[Corrigendum] Long non­coding RNA LINC00238 suppresses the malignant phenotype of liver cancer by sponging miR­522.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that two pairs of data panels featured in Figs. 2E and 6D, portraying the results from cell invasion and migration assay experiments, appeared to contain overlapping sections, such that data which were intended to show the results from differently performed experiments had apparently been derived from a smaller number of original sources. The authors were able to re­examine their original data (which was also presented to the Editorial Office), and realized that errors has been made in the compilation of Fig. 2. The proposed revised version of Fig. 2, now showing the results from the 'field 1' view of the data, is shown on the next page. Note that these errors did not significantly affect either the results or the conclusions reported in this paper,.All the authors agree to the publication of this Corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to correct this error; furthermore, they apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 25: 71, 2022; DOI: 10.3892/mmr.2022.12587].

Long non­coding RNA LINC00238 suppresses the malignant phenotype of liver cancer by sponging miR­522.

Long non­coding RNAs can regulate the malignant tumor phenotype either as tumor suppressors or oncogenes. The present study investigated the underlying mechanism of LINC00238 in liver cancer. LINC00238 was identified as a downregulated molecule in The Cancer Genome Atlas liver hepatocellular carcinoma dataset through Gene Expression Profiling Interactive Analysis software. Through gain­ and loss­of­function experiments, LINC00238 was confirmed as a tumor suppressor that could not only decrease cell viability, migration and invasion in vitro, but also tumorigenesis and tumor metastasis in vivo. By cytoplasmic and nuclear RNA isolation, LINC00238 was confirmed to be predominantly cytoplasmic. Mechanistically, RNA pull­down assays showed that LINC00238 sponged microRNA (miR)­522 and then reversed the inhibitory effects on two downstream targets, secreted frizzled related protein 2 and dickkopf1. Collectively, LINC00238 was identified as a tumor suppressor that acts via sponging miR­522 followed by silencing of downstream targets, suggesting that LINC00238 may have a key role in suppressing the malignant phenotype of liver cancer cells.

Enhanced cancer therapeutic efficiency of NO combined with siRNA by caspase-3 responsive polymers.

The combination of nitric oxide (NO) and siRNA is highly desirable for cancer therapy. Here, the furoxans-grafted PEI polymer (FDP) with caspase-3 responsive cleavable DEVD linker was synthesized, and used to bind siRNAs via electrostatic interaction and self-assembled into FDP/siRNA nanoplexes by hydrophobic force. After cellular uptake and lysosomal escape, the FDP/siRNA nanoplexes could achieve GSH-triggered NO release, and then increase the activity of caspase-3. The activated caspase-3 could specifically cleave the DEVD peptide sequence and enhance cell apoptosis. With the cleavage of DEVD peptide sequence, the disassembly of FDP/siRNA nanoplexes was further promoted, thereby resulting in increased siRNAs of ~40% were released at 48 h compared with the caspase-3 non-responsive FDnP/siRNA nanoplexes. By this way, cell apoptosis promotion and cell proliferation inhibition was achieved by siRNA-based downregulation of EGFR protein and the upregulated activity of caspase-3, followed by the enhanced cascade release of NO from FDP/siRNA nanoplexes. Furthermore, in vivo results demonstrated the improved anti-cancer efficiency of FDP/siEGFR nanoplexes without any detectable side effects. Therefore, it is believed that the caspase-3 responsive cleavable furoxans-grafted PEI polymers could provide a potential and efficient enhancement for cancer therapeutic efficiency by the co-delivery of nitric oxide and siRNA.

Biological activities of siRNA-loaded lanthanum phosphate nanoparticles on colorectal cancer.

Lanthanum can reduce absorption of phosphate by forming lanthanum phosphate complexes after oral administration of lanthanum carbonate tablets (FOSRENOL®) in patients. Based on the pH-responsive interaction of phosphate and lanthanum ions, the chitosan coated siRNA-loaded lanthanum phosphate nanoparticles (CS/LaP/siRNA NPs) were prepared for improving cancer treatment, in which polysaccharide chitosan was used as the outer shell to control the excessive growth of lanthanum phosphate complexes, and enable intestinal mucoadhesion. The CS/LaP/siEGFR NPs exhibited significant biological activities in human colorectal cancer HT-29 cells by the synergistic effects of siEGFRs and lanthanum ions, such as downregulation of EGFR and upregulation of miR-34a. Furthermore, significant tumor growth inhibition was observed in both transgenic C57BL/6-ApcMinC/Nju cancer mouse model and AOM/DSS chemically induced orthotopic colorectal cancer mouse model after intestinal instillation administration of CS/LaP/siEGFR NPs. Therefore, the lanthanum-based siRNA delivery system would provide a potential and efficient strategy for the treatment of colorectal cancers.

