A novel laparoscopic pancreaticoduodenal training model: optimization of the learning curve and simplification of postoperative complications.

PURPOSE: Laparoscopic pancreaticoduodenectomy requires a long learning curve. A preoperative training system was established to optimize the surgeons' learning curve and reduce the incidence rate of complications at the beginning of the curve. METHODS: The laparoscopic pancreaticojejunostomy model, and choledochojejunostomy and gastrojejunostomy training systems were developed, and corresponding evaluation systems were also defined. Surgeons B and C performed laparoscopic pancreaticoduodenectomy after completing training session. Surgical outcomes, postoperative complications and their learning curves were analyzed. RESULTS: Patients operated by surgeons B and C experienced shorter operative durations following training session than those in nontrained group (called A) ( P <0.001). B and C began entering the inflection point at the 26th and 20th case in learning curve, respectively. The incidence of postoperative pancreatic fistula in group B was 3.3%, significantly lower than 13.1% in group A ( P =0.047). Patients in group B showed significantly lower incidence of biliary-enteric anastomosis leakage (0% vs. 8.2%, P =0.029) and Clavien-Dindo classification greater than or equal to 3 (3.3% vs. 14.8%, P =0.027) compared with those in group A. The incidence of surgical site infection in groups B (3.3%, P =0.004) and C (4.9%, P =0.012) was significantly lower than that in group A (19.7%). Moreover, the length of postoperative hospital stay was significantly shorter in groups B (12.5±5.9 days, P =0.002) and C (13.7±6.5 days, P =0.002) compared with group A (16.7±8.5 days). CONCLUSIONS: The laparoscopic pancreaticojejunostomy training model and evaluation system can shorten the operative duration, lower the risk of postoperative complications, and shorten the length of hospital stay.

Effect of Laparoscopic and Open Pancreaticoduodenectomy for Pancreatic or Periampullary Tumors: Three-year Follow-up of a Randomized Clinical Trial.

OBJECTIVE: This study aimed to estimate whether the potential short-term advantages of laparoscopic pancreaticoduodenectomy (LPD) could allow patients to recover in a more timely manner and achieve better long-term survival than with open pancreaticoduodenectomy (OPD) in patients with pancreatic or periampullary tumors. BACKGROUND: LPD has been demonstrated to be feasible and may have several potential advantages over OPD in terms of shorter hospital stay and accelerated recovery than OPD. METHODS: This noninferiority, open-label, randomized clinical trial was conducted in 14 centers in China. The initial trial included 656 eligible patients with pancreatic or periampullary tumors enrolled from May 18, 2018, to December 19, 2019. The participants were randomized preoperatively in a 1:1 ratio to undergo either LPD (n=328) or OPD (n=328). The 3-year overall survival (OS), quality of life, which was assessed using the 3-level version of the European Quality of Life-5 Dimensions, depression, and other outcomes were evaluated. RESULTS: Data from 656 patients [328 men (69.9%); mean (SD) age: 56.2 (10.7) years] who underwent pancreaticoduodenectomy were analyzed. For malignancies, the 3-year OS rates were 59.1% and 54.3% in the LPD and OPD groups, respectively ( P =0.33, hazard ratio: 1.16, 95% CI: 0.86-1.56). The 3-year OS rates for others were 81.3% and 85.6% in the LPD and OPD groups, respectively ( P =0.40, hazard ratio: 0.70, 95% CI: 0.30-1.63). No significant differences were observed in quality of life, depression and other outcomes between the 2 groups. CONCLUSION: In patients with pancreatic or periampullary tumors, LPD performed by experienced surgeons resulted in a similar 3-year OS compared with OPD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03138213.

Short-Term Outcomes Following Laparoscopic vs Open Pancreaticoduodenectomy in Patients With Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial.

