Hepatobiliary and Pancreatic Diseases: Novel Strategies of Diagnosis and Treatments—Second Edition

Topic Information

Dear Colleagues,

Following the success of the first edition, we are pleased to announce the Second Edition of the Topic Issue “Hepatobiliary and Pancreatic Diseases: Novel Strategies of Diagnosis and Treatments—Second Edition.”

Diseases of the liver and pancreas continue to represent a crucial field of interest in clinical, surgical, and translational research. Both benign conditions, such as hepatitis or pancreatitis, and malignant tumors significantly impact patients’ quality of life and survival, highlighting the need for continuous innovation in diagnostic and therapeutic strategies.

In recent years, malignant tumors of the liver, biliary tract, and pancreas have shown a worrying increase in incidence and mortality worldwide. These challenges reinforce the urgent need for novel approaches aimed at improving early detection, precision diagnosis, and effective treatment.

This new edition particularly welcomes original studies and reviews exploring the application of radiomics and artificial intelligence in hepatobiliary and pancreatic diseases. These emerging technologies promise to revolutionize how we interpret imaging data, stratify patient risk, and personalize therapeutic strategies.

We therefore invite researchers and clinicians to contribute their most innovative work, spanning medical, surgical, and technological perspectives, to further advance the understanding and management of HPB pathologies.

Dr. Alessandro Coppola
Dr. Roberta Angelico
Dr. Chiara Mazzarelli
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	4.5	7.8	2013	18.2 Days	CHF 2600	Submit
Cancers cancers	4.8	9.0	2009	17.5 Days	CHF 2900	Submit
Current Oncology curroncol	3.6	6.1	1994	22.6 Days	CHF 2200	Submit
Diagnostics diagnostics	3.8	6.9	2011	20.4 Days	CHF 2600	Submit
Gastrointestinal Disorders gastrointestdisord	1.9	2.1	2019	19.6 Days	CHF 1400	Submit
Journal of Clinical Medicine jcm	3.3	5.2	2012	16.6 Days	CHF 2600	Submit
Therapeutics therapeutics	-	-	2024	59.7 Days	CHF 1000	Submit

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Published Papers (7 papers)

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All Cancers Diagnostics JCM Biomedicines Gastrointestinal Disorders Current Oncology Therapeutics

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12 pages, 387 KB  

Open AccessArticle

First-Line Durvalumab–Tremelimumab in Advanced Hepatocellular Carcinoma: Real-World Data from Turkey

by Mustafa Murat Mıdık, Gökhan Şahin, Bekir Mert Durukan, Fatih Kuş, Kübra Haşimoğlu Gürün, Sinan Ünal, Cem Mirili, Canan Karan, Engin Hendem, Teoman Şakalar, Miray Aydoğan, Bahadır Köylü, Nadiye Sever, Bahattin Engin Kaya, Tülay Kuş, Canberk Şencan, Atike Pınar Erdoğan, Hatime Arzu Yaşar, Hilal Karakaş, Oğuzhan Yıldız, Bahiddin Yılmaz, Murat Alan, Bülent Çetin, Nedim Turan, Melek Karakurt Eryılmaz, Mehmet Artaç, İlkay Tuğba Ünek, Fatih Selçukbiricik, Mehmet Ali Şendur, Hasan Çağrı Yıldırım and Şuayib Yalçınadd Show full author list remove Hide full author list

J. Clin. Med. 2026, 15(15), 5997; https://doi.org/10.3390/jcm15155997 - 1 Aug 2026

Viewed by 517

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Although the STRIDE regimen (durvalumab plus tremelimumab) has demonstrated an overall survival benefit in clinical trials, real-world evidence remains limited, particularly in Turkish clinical practice. This study aimed to [...] Read more.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Although the STRIDE regimen (durvalumab plus tremelimumab) has demonstrated an overall survival benefit in clinical trials, real-world evidence remains limited, particularly in Turkish clinical practice. This study aimed to evaluate the effectiveness and safety of first-line STRIDE therapy in patients with unresectable HCC treated in routine clinical practice. Methods: We conducted a retrospective multicenter study including patients with unresectable HCC who received first-line durvalumab plus tremelimumab through the Turkish national Early Access Program across 18 oncology centers. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and exploratory Cox regression analyses were performed to evaluate baseline prognostic factors. Results: Thirty-two patients were included. The median PFS was 7.25 months (95% CI, 3.68–22.29), and the median OS was 11.43 months (95% CI, 4.50–not reached). The underlying liver disease etiology was non-viral in 53.1% of patients, hepatitis B virus in 40.6%, and hepatitis C virus in 6.3%. Grade ≥ 3 treatment-related adverse events occurred in fewer than 10% of patients. Conclusions: In this multicenter real-world cohort, first-line durvalumab plus tremelimumab appeared to be a feasible treatment option and was generally well tolerated in patients with unresectable HCC. However, given the retrospective design, small sample size, and absence of a control group, these findings should be interpreted cautiously and require confirmation in larger prospective comparative studies. Full article

