Ultrasound-Guided Continuous Thoracic Paravertebral Block Improves Patient's Quality of Recovery After Open Hepatectomy: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background Ultrasound-guided continuous thoracic paravertebral block can provide pain-relieving and opioid-sparing effects in patients receiving open hepatectomy. We hypothesize that these effects may improve the quality of recovery (QoR) after open hepatectomy. Methods Seventy-six patients undergoing open hepatectomy were randomized to receive a continuous thoracic paravertebral block with ropivacaine (CTPVB group) or normal saline (control group). All patients received patient-controlled intravenous analgesia with morphine postoperatively for 48 hours. The primary outcome was the global Chinese 15-item Quality of Recovery score on postoperative day 7, which was statistically analyzed using Student's t-test. Results Thirty-six patients in the CTPVB group and 37 in the control group completed the study. Compared to the control group, the CTPVB group had significantly increased global Chinese 15-item Quality of Recovery scores (133.14 ± 12.97 vs. 122.62 ± 14.89, P = 0.002) on postoperative day 7. Postoperative pain scores and cumulative morphine consumption were significantly lower for up to 8 and 48 hours (P < 0.05; P = 0.002), respectively, in the CTPVB group. Conclusion Perioperative CTPVB markably promotes patient's QoR after open hepatectomy with a profound analgesic effect in the early postoperative period.

Somatostatin Treatment for Ectopic ACTH Syndrome due to Pancreatic Neuroendocrine Tumors: Review of the Literature.

Objectives: To analyze and summarize the effect of SSA treatment on EAS due to p-NETs (EAS-p-NETs). Methods: Thirteen patients with EAS-p-NETs treated with SSAs at our center or described in the literature were included in this study. Clinical characteristics, laboratory data, imaging studies, histopathologic results, the effect of SSA treatment, and the prognosis of these EAS-p-NET patients were evaluated. Results: Four males and 9 females with an average age of 42.9 years were included in the study. The mean duration of follow-up was 38.8 ± 28.2 months. As one of the combined treatment measures, SSAs controlled the levels of ACTH and cortisol in 9 of the 13 patients (69.2%). Partial response was observed in 3 patients (23.1%), stable disease in 2 patients (15.4%), and progressive disease in 6 patients (46.2%). The median time to tumor progression was 24 months, and the median overall survival was 61 months. The side effects of SSA treatment included temporary mild abdominal pain, diarrhea, gallstones, and cholecystitis. Conclusions: As a supplemental therapy, SSA treatment led to clinical and biochemical improvement with a good safety profile in patients exhibiting EAS-p-NET with metastasis. However, tumor progression was inhibited by SSA treatment in only a few patients. Combined with other treatments, SSAs may improve the prognosis of patients with EAS-p-NETs.

γ-glutamyl transferase-to-platelet ratio based nomogram predicting overall survival of gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma (GBC) carries a poor prognosis and requires a prediction method. Gamma-glutamyl transferase-to-platelet ratio (GPR) is a recently reported cancer prognostic factor. Although the mechanism for the relationship between GPR and poor cancer prognosis remains unclear, studies have demonstrated the clinical effect of both gamma-glutamyl transferase and platelet count on GBC and related gallbladder diseases. AIM: To assess the prognostic value of GPR and to design a prognostic nomogram for GBC. METHODS: The analysis involved 130 GBC patients who underwent surgery at Peking Union Medical College Hospital from December 2003 to April 2017. The patients were stratified into a high- or low-GPR group. The predictive ability of GPR was evaluated by Kaplan-Meier analysis and a Cox regression model. We developed a nomogram based on GPR, which we verified using calibration curves. The nomogram and other prognosis prediction models were compared using time-dependent receiver operating characteristic curves and the concordance index. RESULTS: Patients in the high-GPR group had a higher risk of jaundice, were older, and had higher carbohydrate antigen 19-9 levels and worse postoperative outcomes. Univariate analysis revealed that GPR, age, body mass index, tumor-node-metastasis (TNM) stage, jaundice, cancer cell differentiation degree, and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were related to overall survival (OS). Multivariate analysis confirmed that GPR, body mass index, age, and TNM stage were independent predictors of poor OS. Calibration curves were highly consistent with actual observations. Comparisons of time-dependent receiver operating characteristic curves and the concordance index showed advantages for the nomogram over TNM staging. CONCLUSION: GPR is an independent predictor of GBC prognosis, and nomogram-integrated GPR is a promising predictive model for OS in GBC.

