Circ_0005397 inhibits ferroptosis of pancreatic cancer cells by up-regulating PCBP2 through KAT6A/H3K9Ac.

Pancreatic cancer is a highly aggressive and lethal carcinoma. Circular RNAs (circRNAs) serve key regulatory functions in pancreatic cancer. Ferroptosis was induced by erastin treatment and analyzed by examining malondialdehyde (MDA), iron, Fe2+ and glutathione (GSH). C11-BODIPY 581/591 was used to stain cells for analyzing lipid peroxidation. RNA immunoprecipitation, pull-down and chromatin immunoprecipitation assays were applied to evaluate intermolecular interaction. Mice received subcutaneous injection of pancreatic cancer cells as a model of subcutaneous tumor for in vivo tests. Circ_0005397 was abundantly expressed in pancreatic cancer, and its upregulation was associated with low survival of patients with pancreatic cancer. Circ_0005397 expression was induced by EIF4A3. PCBP2 was highly expressed in pancreatic cancer, and circ_0005397 and PCBP2 were positively correlated in patients with pancreatic cancer. Circ_0005397 knockdown sensitized pancreatic carcinoma cells to ferroptosis via downregulating PCBP2. Circ_0005397 promoted PCBP2 transcription via facilitating the binding of KAT6A and H3K9ac to PCBP2 promoter. Silencing of circ_0005397 reduced tumor growth by enhancing erastin-induced ferroptosis in vivo. EIF4A3-induced circ_0005397 inhibited erastin-induced ferroptosis in pancreatic cancer by promoting PCBP2 expression through KAT6A and H3K9ac.

Random laser emission at 1064 and 1550†nm in a Er/Yb co-doped fiber-based dual-wavelength random fiber laser.

Dual-wavelength fiber lasers operating with a wide spectral separation are of considerable importance for many applications. In this study, we propose and experimentally explore an all-fiberized dual-wavelength random fiber laser with bi-directional laser output operating at 1064 and 1550 nm, respectively. A specially designed Er/Yb co-doped fiber, by optimizing the concentrations of the co-doped Er, Yb, Al and P, was developed for simultaneously providing Er ions gain and Yb ions gain for RFL. Two spans of single mode passive fibers are employed to providing random feedback for 1064 and 1550 nm random lasing, respectively. The RFL generates 5.35 W at 1064 nm and 6.61 W at 1550 nm random lasers. Two power amplifiers (PA) enhance the seed laser to 50 W at 1064 nm with a 3 dB bandwidth of 0.31 nm and 20 W at 1550 nm with a 3 dB bandwidth of 1.18 nm. Both the short- and long-term time domain stabilities are crucial for practical applications. The output lasers of 1064 and 1550 nm PAs are in the single transverse mode operating with a nearly Gaussian profile. To the best of our knowledge, this is the first demonstration of a dual-wavelength RFL, with a spectral separation as far as about 500 nm in an all-fiber configuration.

Genomic profiling informs therapies and prognosis for patients with hepatocellular carcinoma in clinical practice.

Hepatocellular carcinoma (HCC) genomic research has discovered actionable genetic changes that might guide treatment decisions and clinical trials. Nonetheless, due to a lack of large-scale multicenter clinical validation, these putative targets have not been converted into patient survival advantages. So, it's crucial to ascertain whether genetic analysis is clinically feasible, useful, and whether it can be advantageous for patients. We sequenced tumour tissue and blood samples (as normal controls) from 111 Chinese HCC patients at Qingdao University Hospital using the 508-gene panel and the 688-gene panel, respectively. Approximately 95% of patients had gene variations related to targeted treatment, with 50% having clinically actionable mutations that offered significant information for targeted therapy. Immune cell infiltration was enhanced in individuals with TP53 mutations but decreased in patients with CTNNB1 and KMT2D mutations. More notably, we discovered that SPEN, EPPK1, and BRCA2 mutations were related to decreased median overall survival, although MUC16 mutations were not. Furthermore, we found mutant MUC16 as an independent protective factor for the prognosis of HCC patients after curative hepatectomy. In conclusion, this study connects genetic abnormalities to clinical practice and potentially identifies individuals with poor prognoses who may benefit from targeted treatment or immunotherapy.