(This article belongs to the Topic Hepatobiliary and Pancreatic Diseases: Novel Strategies of Diagnosis and Treatments—Second Edition)

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14 pages, 4423 KB  

Open AccessArticle

Clinicopathological Features of Intrahepatic Cholangiocarcinoma with Assessment of IDH1 Mutation: A Two-Center Retrospective Study

by Muge Buyukaksoy, Selin Akturk Esen, Nesrin Turhan, Enes Seyda Sahiner, Imdat Eroglu, Aysenur Sert, Ugur Ozberk, Denizcan Hasturk, Oznur Bal, Efnan Algin, Sebnem Yucel, Nuriye Ozdemir, Onur Ertunc and Dogan Uncu

J. Clin. Med. 2026, 15(13), 5290; https://doi.org/10.3390/jcm15135290 - 7 Jul 2026

Viewed by 508

Abstract

Background/Objective: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with limited therapeutic options and poor survival outcomes. Recent advances in molecular oncology have highlighted the significance of isocitrate dehydrogenase 1 (IDH1) mutations as potential therapeutic targets. However, data on the prevalence and [...] Read more.

Background/Objective: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with limited therapeutic options and poor survival outcomes. Recent advances in molecular oncology have highlighted the significance of isocitrate dehydrogenase 1 (IDH1) mutations as potential therapeutic targets. However, data on the prevalence and prognostic implications of IDH1 mutations in patients with iCCA are scarce. This study aimed to retrospectively investigate the IDH1 mutation rate, histopathological features, and survival outcomes of patients with iCCA. Methods: We retrospectively analyzed 88 patients diagnosed and treated between 2005 and 2025 at two tertiary oncology centers. Clinical, pathological, and survival data were obtained from the institutional oncology archives and national population databases. IDH1 mutation status was evaluated using polymerase chain reaction and next-generation sequencing of paraffin-embedded tissue samples. Results: A total of 88 patients with iCCA were included, with a median age of 62 years, and 62.5% were male. Abdominal pain was the most common presenting symptom (67%). The most frequent stages at diagnosis were stage IB and stage IIIB (22.7% each). Histopathologically, the small-duct subtype (55.7%), nodular morphology (67.0%), and solitary tumors (79.5%) predominated. IDH1 mutation was detected in 2.3% of patients. Curative surgery was performed in 78.2% of cases and was more common in early-stage disease. Gemcitabine–capecitabine was the most frequently used adjuvant regimen, whereas gemcitabine–cisplatin was the most common palliative treatment regimen. Median overall survival differed significantly by albumin-bilirubin (ALBI) grade, with 40.1, 11.1, and 4.4 months for grades 1, 2, and 3, respectively (p < 0.001). Conclusions: In this multicenter cohort, iCCA was characterized by diverse clinicopathological features and treatment approaches. Surgical resection remains the main treatment modality for patients with localized disease, whereas systemic therapies are more frequently used in advanced stages. The findings highlight the prognostic relevance of baseline clinical and biochemical characteristics and may improve risk stratification in patients with iCCA. Full article

(This article belongs to the Topic Hepatobiliary and Pancreatic Diseases: Novel Strategies of Diagnosis and Treatments—Second Edition)

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19 pages, 1947 KB  

Open AccessSystematic Review

Chemotherapy Completion as a Quality Metric in Resected Pancreatic Ductal Adenocarcinoma

by Robert C. G. Martin, Ryan A. Cantrell and Jeremy T. Gaskins

Cancers 2026, 18(12), 1912; https://doi.org/10.3390/cancers18121912 - 11 Jun 2026

Cited by 1 | Viewed by 443

Abstract

Background: Over 60,000 patients are diagnosed annually with pancreatic cancer in the United States, most with pancreatic ductal adenocarcinoma (PDAC). Despite multimodality treatment, prognosis remains poor, underscoring the need to better define factors associated with improved survival in resectable disease. The aim [...] Read more.

