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Hussain MS, Prajapati BG, Gandhi SM, Sharma M, Kapoor DU, Elossaily GM, Garg S. Overcoming Obstacles: The Role of Lipid Nanocarriers in Therapeutic Approaches for Pancreatic Cancer. BIONANOSCIENCE 2025; 15:262. [DOI: 10.1007/s12668-025-01873-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/20/2025] [Indexed: 05/04/2025]
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Garcia MA, Braun UK, Imam S, Poon I, Jackson L. Pancreatic Enzyme Supplementation for Patients with Pancreatic Cancer #500. J Palliat Med 2025. [PMID: 39984171 DOI: 10.1089/jpm.2025.0037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/23/2025] Open
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Biswas S, Afrose S, Mita MA, Hasan MR, Shimu MSS, Zaman S, Saleh MA. Next-Generation Sequencing: An Advanced Diagnostic Tool for Detection of Pancreatic Disease/Disorder. JGH Open 2024; 8:e70061. [PMID: 39605899 PMCID: PMC11599877 DOI: 10.1002/jgh3.70061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 11/05/2024] [Accepted: 11/11/2024] [Indexed: 11/29/2024]
Abstract
The pancreas is involved in digestion and glucose regulation in the human body. Given the recognized link between chronic pancreatitis and pancreatic cancer, addressing pancreatic disorders and pancreatic cancer is particularly challenging. This review aims to highlight the limitations of traditional methods in diagnosing pancreatic disorders and cancer and explore several next-generation sequencing (NGS) approaches as a promising alternative. There are distinct clinical symptoms that are shared by a number of clinical phenotypes of pancreatic illness induced by particular genetic mutations. Traditional diagnostic methods encompass computed tomography, magnetic resonance imaging, contrast-enhanced Doppler ultrasound, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, transabdominal ultrasound, laparoscopy, and positron emission tomography have a prognostic ability of only 5% or less and a 5-year survival rate. Genetic sequencing can be employed as an alternative to conventional diagnostic techniques. Sanger sequencing and NGS are currently largely operated genome analysis, with no exception for pancreatic disease diagnosis. The NGS methods can sequence millions to billions of short DNA fragments, enabling enormous sample screening in a short amount of time with low-abundance detection, like in 0.1%-1% mutation prevalence declining approximate cost. Whole-genome sequencing, whole-exome sequencing, RNA sequencing, and single-cell NGS are a few NGS methods utilized to diagnose pancreatic disease. For both research and clinical applications, the NGS techniques can provide a precise diagnosis of pancreatic disorders in a short amount of time at a reasonable expenditure.
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Affiliation(s)
- Suvro Biswas
- Miocrobiology Laboratory, Department of Genetic Engineering and BiotechnologyUniversity of RajshahiBangladesh
| | - Shamima Afrose
- Department of Genetic Engineering and BiotechnologyUniversity of RajshahiRajshahiBangladesh
| | - Mohasana Akter Mita
- Department of Genetic Engineering and BiotechnologyUniversity of RajshahiRajshahiBangladesh
| | - Md. Robiul Hasan
- Department of Genetic Engineering and BiotechnologyUniversity of RajshahiRajshahiBangladesh
| | | | - Shahriar Zaman
- Miocrobiology Laboratory, Department of Genetic Engineering and BiotechnologyUniversity of RajshahiBangladesh
| | - Md. Abu Saleh
- Miocrobiology Laboratory, Department of Genetic Engineering and BiotechnologyUniversity of RajshahiBangladesh
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Machicado JD, Sheth SG, Chalhoub JM, Forbes N, Desai M, Ngamruengphong S, Papachristou GI, Sahai V, Nassour I, Abidi W, Alipour O, Amateau SK, Coelho-Prabhu N, Cosgrove N, Elhanafi SE, Fujii-Lau LL, Kohli DR, Marya NB, Pawa S, Ruan W, Thiruvengadam NR, Thosani NC, Qumseya BJ. American Society for Gastrointestinal Endoscopy guideline on role of endoscopy in the diagnosis and management of solid pancreatic masses: methodology and review of evidence. Gastrointest Endosc 2024; 100:e1-e78. [PMID: 39269378 DOI: 10.1016/j.gie.2024.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 06/02/2024] [Indexed: 09/15/2024]
Affiliation(s)
- Jorge D Machicado
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
| | - Sunil G Sheth
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Jean M Chalhoub
- Division of Gastroenterology and Hepatology, Staten Island University Hospital, Northwell Health, Staten Island, New York, USA
| | - Nauzer Forbes
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Madhav Desai
- Center for Interventional Gastroenterology at UTHealth, McGovern Medical School, Houston, Texas, USA
| | - Saowanee Ngamruengphong
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Georgios I Papachristou
- Division of Gastroenterology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Vaibhav Sahai
- Division of Hematology and Oncology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Ibrahim Nassour
- Division of Surgical Oncology, University of Florida, Gainesville, Florida, USA
| | - Wasif Abidi
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
| | - Omeed Alipour
- Division of Gastroenterology, University of Washington Medical Center, Seattle, Washington, USA
| | - Stuart K Amateau
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | | | - Natalie Cosgrove
- Center for Interventional Endoscopy, AdventHealth, Orlando, Florida, USA
| | - Sherif E Elhanafi
- Division of Gastroenterology, Texas Tech University Health Sciences Center, El Paso, Texas, USA
| | | | - Divyanshoo R Kohli
- Pancreas and Liver Clinic, Providence Sacred Medical Center, Elon Floyd School of Medicine, Washington State University, Spokane, Washington, USA
| | - Neil B Marya
- Division of Gastroenterology, UMass Chan Medical School, Worcester, Massachusetts, USA
| | - Swati Pawa
- Department of Gastroenterology, Wake Forest School of Medicine, Winston Salem, North Carolina, USA
| | - Wenly Ruan
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Nikhil R Thiruvengadam
- Division of Gastroenterology and Hepatology, Loma Linda University, Loma Linda, California, USA
| | - Nirav C Thosani
- Center for Interventional Gastroenterology at UTHealth, McGovern Medical School, Houston, Texas, USA
| | - Bashar J Qumseya
- Department of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
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Yasinzai AQK, Tareen B, Tracy K, Jamil N, Khan M, Ullah H, Raza M, Khan AU, Arif D, Waheed A, Sidhwa F, Misra S, Karki NR, Karim NA, Cavalcante L, Ullah A. Pancreatic ductal adenocarcinoma: exploring clinicopathological trends and racial disparities in a comprehensive U.S. population-based study. Clin Transl Oncol 2024; 26:2618-2628. [PMID: 38615292 DOI: 10.1007/s12094-024-03484-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 03/25/2024] [Indexed: 04/15/2024]
Abstract
INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy about 50% of PDAC are metastatic at presentation. In this study, we evaluated PDAC demographics, annual trend analysis, racial disparities, survival rate, and the role of different treatment modalities in localized and metastatic disease. METHODS A total of 144,824 cases of PDAC were obtained from the SEER database from 2000 to 2018. RESULTS The median age was 69 years, with a slightly higher incidence in males (52%) and 80% of all cases were white. Among cases with available data, 43% were grade III tumors and 57% were metastatic. The most common site of metastasis was the liver (15.7%). The annual incidence has increased steadily from 2000 to 2018. The overall observed (OS) 5-year survival rate was 4.4% (95% CI 4.3-4.6%), and 5 years cause-specific survival (CSS) was 5% (95% CI 5.1-5.4%). The 5-year survival with multimodal therapy (chemotherapy, surgery, and radiation) was 22% (95% CI 20.5-22.8%). 5-year CSS for the blacks was lower at 4.7% (95% CI 4.2-5.1%) compared to the whites at 5.3% (95% CI 5.1-5.4%). Multivariate analysis found male gender and black race associated with worse prognosis. Kaplan-Meier survival analysis found multimodal therapy to have the best outcomes in all three stages. CONCLUSION PDAC is an aggressive malignancy with male gender and black race are associated with a poor prognosis. Surgery with chemoradiation was associated with the best overall survival. With steadily increasing rates of PDAC, improved treatment modalities are paramount to improving survival in these patients.
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Affiliation(s)
| | - Bisma Tareen
- Department of Medicine, Bolan Medical College, Quetta, 83700, Pakistan
| | | | - Nimra Jamil
- Department of Medicine, Bolan Medical College, Quetta, 83700, Pakistan
| | - Marjan Khan
- Internal Medicine, Marshfield Medical Center, Marshfield, USA
| | - Hafeez Ullah
- Department of Medicine, Bolan Medical College, Quetta, 83700, Pakistan
| | - Muhammad Raza
- Department of Medicine, Bolan Medical College, Quetta, 83700, Pakistan
| | - Amin Ullah Khan
- Department of Medicine, Bolan Medical College, Quetta, 83700, Pakistan
| | - Dauod Arif
- Department of Oncology Developmental Therapeutics, Novant Health, Charlotte, NC, USA
| | - Abdul Waheed
- Department of Surgery, San Joaquin General Hospital, French Camp, CA, 95231, USA
| | - Feroze Sidhwa
- Department of Surgery, San Joaquin General Hospital, French Camp, CA, 95231, USA
| | - Subhasis Misra
- Department of Surgery, BayCare Health System, Tampa, FL, USA
| | - Nabin Raj Karki
- Department of Oncology, Mitchell Cancer Institute, University of South Alabama, Mobile, USA
| | - Nagla Abdel Karim
- Department of Hematology-Oncology, Inova Schar Cancer Institute, University of Virginia, Fairfax, VA, 22031, USA
| | - Ludimila Cavalcante
- Department of Oncology Developmental Therapeutics, Novant Health, Charlotte, NC, USA
| | - Asad Ullah
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA
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Elebo N, Mpinganjira MG, Baichan P, Devar J, Omoshoro-Jones J, Francis JM, Smith M, Nweke EE. The need for research targeting the link between occupational carcinogens and hepatopancreatobiliary cancers in Africa: A systematic review. Transl Oncol 2024; 47:102036. [PMID: 38878612 PMCID: PMC11225925 DOI: 10.1016/j.tranon.2024.102036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/25/2024] [Accepted: 06/11/2024] [Indexed: 07/08/2024] Open
Abstract
INTRODUCTION Hepatopancreatobiliary (HPB) cancers encompassing malignancies of the liver, pancreas, gall bladder, and bile ducts pose a significant health burden in Africa. While the association of certain occupational carcinogens in cancer is well established globally, their potential role in HPB cancers remains understudied, especially in an African context. AIM This systematic review delves into the association between occupational carcinogens and HPB cancer in Africa. It examines the current state of research on occupational carcinogens and HPB cancers in Africa, identifying key challenges and knowledge gaps. METHODS This systematic review examined publications (published between 01 January 2012 and 31 May 2023) that highlight occupational carcinogens and HBP cancers in Africa. The search was conducted on electronic databases namely PubMed, Web of Science, and Africa Wide Information. RESULT Due to the lack of information on the association between occupational carcinogens and HPB cancers in Africa, as a result of the paucity of published studies, only four articles were included in this study. Hepatocellular carcinoma (HCC) was the predominant cancer associated with the occupational carcinogen, aflatoxin. Agricultural workers, especially those involved in the production and processing of maize and peanuts, appear to be the most exposed to aflatoxin. CONCLUSION Despite the sample size limitations due to the paucity of research studies on occupational carcinogens and HPB cancers in Africa, this study provides a reasonable tool for subsequent epidemiological studies. There is a need for more research on the association of occupational carcinogens and HPB cancers in Africa, especially with the growing industrialization.
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Affiliation(s)
- Nnenna Elebo
- Department of Surgery, Faculty of Health Sciences, University of Witwatersrand. Johannesburg 2193, Gauteng, South Africa; International Centre for Genetic Engineering and Biotechnology, Anzio Road, Observatory 7925, Cape Town, South Africa
| | - Mafuno Grace Mpinganjira
- Department of Family Medicine, Faculty of Health Sciences, University of Witwatersrand. Johannesburg 2193, Gauteng, South Africa
| | - Pavan Baichan
- Department of Surgery, Faculty of Health Sciences, University of Witwatersrand. Johannesburg 2193, Gauteng, South Africa
| | - John Devar
- Department of Surgery, Faculty of Health Sciences, University of Witwatersrand. Johannesburg 2193, Gauteng, South Africa; Hepatopancreatobiliary unit, Department of Surgery, Chris Hani-Baragwanath Academic Hospital, Soweto Johannesburg, South Africa
| | - Jones Omoshoro-Jones
- Department of Surgery, Faculty of Health Sciences, University of Witwatersrand. Johannesburg 2193, Gauteng, South Africa; Hepatopancreatobiliary unit, Department of Surgery, Chris Hani-Baragwanath Academic Hospital, Soweto Johannesburg, South Africa
| | - Joel Msafiri Francis
- Department of Family Medicine, Faculty of Health Sciences, University of Witwatersrand. Johannesburg 2193, Gauteng, South Africa
| | - Martin Smith
- Department of Surgery, Faculty of Health Sciences, University of Witwatersrand. Johannesburg 2193, Gauteng, South Africa; Hepatopancreatobiliary unit, Department of Surgery, Chris Hani-Baragwanath Academic Hospital, Soweto Johannesburg, South Africa
| | - Ekene Emmanuel Nweke
- Department of Surgery, Faculty of Health Sciences, University of Witwatersrand. Johannesburg 2193, Gauteng, South Africa; Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Florida, Roodepoort, South Africa.