Effect of simethicone for the management of early abdominal distension after laparoscopic cholecystectomy: a multicenter retrospective propensity score matching study.

OBJECTIVE: To investigate whether simethicone expediates the remission of abdominal distension after laparoscopic cholecystectomy (LC). METHODS: This retrospective study involved LC patients who either received perioperative simethicone treatment or not. Propensity score matching (PSM) was employed to minimize bias. The primary endpoint was the remission rate of abdominal distension within 24 h after LC. Univariable and multivariable logistic regression analyses were conducted to identify independent risk factors affecting the early remission of abdominal distension after LC. Subsequently, a prediction model was established and validated. RESULTS: A total of 1,286 patients were divided into simethicone (n = 811) and non-simethicone groups (n = 475) as 2:1 PSM. The patients receiving simethicone had better remission rates of abdominal distension at both 24 h and 48 h after LC (49.2% vs. 34.7%, 83.9% vs. 74.8%, respectively), along with shorter time to the first flatus (14.6 ± 11.1 h vs. 17.2 ± 9.1 h, P < 0.001) compared to those without. Multiple logistic regression identified gallstone (OR = 0.33, P = 0.001), cholecystic polyp (OR = 0.53, P = 0.050), preoperative abdominal distention (OR = 0.63, P = 0.002) and simethicone use (OR = 1.89, P < 0.001) as independent factors contributing to the early remission of abdominal distension following LC. The prognosis model developed for predicting remission rates of abdominal distension within 24 h after LC yielded an area under the curve of 0.643 and internal validation a value of 0.644. CONCLUSIONS: Simethicone administration significantly enhanced the early remission of post-LC abdominal distension, particularly for patients who had gallstones, cholecystic polyp, prolonged anesthesia or preoperative abdominal distention. TRIAL REGISTRATION: ChiCTR2200064964 (24/10/2022).

Clinicopathological characteristics of pheochromocytoma/paraganglioma and screening of prognostic markers.

BACKGROUND: Malignant pheochromocytoma/paraganglioma (PCPG) is lethal and difficult to diagnose before metastasis. This study is aiming to characterize the PCPG and explore novel prognostic markers. METHODS: Clinical data of patients with pathologically confirmed invasive and noninvasive PCPG were collected and analyzed. Then, the differentially expressed genes (DEGs) and HUB genes were identified by R package "limma" in GSE67066-GPL570. Afterward, the prognostic markers were screened out using R packages of "survival" and "survminer" based on the TCGA data. RESULTS: The 34 invasive PCPGs were characterized by irregular contour and unclear boundary on CT and capsule/extracapsule tissue invasion on pathology compared with the 42 noninvasive PCPGs. Then, 29 upregulated and 30 downregulated DEGs were identified in malignant PCPG compared with benign, which were mainly enriched in the terms of calcium ion binding, neuron cell-cell adhesion, axon, regulation of hormone levels, and regulation of secretion by cell. Of which, nine DEGs were furtherly selected as the HUB genes. Finally, CNTN4 and SH3GL2 were found to be highly expressed in malignant PCPGs and negatively correlated with progression-free interval. CONCLUSIONS: Malignant PCPGs tend to be aggressive in imaging and pathology. The high expression of CNTN4 and SH3GL2 in PCPGs may indicate a poor prognosis.

Current diagnosis and treatment of acute pancreatitis in China: a real-world, multicenter study.

