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1
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Nassar A, Conticchio M, Lardinois MJ, Benedetti J, Lartigau L, Marchese U, Tzedakis S, Fuks D. [Prophylactic surgery for hepatic and biliary tumors]. Bull Cancer 2025; 112:270-276. [PMID: 38937178 DOI: 10.1016/j.bulcan.2024.04.015] [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: 03/26/2024] [Revised: 04/21/2024] [Accepted: 04/24/2024] [Indexed: 06/29/2024]
Abstract
Benign tumors of the liver and biliary tract are rare entities, and some of them require surgical management to prevent their malignant transformation. Tumors from the biliary tract with malignant potential are treated either by hepatic resection, for mucinous cystic neoplasm and ciliated hepatic foregut cysts, or by biliary resections, for biliary papillary neoplasm and type I and IV choledochal cysts. The pathologies requiring prophylactic cholecystectomy are polyps larger than 10 mm, porcelain gallbladder and pancreaticobiliary maljunction. Finally, hepatocellular adenoma over 5cm, occurring in male patients, or exon 3 mutated beta-catenin, should lead to prophylactic resection by hepatic segmentectomy. This article describes these different pathologies and their management.
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Affiliation(s)
- Alexandra Nassar
- Service de chirurgie digestive, hépatobiliaire et endocrinienne, hôpital Cochin, AP-HP Centre, université Paris Cité, Paris, France.
| | - Maria Conticchio
- Service de chirurgie digestive, hépatobiliaire et endocrinienne, hôpital Cochin, AP-HP Centre, université Paris Cité, Paris, France
| | - Marie-Julie Lardinois
- Service de chirurgie digestive, hépatobiliaire et endocrinienne, hôpital Cochin, AP-HP Centre, université Paris Cité, Paris, France
| | - Juliette Benedetti
- Service de chirurgie digestive, hépatobiliaire et endocrinienne, hôpital Cochin, AP-HP Centre, université Paris Cité, Paris, France
| | - Lisa Lartigau
- Service de chirurgie digestive, hépatobiliaire et endocrinienne, hôpital Cochin, AP-HP Centre, université Paris Cité, Paris, France
| | - Ugo Marchese
- Service de chirurgie digestive, hépatobiliaire et endocrinienne, hôpital Cochin, AP-HP Centre, université Paris Cité, Paris, France
| | - Stylianos Tzedakis
- Service de chirurgie digestive, hépatobiliaire et endocrinienne, hôpital Cochin, AP-HP Centre, université Paris Cité, Paris, France
| | - David Fuks
- Service de chirurgie digestive, hépatobiliaire et endocrinienne, hôpital Cochin, AP-HP Centre, université Paris Cité, Paris, France.
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2
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Gonzalez C, García-Pérez A, Nervi B, Munoz C, Morales E, Losada H, Merino-Pereira G, Rothhammer F, Lorenzo Bermejo J. Cholecystectomy and digestive cancer in Chile: Complementary results from interrupted time series and aggregated data analyses. Int J Cancer 2025; 156:91-103. [PMID: 39150415 DOI: 10.1002/ijc.35138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 07/02/2024] [Accepted: 07/15/2024] [Indexed: 08/17/2024]
Abstract
Gallbladder cancer (GBC) mortality in Chile is among the highest worldwide. In 2006, the Chilean government launched a programme guaranteeing access to gallbladder surgery (cholecystectomy) for patients aged 35-49 years. We evaluated the impact of this programme on digestive cancer mortality. After conducting an interrupted time series analysis of hospitalisation and mortality data from 2002 to 2018 publicly available from the Chilean Department of Health Statistics and Information, we calculated the change in the proportion of individuals without gallbladder since 10 years. We then estimated age, gender, region, and calendar-year standardised mortality ratios (SMRs) as a function of the change in the proportion of individuals without gallbladder. The cholecystectomy rate increased by 45 operations per 100,000 persons per year (95%CI 19-72) after the introduction of the health programme. Each 1% increase in the proportion of individuals without gallbladder since 10 years was associated with a 0.73% decrease in GBC mortality (95% CI -1.05% to -0.38%), but the negative correlation was limited to women, southern Chile and age over 60. We also found decreasing mortality rates for extrahepatic bile duct, liver, oesophageal and stomach cancer with increasing proportions of individuals without gallbladder. To conclude, 12 years after its inception, the Chilean cholecystectomy programme has markedly and heterogeneously changed cholecystectomy rates. Results based on aggregate data indicate a negative correlation between the proportion of individuals without gallbladder and mortality due to gallbladder and other digestive cancers, which requires validation using individual-level longitudinal data to reduce the potential impact of ecological bias.
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Affiliation(s)
- Constanza Gonzalez
- Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany
- Center for Cancer Prevention and Control (CECAN), Santiago, Chile
| | - Alfonso García-Pérez
- Departamento de Estadística, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain
| | - Bruno Nervi
- Center for Cancer Prevention and Control (CECAN), Santiago, Chile
- Departamento de Hematología y Oncología, Escuela de Medicina Pontificia Universidad Católica de Chile, Santiago, Chile
| | - César Munoz
- Hospital Regional de Talca, Talca, Chile
- Facultad de Medicina, Universidad Católica del Maule, Talca, Chile
| | - Erik Morales
- Hospital Regional de Talca, Talca, Chile
- Facultad de Medicina, Universidad Católica del Maule, Talca, Chile
| | | | - Gina Merino-Pereira
- Departamento Manejo Integral del Cáncer y Otros Tumores, Subsecretaria de Salud Pública, Ministerio de Salud de Chile, Santiago, Chile
| | | | - Justo Lorenzo Bermejo
- Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany
- Center for Cancer Prevention and Control (CECAN), Santiago, Chile
- Laboratory of Biostatistics for Precision Oncology, Institut de Cancérologie Strasbourg Europe, Strasbourg, France
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Pipal DK, Vardhan V, Biswas P, Pipal VR, Jatoliya H. Laparoscopic Cholecystectomy for Entirely Calcified Porcelain Gallbladder: Challenges, Management, and Literature Review. JOURNAL OF THE WEST AFRICAN COLLEGE OF SURGEONS 2024; 14:440-444. [PMID: 39309387 PMCID: PMC11412580 DOI: 10.4103/jwas.jwas_168_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 11/20/2023] [Indexed: 09/25/2024]
Abstract
Commonly referred to as a "porcelain gallbladder (PGB)," gallbladder calcification is usually asymptomatic. It is observed that chronic inflammation of the gallbladder can occur as a result of another underlying condition, specifically gallstone disease. In the past, there was a belief that PGB had a correlation with gallbladder cancer, with an incidence rate of 30%. However, recent studies have indicated that the rate is only 5%-22%. Patients diagnosed with PGB, who are deemed to be at an elevated risk of developing cancer may undergo prophylactic cholecystectomies. However, recent research indicates that a subset of these patients may potentially avoid this surgical intervention. As a result of the increased risk of gallbladder cancer, and the difficulty of holding and retracting the gallbladder, laparoscopic cholecystectomy was not often recommended for patients with PGBs in the past. However, with the advancement of technology laparoscopy is now a choice for such difficult cases. Here we report a case of PGB in a 55-year-old female patient who complained of intermittent pain in the right upper abdomen with vaginal discharge. She was successfully managed laparoscopically.
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Affiliation(s)
- Dharmendra Kumar Pipal
- Department of General Surgery, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh, India
| | - Vikram Vardhan
- Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh, India
| | - Prakash Biswas
- Department of General Surgery, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh, India
| | - Vibha Rani Pipal
- Department of Gynaecology and Obstetrics, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh, India
| | - Himanshu Jatoliya
- Department of General Surgery, Government Medical College, Sirohi, Rajasthan, India
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4
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Kidogawa H, Ootubo K, Noguchi J, Yamayoshi T, Okamoto K. A Case of Porcelain Gallbladder Showing High Levels of CA19-9. Cureus 2024; 16:e72583. [PMID: 39610632 PMCID: PMC11602412 DOI: 10.7759/cureus.72583] [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: 10/28/2024] [Indexed: 11/30/2024] Open
Abstract
Porcelain gallbladder is a rare condition characterized by an extensive calcification of the gallbladder wall. It is associated with an increased risk of gallbladder cancer and elevated levels of tumor marker CA19-9, which is typically seen in pancreatic and biliary cancers. We present a case of a 60-year-old woman who presented with upper abdominal pain and nausea. Imaging revealed both a porcelain gallbladder and common bile duct stones. Initially, the patient underwent endoscopic retrograde cholangiopancreatography (ERCP) for the removal of the common bile duct stones. Notably, following the removal of the stones, the patient's CA19-9 levels were significantly elevated, reaching 6076 U/mL. Subsequently, she underwent a laparoscopic cholecystectomy. Histopathological examination and immunostaining for CA19-9 were performed on the resected specimen. Histopathology revealed marked fibrosis, calcification, and xanthogranulomatous inflammation of the gallbladder wall without evidence of malignancy. Immunostaining showed strong CA19-9 positivity in the inflamed gallbladder mucosal epithelium. Postoperatively, the patient's CA19-9 levels returned to normal (17 U/mL). This case highlights that a benign porcelain gallbladder can present with abnormally high CA19-9 levels, potentially mimicking malignancy. Reports of CA19-9 elevation in porcelain gallbladder are limited, and in most cases, significant CA19-9 elevation has been associated with malignancy. This case also demonstrates that benign conditions such as biliary obstruction, chronic inflammation, and xanthogranulomatous cholecystitis can cause significant elevations in CA19-9 levels. Therefore, careful differentiation and comprehensive evaluation are crucial for accurate diagnosis and appropriate management in such cases.
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Affiliation(s)
- Hideo Kidogawa
- Department of Surgery, Kitakyushu City Yahata Hospital, Kitakyushu, JPN
| | - Kazuhiro Ootubo
- Department of Surgery, Kitakyushu City Yahata Hospital, Kitakyushu, JPN
| | - Junya Noguchi
- Department of Surgery, Kitakyushu City Yahata Hospital, Kitakyushu, JPN
| | | | - Kohji Okamoto
- Department of Surgery, Kitakyushu City Yahata Hospital, Kitakyushu, JPN
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5
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Sun Y, Gong J, Li Z, Han L, Sun D. Gallbladder cancer: surgical treatment, immunotherapy, and targeted therapy. Postgrad Med 2024; 136:278-291. [PMID: 38635593 DOI: 10.1080/00325481.2024.2345585] [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: 03/21/2024] [Accepted: 04/12/2024] [Indexed: 04/20/2024]
Abstract
Gallbladder cancer is a common type of biliary tract tumor. Optimal management for early stage cases typically involves radical excision as the primary treatment modality. Various surgical techniques, including laparoscopic, robotic, and navigational surgery, have demonstrated favorable clinical outcomes in radical gallbladder excision. Unfortunately, most patients are ineligible for surgical intervention because of the advanced stage of the disease upon diagnosis. Consequently, non-surgical interventions, such as chemotherapy, radiotherapy, immunotherapy, and targeted therapy, have become the mainstay of treatment for patients in advanced stages. This review focuses on elucidating various surgical techniques as well as advancements in immunotherapy and targeted therapy in the context of recent advancements in gallbladder cancer research.
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Affiliation(s)
- Yanjun Sun
- Department of General Surgery, The Armed Police Corps Hospital of Anhui, Hefei, China
| | - Junfeng Gong
- Department of General Surgery, The Armed Police Corps Hospital of Anhui, Hefei, China
| | | | - Lin Han
- Department of General Surgery, The Armed Police Corps Hospital of Anhui, Hefei, China
| | - Dengqun Sun
- Department of General Surgery, The Armed Police Corps Hospital of Anhui, Hefei, China
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Quraishi R, Sanyal S, Dwivedi M, Moitra M, Dwivedi M. Genetic Factors and MicroRNAs in the Development of Gallbladder Cancer: The Prospective Clinical Targets. Curr Drug Targets 2024; 25:375-387. [PMID: 38544392 DOI: 10.2174/0113894501182288240319074330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 01/14/2024] [Accepted: 02/01/2024] [Indexed: 07/19/2024]
Abstract
Gallbladder cancer (GBC) is an uncommon condition in which malignant (cancer) cells are detected in gallbladder tissue. Cancer is often triggered when normal cells turn malignant and begin to spread. Cancer can also be caused by genetic anomalies that result in uncontrolled cell proliferation and tumor development. MicroRNAs (also known as miRNAs or miRs) are a group of small, endogenous, non-coding RNAs of 19-23 nucleotides in length, which play a key role in post-transcriptional gene regulation. These miRNAs serve as negative gene regulators by supervising target genes and regulating biological processes, including cell proliferation, migration, invasion, and apoptosis. Cancer development and progression relate to aberrant miRNA expression. This review demonstrated the implication of various genetic factors and microRNAs in developing and regulating GBC. This suggests the potential of genes and RNAs as the diagnostic, prognostic, and therapeutic targets in gallbladder cancer.
