Comparison of prognosis and postoperative morbidities between standard pancreaticoduodenectomy and the TRIANGLE technique for resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Radical surgery combined with systemic chemotherapy offers the possibility of long-term survival or even cure for patients with pancreatic ductal adenocarcinoma (PDAC), although tumor recurrence, especially locally, still inhibits the treatment efficacy. The TRIANGLE technique was introduced as an extended dissection procedure to improve the R0 resection rate of borderline resectable or locally advanced PDAC. However, there was a lack of studies concerning postoperative complications and long-term outcomes of this procedure on patients with resectable PDAC. AIM: To compare the prognosis and postoperative morbidities between standard pancreaticoduodenectomy (PD) and the TRIANGLE technique for resectable PDAC. METHODS: Patients with resectable PDAC eligible for PD from our hospital between June 2018 and December 2021 were enrolled in this retrospective cohort study. All the patients were divided into PDstandard and PDTRIANGLE groups according to the surgical procedure. Baseline characteristics, surgical data, and postoperative morbidities were recorded. All of the patients were followed up, and the date and location of tumor recurrence, and death were recorded. The Kaplan-Meier method and log-rank test were used for the survival analysis. RESULTS: There were 93 patients included in the study and 37 underwent the TRIANGLE technique. Duration of operation was longer in the PDTRIANGLE group compared with the PDstandard group [440 (410-480) min vs 320 (265-427) min] (P = 0.001). Intraoperative blood loss [700 (500-1200) mL vs 500 (300-800) mL] (P = 0.009) and blood transfusion [975 (0-1250) mL vs 400 (0-800) mL] (P = 0.009) were higher in the PDTRIANGLE group. There was a higher incidence of surgical site infection (43.2% vs 12.5%) (P = 0.001) and postoperative diarrhea (54.1% vs 12.5%) (P = 0.001) in the PDTRIANGLE group. The rates of R0 resection and local recurrence, overall survival, and disease-free survival did not differ significantly between the two groups. CONCLUSION: The TRIANGLE technique is safe, with acceptable postoperative morbidities compared with standardized PD, but it does not improve prognosis for patients with resectable PDAC.

Lymphadenectomy with venation is preferred compared to skeletonization for patients with rectal and sigmoid colon cancer: a retrospective cohort study.

Background: For patients with rectal and sigmoid colon cancer, dissecting No. 253 lymph nodes and preserving the left colic artery are the essentials of radical surgery. In clinical work, some surgeons prefer to dissect lymph nodes with skeletonization, believing that lymph nodes can be dissected completely by this method, while other surgeons prefer to dissect lymph nodes with venation. They believe that their method can not only dissect lymph nodes completely but also ensure the safety of patients. This study aimed to investigate whether lymphadenectomy with skeletonization is superior to lymphadenectomy with venation for patients with rectal and sigmoid colon cancer. Methods: We performed a retrospective cohort study between August, 2017 and October, 2019 at the Department of General Surgery, the Affiliated Hospital of Nanjing University Medical School. The inclusion criteria were as follows: diagnosed as rectum or sigmoid colon adenocarcinoma by electronic colonoscopy and histopathology; 18-80 years of age; underwent radical resection. The exclusion criteria were as follows: received neoadjuvant therapy before surgery; combined with distant metastasis. According to the method of lymph node dissection, patients were divided into the skeletonization group and venation group. We then compared the curative effect and safety between the 2 groups. Results: A total of 211 patients were recruited in this retrospective study and assigned as follows: 62 cases to the skeletonization group and 149 patients to the venation group. There were no statistical differences in the total number of lymph nodes (P=0.082), number of positive lymph nodes (P=0.097), total number of No. 253 lymph nodes (P=0.096), number of positive No. 253 lymph nodes (P=0.813), and nodal staging (P=0.254) between the 2 groups. However, the amount of bleeding in the skeletonization group was significantly higher than that in the venation group (P≤0.001), and the operation time in the skeletonization group was also significantly longer than that in the venation group (P≤0.001). Conclusions: Lymphadenectomy with venation is preferred in the radical resection of patients with rectal and sigmoid colon cancer.

