Defining the Role of Adjuvant Therapy: Cholangiocarcinoma and Gall Bladder Cancer

Williams, Terence M.; Majithia, Lonika; Wang, Samuel J.; Thomas, Charles R.

doi:10.1016/j.semradonc.2014.01.001

Cited by 35 publications

(25 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cholangiocarcinoma accounts for about 3% of all gastrointestinal cancers worldwide [2]. Concerning the anatomical location, 60-70% of cholangiocarcinomas are perihilar, 20-30% are distal, and about 10% are intrahepatic [3]. According to the National Cancer Institute's SEER program, the clinical outcomes for patients with perihilar cholangiocarcinoma (pCCA) are poor, with the 5-year survival rate ranging from 25% to 35% for localized cancer to less than 2% for patients with distant metastases [4].…”

Section: Introductionmentioning

confidence: 99%

Establishment and validation of a prognostic nomogram for patients with resectable perihilar cholangiocarcinoma

Chen

Zhu

et al. 2016

Oncotarget

View full text Add to dashboard Cite

As the conventional staging systems have poor prognosis prediction ability for patients with perihilar cholangiocarcinoma (pCCA), we established and validated an effective prognostic nomogram for pCCA patients based on their personal and tumor characteristics. A total of 235 patients who received curative intent resections at the Eastern Hepatobiliary Surgery Hospital from 2000 to 2009 were recruited as the primary training cohort. Age, preoperative CA19-9 levels, portal vein involvement, hepatic artery invasion, lymph node metastases, and surgical treatment outcomes (R0 or R1/2) were independent prognostic factors for pCCA patients in the primary cohort as suggested by the multivariate analyses and these were included in the established nomogram. The calibration curve showed good agreement between overall survival probability of pCCA patients for the nomogram predictions and the actual observations and the concordance index (C-index) was 0.68 (95% CI, 0.61-0.71). The C-index values and time-dependent ROC tests suggested that the nomogram is superior to the conventional staging systems including the Bismuth-Corlette, Gazzaniga, Memorial Sloan Kettering Cancer Center (MSKCC), American Joint Committee on Cancer (AJCC) TNM 7 th edition, and Mayo Clinic. The nomogram also performed better than the traditional staging system in the internal cohort with 93 pCCA patients from the same institution and an external validation cohort including 84 pCCA patients from another institution in predicting the overall survival of the pCCA patients as suggested by the C-index values and the time-dependent ROC tests. In summary, the proposed nomogram has superior predictive accuracy of prognosis for resectable pCCA patients.

show abstract

Section: Introductionmentioning

confidence: 99%

Establishment and validation of a prognostic nomogram for patients with resectable perihilar cholangiocarcinoma

Chen

Zhu

et al. 2016

Oncotarget

View full text Add to dashboard Cite

show abstract

“…Acquired chemoresistance of cancer cells may arise following extended exposure to chemotherapy drugs. The majority of patients with gallbladder cancer that undergo chemotherapy become resistant following consecutive treatments and fail to benefit from chemotherapy (24). Therefore, it is important to clarify the molecular mechanism underlying acquired chemoresistance for an improved treatment of gallbladder cancer.…”

Section: Discussionmentioning

confidence: 99%

miR‑433 accelerates acquired chemoresistance of gallbladder cancer cells by targeting cyclin M