BACKGROUND: Efficacy of pancreatic enzyme inhibitors in acute pancreatitis (AP) is unclear in China. AIMS: We aimed to present the current status of AP and evaluate the efficacy of pancreatic enzyme inhibitors in a larger population in China. METHOD: A retrospective, cross-sectional, real-world, multicenter analysis of a large dataset of patients presenting with AP from four hospitals of China over a two-year period was performed. Data were collected from the existing clinical records and the patients were grouped into medication group (somatostatin or octreotide or somatostatin and octreotide) and no medication group. Pair wise propensity score matching was performed for comparing somatostatin, octreotide and somatostatin/octreotide. The end points were incidence of disease complications, organ failure, hospitalization duration, and recovery time taken (hours) for serum amylase/serum lipase to normalcy. RESULTS: A total of 3900 patients were recruited and 2775 patients were included for analysis. A total of 1100, 661, 676 and 338 patients received either somatostatin or octreotide or somatostatin and octreotide or no medication, respectively. The incidence of complications (7.6% vs 13.6%), organ failure (4.5% vs 7.4%), and the instances of entering ICU (9.3% vs 13.3%) were higher in unmedicated group. Complications at discharge (2.91 times), organ failure (2.53 times), and hospitalization stay were higher in octreotide-treated patients compared with somatostatin-treated patients. In comparison to the octreotide group, the serum amylase/lipase recovery time was shorter in the somatostatin group. CONCLUSION: This real-world study suggested that the use of pancreatic enzyme inhibitors was positively associated with greater clinical efficacy in AP patients and somatostatin might be more effective than octreotide in real-world settings in China.

Kilowatt-level tunable all-fiber narrowband superfluorescent fiber source with 40†nm tuning range.

In this study, we presented a high-power widely tunable all-fiber narrowband superfluorescent fiber source (SFS) by employing two tunable bandpass filters and three amplifier stages. More than 935 W output power is achieved, with a slope efficiency of >75% and a beam quality factor of M2=1.40. The tuning of the narrowband SFS ranges from ∼1045 nm to ∼1085 nm with a full width at half maximum linewidth of less than 0.71 nm. The tunable narrowband SFS stably operates without the influence of parasitic oscillation and self-pulsing effects under maximum power. To the best of our knowledge, this study is the first to demonstrate a widely tunable all-fiber narrowband SFS around 1 µm wavelength region with output power reaching kilowatt-level.

Influence of amplified spontaneous emission on laser linewidth in a fiber amplifier.

Spectral broadening due to amplified spontaneous emission (ASE) in a fiber amplifier is experimentally and theoretically investigated in this paper. By measuring and analyzing the variation in linewidth and noise of the fiber amplifier, the influence of ASE on laser linewidth is studied. The analysis shows that the ASE will cause broadening of the laser linewidth as noise, and the noise is introduced as an additive term rather than a multiplicative one.

Excessively tilted fiber grating based Fe3O4 saturable absorber for passively mode-locked fiber laser.

A novel approach to saturable absorber (SA) formation is presented by taking advantage of the mode coupling property of excessively tilted fiber grating (Ex-TFG). Stable mode-locked operation can be conveniently achieved based on the interaction between Ex-TFG coupled light and deposited ferroferric-oxide (Fe3O4) nanoparticles. The central wavelength, bandwidth and single pulse duration of the output are 1595 nm, 4.05 nm, and 912 fs, respectively. The fiber laser exhibits good long-term stability with signal-to-noise ratio (SNR) of 67 dB. For the first time, to the best of our knowledge, Ex-TFG based Fe3O4 SA for mode-locked fiber laser is demonstrated.

M3 muscarinic acetylcholine receptors regulate epithelial-mesenchymal transition, perineural invasion, and migration/metastasis in cholangiocarcinoma through the AKT pathway.

BACKGROUND: Cholangiocarcinoma is a highly malignant tumor type that is not sensitive to radiotherapy or chemotherapy due to aggressive perineural invasion and metastasis. Unfortunately, the mechanisms underlying these processes and the signaling factors involved are largely unknown. In this study, we analyzed the role of M3 muscarinic acetylcholine receptors (M3-mAChR) in cell migration, perineural invasion, and metastasis during cholangiocarcinoma. METHODS: We assessed 60 human cholangiocarcinoma tissue samples and 30 normal biliary tissues. Immunohistochemical staining was used to detect M3-mAChR expression and the relationship between expression and clinical prognosis was evaluated. The biological functions of M3-mAChR in cholangiocarcinoma cell migration, perineural invasion, and epithelial-mesenchymal transition (EMT) were investigated using the human cholangiocarcinoma cell lines FRH0201 and RBE in conjunction with various techniques, including agonist/antagonist treatment, RNA interference, M3-mAChR overexpression, dorsal root ganglion co-culturing, immunohistochemistry, western blotting, etc. RESULTS: M3-mAChR were highly expressed in cholangiocarcinoma tissue and expression was closely related to differentiation and lymphatic metastasis, affecting patient survival. Treatment with the M3-mAChR agonist pilocarpine and M3-mAChR overexpression significantly promoted migration and perineural invasion, while the M3-mAChR antagonist atropine blocked these effects. Similarly, M3-mAChR knock-down also weakened cell migration and perineural invasion. The expression of phosphatase and tensin homolog, AKT, E-cadherin, vimentin, and Snail, which are components of the phosphatidylinositol 3-kinase/AKT signaling pathway and EMT, were altered by pilocarpine, and these effects were again blocked by atropine. Notably, AKT knock-down decreased M3-mAChR expression and reversed the downstream effects of this receptor. CONCLUSIONS: M3-mAChR are involved in tumor cell migration, perineural invasion, and EMT during cholangiocarcinoma, and these effects are modulated via the AKT signaling pathway.

MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1.

BACKGROUND/AIMS: Doublecortin-like kinase 1 (DCLK1) is emerging as a tumor-specific stem cell marker in pancreatic cancer (PC). MicroRNA-195 (miR-195) plays an important role in many types of tumors. However, the roles of DCLK1 in cancer and miRNAs that directly regulate DCLK1 have not been elucidated. The goal of this study is to assess the effects of miR-195 on inhibiting DCLK1 and to clarify the regulating mechanism of miR-195-DCLK1 in PC cells. METHODS: The expression of DCLK1 protein and miR-195 in PC tissues and adjacent healthy pancreatic tissues was detected by Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively and the correlation between overall survival of PC patients and expression of DCLK1 was measured by Kaplan-Meier analysis. Bioinformatics tools were used to identify the target gene of miR-195. Effects of miR-195 and DCLK1 on proliferation and cell cycle of PC cells were analyzed by MTT, colony formation assays and flow cytometry. Transwell and wound-healing experiments were employed to examine the cellular migration and invasion. A xenograft mouse model was also used to test the effects of miR-195 on tumor growth and metastasis in vivo. RESULTS: The expression level of DCLK1 and miR-195 shows an inverse correlation in PC tissues and cell lines. A higher DCLK1 level is associated with higher TNM (tumor, node, and metastasis) stage, higher rate of lymph node metastasis, and poor survival. Luciferase reporter assay shows that miR-195 directly targets DCLK1. Overexpression of miR-195 inhibits proliferation, migration and invasion of PC cells, whereas downregulation of miR-195 has an opposite role. These actions were similar to the effects of knockdown and overexpression of DCLK1, respectively. CONCLUSIONS: These data suggest that miR-195 has tumor suppressor roles in PC by targeting DCLK1. MiR-195-DCLK1 pathway may provide insight into PC progression and represent a novel, promising diagnostic and therapeutic target for PC.

Roles of microRNA-330 and Its Target Gene ING4 in the Development of Aggressive Phenotype in Hepatocellular Carcinoma Cells.

BACKGROUND: Aberrant expression of microRNAs contributes to tumor growth and progression. AIMS: This study was designed to explore the prognostic and biological significance of miR-330 in hepatocellular carcinoma (HCC). METHODS: The expression of miR-330 and its associations with tumor parameters and overall survival were analyzed in HCC patients. The biological functions of miR-330 in HCC cell growth, invasion, and tumorigenesis were investigated. Bioinformatic analysis and luciferase reporter assays were performed to search for potential targets of miR-330. RESULTS: The miR-330 level was significantly higher in HCCs than in adjacent normal tissues (P = 0.0085). High expression of miR-330 was significantly associated with more aggressive phenotypes and shorter overall survival in HCC. Loss- and gain-of-function studies indicated the favorable effect of miR-330 on tumor cell growth, invasion, and tumorigenesis. Inhibitor of growth 4 (ING4) was identified to be a direct target of miR-330. Overexpression of miR-330 reduced the expression of ING4 in HCC cells. Importantly, restoration of ING4 almost completely reversed the promotion of HCC cell proliferation and invasion by miR-330. CONCLUSIONS: Altogether, this study demonstrates that upregulation of miR-330 is associated with poor prognosis and contributes to more aggressive phenotypes of HCC. The oncogenic role of miR-330 in HCC is linked to downregulation of ING4.

