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Robotic pancreaticoduodenectomy (RPD) has been reported to be safe and feasible for patients with pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head. This study aimed to analyze the surgical outcomes and risk factors for poor long-term prognosis of these patients.Data from patients who underwent RPD for PDAC of pancreatic head were retrospectively analyzed. Multivariate Cox regression analysis was used to seek the independent prognostic factors for overall survival (OS), and an online nomogram calculator was developed based on the independent prognostic factors.Of the 273 patients who met the inclusion criteria, the median operative time was 280.0 minutes, the estimated blood loss was 100.0 mL, the median OS was 23.6 months, and the median recurrence-free survival (RFS) was 14.4 months. Multivariate analysis showed that preoperative carbohydrate antigen 19-9 (CA19-9) [hazard ratio (HR) = 2.607, 95% confidence interval (CI): 1.560-4.354, P 0.001], lymph node metastasis (HR = 1.429, 95% CI: 1.005-2.034, P = 0.047), tumor moderately (HR = 3.190, 95% CI: 1.813-5.614, P 0.001) or poorly differentiated (HR = 5.114, 95% CI: 2.839-9.212, P 0.001), and Clavien-Dindo grade ≥ III (HR = 1.657, 95% CI: 1.079-2.546, P == 0.021) were independent prognostic factors for OS. The concordance index (C-index) of the nomogram constructed based on the above four independent prognostic factors was 0.685 (95% CI: 0.640-0.729), which was significantly higher than that of the AJCC staging (8th edition): 0.541 (95% CI: 0.493-0.589) (P 0.001).This large-scale study indicated that RPD was feasible for PDAC of pancreatic head. Preoperative CA19-9, lymph node metastasis, tumor poorly differentiated, and Clavien-Dindo grade ≥ III were independent prognostic factors for OS. The online nomogram calculator could predict the OS of these patients in a simple and convenient manner.

The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) remains poor even after radical pancreaticoduodenectomy (PD). The study aimed to develop and validate a novel preoperative prognostic model to accurately predict the long-term survival of patients with PDAC.Patients with PDAC of pancreatic head from Chinese PLA General Hospital were included. The preoperative PDAC model with contour plots was developed using a non-linear model in the training cohort and then tested in the validation cohort.Of 421 patients who met the inclusion criteria, 280 were in the training cohort and 141 in the validation cohort. Contour plots for preoperative PDAC model were established to visually predict the survival probabilities of these patients, based on preoperative carbohydrate antigen 19-9, preoperative fibrinogen to albumin ratio and pain symptoms. This model stratified patients into low- and high-risk groups with distinctly different long-term survival in the training cohort [median overall survival (OS) 32.1 vs. 17.5 months; median recurrence-free survival (RFS) 19.3 vs. 10.0 months, both P0.001] and the validation cohort (median OS 28.3 vs. 19.0 months; median RFS 17.5 vs. 11.2 months, both P0.001). Time-dependent receiver operating characteristic and decision curve analyses revealed that the model provided higher diagnostic accuracy and superior net benefit compared to other staging systems.This study constructed and validated a novel preoperative prognostic model that can accurately and conveniently predict the long-term survival of patients with resectable PDAC of pancreatic head. Besides, the model can screen high-risk patients with poor prognosis, which may provide references for personal treatment strategies in the future.

Establishing a stoke experimental model, which is better in line with the physiology and function of human brain, is the bottleneck for the development of effective anti-stroke drugs. A three-dimensional cerebral organoids (COs) from human pluripotent stem cells can mimic cell composition, cortical structure, brain neural connectivity and epigenetic genomics of in-vivo human brain, which provides a promising application in establishing humanized ischemic stroke model. COs have been used for modeling low oxygen condition-induced hypoxic injury, but there is no report on the changes of COs in response to in vitro oxygen-glucose deprivation (OGD)-induced damage of ischemic stroke as well as its application in testing anti-stroke drugs. In this study we compared the cell composition of COs at different culture time and explored the cell types, cell ratios and volume size of COs at 85 days (85 d-CO). The 85 d-CO with diameter more than 2 mm was chosen for establishing humanized ischemic stroke model of OGD. By determining the time-injury relationship of the model, we observed aggravated ischemic injury of COs with OGD exposure time, obtaining first-hand evidence for the damage degree of COs under different OGD condition. The sensitivity of the model to ischemic injury and related treatment was validated by the proven pan-Caspase inhibitor Z-VAD-FMK (20 μM) and Bcl-2 inhibitor navitoclax (0.5 μM). Neuroprotective agents edaravone, butylphthalide, P7C3-A20 and ZL006 (10 μM for each) exerted similar beneficial effects in this model. Taken together, this study establishes a humanized ischemic stroke model based on COs, and provides evidence as a new research platform for anti-stroke drug development.

