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Zhao E, Yu Q, Wang M, Wang Z, Jiang B, Ma X, Zhou B, Dai Q, Li J, Wang S, Chen F, Yang X. Value of serum brain-derived neurotrophic factor and glial fibrillary acidic protein for detecting depression in patients with Helicobacter pylori infection. Neurosci Lett 2024; 825:137687. [PMID: 38403261 DOI: 10.1016/j.neulet.2024.137687] [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: 09/07/2023] [Revised: 01/31/2024] [Accepted: 02/09/2024] [Indexed: 02/27/2024]
Abstract
OBJECTIVE Infection with helicobacter pylori (H. pylori) is associated with depression, and depression can affect the outcome of H. pylori treatment. This study aimed to evaluate the value of serum brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) for predicting depression in H. pylori-positive patients. METHOD A total of 82H. pylori-positive and 82H. pylori-negative patients were recruited for this study. All patients underwent neuropsychological and gastrointestinal assessments and blood sampling. BDNF and GFAP levels were measured in serum. The least absolute shrinkage and selection operator (LASSO) model was used to determine a composite marker. RESULTS H. pylori-positive patients showed significantly increased serum GFAP levels and significantly decreased serum BDNF levels compared to H. pylori-negative patients. Among H. pylori-positive patients, serum levels of gastrin 17 (G-17), pepsinogen (PG) I/PGII, BDNF, and GFAP, as well as Gastrointestinal Symptom Rating Scale (GSRS) scores, were significantly correlated with Hamilton Depression Scale (HAMD-24) overall scores and factor scores. Interactions between serum BDNF/GFAP and gastrointestinal serum indices or GSRS scores were significantly associated with HAMD-24 scores in H. pylori-positive patients. The LASSO model indicated that the combination of serum BDNF, GFAP, and G-17 and GSRS scores could identify H. pylori-positive patients with depression with an area under the curve of 0.879. CONCLUSION Circulating changes in BDNF and GFAP were associated with the occurrence of depression in H. pylori-positive patients. A composite marker including neural and gastrointestinal function-related indices may be of value for identifying depression among H. pylori-positive patients.
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Affiliation(s)
- En Zhao
- Department of Gastroenterology, Xishan People's Hospital of Wuxi City, Wuxi 214105, China.
| | - Qian Yu
- Department of Gastroenterology, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
| | - Meilei Wang
- Department of Neurology, Xishan People's Hospital of Wuxi City, Wuxi 214105, China
| | - Zhengqiu Wang
- Department of Gastroenterology, Xishan People's Hospital of Wuxi City, Wuxi 214105, China
| | - Bin Jiang
- Department of Gastroenterology, Xishan People's Hospital of Wuxi City, Wuxi 214105, China
| | - Xiang Ma
- Department of Gastroenterology, Xishan People's Hospital of Wuxi City, Wuxi 214105, China
| | - Bin Zhou
- Department of Gastroenterology, Xishan People's Hospital of Wuxi City, Wuxi 214105, China
| | - Qingyong Dai
- Department of Neurology, Xishan People's Hospital of Wuxi City, Wuxi 214105, China
| | - Jinyu Li
- Department of Gastroenterology, Xishan People's Hospital of Wuxi City, Wuxi 214105, China
| | - Shiming Wang
- Department of Gastroenterology, Xishan People's Hospital of Wuxi City, Wuxi 214105, China
| | - Fengjuan Chen
- Department of Gastroenterology, Xishan People's Hospital of Wuxi City, Wuxi 214105, China.
| | - Xiaojun Yang
- Department of Gastroenterology, Xishan People's Hospital of Wuxi City, Wuxi 214105, China.
