|
1
|
Christodoulidis G, Kouliou MN, Ragias D, Chatziisaak D, Agko ES, Schizas D, Zacharoulis D. Last decade of advances in gastric neuroendocrine tumors: Innovations, challenges, and future directions. World J Clin Oncol 2025; 16:104577. [DOI: 10.5306/wjco.v16.i5.104577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/27/2025] [Accepted: 03/10/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND Gastric neuroendocrine tumors (G-NETs) are rare tumors originating from enterochromaffin-like cells, with an incidence of 0.4 per 100000 annually. There are three main types: (1) Type I, linked to chronic atrophic gastritis and hypergastrinemia, makes up 75%–80% of G-NETs; (2) Type II, associated with Zollinger-Ellison syndrome (ZES) and multiple endocrine neoplasia, comprises 5%; and (3) Type III, sporadic tumors with a higher metastatic potential, accounting for 15%–25%. Diagnosis involves endoscopy, biopsy, and histological examination. Additional methods include serum gastrin testing, immunohistochemistry, and imaging techniques such as computer tomography or magnetic resonance imaging for detecting metastasis. Type I treatment usually involves endoscopic resection (ER), with surgical resection for recurrence. Somatostatin analogs (SSAs) can reduce tumor size, and the prognosis is generally excellent. Type II treatment centers on surgical removal of the gastrinoma, with ER for smaller lesions and SSAs for symptom management. Type III requires surgical resection (partial or total gastrectomy) with lymph node dissection, and possibly chemotherapy. This type has a worse prognosis due to its aggressive nature. Emerging treatments like Peptide Receptor Radionuclide Therapy are promising for advanced cases, and ongoing research into immunotherapies is expanding future treatment options. Regular endoscopic follow-up is crucial to monitor for recurrence or metastasis across all types. Our literature review explores the current perspectives on G-NETs and highlights the importance of further research to improve diagnostic precision and treatment, particularly for those associated with less favorable cases.
AIM To improve diagnostic precision and treatment, particularly for those associated with less favorable cases.
METHODS A systematic search was conducted in PubMed, Scopus, and Web of Science until September 2024. Two independent reviewers screened titles, abstracts, and full texts for eligibility based on G-NET treatment in adults. Eligible studies included cohort studies, clinical trials, case series, and case reports, while in vitro, pediatric, and non-English studies were excluded. Relevant data were extracted independently, and disagreements were resolved through discussion. Study quality was assessed using appropriate tools.
RESULTS G-NETs are rare, classified into three types: (1) Type I; (2) Type II; and (3) Type III. Type I G-NETs, often associated with chronic atrophic gastritis, are typically slow-growing and low-grade, with favorable outcomes following surgical resection. Type II G-NETs arise in hypergastrinemia conditions like multiple endocrine neoplasia and ZES, showing moderate malignancy risk. Type III G-NETs, the most aggressive and least common, present with distant metastases and poor prognosis. Diagnosis relies on endoscopy, imaging, and biomarkers like chromogranin A. Treatment varies by type, ranging from ER to aggressive surgery and chemotherapy for advanced cases. Regular follow-up is essential to monitor recurrence, particularly for type III G-NETs.
CONCLUSION G-NETs require tailored diagnosis and treatment based on type and stage. Types I and II generally have better prognosis, while types III and IV are linked to poorer outcomes due to invasion and metastasis. Treatment strategies vary from ER for type I to extensive surgery for type III. Emerging therapies, like somatostatin analogs and peptide-receptor radionuclide therapies, show promise in advanced cases. Further research is essential to improve early diagnosis and treatment, particularly for high-risk lesions.
Collapse
Affiliation(s)
| | - Marina Nektaria Kouliou
- Department of Internal Medicine, General Hospital of Argolida-Hospital Unit of Nafplio, Nafplio 21100, Pelopónnisos, Greece
| | - Dimitrios Ragias
- Department of Oncology, 251 Air Force General Hospital, Athens 11525, Greece
| | - Dimitrios Chatziisaak
- Department of Surgery, Kantonsspital St.Gallen, St.Gallen 9000, Switzerland
- Department of Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne 1005, Switzerland
| | - Eirini Sara Agko
- Department of Intensive Care Unit, Asklepios Paulinen Clinic Wiesbaden, Wiesbaden 65197, Germany
| | - Dimitrios Schizas
- Department of Surgery, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Dimitrios Zacharoulis
- Department of General Surgery, University of Thessaly, Larisa 41110, Thessalia, Greece
| |
Collapse
|
|
2
|
Qiao G, Feng L, Wang M, Wang C, Li C, Han S, Wang Y, Li S, Xin S. Eradication of Helicobacter pylori that contributes to hepatogenic ulcer is beneficial to the healing of hepatogenic ulcer. BMC Gastroenterol 2025; 25:359. [PMID: 40355830 PMCID: PMC12067654 DOI: 10.1186/s12876-025-03769-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 03/07/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND This study aimed to explore the role of Helicobacter pylori (Hp) eradication in patients with hepatogenic ulcer (HU). METHODS Patients with HU, patients with liver cirrhosis without peptic ulcer and patients with functional dyspepsia (FD) were selected and the relationship between complications of liver cirrhosis and Hp infection in HU patients was evaluated retrospectively. Furthermore, 60 HU patients with Hp infection were randomly divided into the treatment group with rabeprazole plus amoxicillin and levofloxacin, and the control group with rabeprazole alone and the therapeutic effects then were recorded. This trial was registered at the China Clinical Research Registration Center (Trial registration number: ChiCTR2200061355, 2022/06/21). RESULTS The Hp positive rate in the HU group was significantly higher compared with the liver cirrhosis without ulcer group or the FD group. Moreover, the positive rate of Hp in HU patients with mild esophageal varices was higher than that in HU patients with moderate and severe esophageal varices. Additionally, the rate of Hp eradication and ulcer healing in the treatment group was significantly higher than that in the control group. Importantly, the remission time of ulcer-related symptoms in the treatment group was shorter compared with the control group. CONCLUSION Hp is a contributor to HU and an integrated strategy consisting of rabeprazole, amoxicillin and levofloxacin is effective in the treatment of HU, providing a potential application for HU patients.
Collapse
Affiliation(s)
- Guanen Qiao
- Department of Gastroenterology, Handan First Hospital, Handan, Hebei, 056002, China
| | - Le Feng
- Department of Gastroenterology, Handan First Hospital, Handan, Hebei, 056002, China
| | - Meng Wang
- Department of Gastroenterology, Handan First Hospital, Handan, Hebei, 056002, China
| | - Chaoyang Wang
- Department of Infection, Handan First Hospital, Handan, Hebei, 056002, China
| | - Changjuan Li
- Department of Gastroenterology, Handan First Hospital, Handan, Hebei, 056002, China
| | - Shuxiang Han
- Department of Gastroenterology, Affiliated Hospital of Hebei Engineering University, Handan, Hebei, 056002, China
| | - Yanmei Wang
- Department of General Surgery, Handan Infectious Diseases Hospital, Handan, Hebei, 056008, China
| | - Shubo Li
- Department of Internal Medicine, Handan Cancer Hospital, Handan, Hebei, 056000, China
| | - Shuanli Xin
- Department of Internal Medicine, Handan First Hospital, No. 24 Congtai Road, Congtai District, Handan, Hebei, 056002, China.
| |
Collapse
|
|
3
|
Perez K, Del Rivero J, Kennedy EB, Basu S, Chauhan A, Connolly HM, Dasari AN, Gangi A, Clarke CN, Hallet J, Howe JR, Grady E, Ivanidze J, Mittra ES, White SB, Raj NP, Vijayvergia N, Lewis MA, Chan JA, Kunz PL, Mailman J, Arshad J, Soares HP, Singh S, Chandrasekharan C, Soulen MC, Janson ET, Halfdanarson TR, Strosberg JR, Bergsland EK. Symptom Management for Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline. JCO Oncol Pract 2025:OP2500133. [PMID: 40344544 DOI: 10.1200/op-25-00133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 03/07/2025] [Accepted: 03/24/2025] [Indexed: 05/11/2025] Open
Abstract
PURPOSE To develop a clinical practice guideline and recommendations for symptom management of patients with well-differentiated grade 1 to grade 3 metastatic gastroenteropancreatic neuroendocrine tumors. METHODS ASCO convened an Expert Panel to develop a clinical practice guideline by reviewing the literature for relevant guidelines, systematic reviews, randomized controlled trials (RCTs), and observational studies to develop recommendations for clinical practice. RESULTS The literature review identified eight guidelines, 19 systematic reviews, and three RCTs that informed the development of guideline recommendations. RECOMMENDATIONS Recommendations are included for carcinoid syndrome, carcinoid heart disease and carcinoid crisis, and functional pancreatic neuroendocrine tumor syndromes. Recommendations are provided for surgical management, liver-directed therapy, and systemic therapy options, as well as palliative care. Limited guidance is provided for sequencing of interventions.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.