Relationship between PD-L1 expression, CD8+ T-cell infiltration and prognosis in intrahepatic cholangiocarcinoma patients.

BACKGROUND: Programmed death- ligand 1 (PD-L1) seems to be associated with the immune escape of tumors, and immunotherapy may be a favorable treatment for PD-L1-positive patients. We evaluated intrahepatic cholangiocarcinoma (ICC) specimens for their expression of PD-L1, infiltration of CD8+ T cells, and the relationship between these factors and patient survival. METHODS: In total, 69 resections of ICC were stained by immunohistochemistry for PD-L1, programmed death factor-1 (PD-1), and CD8+ T cells. CD8+ T-cell densities were analyzed both within tumors and at the tumor-stromal interface. Patient survival was predicted based on the PD-L1 status and CD8+ T-cell density. RESULTS: The expression rate of PD-L1 was 12% in cancer cells and 51% in interstitial cells. The expression rate of PD-1 was 30%, and the number of CD8+ T-cells increased with the increase of PD-L1 expression (p < 0.05). The expression of PD-L1 in the tumor was correlated with poor overall survival(OS) (p = 0.004), and the number of tumor and interstitial CD8+ T-cells was correlated with poor OS and disease-free survival (DFS) (All p < 0.001). CONCLUSIONS: The expression of PD-L1 in the tumor is related to poor OS, and the number of tumor or interstitial CD8+ T-cells is related to poor OS and DFS. For patients who lose their chance of surgery, PD-L1 immunosuppressive therapy may be the focus of future research as a potential treatment.

The methods of preoperative biliary drainage for resectable hilar cholangiocarcinoma patients: A protocol for systematic review and meta analysis.

OBJECTIVES: To compare the clinical outcomes of endoscopic biliary drainage (EBD) with those of percutaneous transhepatic biliary drainage (PTBD) in patients with resectable hilar cholangiocarcinoma (HCCA) and evaluate the effect of EBD and PTBD on tumor prognosis. MATERIALS AND METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for articles about the comparison between PTBD and EBD. Data were analyzed by Revman 5.3. RESULTS: PTBD showed a lower risk of drainage-related complications than EBD (OR, 2.73; 95%CI, 1.52-4.91; P < .05). PTBD was also associated with lower risk of pancreatitis (OR, 8.47; 95%CI, 2.28-31.45; P < .05). The differences in preoperative cholangitis, R0 resection, blood loss and recurrence showed no statistically significance between EBD and PTBD (all P > .05). Several literatures have reported the tumor implantation metastasis after PTBD. Since no well-designed prospective randomized controlled studies have explored in this depth, this article is unable to draw conclusions on this aspect. CONCLUSION: PTBD is a reasonable choice for PBD, and EBD should only be used as preoperative drainage for HCCA by more experienced physicians. There is a greater need to design prospective randomized controlled studies to obtain high-level evidence-based medicinal proof. It is worth noting that, whether EBD or PTBD, accurate selective biliary drainage should be the trend.

MUC1 promotes glycolysis through inhibiting BRCA1 expression in pancreatic cancer.

