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Jang DK, Kim SJ, Chung HH, Lee JM, Yoon SB, Lee JC, Shin DW, Hwang JH, Jung MK, Lee YS, Lee HS, Park JK. Outcomes of Palliative Chemotherapy for Ampulla of Vater Adenocarcinoma: A Multicenter Cohort Study. Gut Liver 2024; 18:729-736. [PMID: 38130162 PMCID: PMC11249934 DOI: 10.5009/gnl230164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 09/07/2023] [Accepted: 10/11/2023] [Indexed: 12/23/2023] Open
Abstract
Background/Aims : Palliative chemotherapy (PC) is not standardized for patients with advanced ampulla of Vater adenocarcinoma (AA). This multicenter, retrospective study evaluated first-line PC outcomes in patients with AA. Methods : Patients diagnosed with AA between January 2010 and December 2020 who underwent PC were enrolled from 10 institutions. Overall survival (OS) and progression-free survival (PFS) according to the chemotherapy regimen were analyzed. Results : Of 255 patients (mean age, 64.0±10.0 years; male, 57.6%), 14 (5.5%) had locally advanced AA and 241 (94.5%) had metastatic AA. Gemcitabine plus cisplatin (GP) was administered as first-line chemotherapy to 192 patients (75.3%), whereas capecitabine plus oxaliplatin (CAPOX) was administered to 39 patients (15.3%). The median OS of all patients was 19.8 months (95% confidence interval [CI], 17.3 to 22.3), and that of patients who received GP and CAPOX was 20.4 months (95% CI, 17.2 to 23.6) and 16.0 months (95% CI, 11.2 to 20.7), respectively. The median PFS of GP and CAPOX patients were 8.4 months (95% CI, 7.1 to 9.7) and 5.1 months (95% CI, 2.5 to 7.8), respectively. PC for AA demonstrated improved median outcomes in both OS and PFS compared to conventional bile duct cancers that included AA. Conclusions : While previous studies have shown mixed prognostic outcomes when AA was analyzed together with other biliary tract cancers, our study unveils a distinct clinical prognosis specific to AA on a large scale with systemic anticancer therapy. These findings suggest that AA is a distinct type of tumor, different from other biliary tract cancers, and AA itself could be expected to have a favorable response to PC.
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Affiliation(s)
- Dong Kee Jang
- Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - So Jeong Kim
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Hwe Hoon Chung
- Division of Gastroenterology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Min Lee
- Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
| | - Seung Bae Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jong-Chan Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Dong Woo Shin
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Min Kyu Jung
- Division of Gastroenterology, Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Yoon Suk Lee
- Division of Gastroenterology, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Hee Seung Lee
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Joo Kyung Park
- Division of Gastroenterology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Ahmadi Asouri S, Aghadavood E, Mirzaei H, Abaspour A, Esmaeil Shahaboddin M. PIWI-interacting RNAs (PiRNAs) as emerging biomarkers and therapeutic targets in biliary tract cancers: A comprehensive review. Heliyon 2024; 10:e33767. [PMID: 39040379 PMCID: PMC11261894 DOI: 10.1016/j.heliyon.2024.e33767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 06/09/2024] [Accepted: 06/26/2024] [Indexed: 07/24/2024] Open
Abstract
Cancers affecting the biliary tract, such as gallbladder cancer and cholangiocarcinoma, make up a small percentage of adult gastrointestinal malignancies, but their incidence is on the rise. Due to the lack of dependable molecular biomarkers for diagnosis and prognosis, these cancers are often not detected until later stages and have limited treatment options. Piwi-interacting RNAs (piRNAs) are a type of small noncoding RNA that interacts with Piwi proteins and has been linked to various diseases, especially cancer. Manipulation of piRNA expression has the potential to serve as an important biomarker and target for therapy. This review uncovers the relationship between PIWI-interacting RNA (piRNA) and a variety of gastrointestinal cancers, including biliary tract cancer (BTC). It is evident that piRNAs have the ability to impact gene expression and regulate key genes and pathways related to the advancement of digestive cancers. Abnormal expression of piRNAs plays a significant role in the development and progression of digestive-related malignancies. The potential of piRNAs as potential biomarkers for diagnosis and prognosis, as well as therapeutic targets in BTC, is noteworthy. Nevertheless, there are obstacles and limitations that require further exploration to fully comprehend piRNAs' role in BTC and to devise effective diagnostic and therapeutic approaches using piRNAs. In summary, this review underscores the value of piRNAs as valuable biomarkers and promising targets for treating BTC, as we delve into the association between piRNAs and various gastrointestinal cancers, including BTC, and how piRNAs can impact gene expression and control essential pathways for digestive cancer advancement. The present research consists of a thorough evaluation presented in a storytelling style. The databases utilized to locate original sources were PubMed, MEDLINE, and Google Scholar, and the search was conducted using the designated keywords.
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Affiliation(s)
- Sahar Ahmadi Asouri
- Department of Clinical Biochemistry, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Esmat Aghadavood
- Department of Clinical Biochemistry, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Mirzaei
- Institute for Basic Sciences, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Alireza Abaspour
- Department of Pathobiology and Laboratory Sciences, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Mohammad Esmaeil Shahaboddin
- Department of Clinical Biochemistry, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- Institute for Basic Sciences, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
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Kim EJ. Challenges and Advancements in Palliative Chemotherapy for Ampullary Adenocarcinoma. Gut Liver 2024; 18:560-561. [PMID: 39005199 PMCID: PMC11249936 DOI: 10.5009/gnl240283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/16/2024] Open
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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Lee S, Park SJ, Shin K, Hong TH, Kim IH, Lee MA. Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater. BMC Cancer 2024; 24:634. [PMID: 38783256 PMCID: PMC11119299 DOI: 10.1186/s12885-024-12398-0] [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: 08/12/2023] [Accepted: 05/17/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.
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Affiliation(s)
- Seunghwan Lee
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
| | - Se Jun Park
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kabsoo Shin
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Tae Ho Hong
- Department of General Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - In-Ho Kim
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Myung Ah Lee
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea.
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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Duan XP, Qin BD, Jiao XD, Liu K, Wang Z, Zang YS. New clinical trial design in precision medicine: discovery, development and direction. Signal Transduct Target Ther 2024; 9:57. [PMID: 38438349 PMCID: PMC10912713 DOI: 10.1038/s41392-024-01760-0] [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: 11/30/2023] [Revised: 01/25/2024] [Accepted: 01/29/2024] [Indexed: 03/06/2024] Open
Abstract
In the era of precision medicine, it has been increasingly recognized that individuals with a certain disease are complex and different from each other. Due to the underestimation of the significant heterogeneity across participants in traditional "one-size-fits-all" trials, patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket, umbrella, and platform trial designs under the master protocol framework. In recent years, the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous opportunities. Despite the rapid increase in the number of basket, umbrella, and platform trials, the current clinical and research understanding of these new trial designs, as compared with traditional trial designs, remains limited. The majority of the research focuses on methodologies, and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial designs. Therefore, we provide this comprehensive review of the discovery and development of basket, umbrella, and platform trials and their underlying logic from the perspective of precision medicine. Meanwhile, we discuss future directions on the potential development of these new clinical design in view of the "Precision Pro", "Dynamic Precision", and "Intelligent Precision". This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic, which be essential to accelerate the progression of precision medicine.
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Affiliation(s)
- Xiao-Peng Duan
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Bao-Dong Qin
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Xiao-Dong Jiao
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Ke Liu
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Zhan Wang
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Yuan-Sheng Zang
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China.
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Shin DW. [Treatment of Ampullary Adenocarcinoma]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 82:159-170. [PMID: 37876255 DOI: 10.4166/kjg.2023.110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 09/28/2023] [Accepted: 10/03/2023] [Indexed: 10/26/2023]
Abstract
The ampulla of Vater is a small projection formed by the confluence of the main pancreatic duct and common bile duct in the second part of the duodenum. Primary ampullary adenocarcinoma is a rare malignancy, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. Jaundice from a biliary obstruction is the most common symptom of ampullary adenocarcinoma. In the early stages, radical pancreatoduodenectomy is the standard surgical approach. On the other hand, no randomized controlled trial has provided evidence to guide physicians on the choice of adjuvant/palliative chemotherapy because of the rarity of the disease and the paucity of related research. This paper reports the biology, histology, current therapeutic strategies, and potential future therapies of ampullary adenocarcinoma.
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Affiliation(s)
- Dong Woo Shin
- Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
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Park SJ, Shin K, Hong TH, Lee SH, Kim IH, Kim Y, Lee M. Histologic subtype-based evaluation of recurrence and survival outcomes in patients with adenocarcinoma of the ampulla of Vater. Sci Rep 2023; 13:16547. [PMID: 37783755 PMCID: PMC10545688 DOI: 10.1038/s41598-023-42386-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 09/09/2023] [Indexed: 10/04/2023] Open
Abstract
Patients with ampulla of Vater adenocarcinoma exhibit diverse outcomes, likely since these malignancies can originate from any of the three converging epithelia at this site. Such variability presents difficulties in clinical decision-making processes and in devising therapeutic approaches. In this study, the potential clinical value of histomolecular phenotypes was determined by integrating histopathological analysis with protein expression (MUC1, CDX2, CK20, and MUC2), in a cohort of 87 patients diagnosed with stage IB to III ampulla of Vater adenocarcinoma who underwent curative surgical resection. Of the 87 patients, 54 were classified as pancreato-biliary (PB) subtype and 33 as intestinal subtype. The median follow-up time for all patients was 32.8 months (95% CI, 25.3-49.2). Patients with a histomolecular PB phenotype (CDX2 negative, MUC1 positive, MUC2 negative, and irrespective of the CK20 results) were associated with poor prognostic outcomes in both disease-free survival (DFS) (HR = 1.81; 95% CI, 1.04-3.17; p = 0.054) and overall survival (OS) (HR = 2.01; 95% CI, 1.11-3.66; p = 0.039) compared to those with histomolecular intestinal carcinomas. Patients with the PB subtype were more likely to have local recurrence alone (11 of 37, 29.7%) compared to those with the intestinal subtype (1 of 15, 6.7%). In the context of systemic disease, a notably greater proportion of patients exhibiting elevated carbohydrate antigen 19-9 levels were observed in the PB subtype compared to the intestinal subtype (p = 0.024). In the cohort of 38 patients who received first-line palliative chemotherapy, a diminished median overall survival (OS) was observed in the PB group compared to the intestinal group (10.3 vs. 28.3 months, HR = 2.47; 95% CI, 1.23-4.95; p = 0.025). By integrating histopathologic and molecular criteria, we can identify distinct and clinically relevant histomolecular phenotypes in adenocarcinomas of the ampulla of Vater, which could have considerable impact on existing therapeutic approaches.