Collapse
Affiliation(s)
| | | | | | - Sandip Basu
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Parel, Mumbai, India
| | | | | | | | | | | | - Julie Hallet
- Odette Cancer Center, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | | | | | | | | | | | - Nitya P Raj
- Memorial Sloan Kettering Cancer Center, New York, NY
| | | | | | | | | | | | | | | | - Simron Singh
- Odette Cancer Center, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | | | | | | | | | | | | |
Collapse
|
|
4
|
Phillips HR, Tome J, Loftus CG. 39-Year-Old Man With Reflux, Diarrhea, and Abdominal Pain. Mayo Clin Proc 2025:S0025-6196(24)00435-X. [PMID: 40314630 DOI: 10.1016/j.mayocp.2024.06.015] [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: 05/02/2024] [Revised: 06/11/2024] [Accepted: 06/12/2024] [Indexed: 05/03/2025]
Affiliation(s)
- Hannah R Phillips
- Resident in Internal Medicine, Mayo Clinic School of Graduate Medical Education, Rochester, MN
| | - June Tome
- Fellow in Gastroenterology, Mayo Clinic School of Graduate Medical Education, Rochester, MN
| | - Conor G Loftus
- Advisor to resident and fellow and Consultant in Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
| |
Collapse
|
|
5
|
Koloutsou ME, Soura M, Andreikos D, Spandidos DA, Yavropoulou MP, Georgakopoulou VE. Endocrine paraneoplastic syndromes in lung cancer: A call for clinical vigilance (Review). Mol Clin Oncol 2025; 22:36. [PMID: 40083863 PMCID: PMC11905218 DOI: 10.3892/mco.2025.2831] [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: 01/02/2025] [Accepted: 02/26/2025] [Indexed: 03/16/2025] Open
Abstract
Endocrine paraneoplastic syndromes (PNS) are uncommon but clinically impactful manifestations associated with malignancies, particularly lung cancer, most notably small-cell lung cancer. These syndromes arise from ectopic hormone production by malignant cells, causing systemic effects that are independent of direct tumor invasion or metastasis. Their presentation often precedes or signals recurrence of the primary cancer, underscoring the importance of early recognition and targeted intervention. Common endocrine PNS in lung cancer include syndrome of inappropriate antidiuretic hormone secretion, hypercalcemia, Cushing syndrome, carcinoid syndrome, and other hormonal imbalances such as non-islet cell tumor hypoglycemia, gynecomastia and acromegaly. The pathophysiology of these conditions involves ectopic secretion of bioactive substances such as hormones and cytokines, leading to diverse clinical manifestations. Accurate diagnosis necessitates a combination of biochemical assessments, imaging modalities, and histopathological evaluations to differentiate paraneoplastic processes from primary endocrine disorders. Management strategies emphasize treating the underlying malignancy, often through chemotherapy, radiotherapy, or surgical intervention, alongside symptomatic therapies tailored to the specific endocrine abnormality. Multidisciplinary care is critical for optimizing outcomes and enhancing patients' quality of life. The current review highlights the need for heightened clinical vigilance and a systematic approach to diagnosing and managing endocrine PNS in lung cancer. By fostering early detection and comprehensive management, clinicians can significantly improve prognostic outcomes for affected individuals.
Collapse
Affiliation(s)
- Maria-Evangelia Koloutsou
- First Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Maria Soura
- First Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Dimitrios Andreikos
- School of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Demetrios A. Spandidos
- Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Maria P. Yavropoulou
- Endocrinology Unit, First Department of Propaedeutic and Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | | |
Collapse
|
|
6
|
Spada F, Rossi RE, Modica R, Gelsomino F, Rinzivillo M, Rubino M, Pisa E, La Salvia A, Fazio N. Functioning neuroendocrine tumors (NET): Minimum requirements for a NET specialist. Cancer Treat Rev 2025; 135:102907. [PMID: 40023966 DOI: 10.1016/j.ctrv.2025.102907] [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: 12/23/2024] [Revised: 02/22/2025] [Accepted: 02/24/2025] [Indexed: 03/04/2025]
Abstract
INTRODUCTION AND AIMS Functioning neuroendocrine tumors (f-NETs) represent a minority of all NETs, however their management is challenging due to the impact on patients' survival and quality of life. In addition to f-NETs, paraneoplastic syndromes (PNS) are due to substances that are not related to the primary anatomical site, they can develop in different phases of NETs evolution, and might complicate the patient's clinical course. Dedicated guidelines are still scanty. We aim to review available literature on f-NETs to propose a useful tool for clinicians in order to improve the diagnostic process and the management. METHODS Narrative review focused on f-NETs. RESULTS The most common f-NETs include insulinomas, gastrinomas and carcinoid syndrome (CS)- associated NETs. Symptoms related to hormone production may overlap with other common endocrine and gastrointestinal disorders, highlighting the pivotal role of multidisciplinary management. Somatostatin analogs (SSAs) represent the gold standard first-line treatment of most f-NETs, often followed by or combined with other treatments (surgery, liver-directed therapies, targeted therapies, peptide receptor radionuclide therapy). Paraneoplastic syndromes can develop in different phases of NET evolution and might complicate the patient's clinical course and response to therapy. CONCLUSIONS The management of hormonal syndromes is challenging and must be based on the multidisciplinary approach. Herein, we pointed out the minimal requirements for a NET specialist in the diagnosis and treatment of f-NETs. Efforts should be made to improve the awareness of functioning forms, to understand their pathogenesis and to improve their management.
Collapse
Affiliation(s)
- F Spada
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy
| | - R E Rossi
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - R Modica
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
| | - F Gelsomino
- Department of Oncology and Hematology, Division of Oncology, University Hospital of Modena, Modena, Italy
| | - M Rinzivillo
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, 00189 Rome, Italy
| | - M Rubino
- Onco-Endocrinology Unit, IEO European Institute of Oncology IRCCS, Milano, Italy
| | - E Pisa
- Division of Pathology and Laboratory Medicine, European Institute of Oncology, IEO, IRCCS, Milan, Italy
| | - Anna La Salvia
- National Center for Drug Research and Evaluation, National Institute of Health (ISS), Rome, Italy
| | - N Fazio
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy.
| |
Collapse
|
|
7
|
Sahithi PVL, Nandi VPKR, Kandagaddala Y, Mulagapaka V, Onteddu LP, Onteddu NK. Gastrinoma: A Case of Chronic Diarrhea. Cureus 2025; 17:e81253. [PMID: 40291307 PMCID: PMC12031656 DOI: 10.7759/cureus.81253] [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: 02/08/2025] [Accepted: 03/19/2025] [Indexed: 04/30/2025] Open
Abstract
Gastrinoma is a rare neuroendocrine tumor characterized by the hypersecretion of gastrin. Early diagnosis is challenging due to its rarity, and patients present to the outpatient department with nonspecific complaints such as diarrhea, weight loss, and fatigue, which often lead to a broad differential diagnosis. This report presents the case of a 59-year-old female who has come to the internal medicine department for a workup of chronic diarrhea, low-grade fever, 8kg weight loss, and severe reflux of eight months duration, not responding to empiric therapy. After multiple hospital visits and evaluations, she was found to have duodenal gastrinoma. This case report aims to create awareness and underscores the importance of considering neuroendocrine tumors as an initial differential diagnosis for patients with nonspecific or unexplained gastrointestinal symptoms to facilitate early diagnosis.
Collapse
Affiliation(s)
| | | | | | - Vinusha Mulagapaka
- Internal Medicine, P.E.S. Institute of Medical Sciences and Research, Kuppam, IND
| | | | - Nirmal K Onteddu
- Internal Medicine, University of Florida College of Medicine, Jacksonville, USA
| |
Collapse
|
|
8
|
Yuliantie E, Nh Trinh P, Hick C, Ebenhoch R, Nar H, Weichert D, Christopoulos A, M Sexton P, Wootten D. Isoquinoline small molecule ligands are agonists and probe-dependent allosteric modulators of the glucagon subfamily of GPCRs. Biochem Pharmacol 2024; 229:116483. [PMID: 39147328 DOI: 10.1016/j.bcp.2024.116483] [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: 05/01/2024] [Revised: 08/05/2024] [Accepted: 08/09/2024] [Indexed: 08/17/2024]
Abstract
Class B1 G protein-coupled receptors (GPCRs) are peptide hormone receptors and well validated therapeutic targets, however development of non-peptide drugs targeting this class of receptors is challenging. Recently, a series of isoquinoline-based derivates were reported in the patent literature as allosteric ligands for the glucagon receptor subfamily, and two compounds, LSN3451217 and LSN3556672, were used to facilitate structural studies with the glucagon-like peptide-1 receptor (GLP-1R) and glucose dependent insulinotropic peptide receptor (GIPR) bound to orthosteric agonists. Here we pharmacologically characterized stereoisomers of LSN3451217 and LSN3556672, across the class B1 GPCR family. This revealed LSN3556672 isomers are agonists for the glucagon receptor (GCGR), GLP-1R, GIPR and the calcitonin receptor (CTR), albeit the degree of agonism varied at each receptor. In contrast, LSN3451217 isomers were more selective agonists at the GLP-1R, with lower potency at the GCGR and CTR and no activity at the GIPR. All compounds also modulated peptide-mediated cyclic adenosine monophosphate (cAMP) signaling at the GIPR, and to a lesser extent the GLP-1R, in a probe-dependent manner, with modest positive allosteric modulation observed for some peptides, and negligible effects observed with other peptides. In contrast neutral or weak negative/positive allosteric modulation was observed with peptides assessed at the GCGR and CTR. This study expands our knowledge on class B1 GPCR allosteric modulation and may have implications for future structural and drug discovery efforts targeting the class B1 GPCR subfamily.