The supplementary infomation containing Figure legends, five supplemental figures and 3 supplemental tables. Figure S1 The higher expression of hPCL3s correlated with the poor survival of HCC patients. Figure S2 hPCL3s did not promote the tumorigenesis in vivo. Figure S3 The effects of hPCL3s on the growth of Hep3B, Huh7 and PVTT cells in a 48-hour time window were evaluated using MTT assay. Figure S4 Screening the signal pathways affected by hPCL3s. Figure S5 The AAV delivered Flag-hPCL3s was dominantly expressed in the liver. Table S1 Primer sequences. Table S2 The correlation between the expression of hPCL3s and clinical feature (Tissue array 2). Table S3 Microarray data.

Two isoforms of human Polycomb-like protein 3 (hPCL3) have been reported as components of the nuclear Polycomb repressive complex 2 (PRC2), with the short isoform (hPCL3s) showing a dominant cytoplasmic localization. The function of cytoplasmic hPCL3s has, however, not been addressed. In this study, we report that hPCL3s is upregulated in clinical hepatocellular carcinoma (HCC) samples and its expression correlated with HCC clinical features. hPCL3s positively regulated the migration, invasion, and metastasis of HCC cells. hPCL3s interacted with components of the cytoplasmic β-catenin destruction complex, inhibited β-catenin degradation, and activated β-catenin/T-cell factor signaling. Downstream of the β-catenin cascade, IL6 mediated the motility-promoting functions of hPCL3s. Forced expression of hPCL3s in the liver of a HCC mouse model promoted tumorigenesis and metastasis. Taken together, these data show that hPCL3s promotes the metastasis of HCC by activating the β-catenin/IL6 pathway.Significance: hPCL3s has an oncogenic role in hepatocellular carcinoma by activating the β-catenin/IL6 signaling axis to promote metastasis. Cancer Res; 78(10); 2536–49. ©2018 AACR.

Background The presence of hepatic vein tumor thrombus (HVTT) is a major determinant of survival outcomes in hepatocellular carcinoma (HCC) patients. This study compared survival outcomes between liver resection (LR) and intensity-modulated radiation therapy (IMRT) in HCC patients with HVTT. Methods Data from patients who underwent LR or IMRT for HCC with HVTT at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. Their survival outcomes were compared before and after propensity score matching (PSM). Results Three hundred and seven HCC patients with HVTT who underwent either LR (n=140) or IMRT (n=167) were enrolled. PSM matched 82 pairs of patients. The overall survival (OS) and recurrence-free survival (RFS) rates were significantly higher for patients in the LR group than those in the IMRT group. On subgroup analysis, significantly better survival outcomes were obtained after LR than IMRT in patients with peripheral type of HVTT (pHVTT) and major type of HVTT (mHVTT). However, similar survival outcomes were obtained after LR and IMRT when the HVTT had developed into inferior vena cava tumor thrombus (IVCTT). Conclusions LR resulted in significantly better survival outcomes in HCC patients with HVTT when compared to IMRT. Once the HVTT had developed IVCTT, LR and IMRT resulted in similarly bad survival outcomes.

The technical complexity of robotic pancreaticoduodenectomy (RPD) and lack of technical surgical standardization have slowed its widespread application. RPD is only routinely performed in a few highly specialized centers. This study describes in detail the standard steps and core techniques of an experienced robotic center in China. We took advantage of our single experience to provide a step-by-step technique and surgical video of our RPD standardized procedure. We divided RPD into 18 key steps. Demographics and perioperative outcomes of consecutive 20 patients who underwent the RPD standardized procedure were analyzed. For the 20 consecutive patients, the mean operative time was 253.6 min, and the median estimated blood loss was 210.0 mL. One patient required conversion to laparotomy due to the need for PV reconstruction. One patient had grade 3 complication. The median postoperative hospital stay was 11.0 days. No 90-day mortality was observed. By simplifying and optimizing the surgical techniques, the RPD procedure can be standardized and modeled to improve feasibility and repeatability.

