Stepwise training program: A novel practice schedule for laparoscopic suturing.

Purpose: We establish stepwise training program in which laparoscopic suturing is broken down to discrete steps. The purpose is to evaluate the learning outcomes of stepwise training program. Materials and methods: Volunteer participants were enrolled from medical students and surgical trainees. Students took two courses of 2-h stepwise training, and a post-course (1st & 2nd) test was taken after each course; trainees took one course of stepwise training with a pre-course (1st) and a post-course (2nd) test. Attending surgeons took the test as control. Learning outcomes were assessed with laparoscopic suturing competency assessment tool (LS-CAT) and suturing time. Results: There were 10 students, 8 trainees and 6 surgeon controls. Suturing time and LS-CAT scores significantly improved between the 1st and 2nd test (p < 0.01). In the both tests, suturing time and LS-CAT scores of students and trainees were similar. In the 1st test, surgeons had significantly better performance in suturing time and LS-CAT score than students and trainees; in the 2nd test, the LS-CAT scores of students and trainees were similar to the surgeon controls. Conclusions: Stepwise program effectively enhances laparoscopic suturing skill for medical students and surgical trainees. Catch-up effect was demonstrated in medical students with stepwise training.

CWH43 Is a Novel Tumor Suppressor Gene with Negative Regulation of TTK in Colorectal Cancer.

Colorectal cancer (CRC) ranks among the most prevalent forms of cancer globally, and its late-stage survival outcomes are less than optimal. A more nuanced understanding of the underlying mechanisms behind CRC's development is crucial for enhancing patient survival rates. Existing research suggests that the expression of Cell Wall Biogenesis 43 C-Terminal Homolog (CWH43) is reduced in CRC. However, the specific role that CWH43 plays in cancer progression remains ambiguous. Our research seeks to elucidate the influence of CWH43 on CRC's biological behavior and to shed light on its potential as a therapeutic target in CRC management. Utilizing publicly available databases, we examined the expression levels of CWH43 in CRC tissue samples and their adjacent non-cancerous tissues. Our findings indicated lower levels of both mRNA and protein expressions of CWH43 in cancerous tissues. Moreover, we found that a decrease in CWH43 expression correlates with poorer prognoses for CRC patients. In vitro experiments demonstrated that the suppression of CWH43 led to increased cell proliferation, migration, and invasiveness, while its overexpression had inhibitory effects. Further evidence from xenograft models showed enhanced tumor growth upon CWH43 silencing. Leveraging data from The Cancer Genome Atlas (TCGA), our Gene Set Enrichment Analysis (GSEA) indicated a positive relationship between low CWH43 expression and the activation of the epithelial-mesenchymal Transition (EMT) pathway. We conducted RNA sequencing to analyze gene expression changes under both silenced and overexpressed CWH43 conditions. By identifying core genes and executing KEGG pathway analysis, we discovered that CWH43 appears to have regulatory influence over the TTK-mediated cell cycle. Importantly, inhibition of TTK counteracted the tumor-promoting effects caused by CWH43 downregulation. Our findings propose that the decreased expression of CWH43 amplifies TTK-mediated cell cycle activities, thus encouraging tumor growth. This newly identified mechanism offers promising avenues for targeted CRC treatment strategies.

Robotic versus laparoscopic hepatectomy: A single-center, propensity score- matched study.

BACKGROUND: Although the effectiveness of robotic hepatectomy (RH) has been evaluated in several studies, the superiority of RH over other approaches has not been definitely established. Therefore, in the present propensity score-matched cohort study, we compared RH and laparoscopic hepatectomy (LH) in terms of perioperative and oncologic outcomes. METHODS: This retrospective study included patients who underwent RH or LH for benign and malignant liver lesions at a single center in Taiwan at any time between 2014 and 2020. Confounding factors, specifically age, sex, body mass index, American Society of Anesthesiologists score, IWATE criteria, and Charlson comorbidity index, were adjusted through propensity score matching (PSM). RESULTS: A total of 329 patients were finally included in this study. Two homogeneous groups (RH and LH; n, 72 each) were formed using PSM. The RH group had a longer operative time (median: 231 vs.180 min, respectively; P = .001) and lower conversion (to open surgery) rate (9.7% vs.0.0%, respectively; P = .013) than did the LH group. However, the two groups did not differ in terms of other perioperative outcomes, specifically blood loss, hospital stay, intensive care unit admission, mortality, morbidity, or tumor margin status. CONCLUSIONS: The rate of conversion to open surgery is lower in RH than in LH. Although operative time is longer in RH than in LH, RH is feasible and safe for patients with benign or malignant liver lesion. Our study also demonstrated comparable oncological results in patients with hepatocellular carcinoma between LH and RH group.

