Development and Validation of a Nomogram Model to Predict the Prognosis of Intrahepatic Cholangiocarcinoma

Background: The effective method for predicting prognosis of ICC is still lack. This study aims to establish and verify an effective prognostic nomogram model for intrahepatic cholangiocarcinoma (ICC) after partial hepatectomy. Materials and Methods: A nomogram model was developed in a cohort of 127 patients from January 2015 to December 2019. General clinical characteristics including preoperative physical examination data and postoperative pathological features were obtained. The independent risk factors identified by univariate and multivariate COX proportional hazards regression models were used to construct nomogram model. Predictive accuracy and discriminative ability were determined using a concordance index and a calibration curve. In addition, the clinical significance of postoperative pathological subtypes was analyzed by Kaplan-Meier survival analysis. Results: Univariate analysis and multivariate COX regression analysis revealed that CEA, maximum diameter, tumor number, and large duct type ICC was the independent risk factors. These variables were incorporated into the nomogram and the C-index for one year and three year overall survival prediction was 0.765 (95% CI: 0.672–0.814) and 0.695 (95% CI: 0.672–0.814), respectively. Postoperative pathological analysis showed that the large duct ICC had a distinct clinicopathological features and poor outcome. Conclusion: The proposed nomogram enables a prognostic prediction for patients with ICC and postoperative subclassification of ICC is of great significant to the prognosis of ICC.     

Intrahepatic cholangiocarcinoma: Limitations for resectability,current surgical concepts and future perspectives

Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy and its incidence has been shown to increase significantly during the past decades. Complete surgical resection is currently acknowledged as the only curative treatment option able to provide adequate long-term outcomes. We herein review technical, functional and oncologic limitations for resectability, discuss current surgical aspects as well as highlight the fields in which future research and practice should focus on in order to ameliorate long-term outcomes in patients with iCCA.     

肝内胆管癌术前诊断评估及临床治疗对预后的影响

目的 探讨术前诊断评估及临床治疗对肝内胆管癌患者预后的影响.方法 选取肝内胆管癌患者106例,所有患者行术前诊断评估,并对治疗后影响预后的因素进行分析.结果 肝内胆管癌患者超声检查、CT检查以及MRI检查准确率分别为78.2％、86.8％和91.5％,差异有统计学意义(P＜0.05).术前辅助检查结果单因素分析发现CA19-9、ALT以及淋巴结转移与预后相关(P＜0.05),患者的性别、年龄、肝硬化、白蛋白以及合并结石与预后无关(P＞0.05).106例肝内胆管癌总生存影响因素行Cox回归分析发现,手术方式、淋巴结转移、CA19-9、AJCC分期、肿瘤多发以及谷丙转氨酶为肝内胆管癌患者长期生存不良预后因素.肝内胆管癌采用根治术后1年、3年以及5年生存率显著高于非根治手术或保守非手术治疗,差异具统计学意义(P＜0.05).结论 肝内胆管癌患者术前完善各项相关检查,对疾病准确诊断评估具参考价值,根治性手术治疗可明显改善患者预后.     

不同手术方法治疗肝内胆管癌的临床效果评价及预后危险因素分析

目的探讨不同手术方法治疗肝内胆管癌的临床效果及影响预后的危险因素分析。方法选取肝内胆管癌患者106例,所有患者行术前诊断评估,并根据不同的手术治疗方法分为手术根治切除治疗(根治组)、姑息性切除与辅助治疗(姑息治疗组)、对症治疗(经皮途径也能完成胆道引流)(对症治疗组),并对不同手术切缘的生存率及影响预后的因素进行分析。结果根治组患者的预后优于姑息治疗组,姑息治疗组患者的预后优于对症治疗组,生存率及中位生存时间由高到低为手术根治组>姑息治疗组>对症治疗组。单因素分析发现术前CA19-9、ALT以及淋巴结转移与预后相关(P<0.05),患者的性别、年龄、肝硬化、白蛋白以及合并结石与预后无关(P>0.05);行Cox回归分析发现,淋巴结转移、CA19-9、AJCC分期、肿瘤多发以及谷丙转氨酶为肝内胆管癌患者长期生存预后因素。手术方式及手术切缘对预后均有影响。结论肝内胆管癌患者术前完善各项相关检查,对疾病的准确诊断评估具参考价值,根治性手术治疗可明显改善患者预后。     