Encapsulated microRNA by gemcitabine prodrug for cancer treatment.

Although microRNAs (miRNAs) function as the important tumor gene regulators, they still confront with many challenges in systemic delivery. Here, the amphiphilic gemcitabine-oleic acid prodrugs (GOA) binding miRNAs with hydrogen bond are assembled into nanoparticles (GOA/miR NPs) through hydrophobic interaction via denaturation-annealing processes and nano-precipitation technique. The non-cationic GOA/miR NPs with an average size of ~150 nm and a zeta potential of ~ - 15 mV exhibit a stable encapsulation of miRNAs with non-sequence selectivity. Either miR-122 or miR-34a encapsulated in the GOA/miR NPs is efficiently delivered into HepG2 cells and significantly downregulate the expression levels of target gene after lysosome escape and pH-responsive disassembly. Moreover, in vivo experiments demonstrate that the GOA/miR-122 NPs exhibit higher tumor accumulation. Compared to GOA micelles, GOA/miR-122 NPs displayed stronger tumor inhibition (73% regression) after intravenous injection in nude mice xenografted with HCC, along with rapid clearance in normal liver tissues. Furthermore, there is no significant influence on biochemical indicators and immune factors during the systematic administration of GOA/miR-122 NPs. The non-cationic GOA/miR NPs engineered by hydrogen bond interaction and hydrophobic forces show the enhanced synergistic antitumor efficacy and good biosafety, which will provide a potential nanomedcine for HCC treatment.

Establishment of pancreatic cancer patient-derived xenograft models and comparison of the differences among the generations.

Tumor samples of pancreatic ductal adenocarcinoma patients, who underwent resection surgery, were implanted into NOD/SCID mice to construct pancreatic cancer patient-derived xenograft (PDX) models and explore the biological changes in the different generations of PDXs. Ten PDXs were successfully generated, and the tumor formation rate of F1 PDXs was found to be 38.46%, which was lower than F2 (77.78%) and F3 (71.43%) PDXs. In addition, latent periods of tumorigenesis of F2 and F3 PDXs were significantly shorter, compared to that in F1 PDXs (P<0.05). Comparison of H&E staining of tumor tissue from primary pancreatic cancer and PDXs showed that all three generations of PDXs had similar histopathology to primary pancreatic cancer, indicating that PDXs may well reproduce the histological patterns of primary human cancer. Besides, Ki67 expression was increased in all three generations of PDXs compared to primary tumors of patients, and additionally, EpCAM expression was increased in F3 PDXs. These results were corroborated by the real-time qPCR and western blot results. Therefore, we concluded that PDXs are able to preserve the differentiation degree, morphological characteristics, and structural features of tumor cells. Furthermore, the latent periods of tumorigenesis are shortened after the first generation, which may be attributed to an increase in expression levels of tumor promoters such as Ki67 and EpCAM. PDX models may become an efficient tool for pancreatic cancer research.

Precise Navigation of the Surgical Plane with Intraoperative Real-time Virtual Sonography and 3D Simulation in Liver Resection.

The precise intraoperative navigation of the surgical plane remains challenging in liver surgery; however, an innovative imaging technique-real-time virtual sonography (RVS)-may provide a solution. In this modality, preoperative three-dimensional (3D) resection simulation data are transmitted to an RVS workstation and can be used in combination with intraoperative ultrasound to navigate the surgical plane in real time. This paper describes this technique and our experiences in detail. From November 2015 to March 2017, 26 patients with primary liver cancer underwent liver resection under RVS navigation. The operative procedures employed included hemihepatectomy, bisegmentectomy, segmentectomy, and limited resection. RVS was utilized uneventfully and successfully in each operation. The median time required for spatial position registration was 3 (1-12) min, and as the case volume increased, the time required for registration markedly decreased. The surgical plane under RVS navigation was consistent with that of the preoperative plan, and the resection margin was confirmed negative in each case. In conclusion, RVS in combination with 3D simulation is a feasible, safe, and promising technique for the precise intraoperative navigation of liver resection for primary liver cancer. It could be applied to other resectable liver diseases and may be utilized in other centers.

