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Yadav A, Gupta P, Gupta P, Patil AN, Das CK, Hooda H, Thakur D, Sharma V, Singh AK, Yadav TD, Kaman L, Thakur JS, Sudini HK, Srinivasan R, Dutta U. Aflatoxin exposure is associated with an increased risk of gallbladder cancer. Int J Cancer 2025; 156:322-330. [PMID: 39239866 DOI: 10.1002/ijc.35171] [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: 04/10/2024] [Revised: 08/03/2024] [Accepted: 08/06/2024] [Indexed: 09/07/2024]
Abstract
Gall bladder cancer (GBC) is common among the socioeconomically deprived populations of certain geographical regions. Aflatoxin is a genotoxic hepatocarcinogen, which is recognized to have a role in the pathogenesis of hepatocellular carcinoma. However, the role of aflatoxin in the pathogenesis of GBC is largely unknown. We determined serum AFB1-Lys albumin adduct (AAA) levels as a marker of aflatoxin exposure in the patients with GBC and compared to those without GBC. The relationship of AAA levels to cytogenetic (TP53mutation&HER2/neu amplification) and radiological characteristics of the tumor was assessed. We included GBC cases (n = 51) and non-GBC controls (n = 100). Mean serum AAA levels were higher in the GBC group (n = 51) than those without GBC (n = 100) (26.1 ± 12.2 vs. 13.1 ± 11.9 ng/mL; p < .001). HER2/neu expression was associated with higher AAA levels compared to those with equivocal or negative expression (43.9 ± 3 vs. 28.6 ± 10 vs. 19.3 ± 7 ng/mL; p < .001). Older age (age >50 years) (odds ratio [OR] = 3.2 [CI: 1.3-8.2]; p = .013), positive Helicobacter pylori serology (OR = 5.1 [CI: 1.4-17.8]; p = .012), presence of GS (OR = 5 [CI: 1.5-16.9]; p = .009) and detectable AAA levels (OR = 6.8 [CI: 1.3-35.7]; p = .024) were independent risk factors for the presence of the GBC among all study subjects. Among patients harboring GS, older age (age >50 years) (OR = 4.5 [CI: 1.3-14.9]; p = .015), female gender (OR = 3.8 [CI: 1.2-12.5]; p = .027), presence of multiple GS (OR = 21.9 [CI: 4.8-100.4]; p < .001) and high serum AAA levels (OR = 5.3 [CI: 1.6-17.3]; p = .006) were independent risk factors for the presence of the GBC. Elderly age >50 years (OR = 2.6 [CI: 1.3-5.2]; p = .010) and frequent peanut consumption (OR = 2.3 [CI: 1.1-4.9]; p = .030) were independent risk factors for high serum AAA levels. The current study has implications for the prevention of GBC through the reduction of dietary aflatoxin exposure.
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Affiliation(s)
- Amit Yadav
- Department of Gastroenterology, PGIMER, Chandigarh, India
| | - Pankaj Gupta
- Department of Radiology, PGIMER, Chandigarh, India
| | - Parikshaa Gupta
- Department of Cytology & Gynecological Pathology, PGIMER, Chandigarh, India
| | - Amol N Patil
- Department of Clinical Pharmacology, PGIMER, Chandigarh, India
| | - Chandan K Das
- Department of Medical Oncology, PGIMER, Chandigarh, India
| | - Harish Hooda
- Department of Gastroenterology, PGIMER, Chandigarh, India
| | - Deepa Thakur
- Department of Gastroenterology, PGIMER, Chandigarh, India
| | - Vishal Sharma
- Department of Gastroenterology, PGIMER, Chandigarh, India
| | - Anupam K Singh
- Department of Gastroenterology, PGIMER, Chandigarh, India
| | | | | | - Jarnail Singh Thakur
- Department of Community Medicine and School of Public Health, PGIMER, Chandigarh, India
| | - Hari Kishan Sudini
- International Crops Research Institute for the Semi-Arid Tropics Patancheru, Hyderabad, India
| | - Radhika Srinivasan
- Department of Cytology & Gynecological Pathology, PGIMER, Chandigarh, India
| | - Usha Dutta
- Department of Gastroenterology, PGIMER, Chandigarh, India
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Kumar A, Sarangi Y, Gupta A, Sharma A. Gallbladder cancer: Progress in the Indian subcontinent. World J Clin Oncol 2024; 15:695-716. [PMID: 38946839 PMCID: PMC11212610 DOI: 10.5306/wjco.v15.i6.695] [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: 02/28/2024] [Revised: 04/25/2024] [Accepted: 05/15/2024] [Indexed: 06/24/2024] Open
Abstract
Gallbladder cancer (GBC) is one of the commonest biliary malignancies seen in India, Argentina, and Japan. The disease has dismal outcome as it is detected quite late due to nonspecific symptoms and signs. Early detection is the only way to improve the outcome. There have been several advances in basic as well as clinical research in the hepatobiliary and pancreatic diseases in the West and other developed countries but not enough has been done in GBC. Therefore, it is important and the responsibility of the countries with high burden of GBC to find solutions to the many unanswered questions like etiopathogenesis, early diagnosis, treatment, and prognostication. As India being one of the largest hubs for GBC in the world, it is important to know how the country has progressed on GBC. In this review, we will discuss the outcome of the publications from India highlighting the work and the developments taken place in past several decades both in basic and clinical research.