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Affiliation(s)
- Roshni Quraishi
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Gomtinagar Extension, Lucknow-226028, India
| | - Somali Sanyal
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Gomtinagar Extension, Lucknow-226028, India
| | - Medha Dwivedi
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Gomtinagar Extension, Lucknow-226028, India
| | - Monika Moitra
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Gomtinagar Extension, Lucknow-226028, India
| | - Manish Dwivedi
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Gomtinagar Extension, Lucknow-226028, India
- Research Cell, Amity University Uttar Pradesh, Lucknow Campus, Gomtinagar Extension, Lucknow-226028, India
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Rodas F, Vidal-Vidal JA, Herrera D, Brown-Brown DA, Vera D, Veliz J, Püschel P, Erices JI, Sánchez Hinojosa V, Tapia JC, Silva-Pavez E, Quezada-Monrás C, Mendoza-Soto P, Salazar-Onfray F, Carrasco C, Niechi I. Targeting the Endothelin-1 pathway to reduce invasion and chemoresistance in gallbladder cancer cells. Cancer Cell Int 2023; 23:318. [PMID: 38072958 PMCID: PMC10710704 DOI: 10.1186/s12935-023-03145-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 11/14/2023] [Indexed: 01/03/2025] Open
Abstract
BACKGROUND Gallbladder cancer (GBC) is a prevalent and deadly biliary tract carcinoma, often diagnosed at advanced stages with limited treatment options. The 5-year survival rate varies widely from 4 to 60%, mainly due to differences in disease stage detection. With only a small fraction of patients having resectable tumors and a high incidence of metastasis, advanced GBC stages are characterized by significant chemoresistance. Identification of new therapeutic targets is crucial, and recent studies have shown that the Endothelin-1 (ET-1) signaling pathway, involving ETAR and/or ETBR receptors (ETRs), plays a crucial role in promoting tumor aggressiveness in various cancer models. Blocking one or both receptors has been reported to reduce invasiveness and chemoresistance in cancers like ovarian, prostate, and colon. Furthermore, transcriptomic studies have associated ET-1 levels with late stages of GBC; however, it remains unclear whether its signaling or its inhibition has implications for its aggressiveness. Although the role of ET-1 signaling in gallbladder physiology is minimally understood, its significance in other tumor models leads us to hypothesize its involvement in GBC malignancy. RESULTS In this study, we investigated the expression of ET-1 pathway proteins in three GBC cell lines and a primary GBC culture. Our findings demonstrated that both ETAR and ETBR receptors are expressed in GBC cells and tumor samples. Moreover, we successfully down-regulated ET-1 signaling using a non-selective ETR antagonist, Macitentan, which resulted in reduced migratory and invasive capacities of GBC cells. Additionally, Macitentan treatment chemosensitized the cells to Gemcitabine, a commonly used therapy for GBC. CONCLUSION For the first time, we reveal the role of the ET-1 pathway in GBC cells, providing insight into the potential therapeutic targeting of its receptors to mitigate invasion and chemoresistance in this cancer with limited treatment options. These findings pave the way for further exploration of Macitentan or other ETR antagonists as potential therapeutic strategies for GBC management. In summary, our study represents a groundbreaking contribution to the field by providing the first evidence of the ET 1 pathway's pivotal role in modulating the behavior and aggressiveness of GBC cells, shedding new light on potential therapeutic targets.
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Affiliation(s)
- Francisco Rodas
- Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
| | - Jetzabel A Vidal-Vidal
- Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
| | - Daniela Herrera
- Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
| | - David A Brown-Brown
- Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
| | - Diego Vera
- Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
| | - Joaquín Veliz
- Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
| | - Pilar Püschel
- Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
| | - José I Erices
- Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
| | - Verónica Sánchez Hinojosa
- Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
| | - Julio C Tapia
- Laboratorio de transformación celular, Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, 8380453, Santiago, Chile
| | - Eduardo Silva-Pavez
- Facultad de Odontología y Ciencias de la Rehabilitación, Universidad San Sebastián, Bellavista, Santiago, Chile
| | - Claudia Quezada-Monrás
- Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
- Millennium Institute on Immunology and Immunotherapy, Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
| | - Pablo Mendoza-Soto
- Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile
| | - Flavio Salazar-Onfray
- Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, Universidad de Chile, 8380453, Santiago, Chile
- Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 8380453, Santiago, Chile
| | - Cristian Carrasco
- Subdepartamento de Anatomía Patológica, Hospital Base de Valdivia, 5090000, Valdivia, Chile
| | - Ignacio Niechi
- Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
- Millennium Institute on Immunology and Immunotherapy, Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
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8
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Yıldırım HÇ, Kavgaci G, Chalabiyev E, Dizdar O. Advances in the Early Detection of Hepatobiliary Cancers. Cancers (Basel) 2023; 15:3880. [PMID: 37568696 PMCID: PMC10416925 DOI: 10.3390/cancers15153880] [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: 05/29/2023] [Revised: 07/23/2023] [Accepted: 07/28/2023] [Indexed: 08/13/2023] Open
Abstract
Hepatocellular cancer (HCC) and biliary tract cancers (BTCs) have poor survival rates and a low likelihood of a cure, especially in advanced-stage disease. Early diagnosis is crucial and can significantly improve survival rates through curative treatment approaches. Current guidelines recommend abdominal ultrasonography (USG) and alpha-fetoprotein (AFP) monitoring for HCC screening in high-risk groups, and abdominal USG, magnetic resonance imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP) monitoring for biliary tract cancer. However, despite this screening strategy, many high-risk individuals still develop advanced-stage HCC and BTC. Blood-based biomarkers are being developed for use in HCC or BTC high-risk groups. Studies on AFP, AFP-L3, des-gamma-carboxy prothrombin, glypican-3 (GPC3), osteopontin (OPN), midkine (MK), neopterin, squamous cell carcinoma antigen (SCCA), Mac-2-binding protein (M2BP), cyclic guanosine monophosphate (cGMP), and interleukin-6 biomarkers for HCC screening have shown promising results when evaluated individually or in combination. In the case of BTCs, the potential applications of circulating tumor DNA, circulating microRNA, and circulating tumor cells in diagnosis are also promising. These biomarkers have shown potential in detecting BTCs in early stages, which can significantly improve patient outcomes. Additionally, these biomarkers hold promise for monitoring disease progression and evaluating response to therapy in BTC patients. However, further research is necessary to fully understand the clinical utility of these biomarkers in the diagnosis and management of HCC and BTCs.
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Affiliation(s)
| | | | | | - Omer Dizdar
- Department of Medical Oncology, Faculty of Medicine, Hacettepe University, 06230 Ankara, Turkey; (H.Ç.Y.); (G.K.); (E.C.)
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9
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Papatheodorou P, Frantzeskou K, Konstantinou K, Theophanous E. Gallbladder Clear Cell Carcinoma: Report of a Rare Case and Literature Review. Case Rep Surg 2023; 2023:8104679. [PMID: 37396493 PMCID: PMC10314819 DOI: 10.1155/2023/8104679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 05/10/2023] [Accepted: 06/17/2023] [Indexed: 07/04/2023] Open
Abstract
Carcinoma of the gallbladder is the most common biliary tract cancer. The majority of gallbladder cancers are adenocarcinomas, whereas clear-cell carcinoma of the gallbladder (CCG) is a rarely recorded variant. Usually, diagnosis is established incidentally after cholecystectomy, performed for another reason. Clinically, the different histological types of carcinomas are impossible to be recognized preoperatively, since they present with a wide and common range of symptoms. We present a male patient who underwent an emergency cholecystectomy due to suspected perforation. After an uneventful postoperative period, the histopathological report led to the diagnosis of CCG, but the surgical margins were infiltrated by the tumor. The patient decided not to proceed with any additional treatment and passed away 8 months after the operation. In conclusion, it is of great necessity to record such unusual cases and enriches global knowledge with information clinically and educationally noteworthy.
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Affiliation(s)
| | | | | | - Elena Theophanous
- Histopathology Department, Nicosia General Hospital, Nicosia, Cyprus
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10
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Rathore A, Pathak A, Ranjan S, Sud R, Shivshankara MS, Pandaya T, Arvind P, Singh VP, Nikhil P, Guleria B. A clinicoepidemiological and management profile of metastatic carcinoma gallbladder in the northeast part of Indian patients in a tertiary care center. J Cancer Res Ther 2022; 18:S428-S433. [PMID: 36510998 DOI: 10.4103/jcrt.jcrt_1213_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Introduction Metastatic gallbladder cancer (GBC) is a highly fatal malignancy and it is difficult to treat the advanced stage of GBC. In India, northern and northeastern states are the worst affected by this disease. We, hereby, report the clinicoepidemiological and management profile of 242 patients of metastatic carcinoma of GB. Materials and Methods In this study, a total of 242 cases of metastatic GBC (detected either on the first presentation or during follow-up) were managed at the Department of Medical Oncology tertiary care oncology center in the northeast part of India from May 2018 to September 2019. On presentation, all patients were subjected to detailed history and clinical examination, followed by requisite investigations and were treated as per the existent guidelines. Results One-hundred and forty-two patients were female, while 100 patients were male out of 242 patients. Female patients with metastatic GBC presented with the mean age of 54, while for males, 51.4 years. The most common presentation was pain abdomen (81.8%), while the second most common was anorexia (77.2%), followed by weight loss (62.8%) and mass per abdomen (60.7%). The most common site of metastasis recorded in our study was the liver (79.7%), followed by nonregional abdominal lymph node (69.4%) and ascites (64.4%). Out of the 242 patients, 24 patients had presented in poor Eastern Cooperative Oncology Group Performance Status (≥3) hence were deemed unfit for any oncological interventions. About 136 (56.1%) patients had presented with features of obstructive jaundice, however only 108 patients were subjected to biliary drainage procedure. After the biliary drainage procedures, only one-third (38 out of 136; 35.1%) of patients were finally able to receive chemotherapy. Conclusion In India, unfortunately, many patients present very late during the course of their illness. There is a need for the development of effective chemotherapy or targeted therapy and also there is an unmet need for patients' education. There has been an increase in the incidence of this malignancy, especially in the Northeast part of India; hence, it is the need of the hour to study various epidemiological and causative factors of the disease. Furthermore, the development of therapies for the effective management of this malignancy is really required.
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Affiliation(s)
- Anvesh Rathore
- Department of Medical Oncology, Army Hospital (Research and Referral), Delhi, India
| | - Abhishek Pathak
- Department of Medical Oncology, Command Hospital, Kolkata, India
| | - Subhash Ranjan
- Department of Medical Oncology, Command Hospital, Kolkata, India
| | - Rahul Sud
- Department of Medical Oncology, Command Hospital, Bangalore, India
| | - M S Shivshankara
- Department of Medical Oncology, Army Hospital (Research and Referral), Delhi, India
| | - Tejas Pandaya
- Department of Radiation Oncology, Command Hospital, Kolkata, India
| | - Prince Arvind
- Department of Radiation Oncology, Command Hospital, Kolkata, India
| | - V P Singh
- Department of Surgical oncology Oncology, Command Hospital, Kolkata, India
| | - P Nikhil
- Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, India
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11
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Lv C, Han S, Wu B, Liang Z, Li Y, Zhang Y, Lang Q, Zhong C, Fu L, Yu Y, Xu F, Tian Y. Novel immune scoring dynamic nomograms based on B7-H3, B7-H4, and HHLA2: Potential prediction in survival and immunotherapeutic efficacy for gallbladder cancer. Front Immunol 2022; 13:984172. [PMID: 36159808 PMCID: PMC9493478 DOI: 10.3389/fimmu.2022.984172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 08/18/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundGallbladder cancer (GBC) is a mortal malignancy with limited therapeutic strategies. We aimed to develop novel immune scoring systems focusing on B7-H3, B7-H4, and HHLA2. We further investigated their potential clinical effects in predicting survival and immunotherapeutic efficacy for GBC.MethodsThis was a retrospective cohort study in a single center that explored the expression characteristics of B7-H3, B7-H4, and HHLA2. The immune scoring nomograms for prognostic were developed via logistic regression analyses. Their performance was evaluated using the Harrell concordance index (C-index) and decision curves analysis (DCA), and validated with calibration curves.ResultsB7-H3, B7-H4, and HHLA2 manifested with a relatively high rate of co-expression patterns in GBC tissues. They were associated with worse clinicopathological stage, suppression of immune microenvironment, and unfavorable prognosis in postoperative survival. B7 stratification established based on B7-H3, B7-H4, and HHLA2 was an independent prognostic predictor (p<0.05 in both groups). Moreover, immune stratification was also successfully constructed based on B7 stratification and the density of CD8+ TILs (all p<0.001). The prediction models were developed based on B7-/or immune stratification combined with the TNM/or Nevin staging system. These novel models have excellent discrimination ability in predicting survival and immunotherapeutic efficacy for GBC patients by DCA and clinical impact plots. Finally, dynamic nomograms were developed for the most promising clinical prediction models (B7-TNM model and Immune-TNM model) to facilitate prediction.ConclusionsImmune scoring systems focusing on B7-H3, B7-H4, and HHLA2 may effectively stratify the prognosis of GBC. Prognostic nomograms based on novel immune scoring systems may potentially predict survival and immunotherapeutic efficacy in GBC. Further valid verification is necessary.
