TRIM29 facilitates gemcitabine resistance via MEK/ERK pathway and is modulated by circRPS29/miR-770-5p axis in PDAC.

AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. Chemotherapy based on gemcitabine (GEM) remains the first-line drug for patients with advanced PDAC. However, GEM resistance impairs its therapeutic effectiveness. Therefore, identifying effective therapeutic targets are urgently needed to overcome GEM resistance. METHODS: The clinical significance of Tripartite Motif Containing 29 (TRIM29) was identified by exploring GEO datasets and TCGA database and its potential biological functions were predicted by GSEA analysis. The regulatory axis was established by bioinformatics analysis and validated by mechanical experiments. Then, in vitro and in vivo assays were performed to validate the roles of TRIM29 in PDAC GEM resistance. RESULTS: High TRIM29 expression was associated with poor prognosis of PDAC and functional experiments demonstrated that TRIM29 promoted GEM resistance in PDAC GEM-resistant (GR) cells. Furthermore, we revealed that circRPS29 promoted TRIM29 expression via competitive interaction with miR-770-5p and then activated MEK/ERK signaling pathway. Additionally, both in vitro and in vivo functional experiments demonstrated that circRPS29/miR-770-5p/TRIM29 axis promoted PDAC GEM resistance via activating MEK/ERK signaling pathway. CONCLUSION: Our results identify the significance of the signaling axis, circRPS29/miR-770-5p/TRIM29-MEK/ERK, in PDAC GEM resistance, which will provide novel therapeutic targets for PDAC treatment.

The role of histone H1.2 in pancreatic cancer metastasis and chemoresistance.

AIMS: Pancreatic cancer (PC) is a highly metastatic malignant tumor of the digestive system. Drug resistance frequently occurs during cancer treatment process. This study aimed to explore the link between chemoresistance and tumor metastasis in PC and its possible molecular and cellular mechanisms. METHODS: A Metastasis and Chemoresistance Signature (MCS) scoring system was built and validated based on metastasis- and chemoresistance-related genes using gene expression data of PC, and the model was applied to single-cell RNA sequencing data. The influence of linker histone H1.2 (H1-2) on PC was explored through in vitro and in vivo experiments including proliferation, invasion, migration, drug sensitivity, rescue experiments and immunohistochemistry, emphasizing its regulation with c-MYC signaling pathway. RESULTS: A novel MCS scoring system accurately predicted PC patient survival and was linked to chemoresistance and epithelial-mesenchymal transition (EMT) in PC single-cell RNA sequencing data. H1-2 emerged as a significant prognostic factor, with its high expression indicating increased chemoresistance and EMT. This upregulation was mediated by c-MYC, which was also found to be highly expressed in PC tissues. CONCLUSION: The MCS scoring system offers insights into PC chemoresistance and metastasis potential. Targeting H1-2 could enhance therapeutic strategies and improve PC patient outcomes.

GAP-43 targeted indocyanine green-loaded near-infrared fluorescent probe for real-time mapping of perineural invasion lesions in pancreatic cancer in vivo.

OBJECTIVE: Perineural invasion (PNI) is associated with local recurrence, distant metastasis, and a poor prognosis in pancreatic cancer. However, rare attempt was made to identified the PNI intraoperative. To facilitate precise R0 excision of the tumor, we planned to develop a fluorescent probe for intraoperative imaging of the PNI using GAP-43 as the target and indocyanine green (ICG) as the carrier. METHODS: The probe was created by binding peptide antibody and ICG. Its targeting was tested in vitro and in vivo using a co-culture model of PC12 and tumor cells to create an in vitro neural invasion model and a mouse sciatic nerve invasion model. The small animal imaging system and surgical navigation system confirmed the probe's potential clinical applicability. The sciatic nerve damage model was created to confirm the probe's targeting. RESULTS: We used the pancreatic cancer samples and the public database to confirm that GAP-43 was preferentially overexpressed in pancreatic cancer, particularly in PNI. PC12 cells showed high GAP-43RA-PEG-ICG probe-specific absorption after being co-cultured with tumor cells in vitro. In the sciatic nerve invasion experiment, animals in probe group displayed a significantly stronger fluorescence signal at the PNI compared to ICG-NP and the contralateral normal nerves groups. Although only 60 % of mice appeared to have R0 resections by the naked eye, small animal imaging systems and surgical fluorescence navigation systems could remove the tumor with R0 precision. The injury model used in the probe imaging experimental trials demonstrated that the probe was specifically targeted to the injured nerve, regardless of whether the injury was infiltrated by a tumor or physical. CONCLUSION: We developed the GAP-43Ra-ICG-PEG, an active-targeting near-infrared fluorescent (NIRF) probe, that specifically binds to GAP-43-positive neural cells in an in vitro model of PNI. The probe efficiently visualized PNI lesions in pancreatic cancer in preclinical models, opening up new possibilities for NIRF-guided pancreatic surgery, particularly for PNI patients.

