Topic Editors

Assistant Professor of Surgery, Department of General Surgery, Sapienza Università di Roma, Rome, Italy
Associate Professor of Surgery, Head of the Laparoscopic and Mini-Invasive Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Università Campus Bio-Medico di Roma, Rome, Italy
Associate Professor of Surgery, Department of Surgical Sciences, HPB and Transplant Unit, University of Rome Tor Vergata, Rome, Italy
Dr. Domenech Asbun
Hepato-Biliary and Pancreas Surgery, Miami Cancer Institute, Miami, FL, USA
Dr. Chiara Mazzarelli
Hepatology and Gastroenterology ASSTGOM Niguarda, Milan, Italy

Hepatobiliary and Pancreatic Diseases: Novel Strategies of Diagnosis and Treatments

Abstract submission deadline
20 April 2024
Manuscript submission deadline
20 July 2024
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27738

Topic Information

Dear Colleagues,

Disease of the liver and pancreas plays a significant role in the clinical, surgical, and research activity of the medical community.

Hepatitis or pancreatitis, even if benign, can put patients at risk of life as well as pose important limitations on their quality of life. Therefore, increasingly advanced medical and/or surgical treatments are required to improve the treatment of these pathologies.

Malignant tumors of the liver and pancreas represent an increasingly growing entity in our society. The incidence of pancreatic cancer has now reached a position in the top ten of the most common cancers in the world. Malignant tumors of the liver and biliary tract, fortunately, still maintain a lower incidence, albeit increasing, and are not among the most frequent malignant tumors in the general population. However, malignant tumors of the liver, biliary tract, and pancreas are gaining significance in terms of annual mortality rates.

The increase in research activity and the subsequent clinical application appears to be the only weapon available to be able to deal with cancers with such devastating results.

We therefore invite all colleagues to send us their most promising medical and surgical research in the field of HPB pathologies to make an important scientific contribution in this field.

Dr. Alessandro Coppola
Dr. Damiano Caputo
Dr. Roberta Angelico
Dr. Domenech Asbun
Dr. Chiara Mazzarelli
Topic Editors

Keywords

  • liver benign disease
  • pancreas benign disease
  • chronic liver disease
  • chronic pancreatitis
  • pancreatitis
  • liver cancer
  • biliary cancer
  • pancreatic cancer
  • liver surgery
  • pancreas surgery

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Cancers
cancers
5.2 7.4 2009 17.9 Days CHF 2900 Submit
Diagnostics
diagnostics
3.6 3.6 2011 20.7 Days CHF 2600 Submit
Journal of Clinical Medicine
jcm
3.9 5.4 2012 17.9 Days CHF 2600 Submit
Current Oncology
curroncol
2.6 2.6 1994 18 Days CHF 2200 Submit
Gastrointestinal Disorders
gastrointestdisord
0.7 1.8 2019 21.3 Days CHF 1200 Submit
Biomedicines
biomedicines
4.7 3.7 2013 15.4 Days CHF 2600 Submit

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Published Papers (21 papers)