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Affiliation(s)
- Chao Lv
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Shukun Han
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Baokang Wu
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Zhiyun Liang
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Yang Li
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Yizhou Zhang
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Qi Lang
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Chongli Zhong
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Lei Fu
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Yang Yu
- Department of Surgery, Jinzhou Medical University, Liaoning, China
| | - Feng Xu
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Yu Tian
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
- *Correspondence: Yu Tian,
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Yuan Z, Shui Y, Liu L, Guo Y, Wei Q. Postoperative recurrent patterns of gallbladder cancer: possible implications for adjuvant therapy. Radiat Oncol 2022; 17:118. [PMID: 35799270 PMCID: PMC9264693 DOI: 10.1186/s13014-022-02091-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 06/27/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Gallbladder cancer (GBC) is an uncommon malignancy with high recurrent rate and poor prognosis. This study investigates the recurrent patterns of postoperative GBC, with the aim to guide the adjuvant treatments, including the radiotherapy. METHODS Retrospectively analyzed the 109 GBC patients who underwent surgery in our institution from January 2013 to 2018. Clinical follow-up revealed 54 recurrent cases, of which 40 had detailed locations of recurrence. The sites of recurrence were recorded and divided into the tumor bed, corresponding lymphatic drainage area, intrahepatic recurrence, and the other distant metastasis. RESULTS The median follow-up time is 34 months (IQR: 11-64). The median disease-free survival (DFS) and overall survival (OS) were 48.8 months and 53.7 months, respectively. Through univariate analysis, risk factors for DFS and OS include tumor markers (CA199 and CEA), hepatic invasion, perineural invasion, lymphovascular invasion, TNM staging and tumor differentiation. Through multivariate analysis, risk factors for DFS include hepatic invasion and TNM staging, and for OS is TNM staging only. Of the 40 cases with specific recurrent sites, 29 patients (29/40, 72.5%) had recurrence in the potential target volume of postoperative radiotherapy (PORT), which include tumor bed and corresponding lymphatic drainage area. The common recurrent lymph node groups included abdominal para-aortic lymph node (No.16, 15/29), hepatoduodenal ligament lymph node (No.12, 8/29), retro-pancreatic head lymph node (No.13, 7/29) and celiac axis lymph node (No.9, 4/29). Twenty cases with recurrences inside the potential PORT target volume were accompanied by distant metastasis. Another 11 cases had distant metastasis alone, so totally 31 cases developed distant metastasis (31/40, 77.5%), including 18 cases with hepatic metastasis. CONCLUSION The recurrence and metastasis rates are high in GBC and adjuvant therapy is needed. Up to 75% of the recurrent cases occurred in the potential target volume of postoperative radiotherapy, suggesting that postoperative radiotherapy has the possible value of improving local-regional control. The potential target volume of radiotherapy should include the tumor bed, No.8, No.9, No.11, No.12, No.13, No.14, No. 16a2, No. 16b1 lymph node groups.
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Affiliation(s)
- Zhijun Yuan
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yongjie Shui
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Lihong Liu
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yinglu Guo
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Qichun Wei
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
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Simpson FH, Auld M, Kandpal H, Tran K, Chandrasegaram MD. Double trouble: synchronous extrahepatic cholangiocarcinoma and gallbladder cancer in a Caucasian woman with no pancreaticobiliary maljunction. J Surg Case Rep 2022; 2022:rjab587. [PMID: 35079333 PMCID: PMC8784173 DOI: 10.1093/jscr/rjab587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 12/03/2021] [Indexed: 11/14/2022] Open
Abstract
Synchronous malignancies of the bile duct and the gallbladder are rare. These cases are often associated with pancreaticobiliary maljunction which is characterized by a long common shared pancreatobiliary channel leading to the Sphincter of Oddi. This predisposes the biliary epithelium to pancreatic enzyme reflux and makes the development of neoplasia more likely. We describe the case of a 64-year-old Caucasian female who presented with new jaundice and severe cholecystitis secondary to an impacted gallstone which was seen on ultrasound. Magnetic resonance cholangiopancreatography was organized with suspicion of a possible Mirizzi syndrome. This revealed a mid-distal bile duct cancer in addition to cholecystitis from an impacted gallstone. She was treated with intravenous antibiotics for her cholecystitis and underwent an urgent endoscopic retrograde cholangiopancreatography procedure for biliary decompression and stenting for her obstructive jaundice. The patient proceeded to pancreaticoduodenectomy with final histopathology revealing a synchronous primary gallbladder malignancy in addition to the known bile duct cancer.
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Affiliation(s)
- Fraser Hugh Simpson
- Correspondence address. Northside Clinical School, University of Queensland, The Prince Charles Hospital, Brisbane, Queensland, Australia. Tel: +61 439 637 851; Fax: +61 7 3139 4000; E-mail:
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14
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Wang J, Wang D, Fei Z, Feng D, Zhang B, Gao P, Hu G, Li W, Huang X, Chen D, Ding X, Wu W. KIF15 knockdown suppresses gallbladder cancer development. Eur J Cell Biol 2021; 100:151182. [PMID: 34781077 DOI: 10.1016/j.ejcb.2021.151182] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 10/26/2021] [Accepted: 11/03/2021] [Indexed: 11/17/2022] Open
Abstract
Gallbladder cancer (GBC) is commonly regarded as one of the most lethal malignant tumor types with poor prognosis. Kinesin family member 15 (KIF15) is reported to be tightly related with progression of multiple cancer types which, however, has not been clarified in GBC so far. KIF15 was significantly up-regulated in clinical GBC tissues compared with that in para-carcinoma tissues and the expression level was also correlated with tumor malignancies. In addition to tissues, GBC cells also exhibited a high expression abundance of KIF15. After down-regulating KIF15 via lentiviral transfection, GBC cell proliferation and migration were both inhibited, while cell apoptosis was promoted markedly. Likewise, silencing KIF15 significantly interfered the growth of nude mouse xenografts. Our experiments in GBC cell lines also demonstrated that KIF15 overexpression accelerated cell proliferation but lessened cell apoptosis in both GBC-SD and SGC-996 cells. Further investigation of the mechanism occurring in GBC inhibition mediated by KIF15 knockdown revealed that KIF15 deficiency led to decreased activity of several signaling pathways (TNF, PI3K/AKT and MAPK), a reduction of CDK6 expression regulated by enhanced p21, and HSP60 absence. Following the treatment of shCtrl- and shKIF15-transfected cells with AKT activator, we found that anti-tumor effects resulting from KIF15 deficiency could be relieved by AKT activator in both experimental cells. Overall, for the first time, we demonstrated that KIF15 was overexpressed in GBC and displayed a close relationship between KIF15 levels and GBC clinical stages. Furthermore, low expression of KIF15 resulted in obvious anti-tumor effects.
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Affiliation(s)
- Jun Wang
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China
| | - Dandan Wang
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China
| | - Zhewei Fei
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China
| | - Dongxu Feng
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China
| | - Bo Zhang
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China
| | - Pingfa Gao
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China
| | - Gangfeng Hu
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China
| | - Wenbing Li
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China
| | - Xia Huang
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China
| | - Dawei Chen
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China
| | - Xinde Ding
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China
| | - Wei Wu
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China.
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Appel E, Dommaraju S, Siewert B, Gonzalez RS, Camacho A, Park Y, Brook OR. Clinical Outcomes of Patients with Porcelain Gallbladder Diagnosed on CT. Acad Radiol 2021; 28 Suppl 1:S22-S28. [PMID: 32768350 DOI: 10.1016/j.acra.2020.07.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 07/05/2020] [Accepted: 07/06/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE To evaluate diagnostic accuracy and clinical outcomes of patients with porcelain gallbladder (GB) diagnosed on CT. MATERIALS AND METHODS In this IRB-approved, HIPAA-compliant study, consecutive patients with porcelain gallbladder reported on CT between December 1, 2000 and August 31, 2017 in a tertiary academic center were included. Two radiologists independently reviewed CT images and confirmed presence of porcelain gallbladder. Discrepant cases were reviewed by a third reader with 15 years of experience in abdominal imaging. Porcelain gallbladder diagnosis was confirmed by surgery/pathology or follow-up imaging. RESULTS Porcelain gallbladder was reported in 133 CT studies. Radiologist review and pathology results confirmed porcelain gallbladder in 90/133 (68%) patients (age 71.6 ± 13.8 years, 57% female). One third (42/133; 32%) of CT reports were false positive; 1/133 (1%) remained indeterminate. Frequent pitfalls included: stones filling the whole gallbladder lumen in 39/43 (91%), sludge in 3/43 (7%) and mucosal enhancement in 2/43 (5%). In 5/90 (6%) patients, concurrent gallbladder cancer was noted on the initial CT scan. No patient developed subsequent gallbladder cancer during 6.6 ± 4.6 years of follow-up. One third (30/90, 33%) of patients with porcelain gallbladder have deceased during the follow-up period, all from unrelated causes. CONCLUSION At the time of presentation with porcelain gallbladder, 6% of patients had concurrent gallbladder cancer. No patient with porcelain gallbladder alone diagnosed on CT developed gallbladder cancer during a follow-up of 6.6 ± 4.6 years. Porcelain gallbladder is overcalled on CT, with frequent pitfalls including gallstones filling the whole gallbladder lumen, sludge, and wall enhancement.
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Ali TA, Abougazia AS, Alnuaimi AS, Mohammed MAM. Prevalence and risk factors of gallbladder polyps in primary health care centers among patients examined by abdominal ultrasonography in Qatar: a case-control study. Qatar Med J 2021; 2021:48. [PMID: 34660216 PMCID: PMC8501236 DOI: 10.5339/qmj.2021.48] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Accepted: 08/01/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Gallbladder (GB) polyps are raised lesions from the GB wall and projected into its lumen. The prevalence of GB polyps ranged between 4.3% and 12.3%. The clinical presentation of GB polypoid lesions vary, can be nonspecific and vague, and may be asymptomatic. Identifying malignant and premalignant polyps is important to provide treatment early and prevent cancer spread or development of malignancy. Ultrasonography (US) is the first imaging modality widely used in abdominal imaging. It is a noninvasive, rapid, painless, and safe imaging technique, with no radiation; thus, it is considered the best available examination with good sensitivity and specificity for GB polyps. AIM OF THE WORK This study aimed to determine the relative frequency of the GB polyps and its risk factors among patients who underwent abdominal US in Primary Health Care Corporation, Qatar. MATERIALS AND METHODS This was quantitative multicenter observational case-control study nested in a cross-sectional design. For the cross-sectional top-level study, the first step was to assess available abdominal ultrasound studies for the presence of GB polyps and stones. The second step was to perform a case-control study with three groups (a case group and two control groups; first, participants without GB stones and GB polyps; second, patients with GB stones but without GB polyps). RESULTS The study evaluated the GB images of 7156 individuals. The overall prevalence of GB polyps was 7.4% in the study population. Specifically, the overall prevalence of solitary GB polyp was 4.2% and that of multiple GB polyps was 3.2%. Regarding the size distribution of GB polyps in positive cases, 89.4% were < 6 mm, 9.3% were 69 mm, and 1.3% were ≥ 10 mm. Prevalence rate of selected comorbidities were as follows: liver disease, 1.8%; diabetes mellitus, 25.5%; hypertension, 25.5%; and dyslipidemia, 29.8%. The prevalence in male and female patients was 7.7% and 7%, respectively. The prevalence of GB polyps was higher in south-eastern patients (21.4% of positive cases) and was the highest in the overweight group (8.8%). A higher prevalence was noted in the hypertensive group (hypertensive group, 9.8%; non-hypertensive group, 6.6%) and dyslipidemia group (dyslipidemia group, 7.8%; no dyslipidemia group, 7.2%). Moreover, a higher prevalence was noted in hepatitis B surface (HBS)-positive group (15%) than in the HBS-negative group (8.2%) and slightly higher in Helicobacter pylori antigen positive group than in the negative group. CONCLUSION Abdominal US is an important and commonly used imaging modality in the detection of GB polyps. In this study, the prevalence of GB polyps was approximately 7.4%, with higher prevalence in participants who were overweight and had diabetes mellitus, hypertension, and dyslipidemia.