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Affiliation(s)
- Se Jun Park
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
| | - Kabsoo Shin
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
| | - Tae Ho Hong
- Department of General Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sung Hak Lee
- Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
| | - In-Ho Kim
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea
| | - Younghoon Kim
- Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea.
| | - MyungAh Lee
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea.
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul, Korea.
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Kawata J, Koga Y, Noguchi S, Shimada Y, Yamada Y, Yamamoto T, Shindo K, Nakamura M, Oda Y. Clinicopathologic Features and Genetic Alterations in Mixed-Type Ampullary Carcinoma. Mod Pathol 2023; 36:100181. [PMID: 37004749 DOI: 10.1016/j.modpat.2023.100181] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 03/22/2023] [Accepted: 03/26/2023] [Indexed: 04/03/2023]
Abstract
Mixed-type ampullary carcinoma is a subtype that combines intestinal-type (I-type) and pancreatobiliary-type (PB-type) lesions, but few studies have examined its clinicopathologic features and genetic alterations. The differences in genetic alterations between mixed type and other subtypes, as well as the genetic differences between I-type and PB-type lesions in the mixed type, remain unclear. In this study, we compared the clinicopathologic features and prognosis of 110 ampullary carcinomas classified by hematoxylin and eosin and immunohistochemical staining as follows: 63 PB-type, 35 I-type, and 12 mixed-type carcinomas. A comparative analysis of genetic mutations by targeted sequencing of 24 genes was also performed in 3 I-type cases, 9 PB-type cases, and I and PB-type lesions of 6 mixed-type cases. The mixed subtype had a poorer prognosis than the other subtypes, and there was also a similar tendency in the adjuvant group (n = 22). A total of 49 genetic mutations were detected in all 18 lesions for which genetic alteration was analyzed. No genetic mutations specific to the mixed type were found, and it was not possible to determine genetically whether the mixed type had originally been I or PB type. However, 5 of 6 cases had mutations common to both I and PB-type lesions, and additional mutations were found only in either I or PB-type lesions. In support of this, the mixed type more frequently exhibited genetic heterogeneity intratumorally than the other subtypes. Mixed-type tumors are histologically, immunohistochemically, and genetically heterogeneous, and this heterogeneity is associated with poor prognosis and may affect treatment resistance.
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Affiliation(s)
- Jun Kawata
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
| | - Yutaka Koga
- Department of Pathology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Shoko Noguchi
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
| | - Yuki Shimada
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
| | - Yutaka Yamada
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
| | - Takeo Yamamoto
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
| | - Koji Shindo
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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Liang H, Zhu Y, Wu YK. Ampulla of Vater carcinoma: advancement in the relationships between histological subtypes, molecular features, and clinical outcomes. Front Oncol 2023; 13:1135324. [PMID: 37274233 PMCID: PMC10233008 DOI: 10.3389/fonc.2023.1135324] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 05/03/2023] [Indexed: 06/06/2023] Open
Abstract
The incidence of ampulla of Vater carcinoma, a type of periampullary cancer, has been increasing at an annual percentage rate of 0.9%. However, patients with ampulla of Vater carcinoma have quite different prognoses due to the heterogeneities of the tissue origin of this carcinoma. In addition to TNM staging, histological subtypes and molecular features of ampulla of Vater carcinoma are the key factors for predicting the clinical outcomes of patients. Fortunately, with the development of testing technology, information on the histological subtypes and molecular features of ampulla of Vater carcinoma is increasingly being analyzed in-depth. Patients with the pancreaticobiliary subtype have shorter survival times. In immunohistochemical examination, high cutoff values of positive MUC1 staining can be used to accurately predict the outcome of patients. Mutant KRAS, TP53, negative SMAD4 expression, and microsatellite stability are related to poor prognosis, while the clinical value of BRCA1/BRCA2 mutations is limited for prognosis. Testing the histological subtypes and molecular characteristics of ampulla of Vater carcinoma not only is the key to prognosis analysis but also provides extra information for targeted treatment to improve the clinical outcomes of patients.
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10
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Gkountakos A, Martelli FM, Silvestris N, Bevere M, De Bellis M, Alaimo L, Sapuppo E, Masetto F, Mombello A, Simbolo M, Bariani E, Milella M, Fassan M, Scarpa A, Luchini C. Extrahepatic Distal Cholangiocarcinoma vs. Pancreatic Ductal Adenocarcinoma: Histology and Molecular Profiling for Differential Diagnosis and Treatment. Cancers (Basel) 2023; 15:1454. [PMID: 36900245 PMCID: PMC10001378 DOI: 10.3390/cancers15051454] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 02/20/2023] [Accepted: 02/21/2023] [Indexed: 03/03/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are very aggressive tumors with a high mortality rate. Pancreas and distal bile ducts share a common embryonic development. Hence, PDAC and dCCA exhibit similar histological features that make a differential diagnosis during routine diagnostic practice challenging. However, there are also significant differences, with potential clinical implications. Even if PDAC and dCCA are generally associated with poor survival, patients with dCCA seem to present a better prognosis. Moreover, although precision oncology-based approaches are still limited in both entities, their most important targets are different and include alterations affecting BRCA1/2 and related genes in PDAC, as well as HER2 amplification in dCCA. Along this line, microsatellite instability represents a potential contact point in terms of tailored treatments, but its prevalence is very low in both tumor types. This review aims at defining the most important similarities and differences in terms of clinicopathological and molecular features between these two entities, also discussing the main theranostic implications derived from this challenging differential diagnosis.
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Affiliation(s)
- Anastasios Gkountakos
- ARC-NET Applied Research on Cancer Center, University of Verona, 37134 Verona, Italy
- Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
| | - Filippo M. Martelli
- Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
| | - Nicola Silvestris
- Medical Oncology Unit, Department of Human Pathology “G. Barresi”, University of Messina, 98125 Messina, Italy
| | - Michele Bevere
- ARC-NET Applied Research on Cancer Center, University of Verona, 37134 Verona, Italy
- Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
| | - Mario De Bellis
- Department of Surgery, Dentistry, Gynecology, and Pediatrics, Division of General and Hepatobiliary Surgery, University of Verona, 37134 Verona, Italy
| | - Laura Alaimo
- Department of Surgery, Dentistry, Gynecology, and Pediatrics, Division of General and Hepatobiliary Surgery, University of Verona, 37134 Verona, Italy
| | - Elena Sapuppo
- Medical Oncology Unit, Department of Human Pathology “G. Barresi”, University of Messina, 98125 Messina, Italy
| | - Francesca Masetto
- ARC-NET Applied Research on Cancer Center, University of Verona, 37134 Verona, Italy
| | - Aldo Mombello
- Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
| | - Michele Simbolo
- Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
| | - Elena Bariani
- Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
| | - Michele Milella
- Section of Medical Oncology, Department of Medicine, University of Verona, 37134 Verona, Italy
| | - Matteo Fassan
- Section of Pathology, Department of Medicine (DIMED), University of Padua, 35122 Padua, Italy
| | - Aldo Scarpa
- ARC-NET Applied Research on Cancer Center, University of Verona, 37134 Verona, Italy
- Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
| | - Claudio Luchini
- ARC-NET Applied Research on Cancer Center, University of Verona, 37134 Verona, Italy
- Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
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Luchini C, Scarpa A. Microsatellite instability in pancreatic and ampullary carcinomas: histology, molecular pathology, and clinical implications. Hum Pathol 2023; 132:176-182. [PMID: 35714836 DOI: 10.1016/j.humpath.2022.06.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 06/08/2022] [Indexed: 02/07/2023]
Abstract
Microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) represents an important molecular alteration with diagnostic, prognostic, and predictive value. The increasing interest toward this genetic alteration is given to the high response rate of MSI/dMMR tumors to immunotherapy. There are different cancers in the periampullary region that can harbor MSI/dMMR, and significant morphological-molecular correlates should be acknowledged in this district: (1) pancreatic ductal adenocarcinoma (PDAC): in this tumor category, the prevalence of MSI/dMMR is about 1-2%, and medullary and colloid variants are the most typically involved; (2) ampullary adenocarcinoma: here the prevalence of MSI/dMMR is up to 18%, and in this neoplastic group, MSI/dMMR is more commonly found in the intestinal subtype; (3) pancreatic acinar cell carcinoma: here the prevalence of MSI/dMMR is up to 14%; and (4) pancreatic and ampullary neuroendocrine carcinoma: in this tumor category, the prevalence of MSI/dMMR is up to 5-8%, and this molecular alteration should be assessed also in cases of mixed neuroendocrine-non-neuroendocrine neoplasms. Given the clinical importance of MSI/dMMR and its not-negligible prevalence among the different carcinomas arising in this district, its assessment should become part of the routine diagnostic workflow at least for the most typical histotypes. The test of choice is represented by immunohistochemistry for PDAC and ampullary carcinomas, and by direct molecular analyses including MSI-based polymerase chain reaction and next-generation sequencing for acinar cell and neuroendocrine carcinomas.
