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Mastrangelo S, Attinà G, Rindi G, Romano A, Maurizi P, Ruggiero A. Characteristics and Management of Children with Appendiceal Neuroendocrine Neoplasms: A Single-Center Study. Cancers (Basel) 2024; 16:3440. [PMID: 39456535 PMCID: PMC11506114 DOI: 10.3390/cancers16203440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 10/07/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND/OBJECTIVES Appendiceal neuroendocrine neoplasms (ANENs) are usually found incidentally during histology examination after appendectomy for appendicitis. Due to their rarity in pediatric populations, there is no consensus on treatment or follow-up. The analysis of patients with ANENs of our and other studies will increase the understanding of this tumor. METHODS Pediatric patients with ANENs were uniformly managed at our center between 1998 and 2023. Patients' presenting symptoms, surgery, tumor histology, post-surgical work-up, follow-up and outcome were analyzed. RESULTS Our report describes 17 patients with a diagnosis of ANEN after appendectomy. The median age was 14 years (range of 4-17 years). Tumors were located at the tip of the appendix in 58.8% of cases and only one had a diameter >1 cm. All were well-differentiated tumors with free resection margins. The submucosa was invaded in five cases, muscularis propria in eight and subserosa in four. Post-appendectomy work-up included tumor marker measurement, abdominal ultrasound and computed tomography or magnetic resonance imaging, chest X-ray and octreotide scintigraphy. No residual tumors or metastases were detected. Additional surgery was not necessary. Follow-up was carried out for a median duration of 6 years (range of 1-10 years). Only one patient was lost to follow-up and all other patients are alive without tumor recurrence. CONCLUSIONS The tumor characteristics of our patients confirmed data from the literature. With the lack of a sufficient number of large prospective trials, it is important to add more information to confirm the benign nature and excellent outcome of this tumor, even without additional surgery. Consensus guidelines are needed for ANENs in pediatric populations.
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Affiliation(s)
- Stefano Mastrangelo
- Pediatric Oncology Unit, Department of Woman and Child Health Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy; (G.A.); (A.R.); (P.M.); (A.R.)
- Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
| | - Giorgio Attinà
- Pediatric Oncology Unit, Department of Woman and Child Health Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy; (G.A.); (A.R.); (P.M.); (A.R.)
| | - Guido Rindi
- Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
- Anatomic Pathology Unit, Department of Woman and Child Health Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy
| | - Alberto Romano
- Pediatric Oncology Unit, Department of Woman and Child Health Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy; (G.A.); (A.R.); (P.M.); (A.R.)
| | - Palma Maurizi
- Pediatric Oncology Unit, Department of Woman and Child Health Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy; (G.A.); (A.R.); (P.M.); (A.R.)
- Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
| | - Antonio Ruggiero
- Pediatric Oncology Unit, Department of Woman and Child Health Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy; (G.A.); (A.R.); (P.M.); (A.R.)
- Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
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Ji JN, Yin ZB. Visualizing the landscape of appendiceal tumor research after 2010: A bibliometric study. World J Gastrointest Surg 2024; 16:1894-1909. [PMID: 38983319 PMCID: PMC11230007 DOI: 10.4240/wjgs.v16.i6.1894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 05/03/2024] [Accepted: 05/17/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Despite the rarity of appendiceal tumors, research in this field has intensified, resulting in a growing number of studies and published papers. Surprisingly, no comprehensive bibliometric analysis has specifically addressed appendiceal tumors. AIM To offer a thorough analysis of the current landscape and future trends in appendiceal tumor research. METHODS In our bibliometric analysis studies, we explored the Web of Science Core Collection database. The bibliographic details of the chosen publications were automatically converted and analyzed using the bibliometric package in the R environment. Additionally, we employed VoSviewer to create cooperation network maps for countries, institutions, and authors, as well as clustering maps for keywords. Furthermore, CiteSpace, another software tool, was utilized to build dual-map overlays of journals and analyze references with citation bursts. RESULTS Our study included 780 English-language articles published after 2010. The number of related publications and citations has increased in the past decade. The United States leads in this area, but there is a need to improve cooperation and communication among countries and institutions. Co-occurrence analysis also revealed close collaboration among different authors. Annals of Surgical Oncology was the most influential journal in this field. Analysis of references with high co-citations and references with citation bursts, consistent with analysis of keywords and hotspots, indicated that current research primarily centers on the classification and management of appendiceal mucinous neoplasms and consequent pseudomyxoma peritonei. Despite the abundance of clinical studies, a greater number of in-depth basic research studies should be conducted. CONCLUSION Current research on appendiceal tumors focuses on classification and management of appendiceal mucinous neoplasms and pseudomyxoma peritonei. Enhanced collaboration and basic research are vital for further advancement.
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Affiliation(s)
- Jia-Nan Ji
- Department of General Surgery, The Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, Wuxi 214187, Jiangsu Province, China
| | - Zhi-Bin Yin
- Department of General Surgery, The Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, Wuxi 214187, Jiangsu Province, China
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Nagesh VK, Aguilar IK, Elias D, Mansour C, Tran HHV, Bhuju R, Sethi T, Sanjeeva PRP, Rivas MG, Martinez E, Auda A, Ahmed N, Philip S, Weissman S, Sotiriadis J, Bangolo A. Factors Affecting Survival Outcomes in Neuroendocrine Tumor of the Appendix over the Past Two Decades. Diseases 2024; 12:96. [PMID: 38785751 PMCID: PMC11120129 DOI: 10.3390/diseases12050096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 05/01/2024] [Accepted: 05/06/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND Appendiceal neuroendocrine tumors (NETs) rank as the third most frequent neoplasm affecting the appendix, originating from enterochromaffin cells. This study aims to evaluate the influence of various prognostic factors on the mortality rates of patients diagnosed with NETs of the appendix. METHODS Conducted retrospectively, the study involved 3346 patients, utilizing data sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis centered on investigating demographic characteristics, clinical features, overall mortality (OM), and cancer-specific mortality (CSM) among the cohort. Variables showing a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox regression analysis. A Hazard Ratio (HR) > 1 indicated an unfavorable prognosis. RESULTS In the multivariate analysis, higher OM and CSM were observed in males, older age groups, tumors with distant metastasis, poorly differentiated tumors, and those who underwent chemotherapy. Non-Hispanic Black individuals showed elevated mortality rates. CONCLUSION Delayed diagnosis may contribute to the increased mortality in this community. Improved access to healthcare and treatment is crucial for addressing these disparities. Larger prospective studies are needed to pinpoint the underlying causes of elevated mortality in non-Hispanic Black populations, and randomized controlled trials (RCTs) are warranted to evaluate therapies for advanced-stage appendix NETs.
