Improved survival in resected biliary malignancies

Nakeeb, Attila; Tran, Khoi Q.; Black, Michael J.; Erickson, Beth; Ritch, Paul S.; Quebbeman, Edward J.; Wilson, Stuart D.; Demeure, Michael J.; Rilling, William S.; Dua, Kulwinder S.; Pitt, Henry A.

doi:10.1067/msy.2002.127555

Cited by 169 publications

(108 citation statements)

References 20 publications

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“…5,6,22,23 Surgical hepatic resection of the tumor is the best therapeutic method, and the only generally accepted and potentially curative treatment for patients with CCC in the absence of primary sclerosing cholangitis, however only a small percentage of patients are candidates for curative surgery because of the advanced clinical stage at the time of diagnosis. 14,24,25 Surgical resection showed a median survival time of 13-44 months (26)(27)(28), and a 5-year survival rate of about 4.1-43%. [26][27][28][29][30] For most of the patients, palliative therapeutic options exist and are based on multimodal promising combinations including systemic chemotherapy, endoscopic biliary stenting, radiation therapy and photodynamic treatment.…”

Section: Discussionmentioning

confidence: 99%

“…14,24,25 Surgical resection showed a median survival time of 13-44 months (26)(27)(28), and a 5-year survival rate of about 4.1-43%. [26][27][28][29][30] For most of the patients, palliative therapeutic options exist and are based on multimodal promising combinations including systemic chemotherapy, endoscopic biliary stenting, radiation therapy and photodynamic treatment. 26,[31][32][33][34][35][36] Those palliative treatment options can help to improve survival, relieve symptoms and enhance the patient's quality of life.…”

Section: Discussionmentioning

confidence: 99%

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Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: Results and prognostic factors governing treatment success

Vogl

Naguib

Nour-Eldin

et al. 2011

Intl Journal of Cancer

126

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The aim of the study was to evaluate the effectiveness of transarterial chemoembolization (TACE) with four chemotherapeutic protocols in terms of local tumor control and survival of patients with unresectable cholangiocarcinoma (CCC) and to identify the prognostic factors governing treatment success. In the single-centre study, 115 patients (mean ages 5 60.4 years) with unresectable CCC were repeatedly treated with TACE. In total, 819 chemoembolization sessions were performed in 4 week intervals with a mean of 7.1 (range, 3-30) sessions per patient. The chemotherapeutic used was Mitomycin C only in 20.9% of patients, Gemcitabine only in 7%, Mitomycin C with Gemcitabine in 47% and combination of Gemcitabine, Mitomycin C and Cisplatin in 25.1%. Local tumor response was evaluated by MRI according to RECIST. Survival data were calculated according to the Kaplan-Meier method. Prognostic factors for patient's survival were evaluated using log-rank-test. The local tumor controls were: partial response 8.7%, stable disease 57.4% and progressive disease 33.9% of patients. The median and mean survival times from the start of TACE were 13 and 20.8 months. Survival rate from the start of TACE was 52% after 1-year, 29% after 2-years and 10% after 3-years. Initial tumor response, high tumor vascularity and Child-Pugh class A were statistically significant factors for patient's survival. No statistically significant difference between patients treated with different chemotherapy protocols was noted. In conclusion, TACE is a palliative and safe treatment option for patients with unresectable CCC. Child Pugh class B, tumor hypovascularity and initially progressive disease were poor prognostic factors for patient survival.Cholangiocarcinoma (CCC) is the second most common primary hepatic malignancy following hepatocellular carcinoma. 1 The tumor represents less than 2-3% of all cancers and up to 19% of primary liver cancers worldwide. [1][2][3][4] In Europe and North America, the average incidence of CCC is 1-2/100,000 per year. 5,6 The incidence during the last years is increasing, and this increasing incidence is associated with an increase in mortality. 2,7-10 Because of an advanced nature of the tumor on the time of first diagnosis, the therapeutic options for patients with unresectable CCC are limited.Transarterial chemoembolization (TACE) is a local, catheter-based, minimally invasive therapeutic option for unresectable liver tumors, and is defined as a selective administration of chemotherapy usually combined with embolization of the vascular supply of the tumor. 11 For patients with liver tumors, TACE, as a combination of local-arterial application of chemotherapeutic drugs with additional usage of embolization particles, is an effective and recommended treatment. The concept of TACE has been used in the management of patients with liver metastases from colorectal cancer, breast carcinoma as well as patients with unresectable hepatocellular carcinoma (HCC). [12][13][14][15][16][17] Regarding unresectable CCC there are few...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: Results and prognostic factors governing treatment success

