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Cancers
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Surgical Treatment of Cholangiocarcinoma
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Surgical Treatment of Cholangiocarcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 March 2022) | Viewed by 25896

Special Issue Editor

Prof. Dr. Matteo Ravaioli

E-Mail Website
Guest Editor
Department of Organ Insufficiency and Transplantation, General Surgery and Transplantation, University Hospital of Bologna, Policlinico S. Orsola-Malpighi, 40138 Bologna, Italy
Interests: organ transplantation; liver cancer; liver surgery; HPB cancer; HPB surgery; liver and kidney transplantation

Special Issue Information

Dear Colleagues,

The surgical treatment of cholangiocarcinoma has been changing during the last years, due to the promising results of liver transplantation and the refinement of liver resection techniques. Neoadjuvant/adjuvant chemotherapy and radiotherapy treatments may further improve patient selection and outcomes.

The proposed Special Issue has the objective to present the possible different surgical strategies for this type of disease and the factors guiding their choice.

It will also focus on the management of those categories of patients considered not suitable for therapeutic treatments, who nowadays may be cured following transplant protocols.

Prof. Dr. Matteo Ravaioli
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cholangiocarcinoma
  • liver resection
  • liver transplantation

Published Papers (6 papers)

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Research

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14 pages, 1554 KiB  
Article
The Role of Immunosuppression for Recurrent Cholangiocellular Carcinoma after Liver Transplantation
by Safak Gül-Klein, Paulina Schmitz, Wenzel Schöning, Robert Öllinger, Georg Lurje, Sven Jonas, Deniz Uluk, Uwe Pelzer, Frank Tacke, Moritz Schmelzle, Johann Pratschke, Ramin Raul Ossami Saidy and Dennis Eurich
Cancers 2022, 14(12), 2890; https://doi.org/10.3390/cancers14122890 - 11 Jun 2022
Cited by 3 | Viewed by 1673
Abstract
Liver transplantation (LT) for cholangiocarcinoma (CCA), or biliary tract cancer (BTC), remains controversial regarding high recurrence rates and poor prognosis. Oncological follow-up may benefit from tumor-inhibiting properties of mTOR inhibitors (mTORI), shown with improved survival for recurrent hepatocellular carcinoma (HCC) patients after LT. [...] Read more.
Liver transplantation (LT) for cholangiocarcinoma (CCA), or biliary tract cancer (BTC), remains controversial regarding high recurrence rates and poor prognosis. Oncological follow-up may benefit from tumor-inhibiting properties of mTOR inhibitors (mTORI), shown with improved survival for recurrent hepatocellular carcinoma (HCC) patients after LT. The aim of this study was to investigate the recurrence and survival in relation to tumor type and type of immunosuppression (IS). LT patients with CCA or mixed HCC/CCA (mHCC/CCA) (n = 67) were retrospectively analyzed. Endpoints were the time from LT to recurrence (n = 44) and survival after recurrence. Statistically significant impairment in survival for recurrent CCA (rCCA) was shown in patients not eligible for surgical resection (HR 2.46 (CI: 1.2–5.1; p = 0.02). Histological proven grading >1 and N1 status at initial transplantation were associated with impaired survival (HR 0.13 (CI: 0.03–0.58); p < 0.01 and HR 3.4 (CI: 1.0–11.65); p = 0.05). Reduced IS after tumor recurrence improved survival (HR 4.2/CI: 1.3–13.6; p = 0.02). MTORI initiation before recurrence or after had no significant impact on survival. Our data thereby indicate, similar to findings in recurrent HCC after LT, that patients with rCCA after LT benefit from a reduction in IS upon recurrence. Full article
(This article belongs to the Special Issue Surgical Treatment of Cholangiocarcinoma)
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12 pages, 1225 KiB  
Article
Work-Up and Outcome of Hepatic Resection for Peri-Hilar Cholangiocarcinoma (PH-CCA) without Staging Laparoscopy
by Santhalingam Jegatheeswaran, Panagiotis Stathakis, Harry V. M. Spiers, Fawwaz Mohammed, Panagiotis Petras, Thomas Satyadas, Michael J. Parker, Angela Lamarca, Saurabh Jamdar, Aali J. Sheen and Ajith K. Siriwardena
Cancers 2022, 14(7), 1841; https://doi.org/10.3390/cancers14071841 - 06 Apr 2022
Viewed by 1686
Abstract
Background: This study reports the outcome of a work-up programme for resection of peri-hilar cholangiocarcinoma (PH-CCA) without the use of staging laparoscopy. Methods: This is a clinical case cohort series of patients undergoing surgical resection of PH-CCA without the use of staging laparoscopy [...] Read more.