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Affiliation(s)
- Vignesh Krishnan Nagesh
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (I.K.A.); (D.E.); (H.H.-V.T.); (E.M.); (S.W.)
| | - Izage Kianifar Aguilar
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (I.K.A.); (D.E.); (H.H.-V.T.); (E.M.); (S.W.)
| | - Daniel Elias
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (I.K.A.); (D.E.); (H.H.-V.T.); (E.M.); (S.W.)
| | - Charlene Mansour
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (I.K.A.); (D.E.); (H.H.-V.T.); (E.M.); (S.W.)
| | - Hadrian Hoang-Vu Tran
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (I.K.A.); (D.E.); (H.H.-V.T.); (E.M.); (S.W.)
| | - Ruchi Bhuju
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (I.K.A.); (D.E.); (H.H.-V.T.); (E.M.); (S.W.)
| | - Tanni Sethi
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (I.K.A.); (D.E.); (H.H.-V.T.); (E.M.); (S.W.)
| | - Paranjyothy Rao Pirangi Sanjeeva
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (I.K.A.); (D.E.); (H.H.-V.T.); (E.M.); (S.W.)
| | - Marco Gonzalez Rivas
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (I.K.A.); (D.E.); (H.H.-V.T.); (E.M.); (S.W.)
| | - Emelyn Martinez
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (I.K.A.); (D.E.); (H.H.-V.T.); (E.M.); (S.W.)
| | - Auda Auda
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (I.K.A.); (D.E.); (H.H.-V.T.); (E.M.); (S.W.)
| | - Nazir Ahmed
- Department of Gastroenterology, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (N.A.); (S.P.); (J.S.)
| | - Shawn Philip
- Department of Gastroenterology, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (N.A.); (S.P.); (J.S.)
| | - Simcha Weissman
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (I.K.A.); (D.E.); (H.H.-V.T.); (E.M.); (S.W.)
| | - John Sotiriadis
- Department of Gastroenterology, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (N.A.); (S.P.); (J.S.)
| | - Ayrton Bangolo
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USA; (I.K.A.); (D.E.); (H.H.-V.T.); (E.M.); (S.W.)
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Fransvea P, Puccioni C, Altieri G, D'Agostino L, Costa G, Tropeano G, La Greca A, Brisinda G, Sganga G. Beyond acute appendicitis: a single-institution experience of unexpected pathology findings after 989 consecutive emergency appendectomy. Langenbecks Arch Surg 2024; 409:87. [PMID: 38441707 DOI: 10.1007/s00423-024-03277-0] [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: 12/05/2023] [Accepted: 02/27/2024] [Indexed: 03/07/2024]
Abstract
INTRODUCTION Appendiceal neoplasms (ANs) are rare, with an estimated incidence of around 1%: neuroendocrine tumours (NETs) and low-grade appendiceal mucinous neoplasms (LAMNs) comprise most cases. Most tumours are cured by appendectomy alone, although some require right hemicolectomy and intra-operative chemotherapy. The aim of the present study is to evaluate our institution's experience in terms of the prevalence of AN, their histological types, treatment and outcomes in adult patients undergoing emergency appendectomy. MATERIAL AND METHODS Single-centre retrospective cohort analysis of patients treated for acute appendicitis at a large academic medical centre. Patients with a diagnosis of acute appendicitis (AA) where further compared with patients with acute appendicitis and a histologically confirmed diagnosis of appendiceal neoplasm (AN). RESULTS A diagnosis of acute appendicitis was made in 1200 patients. Of these, 989 patients underwent emergency appendectomy. The overall incidence of appendiceal neoplasm was 9.3% (92 patients). AN rate increased with increasing age. Patients under the age of 30 had a 3.8% (14/367 patients) rate of occult neoplasm, whereas patients between 40 and 89 years and older had a 13.0% rate of neoplasm. No difference was found in clinical presentations and type of approach while we found a lower complicated appendicitis rate in the AN group. CONCLUSION ANs are less rare with respect to the literature; however, clinically, there are no specific signs of suspicious and simple appendicectomy appears to be curative in most cases. However, age plays an important role; older patients are at higher risk for AN. ANs still challenge the non-operative management concept introduced into the surgical literature.
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Affiliation(s)
- Pietro Fransvea
- Fondazione Policlinico Universitario A. Gemelli IRCCS Roma, Rome, Italy.
- Università Cattolica del Sacro Cuore Roma Italia, Rome, Italy.
| | - Caterina Puccioni
- Fondazione Policlinico Universitario A. Gemelli IRCCS Roma, Rome, Italy
- Università Cattolica del Sacro Cuore Roma Italia, Rome, Italy
| | - Gaia Altieri
- Fondazione Policlinico Universitario A. Gemelli IRCCS Roma, Rome, Italy
| | - Luca D'Agostino
- Fondazione Policlinico Universitario A. Gemelli IRCCS Roma, Rome, Italy
| | - Gianluca Costa
- Surgery Center, Colorectal Surgery Clinical and Research Unit - Fondazione Policlinico Universitario Campus Bio-Medico, University Campus Bio-Medico of Rome, Rome, Italy
| | - Giuseppe Tropeano
- Fondazione Policlinico Universitario A. Gemelli IRCCS Roma, Rome, Italy
| | - Antonio La Greca
- Fondazione Policlinico Universitario A. Gemelli IRCCS Roma, Rome, Italy
- Università Cattolica del Sacro Cuore Roma Italia, Rome, Italy
| | - Giuseppe Brisinda
- Fondazione Policlinico Universitario A. Gemelli IRCCS Roma, Rome, Italy
- Università Cattolica del Sacro Cuore Roma Italia, Rome, Italy
| | - Gabriele Sganga
- Fondazione Policlinico Universitario A. Gemelli IRCCS Roma, Rome, Italy
- Università Cattolica del Sacro Cuore Roma Italia, Rome, Italy
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Douglass MB, Carpenter SL, Campbell CH, Hoffman C, Hessey J. Benign or by Chance: A Case Report on Incidental Appendectomy Revealing a Neuroendocrine Tumor During Traumatic Exploratory Laparotomy. Cureus 2024; 16:e54527. [PMID: 38516428 PMCID: PMC10955438 DOI: 10.7759/cureus.54527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/20/2024] [Indexed: 03/23/2024] Open
Abstract
Incidental appendectomies (IAs) are often performed in laparotomies to prevent future complications caused by the buildup of scar tissue. Although neoplastic findings are rare, all appendectomy specimens should be sent for histopathological analysis. We present the case of a 38-year-old man found to have an appendiceal neuroendocrine tumor (NET) after receiving an IA secondary to a traumatic rectal perforation requiring exploratory laparotomy. Well-differentiated NETs isolated to the appendix have an excellent prognosis. Appendectomies are considered curative for NETs smaller than 2 cm that have not metastasized beyond the appendix. Appendiceal NETs are capable of secreting vasoactive substances and, therefore, causing carcinoid syndrome. However, the progression to carcinoid syndrome generally coincides with metastasis to the liver, indicating a poor prognosis. While histopathological analysis of appendectomy specimens rarely yields atypical findings, this analysis is crucial to ensure that the proper treatment is selected based on tumor progression in an appendectomy specimen staining positive for somatotropin and chromogranin.
