Search

Yuying Shan, Xi Yu, Yong Yang, Jiannan Sun, Shengdong Wu, Shuqi Mao, Caide Lu Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, 315041, People’s Republic of ChinaCorrespondence: Caide Lu; Shuqi Mao, Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, 315041, People’s Republic of China, Email lucaide@nbu.edu.cn; mmmaoshuqi@163.comBackground: The macrotrabecular-massive subtype of hepatocellular carcinoma (MTM-HCC) is an aggressive histological type and results in poor prognosis. We developed a nomogram model based on laboratory results to predict the presence of MTM-HCC.Methods: A total of 357 HCC patients who underwent radical surgery between January 2015 and December 2020 at Ningbo Medical Center Lihuili Hospital were grouped according to histological type. After propensity score matching (PSM), 267 patients were divided into MTM-HCC (n = 76) and non-MTM-HCC (n = 191) groups. A LASSO regression analysis model was used to select predictive factors. Finally, a nomogram for predicting the presence of MTM-HCC was established. Decision curve analysis (DCA) was conducted to determine the clinical usefulness of the nomogram model by quantifying the net benefits along with the increase in threshold probabilities.Results: The 1-, 3-, and 5-year disease-free survival (DFS) and overall survival (OS) rates for MTM-HCC were 60.0%, 36.0%, 32.4% and 92.1%, 68.7%, 52.2%, respectively. Survival analysis indicated that the probabilities of achieving DFS and OS were significantly worse in the MTM-HCC group than in the non-MTM-HCC group (P < 0.05). The nomogram model that included AST levels, PT and AFP levels achieved a better C-index of 0.723 (95% CI: 0.659– 0.787). DCA revealed that the nomogram model could lead to net benefits and exhibited a wider range of threshold probabilities in the prediction of MTM-HCC.Conclusion: The nomogram model included AST, PT and AFP could achieve an optimal performance in the preoperative prediction of MTM-HCC.Keywords: hepatocellular carcinoma, macrotrabecular-massive subtype, prognosis, nomogram, aggressiveness

Purpose: To evaluate the efficacy and safety of lenvatinib in combination with transarterial chemoembolization (TACE) as an adjuvant therapy in HCC patients with high-risk of postoperative recurrence. Methods: This study was a prospective cohort study. Patients who met the eligible criteria were recruited between November 2018 to May 2021 from 8 hepatobiliary centers in China. The primary endpoint was disease-free survival (DFS). The secondary endpoints were overall survival (OS) and safety. The treatment-related adverse events (AEs) were recorded throughout the entire study period. Results: A total of 297 patients were enrolled, with 147 patients in the TACE + Lenvatinib (Len) group and 150 patients in the TACE group. The baseline characteristics were well balanced between the two groups. Patients in the TACE + Len group achieved significantly better DFS. The median DFS was 19.0 months [95% confidence interval (CI), 14.0-25.0] and 10.0 months [95% CI, 8.0-13.0] in the TACE + Len and TACE group, respectively (log-rank test p= 0.011). The adjusted hazard ratio (HR) of disease recurrence for baseline prognostic variables between the two groups was 0.68 (95% CI, 0.50–0.91, p = 0.009). Lenvatinib treatment-related AEs of grade 3 or 4 occurred in 28.6% of the patients in TACE + Len group. Conclusions: This study suggested that adjuvantTACE plus lenvatinib a promising approach for HCC patients with high-risk of postoperative recurrence, which could significantly reduce postoperative recurrence and prolong survival with a manageable safety profile.

Immune checkpoint inhibitor therapy has shown promising results in patients with unresectable hepatocellular carcinoma. This study aimed to evaluate the effectiveness and safety of sintilimab, a programmed cell death protein-1 (PD-1) blockade, combined with sorafenib and transhepatic arterial chemotherapy and embolization in this patient population, compared with sintilimab monotherapy and sintilimab-sorafenib duotherapy. This was a 22 months single center retrospective cohort study in China. 80 patients with unresectable hepatocellular carcinoma were included, with diagnosis confirmed by either histologic, cytologic or diagnostic imaging analysis. The patients were divided into three groups based on therapeutic regimen: sintilimab monotherapy (sintilimab group, n = 22), sintilimab-sorafenib duotherapy (duplex group, n = 23), sintilimab-sorafenib and transcatheter arterial chemoembolization combined therapy (triple group, n = 35). The principal evaluation criteria were overall survival and progression free survival in the population, assessed according to response evaluation criteria in solid tumors, version 1.1 (RECIST 1.1). Secondary evaluation criteria were safety, objective response rate and disease control rate. From March 1st, 2019 to December 31, 2020, 80 patients with unresectable hepatocellular carcinoma were included and divided into three treatment groups (22 received sintilimab monotherapy, 23 received sintilimab-sorafenib duotherapy, and 35 received sintilimab-sorafenib combined with transcatheter arterial chemoembolization). The median overall survival of all patients was 11.0 months (95% CI 7.7–14.3). Median overall survival was 13.0 months (95% CI NE–NE), 9.0 months(95% CI 6.3–11.7)and 3.0 months (95% CI 1.9–4.1, p p p p p

