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Cancers
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Improving Surgical Care for Patients with Hepatobiliary and Pancreatic Cancers
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Improving Surgical Care for Patients with Hepatobiliary and Pancreatic Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (28 February 2026) | Viewed by 12782

Special Issue Editors

Dr. Christopher B. Nahm

E-Mail Website
Guest Editor
Westmead Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2565, Australia
Interests: pancreatic cancer; cholangiocarcinoma; biomarkers; colorectal liver metastases; hepatocellular carcinoma
Dr. Kai M. Brown

E-Mail Website
Guest Editor
1. Cancer Surgery and Metabolism Research Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia
2. Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, St Leonards, NSW 2065, Australia
3. Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, NSW 2052, Australia
Interests: cancer; colorectal cancer; research facilitation; surgery; upper gastrointestinal cancer

Special Issue Information

Dear Colleagues, 

Cancers of the hepatic, pancreatic and biliary (HPB) system are associated with poor prognosis, with the majority of cases presenting at an advanced stage, rendering them unsuitable for potentially curative surgical resection. For the proportion of patients who have localized disease amenable to resection, surgery is normally a major under-taking, carrying a moderate risk of short- and medium-term morbidity. This is especially problematic, given that many patients who undergo this major surgery experience the problem of early disease recurrence. There is there-fore a great need for enhancement of patient selection for these procedures, development of alternative treatment strategies for patients at high risk of early disease recurrence, and also a review of peri- and intra-operative strategies to enhance recovery from major HPB surgery. This special edition will address the discovery of prognostic biomarkers in HPB cancer, biomarker-driven treatment strategies for HPB cancer, and the relationship between short-term and oncological outcomes after major HPB surgery. 

Dr. Christopher B. Nahm
Dr. Kai M. Brown
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hepatobiliary
  • pancreatic
  • surgery
  • biomarkers
  • prognosis
  • treatment strategy

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Published Papers (6 papers)

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Research

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15 pages, 1404 KB  
Article
Decoding Surgical Complexity: Measuring the Impact of Operative Difficulty on Quality Outcomes Following Hepatectomy for Liver Cancer over Two Decades
by Meet Patel, Jonathan Ben Daniel, Nazim Bhimani, Anthony R. Glover and Thomas J. Hugh
Cancers 2026, 18(3), 407; https://doi.org/10.3390/cancers18030407 - 27 Jan 2026
Viewed by 791
Abstract
Introduction: Operative time is commonly used as a surrogate marker for operative difficulty in liver resection, but the contribution of other intraoperative factors is less understood. This study aimed to develop an objective, composite score to assess operative difficulty and evaluate its [...] Read more.
Introduction: Operative time is commonly used as a surrogate marker for operative difficulty in liver resection, but the contribution of other intraoperative factors is less understood. This study aimed to develop an objective, composite score to assess operative difficulty and evaluate its association with postoperative and oncological outcomes in liver surgery. Methods: A retrospective cohort study was conducted on patients who underwent liver resection for malignant disease between 1999 and 2023 at an Australian tertiary hospital, using a prospectively maintained database. Principal component analysis (PCA) was applied to operative time, estimated blood loss, total time of hepatic inflow occlusion and the number of packed red bloods transfused intraoperatively to derive a composite operative difficulty score. Patients were then stratified into low, moderate and high difficult groups using Gaussian mixture models (GMM). Comparison of textbook oncological outcomes (TOO) achievement and futile resection rates were assessed using Chi-squared analysis. Kaplan-Meier analysis was used to assess recurrence-free and overall survival in subgroup analysis. Results: Of 729 patients, 699 met the inclusion criteria. GMM identified three distinct operative difficulty groups: low (n = 540), moderate (n = 143), and high (n = 16). TOO and non-futile resection rates declined with increasing difficulty: 77% and 58% (low), 47% and 52% (moderate), and 6% and 19% (high), respectively (p < 0.001, p = 0.004 respectively). Among patients with cholangiocarcinoma, median overall survival was inversely correlated with operative difficulty (40 months low, 16 months moderate, 7 months high, p = 0.004). In patients with colorectal liver metastases, there was a trend towards worse overall survival and disease-free survival with increasing operative difficulty, however, this did not reach statistical significance. Conclusions: An objective intraoperative difficulty score was developed and demonstrated a significant inverse association with both quality and oncological outcomes. While external validation is required, these findings support the potential of operative difficulty assessment to enhance perioperative decision-making, inform patient counselling, and optimise postoperative care planning. Full article
(This article belongs to the Special Issue Improving Surgical Care for Patients with Hepatobiliary and Pancreatic Cancers)
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Review