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Affiliation(s)
- Megan B Douglass
- Surgery, University of South Carolina School of Medicine, Columbia, USA
| | | | - Cayla H Campbell
- Surgery, University of South Carolina School of Medicine, Columbia, USA
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Ahmed FA, Wu VS, Kakish H, Elshami M, Ocuin LM, Rothermel LD, Mohamed A, Hoehn RS. Surgical management of 1- to 2-cm neuroendocrine tumors of the appendix: Appendectomy or right hemicolectomy? Surgery 2024; 175:251-257. [PMID: 37981548 DOI: 10.1016/j.surg.2023.09.048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 08/09/2023] [Accepted: 09/26/2023] [Indexed: 11/21/2023]
Abstract
BACKGROUND The surgical management of 1- to 2-cm neuroendocrine tumors of the appendix is an area of debate. We analyzed the clinical outcomes of appendectomy and compared them to right hemicolectomy. METHODS We queried the National Cancer Database to identify patients treated for 1- to 2-cm ANETs from 2004 to 2018. Patients were stratified by surgical approach (appendectomy vs. hemicolectomy). Multivariable models were used to identify factors associated with the choice of surgical approach and the association between surgical approach and overall survival. RESULTS Of the 3,189 patients we included, 1,573 (49.3%) underwent right hemicolectomy and 1,616 (50.7%) appendectomy. The appendectomy rate increased from 37.7% in 2004 to 58.9% in 2018. On multivariable analysis, patients with grade 2 and 3 tumors were less likely to undergo appendectomy alone (odds ratio = 0.41, 95% confidence interval = 0.26-0.66). Longer travel distance was associated with a higher likelihood of undergoing appendectomy (odds ratio = 2.52, 95% confidence interval = 1.15-5.51). After adjusting for tumor grade, appendectomy alone had similar survival to hemicolectomy (hazard ratio = 1.03, 95% confidence interval = 0.67-1.59). CONCLUSION In this updated analysis of the National Cancer Database, right hemicolectomy was not associated with improved overall survival compared to appendectomy alone for 1- to 2-cm neuroendocrine tumors of the appendix. Although patients with grade 2 or 3 tumors are more likely to undergo right hemicolectomy, this procedure may not improve their treatment or overall outcome.
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Affiliation(s)
- Fasih Ali Ahmed
- Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Victoria S Wu
- Case Western Reserve University School of Medicine, Cleveland, OH
| | - Hanna Kakish
- Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Mohamedraed Elshami
- Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Lee M Ocuin
- Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Luke D Rothermel
- Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Amr Mohamed
- Division of Hematology and Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Richard S Hoehn
- Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH.
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7
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Flood MP, Roberts G, Mitchell C, Ramsay R, Michael M, Heriot AG, Kong JC. Impact of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal adenocarcinoma. Asia Pac J Clin Oncol 2023. [PMID: 36880398 DOI: 10.1111/ajco.13949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 02/07/2023] [Accepted: 02/14/2023] [Indexed: 03/08/2023]
Abstract
AIM Peritoneal dissemination of infiltrative appendiceal tumors is a rare and poorly understood phenomenon. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognized treatment option for selected patients. Neoadjuvant systemic chemotherapy (NAC) has been shown to be associated with improved overall survival (OS) in colorectal peritoneal metastases but little is known of the impact of this from an appendiceal adenocarcinoma perspective. METHOD A prospective database of 294 patients with advanced appendiceal primary tumors undergoing CRS ± HIPEC between June 2009 and December 2020 was reviewed. Baseline characteristics and long-term outcomes were compared between patients with adenocarcinoma who received neoadjuvant chemotherapy or upfront surgery. RESULTS Eighty-six (29%) patients were histologically diagnosed with an appendiceal cancer. These included intestinal-type adenocarcinoma (11.6%), mucinous adenocarcinoma (43%), and goblet cell adenocarcinoma (GCA) or signet ring cell adenocarcinoma (SRCA) (45.4%). Twenty-five (29%) of these underwent NAC, of which eight (32%) exhibited some degree of radiological response. There was no statistical difference in OS at 3 years between the NAC and upfront surgery groups (47.3% vs. 75.8%, p = 0.372). Appendiceal histology subtypes, particularly GCA and SRCA (p = 0.039) and peritoneal carcinomatosis index >10 (p = 0.009), were factors independently associated with worse OS. CONCLUSION Administration of NAC did not appear to prolong OS in the operative management of disseminated appendiceal adenocarcinomas. GCA and SRCA subtypes display a more aggressive biological phenotype.
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Affiliation(s)
- Michael P Flood
- Division of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - Georgia Roberts
- Division of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Catherine Mitchell
- Department of Anatomical Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Robert Ramsay
- Division of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - Michael Michael
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.,Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Alexander G Heriot
- Division of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - Joseph C Kong
- Division of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
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Management and outcome of high-risk neuroendocrine tumors of the appendix in children; A systematic review. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:329-338. [PMID: 36372617 DOI: 10.1016/j.ejso.2022.10.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 10/12/2022] [Accepted: 10/31/2022] [Indexed: 11/11/2022]
Abstract
This study systematically reviewed the literature to investigate the value of secondary surgery for children with a high-risk neuroendocrine tumor (NET) of appendix. A systematic search was performed in PubMed, Embase and Web of Science. All randomized controlled trials, cohort studies, and case series reporting on the management and outcomes of patients (<20 years) with a histopathologically proven NET of the appendix were eligible for inclusion. Two authors independently selected eligible articles, assessed risk of bias, and extracted data. The outcomes of patients with a high-risk NET treated with secondary surgery were compared to those treated without secondary surgery. Primary outcomes were recurrence rate and disease-free survival. The literature search yielded 667 articles, of which 29 were included. These studies reported on 1112 patients, of whom 145 (13%) had high-risk NET. Heterogeneity between studies was large and risk of bias was serious in 26 and moderate in three studies. Secondary surgery after primary appendectomy was performed in 64 of 145 patients (44%). Length of follow-up ranged between 0 and 612 months. In both treatment groups no recurrences were reported, and thus disease-free survival was 100%. Based on current literature, the value of secondary surgery for pediatric high-risk NET of the appendix may be questioned. However, evidence is scarce, of low-quality, and heterogeneity between studies is large. Large international studies with adequate follow-up are needed to generate high-quality evidence on this topic.