Is Central Pancreatectomy Truly Recommendable? A 9-Year Single-Center Experience.

AIMS: To compare the short- and long-term outcomes in patients with pancreatic benign or borderline neoplasm who underwent central pancreatectomy (CP) and distal pancreatectomy (DP). METHODS: The inclusion criteria were as follows: (1) single benign or low-grade malignant tumor; (2) tumor confined to the pancreatic neck or proximal body; and (3) tumor amenable to either CP or DP. Short and long-term outcomes, including complications, pancreatic exocrine and endocrine function, and quality of life (QoL) were analyzed retrospectively. RESULTS: Sixteen patients who underwent CP and 26 patients who underwent DP were included. The median follow-up period was 53 months (range 21-117 months). Patients undergoing CP were significantly more likely to experience complications (68.7 vs. 23%, p = 0.003) especially grade B/C postoperative pancreatic fistula (62.5 vs. 23%, p = 0.011) than those undergoing DP. During the long-term follow-up, 2 patients in the DP group developed new-onset diabetes mellitus, but no patient in CP group developed this condition (8 vs. 0%, p = 0.382). Evidence of exocrine insufficiency, including severe diarrhea or steatorrhea, was not observed in either group. Both groups were equally satisfied with the overall health status and overall QoL. CONCLUSION: CP is associated with excellent pancreatic function but a significantly increased postoperative morbidity and risk compared to DP. Therefore, the indication of CP should be chosen strictly.

Ischemic Liver Injury After Complete Occlusion of Hepatic Artery in the Treatment of Delayed Postoperative Arterial Bleeding.

BACKGROUND: Delayed postoperative arterial bleeding is rare and may be life-threatening. When the bleeding source is the hepatic artery, complete ligation or embolization from the proximal to the distal area of the ruptured lesion usually results in complete occlusion of hepatic arterial flow. METHODS: To evaluate the frequency and severity of ischemic liver injury following complete hepatic artery occlusion, a retrospective study was conducted. Patients who underwent complete hepatic artery occlusion in the treatment of delayed postoperative arterial bleeding between January 2007 and December 2014 in our institution were reviewed. Changes of hepatic function and rates of associated complications and prognosis were analyzed. RESULTS: A total of 24 patients experienced 26 episodes of bleeding. Nineteen experienced transient liver enzyme elevation alone. There were no signs of acute liver failure after complete hepatic artery occlusion. The rates of liver infarction and liver abscess were 23.8 % (5/21) and 19 % (4/21), respectively. The 30-day mortality rate was 8.3 % (2/24). CONCLUSION: Complete occlusion of the hepatic artery does not always result in severe hepatic ischemic injury. As a common cause of delayed postoperative bleeding, intra-abdominal infection may be fatal when it is not controlled successfully.

Reactive lymphoid hyperplasia of the liver mimicking hepatocellular carcinoma: incidental finding of two cases.

Reactive lymphoid hyperplasia is a rare disease that forms a mass-like lesion and is characterized by the proliferation of non-neoplastic, polyclonal lymphocytes forming follicles. We recently encountered 2 cases of reactive lymphoid hyperplasia of liver, both of which were asymptomatic and mimicked hepatocellular carcinoma by various imaging modalities. Based on the clinical impression of hepatocellular carcinoma, surgical resections were performed. Microscopic findings revealed that both lesions consisted of an aggregation of lymphocytes consisting of predominantly B-cells, with multiple lymphoid follicles positive for CD10 and negative for bcl-2, consistent with the diagnosis of reactive lymphoid hyperplasia. Polyclonality of both lesions was further confirmed by B cell receptor gene rearrangement study. The incidence of reactive lymphoid hyperplasia in the liver is exceedingly rare, and it is difficult to differentiate such lesions from hepatic malignancies based upon clinical grounds. The clinicopathological findings and literature review of this report may be helpful to improve the clinical decision-making.