A longitudinal rat model for assessing postoperative recovery and bone healing following tibial osteotomy and plate fixation.

BACKGROUND: Rodent models are commonly employed to validate preclinical disease models through the evaluation of postoperative behavior and allodynia. Our study investigates the dynamic interplay between pain and functional recovery in the context of traumatic osteotomy and surgical repair. Specifically, we established a rat model of tibial osteotomy, followed by internal fixation using a 5-hole Y-plate with 4 screws, to explore the hypothesis that histological bone healing is closely associated with functional recovery. OBJECTIVE: Our primary objective was to assess the correlation between bone healing and functional outcomes in a rat model of tibial osteotomy and plate fixation. METHODS: Seventeen male Sprague-Dawley rats underwent a metaphyseal transverse osteotomy of the proximal tibia, simulating a fracture-like injury. The resultant bone defect was meticulously repaired by realigning and stabilizing the bone surfaces with the Y-plate. To comprehensively assess recovery and healing, we performed quantitative and qualitative evaluations at 2, 4, 6, and 8 weeks post-surgery. Evaluation methods included micro-CT imaging, X-ray analysis, and histological examination to monitor bone defect healing. Concurrently, we employed video recording and gait analysis to evaluate functional recovery, encompassing parameters such as temporal symmetry, hindlimb duty factor imbalance, phase dispersion, and toe spread. RESULTS: Our findings revealed complete healing of the bone defect at 8 weeks, as confirmed by micro-CT and histological assessments. Specifically, micro-CT data showed a decline in fracture volume over time, indicating progressive healing. Histological examination demonstrated the formation of new trabecular bone and the resolution of inflammation. Importantly, specific gait analysis parameters exhibited longitudinal changes consistent with bone healing. Hindlimb duty factor imbalance, hindlimb temporal symmetry, and phase dispersion correlated strongly with the healing process, emphasizing the direct link between bone healing and functional outcomes. CONCLUSIONS: The establishment of this tibia osteotomy model underscores the association between bone healing and functional outcomes, emphasizing the feasibility of monitoring postoperative recovery using endpoint measurements. Our overarching objective is to employ this model for assessing the local efficacy of drug delivery devices in ameliorating post-surgical pain and enhancing functional recovery.

Hsa-miR-3178/RhoB/PI3K/Akt, a novel signaling pathway regulates ABC transporters to reverse gemcitabine resistance in pancreatic cancer.

