Background Liver resection is the most effective treatment for intrahepatic cholangiocarcinoma (IHCC). Recurrent disease is frequent, however, recurrence patterns are ill-defined, and prognostic models are lacking. Study Design A primary cohort of 189 patients who underwent resection for IHCC was used for recurrence patterns analysis within and after 24 months. Based on independent factors for disease free survival (DFS) identified in Cox regression analysis, preoperative and postoperative models were developed using a recursive partitioning method. Models were externally validated using a multicenter cohort of 522 resected patients (Association Française de Chirurgie-IHCC study group). Results Recurrence within 24 months most often involved the liver (82.7%) while most recurrences after 24 months were strictly extrahepatic (61.1%). In multivariable analysis of the primary cohort, independent preoperative factors for DFS were tumor size and multifocality (based on imaging), while tumor size, multifocality, vascular invasion and lymph node metastases (based on pathology) were independent postoperative factors. The preoperative model allowed patient classification into low risk and high risk groups for recurrence. In the validation cohort (n=522), high risk patients had a greater likelihood of recurrence (HR=2.17, 95% CI 1.74–2.72; p<0.001). Postoperative model included tumor size, vascular invasion and positive nodal disease on pathology and classified patients in low, intermediate and high risk groups in the primary cohort. As compared to low risk patients in the validation cohort, intermediate and high risk patients were more likely to experience recurrence (HR=1.9, 95% CI 1.41–2.47; p<0.001 and HR=2.99, 95% CI 2.08–4.31; p<0.001, respectively). Conclusions Recurrence patterns are time dependent. Both models as developed and validated in this study classified patients in distinct recurrence risk groups, which may guide treatment recommendations.

BackgroundMicroRNAs (miRNAs) are potential biomarkers in various malignancies. We aim to characterize miRNA expression in intrahepatic cholangiocarcinoma (ICC) and identify circulating plasma miRNAs with potential diagnostic and prognostic utility.MethodsUsing deep-sequencing techniques, miRNA expression between tumor samples and non-neoplastic liver parenchyma were compared. Overexpressed miRNAs were measured in plasma from an independent cohort of patients with cholangiocarcinoma using RT-qPCR and compared with that healthy volunteers. The discriminatory ability of the evaluated plasma miRNAs between patients and controls was evaluated with receiving operating characteristic (ROC) curves.ResultsSmall RNAs from 12 ICC and 11 tumor-free liver samples were evaluated. Unsupervised hierarchical clustering using the miRNA expression data showed clear grouping of ICC vs. non-neoplastic liver parenchyma. We identified 134 down-regulated and 128 upregulated miRNAs. Based on overexpression and high fold-change, miR21, miR200b, miR221, and miR34c were measured in plasma from an independent cohort of patients with ICC (n = 25) and healthy controls (n = 7). Significant overexpression of miR-21 and miR-221 was found in plasma from ICC patients. Furthermore, circulating miR-21 demonstrated a high discriminatory ability between patients with ICC and healthy controls (AUC: 0.94).ConclusionAmong the differentially expressed miRNAs in ICC, miR-21 and miR-221 are overexpressed and detectable in the circulation. Plasma expression levels of these miRNAs, particularly miR-21, accurately differentiates patients with ICC from healthy controls and could potentially serve as adjuncts in diagnosis. Prospective validation and comparison with other hepatobiliary malignancies is required to establish their potential role as diagnostic and prognostic biomarkers.

Cyst size stability at the 5-year time point did not preclude future growth, cross-over to resection, or carcinoma development. Patients who were stable at 5 years had a nearly 3-fold higher risk of developing cancer compared with the general population and should continue long-term surveillance.

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This multi-institutional study validated 2 CF protein marker models for preoperative identification of high-risk IPMN. When combined with a clinical nomogram, the ability to predict high-grade dysplasia was even stronger.

In this study, 22% of patients had disease progression following resection of noninvasive or microinvasive IPMN; 16% of these progressions represented invasive disease. These patients represent a high-risk group and should undergo long-term radiographic surveillance.

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Background While systems of 3-D image-guided surgery (IGS) are a valuable adjunct across numerous procedures, differences in organ shape between that reflected in the preoperative image data and the intraoperative state can compromise the fidelity of such guidance based on the image. In this work, we assessed in real time a novel, 3-D IGS platform that incorporates soft tissue deformation i. Methods A series of 125 alignment evaluations were performed across 20 patients. During the operation, the surgeon assessed the liver by swabbing an optically tracked stylus over the liver surface and viewing the IGS display. Each patient had approximately 6 intraoperative comparative evaluations. For each assessment, one of only two types of alignments were considered - conventional rigid and novel deformable. The series of alignment types used was randomized and blinded to the surgeon. The surgeon provided a rating, R, from −3 to +3 for each display as compared to the previous display, whereby a negative rating indicated degradation in fidelity and a positive rating an improvement. Results A statistical analysis of the series of rating data by the clinician indicated that the surgeons were able to perceive an improvement (defined as a R > 1) of the model-based registration over the rigid registration (p = 0.01) as well as a degradation (defined as R < −1) when the rigid registration was compared with the novel deformable guidance information(p = 0.03). Conclusions This study provides evidence of the benefit of deformation correction in providing an accurate location for the liver for use in IGS systems.