Importance: The safety and efficacy of laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma remain controversial. Objective: To compare laparoscopic and open pancreaticoduodenectomy performed by experienced surgeons in patients with pancreatic ductal adenocarcinoma. Design, Setting, and Participants: This was a noninferiority, open-label randomized clinical trial between September 20, 2019 and March 20, 2022, at 10 hospitals in China. A total of 412 adult patients were assessed for eligibility; 200 patients with histologically confirmed or clinically diagnosed pancreatic ductal adenocarcinoma who were eligible to undergo pancreaticoduodenectomy were enrolled. Study recruitment is complete, and follow-up is ongoing. This article reports prespecified early safety results from the trial. Interventions: Participants were randomized in a 1:1 ratio to undergo either laparoscopic or open pancreaticoduodenectomy, to be performed by experienced surgeons who had already performed at least 104 laparoscopic pancreaticoduodenectomy operations. Main Outcomes and Measures: The primary end point is 5-year overall survival, but the data for this end point are not yet mature; thus, secondary short-term outcomes, including operative findings, complications, mortality, and oncological results are reported here. The outcomes were analyzed according to a modified intention-to-treat and per-protocol principle. Results: Among 412 patients for eligibility, 200 patients were enrolled and randomly assigned 1:1 to have laparoscopic pancreaticoduodenectomy or open pancreaticoduodenectomy. The mean (SD) age was 61.3 (9.3) years, and 78 participants (39%) were female. Laparoscopic procedures had longer operative times (median [IQR], 330.0 [287.5-405.0] minutes vs 297.0 [245.0-340.0] minutes; P < .001). Patients in the laparoscopic group lost less blood than those in the open group (median [IQR], 145.0 [100.0-200.0] mL vs 200.0 [100.0-425.0] mL; P = .02). Ninety-day mortality occurred in 2 of 100 patients in the laparoscopic group and 0 of 100 patients in the open group. There was no difference in the rates of complications of the Clavien-Dindo grades III-IV (n = 17 [17.0%] vs n = 23 [23.0%]; P = .29), comprehensive complication index (median [IQR], 0.0 [0.0-22.6] vs 8.7 [0.0-26.2]; P = .79) or median (IQR) postoperative length of stay (14.0 [11.0-17.0] days vs 14.0 [12.0-18.5] days; P = .37) between the 2 groups. Conclusions and Relevance: Laparoscopic pancreaticoduodenectomy performed by experienced surgeons in high-volume specialized institutions resulted in similar short-term outcomes compared with open pancreaticoduodenectomy among patients with pancreatic ductal adenocarcinoma. Trial Registration: ClinicalTrials.gov Identifier: NCT03785743.

Clinical and genetic characteristics in pancreatic cancer from Chinese patients revealed by whole exome sequencing.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide, mostly as a result of the absence of early detection and specific treatment solutions. Consequently, identifying mutational profiles and molecular biomarkers is essential for increasing the viability of precision therapy for pancreatic cancer. Methods: We collected blood and tumor tissue samples from 47 Chinese pancreatic cancer patients and used whole-exome sequencing (WES) to evaluate the genetic landscape. Results: Our results showed the most frequently somatic alteration genes were KRAS (74.5%), TP53(51.1%), SMAD4 (17%), ARID1A (12.8%), CDKN2A (12.8%), TENM4 (10.6%), TTN (8.5%), RNF43(8.5%), FLG (8.5%) and GAS6 (6.4%) in Chinese PDAC patients. We also found that three deleterious germline mutations (ATM c.4852C>T/p. R1618*, WRN c.1105C>T/p. R369*, PALB2 c.2760dupA/p. Q921Tfs*7) and two novel fusions (BRCA1-RPRML, MIR943 (intergenic)-FGFR3). When compared to the Cancer Genome Atlas (TCGA) database, there is a greater mutation frequency of TENM4 (10.6% vs. 1.6%, p = 0.01), GAS6(6.4% vs. 0.5%, p = 0.035), MMP17(6.4% vs. 0.5%, p = 0.035), ITM2B (6.4% vs. 0.5%, p = 0.035) and USP7 (6.4% vs. 0.5%, p= 0.035) as well as a reduced mutation frequency of SMAD4 (17.0% vs. 31.5%, p = 0.075) and CDKN2A (12.8% vs. 47.3%, p < 0.001) were observed in the Chinese cohort. Among the 41 individuals examined for programmed cell death ligand 1(PD-L1) expression, 15 (36.6%) had positive PD-L1 expression. The median tumor mutational burden (TMB) was found to be 12muts (range, 0124). The TMB index was higher in patients with mutant-type KRAS MUT/TP53 MUT (p < 0.001), CDKN2A (p = 0.547), or SMAD4 (p = 0.064) compared to patients with wild-type KRAS/TP53, CDKN2A, or SMAD4. Conclusions: We exhibited real-world genetic traits and new alterations in Chinese individuals with cancer of the pancreas, which might have interesting implications for future individualized therapy and medication development.