Pancreatic ductal adenocarcinoma (PDAC) is prone to relapse even after radical pancreaticoduodenectomy (PD) (including robotic, laparoscopic and open approach). This study aimed to develop an online nomogram calculator to predict early recurrence (ER) (within one year after surgery) and long-term survival in patients with PDAC.Patients with PDAC after radical PD were included. Univariate and multivariate logistic regression analysis was used to identify independent risk factors. An online nomogram calculator was developed based on independent risk factors in the training cohort and then tested in the internal and external validation cohorts.Of the 569 patients who met the inclusion criteria, 310, 155, and 104 patients were in the training, internal and external validation cohorts, respectively. Multivariate analysis revealed that preoperative carbohydrate antigen19-9 (CA19-9) [Odds Ratio (OR) 1.002; 95% confidence interval (CI) 1.001-1.003; P = 0.001], fibrinogen/albumin (FAR) (OR 1.132; 95% CI 1.012-1.266; P = 0.029), N stage (OR 2.291; 95% CI 1.283-4.092; P = 0.005), and tumor differentiation (OR 3.321; 95% CI 1.278-8.631; P = 0.014) were independent risk factors for ER. Nomogram based on the above four factors achieved good C-statistics of 0.772, 0.767 and 0.765 in predicting ER in the training, internal and external validation cohorts, respectively. Time-dependent ROC analysis (timeROC) and decision curve analysis (DCA) revealed that the nomogram provided superior diagnostic capacity and net benefit compared with other staging systems.This multi-center study developed and validated an online nomogram calculator that can predict ER and long-term survival in patients with PDAC with high degrees of stability and accuracy.

Microvascular invasion (MVI) is a risk factor for postoperative survival outcomes for hepatocellular carcinoma (HCC) after liver resection (LR). This study aims to investigate the actual long-term survival and its associated prognostic factors after LR for HCC patients with MVI. This study was conducted on HCC patients with MVI who underwent LR from January 2009 to December 2012 at five major hospitals in China. The patients were divided into the ‘long-term survivor group’ and the ‘short-term survivor group’. The clinicopathologic characteristics, perioperative data and survival outcomes were compared between these two groups. Univariate and multivariate regression analyses were performed to identify predictive factors associated with long-term survival outcomes. The study included 1517 patients with an actual 5-year survival rate of 33.3%. Multivariate regression analysis revealed that HBV DNA > 104 IU/mL, alanine aminotransferase > 44 U/L, alpha-fetoprotein > 400 ng/ml, anatomical hepatectomy, varices, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor number, satellite nodules, tumor encapsulation, wide resection margin and adjuvant transarterial chemoembolization (TACE) were independent prognostic factors associated with actual long-term survival. One-third of HCC patients with MVI reached the long-term survival milestone of 5 years after resection. Anatomical hepatectomy, controlling intraoperative blood loss, a wide resection margin, and postoperative adjuvant TACE should be considered for patients to achieve better long-term survival outcomes.

This study aims to investigate the expressions of matrix metalloproteinase-9 (MMP-9), estrogen receptor (ER), and progesterone receptor (PR) in thin endometrium.Patients who received treatment in our hospital between January 2018 and September 2020 were enrolled. Endometrial thickness was measured using transvaginal ultrasound; in patients with a midluteal phase endometrial thickness of7 mm, a sample of endometrial tissue was obtained using a hysteroscope, and the MMP-9, ER, and PR expressions were detected using immunohistochemistry. In addition, the number of endometrial glands was calculated in a complete field of view under a low-power (100×) microscope, and the serum estrogen and progesterone levels were determined. Following hormone therapy, the midluteal phase endometrial thickness was measured again using transvaginal ultrasound, and the patients were divided into two groups: the thin endometrium group and the normal endometrium group (The number of endometrial glands as well as the ER and MMP-9 expressions were lower in the thin endometrium group than in the normal endometrium group; the differences were statistically significant (Compared with other patients with thin endometrium, patients with refractory thin endometrium had a reduced the number of endometrial glands and significantly lower ER and MMP-9 expressions.