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18 pages, 565 KB  
Review
Sarcopenia as a Marker of Immunometabolic Vulnerability in Pancreatic Ductal Adenocarcinoma
by Mukund Karthik, Sara Shahrestani, Jin-soo Park, Christian Ratnayake and Charbel Sandroussi
Cancers 2026, 18(8), 1205; https://doi.org/10.3390/cancers18081205 - 9 Apr 2026
Viewed by 536
Abstract
Despite advances in surgical technique and perioperative care, pancreatic ductal adenocarcinoma (PDAC) remains associated with poor survival. Sarcopenia is highly prevalent in PDAC and is consistently associated with inferior survival and reduced tolerance of systemic therapy. However, interventions primarily aimed at increasing muscle [...] Read more.
Despite advances in surgical technique and perioperative care, pancreatic ductal adenocarcinoma (PDAC) remains associated with poor survival. Sarcopenia is highly prevalent in PDAC and is consistently associated with inferior survival and reduced tolerance of systemic therapy. However, interventions primarily aimed at increasing muscle mass through nutritional supplementation and resistance-based exercise have yielded limited improvements in clinically meaningful postoperative outcomes. This has prompted increasing interest in sarcopenia as a marker of broader biological vulnerability rather than isolated physical deconditioning. Emerging clinical, translational, and experimental evidence demonstrates that skeletal muscle and adipose tissue function as active immunometabolic organs, and that cancer-associated inflammatory pathways drive early muscle loss, immune dysfunction, and impaired physiological recovery. Across multiple clinical cohorts, sarcopenia is reproducibly associated with worse overall survival and failure to complete adjuvant therapy, but not consistently with increased postoperative complications, suggesting that its prognostic relevance lies in impaired recovery and oncological fitness rather than immediate surgical risk. Translational studies further indicate that sarcopenia identifies patients with reduced antitumor immune competence, particularly in early-stage disease. This review synthesizes current evidence linking sarcopenia, immune dysfunction, and surgical outcomes in PDAC and examines implications for perioperative care. We propose that immunometabolic-informed prehabilitation, integrated with existing nutritional and exercise strategies, may represent a more effective approach to improving recovery, treatment tolerance, and durable oncological outcomes following PDAC resection. Full article
(This article belongs to the Special Issue Improving Surgical Care for Patients with Hepatobiliary and Pancreatic Cancers)
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22 pages, 917 KB  
Review
Reducing Complications in Pancreaticoduodenectomy
by Josh B. Karpes, Ken Liu, Michael D. Crawford, Carlo Pulitano, Charbel Sandroussi and Jerome M. Laurence
Cancers 2026, 18(4), 630; https://doi.org/10.3390/cancers18040630 - 14 Feb 2026
Viewed by 983
Abstract
Pancreatic surgery is a technically demanding field associated with frequent morbidity, with pancreatic fistula representing the dominant driver of major complications in pancreaticoduodenectomy (PD). Although refinements in operative technique, perioperative management, and institutional systems have contributed to incremental improvements, the overall incidence of [...] Read more.