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Affiliation(s)
- Tamer A Ali
- Radiology Department, PHCC, Doha, Qatar E-mail:
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17
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Kamal H, Sadr-Azodi O, Engstrand L, Brusselaers N. Association Between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: A Swedish Population-Based Cohort Study. Hepatology 2021; 74:2021-2031. [PMID: 34018229 DOI: 10.1002/hep.31914] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 05/14/2021] [Accepted: 05/16/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Biliary tract cancer is a group of highly aggressive malignant disorders, yet risk factors are poorly understood. In this study, we aim to assess whether prolonged use of proton pump inhibitors (PPIs) increases the risk of incident biliary tract carcinoma in a nation-wide population-based cohort in Sweden. APPROACH AND RESULTS Using nation-wide registries, we identified all adults who received maintenance PPIs (≥180 days) according to the Swedish Prescribed Drug Register from 2005 through 2012. Data on incident biliary tract cancer were retrieved from the Swedish Cancer, Death and Outpatient Registers. Risk of biliary tract cancer in persons who received PPI treatment was compared with the general population of the corresponding age, sex, and calendar year yielding standardized incidence ratios (SIRs) with 95% CIs. Of 738,881 PPI users (median follow-up of 5.3 years), 206 (0.03%) developed gallbladder cancer and 265 (0.04%) extrahepatic and 131 (0.02%) intrahepatic bile duct cancer corresponding to SIRs of 1.58 (95% CI, 1.37-1.81), 1.77 (95% CI, 1.56-2.00), and 1.88 (95% CI, 1.57-2.23), respectively. In sensitivity analyses restricted to persons without a history of gallstones or chronic liver or pancreatic diseases, SIRs were 1.36 (95% CI, 1.17-1.57) and 1.47 (95% CI, 1.19-1.80) for extra- and intrahepatic duct cancer, respectively. The risk remained higher than the corresponding general population with ≥5 years of PPIs use, ruling out confounding by indication. CONCLUSIONS In this study, long-term use of PPIs was associated with an increased risk of gallbladder, intrahepatic, and extrahepatic bile duct cancer compared with the general population.
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Affiliation(s)
- Habiba Kamal
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.,Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Omid Sadr-Azodi
- Unit of Surgery, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.,Department of Surgery, Capio Saint Göran Hospital, Stockholm, Sweden
| | - Lars Engstrand
- Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.,Global Health Institute, Antwerp University, Antwerp, Belgium
| | - Nele Brusselaers
- Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.,Global Health Institute, Antwerp University, Antwerp, Belgium.,Department of Head and Skin, Ghent University Hospital, Ghent, Belgium
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Kim EJ. Gender Difference in Gallbladder Cancer: Focusing on the Clinical Characteristics, Treatment, and Prognosis of Korean Patients. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2021. [DOI: 10.4166/kjg.2021.411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Eui Joo Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
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Tang H, Shi X, Zhu P, Guo W, Li J, Yan B, Zhang S. Melatonin inhibits gallbladder cancer cell migration and invasion via ERK-mediated induction of epithelial-to-mesenchymal transition. Oncol Lett 2021; 22:609. [PMID: 34188711 PMCID: PMC8227585 DOI: 10.3892/ol.2021.12870] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 05/19/2021] [Indexed: 12/13/2022] Open
Abstract
Melatonin is a naturally occurring molecule secreted by the pineal gland that exhibits antitumor properties and prevents the development of human cancer. However, little is known regarding the effects of melatonin on gallbladder cancer (GBC) cells. The present study aimed to investigate the role of melatonin on the prevention of GBC cell invasion. The GBC cell line, GBC-SD, was treated with different concentrations of melatonin for different time periods, and the data indicated that melatonin markedly inhibited the invasion of GBC cells. Following treatment of GBC cells with melatonin, the protein levels of the epithelial marker, E-cadherin, significantly increased, while the expression levels of the mesenchymal markers, N-cadherin, Snail and vimentin, notably decreased. In addition, melatonin inhibited the phosphorylation of ERK1/2. Following treatment of the cells with the ERK activator, tert-Butylhydroquinone, the anti-invasive effects of melatonin were reversed by rescuing epithelial-to-mesenchymal transition in GBC cells. Taken together, these results suggest that melatonin inhibits GBC invasiveness by blocking the ERK signaling pathway. Thus, melatonin may be used as a potential novel cancer therapeutic drug for the treatment of GBC.
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Affiliation(s)
- Hongwei Tang
- ZhengZhou Engineering Laboratory of Organ Transplantation Technique and Application, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.,Henan Engineering Technology Research Center of Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Xiaoyi Shi
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Pengfei Zhu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Jie Li
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Bing Yan
- ZhengZhou Engineering Laboratory of Organ Transplantation Technique and Application, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.,Henan Engineering Technology Research Center of Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Shuijun Zhang
- ZhengZhou Engineering Laboratory of Organ Transplantation Technique and Application, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.,Henan Engineering Technology Research Center of Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
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Morimoto M, Matsuo T, Mori N. Management of Porcelain Gallbladder, Its Risk Factors, and Complications: A Review. Diagnostics (Basel) 2021; 11:1073. [PMID: 34200963 PMCID: PMC8230643 DOI: 10.3390/diagnostics11061073] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/04/2021] [Accepted: 06/07/2021] [Indexed: 02/06/2023] Open
Abstract
The porcelain gallbladder condition describes gallbladder calcification. While gallbladder calcification is believed to increase the risk of developing gallbladder cancer, recent reports have shown that the malignancy risk is much lower than previously reported. Symptomatic patients with porcelain gallbladder should be recommended for cholecystectomy, but the management of asymptomatic patients is debatable. Based on recent evidence, prophylactic cholecystectomy is not routinely recommended in all patients with porcelain gallbladder. From the assessment of the current literature, there are three essential factors in the management of patients with porcelain gallbladder: (1) symptoms or complications of gallbladder disease, (2) calcification pattern and (3) patient age and comorbidities. Patients who do not undergo cholecystectomy should be educated about the symptoms of gallbladder diseases, and a thorough discussion is essential between patients and clinicians.
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Affiliation(s)
- Masaya Morimoto
- Department of Infectious Diseases, St. Luke’s International Hospital, Tokyo 104-8560, Japan; (T.M.); (N.M.)
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Gupta A, Gupta S, Siddeek RAT, Chennatt JJ, Singla T, Rajput D, Kumar N, Sehrawat A, Kishore S, Gupta M. Demographic and clinicopathological Profile of Gall Bladder Cancer Patients: Study from a tertiary care center of the Sub-Himalayan region in Indo-Gangetic Belt. J Carcinog 2021; 20:6. [PMID: 34321956 PMCID: PMC8312375 DOI: 10.4103/jcar.jcar_3_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 01/26/2021] [Accepted: 03/05/2021] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Gall bladder cancer (GBC) accounts for 80%-95% of biliary tract malignancies in the world. There is however striking variability in the global incidence of gallbladder cancer, reaching epidemic levels for some regions and ethnicities. The aim of this study was to evaluate the demographic and clinicopathological profile of the gallbladder cancer patients. MATERIALS AND METHODS All patients of carcinoma gall bladder presenting to department of surgery in hepatopancreaticobiliary unit from July 2017 to November 2020 were included in this study. A proforma containing all the relevant details including history, examination, blood, radiology, and pathological investigations was filled. RESULTS A total of 326 patients of GBC were analyzed. The majority (75%) were found to be females with a mean age of 55 years. Pain abdomen was the most common presenting symptom in 81% of patients. The most common stage of presentation was stage IV and only 6 were in stage I. Two hundred and thirty three (71.4%) patients had metastatic disease at presentation. Liver infiltration at the time of diagnosis was present in 89% of patients. The most common site of metastasis was found in the liver (23.3%). GBC was more common in patients with A blood group. Baseline serum albumin levels were found to be significantly associated with the staging of GBC. CONCLUSIONS Due to the non specific symptoms patients of GBC present at very advanced stages, high index of suspicion and health education seems to play an important role in early detection and improvement of survival.
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Affiliation(s)
- Amit Gupta
- Department of Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Sweety Gupta
- Department of Radiation Oncology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Rohik Anjum T. Siddeek
- Department of Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Jaine John Chennatt
- Department of Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Tanuj Singla
- Department of Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Deepak Rajput
- Department of Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Navin Kumar
- Department of Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Amit Sehrawat
- Department of Medical Oncology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Sanjeev Kishore
- Department of Pathology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Manoj Gupta
- Department of Radiation Oncology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
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22
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Jha AK, Jha P, Jha SK, Keshari R. Plastic versus metal stents for inoperable gallbladder cancer with hilar biliary obstruction: the jury is still out. Ann Gastroenterol 2021; 34:12-19. [PMID: 33414616 PMCID: PMC7774665 DOI: 10.20524/aog.2020.0548] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Accepted: 08/04/2020] [Indexed: 12/09/2022] Open
Abstract
In unresectable malignant hilar obstruction, adequate biliary drainage can be achieved with endoscopic placement of plastic or metal stents. Stent patency and patient survival may differ, depending on the primary disease, disease progression and stent type. Metal and plastic stents were compared in patients with malignant hilar strictures in several studies, but these studies mainly included patients who had cholangiocarcinoma, without taking into consideration potential differences in the invasion properties of tumor cells, histological differentiation and the biological behavior of different tumors. Gallbladder cancer (GBC) is the most common malignancy of the biliary tract, especially in the Indian subcontinent and Latin America. About half the patients with GBC present with jaundice, which usually means the tumor is inoperable. Palliative endoscopic stenting remains the first-line treatment of unresectable GBC with biliary obstruction. Primary disease progression is faster in GBC compared to cholangiocarcinoma. There is a paucity of data on the selection of stents for inoperable GBC with hilar biliary obstruction. This review focuses on the published literature related to the selection of stents for unresectable GBC with hilar obstruction.
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Affiliation(s)
- Ashish Kumar Jha
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Patna, India
| | - Praveen Jha
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Patna, India
| | - Sharad Kumar Jha
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Patna, India
| | - Ravi Keshari
- Department of Gastroenterology, Indira Gandhi Institute of Medical Sciences, Patna, India
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23
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Nagino M, Hirano S, Yoshitomi H, Aoki T, Uesaka K, Unno M, Ebata T, Konishi M, Sano K, Shimada K, Shimizu H, Higuchi R, Wakai T, Isayama H, Okusaka T, Tsuyuguchi T, Hirooka Y, Furuse J, Maguchi H, Suzuki K, Yamazaki H, Kijima H, Yanagisawa A, Yoshida M, Yokoyama Y, Mizuno T, Endo I. Clinical practice guidelines for the management of biliary tract cancers 2019: The 3rd English edition. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2020; 28:26-54. [PMID: 33259690 DOI: 10.1002/jhbp.870] [Citation(s) in RCA: 123] [Impact Index Per Article: 24.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 11/18/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract cancers (cholangiocarcinoma, gallbladder cancer, and ampullary cancer) in 2007, then published the 2nd version in 2014. METHODS In this 3rd version, clinical questions (CQs) were proposed on six topics. The recommendation, grade for recommendation, and statement for each CQ were discussed and finalized by an evidence-based approach. Recommendations were graded as Grade 1 (strong) or Grade 2 (weak) according to the concepts of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS The 31 CQs covered the six topics: (a) prophylactic treatment, (b) diagnosis, (c) biliary drainage, (d) surgical treatment, (e) chemotherapy, and (f) radiation therapy. In the 31 CQs, 14 recommendations were rated strong and 14 recommendations weak. The remaining three CQs had no recommendation. Each CQ includes a statement of how the recommendations were graded. CONCLUSIONS This latest guideline provides recommendations for important clinical aspects based on evidence. Future collaboration with the cancer registry will be key for assessing the guidelines and establishing new evidence.