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Affiliation(s)
- Ashok Kumar
- Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Yajnadatta Sarangi
- Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Annapurna Gupta
- Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Aarti Sharma
- Division of Haematology, Mayo Clinic Arizona, Phoenix, AZ 85054, United States
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Takahashi K, Ozawa E, Shimakura A, Mori T, Miyaaki H, Nakao K. Recent Advances in Endoscopic Ultrasound for Gallbladder Disease Diagnosis. Diagnostics (Basel) 2024; 14:374. [PMID: 38396413 PMCID: PMC10887964 DOI: 10.3390/diagnostics14040374] [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: 12/27/2023] [Revised: 02/01/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Gallbladder (GB) disease is classified into two broad categories: GB wall-thickening and protuberant lesions, which include various lesions, such as adenomyomatosis, cholecystitis, GB polyps, and GB carcinoma. This review summarizes recent advances in the differential diagnosis of GB lesions, focusing primarily on endoscopic ultrasound (EUS) and related technologies. Fundamental B-mode EUS and contrast-enhanced harmonic EUS (CH-EUS) have been reported to be useful for the diagnosis of GB diseases because they can evaluate the thickening of the GB wall and protuberant lesions in detail. We also outline the current status of EUS-guided fine-needle aspiration (EUS-FNA) for GB lesions, as there have been scattered reports on EUS-FNA in recent years. Furthermore, artificial intelligence (AI) technologies, ranging from machine learning to deep learning, have become popular in healthcare for disease diagnosis, drug discovery, drug development, and patient risk identification. In this review, we outline the current status of AI in the diagnosis of GB.
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Affiliation(s)
- Kosuke Takahashi
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan; (E.O.); (T.M.); (H.M.); (K.N.)
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Pavlidis ET, Galanis IN, Pavlidis TE. New trends in diagnosis and management of gallbladder carcinoma. World J Gastrointest Oncol 2024; 16:13-29. [PMID: 38292841 PMCID: PMC10824116 DOI: 10.4251/wjgo.v16.i1.13] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 12/06/2023] [Accepted: 12/19/2023] [Indexed: 01/11/2024] Open
Abstract
Gallbladder (GB) carcinoma, although relatively rare, is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis. It is closely associated with cholelithiasis and long-standing large (> 3 cm) gallstones in up to 90% of cases. The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes, GB wall calcification (porcelain) or mainly mucosal microcalcifications, and GB polyps ≥ 1 cm in size. Diagnosis is made by ultrasound, computed tomography (CT), and, more precisely, magnetic resonance imaging (MRI). Preoperative staging is of great importance in decision-making regarding therapeutic management. Preoperative staging is based on MRI findings, the leading technique for liver metastasis imaging, enhanced three-phase CT angiography, or magnetic resonance angiography for major vessel assessment. It is also necessary to use positron emission tomography (PET)-CT or 18F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake. Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6% of cases. Multimodality treatment is needed, including surgical resection, targeted therapy by biological agents according to molecular testing gene mapping, chemotherapy, radiation therapy, and immunotherapy. It is of great importance to understand the updated guidelines and current treatment options. The extent of surgical intervention depends on the disease stage, ranging from simple cholecystectomy (T1a) to extended resections and including extended cholecystectomy (T1b), with wide lymph node resection in every case or IV-V segmentectomy (T2), hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y, and adjacent organ resection if necessary (T3). Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery, but much attention must be paid to avoiding injuries. In addition to surgery, novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy (neoadjuvant-adjuvant capecitabine, cisplatin, gemcitabine) have yielded promising results even in inoperable cases calling for palliation (T4). Thus, individualized treatment must be applied.
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Affiliation(s)
- Efstathios T Pavlidis
- 2nd Propedeutic Department of Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Ioannis N Galanis
- 2nd Propedeutic Department of Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Theodoros E Pavlidis
- 2nd Propedeutic Department of Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
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Ishikawa M, Ishida K, Machida H, Kato H, Ishizaki S, Nagai T, Matsuyama K, Nozawa Y, Takada-Owada A, Kaneko Y, Sakuma F, Irisawa A. A case of malignant ascites of neuroendocrine carcinoma of the gallbladder diagnosed by endoscopic ultrasound-guided fine-needle aspiration. Diagn Cytopathol 2023; 51:658-661. [PMID: 37501588 DOI: 10.1002/dc.25199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 07/12/2023] [Accepted: 07/18/2023] [Indexed: 07/29/2023]
Affiliation(s)
- Mihoko Ishikawa
- Department of Pathology, Dokkyo Medical University Hospital, Mibu, Japan
| | - Kazuyuki Ishida
- Department of Pathology, Dokkyo Medical University Hospital, Mibu, Japan
- Department of Diagnostic Pathology, Dokkyo Medical University, Mibu, Japan
| | - Hiromi Machida
- Department of Pathology, Dokkyo Medical University Hospital, Mibu, Japan
| | - Hikaru Kato
- Department of Pathology, Dokkyo Medical University Hospital, Mibu, Japan
| | - Satomi Ishizaki
- Department of Pathology, Dokkyo Medical University Hospital, Mibu, Japan
| | - Tamiko Nagai
- Department of Pathology, Dokkyo Medical University Hospital, Mibu, Japan
| | - Kinichi Matsuyama
- Department of Pathology, Dokkyo Medical University Hospital, Mibu, Japan
| | - Yumi Nozawa
- Department of Diagnostic Pathology, Dokkyo Medical University, Mibu, Japan
| | | | - Yuko Kaneko
- Department of Diagnostic Pathology, Dokkyo Medical University, Mibu, Japan
| | - Fumi Sakuma
- Department of Gastroenterology, Dokkyo Medical University, Mibu, Japan
| | - Atsushi Irisawa
- Department of Gastroenterology, Dokkyo Medical University, Mibu, Japan
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