Mass cytometry-based peripheral blood analysis as a novel tool for early detection of solid tumours: a multicentre study.

OBJECTIVE: Early detection of a tumour remains an unmet medical need, and approaches with high sensitivity and specificity are urgently required. Mass cytometry time-of-flight (CyTOF) is a powerful technique to profile immune cells and could be applied to tumour detection. We attempted to establish diagnostic models for hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). DESIGN: We performed CyTOF analysis for 2348 participants from 15 centres, including 1131 participants with hepatic diseases, 584 participants with pancreatic diseases and 633 healthy volunteers. Diagnostic models were constructed through random forest algorithm and validated in subgroups. RESULTS: We determined the disturbance of systemic immunity caused by HCC and PDAC, and calculated a peripheral blood immune score (PBIScore) based on the constructed model. The PBIScore exhibited good performance in detecting HCC and PDAC, with both sensitivity and specificity being around 80% in the validation cohorts. We further established an integrated PBIScore (iPBIScore) by combining PBIScore and alpha-fetoprotein or carbohydrate antigen 19-9. The iPBIScore for HCC had an area under the curve (AUC) of 0.99, 0.97 and 0.96 in training, internal validation and external validation cohorts, respectively. Similarly, the iPBIScore for PDAC showed an AUC of 0.99, 0.98 and 0.97 in the training, internal validation and external validation cohorts, respectively. In early-stage and tumour-marker-negative patients, our iPBIScore-based models also showed an AUC of 0.95-0.96 and 0.81-0.92, respectively. CONCLUSION: Our study proved that the alterations of peripheral immune cell subsets could assist tumour detection, and provide a ready-to-use detection model for HCC and PDAC.

CircFOXM1 promotes proliferation and metastasis of hepatocellular carcinoma via regulating miR-1179/SPAG5 axis.

Hepatocellular carcinoma (HCC) predominantly occurs in patients with chronic liver disease, accounting for 70-90% of all liver cancer cases. The role of circFOXM1/miR-1179/SPAG5 axis in HCC has not been reported. This study aimed to explore the regulatory mechanism of circFOXM1 in HCC proliferation and metastasis. RNA polymerase inhibitor actinomycin D and RNase R exonuclease were used to identify circFOXM1 in HCC cells. The qRT-PCR was used to detect circFOXM1 expression. Specific siRNA for circFOXM1 was designed, and the sequence of circFOXM1 was inserted in pLCDH-ciR to overexpress circFOXM. Cell proliferation was detected by CCK8 in vitro, by tumor volume and tumor weight of HCC xenograft in vivo. Cell migration was detected by transwell test. Binding status of circFOXM1 with miR-1179 was detected by luciferase reporter gene assay. Rescue experiments were applied to identify the oncogenic mechanism of circFOXM1 in HCC cells. Actinomycin D assay confirmed the cyclization of circFOXM1. RNase R treatment showed that circFOXM1 was not affected by RNase R exonuclease. CCK8 assay, tumor volume and tumor weight showed that circFOXM1 effectively promoted HCC cell proliferation. Transwell assay showed that circFOXM effectively promoted migration and invasion abilities of HCC cells. Luciferase reporter gene activity assay showed that miR-1179 had complementary binding sites with circFOXM1 and SPAG5. CircFOXM1 silencing inhibited malignant phenotypes in HCC cells were partly rescued by either miR-1179 silencing or SPAG5 overexpression. CircFOXM1 promoted HCC cell proliferation and metastasis by regulating miR-1179/SPAG5 axis.

Relationship Between Fish Oil Use and Incidence of Primary Liver Cancer: Findings From a Population-Based Prospective Cohort Study.

