Part 2: 5 Advanced-Level MCQs

MCQ 1

Question

A 70-year-old patient with a known primary sclerosing cholangitis (PSC) presents with a 2.5 cm hilar cholangiocarcinoma involving the left hepatic duct. Imaging shows no evidence of extrahepatic or intrahepatic metastatic disease, but there is left lobar atrophy and contralateral portal vein encasement. Which of the following best describes the most appropriate next step in management to potentially achieve curative treatment?

Answer Choices

A. Left hepatectomy without portal reconstruction

B. Preoperative biliary drainage and an extended right hepatectomy

C. Neoadjuvant chemoradiation protocol followed by orthotopic liver transplantation

D. Immediate surgical exploration and segmental excision of the bile duct alone

Correct Answer: C. Neoadjuvant chemoradiation protocol followed by orthotopic liver transplantation

Explanation

Why C is correct: In patients with PSC and unresectable or advanced hilar cholangiocarcinoma—especially those with vascular involvement and associated lobar atrophy—liver transplantation following neoadjuvant chemoradiation (the so-called “Mayo protocol”) can offer a curative approach. This protocol selects patients with tumor size ≤3 cm, no evidence of metastatic disease, and tumor limited to the hilum.
Why A, B, D are incorrect:
- (A) Simple left hepatectomy is inadequate if there is contralateral portal encasement, as negative margins are unlikely.
- (B) The presence of left lobar atrophy and contralateral portal involvement generally indicates non-resectability via standard hepatectomy.
- (D) Segmental excision alone is typically insufficient for advanced hilar lesions with vascular involvement.

Key Takeaways (4–5 sentences)

For certain subsets of hilar cholangiocarcinoma, particularly those with underlying PSC or marginally resectable disease, combining neoadjuvant chemoradiation with orthotopic liver transplantation is increasingly recognized as a viable curative strategy. Stringent selection criteria are essential to achieve optimal outcomes. Straight surgical approaches (e.g., partial hepatectomy plus bile duct excision) may be unfeasible when there is complex lobar atrophy and vascular encasement. Close multidisciplinary evaluation is crucial in deciding between resection or transplantation protocols.

Reference

Shackleford’s Surgery of the Alimentary Tract, 8th edition,

Chapter 112: “Biliary Tract Tumors,” Subtopic: “Surgery & Orthotopic Liver Transplant for Hilar Cholangiocarcinoma” (pp. 1327–1333)

MCQ 2

Question

A 62-year-old patient with cholangiocarcinoma underwent hepatic resection with lymphadenectomy. Postoperative pathology showed a single 6 cm lesion with microscopic vascular invasion, negative surgical margins, and no nodal metastases. Based on current understanding, which of the following best reflects the greatest negative predictor of long-term survival?

Answer Choices

A. Tumor size >5 cm

B. Presence of microscopic vascular invasion

C. Absence of nodal involvement

D. Negative resection margins

Correct Answer: B. Presence of microscopic vascular invasion

Explanation

Why B is correct: According to the excerpt, vascular invasion (even microscopic) is a critical predictor of poor outcome in cholangiocarcinoma. It indicates a higher risk of tumor spread and recurrence.
Why A, C, D are incorrect:
- (A) Tumor size above 5 cm is a concerning feature, but microscopic vascular invasion is generally considered more ominous.
- (C) Absence of nodal disease is actually favorable, not a negative predictor.
- (D) Negative margins (R0) is positive prognostically.

Key Takeaways (4–5 sentences)

Prognostic factors in cholangiocarcinoma include resection margin status, nodal involvement, tumor multiplicity, and vascular invasion. Even subclinical or microscopic vascular invasion can substantially worsen prognosis by fostering metastatic spread. An R0 resection and negative nodal status both improve survival chances. Tumor size also contributes, but it’s less impactful than vascular or nodal factors.

Reference

Shackleford’s Surgery of the Alimentary Tract, 8th edition,

Chapter 112: “Biliary Tract Tumors,” Subtopic: “Prognostic Factors & Survival Outcomes” (pp. 1327–1333)

MCQ 3

Question

You are reviewing a patient 3 months after R0 resection for distal cholangiocarcinoma. The pathology showed moderately differentiated adenocarcinoma with one positive lymph node (N1). There is no residual disease on imaging. Which of the following best reflects the current reasoning on adjuvant therapy for such patients?

Answer Choices

A. There is clear, Level I evidence against using any form of adjuvant therapy

B. Adjuvant gemcitabine-cisplatin combination is recommended based on improved overall survival in large randomized trials focusing solely on resected distal cholangiocarcinoma

C. Systemic chemotherapy or chemoradiotherapy is often offered in node-positive disease despite limited high-level evidence

D. Adjuvant chemotherapy should be avoided because cholangiocarcinoma is largely resistant to chemotherapeutic agents

Correct Answer: C. Systemic chemotherapy or chemoradiotherapy is often offered in node-positive disease despite limited high-level evidence

Explanation

Why C is correct: The excerpt indicates that robust, large-scale trials specifically for adjuvant therapy in resected cholangiocarcinoma are scarce. However, many guidelines and experts advocate for postoperative chemotherapy (or chemoradiation) in node-positive or margin-positive disease to improve locoregional control and potentially survival.
Why A, B, D are incorrect:
- (A) There is not definitive evidence against adjuvant therapy; in fact, many centers do offer it.
- (B) The ABC-02 trial and similar studies included cholangiocarcinoma but were mostly in the advanced or unresectable setting, not specifically resected distal tumors.
- (D) Cholangiocarcinoma can show partial response to certain chemotherapeutic regimens (e.g., gemcitabine-cisplatin), so it is not correct to say it should always be avoided.