Monodispersed Fe3O4 magnetic particles adsorbed by amylase (such as citric acid (CA), carboxymethyl chitosan (CMCH) and β-cyclodextrin (CD)) were prepared by means of co-precipitation method. The absorption character of the samples was investigated by FT-IR, TG and VSM. It was found that the carboxyl (COOH groups) of amylase reacted with the hydroxyl (OH groups) on the surface of Fe3O4 particles, resulting in the formation of iron carboxylate that was adsorbed onto Fe3O4. The induction heating properties of the magnetic Fe3O4 nanoparticles in an alternating current magnetic field were also investigated and the thermo-magnetic stability in induction heating was discussed.

Pancreatoduodenectomy is the only potentially curative treatment for distal cholangiocarcinoma (DCC). In this study, we sought to compare the perioperative and oncological outcomes of robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD) based on a multicenter propensity score-matched study.Consecutive patients with DCC who underwent RPD or OPD from five centers in China between January 2014 and June 2019 were included. A 1:1 propensity score matching (PSM) was performed. Univariable and multivariable Cox regression analyses were used to identify independent prognosis factors for overall survival (OS) and recurrence-free survival (RFS) of these patients.A total of 217 patients and 228 patients underwent RPD and OPD, respectively. After PSM, 180 patients in each group were enrolled. There were no significant differences in operative time, lymph node harvest, intraoperative transfusion, vascular resection, R0 resection, postoperative major morbidity, reoperation, 90-day mortality, and long-term survival between the two groups before and after PSM. Whereas, compared with the OPD group, the RPD group had significantly lower estimated blood loss (150.0 ml vs. 250.0 ml; P 0.001), and a shorter postoperative length of stay (LOS) (12.0 days vs. 15.0 days; P 0.001). Multivariable analysis showed carbohydrate antigen 19-9 (CA19-9), R0 resection, N stage, perineural invasion, and tumor differentiation significantly associated with OS and RFS of these patients.RPD was comparable to OPD in feasibility and safety. For patients with DCC, RPD resulted in similar oncologic and survival outcomes as OPD.

Robotic liver resection (RLR) has increasingly been accepted as it has overcome some of the limitations of open liver resection (OLR), while the outcomes following RLR in elderly patients with hepatocellular carcinoma (HCC) are still uncertain. This study aimed to evaluate the short and long-term outcomes of RLR vs. OLR in elderly HCC patients.Perioperative data of elderly patients (≥ 65 years) with HCC who underwent RLR or OLR between January 2010 and December 2020 were retrospectively analyzed. A 1:2 propensity score-matched (PSM) analysis was performed to minimize the differences between RLR and OLR groups. Univariable and multivariable Cox regression analyses were used to identify independent prognosis factors for overall survival (OS) and recurrence-free survival (RFS) of these patients.Of the 427 elderly HCC patients included in this study, 113 underwent RLR and 314 underwent OLR. After the 1:2 PSM, there were 100 and 178 patients in the RLR and the OLR groups, respectively. The RLR group had a less estimated blood loss (EBL), a shorter postoperative length of stay (LOS), and a lower complications rate (all P 0.05), compared with the OLR group before and after PSM. Univariable and multivariable analyses showed that advanced age and surgical approaches were not independent risk factors for long-term prognosis. The two groups of elderly patients who were performed RLR or OLR had similar OS (median OS 52.8 vs. 57.6 months) and RFS (median RFS 20.4 vs. 24.6 months) rates after PSM.RLR was comparable to OLR in feasibility and safety. For elderly patients with HCC, RLR resulted in similar oncologic and survival outcomes as OLR.

Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported. A nationwide database of HCC patients with PVTT who underwent liver resection with ‘curative’ intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes. The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 μmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (

Background Microvascular invasion (MVI) is a major determinant of survival outcome for hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy of postoperative adjuvant Sorafenib (PA-Sorafenib) in HCC patients with MVI after R0 liver resection (LR). Methods The data of patients who underwent R0 LR for HCC with histologically confirmed MVI at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-Sorafenib were compared with those who underwent R0 LR alone. Propensity score matching (PSM) analysis was performed. Results 728 HCC patients had MVI in the resected specimens after R0 resection, with 581 who underwent LR alone and 147 patients who received in additional adjuvant sorafenib. PSM matched 113 patients in each of these two groups. The overall survival (OS) and recurrence free survival (RFS) were significantly better for patients in the PA-sorafenib group (for OS: before PSM, P = 0.003; after PSM, P = 0.007), (for RFS: before PSM, P = 0.029; after PSM, P = 0.001), respectively. Similar results were obtained in patients with BCLC 0-A, BCLC B and Child-Pugh A stages of disease. Conclusions PA-Sorafenib was associated with significantly better survival outcomes than LR alone for HCC patients with MVI.

Aims To investigate the impact of postoperative intensity modulated radiation therapy (IMRT) in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) after partial hepatectomy +/− thrombectomy. Methods From July 2013 to June 2016, consecutive patients with HCC and PVTT who underwent partial hepatectomy were randomly assigned to 2 groups: a control group and an adjuvant IMRT group. Survival outcomes in the 2 groups were studied. Results The 52 patients in this study were equally randomized into 2 groups with comparable clinicopathological data. The median disease-free survival (DFS) and overall survival (OS) were 9.1 ± 1.6 months, 18.9 ± 1.8 months for the adjuvant RT group and 4.1 ± 0.5 months, 10.8 ± 1.3 months for the control group, respectively. The 1-, 2- and 3-years overall survival rates were significantly better in the adjuvant IMRT group (76.9%, 19.2%, and 11.5%; respectively) than the control group (26.9%, 11.5% and 0%, respectively; p = 0.005). Conclusions Postoperative IMRT significantly improved the overall survival outcomes in patients with HCC and PVTT after partial hepatectomy +/− thrombectomy.

The benefits of adjuvant transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remain controversial. We compared the efficacy and safety of adjuvant TACE and hepatic resection (HR) alone for HCC patients with MVI.The PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched to compare adjuvant TACE and HR alone for the treatment of HCC with MVI from inception to January 1, 2019. The study outcomes, including overall survival (OS) and disease-free survival (DFS), were extracted independently by two authors.12 trials involving 2190 patients were evaluated. A meta-analysis of 11 studies suggested that the 1-, 3-, and 5-year overall survival (OS) rates (OR = 0.33, P 0.001; OR = 0.49, P 0.001; and OR = 0.59, P 0.01; respectively), favored adjuvant TACE over HR alone. 11 studies were included in the meta-analysis of DFS, and adjuvant TACE showed better 1-, 3-, and 5-DFS (OR = 0.45, P 0.001; OR = 0.50, P 0.001; and OR = 0.58, P 0.001; respectively) compared to HR alone. Subgroup analysis demonstrated that adjuvant TACE could benefit HCC patients with MVI with tumor diameter5 cm or multinodular tumors.Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI. However, these results need to be validated through further high-quality clinical studies.The benefits of adjuvant TACE in HCC patients with microvascular invasion remain controversial. Twelve studies involving 2190 patients were include in our meta-analysis. Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI.

Microvascular invasion (MVI) is a significant risk factor affecting survival outcomes of patients after R0 liver resection (LR) for hepatocellular carcinoma (HCC). The current classification of MVI is not refined enough to prognosticate long-term survival of these patients, and a new MVI classification is needed.Patients with HCC who underwent R0 LR at the Eastern Hepatobiliary Surgery Hospital from January 2013 to December 2013 and with resected specimens showing MVI were included in this study with an aim to establish a novel MVI classification. The classification which was developed using multivariate cox regression analysis was externally validated.There were 180 patients in the derivation cohort and 131 patients in the external validation cohort. The following factors were used for scoring: α-fetoprotein level (AFP), liver cirrhosis, tumor number, tumor diameter, MVI number, and distance between MVI and HCC. Three classes of patients could be distinguished by using the total score: class A, ≤3 points; class B, 3.5-5 points and class C,5 points with distinct long-term survival outcomes (median recurrence free survival (mRFS), 22.6, 10.2, and 1.9 months, P 0.001). The predictive accuracy of this classification was more accurate than the other commonly used classifications for HCC patients with MVI. In addition, the mRFS of class C patients was significantly prolonged (1.9 months vs. 6.2 months, P 0.001) after adjuvant transcatheter arterial chemoembolization (TACE).A novel MVI classification was established in predicting prognosis of HCC patients with MVI after R0 LR. Adjuvant TACE was useful for class C patients.

