Alternative splicing of a chromatin modifier alters the transcriptional regulatory programs of stem cell maintenance and neuronal differentiation.

Development of embryonic stem cells (ESCs) into neurons requires intricate regulation of transcription, splicing, and translation, but how these processes interconnect is not understood. We found that polypyrimidine tract binding protein 1 (PTBP1) controls splicing of DPF2, a subunit of BRG1/BRM-associated factor (BAF) chromatin remodeling complexes. Dpf2 exon 7 splicing is inhibited by PTBP1 to produce the DPF2-S isoform early in development. During neuronal differentiation, loss of PTBP1 allows exon 7 inclusion and DPF2-L expression. Different cellular phenotypes and gene expression programs were induced by these alternative DPF2 isoforms. We identified chromatin binding sites enriched for each DPF2 isoform, as well as sites bound by both. In ESC, DPF2-S preferential sites were bound by pluripotency factors. In neuronal progenitors, DPF2-S sites were bound by nuclear factor I (NFI), while DPF2-L sites were bound by CCCTC-binding factor (CTCF). DPF2-S sites exhibited enhancer modifications, while DPF2-L sites showed promoter modifications. Thus, alternative splicing redirects BAF complex targeting to impact chromatin organization during neuronal development.

Early and late recurrence patterns of pancreatic ductal adenocarcinoma after pancreaticoduodenectomy: a multicenter study.

BACKGROUND: Survival after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) remains poor because of high incidences of recurrence. The risk factors, patterns, and long-term prognosis in patients with early recurrence and late recurrence (ER and LR) for PDAC after PD were studied. METHODS: Data from patients who underwent PD for PDAC were analyzed. Recurrence was divided into ER (ER ≤1 years) and LR (LR >1 years) using the time to recurrence after surgery. Characteristics and patterns of initial recurrence, and postrecurrence survival (PRS) were compared between patients with ER and LR. RESULTS: Among the 634 patients, 281 (44.3%) and 249 (39.3%) patients developed ER and LR, respectively. In the multivariate analysis, preoperative CA19-9 levels, resection margin status, and tumor differentiation were significantly associated with both ER and LR, while lymph node metastasis and perineal invasion were associated with LR. Patients with ER, when compared with patients with LR, showed a significantly higher proportion of liver-only recurrence ( P <0.05), and worse median PRS (5.2 vs. 9.3 months, P <0.001). Lung-only recurrence had a significantly longer PRS when compared with liver-only recurrence ( P <0.001). Multivariate analysis demonstrated that ER and irregular postoperative recurrence surveillance were independently associated with a worse prognosis ( P <0.001). CONCLUSION: The risk factors for ER and LR after PD are different for PDAC patients. Patients who developed ER had worse PRS than those who developed LR. Patients with lung-only recurrence had a significantly better prognosis than those with other recurrent sites.

Robotic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: Analysis of surgical outcomes and long-term prognosis in a high-volume center.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

A novel online calculator to predict early recurrence and long-term survival of patients with resectable pancreatic ductal adenocarcinoma after pancreaticoduodenectomy: A multicenter study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Short- and long-term outcomes after robotic and open liver resection for elderly patients with hepatocellular carcinoma: a propensity score-matched study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: RLR was comparable to OLR in feasibility and safety. For elderly patients with HCC, RLR resulted in similar oncologic and survival outcomes as OLR.

Robotic versus open pancreaticoduodenectomy for distal cholangiocarcinoma: a multicenter propensity score-matched study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: RPD was comparable to OPD in feasibility and safety. For patients with DCC, RPD resulted in similar oncologic and survival outcomes as OPD.

Evaluating the learning curve of robotic radical antegrade modular pancreatosplenectomy: A retrospective cohort study.