2,3,5,4'-Tetrahydroxystilbene (TG1), a Novel Compound Derived from 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucoside (THSG), Inhibits Colorectal Cancer Progression by Inducing Ferroptosis, Apoptosis, and Autophagy.

BACKGROUND: Colorectal cancer (CRC) is one of the deadliest cancers worldwide and long-term survival is not guaranteed in metastatic disease despite current multidisciplinary therapies. A new compound 2,3,5,4'-Tetrahydroxystilbene (TG1), derived from THSG (2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-Glucoside), has been developed, and its anticancer ability against CRC is verified in this study. METHODS: HCT116, HT-29, and DLD-1 were treated with TG1 and the IC50 was measured using a sulforhodamine B assay. A Xenograft mouse model was used to monitor tumor growth. Apoptosis and autophagy, induced by TG1 in CRC cells, were examined. RNA-sequencing analysis of CRC cells treated with TG1 was performed to discover underlying pathways and mechanisms. RESULTS: The results demonstrated that treatment with TG1 inhibited CRC proliferation in vitro and in vivo and induced apoptotic cell death, which was confirmed by Annexin V-FITC/PI staining and Western blotting. Additionally, TG1 treatment increased the level of autophagy in cells. RNA-sequencing and GSEA analyses revealed that TG1 was associated with MYC and the induction of ferroptosis. Furthermore, the ferroptosis inhibitor Bardoxolone abrogated the cytotoxic effect of TG1 in CRC cells, indicating that ferroptosis played a crucial role in TG1-induced cytotoxicity. CONCLUSIONS: These findings suggest that TG1 might be a potential and potent compound for clinical use in the treatment of CRC by inhibiting proliferation and inducing ferroptosis through the MYC pathway.

Novel heavily fucosylated glycans as a promising therapeutic target in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is highly prevalent and lethal globally, and its prognosis remains unsatisfactory. Drug resistance is regarded as the main cause of treatment failure leading to tumor recurrence and metastasis. The overexpression of fucosylated epitopes, which are usually modifications of glycoproteins, was reported to occur in various epithelial cancers. However, the effects of treatments that target these antigens in colorectal cancer remain unclear. METHODS: This study investigated the expression of heavily fucosylated glycans (HFGs) in 30 clinical samples from patients with CRC and other normal human tissues. The complement-dependent cytotoxicity was explored in vitro through treatment with anti-HFG monoclonal antibody (mAb) alone or in combination with chemotherapeutic agents. In vivo inhibitory effects were also examined using a xenograft mouse model. RESULTS: Immunohistochemistry staining and western blotting revealed that HFG expression was higher in human colorectal cancer tissues than in normal tissues. In DLD-1 and SW1116 cells, which overexpress fucosylated epitopes, anti-HFG mAb produced observable cytotoxic effects, especially when it was combined with chemotherapeutic agents. The xenograft model also demonstrated that anti-HFG mAb had potent and dose-dependent inhibitory effects on colorectal tumor growth. CONCLUSIONS: As a novel cancer antigen, HFGs are a promising treatment target, and the implementation of anti-HFG mAb treatment for CRC warrants further investigation.

Galectin-1-mediated MET/AXL signaling enhances sorafenib resistance in hepatocellular carcinoma by escaping ferroptosis.

Sorafenib, a small-molecule inhibitor targeting several tyrosine kinase pathways, is the standard treatment for advanced hepatocellular carcinoma (HCC). However, not all patients with HCC respond well to sorafenib, and 30% of patients develop resistance to sorafenib after short-term treatment. Galectin-1 modulates cell-cell and cell-matrix interactions and plays a crucial role in HCC progression. However, whether Galectin-1 regulates receptor tyrosine kinases by sensitizing HCC to sorafenib remains unclear. Herein, we established a sorafenib-resistant HCC cell line (Huh-7/SR) and determined that Galectin-1 expression was significantly higher in Huh-7/SR cells than in parent cells. Galectin-1 knockdown reduced sorafenib resistance in Huh-7/SR cells, whereas Galectin-1 overexpression in Huh-7 cells increased sorafenib resistance. Galectin-1 regulated ferroptosis by inhibiting excessive lipid peroxidation, protecting sorafenib-resistant HCC cells from sorafenib-mediated ferroptosis. Galectin-1 expression was positively correlated with poor prognostic outcomes for HCC patients. Galectin-1 overexpression promoted the phosphorylation of AXL receptor tyrosine kinase (AXL) and MET proto-oncogene, receptor tyrosine kinase (MET) signaling, which increased sorafenib resistance. MET and AXL were highly expressed in patients with HCC, and AXL expression was positively correlated with Galectin-1 expression. These findings indicate that Galectin-1 regulates sorafenib resistance in HCC cells through AXL and MET signaling. Consequently, Galectin-1 is a promising therapeutic target for reducing sorafenib resistance and sorafenib-mediated ferroptosis in patients with HCC.

