Genomic evolution and the impact of SLIT2 mutation in relapsed intrahepatic cholangiocarcinoma

275 Background: Major vascular (IVC or portal vein) resection for Intrahepatic Cholangiocarcinoma (ICC) has traditionally been considered a relative contraindication to resection. We sought to define perioperative outcomes and survival of ICC patients undergoing liver surgery with major vascular resection using a multi-institutional database. Methods: 1,087 ICC patients who underwent liver resection between 1990-2016 were identified from 13 participating institutions. Multivariable logistic and cox regressions were used to determine the impact of major vascular resection on perioperative outcomes and long-term overall survival. Results: Of 1,087 patients who underwent resection, 128(11.8%) also underwent major vascular resection [21(16.4%)IVC resections, 98(76.6%)PV resections, 9(7.0%)combined resections]. One hundred eighty-seven(17.2%) patients received neoadjuvant therapy. Most patients underwent a major hepatectomy involving ≥ 3 liver segments(n = 664,61.1%). On final pathology, the majority of patients had T1(40.4%) or T2(35.5%) tumors; 194(17.8%) had lymph node metastasis. Patients undergoing major vascular resection had more advanced T3/T4 tumors [44(34.4%) vs. 137(14.3%) without resection;P < 0.001]. Of note, major vascular resection was not associated with the risk of any complication (OR .680,95%CI 0.32-1.45) or major complication (OR 0.69,95%CI 0.35-1.33); post-operative mortality was also comparable between groups (OR 1.06, 95%CI 0.32-3.48). In addition, median recurrence-free (14.0 months vs.14.7 months, HR.737,95%CI .49-1.10) and overall (33.4 months vs.40.2 months, HR .709,95%CI.36-1.40) survival were similar among patients who did and did not undergo major vascular resection, respectively(both P > 0.05). Conclusions: Among patients with ICC, major vascular resection was not associated with increased peri-operative morbidity or mortality at major centers. Long-term outcomes following resection of ICC requiring vascular resection were also comparable to outcomes following resection of tumors without vascular involvement. Concurrent major vascular resection should be considered in appropriately selected ICC patients.

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The effect of socioeconomic factors on the outcome of intrahepatic cholangiocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.465 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 465-465

Author(s):

Cortlandt Sellers ◽

Johannes M Ludwig ◽

Johannes Uhlig ◽

Stacey Stein ◽

Jill Lacy ◽

...

Keyword(s):

Socioeconomic Factors ◽

Intrahepatic Cholangiocarcinoma ◽

Private Insurance ◽

Tertiary Care ◽

Locoregional Therapy ◽

Care Hospital ◽

Proportional Hazard ◽

Cox Proportional Hazard ◽

Kaplan Meier ◽

The Impact

465 Background: To investigate the impact of socioeconomic factors on overall survival (OS) for patients with intrahepatic cholangiocarcinoma (ICC) at an inner-city tertiary care hospital. Methods: Consecutive patients treated for ICC diagnosed between 2005 and 2016 in the cancer registry were studied. Patients were stratified by demographic, socioeconomic variables, and treatment course. Kaplan-Meier curves and Cox proportional hazard modeling were performed. Results: Patients were 52% male (95 pts) and 74% white (136 pts) with mean age of 65.7 yrs (SD 10.7 yrs). 82% of patients were married or had been previously married (148 pts). 11% of patients had Medicaid as their primary insurance (20 pts), 45% of patients had Medicare (78 pts) and 44% of patients had private insurance (77 pts). Patients with private insurance (66 pts, 87%) and Medicare (64 pts, 83%) were more likely to have been married than Medicaid (12 pts, 60%) (p = 0.036). Patients with Medicare (mean 72.0 yrs, SD 6.9 yrs) were older than private insurance patients (mean 60.3 yrs, SD 10.3 yrs) and Medicaid patients (mean 61.8 yrs, SD 12.4 yrs) (p < 0.001). Gender and ethnicity were similarly distributed by primary insurance. Median OS stratified by primary insurance demonstrated median OS in private insurance of 13.2 mo (95% CI: 8.2–18.7 mo) vs 7.3 mo (95% CI: 3.8–10.6 mo) for Medicare (HR 1.3, p = 0.11) vs 4.7 mo (95% CI: 1.7–11.3 mo) for Medicaid (HR 1.8, p = 0.0488), (p = 0.0465). Cancer-directed treatments were utilized by 81% in private insurance vs. 67% in Medicare vs 67% in Medicaid (p = 0.18). Median OS stratified by main treatment demonstrated 43.3 mo in resection (37 pts, 21%), 17.3 mo in locoregional therapy (LRT) (22 pts, 13%), 10.0 mo in chemotherapy or radiation (79 pts, 45%), and 1.4 mo in palliative or no treatment (37 pts, 21%) (p < 0.0001). Increased age was associated with decreased median OS (correlation -0.23, p = 0.0019). No differences in median OS were seen with ethnicity, gender, or marital status. Conclusions: Screening and early treatments appear to affect the OS of patients with ICC. Further investigations for preventive care for vulnerable populations to enhance survivals are warranted.