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13 pages, 850 KiB  
Article
Interleukin-6 and Lymphocyte-to-Monocyte Ratio Indices Identify Patients with Intrahepatic Cholangiocarcinoma
by Teerachat Saeheng, Juntra Karbwang and Kesara Na-Bangchang
Biomedicines 2024, 12(4), 844; https://doi.org/10.3390/biomedicines12040844 - 11 Apr 2024
Viewed by 316
Abstract
Background and aims: Intrahepatic cholangiocarcinoma (iCCA) is a fatal biliary tract cancer with a dismal prognosis due to ineffective diagnostic tools with limited clinical utility. This study investigated peripheral blood indices and cytokine levels to diagnose iCCA. Methods: Blood samples were collected from [...] Read more.
Background and aims: Intrahepatic cholangiocarcinoma (iCCA) is a fatal biliary tract cancer with a dismal prognosis due to ineffective diagnostic tools with limited clinical utility. This study investigated peripheral blood indices and cytokine levels to diagnose iCCA. Methods: Blood samples were collected from healthy subjects (n = 48) and patients with advanced-stage iCCA (n = 47) during a phase I and then phase II trial, respectively. Serum cytokines were measured using a flow cytometer. The peripheral blood indices were estimated based on laboratory data. Multi-linear regression analysis was applied, followed by a probability transformation. The cut-off value and model accuracy were determined using the receiver operating curve (ROC) and the area under the curve (AUC). Results: The interleukin-6 (IL6) and lymphocyte-to-monocyte ratio (LMR) were potential predictors of iCCA [AUC = 0.91 (0.85–0.97) and 0.81 (0.68–0.93); sensitivity = 0.70 and 0.91; specificity = 0.91 and 0.85, respectively]. Patients with IL6 concentrations higher than 11.635 pg/mL (OR = 23.33, p < 0.001) or LMR lower than 7.2 (OR = 58.08, p < 0.001) are at risk of iCCA development. Patients with IL6 levels higher than 21.83 pg/mL, between 15.95 and 21.83 pg/mL, between 8.8 and 15.94 pg/mL, and lower than 8.8 pg/mL were classified as very high-, high-, intermediate-, and low-risk, respectively. Patients with an LMR between 1 and 3.37, 3.38 and 5.76, 5.77 and 7.18, and higher than 7.18 were classified as very high-, high-, intermediate-, and low-risk, respectively. Conclusions: LMR is recommended for iCCA screening since the estimation is based on a routine laboratory test, which is available in most hospitals. Full article
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8 pages, 705 KiB  
Article
Efficacy of a Novel Tapered Contrast Catheter for Endoscopic Ultrasound-Guided Hepaticogastrostomy: A Multicenter Study
by Fumitaka Niiya, Tatsunori Sato, Junichi Kaneko, Kazuma Ishikawa, Naoki Tamai, Masataka Yamawaki, Jun Noda, Tetsushi Azami, Fumiya Nishimoto, Yuichi Takano and Masatsugu Nagahama
J. Clin. Med. 2024, 13(6), 1580; https://doi.org/10.3390/jcm13061580 - 10 Mar 2024
Viewed by 437
Abstract
Background: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is an alternative for failed endoscopic retrograde cholangiopancreatography (ERCP), with current success rates of 65–84% considered suboptimal. A novel ERCP catheter (SHOREN, Kaneka Corporation, Osaka, Japan) with a tapered 3.3-French tip may facilitate smoother insertion, potentially improving [...] Read more.
Background: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is an alternative for failed endoscopic retrograde cholangiopancreatography (ERCP), with current success rates of 65–84% considered suboptimal. A novel ERCP catheter (SHOREN, Kaneka Corporation, Osaka, Japan) with a tapered 3.3-French tip may facilitate smoother insertion, potentially improving outcomes. Methods: This retrospective analysis encompassed EUS-HGS procedures conducted from January 2021 to August 2023 at four institutions. The aim of this study was to compare the performance of conventional and novel ERCP contrast catheters regarding the success rate of single-attempt catheter insertion, failure rates, technical success rates, and incidence of adverse events. Results: The study included 48 patients; 26 underwent EUS-HGS using conventional catheters and 22 with the novel catheter. The novel catheter achieved higher success rates in single-attempt insertions (96.5% vs. 80.8%) and lower failure rates (4.6% vs. 7.7%). The occurrence of bile peritonitis was comparable between the two groups. Conclusions: The novel ERCP contrast catheter with a tapered tip appears to contribute to successful catheter insertion and is useful for EUS-HGS. Full article
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17 pages, 1168 KiB  
Article
Extended Right Hepatectomy following Clearance of the Left Liver Lobe and Portal Vein Embolization for Curatively Intended Treatment of Extensive Bilobar Colorectal Liver Metastases: A Single-Center Case Series
by Sebastian Knitter, Linda Sauer, Karl-H. Hillebrandt, Simon Moosburner, Uli Fehrenbach, Timo A. Auer, Nathanael Raschzok, Georg Lurje, Felix Krenzien, Johann Pratschke and Wenzel Schöning
Curr. Oncol. 2024, 31(3), 1145-1161; https://doi.org/10.3390/curroncol31030085 - 21 Feb 2024
Viewed by 686
Abstract
Background: Two-staged hepatectomy (TSH) including portal vein embolization (PVE) may offer surgical treatment for extensive bilobar colorectal liver metastases (CRLM). This study aimed to investigate the feasibility and outcomes of extended right hepatectomy (ERH) within TSH including PVE for patients with extended CRLM. [...] Read more.
Background: Two-staged hepatectomy (TSH) including portal vein embolization (PVE) may offer surgical treatment for extensive bilobar colorectal liver metastases (CRLM). This study aimed to investigate the feasibility and outcomes of extended right hepatectomy (ERH) within TSH including PVE for patients with extended CRLM. Methods: We retrospectively collected data of patients who underwent TSH for extended CRLM between 2015 and 2021 at our institution. Clearance of the left liver lobe (clear-up, CU) associated with PVE was followed by ERH. Results: Minimally invasive (n = 12, 46%, MIH) or open hepatectomy (n = 14, 54%, OH) was performed. Postoperative major morbidity and 90-day mortality were 54% and 0%. Three-year overall survival was 95%. Baseline characteristics, postoperative and long-term outcomes were comparable between MIH and OH. However, hospital stay was significantly shorter after MIH (8 vs. 15 days, p = 0.008). Additionally, the need for intraoperative transfusions tended to be lower in the MIH group (17% vs. 50%, p = 0.110). Conclusions: ERH following CU and PVE for extended CRLM is feasible and safe in laparoscopic and open approaches. MIH for ERH may result in shorter postoperative hospital stays. Further high-volume, multicenter studies are required to evaluate the potential superiority of MIH. Full article