Hepatitis B virus infection is an independent factor influencing the occurrence of liver metastasis in colorectal cancer: a retrospective analysis of 1413 cases.

BACKGROUND/AIMS: The relationships between Hepatitis B virus infection, cirrhosis and colorectal cancer liver metastasis have not been investigated simultaneously and it remained unclear that whether the immune changes caused by Hepatitis B virus infection or the structural changes caused by cirrhosis conduce to the lower incidence of liver metastasis. METHODOLOGY: Data of 1413 colorectal cancer patients were reviewed to investigate the impacts of Hepatitis B virus infection and cirrhosis on the occurrence and prognosis of liver metastasis. RESULTS: The incidence of liver metastasis in the Hepatitis B virus infection group or in the cirrhotic group was lower than the control groups (9.4% vs 23.9%, P<0.001; 6.3% vs 22.9%, P=0.03, respectively). However, a multivariate logistic regression analysis showed that only Hepatitis B virus, the T and N classifications were independent factors for the occurrence of liver metastasis in colorectal cancer. There was no statistically significant difference in 5-years survival rates between hepatitis B virus infection group and the non-infection group, nor between cirrhotic group and non-cirrhosis group (P>0.05). CONCLUSION: Hepatitis B virus infection was one of the independent factors for the occurrence of liver metastasis in colorectal cancer but not for the survival.

En bloc pancreaticoduodenectomy and right colectomy in the treatment of locally advanced colon cancer.

BACKGROUND: Carcinoma of the right colon invading the pancreas or duodenum is rare. Evidence of the indication, operative morbidity, and survival of en bloc pancreaticoduodenectomy and right colectomy for right colon cancer invading adjacent organs is limited. OBJECTIVE: : The goal of this study was to investigate the feasibility, safety, indication, and long-term results of en bloc pancreaticoduodenectomy and right colectomy in the treatment of locally advanced right-sided colon cancer. DESIGN: : This was a retrospective analysis of all inpatients undergoing en bloc pancreaticoduodenectomy and right colectomy. Detailed data of these patients were assessed by a thorough review of medical charts. SETTINGS: The study was conducted using a hospital database. PATIENTS: Fourteen patients who underwent en bloc pancreaticoduodenectomy and right colectomy from January 1989 through December 2011 were included in the study. MAIN OUTCOME MEASURES: In-hospital complications, mortality, and survival were the primary outcomes measured. RESULTS: Major postoperative complications included delayed gastric empting (n = 7), class B pancreatic fistula (n = 3), and bile leakage (n = 1). Postoperative death occurred in 2 patients. The median hospital stay was 22.5 days (range, 17.0-57.0 days). Inflammatory adhesion was confirmed by pathologic examination in only 1 patient. Eight patients (57%) did not have lymph node metastasis. The median follow-up time was 21 months (range, 4-276 months). Ten patients were alive at the time of their last scheduled follow-up. The overall survival rates were 72% at 1 year and 60% at 2 years. No patient was lost to follow-up. Three patients developed tumor recurrence. The outcomes are no worse than those of the stage-matched patients without adjacent organ involvement and are much better than those of the stage-matched patients who underwent bypass surgery and chemotherapy. LIMITATIONS: The number of patients in current studies is limited. CONCLUSIONS: En bloc pancreaticoduodenectomy and right colectomy can be performed safely with an acceptable morbidity and mortality rate in selected patients with locally advanced right-side colon cancer. The long-term results are promising.

[Management of liver metastases of gastrointestinal stromal tumor].

Liver is the most common metastatic site of gastrointestinal stromal tumor(GIST). The recurrence rate is high even after hepatectomy. Although tyrosine kinase inhibitors (TKI) makes the resection feasible for some of the liver metastasis of GIST and significantly increase the overall survival, surgery still can not be substituted. Therefore, it is worth investigating and exploring the most appropriate treatment for the GIST with liver metastasis.

Management of delayed post-pancreaticoduodenectomy arterial bleeding: interventional radiological treatment first.