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Nirmal C, Jayarajah U, Wijesinghe H, Fernandopulle N, Subasinghe D. Atypical hepatic metastases of pancreatic adenocarcinoma unveiled through persistent and unresolved pyrexia: Case report. SAGE Open Med Case Rep 2024; 12:2050313X241264952. [PMID: 39071196 PMCID: PMC11282560 DOI: 10.1177/2050313x241264952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 06/06/2024] [Indexed: 07/30/2024] Open
Abstract
Diagnosing neoplastic fever requires excluding identifiable causes, making it a diagnostic challenge. Fever as a primary manifestation of pancreatic adenocarcinoma is uncommon with few cases reported in the literature. Here we present an unusual case of metastatic pancreatic adenocarcinoma primarily manifesting as pyrexia of unknown origin. A 63-year-old Sri Lankan male, a non-smoker who was diagnosed with diabetes, hypertension and dyslipidaemia presented with a history of fever, anorexia and weight loss for 2 months. Despite the completion of treatment for positive serology for paratyphi, his symptoms and inflammatory markers remained elevated while the rest of the infectious screening was negative. On further evaluation, the patient was found to have a hypodense distal pancreas with ring-enhancing multiple liver lesions on imaging. Histology confirmed pancreatic adenocarcinoma with liver metastasis. Atypical liver metastases may present with evidence of ring enhancement in computed tomography imaging; thus, the biopsy is mandatory for diagnosis and decision-making. Usually, tumours of the pancreatic tail are resectable but if they are associated with liver metastatic disease, surgical resection is not recommended because it is not potentially curative. Therefore, in the context of metastatic pancreatic adenocarcinoma, palliative chemotherapy and pharmacological management of fever are required.
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Affiliation(s)
- Chamod Nirmal
- University Surgical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka
| | - Umesh Jayarajah
- University Surgical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka
- Department of Surgery, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Harshima Wijesinghe
- Department of Pathology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Nilesh Fernandopulle
- University Surgical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka
- Department of Surgery, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Duminda Subasinghe
- University Surgical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka
- Department of Surgery, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
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Yoon WJ. Public Fear of Pancreatic Diseases: Causes and Clinical Outcomes at a Single Korean Center. Gut Liver 2024; 18:756-760. [PMID: 38938175 PMCID: PMC11249942 DOI: 10.5009/gnl240241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 06/09/2024] [Accepted: 06/16/2024] [Indexed: 06/29/2024] Open
Abstract
Background/Aims The public fear of pancreatic diseases including pancreatic cancer (PC) appears to be growing. The aims of this study were to evaluate the causes of fear of pancreatic diseases and assess clinical outcomes of such individuals. Methods This was a retrospective study of 249 individuals who visited the Pancreatobiliary Diseases Center at Ewha Womans University Seoul Hospital due to the fear of pancreatic diseases between January 2019 and August 2021. Those referred from other departments or external medical facilities were excluded. Collected data included demographic details, comorbidities, causes of fear of pancreatic diseases, and the presence of pancreatic lesions in imaging studies. Results The median age was 55 years (range, 22 to 82 years). One hundred eleven subjects (44.6%) were male. The causes of fear of pancreatic diseases were abdominal pain (n=144, 57.8%), back pain (n=114, 45.8%), body weight change (n=35, 14.1%), family history of pancreatic diseases (n=32, 12.9%), and others (n=39, 15.7%). Within the group with family history of pancreatic diseases, 25 subjects had a first-degree relative with PC. Of the 200 subjects who underwent imaging, there was no evidence of pancreatic diseases in 182 (91.0%). Pancreatic lesions identified were cystic lesions (n=15, 7.5%), non-specific calcification (n=1, 0.5%), lipoma (n=1, 0.5%), and solid tumor (n=1, 0.5%), later diagnosed as unresectable PC. Conclusions Abdominal pain and back pain were the major causes of fear of pancreatic diseases. The prevalence of PC among those who underwent imaging was 0.5%. Such characteristics should be considered when consulting individuals with fear of pancreatic diseases.
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Affiliation(s)
- Won Jae Yoon
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
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Fromer MW, Xu Q, Shindorf ML, Mouw TJ, Kong M, Myers J, Feygin Y, Ghosh I, Martin RCG, McMasters KM, Philips P, Scoggins CR, Ellis CT, Egger ME. Diagnosis of Pancreatic Cancer after Cholecystectomy in the Elderly. Am Surg 2024; 90:1195-1201. [PMID: 38205662 DOI: 10.1177/00031348241227165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2024]
Abstract
BACKGROUND Previous studies evaluating whether recent cholecystectomy is associated with a pancreas cancer diagnosis are limited. We aimed to examine if cholecystectomy was performed more frequently in the year prior to cancer diagnosis than would be expected in a similar non-cancer population. METHODS SEER-Medicare linked files were used to identify patients with pancreatic adenocarcinoma. Cancer diagnoses were considered to be "timely" if within 2 months of cholecystectomy or "delayed" if 2-12 months after cholecystectomy. Clinical factors and survival outcomes were compared using chi-square and Kaplan-Meier analyses. RESULTS Rate of cholecystectomy in the year prior to diagnosis of cancer was 1.9% for the cancer group, compared to .4% in the non-cancer group (OR = 4.7, 95% CI 4.4-5.1). Differences in the cancer vs non-cancer cohorts at the time of cholecystectomy included a higher age (74 vs 70, P < .0001), more males (49.9% vs 41.7%, P < .0001), and more frequent open technique (21.0% vs 9.4%, P < .0001). Acute pancreatitis was nearly twice as common in the cancer cohort (19.1%) vs the non-cancer cohort (10.7%), P < .0001. There were no differences between patients who had a timely diagnosis after cholecystectomy compared to a delayed diagnosis with regard to age, gender, comorbidity index, race, or rural/urban designation. The rates of localized disease and subsequent resection were also similar between the delayed and timely groups. Overall unadjusted survival was no different between timely and delayed diagnoses, P = .96. DISCUSSION Elderly patients diagnosed with pancreatic adenocarcinoma are more likely to have had a recent cholecystectomy compared to those without.
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Affiliation(s)
- Marc W Fromer
- Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Qian Xu
- Department of Surgery, University of Louisville, Louisville, KY, USA
| | | | - Tyler J Mouw
- Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Maiying Kong
- Department of Surgery, University of Louisville, Louisville, KY, USA
| | - John Myers
- Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Yana Feygin
- Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Indranil Ghosh
- Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Robert C G Martin
- Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Kelly M McMasters
- Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Prejesh Philips
- Department of Surgery, University of Louisville, Louisville, KY, USA
| | | | - C T Ellis
- Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Michael E Egger
- Department of Surgery, University of Louisville, Louisville, KY, USA
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Cai Z, Yao H, Chen J, Ahmed AA, Li C, Hu X, Tang X, Jiang C. Schwann cells in pancreatic cancer: Unraveling their multifaceted roles in tumorigenesis and neural interactions. Cancer Lett 2024; 587:216689. [PMID: 38367898 DOI: 10.1016/j.canlet.2024.216689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/15/2024] [Accepted: 01/26/2024] [Indexed: 02/19/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC), characterized by heightened neural density, presents a challenging prognosis primarily due to perineural invasion. Recognized for their crucial roles in neural support and myelination, Schwann cells (SCs) significantly influence the process of tumorigenesis. This review succinctly outlines the interplay between PDAC and neural systems, positioning SCs as a nexus in the tumor-neural interface. Subsequently, it delves into the cellular origin and influencers of SCs within the pancreatic tumor microenvironment, emphasizing their multifaceted roles in tumor initiation, progression, and modulation of the neural and immune microenvironment. The discussion encompasses potential therapeutic interventions targeting SCs. Lastly, the review underscores pressing issues, advocating for sustained exploration into the diverse contributions of SCs within the intricate landscape of PDAC, with the aim of enhancing our understanding of their involvement in this complex malignancy.
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Affiliation(s)
- Zhiwei Cai
- Department of General Surgery, Pancreatobiliary Surgery Center, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, PR China
| | - Hongfei Yao
- Department of General Surgery, Pancreatobiliary Surgery Center, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, PR China
| | - Jiahao Chen
- Department of General Surgery, Pancreatobiliary Surgery Center, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, PR China
| | - Abousalam Abdoulkader Ahmed
- Department of General Surgery, Pancreatobiliary Surgery Center, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, PR China
| | - Chunjing Li
- Department of General Surgery, Pancreatobiliary Surgery Center, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, PR China
| | - Xiao Hu
- Department of General Surgery, Pancreatobiliary Surgery Center, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, PR China
| | - Xiaoyan Tang
- Department of General Surgery, Pancreatobiliary Surgery Center, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, PR China
| | - Chongyi Jiang
- Department of General Surgery, Pancreatobiliary Surgery Center, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, PR China.
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Garcia MAG, Imam S, Braun UK, Jackson LK. Rational Prescribing of Pancreatic Enzymes for Patients with Pancreatic Cancer. PHARMACY 2024; 12:47. [PMID: 38525727 PMCID: PMC10961774 DOI: 10.3390/pharmacy12020047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 02/26/2024] [Accepted: 03/01/2024] [Indexed: 03/26/2024] Open
Abstract
Most patients with pancreatic cancer at some point present with symptoms related to exocrine pancreatic insufficiency (EPI). These include diarrhea, abdominal bloating, indigestion, steatorrhea, weight loss, and anorexia. Even though up to 80% of pancreatic cancer patients eventually present with symptoms related to exocrine pancreatic insufficiency, only 21% are prescribed pancreatic enzyme replacement therapy (PERT). Its effectiveness is also highly dependent on its proper timing of administration, and patients must be thoroughly educated about this. The impact of symptoms of EPI can lead to poorer overall well-being. Pharmacists play a crucial role in properly educating patients on the correct use of pancreatic enzyme replacement therapy. PERT is a key strategy in managing the symptoms of EPI and can improve quality of life, which is a central focus in palliative care. This treatment is profoundly underutilized in the palliative care of these patients. The objective of this review is to discuss the pharmacology, pharmacokinetics, side effects, available evidence of the effectiveness of pancreatic enzyme use for patients with pancreatic cancer, and challenges, along with proposed solutions regarding its use.
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Affiliation(s)
- Mary Acelle G. Garcia
- Rehabilitation & Extended Care Line, Section of Palliative Medicine, Michael E DeBakey Veteran Affairs Medical Center, Houston, TX 77030, USA; (S.I.); (U.K.B.); (L.K.J.)
- Department of Medicine, Section of Geriatric and Palliative Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Syed Imam
- Rehabilitation & Extended Care Line, Section of Palliative Medicine, Michael E DeBakey Veteran Affairs Medical Center, Houston, TX 77030, USA; (S.I.); (U.K.B.); (L.K.J.)
- Department of Medicine, Section of Geriatric and Palliative Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Ursula K. Braun
- Rehabilitation & Extended Care Line, Section of Palliative Medicine, Michael E DeBakey Veteran Affairs Medical Center, Houston, TX 77030, USA; (S.I.); (U.K.B.); (L.K.J.)
- Department of Medicine, Section of Geriatric and Palliative Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Leanne K. Jackson
- Rehabilitation & Extended Care Line, Section of Palliative Medicine, Michael E DeBakey Veteran Affairs Medical Center, Houston, TX 77030, USA; (S.I.); (U.K.B.); (L.K.J.)
- Department of Medicine, Section of Geriatric and Palliative Medicine, Baylor College of Medicine, Houston, TX 77030, USA
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12
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Joseph AM, Al Aiyan A, Al-Ramadi B, Singh SK, Kishore U. Innate and adaptive immune-directed tumour microenvironment in pancreatic ductal adenocarcinoma. Front Immunol 2024; 15:1323198. [PMID: 38384463 PMCID: PMC10879611 DOI: 10.3389/fimmu.2024.1323198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 01/11/2024] [Indexed: 02/23/2024] Open
Abstract
One of the most deadly and aggressive cancers in the world, pancreatic ductal adenocarcinoma (PDAC), typically manifests at an advanced stage. PDAC is becoming more common, and by the year 2030, it is expected to overtake lung cancer as the second greatest cause of cancer-related death. The poor prognosis can be attributed to a number of factors, including difficulties in early identification, a poor probability of curative radical resection, limited response to chemotherapy and radiotherapy, and its immunotherapy resistance. Furthermore, an extensive desmoplastic stroma that surrounds PDAC forms a mechanical barrier that prevents vascularization and promotes poor immune cell penetration. Phenotypic heterogeneity, drug resistance, and immunosuppressive tumor microenvironment are the main causes of PDAC aggressiveness. There is a complex and dynamic interaction between tumor cells in PDAC with stromal cells within the tumour immune microenvironment. The immune suppressive microenvironment that promotes PDAC aggressiveness is contributed by a range of cellular and humoral factors, which itself are modulated by the cancer. In this review, we describe the role of innate and adaptive immune cells, complex tumor microenvironment in PDAC, humoral factors, innate immune-mediated therapeutic advances, and recent clinical trials in PDAC.