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Mohamed A, Wu S, Hamid M, Mahipal A, Cjakrabarti S, Bajor D, Selfridge JE, Asa SL. Management of Appendix Neuroendocrine Neoplasms: Insights on the Current Guidelines. Cancers (Basel) 2022; 15:295. [PMID: 36612291 PMCID: PMC9818268 DOI: 10.3390/cancers15010295] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/19/2022] [Accepted: 12/26/2022] [Indexed: 01/03/2023] Open
Abstract
Appendiceal neuroendocrine neoplasms (ANENs) usually present as incidental findings at the time of appendectomy for acute appendicitis. They are rare, accounting for only 0.5-1% of intestinal neoplasms; they are found in 0.3-0.9% of all appendectomy specimens. They are usually sporadic tumors. There are several histological types including well-differentiated neuroendocrine tumors (NETs), poorly differentiated neuroendocrine carcinomas (NECs), and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). Histologic differentiation and the grade of well-differentiated NETs correlate with clinical behavior and prognosis. Management varies based on differentiation, aggressiveness, and metastatic potential. There is debate about the optimal surgical management for localized appendiceal NETs that are impacted by many factors including the tumor size, the extent of mesoappendiceal spread, lymphovascular invasion and perineural involvement. In addition, the data to guide therapy in metastatic disease are limited due to the paucity of these tumors. Here, we review the current advances in the management of ANENs within the context of a multidisciplinary approach to these tumors.
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Affiliation(s)
- Amr Mohamed
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Sulin Wu
- Department of Internal Medicine, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
- Department of Medical Genetics, Center for Human Genetics, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Mohamed Hamid
- Department of Stem Cell Biology and Regenerative Medicine, City of Hope Beckman Research Institute, Duarte, CA 91010, USA
| | - Amit Mahipal
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Sakti Cjakrabarti
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - David Bajor
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - J. Eva Selfridge
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Sylvia L. Asa
- Department of Pathology, UH Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA
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Cho YM, Abidoye O, Wang J, Bhushan S, Miyara SJ, Guevara S, Molmenti EP, LoCicero RJ, Ilyas JA. A rare case of advance goblet cell carcinoma and a narrative review. CURRENT PROBLEMS IN CANCER: CASE REPORTS 2022. [DOI: 10.1016/j.cpccr.2022.100181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022] Open
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Palmer K, Weerasuriya S, Chandrakumaran K, Rous B, White BE, Paisey S, Srirajaskanthan R, Ramage JK. Goblet Cell Adenocarcinoma of the Appendix: A Systematic Review and Incidence and Survival of 1,225 Cases From an English Cancer Registry. Front Oncol 2022; 12:915028. [PMID: 35903705 PMCID: PMC9314749 DOI: 10.3389/fonc.2022.915028] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 06/08/2022] [Indexed: 12/19/2022] Open
Abstract
BackgroundGoblet cell adenocarcinoma (GCA) of the appendix is a rare and aggressive tumour with varying nomenclature and classification systems. This has led to heterogeneity in published data, and there is a lack of consensus on incidence, survival, and management.MethodsWe provide an overview of GCA with a comprehensive systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and a retrospective analysis of all cases recorded in the English National Cancer Registration and Analysis Service database between 1995 and 2018. The Kaplan–Meier estimator was used to calculate overall survival, and Cox proportional hazards regression was used to identify prognostic factors.ResultsThe systematic review demonstrated an incidence of 0.05–0.3 per 100,000 per year among North American registry studies. The 1-, 3-, and 5-year survival rate was 95.5%, 85.9%–87.6%, and 76.0%–80.6%, respectively. Age, stage, and grade were identified as prognostic factors for survival. Our analysis included 1,225 cases. Age-standardised incidence was 0.0335 per year in 1995 and gradually rose to 0.158 per year in 2018. The 1-, 3-, and 5-year survival rate was 90.0% [95% confidence interval (95% CI): 85.4–94.0], 76.0% (95% CI: 73.8–80.9), and 68.6% (95% CI: 65.9–72.2), respectively. On univariate Cox regression analyses, female sex, stage, and grade were associated with worse overall survival. On multivariate analysis, only stage remained a statistically significant prognostic factor.ConclusionsGCA of the appendix is rare, but incidence is increasing. We report a lower incidence and survival than North American registry studies. Higher stage was associated with decreased survival. Further prospective studies are required to establish optimal management.
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Affiliation(s)
- Kieran Palmer
- Barts Cancer Centre, St Bartholomew’s Hospital, London, United Kingdom
- *Correspondence: Kieran Palmer,
| | - Scott Weerasuriya
- Department of Critical Care Medicine, King’s College Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom
| | - Kandiah Chandrakumaran
- Surgical Division, Hampshire Hospitals National Health Service (NHS) Foundation Trust, Basingstoke, United Kingdom
| | - Brian Rous
- National Health Service (NHS) Digital, Leeds, United Kingdom
| | - Benjamin E. White
- Surgical Division, Hampshire Hospitals National Health Service (NHS) Foundation Trust, Basingstoke, United Kingdom
| | - Sangeeta Paisey
- Surgical Division, Hampshire Hospitals National Health Service (NHS) Foundation Trust, Basingstoke, United Kingdom
| | - Rajaventhan Srirajaskanthan
- Department of Critical Care Medicine, King’s College Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom
- Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom
| | - John K. Ramage
- Surgical Division, Hampshire Hospitals National Health Service (NHS) Foundation Trust, Basingstoke, United Kingdom
- Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom
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Muñoz de Nova JL, Hernando J, Sampedro Núñez M, Vázquez Benítez GT, Triviño Ibáñez EM, del Olmo García MI, Barriuso J, Capdevila J, Martín-Pérez E. Management of incidentally discovered appendiceal neuroendocrine tumors after an appendicectomy. World J Gastroenterol 2022; 28:1304-1314. [PMID: 35645544 PMCID: PMC9099182 DOI: 10.3748/wjg.v28.i13.1304] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 02/09/2022] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
Appendiceal neuroendocrine tumors (aNETs) are an uncommon neoplasm that is relatively indolent in most cases. They are typically diagnosed in younger patients than other neuroendocrine tumors and are often an incidental finding after an appendectomy. Although there are numerous clinical practice guidelines on management of aNETs, there is continues to be a dearth of evidence on optimal treatment. Management of these tumors is stratified according to risk of locoregional and distant metastasis. However, there is a lack of consensus regarding tumors that measure 1-2 cm. In these cases, some histopathological features such as size, tumor grade, presence of lymphovascular invasion, or mesoappendix infiltration must also be considered. Computed tomography or magnetic resonance imaging scans are recommended for evaluating the presence of additional disease, except in the case of tumors smaller than 1 cm without additional risk factors. Somatostatin receptor scintigraphy or positron emission tomography with computed tomography should be considered in cases with suspected residual or distant disease. The main point of controversy is the indication for performing a completion right hemicolectomy after an initial appendectomy, based on the risk of lymph node metastases. The main factor considered is tumor size and 2 cm is the most common threshold for indicating a colectomy. Other factors such as mesoappendix infiltration, lymphovascular invasion, or tumor grade may also be considered. On the other hand, potential complications, and decreased quality of life after a hemicolectomy as well as the lack of evidence on benefits in terms of survival must be taken into consideration. In this review, we present data regarding the current indications, outcomes, and benefits of a colectomy.
