Currently, no practical definition of potentially resectable, borderline or unresectable perihilar cholangiocarcinoma (pCCA) is available. Aim of this study was to define criteria to categorize patients for use in a future neoadjuvant or induction therapy study.

Using the modified DELPHI method, hepatobiliary surgeons from all tertiary referral centers in the Netherlands were invited to participate in this study. During five online meetings, predefined factors determining resectability and additional factors regarding surgical resectability and operability were discussed.

The five online meetings resulted in 52 statements. After two surveys, consensus was reached in 63% of the questions. The main consensus included a definition regarding potential resectability. 1) Clearly resectable: no vascular involvement (≤90°) of the future liver remnant (FLR) and expected feasibility of radical biliary resection. 2) Clearly unresectable: non-reconstructable venous and/or arterial involvement of the FLR or no feasible radical biliary resection. 3) Borderline resectable: all patients between clearly resectable and clearly unresectable disease.

This DELPHI study resulted in a practical and applicable resectability, or more accurate, an explorability classification, which can be used to categorize patients for use in future neoadjuvant therapy studies.

Perihilar cholangiocarcinoma (pCCA) is a rare malignancy requiring resection of extrahepatic bile ducts with or without hepatectomy. Prognostic models for post-operative outcomes in pCCA are unusable in pre-operative decision-making as most are based on post-operative variables. Additionally, no pre-operative models include futile laparotomy or benign hilar stenosis (BHS) as possible outcomes. We investigated pre-operative predictive factors for non-resectability, disease-free survival (DFS), and overall survival (OS), in patients referred for resection of suspected pCCA.

Patients with suspected pCCA evaluated at multidisciplinary team (MDT) conference and referred for curative resection at Rigshospitalet, from 2013-2023. Outcomes were preoperative factors related to OS, DFS and non-resectability.

Ninety-three patients with suspected pCCA were considered resectable at MDT, of which 84 (90.3 %) were confirmed pCCA. Nineteen (20.4 %) with pCCA were non-resectable. Patients with non-resectable pCCA had higher pre-operative p-bilirubin and ECOG-performance status (ECOG-PS) compared to resected pCCA and BHS (p=0.02 and 0.01). Portal vein embolization (PVE), higher ECOG-PS and elevated p-bilirubin were associated with worse OS in patients with pCCA undergoing surgical exploration [(HR 2.45 (95% CI 1.32-4.56), p=0.004), (HR 2.32 (95% CI 1.30-4.09), p=0.004) and (HR 2.03 (95% CI 1.17-3.51), p=0.01), respectively]. PVE and larger tumor size were associated with poorer DFS [HR 3.29 (95 % CI 1.64- 6.60), p=0.001) and (HR 1.02 (95% CI 1.00-1.04), p=0.003) respectively].

Poor ECOG-PS, PVE, elevated p-bilirubin and larger tumor size were associated with adverse survival in patients with pCCA undergoing surgical exploration. Non-resectable pCCA were associated with higher rates of elevated p-bilirubin and larger tumor size.

Resection of perihilar cholangiocarcinoma (pCCA) is associated with positive margins in up to half of the patients. It remains unclear whether adjuvant therapies contribute to improved survival in patients undergoing R1 resection for pCCA.

The National Cancer Database was queried for patients diagnosed with pCCA between 2004 and 2016. Patients with metastatic disease at the time of diagnosis were excluded.

A total of 1756 patients were included (286 surgical patients and 1470 nonsurgical patients). Patients who underwent R0 resection showed a significantly better median overall survival (OS) than that of patients who underwent R1 resection (41.7 vs 21.4 months, respectively; P = .003). Nevertheless, OS was better in patients who underwent R1 resection than in nonsurgical patients (21.4 vs 6.3 months, respectively; P < .001). Patients undergoing chemoradiation after R1 resection had similar OS to that of those receiving any other adjuvant therapy (21.4 vs 19.4 months, respectively; P = .789) or no adjuvant treatment (21.4 vs 19.8 months, respectively; P = .925). After uni- and multivariable analyses, T stage ≥3 and R1 margins were independently associated with worse survival after surgery.

As currently neither radiation, chemoradiation, nor chemotherapy seem to significantly improve survival in patients who underwent R1 resection for pCCA, high-quality surgical resection remains critically important. Moreover, the concern of overtreatment of patients who underwent R1 resection with current adjuvant therapeutic regimes exists.

Perihilar cholangiocarcinoma is a rare hepatobiliary malignancy that requires thoughtful, multidisciplinary evaluation in the preoperative setting to ensure optimal patient outcomes. Comprehensive preoperative imaging, including multiphase CT angiography and some form of cholangiographic assessment, is key to assessing resectability. While many staging systems exist, the Blumgart staging system provides the most useful combination of resectability assessment and prognostic information for use in the preoperative setting. Once resectability is confirmed, volumetric analysis should be performed. Upfront resection without biliary drainage or portal venous embolization may be considered in patients without cholangitis and an estimated functional liver remnant (FLR) > 40%. In patients with FLR < 40%, judicious use of biliary drainage is advised, with the goal of selective biliary drainage of the functional liver remnant. Percutaneous biliary drainage may avoid inadvertent contamination of the contralateral biliary tree and associated infectious complications, though the relative effectiveness of percutaneous and endoscopic techniques is an ongoing area of study and debate. Patients with low FLR also require intervention to induce hypertrophy, most commonly portal venous embolization, in an effort to reduce the rate of postoperative liver failure. Even with extensive preoperative workup, many patients will be found to have metastatic disease at exploration and diagnostic laparoscopy may reduce the rate of non-therapeutic laparotomy. Management of perihilar cholangiocarcinoma continues to evolve, with ongoing efforts to improve preoperative liver hypertrophy and to further define the role of transplantation in disease management.

