肝癌患者血清microRNA-363 水平在诊断 和病情评估中的价值

目的 探讨肝癌患者血清microRNA-363（miR-363）水平与肝癌临床病理特征的关系及其在肝 癌诊断中的价值。方法 选取2016 年1 月—2018 年12 月台州医院肝胆胰外科收治的肝细胞肝癌患者86 例作 为肝癌组,选取同期该院健康体检者86 例作为对照组。RT-PCR 测定血清miR-363 水平。结果 肝癌组血 清miR-363 相对表达量低于对照组（P <0.05）,AFP 水平高于对照组（P <0.05）。不同TNM 分期、有无转移 患者血清miR-363 相对表达量比较,差异有统计学意义（P <0.05）。肝癌患者血清miR-363 与AFP 呈负相关 （r =-0.502,P <0.05）。miR-363、AFP 及miR-363+AFP 诊断肝癌的ROC 曲线下面积分别为0.742（95% CI ： 0.740,0.747）、0.884（95% CI ：0.881,0.887）和0.938（95% CI ：0.935,0.941）,敏感性分别为0.907（95% CI ： 0.876,0.932）、0.872（95% CI ：0.843,0.900）和0.826（95% CI ：0.796,0.855）,特异性分别为0.663（95% CI ：0.643,0.673）、0.802（95% CI ：0.782,0.824）和0.930（95% CI ：0.903,0.962）。结论 肝癌患者血清miR-363 水平降低,血清miR-363 与肝癌TNM 分期、转移关系密切,在协助肝癌诊断中具有一定指导价值。     

Serum chitinase-3-like protein 1 is a biomarker of liver fibrosis in patients with chronic hepatitis B in China

BackgroundSerum chitinase-3-like protein 1 (CHI3L1) is a potential biomarker for fibrosis assessment. We aimed to evaluate serum CHI3L1 as a noninvasive diagnostic marker for chronic hepatitis B virus-related fibrosis.MethodsSerum CHI3L1 levels were measured by ELISA in 134 chronic hepatitis B (CHB) patients. Significant fibrosis was defined as a liver stiffness > 9.7 kPa. The performance of CHI3L1 was assessed and compared to that of other noninvasive tests by receiver operating characteristic (ROC) analysis.ResultsSerum CHI3L1 levels were significantly higher in CHB patients with significant hepatic fibrosis (≥ F2) than in those without significant hepatic fibrosis (< F2) (56.5 ng/mL vs. 81.9 ng/mL, P < 0.001). In CHB patients, the specificity and sensitivity of CHI3L1 for predicting significant fibrosis were 75.6% and 59.1%, respectively, with a cut-off of 76.0 ng/mL and an area under the ROC curve of 0.728 (95% CI: 0.637–0.820).ConclusionsSerum CHI3L1 levels could be an effective new serological biomarker for the diagnosis of liver fibrosis. Moreover, CHI3L1 is feasible in monitoring disease progression.     

Immune checkpoint inhibitor for hepatocellular carcinoma recurrence after liver transplantation

To the Editor:Liver cancer is the fifth most common cancer and the second most frequent cause of cancer-related death globally.Hepatocellular carcinoma(HCC)accounts for 90%of primary liver cancers with the highest incidence in China(more than 50%of all cases worldwide)[1].Liver transplantation(LT)is regarded as an optimal therapy for selected HCC patients.The Milan criteria are the benchmark for candidate selection that ensure excellent prognosis for patients with HCC[2].The Hangzhou criteria expand 51.5%more of Milan criteria for LT candidates with comparable posttransplant survivals[3].However,LT recipients fulfilling Milan criteria or Hangzhou criteria are at the risk of up to 13%−18%HCC recurrence rate within five years[4].Only 25%−50%of recurrent HCC patients post-LT are eligible for surgical treatment which have consistently presented favored survival benefit than systemic therapy[5].     