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Affiliation(s)
- José Luis Muñoz de Nova
- Department of General and Digestive Surgery, Hospital Universitario de La Princesa, Madrid 28006, Spain
- Department of Surgery, Universidad Autónoma de Madrid, Madrid 28029, Spain
| | - Jorge Hernando
- Gastrointestinal and Endocrine Tumor Unit, Medical Oncology Department, Vall d´Hebron University Hospital, Vall d´Hebron Institute of Oncology, Barcelona 08035, Spain
| | - Miguel Sampedro Núñez
- Department of Endocrinology and Nutrition, Hospital Universitario de La Princesa, Madrid 28006, Spain
| | - Greissy Tibisay Vázquez Benítez
- Department of Pathology, Hospital Universitario Puerta de Hierro, Madrid 28222, Spain
- Department of Pathology, Universidad Autónoma de Madrid, Madrid 28029, Spain
| | | | | | - Jorge Barriuso
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Jaume Capdevila
- Gastrointestinal and Endocrine Tumor Unit, Medical Oncology Department, Vall d´Hebron University Hospital, Vall d´Hebron Institute of Oncology, Barcelona 08035, Spain
| | - Elena Martín-Pérez
- Department of General and Digestive Surgery, Hospital Universitario de La Princesa, Madrid 28006, Spain
- Department of Surgery, Universidad Autónoma de Madrid, Madrid 28029, Spain
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13
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The association between appendicitis severity and patient age with appendiceal neoplasm histology-a population-based study. Int J Colorectal Dis 2022; 37:1173-1180. [PMID: 35474547 PMCID: PMC9072484 DOI: 10.1007/s00384-022-04132-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/16/2022] [Indexed: 02/04/2023]
Abstract
PURPOSE Recent studies have reported alarming appendiceal tumor rates associated with complicated acute appendicitis, especially in patients presenting with a periappendicular abscess. However, the data on histology of appendiceal tumors among acute appendicitis patients is limited, especially in patient cohorts differentiating between uncomplicated and complicated acute appendicitis. We have previously reported the association of increased appendiceal tumor prevalence with complicated acute appendicitis in this population-based study. The objective of this secondary analysis was to evaluate the association of both appendicitis severity and patient age with appendiceal tumor histology. METHODS This nationwide population-based registry study (The Finnish Cancer Registry) was conducted from 2007 to 2013. All appendiceal tumors (n = 840) and available medical reports (n = 504) of these patients at eight study hospitals were previously evaluated, identifying altogether 250 patients with both acute appendicitis and appendiceal tumor. RESULTS The severity of acute appendicitis was significantly associated with more malignant tumor histology. The risk of adenocarcinoma or pseudomyxoma was significantly higher among patients with periappendicular abscess (OR 15.05, CI 95% 6.98-32.49, p < 0.001) and patients presenting with perforated acute appendicitis (OR 4.09, CI 95% 1.69-9.90, p = 0.0018) compared to patients with uncomplicated acute appendicitis. Similarly, patient age over 40 years was significantly associated with the risk of adenocarcinoma and pseudomyxoma (OR 26.46, Cl 95% 7.95-88.09, p < 0.001). Patient sex was not associated with a more malignant appendiceal tumor histology (p = 0.67). CONCLUSION More malignant appendiceal tumor histology of adenocarcinoma or pseudomyxoma was significantly associated with patient age over 40 years and complicated acute appendicitis, especially periappendicular abscess.
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14
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Kowalsky SJ, Nassour I, AlMasri S, Paniccia A, Zureikat AH, Choudry HA, Pingpank JF. Omission of Right Hemicolectomy May be Safe for Some Appendiceal Goblet Cell Adenocarcinomas: A Survival Analysis of the National Cancer Database. Ann Surg Oncol 2021; 28:8916-8925. [PMID: 34409541 DOI: 10.1245/s10434-021-10191-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 05/05/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND Appendiceal goblet cell adenocarcinomas (GCC) are rare tumors with clinical behavior between classic carcinoids and adenocarcinomas. Current guidelines recommend right hemicolectomy for all GCCs. PATIENTS AND METHODS The National Cancer Database was retrospectively queried for appendiceal GCCs undergoing appendectomy or right hemicolectomy between 2004 and 2016. Demographics, tumor characteristics, and post-operative outcomes were collected. The primary outcome was overall survival, which was examined by surgical type and tumor T stage. Multivariate logistic regression was utilized to identify predictors of survival. RESULTS In total, 1083 GCCs were included, and 81.8% underwent right hemicolectomy. Mean age was 57 years, and 89% were White. Patients undergoing hemicolectomy had higher T-stage tumors (66.6%/14.4% T3/T4 vs. 55.8%/8.1%, p < 0.001). Lymph node positivity increased with T stage (1.1%, 2.1%, 9.9%, and 29.1% for T1-T4). GCCs undergoing colectomy were more frequently moderately or poorly differentiated (16.7%/9.0% vs. 12.2%/6.6%, p = 0.011). Appendectomy surgical margins were positive in 17.3% (3.4% hemicolectomy, p < 0.001). In T3/T4 tumors, a significant survival benefit at 5 years was observed in patients undergoing colectomy as compared with appendectomy (85.4% vs. 82.0%, p = 0.028). On multivariate analysis, lymph node positivity markedly decreased survival overall for the entire cohort (HR 7.58, p < 0.001) and for T3/T4 tumors (HR 7.63, p < 0.001). In patients with T3/T4 tumors, there was a trend towards improved survival with right hemicolectomy (HR 0.42, p = 0.068). CONCLUSION Omitting right hemicolectomy can be considered for select T1/T2 appendiceal GCCs with negative appendectomy margins, given low rates of lymph node metastases and lack of survival benefit with right hemicolectomy.