Enhanced glucose metabolism is one of the hallmarks of pancreatic cancer. MUC1, a transmembrane protein, is a global regulator of glucose metabolism and essential for progression of pancreatic cancer. To clarify the role of MUC1 in glucose metabolism, we knocked out MUC1 in Capan-1 and CFPAC-1 cells. MUC1 knockout (KO) cells uptook less glucose and secreted less lactate with a much lower proliferating rate. The mRNA level of key enzymes in glycolysis also decreased significantly in MUC1 KO cells. We also observed increased expression of breast cancer type 1 susceptibility protein (BRCA1) in MUC1 KO cells. Since BRCA1 has a strong inhibitory effect on glycolysis, we want to know whether the decreased glucose metabolism in MUC1 KO cells is due to increased BRCA1 expression. We treated wild type (WT) and MUC1 KO cells with BRCA1 inhibitor. BRCA1 inhibition significantly enhanced glucose uptake and lactate secretion in both WT and MUC1 KO cells. Expression of key enzymes in glycolysis also elevated after BRCA1 inhibition. Elevated glucose metabolism is known to facilitate cancer cells to gain chemoresistance. We treated MUC1 KO cells with gemcitabine and FOLFIRINOX in vitro and in vivo. The results showed that MUC1 KO sensitized pancreatic cancer cells to chemotherapy both in vitro and in vivo. In conclusion, we demonstrated that MUC1 promotes glycolysis through inhibiting BRCA1 expression. MUC1 may be a therapeutic target in pancreatic cancer treatment.

Risk factors for long-term prognosis of hepatocellular carcinoma patients after anatomic hepatectomy.

BACKGROUND: The risk factors for patients with major postoperative complications immediately after liver resection have been identified; however, the intermediate and long-term prognoses for these patients have yet to be determined. AIM: To evaluate the factors responsible for the long-term recurrence-free survival rate in patients with hepatocellular carcinoma (HCC) following anatomic hepatectomy. METHODS: We performed a retrospective analysis of 74 patients with HCC who underwent precise anatomic hepatectomy at our institution from January 2013 to December 2015. The observational endpoints for this study were the tumor recurrence or death of the HCC patients. The overall follow-up duration was three years. The recurrence-free survival curves were plotted by the Kaplan-Meier method and were analyzed by the log-rank test. The value of each variable for predicting prognosis was assessed via multivariate Cox proportional hazards regression analysis. RESULTS: The 1-year and 3-year recurrence-free survival rates of HCC patients were 68.92% and 55.41%, respectively, following anatomic liver resection. The results showed that the 3-year recurrence-free survival rate in HCC patients was closely related to preoperative cirrhosis, jaundice level, tumor stage, maximal tumor diameter, complications of diabetes mellitus, frequency of intraoperative hypotensive episodes, estimated blood loss (EBL), blood transfusion, fluid infusion, and postoperative infection (P < 0.1). Based on multivariate analysis, preoperative cirrhosis, tumor stage, intraoperative hypotension, and EBL were identified to be predictors of 3-year recurrence-free survival in HCC patients undergoing anatomic hepatectomy (P < 0.05). CONCLUSION: Tumor stage and preoperative cirrhosis adversely affect the recurrence-free survival rate in HCC patients following anatomic hepatectomy. The long-term recurrence-free survival rate of patients with HCC is closely related to intraoperative hypotension and EBL.

Prognostic value of precise hepatic pedicle dissection in anatomical resection for patients with hepatocellular carcinoma.

The present study aimed to investigate the long-term and perioperative outcomes of precise hepatic pedicle dissection in anatomical resection (precise AR) vs non-anatomical resection (NAR) for hepatocellular carcinoma (HCC) patients.Data from a total of 270 consecutive HCC patients who underwent curative hepatectomy were retrospectively collected. Propensity score matching (PSM) analysis was performed. The long-term outcomes of precise AR and NAR were analyzed using the Kaplan-Meier method and the Cox proportional hazards model.The 1-, 3-, and 5-year overall survival (OS) rates were 90.3%, 76.2%, and 65.7% in the PS-precise AR group, respectively (n = 103); and 88.3%, 70.5%, and 52.0% in the PS-NAR group, respectively (n = 103) (P = .043). The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 83.4%, 63.2%, and 46.0% in the PS-precise AR group, respectively; and 75.7%, 47.4%, and 28.3% in the PS-NAR group, respectively (P = .002). Multivariate analysis showed that ICG-R15, BCLC staging, and microvascular invasion (MVI) were independent risk factors for OS; while tumor size, types of resection, surgical margin, and MVI were independent risk factors for RFS. Subgroup analysis indicated that the RFS rate was significantly better in the PS-precise AR group than in the PS-NAR group for patients with MVI and tumor size ≤5 cm.After PSM, precise hepatic pedicle dissection in AR significantly improved the recurrence-free survival rate of solitary HCC patients compared with NAR, especially in those with MVI and tumor size ≤5 cm.