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15 pages, 3915 KiB  
Systematic Review
Promising Results of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy for Perihilar Cholangiocarcinoma in a Systematic Review and Single-Arm Meta-Analysis
by Mohammad Golriz, Ali Ramouz, Ahmed Hammad, Ehsan Aminizadeh, Nastaran Sabetkish, Elias Khajeh, Omid Ghamarnejad, Carlos Carvalho, Hugo Rio-Tinto, De-Hua Chang, Ana Alagoa Joao, Gil Goncalves and Arianeb Mehrabi
Cancers 2024, 16(4), 771; https://doi.org/10.3390/cancers16040771 - 13 Feb 2024
Viewed by 671
Abstract
Background: ALPPS popularity is increasing among surgeons worldwide and its indications are expanding to cure patients with primarily unresectable liver tumors. Few reports recommended limitations or even contraindications of ALPPS in perihilar cholangiocarcinoma (phCC). Here, we discuss the results of ALPPS in patients [...] Read more.
Background: ALPPS popularity is increasing among surgeons worldwide and its indications are expanding to cure patients with primarily unresectable liver tumors. Few reports recommended limitations or even contraindications of ALPPS in perihilar cholangiocarcinoma (phCC). Here, we discuss the results of ALPPS in patients with phCC in a systematic review as well as a pooled data analysis. Methods: MEDLINE and Web of Science databases were systematically searched for relevant literature up to December 2023. All studies reporting ALPPS in the management of phCC were included. A single-arm meta-analysis of proportions was carried out to estimate the overall rate of outcomes. Results: After obtaining 207 articles from the primary search, data of 18 studies containing 112 phCC patients were included in our systematic review. Rates of major morbidity and mortality were calculated to be 43% and 22%, respectively. The meta-analysis revealed a PHLF rate of 23%. One-year disease-free survival was 65% and one-year overall survival was 69%. Conclusions: ALPPS provides a good chance of cure for patients with phCC in comparison to alternative treatment options, but at the expense of debatable morbidity and mortality. With refinement of the surgical technique and better perioperative patient management, the results of ALPPS in patients with phCC were improved. Full article
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14 pages, 3267 KiB  
Article
Multisite Is Superior to Single-Site Intratumoral Chemotherapy to Retard the Outcomes of Pancreatic Ductal Adenocarcinoma in a Murine Model
by Janette Lazarovits, Ron Epelbaum, Jesse Lachter, Yaron Amikam and Jacob Ben Arie
Cancers 2023, 15(24), 5801; https://doi.org/10.3390/cancers15245801 - 11 Dec 2023
Cited by 1 | Viewed by 855
Abstract
Introduction: Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion. Aim: This study explores the efficacy of multisite intratumoral injections in improving a drug’s [...] Read more.
Introduction: Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion. Aim: This study explores the efficacy of multisite intratumoral injections in improving a drug’s distribution while minimizing its side effects. Methods and Results: In mice with orthotopic LAPC tumors, weekly intratumoral injections of oxaliplatin at four separate sites reduced the tumor growth by 46% compared with saline (p < 0.003). Oxaliplatin exhibited the greatest impact on the tumor microenvironment relative to gemcitabine, Abraxane, or their combination, with increased necrosis, apoptosis, fibroblasts, inflammation, and infiltrating lymphocytes (p < 0.008). When combined with intravenous FOLFIRINOX (FFX), multisite intratumoral oxaliplatin reduced the tumor weight by 35% compared with single-site injection (p = 0.007). No additional visible toxicity was observed even at a 10-fold occurrence of intratumoral treatment. This co-modality treatment significantly improved survival compared with other groups (p = 0.007). Conclusions: Multisite intratumoral therapy in tandem with systemic treatment holds promise for reducing the tumor size and enhancing the overall survival in LAPC. Full article
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11 pages, 3197 KiB  
Article
Trends in Selective Internal Radiation Therapy (SIRT) for Treating Hepatocellular Carcinoma, Cholangiocarcinoma, and Liver Metastasis: A Total Population Analysis from 2006 to 2021 in Germany
by Smita George Thoduka, Luka Flegar, Christer Groeben, Johannes Huber, Nicole Eisenmenger, Tobias Paulus, Katharina Vogt, Markus Luster and Nasreddin Abolmaali
Curr. Oncol. 2023, 30(12), 10325-10335; https://doi.org/10.3390/curroncol30120752 - 05 Dec 2023
Viewed by 1288
Abstract
The aim of this study was to investigate trends in selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC), and liver metastasis in Germany. We analyzed the nationwide German hospital billing database from 2006 to 2019 for the diagnosis of HCC, [...] Read more.
The aim of this study was to investigate trends in selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC), and liver metastasis in Germany. We analyzed the nationwide German hospital billing database from 2006 to 2019 for the diagnosis of HCC, CCC or liver metastasis in combination with SIRT. For analyses of SIRT on the hospital level, we used the reimbursement.INFO tool based on German hospitals’ quality reports from 2008 to 2021. Linear regression analysis was performed to detect changes over time. We included a total of 14,165 SIRT procedures. The annual numbers increased from 99 in 2006 to 1605 in 2015 (p < 0.001; increase by 1521%), decreasing to 1175 cases in 2019 (p < 0.001). In 2008, 6 of 21 hospitals (28.6%) performed more than 20 SIRTs per year, which increased to 19 of 53 (35.8%) in 2021. The share of SIRT for HCC increased from 29.8% in 2006 to 44.7% in 2019 (p < 0.001) and for CCC from 0% in 2006 to 9.5% in 2019 (p < 0.001), while the share of SIRT for liver metastasis decreased from 70.2% in 2006 to 45.7% in 2019 (p < 0.001). In-hospital mortality was 0.2% after the SIRT procedure. Gastritis (2.7%), liver failure (0.4%), and sepsis (0.3%) were the most common in-hospital complications reported. We observed an increase in SIRT procedures in Germany, with the number of hospitals offering the procedure going up from 21 in 2008 to 53 in 2021. While the treatment of liver metastasis remains the most common indication, SIRT for HCC and CCC increased significantly over the last few years. The mortality and complication rates show that SIRT is a relatively safe procedure. Full article
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12 pages, 2135 KiB  
Article
Real-World Systemic Treatment Patterns after Atezolizumab and Bevacizumab in Patients with Hepatocellular Carcinoma in the United States