Differential methylation landscape of pancreatic ductal adenocarcinoma and its precancerous lesions

Background: Pancreatic cancer is one of the most lethal diseases with an incidence almost equal to the mortality. In addition to having genetic causes, cancer can also be considered an epigenetic disease. DNA methylation is the premier epigenetic modification and patterns of aberrant DNA methylation are recognized to be a common hallmark of human tumor. In the multistage carcinogenesis of pancreas starting from precancerous lesions to pancreatic ductal adenocarcinoma(PDAC), the epigenetic changes play a significant role. Data sources: Relevant studies for this review were derived via an extensive literature search in Pub Med via using various keywords such as pancreatic ductal adenocarcinoma, precancerous lesions, methylation profile, epigenetic biomarkers that are relevant directly or closely associated with the concerned area of our interest. The literature search was intensively done considering a time frame of 20 years(1998–2018). Result: In this review we have highlighted the hypermethylation and hypomethylation of the precancerous PDAC lesions(pancreatic intra-epithelial neoplasia, intraductal papillary mucinous neoplasm, mucinous cystic neoplasm and chronic pancreatitis) and PDAC along with the potential biomarkers. We have also achieved the early epigenetic driver that leads to progression from precancerous lesions to PDAC. A bunch of epigenetic driver genes leads to progression of precancerous lesions to PDAC( pp ENK, APC, p14/5/16/17, h MLH1 and MGMT) are also documented. We summarized the importance of these observations in therapeutics and diagnosis of PDAC hence identifying the potential use of epigenetic biomarkers in epigenetic targeted therapy. Epigenetic inactivation occurs by hypermethylation of Cp G islands in the promoter regions of tumor suppressor genes. We listed all hyper-and hypomethylation of Cp G islands of several genes in PDAC including its precancerous lesions. Conclusions: The concept of the review would help to understand their biological effects, and to determine whether they may be successfully combined with other epigenetic drugs. However, we need to continue our research to develop more specific DNA-demethylating agents, which are the targets for hypermethylated Cp G methylation sites.     

Hangzhou criteria as downstaging criteria in hepatocellular carcinoma before liver transplantation: A multicenter study from China

BackgroundThe downstaging of hepatocellular carcinoma (HCC) has been confirmed to benefit liver transplantation (LT) patients whose tumors are beyond the transplantation criteria. Milan criteria (MC), a tumor size and number-based assessment, is currently used as the endpoint in these patients. However, many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy. Hence, this study aimed to explore the feasibility of Hangzhou criteria (HC), which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number, as an endpoint of downstaging.MethodsWe performed a multicenter and retrospective study of 206 patients accepted locoregional therapy (LRT) as downstaging/bridge treatment prior to LT in three centers of China.ResultsRecipients were divided into four groups: failed downstaging to the HC (group A, n = 46), successful downstaging to the HC (group B, n = 30), remained within the HC all the time (group C, n = 113), and tumor progressed (group D, n = 17). The 3-year HCC recurrence probabilities of groups B and C were not significantly different (10.3% vs. 11.6%, P = 0.87). The HCC recurrent rate was significantly higher in group A (52.3%) compared with that in group B/C (P < 0.05). Seven patients (7/76, 9.2%) whose tumor exceeded the the HC were successfully downstaged to the MC, and 39.5% (30/76) to the the HC. In group B, 23 patients remained beyond the MC and their survivals were as well as those of patients within the MC.ConclusionsCompared to the MC, HC downstaging criteria can give more HCC patients access to LT and furthermore, the outcome of these patients is the same as those matching MC downstaging criteria. Hangzhou downstaging criteria therefore is applicable in clinical practice.     