BACKGROUND: Although gemcitabine has been considered as the first-line drug for advanced pancreatic cancer (PC), development of resistance to gemcitabine severely limits the effectiveness of this chemotherapy, and the underlying mechanism of gemcitabine resistance remains unclear. Various factors, such as ATP binding cassette (ABC) transporters, microRNAs and their downstream signaling pathways are included in chemoresistance to gemcitabine. This study investigated the potential mechanisms of microRNAs and ABC transporters related signaling pathways for PC resistance to gemcitabine both in vivo and in vitro. METHODS: Immunohistochemistry and Western blotting were applied to detect the expression of ABC transporters. Molecular docking analysis was performed to explore whether gemcitabine interacted with ABC transporters. Gain-of-function and loss-of-function analyses were performed to investigate the functions of hsa-miR-3178 in vitro and in vivo. Bioinformatics analysis, Western blotting and dual-luciferase reporter assay were used to confirm the downstream regulatory mechanisms of hsa-miR-3178. RESULTS: We found that P-gp, BCRP and MRP1 were highly expressed in gemcitabine-resistant PC tissues and cells. Molecular docking analysis revealed that gemcitabine can bind to the ABC transporters. Hsa-miR-3178 was upregulated in gemcitabine resistance PANC-1 cells as compared to its parental PANC-1 cells. Moreover, we found that hsa-miR-3178 promoted gemcitabine resistance in PC cells. These results were also verified by animal experiments. RhoB was down-regulated in gemcitabine-resistant PC cells and it was a downstream target of hsa-miR-3178. Kaplan-Meier survival curve showed that lower RhoB expression was significantly associated with poor overall survival in PC patients. Rescue assays demonstrated that RhoB could reverse hsa-miR-3178-mediated gemcitabine resistance. Interestingly, hsa-miR-3178 promoted gemcitabine resistance in PC by activating the PI3K/Akt pathway-mediated upregulation of ABC transporters. CONCLUSIONS: Our results indicate that hsa-miR-3178 promotes gemcitabine resistance via RhoB/PI3K/Akt signaling pathway-mediated upregulation of ABC transporters. These findings suggest that hsa-miR-3178 could be a novel therapeutic target for overcoming gemcitabine resistance in PC.

Reversal of genetic brain iron accumulation by N,N'-bis(2-mercaptoethyl)isophthalamide, a lipophilic metal chelator, in mice.

N,N'-bis(2-mercaptoethyl)isophthalamide (NBMI) is a novel lipophilic metal chelator and antioxidant used in mercury poisoning. Recent studies have suggested that NBMI may also bind to other metals such as lead and iron. Since NBMI can enter the brain, we evaluated if NBMI removes excess iron from the iron-loaded brain and ameliorates iron-induced oxidative stress. First, NBMI exhibited preferential binding to ferrous (Fe2+) iron with a negligible binding affinity to ferric (Fe3+) iron, indicating a selective chelation of labile iron. Second, NBMI protected SH-SY5Y human neuroblastoma cells from the cytotoxic effects of high iron. NBMI also decreased cellular labile iron and lessened the production of iron-induced reactive oxygen species in these cells. Deferiprone (DFP), a commonly used oral iron chelator, failed to prevent iron-induced cytotoxicity or labile iron accumulation. Next, we validated the efficacy of NBMI in Hfe H67D mutant mice, a mouse model of brain iron accumulation (BIA). Oral gavage of NBMI for 6 weeks decreased iron accumulation in the brain as well as liver, whereas DFP showed iron chelation only in the liver, but not in the brain. Notably, depletion of brain copper and anemia were observed in BIA mice treated with DFP, but not with NBMI, suggesting a superior safety profile of NBMI over DFP for long-term use. Collectively, our study demonstrates that NBMI provides a neuroprotective effect against BIA and has therapeutic potential for neurodegenerative diseases associated with BIA.

Overexpression of ABCG2 confers resistance to pevonedistat, an NAE inhibitor.

Pevonedistat is a potent, selective, first-in-class NEDD8 activating enzyme inhibitor. It is now under multiple clinical trials that investigate its anticancer effect against solid tumors and leukemia. ATP-binding cassette (ABC) transporters are membrane proteins that are involved in mediating multidrug resistance (MDR). In this article, we reveal that pevonedistat is a substrate of ABCG2 which decreases the therapeutic effect of pevonedistat. The cytotoxicity of pevonedistat was significantly weakened in ABCG2-overexpressing cells, and the drug resistance can be reversed by ABCG2 inhibitors. The ATPase assay suggested that pevonedistat can stimulate ABCG2 ATPase activity in a concentration-dependent manner. Pevonedistat showed little effect on the expression level or subcellular localization of ABCG2 after 72 h treatment. Furthermore, a pevonedistat resistance cell line S1-PR was established and overexpressed ABCG2. Generally, our study provides evidence that ABCG2 can be a prominent factor leading to pevonedistat-resistance. Furthermore, ABCG2 may also be utilized as a biomarker to monitor the development of pevonedistat resistance during cancer treatment.

