4025 Background: Cholangiocarcinoma (CCA) is a genetically heterogeneous malignancy for which current anatomic and histologic classifications inadequately predict survival. We hypothesized that unsupervised machine learning clustering of mutations and copy number alterations(CNA) could identify biologically distinct CCA subgroups with clinically meaningful differences in survival. Methods: Genomic and clinical data were obtained from the MSK cholangiocarcinoma dataset from cBioPortal. 790 patients with intrahepatic and extrahepatic CCA with available mutation and CNA data were included. Multiple unsupervised approaches were evaluated, including k-means, hierarchical clustering, non-negative matrix factorization, PCA–k-means, and UMAP–k-means. Model performance was assessed using silhouette scores, with UMAP–k-means (n=4 clusters) selected as the optimal method. Clusters were defined by dominant genetic alterations and compared for overall survival using Kaplan–Meier analysis with pairwise log-rank testing. Subgroup analyses included patients without curative-intent surgery and a young-onset cohort. Results: UMAP–k-means delineated four distinct genomic clusters ordered by progressively worse median survival. Cluster 1, defined by ARID1A or BAP1 mutations, demonstrated the most favorable survival outcomes. Cluster 2 consisted of tumors wild type for recurrent driver alterations. Cluster 3 was characterized by TP53 , KRAS , or IDH1 mutations. Cluster 4, defined by CDKN2A double deletion or ERBB2 amplification, exhibited the poorest median survival. Overall survival differed significantly across clusters, with all pairwise Kaplan–Meier comparisons reaching statistical significance except between clusters 1 and 2. These survival differences remained significant in patients who did not undergo curative-intent surgery. Notably, cluster 4 remained associated with significantly worse survival within the young-onset cohort. Conclusions: Unsupervised genomic clustering using UMAP–k-means identified biologically distinct subtypes of cholangiocarcinoma, with clinically significant survival differences that persist across surgical and age-based subgroups. These findings support future genomic subtyping as a prognostic framework and a rationale for biology-driven clinical trial stratification in cholangiocarcinoma. Unsupervised genetic clustering identifies biologically distinct cholangiocarcinoma subtypes with differential survival. Cluster Primary Genetic alterations N patients Median OS log-rank test P-value vs cluster 2 log-rank test P-value vs cluster 3 log-rank test P-value vs cluster 4 1 ARID1A or BAP1 mutant 120 28.0 0.308 <0.001 <0.001 2 Wild types 224 26.7 - 0.003 <0.001 3 TP53, KRAS or IDH1 mutant 319 22.0 - 0.002 4 CDKN2A deletion or ERBB2 amplification 127 16.9 -
While the incidence of early-onset cancers is rising, it is unclear whether this is the case for early-onset hepatocellular carcinoma (eHCC). Even the definition of eHCC remains unclear. This study was designed to identify an age cutoff for eHCC and to explore trends in its incidence, clinical presentation, surgical outcomes, and long-term survival compared to typical-onset HCC (tHCC). The National Cancer Database was queried for HCC patients (2010–2021). Both eHCC (< 50 years) and tHCC (≥ 50 years) were statistically defined. Propensity score matching adjustment, multivariate hazard ratios, and stage-dependent Kaplan-Meier survival analysis were calculated. Among 207,653 patients, 10,128 (4.88
Understanding the patient-specific anatomy of the superior mesenteric artery (SMA) and its branches is of critical importance when performing a pancreatic surgery. This study assesses deep-learning-based virtual SMA modelling for three-dimensional (3D) visualization of SMA’s course and branching patterns. This model is then used to correlate anatomical features with intra-/postoperative outcomes. Preoperative computed tomography (CT) scans of 124 patients undergoing pancreatic resection for pancreatic malignancy at St. Elizabeth’s Medical Center and Kyoto University were analyzed for course, branching, caliber, and aortic angle using a deep learning modeling software. Following anatomic modelling, the SMA was divided into regions on the basis of its relationship to the pancreas: SMA1 (above pancreas), SMA2 (intrapancreatic), and SMA3 (below pancreas). Univariate and multivariate logistic and linear regression were used to compare anatomical measurements to perioperative outcomes. Differences in anatomic measurements were observed between both populations. The mean caliber of SMA1, SMA2, and SMA3 was 7.05, 6.20, and 5.69 mm, respectively. A mean of 2.21 branches were observed in SMA2, and 4.52 in SMA3. Furthermore, fewer branches in SMA2 was associated with both postoperative pancreatic fistula (POPF) and Clavien–Dindo complication grade ≥ III. Finally, when stratified by minimally invasive approach, a greater distance between the superior border of pancreas and SMA was associated with POPF. This study shows that deep-learning-based virtual three-dimensional reconstruction of SMA enables accurate assessment of the anatomical relationship between the pancreas and SMA. Specific anatomical features were found to be associated with intra- and postoperative outcomes. Therefore, SMA modeling not only contributes to improved preoperative planning and intraoperative navigation, but also to outcome prognostication.