Background: Radical resection is a curative treatment for patients with hepatocellular carcinoma (HCC), but the incidence of recurrence remains high. We aimed to explore the performance of predicting HCC recurrence by longitudinal surveillance of the protein induced by vitamin K absence (PIVKA-II), alpha-fetoprotein (AFP), and lectin-reactive AFP (AFP-L3) during postoperative follow-up. Methods: Patients who underwent radical resection for HCC at the Ningbo Medical Centre Lihuili Hospital between January 2015 and December 2020 were included. All enrolled patients regularly monitor PIVKA-Ⅱ, AFP, AFP-L3 every 3 months during postoperative follow-up. The surveillance performance of PIVKA-Ⅱ, AFP, AFP-L3 during follow-up for the prediction of HCC recurrence was compared in patients. The Generalized Estimation Equation (GEE) was used to analyze the trends of the tumor biomarkers and interactions with time. Area under the receiver operator characteristic (AUROC) curves, the optimal cut-off value, the sensitivity and specificity were calculated to evaluate the performance of the three biomarkers. The recurrence-free survival (RFS) of patients with any of the elevated biomarkers was analyzed by Kaplan-Meier curves and the log-rank test. Results: The GEE analysis indicated that PIVKA-II, AFP, AFP-L3 in the recurrence patients were higher than the no recurrence patients during follow-up, PIVKA-Ⅱ and AFP showed increasing trends from 6 months before recurrence. In predicting recurrence, the AUROCs for PIVKA-Ⅱ, AFP, AFP-L3 and their combination were 0.885, 0.754, 0.781 and 0.885 respectively, the optimal cut-off value for PIVKA-Ⅱ, AFP, AFP-L3 was 29.5 mAU/ml, 10.7 ng/L, 1.5 % respectively. The sensitivity in predicting recurrence for PIVKA-Ⅱ, AFP, AFP-L3 and combination were 75.0%, 54.7%, 57.8% and 79.7% respectively. The RFS of patients with any of the biomarkers elevated during the follow-up was significantly shorter than that without elevated biomarkers (χ2=62.125, PConclusion: Longitudinal surveillance of PIVKA-II, AFP and AFP-L3 can effectively predict recurrence of HCC after operation.

Background This study aimed to investigate the effect of matrix metalloproteinase-9 (MMP-9) copy number variations (CNVs) on hepatocellular carcinoma (HCC) poor prognosis and recurrence. Methods A total of 35 patients were collected between January 2016 and December 2018. The copy number and expression level of MMP-9 were measured in 35 HCC tumor tissues and 35 paired adjacent non-tumor tissues using digital polymerase chain reaction (dPCR) and quantitative reverse transcription polymerase chain reaction (RT-qPCR), respectively. Results Our results showed that MMP-9 expression was significantly upregulated in HCC tumor tissues compared to adjacent non-tumor tissues (5.521±9.545 versus 1.000±0.000, P=0.0047). Interestingly, MMP-9 CNVs only existed in tumor tissues (15/35 versus 0/35, P=0.002). A breakdown analysis by the occurrence of CNVs in tumor tissues had shown that there were significant differences between CNVs group and non-CNVs group in the expression levels of tissue alpha-fetoprotein (AFP) (P=0.015), tumor size (P

In this study, we aimed to develop a prognostic model to predict HCC early recurrence (within 1-year) in patients with microvascular invasion who received postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE).A total of 148 HCC patients with MVI who received PA-TACE were included in this study. The modes were verified in an internal validation cohort (n = 112) and an external cohort (n = 36). Univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factors relevant to early recurrence. A clinical nomogram prognostic model was established, and nomogram performance was assessed via internal validation and calibration curve statistics.After data dimensionality reduction and element selection, multivariate Cox regression analysis indicated that alpha fetoprotein level, systemic inflammation response index, alanine aminotransferase, tumour diameter and portal vein tumour thrombus were independent prognostic factors of HCC early recurrence in patients with MVI who underwent PA-TACE. Nomogram with independent factors was established and achieved a better concordance index of 0.765 (95% CI: 0.691-0.839) and 0.740 (95% CI: 0.583-0.898) for predicting early recurrence in training cohort and validation cohort, respectively. Time-dependent AUC indicated comparative stability and adequate discriminative ability of the model. The DCA revealed that the nomogram could augment net benefits and exhibited a wider range of threshold probabilities than AJCC T stage.The nomogram prognostic model showed adequate discriminative ability and high predictive accuracy.