Comparison of Efficacy and Safety Between Laparoscopic and Open Radical Resection for Hilar Cholangiocarcinoma-A Propensity Score-Matching Analysis.

Background: Radical resection remains the most effective treatment for hilar cholangiocarcinoma (HCCA). However, due to the complex anatomy of the hilar region, the tumor is prone to invade portal vein and hepatic arteries, making the surgical treatment of HCCA particularly difficult. Successful laparoscopic radical resection of HCCA(IIIA, IIIB) requires excellent surgical skills and rich experience. Furthermore, the safety and effectiveness of this operation are still controversial. Aim: To retrospectively analyze and compare the efficacy and safety of laparoscopic and open surgery for patients with HCCA. Methods: Clinical imaging and postoperative pathological data of 89 patients diagnosed with HCCA (IIIA, IIIB) and undergoing radical resection in our center from January 2018 to March 2022 were retrospectively analyzed. Among them, 6 patients (4 were lost to follow-up and 2 were pathologically confirmed to have other diseases after surgery) were ruled out, and clinical data was collected from the remaining 83 patients for statistical analysis. These patients were divided into an open surgery group (n=62) and a laparoscopic surgery group (n=21) according to the surgical methods used, and after 1:2 propensity score matching (PSM), 32 and 16 patients respectively in the open surgery group and laparoscopic surgery group were remained. The demographic data, Bismuth type, perioperative data, intraoperative data, postoperative complications, pathological findings, and long-term survivals were compared between these two groups. Results: After 1:2 PSM, 32 patients in the open surgery group and 16 patients in the laparoscopic surgery group were included for further analysis. Baseline characteristics and pathological outcomes were comparable between the two groups. Statistically significant differences between the two groups were observed in intraoperative blood loss and operative time, as it were 400-800 mL vs 200-400 mL (P=0.012) and (407.97 ± 76.06) min vs (489.69 ± 79.17) min (P=0.001) in the open surgery group and laparoscopic surgery group, respectively. The R0 resection rate of the open group was 28 cases (87.5%), and the R0 resection rate of the laparoscopic group was 15 cases (93.75%). The two groups showed no significant difference in terms of surgical approach, intraoperative blood transfusion, incidence of postoperative complications, and short- and long-term efficacy (P>0.05). Conclusions: Laparoscopic radical resection of HCCA has comparable perioperative safety compared to open surgery group, as it has less bleeding and shorter operation time. Although it is a promising procedure with the improvement of surgical skills and further accumulation of experience, further investigations are warranted before its wider application.

Efficacy and safety of laparoscopic radical resection following neoadjuvant therapy for pancreatic ductal adenocarcinoma: A retrospective study.