Intranasal Delivery and Transfection of mRNA Therapeutics in the Brain Using Cationic Liposomes.

Nucleic acid-based therapeutics, including the use of messenger RNA (mRNA) as a drug molecule, has tremendous potential in the treatment of chronic diseases, such as age-related neurodegenerative diseases. In this study, we have developed a cationic liposomal formulation of mRNA and evaluated the potential of intranasal delivery to the brain in murine model. Preliminary in vitro studies in J774A.1 murine macrophages showed GFP expression up to 24 h and stably expressed GFP protein in the cytosol. Upon intranasal administration of GFP-mRNA/cationic liposomes (3 mg/kg dose) in mice, there was significantly higher GFP-mRNA expression in the brain post 24 h as compared to either naked mRNA or the vehicle-treated group. Luciferase mRNA encapsulated in cationic liposomes was used for quantification of mRNA expression distribution in the brain. The results showed increased luciferase activity in the whole brain in a dose-dependent manner. Specifically, the luciferase-mRNA/cationic liposome group (3 mg/kg dose) showed significantly higher luciferase activity in the cortex, striatum, and midbrain regions as compared with the control groups, with minimal systemic exposure. Overall, the results of this study demonstrate the feasibility of brain-specific, nonviral mRNA delivery for the treatment of various neurological disorders.

Real-time navigation for laparoscopic hepatectomy using image fusion of preoperative 3D surgical plan and intraoperative indocyanine green fluorescence imaging.

BACKGROUND: Understanding the internal anatomy of the liver remains a major challenge in anatomical liver resection. Although virtual hepatectomy and indocyanine green (ICG) fluorescence imaging techniques have been widely used in hepatobiliary surgery, limitations in their application for real-time navigation persist. OBJECTIVE: The aim of the present study was to evaluate the feasibility and clinical utility of the novel laparoscopic hepatectomy navigation system (LHNS), which fuses preoperative three-dimensional (3D) models with ICG fluorescence imaging to achieve real-time surgical navigation. METHODS: We conducted a retrospective review of clinical outcome for 64 patients who underwent laparoscopic hepatectomy from January 2018 to December 2018, including 30 patients who underwent the procedure using the LHNS (LHNS group) and 34 patients who underwent the procedure without LHNS guidance (Non-LHNS group). RESULTS: There was no significant difference in preoperative characteristics between the two groups. The LHNS group had a significantly less blood loss (285.0 ± 163.0 mL vs. 391.1 ± 242.0 mL; P = 0.047), less intraoperative blood transfusion rate (13.3% vs. 38.2%; P = 0.045), and shorter postoperative hospital stay (7.8 ± 2.1 days vs. 10.6 ± 3.8 days; P < 0.001) than the Non-LHNS group. There was no statistical difference in operative time and the overall complication rate between the two groups. The liver transection line was clearly delineated by the LHNS in 27 patients; however, the projection of boundary was unclear in 2 cases, and in 1 case, the boundary was not clearly displayed by ICG fluorescence imaging. CONCLUSIONS: We developed the LHNS to address limitations of current intraoperative imaging systems. The LHNS is hopefully to become a promising real-time navigation system for laparoscopic hepatectomy.

High prevalence of breastmilk-acquired cytomegalovirus infection in jaundiced infants.

BACKGROUND: Our objective was to evaluate the prevalence and different diagnostic methods of breastmilk (BM)-acquired cytomegalovirus (CMV) infection in a pathologically jaundiced cohort. METHODS: A total of 400 infants confirmed with pathological jaundice at The People's Hospital of Qingyang City were screened for BM-acquired CMV infection between February 2018 and February 2019. A total of 300 infants were finally enrolled in our study. CMV infection was confirmed by detecting both CMV-DNA in various samples using FQ-PCR and CMV-IgM with chemiluminescence. Clinical and other laboratory data were collected from these infants during their hospitalization or regular visits. RESULTS: Ninety-eight (32.67%) subjects were confirmed to be BM CMV-DNA-positive, and 18 (18.37%) were diagnosed with a BM-acquired CMV infection. All 18 (100%) infants with a BM-acquired CMV infection were CMV-DNA-positive in urine, while 5 (27.78%) cases and 11 (61.11%) cases were confirmed in plasma and peripheral blood mononuclear cells (PBMCs), respectively. Only 6 (33.33%) infants were CMV-IgM-positive. Birthweight, direct bilirubin, aspartate aminotransferase, and the viral load in BM of the BM-acquired CMV group were higher than those in the non-infected group (P < .05). Low birthweight and viral load in BM were risk factors for BM-acquired CMV infection. Detecting CMV-DNA in urine samples exhibited better performance than the other methods for screening BM-acquired CMV infections. CONCLUSIONS: Our study found a high prevalence of BM-acquired CMV infection in jaundiced infants, and detecting CMV-DNA in a urine sample was the most sensitive method for disease screening.

