Lymphadenectomy ensures accurate staging for patients with intrahepatic cholangiocarcinoma, especially for those without preoperatively suspected positive lymph nodes (clinically node-negative); ...however, its prognostic value has been poorly documented. The aim of this study was to evaluate the prognostic value of lymphadenectomy on long-term outcomes in patients undergoing surgery for clinically node-negative intrahepatic cholangiocarcinoma.
Data from all patients who underwent liver resection with or without lymphadenectomy for preoperatively diagnosed intrahepatic cholangiocarcinoma between 2000 and 2016 at 3 tertiary hepatobiliary centers were analyzed retrospectively. Propensity score matching in a 1:1 ratio was conducted based on clinically relevant covariates between patients with clinically node-negative intrahepatic cholangiocarcinoma who underwent liver resection with (LND group) and without (NLND group) lymphadenectomy. Overall survival and disease-free survival were compared in the matched cohort.
Among 350 patients who underwent surgery during the study period, 192 (55%) with clinically node-negative intrahepatic cholangiocarcinoma met the inclusion criteria. After propensity score matching, 2 well-balanced groups of 56 patients each were analyzed. There was no significant difference regarding postoperative variables among these 112 matched patients. Patients who underwent a liver resection with lymphadenectomy achieved better 3- and 5-year overall survival (78% and 65% vs 52% and 46%, P = .017) and disease-free survival (46% and 34% vs 31% and 31%; P = .042) compared with patients who underwent liver resection without lymphadenectomy.
Lymphadenectomy can be associated with better long-term outcomes in patients with node-negative intrahepatic cholangiocarcinoma. Our data may support routine lymphadenectomy for node-negative intrahepatic cholangiocarcinoma with the objective of achieving better long-term outcomes.
Intrahepatic cholangiocarcinomas (iCCs) are primary tumors of the liver characterized by the presence of a desmoplastic stroma. While tumor stroma may have a protective or a pejorative value ...depending on the type of malignant disease, the precise role of the desmoplastic stroma in iCC remains poorly understood. The aim of the present study was to evaluate the prognostic value of stromal compartment in iCC through a multiparametric morphological analysis. Forty-nine surgically resected iCCs were included. For all cases, tumor paraffin blocks of iCCs were selected for stromal morphological characterization through quantitative and qualitative approaches using immunohistochemistry and second-harmonic generation imaging. Intratumor heterogeneity was also evaluated in regards with the different stromal features. High proportionated stromal area (PSA) (defined by stromal to tumor area ratio) was inversely correlated with vascular invasion (62.5% vs 95.7%, p = 0.006) and positively correlated with well-differentiated grade (60% vs 12.5%, p = 0.001). Patients with high PSA had a better disease-free survival (DFS) than patients with low stromal area (60% vs 10%, p = 0.077). Low activated stroma index (defined by cancer-associated fibroblasts number to stromal area ratio) was associated with a better DFS (60% vs 10%, p = 0.05). High collagen reticulation index (CRI), defined as the number of collagen fiber branches within the entire length of the collagen network, was associated with a poorer overall survival (42% vs NR, p = 0.026). Furthermore, we showed that CRI was also an homogeneous marker throughout the tumor. Based on morphological features, desmoplastic stroma seems to exert a protective effect in patients with iCC. Stromal collagen reticulation may provide additional clinically relevant information. In addition, these data support the potential value to evaluate CRI in biopsy specimen.
Background & Aims Prothrombin induced by vitamin K absence-II (PIVKA-II) is a diagnostic and surveillance marker for HCC mainly used in Asia, and has also been shown to be a predictor of ...microvascular invasion (MVI), a major prognostic factor in HCC. However, experience with PIVKA-II in Europe remains limited. Methods In a French cohort, we conducted a case-control study to compare the performances of α-fetoprotein (AFP) and PIVKA-II serum levels for diagnosis of early stage HCC, and we determined the value of PIVKA-II serum and tissue expression in pre-operative detection of MVI. 43 cirrhotic control patients and 85 HCC cases were included, of which 54 (63.5%) had early stage HCC (n = 22 very early, n = 32 early). PIVKA-II tissue expression was assessed by immunohistochemistry in HCC surgical samples. Results For the diagnosis of early HCC, PIVKA-II had a sensitivity of 77% and a specificity of 82% at a cut-off of 42 mAU/ml, vs. 61% and 50% for AFP at a cut-off of 5.5 ng/ml (AUC 0.81 vs. 0.58, respectively). A PIVKA-II level >90 mAU/ml was an independent predictor of MVI (HR 3.5; 95% CI 1.08–11.8; p = 0.043). High PIVKA-II tissue expression was significantly associated with the presence of MVI ( p = 0.001). When combining PIVKA-II immunostaining with the PIVKA-II serum level, sensitivity and specificity for the diagnosis of MVI increased from 70% to 87% and 63% to 90%, respectively. Conclusions PIVKA-II was more efficient than AFP for the diagnosis of early HCC, and could be used as a predictive biomarker of MVI.