To determine the risk factors for acute rejection in liver transplantation and its impact on the outcomes of the recipients.Clinicopathological data of 290 patients who underwent liver transplantation from January 2012 to December 2021 at our center were retrospectively evaluated. Patients were grouped into an acute rejection (AR) group and a normal (NM) group based on the confirmed histopathological diagnosis of acute rejection. Univariate and multivariate logistic regression were used to determine the risk factors for acute rejection.244 patients were included in the study. Acute rejection occurred in 27 (11.1%) of the patients. Warm ischemia time (P = 0.137), cold ischemia time (P = 0.064) and chronic liver failure (P = 0.001) were potential risk factors for acute rejection. Chronic liver failure (P 0.001, OR = 8.22, 95% CI = 2.47-27.32) was the independent risk factor. There was no significant difference in overall survival between recipients with acute rejection and those without it (P = 0.985). The 1-, 3- and 5-year overall survival in the NM group was 98.1%, 85.7% and 78.6% respectively vs 88.9%, 82.5% and 82.5% respectively in the AR group.Acute rejection does not appear to affect the long-term survival of the recipients. Only chronic liver failure was an independent risk factor for acute rejection. Our findings further illustrate that contradictions still exist on which factors influence acute rejection in liver transplant recipients.Clinicopathological data of 290 liver transplant recipients at our center between January 2012 and December 2021 were retrospectively evaluated to determine the risk factors for acute rejection and its impact on the outcomes of the recipients. 244 patients were included in the analysis. 27 of the 244 experienced acute rejection. Propensity score matching was performed to reduce the confounding effect. Patients were assigned to an acute rejection group (n = 27) and a normal group (n = 54). Chronic liver failure (P 0.001, OR = 8.22, 95% CI = 2.47-27.32) was the determined to be independent risk factor for acute rejection. Acute rejection did not appear to affect the long-term survival of the recipients and there was no significant difference in overall survival between the patients with acute rejection and those without it.

Shuqi Mao,1 Xi Yu,1 Yuying Shan,1 Rui Fan,2 Shengdong Wu,1 Caide Lu1 1Department of Hepatopancreatobiliary Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of China; 2Medical Quality Management Office, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of ChinaCorrespondence: Caide Lu; Shengdong WuDepartment of Hepatopancreatobiliary Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of ChinaTel +86 13957800900; +86 13567886669Email lucaide@nbu.edu.cn; 13567886669@139.comPurpose: In this study, we aimed to develop a novel liver function and inflammatory markers-based nomogram to predict recurrence-free survival (RFS) for AFP-negative (< 20 ng/mL) HCC patients after curative resection.Patients and Methods: A total of 166 pathologically confirmed AFP-negative HCC patients were included at the Ningbo Medical Center Lihuili Hospital. A LASSO regression analysis was used for data dimensionality reduction and element selection. Univariate and multivariate Cox regression analyses were performed to identify the independent risk factors relevant to RFS. Finally, clinical nomogram prediction model for RFS of HCC was established. Nomogram performance was assessed via internal validation and calibration curve statistics. Receiver operating characteristic (ROC) and decision curve analysis (DCA) curve were used to validate the performance and clinical utility of the nomogram.Results: Multivariate Cox regression analysis indicated that ALBI grade (hazard ratio, [HR] = 2.624, 95% confidence interval [CI]: 1.391– 4.949, P = 0.003), INR (HR = 2.605, 95% CI: 1.061– 6.396, P = 0.037), MLR (HR = 1.769, 95% CI: 1.073– 2.915, P = 0.025) and MVI (HR = 4.726, 95% CI: 2.365– 9.444, P < 0.001) were independent prognostic factors of RFS. Nomogram with independent factors was established and achieved a better concordance index of 0.753 (95% CI: 0.672– 0.834) for predicting RFS. The ROC found that the area under curve (AUC) was consistent with the C-index and the sensitivity was 85.4%. The risk score calculated by nomogram could divide AFP-negative HCC patients into high-, moderate- and low-risk groups (P < 0.05). DCA analysis revealed that the nomogram could augment net benefits and exhibited a wider range of threshold probabilities by the risk stratification than the AJCC T and BCLC stage in the prediction of AFP-negative HCC recurrence.Conclusion: The ALBI grade- and MLR-based nomogram prognostic model for RFS showed high predictive accuracy in AFP-negative HCC patients after surgical resection.Keywords: HCC, MLR, ALBI grade, AFP-negative, recurrence-free survival, nomogram