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Affiliation(s)
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Hideyuki Yoshitomi
- Department of Surgery, Saitama Medical Center, Dokkyo Medical University, Koshigaya, Japan
| | - Taku Aoki
- Second Department of Surgery, Dokkyo Medical University, Mibu, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Nagaizumi, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tomoki Ebata
- Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masaru Konishi
- Department of Hepatobiliary Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Keiji Sano
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Kazuaki Shimada
- Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroaki Shimizu
- Department of Surgery, Teikyo University Chiba Medical Center, Ichihara, Japan
| | - Ryota Higuchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Toshio Tsuyuguchi
- Department of Gastroenterology, Chiba Prefectural Sawara Hospital, Sawara, Japan
| | - Yoshiki Hirooka
- Department of Gastroenterology and Gastroenterological Oncology, Fujita Health University, Toyoake, Japan
| | - Junji Furuse
- Department of Medical Oncology, Faculty of Medicine, Kyorin University, Mitaka, Japan
| | - Hiroyuki Maguchi
- Education and Research Center, Teine-Keijinkai Hospital, Sapporo, Japan
| | - Kojiro Suzuki
- Department of Radiology, Aichi Medical University, Nagakute, Japan
| | - Hideya Yamazaki
- Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroshi Kijima
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Akio Yanagisawa
- Department of Pathology, Japanese Red Cross Kyoto Diichi Hospital, Kyoto, Japan
| | - Masahiro Yoshida
- Department of Hepato-Biliary-Pancreatic & Gastrointestinal Surgery, International University of Health and Welfare, Ichikawa, Japan
| | - Yukihiro Yokoyama
- Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Mizuno
- Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan
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Xiong J, Wang Y, Chen G, Jin L. Proton pump inhibitors and the risk of gallbladder cancer: a hospital-based case-control study. Gut 2020; 69:2265-2267. [PMID: 32273291 PMCID: PMC7677475 DOI: 10.1136/gutjnl-2020-321052] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 03/09/2020] [Accepted: 03/15/2020] [Indexed: 12/08/2022]
Affiliation(s)
- Jianping Xiong
- Interventional Radiology, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
| | - Yaqin Wang
- Department of Interventional Radiology, China Medical University First Hospital, Shenyang, China
| | - Guang Chen
- Interventional Radiology, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
| | - Long Jin
- Interventional Radiology, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
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25
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Abstract
Geriatric patients tend to have subtle presentations of biliary disorders and, if untreated, can decompensate acutely. Each biliary disorder warrants formulation of an individualized treatment plan with a multidisciplinary approach. Acute cholecystitis, a common complication of gallstones, is initially managed by conservative measures and subsequently, among patients with optimal surgical risk, through laparoscopic or open cholecystectomy. High-risk patients undergo temporization, percutaneous or endoscopic, followed by definitive intervention. Acute cholecystitis with complications (ie, perforation, gangrene, or small bowel obstruction) warrants emergent cholecystectomy. Gallstone migration into the biliary system can cause choledocholithiasis, often complicated by biliary pancreatitis or cholangitis if not intervened. Therapy for choledocholithiasis is based on biliary clearance through endoscopic and, infrequently, surgical approaches.
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Zheng K, Wang X, Cao G, Xu L, Zhu X, Fu L, Fu S, Cheng H, Yang R. Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Gallbladder Cancer. Cardiovasc Intervent Radiol 2020; 44:271-280. [PMID: 33078235 DOI: 10.1007/s00270-020-02661-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 09/18/2020] [Indexed: 12/13/2022]
Abstract
PURPOSE The aim of this study was to assess the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin and 5-fluorouracil for patients with advanced gallbladder cancer (GBC). MATERIALS AND METHODS Twenty-six patients with advanced GBC, who underwent HAIC with oxaliplatin and 5-fluorouracil from January 2012 to July 2019, were enrolled in this retrospective study. The HAIC regimen consisted of infusions of oxaliplatin at 40 mg/m2 for 2 h, followed by 5-fluorouracil at 800 mg/m2 for 22 h on days 1-3 every 3-4 weeks. A maximum of six cycles of HAIC were applied for tumor control patients followed by maintenance with oral capecitabine or S-1. Overall survival (OS), progression-free survival (PFS), tumor response, and adverse events were investigated. RESULTS Six of the 26 patients (23.1%) had failed systemic chemotherapy, 8/26 (30.8%) patients had failed various local therapies, and 9/26 (34.6%) patients had contraindications to systemic chemotherapy. The median OS was 13.5 months, and the median PFS was 10.0 months. The overall response rate was 69.2% (18/26), and disease control rate was 92.3% (24/26). Carcinoembryonic antigen (CEA) ≥ 10 U/ml (p = 0.003) and carbohydrate antigen 19-9 (CA19-9) ≥ 200 U/ml (p = 0.000) were independent risk factors for decreased survival. The most frequent Grade 3 or 4 treatment-related adverse event was liver dysfunction (4, 15.4%). CONCLUSION HAIC with oxaliplatin and 5-fluorouracil is an acceptable and well-tolerated treatment for advanced gallbladder cancer even for patients in whom systemic chemotherapy had failed or is contraindicated. LEVEL OF EVIDENCE Level 2, Observation Study with Dramatic Effect.
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Affiliation(s)
- Kanglian Zheng
- Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, China
| | - Xiaodong Wang
- Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, China.
| | - Guang Cao
- Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, China
| | - Liang Xu
- Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, China
| | - Xu Zhu
- Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, China
| | - Liqiang Fu
- Department of Biostatistics, School of Public Health, Southern Medical University, 1838 Guangzhou Avenue North, Baiyun District, Guangzhou, China
| | - Shijie Fu
- Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, China
| | - Haihui Cheng
- Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, China
| | - Renjie Yang
- Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 52 Fucheng Road, Haidian District, Beijing, China
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27
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Xie C, McGrath NA, Monge Bonilla C, Fu J. Systemic treatment options for advanced biliary tract carcinoma. J Gastroenterol 2020; 55:944-957. [PMID: 32748173 PMCID: PMC7519922 DOI: 10.1007/s00535-020-01712-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 07/25/2020] [Indexed: 02/04/2023]
Abstract
Advanced biliary tract cancers (BTC) include a diverse collection of rare and heterogenous tumors with poor prognosis. The combination of gemcitabine and cisplatin is the established first-line therapy for advanced BTC. There are no accepted standard treatments in the second line setting, though there are several ongoing clinical trials that implement chemotherapy as a therapeutic strategy. The understanding of the molecular landscape of BTC has offered hope of targeted therapies to the identified actionable genomic aberrations, such as FGFR2 gene fusions, mutations of IDH1/2, HER2, BRAC1/2 and BRAF. Pembigatinib has become the first approved targeted therapy for BTC with FGFR2 fusion or other rearrangements. Recent immunotherapy has opened new therapy avenues in BTC with pembrolizumab approved for either microsatellite instability high (MSI-H) or DNA mismatch repair deficient (dMMR) advanced solid tumors, including BTC. The combination of immunotherapy with other modalities is currently being evaluated in different clinical trials, since single agent immunotherapy appears to provide modest benefits in advanced BTC. In this review, we summarize the current status of treatment options, including systemic chemotherapy, targeted therapy, immunotherapy, and various combinations in advanced BTC.
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Affiliation(s)
- Changqing Xie
- Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
| | - Nicole A McGrath
- Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Cecilia Monge Bonilla
- Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Jianyang Fu
- Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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Loss of desmoglein-2 promotes gallbladder carcinoma progression and resistance to EGFR-targeted therapy through Src kinase activation. Cell Death Differ 2020; 28:968-984. [PMID: 32989241 PMCID: PMC7937683 DOI: 10.1038/s41418-020-00628-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 09/20/2020] [Accepted: 09/21/2020] [Indexed: 12/14/2022] Open
Abstract
Gallbladder carcinoma (GBC) exhibits poor prognosis due to local recurrence, metastasis, and resistance to targeted therapies. Using clinicopathological analyses of GBC patients along with molecular in vitro and tumor in vivo analysis of GBC cells, we showed that reduction of Dsg2 expression was highly associated with higher T stage, more perineural, and lymphatic invasion. Dsg2-depleted GBC cells exhibited significantly enhanced proliferation, migration, and invasiveness in vitro and tumor growth and metastasis in vivo through Src-mediated signaling activation. Interestingly, Dsg2 binding inhibited Src activation, whereas its loss activated cSrc-mediated EGFR plasma membrane clearance and cytoplasmic localization, which was associated with acquired EGFR-targeted therapy resistance and decreased overall survival. Inhibition of Src activity by dasatinib enhanced therapeutic response to anti-EGFR therapy. Dsg2 status can help stratify predicted patient response to anti-EGFR therapy and Src inhibition could be a promising strategy to improve the clinical efficacy of EGFR-targeted therapy.
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Prognostic Evaluation for Patients over 45 Years Old with Gallbladder Adenocarcinoma Resection: A SEER-Based Nomogram Analysis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:6370946. [PMID: 32733948 PMCID: PMC7383319 DOI: 10.1155/2020/6370946] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 06/16/2020] [Accepted: 06/29/2020] [Indexed: 12/14/2022]
Abstract
Gallbladder adenocarcinoma is the main histopathological type of gallbladder cancer (GBC), so it is particularly important to understand its biological characteristics. Due to the low incidence of this type of cancer, there are few studies with large sample sizes. The log of positive lymph nodes (LODDS) has been evaluated by many scholars as a lymph node stage that may play a better role than the 8th edition of the American Joint Committee on Cancer (AJCC) lymph node staging system in many cancers. However, the effect of LODDS has not been proven in gallbladder adenocarcinoma. Our research aimed to identify independent prognostic factors that are closely related to overall survival (OS) in patients with gallbladder adenocarcinoma over 45 years of age using data from the Surveillance, Epidemiology and, End Results (SEER) database. All patients were randomly divided into a modeling cohort and an internal validation cohort. Seven independent prognostic factors associated with OS—age, marital status, grade, tumor size, AJCC 8th edition T stage and M stage, and LODDS—were used to build a nomogram to predict 1-, 3-, and 5-year survival. The C-index of our nomogram was 0.735 (95% CI, 0.716 to 0.754), and together with the calibration curve and ROC curve validation, the results confirmed the prediction effect of our nomogram. We believe that our nomogram will be an accurate and convenient method for patient prognosis assessment in the future.
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30
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Aliniagerdroudbari E, Ershadinia N, Bagherpor G, Babaniamansour S. A Rare Case of Simultaneous Intrahepatic and Porcelain Gallbladder: Case Report. Int Med Case Rep J 2020; 13:271-274. [PMID: 32765122 PMCID: PMC7371554 DOI: 10.2147/imcrj.s261103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Accepted: 07/02/2020] [Indexed: 11/23/2022] Open
Abstract
Intrahepatic gallbladder is a rare anomaly that is due to the failure of gallbladder migration from liver to its proper position. This condition increases the risk of cholelithiasis, hepatic abscess and cholangiocarcinoma. Calcification in the wall of the gallbladder, which is known as porcelain gallbladder, also increases the risk of malignancy. In this report a 47-year-old man presented at the emergency department with continuous right upper quadrant abdominal pain who was misdiagnosed with acute cholecystitis. During abdominal surgery, gallbladder was not detectable in its proper location. Therefore, the patient underwent enhanced abdominal computed tomography scan and magnetic resonance cholangiopancreatography and the results showed an intrahepatic porcelain gallbladder. In order to avoid future complications, intrahepatic gallbladder should always be considered in patients whose physical examination and radiologic findings do not match.