Anti-Proliferative Effects of Compound A and Its Effect in Combination with Cisplatin in Cholangiocarcinoma Cells

Background: Cholangiocarcinoma (CCA) is a fatal cancer with high resistance to anticancer drugs.  The development of new drugs or compounds to be used alone or in combination with currently available chemotherapeutic agents to improve the treatment of CCA is needed. Compound A (CpdA), which is a small plant-derived glucocorticoid receptor modulator, strongly inhibited the growth and survival of several cancers.  However, the effect of CpdA on cholangiocarcinoma has not been elucidated. The aim of this study was to investigate the effect of CpdA on CCA. Methods: Cytotoxicity of CpdA was tested in primary cells including peripheral blood mononuclear cells (PBMCs), fibroblasts, and human umbilical vein endothelial cells (HUVECs), as well as on CCA cell lines (KKU-100, KKU-055, and KKU-213) was examined. Cell cycle distribution and IL-6 expression was assessed by flow cytometry and real-time polymerase chain reaction, respectively.  The effect of combination CpdA and cisplatin was evaluated by cell viability assay. Results: CpdA significantly inhibited cell cycle at G1 phase in CCA cell lines, and reduced IL-6 mRNA expression.  However, combination CpdA and cisplatin did not enhance the inhibitory effect. TGFβR-II expression was increased in CCA cells after the combination treatment. Conclusions: These results indicate the potential of CpdA for CCA treatment. However, combination treatment with CpdA and cisplatin increased CCA cell survival. The molecular mechanism is likely attributable to promotes cell survival via the TGFβR-II signaling pathway. The combination of CpdA with other anticancer drugs for CCA treatment should be further examined.     

肝内胆管细胞癌的诊治分析(附20例报告)

目的：探讨肝内胆管细胞癌的诊断学特点及鉴别诊断，讨论合理的手术方式。方法：回顾性分析自1990年至1995年经我院手术证实的20例肝内胆管细胞癌的临床资料。结果：CT检查19例，B超检查20例，均有不同程度肝内胆管扩张、肝内占位性病变。手术切除9例（45％），姑息性手术10例（55％），单纯剖腹探查1例。结论：CT、B超及肝功能检查相结合明显提高术前诊断率。合理的手术方式包括根治切除及适当的扩大切除。     

血小板及其参数联合肿瘤标志物术前鉴别肝细胞癌及肝内胆管癌的临床价值

目的 探讨血小板(PLT)及其参数和甲胎蛋白(AFP)、糖类抗原199(CA199)、糖类抗原125(CA125)及癌胚抗原(CEA)在术前肝细胞癌(HCC)及肝内胆管癌(ICC)鉴别诊断中的价值.方法 回顾性分析兰州大学第二医院行手术治疗的肝癌患者274例,据术后病理将其分为HCC组229例和ICC组45例.比较两组...     

Patterns of failure after curative surgery for extra-hepatic biliary tract carcinoma: Implications for adjuvant therapy

Curative resection was accomplished in 28 of 82 patients with biopsy-proven carcinoma of the extra-bepstic bile ducts, gallbladder, and ampulla of Vater seen initially at the Massachusetts General Hospital from 1962 through 1978. None of the 28 had adjuvant radiation therapy nor chemotherapy. Later evidence of cancer (failure) was found in 16 of 25 patients who were post-op survivors. Local-regional recurrence ± distant metastases (documented at re-exploration, autopsy, or clinically) occurred in $\text{13}\text{16}$, and only 3 developed distant disease only. Local-regional failure rates varied with anatomic location: $\text{4}\text{10}$ ampulla of Vater, $\text{7}\text{11}$ gallbladder, $\text{1}\text{3}$ common bile duct, land $\text{1}\text{1}$ hepatic duct (“Klatskin”) The time to local-regional recurrence ranged from 2 to 100 months post-operatively with a median of 17 months. Only 5 patients of the 28 are presently alive NED. The prognostic significance of tumor grade, lymph node involvement, perineural-lymphatic-venous invasion, and extension through the waq relative to patterns of failure are presented, and the implications for adjuvant therapy are discussed.     

