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Article: Non-Surgical Interventions for the Prevention of Clinically Relevant Postoperative Pancreatic Fistula-A Narrative Review.

Rykina-Tameeva, Nadya / Samra, Jaswinder S / Sahni, Sumit / Mittal, Anubhav

2023 Volume 15, Issue 24

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- ... ...

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 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.
Language	English
Publishing date	2023-12-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15245865
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Postoperative pancreatitis and pancreatic fistulae: a review of current evidence.

Chui, Juanita N / Sahni, Sumit / Samra, Jaswinder S / Mittal, Anubhav

HPB : the official journal of the International Hepato Pancreato Biliary Association

2023 Volume 25, Issue 9, Page(s) 1011–1021

Abstract: Objectives: Postoperative pancreatic fistula (POPF) represents one of the most severe complications following pancreatic surgery. Despite being a leading cause of morbidity and mortality, its pathophysiology is poorly understood. In recent years, there ... ...

Abstract	Objectives: Postoperative pancreatic fistula (POPF) represents one of the most severe complications following pancreatic surgery. Despite being a leading cause of morbidity and mortality, its pathophysiology is poorly understood. In recent years, there has been growing evidence to support the role of postoperative or post-pancreatectomy acute pancreatitis (PPAP) in the development of POPF. This article reviews the contemporary literature on POPF pathophysiology, risk factors, and prevention strategies. Methods: A literature search was conducted using electronic databases, including Ovid Medline, EMBASE, and Cochrane Library, to retrieve relevant literature published between 2005 and 2023. A narrative review was planned from the outset. Results: A total of 104 studies fulfilled criteria for inclusion. Forty-three studies reported on technical factors predisposing to POPF, including resection and reconstruction technique and adjuncts for anastomotic reinforcement. Thirty-four studies reported on POPF pathophysiology. There is compelling evidence to suggest that PPAP plays a critical role in the development of POPF. The acinar component of the remnant pancreas should be regarded as an intrinsic risk factor; meanwhile, operative stress, remnant hypoperfusion, and inflammation represent common mechanisms for acinar cell injury. Conclusions: The evidence base for PPAP and POPF is evolving. Future POPF prevention strategies should look beyond anastomotic reinforcement and target underlying mechanisms of PPAP development.
MeSH term(s)	Humans ; Pancreatic Fistula/prevention & control ; Pancreatitis/etiology ; Pancreatitis/complications ; Acute Disease ; Pancreas/surgery ; Pancreatectomy/adverse effects ; Pancreatectomy/methods ; Risk Factors ; Postoperative Complications/surgery ; Retrospective Studies ; Pancreaticoduodenectomy/adverse effects
Chemical Substances	N-(3-phenyl-n-propyl)-1-phenyl-2-aminopropane (131903-56-5)
Language	English
Publishing date	2023-05-11
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2131251-5
ISSN	1477-2574 ; 1365-182X
ISSN (online)	1477-2574
ISSN	1365-182X
DOI	10.1016/j.hpb.2023.05.007
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Article: Drain fluid biomarkers for prediction and diagnosis of clinically relevant postoperative pancreatic fistula: A narrative review.

Rykina-Tameeva, Nadya / Samra, Jaswinder S / Sahni, Sumit / Mittal, Anubhav

World journal of gastrointestinal surgery

2022 Volume 14, Issue 10, Page(s) 1089–1106

Abstract: Clinically relevant postoperative pancreatic fistula (CR-POPF) has continued to compromise patient recovery post-pancreatectomy despite decades of research seeking to improve risk prediction and diagnosis. The current diagnostic criteria for CR-POPF ... ...

Abstract	Clinically relevant postoperative pancreatic fistula (CR-POPF) has continued to compromise patient recovery post-pancreatectomy despite decades of research seeking to improve risk prediction and diagnosis. The current diagnostic criteria for CR-POPF requires elevated drain fluid amylase to present alongside POPF-related complications including infection, haemorrhage and organ failure. These worrying sequelae necessitate earlier and easily obtainable biomarkers capable of reflecting evolving CR-POPF. Drain fluid has recently emerged as a promising source of biomarkers as it is derived from the pancreas and hence, capable of reflecting its postoperative condition. The present review aims to summarise the current knowledge of CR-POPF drain fluid biomarkers and identify gaps in the field to invigorate future research in this critical area of clinical need. These findings may provide robust diagnostic alternatives for CR-POPF and hence, to clarify their clinical utility require further reports detailing their diagnostic and/or predictive accuracy.
Language	English
Publishing date	2022-10-26
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2573700-4
ISSN	1948-9366
ISSN	1948-9366
DOI	10.4240/wjgs.v14.i10.1089
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Article ; Online: Novel serum protein biomarker panel for early diagnosis of pancreatic cancer.

