifty-three patients(22.2%) were accompanied by jaundice. All patients underwent radical resection+regional lymphadenectomy.R0 or R1 resection was confirmed by postoperative pathological examination.The different cut-off values of NLNE were determined by the X-tile software, the optimal cut-off values were identified by analyzing the relationship between different cut-off values of NLNE with survival rate. Kaplan-Meier method was used for survival analysis. Univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model. Results: Among the 401 patients enrolled, 135 cases (33.6%) had lymphatic metastasis, of which 98 cases were in N1 stage(24.4%) and 37 cases were in N2 stage(9.2%).A total of 2 794 NLNE were retrieved, with a median count of 6 (5).The median positive lymph nodes count was 0 (1), and the median positive lymph nodes ratio was 0 (IQR, 0-0.2). Since the 12 and 15 were determined as the cut-off values by X-tile, all patients were divided into three groups of 1-11, 12-15 and ≥16.The 3-year survival rate of the three groups was 45.2%, 74.5%, 12.0% respectively, with statistically significant difference between three groups (χ(2)=10.94, P<0.01). The results of multivariate analysis showed that NLNE was an independent prognostic factor for overall survival (P<0.05). Further analysis was performed specifically for subgroup of T stages. For T1b patients, the prognosis of the NLNE with 1-7 group was significantly better than that of the ≥8 group(χ(2)=4.610, P<0.05). For T2 patients, the prognosis of the TLNE ≥7 group was significantly better than that of 1 -6 group (χ(2)=4.287, P<0.05). For T3 and T4 patients, the prognosis of the TLNE with 12 - 15 group was significantly better than that of 1 -11 group (χ(2)=5.007, P<0.01) and ≥16 group (χ(2)=10.158, P<0.01). Conclusions: The NLNE is an independent factor affecting the prognosis of patients with GBC.For patients with stage T1b,8 lymph nodes should be retrieved; for patients with stage T2,extensive dissection of more than 6 lymph nodes can significantly improve the prognosis.For advanced patients (stages T3 and T4), extensive dissection with 12-15 lymph nodes is recommended. However, it fails to get more survival benefits by dissecting more than 16 lymph nodes.

[Pilot study of the relationship between clinical classification of gallbladder cancer and prognosis: a retrospective multicenter clinical study].

Objectives: To propose a novel clinical classification system of gallbladder cancer, and to investigate the differences of clinicopathological characteristics and prognosis based on patients who underwent radical resection with different types of gallbladder cancer. Methods: The clinical data of 1 059 patients with gallbladder cancer underwent radical resection in 12 institutions in China from January 2013 to December 2017 were retrospectively collected and analyzed.There were 389 males and 670 females, aged (62.0±10.5)years(range:22-88 years).According to the location of tumor and the mode of invasion,the tumors were divided into peritoneal type, hepatic type, hepatic hilum type and mixed type, the surgical procedures were divided into regional radical resection and extended radical resection.The correlation between different types and T stage, N stage, vascular invasion, neural invasion, median survival time and surgical procedures were analyzed.Rates were compared by χ(2) test, survival analysis was carried by Kaplan-Meier and Log-rank test. Results: Regional radical resection was performed in 940 cases,including 81 cases in T1 stage,859 cases in T2-T4 stage,119 cases underwent extended radical resection;R0 resection was achieved in 990 cases(93.5%).The overall median survival time was 28 months.There were 81 patients in Tis-T1 stage and 978 patients in T2-T4 stage.The classification of gallbladder cancer in patients with T2-T4 stage: 345 cases(35.3%)of peritoneal type, 331 cases(33.8%) of hepatic type, 122 cases(12.5%) of hepatic hilum type and 180 cases(18.4%) of mixed type.T stage(χ(2)=288.60,P<0.01),N stage(χ(2)=68.10, P<0.01), vascular invasion(χ(2)=128.70, P<0.01)and neural invasion(χ(2)=54.30, P<0.01)were significantly correlated with the classification.The median survival time of peritoneal type,hepatic type,hepatic hilum type and mixed type was 48 months,21 months,16 months and 11 months,respectively(χ(2)=80.60,P<0.01).There was no significant difference in median survival time between regional radical resection and extended radical resection in the peritoneal type,hepatic type,hepatic hilum type and mixed type(all P>0.05). Conclusion: With application of new clinical classification, different types of gallbladder cancer are proved to be correlated with TNM stage, malignant biological behavior and prognosis, which will facilitate us in preoperative evaluation,surgical planning and prognosis evaluation.

