Development and multicenter validation of a nomogram for preoperative prediction of lymph node positivity in pancreatic cancer(NeoPangram)

Background: Neoadjuvant therapy is associated with nodal downstaging and improved oncological outcomes in patients with lymph node(LN)-positive pancreatic cancer. This study aimed to develop and validate a nomogram to preoperatively predict LN-positive disease. Methods: A total of 558 patients with resected pancreatic cancer were randomly and equally divided into development and internal validation cohorts. Multivariate logistic regression analysis was used to construct the nomogram. Model performance was evaluated by discrimination, calibration, and clinical usefulness. An independent multicenter cohort consisting of 250 patients was used for external validation. Results: A four-marker signature was built consisting of carbohydrate antigen 19–9(CA19–9), CA125, CA50, and CA242. A nomogram was constructed to predict LN metastasis using three predictors identified by multivariate analysis: risk score of the four-marker signature, computed tomography-reported LN status, and clinical tumor stage. The prediction model exhibited good discrimination ability, with C-indexes of 0.806, 0.742 and 0.763 for the development, internal validation, and external validation cohorts, respectively. The model also showed good calibration and clinical usefulness. A cut-off value(0.72) for the probability of LN metastasis was determined to separate low-risk and high-risk patients. Kaplan-Meier survival analysis revealed a good agreement of the survival curves between the nomogram-predicted status and the true LN status. Conclusions: This nomogram enables the identification of pancreatic cancer patients at high risk for LN positivity who may have more advanced disease and thus could potentially benefit from neoadjuvant therapy.     

Intérêt du daratumumab dans l’amylose AL réfractaire chez une patiente de 96 ans

Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38 + plasma cells, resulting in organ dysfunction. Cardiac involvement has a major prognostic value. Antiplasma cell chemotherapy reduces the synthesis of immunoglobulin light chains (precursors of amyloid deposits). We describe a case of AL amyloidosis in a 95-year-old patient. Our patient responded poorly to treatment with rituximab, cyclophosphamide-bortezomib-dexamethasone, and rituximab-bendamustine. Finally, the anti-CD38 antibody daratumumab was associated with the best hematologic responsiveness without significant adverse effects. In conclusion, our case suggests that daratumumab is an effective and well-tolerated alternative to chemotherapy in the treatment af AL amyloidosis in very elderly patients.     

Prevalence and Risk Factors for Osteopathy in Chronic Pancreatitis

Digestive Diseases and Sciences - The high incidence of osteopathy among patients with chronic pancreatitis (CP) has garnered increased attention over recent years. The aims of this study were to...     

Too Big to Fail: Successful Resection of a Large Hepatocellular Carcinoma with Portal Tumor Thrombus

Digestive Diseases and Sciences -     

雷帕霉素对内毒素性肝损伤小鼠肝组织Bcl-2表达的影响

目的探讨雷帕霉素对内毒素性肝损伤小鼠肝组织Bcl-2表达的影响。方法健康雄性昆明小鼠36只,随机分为正常组(12)、模型组(12)和雷帕霉素组(12)。应用脂多糖10mg/kg腹腔注射小鼠诱导内毒素肝损伤模型。造模后6h取血,检测小鼠血清谷丙转氨酶(ALT)和谷草转氨酶(AST)活性,免疫组织化学方法和Western blot方法检测各组小鼠肝组织Bcl-2的表达。结果模型组血清ALT、AST含量明显高于正常组(P0.01);雷帕霉素组血清ALT、AST含量明显降于模型组(P0.05)。与正常组相比,模型组小鼠肝组织Bcl-2表达显著降低(P0.01);而与模型组相比,雷帕霉素组小鼠肝组织Bcl-2表达显著升高高于(P0.01)。结论雷帕霉素能够上调内毒素性肝损伤小鼠肝组织Bcl-2的表达。     

神经鞘脂在动脉粥样硬化中的研究进展

动脉粥样硬化是引起大多数心血管疾病的主要原因,但其发病机制复杂,目前尚未完全阐明。越来越多的研究表明,脂质代谢紊乱可能在动脉粥样硬化的形成和发展中发挥重要作用。神经鞘脂作为一类参与机体结构组成、具有信号转导功能的生物活性脂质,在心血管疾病患者的血液和病变血管中水平异常,某些神经鞘脂分子可能是心血管疾病潜在的生物标志物和治疗靶点。文章综述神经鞘脂对动脉粥样硬化的影响和调控机制,为防治动脉粥样硬化寻找新的思路和分子靶点。     

Histopathological growth patterns modify the prognostic impact of microvascular invasion in non-cirrhotic hepatocellular carcinoma