Zhang

et al. 2017

Oncol Lett

View full text Add to dashboard Cite

Abstract. Resistance to chemotherapy is associated with dismal prognosis in patients with gallbladder cancer. Cyclin-dependent kinase 10 (CDK10) influences the chemosensitivity of gallbladder cancer cells, and cyclin M is the activating factor and binding partner of CDK10. To determine the effect of CDK10 or cyclin M overexpression on chemosensitivity, gemcitabine-resistant (GR) subclones were established from CDK10 or cyclin M stable transfectants. Stable overexpression of CDK10 increased the sensitivity to gemcitabine in non-resistant cells and did not further increase the sensitivity to gemcitabine in the GR subclones. GR subclones exhibited a significantly decreased expression of cyclin M while maintaining the expression levels of CDK10, compared with the non-resistant cells. MicroRNA (miR)-433 was identified as a candidate factor involved in the mechanism of the downregulation of M cyclin in GR subclones. Luciferase assays confirmed the interaction between miR-433 and the 3' untranslated region (3'UTR) of cyclin M. Additionally, ectopic expression of miR-433 significantly decreased the expression of cyclin M. Finally, increased expression of circulating miR-433 was associated with poor outcome of chemotherapy. The results of the present study suggest that miR-433 is a potential biomarker for evaluating chemosensitivity in gallbladder cancer. IntroductionGallbladder cancer is a relatively rare disease, with an estimated annual incidence of between 2 and 3 individuals/100,000; however, it is the most frequently encountered malignancy of the biliary tract (1,2). Complete surgical resection is the only potentially curative approach in early stages of the disease; however, the majority of cases are diagnosed in advanced stages. Additionally, because the aggressive malignancy tolerates traditional chemotherapy and radiotherapy, these cases have a dismal prognosis with an overall 5-year survival rate of <5% (3). Therefore, improving the diagnostic accuracy during the early stages and identifying the molecular mechanisms associated with chemotherapy or radiation resistance may provide a potential therapeutic approach for the treatment of gallbladder cancer.Cyclin M, also known as FAM58A, is a member of the cyclin family, which serves important regulatory functions in the cell cycle and transcription (4). Mutations in cyclin M cause toe syndactyly, telecanthus and anogenital and renal malformations syndrome, a human developmental anomaly (4,5). However, the function of cyclin M in other diseases remains unclear. Cyclin M has been identified as the binding partner for cyclin-dependent kinase 10 (CDK10) (5). CDK10 is involved in the regulation of cell division and function in various types of tumor (6-10). It was confirmed that CDK10 functions as a tumor suppressor gene and regulates the survivability of biliary tract cancer cells, including gallbladder cancer cells (8). These results suggest that cyclin M may also be involved in cancer development through binding to CDK10.MicroRNAs (miRNAs) are key negative regulator...

show abstract

“…Treatment options for bile duct cancer remain limited due to the large number of patients with advanced disease at the time of diagnosis [5, 6, 7, 8, 9, 10]. Unresectable bile duct cancers are very difficult to treat with external beam radiotherapy (EBRT) alone due to the proximity of adjacent normal organs and the high doses required to effectively irradiating these neoplasms [2, 11, 12, 13].…”

Section: General Treatment Rulesmentioning

confidence: 99%

Brachytherapy in the treatment of bile duct cancer – a tough challenge

Skowronek¹,

Zwierzchowski²

2017

jcb

View full text Add to dashboard Cite

The majority of patients with bile duct cancer are diagnosed with clinically advanced disease. Most of these patients have a short life expectancy and are treated with palliative aim. Most patients present with locally advanced or metastatic disease, which is not amenable to surgical resection, resulting in poor survival. Adjuvant or definitive radiotherapy, with or without chemotherapy, is therefore used in many centers worldwide for better local control, and with the expectation that it will have a favorable effect on survival. However, the lack of appropriate prospective trials, as well as the small size of the published series and their retrospective nature, has produced insufficient evidence for the best treatment for these patients. Intraluminal brachytherapy is an important component in the multimodality approach to bile duct cancers. The objective of this treatment is to deliver a high local dose of radiation to the tumor while sparing surrounding healthy tissues. The treatment can be safely adapted for right and left hepatic duct, and for common bile duct lesions. Brachytherapy plays a limited but specific role in definitive treatment with curative intent in selected cases of early disease, as well as in the postoperative treatment of small residual disease. Depending on the location of the lesion, in some cases, brachytherapy is a treatment of choice. Clinical indications, different techniques, results, and complications are discussed in this work.

show abstract

Defining the Role of Adjuvant Therapy: Cholangiocarcinoma and Gall Bladder Cancer

Cited by 35 publications

References 49 publications

Establishment and validation of a prognostic nomogram for patients with resectable perihilar cholangiocarcinoma

Establishment and validation of a prognostic nomogram for patients with resectable perihilar cholangiocarcinoma

miR‑433 accelerates acquired chemoresistance of gallbladder cancer cells by targeting cyclin M

Brachytherapy in the treatment of bile duct cancer – a tough challenge

Contact Info

Product

Resources

About