Background: Over 60,000 patients are diagnosed annually with pancreatic cancer in the United States, most with pancreatic ductal adenocarcinoma (PDAC). Despite multimodality treatment, prognosis remains poor, underscoring the need to better define factors associated with improved survival in resectable disease. The aim of this study was to propose “completeness of therapy” in resectable PDAC based on chemotherapy type, relative dose intensity (RDI), duration, and timing of initiation, and to evaluate their association with overall survival (OS). Methods: A systematic review of PubMed identified 34 studies. Hazard ratios (HRs) were extracted and synthesized in forest plots. Outcomes focused on OS in relation to chemotherapy completion (cumulative cycles), time to adjuvant chemotherapy initiation (TTA), RDI, and regimen type. The goal was to conceptualize an evidence-based completeness-of-therapy framework for resected PDAC. Results: Completion of chemotherapy was associated with a 42% reduction in the hazard of death compared with incomplete therapy (HR = 0.58, 95% CI 0.47–0.71, p < 0.01). No significant OS difference was observed for longer TTA within a ≤12-week window after surgery (HR = 1.22, 95% CI 0.95–1.56, p = 0.10). Higher RDI demonstrated a large but non-significant trend toward improved OS (HR = 0.51, p = 0.24). Non-significant trends favoring gemcitabine-based regimens (HR = 0.87, p = 0.26) and FOLFIRINOX (HR = 0.79, p = 0.26) were observed, with FOLFIRINOX suggesting a 21% relative reduction in mortality. Conclusions: Chemotherapy completion is strongly associated with improved OS in resectable PDAC. Initiation of adjuvant therapy within 12 weeks appears sufficient, allowing recovery from surgery. Higher RDI and specific chemotherapy regimens demonstrated numerically favorable hazard ratios; however, these associations were not statistically significant and should be interpreted cautiously. Full article

(This article belongs to the Topic Hepatobiliary and Pancreatic Diseases: Novel Strategies of Diagnosis and Treatments—Second Edition)

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13 pages, 1193 KB  

Open AccessReview

The Role of Laboratory Markers in Primary Biliary Cholangitis: A Clinical Review and a Case Report

by Raffaele Radice, Giulia Pollaroli, Michela Salvatici, Chiara Corrado, Francesca Rispoli, Stefania Pacchetti and Lorenzo Drago

Biomedicines 2026, 14(4), 925; https://doi.org/10.3390/biomedicines14040925 - 18 Apr 2026

Cited by 1 | Viewed by 1090

Abstract

Background: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease characterized by marked clinical and serological heterogeneity. Although diagnosis is mainly based on antimitochondrial antibodies (AMAs) and alkaline phosphatase (ALP), non-classical presentations remain a relevant cause of diagnostic delay. In this context, [...] Read more.

Background: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease characterized by marked clinical and serological heterogeneity. Although diagnosis is mainly based on antimitochondrial antibodies (AMAs) and alkaline phosphatase (ALP), non-classical presentations remain a relevant cause of diagnostic delay. In this context, laboratory medicine plays a pivotal role in both diagnosis and long-term disease management. Methods: This manuscript represents a structured clinical review of laboratory biomarkers relevant to the diagnosis, monitoring, and prognostic stratification of PBC, integrated with a representative atypical case with long-term follow-up to illustrate the practical application of laboratory-driven diagnostic. Results: The analysis confirms the central role of immunological and biochemical markers in treatment monitoring and prognostic assessment, while highlighting their limitations in selected clinical scenarios. The reported case, characterized by persistent AMA negativity and consistently normal ALP levels, illustrates how expanded laboratory testing can support the identification of non-standard disease phenotypes. In this setting, parallel testing for AMA- and PBC-specific autoantibodies was essential to achieve a correct diagnosis. Moreover, alternative biomarkers, including gamma-glutamyl transferase (GGT) and selected immunological markers, provided clinically meaningful information when conventional markers were not informative. Conclusions: By integrating current evidence with a long-term clinical case, this work moves beyond a descriptive overview and proposes a practical, laboratory-driven diagnostic and follow-up framework for PBC. It highlights laboratory opportunities to facilitate timely diagnosis, appropriate prognostic stratification, and disease monitoring, including the assessment of associated comorbidities. Full article

(This article belongs to the Topic Hepatobiliary and Pancreatic Diseases: Novel Strategies of Diagnosis and Treatments—Second Edition)