by Amit G. Singal, Kirhan Özgürdal, Xiaozhou Fan, Zdravko Vassilev, Xiaoyun Pan, Jasjit K. Multani, Chi-Chang Chen, Zifan Zhou, Jing He and Federica Pisa
Cancers 2023, 15(23), 5532; https://doi.org/10.3390/cancers15235532 - 22 Nov 2023
Viewed by 1224
Abstract
Real-world (RW) evidence is needed to evaluate atezolizumab plus bevacizumab (atezo + bev) utilization for hepatocellular carcinoma (HCC) in clinical practice. This retrospective cohort study used administrative claims databases to evaluate treatment patterns in individuals with HCC ≥18 years of age who were [...] Read more.
Real-world (RW) evidence is needed to evaluate atezolizumab plus bevacizumab (atezo + bev) utilization for hepatocellular carcinoma (HCC) in clinical practice. This retrospective cohort study used administrative claims databases to evaluate treatment patterns in individuals with HCC ≥18 years of age who were initiated on atezo + bev between June 2020 and June 2022. The endpoints of this study were the proportion of individuals who discontinued atezo + bev and received subsequent systemic therapies, time to discontinuation (TTD), and time to next treatment. Overall, 825 individuals were eligible (median age 67 years; 80% male). Over a median follow-up of 15.3 months, most (72%) discontinued atezo + bev, with a median TTD of 3.5 months. A minority (19%) received subsequent therapies, with the most common second-line agents being lenvatinib (6%), cabozantinib (4%), and nivolumab (4%). The median time from index to next treatment post-atezo + bev was 5.4 months. Further research is needed to identify the patients who are most likely to benefit from atezo + bev as well as later-line HCC therapies to optimize overall survival. Full article
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17 pages, 1617 KiB  
Article
Combined Serum ALBUMIN with Neutrophil-to-Lymphocyte Ratio Predicts the Prognosis of Biliary Tract Cancer after Curative Resection
by Tai-Jan Chiu, Yueh-Wei Liu, Chee-Chien Yong, Shih-Min Yin, Cheng-His Yeh and Yen-Yang Chen
Cancers 2023, 15(22), 5474; https://doi.org/10.3390/cancers15225474 - 19 Nov 2023
Cited by 1 | Viewed by 1067
Abstract
Background: The mainstay treatment of biliary tract cancer is complete tumor resection. Prior to surgery, risk stratification may help to predict and plan treatment approaches. In this study, we investigated the possibility of combining serum albumin concentrations and neutrophil-to-lymphocyte ratios (NLR) to create [...] Read more.
Background: The mainstay treatment of biliary tract cancer is complete tumor resection. Prior to surgery, risk stratification may help to predict and plan treatment approaches. In this study, we investigated the possibility of combining serum albumin concentrations and neutrophil-to-lymphocyte ratios (NLR) to create a score as ANS to predict the prognoses of biliary tract cancer before surgery. Methods: This study retrospectively collected serum albumin concentration, neutrophil, and lymphocyte data measured in biliary tract cancer patients slated to receive complete tumor resections within two weeks before surgery. From January 2013 to December 2019, 268 biliary tract cancer patients who had received tumor resections at our hospital were categorized into 3 ANS groups: ANS = 0 (high albumin and low NLR), ANS = 1 (low albumin or high NLR), and ANS = 2 (low albumin and high NLR). Results: Five-year survival rates were 70.1%, 47.6%, and 30.8% in the ANS = 0, 1, and 2 groups, respectively. The median overall survival time for the ANS = 0 group could not be determined by the end of the study, while those for ANS = 1 and ANS = 2 groups were 54.90 months and 16.62 months, respectively. The results of our multivariate analysis revealed that ANS could be used as an independent predictor of overall and recurrent-free survival. A high ANS was also correlated with other poor prognostic factors. Conclusions: The ANS devised for this study can be used to predict postoperative survival in patients with BTC and to guide treatment strategies. Full article
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10 pages, 4614 KiB  
Article
Different Oncologic Outcomes According to Margin Status (High-Grade Dysplasia vs. Carcinoma) in Patients Who Underwent Hilar Resection for Mid-Bile Duct Cancer
by Hani Jassim Alramadhan, Soo-Yeun Lim, Hye-Jeong Jeong, Hyun-Jeong Jeon, Hochang Chae, So-Jeong Yoon, Sang-Hyun Shin, In-Woong Han, Jin-Seok Heo and Hongbeom Kim
Cancers 2023, 15(21), 5166; https://doi.org/10.3390/cancers15215166 - 26 Oct 2023
Viewed by 999
Abstract
Margin positivity after hilar resection (HR) for bile duct cancer is commonly observed due to its longitudinal spread along the subepithelial plane; nevertheless, we cannot draw conclusions regarding the prognostic effects of margins with high-grade dysplasia (HGD) or carcinoma. We aimed to investigate [...] Read more.
Margin positivity after hilar resection (HR) for bile duct cancer is commonly observed due to its longitudinal spread along the subepithelial plane; nevertheless, we cannot draw conclusions regarding the prognostic effects of margins with high-grade dysplasia (HGD) or carcinoma. We aimed to investigate the oncologic effect according to the margin status after HR, particularly between the R1 HGD and the R1 carcinoma. From 2008 to 2017, 149 patients diagnosed with mid-bile duct cancer in Samsung Medical Center, South Korea, were divided according to margin status after HR and retrospectively analyzed. Recurrence patterns were also analyzed between the groups. There were 126 patients with R0 margins, nine with R1 HGD, and 14 with R1 carcinoma. The mean age of the patients was 68.3 (±8.1); most patients were male. The mean age was higher in R1 carcinoma patients than in R1 HGD and R0 patients (p = 0.014). The R1 HGD and R1 carcinoma groups had more patients with a higher T-stage than R0 (p = 0.079). In univariate analysis, the prognostic factors affecting overall survival were age, T- and N-stage, CA19-9, and margin status. The survival rate of R0 was comparable to that of R1 HGD, but the survival rate of R0 was significantly better compared to R1 carcinoma (R0 vs. R1 HGD, p = 0.215, R0 vs. R1 carcinoma, p = 0.042, respectively). The recurrence pattern between the margin groups did not differ significantly (p = 0.604). Extended surgery should be considered for R1 carcinoma; however, in R1 HGD, extended operation may not be necessary, as it may achieve oncologic outcomes similar to R0 margins with HR. Full article
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17 pages, 1987 KiB  
Review
Advances and Challenges in Cytomegalovirus Detection Methods for Liver Transplant Donors