Cytotoxic properties of unfractionated and fractionated bromelain alone or in combination with chemotherapeutic agents in colorectal cancer cells.

BACKGROUND: Colorectal cancer (CRC) is one of the most lethal cancers worldwide. Long-term survival is not achieved in metastatic CRC despite the current multidisciplinary therapies. Bromelain, a compound extracted from the pineapple plant, has multiple functions and anticancer properties. Previously, bromelain has been chromatographically separated into four fractions. Fraction 3 (F3) exhibits the highest proteolytic activity. The anticancer effects of F3 bromelain in CRC cells is unknown. METHODS: In vitro cytotoxicity was verified through a sulforhodamine B assay. Apoptosis in CRC cells induced by unfractionated or F3 bromelain was examined using Annexin V-FITC/PI staining and Western blot analysis. ROS status, autophagy and lysosome formation were determined by specific detection kit. RESULTS: The cytotoxicity of F3 bromelain in CRC cells was found to be comparable to that of unfractionated bromelain. F3 bromelain induces caspase-dependent apoptosis in CRC cells. Treatment with unfractionated or F3 bromelain increased superoxide and oxidative stress levels and autophagy and lysosome formation. ATG5/12 and beclin-1 were upregulated, and the conversion of LC3B-I to LC3B-II was increased significantly by treatment with F3 bromelain. Treated CQ, autophagy inhibitor, with unfractionated or F3 bromelain enhances the cytotoxic effects. Finally, the combination of unfractionated and F3 bromelain with a routine chemotherapeutic agent (5-fluourouracil, irinotecan, or oxaliplatin) resulted in synergistically higher cytotoxic potency in CRC cells. CONCLUSION: Unfractionated and F3 bromelain inhibits CRC cell proliferation in vitro, and the cytotoxic effects of unfractionated bromelain are equivalent to F3 bromelain. F3 bromelain may be a potential and potent drug for clinical use due to its anticancer efficacy and high synergistic cytotoxicity when combined with a routine chemotherapeutic agent for CRC.

Inter-rater and intra-rater reliability of the current assessment model and tools for laparoscopic suturing.

BACKGROUND: Moorthy checklist (MC) and laparoscopic skill competency assessment tool (LS-CAT) are tools commonly used to evaluate the quality of laparoscopic suturing. The current assessment model is single measurement by multiple raters. Our aim is to examine the reliability of the current assessment model and tools. METHODS: With IRB approval, participants of three different backgrounds, namely medical students, trainees, and surgeons, were enrolled. The participants each accomplished a standardized laparoscopic suturing task. The performances were video-recorded and reviewed with LS-CAT and MC independently by three blinded raters. Intraclass correlation coefficients (ICC) were calculated for inter-rater and intra-rater reliability. RESULTS: 26 participants were enrolled, comprising 10 students, 10 trainees and 6 surgeons. In regard of inter-rater reliability, ICC values (95% CI) were 0.909 (0.768-0.961) and 0.868 (0.608-0.948) in LS-CAP and MC, respectively. For students, ICC values were 0.908 (0.682-0.976) and 0.815 (0.408-0.951) in LS-CAT and MC, respectively. For trainees, ICC values were 0.812 (0.426-0.947) and 0.717 (0.102-0.925), respectively. For surgeons, ICC values were 0.720 (0.064-0.955) and 0.868 (0.608-0.948), respectively. In regard of intra-rater reliability, ICC values of the mean scores from the three raters were 0.956 (0.905-0.980) and 0.925 (0.842-0.966) in LS-CAP and MC, respectively. CONCLUSION: LS-CAT and MC are both qualified assessment tools for laparoscopic suturing. LS-CAT is more reliable particularly for medical students and trainees. The current assessment model of single measurement by multiple raters provides excellent reliability.

Routine intraoperative cholangiography during laparoscopic cholecystectomy: application of the 2016 WSES guidelines for predicting choledocholithiasis.