Patients with distal cholangiocarcinoma (DCC) are prone to relapse even after radical pancreaticoduodenectomy. In this study, we sought to create an online nomogram calculator to accurately predict the recurrence risk of DCC.A total of 184 patients were included. Multivariate Cox regression analysis was used to identify independent prognosis factors for recurrence-free survival and overall survival. A nomogram was constructed according to the prognostic factors in the training cohort and then tested in the validation cohort.Multivariate Cox analysis showed preoperative carbohydrate antigen 19-9 (p 0.001), maximum tumor size (p = 0.076), perineural invasion (p = 0.044), and N stage (p = 0.076) were independent prognostic factors for DCC relapse. We then constructed a nomogram with these four factors. The consistency index (C-index) of the nomogram in the training and validation cohorts were 0.703 and 0.665, respectively. Time-dependent receiver operating characteristic and decision curve analyses revealed that the nomogram provided higher diagnostic power and net benefit compared with other staging systems.In this study, we developed an online nomogram calculator that can accurately predict the recurrence risk of DCC and identify patients with a high risk of recurrence in a simple and convenient manner.

BACKGROUND Distal cholangiocarcinoma (DCC) is a malignancy associated with a short survival time. In this study, we aimed to create an online nomogram calculator to predict early recurrence and long-term survival in patients with DCC after pancreaticoduodenectomy. METHODS A total of 486 patients with DCC were included. An online nomogram calculator was developed and validated in training, internal validation and external validation cohorts, respectively. RESULTS Of the 486 patients who met the inclusion criteria, we allocated 240, 120, and 126 patients to the training, internal validation, and external validation cohorts, respectively. Multivariable analysis showed that preoperative CA19-9, maximum tumor diameter, perineural invasion, and tumor differentiation were significant risk factors for early recurrence in patients with DCC. Incorporating these four factors, the nomogram achieved good AUC values of 0.788, 0.771, and 0.723 for predicting early recurrence in the training, internal validation, and external validation cohorts, respectively. Notably, this nomogram also had good power to predict overall survival. The discrimination ability of the nomogram was evaluated by dividing the predicted probabilities of early recurrence and survival into two risk groups in the training cohort (low risk ≤ 132; high risk > 132; P

OBJECTIVES This study aimed to perform a multicenter comparison between robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD). BACKGROUND Previous comparisons of RPD versus OPD have only been carried out in small, single-center studies of variable quality. METHODS Consecutive patients who underwent RPD (n = 1032) or OPD (n = 1154) at 7 centers in China between July 2012 and July 2020 were included. A 1:1 propensity score matching (PSM) was performed. RESULTS After PSM, 982 patients in each group were enrolled. The RPD group had significantly lower estimated blood loss (EBL) (190.0 vs 260.0 mL; P < 0.001), and a shorter postoperative 1length of hospital stay (LOS) (12.0 (9.0-16.0) days vs 14.5 (11.0-19.0) days; P < 0.001) than the OPD group. There were no significant differences in operative time, major morbidity including clinically relevant postoperative pancreatic fistula (CR-POPF), bile leakage, delayed gastric emptying, postoperative pancreatectomy hemorrhage (PPH), reoperation, readmission or 90-day mortality rates. Multivariable analysis showed R0 resection, CR-POPF, PPH and reoperation to be independent risk factors for 90-day mortality. Subgroup analysis on patients with pancreatic ductal adenocarcinoma (PDAC) (n = 326 in each subgroup) showed RPD had advantages over OPD in EBL and postoperative LOS. There were no significant differences in median disease-free survival (15.2 vs 14.3 months, P = 0.94) or median overall survival (24.2 vs 24.1 months, P = 0.88) between the 2 subgroups. CONCLUSIONS RPD was comparable to OPD in feasibility and safety. For patients with PDAC, RPD resulted in similar oncologic and survival outcomes as OPD.