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Affiliation(s)
- Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, 37134, Italy; ARC-Net Research Center for Applied Research on Cancer, University of Verona, Verona, 37134, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, 37134, Italy; ARC-Net Research Center for Applied Research on Cancer, University of Verona, Verona, 37134, Italy.
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12
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Shin DW, Kim S, Jung K, Jung JH, Kim B, Ahn J, Kim J, Hwang JH, Lee JC. Impact of histopathological type on the prognosis of ampullary carcinoma: A systematic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:306-315. [PMID: 36272870 DOI: 10.1016/j.ejso.2022.10.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 08/27/2022] [Accepted: 10/05/2022] [Indexed: 02/23/2023]
Abstract
Histologically, ampullary carcinomas (ACs) can be classified into intestinal (INT-AC) and pancreatobiliary (PB-AC) subtypes. However, the prognostic implications of these subtypes remain unclear. This study aimed to evaluate the impact of the histopathologic phenotype of ACs on survival following pancreaticoduodenectomy. We searched PubMed, Embase, and Medline for studies published in English from 1994 to 2021. A meta-analysis was performed using Review Manager 5.3. The primary endpoint was overall survival (OS). We identified 3,890 articles; of these, 37 articles involving 3,455 participants (1,659 INT-ACs and 1,796 PB-ACs) were included. Patients in the PB-ACs group had significantly shorter OS than those in the INT-ACs group (hazard ratio [HR]: 1.79, 95% confidence interval [95% CI]: 1.51-2.13, p < 0.001, I2 = 61%). A similar tendency was observed in the immunohistochemistry staining group (HR: 1.76, 95% CI: 1.33-2.33, p < 0.001, I2 = 67%), which included 24 studies and 1,638 patients, and the non-immunohistochemistry group (HR: 1.84, 95% CI: 1.53-2.22, p = 0.04, I2 = 46%), which included 13 studies and 1,817 patients. Subgroup analysis revealed that patients with PB-AC had higher frequencies of advanced (III, IV) and pT3-4 stage AC, lymph node metastasis, poorly differentiated tumor, positive surgical margins, lymphovascular invasion, and perineural invasion, than those with INT-AC. Patients with PB-AC had a significantly shorter OS than those with INT-AC due to a higher aggressiveness. Because the histopathologic subtype is a major prognostic factor in patients with resected AC, routine histopathologic classification should be considered even in clinical settings without immunohistochemistry.
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Affiliation(s)
- Dong Woo Shin
- Department of Internal Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Republic of Korea
| | - Sihyun Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
| | - Kwangrok Jung
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
| | - Jae Hyup Jung
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
| | - Bomi Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
| | - Jinwoo Ahn
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
| | - Jaihwan Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jong-Chan Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
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13
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Mafficini A, Simbolo M, Shibata T, Hong SM, Pea A, Brosens LA, Cheng L, Antonello D, Sciammarella C, Cantù C, Mattiolo P, Taormina SV, Malleo G, Marchegiani G, Sereni E, Corbo V, Paolino G, Ciaparrone C, Hiraoka N, Pallaoro D, Jansen C, Milella M, Salvia R, Lawlor RT, Adsay V, Scarpa A, Luchini C. Integrative characterization of intraductal tubulopapillary neoplasm (ITPN) of the pancreas and associated invasive adenocarcinoma. Mod Pathol 2022; 35:1929-1943. [PMID: 36056133 PMCID: PMC9708572 DOI: 10.1038/s41379-022-01143-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 07/18/2022] [Accepted: 07/18/2022] [Indexed: 12/24/2022]
Abstract
Pancreatic intraductal tubulopapillary neoplasm (ITPN) is a recently recognized intraductal neoplasm. This study aimed to clarify the clinicopathologic and molecular features of this entity, based on a multi-institutional cohort of 16 pancreatic ITPNs and associated adenocarcinomas. The genomic profiles were analyzed using histology-driven multi-regional sequencing to provide insight on tumor heterogeneity and evolution. Furthermore, an exploratory transcriptomic characterization was performed on eight invasive adenocarcinomas. The clinicopathologic parameters and molecular alterations were further analyzed based on survival indices. The main findings were as follows: 1) the concomitant adenocarcinomas, present in 75% of cases, were always molecularly associated with the intraductal components. These data definitively establish ITPN as origin of invasive pancreatic adenocarcinoma; 2) alterations restricted to infiltrative components included mutations in chromatin remodeling genes ARID2, ASXL1, and PBRM1, and ERBB2-P3H4 fusion; 3) pancreatic ITPN can arise in the context of genetic syndromes, such as BRCA-germline and Peutz-Jeghers syndrome; 4) mutational profile: mutations in the classical PDAC drivers are present, but less frequently, in pancreatic ITPN; 5) novel genomic alterations were observed, including amplification of the Cyclin and NOTCH family genes and ERBB2, fusions involving RET and ERBB2, and RB1 disruptive variation; 6) chromosomal alterations: the most common was 1q gain (75% of cases); 7) by transcriptome analysis, ITPN-associated adenocarcinomas clustered into three subtypes that correlate with the activation of signaling mechanism pathways and tumor microenvironment, displaying squamous features in their majority; and 8) TP53 mutational status is a marker for adverse prognosis. ITPNs are precursor lesions of pancreatic cancer with a high malignant transformation risk. A personalized approach for patients with ITPN should recognize that such neoplasms could arise in the context of genetic syndromes. BRCA alterations, ERBB2 and RET fusions, and ERBB2 amplification are novel targets in precision oncology. The TP53 mutation status can be used as a prognostic biomarker.
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Affiliation(s)
- Andrea Mafficini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Michele Simbolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Tatsuhiro Shibata
- Division of Cancer Genomics, National Cancer Center Research Institute, and Laboratory of Molecular Medicine, The Institute of Medical Sciences, The University of Tokyo, Tokyo, Japan
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Antonio Pea
- Department of General and Pancreatic Surgery - The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Lodewijk A Brosens
- Department of Pathology, University Medical Center, Utrecht, The Netherlands
| | - Liang Cheng
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School of Brown University and Lifespan Academic Medical Center, Providence, RI, USA
| | - Davide Antonello
- Department of General and Pancreatic Surgery - The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | | | - Cinzia Cantù
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Paola Mattiolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | | | - Giuseppe Malleo
- Department of General and Pancreatic Surgery - The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Giovanni Marchegiani
- Department of General and Pancreatic Surgery - The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Elisabetta Sereni
- Department of General and Pancreatic Surgery - The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Vincenzo Corbo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Gaetano Paolino
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Chiara Ciaparrone
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Nobuyoshi Hiraoka
- Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan
| | - Daniel Pallaoro
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Casper Jansen
- Laboratory for Pathology Eastern Nertherlands, Hengelo, The Netherlands
| | - Michele Milella
- Department of Medicine, Section of Oncology, University and Hospital Trust of Verona, Verona, Italy
| | - Roberto Salvia
- Department of General and Pancreatic Surgery - The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Rita T Lawlor
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Volkan Adsay
- Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy.
- ARC-Net Research Center, University of Verona, Verona, Italy.
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy.
- ARC-Net Research Center, University of Verona, Verona, Italy.
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14
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Apurva, Abdul Sattar RS, Ali A, Nimisha, Kumar Sharma A, Kumar A, Santoshi S, Saluja SS. Molecular pathways in periampullary cancer: An overview. Cell Signal 2022; 100:110461. [PMID: 36096460 DOI: 10.1016/j.cellsig.2022.110461] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 08/19/2022] [Accepted: 08/29/2022] [Indexed: 11/22/2022]
Abstract
Molecular alterations in oncogenes and tumor suppressors in various signaling pathways are basis for personalized therapy in cancer. Periampullary carcinoma behaves differently from pancreatic carcinoma both in prognosis and outcome, therefore it needs special attention. Pancreatic cancer have higher incidence of nodal spread and perineural &lymphovascular invasion suggesting it biologically more aggressive tumor compared to periampullary cancer. Since PAC tumors consist of heterogenous tissue of origin, they might contain different mutations in tumor associated genes and other changes in tissue composition among different subgroups clubbed together. Significant progress has been made in understanding the molecular nature of PAC in the previous two decades, and a large number of mutations and other genetic changes have been identified as being responsible for the disease. This review article targets to collate and discuss the molecular evolution of PAC and their implication in its outcome. As per literature, mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and Wnt signaling are the most common pathways involved in PAC. Mutations in KRAS, TP53, CTNNB1, SMAD4 and APC genes were the most frequently reported. I-subtype resembles colorectal cancer while the morphology of PB-type shows close resemblance to pancreatic tumors. The frequency of driver gene mutations is higher in I-type compared to PB-type of PAC indicating I-type to be genetically more unstable. The genetic landscape of PAC obtained from WES data highlighted PI3/AKT pathway to be a primary target in I-type and RAS/RAF in PB-type.
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Affiliation(s)
- Apurva
- Central Molecular Lab, GovindBallabhPant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India; Amity University, Noida, India
| | - Real Sumayya Abdul Sattar
- Central Molecular Lab, GovindBallabhPant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Asgar Ali
- Central Molecular Lab, GovindBallabhPant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Nimisha
- Central Molecular Lab, GovindBallabhPant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Abhay Kumar Sharma
- Central Molecular Lab, GovindBallabhPant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Arun Kumar
- Central Molecular Lab, GovindBallabhPant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | | | - Sundeep Singh Saluja
- Central Molecular Lab, GovindBallabhPant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India; Department of GI Surgery, GovindBallabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India.