The liver cone unit (Tokyo 2020 terminology) of the peripheral portal vein territory represents the smallest anatomical and functional unit of the liver.1, 2 While this unit enables anatomical, subsegmental resection, particularly in patients with cirrhosis, the tumor-bearing cone unit can be challenging to identify intraoperatively.3 A 58-year-old man with hepatitis C-related cirrhosis (Child–Pugh B) was diagnosed with a subcapsular hepatocellular carcinoma (HCC) in segment 8. While ablation can achieve excellent outcomes in small HCC, owing to the superficial- (risk of seeding) and posterior-superior location (possible transdiaphragmatic access) as well as the presence of ascites, resection was offered. Preoperative three-dimensional (3D) reconstruction identified the tumor-bearing cone unit. Owing to cirrhosis-related shunting with its impact on Indocyanine Green (ICG) tumor staining, selective artery embolization of the branch feeding the neighboring cone unit and subsequent ICG injection into the tumor bearing cone unit was performed.4, 5 This allowed for laparoscopic, anatomical ICG-guided resection along the tumor-bearing cone unit’s boundaries. Cone unit-based planning and targeted embolization enabled accurate localization and resection of the tumor-bearing area. Despite impaired ICG uptake due to cirrhosis, fluorescence imaging provided visualization for precise anatomical transection with minimal bleeding. This case demonstrates a novel combined interventional radiology/surgical approach for precise cone unit resection, leading to minimal intraoperative blood loss and function-preserving hepatectomy in a patient with advanced cirrhosis. This conceptional framework can serve as a complement to ultrasound guided cone unit identification in patients with advanced cirrhosis, which can be highly challenging intraoperatively.
Background: 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. Methods: 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. Results: 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. Conclusion: 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. (c) 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.
BACKGROUND:Dissection of para-aortic lymph nodes (Station 16) provides an important prognosticator for patients with gastrointestinal, colorectal, and hepatobiliary cancers.1-4 For example, a positive Station 16 lymph node has been shown to lead to 2-year survival of 3% in patients with pancreas adenocarcinoma, akin to stage IV disease.5,6 Thereby, Station 16 involvement can help with the risk/benefit stratification of the decision to move forward with radical surgery.7-9 Furthermore, it has been shown for gallbladder cancer that involvement of Station 16 cannot necessarily be predicted from the dissection of the hepatoduodenal ligament lymph nodes only.10,11 TECHNIQUE: With the patient in the French position, a complete Kocherization and a Cattel-Braasch maneuver is performed, allowing for visualization of LN station 16b. Station 16b is the inferior border of the station 16 compartment. The left renal vein (LRV) serves as an important landmark to identify the superior border of the dissection comprised by Stations 16a2 and 16b1. Station 16a2 dissection may be associated with a traction injury of the left renal vein or damage of right renal or suprarenal arteries and is dissected if there are specific concerns regarding involvement.CONCLUSIONS:While station 16 provides important prognostic information for risk stratification, a strategic and stepwise approach is needed for a safe sampling. This is accomplished by wide mobilization of the duodenum, implementation of thermal fusion to minimize chyle leak, and careful dissection below the left renal vein.
BACKGROUND:Liver-directed treatments - ablative therapy (AT), surgical resection (SR), liver transplantation (LT), and transarterial chemoembolization (TACE) - improve the overall survival of patients with early-stage hepatocellular carcinoma (HCC). Although racial and socioeconomic disparities affect access to liver-directed therapies, the temporal trends for the curative-intent treatment of HCC remain to be elucidated. METHODS:This study performed chi-square, logistic regression, and temporal trends analyses on data from the Nationwide Inpatient Sample from 2011 to 2019. The outcome of interest was the rate of AT, SR, LT (curative-intent treatments), and TACE utilization, and the primary predictors were racial/ethnic group and socioeconomic status (SES; insurance status). RESULTS:African American and Hispanic patients had lower odds of receiving AT (African American: odds ratio [OR], 0.78; P < .001; Hispanic: OR, 0.84; P = .005) and SR (African American: OR, 0.71; P < .001; Hispanics: OR, 0.64; P < .001) than White patients. Compared with White patients, the odds of LT was lower in African American patients (OR, 0.76; P < .001) but higher in Hispanic patients (OR, 1.25; P = .001). Low SES was associated with worse odds of AT (OR, 0.79; P = .001), SR (OR, 0.66; P < .001), and LT (OR, 0.84; P = .028) compared with high SES. Although curative-intent treatments showed significant upward temporal trends among White patients (10.6%-13.9%; P < .001) and Asian and Pacific Islander/other patients (14.4%-15.7%; P = .007), there were nonsignificant trends among African American patients (10.9%-10.1%; P = .825) or Hispanic patients (12.2%-13.7%; P = .056). CONCLUSION:Our study demonstrated concerning disparities in the utilization of curative-intent treatment for HCC based on race/ethnicity and SES. Moreover, racial/ethnic disparities have widened rather than improved over time.
Laparoscopic hepatectomy has been associated with improved short-term outcomes compared to open hepatectomy. However, laparoscopic major hepatectomy after portal vein embolization (PVE) remains challenging due to the specific changes of the liver following PVE. In this chapter, we will discuss the data and the technical aspect of the laparoscopic right hepatectomy after PVE.
The incidence of a second de novo pancreatic ductal adenocarcinoma (PDAC) among patients with prior cancer has been reported to be 6