Alexandre Doussot

Survival after resection of perihilar cholangiocarcinoma—development and external validation of a prognostic nomogram

BACKGROUND The objective of this study was to derive and validate a prognostic nomogram to predict disease-specific survival (DSS) after a curative intent resection of perihilar cholangiocarcinoma (PHC). PATIENTS AND METHODS A nomogram was developed from 173 patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA. The nomogram was externally validated in 133 patients treated at the Academic Medical Center (AMC), Amsterdam, The Netherlands. Prognostic accuracy was assessed with concordance estimates and calibration, and compared with the American Joint Committee on Cancer (AJCC) staging system. The nomogram will be available as web-based calculator at mskcc.org/nomograms. RESULTS For all 306 patients, the median overall survival (OS) was 40 months and the median DSS 41 months. Median follow-up for patients alive at last follow-up was 48 months. Lymph node involvement, resection margin status, and tumor differentiation were independent prognostic factors in the derivation cohort (MSKCC). A nomogram with these prognostic factors had a concordance index of 0.73 compared with 0.66 for the AJCC staging system. In the validation cohort (AMC), the concordance index was 0.72, compared with 0.60 for the AJCC staging system. Calibration was good in the derivation cohort; in the validation cohort patients had a better median DSS than predicted by the model. CONCLUSIONS The proposed nomogram to predict DSS after curative intent resection of PHC had a better prognostic accuracy than the AJCC staging system. Calibration was suboptimal because DSS differed between the two institutions. The nomogram can inform patients and physicians, guide shared decision making for adjuvant therapy, and stratify patients in future randomized, controlled trials.

Outcomes after Resection of Intrahepatic Cholangiocarcinoma: External Validation and Comparison of Prognostic Models

BACKGROUND Published prognostic models for overall survival after liver resection for intrahepatic cholangiocarcinoma require external validation before use in clinical practice. STUDY DESIGN From January 1993 to May 2013, consecutive patients who underwent resection of intrahepatic cholangiocarcinoma were identified from a prospective database. The Wang nomogram was derived in an Asian cohort (n = 367) and included clinicopathologic variables and preoperative CEA and cancer antigen 19-9 levels. The Hyder nomogram was derived in an Eastern and Western multicenter cohort (n = 514) using clinicopathologic variables only. The AJCC Cancer Staging System (7th ed) and the preoperative Fudan risk score were also evaluated. Prognostic performance was assessed in terms of discrimination, calibration, and stratification. RESULTS One hundred and eighty-eight patients were included, with a median follow-up of 41 months. Median overall survival was 48.7 months and estimated 3-year and 5-year overall survival rates were 59% and 45%, respectively. Overall survival prediction accuracy, according to concordance-index calculation, was 0.72 with the Wang nomogram, 0.66 with the Hyder nomogram, 0.63 with the AJCC system, and 0.55 using the Fudan score. Both nomograms provided effective patient stratification in distinct survival groups. CONCLUSIONS Both the Wang and Hyder nomograms provided accurate patient prognosis estimation after liver resection for intrahepatic cholangiocarcinoma and can be useful for decision making about adjuvant therapy. The Wang nomogram appears to be more appropriate in patients undergoing formal portal lymphadenectomy and requires preoperative CEA and cancer antigen 19-9 levels for optimal performance.

Circulating Plasma Levels of MicroRNA-21 and MicroRNA-221 Are Potential Diagnostic Markers for Primary Intrahepatic Cholangiocarcinoma.

Background MicroRNAs (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. Methods Using 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. Results Small 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). Conclusion Among 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.

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

The impact of morbidity on long‐term outcomes following liver resection for intrahepatic cholangiocarcinoma is currently unclear.

Liver resection and ablation for metastatic melanoma: A single center experience

The median survival for patients with stage IV metastatic melanoma is usually limited to approximately 1 year. In the case of liver metastasis, resection and ablation can achieve long‐term survival. This study aimed to describe the outcomes after liver resection or ablation for metastatic melanoma to the liver and identify preoperative prognostic factors.

Laparoscopic Isolated Resection of Caudate Lobe (Segment 1): A Safe and Versatile Technique

Surgical resection for liver tumors of the caudate lobe is challenging owing to its location between the inferior vena cava and the portal bifurcation and its relationship to the hepatic veins. Some case reports of isolated laparoscopic caudate lobe resection have been reported in the literature with various techniques. The aim of this study was to propose a standardized technique of laparoscopic isolated caudate lobe resection.