by Xiaoping Li, Yiwu Zhong, Yinbiao Qiao, Haoyu Li, Xu Hu, Saber Imani, Shusen Zheng and Jianhui Li
Diagnostics 2023, 13(21), 3310; https://doi.org/10.3390/diagnostics13213310 - 26 Oct 2023
Cited by 1 | Viewed by 1330
Abstract
Cytomegalovirus (CMV) infection is a highly prevalent opportunistic infection among liver transplant recipients. When the liver donor is infected with CMV, there is a risk of transmission to the recipient, leading to CMV infection. To improve the postoperative outcome of liver transplantation, it [...] Read more.
Cytomegalovirus (CMV) infection is a highly prevalent opportunistic infection among liver transplant recipients. When the liver donor is infected with CMV, there is a risk of transmission to the recipient, leading to CMV infection. To improve the postoperative outcome of liver transplantation, it is crucial to shift the focus of CMV detection to the donor and achieve early diagnosis, as well as implement effective preventative and therapeutic measures. However, the commonly used CMV detection methods in the past had limitations that prevented their early and accurate diagnosis in liver transplant donors. This review focuses on the latest advancements in CMV detection methods that can potentially be applied to liver transplant donors. The objective is to compare and evaluate their clinical utility, thereby providing guidance and support for rapid and accurate diagnosis of CMV infection in the clinic. The clustered regularly interspaced short palindromic repeats-associated proteins (CRISPR–Cas) system-based assay emerges as a promising method for detecting the virus, offering great prospects for early and expedient CMV infection diagnosis in clinical settings. Full article
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11 pages, 564 KiB  
Article
Safety and Efficacy of Hepatic Artery Embolization in Heavily Treated Patients with Intrahepatic Cholangiocarcinoma: Analysis of Clinicopathological and Radiographic Parameters Associated with Better Overall Survival
by Sara Velayati, Ahmed Elsakka, Ken Zhao, Joseph P. Erinjeri, Brett Marinelli, Mohamed Soliman, Olivier Chevallier, Etay Ziv, Lynn A. Brody, Constantinos T. Sofocleous, Stephen B. Solomon, James J. Harding, Ghassan K. Abou-Alfa, Michael I. D’Angelica, Alice C. Wei, Peter T. Kingham, William R. Jarnagin and Hooman Yarmohammadi
Curr. Oncol. 2023, 30(10), 9181-9191; https://doi.org/10.3390/curroncol30100663 - 18 Oct 2023
Viewed by 1489
Abstract
The safety and efficacy of hepatic artery embolization (HAE) in treating intrahepatic cholangiocarcinoma (IHC) was evaluated. Initial treatment response, local tumor progression-free survival (L-PFS), and overall survival (OS) were evaluated in 34 IHC patients treated with HAE. A univariate survival analysis and a [...] Read more.
The safety and efficacy of hepatic artery embolization (HAE) in treating intrahepatic cholangiocarcinoma (IHC) was evaluated. Initial treatment response, local tumor progression-free survival (L-PFS), and overall survival (OS) were evaluated in 34 IHC patients treated with HAE. A univariate survival analysis and a multivariate Cox proportional hazard analysis to identify independent factors were carried out. Objective response (OR) at 1-month was 79.4%. Median OS and L-PFS from the time of HAE was 13 (CI = 95%, 7.4–18.5) and 4 months (CI = 95%, 2.09–5.9), respectively. Tumor burden < 25% and increased tumor vascularity on preprocedure imaging and surgical resection prior to embolization were associated with longer OS (p < 0.05). Multivariate logistic regression analysis demonstrated that tumor burden < 25% and hypervascular tumors were independent risk factors. Mean post-HAE hospital stay was 4 days. Grade 3 complication rate was 8.5%. In heavily treated patients with IHC, after exhausting all chemotherapy and other locoregional options, HAE as a rescue treatment option appeared to be safe with a mean OS of 13 months. Tumor burden < 25%, increased target tumor vascularity on pre-procedure imaging, and OR on 1 month follow-up images were associated with better OS. Further studies with a control group are required to confirm the effectiveness of HAE in IHC. Full article
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21 pages, 661 KiB  
Review
Current Evidence for Immune Checkpoint Inhibition in Advanced Hepatocellular Carcinoma
by Victoria Foy, Mairéad G. McNamara, Juan W. Valle, Angela Lamarca, Julien Edeline and Richard A. Hubner
Curr. Oncol. 2023, 30(9), 8665-8685; https://doi.org/10.3390/curroncol30090628 - 21 Sep 2023
Viewed by 1452
Abstract
The treatment of advanced unresectable HCC (aHCC) remains a clinical challenge, with limited therapeutic options and poor prognosis. The results of IMbrave150 and HIMALAYA have changed the treatment paradigm for HCC and established immune checkpoint inhibition (ICI), either combined with anti-angiogenic therapy or [...] Read more.
The treatment of advanced unresectable HCC (aHCC) remains a clinical challenge, with limited therapeutic options and poor prognosis. The results of IMbrave150 and HIMALAYA have changed the treatment paradigm for HCC and established immune checkpoint inhibition (ICI), either combined with anti-angiogenic therapy or dual ICI, as preferred first-line therapy for eligible patients with aHCC. Numerous other combination regimens involving ICI are under investigation with the aim of improving the tumour response and survival of patients with all stages of HCC. This review will explore the current evidence for ICI in patients with advanced HCC and discuss future directions, including the unmet clinical need for predictive biomarkers to facilitate patient selection, the effects of cirrhosis aetiology on response to ICI, and the safety of its use in patients with impaired liver function. Full article
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14 pages, 11758 KiB  
Article
The Multikinase Inhibitor AD80 Induces Mitotic Catastrophe and Autophagy in Pancreatic Cancer Cells
by Keli Lima, Lívia Bassani Lins de Miranda, Anali Del Milagro Bernabe Garnique, Bruna Oliveira de Almeida, Mariane Cristina do Nascimento, Guilherme Augusto Sousa Alcântara, Glaucia Maria Machado-Santelli, Eduardo Magalhães Rego and João Agostinho Machado-Neto
Cancers 2023, 15(15), 3866; https://doi.org/10.3390/cancers15153866 - 29 Jul 2023
Viewed by 1146
Abstract
Significant advances in understanding the molecular complexity of the development and progression of pancreatic cancer have been made, but this disease is still considered one of the most lethal human cancers and needs new therapeutic options. In the present study, the antineoplastic effects [...] Read more.
