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.

The response of Golgi protein 73 to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma may relate to the influence of certain chemotherapeutics.

BACKGROUND: Golgi protein 73 (GP73) is a promising biomarker of hepatocellular carcinoma (HCC). It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoembolization (TACE) have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients after TACE treatment, and the possible underlying mechanisms in the cell cultures. METHODS: Blood samples were collected from 72 HCC patients, before TACE, at day 1 and day 30 after TACE. GP73 levels were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents (5-FU and pirarubicin) on GP73 expression were tested in three HCC cell lines (HepG2, HCCLM3 and MHCC97H). RESULTS: The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure (P<0.05). There was no statistical difference between the two time points after TACE, nor correlation between GP73 levels and clinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, significantly increased GP73 expression in three cell lines. CONCLUSIONS: Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.

Development and validation of web-based nomograms for predicting survival status in patients with intrahepatic cholangiocarcinoma depending on the surgical status: a SEER database analysis.

This study aimed to develop and validate prognostic nomograms that can estimate the probability of 1-, 3- and 5-year overall survival (OS) as well as cancer-specific survival (CSS) for Intrahepatic cholangiocarcinoma (ICCA) patients. Clinical data of 1446 patients diagnosed with ICCA between 2010 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. In both the OS and the CSS group, the training cohort and validation cohort were divided into a 7:3 ratio. Age, sex, AJCC T stage, AJCC N stage, AJCC M stage, surgical status, and tumor grade were selected as independent prognostic risk factors to build the nomograms. To compare the efficacy of predicting 1-, 3-, and 5-year OS and CSS rates of the nomogram with the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, we evaluated the Harrell's index of concordance (C-index), area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) in both cohorts. The results showed the nomogram for 1-, 3-, and 5-year OS and CSS prediction performed better than the AJCC staging system. In the subgroup analysis for patients could not receive surgery as the primary treatment. We developed two nomograms for predicting the 1-, and 2-year OS and CSS rates following the same analysis procedure. Results indicate that the performance of both nomograms, which contained sex, AJCC T stage, AJCC M stage, chemotherapy, and tumor grade and prognostic factors, was also superior to the AJCC staging system. Meanwhile, four dynamic network-based nomograms were published. The survival analysis showed the survival rate of patients classified as high-risk based on the nomogram score was significantly lower compared to those categorized as low-risk (P < 0.0001). Finally, accurate and convenient nomograms were established to assist clinicians in making more personalized prognosis predictions for ICCA patients.

Worldwide research trends on tumor burden and immunotherapy: a bibliometric analysis.

Various immunotherapy has been greatly applied to comprehensive treatment of malignant cancer under different degrees of tumor burden. Scientific researchers have gained considerable progress in the relationship between immunotherapy and tumor burden in recent years. This review aimed to explore the prospect and developing trends in the field of tumor burden and immunotherapy from a bibliometric perspective. Articles about tumor burden and immunotherapy were collected from the Web of Science Core Collection (WoSCC) (retrieved on 3 January 2023). The R package 'Bibliometrix' analyzed the primary bibliometric features and created a three-filed plot to display the relationship between institutions, countries, and keywords. VOSviewer was used for co-authorship analysis, co-occurrence analysis, and their visualization. And CiteSpace calculated the citation burst references and keywords. A total of 1030 publications were retrieved from 35 years of scientific researches. The United States (US) and China published the most articles. The most productive journals were Cancer Immunology Immunotherapy and Journal for ImmunoTherapy of Cancer . The top one institution of the highest output was University of Texas MD Anderson Cancer Center. The hot keywords of strong citation burst strength in recent years were 'nivolumab', 'tumor microenvironment', and 'immune checkpoint inhibitor'. The most popular tumor type is melanoma. This bibliometric analysis mapped a basic knowledge structure. The field of tumor burden and immunotherapy is entering a rapid growing stage and keeping it value for future research.

Primary gastrinoma of the gallbladder: a case report and review of the literature.

Background: Primary gallbladder gastrinoma is an exceptionally uncommon tumor and is a rare form of neuroendocrine neoplasm. Until now, no cases of primary gallbladder gastrinoma and rare cases of primary gastrinoma from the biliary system have been reported. Case presentation: We report a case of a 50-year-old woman with watery diarrhea who intermittently received proton pump inhibitors (PPIs) as treatment. A serum gastrin level of 711 pg/ml was recorded after the withdrawal of PPI over 1 week. Enhanced computed tomography (CT) imaging and octreotide imaging uncovered a solitary tumor at the hepatic hilar region. During the laparoscopic surgery, it was determined that the tumor had its origin in the wall of the gallbladder neck, prompting the implementation of a laparoscopic cholecystectomy. Histological analysis revealed a primary neuroendocrine tumor from the neck of the gallbladder. The patient's symptoms disappeared after the surgery with a follow-up of 6 months. Conclusions: This case confirmed that primary gallbladder gastrinoma represents a distinct nosological entity. Immunohistochemical analysis plays a pivotal role in the diagnostic process. Given the limited understanding of primary gallbladder gastrinoma, our objective is to offer novel insights into this rare disease by delivering distinctive information and highlighting the therapeutic significance of surgical intervention.