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Farhat F, Hussein M, Sbaity E, Alsharm A, Rasul K, Khairallah S, Assi T, Allahverdi N, Othman A, Kattan J. Gastrointestinal stromal tumor in North Africa and the middle east: updates in presentation and management from an 11-year retrospective cohort. Hosp Pract (1995) 2023; 51:275-287. [PMID: 38112178 DOI: 10.1080/21548331.2023.2277682] [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: 02/07/2023] [Accepted: 10/25/2023] [Indexed: 12/21/2023]
Abstract
OBJECTIVES This study described the epidemiological, clinical, and survival profiles of patients with gastrointestinal stromal tumor (GIST) in North Africa and the Middle East (AfME). METHODS This regional, multicenter, observational, retrospective study collected 11-year data on demographics, medical history, disease characteristics, current treatment approaches of GIST, the safety of the most common tyrosine kinase inhibitors (TKIs), second cancers, and survival status. RESULTS Data of 201 eligible patients were analyzed: mean age was 56.9 ± 12.6 years; 111 (55.2%) patients were men, 21 (10.4%) patients had previous personal malignancy. The most common clinical presentation of GIST was dysphagia [92 (45.8%) patients]. The stomach was the most common primary site in 120 (60.7%) patients, 171 (85.1%) patients had localized disease at diagnosis. 198 (98.5%) GIST cases were CD117/CD34-positive. Imatinib was used in the neoadjuvant (18/21 patients), adjuvant (85/89 patients), and first-line metastatic treatment (28/33 patients) settings. The most common non-hematological toxicity associated with TKIs was vomiting in 32/85 (37.6%) patients. Overall, 100 (49.8%) patients (95%CI: 42.8-56.7%) were alive and disease-free while 30 (14.9%) patients were alive with active disease. CONCLUSION Presentation of GIST in our AfME population is consistent with global reports, being more frequent in patients >50 years old and having the stomach as the most common primary site. Unlike what is usually reported, though, we did have more patients with lymphatic spread of the disease. Despite the global trend and advances in the treatment of GIST according to molecular profile, this is still far to happen in our population given the lack of access to molecular profiles and the high associated cost.
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Affiliation(s)
- Fadi Farhat
- Department of Onco-Hematology, Mount Lebanon Hospital University Medical Center, Balamand University, Beirut, Hazmieh, Lebanon
| | - Marwa Hussein
- Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Eman Sbaity
- Department of General Surgery, American University of Beirut Medical Center, Beirut, Lebanon
| | - Abdullah Alsharm
- Oncology Department, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia
| | - Kakil Rasul
- Department of Hematology-Oncology, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar
| | | | - Tarek Assi
- Department of Onco-Hematology, Mount Lebanon Hospital University Medical Center, Balamand University, Beirut, Hazmieh, Lebanon
- Department of Hematology-Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Niloofar Allahverdi
- Translational Cancer Research Facility and Clinical Trial Unit, Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Ahmad Othman
- Department of Hematology-Oncology, Hammoud Hospital University Medical Center, Saida, Lebanon
| | - Joseph Kattan
- Department of Hematology-Oncology, Hôtel-Dieu de France University Hospital, Beirut, Lebanon
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Al-Maqrashi Z, Burney IA, Taqi KM, Al-Sawafi Y, Qureshi A, Lakhtakia R, Mehdi I, Al-Bahrani B, Kumar S, Al-Moundhri M. Clinicopathological Features and Outcomes of Gastrointestinal Stromal Tumours in Oman: A multi-centre study. Sultan Qaboos Univ Med J 2021; 21:e237-e243. [PMID: 34221471 PMCID: PMC8219329 DOI: 10.18295/squmj.2021.21.02.012] [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: 05/11/2020] [Revised: 08/13/2020] [Accepted: 09/09/2020] [Indexed: 11/16/2022] Open
Abstract
Objectives This study aimed to report the clinicopathological features, management and long-term outcomes of patients with gastrointestinal stromal tumours (GISTs) in Oman. Methods This retrospective study was conducted on patients treated for GIST between January 2003 and December 2017 at three tertiary referral centres in Muscat, Oman. All patients with confirmed histopathological diagnoses of GIST and followed-up at the centres during this period were included. Relevant information was retrieved from hospital records until April 2019. Results A total of 44 patients were included in the study. The median age was 55.5 years and 56.8% were female. The most common primary site of disease was the stomach (63.6%) followed by the jejunum/ileum (18.2%). Two patients (4.5%) had c-Kit-negative, discovered on GIST-1-positive disease. A total of 24 patients (54.5%) presented with localised disease and eight (33.3%) were classified as being at high risk of relapse. Patients with metastatic disease received imatinib in a palliative setting, whereas those with completely resected disease in the intermediate and high-risk groups were treated with adjuvant imatinib. Of the six patients (13.6%) with progressive metastatic disease, of which four had mutations on exon 11 and one on exon 9, while one had wild-type disease. Overall, rates of progression-free survival and overall survival (OS) at 100 months were 77.4% and 80.4%, respectively. Rates of OS for patients with localised and metastatic disease were 89.9% and 80.2%, respectively. Conclusion The presenting features and outcomes of patients with GISTs in Oman were comparable to those reported in the regional and international literature.