Textbook outcome of laparoscopic hepatectomy in the context of precision surgery: A single center experience.

OBJECTIVE: Laparoscopic hepatectomy (LH) has become a common surgery for the treatment of liver tumor. To evaluate the surgical quality of laparoscopic hepatectomy under the context of precision surgery with Textbook outcome (TO), a comprehensive and holistic assessment approach. METHODS: A total of 1056 patients who underwent laparoscopic hepatectomy from May 2016 and December 2022 were enrolled in the study. All the patients were performed hepatectomy. The rate of TO and factors associated with achieving TO were examined. RESULTS: Among the 1056 patients, 75 % patients achieved TO. The main reason limited patients achieving textbook outcomes was prolonged length of hospital stay (LOS). The univariate analysis indicated that age>65, ASA classification ≥3, liver cirrhosis, tumor size > 3 cm, tumor number ≥2, type of primary cancer, and IWATE DSS were significantly associated with non-achievement of TO. The multivariate analysis indicated that the ASA classification ≥3 and advanced difficulty level in IWATE DSS independent factors associated with achieving TO. Reaching TO can significantly prolong the postoperative recurrence time and overall survival time of hepatocellular carcinoma patients. CONCLUSION: In the context of precision surgery, 75 % patients undergoing laparoscopic hepatectomy achieved a TO. Patients who achieved TO had significantly improved survival.

Prevalence, patterns, risk factors and outcomes of peritoneal metastases after laparoscopic hepatectomy for hepatocellular carcinoma: a multicenter study from China.

Background: We aim to investigate the prevalence, patterns, risk factors, and outcomes of peritoneal metastases (PM) after curative laparoscopic hepatectomy (LH) for hepatocellular carcinoma (HCC). Methods: A multicenter cohort of 2,138 HCC patients who underwent curative LH from August 2010 to December 2016 from seven hospitals in China was retrospectively analyzed. The incidence of PM following LH was evaluated and compared with that in open hepatectomy (OH) after 1:1 propensity score matching (PSM). Results: PM prevalence was 5.1% (15/295) in the early period [2010-2013], 2.6% (47/1,843) in the later period [2014-2016], and 2.9% (62/2,138) in all LH patients, which was similar to 4.0% (59/1,490) in the OH patients. The recurrence patterns, timing, and treatment did not significantly vary between the LH and OH patients (P>0.05). Multivariate logistic regression revealed that tumor diameter >5 cm, non-anatomical resection, presence of microvascular invasion, and lesions <2 cm from major blood vessels were independent risk factors of PM after LH. Of the 62 cases with PM, 26 (41.9%) had PM only, 34 (54.9%) had intrahepatic recurrence (IHR) and PM, and 2 (3.2%) had synchronous extraperitoneal metastases (EPM). Patients with resectable PM had a 5-year overall survival (OS) of 65.0% compared to 9.0% for unresectable PM (P=0.001). Conclusions: The prevalence, patterns and independent risk factors of PM were identified for HCC patients after LH. LH was not associated with increased incidence of PM in HCC patients for experienced surgeons. Surgical re-excision of PM was associated with prolonged survival.

The potential role and mechanism of circRNA/miRNA axis in cholesterol synthesis.