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Long-Term Survival of Recurrent Intrahepatic Cholangiocarcinoma: The Impact and Selection of Repeat Surgery

World Journal of Surgery ◽

10.1007/s00268-017-4387-7 ◽

2017 ◽

Vol 42 (6) ◽

pp. 1848-1856 ◽

Cited By ~ 15

Author(s):

Tomoaki Yoh ◽

Etsuro Hatano ◽

Satoru Seo ◽

Yukihiro Okuda ◽

Hiroaki Fuji ◽

...

Keyword(s):

Intrahepatic Cholangiocarcinoma ◽

Repeat Surgery ◽

Term Survival ◽

Long Term Survival ◽

The Impact ◽

Selection Of

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Multicentre study of the impact of morbidity on long-term survival following hepatectomy for intrahepatic cholangiocarcinoma

British Journal of Surgery ◽

10.1002/bjs.10780 ◽

2017 ◽

Vol 104 (13) ◽

pp. 1895-1895

Keyword(s):

Multicentre Study ◽

Intrahepatic Cholangiocarcinoma ◽

Term Survival ◽

Long Term Survival ◽

The Impact

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Prognostic Impact of Cirrhosis in Patients with Intrahepatic Cholangiocarcinoma following Hepatic Resection

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2017/6543423 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Seogsong Jeong ◽

Lei Gao ◽

Ying Tong ◽

Lei Xia ◽

Ning Xu ◽

...

Keyword(s):

Hepatic Resection ◽

Intrahepatic Cholangiocarcinoma ◽

Statistical Significance ◽

Prognostic Impact ◽

Relapse Free Survival ◽

Free Survival ◽

Future Studies ◽

B Virus ◽

Cirrhotic Patients ◽

The Impact

Background. Prognostic impact of cirrhosis in patients with intrahepatic cholangiocarcinoma (ICC) upon hepatic resection remains unclear due to lack of studies in the literature.Methods. A total of 106 resected patients with ICC were reviewed, including 25 patients (23.6%) with cirrhosis and 81 noncirrhotic patients (76.4%). Subgroups of cirrhotic patients with and without hepatitis B virus (HBV) infection were studied.Results. The impact of cirrhosis on the overall survival (OS) (hazard ratio [HR], 0.901; 95% confidence interval [CI], 0.510 to 1.592;P=0.720) and the relapse-free survival (RFS) (HR, 0.889; 95% CI, 0.509 to 1.552;P=0.678) revealed no statistical significance. Furthermore, HBV-associated cirrhotic patients and the other cirrhotic patients demonstrated no statistical difference on survival outcomes (1 yr OS, 60.0% versus 70.0%; 5 yr OS, 10.0% versus 0%;P=0.744; 1 yr RFS, 53.3% versus 30.0%; 5 yr RFS, 10.0% versus 0%;P=0.279). In patients with cirrhosis, tumor size larger than 5 cm was found to be the foremost factor that was independently associated with poor prognosis.Conclusion. The presence of liver cirrhosis did not significantly affect prognosis of patients with ICC after resection. Downstaging modality may be in need for patients with ICC underlying cirrhosis, which remains to be validated in future studies.

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Placental growth factor promotes tumour desmoplasia and treatment resistance in intrahepatic cholangiocarcinoma

Gut ◽

10.1136/gutjnl-2020-322493 ◽

2021 ◽

pp. gutjnl-2020-322493

Author(s):

Shuichi Aoki ◽

Koetsu Inoue ◽

Sebastian Klein ◽

Stefan Halvorsen ◽

Jiang Chen ◽

...