Site-specific intestinal DMT1 silencing to mitigate iron absorption using pH-sensitive multi-compartmental nanoparticulate oral delivery system.

Iron is a nutrient metal, but excess iron promotes tissue damage. Since iron chelation therapies exhibit multiple off-target toxicities, there is a substantial demand for more specific approaches to decrease iron burden in iron overload. While the divalent metal transporter 1 (DMT1) plays a well-established role in the absorption of dietary iron, up-regulation of intestinal DMT1 is associated with iron overload in both humans and rodents. Hence, we developed a novel pH-sensitive multi-compartmental particulate (MCP) oral delivery system that encapsulates DMT1 siRNA and validated its efficacy in mice. Using the gelatin NPs coated with Eudragit® L100-55, we demonstrated that DMT1 siRNA-loaded MCPs down-regulated DMT1 mRNA levels in the duodenum, which was consistent with decreased intestinal absorption of orally-administered 59Fe. Together, the Eudragit® L100-55-based oral siRNA delivery system could provide an effective strategy to specifically down-regulate duodenal DMT1 and mitigate iron absorption.

A first-principles study on zigzag phosphorene nanoribbons passivated by iron-group atoms.

We performed a first-principles study on Fe-, Co-, and Ni-terminated zigzag phosphorene nanoribbons (ZPNRs) with different widths. Magnetic edges were observed for Fe- and Co-terminated ZPNRs, whereas Ni-terminated ZPNRs were nonmagnetic. Interestingly, magnetism could be induced in Ni-ZPNRs by external electric fields, and the distribution of the magnetic moments could be tuned by the direction of the electric fields. Furthermore, Fe-ZPNRs and Co-ZPNRs exhibit semi-metallic and metallic characteristics, respectively, whereas Ni-ZPNRs are mainly semiconductors with band gaps generally increasing monotonously with the increase in nanoribbon width. These fascinating properties of iron-group atom terminated ZPNRs indicate their great potential applications in future spintronics, optoelectronics, and information technologies.

Individualized preoperative planning using three-dimensional modeling for Bismuth and Corlette type III hilar cholangiocarcinoma.

BACKGROUND: A detailed evaluation of blood supply anatomy, especially the biliary anatomy at the hepatic hilus, is essential to ensure a complete and curative resection for Bismuth and Corlette type III hilar cholangiocarcinoma. The study aimed to investigate the impact of individualized preoperative planning using 3D modeling on surgical treatment for type III hilar cholangiocarcinoma. METHODS: This was a retrospective study of patients with type III hilar cholangiocarcinoma (n=47) who underwent surgery at the Hepatobiliary Surgery Department of Zhujiang Hospital between March 2007 and January 2015. All patients had undergone preoperative computed tomography (CT) examination, and 3D images were reconstructed. Preoperative surgery simulation was performed, and the simulation was applied in the subsequent surgery. Clinical, surgical, and pathological characteristics were compared between patients undergoing preoperative planning (n=25) and those who did not (n=22). Complications were examined. RESULTS: Surgical time and blood loss were significantly smaller in patients with 3D reconstruction compared to those without. The number of bile duct orifices was correctly estimated in 14/25 (56.0%) patients with preoperative planning. The width of the hepatic surgical margin could be measured for 18 hepatic ducts, and 17 (68.0%) of them were pathologically diagnosed as margin-negative. CONCLUSIONS: This technique has the advantages of precise visualization of the anatomic structures and 3D assessment of biliary branches and vessels, allowing improved operative planning for the treatment of hilar cholangiocarcinoma.