BackgroundMicrovascular invasion (MVI) is an established prognosticator in hepatocellular carcinoma (HCC). Histopathological growth patterns (HGPs) classify the invasive margin of hepatic tumors, with superior survival observed for the desmoplastic HGP. Our aim was to investigate non-cirrhotic HCC in light of MVI and the HGP.MethodsA retrospective cohort study was performed in resected non-cirrhotic HCC. MVI was assessed prospectively. The HGP was determined retrospectively, blinded, and according to guidelines. Overall and disease-free survival (OS, DFS) were evaluated by Kaplan–Meier and multivariable Cox regression.ResultsThe HGP was determined in 155 eligible patients, 55 (35%) featured a desmoplastic HGP. MVI was observed in 92 (59%) and was uncorrelated with HGP (64% vs 57%, p = 0.42). On multivariable analysis, non-desmoplastic and MVI-positive were associated with an adjusted HR [95%CI] of 1.61 [0.98–2.65] and 3.22 [1.89–5.51] for OS, and 1.59 [1.05–2.41] and 2.30 [1.52–3.50] for DFS. Effect modification for OS existed between HGP and MVI (p < 0.01). Non-desmoplastic MVI-positive patients had a 5-year OS of 36% (HR: 5.21 [2.68–10.12]), compared to 60% for desmoplastic regardless of MVI (HR: 2.12 [1.08–4.18]), and 86% in non-desmoplastic MVI-negative.ConclusionHCCs in non-cirrhotic livers display HGPs which may be of prognostic importance, especially when combined with MVI.     

Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: a propensity score matching analysis

BackgroundSurgical resection is a first-line curative option for hepatocellular carcinoma, but its role is still unclear in elderly patients. The aim of our study was to compare short- and long-term outcomes of laparoscopic and open liver resection in elderly patients with hepatocellular carcinoma.MethodsThe study included 665 consecutive hepatocellular carcinoma liver resection cases in patients with ≥70 years of age treated in eight European hospital centres. Patients were divided into laparoscopic and open liver resection groups. Perioperative and long-term outcomes were compared between these groups.ResultsAfter a 1:1 propensity score matching, 219 patients were included in each group. Clavien-Dindo grades III/IV (6 vs. 20%, p = 0.04) were lower in the laparoscopic than in the open matched group. Hospital stay was shorter in the laparoscopic than in the open matched group (5 vs. 7 days, p < 0.001). There were no significant differences between laparoscopic and open groups regarding overall survival and disease-free survival at 1-, 3- and 5- year periods.ConclusionLaparoscopic liver resection for hepatocellular carcinoma is associated with good short-term outcomes in patients with ≥70 years of age compared to open liver resection. Laparoscopic liver resection is safe and feasible in elderly patients with hepatocellular carcinoma.     

Survival after liver resection and liver transplantation for colorectal liver metastases: a comparative analysis stratified by metabolic tumor volume assessed by 18F-FDG PET/CT

BackgroundMany patients undergoing resection for colorectal liver metastases (CRLM) recur with poor survival. Overall survival (OS) following liver transplantation (LT) for CRLM is reported to be about 80% at 5 years. In this study, survival following resection versus transplantation for CRLM in patients with moderate (6–70 cm³) metabolic tumor volume (MTV) from the preoperative positron emission tomography (PET) was compared.MethodsDisease-free survival (DFS), OS and post recurrence survival (PRS) following resection (n = 18) and LT (n = 12) was compared by using the Kaplan Meier method and log rank test for patients with moderate MTV.ResultsPatients undergoing LT had unresectable metastases, significantly lower age, higher tumor burden score and number of liver metastases, longer time from diagnosis to surgery, and more patients received neoadjuvant chemotherapy. OS at 5 years was 39% in the resection group and 83% in the LT group (P = 0.012). PRS was significantly improved in patients treated with LT compared to resection with 71% alive at 5 years from recurrence compared to 17% in the resection group (P = 0.017).ConclusionLT for selected patients seems to be superior to resection as treatment for CRLM for patients with moderate MTV.     

Poorly differentiated hepatocellular carcinoma: resection is equivalent to transplantation in patients with low liver fibrosis

BackgroundOrgan allocation criteria for liver transplantation focus on tumor size and multifocality while tumor differentiation and existing liver damage are omitted. This study analyzes the impact of hepatocellular carcinoma (HCC) grade and liver fibrosis comparing resection (SX) to transplantation (LT).MethodsThe National Cancer Database was queried between 2004 and 2016 for solitary HCC meeting Milan criteria undergoing SX vs LT. Two groups were created: low fibrosis (LF) vs high fibrosis (HF) and stratified by grade. Cox multivariable regression models, Kaplan–Meier survival analyses and log-rank tests were performed.Results1515 patients were identified; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months; LT mOS was 47.9 months vs SX mOS of 34.9 months (P < .001). Multivariate analysis revealed SX, no chemotherapy, longer hospital stays, and age to be associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, SX vs LT did not impact survival for poorly differentiated HCC in LF patients, independent of tumor size.DiscussionHCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vs LT. Therefore, current HCC transplantation criteria should incorporate tumor grade or liver fibrosis for optimal organ allocation.