[Clinical features, diagnosis and treatment of intraductal papillary neoplasm of the bile duct].

Objective: To study the clinicopathologic features of intraductal papillary neoplasm of the bile duct(IPNB) and to analyze the diagnostic and therapeutic patterns. Methods: The data of 46 patients with IPNB undergoing surgery in Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2013 to November 2017 were retrospectively analyzed.There were 23 males and 23 females with age of (64±8)years.Patients were followed up by clinics and telephone inquiry.Categorical data were compared with χ(2) test or Fisher's exact test. Results: Abdominal pain(in 31 patients), fever (in 15 patients) and jaundice (in 11 patients) were the most common symptoms.Twenty-five patients were accompanied with cholangiolithiasis and 25 were accompanied with liver atrophy.Preoperative laboratory examination was mainly manifested as the abnormal liver function caused by biliary obstruction.Typical imaging findings included bile duct dilation (in 45 patients) and mass within bile duct (in 22 patients). All the patients were diagnosed as IPNB histopathologically.Among them, high-grade intraepithelial neoplasia and related adenocarcinoma were more common in mucus-hypersecretion IPNB ((13/15 vs. 51.6%(16/31))(χ(2)=5.331, P=0.021). Hepatectomy was performed in 25 patients, hepatectomy combined with biliary resection and reconstruction in 12 cases, biliary resection and reconstruction in 3 cases, pancreatoduodenectomy in 3 cases, hepatopancreaticoduodenectomy in 1 case, liver transplantation in 1 case and radiofrequency ablation in 1 case.Forty-one patients were followed up with a median of 30 (12, 41) months.Seven patients suffered recurrence and 6 died. Conclusion: IPNB is a rare disease with limited knowledge currently.Images are the main diagnositc means and surgery is the first choice.

Is differential expression of p16INK4a based on the classification of uterine smooth muscle tumors associated with a different prognosis? A meta-analysis.

We conducted a meta-analysis to examine p16INK4a expression in uterine smooth muscle tumors (USMTs). Although the prognostic value of tumor suppressor p16INK4a has been elucidated in a variety of cancers and precancerous lesions, its role in USMTs is not well established. We searched PubMed, Web of Science, and Embase for publication son p16INK4a expression in USMTs. Strict inclusion and exclusion criteria were imposed. Risk ratios (RRs) with 95% confidence intervals (95%CIs) were calculated to assess the strength of association. Publication bias was estimated using funnel plots and the Egger's regression test. Twelve eligible studies comprising 661 patients were included. Compared with leiomyoma (LM), the figures for the strength of association were as follows: LM variants (RR = 1.53, 95%CI = 1.03-2.27, P = 0.036, random effect); leiomyosarcoma (LMS) (RR = 3.20, 95%CI = 1.68-6.12, P < 0.001, random effect); and smooth muscle tumors of uncertain malignant potential (STUMP) (RR = 2.90, 95%CI = 1.17-7.21, P = 0.022, random effect). p16INK4a expression was significantly higher in LMS than in LM variants (RR = 3.74, 95%CI = 1.96-7.13, P < 0.001, random effect) or STUMP (RR = 1.67, 95%CI = 1.26-2.23, P < 0.001, fixed effect). There was a significant correlation between overexpressed p16INK4a and recurrence rates of USMTs (RR = 1.85, 95%CI = 1.11-3.10, P = 0.019, fixed effect). p16INK4a over expression is a potential biomarker for diagnosing problematic USMTs and it might indicate a worse prognosis. However, there is currently insufficient evidence to assess the prognostic value of p16INK4a in USMTs.

Association between the WRAP53 gene rs2287499 C>G polymorphism and cancer risk: A meta-analysis.

