Novel Colorectal Endoscopic Submucosal Dissection With Double-Endoscope and Snare-Based Traction.

BACKGROUND: Colorectal endoscopic submucosal dissection is technically demanding, and the traction offered by gravity, cap, or clip-with-line during conventional endoscopic submucosal dissection remains unsatisfactory. Robotic systems are still under development and are expensive. We proposed double-scope endoscopic submucosal dissection with strong and adjustable traction offered by snaring the lesion with additional scope. OBJECTIVE: This study aimed to test the novel double-scope endoscopic submucosal dissection with snare-based traction. DESIGN: This was a retrospective study that reviewed double-scope endoscopic submucosal dissection compared with matched conventional endoscopic submucosal dissection, and size, location, morphology, and pathology between groups were compared. SETTINGS: This study was conducted in a referral endoscopy center in a local hospital. PATIENTS: This study included patients with colorectal lesions receiving double-scope endoscopic submucosal dissection and matched conventional endoscopic submucosal dissection. MAIN OUTCOME MEASURES: The pathological completeness, procedure time, and complications were analyzed. RESULTS: Fifteen double-scope endoscopic submucosal dissection procedures, with 11 lesions located in the proximal colon with a median size of 40 mm, were performed. The median procedure time of double-scope endoscopic submucosal dissection was 32.45 (interquartile range, 16.03-38.20) minutes. The time required for second scope insertion was 2.57 (interquartile range, 0.95-6.75) minutes; for snaring, 3.03 (interquartile range, 2.12-6.62) minutes; and for actual endoscopic submucosal dissection, 28.23 (interquartile range, 7.90-37.00) minutes. All lesions were resected completely. No major complication was encountered. The procedure time was significantly shorter than that of 14 matched conventional endoscopic submucosal dissections (54.61 [interquartile range, 33.11-97.25] min; p = 0.021). LIMITATIONS: This was a single-center, single-operator, retrospective case-controlled study with limited cases. CONCLUSIONS: This study confirmed the feasibility of double-scope endoscopic submucosal dissection with snare-based traction to shorten procedure time and to simplify endoscopic submucosal dissection. Additional trials are required.

Diving, lifting, and horizontal dissection followed by loop-clip traction (DLH+T) can facilitate mucosal flap creation during colorectal ESD.

BACKGROUND: Colorectal ESD is difficult because of the poor maneuverability and difficulty of mucosal flap creation. Diving, Lifting and Horizontal (DLH) dissection technique and loop-clip traction are two different methods to facilitate mucosal trimming and adequate mucosal flap creation. We combined the advantages of these two techniques (DLH+T) in our daily practice colorectal ESD since July 2020. OBJECTIVE: The purpose of this study was to examine the outcomes of DLH+T dissection compared with the conventional dissection. METHODS: We retrospectively reviewed the clinical using DLH+T dissection compared with the conventional dissection since January 2018 at a single tertiary care institution. Postoperative short-term outcomes were investigated after the procedure including mucosal flap creation time, dissection time, dissection speed, en bloc resection rate, and perioperative complications. RESULTS: 28 lesions were in DLH+T dissection group and 39 lesions in the conventional dissection group. The outcomes including en bloc resection rate, dissection speed, and complication between the two groups were similar. The mean mucosal flap creation time (p = 0.035) and the mean dissection speed (p = 0.041) of the DLH+T dissection group was significantly shorter and faster. CONCLUSION: DLH dissection followed by loop-clip traction (DLH+T) technique is a useful technique for safe, efficient, and adequate mucosal flap creation, which can increase the dissection speed and may prevent complication, especially in biopsy-related submucosal fibrosis.

Shared decision-making and patient decision aids in choosing first-line targeted therapy for metastatic colorectal cancer in Taiwan.

INTRODUCTION: In Taiwan, given the discrepancy between current treatment guidelines and reimbursement options, patients might require a tool to support their decision-making process when selecting a regimen for metastatic colorectal cancer, especially therapeutic strategies, and subsequent costs, along with efficacy and safety outcomes. Therefore, we developed a patient decision aid (PDA) to support patients in choosing between treatment options recommended based on the current evidence and those reimbursed by the Taiwanese National Health Insurance. METHODS: By carefully reviewing the updated data and then interpreting the clinical tool, we conducted a needs assessment using a serial questionnaire to test for a step-by-step adjustment of the PDA. RESULTS: Patients, their relatives, and medical team members were most concerned about outcomes, such as overall survival, progression-free survival, objective response rate, tumor shrinkage to resectable status, total medical cost, severe gastrointestinal perforation, and severe skin reaction. After a serial alpha test for quality, we performed quantitative evaluation and beta tests, revealing average scores of more than 4 points (on a scale of 1-5) for both perceptibility and utility. CONCLUSIONS: The present findings suggest that PDAs are useful and supplement the shared decision-making practice, helping patients make decisions about preferences and consider the pros and cons of treatment regimens, along with insurance reimbursement options.