BACKGROUND: Radical antegrade modular pancreatosplenectomy (RAMPS), a new surgical approach for pancreatic ductal adenocarcinoma of the body and tail, has become increasingly accepted and performed in recent years. Robotic surgery has advantages over open and laparoscopic surgeries in terms of surgical vision and instrument flexibility. However, the lack of comprehension of the learning curve has limited its generalization. This study aimed to evaluate the learning curve of robotic posterior RAMPS. METHODS: Patients who underwent robotic posterior RAMPS between February 2017 and April 2021 at our institution were included in this study. Data on patient characteristics, perioperative outcomes, and pathological outcomes were summarized and analyzed. The cumulative sum (CUSUM) method was used to assess the learning curve and inflection points based on operation time and estimated blood loss. RESULTS: One hundred consecutive patients who underwent robotic posterior RAMPS were enrolled. The median operation time was 235.0 (interquartile range [IQR], 210.0-270.0) min, and the estimated blood loss was 210.0 (IQR, 165.0-245.0) mL. The grade 3/4 Clavien-Dindo complication rate was 8% (8/100). According to the CUSUM plot, the inflection points of the learning curve were 25 and 65 cases, dividing the case series into the learning (1-25 cases), plateau (26-65 cases), and maturation (66-100 cases) phases. The operation time was relatively high in the learning phase, reached a plateau between 25 and 65 cases (270.0 min vs. 220.0 min, p < 0.01), and decreased significantly in the maturation phase (p < 0.01). Estimated blood loss improved in the maturation phase compared to the learning phase (150.0 vs. 245.0 mL, p < 0.01). No significant differences in conversion rate, complications, or mortality were observed among the three phases. CONCLUSION: The inflection points of the learning and plateau phases were the 25th and 65th cases, respectively. Robotic RAMPS is safe and feasible even in the learning phase.

CircuitBot: Learning to survive with robotic circuit drawing.

Robots with the ability to actively acquire power from surroundings will be greatly beneficial for long-term autonomy and to survive in uncertain environments. In this work, a scenario is presented where a robot has limited energy, and the only way to survive is to access the energy from an unregulated power source. With no wires or resistors available, the robot heuristically learns to maximize the input voltage on its system while avoiding potential obstacles during the connection. CircuitBot is a 6 DOF manipulator capable of drawing circuit patterns with graphene-based conductive ink, and it uses a state-of-the-art continuous/categorical Bayesian Optimization to optimize the placement of conductive shapes and maximize the energy it receives. Our comparative results with traditional Bayesian Optimization and Genetic algorithms show that the robot learns to maximize the voltage within the smallest number of trials, even when we introduce obstacles to ground the circuit and steal energy from the robot. As autonomous robots become more present, in our houses and other planets, our proposed method brings a novel way for machines to keep themselves functional by optimizing their own electric circuits.

Step-by-step and orderly lowering of the height of inferior vena cava tumor thrombus is the key to robot-assisted thrombectomy for Mayo III/IV tumor thrombus.

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.

A novel online calculator to predict recurrence risk in patients with distal cholangiocarcinoma after radical pancreaticoduodenectomy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Development and validation of an online calculator to predict early recurrence and long-term survival in patients with distal cholangiocarcinoma after pancreaticoduodenectomy.

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 < .001). Time-dependent ROC and decision curve analysis further revealed that the nomogram provided higher diagnostic capacity and superior net benefit compared to other staging systems. CONCLUSION: This study developed and validated a web-based nomogram calculator that was capable of predicting early recurrence and long-term prognosis in patients with DCC after pancreaticoduodenectomy with high degrees of stability and accuracy.

The standardized technique and surgical video of robotic pancreaticoduodenectomy at the Chinese PLA General Hospital.

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.

Comparison of robotic and laparoscopic liver resection in ordinary cases of left lateral sectionectomy.