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Affiliation(s)
- Stacy J Kowalsky
- Division of Surgical Oncology, Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Ibrahim Nassour
- Division of Surgical Oncology, Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Samer AlMasri
- Division of Surgical Oncology, Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Alessandro Paniccia
- Division of Surgical Oncology, Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Amer H Zureikat
- Division of Surgical Oncology, Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Haroon A Choudry
- Division of Surgical Oncology, Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - James F Pingpank
- Division of Surgical Oncology, Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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15
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Day RW, Chang YH, Stucky CC, Gray R, Pockaj B, Wasif N. A Predictive Model for Nodal Metastases in Patients With Appendiceal Cancers. Ann Surg 2021; 274:155-161. [PMID: 31361626 DOI: 10.1097/sla.0000000000003501] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Histologic subtypes of appendiceal cancer vary in their propensity for metastases to regional lymph nodes (LN). A predictive model would help direct subsequent surgical therapy. METHODS The National Cancer Database was queried for patients with appendiceal cancer undergoing surgery between 1998 and 2012. Multivariable logistic regression was used to develop a predictive model of LN metastases which was internally validated using Brier score and Area under the Curve (AUC). RESULTS A total of 21,647 patients were identified, of whom 9079 (41.9%) had node negative disease, 4575 (21.1%) node positive disease, and 7993 (36.9%) unknown LN status. The strongest predictors of LN positivity were histology (carcinoid tumors OR 12.78, 95% CI 9.01-18.12), increasing T Stage (T3 OR 3.36, 95% CI 2.52-4.50, T4 OR 6.30, 95% CI 4.71-8.42), and tumor grade (G3 OR 5.55, 95% CI 4.78-6.45, G4 OR 5.98, 95% CI 4.30-8.31). The coefficients from the regression analysis were used to construct a calculator that generated predicted probabilities of LN metastases given certain inputs. Internal validation of the overall model showed an AUC of 0.75 (95% CI 0.74-0.76) and Brier score of 0.188. Histology-specific predictive models were also constructed with an AUC that varied from 0.669 for signet cell to 0.75 for goblet cell tumors. CONCLUSIONS The risk for nodal metastases in patients with appendiceal cancers can be quantified with reasonable accuracy using a predictive model incorporating patient age, sex, tumor histology, T-stage, and grade. This can help inform clinical decision making regarding the need for a right hemicolectomy following appendectomy.
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Affiliation(s)
- Ryan W Day
- Division of Surgical Oncology, Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ
| | - Yu-Hui Chang
- Surgical Outcomes Program, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic Arizona, Phoenix, AZ
- Department of Statistics, Mayo Clinic Arizona, Phoenix, AZ
| | - Chee-Chee Stucky
- Division of Surgical Oncology, Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ
| | - Richard Gray
- Division of Surgical Oncology, Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ
| | - Barbara Pockaj
- Division of Surgical Oncology, Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ
| | - Nabil Wasif
- Division of Surgical Oncology, Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ
- Surgical Outcomes Program, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic Arizona, Phoenix, AZ
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16
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Peltrini R, Cantoni V, Green R, Lionetti R, D'Ambra M, Bartolini C, De Luca M, Bracale U, Cuocolo A, Corcione F. Risk of appendiceal neoplasm after interval appendectomy for complicated appendicitis: A systematic review and meta-analysis. Surgeon 2021; 19:e549-e558. [PMID: 33640282 DOI: 10.1016/j.surge.2021.01.010] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 07/31/2020] [Accepted: 01/12/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Non-operative management is often the treatment of choice in cases of complicated appendicitis and routine interval appendectomy is not usually recommended. Actually, recent studies show an alarming number of appendiceal neoplasms following interval appendectomy. The aim of this study is to evaluate the prevalence of appendiceal neoplasms and their histological types after interval appendectomy for complicated appendicitis in adults. METHODS A comprehensive literature search of the PubMed, Scopus and Web of Science databases was conducted according to the PRISMA statement. Studies reporting appendiceal neoplasm rates after interval appendectomy and histopathological characteristics were included. The most recent World Health Organization (WHO) classification of malignant tumours was considered. A pooled prevalence analysis for both prevalence and pathology was performed. RESULTS A total of eight studies was included: seven retrospective series and one randomized controlled trial. The pooled prevalence of neoplasms after interval appendectomy was 11% (95% CI 7-15; I2 = 37.5%, p = 0.13). Appendiceal mucinous neoplasms occurred in 43% (95% CI 19-68), adenocarcinoma in 29% (95% CI 6-51), appendiceal neuroendocrine neoplasm in 21% (95% CI 6-36), globet cell carcinoma in 13% (95% CI -2-28), adenoma or serrated lesions in 20% (95% CI -0-41) of cases. CONCLUSION The risk of appendiceal neoplasm in patients treated with interval appendectomy for complicated appendicitis is 11%; mucinous neoplasm is the most common histopathological type. Further studies should investigate this association in order to clarify the biological pathway and clinical implications.
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Affiliation(s)
- Roberto Peltrini
- Department of Public Health, University of Naples Federico II, Naples, Italy.
| | - Valeria Cantoni
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy.
| | - Roberta Green
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy.
| | - Ruggero Lionetti
- Department of Public Health, University of Naples Federico II, Naples, Italy.
| | - Michele D'Ambra
- Department of Public Health, University of Naples Federico II, Naples, Italy.
| | - Carolina Bartolini
- Department of Public Health, University of Naples Federico II, Naples, Italy.
| | - Marcello De Luca
- Department of Public Health, University of Naples Federico II, Naples, Italy.
| | - Umberto Bracale
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy.
| | - Alberto Cuocolo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy.
| | - Francesco Corcione
- Department of Public Health, University of Naples Federico II, Naples, Italy.
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17
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Aydogan S, Kaya T, Surmelioglu A, Demirli S. Appendix Tumors. COLON POLYPS AND COLORECTAL CANCER 2021:285-306. [DOI: 10.1007/978-3-030-57273-0_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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18
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Keutgen XM, Vaghaiwalla TM. Surgical Evaluation of Appendiceal Neuroendocrine Tumors. NEUROENDOCRINE TUMORS 2021:191-206. [DOI: 10.1007/978-3-030-62241-1_12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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19
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Zakka K, Williamson S, Jiang R, Reid MD, Alese OB, Shaib WL, Wu C, Behera M, El-Rayes BF, Akce M. Is adjuvant chemotherapy beneficial for stage II-III goblet cell carcinoid/goblet cell adenocarcinoma of the appendix? Surg Oncol 2020; 36:120-129. [PMID: 33360118 DOI: 10.1016/j.suronc.2020.12.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 11/06/2020] [Accepted: 12/06/2020] [Indexed: 01/21/2023]
Abstract
BACKGROUND Goblet cell carcinoma (GCC), formerly known as goblet cell carcinoid, of the appendix constitutes less than 14% of all primary appendiceal neoplasms. Surgical resection is the main treatment and the role of adjuvant chemotherapy (AC) is not established. This study aims to evaluate the impact of AC in stage II-III appendiceal GCC. METHODS Patients with pathological stage II and III GCC who underwent surgical resection between 2006 and 2015 were identified from the National Cancer Database (NCDB) using ICD-O-3 morphology and topography codes: 8243/3 (goblet cell carcinoid) and C18.1. Patients treated with neoadjuvant systemic and/or radiation therapy and adjuvant radiation were excluded. Univariate and multivariable analyses were conducted, and Kaplan-Meier Curves were used to compare overall survival (OS) based on treatment received with Log-rank test. RESULTS A total of 619 patients were identified. 54.4% males and 89.0% Caucasian; median age 56 (range, 23-90) years. Distribution across pathological stages II-III was 82.7% (N = 512) and 17.3% (N = 107) respectively. AC was administered in 9.4% (N = 48) of stage II and 47.7% (N = 51) of stage III patients. For stage II patients, AC was not associated with better OS in univariate (HR 0.32; 95% CI 0.04-2.34; p = 0.261) or multivariable analyses (HR 0.29; 95% CI 0.04-2.12; p = 0.221). By contrast, in stage III patients, AC was associated with better OS in univariate (HR 0.35; 95% CI 0.17-0.71; p = 0.004) and multivariable analyses (HR 0.25; 95% CI 0.07-0.88; p = 0.031). In the entire cohort 5-year OS for patients that received AC was 85.5% (74.0%, 92.1%) versus 82.7% (77.5%, 86.8%) (p = 0.801) with no AC. For stage II patients, 5-year OS was 96.9% with AC vs. 89.1% with no AC (p = 0.236). For stage III patients, 5-year OS was 77.1% with AC vs. 42.8% with no AC (p = 0.003). CONCLUSION AC was associated with improved OS in patients with pathological stage III GCC of the appendix, but not with pathological stage II.