Background: The gap between the demand and supply of donor livers is still a considerable challenge. Since static cold storage is not sufficient in marginal livers, machine perfusion is being explored as an alternative. The objective of this study was to assess (dual) hypothermic oxygenated machine perfusion (HOPE/D-HOPE) and normothermic machine perfusion (NMP) in contrast to static cold storage (SCS). Methods: Three databases were searched to identify studies about machine perfusion. Graft and patient survival and postoperative complications were evaluated using the random effects model. Results: the incidence of biliary complications was lower in HOPE vs. SCS (OR: 0.59, 95% CI: 0.36–0.98, p = 0.04, I2: 0%). There was no significant difference in biliary complications between NMP and SCS (OR: 0.76, 95% CI: 0.41–1.40, p = 0.38, I2: 55%). Graft and patient survival were significantly better in HOPE than in SCS (HR: 0.40, 95% CI: 0.23–0.71, p = 0.002, I2: 0%) and (pooled HR: 0.43, 95% CI: 0.20–0.93, p = 0.03, I2: 0%). Graft and patient survival were not significantly different between NMP and SCS. Conclusion: HOPE/D-HOPE and NMP are promising alternatives to SCS for donor liver preservation. They may help address the widening gap between the demand for and availability of donor livers by enabling the rescue and transplantation of marginal livers.

Undifferentiated pancreatic carcinomas are rare malignant tumors of the pancreas that are very aggressive and challenging to diagnose. The WHO categorizes them into undifferentiated osteoclast-like giant cell, sarcomatoid, and rhabdoid pancreatic carcinomas. Patients present with nonspecific symptoms such as jaundice, vague abdominal or back pain and itchy skin. Their histological characteristics include positive pan-cytokeratin mononuclear pleomorphic cells, osteoclast-like giant cells and CD68. Patients may have KRAS, TP53 and SMAD4 alterations, homozygous deletions of CDKN2A and CDKN2B, as well as INI1 deficiency. Surgical resection is the only curative treatment. Patients may benefit from postoperative adjuvant therapy. There are no widely accepted guidelines specific to this type of tumor; however, some chemotherapy regimens may be promising. The patient prognosis is mostly poor, especially in patients with unresectable tumors. However, several studies have shown patients achieving long-term survival with adjuvant therapy. In conclusion, although undifferentiated pancreatic carcinoma is rare and very aggressive, there is still potential for improved patient survival with proper diagnosis and treatment.

The presence of microvascular invasion (MVI) is a critical determinant of early hepatocellular carcinoma (HCC) recurrence and prognosis. We developed a nomogram model integrating clinical laboratory examinations and radiological imaging results from our clinical database to predict microvascular invasion presence at preoperation in HCC patients. 242 patients with pathologically confirmed HCC at the Ningbo Medical Centre Lihuili Hospital from September 2015 to January 2021 were included in this study. Baseline clinical laboratory examinations and radiological imaging results were collected from our clinical database. LASSO regression analysis model was used to construct data dimensionality reduction and elements selection. Multivariate logistic regression analysis was performed to identify the independent risk factors associated with MVI and finally a nomogram for predicting MVI presence of HCC was established. Nomogram performance was assessed via internal validation and calibration curve statistics. Decision curve analysis (DCA) was conducted to determine the clinical usefulness of the nomogram model by quantifying the net benefits along with the increase in threshold probabilities. Survival analysis indicated that the probability of overall survival (OS) and recurrence-free survival (RFS) were significantly different between patients with MVI and without MVI (P 0.05). Histopathologically identified MVI was found in 117 of 242 patients (48.3%). The preoperative factors associated with MVI were large tumor diameter (OR = 1.271, 95%CI: 1.137-1.420, P 0.001), AFP level greater than 20 ng/mL (20-400 vs. ≤ 20, OR = 2.025, 95%CI: 1.056-3.885, P = 0.034; 400 vs. ≤ 20, OR = 3.281, 95%CI: 1.661-6.480, P = 0.001), total bilirubin level greater than 23 umol/l (OR = 2.247, 95%CI: 1.037-4.868, P = 0.040). Incorporating tumor diameter, AFP and TB, the nomogram achieved a better concordance index of 0.725 (95%CI: 0.661-0.788) in predicting MVI presence. Nomogram analysis showed that the total factor score ranged from 0 to 160, and the corresponding risk rate ranged from 0.20 to 0.90. The DCA showed that if the threshold probability was 5%, using the nomogram to diagnose MVI could acquire much more benefit. And the net benefit of the nomogram model was higher than single variable within 0.3-0.8 of threshold probability. In summary, the presence of MVI is an independent prognostic risk factor for RFS. The nomogram detailed here can preoperatively predict MVI presence in HCC patients. Using the nomogram model may constitute a usefully clinical tool to guide a rational and personalized subsequent therapeutic choice.

