Non-surgical treatment of hilar cholangiocarcinoma

Inchingolo, Riccardo; Acquafredda, Fabrizio; Ferraro, Valentina; Laera, Letizia; Surico, Giammarco; Surgo, A.; Fiorentino, Alba; Marini, Stefania; de’Angelis, Nicola; Méméo, Riccardo; Spiliοpoulos, Stavros

doi:10.4251/wjgo.v13.i11.1696

Cited by 14 publications

(7 citation statements)

References 64 publications

(71 reference statements)

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“…Проведение лучевой терапии после холангиодренирования ограничено критерием отбора пациентов. Для системной химиотерапии используют следующие схемы: GemCis (сочетание гемцитабина и цисплатина с наб-пак литак селом) или S1 (тегафур+гимерацил+оте рацил), FOLFIRINOX (5-фторурацил+лейковорин+окса липла тин+иринотекан), однако доказана эффективность только первой линии [2]. Причина исключения больных опухолью Клацкина из протокола специфического лечения связана с некупируемой желтухой, рецидивирующим холангитом, тяжестью общего самочувствия пациентов .…”

Section: Discussionunclassified

Intraductal photodynamic therapy and its combination with intra-arterial chemoinfusion in the treatment of inoperable patients with Klatskin tumor

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Таразов

et al. 2023

Journal of Clinical Practice

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Background: A palliative or symptomatic treatment is indicated for 7080% of patients with Klatskins tumor because of the advanced lesion volume and the patients grave condition. Hepatic arterial infusion chemotherapy, chemoembolization, radioembolization are successfully used in the treatment of hepatocellular carcinoma and liver metastases. Aim: to estimate the immediate and long-term results of photodynamic therapy (PDT) and its combination with hepatic arterial infusion in inoperable patients with Klatskin tumors. Methods: Between 2010 and 2021, 83 palliative PDT sessions (from 1 to 8, average 2.4) were performed in 82 patients as a single treatment or in combination with hepatic arterial infusion. In all cases, percutaneous transhepatic biliary drainage was previously performed; no chemotherapy was applied. Two groups of 48 patients were stratified according to the ECOG status (23) and the numbers of PDT sessions (no more than two). The treatment group of the combination therapy consisted of 24 patients (13 male, 11 female) aged 38 to 85 (mean 63) years with the ECOG status of 24 (mean 2.4). This group received PDT with hepatic arterial infusion using a GemCis regimen. On average, 1.4 PDT sessions were performed, the treatment started on the 89th (27225) day after the biliary drainage. The hepatic arterial infusion was performed on the 2d3th day after the PDT. The control group received only PDT and consisted of 24 patients (13 male, 11 female) aged 51 to 83 (66 on average) years, with the ECOG status of 23 (mean 2.6). On average, 1.4 PDT sessions were performed, starting on the 106th (32405) day after the biliary drainage. Results: There were no serious adverse events associated with PDT in both groups. Toxic complications of hepatic arterial infusion were observed in 13 of 24 patients (54%): III grade hematological (54%) and gastrointestinal (69%); all were eliminated with medical therapy. Complications of the percutaneous transhepatic biliary drainage in three patients (hemobilia, n=2, and sepsis, n=1) were estimated as grade III by the CIRSE classification (2017) and successfully treated without surgery. In the combination treatment group, the overall mean survival and median survival were higher than those in the control group: 327.939.8 days (10.9 mo) versus 246.931.2 days (8.2 mo) and 275 days versus 244 days. However, these differences did not reach the statistical significance (p=0.12). Conclusions: PDT is a safe method of a palliative treatment of critically ill patients with Klatskin tumor (ECOG 23). PDT alone has limited clinical efficacy. A combination of PDT and hepatic arterial infusion does not cause serious complications and may increase the survival rates.