The efficacy and toxicity of chemotherapy in the elderly with advanced pancreatic cancer

ObjectivesFOLFIRINOX (FFX) or abraxane plus gemcitabine (AG)-based chemotherapy is used widely as firstline treatment for patients with pancreatic cancer. However, their use in the elderly is discouraged because of adverse events. More clinical data about the therapeutic response and tolerability to FFX or AG in elderly patents (over 70 years old) are required.MethodsPatients with advanced pancreatic cancer (n = 203; 131 metastatic pancreatic cancer patients (MPC) and 72 locally advanced pancreatic cancer patients (LAPC)) were treated using modified-FFX (mFFX) or AG and mFFX sequentially. The patients were grouped according to their age, patients below 70 years old and patients above 70 years old. The objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and adverse events were compared between the groups.ResultsThe ORRs in the elderly and in patients below 70 were similar (30.0% versus 32.3%). The median OS and PFS were also similar between the groups (mOS 13.3 m vs 12.7 m, p = 0.729, HR 0.874 (95% CI 0.5310 to 1.438); mPFS mPFS 10.6 m vs 10.3 m, p = 0.363, HR 0.800 (95% CI 0.4954 to 1.293)). However, the elderly patients suffered a higher incidence of severe adverse events (50% vs. 28.3%).ConclusionsThese data could provide guidance for chemotherapy use in elderly patients with advanced pancreatic cancer. Age did not affect treatment outcome; however, supportive treatment is very important for elderly patients receiving chemotherapy.     

A systemic inflammation response index (SIRI) correlates with survival and predicts oncological outcome for mFOLFIRINOX therapy in metastatic pancreatic cancer

ObjectivesSystemic inflammatory response and survival has not been evaluated as a predictive factor of chemotherapy in metastatic pancreatic cancer. The aim of this study was to evaluate the prognostic and predictive value of a baseline Systemic Inflammation Response Index (SIRI) in metastatic pancreatic cancer.MethodsRetrospective study of 164 metastatic pancreatic cancer patients. Associations between overall survival (OS), progression free survival (PFS), chemotherapy and SIRI were analyzed. SIRI is defined by neutrophil x monocyte/lymphocyte 10⁹/L.ResultsMedian age 66 years. 22 (13%) received mFOLFIRINOX, 59 (36%) gemcitabine + nab-paclitaxel, 40 (24%) gemcitabine, 13 (8%) other regimens and 30 (18%) had not received treatment. Patients with SIRI<2.3 × 10⁹/L showed a statistically significant improvement in OS compared to SIRI≥2.3 × 10⁹/L [16 months versus 4.8 months, Hazard Ratio (HR) 2.87, Confidence Interval (CI) 95% 2.02–4.07, p < 0.0001] that was confirmed in multivariate analysis. In addition, patients with SIRI<2.3 × 10⁹ showed a longer PFS (12 versus 6 months, HR 1.92, IC 95% 1.314–2.800, P = 0.001). Furthermore, we observed that patients with SIRI ≥2.3 × 10⁹/L were more likely to benefit from mFOLFIRINOX therapy. Patients with an elevated SIRI treated with mFOLFIRINOX versus gemcitabine plus nab-paclitaxel and gemcitabine showed a clinically and statistically significant difference in median OS of 17 months compared to 6 and 4 months respectively (p < 0.001). Conversely, the difference was not clinically significant in the SIRI<2.3 × 10⁹/L subgroup: 15.9 months versus 16.5 and 16, respectively.ConclusionAn elevated SIRI (≥2.3 × 10⁹/L) was an independent prognostic factor for patients with metastatic pancreatic cancer, warranting prospective evaluation.     

International consensus guidelines for surgery and the timing of intervention in chronic pancreatitis