Background Inflammation plays a significant role in tumour development, progression, and metastasis. In this study, we focused on comparing the predictive potential of inflammatory markers for overall survival (OS), recurrence-free survival (RFS), and 1- and 2-year RFS in hepatocellular carcinoma (HCC) patients. Methods A total of 360 HCC patients were included in this study. A LASSO regression analysis model was used for data dimensionality reduction and element selection. Univariate and multivariate Cox regression analyses were performed to identify the independent risk factors for HCC prognosis. Nomogram prediction models were established and decision curve analysis (DCA) was conducted to determine the clinical utility of the nomogram model. Results Multivariate Cox regression analysis indicated that the prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR) were independent prognostic factors of OS, and aspartate aminotransferase-to-platelet ratio (APRI) was a common independent prognostic factor among RFS, 1-year RFS, and 2-year RFS. The systemic inflammation response index (SIRI) was an independent prognostic factor for 1-year RFS in HCC patients after curative resection. Nomograms established and achieved a better concordance index of 0.772(95% CI: 0.730-0.814), 0.774(95% CI: 0.734-0.815), 0.809(95% CI: 0.766-0.852), and 0.756(95% CI: 0.696-0.816) in predicting OS, RFS, 1-year RFS, and 2-year RFS respectively. The risk scores calculated by nomogram models divided HCC patients into high-, moderate- and low-risk groups (P < 0.05). DCA analysis revealed that the nomogram models could augment net benefits and exhibited a wider range of threshold probabilities in the prediction of HCC prognosis. Conclusions The nomograms showed high predictive accuracy for OS, RFS, 1-year RFS, and 2-year RFS in HCC patients after surgical resection. The nomograms could be useful clinical tools to guide a rational and personalized treatment approach and prognosis judgement.

PurposeImmune checkpoint inhibitor therapy has shown promising results in patients with unresectable hepatocellular carcinoma. This study aimed to evaluate the effectiveness and safety of sintilimab, a programmed cell death protein-1 (PD-1) blockade, combined with sorafenib and transhepatic arterial chemotherapy and embolization in this patient population, compared with sintilimab monotherapy and sintilimab-sorafenib duotherapy.MethodsThis was a 22 months single center retrospective cohort study in China. 80 patients with unresectable hepatocellular carcinoma were included, with diagnosis confirmed by either histologic, cytologic or diagnostic imaging analysis. The patients were divided into three groups based on therapeutic regimen: sintilimab monotherapy (sintilimab group, n=22), sintilimab-sorafenib duotherapy (duplex group, n=23), sintilimab-sorafenib and transcatheter arterial chemoembolization combined therapy (triple group, n=35). The principal evaluation criteria were overall survival and progression free survival in the intention-to-treat population, assessed according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). Furthermore, safety, objective response rate, disease control rate and so on were analyzed.ResultsFrom March 1st, 2019 to December 31, 2020, 80 intend-to-treat patients with unresectable hepatocellular carcinoma were included into three treatment groups (22 received sintilimab monotherapy, 23 received sintilimab-sorafenib duotherapy, and 35 received sintilimab-sorafenib combined with transcatheter arterial chemoembolization). The median overall survival of all patients was 11.0 months (95% CI, 7.7-14.3). Median overall survival was 13.0 months (95% CI, NE-NE), 9.0 months（95% CI，6.3-11.7）and 3.0 months (95% CI，1.9-4.1, p < 0.0001) in the triple therapy, duplex and sintilimab groups respectively, while the corresponding median progression-free survival were 5.0 months (95% CI，2.9-7.1 , p < 0.001), 4.0 months (95% CI，2.8-5.2) and 2.0 months (95% CI，1.7-2.3). Disease control and clinical benefits rates were higher in the triple therapy group (80%, 95% CI, 63.1-91.6, p < 0.001; 54.3%, 95% CI, 36.6-71.2, p < 0.01) compared to the sintilimab group. Median duration of disease control was 4.0 months (95% CI, NE-NE, p < 0.01) in the triple therapy group, longer than that of the duplex group (2.0 months, 95% CI, 0.9-3.1) and sintilimab group (2.0 months, 95% CI, 0.8-3.2). Grade 3 or 4 treatment-related adverse events occurred in 26.3% of 80 patients with hypertension was the most common event observed (38, 47.5%), however, other severe toxic effects were infrequent. ConclusionsSintilimab combined with sorafenib and transcatheter arterial chemoembolization might have more beneficial effects on overall and progression-free survival and on the duration of disease control outcomes than both sintilimab monotherapy and sintilimab-sorafenib duotherapy in patients with unresectable hepatocellular carcinoma. This triple therapy model might represent an innovative and effective option for inoperable liver cancer.