Byeon, Sooin / McKay, Matthew J / Molloy, Mark P / Gill, Anthony J / Samra, Jaswinder S / Mittal, Anubhav / Sahni, Sumit

International journal of cancer

2024

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Late presentation of disease at the time of diagnosis is one of the major reasons for dismal prognostic outcomes for PDAC patients. Currently, there is a lack of clinical biomarkers, ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Late presentation of disease at the time of diagnosis is one of the major reasons for dismal prognostic outcomes for PDAC patients. Currently, there is a lack of clinical biomarkers, which can be used to diagnose PDAC patients at an early resectable stage. This study performed proteomic mass spectrometry to identify novel blood-based biomarkers for early diagnosis of PDAC. Serum specimens from 88 PDAC patients and 88 healthy controls (60 discovery cohort and 28 validation cohort) were analyzed using data independent acquisition high resolution mass spectrometry to identify candidate biomarker proteins. A total of 249 proteins were identified and quantified by the mass spectrometric analysis. Six proteins were markedly (>1.5 fold) and significantly (p < .05; q < 0.1) increased in PDAC patients compared to healthy controls in discovery cohort. Notably, four of these six proteins were significantly upregulated in an independent validation cohort. The top three upregulated proteins (i.e., Polymeric Immunoglobulin Receptor [PIGR], von Willebrand Factor [vWF], and Fibrinogen) were validated using enzyme linked immunosorbent assay, which led to selection of PIGR and vWF as a diagnostic biomarker panel for PDAC. The panel showed high ability to diagnose early stage (stage I and II) PDAC patients (area under the curve [AUC]: 0.8926), which was further improved after the addition of clinically used prognostic biomarker (Ca 19-9) to the panel (AUC: 0.9798). In conclusion, a novel serum protein biomarker panel for early diagnosis of PDAC was identified.
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.34928
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Article ; Online: Drain fluid biomarkers for the diagnosis of clinically relevant postoperative pancreatic fistula: a diagnostic accuracy systematic review and meta-analysis.

Rykina-Tameeva, Nadya / MacCulloch, Daniel / Hipperson, Luke / Ulyannikova, Yulia / Samra, Jaswinder S / Mittal, Anubhav / Sahni, Sumit

International journal of surgery (London, England)

2023 Volume 109, Issue 8, Page(s) 2486–2499

Abstract: Background: Pancreatectomy is the only curative treatment available for pancreatic cancer and a necessity for patients with challenging pancreatic pathology. To optimize outcomes, postsurgical complications such as clinically relevant postoperative ... ...

Abstract	Background: Pancreatectomy is the only curative treatment available for pancreatic cancer and a necessity for patients with challenging pancreatic pathology. To optimize outcomes, postsurgical complications such as clinically relevant postoperative pancreatic fistula (CR-POPF) should be minimized. Central to this is the ability to predict and diagnose CR-POPF, potentially through drain fluid biomarkers. This study aimed to assess the utility of drain fluid biomarkers for predicting CR-POPF by conducting a diagnostic test accuracy systematic review and meta-analysis. Methods: Five databases were searched for relevant and original papers published from January 2000 to December 2021, with citation chaining capturing additional studies. The QUADAS-2 tool was used to assess the risk of bias and concerns regarding applicability of the selected studies. Results: Seventy-eight papers were included in the meta-analysis, encompassing six drain biomarkers and 30 758 patients with a CR-POPF prevalence of 17.42%. The pooled sensitivity and specificity for 15 cut-offs were determined. Potential triage tests (negative predictive value >90%) were identified for the ruling out of CR-POPF and included postoperative day 1 (POD1) drain amylase in pancreatoduodenectomy (PD) patients (300 U/l) and in mixed surgical cohorts (2500 U/l), POD3 drain amylase in PD patients (1000-1010 U/l) and drain lipase in mixed surgery groups (180 U/l). Notably, drain POD3 lipase had a higher sensitivity than POD3 amylase, while POD3 amylase had a higher specificity than POD1. Conclusions: The current findings using the pooled cut-offs will offer options for clinicians seeking to identify patients for quicker recovery. Improving the reporting of future diagnostic test studies will further clarify the diagnostic utility of drain fluid biomarkers, facilitating their inclusion in multivariable risk-stratification models and the improvement of pancreatectomy outcomes.
MeSH term(s)	Humans ; Pancreatic Fistula/diagnosis ; Pancreatic Fistula/etiology ; Pancreatic Fistula/surgery ; Pancreas/surgery ; Pancreatectomy/adverse effects ; Pancreaticoduodenectomy/adverse effects ; Postoperative Complications/diagnosis ; Postoperative Complications/etiology ; Postoperative Complications/surgery ; Drainage/adverse effects ; Biomarkers ; Amylases ; Risk Factors
Chemical Substances	Biomarkers ; Amylases (EC 3.2.1.-)
Language	English
Publishing date	2023-08-01
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	2212038-5
ISSN	1743-9159 ; 1743-9191
ISSN (online)	1743-9159
ISSN	1743-9191
DOI	10.1097/JS9.0000000000000482
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Article ; Online: Heterogeneous tumor microenvironment in pancreatic ductal adenocarcinoma: An emerging role of single-cell analysis.