Collapse
MESH Headings
- Humans
- Ligands
- Allosteric Regulation/drug effects
- Allosteric Regulation/physiology
- Isoquinolines/pharmacology
- Isoquinolines/chemistry
- Receptors, Glucagon/agonists
- Receptors, Glucagon/metabolism
- Glucagon-Like Peptide-1 Receptor/agonists
- Glucagon-Like Peptide-1 Receptor/metabolism
- HEK293 Cells
- Animals
- Cricetulus
- Receptors, Gastrointestinal Hormone/agonists
- Receptors, Gastrointestinal Hormone/metabolism
- Receptors, Gastrointestinal Hormone/chemistry
- Small Molecule Libraries/pharmacology
- Small Molecule Libraries/chemistry
- CHO Cells
- Receptors, Calcitonin/agonists
- Receptors, Calcitonin/metabolism
- Receptors, Calcitonin/chemistry
- Receptors, G-Protein-Coupled/agonists
- Receptors, G-Protein-Coupled/metabolism
- Receptors, G-Protein-Coupled/chemistry
- Glucagon/metabolism
- Glucagon/agonists
- Glucagon/chemistry
- Molecular Probes/chemistry
- Molecular Probes/pharmacology
Collapse
Affiliation(s)
- Elita Yuliantie
- Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia
| | - Phuc Nh Trinh
- Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia
| | - Caroline Hick
- Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia
| | - Rebecca Ebenhoch
- Boehringer-Ingelheim Pharma, GmbH & Co KG, 88400 Biberach an der Riss, Germany
| | - Herbert Nar
- Boehringer-Ingelheim Pharma, GmbH & Co KG, 88400 Biberach an der Riss, Germany
| | - Dietmar Weichert
- Boehringer-Ingelheim Pharma, GmbH & Co KG, 88400 Biberach an der Riss, Germany
| | - Arthur Christopoulos
- Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia; ARC Centre for Cryo-Electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia; Neuromedicines Discovery Centre, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
| | - Patrick M Sexton
- Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia; ARC Centre for Cryo-Electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia.
| | - Denise Wootten
- Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia; ARC Centre for Cryo-Electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia.
| |
Collapse
|
|
9
|
Kaur P, Raghav N, Berar U. Chalcones as potential pepsin inhibitors: Synthesis, characterization, DFT and molecular docking studies. Int J Biol Macromol 2024; 282:137009. [PMID: 39476922 DOI: 10.1016/j.ijbiomac.2024.137009] [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: 08/05/2024] [Revised: 10/22/2024] [Accepted: 10/26/2024] [Indexed: 11/08/2024]
Abstract
Pepsin, a unique protease activity at acidic environment in the stomach, can cause chronic inflammation in surrounding tissues after becoming hyperactive lead to enlarged tonsils, vocal fold polyps, laryngopharyngeal cancers, and other diseases. Therefore, design and development of new effective pepsin inhibitors becomes significant. In the present work, we synthesized, and characterized thiophene-based chalcones as anti-pepsin agents. The synthesized chalcones exhibited significantly better pepsin inhibition than commercially available drugs omeprazole and pantoprazole. The in-vitro screening revealed that the synthesized compounds exhibited pepsin inhibition in the range of 53.19-91.14 % at 3 × 10-8 M concentration showing promising results controlling elevated pepsin levels. Compound 3p was found the best inhibitor with an IC50 value 1.02 × 10-9 M. Molecular docking studies executed show the decrease in energy of interaction between pepsin and the synthesized compounds 3(a-t) varies from -69.104 to -83.124 kcal/mol and the highest decreased interaction energy with compound 3p. DFT analyses were conducted to gain a deeper understanding of the structural parameters. Energy minimization and quantum chemical parameters computed using Avagadro and ORCA software indicated ΔE values in the range 9.593-10.246 eV as per DFT calculations. The results obtained from the in vitro studies were supported with in silico studies.
Collapse
Affiliation(s)
- Prabhjot Kaur
- University Institute of Engineering and Technology, Kurukshetra University, Kurukshetra, Haryana 136119, India
| | - Neera Raghav
- Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana 136119, India.
| | - Urmila Berar
- University Institute of Engineering and Technology, Kurukshetra University, Kurukshetra, Haryana 136119, India.
| |
Collapse
|
|
10
|
Ammann M, Gudmundsdottir H, Hackl H, Antwi SKA, Santol J, Habermann EB, Thiels CA, Warner SG, Truty MJ, Kendrick ML, Smoot RL, Nagorney DM, Cleary SP, Halfdanarson TR, Starlinger PP. Neuroendocrine Tumors of Unknown Primary in the Setting of Cytoreductive Hepatectomy. Ann Surg Oncol 2024; 31:4931-4941. [PMID: 38717544 DOI: 10.1245/s10434-024-15374-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 04/09/2024] [Indexed: 07/13/2024]
Abstract
BACKGROUND Surgical cytoreduction for neuroendocrine tumor liver metastasis (NETLM) consistently shows positive long-term outcomes. Despite reservations in guidelines for surgery when the primary tumor is unidentified (UP-NET), this study compared the surgical and oncologic long-term outcomes between patients with these rare cases undergoing cytoreductive surgery and patients who had liver resection for known primaries. METHODS The study identified 32 unknown primary liver metastases (UP-NETLM) in 522 retrospectively evaluated patients who underwent resection of well-differentiated NETLM between January 2000 and December 2020. Tumor and patient characteristics were compared with those in 490 cases of liver metastasis from small intestinal (SI-NETLM) or pancreatic (pNETLM) primaries. Survival analysis was performed to highlight long-term outcome differences. Surgical outcomes were compared between liver resections alone and simultaneous primary resections to assess surgical risk distinctions. RESULTS The UP-NET patients had fewer NETLMs (p = 0.004), which on the average were larger than SI-NETLMs or pNETLMs (p = 0.002). Expression of Ki-67 was balanced among the groups. Major hepatectomy was performed more often in the UP-NETLM group (p = 0.017). The 10-year survival rate of 53% for UP-NETLM was comparable with that for SI-NETML (58%; p = 0.463) and pNETLMs (47%; p = 0.497). The median hepatic progression-free survival was 26 months for the UP-NETLM patients and 25 months for the SI-NETLM patients compared to 12 months for the pNETLM patients (p < 0.001). Perioperative mortality was lower than 2%, and severe postoperative morbidity occurred in 21%, similarly distributed among all the groups. CONCLUSION The surgical risk and long-term outcomes for the UP-NETLM patients were comparable with those for other NETLM cases, affirming the validity of equally aggressive surgical cytoreduction as a therapeutic option in carefully selected cases.
Collapse
Affiliation(s)
- Markus Ammann
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Surgery, State Hospital Wiener Neustadt, Wiener Neustadt, Austria
| | - Hallbera Gudmundsdottir
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
- Division of Health Care Delivery Research, Robert D. and Patricia E. Kern Center for Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Hubert Hackl
- Institute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
| | - Stella K Adjei Antwi
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Surgery, University Milano-Bicocca, Minao, Italy
| | - Jonas Santol
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Surgery, HPB Center, Vienna Health Network, Clinic Favoriten and Sigmund Freud Private University, Vienna, Austria
| | - Elizabeth B Habermann
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
- Division of Health Care Delivery Research, Robert D. and Patricia E. Kern Center for Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Cornelius A Thiels
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Susanne G Warner
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Mark J Truty
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Michael L Kendrick
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Rory L Smoot
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - David M Nagorney
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Sean P Cleary
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
- Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Canada
| | | | - Patrick P Starlinger
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA.
| |
Collapse
|
|
11
|
Franchina M, Cavalcoli F, Falco O, La Milia M, Elvevi A, Massironi S. Biochemical Markers for Neuroendocrine Tumors: Traditional Circulating Markers and Recent Development-A Comprehensive Review. Diagnostics (Basel) 2024; 14:1289. [PMID: 38928704 PMCID: PMC11203125 DOI: 10.3390/diagnostics14121289] [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: 05/08/2024] [Revised: 06/13/2024] [Accepted: 06/15/2024] [Indexed: 06/28/2024] Open
Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms presenting unique challenges in diagnosis and management. Traditional markers such as chromogranin A (CgA), pancreatic polypeptide (PP), and neuron-specific enolase (NSE) have limitations in terms of specificity and sensitivity. Specific circulating markers such as serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and various gastrointestinal hormones such as gastrin, glucagon, somatostatin, and vasoactive intestinal peptide (VIP) have a role in identifying functional NENs. Recent advances in molecular and biochemical markers, also accounting for novel genomic and proteomic markers, have significantly improved the landscape for the diagnosis and monitoring of NENs. This review discusses these developments, focusing on both traditional markers such as CgA and NSE, as well as specific hormones like gastrin, insulin, somatostatin, glucagon, and VIP. Additionally, it covers emerging genomic and proteomic markers that are shaping current research. The clinical applicability of these markers is highlighted, and their role in improving diagnostic accuracy, predicting surgical outcomes, and monitoring response to treatment is demonstrated. The review also highlights the need for further research, including validation of these markers in larger studies, development of standardized assays, and integration with imaging techniques. The evolving field of biochemical markers holds promise for improving patient outcomes in the treatment of NENs, although challenges in standardization and validation remain.