Background: This study reports the outcome of a work-up programme for resection of peri-hilar cholangiocarcinoma (PH-CCA) without the use of staging laparoscopy. Methods: This is a clinical case cohort series of patients undergoing surgical resection of PH-CCA without the use of staging laparoscopy in the work-up algorithm. During the 13 years from 1 January 2009 to 1 January 2022, 32 patients underwent laparotomy for planned surgical resection of PH-CCA. Data were collected on demographic profile, admission biochemistry, radiology, pre-operative intervention, operation and outcome, together with post-operative complications and disease-free and overall survival. Results: All patients underwent pre-operative contrast-enhanced CT. Twenty-four (75%) underwent pre-operative MR. Twenty-three (72%) underwent pre-operative biliary drainage. Twenty-nine patients (91%) had either type III or IV peri-hilar cholangiocarcinoma. One patient (3%) in this series underwent a non-resectional laparotomy. Twenty-nine (91%) had a final histopathological diagnosis of PH-CCA. One further patient had a final diagnosis of an intraductal papillary neoplasm of the biliary tree (IPNB) with high-grade dysplasia but no invasive cancer. Eleven patients (36%) received chemotherapy after surgery. The median (95% CI) time to recurrence was 14 (7–31) months. The median survival was 25 (18-upper limit not reached) months. Conclusion: This cohort of 32 patients undergoing attempted resection for PH-CCA without the use of staging laparoscopy in the work-up algorithm indicates that with careful attention to patient fitness and cross-sectional and interventional radiologic/endoscopic imaging, a very low non-therapeutic laparotomy rate of 3% can be achieved and sustained. Full article
(This article belongs to the Special Issue Surgical Treatment of Cholangiocarcinoma)
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16 pages, 714 KiB  
Article
Impact of Body Mass Index on Tumor Recurrence in Patients Undergoing Liver Resection for Perihilar Cholangiocarcinoma (pCCA)
by Hans-Michael Hau, Mareen Devantier, Nora Jahn, Elisabeth Sucher, Sebastian Rademacher, Daniel Seehofer and Robert Sucher
Cancers 2021, 13(19), 4772; https://doi.org/10.3390/cancers13194772 - 24 Sep 2021
Cited by 2 | Viewed by 1475
Abstract
Background: The association of body mass index (BMI) and long-term prognosis and outcome of patients with perihilar cholangiocarcinoma (pCCA) has not been well defined. The aim of this study was to evaluate clinicopathologic and oncologic outcomes with pCCA undergoing resection, according to their [...] Read more.
Background: The association of body mass index (BMI) and long-term prognosis and outcome of patients with perihilar cholangiocarcinoma (pCCA) has not been well defined. The aim of this study was to evaluate clinicopathologic and oncologic outcomes with pCCA undergoing resection, according to their BMI. Methods: Patients undergoing liver resection in curative intention for pCCA at a tertiary German hepatobiliary (HPB) center were identified from a prospective database. Patients were classified as normal weight (BMI 18.5–24.9 kg/m2), overweight (BMI 25.0–29.9 kg/m2) and obese (>30 kg/m2) according to their BMI. Impact of clinical and histo-pathological characteristics on recurrence-free survival (RFS) were assessed using Cox proportional hazard regression analysis among patients of all BMI groups. Results: Among a total of 95 patients undergoing liver resection in curative intention for pCCA in the analytic cohort, 48 patients (50.5%) had normal weight, 33 (34.7%) were overweight and 14 patients (14.7%) were obese. After a median follow-up of 4.3 ± 2.9 years, recurrence was observed in totally 53 patients (56%). The cumulative recurrence probability was higher in obese and overweight patients than normal weight patients (5-year recurrence rate: obese: 82% versus overweight: 81% versus normal weight: 58% at 5 years; p = 0.02). Totally, 1-, 3-, 5- and 10-year recurrence-free survival rates were 68.5%, 44.6%, 28.9% and 13%, respectively. On multivariable analysis, increased BMI (HR 1.08, 95% CI: 1.01–1.16; p = 0.021), poor/moderate tumor differentiation (HR 2.49, 95% CI: 1.2–5.2; p = 0.014), positive lymph node status (HR 2.01, 95% CI: 1.11–3.65; p = 0.021), positive resection margins (HR 1.89, 95% CI:1.02–3.4; p = 0.019) and positive perineural invasion (HR 2.92, 95% CI: 1.02–8.3; p = 0.045) were independent prognostic risk factors for inferior RFS. Conclusion: Our study shows that a high BMI is significantly associated with an increased risk of recurrence after liver resection in curative intention for pCCA. This factor should be considered in future studies to better predict patient’s individual prognosis and outcome based on their BMI. Full article
(This article belongs to the Special Issue Surgical Treatment of Cholangiocarcinoma)
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Review