Byeon, Sooin / du Toit-Thompson, Taymin / Gillson, Josef / Gill, Anthony J / Samra, Jaswinder S / Mittal, Anubhav / Sahni, Sumit

Cancer medicine

2023 Volume 12, Issue 17, Page(s) 18020–18031

Abstract: Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies in the world, for which the mortality is almost as high as the disease incidence and is predicted to be the second-highest cause of cancer-related deaths by 2030. ... ...

Abstract	Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies in the world, for which the mortality is almost as high as the disease incidence and is predicted to be the second-highest cause of cancer-related deaths by 2030. These cancerous tumors consist of diversified gene expressions within the different cellular subpopulations that include neoplastic ductal cells, cancer-associated fibroblasts, and immune cells, all of which collectively facilitate cellular heterogeneity in the PDAC tumor microenvironment (TME). Active intratumoral interaction within the cell populations in TME induces the proliferation of cancerous cells, accounting for tumorigenesis and rapid metastasis. Methods: This review will focus on novel findings uncovering PDAC heterogeneity in different cellular subpopulations using single-cell RNA-sequencing (scRNA-seq) and other single-cell analysis technologies. It will further explore the emerging role of single-cell technologies in assessing the role of different subpopulations of neoplastic ductal cells, cancer-associated fibroblasts, and immune cells in PDAC progression. Results and conclusion: The application of scRNA-seq in PDAC has started to unveil associations between disease progression and heterogeneity in pancreatic TME and could influence future PDAC treatment. Recent advances in scRNA-seq have uncovered comprehensive analyses of heterogeneous ecosystems present within the TME. These emerging findings underpins further need for a more in-depth understanding of intratumoral heterogeneity in the PDAC microenvironment.
Language	English
Publishing date	2023-08-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.6407
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The role of diagnostic, prognostic, and predictive biomarkers in the management of early pancreatic cancer.

Maloney, Sarah / Clarke, Stephen J / Sahni, Sumit / Hudson, Amanda / Colvin, Emily / Mittal, Anubhav / Samra, Jaswinder / Pavlakis, Nick

Journal of cancer research and clinical oncology

2023 Volume 149, Issue 14, Page(s) 13437–13450

Abstract: Despite modern advances in cancer medicine, pancreatic cancer survival remains unchanged at just 12%. For the small proportion of patients diagnosed with 'early' (upfront or borderline resectable) disease, recurrences are common, and many recur soon ... ...

Abstract	Despite modern advances in cancer medicine, pancreatic cancer survival remains unchanged at just 12%. For the small proportion of patients diagnosed with 'early' (upfront or borderline resectable) disease, recurrences are common, and many recur soon after surgery. Whilst chemotherapy has been shown to increase survival in this cohort, the morbidity of surgery renders many candidates unsuitable for adjuvant treatment. Due to this, and the success of upfront chemotherapy in the advanced setting, use of neoadjuvant chemotherapy has been introduced in patients with upfront or borderline resectable disease. Randomized controlled trials have been conducted to compare upfront surgery to neoadjuvant chemotherapy in this patient cohort, opinions on the ideal upfront treatment approach are divided. This lack of consensus has highlighted the need for biomarkers to assist in clinical decision making. This review analyses the potential diagnostic, prognostic and predictive biomarkers that may assist in the diagnosis and management of early (upfront and borderline resectable) pancreatic cancer.
Language	English
Publishing date	2023-07-17
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-023-05149-4
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Article ; Online: Serum and tissue metallome of pancreatic ductal adenocarcinoma.

Byeon, Sooin / du Toit-Thompson, Taymin / Hipperson, Luke / Maloney, Sarah / Wenzel, Ross / Gill, Anthony J / Samra, Jaswinder S / Mittal, Anubhav / Sahni, Sumit