Collapse
Affiliation(s)
- Marianna Franchina
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Federica Cavalcoli
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
| | - Olga Falco
- Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy
| | - Marta La Milia
- Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy
| | - Alessandra Elvevi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Sara Massironi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| |
Collapse
|
|
12
|
Jadhav A, Ayyat M, Serafini FM. Presentation, Diagnosis, and Treatment of a Sporadic Gastrinoma With Liver Metastases. Cureus 2024; 16:e61426. [PMID: 38947692 PMCID: PMC11214729 DOI: 10.7759/cureus.61426] [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: 05/31/2024] [Indexed: 07/02/2024] Open
Abstract
A gastrinoma is a rare and potentially deadly tumor. Gastrinomas can be difficult to detect at first, given that affected patients can present with nonspecific symptoms, such as anemia, weight loss, and diarrhea, leading to a large list of differentials. The symptoms can be hard to manage, and the treatment almost always includes surgical intervention. Gastrinomas often metastasize to the liver, in which case, the only curative treatment option is surgical resection of the primary tumor along with as many metastatic lesions as possible. This report reviews the case of a 59-year-old female who presented with symptoms of anemia and an upper gastrointestinal bleed, who was discovered to have a pancreatic gastrinoma with more than 12 liver metastases. It also describes the management of her critical condition, which was used to give her the best chance of survival.
Collapse
Affiliation(s)
- Alisha Jadhav
- Surgery, St. George's University School of Medicine, Brooklyn, USA
| | - Mumen Ayyat
- Surgery, Brookdale University Hospital Medical Center, Brooklyn, USA
| | | |
Collapse
|
|
13
|
Rehfeld JF. The cckOMA syndrome and its relation to the Zollinger-Ellison syndrome: a diagnostic challenge. Scand J Gastroenterol 2024; 59:533-542. [PMID: 38299632 DOI: 10.1080/00365521.2024.2308532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 01/12/2024] [Accepted: 01/14/2024] [Indexed: 02/02/2024]
Abstract
OBJECTIVE Among patients with enteropancreatic neuroendocrine tumor syndromes only one case with a cholecystokinin (CCK) secreting tumor has been reported. She had significant hyperCCKemia leading to a specific syndrome of severe diarrheas, weight loss, repeated duodenal ulcers and a permanently contracted gallbladder with gallstones. There are, however, reasons to believe that further CCKomas exist, for instance among Zollinger-Ellison patients with normal plasma gastrin concentrations. The present review is a call to gastroenterologists for awareness of such CCKoma patients. METHOD After a short case report, the normal endocrine and oncological biology of CCK is described. Subsequently, the CCKoma symptoms are discussed with particular reference to the partly overlapping symptoms of the Zollinger-Ellison syndrome. In this context, the diagnostic use of truly specific CCK and gastrin assays are emphasized. The discussion also entails the problem of access to accurate CCK measurements. CONCLUSION Obviously, the clinical awareness about the CCKoma syndrome is limited. Moreover, it is also likely that the knowledge about the necessary specificity demands of diagnostic gastrin and CCK assays have obscured proper diagnosis of the CCKoma syndromes in man.
Collapse
Affiliation(s)
- Jens F Rehfeld
- Department of Clinical Biochemistry, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark
| |
Collapse
|
|
14
|
Kartik A, Armstrong VL, Stucky CC, Wasif N, Fong ZV. Contemporary Approaches to the Surgical Management of Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2024; 16:1501. [PMID: 38672582 PMCID: PMC11048062 DOI: 10.3390/cancers16081501] [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: 02/20/2024] [Revised: 04/04/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
The incidence of pancreatic neuroendocrine tumors (PNETs) is on the rise primarily due to the increasing use of cross-sectional imaging. Most of these incidentally detected lesions are non-functional PNETs with a small proportion of lesions being hormone-secreting, functional neoplasms. With recent advances in surgical approaches and systemic therapies, the management of PNETs have undergone a paradigm shift towards a more individualized approach. In this manuscript, we review the histologic classification and diagnostic approaches to both functional and non-functional PNETs. Additionally, we detail multidisciplinary approaches and surgical considerations tailored to the tumor's biology, location, and functionality based on recent evidence. We also discuss the complexities of metastatic disease, exploring liver-directed therapies and the evolving landscape of minimally invasive surgical techniques.
Collapse
Affiliation(s)
| | | | | | | | - Zhi Ven Fong
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ 85054, USA
| |
Collapse
|
|
15
|
Fang S, Shi YP, Wang L, Han S, Shi YQ. Clinical features and prognostic factors of duodenal neuroendocrine tumours: A comparative study of ampullary and nonampullary regions. World J Gastrointest Oncol 2024; 16:907-918. [PMID: 38577444 PMCID: PMC10989361 DOI: 10.4251/wjgo.v16.i3.907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 01/05/2024] [Accepted: 01/29/2024] [Indexed: 03/12/2024] Open
Abstract
BACKGROUND Duodenal neuroendocrine tumours (DNETs) are rare neoplasms. However, the incidence of DNETs has been increasing in recent years, especially as an incidental finding during endoscopic studies. Regrettably, there is no consensus regarding the ideal treatment of DNETs. Even there are few studies on the clinical features and survival analysis of DNETs. AIM To analyze the clinical characteristics and prognostic factors of patients with duodenal neuroendocrine tumours. METHODS The clinical data of DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected. Neuroendocrine tumours located in the ampulla area of the duodenum were divided into the ampullary region group; neuroendocrine tumours in any part of the duodenum outside the ampullary area were divided into the nonampullary region group. Using a retrospective study, the clinical characteristics of the two groups and risk factors affecting the survival of DNET patients were analysed. RESULTS Twenty-nine DNET patients were screened. The male to female ratio was 1:1.9, and females comprised the majority. The ampullary region group accounted for 24.1% (7/29), while the nonampullary region group accounted for 75.9% (22/29). When diagnosed, the clinical symptoms of the ampullary region group were mainly abdominal pain (85.7%), while those of the nonampullary region groups were mainly abdominal distension (59.1%). There were differences in the composition of staging of tumours between the two groups (Fisher's exact probability method, P = 0.001), with nonampullary stage II tumours (68.2%) being the main stage (P < 0.05). After the diagnosis of DNETs, the survival rate of the ampullary region group was 14.3% (1/7), which was lower than that of 72.7% (16/22) in the nonampullary region group (Fisher's exact probability method, P = 0.011). The survival time of the ampullary region group was shorter than that of the nonampullary region group (P < 0.000). The median survival time of the ampullary region group was 10.0 months and that of the nonampullary region group was 451.0 months. Multivariate analysis showed that tumours in the ampulla region and no surgical treatment after diagnosis were independent risk factors for the survival of DNET patients (HR = 0.029, 95%CI 0.004-0.199, P < 0.000; HR = 12.609, 95%CI: 2.889-55.037, P = 0.001). Further analysis of nonampullary DNET patients showed that the survival time of patients with a tumour diameter < 2 cm was longer than that of patients with a tumour diameter ≥ 2 cm (t = 7.243, P = 0.048). As of follow-up, 6 patients who died of nonampullary DNETs had a tumour diameter that was ≥ 2 cm, and 3 patients in stage IV had liver metastasis. Patients with a tumour diameter < 2 cm underwent surgical treatment, and all survived after surgery. CONCLUSION Surgical treatment is a protective factor for prolonging the survival of DNET patients. Compared to DNETs in the ampullary region, patients in the nonampullary region group had a longer survival period. The liver is the organ most susceptible to distant metastasis of nonampullary DNETs.
Collapse
Affiliation(s)
- Sa Fang
- Department of Gastroenterology, Honghui Hospital, Xi’an Jiaotong University, Xi'an 710054, Shanxi Province, China
| | - Yu-Peng Shi
- Department of Gastroenterology, Honghui Hospital, Xi’an Jiaotong University, Xi'an 710054, Shanxi Province, China
| | - Lu Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710032, Shaanxi Province, China
| | - Shuang Han
- Department of Gastroenterology, Honghui Hospital, Xi’an Jiaotong University, Xi'an 710054, Shanxi Province, China
| | - Yong-Quan Shi
- Department of Gastroenterology, Xijing Hospital Affiliated to Air Force Medical University, Xi'an 710032, Shaanxi Province, China
| |
Collapse
|
|
16
|
Sok C, Ajay PS, Tsagkalidis V, Kooby DA, Shah MM. Management of Gastric Neuroendocrine Tumors: A Review. Ann Surg Oncol 2024; 31:1509-1518. [PMID: 38062290 PMCID: PMC10922891 DOI: 10.1245/s10434-023-14712-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 11/20/2023] [Indexed: 01/30/2024]
Abstract
Gastric neuroendocrine tumors (G-NET) are rare tumors arising from enterochromaffin-like cells of the gastric mucosa. They belong to a larger group called gastroenteropancreatic neuroendocrine tumors and are classified as low, intermediate, or high-grade tumors based on their proliferative indices. They are further categorized into three subtypes based on their morphologic characteristics, pathogenesis, and behavior. Types 1 and 2 tumors are characterized by elevated serum gastrin and are usually multifocal. They typically occur in the setting of atrophic gastritis or MEN1/Zollinger Ellison syndrome, respectively. Type 2 tumors are associated with the most symptoms, such as abdominal pain and diarrhea. Type 3 tumors are associated with normal serum gastrin, are usually solitary, and occur sporadically. This type has the most aggressive phenotype and metastatic potential. Treatment and prognosis for G-NET is dependent on their type, size, and stage. Type 1 has the best prognosis, and Type 3 has the worst. This review discusses the presentation, workup, and surgical management of these tumors.