Biologics,Immunotherapy, and Future Directions in the Treatment of Advanced Cholangiocarcinoma

Gemcitabine plus cisplatin remains the standard first-line systemic therapy for advanced cholangiocarcinoma and offers a median survival of approximately 1 year. No standard regimens beyond the first line and no targeted or immunotherapy agents are approved yet in this disease. Development of molecular targeted therapy in this heterogenous and relatively rare malignancy continues to be a challenging area. The rapidly growing precision medicine efforts have uncovered the underlying mutational landscape of this lethal disease and paved the way for molecularly oriented clinical trials. The early results from such trials like those exploring IDH and FGFR2 derangements have highlighted its promising potential as alternative therapeutic options. Additionally, advances in cancer immunology have identified certain correlates as biomarkers of response to immune modulatory approaches. For instance, the presence of tumor DNA mismatch repair (MMR) deficiency and/or microsatellite instability (MSI), in 5% to 10% of cholangiocarcinoma, is associated with high rates and durability of responses to immune checkpoint blockade. Beside checkpoint inhibitors, other types of immune therapeutics like peptide and dendritic cell-based vaccines and adoptive cell therapies have been developed and are undergoing active evaluation in cholangiocarcinoma. With further research effort, the integration of tumor molecular profiling in trials exploring targeted immunotherapy will lead to better understanding of the predictive role of various molecular and immune biomarkers and ultimately shine the horizon for this patient population.     

微小 RNA：胆管癌中新的调节分子与生物标志物

微小 RNA（miRNA）与胆管癌（CCA）的发生发展、浸润、转移和预后密切相关。CCA 细胞中异常表达的 miRNA 在调控细胞遗传变异、细胞周期、浸润转移能力及其凋亡过程中起重要作用,有望作为 CCA 早期诊断、预后判断的生物学标志物及治疗靶点。     

液体活检及其在非小细胞肺癌诊治中的研究进展

随着近几年科学技术的进步,液体活检技术也有了长足的发展,并在肿瘤的早期诊断及后期治疗中扮演着越来越重要的角色。相比于传统的组织活检,液体活检以其独有的无创性、便捷性、高重复性等特点在临床上得到更多的青睐,在未来有着巨大的发展潜力。本文重点探讨了循环肿瘤细胞（circulating tumor cells, CTCs）和循环肿瘤DNA（circulating tumor DNA, ctDNA）,作为液体活检最重要的两个检测对象,其历史、生物学特性,检测手段,局限性及其在非小细胞肺癌诊治中的应用。     

Clinicopathologic features,treatment, survival,and prognostic factors of combined hepatocellular and cholangiocarcinoma: A nomogram development based on SEER database and validation in multicenter study

PurposeThe aim of the study was to comprehensively understand the combined hepatocellular and cholangiocarcinoma (CHC) and develop a nomogram for prognostic prediction of CHC.MethodsData were collected from the Surveillance, Epidemiology and End Results (SEER) database (year 2004–2014). Propensity-score matching (PSM) was used to match the demographic characteristic of the CHC versus hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). A nomogram model was established to predict the prognosis in terms of cancer specific survival (CSS). The established nomogram was externally validated by a multicenter cohort.ResultsA total of 71,756 patients enrolled in our study including 62,877 HCC patients, 566 CHC patients, and 8303 ICC patients. The CHC, HCC, and ICC are not exactly similar in clinical characteristic. After PSM, the CSS of CHC was better than HCC but comparable to ICC. Tumor size, M stage, surgery, chemotherapy, and surgery were independently prognostic factors of CHC and were included in the establishment of novel nomogram.The c-index of the novel nomogram in SEER training set and multicenter validation was 0.779 and 0.780, respectively, which indicated that the model was with better discrimination power. In addition, decision curve analyses proved the favorable potential clinical effect of the predictive model. Lastly, a risk classification based on nomogram also verified the reliability of the model.ConclusionCHC had better survival than HCC but was comparable to ICC. The nomogram was established based on tumor size, M stage, chemotherapy, surgery, and radiotherapy and well validated by external multicenter cohort.     