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15
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Giehl-Brown E, Weitz J, Distler M. Das Ampullenkarzinom – prognostische und therapeutische Unterschiede zum duktalen Adenokarzinom des Pankreas. Zentralbl Chir 2022; 147:160-167. [DOI: 10.1055/a-1775-9024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
ZusammenfassungDas Ampullenkarzinom stellt eine seltene, jedoch in seiner Inzidenz steigende Entität gastrointestinaler Tumoren dar. Aufgrund der anatomischen Lokalisation führt es vergleichsweise früh im
Erkrankungsprozess zu einer biliären Gangobstruktion, wodurch eine schnellere Diagnosestellung erleichtert und eine bessere Prognose bedingt werden. Adenome der Ampulla hepatopancreatica und
der Papilla duodeni major stellen Vorläuferläsionen des Ampullenkarzinoms dar und besitzen ein 30–40%iges Risiko zur malignen Transformation. Diese Entartungstendenz begründet die
Notwendigkeit zur vollständigen/kompletten Abtragung im Rahmen der endoskopischen Therapie. Der Erfolg der endoskopischen Papillektomie wird durch eine Ausdehnung des Befundes in den
Pankreashauptgang oder Ductus choledochus erschwert. Endoskopisch nicht sanierbare Adenome und Ampullenkarzinome stellen Indikationen für chirurgische Therapieverfahren dar. Grundsätzlich
sollte für benigne Befunde die transduodenale Papillenresektion bervorzugt werden, für maligne Befunde stellt die Pankreaskopfresektion mit systematischer Lymphadenektomie und
Level-II-Dissektion des Mesopankreas die onkologisch korrekte Operation dar. Prognostische Faktoren beim Ampullenkarzinom sind: der pankreatobiliäre Subtyp, eine Lymphknoteninfiltration und
eine Perineuralscheideninvasion. Die Differenzierung in histopathologische Subtypen gewinnt zunehmend in der Indikationsstellung zur Systemtherapie an Bedeutung. Der Einsatz der
neoadjuvanten und adjuvanten Therapie für das Ampullenkarzinom konnte bisher nicht klar definiert werden. Jedoch scheinen Patienten mit dem pankreatobiliären Subtyp oder anderen
prognoselimitierenden Faktoren von einer adjuvanten Therapie zu profitieren. Zukünftige Studien werden zur zielgerichteten Therapiefestlegung benötigt.
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Affiliation(s)
- Esther Giehl-Brown
- Klinik und Poliklinik für Viszeral-, Thorax- u. Gefäßchirurgie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Deutschland
| | - Jürgen Weitz
- Klinik und Poliklinik für Viszeral-, Thorax- u. Gefäßchirurgie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Deutschland
| | - Marius Distler
- Klinik und Poliklinik für Viszeral-, Thorax- u. Gefäßchirurgie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Deutschland
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16
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Fernandez-Placencia RM, Montenegro P, Guerrero M, Serrano M, Ortega E, Bravo M, Huanca L, Bertani S, Trejo JM, Webb P, Malca-Vasquez J, Taxa L, Lachos-Davila A, Celis-Zapata J, Luque-Vasquez C, Payet E, Ruiz E, Berrospi F. Survival after curative pancreaticoduodenectomy for ampullary adenocarcinoma in a South American population: A retrospective cohort study. World J Gastrointest Surg 2022; 14:24-35. [PMID: 35126860 PMCID: PMC8790327 DOI: 10.4240/wjgs.v14.i1.24] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 09/28/2021] [Accepted: 01/13/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Ampullary adenocarcinoma (AAC) is a rare neoplasm that accounts for only 0.2% of all gastrointestinal cancers. Its incidence rate is lower than 6 cases per million people. Different prognostic factors have been described for AAC and are associated with a wide range of survival rates. However, these studies have been exclusively conducted in patients originating from Asian, European, and North American countries. AIM To evaluate the histopathologic predictors of overall survival (OS) in South American patients with AAC treated with curative pancreaticoduodenectomy (PD). METHODS We analyzed retrospective data from 83 AAC patients who underwent curative (R0) PD at the National Cancer Institute of Peru between January 2010 and October 2020 to identify histopathologic predictors of OS. RESULTS Sixty-nine percent of patients had developed intestinal-type AAC (69%), 23% had pancreatobiliary-type AAC, and 8% had other subtypes. Forty-one percent of patients were classified as Stage I, according to the AJCC 8th Edition. Recurrence occurred primarily in the liver (n = 8), peritoneum (n = 4), and lung (n = 4). Statistical analyses indicated that T3 tumour stage [hazard ratio (HR) of 6.4, 95% confidence interval (CI) of 2.5-16.3, P < 0.001], lymph node metastasis (HR: 4.5, 95%CI: 1.8-11.3, P = 0.001), and pancreatobiliary type (HR: 2.7, 95%CI: 1.2-6.2, P = 0.025) were independent predictors of OS. CONCLUSION Extended tumour stage (T3), pancreatobiliary type, and positive lymph node metastasis represent independent predictors of a lower OS rate in South American AAC patients who underwent curative PD.
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Affiliation(s)
| | - Paola Montenegro
- Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Melvy Guerrero
- Department of Pathology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Mariana Serrano
- Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Emperatriz Ortega
- Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Mercedes Bravo
- Department of Pathology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Lourdes Huanca
- Department of Pathology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Stéphane Bertani
- International Joint Laboratory of Molecular Anthopological Oncology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
- Unite Pharmacochim & Pharmacol Dev, UMR152, F-31062 Toulouse, France
| | - Juan Manuel Trejo
- Department of Radiation Oncology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Patricia Webb
- Department of Pathology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Jenny Malca-Vasquez
- Department of Radiation Oncology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Luis Taxa
- Department of Pathology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Alberto Lachos-Davila
- Department of Radiation Oncology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Juan Celis-Zapata
- Hepato-Pancreato-Biliary Section, Department of Abdominal Surgery, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Carlos Luque-Vasquez
- Department of Abdominal Surgery, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Eduardo Payet
- Department of Abdominal Surgery, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Eloy Ruiz
- Hepato-Pancreato-Biliary Section, Department of Abdominal Surgery, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
| | - Francisco Berrospi
- Hepato-Pancreato-Biliary Section, Department of Abdominal Surgery, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru
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17
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Sun H, Liu Y, Lv L, Li J, Liao X, Gong W. Prognostic Factors and Clinical Characteristics of Duodenal Adenocarcinoma With Survival: A Retrospective Study. Front Oncol 2022; 11:795891. [PMID: 34976838 PMCID: PMC8715708 DOI: 10.3389/fonc.2021.795891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 11/16/2021] [Indexed: 12/03/2022] Open
Abstract
Background To evaluate the clinical risk factors that influence the overall survival in patients with duodenal adenocarcinoma (DA) after tumor resection. Methods This study retrospectively analyzed 188 patients who underwent tumor resection for DA between January 2005 and June 2020 at Xiangyang Central Hospital. Results The median survival of the patients who underwent resectional operation was 54 months, longer than of those who underwent palliative surgery (20.8 months) (2,916.17; 95% CI, 916.3−9,280.5; p < 0.001). Survival of non-ampullary duodenal carcinoma patients (50.3 months; 95% CI, 39.7−61.8) was similar to that of ampullary duodenal carcinoma patients (59.3 months; 95% CI, 38.6−66.7) but was significantly better than that of papillary adenocarcinoma patients (38.9 months; 95% CI, 29.8−54.8; p = 0.386). Those with intestinal-type ductal adenocarcinomas had a longer median overall survival than those with the gastric type (61.8 vs. 46.7 months; p < 0.01) or pancreatic type (32.2 months; p < 0.001). Clinical DA samples had significantly diverse expressions of ATG12, IRS2, and IGF2. Higher expressions of the ATG12 and IRS2 proteins were significantly correlated with worse survival. Multivariate Cox regression analysis revealed that lymph node metastasis (hazard ratio (HR), 6.44; 95% CI, 3.68−11.27; p < 0.0001), margin status (HR, 4.94; 95% CI, 2.85−8.54; p < 0.0001), and high expression of ATG12 (HR, 1.89; 95% CI, 1.17−3.06; p = 0.0099) were independent prognostic factors negatively associated with survival in patients undergoing curative resection. There was no survival difference between the groups with ampullary, non-ampullary, and papillary adenocarcinomas treated with adjuvant chemotherapy (p = 0.973). Conclusion Gastric/pancreatic type, high expression of ATG12, lymph node metastases, and margin status were negative prognosticators of survival in patients with DAs than in those with tumor anatomical location. Curative resection is the best treatment option for appropriate patients.
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Affiliation(s)
- Huapeng Sun
- Department of General Surgery, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
| | - Yi Liu
- Department of Medicinal Chemistry, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Long Lv
- Department of General Surgery, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
| | - Jingwen Li
- Department of Oncology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
| | - Xiaofeng Liao
- Department of General Surgery, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
| | - Wei Gong
- Department of Oncology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
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18
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Ampullary Carcinoma: An Overview of a Rare Entity and Discussion of Current and Future Therapeutic Challenges. Curr Oncol 2021; 28:3393-3402. [PMID: 34590592 PMCID: PMC8482111 DOI: 10.3390/curroncol28050293] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 08/27/2021] [Accepted: 08/30/2021] [Indexed: 12/29/2022] Open
Abstract
Ampullary carcinomas (ACs) represent a rare entity, accounting for approximately 0.2% of all gastrointestinal solid tumors and 20% of all periampullary cancers (PACs). Unfortunately, few data are available regarding the optimal therapeutic strategy for ACs due to their rarity, and physicians frequently encounter significant difficulties in the management of these malignancies. In this review, we will provide an overview of current evidence on AC, especially focusing on biological features, histological characteristics, and available data guiding present and future therapeutic strategies for these rare, and still barely known, tumors.