Background/objectivesChronic pancreatitis (CP) is a complex inflammatory disease with pain as the predominant symptom. Pain relief can be achieved using invasive interventions such as endoscopy and surgery. This paper is part of the international consensus guidelines on CP and presents the consensus guideline for surgery and timing of intervention in CP.MethodsAn international working group with 15 experts on CP surgery from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 20 statements generated from evidence on 5 questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available for each statement. To determine the level of agreement, the working group voted on the 20 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach’s alpha reliability coefficient.ResultsStrong consensus was obtained for the following statements: Surgery in CP is indicated as treatment of intractable pain and local complications of adjacent organs, and in case of suspicion of malignant (cystic) lesion; Early surgery is favored over surgery in a more advanced stage of disease to achieve optimal long-term pain relief; In patients with an enlarged pancreatic head, a combined drainage and resection procedure, such as the Frey, Beger, and Berne procedure, may be the treatment of choice; Pancreaticoduodenectomy is the most suitable surgical option for patients with groove pancreatitis; The risk of pancreatic carcinoma in patients with CP is too low (2% in 10 year) to recommend active screening or prophylactic surgery; Patients with hereditary CP have such a high risk of pancreatic cancer that prophylactic resection can be considered (lifetime risk of 40–55%). Weak agreement for procedure choice in patients with dilated duct and normal size pancreatic head: both the extended lateral pancreaticojejunostomy and Frey procedure seems to provide equivalent pain control in patients.ConclusionsThis international expert consensus guideline provides evidenced-based statements concerning key aspects in surgery and timing of intervention in CP. It is meant to guide clinical practitioners and surgeons in the treatment of patients with CP.     

Disconnected pancreatic duct syndrome: Updated review on clinical implications and management

Disconnected Pancreatic Duct Syndrome (DPDS) is an important but often overlooked complication of acute necrotising pancreatitis (ANP) that occurs due to necrosis of the main pancreatic duct (PD). This segmental necrosis leads on to disconnection between the viable upstream pancreatic parenchyma and the duodenum. The disconnected and functional segment of pancreas continues to secrete pancreatic juice that is not drained into the gastrointestinal tract and lead on to recurrent pancreatic fluid collections (PFC), refractory external pancreatic flstulae and chronic abdominal pain/recurrent pancreatitis. Because of lack of awareness of this important complication of ANP, the diagnosis of DPDS is usually delayed. The delay in diagnosis increases the morbidity of the disease as well as increase the cost of treatment and duration of hospital stay. Surgery has remained the cornerstone for management of patients with DPDS. The conventional surgical approaches have been either resection or internal drainage procedures. Surgery for DPDS in the setting of ANP is often difficult due to presence of local inflammation and extensive venous collaterals in the operative field due to splenic vein thrombosis and therefore is associated with significant morbidity. Advancement in therapeutic endoscopy, especially advent of therapeutic endoscopic ultrasound has opened an exciting new field of minimally invasive therapeutic options for management of DPDS. The present review discusses the current understanding of the clinical manifestations, imaging features and management strategies in patients with DPDS.     

Three-dimensional remnant pancreatic volume ratio indicates postoperative pancreatic exocrine insufficiency in pancreatic cancer patients after distal pancreatectomy

BackgroundPancreatectomy may cause serious pancreatic exocrine insufficiency (PEI), which can lead to some nutritional problems, including new-onset diabetes mellitus (DM) or non-alcoholic fatty liver disease (NAFLD). Recent studies have reported that remnant pancreatic volume (RPV) significantly influences postoperative PEI. However, the specific correlation between RPV and postoperative PEI remains unclear. Here, we compare various pre-, peri-, and postoperative risk factors in a retrospective cohort to address whether preoperatively measured RPV is a predictor of postoperative PEI in pancreatic cancer patients after distal pancreatectomy (DP).MethodsSixty-one pancreatic cancer patients who underwent DP were retrospectively enrolled. Pancreatic volume was measured using preoperative 3D images, which simulated the actual intraoperative pancreatic parenchymal volume. We obtained the 3D-measured RPV and resected pancreatic volume. We calculated the ratio of the RPV to the total pancreatic volume and then divided the cohort into high- and low-RPV ratio groups based on a cut-off value (>0.35, n = 37 and ≤ 0.35, n = 24). Using multivariate analysis, the RPV ratio as well as pre-, peri- and postoperative PEI risk factors were independently assessed.ResultsThe multivariate analysis revealed that a low RPV ratio (odds ratio [OR], 5.911; p = 0.001), a hard pancreatic texture (OR, 3.313; p = 0.023) and TNM stage III/IV (OR, 3.515; p = 0.031) were strong predictors of the incidence of PEI.ConclusionsThe present study indicates that the RPV ratio is an additional useful predictor of postoperative nutrition status in pancreatic cancer patients.