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Affiliation(s)
| | - Nazanin Ershadinia
- Department of Surgery, Islamic Azad University of Medical Sciences, Sari, Mazandaran, Iran
| | - Ghasem Bagherpor
- Department of Surgery, Valiasr Hospital of Qaemshahr, Islamic Azad University of Medical Sciences, Sari, Mazandaran, Iran
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31
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Chen K, Tang H, Zhu P, Ye J, Liu D, Pu Y, Zhang L, Zhai W. Interleukin 17A promotes gallbladder cancer invasiveness via ERK/NF-κB signal pathway mediated epithelial-to-mesenchymal transition. J Cancer 2020; 11:4406-4412. [PMID: 32489459 PMCID: PMC7255371 DOI: 10.7150/jca.40656] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 03/27/2020] [Indexed: 01/17/2023] Open
Abstract
As a pro-inflammatory cytokine, Interleukin 17A (IL-17A) plays an important role in pathology of tumor microenvironment and inflammatory diseases. In this study, we intend to investigate the role of IL-17A on the metastasis of gallbladder cancer (GBC) and related mechanisms. The serum levels of IL-17A were associated with node metastasis and advanced stage. We also found the pro-invasion effect of IL-17A on GBC cells. When treated with IL-17A, the protein level of epithelial marker E-cadherin in GBC cells was significantly down-regulated, while the protein level of the mesenchymal phenotype marker vimentin was significantly increased. IL-17A increased the expression of transcription factor slug, the phosphorylation of ERK1/2 and the nuclear translocation of NF-κB/p50 and p65 in a concentration-dependent manner. Pretreatment of cells with U0126 could reverse the nuclear translocation of NF-κB/p50 and p65 and EMT induced by IL-17A. IL-17A promotes gallbladder cancer invasiveness via ERK/NF-κB signal pathway mediated epithelial-to-mesenchymal transition. As a new therapeutic targets and diagnostic marker, IL-17A may play an important role in the treatment of GBC.
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Affiliation(s)
- Kunlun Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Hongwei Tang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Pengfei Zhu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Jianwen Ye
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Dong Liu
- Departments of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, China
| | - Yansong Pu
- Departments of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, China
| | - Lei Zhang
- Hepatic Surgery Center, Institute of Hepato-Pancreato-Bililary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Wenlong Zhai
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
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32
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Abstract
PURPOSE Gallbladder cancer (GBC) is the most common malignancy of the biliary tract. The median survival of the disease is around 6 months. In this study, we explore clinical trials related to non-resectable GBC, determine the shortcomings leading to the lack of development of new treatment, and shed light on possible areas of improvement. METHODS On April 20, 2019 the authors completed a search on ClinicalTrials.gov for all therapeutic and interventional clinical trials involving non-resectable GBC, without any limits on date or location. Trial characteristics such as duration, phase, sample size, and whether a publication was produced were collected and analyzed. RESULTS Sixty-two trials met our selection criteria. The average duration of trials was 5 years. Trials were conducted in 8 different countries: most of them in North America (USA and Canada). About 88% of trials were in early phases (I, I/II, and II) and 85% of trials were completed. Only 4 relevant publications were produced from all the trials in our study. Gemcitabine was the most common drug used. Use of gemcitabine alone or in combination with either capecitabine or cisplatin showed significant increase mean progression-free survival. CONCLUSION This study revealed a low number of trials, lack of geographic diversity, and scarcity of publications concerning non-resectable GBC. Adequate management of is of great importance to reach effective therapies for this disease.
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33
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Holanda AKG, Lima Júnior ZB. Gallbladder histological alterations in patients undergoing cholecystectomy for cholelithiasis. ACTA ACUST UNITED AC 2020; 46:e20192279. [PMID: 31967243 DOI: 10.1590/0100-6991e-20192279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 07/28/2019] [Indexed: 12/26/2022]
Abstract
OBJECTIVE to describe the histological findings of the gallbladders of patients undergoing cholecystectomy and to evaluate the presence of factors associated with gallbladder incidental cancer. METHODS we conducted a descriptive, cross-sectional, observational study with 1,278 histopathological exams of gallbladders coming from cholecystectomy for cholelithiasis and of their reports, held from January 2008 to December 2017. RESULTS the most common pathological finding was chronic cholecystitis, present in 1,251 patients (97.8%), followed by gallbladder cholesterolosis, in 131 (10.2%). Gallbladder cancer was identified in six patients, with a prevalence of 0.5% in this sample. There was a significant association between the presence of cancer and age ≥60 years and wall thickness ≥0.3cm. CONCLUSION there was low prevalence of gallbladder cancer in this population, higher occurrence in the elderly and association of the tumor with gallbladder wall thickness.
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Affiliation(s)
- Ana Karolina Gama Holanda
- Universidade Federal da Paraíba (UFPB), Centro de Ciências Médicas, Curso de Medicina, João Pessoa, Paraíba, Brasil
| | - Zailton Bezerra Lima Júnior
- Universidade Federal da Paraíba (UFPB), Centro de Ciências Médicas, Curso de Medicina, Departamento de Cirurgia, João Pessoa, Paraíba, Brasil
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34
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Lee W. Diagnostic and Therapeutic Algorithm: Polypoid Lesions of the Gallbladder. DISEASES OF THE GALLBLADDER 2020:255-268. [DOI: 10.1007/978-981-15-6010-1_26] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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35
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Wang J, Bo X, Wang C, Xin Y, Nan L, Luo R, Chen L, Shi X, Suo T, Ni X, Liu H, Shen S, Li M, Lu P, Wang Y, Liu H. Low immune index correlates with favorable prognosis but with reduced benefit from chemotherapy in gallbladder cancer. Cancer Sci 2019; 111:219-228. [PMID: 31729088 PMCID: PMC6942443 DOI: 10.1111/cas.14239] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 10/22/2019] [Accepted: 10/25/2019] [Indexed: 12/24/2022] Open
Abstract
Use of immune index is a new potential approach for cancer classification and prediction. To investigate the status and clinical effect of immune index in gallbladder cancer (GBC), 238 GBC patients from Zhongshan Hospital affiliated to Fudan University were involved in the present study, including 113 patients in a training set and 125 patients in a validation set. Five immune cells (macrophages, neutrophils, regulatory T cells, cytotoxic T cells and mast cells) were selected based on a literature review and the immune index for each patient was calculated using the LASSO regression. A low immune index (<1) was defined as immunotype A and a high immune index (≥1) was defined as immunotype B. The 5-year overall survival rate for immunotype A was higher than that for immunotype B in the training set and the validation set (70.0% vs 37.0%, P < 0.001; 68.9% vs 47.5%, P = 0.002; respectively). Moreover, the immune index showed higher prediction efficiency compared with all the single immune cells which we selected. When combined with the immune index, the areas under the curve (AUC) of the TNM staging system in both sets were elevated from 0.677 to 0.787 and from 0.631 to 0.694, respectively. Interestingly, gemcitabine-based chemotherapy only benefits stage II patients of immunotype B and stage III patients of both immunotype A and immunotype B (P = 0.015, P = 0.030, P = 0.011, respectively) but does not work in stage II patients of immunotype A (P = .307). Taken together, the immune index could effectively predict prognosis and the benefits of gemcitabine-based chemotherapy and might improve on the TNM staging system.
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Affiliation(s)
- Jie Wang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Biliary Tract Diseases Institute, Fudan University, Shanghai, China
| | - Xiaobo Bo
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Biliary Tract Diseases Institute, Fudan University, Shanghai, China
| | - Changcheng Wang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Biliary Tract Diseases Institute, Fudan University, Shanghai, China
| | - Yanlei Xin
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Biliary Tract Diseases Institute, Fudan University, Shanghai, China
| | - Lingxi Nan
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Biliary Tract Diseases Institute, Fudan University, Shanghai, China
| | - Rongkui Luo
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lingli Chen
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiao Shi
- Department of Head and Neck Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
| | - Tao Suo
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Biliary Tract Diseases Institute, Fudan University, Shanghai, China
| | - Xiaoling Ni
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Biliary Tract Diseases Institute, Fudan University, Shanghai, China
| | - Han Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Biliary Tract Diseases Institute, Fudan University, Shanghai, China
| | - Sheng Shen
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Biliary Tract Diseases Institute, Fudan University, Shanghai, China
| | - Min Li
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Biliary Tract Diseases Institute, Fudan University, Shanghai, China
| | - Pinxiang Lu
- Department of General Surgery, Zhongshan-Xuhui Hospital Affiliated to Fudan University, Shanghai, China
| | - Yueqi Wang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Biliary Tract Diseases Institute, Fudan University, Shanghai, China
| | - Houbao Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Biliary Tract Diseases Institute, Fudan University, Shanghai, China.,Department of General Surgery, Zhongshan-Xuhui Hospital Affiliated to Fudan University, Shanghai, China
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Firat YD, Idiz UO, Cakir C, Yardimci E, Yazici P, Bektasoglu H, Bozkurt E, Ucak R, Gucin Z, Uresin T, Hasbahceci M. Prospective multi-center study of surgeon's assessment of the gallbladder compared to histopathological examination to detect incidental malignancy. Langenbecks Arch Surg 2019; 404:573-579. [PMID: 31297608 DOI: 10.1007/s00423-019-01800-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2019] [Accepted: 06/13/2019] [Indexed: 12/11/2022]
Abstract
PURPOSE Routine histopathological examination after cholecystectomy for gallstones is performed despite the low rates of incidental findings of malignancy. The aim of this study was to assess predictive values of macroscopic examination of cholecystectomy specimens by surgeons in gallstone disease. METHODS A prospective multi-center diagnostic study was carried out between December 2015 and March 2017 at four different centers. All patients undergoing cholecystectomy for gallstone disease were consecutively screened for eligibility. Patients whose ages are 18 to 80 years, and preoperative imaging findings without any pathology except cholelithiasis were included. The gallbladder was first evaluated macroscopically ex situ by two operating surgeons and rated as macroscopically benign (group S1), suspicious for a benign diagnosis (group S2), and suspicious for malignancy (group S3). Thereafter, a pathologist made a final histopathological examination whose results are grouped as chronic cholecystitis (group P1), benign or precancerous lesions in which only cholecystectomy is the adequate treatment modality (group P2), and carcinoma (group P3). Diagnostic accuracy of the surgeon's assessment to the histopathological examination was evaluated using sensitivity, specificity, positive and negative predictive values, and accuracy, and correlated by a kappa agreement coefficient. RESULTS A total of 1112 patients were included in this trial. The specificity rates were 96.5%, 100%, and 98.7% for group S1-group S2, group S1-group S3, and group S2-group S3, respectively. Accuracy rates to detect malignancy were 100% and 95. 2% for group S1 and group S2, respectively. Kappa coefficient values were 1.0 and 0.64 for group S1-group S3 and group S2-group S3, respectively (p < 0.001 for both). CONCLUSION Assessment of the gallbladder specimen and selective histopathological examination may be adequate after cholecystectomy for gallstone diseases. Such a procedure would have the potential to reduce costs and prevent unnecessary loss of labor productivity without affecting patients' safety. However, higher number of patients in more centers is needed to confirm this hypothesis.
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Affiliation(s)
- Yurdakul Deniz Firat
- Department of General Surgery, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey
| | - Ufuk Oguz Idiz
- Department of General Surgery, Istanbul Training and Research Hospital, Istanbul, Turkey.
| | - Coskun Cakir
- Department of General Surgery, Istanbul Training and Research Hospital, Istanbul, Turkey
| | - Erkan Yardimci
- Department of General Surgery, Bezmialem Vakif University, Istanbul, Turkey
| | - Pinar Yazici
- Department of General Surgery, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
| | - Huseyin Bektasoglu
- Department of General Surgery, Bezmialem Vakif University, Istanbul, Turkey
| | - Emre Bozkurt
- Department of General Surgery, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
| | - Ramazan Ucak
- Department of Pathology, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
| | - Zuhal Gucin
- Department of Pathology, Bezmialem Vakif University, Istanbul, Turkey
| | - Taskin Uresin
- Department of Pathology, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey
| | - Mustafa Hasbahceci
- General Surgery Clinic, Medical Park Fatih Hospital, Fatih, Istanbul, Turkey
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Endoscopic Retrograde Cholangiopancreatography and Endoscopic Ultrasound-Guided Gallbladder Drainage. Gastrointest Endosc Clin N Am 2019; 29:293-310. [PMID: 30846154 DOI: 10.1016/j.giec.2018.12.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
"Gallbladder disease is one of the most common gastrointestinal diseases encountered in clinical practice. Surgical removal and percutaneous drainage are both widely available and effective in the management of acute cholecystitis. Several endoscopic approaches exist as an alternative to these interventions. These include transpapillary approaches via endoscopic retrograde cholangiopancreatography (ERCP), transmural drainage and access approaches via endoscopic ultrasound (EUS), and endoscopic surgical approaches using natural orifice transluminal endoscopic surgery (NOTES) techniques. This article reviews the epidemiology and pathophysiology of gallbladder diseases and discusses the various percutaneous, surgical, and endoscopic approaches to managing gallbladder disease."