Background: N-3 long-chain polyunsaturated fatty acids (LCPUFAs) prevented non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) in studies of mouse models. We examined prospective relationships between fish oil use and risk of primary liver cancer and the major histological subtypes, such as HCC and intrahepatic cholangiocarcinoma (ICC). Methods: We included 434,584 middle-aged and older men and women who were free of cancer at recruitment of the UK Biobank (2006-2010). Information on fish oil use and other dietary habits was collected via questionnaires. Cox proportional hazards models were used to compute the hazard ratio (HR) and 95% CI of liver cancer associated with fish oil use, with adjustment for socio-demographic, lifestyle, dietary, and other clinical risk factors. Results: At baseline, 31.4% of participants reported regular use of fish oil supplements. During a median of 7.8 years of follow-up, 262 incident liver cancer cases were identified, among which 127 were HCC and 110 were ICC cases. As compared with non-users, fish oil users had a significantly 44% (95% CI: 25-59%) lower risk of total liver cancer, and 52% (95% CI: 24-70%) and 40% (95% CI: 7-61%) lower risk of HCC and ICC, respectively. Higher intake of oily fish also was associated with a lower risk of HCC (≥2 vs. <1 serving/week: HR = 0.46; 95% CI: 0.23-0.96; P-trend = 0.027) but not ICC (P-trend = 0.96). Conclusion: Habitual use of fish oil supplements was associated lower risk of primary liver cancer regardless of cancer histological subtypes, potentially supporting a beneficial role of dietary n-3 LCPUFAs in liver cancer prevention.

Meta-analysis of fish consumption and risk of pancreatic cancer in 13 prospective studies with 1.8 million participants.

A previous meta-analysis suggested no association between fish consumption and risk of pancreatic cancer. As several prospective studies with a large number of pancreatic cancer cases have emerged after that meta-analysis, we updated the evidence and examined the relationship in greater depth. We performed a literature search on PubMed and EMBASE databases through March 30, 2019 to identify potentially eligible studies. We used a random-effects model to compute summary relative risk (RR) with corresponding 95% confidence interval (CI). A total of 13 prospective studies comprising 4994 pancreatic cancer cases and 1,794,601 participants were included in the final analyses. Results of the meta-analysis showed that fish consumption was not significantly associated with risk of pancreatic cancer (RR 50-g/day = 1.03, 95% CI: 0.95-1.12), which was confirmed when stratifying the analysis by various methodological and population characteristics. There was a suggestion of difference by adjustment for family history of pancreatic cancer (Pdifference = 0.05), with fish consumption being associated with higher risk of pancreatic cancer in studies without adjustment for participants' family history (RR50-g/day = 1.09, 95% CI: 1.02-1.18), and a non-significant inverse association among studies with the adjustment (RR50-g/day = 0.93, 95% CI: 0.82-1.05). Results of this updated meta-analysis suggest that fish consumption is unlikely to be substantially associated with risk of pancreatic cancer.

Preoperative risk factors for conversion and learning curve of minimally invasive distal pancreatectomy.

BACKGROUND: Although laparoscopic distal pancreatectomy is considered a standard approach, 10% to 40% of these are converted. The preoperative risk factors for conversion are not well described. The aim of this study was to identify risk factors associated with conversion. METHODS: Clinicopathological variables of 211 consecutive patients who underwent laparoscopic distal pancreatectomy between January 2007 and December 2015 at Johns Hopkins were analyzed to identify factors associated with conversion. Furthermore, the learning curve for laparoscopic distal pancreatectomy was studied. RESULTS: On univariate analysis of diabetes mellitus, preoperative diagnosis of malignant disease, multiorgan resection, surgeons' years and case experience were significantly associated with conversion (all P < .05). Risk factors independently associated with conversion included diagnosis of malignant disease (odds ratio = 5.40; 95% confidence interval, 1.93-15.12, P = .001), multiorgan resection (odds ratio = 7.10; 95% confidence interval, 1.60-31.53, P = .01), and surgeons' case experience (odds ratio = 0.32; 95% confidence interval, 0.12-0.85, P = .023). Intraoperative reasons for conversion included presence of excessive intraabdominal and retroperitoneal fat (N = 10, 32.3%), adhesions (N = 10, 32.3%), extent of tumor invasion (N = 8, 25.8%), anatomy of vessels (N = 6, 19.4%), and intraoperative bleeding (N = 2, 6.5%). CONCLUSION: Patients undergoing laparoscopic distal pancreatectomy with a preoperative diagnosis of malignant disease or possible multiorgan resection are at a higher risk of conversion. Surgeon experience of performing >15 procedures significantly reduces the risk of conversion.

A novel technique of inserting pancreaticogastrostomy with duct-to-mucosa anastomosis can potentially reduce postoperative pancreatic fistula.