OBJECTIVE: To investigate the diagnosis and treatment of delayed post-pancreaticoduodenectomy arterial bleeding (DPPAB). METHODS: Records of 336 patients who underwent pancreaticoduodenectomy (PD) between January 2000 and December 2010 were retrospectively analyzed. Detailed data of patients with DPPAB were assessed by a thorough review of medical records. RESULTS: 14 patients developed DPPAB. The mean time interval between the initial surgery and DPPAB was 33 days (range 7-72). Three patients experienced sentinel bleeding 5-8 days before DPPAB. All DPPAB patients had intra-abdominal septic complications before bleeding. The overall prevalence of success of angiography and transcatheter arterial embolization (TAE) was 85.7% (12/14), including 3 patients who achieved complete hemostasis by TAE after unsuccessful re-laparotomy. The prevalence of mortality of DPPAB was 28.6% (4/14). After hemostasis was achieved, intra-abdominal septic complications were controlled by percutaneous catheter drainage or re-laparotomy with drain replacement. CONCLUSION: Angiography and TAE are recommended as the first-line diagnostic and treatment choice for DPPAB, respectively. Surgical intervention should be preserved to eliminate the cause of bleeding.

[A scoring system to predict ascites after hepatectomy for hepatocellular carcinoma].

OBJECTIVE: To establish a scoring system predicting the ascites postoperatively by analyzing the variant factors associated with massive ascites after hepatectomy in the patients with hepatocellular carcinoma (HCC). METHODS: From January 2005 to January 2010, 324 patients with HCC underwent hepatectomy were analyzed retrospectively. There were 282 male and 42 female, aging from 17 to 84 years (mean age, 54 years). They were divided into two groups according to the volume of ascites. Variant preoperative, intraoperative and postoperative factors were compared and a scoring system was established to predict the postoperative ascites. RESULTS: The univariate analyses revealed that various preoperative factors including prothrombin time, activated partial thromboplastin time, platelet count, albumin, aspartate aminotransferase had significantly difference in the two groups (P < 0.05). The operation time, intraoperative bleeding, hemihepatectomy or extended hemi-hepatectomy and the request of blood and serum transfusion had significantly difference in the two groups (P < 0.05). The multivariate analysis showed that the PLT, AST and the intraoperative plasma transfusion, hemihepatectomy or extended hemi-hepatectomy, the urine output and the drainage in the first postoperative day were independent factors (P < 0.05) for ascites. A scoring system was established based on the analysis. The specificity and the sensitivity were 86.2% and 83.3% respectively. CONCLUSION: Variant factors are associated with postoperative ascites for hepatocellular carcinoma and the scoring system established can predict the ascites after hepatectomy accurately.

[Association of hepatitis B virus infection and cirrhosis with liver metastasis in colorectal cancer].

OBJECTIVE: To explore the relationship of hepatitis B virus (HBV) infection and cirrhosis with liver metastasis in colorectal cancer. METHODS: Clinical date of 1176 colorectal cancer patients undergone surgical treatment in the Peking University School of Oncology between January 1999 and August 2004 were analyzed retrospectively to investigate the impact of HBV infection and cirrhosis on the occurrence of liver metastasis and prognosis of patients. RESULTS: The incidence of liver metastasis was 8.8% (10/114) in the HBV infection group and 23.9% (254/1062) in the non-infection group (P<0.01). The 5-year survival rates of these two groups were 54.2% and 60.7% ( P>0.05). The incidence of liver metastasis was 3.8% (1/26) in the cirrhotic group and 22.9% (263/1150) in the non-cirrhotic group (P<0.05). The 5-year survival rates of these two groups were 60.9% and 59.9% ( P>0.05). CONCLUSION: Both hepatitis B virus infection and cirrhosis are associated with less liver metastasis in colorectal cancer, but have no impact on the survival.

Long mesentericoportal vein resection and end-to-end anastomosis without graft in pancreaticoduodenectomy.

INTRODUCTION: The feasibility and safety of pancreaticoduodenectomy (PD) combined with long segmental mesentericoportal vein (MPV; >5 cm) resection and end-to-end anastomosis without graft has rarely been demonstrated. MATERIALS AND METHODS: Eight patients with pancreatic head adenocarcinoma underwent PD combined with long MPV resection between August 2006 and May 2008 in Peking University School of Oncology. RESULTS: By liver mobilization and Cattell-Braasch maneuver, direct and tension-free end-to-end anastomosis was easily performed even when the resected segment of the MPV was longer than 5 cm. All the eight patients experienced uneventful recovery without severe complications. CONCLUSIONS: PD with long MPV resection and direct end-to-end anastomoses is safe and effective.