The emerging roles of non-coding competing endogenous RNA in hepatocellular carcinoma.

Accumulating evidence has emerged revealing that noncoding RNAs (ncRNAs) play essential roles in the occurrence and development of hepatocellular carcinoma (HCC). However, the complicated regulatory interactions among various ncRNAs in the development of HCC are not entirely understood. The newly discovered mechanism of competing endogenous RNAs (ceRNAs) uncovered regulatory interactions among different varieties of RNAs. In recent years, a growing number of studies have suggested that ncRNAs, including long ncRNAs, circular RNAs and pseudogenes, play major roles in the biological functions of the ceRNA network in HCC. These ncRNAs can share microRNA response elements to affect microRNA affinity with target RNAs, thus regulating gene expression at the transcriptional level and both physiological and pathological processes. The ncRNAs that function as ceRNAs are involved in diverse biological processes in HCC cells, such as tumor cell proliferation, epithelial-mesenchymal transition, invasion, metastasis and chemoresistance. Based on these findings, ncRNAs that act as ceRNAs may be promising candidates for clinical diagnosis and treatments. In this review, we discuss the mechanisms and research methods of ceRNA networks. We also reviewed the recent advances in studying the roles of ncRNAs as ceRNAs in HCC and highlight possible directions and possibilities of ceRNAs as diagnostic biomarkers or therapeutic targets. Finally, the limitations, gaps in knowledge and opportunities for future research are also discussed.

Top 100 most frequently cited papers in liver cancer: a bibliometric analysis.

BACKGROUND: Bibliometric analysis has become popular in recent years, and increasingly more articles focusing on a particular disease are being published. The present study was performed to analyse the 100 most frequently cited papers in liver cancer (LC). METHODS: We searched the Thomson Reuters Web of Science database on 14 July 2018 to identify all potential manuscripts for this study. The search terms were 'liver cancer' and its synonyms. Manuscripts were listed in descending order by the total citations (TCs), and the 100 most frequently cited papers were identified and analysed by topic, journal, author, year and institution. RESULTS: We retrieved 235 687 papers from the Web of Science database. The TC of the 100 most frequently cited papers in LC ranged from 612 to 5358. The 100 papers were published in 31 journals and came from nine countries. The University of Barcelona published the highest number of papers and had the most TC. Ten authors published more than one paper. Treatment of LC was the most widely studied topic. A significant correlation was found between the journal's 2017 impact factor and the TC (P = 0.003). CONCLUSION: We assessed the landmark papers in the field of LC. These 100 most frequently cited papers reflect major advances and several hot topics in LC during the recent decades. Our study is of great value for young investigators, provides insights into the trends of LC and can guide directions for future academic research.

Hepatobiliary case report and literature review of hepatic reactive lymphoid hyperplasia with positive anti-smooth muscle antibody and anti-nuclear antibody tests.

Hepatic reactive lymphoid hyperplasia (RLH) is a rare benign tumor of the liver that exhibits similar imaging characteristics to those of other hepatic malignant tumors; therefore, it requires novel biomarkers to be differentiated from the other tumors. A 69-year-old female was found to have a mass in the liver and was admitted to Peking Union Medical College Hospital for further evaluation. Most laboratory tests, including liver function tests, tumor biomarkers, and autoimmune markers were within normal range, except for positive antinuclear antibody and anti-smooth muscle antibody (SMA) tests. Diagnostic imaging, including ultrasonography, computerized tomography and magnetic resonance imaging displayed a small hepatic mass suggestive of hepatocellular carcinoma (HCC). Partial hepatectomy was performed, and histological diagnosis suggested RLH. Postoperative treatments included anti-infection, nutritional enhancement and liver protection. The suspicion of autoimmune hepatitis could not be confirmed. No recurrence or autoimmune disease was observed over 6-month follow-up. Positive anti-nuclear antibody (ANA) and anti-SMA may be potential biomarkers for hepatic RLH.