Worldwide productivity and research trend of publications concerning tumor immune microenvironment (TIME): a bibliometric study.

BACKGROUND: As the complexity and diversity of the tumor immune microenvironment (TIME) are becoming better understood, burgeoning research has progressed in this field. However, there is a scarcity of literature specifically focused on the bibliometric analysis of this topic. This study sought to investigate the development pattern of TIME-related research from 2006 to September 14, 2022, from a bibliometric perspective. METHODS: We acquired both articles and reviews related to TIME from the Web of Science Core Collection (WoSCC) (retrieved on September 14, 2022). R package "Bibliometrix" was used to calculate the basic bibliometric features, present the collaborative conditions of countries and authors, and generate a three-field plot to show the relationships among authors, affiliations, and keywords. VOSviewer was utilized for co-authorship analysis of country and institution and keyword co-occurrence analysis. CiteSpace was used for citation burst analysis of keywords and cited references. In addition, Microsoft Office Excel 2019 was used to develop an exponential model to fit the cumulative publication numbers. RESULTS: A total of 2545 publications on TIME were included, and the annual publication trend exhibited a significant increase over time. China and Fudan University were the most productive country and institution, with the highest number of publications of 1495 and 396, respectively. Frontiers in Oncology held the highest number of publications. A number of authors were recognized as the main contributors in this field. The clustering analysis revealed six clusters of keywords that highlighted the research hot spots in the fields of basic medical research, immunotherapy, and various cancer types separately. CONCLUSIONS: This research analyzed 16 years of TIME-related research and sketched out a basic knowledge framework that includes publications, countries, journals, authors, institutions, and keywords. The finding revealed that the current research hot spots of the TIME domain lie in "TIME and cancer prognosis", "cancer immunotherapy", and "immune checkpoint". Our researchers identified the following areas: "immune checkpoint-based immunotherapy", "precise immunotherapy" and "immunocyte pattern", which may emerge as frontiers and focal points in the upcoming years, offering valuable avenues for further exploration.

Pancreatic ductal adenocarcinoma with synchronous and metachronous hepatic metastasis predicted by contrast-enhanced ultrasound.

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

Systems biology approach reveals a common molecular basis for COVID-19 and non-alcoholic fatty liver disease (NAFLD).

BACKGROUND: Patients with non-alcoholic fatty liver disease (NAFLD) may be more susceptible to coronavirus disease 2019 (COVID-19) and even more likely to suffer from severe COVID-19. Whether there is a common molecular pathological basis for COVID-19 and NAFLD remains to be identified. The present study aimed to elucidate the transcriptional alterations shared by COVID-19 and NAFLD and to identify potential compounds targeting both diseases. METHODS: Differentially expressed genes (DEGs) for COVID-19 and NAFLD were extracted from the GSE147507 and GSE89632 datasets, and common DEGs were identified using the Venn diagram. Subsequently, we constructed a protein-protein interaction (PPI) network based on the common DEGs and extracted hub genes. Then, we performed gene ontology (GO) and pathway analysis of common DEGs. In addition, transcription factors (TFs) and miRNAs regulatory networks were constructed, and drug candidates were identified. RESULTS: We identified a total of 62 common DEGs for COVID-19 and NAFLD. The 10 hub genes extracted based on the PPI network were IL6, IL1B, PTGS2, JUN, FOS, ATF3, SOCS3, CSF3, NFKB2, and HBEGF. In addition, we also constructed TFs-DEGs, miRNAs-DEGs, and protein-drug interaction networks, demonstrating the complex regulatory relationships of common DEGs. CONCLUSION: We successfully extracted 10 hub genes that could be used as novel therapeutic targets for COVID-19 and NAFLD. In addition, based on common DEGs, we propose some potential drugs that may benefit patients with COVID-19 and NAFLD.

Immune-related adverse events: A bibliometric analysis.