Evidence for a role of geranylgeranylation in renal angiomyolipoma and renal epithelioid angiomyolipoma.

Research on mevalonate kinase deficiency has revealed that it may lead to the development of renal angiomyolipomas (RAMLs). Thus, it was suspected that geranylgeranyl pyrophosphate synthase (GGPPS), a key enzyme in the mevalonate pathway, may be involved in the development of RAMLs. In the present study, the expression of GGPPS in RAMLs and renal epithelioid angiomyolipomas (REAs) was assessed, and paraffin embedded specimens from 60 patients, including 9 cases with REA and 51 cases with RAML, were examined. Immunoreactivity was evaluated semi-quantitatively according to the intensity of staining and the percentage of positively stained cells. The results indicated that GGPPS was predominantly present in the cytoplasm, and REA tissues exhibited higher expression of GGPPS in the cytoplasm compared with RAML tissues. It was also identified that GGPPS was upregulated in TSC2-null cells, and inhibition of GGPPS could induce apoptosis of TSC2-null cells by autophagy. In conclusion, the increased expression of GGPPS in RAMLs and REAs indicated that mevalonate pathways may be involved in disease progression. GGPPS may serve as a potential therapeutic target and the current results may provide a novel therapeutic strategy for RAML and lymphangioleiomyomatosis.

The differential enhancement pattern of contrast enhanced ultrasound and magnetic resonance imaging characteristics in hepatic angiomyolipoma: 7 case reports.

OBJECTIVE: To compare the enhancement pattern of hepatic angiomyolipoma (HAML) on contrast enhanced ultrasound (CEUS) and magnetic resonance (MR). METHODS: The data of seven patients (females; age 28-52 years; mean, 42 years) with histologically proven HAMLs were retrospectively reviewed. All patients underwent CEUS and MR examination. The images were analyzed by two experienced doctors who blinded to the clinical and pathological information of cases. RESULTS: The mean diameter of the nodule was 5.7 cm (range: 3.2-10 cm). Histopathologic results revealed 4 nodules to be myomatous type and 3 nodules to be mixed type. All nodules showed hyperenhanced during arterial phase on both CEUS and MRI. During portal and delayed phase, washout was more showed on MRI (5/7, 71.4%) than on CEUS (2/7, 28.6%). CONCLUSIONS: There is discrepancy of enhancement pattern between CEUS and MRI. The quick wash-in and sustained hyperenhancement on CEUS may be helpful for the diagnosis of HAML.

Application of contrast enhanced ultrasound in gallbladder lesion: is it helpful to improve the diagnostic capabilities?

The aim of this study is to evaluate if contrast enhanced ultrasound (CEUS) can improve the differential diagnostic performance of gallbladder (GB) lesions. MATERIALS AND METHODS: Forty-nine patients (18 men, 31 women; mean age, 54.8±14.4 years, range age, 22-78 years) with GB lesions (mass-forming and wall-thickened types) were enrolled in this study. All patients underwent conventional ultrasonography (US) and CEUS examination. The imaging characteristics of GB lesions were analyzed to compare the diagnostic performance of US and CEUS. The final diagnosis was obtained by histopathology. RESULTS: There were significant differences between benign and malignant GB lesions with regards to size, shape, vascularity, the integrity and margin of GB wall and time to iso-enhancement on CEUS (p<0.05). However, no significant difference was found concerning the enhancement patterns between the two groups (p>0.05). Logistic regression analysis showed that the boundary between liver and GB wall (p=0.017) and vascularity on color Doppler flow imaging (p=0.013) were two independent predictors of malignancy. The diagnostic accuracy of US could be improved in combination with CEUS (65.3% vs 83.7%). The diagnostic accuracy of the GB wall thickening type was higher than the mass forming type. CONCLUSION: CEUS could improve the diagnostic performance of GB lesions, especially for wall-thickened type lesions.