BACKGROUND: Multiple studies have demonstrated that neoadjuvant chemotherapy (NACT) can prolong the overall survival of pancreatic ductal adenocarcinoma (PDAC) patients. However, most studies have focused on open surgery following NACT. AIM: To investigate the efficacy and safety of laparoscopic radical resection following NACT for PDAC. METHODS: We retrospectively analyzed the clinical data of 15 patients with pathologically confirmed PDAC who received NACT followed by laparoscopic radical surgery in our hospital from December 2019 to April 2022. All patients underwent abdominal contrast-enhanced computed tomography (CT) and positron emission tomography-CT before surgery to accurately assess tumor stage and exclude distant metastasis. RESULTS: All 15 patients with pancreatic cancer were successfully converted to surgical resection after NACT, including 8 patients with pancreatic head cancer and 7 patients with pancreatic body and tail cancer. Among them, 13 patients received the nab-paclitaxel plus gemcitabine regimen (gemcitabine 1000 mg/m2 plus nab-paclitaxel 125 mg/m2 on days 1, 8, and 15 every 4 wk) and 2 patients received the modified FOLFIRINOX regimen (intravenous oxaliplatin 68 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 on day 1 and fluorouracil 400 mg/m2 on day 1, followed by 46-h continuous infusion of fluorouracil 2400 mg/m2). After each treatment cycle, abdominal CT, tumor markers, and circulating tumor cell counts were reviewed to evaluate the treatment efficacy. All 15 patients achieved partial remission. The surgical procedures included laparoscopic pancreaticoduodenectomy (LPD, n = 8) and laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS, n = 7). None of them were converted to a laparotomy. One patient with pancreatic head carcinoma was found to have portal vein involvement during the operation, and LPD combined with vascular resection and reconstruction was performed. The amount of blood loss and operation times of L-RAMPS vs LPD were 435.71 ± 32.37 mL vs 343.75 ± 145.01 mL and 272.52 ± 49.14 min vs 444.38 ± 68.63 min, respectively. The number of dissected lymph nodes was 16.87 ± 4.10, and 3 patients had positive lymph nodes. One patient developed grade B postoperative pancreatic fistula (POPF) after L-RAMPS, and one patient experienced jaundice after LPD. None of the patients died after surgery. As of April 2022, progressive disease was noted in 4 patients, 2 patients had liver metastasis, and one had both liver metastasis and lymph node metastasis and died during the follow-up period. CONCLUSION: Laparoscopic radical resection of PDAC after NACT is safe and effective if it is performed by a surgeon with rich experience in LPD and in a large center of pancreatic surgery.

Preliminary experience on laparoscopic pancreaticoduodenal combined with major venous resection and reconstruction anastomosis.

Objective: This study aims to summarize our experience in laparoscopic pancreatoduodenectomy (LPD) combined with major venous resection and reconstruction, as well as to evaluate its safety and discuss the surgical approach. Methods: We retrospectively analyzed 14 cases of patients diagnosed with pancreatic tumors invaded the superior mesenteric vein or portal vein who had undergone LPD combined with major venous resection and reconstruction in our center from May 2016 to May 2020. Clinical data of these 14 patients were collected and analyzed, including general information (age, gender, pathological diagnosis, body mass index, etc.), intraoperative data (operation time, intraoperative blood loss, transit rate, blood transfusion, tumor diameter, R0 resection rate, cleaning lymph node number, removal vessel length, venous reconstruction time), and postoperative results (gastrointestinal function recovery, postoperative hospital time, complications, and fatality rate). Patients were followed up after surgery, and data were collected for statistical analysis. Results: A total of 14 patients (9 males and 5 females) received LPD combined with major venous resection and reconstruction by arterial approach. The mean age was 52.5 (43-74) years old. Three of these 14 patients had routine wedge resection, 9 had opposite-to-end anastomosis after venous resection, 2 had artificial venous replacement, and the average length of removal vessel was 3.1 (2-4.5) cm. The operation time was 395 (310-570) min; the venous blocking time was 29.7 (26-50) min; the hospitalization stay was 13.6 (9-39) days. There was no grade B or C postoperative pancreatic fistula (POPF) that occurred, only one patient had biochemical fistula. One patient had upper gastrointestinal bleeding after subcutaneous injection of low molecular weight (LMW) heparin, and the condition was alleviated after conservative treatment, and one had pulmonary infection. The 12-month disease-free survival rate was 85.7%, and the 12-month overall survival rate was 92.8%. No patients had 30-day re-admission or death. Conclusion: On the basis of the surgeon's proficiency in open pancreatoduodenectomy combined with venous resection and reconstruction and standard LPD, the arterial approach for LPD combined with major venous resection and reconstruction is safe and feasible.

Association of a Modified Blumgart Anastomosis With the Incidence of Pancreatic Fistula and Operation Time After Laparoscopic Pancreatoduodenectomy: A Cohort Study.