BACKGROUND: Laparoscopy was considered the standard method of left lateral sectionectomy. The robotic approach showed advantages in complex cases of left lateral sectionectomy. However, the impact of the robotic system on ordinary cases is still unknown. METHODS: Retrospective review of consecutive robotic left lateral sectionectomy (R-LLS) and laparoscopic left lateral sectionectomy (L-LLS) from January 2015 to December 2019. Univariate and multivariate logistic regression was used to determine the effects of surgical method and surgical complexity on postoperative length of stay, surgical and overall cost. RESULTS: 258 consecutive patients who underwent minimally invasive left lateral sectionectomy were analyzed. L-LLS had comparable outcomes and decreased surgery (USD 2416.3 vs 4624.5; p < 0.001) and overall costs (USD 8004.5 vs 11897.1; p < 0.001) compared with R-LLS in the ordinary-case group, whereas R-LLS was associated with shorter postoperative LOS (5.0 vs 3.5 days; p = 0.004) in the complex-case group. On multivariable analysis, R-LLS was predictive of shorter postoperative LOS [odds ratio (OR) 0.388, 95% confidence interval (CI) 0.198-0.760, p = 0.006], whereas R-LLS was predictive of higher surgery (OR 65.640, 95% CI 17.406-247.535, p < 0.001) and overall costs (OR 102.233, 95% CI 22.241-469.931, p < 0.001). CONCLUSION: Results of this study showed no clinical benefit to the R-LLS compared with L-LLS in ordinary cases. R-LLS had potential advantages in selected complex cases.

Comparison of robotic and open pancreaticoduodenectomy for primary nonampullary duodenal adenocarcinoma: a retrospective cohort study.

PURPOSE: Robotic surgery has been increasingly applied in pancreatic surgery and showed many advantages over conventional open surgery. The robotic pancreaticoduodenectomy (RPD) is a surgical option for primary nonampullary duodenal adenocarcinoma (PNDA). However, whether RPD is superior to open pancreaticoduodenectomy (OPD) for PNDA has not been reported. The comparative study was designed to analyze the short- and long-term outcomes of RPD versus OPD on patients with PNDA. METHODS: Demographics, perioperative, and survival outcomes among patients who underwent RPD (n = 49) versus OPD (n = 43) for PNDAs between January 2013 and March 2018 were collected and analyzed RESULTS: Demographic characteristics were comparable between the RPD group and the OPD group. The RPD group demonstrated a decreased estimated blood loss (100 vs. 200 ml, p < 0.001), time to oral intake (4.0 vs. 4.0 days, p = 0.04), and postoperative hospital stay (12.9 vs. 15.0 days, p = 0.01) compared with the OPD group. However, no differences were observed between the two groups in terms of operative time and the rates of major complications, grade B and C POPF, PPH, grade B and C DGE, biliary fistular, reoperation, and 90-day readmission. No patient died within 90 days. There were no significant differences in tumor size, differentiation, TNM stage, number of harvested lymph nodes, and the rates of nerve invasion, lymph node invasion, R0 resection, and the median overall survival between the two groups (p > 0.05) CONCLUSIONS: RPD is a safe, feasible, and effective treatment for PNDA compared with OPD and can be used as an alternative for surgeons in the treatment of PNDA. Further multicenter randomized controlled trials are needed to evaluate the effectiveness of RPD in patients with PNDA.

A Novel Nomogram Based on Log Odds of Metastatic Lymph Nodes to Predict Overall Survival in Patients With Perihilar Cholangiocarcinoma After Surgery.

BACKGROUND: Various lymph node staging strategies were reported to be significantly correlated with perihilar cholangiocarcinoma(pCCA) prognosis. This study aimed to evaluate their predictive abilities and construct an optimal model predicting overall survival (OS). METHODS: Patients with pCCA were collected as the training cohort from the Surveillance, Epidemiology, and End Results (SEER) database. Four models were constructed, involving four LNs staging strategies. The optimal model for predicting OS was evaluated by calculation of the concordance index (C-index) and Akaike information criterion (AIC), and validated by using the area under curve (AUC) and calibration curves. The clinical benefits of nomogram were evaluated by decision curve analysis (DCA). A Chinese cohort was collected to be an external validation cohort. RESULTS: There were 319 patients and 109 patients in the SEER database and Chinese cohort respectively. We developed an optimal model involving age, T stage, tumor size, LODDS, which showed better predictive accuracy than others. The C-index of the nomogram was 0.695, the time-dependent AUC exceeded 0.7 within 36 months which was significantly higher than that of the American Joint Committee on Cancer (AJCC) stage. The calibration curves for survival probability showed the nomogram prediction had good uniformity of the practical survival. The DCA curves exhibited our nomogram with higher clinical utility compared with the AJCC stage and single LOODS. CONCLUSIONS: LODDS is a strong independent prognostic factor, and the nomogram has a great ability to predict OS, which helps assist clinicians to conduct personalized clinical practice.