The efficacy of combination of induction chemotherapy and irreversible electroporation ablation for patients with locally advanced pancreatic adenocarcinoma.

BACKGROUND AND OBJECTIVES: Irreversible electroporation (IRE) is a non-thermal focal therapy that utilizes high voltage electric pulses to permanently rupture the cellular membrane and induce cell death. In this multi-center study, we evaluated the safety and efficacy of IRE in patients with locally advanced pancreatic cancer (LAPC). METHODS: From 2012 to 2015, we performed laparotomic and laparoscopic IRE in a total of 70 patients with stage III LAPC. Either gemcitabine-based or TS-1 (Tegafur, Gimeracil, and Oteracil) chemotherapy was applied for at least 3 months before the IRE. RESULTS: No IRE-related deaths occurred. A median follow-up of 28.1 months showed that six patients (8.6%) experienced local recurrence and 24 (34%) experienced distant progression. The overall median survival from the time of treatment was 22.6 months, and the progression-free survival (PFS) was 15.4 months. The overall survival in the patients who used gemcitabine-based reagents was 19.1 months and that of those who used TS-1 was 28.7 months. The PFS for these two groups were 13.2 months and 26.4 months; the difference is significant. CONCLUSIONS: Our study suggests that IRE is safe and effective for the control of LAPC. We surmise that the addition of IRE to a chemotherapy regimen may provide a survival advantage.

Low-level clonal FGFR2 amplification defines a unique molecular subtype of intrahepatic cholangiocarcinoma in a Chinese population.

Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer rarely curable by surgery that is increasing rapidly in incidence. Chromosomal translocations and amplifications of the fibroblast growth factor receptor 2 (FGFR2) locus are present in several kinds of tumors including ICC, but their incidence has not been assessed in Chinese patients. Using break-apart probes and by determining the ratios of FGFR2/chromosome enumeration probe (CEP) 10 double-color probes, we evaluated 122 ICCs for the presence of FGFR2 translocations and amplifications, respectively, by fluorescence in situ hybridization. We further determined FGFR2 protein expression by immunohistochemistry and analyzed the clinicopathologic records of the patients. Eight tumors (6.6%) had FGFR2 translocations, whereas 15 (12.3%) had low-level FGFR2 amplification. Interestingly, the tumors that showed both translocation and low-level amplification frequently were of the mass-forming type. Compared with the ICCs with normal FGFR2s, tumors with amplifications secreted less mucus (P = .017) and typically were accompanied by hepatitis B virus infection (P = .004). Tumors with low-level amplification generally were of lower stage (P = .013) and associated with better overall survival (P = .017). As tumors with FGFR2 amplification exhibit different biology from lesions with a normal gene, low-level amplification of FGFR2 may play an important role in tumor progression and may be a marker for targeted therapy.

Reduced triglyceride accumulation due to overactivation of farnesoid X receptor signaling contributes to impaired liver regeneration following 50% hepatectomy in extra­cholestatic liver tissue.