Surgery is one of the main effective strategies for the treatment of solid tumors, but high postoperative recurrence is also the main cause of death in current cancer therapy. The prevention of postoperative hepatocellular carcinoma (HCC) recurrence is a clinical problem that needs to be solved urgently. At present, there are still some problems to be solved, such as, how to achieve free drugs to target the site of surgical resection; develop a strategy for the simultaneous administration of multiple drugs to inhibit postoperative recurrence; and provide the appropriate animal model that mimics the process of postoperative HCC recurrence. In this study, we used a facile and reproducible method to successfully prepare amphiphilic Janus nanoparticles (JNPs). In order to improve targeting of the JNPs to residual HCC cells after surgery, we modified the side of gold nanorods (GNRs) with lactobionic acid (LA), thus creating LA-JNPs. This provided an active and targeted co-delivery system for hydrophilic and hydrophobic drugs in separate rooms, thus avoiding mutual effects. Next, we established two models to simulate postoperative HCC recurrence: a subcutaneous postoperative recurrence model based on patient-derived tumor xenograft (PDX) tissues and a postoperative recurrence model of orthotopic HCC. By applying these models, the enhanced permeability and retention effect (EPR) based tumor targeting and LA based active targeting can jointly promote the enrichment and uptake of JNPs at tumor site. LA-JNPs represented an efficient targeting system for the co-delivery of Sorafenib/Doxorubicin with an optimized anti-recurrence effect and significantly improved the survival of mice during treatment for postoperative recurrence.

Background The surgical management of Mayo III/IV tumor thrombi is difficult and risky, and robotic surgery is even more difficult. The purpose of this study was to introduce the step-by-step and orderly lowering of the height of inferior vena cava tumor thrombus, which was the core technique of robot operation for Mayo III/IV tumor thrombus. Method A total of 18 patients were included in this study. The average tumor thrombus height was 2.4 cm above the level of the second porta hepatis (SPH), and 9 patients were prepared for cardiopulmonary bypass (CPB) before surgery. During the operation, the height of the tumor thrombus was lowered orderly for 2-3 times, and the blood flow blocking method was changed sequentially. The CPB was required when tumor thrombus in the atrium; After the height of the thrombus was lowered to the atrium entrance, CPB was stopped and the blood flow was blocked in the upper- and retro-hepatic inferior vena cava (IVC); After the tumor thrombus continued to descend to the lower part of the SPH, liver blood flow could be restored, and then, the blood flow was simply blocked in the retro-hepatic IVC to complete the removal of the thrombus and the repair or resection of the IVC. Finally, the diseased kidney and renal vein were removed. Results All operations were successfully completed, and 2 cases were transferred to laparotomy. Seven cases received CPB, while the other 11 did not. 15 patients underwent two times of the lowering of the tumor thrombus, 2 patients underwent one time and 1 patient underwent three times. The mean liver/IVC dissociation and vascular suspension time was 22.0 min. All patients had less than Clavien-Dindo grade III complications, no serious complications occurred during operation, and no patient died within 90 days. Conclusions The step-by-step and orderly decline of tumor thrombus height is the key to the success of robot Mayo III / IV tumor thrombus surgery. This method can shorten FPH and CPB time and improve the success rate of surgery.

Portal vein tumor thrombus (PVTT) is one of the most serious forms of hepatocellular carcinoma (HCC) vessel metastasis and has a poor survival rate. However, the molecular mechanism of PVTT has not yet been elucidated. In this study, the molecular mechanism of AXL expressed in tumor-derived endothelial cells (TECs) in vessel metastasis was investigated. High AXL expression was observed in TECs, but not in the tumor cells of HCC patients with PVTT and this was associated with poor overall survival (OS) and disease-free survival (DFS). AXL overexpression was positively associated with CD 31 expression both in vitro and in vivo. AXL promoted the cell proliferation, tube formation, and migration of both TECs and normal endothelial cells (NECs). High expression of AXL in TECs promoted the cell migration, but not the proliferation of HCC cells. Further studies demonstrated that AXL promoted cell migration and tube formation through activation of the PI3K/AKT/SOX2/DKK-1 axis. AXL overexpression in HUVECs promoted tumor growth and liver or vessel metastasis of HCC in xenograft nude mice, which could be counteracted by treatment with R428, an AXL inhibitor. R428 reduced tumor growth and CD 31 expression in HCC in PDX xenograft nude mice. Therefore, AXL over-expression in TECs promotes vessel metastasis of HCC, which indicates that AXL in TECs could be a potential therapeutic target in HCC patients with PVTT.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with aggressive biological behaviour. Its rapid proliferation and tumour growth require reprogramming of glucose metabolism or the Warburg effect. However, the association between glycolysis‐related genes with clinical features and prognosis of PDAC is still unknown. Here, we used the meta‐analysis to correlate the hazard ratios (HR) of 106 glycolysis genes from MSigDB by the cox proportional hazards regression analysis in 6 clinical data sets of PDAC patients to form a training cohort, and a single group of PDAC patients from the TCGA, ICGC, Arrayexpress and GEO databases to form the validation cohort. Then, a glycolysis‐related prognosis (GRP) score based on 29 glycolysis prognostic genes was established in 757 PDAC patients from the training composite cohort and validated in 267 ICGC‐CA validation cohort (all P