BACKGROUND: We describe our novel technique of inserting pancreaticogastrostomy (IPG) after pancreaticoduodenectomy. In our technique, the seromuscular and mucosal layers of the posterior gastric wall are separated to create a mucosal pouch. A duct-to-mucosa anastomosis is performed through a small incision in the mucosal layer. An inner suture at the seromuscular-mucosal margin incorporating the pancreatic parenchyma and an outer suture on the exterior margin of the seromuscular layer to wrap the pouch around the pancreas are placed to complete the IPG. MATERIALS AND METHODS: We examined the clinicopathological features and outcomes of 259 patients who underwent pancreaticoduodenectomy between January 2010 and April 2014. RESULTS: One hundred forty-three (55.2%) patients underwent IPG, while 116 (44.8%) had conventional pancreaticojejunostomy. Most preoperative and intraoperative parameters were comparable. Overall morbidity in the IPG group was 28.7%. The rate of grade A postoperative pancreatic fistula (POPF) was 7.0%, and the rates of grade B and C POPF were 0.7% and 0.0%, respectively. The corresponding rates of grade A, B, and C fistulae were 5.2%, 8.6%, and 5.2%, respectively. CONCLUSIONS: In selected patients, our novel technique can be performed safely and may reduce the rates of POPF.

Vitamin C Intake and Pancreatic Cancer Risk: A Meta-Analysis of Published Case-Control and Cohort Studies.

BACKGROUND: Observational studies inconsistently reported the relationship between vitamin C intake and risk of pancreatic cancer. We conducted a meta-analysis of published case-control and cohort studies to quantify the association. METHODS: Potentially eligible studies were found on PubMed and EMBASE databases through May 31, 2015. A random-effects model was assigned to compute summary point estimates with corresponding 95% confidence intervals (CIs). Subgroup and meta-regression analyses were also performed to explore sources of heterogeneity. RESULTS: Our final analyses included 20 observational studies comprising nearly 5 thousand cases of pancreatic cancer. When comparing the highest with the lowest categories of vitamin C intake, the summary odds ratio/relative risk for case-control studies (14 studies), cohort studies (6 studies) and all studies combined was 0.58 (95% CI: 0.52-0.66), 0.93 (95% CI: 0.78-1.11) and 0.66 (95% CI: 0.58-0.75), respectively. The difference in the findings between case-control and cohort studies was statistically significant (P < .001). Possible publication bias was shown in the meta-analysis of case-control studies. CONCLUSION: There is insufficient evidence to conclude any relationship between vitamin C intake and risk of pancreatic cancer. The strong inverse association observed in case-control studies may be affected by biases (eg, recall and selection biases) that particularly affect case-control studies and/or potential publication bias. Future prospective studies of vitamin C intake and pancreatic cancer are needed.

[Value and safety of the surgery with vascular resection and reconstruction for pancreatic cancer].

OBJECTIVE: To investigate the value and safety of the surgery with vascular resection and reconstruction during pancreatectomy for pancreatic cancer. METHODS: The clinical data of 206 patients with pancreatic cancer who underwent radical resection were retrospectively analyzed from January 2009 to March 2014 in Lihuili Hospital, Medical center of Ningbo.All cases were divided into non-vascular resection group(132 cases), the combined vein resection group(66 cases) and the combined arterial resection group(8 cases). The peri-operation data, the incidence of postoperative complications and the survival were compared in pairs among three groups.All patients were followed up till September 2014. RESULTS: There were no statistical differences for the preoperative data among three groups.The operation time and the blood loss (M(QR)) were (347±96)minutes and (500(400)) ml in non-vascular resection group, (425±91)minutes and (800(500))ml in combined vein resection group, (508±120)minutes and (1 750(2 075))ml in combined arterial resection group, with significant differences among three groups(all P<0.01). The incidence of postoperative complication was 16.7%(22/132) in non-vascular resection group, 28.8%(19/66) in combined vein resection group, and 6 cases in combined arterial resection group, respectively.There were significant differences between non-vascular resection group and combined vein resection group(P<0.05), non-vascular resection group and combined arterial resection group(P<0.05), as well as between combined vein resection group and combined arterial resection group(P<0.05). The median survival time was 15 months for non-vascular resection group, 15 months for combined vein resection group, and 12 months for combined arterial resection group.No significant difference was found among three groups(all P>0.05). The postoperative mortality was nil for all of groups. CONCLUSIONS: Compared with non-vascular resection, combined vein resection can be performed safely with a similar prognosis. The surgery of combined arterial resection could only be justified when R0 resection for pancreatic cancer could be achieved for highly selected patients.