Collapse
Affiliation(s)
- Caitlin Sok
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Pranay S Ajay
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Vasileios Tsagkalidis
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - David A Kooby
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Mihir M Shah
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
| |
Collapse
|
|
17
|
Sok C, Shah MM. ASO Author Reflections: Simplifying the Fundamentals of Gastric Neuroendocrine Tumor Management. Ann Surg Oncol 2024; 31:1519-1520. [PMID: 38123732 DOI: 10.1245/s10434-023-14820-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 12/07/2023] [Indexed: 12/23/2023]
Affiliation(s)
- Caitlin Sok
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Mihir M Shah
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
| |
Collapse
|
|
18
|
Massironi S. The diagnostic challenges of functioning neuroendocrine tumors: balancing accuracy, availability, and personalized care. Expert Rev Endocrinol Metab 2024; 19:99-101. [PMID: 38390719 DOI: 10.1080/17446651.2024.2320639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 02/15/2024] [Indexed: 02/24/2024]
Affiliation(s)
- Sara Massironi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca, School of Medicine, Monza, Italy
| |
Collapse
|
|
19
|
Efared B, Tassiou EIM, Bako ABA, Boubacar I, Boureima HS, Nouhou H. Sporadic Zollinger-Ellison syndrome in a patient with isolated mesenteric gastrinoma. Int J Surg Case Rep 2024; 116:109474. [PMID: 38447521 PMCID: PMC10926117 DOI: 10.1016/j.ijscr.2024.109474] [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: 02/04/2024] [Revised: 02/27/2024] [Accepted: 02/29/2024] [Indexed: 03/08/2024] Open
Abstract
INTRODUCTION Zollinger-Ellison syndrome (ZES) is due to a gastrin-producing neuroendocrine tumor (gastrinoma) with subsequent gastric acid hypersecretion, gastroesophageal reflux disease (GERD), peptic ulcers, and chronic diarrhea. CASE PRESENTATION A 40-year old patient presented with epigastric pain associated with diarrhea evolving for 10 years, he has been treated by acid-suppressive medications without substantial clinical improvement. Gastro-duodenal endoscopy was performed with gastric biopsies that showed peptic ulcerations, a serum gastrin assay that showed high levels exceeding 10 times the upper limit of the normal range. The abdominal contrast-enhanced computed tomography scan (CT-Scan) showed a solid-cystic mass with contrast enhancement in the right colon mesentery. The histopathological analysis of the resected mass showed a well-differentiated neuroendocrine tumor, and the diagnosis of a sporadic Zollinger-Ellison syndrome (ZES) was disclosed. Eighteen months after the surgical treatment the patient has no symptoms of the disease. CLINICAL DISCUSSION Patients with ZES present often with long-standing clinical symptoms with delayed diagnosis. The surgical resection of the causative gastrinoma remains the most effective therapeutic treatment. CONCLUSION Patients with refractory chronic diarrhea and epigastric pain should be suspected of having ZES in order to benefit from adequate clinical management.
Collapse
Affiliation(s)
- Boubacar Efared
- Faculté des Sciences de la Santé, Université Abdou Moumouni, Niamey, Niger; Laboratoire d'anatomie et cytologie pathologiques, Hôpital National de Niamey, Niger.
| | - Elh I M Tassiou
- Service de chirurgie viscérale, Hôpital National Amirou B. Diallo, Niamey, Niger
| | - Aïchatou Balaraba Abani Bako
- Faculté des Sciences de la Santé, Université Abdou Moumouni, Niamey, Niger; Hôpital Général de Référence, Niamey, Niger
| | - Idrissa Boubacar
- Laboratoire d'anatomie et cytologie pathologiques, Hôpital National de Niamey, Niger
| | | | - Hassan Nouhou
- Faculté des Sciences de la Santé, Université Abdou Moumouni, Niamey, Niger
| |
Collapse
|
|
20
|
Durma AD, Saracyn M, Kołodziej M, Jóźwik-Plebanek K, Dmochowska B, Kapusta W, Żmudzki W, Mróz A, Kos-Kudła B, Kamiński G. Epidemiology of Neuroendocrine Neoplasms and Results of Their Treatment with [ 177Lu]Lu-DOTA-TATE or [ 177Lu]Lu-DOTA-TATE and [ 90Y]Y-DOTA-TATE-A Six-Year Experience in High-Reference Polish Neuroendocrine Neoplasm Center. Cancers (Basel) 2023; 15:5466. [PMID: 38001726 PMCID: PMC10670106 DOI: 10.3390/cancers15225466] [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: 10/09/2023] [Revised: 11/10/2023] [Accepted: 11/16/2023] [Indexed: 11/26/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a group of neoplasms arising from neuroendocrine cells. The worldwide incidence and prevalence of the NENs are estimated to be 6/100,000 and 35/100,000, respectively. Those numbers are increasing every decade, requiring higher and higher diagnosis and treatment costs. Radioligand therapy (RLT) using beta-emitting radioisotopes is an efficient and relatively safe method of treatment, typically used as a second-line treatment. RLT tolerability is higher than other available pharmacotherapies (chemotherapy or tyrosine kinase inhibitors). Recent studies show an increase in overall survival among patients treated with RLT. The present study aimed to learn the epidemiology of NENs in Poland and assess the effectiveness of RLT in a high-reference center. A prospective analysis of 167 patients treated with RLT in one of Poland's highest-reference NEN centers was performed. The analysis covered 66 months of observation (1 December 2017-30 May 2023), during which 479 RLT single administrations of radioisotope were given. The standard procedure was to give four courses of [177Lu]Lu-DOTA-TATE alone, or tandem therapy-[177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE. Grading analysis showed that most patients had non-functioning G2 NEN with a mean Ki-67 of 6.05% (SD ± 6.41). The most common primary tumor location was the pancreas. Over two-thirds of patients did undergo surgery due to primary tumors or distant metastases. The majority of patients were using lanreotide as a chronically injected somatostatin analog. Median progression-free survival (PFS) on somatostatin analogs was 21.0 (IQR = 29.0) months. Directly after the last course of RLT, disease stabilization was noted in 69.46% of patients, partial regression was noted in 20.36% of patients, complete regression was noted in 0.60% of patients, and progression was noted in 9.58% of patients. In long-term follow-up, the median observation time among patients who underwent four treatment cycles (n = 108) was 29.8 (IQR = 23.9) months. Stabilization of the disease was observed in 55.56% of the patients and progression was observed in 26.85% of the patients, while 17.59% of patients died. Median PFS was 29.3 (IQR 23.9), and the median OS was 34.0 months (IQR 16.0). The mean age of NEN diagnosis is the sixth decade of life. It takes almost three years from NEN diagnosis to the start of RLT. In long-term observation, RLT leads to disease stabilization in over half of the patients with progressive disease. No differences in PFS or OS depend on the radioisotope used for RLT. In Poland, organized coordination of NEN treatment in high-reference centers ensures the continuity of patient care.
Collapse
Affiliation(s)
- Adam Daniel Durma
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Marek Saracyn
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Maciej Kołodziej
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Katarzyna Jóźwik-Plebanek
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Beata Dmochowska
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Waldemar Kapusta
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Wawrzyniec Żmudzki
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Adrianna Mróz
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Beata Kos-Kudła
- Department of Endocrinology and Neuroendocrine Tumors, Department of Pathophysiology and Endocrinology in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
| | - Grzegorz Kamiński
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| |
Collapse
|
|
21
|
Bentley B, Chanaa F, Clayton S. Complete Esophageal Obstruction: A Rare Complication of Zollinger-Ellison Syndrome. ACG Case Rep J 2023; 10:e01205. [PMID: 38025843 PMCID: PMC10651347 DOI: 10.14309/crj.0000000000001205] [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: 11/03/2022] [Accepted: 10/17/2023] [Indexed: 12/01/2023] Open
Abstract
Complete esophageal obstruction (CEO) is a rare phenomenon usually observed after receiving head and neck radiation. Zollinger-Ellison syndrome (ZES) is typically associated with minimal esophageal morbidity because of advancements in antisecretory medications. There are currently no documented reports of CEO in patients with ZES. Although surgeries are available for the treatment of CEO, there is no established method for endoscopic lumen restoration, given its rarity. This case documents potential sequala of modern-day patients with ZES.
Collapse
Affiliation(s)
- Blake Bentley
- Section on Gastroenterology and Hepatology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC
| | - Fadi Chanaa
- Section on Gastroenterology and Hepatology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC
| | - Steven Clayton
- Section on Gastroenterology and Hepatology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC
| |
Collapse
|
|
22
|
Cavalcoli F, Gallo C, Coltro LA, Rausa E, Cantù P, Invernizzi P, Massironi S. Therapeutic Challenges for Gastric Neuroendocrine Neoplasms: Take It or Leave It? MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1757. [PMID: 37893475 PMCID: PMC10608689 DOI: 10.3390/medicina59101757] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 09/23/2023] [Accepted: 09/28/2023] [Indexed: 10/29/2023]
Abstract
Background and Objectives: Gastric neuroendocrine neoplasms (gNENs) represent rare but increasingly recognized tumors. They are distinguished into three main clinical types (type-1, type-2, and type-3) according to gastrin level and at histological evaluation in well-differentiated G1, G2, or G3 lesions, as well as poorly-differentiated lesions. Small type-1 and type-2 neoplasms with low proliferation indices demonstrated excellent survival without progression during an extended follow-up period, and for these reasons, active endoscopic observation or endoscopic resection are feasible options. On the other hand, surgery is the treatment of choice for more aggressive type-3, G3, or infiltrating neoplasms. The present study aims to comprehensively review and compare the available therapeutic strategies for gNENs. Materials and Methods: A computerized literature search was performed using relevant keywords to identify all of the pertinent articles with particular attention to gNEN endoscopic treatment. Results: In recent years, different endoscopic resective techniques (such as endoscopic mucosal dissection, modified endoscopic mucosal resection, and endoscopic full-thickness resection) have been developed, showing a high rate of complete resection for advanced and more aggressive lesions. Conclusions: Overall, gNENs represent a heterogeneous group of lesions with varying behavior which require personalized management. The non-operative approach for small type-1 gNENs seems to be feasible and should be promoted. A step-up approach with minimally invasive endoscopic therapies might be proposed, particularly for type-1 gNEN. On the other hand, it is important to recognize the negative prognostic factors in order to identify those rare cases requiring more aggressive approaches. A possible therapeutic algorithm for localized gNEN management is provided.