Snare Tip Is an Alternative Tool for Colorectal Endoscopic Submucosal Dissection.

BACKGROUND: Colorectal endoscopic submucosal dissection is typically performed by specialized knife, such as a dual knife. However, it is not covered by Taiwan's National Health Insurance. In the literature review, using a traditional snare tip for endoscopic submucosal dissection has been reported for stomach lesions only. OBJECTIVE: The purpose of this study was to evaluate the outcomes of colorectal endoscopic submucosal dissection using a snare tip. DESIGN: We retrospectively reviewed the clinical using of a snare tip compared with a dual knife for colorectal endoscopic submucosal dissection. Postoperative short- and long-term outcomes were investigated after the procedure. SETTINGS: This study was conducted at a single tertiary care institution. PATIENTS: Patients who could not afford the expense of a specialized knife were included. MAIN OUTCOME MEASURES: Dissection time, dissection speed, and perioperative complications were used for short-term outcome measurement. Recurrence-free rate was used for long-term outcome measurement. RESULTS: Twenty-one lesions were in the snare tip group and 57 lesions in the dual knife group. The outcomes, including rate of en bloc resection, complication, local recurrence, and recurrence-free interval, between the 2 groups were similar. The mean resected specimen diameter in the dual knife group is larger than the snare tip group (p = 0.041). The dissection time of the snare tip group was shorter than the dual knife group (p = 0.025). However, the dissection speed was significantly slower in the snare tip group than in the dual knife group (p = 0.008). LIMITATIONS: This study was a retrospective and single doctor chart review in nature with a limited patient number. CONCLUSIONS: The snare tip is an alternative tool for colorectal endoscopic submucosal dissection in a selected population without the support of specialized knives, such as the dual knife. Although the dissection speed is slower using a snare tip, it is still a recommended technique for developing country or low-income patients.

Detection and clinical characteristics of serrated polyps and conventional adenomas between patients in the outpatient and physical checkup unit receiving colonoscopy.

PURPOSE: The sessile serrated adenoma/polyp detection rate (SSA/PDR) among different colonoscopy indications from daily practice has not been fully understood. This study aimed to evaluate the detection and clinical characteristics of serrated polyps and conventional adenomas between outpatient department (OPD) and physical checkup unit (PCU) patients receiving colonoscopy. METHODS: The data for this retrospective study were collected between 2016 and 2017 at Kaohsiung Veterans General Hospital in Taiwan. A total of 7047 individuals were included, and information on polyp and adenoma detection was extracted from the colonoscopy reports. RESULTS: The adenoma detection rate, the SSA/PDR, and the detection rate of traditional serrated adenoma (TSA) were 32.2%, 0.60%, and 0.50%, respectively. Risk analysis revealed no significant difference (p = 0.095) in SSA/PDR between individuals < 50 years and ≥ 50 years, and no trend of increased SSA/PDR as age increased was observed (p = 0.320). SSA/P and TSA had higher risks for synchronous advanced neoplasia than conventional adenoma, but with proximal hyperplastic polyps lower (p < 0.001, respectively). No significant difference of SSA/PDR between OPD and PCU patients was observed (p = 1.000); however, the age of SSA/P was significantly older in OPD than in PCU patients (p = 0.048). CONCLUSION: The detection rates of CA and TSA were associated with age groups; however, SSA/PDR was insignificantly higher among individuals aged < 50 years than those with other age groups. In addition, SSA/PDR between OPD and PCU patients was not significantly found in daily practice of colonoscopies.

Endoscope rotating technique is useful for difficult colorectal endoscopic submucosal dissection.