Vogl

Naguib

Nour-Eldin

et al. 2011

Intl Journal of Cancer

126

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“…Surgery offers the only hope of cure and, with careful selection and increasingly radical surgical strategies, 5-year survival as high as 41% has been reported (6)(7)(8)(9). However, existing pre-operative radiological, pathological and operative (laparoscopic) staging strategies do not allow accurate determination of long term prognosis in operable patients.…”

Section: Introductionmentioning

confidence: 99%

Prognostic molecular markers in cholangiocarcinoma: A systematic review

Briggs

Neal

Mann

et al. 2009

European Journal of Cancer

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The worldwide incidence of cholangiocarcinoma (CC) is steadily rising, the United Kingdom incidence now exceeding 1000 cases per year. It is an aggresive malignancy typified by unresponsiveness to existing chemotherapy and radiotherapy regimes in the vast majority of cases. Surgery offers the only hope of a cure, though postoperative disease recurrence is common, with 5-year survival rates following resection of less then 25%. Developments in molecular techniques and improved understanding of the basis of carcinogenesis in CC has led to examination of the role of biomarkers in predicting poor outcome. This systematic review examines published evidence relating to the prognostic significance of these molecular markers in CC. Of the molecular markers which have been investigated to date p53 mutation, cyclins, proliferation indices, mucins, CA19-9, CRP, and aneuploidy appear to hold significant potential as predictors of outcome in CC. These and other biomarkers may themselves represent novel therapeutic targets for CC.

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“…Although it is relatively rare, hilar cholangiocarcinoma displays highly aggressive malignancy and is considered to be an incurable and rapidly lethal disease despite recent progresses in diagnostic and therapeutic techniques. Five-year overall survival after curative resection ranges from 20 to 40% and 10-year survival is almost zero (3,4). Furthermore, patients with inoperable, recurrent, or metastatic disease can only be treated with palliative therapy, such as endoscopic, percutaneous biliary drainage (5) combination with radiotherapy and chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Methyl-CpG binding protein MBD2 is implicated in methylation-mediated suppression of miR-373 in hilar cholangiocarcinoma

Chen

Gao²,

Luo³

et al. 2011

Oncol Rep

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Abstract. Aberrant expression of miRNAs is associated with particular cancers showing tissue-and clinical-featurespecificity patterns. Some miRNA genes harboring or being embedded in CpG islands undergo methylation mediated silencing. MBP, methyl CpG binding protein, suppresses transcription through binding to methylated CpG dinucleotides. Expression of miR-373 has been reported to be suppressed in malignant bile duct cell lines. Bioinformatic prediction reveals that the transcription start site (TSS) of miR-373 is implanted in a 402 bp canonical CpG island containing 26 CpG dinucleotides. In this study, we aim to determine the epigenetic regulation of miR-373 gene in hilar cholangiocarcinoma. TaqMan microRNA assay shows that downregulation of miR-373 is closely associated with poor cell differentiation, advanced clinical stage and shorter overall and disease-free survival in hilar cholangiocarcinomas. Methylation analysis shows that the promoter-associated CpG island is hypermethylated which is consistent with the inhibition of miR-373. Chromatin immunoprecipitation (ChIP) assay indicates that down-regulation of miR-373 resultes from the selective recruitment of MBD2 to methylated CpG islands. In contrast, MBD2 knock-down by use of a specific siRNA promoted the expression of miR-373. Reactivation of miR-373 by pharmacologic induction of 5-aza-CdR and trichostatin A (TSA) led to decreased enrichment of MBD2 at CpG island regions. Enhanced expression of exogenous MBD2 in stable QBC 939 cells which stably express pGL4-m373-prom induces strengthened recruitment of MBD2. Our findings suggest that miR-373 is a methylationmediated gene and the implication of MBD2 in methylationmediated suppression of miR-373 plays an important role in tumourigenesis and development in hilar cholangiocarcinoma.

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Improved survival in resected biliary malignancies

Cited by 169 publications

References 20 publications

Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: Results and prognostic factors governing treatment success

Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: Results and prognostic factors governing treatment success

Prognostic molecular markers in cholangiocarcinoma: A systematic review

Methyl-CpG binding protein MBD2 is implicated in methylation-mediated suppression of miR-373 in hilar cholangiocarcinoma

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