Comparison of liver volumetry on contrast-enhanced CT images: one semiautomatic and two automatic approaches.

This study was to evaluate the accuracy, consistency, and efficiency of three liver volumetry methods- one interactive method, an in-house-developed 3D medical Image Analysis (3DMIA) system, one automatic active shape model (ASM)-based segmentation, and one automatic probabilistic atlas (PA)-guided segmentation method on clinical contrast-enhanced CT images. Forty-two datasets, including 27 normal liver and 15 space-occupying liver lesion patients, were retrospectively included in this study. The three methods - one semiautomatic 3DMIA, one automatic ASM-based, and one automatic PA-based liver volumetry - achieved an accuracy with VD (volume difference) of -1.69%, -2.75%, and 3.06% in the normal group, respectively, and with VD of -3.20%, -3.35%, and 4.14% in the space-occupying lesion group, respectively. However, the three methods achieved an efficiency of 27.63 mins, 1.26 mins, 1.18 mins on average, respectively, compared with the manual volumetry, which took 43.98 mins. The high intraclass correlation coefficient between the three methods and the manual method indicated an excel-lent agreement on liver volumetry. Significant differences in segmentation time were observed between the three methods (3DMIA, ASM, and PA) and the manual volumetry (p < 0.001), as well as between the automatic volumetries (ASM and PA) and the semiautomatic volumetry (3DMIA) (p < 0.001). The semiautomatic interactive 3DMIA, automatic ASM-based, and automatic PA-based liver volum-etry agreed well with manual gold standard in both the normal liver group and the space-occupying lesion group. The ASM- and PA-based automatic segmentation have better efficiency in clinical use.

Computer-aided rigid choledochoscopy lithotripsy for hepatolithiasis.

BACKGROUND: Hepatolithiasis is challenging for surgeons to treat especially in patients with previous hepatobiliary surgery. The aim of the study was to report our experience of rigid choledochoscopy lithotripsy in targeted treatment of hepatolithiasis under the guidance of a medical image three-dimensional visualization system, which we developed and patented (software copyright no: 2008SR18 798) by comparing it with hepatectomy without a three-dimensional (3D) reconstruction technique. METHODS: Between December 2007 and March 2013, 64 patients underwent rigid choledochoscopy lithotripsy based on 3D visualization technology conducted by a medical image three-dimensional visualization system for hepatolithiasis (group A). During the same period, 61 patients with hepatolithiasis were selected for hepatectomy (group B). Comparative analysis was made of demographic and perioperative characteristics of the two groups. RESULTS: 3D visualization was instructive for surgeons on how the stones were distributed and what the spatial relationship was between stones and the intrahepatic vascular system. Compared with patients in group B, those in group A had a significantly lower intermediate residual stone rate, a faster operating time, a lower intraoperative blood loss and intraoperative blood transfusion, a shorter postoperative hospital stay, less postoperative complications, and more liver function reserved (P < 0.05 for all). Final residual stone rate, stone recurrence rate, and recurrent cholangitis rate were similar. CONCLUSIONS: 3D visualization technology provides an important reference and a valuable planning for rigid choledochoscopy lithotripsy, which is a feasible and effective method for management of hepatolithiasis.

An Experimental Model Design for Photoaging.