Objective: To explore the association between a modified Blumgart anastomosis technique and the operative time and surgical complications. Methods: This is a retrospective cohort study that analyzed the data of patients who underwent laparoscopic pancreaticoduodenectomy from January 2015 to March 2021. The primary outcome was to explore the association between the modified Blumgart anastomosis technique and operative time. Results: A total of 282 patients were enrolled. There were 177 cases of pancreatic duct-to-mucosa anastomosis in the traditional surgery group, and 105 cases of the modified three-step Blumgart anastomosis in the modified group. There were no statistically significant differences in the general and intraoperative characteristics found between the two groups (P > 0.05). The surgical method was an independent predictor of operative time. Overall complications postsurgery were less common in the modified group than in the traditional group. The incidence of postoperative pancreatic fistula was higher in the traditional group than in the modified group (45 cases (25.4%) and 11 cases (10.5%), respectively). Fourteen cases (7.9%) in the traditional group and four case (3.8%) in the modified group had postoperative pancreatic fistula of grades B + C. The two groups had statistically significant differences (P < 0.05). The results of the linear regression showed that the type of surgical method was associated with operation time (95% CI, -73.074 to -23.941, ß: -0.438, P < 0.001). Conclusion: This modified three-step Blumgart pancreaticojejunostomy was associated with the operation time.

Camrelizumab Combined With Gemcitabine and Albumin-Bound Paclitaxel for Neoadjuvant Therapy in the Treatment of Progressive Gallbladder Cancer: A Case Report.

Background: The roles of immune checkpoint inhibitors in the treatment of gallbladder cancer are still unclear and challenged by controversial findings. Recent research has shown that immune checkpoint inhibitors in combination with chemotherapy may alleviate disease progression. Case Summary: A 45-year-old female patient with gallbladder cancer accompanied by multiple abdominal lymph node metastasis was treated with camrelizumab combined with paclitaxel for injection (albumin-bound) and gemcitabine (AG) to downstage the tumor before a radical surgery could be performed. The postoperative quality of life was superior to the preoperative level. Conclusion: Camrelizumab + AG offers a new therapeutic option for gallbladder cancer with multiple abdominal lymph node metastasis, which, however, warrants further validation in clinical trials.

Comparative study between follicular unit transplantation with intact and non-intact hair bulb in treatment for stable vitiligo.

OBJECTIVE: To compare the cosmetic efficacy of the transplantation of follicles with intact and non-intact hair bulbs in the treatment for vitiligo. METHODS: The single-hair follicle units with intact hair bulbs and un-intact hair bulbs were transplanted into the skin of vitiligo. The diameters of regrowing hair shafts and repigmentation of implanted follicles were detected analyzed by dermatoscopy (Beining BN-PFMF Skin and Hair Visualizer). RESULTS: The survival rates of follicles with intact and non-intact hair bulbs were 60.00% and 50.62%, respectively. The average diameters of hair shafts and repigmentation of the two groups were 92.83 ± 7.26 µm vs 55.86 ± 2.64 µm (p < .05), 2.62 ± 0.13 mm vs 2.63 ± 0.17 mm (p > .05), respectively. CONCLUSION: Single follicle transplantation was an alternative effective choice for the treatment of vitiligo. The skin implanted with follicle with non-intact hair bulb was less hairy.

Actin gamma 1 is a critical regulator of pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of pancreatic cancers, which represents one of the most lethal malignancies with a 5-year overall survival less than 10%. Identifying molecular biomarkers is invaluable in helping to predict clinical outcomes and developing targeted chemotherapies. Actin gamma 1 (ACTG1) is a kind of actin isoform that exists in almost all cell types as a component of the cytoskeleton, thus mediating cell viability. Although there have been studies revealing the prognostic significance of ACTG1 in several malignancies such as glioblastoma and hepatocellular carcinoma, its involvement and function in pancreatic cancer needs to be elucidated. Methods: We retrospectively enrolled a cohort of PDAC patients after surgical resection (n = 149) and conducted immunohistochemistry experiments to explore the expression profile of ACTG1. Univariate and multivariate analyses were performed to investigate the clinical relevance of ACTG1. The functional role of ACTG1 in PDAC progression was further validated via both in vitro and in vivo studies. Results: ACTG1 presented a higher expression in PDAC tissues than in nontumorous pancreatic tissues. ACTG1 level positively correlated with tumor stage, implying its potential role as a tumor promoter. Univariate and multivariate analyses identified that patients with lower ACTG1 showed a better overall survival compared to those with higher ACTG1 expression. Cellular and xenograft experiments confirmed the role of ACTG1 on facilitating tumor proliferation both in vitro and in vivo. Conclusions: Our study revealed a pro-oncogenic role of ACTG1 in PDAC, which may help predict prognosis and serve as a novel therapeutic target.