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Affiliation(s)
- Ann Mary Joseph
- Department of Veterinary Medicine (CAVM), United Arab Emirates University, Al Ain, United Arab Emirates
| | - Ahmad Al Aiyan
- Department of Veterinary Medicine (CAVM), United Arab Emirates University, Al Ain, United Arab Emirates
| | - Basel Al-Ramadi
- Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
- Zayed Center for Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
- ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Shiv K. Singh
- Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center, Goettingen, Germany
| | - Uday Kishore
- Department of Veterinary Medicine (CAVM), United Arab Emirates University, Al Ain, United Arab Emirates
- Zayed Center for Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
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13
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Salu P, Reindl KM. Advancements in Preclinical Models of Pancreatic Cancer. Pancreas 2024; 53:e205-e220. [PMID: 38206758 PMCID: PMC10842038 DOI: 10.1097/mpa.0000000000002277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2024]
Abstract
ABSTRACT Pancreatic cancer remains one of the deadliest of all cancer types with a 5-year overall survival rate of just 12%. Preclinical models available for understanding the disease pathophysiology have evolved significantly in recent years. Traditionally, commercially available 2-dimensional cell lines were developed to investigate mechanisms underlying tumorigenesis, metastasis, and drug resistance. However, these cells grow as monolayer cultures that lack heterogeneity and do not effectively represent tumor biology. Developing patient-derived xenografts and genetically engineered mouse models led to increased cellular heterogeneity, molecular diversity, and tissues that histologically represent the original patient tumors. However, these models are relatively expensive and very timing consuming. More recently, the advancement of fast and inexpensive in vitro models that better mimic disease conditions in vivo are on the rise. Three-dimensional cultures like organoids and spheroids have gained popularity and are considered to recapitulate complex disease characteristics. In addition, computational genomics, transcriptomics, and metabolomic models are being developed to simulate pancreatic cancer progression and predict better treatment strategies. Herein, we review the challenges associated with pancreatic cancer research and available analytical models. We suggest that an integrated approach toward using these models may allow for developing new strategies for pancreatic cancer precision medicine.
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Affiliation(s)
- Philip Salu
- From the Department of Biological Sciences, North Dakota State University, Fargo, ND
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14
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Wang B, Deng J, Donati V, Merali N, Frampton AE, Giovannetti E, Deng D. The Roles and Interactions of Porphyromonas gingivalis and Fusobacterium nucleatum in Oral and Gastrointestinal Carcinogenesis: A Narrative Review. Pathogens 2024; 13:93. [PMID: 38276166 PMCID: PMC10820765 DOI: 10.3390/pathogens13010093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 01/12/2024] [Accepted: 01/15/2024] [Indexed: 01/27/2024] Open
Abstract
Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. Porphyromonas gingivalis and Fusobacteria nucleatum, which are known periodontal pathogens, have emerged as extensively studied participants with potential pathogenic abilities in carcinogenesis. However, the complex dynamics arising from interactions between these two pathogens were less addressed. This narrative review aims to summarize the current knowledge on the prevalence and mechanism implications of P. gingivalis and F. nucleatum in the carcinogenesis of oral squamous cell carcinoma (OSCC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). In particular, it explores the clinical and experimental evidence on the interplay between P. gingivalis and F. nucleatum in affecting oral and gastrointestinal carcinogenesis. P. gingivalis and F. nucleatum, which are recognized as keystone or bridging bacteria, were identified in multiple clinical studies simultaneously. The prevalence of both bacteria species correlated with cancer development progression, emphasizing the potential impact of the collaboration. Regrettably, there was insufficient experimental evidence to demonstrate the synergistic function. We further propose a hypothesis to elucidate the underlying mechanisms, offering a promising avenue for future research in this dynamic and evolving field.
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Affiliation(s)
- Bing Wang
- Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands; (B.W.); (J.D.); (V.D.); (E.G.)
| | - Juan Deng
- Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands; (B.W.); (J.D.); (V.D.); (E.G.)
| | - Valentina Donati
- Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands; (B.W.); (J.D.); (V.D.); (E.G.)
- Unit of Pathological Anatomy 2, Azienda Ospedaliero-Universitaria Pisana, 56100 Pisa, Italy
| | - Nabeel Merali
- Minimal Access Therapy Training Unit (MATTU), Royal Surrey County Hospital, NHS Foundation Trust, Egerton Road, Guildford GU2 7XX, UK; (N.M.); (A.E.F.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, NHS Foundation Trust, Egerton Road, Guildford GU2 7XX, UK
- Section of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Medical Science, University of Surrey, Guilford GU2 7WG, UK
| | - Adam E. Frampton
- Minimal Access Therapy Training Unit (MATTU), Royal Surrey County Hospital, NHS Foundation Trust, Egerton Road, Guildford GU2 7XX, UK; (N.M.); (A.E.F.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, NHS Foundation Trust, Egerton Road, Guildford GU2 7XX, UK
- Section of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Medical Science, University of Surrey, Guilford GU2 7WG, UK
| | - Elisa Giovannetti
- Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands; (B.W.); (J.D.); (V.D.); (E.G.)
- Fondazione Pisana per la Scienza, 56100 Pisa, Italy
| | - Dongmei Deng
- Department of Prevention Dentistry, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universitreit Amsterdam, 1081 LA Amsterdam, The Netherlands
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15
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Behrens D, Pfohl U, Conrad T, Becker M, Brzezicha B, Büttner B, Wagner S, Hallas C, Lawlor R, Khazak V, Linnebacher M, Wartmann T, Fichtner I, Hoffmann J, Dahlmann M, Walther W. Establishment and Thorough Characterization of Xenograft (PDX) Models Derived from Patients with Pancreatic Cancer for Molecular Analyses and Chemosensitivity Testing. Cancers (Basel) 2023; 15:5753. [PMID: 38136299 PMCID: PMC10741928 DOI: 10.3390/cancers15245753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 12/02/2023] [Accepted: 12/05/2023] [Indexed: 12/24/2023] Open
Abstract
Patient-derived xenograft (PDX) tumor models are essential for identifying new biomarkers, signaling pathways and novel targets, to better define key factors of therapy response and resistance mechanisms. Therefore, this study aimed at establishing pancreas carcinoma (PC) PDX models with thorough molecular characterization, and the identification of signatures defining responsiveness toward drug treatment. In total, 45 PC-PDXs were generated from 120 patient tumor specimens and the identity of PDX and corresponding patient tumors was validated. The majority of engrafted PDX models represent ductal adenocarcinomas (PDAC). The PDX growth characteristics were assessed, with great variations in doubling times (4 to 32 days). The mutational analyses revealed an individual mutational profile of the PDXs, predominantly showing alterations in the genes encoding KRAS, TP53, FAT1, KMT2D, MUC4, RNF213, ATR, MUC16, GNAS, RANBP2 and CDKN2A. Sensitivity of PDX toward standard of care (SoC) drugs gemcitabine, 5-fluorouracil, oxaliplatin and abraxane, and combinations thereof, revealed PDX models with sensitivity and resistance toward these treatments. We performed correlation analyses of drug sensitivity of these PDX models and their molecular profile to identify signatures for response and resistance. This study strongly supports the importance and value of PDX models for improvement in therapies of PC.
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Affiliation(s)
- Diana Behrens
- Experimental Pharmacology and Oncology GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany (M.D.)
| | - Ulrike Pfohl
- Experimental Pharmacology and Oncology GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany (M.D.)
- CELLphenomics GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany
| | - Theresia Conrad
- Experimental Pharmacology and Oncology GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany (M.D.)
| | - Michael Becker
- Experimental Pharmacology and Oncology GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany (M.D.)
| | - Bernadette Brzezicha
- Experimental Pharmacology and Oncology GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany (M.D.)
| | - Britta Büttner
- Experimental Pharmacology and Oncology GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany (M.D.)
| | - Silvia Wagner
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, 72076 Tübingen, Germany
| | - Cora Hallas
- Institut für Hämatopathologie, Fangdieckstr. 75, 22547 Hamburg, Germany
| | - Rita Lawlor
- ARC-Net Research Center, University and Hospital Trust of Verona, Piazzale A. Scuro 10, 37134 Verona, Italy
| | | | - Michael Linnebacher
- Clinic of General Surgery, Molecular Oncology and Immunotherapy, University Medical Center Rostock, 18057 Rostock, Germany
| | - Thomas Wartmann
- University Clinic for General, Visceral, Vascular and Transplantation Surgery, Faculty of Medicine, Otto-von-Guericke-University, 39120 Magdeburg, Germany
| | - Iduna Fichtner
- Experimental Pharmacology and Oncology GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany (M.D.)
| | - Jens Hoffmann
- Experimental Pharmacology and Oncology GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany (M.D.)
| | - Mathias Dahlmann
- Experimental Pharmacology and Oncology GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany (M.D.)
| | - Wolfgang Walther
- Experimental Pharmacology and Oncology GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany (M.D.)
- Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin, Lindenberger Weg 80, 13125 Berlin, Germany
- Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany
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16
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Thalji SZ, Fernando D, Dua KS, Madhavan S, Chisholm P, Smith ZL, Aldakkak M, Christians KK, Clarke CN, George B, Kamgar M, Erickson BA, Hall WA, Evans DB, Tsai S. Biliary Adverse Events During Neoadjuvant Therapy for Pancreatic Cancer. Ann Surg 2023; 278:e1224-e1231. [PMID: 37078282 DOI: 10.1097/sla.0000000000005884] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/21/2023]
Abstract
OBJECTIVE To describe a high-volume experience with biliary drainage before neoadjuvant therapy (NAT) for patients with operable pancreatic cancer (PC) and characterize the association between biliary adverse events (BAEs) and patient outcome. BACKGROUND Patients with PC presenting with biliary obstruction require durable decompression before NAT. METHODS Patients with operable PC and tumor-associated biliary obstruction were examined and grouped by the presence or absence of a BAE during NAT. The incidence, timing, and management of BAEs are described, and outcomes, including the completion of all treatment and overall survival (OS), were compared. RESULTS Of 426 patients who received pretreatment biliary decompression, 92 (22%) experienced at least 1 BAE during NAT, and 56 (13%) required repeat intervention on their biliary stent. The median duration of NAT was 161 days for all patients and was not different in the group that experienced BAEs. The median time from initial stent placement to BAE was 64 days. An interruption in the delivery of NAT (median 7 days) occurred in 25 (6%) of 426 patients. Among 426 patients, 290 (68%) completed all NAT, including surgery: 60 (65%) of 92 patients with BAE and 230 (69%) of 334 patients without BAE ( P =0.51). Among 290 patients who completed NAT and surgery, the median OS was 39 months, 26 months for the 60 patients with BAE, and 43 months for the 230 patients without BAE ( P =0.02). CONCLUSIONS During extended multimodal NAT for PC, 22% of patients experienced a BAE. Although BAEs were not associated with a significant interruption of treatment, patients who experienced a BAE had worse OS.
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Affiliation(s)
- Sam Z Thalji
- Division of Surgical Oncology, Department of Surgery, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Deemantha Fernando
- Division of Surgical Oncology, Department of Surgery, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Kulwinder S Dua
- Division of Gastroenterology, Department of Medicine, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Srivats Madhavan
- Division of Gastroenterology, Department of Medicine, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Phillip Chisholm
- Division of Gastroenterology, Department of Medicine, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Zachary L Smith
- Division of Gastroenterology, Department of Medicine, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Mohammed Aldakkak
- Division of Surgical Oncology, Department of Surgery, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Kathleen K Christians
- Division of Surgical Oncology, Department of Surgery, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Callisia N Clarke
- Division of Surgical Oncology, Department of Surgery, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Ben George
- Division of Medical Oncology, Department of Medicine, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Mandana Kamgar
- Division of Medical Oncology, Department of Medicine, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Beth A Erickson
- Department of Radiation Oncology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - William A Hall
- Department of Radiation Oncology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Douglas B Evans
- Division of Surgical Oncology, Department of Surgery, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
| | - Susan Tsai
- Division of Surgical Oncology, Department of Surgery, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI
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17
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Chen YI, Sahai A, Donatelli G, Lam E, Forbes N, Mosko J, Paquin SC, Donnellan F, Chatterjee A, Telford J, Miller C, Desilets E, Sandha G, Kenshil S, Mohamed R, May G, Gan I, Barkun J, Calo N, Nawawi A, Friedman G, Cohen A, Maniere T, Chaudhury P, Metrakos P, Zogopoulos G, Bessissow A, Khalil JA, Baffis V, Waschke K, Parent J, Soulellis C, Khashab M, Kunda R, Geraci O, Martel M, Schwartzman K, Fiore JF, Rahme E, Barkun A. Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial). Gastroenterology 2023; 165:1249-1261.e5. [PMID: 37549753 DOI: 10.1053/j.gastro.2023.07.024] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 07/21/2023] [Accepted: 07/29/2023] [Indexed: 08/09/2023]
Abstract
BACKGROUND & AIMS Endoscopic ultrasound-guided choledochoduodenostomy with a lumen-apposing metal stent (EUS-CDS) is a promising modality for management of malignant distal biliary obstruction (MDBO) with potential for better stent patency. We compared its outcomes with endoscopic retrograde cholangiopancreatography with metal stenting (ERCP-M). METHODS In this multicenter randomized controlled trial, we recruited patients with MDBO secondary to borderline resectable, locally advanced, or unresectable peri-ampullary cancers across 10 Canadian institutions and 1 French institution. This was a superiority trial with a noninferiority assessment of technical success. Patients were randomized to EUS-CDS or ERCP-M. The primary end point was the rate of stent dysfunction at 1 year, considering competing risks of death, clinical failure, and surgical resection. Analyses were performed according to intention-to-treat principles. RESULTS From February 2019 to February 2022, 144 patients were recruited; 73 were randomized to EUS-CDS and 71 were randomized to ERCP-M. The mean (SD) procedure time was 14.0 (11.4) minutes for EUS-CDS and 23.1 (15.6) minutes for ERCP-M (P < .01); 40% of the former was performed without fluoroscopy. Technical success was achieved in 90.4% (95% CI, 81.5% to 95.3%) of EUS-CDS and 83.1% (95% CI, 72.7% to 90.1%) of ERCP-M with a risk difference of 7.3% (95% CI, -4.0% to 18.8%) indicating noninferiority. Stent dysfunction occurred in 9.6% vs 9.9% of EUS-CDS and ERCP-M cases, respectively (P = .96). No differences in adverse events, pancreaticoduodenectomy and oncologic outcomes, or quality of life were noted. CONCLUSIONS Although not superior in stent function, EUS-CDS is an efficient and safe alternative to ERCP-M in patients with MDBO. These findings provide evidence for greater adoption of EUS-CDS in clinical practice as a complementary and exchangeable first-line modality to ERCP in patients with MDBO. CLINICALTRIALS gov, Number: NCT03870386.