Cholesterol levels are an initiating risk factor for atherosclerosis. Many genes play a central role in cholesterol synthesis, including HMGCR, SQLE, HMGCS1, FDFT1, LSS, MVK, PMK, MVD, FDPS, CYP51, TM7SF2, LBR, MSMO1, NSDHL, HSD17B7, DHCR24, EBP, SC5D, DHCR7, IDI1/2. Especially, HMGCR, SQLE, FDFT1, LSS, FDPS, CYP51, and EBP are promising therapeutic targets for drug development due to many drugs have been approved and entered into clinical research by targeting these genes. However, new targets and drugs still need to be discovered. Interestingly, many small nucleic acid drugs and vaccines were approved for the market, including Inclisiran, Patisiran, Inotersen, Givosiran, Lumasiran, Nusinersen, Volanesorsen, Eteplirsen, Golodirsen, Viltolarsen, Casimersen, Elasomeran, Tozinameran. However, these agents are all linear RNA agents. Circular RNAs (circRNAs) may have longer half-lives, higher stability, lower immunogenicity, lower production costs, and higher delivery efficiency than these agents due to their covalently closed structures. CircRNA agents are developed by several companies, including Orna Therapeutics, Laronde, and CirCode, Therorna. Many studies have shown that circRNAs regulate cholesterol synthesis by regulating HMGCR, SQLE, HMGCS1, ACS, YWHAG, PTEN, DHCR24, SREBP-2, and PMK expression. MiRNAs are essential for circRNA-mediated cholesterol biosynthesis. Notable, the phase II trial for inhibiting miR-122 with nucleic acid drugs has been completed. Suppressing HMGCR, SQLE, and miR-122 with circRNA_ABCA1, circ-PRKCH, circEZH2, circRNA-SCAP, and circFOXO3 are the promising therapeutic target for drug development, specifically the circFOXO3. This review focuses on the role and mechanism of the circRNA/miRNA axis in cholesterol synthesis in the hope of providing knowledge to identify new targets.

Prognosis value of microscopic bile duct invasion in hepatocellular carcinoma: A multicenter study.

OBJECTIVE: To evaluate the prognostic significance of microscopic bile duct invasion (MiBDI) in hepatocellular carcinoma (HCC) following R0 resection. PATIENTS AND METHODS: Patients who underwent R0 resection for HCC at nine medical centers were stratified into five groups: neither bile duct nor vascular invasion (MiBDI-MVI-), microscopic bile duct invasion alone (MiBDI+MVI-), both microscopic bile duct and vascular invasion (MiBDI+MVI+), microscopic vascular invasion alone (MiBDI-MVI+), and macroscopic bile duct invasion (MaBDI). Overall survival (OS) was assessed using Kaplan-Meier analysis, and independent risk factors of OS were determined using Cox proportional hazards models. RESULTS: A total of 377 HCC cases were analyzed. The OS for MiBDI+MVI- was similar to that of MiBDI-MVI- (p > 0.05) but better than MiBDI+MVI+, MiBDI-MVI+, and MaBDI (all p < 0.05). Multivariate analysis indicated that MiBDI was not an independent risk factor for OS, while MVI and MaBDI were. CONCLUSIONS: Overall survival (OS) in patients with MiBDI was superior to those with MVI and MaBDI. Isolated MiBDI did not influence OS in patients with HCC after R0 resection.

International experts consensus guidelines on robotic liver resection in 2023.

The robotic liver resection (RLR) has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system, however, controversies still exist. Based on the foundation of the previous consensus statement, this new consensus document aimed to update clinical recommendations and provide guidance to improve the outcomes of RLR clinical practice. The guideline steering group and guideline expert group were formed by 29 international experts of liver surgery and evidence-based medicine (EBM). Relevant literature was reviewed and analyzed by the evidence evaluation group. According to the WHO Handbook for Guideline Development, the Guidance Principles of Development and Amendment of the Guidelines for Clinical Diagnosis and Treatment in China 2022, a total of 14 recommendations were generated. Among them were 8 recommendations formulated by the GRADE method, and the remaining 6 recommendations were formulated based on literature review and experts' opinion due to insufficient EBM results. This international experts consensus guideline offered guidance for the safe and effective clinical practice and the research direction of RLR in future.

New insights into a microvascular invasion prediction model in hepatocellular carcinoma: A retrospective study from the SEER database and China.