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19
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Mishra SK, Kumari N, Krishnani N, Singh RK, Mohindra S. Identification and prevalence of potentially therapeutic targetable variants of major cancer driver genes in ampullary cancer patients in India through deep sequencing. Cancer Genet 2021; 258-259:41-48. [PMID: 34455261 DOI: 10.1016/j.cancergen.2021.08.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 07/19/2021] [Accepted: 08/13/2021] [Indexed: 12/26/2022]
Abstract
Ampulla is a complex region located at the confluence of pancreatic and common bile duct and intestinal epithelium. Tumors arising in this region are anatomically and morphologically heterogenous, however they show unique as well as overlapping molecular features. Cancers of both these anatomic sites share morphological as well as genetic profile despite having few unique differences. Targeted therapies are currently emerging as one of the demanding approaches for treatment in most cancer types especially for malignant epithelial tumors and therefore genetic profiling of cancers is the key for identification of potentially therapeutic targetable mutations to know their prevalence and prognostic impact. We studied 97 resected cases of formalin fixed paraffin-embedded AC by deep targeted sequencing using Ampliseq cancer hotspot panel comprising of 50 oncogenes and tumor suppressor genes. Potentially therapeutic targetable mutations were observed in 58/83 (70%) cases. Fourteen patients did not show any pathogenic mutation. TP53 (48.1%), KRAS (37.3%), APC (25.3%), SMAD4 (22.8%), MET (16.8%), CTNNB1 (15.6%) and PIK3CA (10.8%) were the major mutated potential therapeutic targets. KRAS mutation (43.2 Vs. 32.6%) was more prevalent in pancreatobiliary subtype, while TP53 (58.6 Vs 35.1), APC (36.9 Vs 10.8), SMAD4 (28.2 Vs 16.2), MET (21.7 Vs 10.8) and CTNNB1 (19.5 Vs 10.8) were more prevalent in intestinal subtype. WNT signaling pathway was the major altered pathway in intestinal subtype. These mutated genes and pathways may be targeted with currently available drugs and may be explored for future development of targetable agents to improve the disease course in patients of AC.
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Affiliation(s)
- Shravan Kumar Mishra
- Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP, India
| | - Niraj Kumari
- Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Raebareli, UP, India.
| | - Narendra Krishnani
- Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP, India
| | - Rajneesh Kumar Singh
- Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP, India
| | - Samir Mohindra
- Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP, India
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20
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Vanoli A, Grillo F, Furlan D, Arpa G, Grami O, Guerini C, Riboni R, Mastracci L, Di Sabatino A. Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations. Int J Mol Sci 2021; 22:ijms22094388. [PMID: 33922305 PMCID: PMC8122855 DOI: 10.3390/ijms22094388] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 04/18/2021] [Accepted: 04/20/2021] [Indexed: 12/15/2022] Open
Abstract
The wider use of gastrointestinal endoscopic procedures has led to an increased detection of small intestinal preneoplastic and neoplastic epithelial lesions, most of which are identified in the duodenum and ampullary region. Like their malignant counterparts, small intestinal glandular precursor lesions, which include adenomas and hamartomas, may arise sporadically or be associated with hereditary tumor syndromes, such as familial adenomatous polyposis, MUTYH-associated polyposis, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and Cowden syndrome. In addition, dysplastic, preinvasive lesions have been observed adjacent to small bowel adenocarcinomas complicating immune-related disorders, such as celiac or Crohn’s disease. Adenomatous lesions may exhibit an intestinal-type, gastric-type, or, very rarely, serrated differentiation, related to different molecular pathogenetic mechanisms. Finally, in the background of multiple endocrine neoplasia 1 syndrome, precursor neuroendocrine growths have been described. In this review we offer a comprehensive description on the histo-molecular features of the main histotypes of small bowel epithelial precursors lesions, including: (i) sporadic adenomas (intestinal-type and gastric-type; non-ampullary and ampullary); (ii) syndromic adenomas; (iii) small bowel dysplasia in celiac and Crohn’s disease; (iv) serrated lesions; (v) hamartomatous lesions; and (vi) neuroendocrine precursor lesions.
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Affiliation(s)
- Alessandro Vanoli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy; (G.A.); (O.G.); (C.G.); (R.R.)
- Correspondence: ; Tel.: +39-0382503612
| | - Federica Grillo
- Pathology Unit, Department of Surgical and Diagnostic Sciences, University of Genoa and Ospedale Policlinico San Martino University Hospital, 16132 Genoa, Liguria, Italy; (F.G.); (L.M.)
| | - Daniela Furlan
- Pathology Unit, Department of Medicine and Surgery, University of Insubria, 21100 Varese, Lombardy, Italy;
| | - Giovanni Arpa
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy; (G.A.); (O.G.); (C.G.); (R.R.)
| | - Oneda Grami
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy; (G.A.); (O.G.); (C.G.); (R.R.)
| | - Camilla Guerini
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy; (G.A.); (O.G.); (C.G.); (R.R.)
| | - Roberta Riboni
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy; (G.A.); (O.G.); (C.G.); (R.R.)
| | - Luca Mastracci
- Pathology Unit, Department of Surgical and Diagnostic Sciences, University of Genoa and Ospedale Policlinico San Martino University Hospital, 16132 Genoa, Liguria, Italy; (F.G.); (L.M.)
| | - Antonio Di Sabatino
- Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, 27100 Pavia, Lombardy, Italy;
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21
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Chuang PJ, Wang HP, Lin YJ, Chen CC, Tien YW, Hsieh MS, Yang SH, Yen RF, Ko CL, Wu YW, Cheng MF. Preoperative 2-[ 18F]FDG PET-CT aids in the prognostic stratification for patients with primary ampullary carcinoma. Eur Radiol 2021; 31:8040-8049. [PMID: 33864503 DOI: 10.1007/s00330-021-07923-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 03/01/2021] [Accepted: 03/22/2021] [Indexed: 11/24/2022]
Abstract
OBJECTIVES We sought to investigate whether preoperative dual-phase 2-[18F]FDG PET-CT identify predictors for poor survival in patients with ampullary carcinoma receiving pancreaticoduodenectomy. METHODS The preoperative PET-CT images of patients with resected ampullary carcinoma from June 2007 to July 2017 were analyzed. Survival curves were analyzed using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard model was used to identify potential prognostic factors associated with disease-free survival (DFS) and overall survival (OS). RESULTS Fifty-four subjects (26 men, 28 women) were enrolled with a median tumor size of 20 mm. All patients were followed for a median period of 36.9 months with 3- and 5-year DFS of 50.3% and 44.2%, and OS of 77.0% and 68.2%, respectively. Parameters associated with DFS in multivariate analysis were lymphovascular invasion (hazard ratio [HR]: 9.45, p < 0.001), involved margin in pathology (HR: 7.67, p < 0.001), and tumor retention index (RI) from the dual-phase PET (HR: 2.41, p = 0.03), whereas involved margin (HR: 13.14, p < 0.001), post-recurrence chemotherapy (HR: 0.10, p < 0.001), and metabolic tumor volume (MTV) (HR: 4.62, p = 0.009) emerged as independent prognostic factors for OS. CONCLUSIONS Preoperative 2-[18F]FDG PET-CT offered independent prognostic biomarkers in patients with ampullary carcinoma receiving standard surgical resection. KEY POINTS • 2-[18F]FDG PET-CT offers good survival prediction before operation in primary malignant neoplasms at ampulla of Vater. • Dual-phase PET scan with bowel distention can better delineate Ampulla of Vater and characterize tumor physiology. • Preoperative risk stratification might aid in better treatment planning.
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Affiliation(s)
- Pei-Ju Chuang
- Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No.7, Chung-Shan South Road, Chung-Cheng District, Taipei, 100, Taiwan, Republic of China
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yu-Jen Lin
- Institute of Environmental and Occupational Health Sciences, National Taiwan University, Taipei, Taiwan
| | - Chieh-Chang Chen
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yu-Wen Tien
- Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Min-Shu Hsieh
- Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shih-Hung Yang
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ruoh-Fang Yen
- Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No.7, Chung-Shan South Road, Chung-Cheng District, Taipei, 100, Taiwan, Republic of China
| | - Chi-Lun Ko
- Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No.7, Chung-Shan South Road, Chung-Cheng District, Taipei, 100, Taiwan, Republic of China
| | - Yen-Wen Wu
- National Yang-Ming University School of Medicine, Taipei, Taiwan.,Department of Nuclear Medicine and Cardiovascular Medical Centre (Cardiology), Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Mei-Fang Cheng
- Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No.7, Chung-Shan South Road, Chung-Cheng District, Taipei, 100, Taiwan, Republic of China. .,Institute of Environmental and Occupational Health Sciences, National Taiwan University, Taipei, Taiwan.
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22
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Ampullary carcinoma of the duodenum: current clinical issues and genomic overview. Surg Today 2021; 52:189-197. [PMID: 33797636 DOI: 10.1007/s00595-021-02270-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 01/17/2021] [Indexed: 02/07/2023]
Abstract
Ampullary carcinomas of the duodenum are uncommon. Moreover, the diversity in the clinical outcomes of these patients makes it difficult to interpret previous studies and clinical trial results. The difficulty in proper staging of ampullary carcinomas, especially with regard to the T category of the tumor in the TNM system, reflects the anatomic complexity and non-uniform histopathologic subtypes. One major reason for this difficulty in interpretation is that the tumors may arise from any of the three epithelia (duodenal, biliary, or pancreatic) that converge at this location. Generally, ampullary carcinomas are classified into intestinal and pancreaticobiliary types based on morphology and immunohistochemical features. While many studies have described their specific characteristics and clinical impact, the prognostic value of these subtypes is controversial. In recent years, whole-exome sequencing analyses have advanced our understanding of the genomic overview of ampullary carcinoma. Gene mutations serve as prognostic and predictive biomarkers for this disease. Therefore, basic knowledge of the genomic profile of ampullary carcinomas is required for surgeons to understand how best to apply precision medicine as well as surgery and adjuvant therapies. This review provides an overview of the current basic and clinical issues of ampullary carcinoma.