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Affiliation(s)
- Yen-I Chen
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada.
| | - Anand Sahai
- Service de Gastroentérologie, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada
| | - Gianfranco Donatelli
- Unité d'Endoscopie Interventionnelle, Hôpital Privé des Peupliers, Paris, France
| | - Eric Lam
- Division of Gastroenterology and Hepatology, St-Paul Hospital, Vancouver, British Columbia, Canada
| | - Nauzer Forbes
- Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
| | - Jeffrey Mosko
- Division of Gastroenterology, St-Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Sarto C Paquin
- Service de Gastroentérologie, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada
| | - Fergal Donnellan
- Division of Gastroenterology and Hepatology, Vancouver General Hospital, Vancouver, British Columbia, Canada
| | - Avijit Chatterjee
- Division of Gastroenterology and Hepatology, Ottawa Hospital, Ottawa, Ontario, Canada
| | - Jennifer Telford
- Division of Gastroenterology and Hepatology, St-Paul Hospital, Vancouver, British Columbia, Canada
| | - Corey Miller
- Division of Gastroenterology and Hepatology, Jewish General Hospital, Montreal, Quebec, Canada
| | - Etienne Desilets
- Division of Gastroenterology, Hôpital Charles-Le Moyne, Longeuil, Quebec, Canada
| | - Gurpal Sandha
- Division of Gastroenterology and Hepatology, University of Alberta Hospital, Edmonton, Alberta, Canada
| | - Sana Kenshil
- Division of Gastroenterology and Hepatology, Ottawa Hospital, Ottawa, Ontario, Canada
| | - Rachid Mohamed
- Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
| | - Gary May
- Division of Gastroenterology, St-Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Ian Gan
- Division of Gastroenterology and Hepatology, Vancouver General Hospital, Vancouver, British Columbia, Canada
| | - Jeffrey Barkun
- Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Natalia Calo
- Division of Gastroenterology and Hepatology, Vancouver General Hospital, Vancouver, British Columbia, Canada
| | - Abrar Nawawi
- Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Gad Friedman
- Division of Gastroenterology and Hepatology, Jewish General Hospital, Montreal, Quebec, Canada
| | - Albert Cohen
- Division of Gastroenterology and Hepatology, Jewish General Hospital, Montreal, Quebec, Canada
| | - Thibaut Maniere
- Division of Gastroenterology, Hôpital Charles-Le Moyne, Longeuil, Quebec, Canada
| | - Prosanto Chaudhury
- Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Peter Metrakos
- Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - George Zogopoulos
- Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Ali Bessissow
- Department of Radiology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Jad Abou Khalil
- Division of Gastroenterology and Hepatology, Ottawa Hospital, Ottawa, Ontario, Canada
| | - Vicky Baffis
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Kevin Waschke
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Josee Parent
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Constantine Soulellis
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Mouen Khashab
- Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, Maryland
| | - Rastislav Kunda
- Department of Surgery, Department of Gastroenterology-Hepatology, Department of Advanced Interventional Endoscopy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium
| | - Olivia Geraci
- Research Institute McGill University Health Centre, Montreal, Quebec, Canada
| | - Myriam Martel
- Research Institute McGill University Health Centre, Montreal, Quebec, Canada
| | - Kevin Schwartzman
- Respiratory Division, McGill University Health Centre, Montreal, Quebec, Canada
| | - Julio F Fiore
- Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Elham Rahme
- Department of Medicine, Division of Clinical Epidemiology, McGill University, Montreal, Quebec, Canada
| | - Alan Barkun
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
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18
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Carnie LE, Shah D, Vaughan K, Kapacee ZA, McCallum L, Abraham M, Backen A, McNamara MG, Hubner RA, Barriuso J, Gillespie L, Lamarca A, Valle JW. Prospective Observational Study of Prevalence, Assessment and Treatment of Pancreatic Exocrine Insufficiency in Patients with Inoperable Pancreatic Malignancy (PANcreatic Cancer Dietary Assessment-PanDA). Cancers (Basel) 2023; 15:cancers15082277. [PMID: 37190204 DOI: 10.3390/cancers15082277] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 04/07/2023] [Accepted: 04/11/2023] [Indexed: 05/17/2023] Open
Abstract
INTRODUCTION Pancreatic exocrine insufficiency (PEI) in patients with advanced pancreatic cancer (aPC) is well documented, but there is no consensus regarding optimal screening. METHODS AND ANALYSIS Patients diagnosed with aPC referred for palliative therapy were prospectively recruited. A full dietetic assessment (including Mid-Upper Arm Circumference (MUAC), handgrip and stair-climb test), nutritional blood panel, faecal elastase (FE-1) and 13C-mixed triglyceride breath tests were performed. PRIMARY OBJECTIVE prevalence of dietitian-assessed PEI (demographic cohort (De-ch)); design (diagnostic cohort (Di-ch)) and validation (follow-up cohort (Fol-ch)) of a PEI screening tool. Logistic and Cox regressions were used for statistical analysis. RESULTS Between 1 July 2018 and 30 October 2020, 112 patients were recruited (50 (De-ch), 25 (Di-ch) and 37 (Fol-ch)). Prevalence of PEI (De-ch) was 64.0% (flatus (84.0%), weight loss (84.0%), abdominal discomfort (50.0%) and steatorrhea (48.0%)). The derived PEI screening panel (Di-ch) included FE-1 (normal/missing (0 points); low (1 point)) and MUAC (normal/missing (>percentile 25) (0 points); low (2 points)) and identified patients at high-risk (2-3 total points) of PEI [vs. low-medium risk (0-1 total points)]. When patients from the De-ch and Di-ch were analysed together, those classified by the screening panel as "high-risk" had shorter overall survival (multivariable Hazard Ratio (mHR) 1.86 (95% CI 1.03-3.36); p-value 0.040). The screening panel was tested in the Fol-ch; 78.4% patients classified as "high-risk", of whom 89.6% had dietitian-confirmed PEI. The panel was feasible for use in clinical practice (64.8% patients completed all assessments), with high acceptability (87.5% would repeat it). Most patients (91.3%) recommended dietetic input for all patients with aPC. CONCLUSIONS PEI is present in most patients with aPC; early dietetic input provides a holistic nutritional overview, including, but not limited to, PEI. This proposed screening panel may help to prioritise those at higher risk of PEI, requiring urgent dietitian input. Its prognostic role needs further validation.
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Affiliation(s)
- Lindsay E Carnie
- Nutrition & Dietetics, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Dinakshi Shah
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Kate Vaughan
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
- Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK
| | - Zainul Abedin Kapacee
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | | | - Marc Abraham
- Nutrition & Dietetics, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Alison Backen
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
- Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK
| | - Mairéad G McNamara
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
- Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK
| | - Richard A Hubner
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
- Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK
| | - Jorge Barriuso
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
- Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK
| | - Loraine Gillespie
- Nutrition & Dietetics, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
- Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK
| | - Juan W Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
- Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK
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Spadaccini M, Conti Bellocchi MC, Mangiavillano B, Fantin A, Rahal D, Manfrin E, Gavazzi F, Bozzarelli S, Crinò SF, Terrin M, Di Leo M, Bonifacio C, Facciorusso A, Realdon S, Cristofori C, Auriemma F, Fugazza A, Frulloni L, Hassan C, Repici A, Carrara S. Secondary Tumors of the Pancreas: A Multicenter Analysis of Clinicopathological and Endosonographic Features. J Clin Med 2023; 12:2829. [PMID: 37109171 PMCID: PMC10145689 DOI: 10.3390/jcm12082829] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 03/17/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Many tumors may secondarily involve the pancreas; however, only retrospective autopic and surgical series are available. We retrospectively collected data from all consecutive patients with histologically confirmed secondary tumors of the pancreas referred to five Italian centers between 2010 and 2021. We described clinical and pathological features, therapeutic approach and treatment outcomes. EUS characteristics of the lesions and the tissue acquisition procedures (needle, passages, histology) were recorded. A total of 116 patients (males/females 69/47; mean age 66.7) with 236 histologically confirmed pancreatic metastases were included; kidney was the most common primary site. EUS was performed to confirm the diagnosis in 205 lesions which presented as predominantly solitary (59), hypoechoic (95) and hypervascular (60), with a heterogeneous (n = 54) pattern and well-defined borders (n = 52). EUS-guided tissue acquisition was performed in 94 patients with an overall accuracy of 97.9%. Histological evaluation was possible in 88.3% of patients, obtaining final diagnosis in all cases. When cytology alone was performed, the final diagnosis was obtained in 83.3% of cases. A total of 67 patients underwent chemo/radiation therapy, and surgery was attempted in 45 (38.8%) patients. Pancreatic metastases are a possible event in the natural history of solid tumors, even long after the diagnosis of the primary site. EUS-guided fine needle biopsy may be suggested to implement the differential diagnosis.
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Affiliation(s)
- Marco Spadaccini
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy; (M.S.)
- Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, 20089 Milan, Italy
| | - Maria Cristina Conti Bellocchi
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, 37134 Verona, Italy
| | - Benedetto Mangiavillano
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Mater Domini, 21053 Castellanza, Italy
| | - Alberto Fantin
- Gastroenterology Unit, Istituto Oncologico Veneto IOV-IRCCS, 35128 Padova, Italy
| | - Daoud Rahal
- Department of Pathology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Erminia Manfrin
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, 37134 Verona, Italy
| | - Francesca Gavazzi
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Silvia Bozzarelli
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Stefano Francesco Crinò
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, 37134 Verona, Italy
| | - Maria Terrin
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy; (M.S.)
- Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, 20089 Milan, Italy
| | - Milena Di Leo
- Digestive Endoscopy Unit, Division of Gastroenterology, San Paolo Hospital, 20090 Milan, Italy
| | - Cristiana Bonifacio
- Department of Radiology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Surgical and Medical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Stefano Realdon
- Gastroenterology Unit, Istituto Oncologico Veneto IOV-IRCCS, 35128 Padova, Italy
| | - Chiara Cristofori
- Gastroenterology Unit, Istituto Oncologico Veneto IOV-IRCCS, 35128 Padova, Italy
| | - Francesco Auriemma
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Mater Domini, 21053 Castellanza, Italy
| | - Alessandro Fugazza
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy; (M.S.)
| | - Luca Frulloni
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, 37134 Verona, Italy
| | - Cesare Hassan
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy; (M.S.)
- Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, 20089 Milan, Italy
| | - Alessandro Repici
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy; (M.S.)
- Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, 20089 Milan, Italy
| | - Silvia Carrara
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy; (M.S.)
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20
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Bashinskaya A, Kammerman J, Butson D, Moody P. Metastatic Pancreatic Acinar Cell Carcinoma: An Unlikely Culprit. Cureus 2023; 15:e38288. [PMID: 37255915 PMCID: PMC10226385 DOI: 10.7759/cureus.38288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/29/2023] [Indexed: 06/01/2023] Open
Abstract
Although acinar cells comprise a large volume of the pancreas, they rarely transform into malignant neoplasms. Once they arise, they rapidly metastasize via hematogenous spread to other organs such as the brain, liver, lung, and skeletal system. Cutaneous involvement, however, is rarely seen in all patients with primary pancreatic neoplasms. The most frequently reported site of cutaneous manifestations is the umbilicus, with the other sites including the trunk, lower extremities, head, and neck. Here, we report a case of metastatic pancreatic acinar cell carcinoma with cutaneous involvement of the patient's scalp.
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Affiliation(s)
- Alena Bashinskaya
- Osteopathic Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Clearwater, USA
| | - Jay Kammerman
- Osteopathic Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Clearwater, USA
| | - David Butson
- Dermatology, HCA Florida Brandon Hospital, Brandon, USA
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21
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Chatterjee A, Sharma N, Singh A, Franklin M, Garg R, Chahal P. Synchronous Pancreatic Masses. ACG Case Rep J 2023; 10:e01037. [PMID: 37091201 PMCID: PMC10118356 DOI: 10.14309/crj.0000000000001037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 03/27/2023] [Indexed: 04/25/2023] Open
Abstract
Any mass lesion in the pancreas usually raises the possibility of undiagnosed pancreatic cancer. With the advancement of imaging modalities, we are seeing an increasing number of incidental findings, some of which may be clinically significant. When dealing with incidental pancreatic findings, it is critical to keep a broad differential in mind in addition to ruling out pancreatic malignancy. We present 3 rare cases of patients with 2 or more synchronous solid masses in the pancreas caused by pancreatic cancer, type 1 autoimmune pancreatitis, and sarcoidosis.