Background: Recombinase-aided amplification(RAA) is a new, simple, and ultrafast isothermal molecular diagnostic technique performed within 30min at 39°C–42°C.In this study, we evaluated the clinical performance of four duplex RAA kits for hepatitis B virus(HBV), human adenovirus 3(HAdV3), human adenovirus 7(HAdV7), and Bordetella pertussis and one duplex reverse-transcription RAA (RT-RAA) kit for respiratory syncytial virus (RSV).Methods: A total of 392 sera and 374 respiratory tract samples were collected from five institutions in four China regions. Each RAA kit’s sensitivity and specificity were compared with those of real-time quantitative polymerase chain reaction(qPCR),real-time quantitative reverse-transcription polymerase chain reaction(qRT-PCR), or sequencing. Results: Compared with qPCR or qRT-PCR, the sensitivities of HBV RAA,RSV RT-RAA, and B.pertussis RAA were 97.55%,96.67%, and 100%,respectively,and all of the specificities were 100%.The total coincidence rates were 97.78%(383/392,95%CI:95.63%–98.85%),97.70%(212/217, 95%CI:94.57%–99.16%), and 100%(60/60,95%CI:92.80%–100%),respectively. The Kappa values were 0.977,0.947, and 1,respectively(PConclusions: With comparable clinical performance, these RAA kits are suitable assays for rapidly detecting pathogens in resource-limited laboratories.

Background Laparoscopic distal pancreatosplenectomy is an effective and safe surgical modality for treating benign and borderline distal pancreatic tumors, but rarely for pancreatic cancer. This study aimed to compare the feasibility and safety of laparoscopic and open radical antegrade modular pancreatosplenectomy for pancreatic cancer. Methods Fifty-one patients with pancreatic cancer who underwent radical antegrade modular pancreatosplenectomy at Ningbo Medical Center Lihuili Hospital between January 2014 and July 2018 were enrolled. 20 patients underwent laparoscopic radical antegrade modular pancreatosplenectomy and 31 patients received open radical antegrade modular pancreatosplenectomy. Postoperative and short-term outcomes of the two groups of patients were analyzed. Results The mean operation time, length of postoperative hospital stay, and overall postoperative morbidity were similar in the two groups (P>0.05). The laparoscopic radical antegrade modular pancreatosplenectomy group lost less blood (252.5±198.3 vs. 472.6±428.0 mL, P=0.037) and had lower transfusion rates (10.0% vs. 35.4%, P=0.041) than the open radical antegrade modular pancreatosplenectomy group. The laparoscopic group also had statistically significantly earlier passing of first flatus (2.5±0.8 vs. 3.2±1.2 days, P=0.028) and first oral intake (2.9±1.0 vs. 3.7±1.6 days, P=0.042). Furthermore, the rates of postoperative pancreatic fistula (45.0% vs. 32.3%) and overall complications (70.0% vs. 74.2%) were not statistically difference between the two groups. The survival rates at 6 months, 1 year, and 2 years after surgery were not statistically difference between the laparoscopic and open groups (94.4% vs. 93.5, 67.0% vs. 78.0%, and 50.2% vs. 38.3%, respectively). Conclusions The results of this study show that laparoscopic radical antegrade modular pancreatosplenectomy is feasible and safe for the treatment of pancreatic cancer.