The accuracy of pre-operative imaging in the management of hepatic cysts

BACKGROUND Biliary cystic tumours (BCT) [biliary cystadenoma (BCA) and cystadenocarcinoma (BCAC)] warrant complete resection. Simple liver cysts (SLC) require fenestration when symptomatic. Distinguishing between BCT and atypical SLC with pre-operative imaging is not well studied. METHODS All patients undergoing surgery for a pre-operative suspected SLC or BCT between 1992 and 2014 were included. Peri-operative data were retrospectively reviewed. A blind radiological review of pre-operative imaging was performed. RESULTS Ninety-four patients underwent fenestration (n = 54) or complete excision (n = 40). Final pathology was SLC (n = 74), BCA (n = 15), BCAC (n = 2) and other primary malignancies (n = 3). A frozen section (FS) was performed in 36 patients, impacting management in 10 (27.8%) by avoiding (n = 1) or mandating a liver resection (n = 9). Frozen section results were always concordant with final pathology. Upon blind review, a solitary lesion, suspicious intracystic component, septation and biliary dilatation were associated with BCT (P < 0.05). Diagnostic sensitivity was high (87.5-100%) but specificity was poor (43.1-53.4%). The diagnostic value of imaging was most accurate when negative for BCT (negative predictive value: 92.5-100%). CONCLUSION Radiological assessment of hepatic cysts is relatively inaccurate as SLC frequently present with concerning features. In the absence of a strong suspicion of malignancy, fenestration and FS should be considered prior to a complete resection.

BRAF mutation screening in melanoma: is sentinel lymph node reliable?

As the detection of the BRAF V600E mutation has a direct impact on treatment decision, an accurate screening for BRAF mutations in patients with advanced or metastatic melanoma is mandatory. Nevertheless, BRAF oncogene mutation status between different samples from the same patient has been studied with conflicting results. This study investigated the intrapatient homogeneity of BRAF mutation status using pyrosequencing in primary tumors and different metastatic sites of melanoma patients. Paired samples of lymphatic, visceral, and subcutaneous metastases and primary melanoma from 45 metastatic melanoma patients were tested for BRAF mutations using a pyrosequencing assay and by Sanger sequencing. Overall, sequencing for BRAF mutation status was performed in 114 paired samples from 45 patients. Eighteen patients (40%) carried a BRAF mutation, including BRAF V600E (12/18), BRAF V600K (5/18), and BRAF V600R (1/18) mutations. Multiple BRAF mutations (V600E and V600K) were found in one patient. Among the patients with BRAF mutations, a good agreement in BRAF mutation status was found between the first and second tumor samples genotyped (91%; Cohen’s &kgr; coefficient: 0.81). Discordance in BRAF mutation status was found only in four patients, involving all three patients in whom sentinel lymph node (SLN) metastases were sampled. These SLNs exhibited a wild-type genotype and were discordant with the other BRAF-mutated samples found in the same patient. The intrapatient BRAF status was predominantly homogeneous. However, SLN genotyping using pyrosequencing might be inaccurate in determining the actual mutation status of melanoma. Further studies are required to confirm the lack of reliability of SLN.

Impact of intraoperative blood transfusion on short and long term outcomes after curative hepatectomy for intrahepatic cholangiocarcinoma: a propensity score matching analysis by the AFC-IHCC study group

BACKGROUND The impact of intraoperative blood transfusion (IBT) on outcomes following intrahepatic cholangiocarcinoma (IHCC) resection remains to be ascertained. METHODS All consecutive IHCC resected were analyzed. A first cohort (n = 569) was used for investigating short-term outcomes (morbidity and mortality). A second cohort (n = 522) excluding patients dead within 90 days of surgery was analyzed for exploring overall survival (OS) and disease free survival (DFS). Patients who received IBT were compared to those who did not, after using a propensity score matching (PSM) method. RESULTS Among 569 patients, 90-day morbidity and mortality rates were 47% (n = 269) and 8% (n = 47). After PSM, 208 patients were matched. There was an association between IBT and increased overall morbidity and severe morbidity (p = 0.010). However, IBT did not impact 90-day mortality rate (p > 0.999). Regarding long-term outcomes analysis in the second cohort (n = 522), 5-year OS and DFS rates were 39% and 25%. Using PSM, 196 patients were matched and no association between IBT and OS or DFS was found (p = 0.333 and p = 0.491). CONCLUSIONS IBT is associated with an increased risk of morbidity but does not impact on long-term outcomes. Need for IBT should be considered as a surrogate of advanced disease requiring complex resection. Still, restricted transfusion policy should remain advocated for IHCC resection.

Robot-Assisted Choledochoduodenostomy: A Safe and Reproducible Procedure for Benign Common Bile Duct Obstruction

Background: Choledochoduodenostomy (CD) is an option for treating choledocholithiasis and benign biliary obstruction after failure of endoscopic treatment. Nevertheless, this procedure is rarely performed using a mini-invasive approach because of its technical complexity. Robotic assistance could be a safer approach to overcome such technical issues. Methods: All consecutive patients who underwent a robot-assisted CD for benign biliary obstruction were included. Results: Between 2012 and 2016, 12 patients were operated on, 7 of whom had a body mass index over 25 (58%) and 7 were ASA class 3 (58%). The median age was 73 years (range 49-93). Median operative time was 140 min (range 105-208) and median blood loss was 90 mL (range 5-500). One patient presented with cholangitis 1 month after surgery (treated medically, Clavien-Dindo grade 2). Median length of stay was 7 days (range 3-8). None of the patients experienced severe morbidity after a median follow-up of 15 months. Conclusion: Robot-assisted CD is safe and feasible in benign biliary obstruction.