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Affiliation(s)
| | - Ikram A Burney
- Department of Medicine, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman
| | - Kadhim M Taqi
- Division of General Surgery, Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - Yaqoob Al-Sawafi
- Department of General Surgery, Armed Forces Hospital, Muscat, Oman
| | - Asim Qureshi
- Department of Pathology, King's Mill Hospital, Sherwood Forest Hospitals National Health Service Foundation Trust, Mansfield, Nottinghamshire, UK.,Department of Pathology, Sultan Qaboos University Hospital, Muscat, Oman
| | - Ritu Lakhtakia
- Department of Pathology, Mohammed bin Rashid University of Medicine & Health Sciences, Dubai, United Arab Emirates
| | - Itrat Mehdi
- National Oncology Centre, Royal Hospital, Muscat, Oman
| | | | - Shiyam Kumar
- Department of Medical Oncology, Yeovil District Hospital NHS Foundation Trust, Somerset, UK
| | - Mansour Al-Moundhri
- Department of Medicine, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman
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Rare Tumors GI Group, Farhat F, Farsi AA, Mohieldin A, Bahrani BA, Sbaity E, Jaffar H, Kattan J, Rasul K, Saad K, Assi T, Morsi WE, Abood RA. Comprehensive review into the challenges of gastrointestinal tumors in the Gulf and Levant countries. World J Clin Cases 2020; 8:487-503. [PMID: 32110658 PMCID: PMC7031830 DOI: 10.12998/wjcc.v8.i3.487] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 12/13/2019] [Accepted: 01/01/2020] [Indexed: 02/05/2023] Open
Abstract
Although gastrointestinal stromal tumors (GISTs) are rare, with an incidence of 1/100000 per year, they are the most common sarcomas in the peritoneal cavity. Despite considerable progress in the diagnosis and treatment of GIST, about half of all patients are estimated to experience recurrence. With only two drugs, sunitinib and regorafenib, approved by the Food and Drug Administration, selecting treatment options after imatinib failure and coordinating multidisciplinary care remain challenging. In addition, physicians across the Middle East face some additional and unique challenges such as lack of published local data from clinical trials, national disease registries and regional scientific research, limited access to treatment, lack of standardization of care, and limited access to mutational analysis. Although global guidelines set a framework for the management of GIST, there are no standard local guidelines to guide clinical practice in a resource-limited environment. Therefore, a group of 11 experienced medical oncologists from across the Gulf and Levant region, part of the Rare Tumors Gastrointestinal Group, met over a period of one year to conduct a narrative review of the management of GIST and to describe regional challenges and gaps in patient management as an essential step to proposing local clinical practice recommendations.
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Affiliation(s)
| | - Fadi Farhat
- Hammoud Hospital UMC, Saida PO Box 652, Lebanon
| | | | - Ahmed Mohieldin
- Medical Oncology Department, Kuwait Cancer Control Center, Kuwait PO Box 42262, Kuwait
| | - Bassim Al Bahrani
- Medical Oncology Department, Royal Hospital, Muscat PO Box 1331, Oman
| | - Eman Sbaity
- Division of General Surgery, American University of Beirut, Beirut 1107 2180, Lebanon
| | - Hassan Jaffar
- Oncology Department, Tawam Hospital, Al Ain PO Box 15258, United Arab Emirates
| | - Joseph Kattan
- Hemato-oncology Department, Hotel Dieu de France, Beirut, Lebanon
| | - Kakil Rasul
- Hemato-oncology Department, National Center for Cancer Care and Research, Doha, Qatar
| | - Khairallah Saad
- Pathology Department, Institute National de Pathologic, Beirut, Lebanon
| | - Tarek Assi
- Oncology Department, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
| | - Waleed El Morsi
- Pfizer Oncology-Emerging Markets, Dubai Media City, Dubai, United Arab Emirates
| | - Rafid A Abood
- Oncology Department, Basra College of Medicine, Basra, Iraq
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Lopes LF, Ojopi EB, Bacchi CE. Gastrointestinal stromal tumor in Brazil: clinicopathology, immunohistochemistry, and molecular genetics of 513 cases. Pathol Int 2008; 58:344-52. [PMID: 18477213 DOI: 10.1111/j.1440-1827.2008.02235.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