BACKGROUND: Conventional lesion-up colorectal ESD has the potential risk of iatrogenic perforation due to the knife's direction toward the muscular layer of the bowel wall. If we rotate the endoscope to the proper position, the mucosal flap is easy to be lifted down by tip attachment and the knife is easy to approach the proper dissection plane, which may prevent the perforation and facilitate difficult ESD. METHODS: We aimed to retrospectively assess the safety and efficacy of this rotating technique compared with the conventional lesion-up dissection regardless of shape, location, or size of the tumor, and investigated in short- and long-term outcomes following the ESD procedure. RESULTS: 41 lesions were enrolled into rotating technique group and 37 lesions in lesion-up group. The dissection speed was significantly faster in the rotating technique group (p = 0.023). R0 resection rate was significantly higher in rotating technique group (p = 0.008). The rate of perioperative complication was significantly higher in lesion-up method group (p = 0.003). Local recurrence was higher in lesion-up group (p = 0.001). Recurrence-free rate was higher in rotating technique group (p = 0.018). CONCLUSION: The endoscope rotating is a useful technique for difficult colorectal ESD due to easy approaching the proper dissection plane. This technique also increases the rate of en bloc resections, R0 resections regardless of size, shape, and location and improves dissection speed without increasing the incidence of adverse events.

Placement of SurgiWrap® adhesion barrier film around the protective loop stoma after laparoscopic colorectal cancer surgery may reduce the peristomal adhesion severity and facilitate the closure.

PURPOSE: A temporary loop stoma is often created after laparoscopic colorectal cancer surgery. Peristomal adhesions may make stoma closure into a complicated operation. We demonstrated how to place the SurgiWrap® adhesion barrier film and evaluated the peristomal adhesion severity and feasibility of stoma closure. METHODS: This is a retrospective case-control study. Patients were divided into a study group (placement of adhesion barrier film) and a control group (no placement). Patient characteristics, operative data, and severity of adhesions were recorded. We used logistic regression to probe the association between the variables and the adhesion severity. RESULTS: A total of 180 patients were identified with 60 in the study group and 120 in the control group. In the study group, the adhesion severity (p < 0.001), operative time (p = 0.025), and time to flatus (p = 0.042) are significantly reduced. In logistic regression analysis, placement of the film (p < 0.001), neoadjuvant concurrent chemoradiotherapy (p = 0.041), and time interval between stoma creation and closure ≧ 12 weeks (p = 0.038) are three significant factors influencing the peristomal adhesion. CONCLUSION: The placement of SurgiWrap® adhesion barrier film around the loop stoma after laparoscopic colorectal cancer surgery may reduce the peristomal adhesion severity and facilitate the stoma closure in terms of operative time and time to flatus.

What is the predictor of surgical mortality in adult colorectal perforation? The clinical characteristics and results of a multivariate logistic regression analysis.

PURPOSE: Colorectal perforations are a serious condition associated with a high mortality. The aim of this study was to describe the clinical characteristics and identify predictors for the surgical mortality in adult patients with colorectal perforation, thereby achieving better outcomes. METHODS: A retrospective study of adult patients diagnosed with colorectal perforation operated was performed. The clinical variables that might influence the surgical mortality were first analyzed, and the significant variables were then analyzed using a logistic regression model. RESULTS: A total of 423 patients were identified, and the surgical mortality rate was 36.9 %. The most common etiology was diverticulitis (38.2 %). The highest etiology-specific mortality was for colorectal cancer (61.5 %) and ischemic proctocolitis (59.8 %). In a logistic analysis, the significant predictors for the surgical mortality were ≥3 comorbidities (p = 0.034), preoperation American Society of Anesthesiologists score ≥4 (p = 0.025), preoperative sepsis or septic shock (p < 0.001), colorectal cancer or ischemic proctocolitis (p = 0.035), reoperation (p = 0.041), and Hinchey classification grade IV (p = 0.024). CONCLUSION: We demonstrated that ≥3 comorbidities, a preoperation American Society of Anesthesiologists score ≥4, preoperative sepsis or septic shock, colorectal cancer or ischemic proctocolitis, reoperation, and Hinchey classification grade IV are predictors for the surgical mortality in the adult cases of colorectal perforation. These predictors should be taken into consideration to prevent surgical mortality and to reduce potentially unnecessary medical expenses.

Heteronemin Is a Novel c-Met/STAT3 Inhibitor Against Advanced Prostate Cancer Cells.