[Clinical analysis of curative resection with hemihepatectomy for advanced hilar cholangiocarcinoma].

OBJECTIVE: To investigate the superiority of curative resection with hemihepatectomy in treatment of hilar cholangiocarcinoma and the strategy to lower the incidence of complications and mortality. METHODS: The clinical data of 50 patients with hilar cholangiocarcinoma who underwent surgical procedures in Peking University School of Oncology from January 1998 to May 2006 were retrospectively analyzed. RESULTS: Forty-one patients (56.9%) underwent surgical resection. Twenty-two (53.6%) received a radical operation (RO). Thirty patients underwent preoperative percutaneous transhepatic cholangio-drainage (PTCD) to reduce the jaundice. Curative resection with hemihepatectomy was performed on 19 cases including 14 cases undergoing RO. Two patients who had undergone hemihepatectomy died of liver failure. The postoperative morbidity rate was 62% in all 50 cases, 78% in the hemihepatectomy group. The 1- and 2-year survival rates of the hemihepatectomy group were 57.1% and 27.3% respectively. CONCLUSION: Curative resection with hemihepatectomy is a safe and effective option for hilar cholangiocarcinoma, especially for Bismuth III or IV type. Preoperative biliary drainage is necessary before a major hepatic resection.

[Spleen-preserving distal pancreatectomy in treatment of solid-pseudopapillary neoplasm].

OBJECTIVE: To investigate the feasibility and safety of spleen-preserving distal pancreatectomy with conservation of the splenic arteries and veins in treatment of benign neoplasms of distal pancreas. METHODS: Four patients with solid-pseudopapillary neoplasm, 1 males and 3 females, aged 30 (17 - 37), underwent laparotomy. The distal pancreas with tumor was cut. The perforating branches between the splenic artery and vein and the distal pancreas were isolated, ligated, and cut. The splenic artery and vein and the short and left gastric vessels were all preserved. The spleen remained intact. RESULTS: The mean operation time was 208 minutes +/- 52 minutes, and the mean blood loss was 475 ml +/- 96 ml. Blood transfusion was not necessary. The mean post-operative hospital stay was 18 days +/- 13 days. No post-operative complications were found except for pancreatic leakage occurring in one patient that was cured by conservative treatment. No metastasis and recurrence was found. CONCLUSION: Safe and feasible, spleen-preserving distal pancreatectomy with conservation of the splenic arteries and veins is one of the best choices for treatment of benign and borderline tumors of pancreas.

Preliminary study on proteomics of gastric carcinoma and its clinical significance.

AIM: To explore the preliminary identification of serum protein pattern models that may be novel potential biomarkers in the detection of gastric cancer. METHODS: A total of 130 serum samples, including 70 from patients with gastric cancer and 60 from healthy adults, were detected by surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The data of spectra were analyzed by Biomarker Patterns Software (BPS). Thirty serum samples of gastric cancer patients and 30 serum samples of healthy adults were grouped into the training group to build models, and the other 70 samples were used to test and evaluate the models. The samples of the test group were judged only with their peaks' height and were separated into cancer group or healthy control group by BPS automatically and the judgments were checked with the histopathologic diagnosis of the samples. RESULTS: Sixteen mass peaks were found to be potential biomarkers with a significant level of P< 0.01. Among them, nine mass peaks showed increased expression in patients with gastric cancer. Analyzed by BPS, two peaks were chosen to build the model for gastric cancer detection. The sensitivity, specificity, and accuracy of the model were 90%, 36/40, 86.7%, 26/30, and 88.6%, 62/70, respectively, which were greatly higher than those of clinically used serum biomarkers CEA (carcinoembryonic antigen), CA19-9 and CA72-4. Stage I/II gastric cancer samples of the test group were all judged correctly. CONCLUSION: The novel biomarkers in serum and the established model could be potentially used in the detection of gastric cancer. However, large-scale studies should be carried on to further explore the clinical impact on the model.