Significant advances in understanding the molecular complexity of the development and progression of pancreatic cancer have been made, but this disease is still considered one of the most lethal human cancers and needs new therapeutic options. In the present study, the antineoplastic effects of AD80, a multikinase inhibitor, were investigated in models of pancreatic cancer. AD80 reduced cell viability and clonogenicity and induced polyploidy in pancreatic cancer cells. At the molecular level, AD80 reduced RPS6 and histone H3 phosphorylation and induced γH2AX and PARP1 cleavage. Additionally, the drug markedly decreased AURKA phosphorylation and expression. In PANC-1 cells, AD80 strongly induced autophagic flux (consumption of LC3B and SQSTM1/p62). AD80 modulated 32 out of 84 autophagy-related genes and was associated with vacuole organization, macroautophagy, response to starvation, cellular response to nitrogen levels, and cellular response to extracellular stimulus. In 3D pancreatic cancer models, AD80 also effectively reduced growth independent of anchorage and cell viability. In summary, AD80 induces mitotic aberrations, DNA damage, autophagy, and apoptosis in pancreatic cancer cells. Our exploratory study establishes novel targets underlying the antineoplastic activity of the drug and provides insights into the development of therapeutic strategies for this disease. Full article
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14 pages, 691 KiB  
Review
Anti-Glycolytic Drugs in the Treatment of Hepatocellular Carcinoma: Systemic and Locoregional Options
by Miles Pourbaghi, Leila Haghani, Ken Zhao, Anita Karimi, Brett Marinelli, Joseph P. Erinjeri, Jean-Francois H. Geschwind and Hooman Yarmohammadi
Curr. Oncol. 2023, 30(7), 6609-6622; https://doi.org/10.3390/curroncol30070485 - 10 Jul 2023
Cited by 3 | Viewed by 1920
Abstract
Hepatocellular cancer (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death. Locoregional therapies, including transarterial embolization (TAE: bland embolization), chemoembolization (TACE), and radioembolization, have demonstrated survival benefits when treating patients with unresectable HCC. TAE and TACE [...] Read more.
Hepatocellular cancer (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death. Locoregional therapies, including transarterial embolization (TAE: bland embolization), chemoembolization (TACE), and radioembolization, have demonstrated survival benefits when treating patients with unresectable HCC. TAE and TACE occlude the tumor’s arterial supply, causing hypoxia and nutritional deprivation and ultimately resulting in tumor necrosis. Embolization blocks the aerobic metabolic pathway. However, tumors, including HCC, use the “Warburg effect” and survive hypoxia from embolization. An adaptation to hypoxia through the Warburg effect, which was first described in 1956, is when the cancer cells switch to glycolysis even in the presence of oxygen. Hence, this is also known as aerobic glycolysis. In this article, the adaptation mechanisms of HCC, including glycolysis, are discussed, and anti-glycolytic treatments, including systemic and locoregional options that have been previously reported or have the potential to be utilized in the treatment of HCC, are reviewed. Full article
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11 pages, 1095 KiB  
Article
Tissue Expression of Programmed Cell Death 1 Ligand1 (PD-L1) in Biopsies of Transplant Livers of Pediatric Patients as a Possible Marker of Acute Cellular Rejection
by Sylwia Szymanska, Malgorzata Markiewicz-Kijewska, Michal Pyzlak, Agnieszka Karkucinska-Wienckowska, Mateusz Ciopinski, Piotr Czubkowski and Piotr Kaliciński
J. Clin. Med. 2023, 12(13), 4269; https://doi.org/10.3390/jcm12134269 - 26 Jun 2023
Viewed by 847
Abstract
Introduction: Preclinical models have demonstrated that PD-1 and its ligand programmed death ligand1 (PD-L1) play significant roles in both graft induction and the maintenance of immune tolerance. It has also been suggested that PD-L1 tissue expression may predict graft rejection; however, the available [...] Read more.
Introduction: Preclinical models have demonstrated that PD-1 and its ligand programmed death ligand1 (PD-L1) play significant roles in both graft induction and the maintenance of immune tolerance. It has also been suggested that PD-L1 tissue expression may predict graft rejection; however, the available data are sparse and inconclusive. Some studies were conducted on patients with cancer; most of them do not concern the liver, especially within the context of the use of immunohistochemical tests. Therefore, the aim of our study was to assess the relationship between tissue expression of PD-L1 in a unique material, i.e., in the liver biopsies of pediatric patients after transplantation with the presence of acute cellular rejection (ACR). Material and Methods: This retrospective study enrolled 55 biopsies from 55 patients who underwent protocol liver biopsies. The control group consisted of 19 biopsies from 13 patients diagnosed with acute cellular rejection (rejection activity index/RAI/ from 2 to 8). An immunohistochemical (IHC) staining for PD-L1 was performed in all of the liver specimens; its expression was analyzed in different regions of liver tissue (in inflammatory infiltrates and within the endothelium and hepatocytes). The following changes were re-evaluated in each specimen: features of any kind of rejection (acute cellular, antibody-mediated, chronic); the presence and severity of fibrosis (Ishak scale); and the presence of cholestasis and steatosis. Clinical parameters were also evaluated, including tests of liver function (AST, ALT, GGT, bilirubin). Results: The age of patients in the study group ranged from 2.37 to 18.9 years (median 13.87 years), with the time after transplantation being 1–17 years (median 8.36 years). The age of patients in the control group ranged from 1.48 to 17.51 years (median 7.93 years), with their biopsies being taken 0.62–14.39 years (median 1.33 years) after transplantation. We found a statistically significant relationship between PD-L1 expression on inflammatory infiltrates and ACR; however, there was no statistically significant relationship between PD-L1 endothelial expression and ACR. PD-L1 was not positive in the hepatocytes regardless of if it was the study or control group that was under observation. Conclusion: PD-L1 appears to be a promising marker to predict graft rejection. Full article
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13 pages, 1726 KiB  
Article
Mendelian Randomization Analyses of Chronic Immune-Mediated Diseases, Circulating Inflammatory Biomarkers, and Cytokines in Relation to Liver Cancer
by Qiushi Yin, Qiuxi Yang, Wenjie Shi, Ulf D. Kahlert, Zhongyi Li, Shibu Lin, Qifeng Song, Weiqiang Fan, Li Wang, Yi Zhu and Xiaolong Huang