Collapse
Affiliation(s)
- Federica Cavalcoli
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; (F.C.); (P.C.)
| | - Camilla Gallo
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca School of Medicine, 20900 Monza, Italy; (C.G.)
| | - Lorenzo Andrea Coltro
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca School of Medicine, 20900 Monza, Italy; (C.G.)
| | - Emanuele Rausa
- Unit of Hereditary Digestive Tract Tumours, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy;
| | - Paolo Cantù
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; (F.C.); (P.C.)
| | - Pietro Invernizzi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca School of Medicine, 20900 Monza, Italy; (C.G.)
| | - Sara Massironi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca School of Medicine, 20900 Monza, Italy; (C.G.)
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, ASST Monza, 20900 Monza, Italy
| |
Collapse
|
|
23
|
Helderman NC, Suerink M, Kilinç G, van den Berg JG, Nielsen M, Tesselaar ME. Relation between WHO Classification and Location- and Functionality-Based Classifications of Neuroendocrine Neoplasms of the Digestive Tract. Neuroendocrinology 2023; 114:120-133. [PMID: 37690447 PMCID: PMC10836754 DOI: 10.1159/000534035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 08/21/2023] [Indexed: 09/12/2023]
Abstract
Practice of neuroendocrine neoplasms (NENs) of the digestive tract, which comprise of a highly diverse group of tumors with a rising incidence, faces multiple biological, diagnostic, and therapeutic issues. Part of these issues is due to misuse and misinterpretation of the classification and terminology of NENs of the digestive tract, which make it increasingly challenging to evaluate and compare the literature. For instance, grade 3 neuroendocrine tumors (NETs) are frequently referred to as neuroendocrine carcinomas (NECs) and vice versa, while NECs are, by definition, high grade and therefore constitute a separate entity from NETs. Moreover, the term NET is regularly misused to describe NENs in general, and NETs are frequently referred to as benign, while they should always be considered malignancies as they do have metastatic potential. To prevent misconceptions in future NEN-related research, we reviewed the most recent terminology used to classify NENs of the digestive tract and created an overview that combines the classification of these NENs according to the World Health Organization (WHO) with location- and functionality-based classifications. This overview may help clinicians and researchers in understanding the current literature and could serve as a guide in the clinic as well as for writing future studies on NENs of the digestive tract. In this way, we aim for the universal use of terminology, thereby providing an efficient foundation for future NEN-related research.
Collapse
Affiliation(s)
- Noah C. Helderman
- Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
| | - Manon Suerink
- Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
| | - Gül Kilinç
- Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands
| | - José G. van den Berg
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Maartje Nielsen
- Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
| | - Margot E.T. Tesselaar
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| |
Collapse
|
|
24
|
Rossi RE, Corti F, Pusceddu S, Milione M, Coppa J, Masoni B, Oldani S, Sabella G, Cafaro P, Repici A. Multidisciplinary Approach to the Diagnosis of Occult Primary Neuroendocrine Neoplasm: A Clinical Challenge. J Clin Med 2023; 12:5537. [PMID: 37685605 PMCID: PMC10488469 DOI: 10.3390/jcm12175537] [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: 06/27/2023] [Revised: 07/31/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
Approximately 11% to 14% of subjects with neuroendocrine neoplasms (NENs) have metastatic lesions with unknown primary origin (UPO), with the majority of UPO-NENs found in the small bowel. Herein, we assessed the available literature on UPO-NENs, focusing on clinical presentation and diagnostic techniques to identify the primary site. The identification of the primary tumor is important as it affects the prognosis; however, the clinical presentation can be non-specific in non-functioning forms. In the presence of metastatic disease, the histological sample is fundamental to obtain immunohistochemical markers that might orientate the clinician in the search for the primary tumor through radiology, functional imaging and endoscopic techniques. In summary, multidisciplinary management plays a key role in UPO-NENs, even more than in other NENs. Molecular biology and gene-expression profiling represent areas of great interest which might be developed in the near future for both the diagnosis and the treatment of these neoplasms.
Collapse
Affiliation(s)
- Roberta Elisa Rossi
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (B.M.); (A.R.)
| | - Francesca Corti
- Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori Monza, Via G.B. Pergolesi, 20900 Monza, Italy; (F.C.); (P.C.)
| | - Sara Pusceddu
- Gastro-Entero-Pancreatic and Neuroendocrine Tumor Unit 1, Department of Medical Oncology, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (S.P.); (S.O.)
| | - Massimo Milione
- Department of Pathology and Laboratory Medicine, Fondazione IRCCS–Istituto Nazionale dei Tumori, 20133 Milan, Italy; (M.M.); (G.S.)
| | - Jorgelina Coppa
- Hepatology and Hepato-Pancreatic-Biliary Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy;
| | - Benedetta Masoni
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (B.M.); (A.R.)
| | - Simone Oldani
- Gastro-Entero-Pancreatic and Neuroendocrine Tumor Unit 1, Department of Medical Oncology, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (S.P.); (S.O.)
| | - Giovanna Sabella
- Department of Pathology and Laboratory Medicine, Fondazione IRCCS–Istituto Nazionale dei Tumori, 20133 Milan, Italy; (M.M.); (G.S.)
| | - Pietro Cafaro
- Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori Monza, Via G.B. Pergolesi, 20900 Monza, Italy; (F.C.); (P.C.)
| | - Alessandro Repici
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy; (B.M.); (A.R.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Milan, Italy
| |
Collapse
|
|
25
|
Elkelany OO, Karaisz FG, Davies B, Krishna SG. An Overview of Pancreatic Neuroendocrine Tumors and an Update on Endoscopic Techniques for Their Management. Curr Oncol 2023; 30:7566-7580. [PMID: 37623030 PMCID: PMC10453483 DOI: 10.3390/curroncol30080549] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 07/25/2023] [Accepted: 07/31/2023] [Indexed: 08/26/2023] Open
Abstract
The growing importance of advanced endoscopy in the diagnosis and treatment of pancreatic neuroendocrine neoplasms (PanNETs) necessitates a comprehensive understanding of various biochemical markers, genetic testing methods, radiological techniques, and treatment approaches that encompass multiple disciplines within and beyond gastrointestinal oncology. This review aims to highlight key aspects of these topics, with a specific focus on emerging EUS-guided procedures for the management of PanNETs.
Collapse
Affiliation(s)
- Osama O. Elkelany
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Fred G. Karaisz
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Benjamin Davies
- College of Medicine, The Ohio State University, Columbus, OH 43201, USA
| | - Somashekar G. Krishna
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| |
Collapse
|
|
26
|
Sultana Q, Kar J, Verma A, Sanghvi S, Kaka N, Patel N, Sethi Y, Chopra H, Kamal MA, Greig NH. A Comprehensive Review on Neuroendocrine Neoplasms: Presentation, Pathophysiology and Management. J Clin Med 2023; 12:5138. [PMID: 37568540 PMCID: PMC10420169 DOI: 10.3390/jcm12155138] [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: 07/13/2023] [Revised: 08/01/2023] [Accepted: 08/02/2023] [Indexed: 08/13/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors with neuroendocrine differentiation that can arise from any organ. They account for 2% of all malignancies in the United States. A significant proportion of NEN patients experience endocrine imbalances consequent to increased amine or peptide hormone secretion, impacting their quality of life and prognosis. Over the last decade, pathologic categorization, diagnostic techniques and therapeutic choices for NENs-both well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs)-have appreciably evolved. Diagnosis of NEN mostly follows a suspicion from clinical features or incidental imaging findings. Hormonal or non-hormonal biomarkers (like serum serotonin, urine 5-HIAA, gastrin and VIP) and histology of a suspected NEN is, therefore, critical for both confirmation of the diagnosis and classification as an NET or NEC. Therapy for NENs has progressed recently based on a better molecular understanding, including the involvement of mTOR, VEGF and peptide receptor radionuclide therapy (PRRT), which add to the growing evidence supporting the possibility of treatment beyond complete resection. As the incidence of NENs is on the rise in the United States and several other countries, physicians are more likely to see these cases, and their better understanding may support earlier diagnosis and tailoring treatment to the patient. We have compiled clinically significant evidence for NENs, including relevant changes to clinical practice that have greatly updated our diagnostic and therapeutic approach for NEN patients.