The aim of the present study was to investigate the role of triglyceride metabolism in the effect of obstructive cholestasis on liver regeneration following 50% partial hepatectomy (PH). Obstructive cholestatic rat models were achieved via ligation of the common bile duct (BDL). Following comparisons between hepatic pathological alterations with patients with perihilar cholangiocarcinoma, rats in the 7 day post­BDL group were selected as the BDL model for subsequent experiments. Liver weight restoration, proliferating cell nuclear antigen labeling index, cytokine and growth factor expression levels, and hepatic triglyceride content were evaluated to analyze liver regeneration post­PH within BDL and control group rats. The results of the present study revealed that obstructive cholestasis impaired liver mass restoration, which occurred via inhibition of early stage hepatocyte proliferation. In addition, reduced triglyceride content and inhibited expression of fatty acid ß­oxidation­associated genes, peroxisome proliferator activated receptor α and carnitine palmitoyltransferase, were associated with an insufficient energy supply within the BDL group post­PH. Notably, the expression levels of fatty acid synthesis­associated genes, including sterol­regulatory element­binding protein­1c, acetyl­coA carboxylase 1 and fatty acid synthase were also reduced within the BDL group, which accounted for the reduced triglyceride content and fatty acid utilization. Further investigation revealed that overactivated farnesoid X receptor (FXR) signaling may inhibit fatty acid synthesis within BDL group rats. Collectively, the role of triglycerides in liver regeneration following PH in extra­cholestatic livers was identified in the present study. Additionally, the results indicated that overactivated FXR signaling­induced triglyceride reduction is associated with insufficient energy supply and therefore contributes to the extent of impairment of liver regeneration following PH within extra­cholestatic livers.

Strategies for Bispecific Single Chain Antibody in Cancer Immunotherapy.

Genetic engineering has resulted in more than 50 recombinant bispecific antibody formats over the past two decades. Bispecific scFv antibodies represent a successful and promising immunotherapy platform that retargets cytotoxic T cells to tumor cells, with one scFv directed to tumor-associated antigens and the other to T cells. Based on this antibody construct, strategies for both specific tumor targeting and T cell activation are reviewed here. Three distinct types of tumor antigens are considered to optimize specificity and safety in bispecific scFv based treatment: cancer-testis antigens, neo-antigens and virus-associated antigens. In terms of T cell activation, although CD3 has been widely applied in bispecific scFvs being developed, CD28 and CD137 among co-stimulatory signals are also ideal candidates to be evaluated. Besides, LIGHT and HIV-Tat101 have drawn much attention as their potential roles in modulating antitumor responses.

Clinicopathological, radiologic, and molecular study of 23 combined hepatocellular-cholangiocarcinomas with stem cell features, cholangiolocellular type.

Cholangiolocellular carcinoma is a type of intrahepatic cholangiocarcinoma (ICC). According to the 2010 World Health Organization classification, this carcinoma is a combined hepatocellular-cholangiocarcinoma with stem cell features, cholangiolocellular type (CHC-SC-CLC). The aim of this study was to compare the clinicopathological characteristics of CHC-SC-CLC and conventional ICC. Based on the gross and histologic characteristics, we divided consecutive ICC tumors into CHC-SC-CLC (n = 23), mass-forming (MF; n = 57), and non-MF (n = 22) groups. Compared with MF and non-MF groups, the CHC-SC-CLC group featured history of hepatolithiasis or bile duct operation in significantly fewer patients (4.3% versus 14.8% and 86.4%, respectively; P < .001) and was more common in the right lobe (70% versus 47% and 27%; P = .033) but lower frequency of invasive growth or peritumoral Glisson sheath invasion (61% and 22% versus 77% and 33% and 100% and 86%, respectively; P = .002 and P < .001) and absence of mucous production (0 versus 77% and 96%; P < .001). In CHC-SC-CLCs, the mutation rate of isocitrate dehydrogenase 1 (IDH1) or IDH2 was significantly higher (35%) than in MF (4%) or non-MF (0) ICCs (P < .001). The 1-, 3-, and 5-year postresection survival rates were also significantly better with CHC-SC-CLCs (93%, 79%, and 52%, respectively) than with MF (72%, 46%, and 40%) or non-MF (61%, 18%, and 0) ICCs (P = .041). Thus, CHC-SC-CLC tumors demonstrated an indolent growth pattern, more frequent IDH1/2 gene mutations, and better prognosis than did MF or non-MF ICC tumors.