The TP53 5'-untranslated region flanking the gene WRAP53 (also known as WDR79 and TCAB1) has been hypothesized to be associated with cancer risk due to its critical function in regulating p53 levels. In this review, we analyzed the association between the WRAP53 gene rs2287499 C>G polymorphism and risk of cancer using five case-control studies, comprising seven datasets. All analyses were performed using RevMan software. In the overall analysis, no significant association between rs2287499 and risk of cancer was found. We then conducted subgroup tests, stratifying the data by cancer type, ethnicity, sample source, and quality score. Only the brain and breast cancer subgroups returned significant results, but with conflicting implications. Our concerns regarding this are discussed in detail. In conclusion, the rs2287499 polymorphism may be associated with risk of cancer. Further studies taking into consideration a broader range of cancer types and different ethnicities are warranted.

Long non-coding RNA SUMO1P3 promotes glioma progression via the Wnt/ß-catenin pathway.

OBJECTIVE: Long non-coding RNA SUMO1P3 has been reported to act as an oncogene in the tumorigenesis of several types of human malignancy. However, to the best of our knowledge, the exact biological functions and potential mechanism of lncRNA SUMO1P3 in glioma remains unknown. Therefore, the aim of this study was to investigate the potential role of SUMO1P3 in glioma and to explore the underlying mechanism. PATIENTS AND METHODS: The present study examined SUMO1P3 expression in glioma tissues and cell lines using reverse transcription-quantitative polymerase chain reaction. Cell Counting Kit-8 (CCK-8) and transwell assays were used to examine the effects of SUMO1P3 on the proliferation and invasion of glioma cells, respectively. Furthermore, Western blot was used to detect the expression levels of proteins in the epithelial-mesenchymal transition (EMT) process. RESULTS: The expression level of SUMO1P3 was higher in glioma tissues compared with corresponding adjacent normal tissues. In addition, a high expression level of SUMO1P3 was significantly associated with clinical progression and poor survival for patients with glioma. Furthermore, the knockdown of SUMO1P3 inhibited the proliferation, migration and invasion of U87 and U251 cells. In addition, the knockdown of SUMO1P3 inhibits glioma growth in vivo. Finally, the knockdown of SUMO1P3 inhibited the epithelial-mesenchymal transition and reduced the expression levels of active ß-catenin, C-myc, and cyclin D1 in U87 and U251 cells. By contrast, the overexpression of SUMO1P3 promoted glioma cell proliferation, migration, and invasion. CONCLUSIONS: SUMO1P3 promotes glioma cell proliferation, migration, and invasion, and may be involved in Wnt/ß-catenin signaling.

Aeolian flux of metals in Taiwan in the past 2600 years.

To identify anthropogenic sources of pollution, it is useful to compare recent and historical data, yet unfortunately such data are lacking in Taiwan. Thus, we studied the sediments deposited in the remote anoxic, subalpine Great Ghost Lake over a time span of 2600 yrs. Not only could a baseline be established, but also natural variations could be identified. Aeolian Asian dust particles seem to have played a significant role in the flux of 26 elements (Al, As, Ba, Br, Ca, Cd, Ce, Cl, Cr, Cs, Cu, Fe, Ga, K, Mg, Mn, Na, Ni, Pb, Rb, Si, Sr, Ti, V, Zn and Zr) in Great Ghost Lake. The fluxes have generally been higher during dry periods, especially since 1350 AD. On the other hand, local pollution from lead seems to have gained importance since 1945 AD. Recent aeolian fluxes were also calculated based on sediment data, and those results agree with direct measurements obtained in the region.

The anti-tumoral efficacy of a docetaxel-loaded liposomal drug delivery system modified with transferrin for ovarian cancer.

To reduce the toxic effect on normal cells and improve the treatment effects of docetaxel, a novel transferrin modified docetaxel-loaded long circulating liposome for ovarian tumor was established for the first time. The transferrin-modified long-circulating liposomes loaded with docetaxel (TF-LP-DOC) were prepared by the post-insertion method and exhibited excellent characteristics in terms of particle size, encapsulation efficiency and stability. We investigated the targeting efficiencies of liposomes by the cellular uptake in vitro and biodistribution in vivo, and identified the therapeutic effects using cytotoxicity experiment (in vitro)and tumor growth inhibition (in vivo) on ovarian cancer. The in vitro and in vivo results showed that TF-LP-DOC were successfully established and presented an enhanced targeting ability. With decreased side effect and improved anti-tumor efficacy of chemotherapeutic drugs, TF-LP-DOC proved itself to be a very promising tumor targeted drug delivery system.