Balanced, Orientation-Dependent Dichoptic Masking in Cortex of Visually Normal Humans Measured Using Electroencephalography (EEG).

In the human visual system, cerebral cortex combines left- and right-eye retinal inputs, enabling single, comfortable binocular vision. In visual cortex, the signals from each eye inhibit one another (interocular suppression). While this mechanism may be disrupted by e.g. traumatic brain injury, clinical assessments of interocular suppression are subjective, qualitative, and lack reliability. EEG is a potentially useful clinical tool for objective, quantitative assessment of binocular vision. In a cohort of normal participants, we measured occipital, visual evoked potentials (VEPs) in response to dichoptically-presented vertical and/or horizontal sine-wave gratings. Response amplitudes to orthogonal gratings were greater than that of parallel gratings, which were in turn greater than that of monocular gratings. Our results indicate that interocular suppression is (normally) balanced, orientation-tuned, and that suppression per se is reduced for orthogonal gratings. This objective measure of suppression may have application in clinical settings.

Towards the Classification of Error-Related Potentials using Riemannian Geometry.

The error-related potential (ErrP) is an event-related potential (ERP) evoked by an experimental participant's recognition of an error during task performance. ErrPs, originally described by cognitive psychologists, have been adopted for use in brain-computer interfaces (BCIs) for the detection and correction of errors, and the online refinement of decoding algorithms. Riemannian geometry-based feature extraction and classification is a new approach to BCI which shows good performance in a range of experimental paradigms, but has yet to be applied to the classification of ErrPs. Here, we describe an experiment that elicited ErrPs in seven normal participants performing a visual discrimination task. Audio feedback was provided on each trial. We used multi-channel electroencephalogram (EEG) recordings to classify ErrPs (success/failure), comparing a Riemannian geometry-based method to a traditional approach that computes time-point features. Overall, the Riemannian approach outperformed the traditional approach (78.2% versus 75.9% accuracy, p <0.05); this difference was statistically significant (p <0.05) in three of seven participants. These results indicate that the Riemannian approach better captured the features from feedback-elicited ErrPs, and may have application in BCI for error detection and correction.

Single-cell transcriptomic analysis reveals the critical molecular pattern of UV-induced cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer characterized by high invasiveness, heterogeneity, and mainly occurs in the ultraviolet (UV)-exposed regions of the skin, but its pathogenesis is still unclear. Here, we generated single-cell transcriptome profiles for 350 cells from six primary UV-induced cSCCs, together with matched adjacent skin samples, and three healthy control skin tissues by single-cell RNA-sequencing technology based on Smart-seq2 strategy. A series of bioinformatics analyses and in vitro experiments were used to decipher and validate the critical molecular pattern of cSCC. Results showed that cSCC cells and normal keratinocytes were significantly distinct in gene expression and chromosomal copy number variation. Furthermore, cSCC cells exhibited 18 hallmark pathways of cancer by gene set enrichment analysis. Differential expression analysis demonstrated that many members belonging to S100 gene family, SPRR gene family, and FABP5 were significantly upregulated in cSCC cells. Further experiments confirmed their upregulation and showed that S100A9 or FABP5 knockdown in cSCC cells inhibited their proliferation and migration through NF-κB pathway. Taken together, our data provide a valuable resource for deciphering the molecular pattern in UV-induced cSCC at a single-cell level and suggest that S100A9 and FABP5 may provide novel targets for therapeutic intervention of cSCC in the future.

Determination of COL1A1-PDGFB breakpoints by next-generation sequencing in the molecular diagnosis of dermatofibrosarcoma protuberans.