Keyword(s):

Growth Factor ◽

Intrahepatic Cholangiocarcinoma ◽

Treatment Resistance ◽

Blood Perfusion ◽

Placental Growth Factor ◽

Liver Malignancy ◽

Vascular Abnormalities ◽

Akt Phosphorylation ◽

The Impact

ObjectiveIntrahepatic cholangiocarcinoma (ICC)—a rare liver malignancy with limited therapeutic options—is characterised by aggressive progression, desmoplasia and vascular abnormalities. The aim of this study was to determine the role of placental growth factor (PlGF) in ICC progression.DesignWe evaluated the expression of PlGF in specimens from ICC patients and assessed the therapeutic effect of genetic or pharmacologic inhibition of PlGF in orthotopically grafted ICC mouse models. We evaluated the impact of PlGF stimulation or blockade in ICC cells and cancer-associated fibroblasts (CAFs) using in vitro 3-D coculture systems.ResultsPlGF levels were elevated in human ICC stromal cells and circulating blood plasma and were associated with disease progression. Single-cell RNA sequencing showed that the major impact of PlGF blockade in mice was enrichment of quiescent CAFs, characterised by high gene transcription levels related to the Akt pathway, glycolysis and hypoxia signalling. PlGF blockade suppressed Akt phosphorylation and myofibroblast activation in ICC-derived CAFs. PlGF blockade also reduced desmoplasia and tissue stiffness, which resulted in reopening of collapsed tumour vessels and improved blood perfusion, while reducing ICC cell invasion. Moreover, PlGF blockade enhanced the efficacy of standard chemotherapy in mice-bearing ICC.ConclusionPlGF blockade leads to a reduction in intratumorous hypoxia and metastatic dissemination, enhanced chemotherapy sensitivity and increased survival in mice-bearing aggressive ICC.

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The Clinical Value of Regional Lymphadenectomy for Intrahepatic Cholangiocarcinoma: Results of A Retrospective Cohort Study

10.21203/rs.3.rs-117740/v1 ◽

2020 ◽

Author(s):

Facai YANG ◽

Changkang WU ◽

Taian CHEN ◽

Anqi DUAN ◽

Jian XU ◽

...

Keyword(s):

Lymph Node ◽

Intrahepatic Cholangiocarcinoma ◽

Survival Rates ◽

Clinical Value ◽

Regional Lymphadenectomy ◽

Group A ◽

Hospital Stays ◽

Independent Risk Factors ◽

Group B ◽

The Impact

Abstract Objective: The aim of this study was to explore the clinical value of lymph node dissection (LND) for intrahepatic cholangiocarcinoma (ICC). Methods: Clinical and pathological data were collected from 147 ICC patients who attended two tertiary centers over the past 5 years. The patients were classified into two groups: the LND group (group A) and the no-performance LND (NLND) group (group B). Clinical and pathological parameters were compared between the two groups to analyze the impact of LND on the prognosis of ICC patients. Results: Of the 147 patients, 54.4% (80) received LND and 42.5% (34/80) of these were found to have lymph node metastasis (LNM) in postoperative pathological diagnosis. Patients undergoing LND usually have a larger surgical range, including hemihepatectomy and enlarged hemihepatectomy (P = 0.001). LND did not increase postoperative complications (27.5%, P = 0.354), but postoperative hospital stays were longer (12.2 ± 6.3 d, P = 0.005) in group A compared with group B (20.9%, 9.5 ± 3.5 d). The 5-year survival rates of groups A and B are almost similar (21% vs 29%, P=0.905). The overall survival rate of cN0 (diagnosis obtained by imaging) is better than pN1 (diagnosis obtained by histopathology), but lower than pN0. (all P < 0.05). Elevated CA19-9 level (HR = 1.764, 95% CI: 1.113 ~ 2.795 , P = 0.016), vascular invasion (HR = 2.697, 95% CI: 1.103 ~ 6.599, P = 0.030), and T staging (HR = 1.848, 95% CI: 1.059 ~ 3.224, P = 0.031) were independent risk factors for poor ICC prognosis (all P values > 0.05).Conclusion: ICC patients with cN0 may have LNM, and the prognosis of LNM patients is usually poor. Our data may support routine lymphadenectomy for ICC.

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