Intestinal epithelial barrier disruption and bacterial translocation exacerbates the progression of alcoholic liver disease. Lactobacillus rhamnosus GG (LGG), a probiotic, has been shown benefits in chronic liver disease and in regulating gut dysbiosis. Previous studies showed the protective roles of LGG in ethanol-disrupted gut barrier functions and liver injury. Inosine, a metabolite produced by intestinal bacteria, has the anti-inflammatory and immunregulatory functions. In this study, the synergistic effect of LGG and inosine was investigated in a mouse model of alcohol-induced liver disease (ALD).Male C57BL/6 mice were fed with a Lieber-DeCarli diet containing 5% alcohol for four weeks to establish a model of alcohol-induced liver injury. LGG or a combination of LGG and inosine were administrated orally to explore a new therapeutic method for alcohol-induced liver disease and to investigate the underlying mechanisms. Liver damage was evaluated by transaminases and pathological changes. Tight junction proteins, composition of the gut microbiome, cytokines, lipopolysaccharides (LPS), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), F4/80+ macrophages, as well as p38, Jun N-terminal kinase (JNK), were determined by qRT-PCR, RNAseq, ELISA, IHC and western blot. Regulatory T (Treg) cells were characterized by positive staining of CD4, CD25 and Foxp3 using flow cytometry. IFN-γ-producing CD4Alcohol consumption induced elevated liver enzymes, steatosis and inflammation, while LGG combined with inosine treatment was more significant to ameliorate these symptoms compared with LGG alone. When LGG combined with inosine were administered to ALD mice, intestinal microecology significantly improved reflected by intestinal villi and tight junction proteins recovery and the restoration of intestinal flora. Combined therapy inhibited phosphorylation of p38 and JNK to alleviate hepatic inflammation. Moreover, flow cytometry analysis showed that long-term excessive alcohol consumption reduced Tregs population while increased Th1 population, which was restored by a combination of LGG and inosine treatment.The findings from the study indicate that the combined LGG and inosine treatment ameliorates ALD by improving the gut ecosystem, intestinal barrier function, immune homeostasis and liver injury.

Early diagnosis of pancreatic cancer, one of the most deadly cancers with low survival rates, is difficult, and effective biomarkers are urgently needed. Lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) has been recently proposed as a potential tumor suppressor gene in several types of cancer. Here, we analyzed the biological function of LITAF in pancreatic cancer. The LITAF gene and protein levels were decreased in pancreatic tumor tissues compared with their paired adjacent non-cancerous tissues. In addition, patients with the lower LITAF protein expression had lower disease-free survival rates. The decreased LITAF expression correlated with LITAF promoter hypermethylation in pancreatic cancer cells and tissues. Moreover, promoter demethylation dose-dependently increased the LITAF transcription. Importantly, LITAF demethylation suppressed proliferation and cell cycle progression, and enhanced apoptosis of pancreatic cancer cells. Together, our results indicate that LITAF functions as a tumor suppressor gene in pancreatic cancer cells, and might serve as a novel biomarker for early diagnosis of pancreatic cancer.

Introduction SMARCB1/INI1 gene deletion appears to be associated with a rare, malignant and aggressive form of pancreatic carcinoma whose diagnosis is challenging. Our objective is to illustrate that the tumor may masquerade as a duodenal papillary carcinoma, be difficulty to identify on diagnostic imaging and that making an accurate diagnosis may be challenging, however surgical resection may be possible. Case report We present a case of a 24-year old male patient presenting with jaundice and itchy skin, elevated TBIL, AST, ALP and CA125. A 2.2 × 1.7 cm pancreatic nodule, later diagnosed as a SMARCB1/INI deficient pancreatic carcinoma was detected on Endoscopic Ultrasound - Fine Needle Aspiration (EUS-FNA). The patient was successfully treated with extended pancreato-duodenectomy coupled with adjuvant chemotherapy, a 7 × 5 × 5 cm tumor resected. Discussion SMARCB1/INI deficient pancreatic carcinoma has been reported in couple of other articles. However, unlike other cases, in our case identification and accurate assessment of the tumor was particularly difficulty both on imaging and during operation. Our patient has thus far had a positive outcome with no recurrence. Conclusion For rare forms of pancreatic carcinoma, identification and assessment of the tumor size may be challenging on imaging and during operation. However, careful assessment should be performed before ruling out surgical resection. Furthermore, adjuvant chemotherapy may be beneficial to the patient., Highlights • SMARCB1/INI gene deletion is associated with undifferentiated carcinoma characterized by malignancy and aggressiveness. • This case highlights the ambiguity in manifestation and diagnosis of SMARCB1 pancreatic carcinoma. • Assessment and accurate determination of the tumor size may not be possible on imaging and preoperatively. • Adjuvant chemotherapy may be beneficial to patient prognosis post-surgery.