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23
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García P, Lamarca A, Díaz J, Carrera E, Roa JC. Current and New Biomarkers for Early Detection, Prognostic Stratification, and Management of Gallbladder Cancer Patients. Cancers (Basel) 2020; 12:E3670. [PMID: 33297469 PMCID: PMC7762341 DOI: 10.3390/cancers12123670] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 11/06/2020] [Accepted: 11/11/2020] [Indexed: 01/17/2023] Open
Abstract
Gallbladder cancer (GBC) is an aggressive disease that shows evident geographic variation and is characterized by a poor prognosis, mainly due to the late diagnosis and ineffective treatment. Genetic variants associated with GBC susceptibility, including polymorphisms within the toll-like receptors TLR2 and TLR4, the cytochrome P450 1A1 (CYP1A1), and the ATP-binding cassette (ABC) transporter ABCG8 genes, represent promising biomarkers for the stratification of patients at higher risk of GBC; thus, showing potential to prioritize cholecystectomy, particularly considering that early diagnosis is difficult due to the absence of specific signs and symptoms. Similarly, our better understanding of the gallbladder carcinogenic processes has led to identify several cellular and molecular events that may influence patient management, including HER2 aberrations, high tumor mutational burden, microsatellite instability, among others. Despite these reports on interesting and promising markers for risk assessment, diagnosis, and prognosis; there is an unmet need for reliable and validated biomarkers that can improve the management of GBC patients and support clinical decision-making. This review article examines the most potentially significant biomarkers of susceptibility, diagnosis, prognosis, and therapy selection for GBC patients, highlighting the need to find and validate existing and new molecular biomarkers to improve patient outcomes.
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Affiliation(s)
- Patricia García
- Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile;
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK;
| | - Javier Díaz
- Departamento del Aparato Digestivo, Hospital Nacional Edgardo Rebagliati Martins-Essalud, School of Medicine, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru;
| | - Enrique Carrera
- Department of Gastroenterology, Hospital Especialidades Eugenio Espejo, Universidad San Francisco de Quito, Quito 170136, Ecuador;
| | - Juan Carlos Roa
- Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile;
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24
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Increased expression of secreted frizzled related protein 1 (SFRP1) predicts ampullary adenocarcinoma recurrence. Sci Rep 2020; 10:13255. [PMID: 32764696 PMCID: PMC7413269 DOI: 10.1038/s41598-020-69899-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 07/20/2020] [Indexed: 12/20/2022] Open
Abstract
Ampullary adenocarcinoma is a rare gastrointestinal cancer in which WNT signalling dysregulation has been previously reported. Secreted frizzled related protein 1 (SFRP1) is one of the extracellular ligands of WNT signalling. We performed bioinformatics analyses of SFRP1 expression in human cancer. Microarray analysis of SFRP1 in periampullary adenocarcinoma was obtained from the Gene Expression Omnibus GSE39409 dataset. SFRP1 expression in ampullary adenocarcinoma was detected by immunohistochemistry staining and correlated with patients’ clinical outcomes. Our results showed that SFRP1 expression had different clinical applications in all types of human cancer. No detected alteration of SFPR1 gene and SFRP1 expression in ampullary adenocarcinoma was lower than that in other periampullary adenocarcinomas. However, high expression levels of SFRP1 protein were correlated with cancer recurrence, peritoneal carcinomatosis and poor patient prognosis. Gene set enrichment analysis showed downregulation of multiple WNT-related genes in primary culture cells from ampullary adenocarcinoma, but SFRP1 expression was increased. We found an interaction between WNT, bone morphogenetic protein and hedgehog signalling with SFRP1. Furthermore, a high expression of SFRP1 predicted poor prognosis for ampullary adenocarcinoma patients. Because it is a multifunctional protein, SFRP1 targeting serves as a potential therapy for ampullary adenocarcinoma patients.
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25
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Abstract
The ampulla of Vater gives rise to a versatile group of cancers of mixed/hybrid histologic phenotype. Ampullary carcinomas (ACs) are most frequently intestinal or pancreatobiliary adenocarcinomas but other subtypes, such as medullary, mucinous, or signet ring/poorly cohesive cell carcinoma, may be encountered. Ampullary cancer can also be subclassified based on immunohistochemical features, however these classification systems fail to show robust prognostic reliability. More recently, the molecular landscape of AC has been uncovered, and has been shown to have prognostic and predictive significance. In this article, the site-specific, histologic, and genetic characteristics of ampullary carcinoma and its precursor lesions are discussed.
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Affiliation(s)
- Yue Xue
- Department of Pathology and Laboratory Medicine, Northwestern University, 251 East Huron Street, Room 7332, Chicago, IL 60611, USA
| | - Michelle D Reid
- Department of Pathology and Laboratory Medicine, Emory University Hospital, 1364 Clifton Road Northeast, Room H 180A, Atlanta, GA 30322, USA.
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26
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Vicentini C, Calore F, Nigita G, Fadda P, Simbolo M, Sperandio N, Luchini C, Lawlor RT, Croce CM, Corbo V, Fassan M, Scarpa A. Exosomal miRNA signatures of pancreatic lesions. BMC Gastroenterol 2020; 20:137. [PMID: 32375666 PMCID: PMC7204029 DOI: 10.1186/s12876-020-01287-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 04/29/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Pancreatic and peri-pancreatic neoplasms encompass a variety of histotypes characterized by a heterogeneous prognostic impact. miRNAs are considered efficient candidate biomarkers due to their high stability in tissues and body fluids. We applied Nanostring profiling of circulating exosomal miRNAs to distinct pancreatic lesions in order to establish a source for biomarker development. METHODS A series of 140 plasma samples obtained from patients affected by pancreatic ductal adenocarcinoma (PDAC, n = 58), pancreatic neuroendocrine tumors (PanNET, n = 42), intraductal papillary mucinous neoplasms (IPMN, n = 20), and ampulla of Vater carcinomas (AVC, n = 20) were analyzed. Comprehensive miRNA profiling was performed on plasma-derived exosomes. Relevant miRNAs were validated by qRT-PCR and in situ hybridization (ISH). RESULTS Lesion specific miRNAs were identified through multiple disease comparisons. Selected miRNAs were validated in the plasma by qRT-PCR and at tissue level by ISH. We leveraged the presence of clinical subtypes with each disease cohort to identify miRNAs that are differentially enriched in aggressive phenotypes. CONCLUSIONS This study shows that pancreatic lesions are characterized by specific exosomal-miRNA signatures. We also provide the basis for further explorations in order to better understand the relevance of these signatures in pancreatic neoplasms.
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Affiliation(s)
| | - Federica Calore
- Department of Cancer Biology and Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USA
| | - Giovanni Nigita
- Department of Cancer Biology and Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USA
| | - Paolo Fadda
- Department of Cancer Biology and Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USA
| | - Michele Simbolo
- Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, Verona, Italy
| | | | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Rita T Lawlor
- ARC-NET Research Centre, University of Verona, Verona, Italy
| | - Carlo Maria Croce
- Department of Cancer Biology and Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USA
| | - Vincenzo Corbo
- ARC-NET Research Centre, University of Verona, Verona, Italy
- Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Matteo Fassan
- ARC-NET Research Centre, University of Verona, Verona, Italy.
- Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Via Aristide Gabelli 61, 35121, Padua, PD, Italy.
| | - Aldo Scarpa
- ARC-NET Research Centre, University of Verona, Verona, Italy
- Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, Verona, Italy
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27
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Regalla DKR, Jacob R, Manne A, Paluri RK. Therapeutic options for ampullary carcinomas. A review. Oncol Rev 2019; 13:440. [PMID: 31565197 PMCID: PMC6747019 DOI: 10.4081/oncol.2019.440] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 08/28/2019] [Indexed: 02/08/2023] Open
Abstract
Ampullary Carcinoma arises from a histologically heterogeneous region where three different epithelia converge. Even though Ampullary Carcinoma has a superior prognosis compared to pancreatic and biliary ductal neoplasms, at least half of the patients turn up at an advanced stage that limits the treatment prospects. In addition to surgery for early-stage disease, several studies have shown that chemoradiotherapy confers additional benefits in the management of Ampullary Carcinoma. Analogously, chemotherapy plays a crucial role in treating advanced Ampullary Carcinoma with distant metastasis/recurrences. Although, stage of the disease, lymph node status, and histo-morphology are three critical prognostic variables, recently much attention is being placed on the genetic landscape of Ampullary Carcinoma. In this review, we have discussed various studies describing the role of chemoradiation and chemotherapy in the treatment of early and advanced stage Ampullary Carcinoma. Also, we have summarized the molecular landscape of Ampullary Carcinoma and the novel therapeutic strategies which could possibly target the genetic alterations involving the tumor cells.
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Affiliation(s)
| | - Rojymon Jacob
- Radiation Oncology, University of Alabama at Birmingham Hospital, Birmingham, AL
| | - Ashish Manne
- Medical Oncology, University of South Alabama Hospital, Mobile, AL
| | - Ravi Kumar Paluri
- Hematology-Oncology, University of Alabama at Birmingham Hospital, Birmingham, AL, USA
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28
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Ferchichi M, Jouini R, Koubaa W, Khanchel F, Helal I, Hadad D, Bibani N, Chadli-Debbiche A, BenBrahim E. Ampullary and pancreatic adenocarcinoma-a comparative study. J Gastrointest Oncol 2019; 10:270-275. [PMID: 31032094 DOI: 10.21037/jgo.2018.09.09] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Background Pancreatic ductal adenocarcinoma (PDAC) and ampullary adenocarcinoma (AAC) are 2 gastrointestinal cancers that share overlapping symptoms. Although some studies have proposed the hypothesis of differences in pathogenesis and prognosis in these 2 cancers; they remain treated similarly. The classification of AAC into three subtypes [pancreatobiliary (PB), intestinal (IT) and mixed (M)] is especially crucial for the 3 axes of patients management (diagnosis, prognosis and therapy). Some studies suggest that PB subtype pathogenesis is comparable to PDAC. The objective of this study was to conduct a comparative analysis between PDAC and AAC; notably PB subtype; via mutational status analysis of 3 oncogenes (KRAS, NRAS and BRAF) hoping to consolidate AAC biology understanding. Methods Nine hot spot mutation sites of KRAS, NRAS and BRAF were analysed using pyrosequencing in 39 PDAC and 21 AAC from Tunisian patients. Comparative study was performed using SPSS software. Results Mutations in oncogenes were detected in almost 43% of AAC, especially in PB (47%) and 95% of PDAC. KRAS was the most mutated oncogene. There were statistical significant differences between PDAC and AAC in tumor differentiation (P<0.001), perineural invasion (P<0.001), vascular emboli (P=0.001), T stage (P=0.007), N stage (P=0.001) and mutational status (P<0.001). When comparing PDAC and PB subtype, there were also significant differences in tumor size (P=0.001), tumor differentiation (P<0.001), perineural invasion (P<0.001), vascular emboli (P=0.001), T stage (P=0.033), N stage (P<0.001) and mutational status (P<0.001). Conclusions AAC even PB subtype is different from PDAC. We think that these different tumor types require highly individualized therapy guided by their histomolecular characteristics and that we should stop diagnosing and treating them as a unique entity.