BACKGROUND: Prostate cancer is one of the most prevalent cancers in men worldwide. Aberrant activation of c-Met/signal transducer and activator of transcription-3 (STAT3) signaling is involved in prostate carcinogenesis, underscoring the demand for developing c-Met/STAT3-targeting drugs. Thus, we first utilized virtual screening strategy to identify STAT3-inhibiting marine compound, heteronemin, and then validated the STAT3-inhibiting function of heteronemin in prostate cancer cells. METHODS: Human prostate cancer LNCaP, DU145, and PC-3 cell lines were treated with heteronemin for 24 hr, then the cell viability was evaluated by MTT assay. Flow cytometry was performed to analyze the apoptosis in heteronemin-treated cells. Western blot and quantitative real-time PCR were executed to further confirm the c-Met/STAT3 signaling inhibition by heteronemin in DU145 and PC-3 cells. RESULTS: In this study, we employed the virtual screening strategy to identify heteronemin, a spongean sesterterpene, as a potential STAT3 inhibitor from Taiwan marine drugs library. Application of heteronemin potently suppressed the viability and anchorage-independent growth of human prostate cancer cells. Besides, heteronemin induced apoptosis in prostate cancer cells by activation of both intrinsic (caspase-9) and extrinsic (caspase-8) apoptotic pathways. By luciferase assay and expression analysis, it was confirmed that heteronemin inhibited the phosphorylation of c-Met/src/STAT3 signaling axis, STAT3-driven luciferase activities and expression of STAT3-regulated genes including Bcl-xL, Bcl-2, and Cyclin D1. Finally, heteronemin effectively antagonized the hepatocyte growth factor (HGF)-stimulated c-Met/STAT3 activation as well as the proliferation and colonies formation in refractory prostate cancer cells. CONCLUSIONS: These findings suggest that heteronemin may constitute a novel c-Met/STAT3-targeting agent for prostate cancer. Prostate 76:1469-1483, 2016. © 2016 Wiley Periodicals, Inc.

Clinical outcomes and safety of remdesivir in hospitalized individuals with COVID-19, with or without severe renal impairment.

BACKGROUND: The use of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal impairment has been approved; however, limited clinical data exist. Accordingly, we aimed to compare outcomes and adverse events associated with remdesivir in hospitalized patients with COVID-19, with and without severe renal impairment. METHODS: Hospitalized patients with COVID-19 undergoing a 5-day remdesivir course at Taipei Veterans General Hospital from April 1 to July 31, 2022, were enrolled. Comparative analysis of outcomes and safety between patients with or without severe renal impairment (estimated glomerular filtration rate of < 30 mL/min per 1.73 m2) were conducted. Prognostic factors associated with 28-day mortality in patients with severe renal impairment were investigated using logistic regression analysis. RESULTS: A total of 671 hospitalized patients, including 132 patients with severe renal impairment, who received a 5-day course of remdesivir were analyzed. The 28-day mortality was higher in patients with severe renal impairment than in patients without severe renal impairment (15.2% vs. 7.8%). The proportion of patients with acute kidney injury (AKI) and deteriorated liver function after completing remdesivir therapy was similar between the patients with and without severe renal impairment, and the recovery rate of AKI was similar in both groups. The sequential organ failure assessment score was an independent factor associated with 28-day mortality in patients with severe renal impairment. CONCLUSIONS: Remdesivir was well-tolerated in hospitalized patients with COVID-19, regardless of renal function. Our findings support the recent recommendation to administer remdesivir in patients with severe renal impairment.

Comparison of the feasibility of laparoscopic resection of the primary tumor in patients with stage IV colon cancer with early and advanced disease: the short- and long-term outcomes at a single institution.