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14 pages, 1340 KB  

Open AccessSystematic Review

Cardiovascular Risk in Pancreatic Cancer: A Meta-Analysis of 197 Studies

by Jázmin Németh, Jimin Lee, Orsolya Eperjesi, Endre Botond Gagyi, Zoltán Bánfalvi, Veronika Lillik, Ioana Creanga-Murariu, Réka Tóth, Eszter Ágnes Szalai, Mahmoud Obeidat, Szilárd Váncsa, Stefania Bunduc and Péter Hegyi

Cancers 2026, 18(7), 1108; https://doi.org/10.3390/cancers18071108 - 29 Mar 2026

Viewed by 1487

Abstract

Background/Objectives: Cardiovascular diseases (CVDs) frequently limit the feasibility and effectiveness of cancer treatment. However, CVD burden has not been comprehensively described in pancreatic cancer. In our systematic review and meta-analysis, we evaluated the prevalence and incidence of CVDs in pancreatic ductal adenocarcinoma [...] Read more.

Background/Objectives: Cardiovascular diseases (CVDs) frequently limit the feasibility and effectiveness of cancer treatment. However, CVD burden has not been comprehensively described in pancreatic cancer. In our systematic review and meta-analysis, we evaluated the prevalence and incidence of CVDs in pancreatic ductal adenocarcinoma (PDAC). Methods: We conducted the systematic search in PubMed, EMBASE, and CENTRAL on 5 February 2024. Studies reporting the prevalence or incidence of CVDs in PDAC were included. Subgroup analyses were performed based on cancer stage and treatment type. Pooled proportions with the 95% confidence interval (CI) were calculated using a random-effects model. (PROSPERO: CRD42023482295). Results: We included 197 articles. At PDAC diagnosis, non-thrombotic cardiovascular diseases (NT-CVDs) were as prevalent as in the general population: hypertension in 33% (CI: 27–40%), ischemic heart disease in 6% (CI: 3–12%), and heart failure, arrhythmia, and stroke each in 2–3%. Their incidence during treatment remained low (1–10%). Thrombotic events, excluding pulmonary embolism, were present in 11% (CI: 7–15%) at diagnosis, with an incidence of 8–10% regardless of stage or treatment. Pulmonary embolism affected 3% at diagnosis and occurred at a similar rate during treatment. Conclusions: Thromboembolic events are common in PDAC and occur both at diagnosis and during follow-up. Their incidence remains stable across treatment modalities and disease stages, suggesting that the tumor itself is the primary driver of thrombotic risk. The prevalence of NT-CVDs in PDAC is comparable to that in the general population and shows minimal variation across cancer stages or treatment modalities. Full article

(This article belongs to the Topic Hepatobiliary and Pancreatic Diseases: Novel Strategies of Diagnosis and Treatments—Second Edition)

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30 pages, 7385 KB  

Open AccessReview

Spectrum of Biliary Lesions/Neoplasms in Hepatic Parenchyma with Reference to a Precursor of Small Duct-Type Intrahepatic Cholangiocarcinoma: Comprehensive Categorization into Three Groups

by Yasuni Nakanuma, Motoko Sasaki, Yuko Kakuda and Takuma Oishi

Cancers 2026, 18(2), 328; https://doi.org/10.3390/cancers18020328 - 21 Jan 2026

Viewed by 1606

Abstract

Intrahepatic cholangiocarcinomas (iCCAs) are histologically subdivided into small duct-type (SD-iCCA) and large duct-type (LD-iCCA). LD-iCCA versus SD-iCCA may differ in the molecular/genetic profiles and oncogenesis, including precursor lesions. While several precursors, such as high-grade biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm of [...] Read more.