Background: Despite providing clinical benefit, immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in a number of patients. This study explored the development pattern in irAEs research from a bibliometric perspective. Methods: We obtained articles and reviews related to irAEs from the Web of Science Core Collection (WoSCC) (retrieved on September 13, 2022). Using the R package "Bibliometrix", the main bibliometric features were calculated, and a three-filed plot was generated to show the relationship between authors, institutions, and topics. VOSviewer was used for co-authorship and keyword co-occurrence analysis and visualization. CiteSpace was used to detect burst references and keywords. Results: A total of 3995 publications on irAEs were included. The United States (US), Japan, and China had the highest publications. The Journal for ImmunoTherapy of Cancer had the highest number of publications. In addition to "immune-related adverse events", "immune checkpoint inhibitors", "immunotherapy", and "nivolumab" were the most frequently used keywords. Conclusions: A bibliometric analysis of 17 years of irAEs research was conducted to map a basic knowledge structure including countries, institutions, authors, journals, and publications. The findings provided a comprehensive perspective on the broad future of this research area.

Age, gender, geographic and clinical differences for gallstones in China: a nationwide study.

Background: The etiology of gallstones at different anatomical locations may be varied. However, it has not been well studied about the prevalence of gallstones by anatomical locations and their associated factors in China. Methods: We used the data set from preventive health screening centers covering all provinces in mainland China except for Tibet, and a total of 10,937,993 adults were included, who received abdominal ultrasonography in 2017. We analyzed the prevalence of gallstones classified by anatomical locations, including gallbladder (GB) stones, intrahepatic bile duct (IHD) stones, and extrahepatic bile duct (EHD) stones. Further, their associated factors were investigated using a logistic regression model with body mass index (BMI), fasting glucose, total triglyceride, and previous cholecystectomy, with covariates of age and sex. Results: The age- and gender-standardized prevalence (AGS-prevalence) of gallstone diseases was 5.13% (95% CI: 5.11-5.14%). GB, IHD, and EHD stones accounted for 76.3%, 24.3%, and 0.2% of all gallstone cases (concomitant cases were present). GB, IHD, and EHD gallstones presented different patterns by the age, gender, geographic and metabolic factors. Overall, the age-standardized prevalence was higher in women than that in men (5.41% vs. 4.85%, P<0.001). The gender standardized prevalence of all gallstone subtypes apparently increased with age (P<0.001), especially for GB stones from 1.05% (age 18-30) to 11.6% (age ≥70) (P<0.001). There was a marked geographic variation with AGS-prevalence ranging from 3.00% to 8.86% among different provinces. Noticeably, higher BMI, fasting glucose level, or total triglyceride level was associated with a higher prevalence of overall gallstones and GB stones (OR >1), but associated with a lower prevalence of IHD and EHD stones. Conclusions: The prevalence of gallstones in China largely varied in its anatomical location, demographic factors, geographic location, and metabolic factors, suggesting that the etiology of each subtype may be different. Further investigation should be conducted.

[Diagnosis and treatment of primary hepatic angiosarcoma: a report of 7 cases with a literature review].

OBJECTIVE: To explore the clinical features, diagnosis, treatment and prognosis of primary hepatic angiosarcoma (PHA). METHODS: The clinical data of 7 PHA patients admitted to our hospital from December 2004 to December 2010 were retrospectively analyzed and the relevant literatures reviewed. RESULTS: Seven cases (5 males and 2 females) were diagnosed as PHA among 1027 (0.68%) patients with primary hepatic malignant tumors. Their mean age was 43.3 years old (range: 33 - 74). Four cases were of solitary lesion and three of multiple lesions. No specific clinical features were observed. The PHA lesions were easily misdiagnosed as benign or hepatic metastatic tumors. Contrast enhanced ultrasound (CEUS) showed the lesions with characteristic manifestations. And the positron emission tomography (PET-CT) could confirm the hepatic lesions as malignant tumors. The survival time for two untreated cases was 3 & 5 months, for two cases with liver transplantation (LTx) 3 & 8 months and for two cases treated with surgical resection & targeted therapy was 14 & 19 months respectively. One case was lost to follow-up at 6 months after hepatic resection. CONCLUSION: PHA is a clinically rare and highly malignant tumor with a rapid progression and a poor prognosis. Both CEUS and PET-CT are helpful for its differential and confirmative diagnosis. LTx should be considered as a contraindication for PHA. Hepatic resection has proven to be beneficial for PHA patients with solitary lesion. Surgical resection plus targeted medicines may improve their survival.