BACKGROUND: Routine use of intraoperative cholangiography (IOC) during laparoscopic cholecystectomy (LC) for detecting common bile duct stones remains controversial. The 2016 World Society of Emergency Surgery (WSES) guidelines on acute calculous cholecystitis proposed a risk stratification for choledocholithiasis. Our present study aimed to (1) examine the findings of common bile duct (CBD) stones in patients underwent LC with routine use of IOC, and (2) validate the 2016 WSES risk classes for predicting choledocholithiasis. METHODS: All patients had LC with IOC routinely performed from November 2012 to December 2017 were reviewed retrospectively. Patients were classified into high-, intermediate-, and low-risk groups based on the 2016 WSES risk classes with modification. RESULTS: A total of 990 patients with LC and routine IOC were enrolled. CBD stones were detected in 197 (19.9%) patients. The rate of CBD stone detected in low-, intermediate-, high-risk groups were 0%, 14.2%, and 89.6%, respectively. Predictors as following: evidence of CBD stones on abdominal ultrasound or computed tomography, CBD diameter > 6 mm, total bilirubin > 4 mg/dL, bilirubin level = 1.8-4 mg/dL, abnormal liver biochemical test result other than bilirubin, presence of clinical gallstone pancreatitis had statistical significance between patients with and without CBD stones. Major bile duct injury was found in 4 patients (0.4%). All 4 patients had uneventful recovery after repair surgery. CONCLUSIONS: Based on our study results, the 2016 WSES risk classes for choledocholithiasis could be an effective approach for predicting the risk of choledocholithiasis. Considering its advantages for detecting CBD stones and biliary injuries, the routine use of IOC is still suggested.

Comparison of surgical outcomes for laparoscopic liver resection of large hepatocellular carcinomas: A retrospective observation from single-center experience.

BACKGROUND/PURPOSE: Although laparoscopic liver resection (LLR) is a common surgical procedure for hepatocellular carcinoma (HCC), its suitability for large HCCs (≥5 cm) remains controversial. This study compared surgical outcomes of open hepatectomy with LLR for large HCCs. METHODS: A total of 313 patients with HCC who underwent hepatectomy between January 2010 and June 2017 were analyzed retrospectively. Demographic data, short-term outcomes, and long-term survivals were analyzed. RESULTS: Among patients with large HCCs (n = 122), the open group (n = 85) had larger tumor sizes (10.91 ± 4.72 vs. 7.45 ± 2.95 cm; p < 0.001) and more advanced stages (stages 3/4: 71.8% vs. 45.9%; p = 0.029) than the LLR group (n = 37), while LLR group achieved less blood loss (623.24 ± 841.75 mL vs. 1091.76 ± 1004.72 mL, p = 0.014) and shorter LOS (9.00 ± 5.13 d vs. 12.82 ± 8.51 d, p = 0.013). There were no significant differences in complication and mortality rates between groups. The 5-year overall and recurrence-free survival rates between the two groups were not significantly different (p = 0.408 and 0.644 respectively). The surgical outcomes showed equal benefit of the two operation types. CONCLUSION: With sufficient surgeon experience and appropriate patient selection, LLR is a feasible treatment choice for large HCCs.

Long-term and short-term surgical outcomes of single-incision laparoscopic hepatectomy on anterolateral liver segments.

BACKGROUND: Laparoscopic liver resection yields improved short-term surgical outcomes, whereas the reports about clinical benefits of single-incision laparoscopic hepatectomy (SILH) are scarce. This retrospective study is to compare the surgical outcomes of SILH with those of multi-incision laparoscopic hepatectomy (MILH). METHODS: The study included 54 patients who had undergone SILH and 184 patients who had undergone MILH between January 2010 and December 2017. Short-term outcomes were compared in those of patients who underwent left lateral sectionectomy and partial hepatectomy of segment 5-6. A subgroup analysis of hepatocellular carcinoma (HCC) was also performed for long-term outcome comparisons. RESULTS: In those of patients who underwent left lateral sectionectomy, SILH group had less chronic hepatitis B (15.2 vs. 45.8%; p = 0.004), less liver cirrhosis (12.1 vs. 50.0%; p = 0.002), less tumor proximal to major vessel (6.1 vs. 29.2%; p = 0.018), shorter surgical time (113.2 ± 37.9 vs. 146.0 ± 50.5 min; p = 0.007), and shorter postoperative hospital stays (4.4 ± 1.1 vs. 5.4 ± 1.3 days; p = 0.002) compared with MILH group. In those of patients with tumor located at segment 5-6, no significant differences were observed in surgical time, blood loss, complications, and mortality. Single-incision laparoscopic partial hepatectomy was only associated with wider surgical margins (11.8 ± 7.0 vs. 5.3 ± 5.2 mm; p = 0.003). In the HCC subgroup, SILH had similar 1-, 3-, and 5-year overall survival and 1-, 3-, and 5-year recurrence-free survival rates compared with patients who had undergone MILH. CONCLUSIONS: The study demonstrates the safety and feasibility of single-incision laparoscopic liver resection for left lateral sectionectomy and partial hepatectomy for segment 5-6. In selected patients within the group and by experienced surgical team, the SILH technique results in comparable short-term surgical outcomes and long-term oncological outcomes.