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Affiliation(s)
- Marwa Ferchichi
- University of Sciences, Farhat Hached Campus, Tunis El Manar, Tunis, Tunisia.,Pathology Department, Habib Thameur Hospital, University of Medicine, Tunis, Tunisia
| | - Raja Jouini
- Pathology Department, Habib Thameur Hospital, University of Medicine, Tunis, Tunisia
| | - Wafa Koubaa
- Pathology Department, Habib Thameur Hospital, University of Medicine, Tunis, Tunisia
| | - Fatma Khanchel
- Pathology Department, Habib Thameur Hospital, University of Medicine, Tunis, Tunisia
| | - Imen Helal
- Pathology Department, Habib Thameur Hospital, University of Medicine, Tunis, Tunisia
| | - Dhafer Hadad
- Surgery Department, Habib Thameur Hospital, Tunis, Tunisia
| | - Norsaf Bibani
- Gastroenterology Department, Habib Thameur Hospital, Tunis, Tunisia
| | | | - Ehsen BenBrahim
- Pathology Department, Habib Thameur Hospital, University of Medicine, Tunis, Tunisia
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29
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Tariq NUA, McNamara MG, Valle JW. Biliary tract cancers: current knowledge, clinical candidates and future challenges. Cancer Manag Res 2019; 11:2623-2642. [PMID: 31015767 PMCID: PMC6446989 DOI: 10.2147/cmar.s157092] [Citation(s) in RCA: 75] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Biliary tract cancers (BTCs) are rare with poor prognosis. Due to the advent of genomic sequencing, new data have emerged regarding the molecular makeup of this disease. To add to the complexity, various subtypes also harbor a varied genetic composition. The commonly mutated genes associated with this cancer are KRAS, EGFR, IDH, FGFR and BAP1. Various clinical studies are looking at targeting these genetic mutations. Another therapeutic area of note is the potential for the use of immunotherapy in patients with BTC. Although BTC may be a result of chronic inflammation, this does not necessarily translate into increased immunogenicity. This literature review discusses the diverse molecular and immune-related pathways in patients with BTC and their potential therapeutic implications.
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Affiliation(s)
- Noor-Ul-Ain Tariq
- Faculty of Biomedicine and Health Sciences, Division of Cancer Sciences, University of Manchester, Manchester M13 9NT, UK,
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK,
| | - Mairéad G McNamara
- Faculty of Biomedicine and Health Sciences, Division of Cancer Sciences, University of Manchester, Manchester M13 9NT, UK,
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK,
| | - Juan W Valle
- Faculty of Biomedicine and Health Sciences, Division of Cancer Sciences, University of Manchester, Manchester M13 9NT, UK,
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK,
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30
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Perkins G, Svrcek M, Bouchet-Doumenq C, Voron T, Colussi O, Debove C, Merabtene F, Dumont S, Sauvanet A, Hammel P, Cros J, André T, Bachet JB, Bardier A, Douard R, Meatchi T, Peschaud F, Emile JF, Cojean-Zelek I, Laurent-Puig P, Taieb J. Can we classify ampullary tumours better? Clinical, pathological and molecular features. Results of an AGEO study. Br J Cancer 2019; 120:697-702. [PMID: 30837681 PMCID: PMC6462032 DOI: 10.1038/s41416-019-0415-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 02/05/2019] [Accepted: 02/13/2019] [Indexed: 12/11/2022] Open
Abstract
Background Ampullary adenocarcinoma (AA) originates from either intestinal (INT) or pancreaticobiliary (PB) epithelium. Different prognostic factors of recurrence have been identified in previous studies. Methods In 91 AA patients of the AGEO retrospective multicentre cohort, we evaluated the centrally reviewed morphological classification, panel markers of Ang et al. including CK7, CK20, MUC1, MUC2 and CDX2, the 50-gene panel mutational analysis, and the clinicopathological AGEO prognostic score. Results Forty-three (47%) of the 91 tumours were Ang-INT, 29 (32%) were Ang-PB, 18 (20%) were ambiguous (Ang-AMB) and one could not be classified. Among these 90 tumours, 68.7% of INT tumours were Ang-INT and 78.2% of PB tumours were Ang-PB. MUC5AC expression was detected in 32.5% of the 86 evaluable cases. Among 71 tumours, KRAS, TP53, APC and PIK3CA were the most frequently mutated genes. The KRAS mutation was significantly more frequent in the PB subtype. In multivariate analysis, only AGEO prognostic score and tumour subtype were associated with relapse-free survival. Only AGEO prognostic score was associated with overall survival. Conclusions Mutational analysis and MUC5AC expression provide no additional value in the prognostic evaluation of AA patients. Ang et al. classification and the AGEO prognostic score were confirmed as a strong prognosticator for disease recurrence.
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Affiliation(s)
- Geraldine Perkins
- Sorbonne Paris - Cité, Paris Descartes University, Department of Gastroenterology and GI Oncology, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.,Centre de Recherche UMR-S 1147, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique, Institut National de la Santé et de la Recherche Médicale, Paris, France
| | - Magali Svrcek
- Sorbonne-Université, Department of Pathology, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.,INSERM, UMR S 938, Sorbonne-Université, Université Pierre et Marie Curie - Paris 6, Paris, France
| | - Cecile Bouchet-Doumenq
- Centre de Recherche UMR-S 1147, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique, Institut National de la Santé et de la Recherche Médicale, Paris, France.,Department of Gastrointestinal Surgery, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Thibault Voron
- Department of Gastrointestinal Surgery, Saint Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Orianne Colussi
- Sorbonne Paris - Cité, Paris Descartes University, Department of Gastroenterology and GI Oncology, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Clotilde Debove
- Department of Gastrointestinal Surgery, Saint Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Fatiha Merabtene
- INSERM, UMR S 938, Sorbonne-Université, Université Pierre et Marie Curie - Paris 6, Paris, France
| | - Sylvie Dumont
- INSERM, UMR S 938, Sorbonne-Université, Université Pierre et Marie Curie - Paris 6, Paris, France
| | - Alain Sauvanet
- Department of Digestive Surgery, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Pascal Hammel
- Department of Digestive Oncology, Beaujon University Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France.,Centre de Recherche sur l'Inflammation (CRI), INSERM UMR 1149, University of Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Jerome Cros
- Centre de Recherche sur l'Inflammation (CRI), INSERM UMR 1149, University of Paris Diderot, Sorbonne Paris Cité, Paris, France.,Department of Pathology, Beaujon University Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France
| | - Thierry André
- Sorbonne-Université, and department of Medical Oncology, Saint Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Jean-Baptiste Bachet
- Centre de Recherche UMR-S 1147, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique, Institut National de la Santé et de la Recherche Médicale, Paris, France.,Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Armelle Bardier
- Surgical Pathology Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Richard Douard
- Paris Descartes University, Department of Digestive Surgery, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Tchao Meatchi
- Paris Descartes University, Department of Pathology, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Frederique Peschaud
- Department of Surgery and Oncology, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt, France
| | - Jean-Francois Emile
- Department of Pathology, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt, France.,EA4340, Biomarqueurs en Cancérologie et Onco-Hématologie, UVSQ, Paris-Saclay University, Boulogne-Billancourt, France
| | | | - Pierre Laurent-Puig
- Centre de Recherche UMR-S 1147, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique, Institut National de la Santé et de la Recherche Médicale, Paris, France
| | - Julien Taieb
- Sorbonne Paris - Cité, Paris Descartes University, Department of Gastroenterology and GI Oncology, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
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Bowitz Lothe IM, Kleive D, Pomianowska E, Cvancarova M, Kure E, Dueland S, Gladhaug IP, Labori KJ. Clinical relevance of pancreatobiliary and intestinal subtypes of ampullary and duodenal adenocarcinoma: Pattern of recurrence, chemotherapy, and survival after pancreatoduodenectomy. Pancreatology 2019; 19:316-324. [PMID: 30713128 DOI: 10.1016/j.pan.2019.01.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Revised: 11/07/2018] [Accepted: 01/24/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND The clinical relevance of the classification of ampullary adenocarcinoma (AC) into pancreatobiliary (PB) or intestinal (Int) subtypes has not been resolved. METHODS Clinicopathological factors, survival, and localization and treatment of recurrence were investigated for patients with AC and duodenal adenocarcinoma (DC) treated by pancreatoduodenectomy from 2000 to 2015. RESULTS A total of 109 AC (45 PB, 64 Int) and 71 DC (all Int) were identified. Median overall survival (OS) for ACPB vs DC vs ACInt was 43.6 vs 51 vs 75 months, respectively. ACPB had significantly shorter OS than ACInt (p = 0.036). However, for AC stage (HR = 2.39; 95 %CI 1.23-4.64, p = 0.010) was the only factor associated with mortality risk in multivariate analysis. Localization of recurrence (n = 88) was predominantly distant (ACPB 81.5%; ACInt 92%; DC 91.7%, p = 0.371). Post-recurrence survival (PRS) for ACPB, ACInt and DC did not differ (6.9 vs 9.2 vs 7.5 months, p = 0.755). Best supportive care or palliative chemotherapy were offered for recurrent disease to 44.5%/48.1% for ACPB, 40%/56% for ACInt, and 41.7%/52.8% for DC (p = 0.947). The choice of chemotherapy regimen varied considerably. Five patients underwent surgical resection or ablation with curative intent. All deaths among ACPB were caused by recurrent disease, whereas 29.4% of ACInt and 23.1% of DC deaths was non-cancer related or caused by other specific cancer. CONCLUSION ACPB, ACInt and DC have similar recurrence patterns and PRS. The difference in survival between ACPB and ACInt was not statistically significant when stratified by stage. The optimal chemotherapy in patients with recurrent AC remains undefined.