Safety and efficacy for laparoscopic versus open hepatectomy: A meta-analysis.

BACKGROUND: Laparoscopic hepatectomy (LH) is growing in popularity, but its efficacy and safety are still controversial. Few multicenter, large, population-based, prospective, randomized studies have compared LH with open hepatectomy (OH). We performed a meta-analysis to compare the treatment outcome of patients undergoing LH versus OH. METHODS: We searched PubMed, EMBASE, Cochrane Central Register, CNKI, and WanFang Med Online databases to November 30th, 2016 for randomized controlled trials (RCTs) that compared treatment outcome for LH and OH. Eligibility criteria included evaluation of operation time, blood loss, complications, and hospital stay after surgery for adult patients who underwent LH or OH. Reviewers in pairs independently screened the studies, extracted data and assessed the risk of bias of included studies. Agreement was achieved. RevMan 5.3 was used to conduct meta-analysis. Complete case analysis was used as primary analysis. Predefined subgroup analysis includes benign and malignant disease. RESULTS: Eight RCTs with a total of 554 patients were included in the meta-analysis, 275 types of LH and 279 types of OH. LH reduced the hospital stay after surgery (8 trials, 554 patients, MD = -3.84 days, 95%CI: -5.05 to -2.63, P < 0.0001, I2 = 88%) and the complication rate (8 trials, 554 patients, RR = 0.29, 95%CI: 0.17-0.50, P < 0.0001, I2 = 0%, absolute 13 to 40 fewer), shortened the time to first flatus (3 trials, 264 patients, MD = -1.41 days, 95%CI: -1.98 to -0.83, P < 0.0001, I2 = 92%), and had less blood loss (8 trials, 554 patients, MD = -164.31 ml, 95%CI: -220.91 to -107.72, P < 0.0001, I2 = 98%) without increasing the operation time (MD = -7.96 min, 95%CI: -24.99 to 9.07, P = 0.36, I2 = 91%) compared with OH. CONCLUSIONS: Laparoscopy is more effective in terms of hospital stay after surgery and time to first flatus with fewer blood loss and complication rate for hepatic resection compared with open surgery.

Potential application of neogalactosylalbumin in positron emission tomography evaluation of liver function.

AIM: To investigate the evaluation of neogalactosylalbumin (NGA) for liver function assessment based on positron emission tomography technology. METHODS: Female Kunming mice were assigned randomly to two groups: fibrosis group and normal control group. A murine hepatic fibrosis model was generated by intraperitoneal injection of 10% carbon tetrachloride (CCl4) at 0.4 mL every 48 h for 42 d. 18F-labeled NGA ([18F]FNGA) was synthesized and administered at a dosage of 3.7 MBq/mouse to both fibrosis mice and normal control mice. Distribution of [18F]FNGA amongst organs was examined, and dynamic scanning was performed. Parameters were set up to compare the uptake of tracers by fibrotic liver and healthy liver. Serologic tests for liver function were also performed. RESULTS: The liver function of the fibrosis model mice was significantly impaired by the use of CCl4. In the fibrosis model mice, hepatic fibrosis was verified by naked eye assessment and pathological analysis. [18F]FNGA was found to predominantly accumulate in liver and kidneys in both control group (n = 21) and fibrosis group (n = 23). The liver uptake ability (LUA), peak time (Tp), and uptake rate (LUR) of [18F]FNGA between healthy liver (n = 8) and fibrosis liver (n = 10) were significantly different (P < 0.05, < 0.01, and < 0.05, respectively). LUA was significantly correlated with total serum protein level (TP) (P < 0.05). Tp was significantly correlated with both TP and glucose (Glu) concentration (P < 0.05 both), and LUR was significantly correlated with both total bile acid and Glu concentration (P < 0.01 and < 0.05, respectively). CONCLUSION: [18F]FNGA mainly accumulated in liver and remained for sufficient time. Functionally-impaired liver showed a significant different uptake pattern of [18F]FNGA compared to the controls.