Background and Aims: The prognosis of liver cancer is strongly influenced by microvascular infiltration (MVI). Accurate preoperative MVI prediction can aid clinicians in the selection of suitable treatment options. In this study, we constructed a novel, reliable, and adaptable nomogram for predicting MVI. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we extracted the clinical data of 1,063 patients diagnosed with hepatocellular carcinoma (HCC) and divided it into either a training (n = 739) or an internal validation cohort (n = 326). Based on multivariate analysis, the training cohort data were analyzed and a nomogram was generated for MVI prediction. This was further verified using an internal validation cohort and an external validation cohort involving 293 Chinese patients. Furthermore, to evaluate the efficacy, accuracy, and clinical use of the nomogram, we used concordance index (C-index), calibration curve, and decision curve analysis (DCA) techniques. Results: In accordance with the multivariate analysis, tumor size, tumor number, alpha-fetoprotein (AFP), and histological grade were independently associated with MVI. The established model exhibited satisfactory performance in predicting MVI. The C-indices were 0.719, 0.704, and 0.718 in the training, internal validation, and external validation cohorts, respectively. The calibration curves showed an excellent consistency between the predictions and actual observations. Finally, DCA demonstrated that the newly developed nomogram had favorable clinical utility. Conclusions: We established and verified a novel preoperative MVI prediction model in HCC patients. This model can be a beneficial tool for clinicians in selecting an optimal treatment plan for HCC patients.

Establishment and Application of a Novel Difficulty Scoring System for da Vinci Robotic Pancreatoduodenectomy.

Background: Robotic pancreatoduodenectomy (RPD) technology is developing rapidly, but there is still a lack of a specific and objective difficulty evaluation system in the field of application and training of RPD surgery. Methods: The clinical data of patients who underwent RPD in our hospital from November 2014 to October 2020 were analyzed retrospectively. Univariate and multivariate logistic regression analyses were used to determine the predictors of operation difficulty and convert into a scoring system. Results: A total of 72 patients were enrolled in the group. According to the operation time (25%), intraoperative blood loss (25%), conversion to laparotomy, and major complications, the difficulty of operation was divided into low difficulty (0-2 points) and high difficulty (3-4 points). The multivariate logistic regression model included the thickness of mesenteric tissue (P1) (P = 0.035), the thickness of the abdominal wall (B1) (P = 0.017), and the preoperative albumin (P = 0.032), and the nomogram was established. AUC = 0.773 (0.645-0.901). Conclusions: The RPD difficulty evaluation system based on the specific anatomical relationship between da Vinci's laparoscopic robotic arm and tissues/organs in the operation area can be used as a predictive tool to evaluate the surgical difficulty of patients before operation and guide clinical practice.

Prognostic analysis of hepatocellular carcinoma with macrovascular invasion after liver resection and a successful case of conversion therapy.

Objective: Macrovascular invasion (MVI) is an important factor leading to poor prognosis in hepatocellular carcinoma (HCC). Liver resection may offer favorable prognosis for selected patients with HCC. This study aimed to analyze the prognostic factors of HCC with MVI after liver resection as well as demonstrate a case of conversion therapy in an HCC patient with portal vein tumor thrombus (PVTT). Methods: A total of 168 HCC patients with MVI who underwent primary liver resection at the Affiliated Hospital of Qingdao University between January 2013 and October 2021 were enrolled in the study. Clinicopathological data were collected retrospectively. Univariate and multivariate regression analyses were used to investigate the risk factors influencing recurrence and overall survival. Additionally, conversion therapy with drug-eluting bead transarterial chemoembolization (D-TACE), and sorafenib plus sintilimab treatment was performed in an HCC patient with PVTT. Results: Among the 168 patients with HCC, 11 were diagnosed with hepatic vein tumor thrombosis, and the rest were diagnosed with PVTT. The 1-year disease-free survival rate was 37.5%, and the 3-year overall survival rate was 52.7%. Univariate and multivariate regression analyses revealed that HBsAg positivity, alpha-fetoprotein (AFP) level ≥400 ng/ml, liver capsule invasion, and tumor number ≥2 were independent prognostic factors for tumor recurrence, whereas HBsAg positivity was an independent risk factor for overall survival. Postoperative prophylactic medication did not significantly prolong the recurrence time. The median survival time (MST) after tumor recurrence was 13.4 months. In the patient treated with conversion therapy, the tumor gradually shrank and was eventually surgically resected. Conclusions: This study identified the independent prognostic and risk factors associated with recurrence and overall survival in HCC patients with MVI. Additionally, we successfully performed conversion therapy in an HCC patient with PVTT. The findings would help identify patients at high risk of recurrence and indicate that combined therapy may prolong the survival of HCC patients with PVTT.