UNLABELLED: Autologous adipose-derived stem cells have shown great promise in applications that treat photodamaged skin. Adipose-derived stem cells also have an antiwrinkle effect; consequently, they have become a topic of primary interest. Nude mice have been used extensively in studies of adipose-derived stem cells, human dermal fibroblasts, and other filler injections. However, a nude mouse model of photoaging has not yet been developed. Thus, we attempted to develop a nude mouse model of photoaging in this study. MATERIALS AND METHODS: Fourteen, 5-week-old female BALB/c nude mice were irradiated with ultraviolet-B rays, 6 times a week for 6 weeks. The minimum erythema dose was established before the mice underwent ultraviolet irradiation to minimize the inflammation of the irradiated skin and to determine the initial irradiation dosage. The mean sizes of the wrinkled areas of skin and the mean depths of the wrinkles were compared between the study groups using replica analysis. Skin biopsies were performed on the 6th and 10th weeks of the study. RESULTS: The mean sizes of the wrinkled areas of skin and the mean depths of the wrinkles increased significantly in the ultraviolet-B-irradiated nude mice compared with the nonirradiated mice, and the thicknesses of the epidermis and dermis of the skin from the upper and lower back were significantly greater after ultraviolet-B irradiation up to the 6th week of treatment (P < 0.05). Furthermore, the ultraviolet-B-irradiated group demonstrated reduced collagen fiber levels. CONCLUSIONS: We have successfully developed a nude mouse model for research into photoaging, and these results indicate that the nude mouse is a suitable model for investigating the development of photoaging.

[Efficacy of three dimensional visualization technique assisted hepatectomy for the treatment of primary liver cancer].

OBJECTIVE: To study the clinical efficacy of three dimensional visualization technique assisted hepatectomy for the treatment of primary liver cancer. METHODS: A total of 108 primary liver cancer patients who had been admitted to Zhujiang Hospital of Southern Medical University from September 2013 to December 2014 were assigned to three dimensional visualization technique assisted hepatectomy group (n = 55) and routine hepatectomy group (n = 53) according to different methods of hepatectomy. The observed variable in two groups as fellow: the operative time, intraoperative blood loss, intraoperative blood transfusion, the change of postoperative liver function and biochemical indicators in 1, 3, 5 days, postoperative complication. The patients were followed up via-return visit or telephone.A student's t test was used to compare continuous parametric variables, and the Mann-Whitney U test was used to compare non-parametric or discrete variables, as appropriate. Categorical data were compared using the Chi-square test or Fisher's exact test. RESULTS: In 3D group and routine hepatectomy group, the patients' intraoperative blood transfusion volume were 300 ml (200-600 ml) and 400 ml (300-700 ml) (χ² = -2.609, P = 0.009) respectively, intraoperative blood loss volume were 400 ml (250-600 ml) and 550 ml (400-800 ml) (χ² = -2.277, P = 0.023), the operative time were (247 ± 57) min and (262 ± 53) min (χ² = -1.787, P = 0.074), the deterioration of the mainly liver function indicators peak in routine hepatectomy group were higher than that in 3D group (P < 0.05). The ALT, AST, TBIL in 3D group were lower than that in routine group on postoperative day 1, 3, 5, respectively (χ² = -5.740- -0.692, all P < 0.05). The ALB in 3D group was higher than that in routine group on postoperative day 3, 5 ((33.0 ± 5.6) g/L vs. (31.2 ± 4.1) g/L, (36.7 ± 4.4) g/L vs. (34.7 ± 4.2) g/L) (t = 1.922-2.573, both P < 0.05). In 3D group and routine hepatectomy group, the incidence of postoperative complications were 10.9% and 30.1% (χ² = 6.185, P = 0.013), the length of postoperative hospital day were (12.6 ± 3.6) days and (14.4 ± 3.5) days (χ² = -3.384, P = 0.031), the positive rate of resection margin were 0 and 9.4% respectively (Fisher test: P = 0.026), the 1-year tumor recurrence rate were 22.2% and 37.5% (P > 0.05), 1-year survival rate was 82.2% and 77.5% (P > 0.05). No perioperative mortality was occured in the two groups. CONCLUSION: Three dimensional visualization technique assisted hepatectomy for the treatment of primary liver cancer could reduce surgical injury, lower the rate of postoperative complications, improve the safety and the efficacy of the operation and achieve a good prognosis.

A comparative study of the diagnostic accuracy of the medical image three-dimensional visualization system, MRCP, CT and US in hepatolithiasis.