Long-term and short-term surgical outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma: might laparoscopic approach be better in early HCC?

BACKGROUND: This retrospective study compared the short- and long-term outcomes of laparoscopic liver resection (LLR) and open liver resection (OLR) and identified patients who might gain more benefits from LLR. METHODS: The demographic and perioperative data, short-term surgical outcomes, and long-term oncological results of all 313 patients who received elective liver resection for hepatocellular carcinoma (HCC) between January 2010 and June 2017 were analyzed. The patients were then divided into stage-specific subgroups according to the TNM staging system for comparison. RESULTS: LLR was performed in 153 patients and OLR in 160 patients. LLR is associated with less blood loss (p < 0.001), shorter surgical time (p = 0.001), shorter length of hospital stay (p < 0.001), and lower morbidity rate (p = 0.034). The 5-year overall survival (OS) rates in the LLR group were higher than those in the OLR group (78.1 vs. 57.6%; p = 0.002). Stage-specific subgroup analysis revealed similar 5-year OS in the two groups (stage I: 82.8 vs. 82.6%, p = 0.845; stage II: 80.3 vs. 69.2%, p = 0.638; stage III: 55.6 vs. 34.8%, p = 0.681), as did the 5-year recurrence-free survival. Moreover, the short-term outcomes were better in the LLR group in terms of surgical time, blood loss, and length of hospital stay, and these benefits attenuated with advancing tumor stage. CONCLUSIONS: LLR for HCC is a safe and feasible procedure that does not compromise long-term oncological outcomes. In early tumor stages, LLR might be better in terms of short-term surgical outcomes.

Risk Factors Analysis of Postoperative Pleural Effusion after Liver Resection.

BACKGROUND: Pulmonary complications remain relatively high in morbidities that arise after liver surgery and are associated with increased length of hospital stay and higher cost. Identification of possible risk factors in this retrospective analysis may help reduce operative morbidity and achieve better outcomes. METHODS: In all, 363 consecutive patients underwent elective hepatectomies between July 2008 and November 2013 and these were identified and analyzed retrospectively. Patient demographics and perioperative variables were collected. The main outcome was an analysis of risk factors associated with postoperative pleural effusion (PPE). RESULTS: Of 363 patients receiving hepatectomies, 80 patients (22.0%) developed pulmonary complications. The predominant pulmonary complication in this series is pleural effusion (76 patients, 95%). Univariate analysis found that older age, higher body mass index (BMI), chronic obstructive lung disease, asthma, heart disease, hepatitis C infection, heavy smoking, American Society of Anesthesiology class III and IV, hepatectomy site, combined surgeries, perioperative blood transfusion, and cirrhosis of liver were associated with PPE. Only older age, higher BMI, asthma, heavy smoker, combined gastrointestinal surgeries, and perioperative blood transfusion were identified as independent risk factors in multivariate analysis. CONCLUSION: This study identifies 6 risk factors for PPE. Identification and management of some of these factors could possibly reduce morbidity and improve short-term surgical outcomes.

The learning curve for laparoscopic colectomy in colorectal cancer at a new regional hospital.

BACKGROUND: Laparoscopic colorectal surgery has been extensively used, although mostly performed in medical centers or university hospitals. We analyzed the learning curve of laparoscopic colectomy in a new regional hospital and determined the experience necessary to achieve proficiency. METHODS: From July 2008 to December 2013, the retrospective clinical study enrolled 240 patients who underwent laparoscopic colectomy. They were sequentially divided into Group A (Patients 1-80), Group B (Patients 81-160), and Group C (Patients 161-240). Patient demographics and perioperative parameters were analyzed. Operation time, as a measure of learning time, was analyzed using the moving-average method. RESULTS: All patients were comparable for age, gender, body mass index, tumor location, cancer stage, length of hospital stay, intraoperative complication, morbidity, and mortality. Group A experienced more blood loss (p < 0.01) and longer operation time (p < 0.001). All laparoscopic operation time stabilized after 85 cases. Subgroup analysis showed that operation time stabilized after 15 cases for right hemicolectomy, 15 cases for sigmoidectomy, and 22 cases for low anterior resection with total mesorectal excision. CONCLUSION: Laparoscopic colectomy for colorectal cancer in a new regional hospital is feasible and safe. It does not need additional time for learning. Laparoscopic sigmoidectomy can be considered as the initial surgery for a trainee.