Background Portal vein tumour thrombus (PVTT) is a significant poor prognostic factor for hepatocellular carcinoma (HCC). Patients with PVTT limited to a first-order branch or above of the main portal vein (MPV) could benefit from R0 liver resection (LR). A nomogram is needed to predict early postoperative recurrence (ER) in HCC patients with PVTT and to guide selection of these patients for adjuvant therapy to reduce postoperative recurrence risks. Methods HCC patients with PVTT limited to a first-order branch or above of the MPV after R0 LR as an initial therapy were included. A nomogram using data from a retrospective training cohort was developed with the Cox regression model. The model was tested in a prospective internal validation cohort and three external validation cohorts. Results Of 979 patients, 657 developed postoperative ER (67.1%). ER occurred in 165 of 264 patients (62.5%) in the training cohort, 146 of 218 patients (70.0%) in the internal validation cohort, and 204 of 284 patients (71.8%), 77 of 113 patients (68.1%), and 65 of 100 patients (65%) in the three external validation cohorts, respectively. The nomogram included the following variables: hepatitis B surface antigen (HBsAg), PVTT, HBV DNA, satellite nodules, α-fetoprotein, and tumour diameter. The ROC were 0.836, 0.763, 0.802, 0.837, and 0.846 in predicting ER in the five respective cohorts. Conclusion A nomogram was developed and validated to predict postoperative ER in patients with HCC with PVTT after R0 LR. This nomogram could select appropriate patients with high ER risks for postoperative adjuvant therapy.

PURPOSE To compare the survival outcomes of neoadjuvant three-dimensional conformal radiotherapy (RT) followed by hepatectomy with hepatectomy alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). PATIENTS AND METHODS A randomized, multicenter controlled study was conducted from January 2016 to December 2017 in patients with resectable HCC and PVTT. Patients were randomly assigned to receive neoadjuvant RT followed by hepatectomy (n = 82) or hepatectomy alone (n = 82). The modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines were used to evaluate the therapeutic effects of RT. The primary end point was overall survival. The expression of interleukin-6 (IL-6) in patients’ serum before RT and in surgical specimens was correlated with response to RT. RESULTS In the neoadjuvant RT group, 17 patients (20.7%) had partial remission. The overall survival rates for the neoadjuvant RT group at 6, 12, 18, and 24 months were 89.0%, 75.2%, 43.9%, and 27.4%, respectively, compared with 81.7%, 43.1%, 16.7%, and 9.4% in the surgery-alone group ( P < .001). The corresponding disease-free survival rates were 56.9%, 33.0%, 20.3%, and 13.3% versus 42.1%, 14.9%, 5.0%, and 3.3% ( P < .001). On multivariable Cox regression analyses, neoadjuvant RT significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone (hazard ratios, 0.35 [95% CI, 0.23 to 0.54; P < .001] and 0.45 [95% CI, 0.31 to 0.64; P < .001]). Increased expressions of IL-6 in pre-RT serum and tumor tissues were significantly associated with resistance to RT. CONCLUSION For patients with resectable HCC and PVTT, neoadjuvant RT provided significantly better postoperative survival outcomes than surgery alone. IL-6 may predict response to RT in these patients.