Contribution of contrast-enhanced sonography in the detection of intrahepatic cholangiocarcinoma.

OBJECTIVES: The purpose of this study was to evaluate the contribution of contrast-enhanced sonography in the diagnosis of intrahepatic cholangiocarcinoma up to 3 cm and analyze its dynamic enhancement patterns. METHODS: Forty-five patients (29 male and 16 female; mean age ± SD, 61.3 ± 10.7 years; range, 38-79 years) with a preliminary diagnosis of intrahepatic cholangiocarcinoma by contrast-enhanced sonography were retrospectively analyzed. For each nodule, the enhancement pattern, level, and dynamic change during the arterial, portal, and late phases after the injection of a sulfur hexafluoride microbubble contrast agent were evaluated. RESULTS: Among the 35 patients with a histopathologic diagnosis of intrahepatic cholangiocarcinoma, 18 nodules showed hyperenhancement during the arterial phase, and 17 showed hypoenhancement. Heterogeneous, peripheral, and partial enhancement were found in 24, 8, and 2 nodules, respectively. However, only 1 nodule showed homogeneous enhancement. During the portal phase, 34 nodules showed hypoenhancement, and 1 showed isoenhancement. Hypoenhancement during the late phase was observed in all cases. Ten patients had a misdiagnosis of intrahepatic cholangiocarcinoma. CONCLUSIONS: Intrahepatic cholangiocarcinoma up to 3 cm may display a variety of arterial enhancement patterns on contrast-enhanced sonography. However, some other nodules may manifest findings similar to those of intrahepatic cholangiocarcinoma.

Effect of early enteral combined with parenteral nutrition in patients undergoing pancreaticoduodenectomy.

AIM: To investigate the effect of early enteral nutrition (EEN) combined with parenteral nutritional support in patients undergoing pancreaticoduodenectomy (PD). METHODS: From January 2006, all patients were given EEN combined with parenteral nutrition (PN) (EEN/PN group, n = 107), while patients prior to this date were given total parenteral nutrition (TPN) (TPN group, n = 67). Venous blood samples were obtained for a nutrition-associated assessment and liver function tests on the day before surgery and 6 d after surgery. The assessment of clinical outcome was based on postoperative complications. Follow-up for infectious and noninfectious complications was carried out for 30 d after hospital discharge. Readmission within 30 d after discharge was also recorded. RESULTS: Compared with the TPN group, a significant decrease in prealbumin (PAB) (P = 0.023) was seen in the EEN/PN group. Total bilirubin (TB), direct bilirubin (DB) and lactate dehydrogenase (LDH) were significantly decreased on day 6 in the EEN/PN group (P = 0.006, 0.004 and 0.032, respectively). The rate of grade I complications, grade II complications and the length of postoperative hospital stay in the EEN/PN group were significantly decreased (P = 0.036, 0.028 and 0.021, respectively), and no hospital mortality was observed in our study. Compared with the TPN group (58.2%), the rate of infectious complications in the EEN/PN group (39.3%) was significantly decreased (P = 0.042). Eleven cases of delayed gastric emptying were noted in the TPN group, and 6 cases in the EEN/PN group. The rate of delayed gastric emptying and hyperglycemia was significantly reduced in the EEN/PN group (P = 0.031 and P = 0.040, respectively). CONCLUSION: Early enteral combined with PN can greatly improve liver function, reduce infectious complications and delayed gastric emptying, and shorten postoperative hospital stay in patients undergoing PD.

Liver-protecting effects of omega-3 fish oil lipid emulsion in liver transplantation.