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Di Ciaula A, Wang DQH, Portincasa P. Cholesterol cholelithiasis: part of a systemic metabolic disease, prone to primary prevention. Expert Rev Gastroenterol Hepatol 2019; 13:157-171. [PMID: 30791781 DOI: 10.1080/17474124.2019.1549988] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cholesterol gallstone disease have relationships with various conditions linked with insulin resistance, but also with heart disease, atherosclerosis, and cancer. These associations derive from mechanisms active at a local (i.e. gallbladder, bile) and a systemic level and are involved in inflammation, hormones, nuclear receptors, signaling molecules, epigenetic modulation of gene expression, and gut microbiota. Despite advanced knowledge of these pathways, the available therapeutic options for symptomatic gallstone patients remain limited. Therapy includes oral litholysis by the bile acid ursodeoxycholic acid (UDCA) in a small subgroup of patients at high risk of postdissolution recurrence, or laparoscopic cholecystectomy, which is the therapeutic radical gold standard treatment. Cholecystectomy, however, may not be a neutral event, and potentially generates health problems, including the metabolic syndrome. Areas covered: Several studies on risk factors and pathogenesis of cholesterol gallstone disease, acting at a systemic level have been reviewed through a PubMed search. Authors have focused on primary prevention and novel potential therapeutic strategies. Expert commentary: The ultimate goal appears to target the manageable systemic mechanisms responsible for gallstone occurrence, pointing to primary prevention measures. Changes must target lifestyles, as well as experimenting innovative pharmacological tools in subgroups of patients at high risk of developing gallstones.
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Affiliation(s)
- Agostino Di Ciaula
- a Division of Internal Medicine , Hospital of Bisceglie , Bisceglie , Italy
| | - David Q-H Wang
- b Department of Medicine, Division of Gastroenterology and Liver Diseases , Marion Bessin Liver Research Center, Albert Einstein College of Medicine , Bronx , NY , USA
| | - Piero Portincasa
- c Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri" , University of Bari Medical School , Bari , Italy
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You MS, Ryu JK, Choi YH, Choi JH, Huh G, Paik WH, Lee SH, Kim YT. Therapeutic outcomes and prognostic factors in unresectable gallbladder cancer treated with gemcitabine plus cisplatin. BMC Cancer 2019; 19:10. [PMID: 30611225 PMCID: PMC6321682 DOI: 10.1186/s12885-018-5211-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 12/12/2018] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Gallbladder cancer (GBC) is likely to be diagnosed at progressive stages and shows a very poor prognosis. Combination therapy with gemcitabine and cisplatin (GEMCIS) has been widely used as first-line palliative chemotherapy for advanced GBC. This study was designed to investigate the efficacy of GEMCIS and identify prognostic factors in patients with unresectable GBC. METHODS Patients with GBC who were treated with GEMCIS from January 2008 to June 2017 in a single tertiary hospital were included. All cases of GBC were diagnosed by pathologic findings and extent of the tumour was assessed by imaging tests. Combination chemotherapy consisted of cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 intravenously on days 1 and 8 every 3 weeks. To determine factors affecting prognosis, Kaplan-Meier survival analysis, log-rank test and the Cox proportional hazard regression linear model were used. All variables with P < 0.1 in univariable analysis were included in the multivariable model. RESULTS A total of 173 patients received a median of 5.3 ± 4.4 cycles of chemotherapy over 3.8 ± 3.9 months. Most of the patients (94.8%) were stage IVB at the time of diagnosis and the most common site of metastasis was the liver (42.8%). Disease control rate was 59.5%: 2 (1.2%) patients with complete response, 26 (15.0%) patients with partial response and 75 (43.4%) patients with stable disease. Overall survival (OS) and progression-free survival were 8.1 (95% confidence interval [CI], 7.1-10.2) and 5.6 (95% CI 4.5-6.8) months, respectively. Multivariable regression model indicated that metastasis to liver (hazard ratio [HR] = 1.63, 95% CI 1.11-2.40; P = 0.013), neutrophil-to-lymphocyte ratio (NLR) ≥3 (HR 1.65, 95% CI 1.09-2.49; P = 0.017), CEA ≥ 5 ng/mL (HR 1.50, 95% CI 1.02-2.19; P = 0.038), and CA19-9 ≥ 500 U/mL (HR 1.59, 95% CI 1.01-2.50; P = 0.043) were significantly associated with OS. CONCLUSIONS GEMCIS demonstrated a high disease control rate in patients with unresectable GBC. Factors independently related to OS were metastasis to liver, NLR ≥ 3, CEA ≥ 5 ng/mL and CA19-9 ≥ 500 U/mL.
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Affiliation(s)
- Min Su You
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea
| | - Ji Kon Ryu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.
| | - Young Hoon Choi
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea
| | - Jin Ho Choi
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea
| | - Gunn Huh
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea
| | - Woo Hyun Paik
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea
| | - Sang Hyub Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea
| | - Yong-Tae Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea
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Oweira H, Mehrabi A, Giryes A, Tekbas A, Abdel-Rahman O. External validation of the 8 th American Joint Committee on Cancer staging system for gall bladder carcinoma. J Gastrointest Oncol 2018; 9:1084-1090. [PMID: 30603127 DOI: 10.21037/jgo.2018.08.10] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background To validate the changes within the American Joint Committee on Cancer (AJCC) 8th staging system for gall bladder carcinoma compared to AJCC 7th staging system. Methods Surveillance, Epidemiology and End Results (SEER) database [2004-2014] was queried. Kaplan-Meier survival analyses and Log-rank testing were assessed according to both AJCC 7th and 8th staging systems. Likewise, Cox cancer-specific hazard ratio was evaluated according to both staging systems. Results Overall survival was assessed according to the two staging systems; and P values for overall trend (log/rank test) were significant (P<0.001) for both scenarios. Cox regression cancer-specific hazard adjusted for age, gender, histology, gender and surgery was evaluated according to the two staging systems. According to AJCC 7th staging system, the following pair wise hazard ratio comparisons were significant (II vs. IIIA; IIIB vs. IVA; IVA vs. IVB). According to AJCC 8th staging system, the following pair wise hazard ratio comparisons were significant (II vs. IIIA; IVA vs. IVB). C-statistic was assessed using death from gall bladder carcinoma as the dependent variable; and the findings for the two staging systems were as follows: AJCC 7th staging system: 0.684 (SE: 0.008; 95% CI: 0.667-0.701); AJCC 8th staging system: 0.682 (SE: 0.009; 95% CI: 0.665-0.698). Conclusions There is a comparable discriminatory performance for AJCC 8th staging system compared to AJCC 7th staging system. Change form location-based to number-based N category assessment does not improve the overall prognostic performance of the staging system.
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Affiliation(s)
- Hani Oweira
- Oncology Department, Swiss Cancer Institute, Cham, Switzerland.,Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
| | - Anwar Giryes
- Oncology Department, Swiss Cancer Institute, Cham, Switzerland
| | - Aysun Tekbas
- Surgery Department, University of Jena, Jena, Germany
| | - Omar Abdel-Rahman
- Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.,Department of Oncology, University of Calgary, Tom Baker Cancer Centre, Calgary, Alberta, Canada
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Köhn N, Maubach J, Warschkow R, Tsai C, Nussbaum DP, Candinas D, Gloor B, Schmied BM, Blazer DG, Worni M. High rate of positive lymph nodes in T1a gallbladder cancer does not translate to decreased survival: a population-based, propensity score adjusted analysis. HPB (Oxford) 2018; 20:1073-1081. [PMID: 29891423 DOI: 10.1016/j.hpb.2018.05.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Accepted: 05/12/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Current consensus guidelines suggest that gallbladder cancer (GBC) patients with resected T1a disease can be observed while patients with T1b or greater lesions should undergo lymphadenectomy (LNE). The primary aim of this study was to critically explore the impact of LNE in early-stage GBC on overall survival (OS) on a population-based level. METHOD The 2004-2014 National Cancer Database was reviewed to identify non-metastatic GBC patients with T1a, T1b, or T2 disease and grouped whether a dedicated LNE was performed. OS and relative survival were assessed using Cox proportional hazard regression analyses before and after propensity score adjustments. RESULTS 4015 patients were included, 246 (6%) had T1a, 654 (16%) T1b, and 3115 (78%) T2 GBC. The rate of positive lymph nodes was 13%, 12%, and 40% for T1a, T1b, and T2 tumors, respectively. Even after propensity score adjustment, no OS benefit was found if LNE was performed for T1a disease (HR:0.63, 95%CI:0.35-1.13) while OS was improved for T1b (HR:0.65, 95%CI:0.49-0.87) and T2 tumors (HR:0.65, 95%CI:0.57-0.73). CONCLUSION Despite a higher rate of nodal positivity among patients with T1a disease compared to previous reports, there was no impact on survival and current treatment guidelines appear appropriate for the management of T1a disease.
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Affiliation(s)
- Nastassja Köhn
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Johannes Maubach
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Rene Warschkow
- Department of Surgery, Kantonsspital St. Gallen, 9007, St. Gallen, Switzerland
| | - Catherine Tsai
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Daniel P Nussbaum
- Department of Surgery, Duke University Medical Center, Duke University, Durham, NC, USA
| | - Daniel Candinas
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Beat Gloor
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Bruno M Schmied
- Department of Surgery, Kantonsspital St. Gallen, 9007, St. Gallen, Switzerland
| | - Dan G Blazer
- Department of Surgery, Duke University Medical Center, Duke University, Durham, NC, USA
| | - Mathias Worni
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Surgery, Duke University Medical Center, Duke University, Durham, NC, USA.
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Malhotra RK, Manoharan N, Shukla NK, Rath GK. Gallbladder cancer incidence in Delhi urban: A 25-year trend analysis. Indian J Cancer 2018; 54:673-677. [PMID: 30082556 DOI: 10.4103/ijc.ijc_393_17] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Gallbladder cancer (GBC) falls into the top ten leading cancer sites in urban Delhi. The incidence of GBC in females is more than that among males worldwide. The present study evaluates the temporal variation of GBC incidence in an urban Delhi population. MATERIALS AND METHODS The 25-year GBC incidence data were obtained from Population-Based Cancer Registry (PBCR) of Delhi which covered nearly 97.5% of the population and 75% of Delhi. We applied joinpoint regression method to determine the trend of GBC incidence from 1988 to 2012. The estimated cumulative risk (0-74) and lifetime risk of developing GBC were also calculated. RESULTS GBC contributed 6% of total cancer cases in Delhi during the year 2012. In the past 25 years, 12,410 GBC cases (4010 males and 8400 females) were registered and contributed approximately 3% of male cancer cases and 6.5% of female cancer cases. The median age at diagnosis of GBC was 60.13 years and 57.22 years in males and females, respectively. Joinpoint analysis showed an overall increasing trend of age-adjusted rates of GBC incidence over 25 years. In females, a downward trend was observed during 1992-2004, whereas in males, the trend remained consistent during 1991-2005; however, thereafter, it started significant increasing for both the genders. Age-specific trend of GBC also reflects an increasing trend among males and females after 2004. CONCLUSION The total and age-specific GBC cases have show an increasing trend in the past 25 years in urban Delhi. Stringent steps are required to control the modifiable risk factors for reducing the incidence of GBC in Delhi. In addition, individuals should also practice a healthy lifestyle to reduce the likelihood of GBC as well as other diseases.
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Affiliation(s)
- Rajeev Kumar Malhotra
- Delhi Cancer Registry, Dr. BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Nalliah Manoharan
- Delhi Cancer Registry, Dr. BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - N K Shukla
- Department of Surgical Oncology, Dr. BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Gourva Kishore Rath
- Department of Radiation Oncology, Dr. BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
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Long noncoding RNA MEG3 regulates LATS2 by promoting the ubiquitination of EZH2 and inhibits proliferation and invasion in gallbladder cancer. Cell Death Dis 2018; 9:1017. [PMID: 30282996 PMCID: PMC6170488 DOI: 10.1038/s41419-018-1064-1] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 08/29/2018] [Accepted: 09/10/2018] [Indexed: 02/06/2023]
Abstract
Gallbladder cancer (GBC) is the most common type of biliary tract cancer worldwide. Long noncoding RNAs (lncRNAs) play essential roles in physiological and pathological development. LncRNA MEG3, a tumor suppressor, has been reported to play important roles in some cancers, but the role of MEG3 in GBC remains largely unknown. The purpose of the present study was to explore the role of MEG3 in proliferation and invasion and the potential molecular mechanism in GBC. We found that MEG3 was downregulated in GBC tissues and cells, and low expression of MEG3 was correlated with poor prognostic outcomes in patients. Overexpression of MEG3 inhibited GBC cell proliferation and invasion, induced cell apoptosis and decreased tumorigenicity in nude mice. Moreover, we found that MEG3 was associated with EZH2 and attenuated EZH2 by promoting its ubiquitination. Furthermore, MEG3 executed its functions via EZH2 to regulate the downstream target gene LATS2. Taken together, these findings suggest that MEG3 is an effective target for GBC therapy and may facilitate the development of lncRNA-directed diagnostics and therapeutics against GBC.