BACKGROUND/AIMS: The aim of this study was to compare the results of the Three-Dimensional Visualization System (MI-3DVS or 3D) in the diagnostic accuracy of hepatolithiasis. METHODOLOGY: From February 2007 to March 2013, forty-eight patients with hepatolithiasis were admitted to our department. Meanwhile, choosing forty-one patients without hepatolithiasis as controlgroup. MI-3DVS, MRCP, CT, and US were performed and the results of these imaging methods in detecting calculi distribution, bile duct dilatation/stricture, and liver atrophy/hypertrophy were analyzed. RESULTS: The total display accuracy on bile duct stricture/dilatation using by 3D was higher than using by MRCP, CT, US. The total accuracy of 3D in detecting the liver atrophy was 96.6%, which was superior to that of US (p=0.009) and CT (p=0.044), and there was no significant difference compared with MRCP (P=0.120). The results on diagnosis of calculi distribution by 3D was better than US (p=0.003) and MRCP (p=0.029), but had no significantly difference compared with CT (P=0.246), and they were all close to intraoperative findings. CONCLUSIONS: MI-3DVS could be used to select patients with hepatolithiasis as a supplement approach to other imaging methods and as an innovative means in pre-operative assessment and post-operative follow-ups in hepatolithiasis.

Management complicated hepatolithiasis with operative rigid choledochoscope guided by computed tomography (CT)-based 3D reconstruction technique.

BACKGROUND: Treatment of complicated hepatolithiasis is complex and difficult. In this report, we present a novel approach to manage complicated hepatolithiasis using the rigid choledochoscope guided by CT-based 3D reconstruction technique with or without hepatectomy. METHODS: Between February 2012 to December 2013, 25 patients with complicated hepatolithiasis underwent rigid choledochoscope guided by CT-based 3D reconstruction technique combined with or without hepatectomy. 27 patients with complicated hepatolithiasis underwent a traditional operation (traditional method group) from June 2011 to January 2012. All operations were performed by the authors. RESULTS: The final stone clearance rate of the rigid choledochoscope group was 96%, whereas that of the traditional method group was 74.1% (P=0.032). There was no patient died of postoperative mortality in two groups. Moreover, the operative time in the traditional method group was significantly longer than that in the rigid choledochoscope group (P=0.010). Recurrent intrahepatic bile duct stones were not found during the follow-up period in the two groups. CONCLUSIONS: Operative rigid choledochoscope guided by CT-based 3D reconstruction technique combined with or without hepatectomy may be an effective and safe treatment for complicated hepatolithiasis.

3D Reconstruction Aids Surgery For Complicated Hepatolithiasis.

BACKGROUND/AIMS: Three-dimensional (3D) imaging may improve surgical interventions for complicated hepatolithiasis. METHODOLOGY: Between July 2008 and December 2012 a total of 131 patients with complicated hepatolithiasis underwent surgical therapy in the Department of Hepatobiliary Surgery Zhujiang Hospital, Southern Medical University. 77 patients received preoperative planning using a computed tomography (CT)-based 3D reconstruction technique, and 54 received treatment based on preoperative planning with traditional imaging (CT, ultrasonography, magnetic resonance imaging/magnetic resonance cholangiography). Perioperative and long-term outcomes were analyzed. RESULTS: 3D reconstruction facilitated significantly more accurate diagnosis of pathological morphology than conventional imaging methods, as confirmed during surgery. Patients that received 3D reconstruction preoperative planning had significantly better clinical outcomes. The immediate stone clearance rates were 92.2% and 61.1%, respectively. Additional postoperative choledochoscopic lithotripsy raised the clearance rates to 94.8% and 81.5%, respectively. The hospital mortality rates were 0% and 1.9%, respectively, and the complication rates were 33.8% and 44.4%, respectively. With a median follow-up of 28 months (5-38 months), the long-term overall asymptomatic survival rates were 80.5% and 46.3%, respectively. 3D reconstruction preoperative planning was a significant prognostic protective factor of long-term asymptomatic survival for the patients with complicated hepatolithiasis (Cox regression analysis, RR = 0.348, 95% confidence interval 0.185-0.657, p = 0.001). CONCLUSION: Surgical therapy conducted following preoperative planning using 3D reconstruction achieved better clinical outcomes than conventional imaging techniques. Whilst conventional imaging techniques accurately identify intrahepatic stones, they are less capable of identifying bile duct stricture.