Cancers 2023, 15(11), 2930; https://doi.org/10.3390/cancers15112930 - 26 May 2023
Cited by 4 | Viewed by 2689
Abstract
Liver cancer is closely linked to chronic inflammation. While observational studies have reported positive associations between extrahepatic immune-mediated diseases and systemic inflammatory biomarkers and liver cancer, the genetic association between these inflammatory traits and liver cancer remains elusive and merits further investigation. We [...] Read more.
Liver cancer is closely linked to chronic inflammation. While observational studies have reported positive associations between extrahepatic immune-mediated diseases and systemic inflammatory biomarkers and liver cancer, the genetic association between these inflammatory traits and liver cancer remains elusive and merits further investigation. We conducted a two-sample Mendelian randomization (MR) analysis, using inflammatory traits as exposures and liver cancer as the outcome. The genetic summary data of both exposures and outcome were retrieved from previous genome-wide association studies (GWAS). Four MR methods, including inverse-variance-weighted (IVW), MR-Egger regression, weighted-median, and weighted-mode methods, were employed to examine the genetic association between inflammatory traits and liver cancer. Nine extrahepatic immune-mediated diseases, seven circulating inflammatory biomarkers, and 187 inflammatory cytokines were analyzed in this study. The IVW method suggested that none of the nine immune-mediated diseases were associated with the risk of liver cancer, with odds ratios of 1.08 (95% CI 0.87–1.35) for asthma, 0.98 (95% CI 0.91–1.06) for rheumatoid arthritis, 1.01 (95% CI 0.96–1.07) for type 1 diabetes, 1.01 (95% CI 0.98–1.03) for psoriasis, 0.98 (95% CI 0.89–1.08) for Crohn’s disease, 1.02 (95% CI 0.91–1.13) for ulcerative colitis, 0.91 (95% CI 0.74–1.11) for celiac disease, 0.93 (95% CI 0.84–1.05) for multiple sclerosis, and 1.05 (95% CI 0.97–1.13) for systemic lupus erythematosus. Similarly, no significant association was found between circulating inflammatory biomarkers and cytokines and liver cancer after correcting for multiple testing. The findings were consistent across all four MR methods used in this study. Our findings do not support a genetic association between extrahepatic inflammatory traits and liver cancer. However, larger-scale GWAS summary data and more genetic instruments are needed to confirm these findings. Full article
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18 pages, 29443 KiB  
Article
Immune Checkpoint Neuropilins as Novel Biomarkers and Therapeutic Targets for Pancreatic Cancer
by Li-Hong He, Xiao-Zhen Zhang, Meng-Yi Lao, Han-Jia Zhang, Han-Shen Yang and Xue-Li Bai
Cancers 2023, 15(8), 2225; https://doi.org/10.3390/cancers15082225 - 10 Apr 2023
Viewed by 1583
Abstract
The traditional immune checkpoint blockade therapy benefits some patients with cancer, but elicits no response in certain cancers, such as pancreatic adenocarcinoma (PAAD); thus, novel checkpoints and effective targets are required. Here, we found that there was a higher Neuropilin (NRP) expression in [...] Read more.
The traditional immune checkpoint blockade therapy benefits some patients with cancer, but elicits no response in certain cancers, such as pancreatic adenocarcinoma (PAAD); thus, novel checkpoints and effective targets are required. Here, we found that there was a higher Neuropilin (NRP) expression in tumor tissues as novel immune checkpoints, which was associated with poor prognosis and pessimistic responses to immune checkpoint blockade therapy. In the tumor microenvironment of PAAD samples, NRPs were widely expressed in tumor, immune and stromal cells. The relationship of NRPs with tumor immunological features in PAAD and pan-cancer was evaluated using bioinformatics methods; it was positively correlated with the infiltration of myeloid immune cells and the expression of most immune checkpoint genes. Bioinformatics analysis, in vitro and in vivo experiments suggested that NRPs exhibit potential immune-related and immune-independent pro-tumor effects. NRPs, especially NRP1, are attractive biomarkers and therapeutic targets for cancers, particularly PAAD. Full article
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16 pages, 2834 KiB  
Article
Albumin–Globulin Score Combined with Skeletal Muscle Index as a Novel Prognostic Marker for Hepatocellular Carcinoma Patients Undergoing Liver Transplantation
by Yang Huang, Ning Wang, Liangliang Xu, Youwei Wu, Hui Li, Li Jiang and Mingqing Xu
J. Clin. Med. 2023, 12(6), 2237; https://doi.org/10.3390/jcm12062237 - 14 Mar 2023
Cited by 2 | Viewed by 1543
Abstract
Background: Sarcopenia was recently identified as a poor prognostic factor in patients with malignant tumors. The present study investigated the effect of the preoperative albumin–globulin score (AGS), skeletal muscle index (SMI), and combination of AGS and SMI (CAS) on short- and long-term survival [...] Read more.
Background: Sarcopenia was recently identified as a poor prognostic factor in patients with malignant tumors. The present study investigated the effect of the preoperative albumin–globulin score (AGS), skeletal muscle index (SMI), and combination of AGS and SMI (CAS) on short- and long-term survival outcomes following deceased donor liver transplantation (DDLT) for hepatocellular carcinoma (HCC) and aimed to identify prognostic factors. Methods: A total of 221 consecutive patients who underwent DDLT for HCC were enrolled in this retrospective study between January 2015 and December 2019. The skeletal muscle cross-sectional area was measured by CT (computed tomography). Clinical cutoffs of albumin (ALB), globulin (GLB), and sarcopenia were defined by receiver operating curve (ROC). The effects of the AGS, SMI, and CAS grade on the preoperative characteristics and long-term outcomes of the included patients were analyzed. Results: Patients who had low AGS and high SMI were associated with better overall survival (OS) and recurrence-free survival (RFS), shorter intensive care unit (ICU) stay, and fewer postoperative complications (grade ≥ 3, Clavien–Dindo classification). Stratified by CAS grade, 46 (20.8%) patients in grade 1 were associated with the best postoperative prognosis, whereas 79 (35.7%) patients in grade 3 were linked to the worst OS and RFS. The CAS grade showed promising accuracy in predicting the OS and RFS of HCC patients [areas under the curve (AUCs) were 0.710 and 0.700, respectively]. Male recipient, Child–Pugh C, model for end-stage liver disease (MELD) score > 20, and elevated CAS grade were identified as independent risk factors for OS and RFS of HCC patients after DDLT. Conclusion: CAS grade, a novel prognostic index combining preoperative AGS and SMI, was closely related to postoperative short-term and long-term outcomes for HCC patients who underwent DDLT. Graft allocation and clinical decision making may be referred to CAS grade evaluation. Full article