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Affiliation(s)
- Katerina Zakka
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Shayla Williamson
- Winship Research Informatics, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Renjian Jiang
- Winship Research Informatics, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Michelle D Reid
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, USA
| | - Olatunji B Alese
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Walid L Shaib
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Christina Wu
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Madhusmita Behera
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA; Winship Research Informatics, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Bassel F El-Rayes
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Mehmet Akce
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
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20
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Alabraba E, Pritchard DM, Griffin R, Diaz-Nieto R, Banks M, Cuthbertson DJ, Fenwick S. The impact of lymph node metastases and right hemicolectomy on outcomes in appendiceal neuroendocrine tumours (aNETs). Eur J Surg Oncol 2020; 47:1332-1338. [PMID: 33004273 DOI: 10.1016/j.ejso.2020.09.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 08/24/2020] [Accepted: 09/12/2020] [Indexed: 01/15/2023] Open
Abstract
INTRODUCTION European Neuroendocrine Tumour Society (ENETS) recommends managing appendiceal neuroendocrine tumours (aNET) with appendicectomy and possibly completion right hemicolectomy (CRH). However, disease behaviour and survival patterns remain uncertain. MATERIALS AND METHODS We retrospectively assessed the impact of lymph nodes and CRH on outcomes, including survival, in all aNET patients diagnosed between 1990 and 2016. RESULTS 102 patients (52F, 50 M), median age 39.4 (range 16.3-81.1) years, were diagnosed with aNET. Mean tumour size was 12.7 (range 1-60) mm, most sited in appendiceal tip (63%). Index surgery was appendicectomy in 79% of cases while the remainder underwent colectomy. CRH performed in 30 patients at a median 3.2 (range 1.4-9.8) months post-index surgery yielded residual disease in nine: lymph nodes (n = 8) or residual tumour (n = 1). Univariate logistic regression showed residual disease was significantly predicted by tumour size ≥2 cm (p = 0.020). Four patients declined CRH, but did not suffer relapse or reduced survival. One patient developed recurrence after 16.5 years of follow-up and another patient developed a second neuroendocrine tumour after 18.8 years follow-up. There were 5 deaths; one being aNET-related. 5-year and 10-year overall survival were 99% and 92% respectively; 5-year and 10-year relapse-free survival were 98% and 92% respectively. Only 5-year relapse-free survival was affected by ENETS stage (p = 0.002). CONCLUSION aNETs are indolent with very high rates of overall and relapse-free survival. Recurrence is rare, and in this series only occurred decades later, making a compelling case for selective surveillance and follow-up. The significance of positive lymph nodes and the necessity for completion right hemicolectomy remain unclear.
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Affiliation(s)
- Edward Alabraba
- ENETS Centre of Excellence, Liverpool University Hospitals, NHS Foundation Trust, UK.
| | - David Mark Pritchard
- ENETS Centre of Excellence, Liverpool University Hospitals, NHS Foundation Trust, UK; Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, UK
| | - Rebecca Griffin
- Liverpool Clinical and Cancer Research, UK Trials Unit, University of Liverpool, UK
| | - Rafael Diaz-Nieto
- ENETS Centre of Excellence, Liverpool University Hospitals, NHS Foundation Trust, UK
| | - Melissa Banks
- ENETS Centre of Excellence, Liverpool University Hospitals, NHS Foundation Trust, UK
| | - Daniel James Cuthbertson
- ENETS Centre of Excellence, Liverpool University Hospitals, NHS Foundation Trust, UK; Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, UK
| | - Stephen Fenwick
- ENETS Centre of Excellence, Liverpool University Hospitals, NHS Foundation Trust, UK
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21
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Ahmed M. Gastrointestinal neuroendocrine tumors in 2020. World J Gastrointest Oncol 2020; 12:791-807. [PMID: 32879660 PMCID: PMC7443843 DOI: 10.4251/wjgo.v12.i8.791] [Citation(s) in RCA: 130] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 05/26/2020] [Accepted: 07/18/2020] [Indexed: 02/05/2023] Open
Abstract
Gastrointestinal neuroendocrine tumors are rare slow-growing tumors with distinct histological, biological, and clinical characteristics that have increased in incidence and prevalence within the last few decades. They contain chromogranin A, synaptophysin and neuron-specific enolase which are necessary for making a diagnosis of neuroendocrine tumor. Ki-67 index and mitotic index correlate with cellular proliferation. Serum chromogranin A is the most commonly used biomarker to assess the bulk of disease and monitor treatment and is raised in both functioning and non-functioning neuroendocrine tumors. Most of the gastrointestinal neuroendocrine tumors are non-functional. World Health Organization updated the classification of neuroendocrine tumors in 2017 and renamed mixed adenoneuroendocrine carcinoma into mixed neuroendocrine neoplasm. Gastric neuroendocrine tumors arise from enterochromaffin like cells. They are classified into 4 types. Only type I and type II are gastrin dependent. Small intestinal neuroendocrine tumor is the most common small bowel malignancy. More than two-third of them occur in the terminal ileum within 60 cm of ileocecal valve. Patients with small intestinal neuroendrocrine tumors frequently show clinical symptoms and develop distant metastases more often than those with neuroendocrine tumors of other organs. Duodenal and jejuno-ileal neuroendocrine tumors are distinct biologically and clinically. Carcinoid syndrome generally occurs when jejuno-ileal neuroendocrine tumors metastasize to the liver. Appendiceal neuroendocrine tumors are generally detected after appendectomy. Colonic neuroendocrine tumors generally present as a large tumor with local or distant metastasis at the time of diagnosis. Rectal neuroendocrine tumors are increasingly being diagnosed since the implementation of screening colonoscopy in 2000. Gastrointestinal neuroendocrine tumors are diagnosed and staged by endoscopy with biopsy, endoscopic ultrasound, serology of biomarkers, imaging studies and functional somatostatin scans. Various treatment options are available for curative and palliative treatment of gastrointestinal neuroendocrine tumors.