胃镜活检与外科病理检查对早期胃癌的诊断价值比较

目的探讨胃镜活检与外科病理检查对早期胃癌诊断的一致性。方法选择行胃镜活检、外科手术切除及病理检查确诊的早期胃癌病例58例,比较胃镜活检与术后病理检查的诊断一致率。结果胃镜活检诊断早期胃癌47例,诊断一致率为89.65%。胃镜活检与病理检查对于早期胃癌的组织分型诊断一致率为79.31%(46/58),Kappa值为0.708。两种方法对癌细胞分化程度的诊断一致率为86.21%(50/58),Kappa值为0.718。两种方法对癌细胞浸润深度的诊断一致率为94.83%(55/58),Kappa值为0.884。结论胃镜活检对早期胃癌有较高的诊断价值,但与外科病理检查结果仍具有一定的差异,可依据胃镜下病变实际情况合理取材,以提高胃镜活检的准确率。     

Invasive Breast Carcinoma Tumor Size on Core Needle Biopsy: Analysis of Practice Patterns and Effect on Final Pathologic Tumor Stage

Introduction

In the absence of nodal metastasis, pathologic tumor (pT) size remains one of the most important factors in adjuvant treatment decisions and patient prognosis in breast cancer. The aim of this study was to evaluate the effect of core needle biopsy (CNB) tumor size on final pT stage.

Comparison of Cancer Detection Rates Between TRUS-Guided Biopsy and MRI-Targeted Biopsy According to PSA Level in Biopsy-Naive Patients: A Propensity Score Matching Analysis

Background

The purpose of the study was to compare cancer detection rates between 12-core transrectal ultrasound-guided prostate biopsy (TRUS-Bx) and multiparametric magnetic resonance imaging (mpMRI)-guided target prostate biopsy (MRI-TBx) according to prostate-specific antigen (PSA) level in biopsy-naive patients.

Identification and In-Depth Analysis of the Novel FGFR2-NDC80 Fusion in a Cholangiocarcinoma Patient: Implication for Therapy

Fibroblast growth factor receptor 2 (FGFR2) fusions have emerged as a new therapeutic target for cholangiocarcinoma in clinical practice following the United States Food and Drug Administration (FDA) approval of Pemigatinib in May 2020. FGFR2 fusions can result in a ligand-independent constitutive activation of FGFR2 signaling with a downstream activation of multiple pathways, including the mitogen-activated protein (MAPK) cascade. Until today, only a limited number of fusion partners have been reported, of which the most prevalent is BicC Family RNA Binding Protein (BICC1), representing one-third of all detected FGFR2 fusions. Nonetheless, in the majority of cases rare or yet unreported fusion partners are discovered in next-generation sequencing panels, which confronts clinicians with a challenging decision: Should a therapy be based on these variants or should the course of treatment follow the (limited) standard regime? Here, we present the case of a metastasized intrahepatic cholangiocarcinoma harboring a novel FGFR2-NDC80 fusion, which was discussed in our molecular tumor board. The protein NDC80 kinetochore complex component (NDC80) is an integral part of the outer kinetochore, which is involved in microtubule binding and spindle assembly. For additional therapeutic guidance, an immunohistochemical analysis of the predicted fusion and downstream effector proteins was performed and compared to cholangiocarcinoma samples of a tissue microarray. The FGFR2-NDC80 fusion resulted in strong activation of the FGFR2 signaling pathway. These supporting results led to a treatment recommendation of Pemigatinib. Unfortunately, the patient passed away before the commencement of therapy.