Molecular subtypes based on immune-related genes predict the prognosis for hepatocellular carcinoma patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignancy exhibiting the highest lethality. The present study aimed to identify different immune-related clusters in HCC and a robust tumor gene signature to facilitate the prognosis prediction for HCC patients. METHODS: For the 375 HCC cases collected from the dataset of Cancer Genome Atlas (TCGA), their overall survival (OS) and immune-related genes (IRGs) expression patterns were collected. Thereafter, consensus clustering was employed for grouping and functional enrichment, whereas the ESTIMATE algorithm and the CIBERSORT algorithm were used in subsequent assessment. Immunohistochemistry (IHC) was conducted to verify the protein expression of model genes in HCC and adjacent tissues. RESULTS: According to consensus clustering with 93-survival related IRGs, a total of five subgroups were found. These five clusters had different prognoses, immune statuses, and expression of immune checkpoints. Afterwards, 11 genes were enrolled for constructing the OS-related prediction model for TCGA HCC cases, which was then validated using the database of International Cancer Genome Consortium (ICGC). The protein expression of LCN2, S100A10, FABP6, PLXNA1, KITLG and OXTR were enhanced in HCC tissues relative to that in normal hepatic tissues, while the protein expression of S100A1, CCL26, CMTM4, IL1RN and RARG were reduced in HCC compared with normal tissues. In addition, different immunocyte infiltration levels between low- and high- groups were further examined. CONCLUSIONS: According to our results, the IRGs-based classifications assist in explaining the HCC heterogeneity, which may help to develop the more efficient individualized treatments.

[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.

Construction of a lipid metabolism-related and immune-associated prognostic signature for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. We aimed to identify a robust lipid metabolism-related signature associated with the HCC microenvironment to improve the prognostic prediction of HCC patients. METHODS: We analyzed the gene expression profiles of lipid metabolism from Molecular Signatures Database and information of patients from The Cancer Genome Atlas. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and principal component analysis (PCA) were employed for functional annotation. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to verify the expression of model genes in HCC and adjacent tissues. RESULTS: As a result, a lipid metabolism-related signature consisting of acyl-CoA synthetase long-chain family member 6 (ACSL6), lysophosphatidylcholine acyltransferase 1, phospholipase A2 group 1B, lecithin-cholesterol acyltransferase (LCAT), and sphingomyelin phosphodiesterase 4 (SMPD4) was identified among HCC patients. Lysophosphatidylcholine acyltransferase 1, PLA2G1B, and SMPD4 were proved significantly high expression while ACSL6 and LCAT were remarkably low expression in our 15 pairs of matched HCC and normal tissues by qRT-PCR. Under different conditions, the overall survival (OS) of patients in low-risk group was prolonged than that in high-risk group. Moreover, the as-constructed signature was an independent factor, which was remarkably associated with gender, histologic grade, and platelet level of HCC patients. In addition, the receiver operating characteristic (ROC) curve analysis confirmed the good potency of the model. Functional enrichment analysis further revealed that lower fatty acid (FA) oxidation and higher infiltration of immunocytes were detected in patients from the high-risk group compared with those in the low-risk group. CONCLUSIONS: Our findings indicate that the lipid metabolism-related signature shows prognostic significance for HCC.

Development and Verification of the Hypoxia-Related and Immune-Associated Prognosis Signature for Hepatocellular Carcinoma.

BACKGROUND: It has been widely suggested that the association of hypoxia with the immune status within the microenvironment of hepatocellular carcinoma (HCC) is of great clinical significance. The present work was carried out aiming to establish the hypoxia-related and immune-associated gene signature to stratify the risks in HCC. PATIENTS AND METHODS: The ssGSEA and t-SNE algorithms were utilized to estimate the immune and hypoxia statuses, respectively, using the TCGA database-derived cohort transcriptome profiles. Different immune groups are distinguished according to the ssGSEA scores, while the hypoxia-high and -low groups are inferred based on the distinct overall survival (OS) of the two groups of patients. Moreover, prognostic genes were identified using the Cox regression model in combination with the LASSO approach, which were later used to establish the hypoxia-related and immune-associated gene signature. At the same time, an ICGC cohort was used for external validation. RESULTS: A total of 13 genes, namely, HAVCR1, PSRC1, CCNJL, PDSS1, MEX3A, EID3, EPO, PLOD2, KPNA2, CDCA8, ADAMTS5, SLC1A7 and PIGZ, were discovered by the LASSO approach for constructing a gene signature to stratify the risk of HCC. Those low-risk cases showed superior prognosis (OS) to the high-risk counterparts (p<0.05). Moreover, it was suggested by multivariate analysis that our constructed hypoxia-related and immune-associated prognosis signature might be used as the independent factor for prognosis prediction (p<0.001). Patients in high-risk groups had severe hypoxia, higher immune checkpoint expression such as PD-L1, and different immunocyte infiltration states (eg, higher infiltration of regulatory T cells in the high-risk group) compared with those low-risk patients. CONCLUSION: Our as-constructed hypoxia-related and immune-associated prognosis signature can be used as an approach to stratify the risk of HCC.