Collapse
Affiliation(s)
- Qamar Sultana
- Department of Medicine, Deccan College of Medical Sciences, Hyderabad 500058, India;
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
| | - Jill Kar
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Department of Medicine, Lady Hardinge Medical College, New Delhi 110001, India
| | - Amogh Verma
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Rama Medical College Hospital and Research Centre, Hapur 245304, India
| | - Shreya Sanghvi
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai 400022, India
| | - Nirja Kaka
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Department of Medicine, GMERS Medical College, Himmatnagar 390021, India
| | - Neil Patel
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Department of Medicine, GMERS Medical College, Himmatnagar 390021, India
| | - Yashendra Sethi
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Government Doon Medical College, HNB Uttarakhand Medical Education University, Dehradun 248001, India
| | - Hitesh Chopra
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, India;
| | - Mohammad Amjad Kamal
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610017, China;
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1216, Bangladesh
- Enzymoics, Hebersham, NSW 2770, Australia
- Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia
| | - Nigel H. Greig
- Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
| |
Collapse
|
|
27
|
Zaher EA, Eshan SH, Patel P, Rafa ZI, Zaher D. A Rare Case of Hepatic Gastrinoma. Cureus 2023; 15:e43383. [PMID: 37700944 PMCID: PMC10495076 DOI: 10.7759/cureus.43383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/12/2023] [Indexed: 09/14/2023] Open
Abstract
Zollinger-Ellison syndrome (ZES) is a rare condition caused by gastrin-secreting neuroendocrine tumors known as gastrinomas. We present a case of hepatic ZES presenting as upper gastrointestinal (GI) bleeding in a 70-year-old female. Initial evaluation revealed the patient to be in severe sepsis with septic shock secondary to a urinary tract infection, and her hospitalization was complicated by hematemesis and melena in the setting of multiple duodenal ulcers. Subsequent investigations, including elevated gastrin levels and a somatostatin receptor scan, confirmed the diagnosis of gastrinoma.
Collapse
Affiliation(s)
- Eli A Zaher
- Department of Internal Medicine, Ascension Saint Joseph Hospital, Chicago, USA
| | | | - Parth Patel
- Department of Internal Medicine, Ascension Saint Joseph Hospital, Chicago, USA
| | - Zahin Islam Rafa
- Department of Internal Medicine, Ibn Sina Medical College Hospital, Dhaka, BGD
| | - Daria Zaher
- Department of Internal Medicine, University Clinical Hospital in Bialystok, Bialystok, POL
| |
Collapse
|
|
28
|
Kann PH. Relevance of Endoscopic Ultrasound in Endocrinology Today: Multiple Endocrine Neoplasia Type 1, Insulinoma, Primary Aldosteronism-An Expert's Perspective Based on Three Decades of Scientific and Clinical Experience. Cancers (Basel) 2023; 15:3494. [PMID: 37444604 DOI: 10.3390/cancers15133494] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/30/2023] [Accepted: 07/03/2023] [Indexed: 07/15/2023] Open
Abstract
In endocrinology, endoscopic ultrasound (EUS) may be used to image the adrenals, the endocrine pancreas, and other organs where endocrine neoplasms may occur. During the recent decades, EUS has been established predominantly to assess multiple endocrine neoplasia type 1, to localize insulinomas, and to identify aldosterone-producing adenomas. EUS in endocrinology requires special skills and individual experience in order to provide reliable diagnostic information.
Collapse
Affiliation(s)
- Peter Herbert Kann
- German Center for Endocrine Care DEVZ, Düsseldorfer Strasse 1-7, 60329 Frankfurt am Main, Germany
- Faculty of Medicine, Philipp's University, Baldinger Strasse, 35033 Marburg, Germany
| |
Collapse
|
|
29
|
Magi L, Marasco M, Rinzivillo M, Faggiano A, Panzuto F. Management of Functional Pancreatic Neuroendocrine Neoplasms. Curr Treat Options Oncol 2023; 24:725-741. [PMID: 37103745 PMCID: PMC10272249 DOI: 10.1007/s11864-023-01085-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/20/2023] [Indexed: 04/28/2023]
Abstract
OPINION STATEMENT Functional pancreatic neuroendocrine neoplasms (pNENs) are rare and heterogeneous diseases in terms of both clinical and pathological aspects. These tumors secrete hormones or peptides, which may cause a wide variety of symptoms related to a clinical syndrome. The management of functional pNENs is still challenging for clinicians due to the need to control both tumor growth and specific symptoms. Surgery remains the cornerstone in the management of local disease because it can definitively cure the patient. However, when the disease is not resectable, a broad spectrum of therapeutic options, including locoregional therapy, somatostatin analogs (SSAs), targeted therapies, peptide-receptor radionuclide therapy (PRRT), and chemotherapy, are available. The present review summarizes the main key issues regarding the clinical management of these tumors, providing a specific highlight on their therapeutic approach.
Collapse
Affiliation(s)
- Ludovica Magi
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Via di Grottarossa 1035, 00189, Rome, Italy
| | - Matteo Marasco
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Via di Grottarossa 1035, 00189, Rome, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Via di Grottarossa 1035, 00189, Rome, Italy
| | - Antongiulio Faggiano
- Endocrinology Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Via Di Grottarrossa 1035, 00189, Rome, Italy
| | - Francesco Panzuto
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Via di Grottarossa 1035, 00189, Rome, Italy.
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Via di Grottarossa 1035, 00189, Rome, Italy.
| |
Collapse
|
|
30
|
Massironi S, Rossi RE, Laffusa A, Eller-Vainicher C, Cavalcoli F, Zilli A, Ciafardini C, Sciola V, Invernizzi P, Peracchi M. Sporadic and MEN1-related gastrinoma and Zollinger-Ellison syndrome: differences in clinical characteristics and survival outcomes. J Endocrinol Invest 2023; 46:957-965. [PMID: 36436191 PMCID: PMC10105668 DOI: 10.1007/s40618-022-01961-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 11/04/2022] [Indexed: 11/28/2022]
Abstract
PURPOSE Gastrinoma with Zollinger-Ellison syndrome (ZES) may occur sporadically (Sp) or as part of the inherited syndrome of multiple endocrine neoplasia 1 (MEN-1). Data comparing Sp and MEN-1/ZES are scanty. We aimed to identify and compare their clinical features. METHODS Consecutive patients with ZES were evaluated between 1992 and 2020 among a monocentric Italian patient cohort. RESULTS Of 76 MEN-1 patients, 41 had gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN), 18 of whom had ZES; of 320 Sp-GEP-NEN, 19 had Sp-ZES. MEN-1/ZES patients were younger (p = 0.035) and the primary MEN-1/ZES gastrinoma was smaller than Sp-ZES (p = 0.030). Liver metastases occurred in both groups, but only Sp-ZES developed extrahepatic metastases. 13 Sp-ZES and 8 MEN-1/ZES underwent surgery. 8 Sp-ZES and 7 MEN-1/ZES received somatostatin analogs (SSAs). Median overall survival (OS) was higher in MEN-1/ZES than in Sp-ZES (310 vs 168 months, p = 0.034). At univariate-logistic regression, age at diagnosis (p = 0.01, OR = 1.1), G3 grading (p = 0.003, OR = 21.3), Sp-ZES (p = 0.02, OR = 0.3) and presence of extrahepatic metastases (p = 0.001, OR = 7.2) showed a significant association with OS. At multivariate-COX-analysis, none of the variables resulted significantly related to OS. At univariate-logistic regression, age (p = 0.04, OR = 1.0), size (p = 0.039, OR = 1.0), G3 grade (p = 0.008, OR = 14.6) and extrahepatic metastases (p = 0.005, OR = 4.6) were independently associated with progression-free survival (PFS). In multivariate-COX-analysis, only extrahepatic metastases (p = 0.05, OR = 3.4) showed a significant association with PFS. Among SSAs-treated patients, MEN-1/ZES showed better PFS (p = 0.0227). After surgery, the median PFS was 126 and 96 months in MEN-1 and Sp, respectively. CONCLUSION MEN-1/ZES patients generally show better OS and PFS than Sp-ZES as well as better SSAs response.
Collapse
Affiliation(s)
- S Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital, Via Pergolesi 3, Monza, Italy.
- Department of Medicine and Surgery, European Reference Network on Hepatological Diseases (ERN RARE LIVER), San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
| | - R E Rossi
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy
| | - A Laffusa
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital, Via Pergolesi 3, Monza, Italy
- Department of Medicine and Surgery, European Reference Network on Hepatological Diseases (ERN RARE LIVER), San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
| | - C Eller-Vainicher
- Endocrinology, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milan, Italy
| | - F Cavalcoli
- Diagnostic and Therapeutic Endoscopy Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - A Zilli
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy
| | - C Ciafardini
- Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milan, Italy
| | - V Sciola
- Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milan, Italy
| | - P Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital, Via Pergolesi 3, Monza, Italy
- Department of Medicine and Surgery, European Reference Network on Hepatological Diseases (ERN RARE LIVER), San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
| | - M Peracchi
- Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milan, Italy
| |
Collapse
|
|
31
|
Wydra A, Cylke-Falkowska K, Czajka-Oraniec I, Kolasińska-Ćwikła A, Ćwikła J, Zgliczyński W, Stelmachowska-Banaś M. Severe ectopic Cushing syndrome in a transgender man with a metastatic gastrinoma and an adrenal tumor-A case report and review of the literature. Front Endocrinol (Lausanne) 2023; 14:1135016. [PMID: 37008936 PMCID: PMC10061007 DOI: 10.3389/fendo.2023.1135016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 02/27/2023] [Indexed: 03/18/2023] Open
Abstract
A 38-year-old transgender man with advanced metastatic functional pancreatic neuroendocrine neoplasm (PanNEN) gastrinoma was admitted to the Department of Endocrinology due to severe ACTH-dependent hypercortisolemia. An ectopic production of ACTH by PanNEN was suspected. The patient qualified for bilateral adrenalectomy after preoperative treatment with metyrapone. Finally, the patient underwent resection of the left adrenal gland with the tumor only, which surprisingly resulted in a significant decrease in ACTH and cortisol levels, leading to clinical improvement. Pathology report revealed an adenoma of the adrenal cortex with positive ACTH staining. The result of the simultaneous liver lesion biopsy confirmed a metastatic NEN G2 with positive ACTH immunostaining as well. We looked for a correlation between gender-affirming hormone treatment and the onset of the disease and its rapid progression. This may be the first case describing the coexistence of gastrinoma and ectopic Cushing disease in a transsexual patient.