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19 pages, 1774 KiB  
Review
Vascular Involvements in Cholangiocarcinoma: Tips and Tricks
by Roberta Angelico, Bruno Sensi, Alessandro Parente, Leandro Siragusa, Carlo Gazia, Giuseppe Tisone and Tommaso Maria Manzia
Cancers 2021, 13(15), 3735; https://doi.org/10.3390/cancers13153735 - 25 Jul 2021
Cited by 6 | Viewed by 6215
Abstract
Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract. To date, surgical treatment remains the only hope for definitive cure of CCA patients. Involvement of major vascular structures was traditionally considered a contraindication for resection. Nowadays, selected cases of CCA with vascular [...] Read more.
Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract. To date, surgical treatment remains the only hope for definitive cure of CCA patients. Involvement of major vascular structures was traditionally considered a contraindication for resection. Nowadays, selected cases of CCA with vascular involvement can be successfully approached. Intrahepatic CCA often involves the major hepatic veins or the inferior vena cava and might necessitate complete vascular exclusion, in situ hypothermic perfusion, ex situ surgery and reconstruction with autologous, heterologous or synthetic grafts. Hilar CCA more frequently involves the portal vein and hepatic artery. Resection and reconstruction of the portal vein is now considered a relatively safe and beneficial technique, and it is accepted as a standard option either with direct anastomosis or jump grafts. However, hepatic artery resection remains controversial; despite accumulating positive reports, the procedure remains technically challenging with increased rates of morbidity. When arterial reconstruction is not possible, arterio-portal shunting may offer salvage, while sometimes an efficient collateral system could bypass the need for arterial reconstructions. Keys to achieve success are represented by accurate selection of patients in high-volume referral centres, adequate technical skills and eclectic knowledge of the various possibilities for vascular reconstruction. Full article
(This article belongs to the Special Issue Surgical Treatment of Cholangiocarcinoma)
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28 pages, 470 KiB  
Review
Current Surgical Management of Peri-Hilar and Intra-Hepatic Cholangiocarcinoma
by Andrea Lauterio, Riccardo De Carlis, Leonardo Centonze, Vincenzo Buscemi, Niccolò Incarbone, Ivan Vella and Luciano De Carlis
Cancers 2021, 13(15), 3657; https://doi.org/10.3390/cancers13153657 - 21 Jul 2021
Cited by 51 | Viewed by 5530
Abstract
Cholangiocarcinoma accounts for approximately 10% of all hepatobiliary tumors and represents 3% of all new-diagnosed malignancies worldwide. Intrahepatic cholangiocarcinoma (i-CCA) accounts for 10% of all cases, perihilar (h-CCA) cholangiocarcinoma represents two-thirds of the cases, while distal cholangiocarcinoma accounts for the remaining quarter. Originally [...] Read more.
Cholangiocarcinoma accounts for approximately 10% of all hepatobiliary tumors and represents 3% of all new-diagnosed malignancies worldwide. Intrahepatic cholangiocarcinoma (i-CCA) accounts for 10% of all cases, perihilar (h-CCA) cholangiocarcinoma represents two-thirds of the cases, while distal cholangiocarcinoma accounts for the remaining quarter. Originally described by Klatskin in 1965, h-CCA represents one of the most challenging tumors for hepatobiliary surgeons, mainly because of the anatomical vascular relationships of the biliary confluence at the hepatic hilum. Surgery is the only curative option, with the goal of a radical, margin-negative (R0) tumor resection. Continuous efforts have been made by hepatobiliary surgeons in order to achieve R0 resections, leading to the progressive development of aggressive approaches that include extended hepatectomies, associating liver partition, and portal vein ligation for staged hepatectomy, pre-operative portal vein embolization, and vascular resections. i-CCA is an aggressive biliary cancer that arises from the biliary epithelium proximal to the second-degree bile ducts. The incidence of i-CCA is dramatically increasing worldwide, and surgical resection is the only potentially curative therapy. An aggressive surgical approach, including extended liver resection and vascular reconstruction, and a greater application of systemic therapy and locoregional treatments could lead to an increase in the resection rate and the overall survival in selected i-CCA patients. Improvements achieved over the last two decades and the encouraging results recently reported have led to liver transplantation now being considered an appropriate indication for CCA patients. Full article
(This article belongs to the Special Issue Surgical Treatment of Cholangiocarcinoma)
13 pages, 632 KiB  
Review
PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer
by Alessandro Rizzo, Angela Dalia Ricci and Giovanni Brandi
Cancers 2021, 13(3), 558; https://doi.org/10.3390/cancers13030558 - 01 Feb 2021
Cited by 147 | Viewed by 8278
Abstract
Biliary tract cancer (BTC) represents the second most frequently diagnosed primary liver cancer worldwide following hepatocellular carcinoma, and the overall survival of patients with unresectable disease remains poor. In recent years, the advent of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic landscape [...] Read more.
Biliary tract cancer (BTC) represents the second most frequently diagnosed primary liver cancer worldwide following hepatocellular carcinoma, and the overall survival of patients with unresectable disease remains poor. In recent years, the advent of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic landscape of several malignancies with these agents, which have also been explored in advanced BTC, as monotherapy or in combination with other anticancer agents. However, clinical trials evaluating ICIs in BTC have shown conflicting results, and the clinical benefit provided by immunotherapy seems limited to a small subgroup of BTC patients. Thus, the identification of reliable predictors of the response to immunotherapy represents a significant challenge in this setting. This review provides an overview of the available evidence on the biomarkers predictive of the response to ICIs in patients with advanced BTC, especially focusing on programmed death-ligand 1 (PD-L1), tumor mutational burden (TMB), microsatellite instability (MSI), and other emerging biomarkers. Full article
(This article belongs to the Special Issue Surgical Treatment of Cholangiocarcinoma)
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