Results of Radiation Therapy in Carcinoma of the Proximal Bile Duct (Klatskin Tumor)

D, Gonzàlez Gonzàlez; Jp, Gérard; Aw, Maners; B, De la Lande-Guyaux; A, Van Dijk-Milatz; Jh, Meerwaldt; Jf, Bosset; Dijk, van Sanne

doi:10.1055/s-2008-1040466

Cited by 95 publications

(33 citation statements)

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“…43 In a study of 71 patients with hilar CC, tumor resection was combined with postperative irradiation (52 patients) or preoperative plus postoperative irradiation (19 patients). 44 Although the 1-year survival rate was similar to that in our study, Gonzalez-Gonzalez et al warned that high radiation doses could be dangerous and could worsen the prognosis. In this series, late complications consisted of duodenal stenosis, upper digestive tract bleeding, and cholangitis, adverse effects that are not seen with neoadjuvant PDT treatment.…”

Section: Discussionsupporting

confidence: 86%

Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma

Wiedmann

Caca

Berr

et al. 2003

Cancer

162

105

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BACKGROUNDOnly 20–30% of patients with hilar cholangiocarcinomas (CC) are candidates for potentially curative resection. However, even after curative (R0) resection, these patients have a disease recurrence rate of up to 76%. The current prospective Phase II study investigated photodynamic therapy (PDT) as a neoadjuvant treatment for CC.METHODSSeven patients with advanced proximal bile duct carcinoma were evaluated. Patients were treated with PDT at the area of tumor infiltration and 2 cm beyond and underwent surgery after a median period of 6 weeks (range, 3–44 weeks).RESULTSOne patient had a Bismuth–Corlette Type II tumor, two patients had Type IIIa, one patient had Type IIIb, and three patients had Type IV. Cholestasis parameters after PDT decreased significantly. No relevant adverse events from PDT occurred except for minor intraoperative phototoxicity in one patient. Three patients underwent right‐sided liver resections, two patients underwent left‐sided liver resections, and one patient received a combined hilar resection with partial pancreatoduodenectomy (PD) due to tumor extension into the distal bile duct. Liver transplantation and PD were performed in another patient. In all patients, R0 resection was achieved. Four patients developed minor surgical complications, even though the bilioenteric anastomoses were sewn to PDT‐pretreated bile ducts. No viable tumor cells were found in the inner 4 mm layer of the surgical specimens. The PDT‐pretreated epithelium of the tumor‐free proximal resection margins exhibited only minimal inflammatory infiltration. Tumors recurred in 2 patients 6 and 19 months after surgery. The 1‐year recurrence free survival rate was 83%.CONCLUSIONSNeoadjuvant PDT for hilar CC is a low‐risk procedure with efficient selective destruction of the superficial 4 mm layer of bile duct tumor without complications exceeding series without neoadjuvant PDT. Neoadjuvant PDT should be evaluated prospectively to determine whether it reduces the rate of local disease recurrence after potentially curative resection. Cancer 2003;97:2783–90. © 2003 American Cancer Society.DOI 10.1002/cncr.11401

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Section: Discussionsupporting

confidence: 86%

Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma

Wiedmann

Caca

Berr

et al. 2003

Cancer

162

105

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“…Chemoradiation therapy is often used for unresectable, locally advanced tumors or for local/regional recurrences, and may provide some measure of disease control, although a clear survival benefit has not been demonstrated. [3][4][5] A major limitation of such treatment, particularly radiation therapy, is toxicity. If mortality related to cholangiocarcinoma is to be reduced beyond its current high level, more effective therapies must be developed.…”

Section: Discussionmentioning

confidence: 99%

“…Radiation therapy is often used in patients with locally advanced disease and may offer some benefit but can be associated with significant toxicity. [3][4][5] Clearly, for the majority of patients with unresectable tumors, more effective treatment strategies are necessary if morbidity and mortality related to cholangiocarcinoma are to be reduced.…”