Robotic resection of duodenal gastrointestinal stromal tumour: Preliminary experience from a single centre.

BACKGROUND: Experience in minimally invasive surgery in the treatment of duodenal gastrointestinal stromal tumors (DGISTs) is accumulating, but there is no consensus on the choice of surgical method. AIM: To summarize the technique and feasibility of robotic resection of DGISTs. METHODS: The perioperative and demographic outcomes of a consecutive series of patients who underwent robotic resection and open resection of DGISTs between May 1, 2010 and May 1, 2020 were retrospectively analyzed. The patients were divided into the open surgery group and the robotic surgery group. Pancreatoduodenectomy (PD) or limited resection was performed based on the location of the tumour and the distance between the tumour and duodenal papilla. Age, sex, tumour location, tumour size, operation time (OT), estimated blood loss (EBL), postoperative hospital stay (PHS), tumour mitosis, postoperative risk classification, postoperative recurrence and recurrence-free survival were compared between the two groups. RESULTS: Of the 28 patients included, 19 were male and 9 were female aged 51.3 ± 13.1 years. Limited resection was performed in 17 patients, and PD was performed in 11 patients. Eleven patients underwent open surgery, and 17 patients underwent robotic surgery. Two patients in the robotic surgery group underwent conversion to open surgery. All the tumours were R0 resected, and there was no significant difference in age, sex, tumour size, operation mode, PHS, tumour mitosis, incidence of postoperative complications, risk classification, postoperative targeted drug therapy or postoperative recurrence between the two groups (P > 0.05). OT and EBL in the robotic group were significantly different to those in the open surgery group (P < 0.05). All the patients survived during the follow-up period, and 4 patients had recurrence and metastasis. No significant difference in recurrence-free survival was noted between the open surgery group and the robotic surgery group (P > 0.05). CONCLUSION: Robotic resection is safe and feasible for patients with DGISTs, and its therapeutic effect is equivalent to open surgery.

The Pol II preinitiation complex (PIC) influences Mediator binding but not promoter-enhancer looping.

Knowledge of how Mediator and TFIID cross-talk contributes to promoter-enhancer (P-E) communication is important for elucidating the mechanism of enhancer function. We conducted an shRNA knockdown screen in murine embryonic stem cells to identify the functional overlap between Mediator and TFIID subunits on gene expression. Auxin-inducible degrons were constructed for TAF12 and MED4, the subunits eliciting the greatest overlap. Degradation of TAF12 led to a dramatic genome-wide decrease in gene expression accompanied by destruction of TFIID, loss of Pol II preinitiation complex (PIC) at promoters, and significantly decreased Mediator binding to promoters and enhancers. Interestingly, loss of the PIC elicited only a mild effect on P-E looping by promoter capture Hi-C (PCHi-C). Degradation of MED4 had a minor effect on Mediator integrity but led to a consistent twofold loss in gene expression, decreased binding of Pol II to Mediator, and decreased recruitment of Pol II to the promoters, but had no effect on the other PIC components. PCHi-C revealed no consistent effect of MED4 degradation on P-E looping. Collectively, our data show that TAF12 and MED4 contribute mechanistically in different ways to P-E communication but neither factor appears to directly control P-E looping, thereby dissociating P-E communication from physical looping.

Robotic versus open total pancreatectomy: a retrospective cohort study.