In approximately 40% of patients with perihilar cholangiocarcinoma (PHC), the tumor is deemed unresectable at laparotomy, often due to vascular involvement. On imaging, occlusion, narrowing, wall irregularity and >180° tumor-vessel contact have been suggested to predict vascular involvement in patients with PHC. The objective of this study was to correlate computed tomography (CT) findings in PHC with surgical and histopathological results, in order to evaluate the accuracy of currently used CT criteria for vascular involvement.

Patients with PHC undergoing exploration in a single tertiary center (2015-2018) were included. Tumor-vessel relation of portal vein and hepatic artery on CT were scored by two independent radiologists, blinded for surgical and pathological outcomes. Intraoperative findings were scored by the surgeon in theatre or derived from operation/pathology reports.

A total of 42 CT scans were evaluated, resulting in assessment of 115 vessels. Portal vein occlusion, narrowing and presence of an irregular wall on CT corresponded with a positive predictive value (PPV) for involvement of 100%, 83% and 75%, respectively. For the hepatic artery, PPV of occlusion and stenosis was 100%, whilst other criteria had PPV <70%. Combining potential criteria (>180° contact, narrowing, irregularity or occlusion) resulted in PPV, sensitivity and specificity of 85%, 67% and 94%, respectively, for the portal vein and 53%, 40% and 75%, respectively, for the hepatic artery.

Prediction of vascular involvement on CT is more difficult for the hepatic artery than for the portal vein. Suggestion of hepatic artery invasion on imaging, other than occlusion or stenosis, should not preclude surgical exploration.

Resection for perihilar cholangiocarcinoma (pCCA) in primary sclerosing cholangitis (PSC) has been reported to lead to worse outcomes than resection for non-PSC pCCA. The aim of this study was to compare prognostic factors and outcomes after resection in patients with PSC-associated pCCA and non-PSC pCCA.

The international retrospective cohort comprised patients resected for pCCA from 21 centres (2000-2020). Patients operated with hepatobiliary resection, with pCCA verified by histology and with data on PSC status, were included. The primary outcome was overall survival. Secondary outcomes were disease-free survival and postoperative complications.

Of 1128 pCCA patients, 34 (3.0%) had underlying PSC. Median overall survival after resection was 33 months for PSC patients and 29 months for non-PSC patients (p = .630). Complications (Clavien-Dindo grade ≥ 3) were more frequent in PSC pCCA (71% versus 44%, p = .003). The rate of posthepatectomy liver failure (21% versus 17%, p = .530) and 90-day mortality (12% versus 13%, p = 1.000) was similar for PSC and non-PSC patients.

Median overall survival after resection for pCCA was similar in patients with underlying PSC and non-PSC patients. Complications were more frequent after resection for PSC-associated pCCA, with no difference in postoperative mortality.

Clinical tumor staging is essential information for making a therapeutic decision in cancer. This study aimed to identify the optimal tumor classification system for predicting resectability and survival probability in perihilar cholangiocarcinoma.

Patients who were treated for perihilar cholangiocarcinoma between 2009 and 2018 were enrolled. Local tumor extension was staged radiologically according to a diameter-based classification system in addition to the AJCC, Blumgart, and Bismuth systems. Survival and resectability were compared between T subgroups, and the discriminability of the four systems was assessed with Harrell's concordance index (C-index).

Among 702 study patients, 559 (80.0%) underwent laparotomy, 489 (70.0%) of whom underwent resection. The resectability significantly decreased for more advanced tumors in all systems (P < .001); the AJCC system had the greatest discriminability for resectability (area under the curve 0.721). Overall survival at 5 years was 69.9% for AJCC cT1, 45.8% for cT2, 31.8% for cT3, and 15.3% for cT4 tumors (cT1 vs cT2; P = .002, cT2 vs cT3; P = .008 and cT3 vs cT4; P < .001). The AJCC system had the largest C-index of 0.627.

The AJCC T system was the optimal classification system for predicting resectability and survival in perihilar cholangiocarcinoma.

The Blumgart system has been used for local tumor assessment in perihilar cholangiocarcinoma to predict resectability and survival, and T3 tumors are considered unresectable disease. The aim was to validate the predictive performance of this system using a Japanese cohort.

Medical records of consecutive patients with perihilar cholangiocarcinoma between 2006 and 2016 were retrospectively reviewed. Resectability, surgical procedure, R0 resection rate, and survival were compared among T stages.

Among 729 study patients, 191 patients had T1 tumors, 94 patients had T2 tumors, and 444 (60.9%) patients had T3 tumors according to the Blumgart T stage. Resection was performed in 513 (70.4%) patients; resectability rate decreased with the progression of T stage: 89.0% in T1, 79.8% in T2, and 60.4% in T3 tumors (P < 0.001). The incidences of left hepatic trisectionectomy and portal vein resection were 44.0% and 54.1%, respectively, in patients with T3 tumors, which were significantly greater than those of T1/2 tumors (P = 0.001 and P < 0.001). R0 resection reduced with advanced T stage: 92.4% in T1, 81.3% in T2, and 70.9% in T3 tumors (P < 0.001). The 5-year survival rate was 53.4%, 38.4%, and 19.7% in T1, T2, and T3 tumors, respectively (P < 0.001); that was 59.6%, 48.6%, and 30.7%, respectively, in the resected cohort (P < 0.001).

Blumgart T stage was closely associated with the resectability rate, surgical procedures, R0 resection rate, and survival time, suggesting that the T stage works as well as a presurgical staging system. However, the unresectable classification of T3 tumors should be revised.