Cancer science

2024

Abstract: Pancreatic ductal adenocarcinoma (PDAC) patients have late presentation at the time of diagnosis and a poor prognosis. Metal dyshomeostasis is known to play a role in cancer progression. However, the blood and tissue metallome of PDAC patients has not ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) patients have late presentation at the time of diagnosis and a poor prognosis. Metal dyshomeostasis is known to play a role in cancer progression. However, the blood and tissue metallome of PDAC patients has not been assessed. This study aimed to determine the levels of essential and toxic metals in the serum and pancreatic tissue from PDAC patients. Serum samples were obtained from PDAC patients before surgical resection. Tissue (tumor and adjacent normal pancreas) were obtained from the surgically resected specimen. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis was performed to quantify the levels of 10 essential and 3 toxic metals in these samples. Statistical analysis was performed to identify dysregulated metals in PDAC and their role as potential diagnostic and prognostic biomarkers. Significantly decreased serum levels of magnesium, potassium, calcium, iron, zinc, selenium, arsenic, and mercury and increased levels of molybdenum were shown to be associated with PDAC. There were significantly decreased levels of zinc, manganese and molybdenum, and increased levels of calcium and selenium in the pancreatic tumor tissue compared with the adjacent normal pancreas. Notably, lower serum levels of calcium, iron, and selenium, and higher levels of manganese, were significantly associated with a poor prognosis (i.e., overall survival) in PDAC patients. In conclusion, this is the first study to comprehensively assess the serum and tissue metallome of PDAC patients. It identified the association of metals with PDAC diagnosis and prognosis.
Language	English
Publishing date	2024-03-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1349-7006
ISSN (online)	1349-7006
ISSN	1349-7006
DOI	10.1111/cas.16124
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Article ; Online: Data independent acquisition of plasma biomarkers of response to neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma

O'Rourke, Matthew B. / Sahni, Sumit / Samra, Jaswinder / Mittal, Anubhav / Molloy, Mark P.

Journal of Proteomics. 2021 Jan., v. 231 p.103998-

2021

Abstract: The detection of disease-related plasma biomarkers has challenged the proteomic community for years. Attractive features for plasma proteomics includes the ease of collection and small volume needed for analysis, but on the other hand, the presence of ... ...

Abstract	The detection of disease-related plasma biomarkers has challenged the proteomic community for years. Attractive features for plasma proteomics includes the ease of collection and small volume needed for analysis, but on the other hand, the presence of highly abundant proteins complicates sample preparation procedures and reduces dynamic range. Data independent acquisition label free quantitation (DIA-LFQ) by mass spectrometry partly overcomes the dynamic range issue; however, generating the peptide spectral reference libraries that allow extensive analysis of the plasma proteome can be a slow and expensive task which is unattainable for many laboratories. We investigated the re-purposing of publically available plasma proteome datasets and the impact on peptide/protein detection for DIA-LFQ. We carried out these studies in the context of identifying putative biomarkers of response to neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma, as no useful plasma biomarkers have been clinically adopted. We demonstrated the benefit in searching DIA data against multiple spectral libraries to show that complement proteins were linked to NAC response in PDAC patients, confirming previous observations of the prognostic utility of complement following adjuvant chemotherapy. Our workflow demonstrates that DIA-LFQ can be readily applied in the oncology setting for the putative assignment of clinically relevant plasma biomarkers. The proteomic mass spectrometry analysis of undepleted, unfractionated human plasma has benefits for sample throughput but remains challenging to obtain deep coverage. This work evaluated the re-purposing of open source peptide mass spectrometry data from human plasma to create spectral reference libraries for use in Data independent acquisition (DIA). We showed how seeding in locally acquired data to integrate iRT peptides into spectral libraries increased identification confidence by facilitating querying of multiple libraries. This workflow was applied to the discovery of putative plasma biomarkers for response to neoadjuvant chemotherapy (NAC) in pancreatic ductal adenocarcinoma patients. There is a paucity of prior information in the literature on this topic and we show that good responder patients have reduced levels of complement proteins.
Keywords	adenocarcinoma ; adjuvants ; biomarkers ; complement ; data collection ; drug therapy ; humans ; mass spectrometry ; peptides ; proteome ; proteomics ; Data-independent acquisition ; Pancreatic cancer ; Plasma ; Biomarker ; Neoadjuvant chemotherapy
Language	English
Dates of publication	2021-01
Publishing place	Elsevier B.V.
Document type	Article ; Online
ZDB-ID	2400835-7
ISSN	1876-7737 ; 1874-3919
ISSN (online)	1876-7737
ISSN	1874-3919
DOI	10.1016/j.jprot.2020.103998
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Article: Corrigendum: Serum Biomarker Panel for Diagnosis and Prognosis of Pancreatic Ductal Adenocarcinomas.

Mehta, Shreya / Bhimani, Nazim / Gill, Anthony J / Samra, Jaswinder S / Sahni, Sumit / Mittal, Anubhav

Frontiers in oncology

2021 Volume 11, Page(s) 774861

Abstract: This corrects the article DOI: 10.3389/fonc.2021.708963.]. ...

Abstract	[This corrects the article DOI: 10.3389/fonc.2021.708963.].
Language	English
Publishing date	2021-10-06
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.774861
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