Pancreatic surgery is a technically demanding field associated with frequent morbidity, with pancreatic fistula representing the dominant driver of major complications in pancreaticoduodenectomy (PD). Although refinements in operative technique, perioperative management, and institutional systems have contributed to incremental improvements, the overall incidence of clinically relevant complications has remained largely unchanged over recent decades. This narrative review provides a comprehensive overview of current strategies aimed at reducing morbidity and mortality after pancreaticoduodenectomy, focusing on modifiable technical, pharmacological, nutritional, and systems-based interventions, whilst acknowledging the underlying biological determinants that remain difficult to alter. This review synthesises contemporary evidence on fistula risk modelling, anastomotic reconstruction, and adjunctive operative techniques. The role of pharmacological interventions is examined alongside an evaluation of perioperative nutritional optimisation and enhanced recovery frameworks. Systems-based strategies such as centralisation, failure-to-rescue performance, protocolised pathways, and algorithm-driven postoperative surveillance are highlighted as emerging areas with substantial potential to impact survival independently of complication rates. Finally, this review explores future directions, including radiomics-based risk stratification, intraoperative imaging, and tailored postoperative care. Together, these domains provide a platform for reducing complication severity, standardising postoperative care, and ultimately improving patient outcomes. By integrating these perspectives, this review aims to present a comprehensive and in-depth narrative of how to reduce complications in pancreas surgery. Overall, this narrative review proposes that meaningful improvements in outcomes after PD likely do not arise from the elimination of complications altogether, but rather from improved prediction, prevention where possible, and critically, more effective systems of care that reduce the severity and consequences of complications when they occur. Full article
(This article belongs to the Special Issue Improving Surgical Care for Patients with Hepatobiliary and Pancreatic Cancers)
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27 pages, 730 KB  
Review
Non-Surgical Interventions for the Prevention of Clinically Relevant Postoperative Pancreatic Fistula—A Narrative Review
by Nadya Rykina-Tameeva, Jaswinder S. Samra, Sumit Sahni and Anubhav Mittal
Cancers 2023, 15(24), 5865; https://doi.org/10.3390/cancers15245865 - 15 Dec 2023
Cited by 8 | Viewed by 4378
Abstract
Clinically relevant postoperative pancreatic fistula (CR-POPF) is the leading cause of morbidity and mortality after pancreatic surgery. Post-pancreatectomy acute pancreatitis (PPAP) has been increasingly understood as a precursor and exacerbator of CR-POPF. No longer believed to be the consequence of surgical technique, the [...] Read more.
Clinically relevant postoperative pancreatic fistula (CR-POPF) is the leading cause of morbidity and mortality after pancreatic surgery. Post-pancreatectomy acute pancreatitis (PPAP) has been increasingly understood as a precursor and exacerbator of CR-POPF. No longer believed to be the consequence of surgical technique, the solution to preventing CR-POPF may lie instead in non-surgical, mainly pharmacological interventions. Five databases were searched, identifying eight pharmacological preventative strategies, including neoadjuvant therapy, somatostatin and its analogues, antibiotics, analgesia, corticosteroids, protease inhibitors, miscellaneous interventions with few reports, and combination strategies. Two further non-surgical interventions studied were nutrition and fluids. New potential interventions were also identified from related surgical and experimental contexts. Given the varied efficacy reported for these interventions, numerous opportunities for clarifying this heterogeneity remain. By reducing CR-POPF, patients may avoid morbid sequelae, experience shorter hospital stays, and ensure timely delivery of adjuvant therapy, overall aiding survival where prognosis, particularly in pancreatic cancer patients, is poor. Full article
(This article belongs to the Special Issue Improving Surgical Care for Patients with Hepatobiliary and Pancreatic Cancers)
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Other