Surgical Treatment Strategies of Intravenous Leiomyomatosis withRight Cardiac Cavities Extension.

Objective To investigate the diagnosis and surgical treatment strategies of intravenous leiomyomatosis(IVL)extending through inferior vena cava into the right cardiac cavities. Methods Thirty patients of IVL extending through inferior vena cava into the right cardiac cavities were treated in Peking Union Medical College Hospital from November 2002 to January 2015.The following variables were studied: age,cardiopulmonary bypass time,deep hypothermic circulatory arrest time,origins of IVL,blood loss,duration of post-operative hospital stay,hospitalization expenses,edema of lower extremity,blood transfusion,postoperative complication,residual IVL,and re-grow or recurrence. Results Thirteen of 30 patients reported double lower limb edema. The cardiopulmonary bypass was applied in 27 cases,and the average duration of cardiopulmonary bypass was(106.9±53.7)min. Then,21 patients were treated with the deep hypothermic circulatory arrest,and the mean time was(28.2±11.6) min. The tumors originated from the genital veins in 9 cases,the iliac vein in 13 cases,and both veins in 8 cases. The average intra-operative blood loss volume was (2060.5±2012.3)ml,and 21 patients received blood transfusion. The average hospitalization time was(18.9±8.3)days and the average hospitalization expenses was (80 840.4±28 264.2)RMB yuan. While 14 patients had postoperative complications,there was no serious postoperative complication or death.All patients have shown a favorable outcome.Conclusions Tumor embolus extending through inferior vena cava into the right cardiac cavities should be suspected in patients with multiple hysteromyoma. Successful therapy for IVL with right cardiac cavities extension is dependent on reasonable surgical treatment strategies. Surgical removal of the ovaries is vital to avoid IVL re-grow or recurrence.

Advances in preoperative assessment of liver function.

BACKGROUND: Postoperative liver failure remains a life-threatening complication. Preoperative evaluation of liver function is essential in reducing the complications after hepatectomy. However, it is difficult to accurately evaluate liver function before surgery because of the limitations of the liver function tests available. Recent advances in liver function tests improved the ability to assess liver function. The present review was to analyze these methods and their advantages. DATA SOURCES: MEDLINE was searched using the terms of "liver function test", "liver function evaluation" and "galactosyl serum albumin". Relevant articles published in English and Chinese from 1961 to 2014 were reviewed. RESULTS: Although serological tests are used frequently in practice, they reflect the degree of total liver damage or function, not the remnant of liver function. Child-Pugh score and model for end-stage liver disease (MELD) score assess whole liver function, and are particularly useful in determining whether patients with hepatocellular carcinoma and cirrhosis are candidates for resection or transplantation, but cannot determine the safe extent or removal. The indocyanine green and other metabolic quantitative liver function tests can evaluate functional hepatocytes, making them more accurate in predicting liver function. Computed tomography (CT) volumetry can provide anatomic information on the remnant liver volume but not on functional volume. 99mTc-galactosyl serum albumin scintigraphy, combined with single photon emission computed tomography, CT and three-dimensional reconstruction, may be a better quantitative measure of liver function, especially of remnant liver function. CONCLUSIONS: Tests used to evaluate liver functional reserve and to predict surgical risk have limitations. 99mTc-galactosyl serum albumin scintigraphy, which can more accurately evaluate the whole and regional liver function, may be promising in predicting resection margins and risks of liver failure.

[Parameter optimization for non-contrast-enhanced selective magnetic resonance portography imaging].