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Affiliation(s)
- Inger Marie Bowitz Lothe
- Department of Pathology, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Dyre Kleive
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Norway
| | - Ewa Pomianowska
- Department of Surgery, Baerum Hospital, Vestre Viken Hospital Trust, Norway
| | - Milada Cvancarova
- Faculty of Health Sciences, Department of Nursing and Health Promotion, Oslo Metropolitan University, Oslo, Norway
| | - Elin Kure
- Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
| | - Svein Dueland
- Department of Oncology, Oslo University Hospital, Norway
| | - Ivar P Gladhaug
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Norway
| | - Knut Jørgen Labori
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Norway.
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Abstract
OBJECTIVE Ampulla of Vater carcinoma (AVC) has a broad spectrum of different prognoses. As such, new moderators of survival are urgently needed. We aimed at clarifying the prognostic role of perineural invasion in AVC. METHODS Using PubMed and SCOPUS databases, we conducted the first systematic review and meta-analysis on this topic. RESULTS Analyzing 29 articles for a total of 2379 patients, we found that the presence of perineural invasion increased the risk of all-cause mortality more than 2 times (relative risk [RR], 2.07; 95% confidence interval [CI], 1.78-2.42 [P < 0.0001]; hazard ratio [HR], 2.72; 95% CI, 1.86-3.97 [P < 0.0001]), of cancer-specific mortality more than 6 times (RR, 6.12; 95% CI, 3.25-11.54 [P < 0.0001]; HR, 6.59; 95% CI, 2.29-3.49 [P < 0.0001]), and of recurrence more than 2 times (RR, 2.63; 95% CI, 1.89-3.67 [P < 0.0001]; HR, 2.54; 95% CI, 1.24-5.21 [P = 0.01]). CONCLUSIONS Perineural invasion is strongly associated with a poorer prognosis in AVC, influencing both survival and risk of recurrence. It should be reported in the final pathology report and should be taken into account by future oncologic staging systems, identifying a group of AVC with a more malignant biological behavior.
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Ferchichi M, Jouini R, Ayari I, Koubaa W, Chadli-Debbiche A, BenBrahim E. KRAS, NRAS and BRAF analysis of ampullary adenocarcinoma classified using CK7, CK20, MUC1 and MUC2. J Gastrointest Oncol 2018; 9:820-827. [PMID: 30505580 DOI: 10.21037/jgo.2018.05.03] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background Ampullary carcinomas are rare and dominated by adenocarcinomas. They account for only 0.5% of all gastrointestinal malignancies. Ampullary adenocarcinoma (AAC) with pancreaticobiliary (PB) histology has a worse outcome than that with intestinal (IT) histology. The mixed subtype contains the two epitheliums. This subclassification remains a challenge for pathologists and induces a reasonable level of disagreement. Genetic features of these subtypes are unclear. In this study, we aimed to reclassify AAC cases then to evaluate differences in prognostic, pathological and molecular parameters including mutational status of three oncogenes between these subtypes. Methods AACs from 21 Tunisian patients were used in this study. Reclassification was made based on histology and immunohistochemistry (IHC) using CK7, CK20, MUC1 and MUC2. Mutational analysis included the pyrosequencing of KRAS, NRAS and BRAF. Results Fifteen cases were PB subtype, 2 cases were IT subtype and 4 cases were mixed subtype. CK20 and MUC2 were associated with N stage, MUC1 and histomolecular subtype with T stage. Nine cases were mutated and 12 were wild-type. Eight cases were KRAS mutated (5 G12D and 3 G12V). Only 1 case was NRAS mutated (G12D). No BRAF mutation was found. Genetic alterations didn't influence prognostic factors. Conclusions We validate the prognostic utility of AAC histomolecular classification.
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Affiliation(s)
- Marwa Ferchichi
- University of Sciences, Farhat Hached Campus, Tunis El Manar, Tunis, Tunisia.,Pathology Department, Habib Thameur Hospital, Tunis, Tunisia
| | - Raja Jouini
- Pathology Department, Habib Thameur Hospital, Tunis, Tunisia
| | - Imen Ayari
- University of Sciences, Farhat Hached Campus, Tunis El Manar, Tunis, Tunisia.,Pathology Department, Habib Thameur Hospital, Tunis, Tunisia
| | - Wafa Koubaa
- Pathology Department, Habib Thameur Hospital, Tunis, Tunisia
| | | | - Ehsen BenBrahim
- Pathology Department, Habib Thameur Hospital, Tunis, Tunisia
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Pea A, Riva G, Bernasconi R, Sereni E, Lawlor RT, Scarpa A, Luchini C. Ampulla of Vater carcinoma: Molecular landscape and clinical implications. World J Gastrointest Oncol 2018; 10:370-380. [PMID: 30487949 PMCID: PMC6247104 DOI: 10.4251/wjgo.v10.i11.370] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 08/08/2018] [Accepted: 10/08/2018] [Indexed: 02/05/2023] Open
Abstract
Ampulla of Vater is a peculiar anatomical structure, characterized by the crossroad of three distinct epithelia: Intestinal, ductal pancreatic and biliary. Adenocarcinomas arising in this area represent an opportunity to understand the comparative biology of all periampullary malignancies. These neoplasms can exhibit intestinal, pancreaticobiliary or mixed features, whereas the subclassification based on morphology and immunohistochemical features failed in demonstrating a robust prognostic reliability. In the last few years, the molecular landscape of this tumor entity has been uncovered, identifying alterations that may serve as prognostic and predictive biomarkers. In this review, the histological and genetic characteristics of ampullary carcinomas are discussed, taking into account the main clinical and therapeutic implications related to this tumor type as well.
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Affiliation(s)
- Antonio Pea
- Department of Surgery, University and Hospital Trust of Verona, Verona 37134, Italy
| | - Giulio Riva
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona 37134, Italy
| | - Riccardo Bernasconi
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona 37134, Italy
| | - Elisabetta Sereni
- Department of Surgery, University and Hospital Trust of Verona, Verona 37134, Italy
| | - Rita Teresa Lawlor
- ARC-Net Research Center, University and Hospital Trust of Verona, Verona 37134, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona 37134, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona 37134, Italy
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Kaavya J, Mahalaxmi I, Devi SM, Santhy KS, Balachandar V. Targeting phosphoinositide-3-kinase pathway in biliary tract cancers: A remedial route? J Cell Physiol 2018; 234:8259-8273. [PMID: 30370571 DOI: 10.1002/jcp.27673] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 10/04/2018] [Indexed: 01/17/2023]
Abstract
Biliary tract cancers (BTC) are aggressive tumours with a low survival rate. At the advent of the genomic era, various genetic mutations in cell signalling pathways have been incriminated in carcinogenesis. Genomic analysis studies have connected main components of the phosphoinositide-3-kinase (PI3K) signalling pathway to BTC. PI3K pathway playing a central role in cell signalling and being deregulated in various tumours has been studied as a target for chemotherapy. Novel compounds have also been identified in preclinical trials that specifically target the PI3K pathway in BTCs, but these studies have not accelerated to clinical use. These novel compounds can be examined in upcoming studies to validate them as potential therapeutic agents, as further research is required to combat the growing need for adjuvant chemotherapy to successfully battle this tumour type. Furthermore, these molecules could also be used along with gemcitabine, cisplatin and 5-fluorouracil to improve sensitivity of the tumour tissue to chemotherapy. This review focuses on the basics of PI3K signalling, genetic alterations of this pathway in BTCs and current advancement in targeting this pathway in BTCs. It emphasizes the need for gene-based drug screening in BTC. It may reveal various novel targets and drugs for amelioration of survival in patients with BTC and serve as a stepping stone for further research.
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Affiliation(s)
- Jayaramayya Kaavya
- Department of Zoology, Avinashilingam Institute for Home Science and Higher Education for Women, Avinashilingam University for Women, Coimbatore, India
| | - Iyer Mahalaxmi
- Department of Zoology, Avinashilingam Institute for Home Science and Higher Education for Women, Avinashilingam University for Women, Coimbatore, India
| | | | - K S Santhy
- Department of Zoology, Avinashilingam Institute for Home Science and Higher Education for Women, Avinashilingam University for Women, Coimbatore, India
| | - Vellingiri Balachandar
- Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, India
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Saraggi D, Galuppini F, Fanelli GN, Remo A, Urso ED, Bao RQ, Bacchin D, Guzzardo V, Luchini C, Braconi C, Farinati F, Rugge M, Fassan M. MiR-21 up-regulation in ampullary adenocarcinoma and its pre-invasive lesions. Pathol Res Pract 2018; 214:835-839. [PMID: 29731265 DOI: 10.1016/j.prp.2018.04.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 04/27/2018] [Accepted: 04/27/2018] [Indexed: 02/07/2023]
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