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12 pages, 4429 KiB  
Technical Note
Optimizing Growth of the Future Liver Remnant and Making In-Situ Liver Transsection Safe—A Standardized Approach to ISLT or ALPPS
by Andrea Alexander, Nadja Lehwald-Tywuschik, Alexander Rehders, Levent Dizdar, Georg Fluegen, Sami Alexander Safi and Wolfram Trudo Knoefel
Curr. Oncol. 2023, 30(3), 3277-3288; https://doi.org/10.3390/curroncol30030249 - 13 Mar 2023
Cited by 2 | Viewed by 1439
Abstract
In-situ splitting of the liver before extended resection has gained broad attention. This two-step procedure requires several measures to make an effective and safe procedure. Although the procedure is performed in many institutions, there is no consensus on a uniform technique. The two [...] Read more.
In-situ splitting of the liver before extended resection has gained broad attention. This two-step procedure requires several measures to make an effective and safe procedure. Although the procedure is performed in many institutions, there is no consensus on a uniform technique. The two steps can be divided into different parts and a standardized technique may render the procedure safer and the results will be easier to evaluate. In this paper, we describe a detailed approach to in-situ splitting that allows making both procedures safe, avoids liver necrosis, and is easily reproducible. In the first procedure the portal branches to segments I and IV to VIII are divided, the arterial branches and bile ducts to these segments are preserved and encircled and the parenchyma between segments II/III and IVa/b is divided. This avoids necrosis and bile leaks of segments I and IV and avoids urgent completion operations. In particular, the handling of vital structures close to the dissection line seems important to us. Complete splitting and securing the right and middle hepatic vein will make the second step of this procedure a minimal-risk procedure at a stage where the patient is still recovering from the more demanding first step. Full article
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12 pages, 1298 KiB  
Article
Outcomes of Intraductal Placement of Covered Metal Stents for Unresectable Distal Malignant Biliary Obstruction
by Manabu Yamada, Tsuyoshi Takeda, Takashi Sasaki, Takeshi Okamoto, Tsuyoshi Hamada, Takahiro Ishitsuka, Hiroki Nakagawa, Takafumi Mie, Takaaki Furukawa, Akiyoshi Kasuga, Masato Matsuyama, Masato Ozaka, Hideki Kobara, Tsutomu Masaki and Naoki Sasahira
J. Clin. Med. 2023, 12(5), 2001; https://doi.org/10.3390/jcm12052001 - 02 Mar 2023
Viewed by 1226
Abstract
Intraductal self-expandable metal stent (SEMS) placement may prolong stent patency by reducing duodenobiliary reflux. This study aimed to evaluate the efficacy and safety of this biliary drainage method in patients with unresectable distal malignant biliary obstruction (MBO). Consecutive patients with unresectable MBO who [...] Read more.
Intraductal self-expandable metal stent (SEMS) placement may prolong stent patency by reducing duodenobiliary reflux. This study aimed to evaluate the efficacy and safety of this biliary drainage method in patients with unresectable distal malignant biliary obstruction (MBO). Consecutive patients with unresectable MBO who underwent initial covered SEMS placement between 2015 and 2022 were retrospectively reviewed. We compared the causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and reintervention rates between two biliary drainage methods (SEMSs placed above and across the papilla). A total of 86 patients were included (above: 38 and across: 48). Overall RBO rates (24% vs. 44%, p = 0.069) and median TRBO (11.6 months vs. 9.8 months, p = 0.189) were not significantly different between the two groups. The frequency of overall AEs was similar between the two groups in the entire cohort, but was significantly lower in patients with non-pancreatic cancer (6% vs. 44%, p = 0.035). Reintervention was successfully performed in the majority of patients in both groups. Intraductal SEMS placement was not associated with a prolonged TRBO in this study. Larger studies are warranted to further evaluate the benefit of intraductal SEMS placement. Full article
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11 pages, 639 KiB  
Article
Survival Benefit of Surgical Treatment for Elderly Patients with Intrahepatic Cholangiocarcinoma: A Retrospective Cohort Study in the SEER Database by Propensity Score Matching Analysis
by Kaiyu Chen, Haitao Yu, Jinhuan Yang, Zhiyuan Bo, Chen Jin, Lijun Wu, Yi Wang and Gang Chen
Curr. Oncol. 2023, 30(3), 2642-2652; https://doi.org/10.3390/curroncol30030201 - 22 Feb 2023
Viewed by 1587
Abstract
Despite a rising trend in intrahepatic cholangiocarcinoma (ICC) incidence in the elderly population worldwide, the benefit of surgery for those patients is still controversial. Data from 811 elderly patients diagnosed with non-metastatic ICC were obtained from the US surveillance, epidemiology, and end results [...] Read more.
Despite a rising trend in intrahepatic cholangiocarcinoma (ICC) incidence in the elderly population worldwide, the benefit of surgery for those patients is still controversial. Data from 811 elderly patients diagnosed with non-metastatic ICC were obtained from the US surveillance, epidemiology, and end results (SEER) program database. Propensity score matched (PSM) was conducted for the better balance of baseline. The associations between tumor characteristics and surgery with overall survival (OS) and cancer specific survival (CSS) were estimated using hazard ratios (HR) and 95% confidence intervals (CI). The results showed that ICC patients above 60 years old taking surgery had better OS (hazard ratio [HR], 0.258; 95% CI, 0.205–0.324) and CSS (hazard ratio [HR], 0.239; 95% CI, 0.188–0.303) than patients without surgery. Similar trends in patients above 65 years old, above 70 years old, above 75 years old, and above 80 years old were observed, separately. This benefit was also showed in lymph node-negative (N0) and lymph node-positive (N1) subgroups and N0 patients are more likely to take an advantage from surgery than N1 patients. The different outcomes between surgery and non-surgery suggest that surgical treatment may be recommended for elderly ICC if the tumor is resectable to ensure optimal treatment. Full article
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