PURPOSE: The role of resection of the primary tumor in patients with stage IV colorectal cancer (CRC) remains controversial. Laparoscopic resection has become an accepted therapeutic option for treating early stage I-III CRC; however, it has not been evaluated for use in patients with advanced stage disease. METHODS: We conducted a retrospective observational study to evaluate the feasibility of laparoscopic resection of the primary tumor exclusively in patients with stage IV colon cancer compared to open resection in patients with stage IV colon cancer and laparoscopic resection in patients with stage I-III colon cancer in terms of operative results and short- and long-term outcomes. RESULTS: Laparoscopic resection was performed in 35 stage IV patients and open resection was performed in 40 stage IV patients. One hundred and eighteen stage I-III patients who underwent laparoscopic resection were evaluated. In the comparison between the laparoscopic group and the open group among patients with stage IV colon cancer, postoperative recovery appeared to be better in the laparoscopic group than in the open group, as reflected by shorter times to resumption of a regular diet (p = 0.049), shorter lengths of hospitalization (p = 0.083), increased feasibility of postoperative chemotherapy (p < 0.001), shorter time intervals from surgery to chemotherapy (p = 0.031) and longer median survival (p = 0.078) at the expense of longer operative times (p = 0.025). In the comparison between the laparoscopic resection in stage IV and stage I-III disease groups, no significant differences were observed in operative results and short- and long-term outcomes, except for the rate of ostomy creation (48.5 vs. 8.5%, p = 0.02). CONCLUSION: Laparoscopic resection of the primary tumor in patients with stage IV colon cancer achieves equivalent results to that performed in patients with stage I-III disease and that performed in patients with stage IV disease using open resection. The use of a minimally invasive approach in the laparoscopic procedure is beneficial because it results in shorter times to resumption of a normal diet, shorter lengths of hospitalization, increased feasibility of postoperative chemotherapy and shorter time intervals from surgery to chemotherapy at the expense of longer operative times. We believe that patients undergoing laparoscopic resection can receive targeted chemotherapy earlier and more aggressively, which might provide a survival benefit.

Optimal Sequence and Second-Line Systemic Treatment of Patients with RAS Wild-Type Metastatic Colorectal Cancer: A Meta-Analysis.

Although several sequential therapy options are available for treating patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), the optimal sequence of these therapies is not well established. A systematic review and meta-analysis of 13 randomized controlled trials and 4 observational studies were performed, resulting from a search of the Cochrane Library, PubMed, and Embase databases. Overall survival (OS) did not differ significantly in patients with RAS-WT failure who were administered a second-line regimen of changed chemotherapy (CT) plus anti-epidermal growth factor receptor (EGFR) versus only changed CT, changed CT plus bevacizumab versus changed CT plus anti-EGFR, or changed CT versus maintaining CT plus anti-EGFR after first-line therapy with CT, plus bevacizumab. However, OS was significantly different with a second-line regimen that included changed CT plus bevacizumab, versus only changing CT. Analysis of first-line therapy with CT plus anti-EGFR for treatment of RAS-WT mCRC indicated that second-line therapy of changed CT plus an anti-EGFR agent resulted in better outcomes than changing CT without targeted agents. The pooled data study demonstrated that the optimal choice of second-line treatment for improved OS was an altered CT regimen with retention of bevacizumab after first-line bevacizumab failure. The best sequence for first-to-second-line therapy of patients with RAS-WT mCRC was cetuximab-based therapy, followed by a bevacizumab-based regimen.

Incidence and Clinical Outcomes of Gonadal Artery Injury during Colorectal Surgery in Male Patients.

BACKGROUND: Gonadal artery is susceptible to accidental injury due to their anatomical proximity to the colon and rectum. There are few literature reviews focusing on this injury during colorectal surgery. We conduct a retrospective study to evaluate the incidence and the clinical significance of these injuries in terms of testicular size and testicular enhancement on the contrast CT scan. METHODS: Patients' characteristic data included age, body mass index (BMI), diagnosis, operation type, cause of gonadal artery injury, side of injury, level of injury, method of vessel ligation, and follow-up period. We measured the testicular sizes before and after gonadal artery injury and measured the enhancement level by recording the mean attenuation value on the injury side and non-injury side of the testis on the CT scan. RESULTS: The incidence of gonadal artery injury was 3.61% and 15 male patients with this injury were enrolled. There were 5 patients with iatrogenic injury and 10 patients with non-iatrogenic injury due to advanced tumor or inflammation. No patients had any complaints of testicular discomforts or atrophy after the surgery. The testicular sizes before and after the surgery showed no significant difference (p = 0.877). The mean attenuation values of the injury side and non-injury side of the testis also showed no significant difference (p = 0.79). CONCLUSIONS: Gonadal artery injury during colorectal surgery is not a rare complication. To prevent this injury, knowledge of the anatomy and staying in the proper plane of dissection are the key points. In patients with gonadal artery injury during colorectal surgery, sacrifice of the gonadal artery is safe without clinical significance in terms of testicular size and testicular enhancement on the contrast CT scan.

Comparison of laparoscopic versus open surgery in a three-stage operation for obstructive left-sided colorectal cancer.