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Affiliation(s)
- Arjun Chatterjee
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH
| | - Neha Sharma
- Department of Internal Medicine, University Health, San Antonio, TX
| | - Amandeep Singh
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH
| | - Matthew Franklin
- Department of Pathology, Cleveland Clinic Foundation, Cleveland, OH
| | - Rajat Garg
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH
| | - Prabhleen Chahal
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH
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22
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Lan X, Robin G, Kasnik J, Wong G, Abdel-Rahman O. Challenges in Diagnosis and Treatment of Pancreatic Exocrine Insufficiency among Patients with Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2023; 15:1331. [PMID: 36831673 PMCID: PMC9953920 DOI: 10.3390/cancers15041331] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 02/14/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas and is associated with an extremely poor prognosis. Many PDAC patients suffer from profound nutritional complications such as nutrient deficiencies, weight loss, malnutrition, and cancer cachexia. These complications cause barriers to effective anticancer treatments, gravely influence their quality of life, and decrease their overall survival. Pancreatic exocrine insufficiency (PEI) is defined as impaired digestion due to inadequate secretion of pancreatic enzymes and is a common cause of malnutrition in PDAC. This review first summarizes the existing literature around malnutrition in PDAC, with a particular focus on PEI and its management with pancreatic enzyme replacement therapy (PERT). Second, we summarize existing guidelines and recommendations for the management of PEI among patients with PDAC. Lastly, we highlight potential gaps of knowledge of PEI among healthcare providers resulting in underdiagnosis and treatment, which may have implications for the quality of life and overall survival of PDAC patients.
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Affiliation(s)
- Xiaoyang Lan
- Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Gabrielle Robin
- Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Jessica Kasnik
- Nutrition Services, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada
| | - Grace Wong
- Pharmacy Department, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada
| | - Omar Abdel-Rahman
- Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada
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23
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Montalvo-Javé EE, Nuño-Lámbarri N, López-Sánchez GN, Ayala-Moreno EA, Gutierrez-Reyes G, Beane J, Pawlik TM. Pancreatic Cancer: Genetic Conditions and Epigenetic Alterations. J Gastrointest Surg 2023; 27:1001-1010. [PMID: 36749558 DOI: 10.1007/s11605-022-05553-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 11/19/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND Pancreatic cancer is a lethal proliferative disease driven by multiple genetic and epigenetic alterations. Microarrays and omics-based sequencing techniques are potent tools that have facilitated a broader understanding of the complex biological processes that drive pancreatic ductal adenocarcinoma (PDAC). In turn, these tools have resulted in the identification of novel disease markers, prognostic factors, and therapeutic targets. Herein, we provide a review of the genetic and epigenetic drivers of PDAC relative to recent discoveries that impact patient management. METHODS A review of PubMed, Medline, Clinical Key, and Index Medicus was conducted to identify literature from January 1995 to July 2022 that is related to PDAC genetics and epigenetics. Articles in Spanish and English were considered during selection. RESULTS Molecular, genetic, and epigenetic diagnostic tools, novel biomarkers, and promising therapeutic targets have emerged in the treatment of pancreatic cancer. The implementation of microarray technology and application of large omics-based data repositories have facilitated recent discoveries in PDAC. Multiple molecular analyses based on RNA interference have been instrumental in the identification of novel therapeutic targets for patients with PDAC. Moreover, microarrays and next-generation omics-based discoveries have been instrumental in the characterization of subtypes of pancreatic cancer, thereby improving prognostication and refining patient selection for available targeted therapies. CONCLUSION Advances in molecular biology, genetics, and epigenetics have ushered in a new era of discovery in the pathobiology of PDAC. Current efforts are underway to translate these findings into clinical tools and therapies to improve outcomes in patients with PDAC.
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Affiliation(s)
- Eduardo E Montalvo-Javé
- Hepatopancreatobiliary Clinic, Department of Surgery, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico. .,Department of Surgery, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico.
| | | | | | - Edwin A Ayala-Moreno
- Department of Surgery, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico
| | - Gabriela Gutierrez-Reyes
- Liver, Pancreas and Motility Laboratory, Unit of Experimental Medicine, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico
| | - Joal Beane
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
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24
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Eptaminitaki GC, Zaravinos A, Stellas D, Panagopoulou M, Karaliota S, Baltsavia I, Iliopoulos I, Chatzaki E, Iliopoulos D, Baritaki S. Genome-Wide Analysis of lncRNA-mRNA Co-Expression Networks in CD133+/CD44+ Stem-like PDAC Cells. Cancers (Basel) 2023; 15:cancers15041053. [PMID: 36831395 PMCID: PMC9954787 DOI: 10.3390/cancers15041053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 01/20/2023] [Accepted: 02/03/2023] [Indexed: 02/11/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC), the second most prevalent gastrointestinal malignancy and the most common type of pancreatic cancer is linked with poor prognosis and, eventually, with high mortality rates. Early detection is seldom, while tumor heterogeneity and microarchitectural alterations benefit PDAC resistance to conventional therapeutics. Although emerging evidence suggest the core role of cancer stem cells (CSCs) in PDAC aggressiveness, unique stem signatures are poorly available, thus limiting the efforts of anti-CSC-targeted therapy. Herein, we report the findings of the first genome-wide analyses of mRNA/lncRNA transcriptome profiling and co-expression networks in PDAC cell line-derived CD133+/CD44+ cells, which were shown to bear a CSC-like phenotype in vitro and in vivo. Compared to CD133-/CD44- cells, the CD133+/CD44+ population demonstrated significant expression differences in both transcript pools. Using emerging bioinformatic tools, we performed lncRNA target coding gene prediction analysis, which revealed significant Gene Ontology (GO), pathway, and network enrichments in many dyregulated lncRNA nearby (cis or trans) mRNAs, with reported involvement in the regulation of CSC phenotype and functions. In this context, the construction of lncRNA/mRNA networks by ingenuity platforms identified the lncRNAs ATF2, CHEK1, DCAF8, and PAX8 to interact with "hub" SC-associated mRNAs. In addition, the expressions of the above lncRNAs retrieved by TCGA-normalized RNAseq gene expression data of PAAD were significantly correlated with clinicopathological features of PDAC, including tumor grade and stage, nodal metastasis, and overall survival. Overall, our findings shed light on the identification of CSC-specific lncRNA signatures with potential prognostic and therapeutic significance in PDAC.
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Affiliation(s)
- Giasemi C. Eptaminitaki
- Laboratory of Experimental Oncology, Division of Surgery, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Apostolos Zaravinos
- Basic and Translational Cancer Research Center (BTCRC), Genomics and Systems Biology Laboratory, Cancer Genetics, Nicosia 1516, Cyprus
- Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 2404, Cyprus
| | - Dimitris Stellas
- Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece
| | - Maria Panagopoulou
- Laboratory of Pharmacology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
- Institute of Agri-Food and Life Sciences, Hellenic Mediterranean University Research Centre, 71410 Heraklion, Greece
| | - Sevasti Karaliota
- Laboratory of Experimental Oncology, Division of Surgery, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Ismini Baltsavia
- Laboratory of Computational Biology, Division of Basic Sciences, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Ioannis Iliopoulos
- Laboratory of Computational Biology, Division of Basic Sciences, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Ekaterini Chatzaki
- Laboratory of Pharmacology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
- Institute of Agri-Food and Life Sciences, Hellenic Mediterranean University Research Centre, 71410 Heraklion, Greece
| | | | - Stavroula Baritaki
- Laboratory of Experimental Oncology, Division of Surgery, School of Medicine, University of Crete, 71003 Heraklion, Greece
- Correspondence: ; Tel.: +30-281-039-4727
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25
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Thalmann NF, Rimensberger C, Blum MR, Liechti FD, Wertli MM. [Internal differential diagnoses in acute back pain : An internal perspective on the possible causes of acute back pain]. Z Rheumatol 2023; 82:3-9. [PMID: 36094629 PMCID: PMC9894948 DOI: 10.1007/s00393-022-01257-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/06/2022] [Indexed: 02/06/2023]
Abstract
The majority of patients with acute back pain have no serious underlying disease; however, many internal diseases can be manifested as acute or chronic back pain. Therefore, in the assessment of patients with back pain the clinical history and clinical examination are important in order to detect indications for a possible underlying disease. Particularly red flags that indicate an acute or life-threatening disease should not be missed. In most cases where such red flags, risk factors or clinical indications are not present, no systematic search for internal underlying diseases is necessary. This article summarizes the most relevant differential diagnoses and clinical indications as well as warning symptoms.
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Affiliation(s)
- Nicolas F Thalmann
- Allgemeine Innere Medizin, Universitätsspital Bern, Inselspital, Freiburgstr. 18, 3010, Bern, Schweiz.
| | - Caroline Rimensberger
- Allgemeine Innere Medizin, Universitätsspital Bern, Inselspital, Freiburgstr. 18, 3010, Bern, Schweiz
| | - Manuel R Blum
- Allgemeine Innere Medizin, Universitätsspital Bern, Inselspital, Freiburgstr. 18, 3010, Bern, Schweiz
- Berner Institut für Hausarztmedizin (BIHAM), Universität Bern, Mittelstr. 43, 3012, Bern, Schweiz
| | - Fabian D Liechti
- Allgemeine Innere Medizin, Universitätsspital Bern, Inselspital, Freiburgstr. 18, 3010, Bern, Schweiz
| | - Maria M Wertli
- Allgemeine Innere Medizin, Universitätsspital Bern, Inselspital, Freiburgstr. 18, 3010, Bern, Schweiz
- Departement Innere Medizin, Kantonsspital Baden, Im Ergel 1, 5404, Baden, Schweiz
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26
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Gheorghe G, Ionescu VA, Moldovan H, Diaconu CC. Clinical and Biological Data in Patients with Pancreatic Cancer vs. Chronic Pancreatitis-A Single Center Comparative Analysis. Diagnostics (Basel) 2023; 13:369. [PMID: 36766475 PMCID: PMC9914010 DOI: 10.3390/diagnostics13030369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/15/2023] [Accepted: 01/17/2023] [Indexed: 01/21/2023] Open
Abstract
INTRODUCTION In some patients with chronic pancreatitis, the diagnosis of pancreatic cancer can be missed. The objective of the study was to identify clinical and paraclinical data with statistical significance in the differential diagnosis between chronic pancreatitis and pancreatic cancer. MATERIALS AND METHODS We conducted a retrospective, observational study on a cohort of 120 patients hospitalized over 3 years. The patients were equally distributed in two groups: group A, with 60 patients with pancreatic cancer, and group B, with 60 patients with chronic pancreatitis. The statistical analysis was carried out by using the R program. RESULTS The comparative analysis of pancreatic cancer vs. chronic pancreatitis revealed a stronger link between pancreatic cancer, female gender (p = 0.001) and age over 60 years (p < 0.001). Patients with pancreatic cancer had higher serum values of aspartate aminotransferase (p 0.005), alanine aminotransferase (p 0.006), total bilirubin (p < 0.001), direct bilirubin (p < 0.001), alkaline phosphatase (p 0.030), C-reactive protein (p = 0.049) and uric acid (p 0.001), while patients with chronic pancreatitis presented slightly higher values of amylase (p 0.020) and lipase (p 0.029). CONCLUSIONS Female gender, advanced age, elevated aminotransferases, cholestasis markers and uric acid were associated with a higher probability of pancreatic cancer.
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Affiliation(s)
- Gina Gheorghe
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania
- Gastroenterology Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Vlad Alexandru Ionescu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania
- Gastroenterology Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Horatiu Moldovan
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania
- Department of Cardiovascular Surgery, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Medical Sciences Section, Academy of Romanian Scientists, 050085 Bucharest, Romania
| | - Camelia Cristina Diaconu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania
- Medical Sciences Section, Academy of Romanian Scientists, 050085 Bucharest, Romania
- Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
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27
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Bernardes JDO, Toledo-Silva G. O Uso do Sequenciamento Total do Exoma no Diagnóstico do Adenocarcinoma Ductal Pancreático. REVISTA BRASILEIRA DE CANCEROLOGIA 2023. [DOI: 10.32635/2176-9745.rbc.2023v69n1.3006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Introdução: O adenocarcinoma ductal pancreático (PDAC) é uma doença agressiva responsável no Brasil por 2% das neoplasias e 5% das mortes por câncer. A análise do exoma – parte do DNA que codifica as proteínas – permite identificar as variantes somáticas do tumor e as germinativas do paciente. Essa informação é necessária para implementar a terapia-alvo para o PDAC, pois fornece evidência para selecionar, ou excluir, tratamentos para a doença. Objetivo: Identificar as variantes de interesse clínico e farmacológico presentes no PDAC de quatro pacientes, por meio da técnica de sequenciamento total do exoma (WES). Método: Foram utilizados dados públicos de quatro amostras de pares tumor-normal de PDAC, localizados na cabeça do pâncreas de pacientes caucasianos, estádio T3N1M0, sequenciadas e publicizadas pelo Texas Cancer Research Biobank. Para identificar as variações somáticas e germinativas, utilizou-se o software GATK. As consequências clínicas e farmacológicas dessas variações foram anotadas por meio do software VEP e analisadas mediante o software estatístico R. Resultados: Dos quatro tumores, um possui variante estrutural com duplicação do gene AKT2; outro, variantes nos genes da via das ciclinas CDK14 e CDKN2C, o que altera o regime quimioterápico; na linhagem germinativa, um paciente tem variantes no gene XRCC1, que sugere aumento da resposta à platina. Conclusão: Embora a patologia classifique todos os tumores como PDAC, cada paciente – bem como o respectivo tumor – apresenta especificidades que afetam o diagnóstico e as possibilidades terapêuticas. O WES permite identificá-las a um custo baixo, o que amplia as possibilidades de tratamento do PDAC.