Section: Introductionmentioning

confidence: 99%

Treatment of cholangiocarcinoma with oncolytic herpes simplex virus combined with external beam radiation therapy

et al. 2005

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Replication-competent oncolytic herpes simplex viruses (HSV), modified by deletion of certain viral growth genes, can selectively target malignant cells. The viral growth gene g 1 34.5 has significant homology to GADD34 (growth arrest and DNA damage protein 34), which promotes cell cycle arrest and DNA repair in response to stressors such as radiation (XRT). By upregulating GADD34, XRT may result in greater oncolytic activity of HSV strains deficient in the g 1 34.5 gene. The human cholangiocarcinoma cell lines KMBC, SK-ChA-1 and YoMi were treated with NV1023, an oncolytic HSV lacking one copy of g 1 34.5. Viral proliferation assays were performed at a multiplicity of infection (MOI, number of viral particles per tumor cell) equal to 1, either alone or after XRT at 250 or 500 cGy. Viral replication was assessed by plaque assay. In vitro cytotoxicity assays were performed using virus at MOIs of 0.01 and 0.1, with or without XRT at 250 cGy and cell survival determined with lactate dehydrogenase assay. Established flank tumors in athymic mice were treated with a single intratumoral injection of virus (10 3 or 10 4 plaque forming units), either alone or after a single dose of XRT at 500 cGy, and tumor volumes measured. RT-PCR was used to measure GADD34 mRNA levels in all cell lines after a single dose of XRT at 250 or 500 cGy. NV1023 was tumoricidal in all three cell lines, but sensitivity to the virus varied.XRT enhanced viral replication in vitro in all cell lines. Combination treatment with low-dose XRT and virus was highly tumoricidal, both in vitro and in vivo. The greatest tumor volume reduction with combination therapy was seen with YoMi cells, the only cell line with increased GADD34 expression after XRT and the only cell line in which a synergistic treatment effect was suggested. In KMBC and SK-ChA-1 cells, neither of which showed increased GADD34 expression after XRT, tumor volume reduction was less pronounced and there was no suggestion of a synergistic effect in either case. Oncolytic HSV are effective in treating human cholangiocarcinoma cell lines, although sensitivity to virus varies. XRT-enhanced viral replication occurs through a mechanism that is not necessarily dependent on GADD34 upregulation. However, XRT-induced upregulation of GADD34 further promotes tumoricidal activity in viral strains deficient in the g 1 34.5 gene, resulting in treatment synergy; this effect is cell type dependent. Combined XRT and oncolytic viral therapy is a potentially important treatment strategy that may enhance the therapeutic ratios of both individual therapies.

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“…Biliary reconstruction was accomplished in all patients by Roux-en-Y hepatico-jejunostomy either to: one duct (n=17); two ducts (n=6); three ducts or more (n=5) (10,(30)(31)(32)34). Of these 24, 22 (92%) received either radiotherapy (n=6), chemotherapy (n=I), or both (n=15) (35,36).…”

Section: Surgical Proceduresmentioning

confidence: 99%

Liver Resection for Hilar and Peripheral Cholangiocarcinomas: A Study of 62 Cases

Madariaga¹,

Iwatsuki²,

Todo³

et al. 1998

Annals of Surgery

239

144

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MINI ABSTRACTWe present our 14-year experience of liver resection for hilar and peripheral cholangiocarcinomas with an analysis of the clinical and pathologic prognostic factors, overall survival and disease-free survival. ResultsThe survival rates for HCCA and PCCA at one-year were 79% (± 8%) and 67% (± 8%); at three years, 39<'10 (± 10%) and 40% (± 9%); and at five years, 8% (± 7%) and 35% (± 10%), respectively. The disease-free survival rates for HCCA and PCCA were 85% (±1O%) and 77% (±9<'Io) at 1 year; 18% (±11%) and 41% (± 12%) at 3 years; and 18% (±11 %) and 41 % (±12%) at 5 years, respectively. With HCCA, no risk factors were associated with patient survival. For PCCA, multiple tumors (RR=3.5; 95% confidence interval=1.2 to 10.5) and incomplete resection (RR=8.3; 95% confidence interval=2.3 to 29.6) were independently associated with a worse prognosis. For HCCA, there was a trend for lower disease-free survival in female patients (p=O.056; logrank test). For PCCA, tumor size greater than 5 cm was the only factor associated with disease-recurrence (p=0.024; logrank) . Postoperative morbidity and mortality (30 day) were 32% and 14%, respectively for HCCA, and 24% and 3 6% forPCCA. ConclusionsEven though rare, five year survival by resection can be achieved in both HCCA and PCCA; but new adjuvant treatments are clearly needed. ABSTRACTBackground. Long term survival achieved after surgical treatment of hilar

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Results of Radiation Therapy in Carcinoma of the Proximal Bile Duct (Klatskin Tumor)

Cited by 95 publications

References 0 publications

Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma

Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma

Treatment of cholangiocarcinoma with oncolytic herpes simplex virus combined with external beam radiation therapy

Liver Resection for Hilar and Peripheral Cholangiocarcinomas: A Study of 62 Cases

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