PURPOSE: Robotic total pancreatectomy (RTP), although considered safe and feasible, has rarely been reported. This study aimed to evaluate whether RTP has advantages over open TP (OTP). METHODS: Demographics and perioperative outcomes among patients who underwent RTP (n=14) versus OTP (n=15) between May 2015 and September 2020 were retrospectively analyzed. RESULTS: RTP reduced the operative time (307.2 vs. 382.0 min, p=0.01) and estimated blood loss (EBL) (200 vs. 700 ml, p=0.002) compared to those of OTP. The patients in the RTP group got out of their beds and stood, received their first liquid, and took oral diets earlier (2.0 vs. 3.0 days, p=0.002; 2.0 vs. 4.0 days, p=0.009; 3.0 vs. 5.0 days, p=0.006) and experienced a shorter postoperative hospital stay (PHS) (9.0 vs. 12.0 days, p=0.03). There were no significant differences in the rates of spleen preservation, splenic vessel preservation, bile leakage, delayed gastric emptying, morbidity, or the number of lymph nodes harvest between the two groups. CONCLUSION: This study demonstrates that RTP is safe and feasible in selected patients with different indications in experienced robotic center. RTP was associated with a shorter operative time, lower EBL, and shorter PHS than OTP.

A comparative study of end-to-end pancreatic anastomosis versus pancreaticojejunostomy after robotic central pancreatectomy.

Robotic central pancreatectomy has been applied for 20 years with the advantage of minimally invasive surgery. The general pancreatic reconstruction approaches include pancreaticojejunostomy and pancreaticogastrostomy. Recently, our group reported a few preliminary cases of application of end-to-end pancreatic anastomosis in robotic central pancreatectomy. This novel approach has not been compared with the conventional approach on a large scale. The objective of this study is to compare end-to-end pancreatic anastomosis with pancreaticojejunostomy after robotic central pancreatectomy based on the perioperative and long-term outcomes. Clinical data consist of demographics, clinicopathologic characteristics, perioperative and long-term outcomes of patients who underwent robotic central pancreatectomy from March 2015 to December 2019 were collected and analyzed. Seventy-four patients received a robotic central pancreatectomy with either end-to-end pancreatic anastomosis (n = 52) or pancreaticojejunostomy (n = 22). End-to-end pancreatic anastomosis was associated with shorter operative time and reduced blood loss. Despite a higher incidence of clinically relevant postoperative pancreatic fistula (69.2% vs. 36.4%, p = 0.009), the newer anastomotic technique was also associated with earlier removal of nasogastric tube and resumption of oral intake. Long-term results, in terms of either endocrine or exocrine function, were not affected by the anastomotic technique. We have shown the feasibility of robotic central pancreatectomy with end-to-end pancreatic anastomosis. Despite streamlined technique, the newer anastomosis appears to improve early post-operative results while preserving endocrine and exocrine functions in the long-term period. Evaluation of the true potential of robotic central pancreatectomy with end-to-end pancreatic anastomosis requires a prospective and randomized study enrolling a large number of patients.

Methylation patterns partition pancreatic cancer into distinct prognostic subtypes.

In the initiation and progression of pancreatic cancer, DNA methylation plays a critical role. The present study attempts to explore specific prognosis subtypes based on DNA methylation data and develop an epigenetic signature to predict the overall survival (OS) of patients with pancreatic cancer.147 samples were included in the training cohort, whereas the validation cohort included 226 samples. The 298 OS-related methylation sites in the training cohort were selected for consensus clustering, and the authors identified three subtypes with a significant difference in prognosis. Cluster1 was associated with poor OS, low-grade disease and high lymph node involvement. In addition, we identified 33 specific methylation sites in Cluster1. Subsequently, we developed a robust qualitative signature consisting of 14 methylation sites to individually predict OS in the training cohort, and the predictive accuracy of this model was confirmed in the validation cohort. Functional enrichment analysis showed that the selected genes in the model were mainly enriched in known cancer-related pathways. Patients were divided into high- and low-risk groups by the model, and a significant difference in OS was observed between these groups. Classification based on the modeling of a specific DNA methylation site can reveal the heterogeneity of pancreatic cancer and provide guidance for clinicians in predicting the prognosis of pancreatic cancer and providing personalized treatment.