AIM: To investigate the liver-protecting effect of parenteral nutrition (PN) support with omega-3 fatty acids in a randomized controlled clinical trial. METHODS: Sixty-six patients with the diagnosis of end-stage liver disease or hepatic cellular carcinoma were admitted to the Affiliated Drum Tower Hospital, Nanjing University, China for orthotopic liver transplantation. The patients were randomly divided into two groups: PN group (n = 33) and polyunsaturated fatty acid (PUFA) group (n = 33). All patients received isocaloric and isonitrogenous PN for seven days after surgery, and in PUFA group omega-3 fish oil lipid emulsion replaced part of the standard lipid emulsion. Liver function was tested on days 2 and 9 after surgery. Pathological examination was performed after reperfusion of the donor liver and on day 9. Clinical outcome was assessed based on the post-transplant investigations, including: (1) post-transplant mechanical ventilation; (2) total hospital stay; (3) infectious morbidities; (4) acute and chronic rejection; and (5) mortality (intensive care unit mortality, hospital mortality, 28-d mortality, and survival at a one-year post-transplant surveillance period). RESULTS: On days 2 and 9 after operation, a significant decrease of alanine aminotransferase (299.16 U/L ± 189.17 U/L vs 246.16 U/L ± 175.21 U/L, P = 0.024) and prothrombin time (5.64 s ± 2.06 s vs 2.54 s ± 1.15 s, P = 0.035) was seen in PUFA group compared with PN group. The pathological results showed that omega-3 fatty acid supplement improved the injury of hepatic cells. Compared with PN group, there was a significant decrease of post-transplant hospital stay in PUFA group (18.7 d ± 4.0 d vs 20.6 d ± 4.6 d, P = 0.041). Complications of infection occurred in 6 cases of PN group (2 cases of pneumonia, 3 cases of intra-abdominal abscess and 1 case of urinary tract infection), and in 3 cases of PUFA group (2 cases of pneumonia and 1 case of intra-abdominal abscess). No acute or chronic rejection and hospital mortality were found in both groups. The one-year mortality in PN group was 9.1% (3/33), one died of pulmonary infection, one died of severe intra-hepatic cholangitis and hepatic dysfunction and the other died of hepatic cell carcinoma recurrence. Only one patient in PUFA group (1/33, 3.1%) died of biliary complication and hepatic dysfunction during follow-up. CONCLUSION: Post-transplant parenteral nutritional support combined with omega-3 fatty acids can significantly improve the liver injury, reduce the infectious morbidities, and shorten the post-transplant hospital stay.

Omega-3 polyunsaturated fatty acids promote liver regeneration after 90% hepatectomy in rats.

AIM: To evaluate the effectiveness of omega-3 polyunsaturated fatty acid (ω-3 PUFA) administration on liver regeneration after 90% partial hepatectomy (PH) in rats. METHODS: ω-3 PUFAs were intravenously injected in the ω-3 PUFA group before PH surgery. PH, sparing only the caudate lobe, was performed in both the control and the ω-3 PUFA group. Survival rates, liver weight/body weight ratios, liver weights, HE staining, transmission electron microscope imaging, nuclear-associated antigen Ki-67, enzyme-linked immunosorbent assay and signal transduction were evaluated to analyze liver regeneration. RESULTS: All rats in the control group died within 30 h after hepatectomy. Survival rates in the ω-3 PUFA group were 20/20 at 30 h and 4/20 1 wk after PH. Liver weight/body weight ratios and liver weights increased significantly in the ω-3 PUFA group. The structure of sinusoidal endothelial cells and space of Disse was greatly restored in the ω-3 PUFA group compared to the control group after PH. In the ω-3 PUFA group, interleukin (IL)-4 and IL-10 levels were significantly increased whereas IL-6 and tumor necrosis factor-α levels were dramatically decreased. In addition, activation of protein kinase B (Akt) and of signal transducer and activator of transcription 3 signaling pathway were identified at an earlier time after PH in the ω-3 PUFA group. CONCLUSION: Omega-3 polyunsaturated fatty acids may prevent acute liver failure and promote liver regeneration after 90% hepatectomy in rats.