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RNF7 Facilitated the Tumorigenesis of Pancreatic Cancer by Activating PI3K/Akt Signaling Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023; 2023:1728463. [PMID: 36644576 PMCID: PMC9833898 DOI: 10.1155/2023/1728463] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 12/03/2022] [Accepted: 12/14/2022] [Indexed: 01/06/2023]
Abstract
RING finger protein-7 (RNF7) functions as a positive regulator in the progression of multiple malignancies. However, the underlying mechanism by which RNF7 contributes to pancreatic cancer (PC) is lacking. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to test the level of RNF7expression in PC cell lines and tissues. The role of RNF7 in PC tumorigenesis was analyzed by Cell Counting Kit-8 (CCK-8). 5-Ethynyl-20-deoxyuridine (EdU), wound-healing/Transwell assays, as well as a subcutaneous tumorigenesis model were constructed to assess the role of RNF7 in PC cells. The association between RNF7 and PI3K/Akt signaling were assessed by western blot and further confirmed by rescue experiments. The PC patients with upregulated expression of RNF7 had poor survival. Overexpression of RNF7 significantly facilitated PC proliferative and migrative and invasive properties in vitro and vivo; however, knockdown of RNF7exhibited the opposite results. Mechanistically, RNF7 promoted PANC-1 and SW1990 cell growth through impacting the activation of the PI3K/Akt signaling pathway. Our data demonstrated that RNF7 promoted PC tumorigenesis via activating the PI3K/Akt signaling pathway and might be regarded as one of the potential therapies to PC.
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29
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Balzano V, Laurent E, Florence AM, Lecuyer AI, Lefebvre C, Heitzmann P, Hammel P, Lecomte T, Grammatico-Guillon L. Time interval from last visit to imaging diagnosis influences outcome in pancreatic adenocarcinoma: A regional population-based study on linked medico-administrative and clinical data. Ther Adv Med Oncol 2022; 14:17588359221113264. [PMID: 36090802 PMCID: PMC9449516 DOI: 10.1177/17588359221113264] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 06/24/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Excessive waiting time intervals for the diagnosis and treatment of patients with pancreatic cancer can influence their prognosis but they remain unclear. The objective was to describe time intervals from the medical visit to diagnostic imaging and to treatment and their prognostic impact in pancreatic cancer in one French region. Methods: This retrospective observational multicentre study included all patients with pancreatic cancer seen for the first time in 2017 in multidisciplinary team meetings (MTMs), where clinical data were collected. A probabilistic matching with the medico-administrative data from the French national healthcare database (Système National des Données de Santé) was performed to define the care pathway from clinical presentation to the beginning of treatment. Median key time intervals were estimated for both resected and unresected tumours. Factors associated with 1-year survival were studied using Cox model. Results: A total of 324 patients (88% of total patients with MTM presentation) were matched and included: male 54%, mean age 72 years ±9.2, Eastern Cooperative Oncology Group (ECOG) PS > 1 19.5%, metastatic disease at diagnosis 47.4%, tumour resection 16%. At 1 year, 57% had died (65% in the unresected group and 17% in the resected group). The median time interval from the medical visit to diagnostic imaging was 15 days [Q1–Q3: 8–44]. After imaging, median time intervals to definite diagnosis and to first treatment were 11 and 20 days, respectively. Significant prognostic factors associated with the risk of death at 1 year were ECOG PS > 1 (hazard ratio (HR) 2.1 [1.4–3.0]), metastasis (HR 2.7 [1.9–3.9]), no tumour resection (HR 2.7 [1.3–5.6]) and time interval between the medical visit and diagnostic imaging ⩾25 days (HR 1.7 [1.2–2.3]). Conclusion: Delay in access to diagnostic imaging impacted survival in patients with pancreatic cancer, regardless of whether tumour resection had been performed.
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Affiliation(s)
- Vittoria Balzano
- OncoCentre, Cancer network of the Centre-Val de Loire region, Tours, France.,Gastroenterology and Digestive Oncology Department, Teaching Hospital of Tours, Tours, France
| | - Emeline Laurent
- Public Health Unit, Epidemiology (EpiDcliC), Teaching Hospital of Tours, Tours, France.,Research Unit EA7505 "Education, Ethics and Health", University of Tours, Tours, France
| | - Aline-Marie Florence
- Public Health Unit, Epidemiology (EpiDcliC), Teaching Hospital of Tours, Tours, France.,Department of Public Healht, Faculty of Medicine,University of Tours, France
| | - Anne-Isabelle Lecuyer
- Public Health Unit, Epidemiology (EpiDcliC), Teaching Hospital of Tours, Tours, France.,Research Unit EA7505 "Education, Ethics and Health", University of Tours, Tours, France
| | - Carole Lefebvre
- OncoCentre, Cancer network of the Centre-Val de Loire region, Tours, France
| | - Patrick Heitzmann
- OncoCentre, Cancer network of the Centre-Val de Loire region, Tours, France
| | - Pascal Hammel
- Digestive and Medical Oncology Department, Paul Brousse University Hospital, Villejuif, France.,Paris-Saclay University, Villejuif, France
| | - Thierry Lecomte
- OncoCentre, Cancer network of the Centre-Val de Loire region, Tours, France.,University of Tours, Faculty of Medicine, Tours, France.,Gastroenterology and Digestive Oncology Department, Teaching Hospital of Tours, Tours, France
| | - Leslie Grammatico-Guillon
- Department of Public Healht, Faculty of Medicine, University of Tours, France.,Public Health Unit, Epidemiology (EpiDcliC), Teaching Hospital of Tours, 2 Boulevard Tonnellé, 37044 Tours cedex 9, France
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30
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Smith C, Zheng W, Dong J, Wang Y, Lai J, Liu X, Yin F. Tumor microenvironment in pancreatic ductal adenocarcinoma: Implications in immunotherapy. World J Gastroenterol 2022; 28:3297-3313. [PMID: 36158269 PMCID: PMC9346457 DOI: 10.3748/wjg.v28.i27.3297] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 04/22/2022] [Accepted: 06/19/2022] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers. Surgical resection is the only curable treatment option, but it is available for only a small fraction of patients at the time of diagnosis. With current therapeutic regimens, the average 5-year survival rate is less than 10% in pancreatic cancer patients. Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage. However, its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer. Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug efficacy in pancreatic cancer. In this review, we discuss the role of the tumor microenvironment in pancreatic cancer and the latest advances in immunotherapy on pancreatic cancer.
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Affiliation(s)
- Caitlyn Smith
- Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, United States
| | - Wei Zheng
- Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, United States
| | - Jixin Dong
- Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Yaohong Wang
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, United States
| | - Jinping Lai
- Department of Pathology and Laboratory Medicine, Kaiser Permanente Sacramento Medical Center, Sacramento, CA 95825, United States
| | - Xiuli Liu
- Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, United States
| | - Feng Yin
- Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO 65212, United States
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31
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Biohumoral Predictors of Advanced Pancreatic Carcinoma Not Shown at Pre-operative Imaging. Indian J Surg 2022. [DOI: 10.1007/s12262-022-03493-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
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32
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Yau CC, Leeds J. Managing inoperable pancreatic cancer: the role of the pancreaticobiliary physician. Frontline Gastroenterol 2022; 13:e88-e93. [PMID: 35812020 PMCID: PMC9234734 DOI: 10.1136/flgastro-2022-102124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 05/21/2022] [Indexed: 02/04/2023] Open
Abstract
Despite our understanding of pancreatic cancer (PC), the majority of patients with this disease are incurable. Both the incidence and mortality rates for PC have increased over the last decade. At diagnosis, the majority of patients have locally advanced PC, less than 20% of patients are eligible for potentially curative resection and approximately one-third have metastatic disease. The combination of frequent advanced presentation, low resection rates and poor responses to chemotherapy make PC one of the most lethal tumours. The treatment goals are to maintain local control, manage tumour-related morbidities and improve quality of life. Patients with inoperable PC are likely to experience significant symptoms associated with their tumour, including pancreatic insufficiency, nutritional deficiencies, pain, biliary obstruction, gastric outlet obstruction and diabetes. As a result, guidance on the management of patients with inoperable PC is critical. PC is commonly referred centrally to specialist centres particularly for surgery; however, the majority do not undergo surgical intervention and thus the importance of pancreaticobiliary physicians and endoscopists. This review will focus on the non-operative management of patients with unresectable pancreatic adenocarcinoma and review some of the issues that centralisation has contributed to.
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Affiliation(s)
- Chia Chuin Yau
- Gastroenterology, Freeman Hospital, Newcastle upon Tyne, UK
| | - John Leeds
- Gastroenterology, Freeman Hospital, Newcastle upon Tyne, UK,Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
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33
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Ilyas AM, Bohra M, More NM, Naik LP. Papanicolaou society of cytopathology system for reporting pancreaticobiliary cytology: Risk stratification and cytology scope - 2.5-year study. Cytojournal 2022; 19:33. [PMID: 35673695 PMCID: PMC9168400 DOI: 10.25259/cytojournal_46_2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 09/03/2021] [Indexed: 11/17/2022] Open
Abstract
Objectives: Diagnosis of pancreatic lesions remains a clinical challenge. Early and accurate diagnosis is extremely important for improving the therapeutic usefulness of pancreatic cancers and Endoscopic ultrasonography - fine needle aspiration (EUS-FNA) cytology has come up with this advantage. For current study the authors evaluated the diagnostic accuracy of EUS-FNAC by applying PSC system for reporting pancreaticobiliary cytology and Calculated the malignancy risk associated with the diagnostic categories. Material and Methods: A retrospective study over the period of 2.5 years (April 2017 to Oct 2019) 60 patients in our cohort EUS-FNAC guided unstained fixed and unfixed slides received of pancreatic lesion and were stained with Papanicolau and Giemsa using standard technique and immunocytochemistry, where required Application of Papanicolaou Society of Cytopathology system for reporting pancreaticobiliary cytology Histopathological and clinical follow-up were retrieved. Results: Our study has comparable results with sensitivity, specificity, PPV, and NPV of 92.8%, 100%, 100%, and 92.59%, respectively. Fuurthermore, a diagnostic accuracy of 96.2%. Risk of malignancy is lower for benign and indeterminate category whereas it is higher for suspicious and malignant categories. Conclusion: The application of the new proposed terminology for pancreaticobiliary cytology brings standardization. Final diagnosis can be reached by the multidisciplinary approach of EUS-FNA cytology, cell block preparation, immunocytochemistry, and immunohistochemistry; if required, can be adopted as an alternative approach to biopsy. The present study showed high sensitivity and specificity for EUS-FNA in the diagnosis of pancreatic carcinoma, which may influence the treatment plans of both surgeons and oncologists.
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Affiliation(s)
- Abeer M Ilyas
- Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India,
| | - Mamta Bohra
- Department of Pathology, Lokmanya Tilak Municipal General Hospital and Medical College, Mumbai, Maharashtra, India,
| | - Nilam M. More
- Department of Pathology, Lokmanya Tilak Municipal General Hospital and Medical College, Mumbai, Maharashtra, India,
| | - Leena P. Naik
- Department of Pathology, Lokmanya Tilak Municipal General Hospital and Medical College, Mumbai, Maharashtra, India,
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34
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Zakaria A, Al-Share B, Klapman JB, Dam A. The Role of Endoscopic Ultrasonography in the Diagnosis and Staging of Pancreatic Cancer. Cancers (Basel) 2022; 14:1373. [PMID: 35326524 PMCID: PMC8946253 DOI: 10.3390/cancers14061373] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 03/05/2022] [Accepted: 03/07/2022] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is the fourth leading cause of cancer-related death and the second gastrointestinal cancer-related death in the United States. Early detection and accurate diagnosis and staging of pancreatic cancer are paramount in guiding treatment plans, as surgical resection can provide the only potential cure for this disease. The overall prognosis of pancreatic cancer is poor even in patients with resectable disease. The 5-year survival after surgical resection is ~10% in node-positive disease compared to ~30% in node-negative disease. The advancement of imaging studies and the multidisciplinary approach involving radiologists, gastroenterologists, advanced endoscopists, medical, radiation, and surgical oncologists have a major impact on the management of pancreatic cancer. Endoscopic ultrasonography is essential in the diagnosis by obtaining tissue (FNA or FNB) and in the loco-regional staging of the disease. The advancement in EUS techniques has made this modality a critical adjunct in the management process of pancreatic cancer. In this review article, we provide an overall description of the role of endoscopic ultrasonography in the diagnosis and staging of pancreatic cancer.
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Affiliation(s)
- Ali Zakaria
- Department of Gastroenterology-Advanced Endoscopy, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA; (J.B.K.); (A.D.)
| | - Bayan Al-Share
- Department of Hematology and Oncology, Karmanos Cancer Center, Wayne State University, Detroit, MI 48201, USA;
| | - Jason B. Klapman
- Department of Gastroenterology-Advanced Endoscopy, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA; (J.B.K.); (A.D.)
| | - Aamir Dam
- Department of Gastroenterology-Advanced Endoscopy, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA; (J.B.K.); (A.D.)