OBJECTIVE: To evaluate subtraction images acquired with 3D true steady-state free-precession(SSFP)sequence combined with time-spatial labeling inversion pulse(T-SLIP)for selective and non-contrast-enhanced(non-CE)visualization of the portal venous system,and explore the optimization of this protocol. METHODS: Totally 13 healthy volunteers were recruited.Respiratory-triggered 3D true SSFP sequences on a 1.5T MRI system combined with T-SLIP placed on the spleen and mesenteric area were performed.The portographic images were generated from the subtraction between the pulse on and off images.According to the difference in inversion time(TI)of T-SLIP,four image groups group A(TI of 1300 ms),group B(TI of 1100 ms),group C(TI of 900 ms)and group D(TI of 700 ms),were assigned and compared to detect the optimal TI for portography.For quantitative analysis,the signal intensity(SI)of left and right liver lobe,the large vessels as main,right and left portal vein(MPV,RPV and LPV,respectively)and small vessels as branches of segments four(P4),six(P6)and eight(P8)were measured.The relative SI of MPV,RPV and LPV,as well as P4,P6 and P8 were also compared.For qualitative evaluation,the quality score of visualization was also evaluated using a 4-point scale.One-Way ANOVA and LSD test were used for comparison of quantitative data,and Friedman signed rank test was used for comparison of qualitative scores. RESULTS: In 52 sequences of 13 volunteers,the selective visualization of the portal vein was all successfully conducted.Quantitative evaluation showed significant increased SI at the left lobe between C and D groups and A and B groups(comparison of group C to group A and BP=0.004,0.011;comparison of group D to group A and BP=0.001,0.004),while relative SI of LPV of groups C and D were lower than groups A and B(comparison of group C to group A and BP=0.015,0.015;comparison of group D to group A and BP=0.000,0.000).The relative SI of MPV in group D were decreased than groups A(P=0.000),B(P=0.000),and C(P=0.019).There was no significant difference in relative SI of small vessels among four groups(P>0.05).The image score of portal vessels in four groups also showed no differences(P>0.05). CONCLUSIONS: 3D true SSFP scan with T-SLIP enabled selective non-CE visualization of the portal vein with digital subtraction method.A fixed TI of both 1300 and 1100 ms can be preferable.

Surgical resection plus biotherapy/chemotherapy improves survival of hepatic metastatic melanoma.

AIM: To analyze the correlation of treatment method with the outcome of all the hepatic metastatic melanoma (HMM) patients from our hospital. METHODS: There were altogether nine cases of HMM that had been treated in the PUMCH hospital during the past 25 years, from December 1984 to February 2010. All of the cases developed hepatic metastasis from primary cutaneous melanoma. A retrospective review was performed on all the cases in order to draw informative conclusion on diagnosis and treatment in correlation with the prognosis. Clinical features including symptoms, signs, blood test results, B-ultrasound and computed tomography (CT) imaging characteristics, and pathological data were analyzed in each case individually. A simple comparison was made on case by case basis instead of performing statistical analysis since the case numbers are low and patients were much diversified in each item that has been analyzed. Literatures on this subject were reviewed in order to draw a safe conclusion and found to be supportive to our finding in a much broad scope. RESULTS: There are six males and three females whose ages ranged 39-74 years old with an average of 58.8. Patients were either with or without symptoms at the time of diagnosis. The liver function and tumor marker exam were normal in all but one patient. The incidence of HMM does not affect liver function and was not related to virus infection status in the liver. Most of these HMM patients were also accompanied by the metastases of other locations, including lung, abdominal cavity, and cervical lymph nodes. Ultrasound examinations showed lesions ranging 2-12 cm in diameter, with no- or low-echo peripheral areola. Doppler showed blood flow appeared inside some tumors as well as in the surrounding area. CT image demonstrated low density without uniformed lesions, characterized with calcification in periphery, and enhanced in the arterial phase. Contrast phase showed heterogeneous enhancement, with a density higher than normal liver tissue, which was especially apparent at the edge. Patients were treated differently with following procedures: patients #1, #6 and #8 were operated with hepatectomy with or without removal of primary lesion, and followed by comprehensive biotherapy/chemotherapy; patient #9 received hepatectomy only; patient #2 received bacille calmette-guerin treatment only; patient #7 had Mile's surgery but no hepatectomy; and patients #3, #4 and #5 had supportive treatment without specific measurement. The patients who had resections of metastatic lesions followed by post-operative comprehensive therapy have an average survival time of 30.7 mo, which is much longer than those did not receive surgery treatment (4.6 mo). Even for the patient receiving a resection of HMM only, the post-operative survival time was 18 mo at the time we reviewed the data. This patient and the patient #6 are still alive currently and subjected to continue following up. CONCLUSION: Surgical operation should be first choice for HMM treatment, and together with biotherapy/chemotherapy, hepatectomy is likely to bring better prognosis.