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20 pages, 892 KB  
Systematic Review
Evidence Mapping of ctDNA Reporting in Pancreatic Ductal Adenocarcinoma: Toward a Shared Quantitative Language for ctDNA
by Daniel Croagh and Saeed Aslani
Cancers 2026, 18(8), 1318; https://doi.org/10.3390/cancers18081318 - 21 Apr 2026
Viewed by 563
Abstract
Background/Objectives: Circulating tumour DNA (ctDNA) assays enable non-invasive assessment of tumour burden and treatment response in oncology. However, quantitative ctDNA outputs (such as variant allele frequency, tumour fraction, and aggregate burden scores) remain difficult to interpret and compare across platforms. This evidence-mapping [...] Read more.
Background/Objectives: Circulating tumour DNA (ctDNA) assays enable non-invasive assessment of tumour burden and treatment response in oncology. However, quantitative ctDNA outputs (such as variant allele frequency, tumour fraction, and aggregate burden scores) remain difficult to interpret and compare across platforms. This evidence-mapping review evaluates current quantitative reporting approaches in pancreatic ductal adenocarcinoma (PDAC) and examines the potential role of KRAS mutant ctDNA as a biologically grounded reference metric. Methods: A systematic literature search was conducted across PubMed/MEDLINE and Scopus to identify studies reporting quantitative ctDNA metrics in PDAC. Eligible studies included those measuring plasma KRAS mutations and/or reporting variant allele frequency, tumour fraction, or multi-locus aggregate metrics. Additional relevant primary studies identified through broader manual searching of PubMed were assessed against the same prespecified eligibility and classification criteria before inclusion. Data were synthesised narratively, focusing on reporting frameworks, units of measurement, assay characteristics, and the interpretability of quantitative outputs across platforms. Results: Substantial heterogeneity was observed in ctDNA quantification methods and reporting standards. Ratio-based metrics such as variant allele frequency and tumour fraction were commonly used but varied according to assay design, plasma input volume, and background cell-free DNA levels. Few studies reported absolute mutant molecule counts per unit volume. Given that approximately 90–95% of PDACs harbour truncal activating KRAS mutations, plasma KRAS was consistently represented across platforms and demonstrated potential as a shared quantitative anchor. Limited standardisation was noted in distinguishing detectability from quantifiability based on sampling depth and counting statistics. Conclusions: Current ctDNA reporting in PDAC lacks a shared quantitative reference, limiting cross-study comparability. Reporting KRAS mutant molecules per millilitre and adopting an assay-agnostic framework distinguishing detection from quantification may improve interpretability, support harmonisation across platforms, and facilitate cumulative learning in pancreatic cancer ctDNA research. Full article
(This article belongs to the Special Issue Improving Surgical Care for Patients with Hepatobiliary and Pancreatic Cancers)
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24 pages, 603 KB  
Systematic Review
Systematic Review of Preoperative Prognostic Biomarkers in Perihilar Cholangiocarcinoma
by Rishaan Pawaskar, Kevin Zhang Huang, Helen Pham, Adnan Nagrial, Mark Wong, Siobhan O’Neill, Henry Pleass, Lawrence Yuen, Vincent W. T. Lam, Arthur Richardson, Tony Pang and Christopher B. Nahm
Cancers 2024, 16(4), 698; https://doi.org/10.3390/cancers16040698 - 7 Feb 2024
Cited by 9 | Viewed by 4253
Abstract
Perihilar cholangiocarcinoma (pCCA) is an uncommon malignancy with generally poor prognosis. Surgery is the primary curative treatment; however, the perioperative mortality and morbidity rates are high, with a low 5-year survival rate. Use of preoperative prognostic biomarkers to predict survival outcomes after surgery [...] Read more.
Perihilar cholangiocarcinoma (pCCA) is an uncommon malignancy with generally poor prognosis. Surgery is the primary curative treatment; however, the perioperative mortality and morbidity rates are high, with a low 5-year survival rate. Use of preoperative prognostic biomarkers to predict survival outcomes after surgery for pCCA are not well-established currently. This systematic review aimed to identify and summarise preoperative biomarkers associated with survival in pCCA, thereby potentially improving treatment decision-making. The Embase, Medline, and Cochrane databases were searched, and a systematic review was performed using the PRISMA guidelines. English-language studies examining the association between serum and/or tissue-derived biomarkers in pCCA and overall and/or disease-free survival were included. Our systematic review identified 64 biomarkers across 48 relevant studies. Raised serum CA19-9, bilirubin, CEA, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and tumour MMP9, and low serum albumin were most associated with poorer survival; however, the cutoff values used widely varied. Several promising molecular markers with prognostic significance were also identified, including tumour HMGA2, MUC5AC/6, IDH1, PIWIL2, and DNA index. In conclusion, several biomarkers have been identified in serum and tumour specimens that prognosticate overall and disease-free survival after pCCA resection. These, however, require external validation in large cohort studies and/or in preoperatively obtained specimens, especially tissue biopsy, to recommend their use. Full article
(This article belongs to the Special Issue Improving Surgical Care for Patients with Hepatobiliary and Pancreatic Cancers)
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