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35
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Ward A. Pancreatic Cancer Risk and Screening Recommendations: Practice Impact. J Nurse Pract 2022. [DOI: 10.1016/j.nurpra.2022.02.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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36
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Nissinen SI, Venäläinen M, Kumpulainen P, Roine A, Häkkinen MR, Vepsäläinen J, Oksala N, Rantanen T. Discrimination between Pancreatic Cancer, Pancreatitis and Healthy Controls Using Urinary Polyamine Panel. Cancer Control 2022; 28:10732748211039762. [PMID: 35135363 PMCID: PMC8832577 DOI: 10.1177/10732748211039762] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
BACKROUND Polyamines play an important role in cellular proliferation, and the change in polyamine metabolism is reported in various cancers. We searched for urinary polyamine signature for distinguishing between pancreatic cancer, premalignant lesions of the pancreas (PLP), acute and chronic pancreatitis, and controls. METHODS Patients and controls were prospectively recruited in three Finnish hospitals between October 2013 and June 2016. The patients provided a urine sample at the time of the diagnosis. The panel of 14 polyamines was obtained in a single run with mass spectrometry. The polyamine concentrations were analysed with quadratic discriminant analysis and cross-validated with leave-one-out cross-validation. RESULTS Sixty-eight patients with pancreatic cancer, 36 with acute pancreatitis, 18 with chronic pancreatitis and 7 with PLP were recruited, as were 53 controls. The combination of 4 polyamines - acetylputrescine, diacetylspermidine, N8-acetylspermidine and diacetylputrescine - distinguished pancreatic cancer and PLP from controls (sensitivity = 94%, specificity = 68% and AUC = 0.88). The combination of diacetylspermidine, N8-acetylspermidine and diacetylspermine distinguished acute pancreatitis from controls (sensitivity = 94%, specificity = 92%, AUC = 0.98). The combination of acetylputrescine, diacetylspermidine and diacetylputrescine distinguished chronic pancreatitis from controls (sensitivity = 98%, specificity = 71%, AUC = 0.93). CONCLUSIONS Optimally selected urinary polyamine panels discriminate between pancreatic cancer and controls, as well as between acute and chronic pancreatitis and controls.
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Affiliation(s)
- Samuli I Nissinen
- Department of Internal Medicine, School of Medicine, 205537University of Eastern Finland, Kuopio, Finland.,Department of Internal Medicine, 3701Kanta-Häme Central Hospital, Hämeenlinna, Finland
| | - Markus Venäläinen
- Department of Internal Medicine, School of Medicine, 205537University of Eastern Finland, Kuopio, Finland
| | | | - Antti Roine
- Faculty of Medicine and Health Technology, 7840Tampere University, Tampere, Finland
| | - Merja R Häkkinen
- School of Pharmacy, Biocenter Kuopio, 205537University of Eastern Finland, Kuopio, Finland
| | - Jouko Vepsäläinen
- School of Pharmacy, Biocenter Kuopio, 205537University of Eastern Finland, Kuopio, Finland
| | - Niku Oksala
- Faculty of Medicine and Health Technology, 7840Tampere University, Tampere, Finland.,Centre for Vascular Surgery and Interventional Radiology, 60670Tampere University Hospital, Tampere, Finland
| | - Tuomo Rantanen
- Department of Surgery, School of Medicine, 205537University of Eastern Finland, Kuopio, Finland
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37
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Kochhar S, Zuckerberg A, Kocur M, Bommu VJL, Ikwuanusi I, Lake T, Cotler H, Cheriyath P. A Unique Case of Exploratory Laparotomy in the Setting of Large Bowel Obstruction Led to the Detection of Pancreatic Carcinoma. Cureus 2022; 14:e21565. [PMID: 35228924 PMCID: PMC8865910 DOI: 10.7759/cureus.21565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/24/2022] [Indexed: 11/25/2022] Open
Abstract
Pancreatic adenocarcinoma is the second most common gastrointestinal cancer after colon cancer. There is a delay in the detection of pancreatic adenocarcinoma as it remains asymptomatic in many individuals until it has metastasized to different parts of the body. We present a case of pancreatic cancer causing a large bowel obstruction in a 78-year-old female, detected during an exploratory laparotomy. Despite the increased incidence of pancreatic cancer, there are no screening guidelines that have been enacted for early detection and cure. Practicing clinicians should keep pancreatic cancer in the differential in high-risk individuals.
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38
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Osei-Bordom DC, Sachdeva G, Christou N. Liquid Biopsy as a Prognostic and Theranostic Tool for the Management of Pancreatic Ductal Adenocarcinoma. Front Med (Lausanne) 2022; 8:788869. [PMID: 35096878 PMCID: PMC8795626 DOI: 10.3389/fmed.2021.788869] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Accepted: 12/02/2021] [Indexed: 12/24/2022] Open
Abstract
Pancreatic ductal adenocarcinomas (PDAC) represent one of the deadliest cancers worldwide. Survival is still low due to diagnosis at an advanced stage and resistance to treatment. Herein, we review the main types of liquid biopsy able to help in both prognosis and adaptation of treatments.
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Affiliation(s)
- Daniel C Osei-Bordom
- Department of General Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Centre for Liver and Gastroenterology Research, University of Birmingham, Birmingham, United Kingdom
| | - Gagandeep Sachdeva
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Niki Christou
- Department of General Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, United Kingdom
- Department of General Surgery, University Hospital of Limoges, Limoges, France
- EA3842 CAPTuR Laboratory "Cell Activation Control, Tumor Progression and Therapeutic Resistance", Faculty of Medicine, Limoges, France
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39
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Kruger D, Lahoud N, Yako YY, Devar J, Smith M. Pancreatic ductal adenocarcinoma: Prognostic indicators of advanced disease. PLoS One 2022; 17:e0262439. [PMID: 35020761 PMCID: PMC8754286 DOI: 10.1371/journal.pone.0262439] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 12/21/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND/OBJECTIVES Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with high metastatic risk. Prognosis remains poor even after resection. Previously our group identified biomarkers that improved diagnostic accuracy in PDAC beyond the established diagnostic tumour marker, CA19-9. Risk factors, symptoms and circulating biomarkers associated with a PDAC diagnosis may differ from those that alter disease progression and metastasis. This study aimed at assessing the risk factors, presenting symptoms and potential prognostic biomarkers in PDAC and determine their relationship with PDAC stage and/or metastatic status. METHODS Seventy-two PDAC patients with imaging available for TNM staging at presentation were enrolled following informed consent. Demographic and clinical data were captured. Blood was collected and 38 cytokines/angiogenic factors measured. Nonparametric association tests, univariate and multivariate logistic regression were performed using STATA version 14.2. A p-value≤0.05 was considered significant and odds ratios reported for effect size. RESULTS Most risk factors and symptoms did not differ across the stages of cancer. Although male gender and smoking are risk factors for PDAC, the majority of study patients with metastatic PDAC were non-smoking females. In addition to CA19-9, the platelet count (p<0.01), IL-15 (p = 0.02) and GM-CSF (p<0.01) were significant, independent negative predictors of metastatic PDAC. Moreover, using specific cut-off values in a combined panel, the odds in a patient with all three biomarker levels below the cut-offs is 21 times more likely to have metastatic PDAC (p<0.0001). CONCLUSIONS Platelet count, IL-15 and GM-CSF are potential prognostic indicators of metastatic disease in PDAC patients from our local South African population.
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Affiliation(s)
- Deirdré Kruger
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Nicola Lahoud
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Yandiswa Y. Yako
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - John Devar
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Hepato-Pancreatico-Biliary Unit, Department of General Surgery, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa
| | - Martin Smith
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Hepato-Pancreatico-Biliary Unit, Department of General Surgery, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa
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40
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Lew D, Kwok K. Diagnosis and Evaluation of Pancreatic and Periampullary Adenocarcinoma. HEPATO-PANCREATO-BILIARY MALIGNANCIES 2022:431-459. [DOI: 10.1007/978-3-030-41683-6_29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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41
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Pumarega J, Camargo J, Gasull M, Olshan AF, Soliman A, Chen Y, Richardson D, Alguacil J, Poole C, Trasande L, Porta M. Timing of Toenail Collection and Concentrations of Metals in Pancreatic Cancer. Evidence Against Disease Progression Bias. EXPOSURE AND HEALTH 2021; 14:581-593. [PMID: 34722949 PMCID: PMC8533671 DOI: 10.1007/s12403-021-00436-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 09/27/2021] [Accepted: 09/30/2021] [Indexed: 05/03/2023]
Abstract
Trace elements such as cadmium, arsenic, zinc or selenium increase or decrease risk of a wide range of human diseases. Their levels in toenails may provide a measure of mid-term intake of trace elements for studies in humans. However, in biologically and clinically aggressive diseases as pancreatic cancer, the progression of the disease could modify such concentrations and produce reverse causation bias. The aim was to analyze the influence of specific time intervals between several clinical events and the collection of toenails upon concentrations of trace elements in patients with pancreatic cancer. Subjects were 118 incident cases of pancreatic adenocarcinoma prospectively recruited in eastern Spain. Toenails were collected at cancer diagnosis, and soon thereafter interviews were conducted. Information on cancer signs and symptoms was obtained from medical records and patient interviews. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. General linear models adjusting for potential confounders were applied to analyze relations between log concentrations of trace elements and the time intervals, including the interval from first symptom of cancer to toenail collection (iST). Toenail concentrations of the 12 trace elements were weakly or not influenced by the progression of the disease or the diagnostic procedures. Concentrations of aluminum were slightly higher in subjects with a longer iST (age, sex and stage adjusted geometric means: 11.44 vs. 7.75 µg/g for iST > 120 days vs. ≤ 40 days). There was a weak inverse relation of iST with concentrations of zinc and selenium (maximum differences of about 20 and 0.08 µg/g, respectively). Conclusions: concentrations of the trace elements were weakly or not influenced by the development of the disease before toenail collection. Only concentrations of aluminum increased slightly with increasing iST, whereas levels of zinc and selenium decreased weakly. Even in an aggressive disease as pancreatic cancer, toenail concentrations of trace elements may provide a valid measure of mid-term intake of trace elements, unaffected by clinical events and disease progression. Supplementary Information The online version contains supplementary material available at 10.1007/s12403-021-00436-2.
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Affiliation(s)
- José Pumarega
- Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- School of Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain
| | - Judit Camargo
- Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
- School of Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain
| | - Magda Gasull
- Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- School of Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain
- Universitat Pompeu Fabra, Barcelona, Spain
| | - Andrew F. Olshan
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA
| | - Amr Soliman
- Medical School of the City University of New York, New York, USA
| | - Yu Chen
- Departments of Environmental Medicine, and Population Health, New York University School of Medicine, New York, USA
| | - David Richardson
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA
| | - Juan Alguacil
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Universidad de Huelva, Huelva, Spain
| | - Charles Poole
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA
| | - Leonardo Trasande
- Departments of Environmental Medicine, and Population Health, New York University School of Medicine, New York, USA
- Department of Pediatrics, New York University School of Medicine, New York, USA
- New York University College of Global Public Health, New York, USA
| | - Miquel Porta
- Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- School of Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA
- Department of Pediatrics, New York University School of Medicine, New York, USA
| | - for the PANKRAS II Study Group
- Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- School of Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain
- Universitat Pompeu Fabra, Barcelona, Spain
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA
- Medical School of the City University of New York, New York, USA
- Departments of Environmental Medicine, and Population Health, New York University School of Medicine, New York, USA
- Universidad de Huelva, Huelva, Spain
- Department of Pediatrics, New York University School of Medicine, New York, USA
- New York University College of Global Public Health, New York, USA
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42
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Santos I, Mendes L, Mansinho H, Santos CA. Nutritional status and functional status of the pancreatic cancer patients and the impact of adjacent symptoms. Clin Nutr 2021; 40:5486-5493. [PMID: 34656030 DOI: 10.1016/j.clnu.2021.09.019] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 08/20/2021] [Accepted: 09/12/2021] [Indexed: 01/04/2023]
Abstract
RATIONALE & AIMS Pancreatic cancer (PC) is the third most common type of gastrointestinal tract cancer in Europe and the fourth leading cause of death by cancer. Its initial stage is asymptomatic Therefore, the diagnosis tends to be late leading to locally advanced stages that presuppose late and debilitating symptoms, which consequently makes the Nutritional Status (NS) get worse. The weight loss (WL), malnutrition, and oncologic cachexia, which are quite prevalent in PC patients, reflect a poor prognosis. We aimed to track and evaluate the NS and Functional Status (FS) of PC patients (hospitalized patients - HP and Day Hospital patients - DHP) and associate NS with symptoms with nutritional impact and FS. METHODS Observational cohort study in PC patients from Garcia de Orta Hospital. NS was tracked and evaluated using Nutritional Risk Screening (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA). To assess FS we used the Eastern Cooperative Oncology Group (ECOG), Karnofsky Performance Scale Index (KPSI) and Handgrip Dynamometer (HGD). RESULTS 41 PC patients (30-HP and 11-DHP). 29 patients in stage IV of the tumor. 24 with a WL >10% in the last 6 months. 37 manifest symptoms with nutritional impact. 30 to 34 malnourished according to the GLIM criteria and PG-SGA, respectively. 11 in ECOG level 2 and corresponding KPSI, 10 in level 3 and 8 in level 4. 28 patients had a value of HGD below the 10th percentile. NRS-2002, PG-SGA and GLIM criteria were positively correlated with the symptoms (p < 0.01), % WL (p < 0.01) and ECOG (p < 0.01) and negatively correlated with HGS (p < 0.05 - NRS-2002; p < 0.01 - PG-SGA and GLIM criteria). CONCLUSIONS PC patients manifest debilitating symptoms with nutritional impact, namely severe WL and anorexia, which in turn lead to deterioration of the NS and FS. It is an oncology population with high nutritional risk and a higher prevalence of malnutrition, associated with severe % WL and symptoms and a sharp decline in FS.