The aim of the present study was to evaluate the clinicopathological, immunohistochemical, and molecular genetic features of gastrointestinal stromal tumors in Brazil and compare them with cases from other countries. Five hundred and thirteen cases were retrospectively analyzed. HE-stained sections and clinical information were reviewed and the immunohistochemical expression of CD117, CD34, smooth-muscle actin, S-100 protein, desmin, CD44v3 adhesion molecule, p53 protein, epidermal growth factor receptor, and Ki-67 antigen was studied using tissue microarrays. Mutation analysis of KIT and platelet-derived growth factor receptor-alpha genes was also performed. There was a slight female predominance (50.3%) and the median age at diagnosis was 59 years. The tumors were mainly located in the stomach (38.4%). Immunohistochemistry showed that CD117 was expressed in 95.7% of cases. Epidermal growth factor receptor expression was observed in 84.4% of tumors. p53 protein expression was found only in 2.6% of cases but all belonged to the high-risk group for aggressive behavior according to the National Institutes of Health consensus approach. No CD44v3 adhesion molecule expression was detected. KIT exon 11 mutations were the most frequent (62.2%). The present data confirm that gastrointestinal stromal tumors in Brazilian patients do not differ from tumors occurring in other countries.
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Affiliation(s)
- Lisandro Ferreira Lopes
- Department of Pathology, University of Sao Paulo Medical School and Pathology Reference Lab, Botucatu, Sao Paulo, Sau Paulo State, Brazil
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Sabah M, Cummins R, Leader M, Kay E. Altered expression of cell cycle regulatory proteins in gastrointestinal stromal tumors: markers with potential prognostic implications. Hum Pathol 2006; 37:648-55. [PMID: 16733203 DOI: 10.1016/j.humpath.2006.01.023] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2005] [Accepted: 01/20/2006] [Indexed: 10/24/2022]
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract. The prediction of the malignant potential of GISTs is still difficult. Altered cell cycle regulation may underlie the tumorigenesis and/or the progression of human malignancies. Although p53 and Bcl-2 have been extensively investigated in GISTs, little is known about the frequency of expression and possible clinical implications of alterations of other cell cycle regulatory proteins in these neoplasms. We have previously investigated the role of loss of p16(INK4A) by loss of heterozygosity and immunohistochemistry in the progression of GISTs and found that loss of heterozygosity of 9p and loss of p16 expression are confined to malignant GISTs. This has led us to investigate the role of other cell cycle regulatory proteins in these tumors. Twenty-three cases of GIST (9 low malignant potential [LMP], 10 primary malignant, and 4 intra-abdominal recurrences) were examined. All cases were strongly positive for KIT (CD117). Immunohistochemical stains were carried out on tissue microarrays to evaluate the expression of proteins involved in the G(1)-S transition and proteins that regulate apoptosis including Rb, E2F1, cyclin D1, CDK4, CDK6, p27(KIP1), p21(WAF1/CIP1), p53, Mdm2, Bcl-2, and Bax. The positive phenotypes identified were as follows: Rb, 39.1%; E2F1, 69.6%; cyclin D1, 30.4%; CDK4, 100%; CDK6, 30.4%; 39.1%; p27(KIP1), 47.8%; p21(WAF1/CIP1), 39.1%; p53, 43.5%; Mdm2, 17.4%; Bcl-2, 91.3%; and Bax, 100%. Malignant GISTs are more likely to be associated with a positive E2F1 and p53 phenotype and a negative p16 and p27(KIP1) phenotype. It was concluded that aberration of the cell cycle regulators is a frequent finding and may be a contributing factor to the pathogenesis of GISTs. While some alterations are seen in LMP and malignant GISTs and therefore may represent an early event in molecular tumorigenesis of GISTs, other alterations are more common in malignant GISTs than LMP and therefore have potential utility as complementary tools for the prognostication of GISTs.
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Affiliation(s)
- Muna Sabah
- Department of Histopathology, Education and Research Centre, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin 9, Ireland
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