Objectives Chlorogenic acid (CGA) is one of the most widely consumed polyphenols in diets and is recognized to be a natural hepatoprotective agent. Here, we evaluated the protective effect and the potential mechanism of CGA against ɑ-naphthylisothiocyanate (ANIT)-induced cholestasis and liver injury. Methods Twenty-five male 129/Sv mice were administered with CGA, and ANIT challenge was performed at 75 mg/kg on the 4th day. Blood was collected and subjected to biochemical analysis; the liver tissues were examined using histopathological analysis and signalling pathways. Key findings Chlorogenic acid almost totally attenuated the ANIT-induced liver damage and cholestasis, compared with the ANIT group. Dose of 50 mg/kg of CGA significantly prevented ANIT-induced changes in serum levels of alanine aminotransferase, alkaline phosphatases, total bile acid, direct bilirubin, indirect bilirubin (5.3-, 6.3-, 18.8-, 158-, 41.4-fold, P Conclusions These data suggest that CGA inhibits both ANIT-induced intrahepatic cholestasis and the liver injury. This protective effect involves down-regulation of STAT3 and NFκB signalling.

Animal models are indispensable for the study of tumorigenesis and the development of anti-cancer drugs for human pancreatic cancer. In the present study, two orthotopic xenograft mouse models were developed. AsPC-1 human pancreatic cancer cells were stably labeled with red fluorescent protein (RFP) and injected subcutaneously into nude mice. For the orthotopic tumor mass model, the formed subcutaneous tumors were cut into blocks and implanted into the pancreas of nude mice via laparotomy. For the Matrigel™ tumor block model, solidified Matrigel containing RFP-labeled AsPC-1 cells was cut into blocks and implanted into the pancreas of nude mice. A subcutaneous tumor xenograft model was used as a control. Tumor growth and metastasis were assessed using an in vivo fluorescence imaging system. Thirty-six days after implantation, all mice from the two orthotopic xenograft models (n=20 per group) and 55% of the subcutaneous xenograft mice (n=20) developed tumors. The tumor growth rate was significantly higher in the orthotopic models than that in the subcutaneous model (P

To investigate the value and safety of the surgery with vascular resection and reconstruction during pancreatectomy for pancreatic cancer.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.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 P0.01). 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(P0.05), non-vascular resection group and combined arterial resection group(P0.05), as well as between combined vein resection group and combined arterial resection group(P0.05). 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 P0.05). The postoperative mortality was nil for all of groups.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.

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.

BACKGROUND Angiogenesis is essential for the growth of solid tumors. Intratumoral microvessel count, which represents a measure of tumor angiogenesis, has been associated with the overall survival of patients with a variety of malignancies. However, little is known about the significance of neovascularization in esophageal squamous cell carcinoma. METHODS In this study, the role of tumor angiogenesis as a prognostic indicator was examined in esophageal squamous cell carcinomas from 43 patients. Vascular endothelial cells were stained with anti-CD34 and anti-von Willebrand factor monoclonal antibodies before being quantitated by light microscopy (× 200). RESULTS Significant correlation between vessel counts for two antibodies was observed, although counts for CD34 were approximately three times higher. Intratumoral vessel counts were significantly higher in tumors with deeper penetration. Multivariate analyses indicated that vessel counts determined by either CD34 or von Willebrand factor staining, as well as lymph node metastasis, were identified as significant and independent prognostic factors in patients with esophageal squamous cell carcinoma. CONCLUSIONS These findings support the hypothesis that tumor angiogenesis is closely related to the overall survival of patients with esophageal squamous cell carcinoma. The extent of tumor vascularity may serve as a reliable prognostic marker with which patients at risk for recurrence can be identified. Cancer 1997; 79:220-5. © 1997 American Cancer Society.

Lymphotoxin-alpha (LTA) polymorphism rs909253 has been reported to be a risk factor for cancers, but some results are inconsistent. To establish a more conclusive association, we performed a meta-analysis of this variant with cancers. A systematic search was performed for informative case–control studies of rs909253 with cancers among literature databases, including PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Chinese Periodical Database. After a comprehensive filtration procedure, 36 publications involved with 35,677 participants were selected for the current meta-analysis. Stratified factors, such as cancer type, populations, and source of control, were used for a better interpretation of this variant. Minimal heterogeneity was shown in the current meta-analysis (I 2 = 0.0 %, P = 0.48). Our results show a significant association of rs909253 and cancer risk (odds ratio (OR) = 1.12, P (z)