Collapse
Affiliation(s)
- Arnika Wydra
- Department of Endocrinology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | | | | | - Agnieszka Kolasińska-Ćwikła
- Department of Oncology and Radiotherapy, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw, Poland
- Department of Radiology, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw, Poland
| | - Jarosław Ćwikła
- Department of Cardiology and Internal Medicine, Medical School University of Warmia and Mazury, Olsztyn, Poland
- Diagnostic and Therapy Center – Gammed, Warsaw, Poland
| | - Wojciech Zgliczyński
- Department of Endocrinology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | | |
Collapse
|
|
32
|
Kaur J, Stoukides G, Amaturo M. Closed-Loop Gastric Outlet Obstruction Secondary to Duodenal Ulcer in a Patient With Esophageal Stricture. Cureus 2023; 15:e36507. [PMID: 37090344 PMCID: PMC10121273 DOI: 10.7759/cureus.36507] [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: 01/12/2023] [Accepted: 03/22/2023] [Indexed: 04/25/2023] Open
Abstract
Closed-loop gastric outlet obstruction (GOO) is a rare complication that results from a mechanical obstruction in the pylorus or duodenum. In the early 1990s, the common cause of GOO was peptic ulcer disease, accounting for 5% to 10% of hospital admissions. Peptic ulcer disease is the disruption of the mucosal integrity in the stomach and duodenum and can be categorized into gastric ulcers and duodenal ulcers. With the treatment for Helicobacter pylori and the increased use of proton pump inhibitors (PPI), GOO now occurs in fewer than 5% of patients with duodenal ulcer disease and even less in those with gastric ulcer disease. Although the morbidity of duodenal ulcers has been declining in recent years, the incidence of post-bulbar duodenal ulcer (PBDU) remains at a constant 9.33%, primarily due to diagnostic and therapeutic difficulties. Additionally, fewer than 5% of obstructing duodenal ulcers are caused by PBDU, and even fewer are located in the second or third portions of the duodenum. Ulcers located in the distal part of the duodenum raise concern for syndromes associated with hypersecretion of acid, including Zollinger-Ellison syndrome (ZES). The ZES is rare, accounting only for 0.1% of all duodenal ulcers. Here, we present a case where a patient with esophageal stricture developed a rare case of closed-loop GOO secondary to a duodenal ulcer. The patient, initially treated for esophageal perforation, developed an esophageal stricture. The patient was being worked up for ZES and multiple endocrine neoplasia link type 1 (MEN1) syndrome due to his concerning laboratory findings and rare clinical presentation.
Collapse
Affiliation(s)
- Jashandeep Kaur
- Medicine, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, USA
| | - Georgianna Stoukides
- Medicine, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, USA
| | - Michael Amaturo
- General Surgery, Jamaica Hospital Medical Center, New York, USA
| |
Collapse
|
|
33
|
Emerging Immunotherapeutic and Diagnostic Modalities in Carcinoid Tumors. Molecules 2023; 28:molecules28052047. [PMID: 36903295 PMCID: PMC10004351 DOI: 10.3390/molecules28052047] [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: 10/28/2022] [Revised: 01/26/2023] [Accepted: 02/08/2023] [Indexed: 02/25/2023] Open
Abstract
Evasion of innate immunity represents a frequently employed method by which tumor cells survive and thrive. Previously, the development of immunotherapeutic agents capable of overcoming this evasion has realized pronounced clinical utility across a variety of cancer types. More recently, immunological strategies have been investigated as potentially viable therapeutic and diagnostic modalities in the management of carcinoid tumors. Classic treatment options for carcinoid tumors rely upon surgical resection or non-immune pharmacology. Though surgical intervention can be curative, tumor characteristics, such as size, location, and spread, heavily limit success. Non-immune pharmacologic treatments can be similarly limited, and many demonstrate problematic side effects. Immunotherapy may be able to overcome these limitations and further improve clinical outcomes. Similarly, emerging immunologic carcinoid biomarkers may improve diagnostic capabilities. Recent developments in immunotherapeutic and diagnostic modalities of carcinoid management are summarized here.
Collapse
|
|
34
|
Bevere M, Gkountakos A, Martelli FM, Scarpa A, Luchini C, Simbolo M. An Insight on Functioning Pancreatic Neuroendocrine Neoplasms. Biomedicines 2023; 11:303. [PMID: 36830839 PMCID: PMC9953748 DOI: 10.3390/biomedicines11020303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Revised: 01/16/2023] [Accepted: 01/18/2023] [Indexed: 01/24/2023] Open
Abstract
Pancreatic neuroendocrine neoplasms (PanNENs) are rare neoplasms arising from islets of the Langerhans in the pancreas. They can be divided into two groups, based on peptide hormone secretion, functioning and nonfunctioning PanNENs. The first group is characterized by different secreted peptides causing specific syndromes and is further classified into subgroups: insulinoma, gastrinoma, glucagonoma, somatostatinoma, VIPoma and tumors producing serotonin and adrenocorticotrophic hormone. Conversely, the second group does not release peptides and is usually associated with a worse prognosis. Today, although the efforts to improve the therapeutic approaches, surgery remains the only curative treatment for patients with PanNENs. The development of high-throughput techniques has increased the molecular knowledge of PanNENs, thereby allowing us to understand better the molecular biology and potential therapeutic vulnerabilities of PanNENs. Although enormous advancements in therapeutic and molecular aspects of PanNENs have been achieved, there is poor knowledge about each subgroup of functioning PanNENs.Therefore, we believe that combining high-throughput platforms with new diagnostic tools will allow for the efficient characterization of the main differences among the subgroups of functioning PanNENs. In this narrative review, we summarize the current landscape regarding diagnosis, molecular profiling and treatment, and we discuss the future perspectives of functioning PanNENs.
Collapse
Affiliation(s)
- Michele Bevere
- Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
- ARC-Net Applied Research on Cancer Centre, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Anastasios Gkountakos
- Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
- ARC-Net Applied Research on Cancer Centre, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Filippo Maria Martelli
- Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
- ARC-Net Applied Research on Cancer Centre, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Michele Simbolo
- Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
| |
Collapse
|
|
35
|
Alzerwi N. Post-bulbar duodenal ulcer with anterior perforation with kissing ulcer and duodenocaval fistula: A case report and review of literature. World J Clin Cases 2022; 10:9071-9077. [PMID: 36157647 PMCID: PMC9477055 DOI: 10.12998/wjcc.v10.i25.9071] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 05/27/2022] [Accepted: 07/25/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND A post-bulbar duodenal ulcer (PBDU) is an ulcer in the duodenum that is distal to the duodenal bulb. PBDU may coexist with a synchronous posterior ulcer in rare occurrences, resulting in a kissing ulcer (KU). Duodenocaval fistula (DCF) is another uncommon but potentially fatal complication related to PBDU. There is limited knowledge of the scenarios in which PBDU is complicated by KU and DCF simultaneously.
CASE SUMMARY A 22-year-old man was admitted to the emergency department with abdominal pain, stiffness, and vomiting. The X-ray showed pneumoperitoneum, suggesting a perforated viscus. Laparotomy revealed a KU with anterior perforation and a DCF. After Kocherization, venorrahphy was used to control caval bleeding. Due to the critical condition of the patient, only primary duodenorrahphy with gastrojejunostomy was performed as a damage control strategy. However, later, the patient developed obstructive jaundice and leakage, and two additional jejunal perforations were detected. Due to the poor condition of the duodenum and the involvement of the ampulla in the posterior ulcer, neither primary repair nor pancreatic-free duodenectomy and ampulloplasty/ampullary reimplantation were considered viable; therefore, an emergency pancreaticoduodenectomy was performed, along with resection and anastomosis of the two jejunal perforations. The patient had a smooth recovery after surgery and was discharged after 27 d.
CONCLUSION The timely diagnosis of PBDU and radical surgery can aid in the smooth recovery of patients, even in the most complex cases.
Collapse
Affiliation(s)
- Nasser Alzerwi
- Department of Surgery, College of Medicine, Majmaah University, Riyadh 66, Riyadh , Saudi Arabia
| |
Collapse
|
|
36
|
Jeong JH, Lee SY, Han HS. Gastric Corpus Hypertrophy with a Bleeding Hyperplastic Polyp in a Helicobacter pylori-naive Subject After Long-term Proton Pump Inhibitor Use. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2022. [DOI: 10.7704/kjhugr.2021.0062] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
|