OBJECTIVE: In most cases, dermatofibrosarcoma protuberans (DFSP) is characterized by the chromosomal translocation t (17; 22) (q22; q13) that leads to a fusion of collagen type 1 alpha 1 (COL1A1) and platelet-derived growth factor beta chain (PDGFB). Recently, next-generation sequencing (NGS) has been reported to detect fusion transcripts in some malignancies. Therefore, the present study aimed to evaluate the utility of the targeted NGS in detecting the COL1A1-PDGFB fusion in patients with DFSP. METHODS: We designed a targeted DNA capture panel to tile along the fusion regions, including exon, intron, and untranslated regions of the COL1A1 and PDGFB. A cohort of 18 DNA samples extracted from formalin-fixed, paraffin-embedded tissues was used to evaluate the targeted NGS. The results were compared with that of fluorescence in situ hybridization (FISH). RESULTS: The COL1A1-PDGFB fusion was identified in 13 of 18 cases (72.2%) by targeted NGS assay. PDGFB breakpoints were constantly found in exon 2, while breakpoints in COL1A1 varied from exon 15 to 46. Of these 18 cases assayed by FISH, 12 (66.7%) exhibited COL1A1-PDGFB fusion signals. One case (P9), which was FISH-negative, was demonstrated with the fusion by targeted NGS and validated by PCR and Sanger sequencing. The targeted NGS results showed a high concordance with the results of the FISH assay (94.4%). CONCLUSION: Our study reported a targeted NGS assay for detecting the breakpoints of the COL1A1-PDGFB fusion gene, which can be implemented in diagnosing patients with DFSP.

Sequential therapy with combined trans-papillary endoscopic naso-pancreatic and endoscopic retrograde pancreatic drainage for pancreatic pseudocysts.

BACKGROUND: Endoscopic retrograde pancreatic drainage (ERPD) and stent implantation has become the major treatment method for pancreatic pseudocysts. However, it is associated with a high recurrence rate and infection. AIM: To manage pancreatic pseudocysts by sequential therapy with endoscopic naso-pancreatic drainage (ENPD) combined with ERPD and evaluate the treatment outcome. METHODS: One hundred and sixty-two cases of pancreatic pseudocyst confirmed by endoscopic examination at our hospital between January 2014 and January 2020 were retrospectively analyzed. There were 152 cases of intubation via the duodenal papilla, of which 92 involved pancreatic duct stent implantation and 60 involved sequential therapy with combined ENPD and ERPD (two-step procedure). The success rate of the procedure, incidence of complications (infection, bleeding, etc.), recurrence, and length and cost of hospitalization were compared between the two groups. RESULTS: The incidence of infection was significantly higher in the ERPD group (12 cases) than in the two-step procedure group (2 cases). Twelve patients developed infection in the ERPD group, and anti-infection therapy was effective in five cases but not in the remaining seven cases. Infection presented as fever and chills in the two-step procedure group. The reoperation rate was significantly higher in the ERPD group with seven cases compared with zero cases in the two-step procedure group (P < 0.05). Similarly, the recurrence rate was significantly higher in the ERPD group (19 cases) than in the two-step procedure group (0 cases). CONCLUSION: Sequential therapy with combined ENPD and ERPD is safe and effective in patients with pancreatic pseudocysts.

Circ_0062270 upregulates EPHA2 to facilitate melanoma progression via sponging miR-331-3p.