Metabolic syndrome (MS) is becoming the leading risk factor for hepatocellular carcinoma (HCC). HCC development related to MS may occur in advanced or non-advanced liver fibrosis, suggesting specific ...molecular pathways. Among these pathways, basal inflammatory state and adipokines production are involved. The aim of this study was to evaluate the role of fatty acid-binding protein 4 (FABP4). In this study, we demonstrate the specific overexpression of FABP4 in human HCC samples from patients with MS compared to other risk factors for chronic liver disease with FABP4 expression restricted to peritumoral endothelial cells. In vitro, glucose, insulin, VEGFA and hypoxia upregulated endothelial FABP4, which was reversed by metformin through mTOR pathway inhibition. FABP4 exerts oncogenic effects on hepatoma cell lines by upregulating the angiogenesis gene signature and pathways involved in the cell cycle, leading to increased cell proliferation and migration, and downregulating HIF1 pathway; effects were reversed in the presence of a specific FABP4 inhibitor (BMS309403). We showed the role of microvesicles as FABP4 vectors between endothelial and tumor cells. In vivo, BMS309403 significantly reduces tumor growth in heterotopic and orthotopic xenografted mice model. In conclusion, this study demonstrates the emerging oncogenic role of liver endothelial cells through FABP4 in HCC related to MS, and highlights new anti-neoplastic mechanism of metformin.
Background
A standardized laparoscopic right hepatectomy (LRH) approach named the “caudal approach” was recently reported. Yet, the value of this approach compared with state-of-the-art open right ...hepatectomy (ORH) remains unknown. The purpose of this study was therefore to compare the short-term outcomes of LRH using the caudal approach and ORH with anterior approach and liver hanging maneuver.
Methods
One-hundred eleven consecutive patients who underwent LRH with caudal approach were prospectively collected; 346 patients who underwent ORH with anterior approach and liver hanging maneuver were enrolled as a control group. Propensity score matching (PSM) of patients in a ratio of 1: 1 was conducted and the perioperative outcomes were compared.
Results
After PSM, two well-balanced groups of 72 patients each were analyzed and compared. The conversion rate in the LRH group was 18.1%. Perioperative blood loss and transfusion rates were significantly lower in the LRH group as compared to the ORH group (median, 200 ml vs. 500 ml,
p
< 0.001 and 9.9% vs. 26.8%,
p
= 0.009, respectively), while operation time was significantly longer (median, 348 min vs. 290 min,
p
< 0.001). Overall (26.4% vs. 48.6%,
p
= 0.006) and symptomatic pulmonary (6.9% vs. 19.4%,
p
= 0.027) complication rates were significantly lower in the LRH group. Hospital stay was significantly shorter in the LRH group (median, 8 days vs. 9 days,
p
= 0.013).
Conclusions
LRH using the caudal approach is associated with improved short-term outcomes compared to state-of-the-art ORH in patients qualifying for both approaches, and can be proposed as standard practice.
Background
The predictive risk factors of clinically relevant pancreatic fistula (CR-PF) following distal pancreatectomy (DP) remain to be identified.
Methods
This is a retrospective cohort analysis ...of a single-institution database of patients undergoing DP, taking into account usual demographic, operative, and pathologic variables and visceral fat area (VFA), total muscle area (TMA), and surface muscle index (SMI) measured on preoperative CT scan. The primary end point was CR-PF. All variables associated with a
p
value < 0.05 on univariate analysis were included in a logistic regression model for multivariate analysis.