BACKGROUND: Treatment for obstructive left-sided colorectal cancer (OLCC) typically consists of a three-staged procedure. During the first stage, the obstruction is managed with diversion colostomy. Traditionally in the second stage, we perform open resection for the primary tumor. In this study, we evaluated the feasibility of laparoscopic resection of OLCC with diversion colostomy in terms of operative results and short-term outcomes. METHODS: A total of 20 patients underwent laparoscopic resection for OLCC (study group), 48 patients underwent open resection for OLCC (control group 1), and 53 patients underwent laparoscopic resection for non-OLCC (control group 2). Afterwards, results from the procedures were obtained and clinical data were analyzed. RESULTS: The operative time was significantly longer in the study group than in the control group 1 (153 minutes vs. 126 minutes, p = 0.041), and the length of hospitalization was shorter in the study group than in the control group 1 (5.3 days vs. 7.6 days, p = 0.032). Regarding the operative results and short-term outcomes, there were no significant differences between the study group and control group 2. Colostomy retraction was a specific morbidity which occurred in two patients of the study group. CONCLUSION: Laparoscopic resection of OLCC with diversion colostomy is feasible. Abdominal cavity adhesion is only limited. We strongly recommend that laparoscopic resection should be performed at least 2 weeks after diversion colostomy, and the plastic rod should be left in place during the pneumoperitoneum to reduce the risk of colostomy retraction.

Measurement of peritoneal fluid urea nitrogen and creatinine levels is useful to detect iatrogenic urinary tract leakage in colorectal surgery.

BACKGROUND: Increased peritoneal drainage after colorectal surgery is a common problem. Measurement of peritoneal fluid urea nitrogen (UN) and creatinine (Cr) is a diagnostic tool to detect the urinary tract leakage (UTL). We evaluated its application in colorectal surgery. METHODS: We conducted a retrospective chart review study. We enrolled patients with iatrogenic UTL, and measured their UN and Cr levels in peritoneal fluid and compared them with those in blood and urine. Meanwhile, we assigned patients without UTL to a control group and compared clinical parameters of both groups. RESULTS: Twenty-three patients with iatrogenic UTL were recruited. The overall incidence was 0.5%. UN level in peritoneal fluid (322 ± 56 mg/dL) was significantly higher than that in blood (18.7 ± 4.0 mg/dL, p < 0.001); Cr level in peritoneal fluid (69.7 ± 14.3 mg/dL) was also significantly higher than that in blood (1.5 ± 0.5 mg/dL, p < 0.001). UN level in peritoneal fluid was significantly higher in the iatrogenic UTL group than in the control group (322 mL/dL vs. 9.3 mL/dL, p < 0.001); Cr level in peritoneal fluid was also significantly higher (69.7 mg/dL vs. 0.98 mg/dL, p < 0.001). CONCLUSION: When increased peritoneal drainage is found postoperatively in colorectal surgery, measurement of UN and Cr levels in peritoneal fluid can be a useful diagnostic tool to determine intraperitoneal iatrogenic UTL.

Hepatoma-derived growth factor/nucleolin axis as a novel oncogenic pathway in liver carcinogenesis.

Hepatoma-derived growth factor (HDGF) overexpression is involved in liver fibrosis and carcinogenesis. However, the receptor(s) and signaling for HDGF remain unclear. By using affinity chromatography and proteomic techniques, nucleolin (NCL) was identified and validated as a HDGF-interacting membrane protein in hepatoma cells. Exogenous HDGF elicited the membrane NCL accumulation within 0.5 hour by protein stabilization and transcriptional NCL upregulation within 24 hours. Blockade of surface NCL by antibodies neutralization potently suppressed HDGF uptake and HDGF-stimulated phosphatidylinositol 3-kinase (PI3K)/Akt signaling in hepatoma cells. By using rescectd hepatocellular carcinoma (HCC) tissues, immunohistochemical analysis revealed NCL overexpression was correlated with tumour grades, vascular invasion, serum alpha-fetoprotein levels and the poor survival in HCC patients. Multivariate analysis showed NCL was an independent prognostic factor for survival outcome of HCC patients after surgery. To delineate the role of NCL in liver carcinogenesis, ectopic NCL overexpression promoted the oncogenic behaviours and induced PI3K/Akt activation in hepatoma cells. Conversely, NCL knockdown by RNA interference attenuated the oncogenic behaviours and PI3K/Akt signaling, which could be partially rescued by exogenous HDGF supply. In summary, this study provides the first evidence that surface NCL transmits the oncogenic signaling of HDGF and facilitates a novel diagnostic and therapeutic target for HCC.