BACKGROUND: Circular RNA (circRNA) has been confirmed to play a vital role in melanoma progression. OBJECTIVE: The regulatory function of circ_0062270, a novel circRNA, in melanoma progression is unclear. METHODS: Relative expression levels of circ_0062270 and microRNA (miR)-331-3p were determined using qRT-PCR. Cell counting kit 8 assay, EdU staining and flow cytometry were used to measure cell proliferation, cell cycle distribution and apoptosis. The protein levels of proliferation, apoptosis and metastasis-related markers, as well as EPH receptor A2 (EPHA2), were tested using western blot analysis. Besides, cell migration and invasion were evaluated using transwell assay. Meanwhile, the interaction between miR-331-3p and circ_0062270 or EPHA2 was confirmed by dual-luciferase reporter assay or RIP assay. Additionally, tumor xenograft models were constructed to investigate the function of circ_0062270 on melanoma tumor growth in vivo. RESULTS: The expression of circ_0062270 was increased in melanoma tissues and cells. Knockdown of circ_0062270 inhibited proliferation, promoted apoptosis, and repressed metastasis in melanoma. Moreover, circ_0062270 could serve as miR-331-3p sponge, and miR-331-3p could target EPHA2. Furthermore, miR-331-3p inhibitor and EPHA2 overexpression reversed the inhibitory effect of circ_0062270 silencing on melanoma progression. In addition, silenced circ_0062270 also could inhibit melanoma tumor growth in vivo. CONCLUSION: Circ_0062270 accelerated the progression of melanoma through regulating the miR-331-3p/EPHA2 axis, suggesting that circ_0062270 might be a novel potential therapeutic target for melanoma.

Laparoscopic versus open pancreatoduodenectomy for pancreatic or periampullary tumours: a multicentre, open-label, randomised controlled trial.

BACKGROUND: The benefit and safety of laparoscopic pancreatoduodenectomy (LPD) for the treatment of pancreatic or periampullary tumours remain controversial. Studies have shown that the learning curve plays an important role in LPD, yet there are no randomised studies on LPD after the surgeons have surmounted the learning curve. The aim of this trial was to compare the outcomes of open pancreatoduodenectomy (OPD) with those of LPD, when performed by experienced surgeons. METHODS: In this multicentre, open-label, randomised controlled trial done in 14 Chinese medical centres, we recruited patients aged 18-75 years with a benign, premalignant, or malignant indication for pancreatoduodenectomy. Eligible patients were randomly assigned (1:1) to undergo either LPD or OPD. Randomisation was centralised via a computer-generated system that used a block size of four. The patients and surgeons were unmasked to study group, whereas the data collectors, outcome assessors, and data analysts were masked. LPD and OPD were performed by experienced surgeons who had already done at least 104 LPD operations. The primary outcome was the postoperative length of stay. The criteria for discharge were based on functional recovery, and analyses were done on a modified intention-to-treat basis (ie, including patients who had a pancreatoduodenectomy regardless of whether the operation was the one they were assigned to). This trial is registered with Clinicaltrials.gov, number NCT03138213. FINDINGS: Between May 18, 2018, and Dec 19, 2019, we assessed 762 patients for eligibility, of whom 656 were randomly assigned to either the LPD group (n=328) or the OPD group (n=328). 31 patients in each group were excluded and 80 patients crossed over (33 from LPD to OPD, 47 from OPD to LPD). In the modified intention-to-treat analysis (297 patients in the LPD group and 297 patients in the OPD group), the postoperative length of stay was significantly shorter for patients in the LPD group than for patients in the OPD group (median 15·0 days [95% CI 14·0-16·0] vs 16·0 days [15·0-17·0]; p=0·02). 90-day mortality was similar in both groups (five [2%] of 297 patients in the LPD group vs six [2%] of 297 in the OPD group, risk ratio [RR] 0·83 [95% CI 0·26-2·70]; p=0·76). The incidence rate of serious postoperative morbidities (Clavien-Dindo grade of at least 3) was not significantly different in the two groups (85 [29%] of 297 patients in the LPD group vs 69 [23%] of 297 patients in OPD group, RR 1·23 [95% CI 0·94-1·62]; p=0·13). The comprehensive complication index score was not significantly different between the two groups (median score 8·7 [IQR 0·0-26·2] vs 0·0 [0·0-20·9]; p=0·06). INTERPRETATION: In highly experienced hands, LPD is a safe and feasible procedure. It was associated with a shorter length of stay and similar short-term morbidity and mortality rates to OPD. Nonetheless, the clinical benefit of LPD compared with OPD was marginal despite extensive procedural expertise. Future research should focus on identifying the populations that will benefit from LPD. FUNDING: National Natural Science Foundation of China and Tongji Hospital, Huazhong University of Science and Technology, China.