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Affiliation(s)
- I Santos
- Serviço de Nutrição, Hospital Garcia de Orta, Portugal; Dietética e Nutrição, Escola Superior de Tecnologia da Saúde de Lisboa, IPL, Portugal; Faculdade de Medicina, Universidade de Lisboa, Portugal.
| | - L Mendes
- Dietética e Nutrição, Escola Superior de Tecnologia da Saúde de Lisboa, IPL, Portugal; Faculdade de Medicina, Universidade de Lisboa, Portugal; Centro de Investigação em Saúde e Tecnologia (H&TRC), Portugal
| | - H Mansinho
- Serviço de Hemato-Oncologia, Hospital Garcia de Orta, Portugal
| | - C A Santos
- Serviço de Nutrição, Hospital Garcia de Orta, Portugal; Dietética e Nutrição, Escola Superior de Tecnologia da Saúde de Lisboa, IPL, Portugal; Centro de Investigação em Saúde e Tecnologia (H&TRC), Portugal
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Serum Metabolomic and Lipoprotein Profiling of Pancreatic Ductal Adenocarcinoma Patients of African Ancestry. Metabolites 2021; 11:metabo11100663. [PMID: 34677378 PMCID: PMC8540259 DOI: 10.3390/metabo11100663] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 09/06/2021] [Accepted: 09/08/2021] [Indexed: 12/12/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman's correlation and Kapan Meier tests were conducted for correlation and survival analyses, respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose and lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used to predict patient survival and inform treatment intervention.
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Tonini V, Zanni M. Pancreatic cancer in 2021: What you need to know to win. World J Gastroenterol 2021; 27:5851-5889. [PMID: 34629806 PMCID: PMC8475010 DOI: 10.3748/wjg.v27.i35.5851] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 07/14/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is one of the solid tumors with the worst prognosis. Five-year survival rate is less than 10%. Surgical resection is the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage of the disease and surgery could be performed in a very limited number of patients. Moreover, surgery is still associated with high post-operative morbidity, while other therapies still offer very disappointing results. This article reviews every aspect of pancreatic cancer, focusing on the elements that can improve prognosis. It was written with the aim of describing everything you need to know in 2021 in order to face this difficult challenge.
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Affiliation(s)
- Valeria Tonini
- Department of Medical Sciences and Surgery, University of Bologna- Emergency Surgery Unit, IRCCS Sant’Orsola Hospital, Bologna 40121, Italy
| | - Manuel Zanni
- University of Bologna, Emergency Surgery Unit, IRCCS Sant'Orsola Hospital, Bologna 40121, Italy
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Støer NC, Bouche G, Pantziarka P, Sloan EK, Andreassen BK, Botteri E. Use of non-cancer drugs and survival among patients with pancreatic adenocarcinoma: a nationwide registry-based study in Norway. Acta Oncol 2021; 60:1146-1153. [PMID: 34338111 DOI: 10.1080/0284186x.2021.1953136] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The prognosis of pancreatic cancer is poor and new treatment strategies are urgently needed. To identify non-cancer drugs that could be re-purposed for cancer, we investigated the association between the use of selected drugs and cancer-specific mortality in a nationwide cohort of pancreatic cancer patients. MATERIAL AND METHODS The study is based on linkage between the Cancer Registry of Norway and the Norwegian Prescription Database, comprising 2614 pancreatic cancer patients diagnosed between 2007 and 2014. We evaluated the association between use at diagnosis of a pre-defined list of non-cancer drugs, including metformin, antihypertensives, and statins, and pancreatic cancer-specific mortality, using Cox regression. Patients were defined as users of a particular drug if it was prescribed before diagnosis, and the prescription covered the date of diagnosis. RESULTS In total, 2096 (80.2%) patients died from pancreatic cancer; median survival was 6 months. Statin users (n = 621) had lower mortality (hazard ratio (HR): 0.86; 95% confidence interval (CI) 0.76-0.97) compared to non-users (n = 1993). This association was more pronounced (P-heterogeneity 0.062) in users of hydrophilic (n = 37, HR: 0.61; 95% CI 0.42-0.90) than lipophilic (n = 587, HR: 0.87; 95% CI 0.78-0.98) statins. An indication for lower mortality (HR: 0.85; 95% CI 0.69-1.05) was observed in users of non-selective beta-blockers (n = 113) compared to non-users (n = 2501). Notably, when compared to users of other antihypertensives (n = 643), users of non-selective beta-blockers (n = 40) had lower mortality (HR 0.67; 95% CI 0.47-0.96). The use of other drugs, including selective beta-blockers and metformin, was not associated with mortality. CONCLUSION The findings suggest an association between the use of statins and non-selective beta-blockers and reduced pancreatic cancer mortality, and add to the literature supporting the design of randomised clinical trials to evaluate those drugs in the management of pancreatic cancer.
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Affiliation(s)
| | | | | | - Erica K. Sloan
- Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
- Division of Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | | | - Edoardo Botteri
- Department of Research, Cancer Registry of Norway, Oslo, Norway
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway
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Abstract
Biliary strictures have several etiologies that can broadly be classified into benign and malignant causes. The clinical presentation is variable with strictures identified incidentally on imaging or during the evaluation of routine laboratory abnormalities. Symptoms and cholangitis lead to imaging that can diagnose biliary strictures. The diagnosis and medical management of biliary strictures will be discussed in this article.
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Affiliation(s)
- Terrance Rodrigues
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Justin R Boike
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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Purnak T, El Hajj II, Sherman S, Fogel EL, McHenry L, Lehman G, Gromski MA, Al-Haddad M, DeWitt J, Watkins JL, Easler JJ. Combined Versus Separate Sessions of Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography for the Diagnosis and Management of Pancreatic Ductal Adenocarcinoma with Biliary Obstruction. Dig Dis Sci 2021; 66:2786-2794. [PMID: 32852695 PMCID: PMC8121246 DOI: 10.1007/s10620-020-06564-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 08/12/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND A single-procedure session combining EUS and ERCP (EUS/ERCP) for tissue diagnosis and biliary decompression for pancreatic duct adenocarcinoma (PDAC) is technically feasible. While EUS/ERCP may offer expedience and convenience over an approach of separate procedures sessions, the technical success and risk for complications of a combined approach is unclear. AIMS Compare the effectiveness and safety of EUS/ERCP versus separate session approaches for PDAC. METHODS Study patients (2010-2015) were identified within our ERCP database. Patients were analyzed in three groups based on approach: Group A: Single-session EUS-FNA and ERCP (EUS/ERCP), Group B: EUS-FNA followed by separate, subsequent ERCP (EUS then ERCP), and Group C: ERCP with/without separate EUS (ERCP ± EUS). Rates of technical success, number of procedures, complications, and time to initiation of PDAC therapies were compared between groups. RESULTS Two hundred patients met study criteria. EUS/ERCP approach (Group A) had a longer index procedure duration (median 66 min, p = 0.023). No differences were observed between Group A versus sequential procedure approaches (Groups B and C) for complications (p = 0.109) and success of EUS-FNA (p = 0.711) and ERCP (p = 0.109). Subgroup analysis (> 2 months of follow-up, not referred to hospice, n = 126) was performed. No differences were observed for stent failure (p = 0.307) or need for subsequent procedures (p = 0.220). EUS/ERCP (Group A) was associated with a shorter time to initiation of PDAC therapies (mean, 25.2 vs 42.7 days, p = 0.046). CONCLUSIONS EUS/ERCP approach has comparable rates of success and complications compared to separate, sequential approaches. An EUS/ERCP approach equates to shorter time interval to initiation of PDAC therapies.
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Affiliation(s)
- Tugrul Purnak
- Hacettepe University Medical School, Department of Gastroenterology, Sihhiye/Ankara/Turkey
| | - Ihab I. El Hajj
- Division of Gastroenterology, Saint George Hospital University Medical Center, University of Balamand, Beirut, Lebanon
| | - Stuart Sherman
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Evan L. Fogel
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Lee McHenry
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Glen Lehman
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mark A. Gromski
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mohammad Al-Haddad
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - John DeWitt
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - James L. Watkins
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Jeffrey J. Easler
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
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Uozumi N, Oura S, Makimoto S. Subclinical Needle Tract Seeding by Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Pancreatic Cancer. Case Rep Oncol 2021; 14:977-982. [PMID: 34326732 PMCID: PMC8299394 DOI: 10.1159/000516756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 04/14/2021] [Indexed: 11/19/2022] Open
Abstract
A 77-year-old woman with epigastralgia was referred to our hospital. Abdominal computed tomography showed a hypointense mass in the pancreatic tail. Abdominal and endoscopic ultrasonography (EUS) showed a hypo-echoic mass, 25 × 25 mm in size, with pancreatic duct dilatation. EUS-guided fine-needle aspiration (EUS-FNA) was performed to the mass through gastric posterior wall. Pathological examination showed atypical cells growing papillary or tubular fashion, leading to the diagnosis of adenocarcinoma. Under the preoperative diagnosis of T2N0M0 pancreatic cancer, the patient underwent distal pancreatectomy and splenectomy. Macroscopic view of the resected specimen showed a presumed puncture-induced pancreatic pseudocyst adjacent to the pancreas. Pathological examination showed well-differentiated adenocarcinoma and a pseudocyst with presumed migrated atypical cells in the pseudocyst wall. The patient recovered uneventfully and has been on outpatient follow-up with adjuvant TS-1 therapy. Optimal treatment of pancreatic cancer naturally needs preoperative definitive diagnosis more strictly than other solid malignancies due to its much higher operative harm to the patients. EUS-FNA is a safe and effective diagnostic method but needs careful attention to the needle tract seeding.
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Affiliation(s)
- Nozomi Uozumi
- Department of Surgery, Kishiwada Tokushukai Hospital, Kishiwada, Japan
| | - Shoji Oura
- Department of Surgery, Kishiwada Tokushukai Hospital, Kishiwada, Japan
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Zeeshan MS, Ramzan Z. Current controversies and advances in the management of pancreatic adenocarcinoma. World J Gastrointest Oncol 2021; 13:472-494. [PMID: 34163568 PMCID: PMC8204360 DOI: 10.4251/wjgo.v13.i6.472] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 03/22/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic adenocarcinoma is a lethal disease with a mortality rate that has not significantly improved over decades. This is likely due to several challenges unique to pancreatic cancer. Most patients with pancreatic cancer are diagnosed at a late stage of disease due to the lack of specific symptoms prompting an early investigation. A small subset of patients who are diagnosed at an early stage have a better chance at survival with curative surgical resection, but most patients still succumb to the disease in a few years. The dismal overall prognosis is due to suspected micro-metastasis at an early stage. Due to this reason, there is a recent interest in treating all patients with pancreatic cancers with systemic therapy upfront (including the ones that are surgically resectable). This approach is still not the standard of care due to the lack of robust prospective data available. Recent advancements in treatment regimens of chemotherapy, radiation and immunotherapy have improved the overall short-term survival but the long-term survival still remains poor. Novel approaches in diagnosis and treatment have shown promise in clinical studies but long-term clinical data is lacking. The following manuscript presents an overview of the epidemiology, diagnosis, staging, recent advances, novel approaches and controversies in the management of pancreatic adenocarcinoma.
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Affiliation(s)
- Muhammad Shehroz Zeeshan
- Gastrointestinal Section, Department of Medicine, Texas Health Harris Methodist Hospital, Fort Worth, TX 76104, United States
| | - Zeeshan Ramzan
- Gastrointestinal Section, Department of Medicine, Texas Health Harris Methodist Hospital, Fort Worth, TX 76104, United States
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Carnie LE, Lamarca A, Vaughan K, Kapacee ZA, McCallum L, Backen A, Barriuso J, McNamara MG, Hubner RA, Abraham M, Valle JW. Prospective observational study of prevalence, assessment and treatment of pancreatic exocrine insufficiency in patients with inoperable pancreatic malignancy (PANcreatic cancer Dietary Assessment (PanDA): a study protocol. BMJ Open 2021; 11:e042067. [PMID: 33986039 PMCID: PMC8126274 DOI: 10.1136/bmjopen-2020-042067] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 10/11/2020] [Accepted: 03/12/2021] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Pancreatic exocrine insufficiency (PEI) in patients with pancreatic malignancy is well documented in the literature and is known to negatively impact on overall survival and quality of life. A lack of consensus opinion remains on the optimal diagnostic test that can be adapted for use in a clinical setting for this cohort of patients. This study aims to better understand the prevalence of PEI and the most suitable diagnostic techniques in patients with advanced pancreatic malignancy. METHODS AND ANALYSIS This prospective observational study will be carried out in patients with pancreatic malignancy (including adenocarcinoma and neuroendocrine neoplasms). Consecutive patients with inoperable pancreatic malignancy referred for consideration of first-line chemotherapy will be considered for eligibility. The study comprises three cohorts: demographic cohort (primary objective to prospectively investigate the prevalence of PEI in patients with inoperable pancreatic malignancy); sample size 50, diagnostic cohort (primary objective to design and evaluate an optimal diagnostic panel to detect PEI in patients with inoperable pancreatic malignancy); sample size 25 and follow-up cohort (primary objective to prospectively evaluate the proposed PEI diagnostic panel in a cohort of patients with inoperable pancreatic malignancy); sample size 50. The following is a summary of the protocol and methodology. ETHICS AND DISSEMINATION Full ethical approval has been granted by the North West Greater Manchester East Research and Ethics Committee, reference: 17/NW/0597. This manuscript reflects the latest protocol V.8 approved 21 April 2020. Findings will be disseminated by presentation at national/international conferences, publication in peer-review journals and distribution via patient advocate groups. TRIAL REGISTRATION NUMBER 194255, NCT0361643.
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Affiliation(s)
- Lindsay E Carnie
- Nutrition & Dietetics, The Christie NHS Foundation Trust, Manchester, UK
| | - Angela Lamarca
- Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
| | - Kate Vaughan
- Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
| | | | | | - Alison Backen
- Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
| | - Jorge Barriuso
- Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
| | - Mairéad G McNamara
- Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
| | - Richard A Hubner
- Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
| | - Marc Abraham
- Nutrition & Dietetics, The Christie NHS Foundation Trust, Manchester, UK
| | - Juan W Valle
- Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
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