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Section: Discussionunclassified

Intraductal photodynamic therapy and its combination with intra-arterial chemoinfusion in the treatment of inoperable patients with Klatskin tumor

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Поликарпов

Таразов

et al. 2023

Journal of Clinical Practice

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“…Таким образом, число пациентов, подходящих для специфического лечения, крайне мало. Именно поэтому вторая линия химиотерапии опухоли Клацкина в настоящее время не определена [8].…”

Section: Discussionunclassified

“…Таким образом, регионарную химиотерапию можно рассматривать в качестве потенцирующего метода при комбинированном лечении больных опухолью Клацкина [8,[17][18][19]. Author contribution.…”

Section: Discussionunclassified

Intra-arterial chemotherapy in the treatment of inoperable patients with Klatskin tumor: preliminary results

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et al. 2022

Journal of Clinical Practice

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Aim. To evaluate the safety and efficacy of hepatic arterial infusion (HAI) in patients with Klatskin tumor. Materials and methods. Between 2010-2021, 14 of 119 patients with inoperable Klatskin tumor were treated with HAI of GEMICS. All patients had obstructive jaundice and received percutaneous transhepatic biliary drainage (PTBD). Chemotherapy was started when serum bilirubin level became normal (average on the 106th day from PTBD). In total, 19 (from 1 to 4 per patient) HAI cycles were performed. Results. PTBD complications such as cholangitis (n=2) and local peritonitis (n=1) developed in 3 patients (21%) and were successfully treated using minimally invasive techniques. Toxicity of chemotherapy were observed in 8 of 14 patients (57%): I-II degree hematological (43%) and gastrointestinal (50%); all were cured by medical therapy. The overall mean survival was 286 days (9.6 months), median survival 283 days (9.4 months). Conclusions. Our preliminary results showed that HAI in patients with Klatskin tumor is safe, but has limited effectiveness. The combination of arterial infusion with other methods such as radiotherapy, intra-ductal photodynamic therapy, radiofrequency ablation, target therapy, should be investigated.

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“…At present, treatment of unresectable CCA remains challenging for clinicians because response to conventional chemotherapeutic agents is poor. 4 Moreover, dysregulation of intracellular signaling networks in CCA cells leads to an aggressive metastatic feature which significantly affects the prognosis of the disease. 5 Previous studies have shown that metastasis contributed to the failure of cancer treatment and was a significant clinical predictor of mortality among CCA patients.…”

Section: Introductionmentioning

confidence: 99%

Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein

et al. 2022

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Owing to the crucial role of Src in cancer metastasis, interruption of Src and its signaling has been considered a promising strategy for cancer metastasis treatment. Cucurbitacin B, a dietary triterpenoid, has been shown to possess anti-proliferative and apoptosis-inducing activities in cholangiocarcinoma (CCA) cells via suppressing the activation of FAK which is a main downstream Src effector. We hypothesized that cucurbitacin B might act as a Src suppressant which conferring anti-metastasis effect against CCA cells. To investigate this, the role of Src in regulating metastasis behavior of CCA cells and the effect of cucurbitacin B on Src-mediated metastatic phenotype of these cells were determined. The results showed that activation of Src significantly enhanced the migratory and invasive abilities of CCA cells. Molecular analysis revealed that Src-facilitated metastasis behavior of CCA cells occurred by modifying expression of a wide range of metastasis-related genes in the cells. Consistent with gene expression results, activation of Src significantly induced the protein expression of 2 important metastasis-associated molecules, MMP-9 and VEGF. Cucurbitacin B markedly suppressed activation of Src and its key effector, FAK. As a consequence, the alteration of expression profiles of metastasis-associated genes induced by Src activator in CCA cells was diminished by cucurbitacin B treatment. The compound also down-regulated Src-induced expression of MMP-9 and VEGF proteins in the cells. Moreover, molecular docking analysis revealed that cucurbitacin B could interact with Src kinase domain and possibly restrain the kinase from being activated by hindering the ATP binding. In conclusion, cucurbitacin B exhibited anti-metastatic property in CCA cells via negatively influencing Src and Src-related oncogenic signaling. This compound may therefore be a potential therapeutic drug for further development as an anti-Src agent for treatment of metastatic CCA.

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Non-surgical treatment of hilar cholangiocarcinoma

Cited by 14 publications

References 64 publications

Intraductal photodynamic therapy and its combination with intra-arterial chemoinfusion in the treatment of inoperable patients with Klatskin tumor

Intraductal photodynamic therapy and its combination with intra-arterial chemoinfusion in the treatment of inoperable patients with Klatskin tumor

Intra-arterial chemotherapy in the treatment of inoperable patients with Klatskin tumor: preliminary results

Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein

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