Intrahepatic cholangiocarcinomas (iCCAs) are histologically subdivided into small duct-type (SD-iCCA) and large duct-type (LD-iCCA). LD-iCCA versus SD-iCCA may differ in the molecular/genetic profiles and oncogenesis, including precursor lesions. While several precursors, such as high-grade biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm of bile duct (IPNB), have been proposed for LD-iCCA, the potential SD-iCCA precursors remain to be identified. Amid growing interests in the precursors of SD-iCCA, benign “biliary lesions/neoplasms developing in the hepatic parenchyma (BLNP)” such as von Meyenburg complexes (VMCs), bile duct adenomas (BDAs), and biliary adenofibroma (BAF), have been noted to determine whether they have the potential for precursor of SD-iCCA. Herein, these BLNPs were reviewed. BLNP can be classified into three categories. First, traditional VMC and BDA in normal livers which lack atypical features are categorized as “traditional BLNP”. Second, a constellation of several lesions such as VMC and BDA detectable in the background livers of SD-iCCA and in chronic liver disease (unusual VMC and BDA), VMC with dysplastic features, BDA located in the deep hepatic parenchyma, multiple BDA, BDA presenting the BRAF V600E mutation, and BAF harboring variable dysplasia or in situ carcinomas, which may include neoplastic lesions but do not show invasive growth, are categorized as “unusual/dysplastic BLNP”. Third, tubulocystic carcinoma with BAF-like features (AI-TCC) and SD-iCCA with ductal plate malformation (DPMP) which share overlapping features and show relatively good post-operative outcomes and retained features of VMC or DPM, and BDA and BAF, are categorized as “low-grade malignant BLNP”. While the first category is benign and may not be related to SD-iCCA, some of the second category may be related to SD-iCCA, and the third category is malignant and shows invasive growth. The latter two categories may form a common biliary tumorigenic spectrum involving BLNP. Precursors of SD-iCCA, if they exist, may be included in the second category, and the third category may represent unique carcinomas possibly associated with or followed by conventional SD-iCCA. In conclusion, this novel approach to categorize BLNPs into three categories guarantees further studies of precursors of and their progression to conventional SD-iCCA. Full article

(This article belongs to the Topic Hepatobiliary and Pancreatic Diseases: Novel Strategies of Diagnosis and Treatments—Second Edition)

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14 pages, 1176 KB  

Open AccessSystematic Review

The Efficacy of Electronic Health Record-Based Artificial Intelligence Models for Early Detection of Pancreatic Cancer: A Systematic Review and Meta-Analysis

by George G. Makiev, Igor V. Samoylenko, Valeria V. Nazarova, Zahra R. Magomedova, Alexey A. Tryakin and Tigran G. Gevorkyan

Cancers 2026, 18(2), 315; https://doi.org/10.3390/cancers18020315 - 20 Jan 2026

Viewed by 1809

Abstract

Background: The persistently low 5-year survival rate for pancreatic cancer (PC) underscores the critical need for early detection. However, population-wide screening remains impractical. Artificial Intelligence (AI) models using electronic health record (EHR) data offer a promising avenue for pre-symptomatic risk stratification. Objective: To [...] Read more.

Background: The persistently low 5-year survival rate for pancreatic cancer (PC) underscores the critical need for early detection. However, population-wide screening remains impractical. Artificial Intelligence (AI) models using electronic health record (EHR) data offer a promising avenue for pre-symptomatic risk stratification. Objective: To systematically review and meta-analyze the performance of AI models for PC prediction based exclusively on structured EHR data. Methods: We systematically searched PubMed, MedRxiv, BioRxiv, and Google Scholar (2010–2025). Inclusion criteria encompassed studies using EHR-derived data (excluding imaging/genomics), applying AI for PC prediction, reporting AUC, and including a non-cancer cohort. Two reviewers independently extracted data. Random-effects meta-analysis was performed for AUC, sensitivity (Se), and specificity (Sp) using R software version 4.5.1. Heterogeneity was assessed using I² statistics and publication bias was evaluated. Results: Of 946 screened records, 19 studies met the inclusion criteria. The pooled AUC across all models was 0.785 (95% CI: 0.759–0.810), indicating good overall discriminatory ability. Neural Network (NN) models demonstrated a statistically significantly higher pooled AUC (0.826) compared to Logistic Regression (LogReg, 0.799), Random Forests (RF, 0.762), and XGBoost (XGB, 0.779) (all p < 0.001). In analyses with sufficient data, models like Light Gradient Boosting (LGB) showed superior Se and Sp (99% and 98.7%, respectively) compared to NNs and LogReg, though based on limited studies. Meta-analysis of Se and Sp revealed extreme heterogeneity (I² ≥ 99.9%), and the positive predictive values (PPVs) reported across studies were consistently low (often < 1%), reflecting the challenge of screening a low-prevalence disease. Conclusions: AI models using EHR data show significant promise for early PC detection, with NNs achieving the highest pooled AUC. However, high heterogeneity and typically low PPV highlight the need for standardized methodologies and a targeted risk-stratification approach rather than general population screening. Future prospective validation and integration into clinical decision-support systems are essential. Full article

(This article belongs to the Topic Hepatobiliary and Pancreatic Diseases: Novel Strategies of Diagnosis and Treatments—Second Edition)

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