Results
From 2012 to 2016, 208 patients operated by 4 pancreatic surgeons underwent DP including 32 (15%) who developed CR-PF. Risk factors of CR-PF on univariate analysis were: BMI ≥ 25 kg/m
2
(
p
= 0.050), VFA ≥ 92 cm
2
(
p
= 0.006), laparotomy (
p
= 0.023), main pancreatic duct dilatation (
p
= 0.035), open passive drainage (versus closed suction drainage) (
p
= 0.001), and blood loss ≥ 225 ml (
p
= 0.001). Sarcopenia did not influence the risk of CR-PF (
p
= 0.076). On multivariate analysis, VFA ≥ 92 cm
2
(OR 3.14; IC 95% (1.18–8.31),
p
= 0.022), blood loss ≥ 225 ml (OR: 2.72; IC 95% (1.06–6.96),
p
= 0.037), and open passive drainage (OR 3.72; IC 95% (1.40–9.87)
p
= 0.008) were three independent predictive factors of CR-PF. A CR-PF risk score was developed, predicting a 0% risk of CR-PF when no risk factors were present and a 39% risk when the 3 risk factors were present.
Conclusions
Visceral obesity, blood loss ≥ 225 ml and open passive drainage significantly increase the risk of CR-PF following DP.
With the development of chemotherapy regimens, targeted therapies, and hepatic surgery, the survival of patients with colorectal liver metastases (CRLM) has dramatically improved. Imaging plays a ...central role for the diagnosis, staging, and treatment allocation in these patients. To interpret CRLM on imaging, radiologists must be familiar with the main imaging features of untreated tumors as well as the modifications induced by systemic therapies, and their meaning in relation to pathological tumor response and tumor biology. CRLM have the same histological features as the primary tumor. Most are “non-otherwise specified” (NOS) adenocarcinomas. The mucinous tumor is the most common of the rare subtypes. In NOS tumors, imaging usually differentiates central areas of necrosis from peripheral proliferating tumors and desmoplastic reaction. Areas of mucin mixed with fibrosis are seen in mucinous subtypes to help differentiate the metastases from other tumors cysts or hemangiomas. After treatment, the viable tumor is gradually replaced by ischemic-like necrosis and fibrosis, and remnants cells are mainly located on the periphery of tumors. Imaging can help predict the degree of tumor response, but changes can be difficult to differentiate from the pretherapeutic appearance. When chemotherapy is interrupted or in case of resistance to treatment, a peripheral infiltrating halo of tumor growth may appear. The purpose of the article is to illustrate the significance of the imaging features of colorectal liver metastases during systemic therapy, using radiopathological correlations.
Objective
The aim of this study was to assess the prognostic value of liver surface nodularity (LSN) and sarcopenia from preoperative computed tomography (CT) in patients with resectable metabolic ...syndrome (MS)-related hepatocellular carcinoma (HCC).
Methods
Patients with MS undergoing hepatectomy for HCC between 2006 and 2018 at a single center were retrospectively analyzed. LSN and sarcopenia were assessed on preoperative CT scans, and their association with severe (Clavien–Dindo grade 3–5) postoperative complications was analyzed on multivariate analysis. The influence of LSN and sarcopenia on overall survival (OS) and recurrence-free survival (RFS) was assessed.
Results
Overall, 110 patients (92 men 84%, mean 67.7 ± 7.7 years of age) were analyzed. Severe postoperative complications occurred in 34/110 (31%) patients. Patients with severe complications had a significantly higher LSN score (area under the receiver operating characteristic curve 0.68 ± 0.05, optimal cut-off > 2.50) and were more frequently sarcopenic (47% vs. 13% without major complications,
p
< 0.001). Multivariate analysis identified sarcopenia (odds ratio OR 6.51, 95% confidence interval CI 2.08–20.39;
p
< 0.001), LSN > 2.50 (OR 7.05, 95% CI 2.13–23.35;
p
< 0.001), and preoperative portal vein embolization (PVE; OR 6.06, 95% CI 1.71–21.48;
p
= 0.005) as independent predictors of severe complications. LSN and sarcopenia had no influence on OS. Stratification according to a combination of LSN > 2.50 and sarcopenia predicted the risk of severe postoperative complications from 7% (no sarcopenia and LSN ≤2.50) to 71% (sarcopenia and LSN > 2.50;
p
< 0.001), as well as RFS from 61 months (95% CI 40–82) to 17 months (95% CI 9–25;
p
= 0.033). Results remained significant in 52 patients without advanced fibrosis.
Conclusions
The combination of LSN and sarcopenia derived from routine preoperative CT seems to help predict severe postoperative complications and stratification of RFS in patients with MS and resectable HCC.
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