[A survival analysis of patients with early-stage hepatocellular carcinoma fulfilling Milan criteria and undergoing hepatectomy].

OBJECTIVE: To summarize the experience of hepatectomy in patients with hepatocellular carcinoma fulfilling the Milan criteria and analyze the clinicopathological factors for patient survival and tumor recurrence. METHODS: The clinicopathological data of 104 patients with early-stage hepatocellular carcinoma fulfilling the Milan criteria and underwent hepatectomy at Peking Union Medical College Hospital between April 2003 and June 2009 were retrospectively analyzed. RESULTS: The median follow-up was 24 months. There were 54 recurrent cases. The 1-, 3- and 5-year cumulative disease-free survival rate were 63.0%, 32.6% and 22.4% respectively. Neither univariate analysis nor multivariate analysis indicated any factor significantly correlated with recurrence (P>0.05). The cumulative overall survival rate at 1, 3 and 5 years were 88.8%, 68.1% and 68.1% respectively. Univariate analysis revealed that blood transfusion (P=0.000), involvement of hepatic capsule (P=0.000) and postoperative transarterial chemotherapy (P=0.049) were significantly correlated with survival. And multivariate analysis indicated that blood transfusion (P=0.001) and involvement of hepatic capsule (P=0.000) were independent prognostic factors for survival. CONCLUSION: For the patients with early-stage hepatocellular carcinoma and compensated liver function fulfilling the Milan criteria, hepatectomy serves as the preferred treatment strategy.

[Clinical experiences of surgical manipulations for hepatic masses in difficult sites].

OBJECTIVE: To summarize the surgical experiences, risks, complications, and managements for hepatic masses in difficult sites. METHODS: Totally 47 patients were divided into three groups based on the liver tumor sites: primary porta hepatis group, secondary porta hepatis group, and caudate lobe group. All patients underwent different portion of hepatectomy. RESULTS: The surgery duration was (289.6 +/- 62.2) ml-nutes, intra-operative blood loss was (602.3 +/- 256.4) ml, and intra-operative blood transfusion was (524.0 +/- 325.9) ml. Incidence of surgical complications in each group was 61.5%, 26.9%, and 25%, respectively. Serious complications observed were biliary leakage (27.7%), bleeding (6.4%), and post-operative liver failure (2.1%). Three perioperative deaths were reported: two patients died of bleeding, and one patient died from liver failure. CONCLUSIONS: Dissection of the liver and exposure of major blood vessels and biliary ducts are of critical importance in the surgeries for hepatic masses in difficult sites, and post-operative complications may be remarkably reduced through delicate manipulations of the small intra-hepatic vessels and biliary ducts during resection. A thorough pre-operative evaluation plays a key role in predicting the feasibility and risks of the surgery. Damage to the major blood vessels adjacent to the tumor, in addition to bleeding, may result in in-flow or outflow obstruction and cause necrosis of the corresponding hepatic lobe. Compared with damage to the primary portal area, vascular damage to the secondary porta is generally associated with higher fatality.