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Lin J, Long J, Wan X, Chen J, Bai Y, Wang A, Yang X, Wu Y, Robson SC, Sang X, Zhao H. Classification of gallbladder cancer by assessment of CD8 + TIL and PD-L1 expression. BMC Cancer 2018; 18:766. [PMID: 30055582 PMCID: PMC6064069 DOI: 10.1186/s12885-018-4651-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Accepted: 06/29/2018] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Programmed death ligand 1/2 (PD-L1/PD-L2) expression has been established as a prognostic factor for various solid tumors and as a predictive factor for PD-1 blockade therapy, but scant data on its role in gallbladder cancer (GBC). The aims of this study were to assess the expression of PD-L1/PD-L2 and the density of CD8+ tumor-infiltrating lymphocytes (TIL) from GBC samples and to quantify the association between survival prognosis and these factors. METHODS CD8+ TILs density and the expression of PD-1, PD-L1, PD-L2 and CD133 were assessed using immunohistochemistry in tumor specimens from 66 patients with gallbladder adenocarcinoma. These indexes were correlated with the clinicopathological features. RESULTS The rate of PD-L1-positive (PD-L1+) was 54%, which included 18% positivity in tumor cells, and 36% in peritumoral immune stroma. High CD8+ TIL density (CD8high) was observed in PD-L1+ GBC, and PD-L1+ was positively associated with PD-L2+ expression. Regarding prognostic factors, PD-L1+ expression was related to worse overall survival (OS), and CD8high indicated better OS and progression-free survival (PFS). The combination of CD8high with PD-L1+ serves as a prognostic factor for improved OS (P < 0.001) and PFS (P = 0.014). CONCLUSION Analysis of the tumor immune microenvironment based on CD8+ TIL and PD-L1 expression is a promising independent predictor for the clinical outcome of GBC patients.
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Affiliation(s)
- Jianzhen Lin
- Department of Liver Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Peking Union Medical College Hospital, #1 Shuaifuyuan, Wangfujing, Beijing, 100730, China
| | - Junyu Long
- Department of Liver Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Peking Union Medical College Hospital, #1 Shuaifuyuan, Wangfujing, Beijing, 100730, China
| | - Xueshuai Wan
- Department of Liver Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Peking Union Medical College Hospital, #1 Shuaifuyuan, Wangfujing, Beijing, 100730, China
| | - Jingci Chen
- School of Medicine, Tsinghua University, Beijing, China
| | - Yi Bai
- Department of Liver Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Peking Union Medical College Hospital, #1 Shuaifuyuan, Wangfujing, Beijing, 100730, China
| | - Anqiang Wang
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiaobo Yang
- Department of Liver Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Peking Union Medical College Hospital, #1 Shuaifuyuan, Wangfujing, Beijing, 100730, China
| | - Yan Wu
- Liver Center and The Transplant Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Simon C Robson
- Liver Center and The Transplant Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Xinting Sang
- Department of Liver Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Peking Union Medical College Hospital, #1 Shuaifuyuan, Wangfujing, Beijing, 100730, China.
| | - Haitao Zhao
- Department of Liver Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Peking Union Medical College Hospital, #1 Shuaifuyuan, Wangfujing, Beijing, 100730, China. .,Center of Translational Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Beijing, China.
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47
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Khan S, Beard RE, Kingham PT, Fong Y, Boerner T, Martinie JB, Vrochides D, Buell JF, Berber E, Kahramangil B, Troisi RI, Vanlander A, Molinari M, Tsung A. Long-Term Oncologic Outcomes Following Robotic Liver Resections for Primary Hepatobiliary Malignancies: A Multicenter Study. Ann Surg Oncol 2018; 25:2652-2660. [PMID: 29987604 DOI: 10.1245/s10434-018-6629-9] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2018] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Robotic liver surgery (RLS) has emerged as a feasible alternative to laparoscopic or open resections with comparable perioperative outcomes. Little is known about the oncologic adequacy of RLS. The purpose of this study was to investigate the long-term oncologic outcomes for patients undergoing RLS for primary hepatobiliary malignancies. METHODS We performed an international, multicenter, retrospective study of patients who underwent RLS for hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), or gallbladder cancer (GBC) between 2006 and 2016. Age, gender, histology, resection margin status, extent of surgical resection, disease-free survival (DFS), and overall survival (OS) were retrospectively collected and analyzed. RESULTS Of the 61 included patients, 34 (56%) had RLS performed for HCC, 16 (26%) for CC, and 11 (18%) for GBC. The majority of resections were nonanatomical or segmental resections (39.3%), followed by central hepatectomy (18%), left-lateral sectionectomy (14.8%), left hepatectomy (13.1%), right hepatectomy (13.1%), and right posterior segmentectomy (1.6%). R0 resection was achieved in 94% of HCC, 68% of CC, and 81.8% of GBC patients. Median hospital stay was 5 days, and conversion to open surgery was needed in seven patients (11.5%). Grade III-IV Dindo-Clavien complications occurred in seven patients with no perioperative mortality. Median follow-up was 75 months (95% confidence interval 36-113), and 5-year OS and DFS were 56 and 38%, respectively. When stratified by tumor type, 3-year OS was 90% for HCC, 65% for GBC, and 49% for CC (p = 0.01). CONCLUSIONS RLS can be performed for primary hepatobiliary malignancies with long-term oncologic outcomes comparable to published open and laparoscopic data.
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Affiliation(s)
- Sidrah Khan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Rachel E Beard
- Department of Surgery, Rhode Island Hospital, Providence, RI, USA
| | - Peter T Kingham
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Thomas Boerner
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
| | - John B Martinie
- Department of Surgery, Carolinas Medical Center, Charlotte, NC, USA
| | | | - Joseph F Buell
- Department of Surgery, Tulane University, New Orleans, LA, USA
| | - Eren Berber
- Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Bora Kahramangil
- Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Roberto I Troisi
- Department of General, Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital Medical School, Ghent, Belgium
| | - Aude Vanlander
- Department of General, Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital Medical School, Ghent, Belgium
| | - Michele Molinari
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Allan Tsung
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
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48
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Wang J, Bo X, Suo T, Liu H, Ni X, Shen S, Li M, Xu J, Liu H, Wang Y. Tumor-infiltrating neutrophils predict prognosis and adjuvant chemotherapeutic benefit in patients with biliary cancer. Cancer Sci 2018; 109:2266-2274. [PMID: 29723922 PMCID: PMC6029827 DOI: 10.1111/cas.13627] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Revised: 04/20/2018] [Accepted: 04/22/2018] [Indexed: 12/29/2022] Open
Abstract
Tumor-infiltrating neutrophils (TIN) carry out quite significant but opposite functions in different cancers, and their function in biliary cancer has not been fully characterized. To investigate the prognostic significance of TIN in biliary cancer, a training set (n = 118) and a validation set (n = 127) were involved in this study. TIN were evaluated by immunohistochemical staining of CD66b, and then defined as low (neutrophils <18/high-power field [HPF]) vs high (neutrophils ≥18/HPF). Kaplan-Meier curve, Cox proportional hazards models and receiver operating characteristic curve were used to assess the prognostic significance. TIN was identified as an independent prognostic factor for overall survival in the training set (HR: 4.720; 95% CI: 2.623-8.493; P < .001) which was confirmed in the validation set (HR: 4.993; 95% CI: 2.626-9.492; P < .001). Notably, among patients with stage III and IV disease, those with low TIN could benefit from adjuvant chemotherapy, with a reduced risk of compromised survival compared with those with high TIN (HR: 0.294; 95% CI: 0.099-0.873; P = .047 in the training set; and HR: 0.100; 95% CI: 0.022-0.462; P = .006 in the validation set). In addition, TIN were negatively related to biological pathways as regulation of activated T-cell proliferation and lymphocyte-mediated immunity, and showed a negative correlation with CD8 + T cells (r = -.324, P < .001). Taken together, our results implicate TIN as an independent marker of prognosis and indicator of patients who would benefit from adjuvant chemotherapy in biliary cancer.
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Affiliation(s)
- Jie Wang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaobo Bo
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tao Suo
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Han Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaoling Ni
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Sheng Shen
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Min Li
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jiejie Xu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Houbao Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yueqi Wang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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49
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Yifan T, Zheyong L, Miaoqin C, Liang S, Xiujun C. A predictive model for survival of gallbladder adenocarcinoma. Surg Oncol 2018; 27:365-372. [PMID: 30217289 DOI: 10.1016/j.suronc.2018.05.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 02/23/2018] [Accepted: 05/02/2018] [Indexed: 01/19/2023]
Abstract
BACKGROUND Gallbladder cancer (GBC) is a life-threatening disease with a poor prognosis worldwide. Although several risk factors for survival have been identified, an ideal model for predicting prognosis has still not been developed due to the low incidence of GBC. This study aims to solve this dilemma by attempting to develop an efficient survival prediction model for GBC. METHODS This is a retrospective study. From January 2009 to June 2016, 164 patients with a confirmed histological diagnosis of gallbladder adenocarcinoma were enrolled in this study. The cohort was randomly divided into two cohorts, the development cohort (n = 110) and validation cohort (n = 54). On the basis of the risk factors identified in the development cohort, a nomogram-based predictive model (P-risk Plus), composed of carbohydrate antigen 199 and pathological characteristics, was established for prognosis. RESULTS In this model, the calibration curves for the 1-, 2-, and 3-year survival probabilities were well-matched with the actual survival rates. In addition, the highest C-index and best decision curve analysis were able to be obviously determined. Meanwhile, the P-risk Plus model result yielded a better fit for survival between the development and validation groups. CONCLUSION Compared with conventional tumor stages, our nomogram-based P-risk Plus model for gallbladder adenocarcinoma has a better predictive capacity and thereby has a better potential to facilitate decision-making clinically.
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Affiliation(s)
- Tong Yifan
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Li Zheyong
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Chen Miaoqin
- Department of Biological Treatment Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shi Liang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Cai Xiujun
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
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50
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Lin B, Hong H, Jiang X, Li C, Zhu S, Tang N, Wang X, She F, Chen Y. c‑Jun suppresses the expression of WNT inhibitory factor 1 through transcriptional regulation and interaction with DNA methyltransferase 1 in gallbladder cancer. Mol Med Rep 2018; 17:8180-8188. [PMID: 29693707 PMCID: PMC5983991 DOI: 10.3892/mmr.2018.8890] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 07/04/2017] [Indexed: 11/22/2022] Open
Abstract
WNT inhibitory factor 1 (WIF-1) is involved in the tumorigenicity and progression of several types of tumor, which has been attributed to aberrant hypermethylation of its promoter. However, the role of WIF-1 in the pathogenesis of gallbladder cancer (GBC) remains to be fully elucidated, and the data available are insufficient to identify the upstream molecular mechanisms involved. In the present study, the methylation status of the WIF-1 promoter was investigated using methylation-specific polymerase chain reaction (PCR) and bisulfate sequencing PCR in GBC cells. Immunohistochemistry, reverse transcription-quantitative PCR and western blotting were used to analyze the expression of WIF-1 and c-Jun. In addition, a co-immunoprecipitation assay was designed to determine the DNA methyltransferase that was implicated in WIF-1 methylation. The results revealed that the expression of WIF-1 was low in GBC, and that this was caused by aberrant DNA hypermethylation. However, there were no significant correlations between the expression of WIF-1 and certain key clinicopathological characteristics of GCB. Subsequently, a negative correlation was found between the protein expression of c-Jun and WIF-1 in 50 GBC specimens using immunohistochemistry. The demethylation and re-expression of WIF-1 was observed when the expression of c-Jun was silenced. Finally, it was found that the knockdown of c-Jun downregulated the expression of DNA methyltransferase 1 (DNMT1) and that c-Jun interacted with DNMT1. Taken together, the present study suggested that c-Jun suppressed the expression of WIF-1 through transcriptional regulation and interaction with DNMT1 in GBC. These findings provide an alternative pathogenesis of GBC, which may be promising as a novel reference for early diagnosis or future treatment.
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Affiliation(s)
- Bin Lin
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Haijie Hong
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Xiaojie Jiang
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Chengzong Li
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Siyuan Zhu
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Nanhong Tang
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Xiaoqian Wang
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Feifei She
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian 350108, P.R. China
| | - Yanling Chen
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
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