Key Takeaways (4–5 sentences)

Adjuvant therapy for cholangiocarcinoma remains controversial, partly because large-scale, dedicated randomized trials are lacking. However, many clinicians recommend chemotherapy or combined chemoradiation in patients with node-positive or margin-positive disease. Extrapolation from advanced disease trials (e.g., ABC-02) and smaller retrospective series supports this approach. Optimal duration and regimen remain under active investigation.

Reference

Shackleford’s Surgery of the Alimentary Tract, 8th edition,

Chapter 112: “Biliary Tract Tumors,” Subtopic: “Adjuvant Therapy Considerations” (pp. 1327–1333)

MCQ 4

“All are true EXCEPT…” Question

Question

All of the following statements regarding the Mayo Clinic protocol (neoadjuvant chemoradiation followed by orthotopic liver transplantation) for hilar cholangiocarcinoma are TRUE, EXCEPT:

Answer Choices

A. It mandates no radiologic or laparoscopic evidence of metastatic disease

B. Tumor diameter must generally be ≤3 cm

C. Patients with underlying primary sclerosing cholangitis (PSC) tend to have worse outcomes

D. A staging laparotomy is required before proceeding to transplantation

Correct Answer: C. Patients with underlying primary sclerosing cholangitis (PSC) tend to have worse outcomes

Explanation

Why C is correct (the false statement): The Mayo Clinic experience actually showed better 5-year survival in patients with PSC (79%) compared to de novo cholangiocarcinoma (63%).
Why A, B, D are incorrect (all true):
- (A) Strict exclusion of metastatic disease is essential; any detected metastases or advanced nodal disease disqualify a patient from the protocol.
- (B) Tumor size >3 cm is typically an exclusion criterion because larger lesions have poorer transplant outcomes.
- (D) A staging laparotomy is used to rule out hidden metastatic disease prior to transplant.

Key Takeaways (4–5 sentences)

The Mayo Clinic’s neoadjuvant protocol plus transplantation has shown success in selected patients with hilar cholangiocarcinoma. Stringent criteria, including tumor size ≤3 cm and no extrahepatic spread, must be met. Interestingly, patients with PSC have better survival outcomes than those with de novo cholangiocarcinoma under this protocol. Staging surgery is essential to confirm the absence of disseminated disease.

Reference

Shackleford’s Surgery of the Alimentary Tract, 8th edition,

Chapter 112: “Biliary Tract Tumors,” Subtopic: “Orthotopic Liver Transplant in Cholangiocarcinoma” (pp. 1327–1333)

MCQ 5

Question

A 58-year-old patient with advanced intrahepatic cholangiocarcinoma is found to have an FGFR2 fusion mutation. Based on emerging targeted molecular therapies, which statement is MOST accurate regarding the use of targeted agents in cholangiocarcinoma?

Answer Choices

A. KRAS mutations predict an excellent response to targeted therapies

B. FGFR inhibitors have shown promising activity in tumors harboring FGFR fusions or aberrations

C. Molecular profiling is rarely helpful because standard chemotherapy universally outperforms targeted approaches

D. BRAF mutations are the most common genetic aberration in cholangiocarcinoma

Correct Answer: B. FGFR inhibitors have shown promising activity in tumors harboring FGFR fusions or aberrations

Explanation

Why B is correct: The excerpt highlights that FGFR aberrations can confer an indolent course and a distinct therapeutic vulnerability—patients with these specific mutations/fusions may respond to FGFR inhibitors.
Why A, C, D are incorrect:
- (A) KRAS mutations generally portend worse outcomes and reduced responsiveness to certain targeted therapies.
- (C) Molecular profiling can be quite helpful to identify actionable targets (e.g., FGFR, IDH1, etc.).
- (D) BRAF mutations are rare in cholangiocarcinoma—far less common than in, for example, melanoma or certain colorectal cancers.

Key Takeaways (4–5 sentences)

Molecular profiling in cholangiocarcinoma helps identify actionable targets that may respond to novel agents. FGFR fusions, in particular, have been associated with encouraging results using FGFR inhibitors. KRAS mutations, on the other hand, often imply a more aggressive course. Identifying such molecular signatures can help tailor therapy, especially in advanced or unresectable disease.

Reference

Shackleford’s Surgery of the Alimentary Tract, 8th edition,

Chapter 112: “Biliary Tract Tumors,” Subtopic: “Molecular Therapy & Targeted Approaches” (pp. 1327–1333)

Key Takeaways for the Entire Topic

Anatomical Subtypes and Impact: Cholangiocarcinoma subtypes (intrahepatic, hilar, distal) differ in presentation, management, and prognosis. Hilar tumors (Klatskin) are the most common.
Risk Factors: Known risk factors include primary sclerosing cholangitis, certain liver flukes (Opisthorchis viverrini), chronic biliary pathology, and cirrhosis.
Diagnostic Workup: Imaging with thin-section multiphasic CT is crucial for vascular assessment, while MRI/MRCP can better delineate biliary anatomy. CA 19-9 can be elevated but must be interpreted in the context of biliary obstruction.
Surgical Resection and Transplant: Surgical resection (often with partial hepatectomy) is the primary curative approach. Selected patients with hilar cholangiocarcinoma and strict inclusion criteria may benefit from neoadjuvant therapy plus liver transplantation.
Adjuvant and Emerging Therapies: Although high-level evidence is limited, many centers use chemotherapy or chemoradiotherapy in node-positive or margin-positive cases. Molecular profiling is increasingly important in advanced or unresectable disease to identify FGFR, IDH1, or other targetable mutations.