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Affiliation(s)
- Monjur Ahmed
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Thomas Jefferson University, Philadelphia, PA 19107, United States
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Wang J, He A, Feng Q, Hou P, Wu J, Huang Z, Xiao Z, Sun C, Liao W, Wu L. Gastrointestinal mixed adenoneuroendocrine carcinoma: a population level analysis of epidemiological trends. J Transl Med 2020; 18:128. [PMID: 32169074 PMCID: PMC7071749 DOI: 10.1186/s12967-020-02293-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Accepted: 03/07/2020] [Indexed: 02/06/2023] Open
Abstract
Background The rise in incidence and mortality of gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC) has not been well focused. The aim of our study was to examine epidemiological trends in incidence and incidence-based (IB) mortality of gastrointestinal MANEC at a population level. Methods The incidence and IB mortality of gastrointestinal MANEC as well as data on affected patients from 2000 to 2016 were obtained from the Surveillance, Epidemiology, and End Results database. Trends in incidence and IB mortality were assessed using Joinpoint regression. The Kaplan–Meier method and log-rank test were used for survival analysis. Cox proportional hazards regression was used to identify independent predictors of mortality. Results 581 patients diagnosed with gastrointestinal MANEC were enrolled. Gastrointestinal MANEC incidence was 0.23 cases per 1,000,000 individuals in 2000 and 1.16 cases per 1,000,000 individuals in 2016, with an annual percent change (APC) of 8.0% (95% CI 5.7–10.3%, P < 0.05). IB mortality also showed a sustained increase (APC 12.9%, 95% CI 9.0–16.8%, P < 0.05). In Cox regression analysis, age at diagnosis, tumor grade and stage, lymph node metastasis, surgery, and tumor size were independently associated with mortality. Median survival was 75 months (95% CI 60–128 months). Median survival of appendiceal MANEC was significantly longer than that of cecal MANEC (115 vs. 31 months; P < 0.001). Conclusions We found a sustained and rapid increase both in incidence and IB mortality of gastrointestinal MANEC, manifesting that there has been no significant improvement in patient outcomes, nor progress in prevention and treatment. Additional resources should be devoted to gastrointestinal MANEC research.
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Affiliation(s)
- Jiakun Wang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Aoxiao He
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Qian Feng
- Department of Emergency, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Ping Hou
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Junjun Wu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Zhihao Huang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Zhouqing Xiao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Chi Sun
- Department of Nursing, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Wenjun Liao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China.
| | - Linquan Wu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China.
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The American Society of Colon and Rectal Surgeons, Clinical Practice Guidelines for the Management of Appendiceal Neoplasms. Dis Colon Rectum 2019; 62:1425-1438. [PMID: 31725580 DOI: 10.1097/dcr.0000000000001530] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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24
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Fields AC, Lu P, Enzinger A, Goldberg J, Irani J, Bleday R, Nash G, Melnitchouk N. Treatment patterns and outcomes in goblet cell carcinoid tumors of the appendix. J Surg Oncol 2019; 120:1096-1101. [PMID: 31592538 DOI: 10.1002/jso.25723] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 09/21/2019] [Indexed: 01/16/2023]
Abstract
BACKGROUND Goblet cell carcinoid (GCC) tumors of the appendix are a rare malignancy. We aim to examine the overall survival per stage and the relationship between different treatment modalities and outcomes for patients with GCC tumors of the appendix. METHODS We identified patients with GCC tumors of the appendix from the National Cancer Database. The main outcome was overall patient survival and cox proportional hazard models were used to ascertain predictors of survival. RESULTS There were 2552 patients identified. The median age of diagnosis was 57 (interquartile range: 49-65) and 52.3% of patients were female. The 5-year survival for Stage I disease was 91.1% (95% confidence interval [CI]: 82.2%-95.7%), for Stage II disease was 90.5% (95% CI: 85.8%-93.7%), for Stage III disease was 57.0% (95% CI: 45.0%-67.3%), and for Stage IV disease was 18.9% (95% CI: 9.3%-31.0%). In a Cox proportional hazard model, older age (hazard ratio [HR]: 1.1; 95% CI: 1.03-1.12; P < .001), lymph node metastasis (HR: 6.9; 95% CI: 2.76-17.01; P < .001), and positive surgical margins (HR: 2.9; 95% CI:1.13-7.26; P = .003) were associated with worse overall survival for Stages I to III disease while only older age (HR: 1.03; 95% CI: 1.002-1.06; P = .04) was associated with worse overall survival for Stage IV disease. CONCLUSIONS Patients with GCC tumors of the appendix who have the nonmetastatic disease have a high 5-year survival. We have identified several prognostic factors for GCC.
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Affiliation(s)
- Adam C Fields
- Division of Colorectal Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Pamela Lu
- Division of Colorectal Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.,Department of Surgery, Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Andrea Enzinger
- Center for Gastrointestinal Oncology, Dana Farber Cancer Center, Boston, Massachusetts
| | - Joel Goldberg
- Division of Colorectal Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Jennifer Irani
- Division of Colorectal Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Ronald Bleday
- Division of Colorectal Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Garrett Nash
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Nelya Melnitchouk
- Division of Colorectal Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.,Department of Surgery, Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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25
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Blakely AM, Raoof M, Ituarte PHG, Fong Y, Singh G, Lee B. Lymphovascular Invasion Is Associated with Lymph Node Involvement in Small Appendiceal Neuroendocrine Tumors. Ann Surg Oncol 2019; 26:4008-4015. [PMID: 31359272 DOI: 10.1245/s10434-019-07637-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Indexed: 01/07/2023]
Abstract
BACKGROUND Appendiceal neuroendocrine tumors (NETs) are incidentally found in up to 1% of appendectomy specimens. The association of lymphovascular invasion (LVI) with risk of regional lymph node involvement is unclear. METHODS From the National Cancer Database, 2004-2015, this study identified patients who had tumors 2 cm or smaller with one or more lymph nodes (LNs) pathologically evaluated. The histology was defined as typical, goblet cell, or composite NETs. Patient demographics, tumor characteristics, and treatment variables were analyzed. RESULTS The histologies for the 1767 identified patients were typical (n = 921, 52.1%), goblet cell (n = 556, 31.5%), and composite (n = 290, 16.4%). The tumor grades were low (70.4%), moderate (18.6%), and high (11%). The overall LN positivity was 17%. Of 1052 tumors evaluated, 215 (20.4%) had LVI. Overall survival decreased with node involvement (mean 84 vs. 124 months; p < 0.0001, log-rank). In the multivariate logistic regression analysis, LVI was independently associated with node involvement [odds ratio (OR) 5.0; p < 0.0001] after adjustment for patient age and tumor histologic subtype, size, and grade. In the subset analysis of typical NETs, tumor size of 1-2 cm (ref. < 1 cm; OR 5.5; p < 0.001) and presence of LVI (ref. absence of LVI; OR 4.8; p < 0.0001) were the only factors independently associated with LN involvement. CONCLUSIONS Node involvement is associated with worse overall survival in appendiceal NETs. The presence of LVI was strongly associated with lymph node involvement. An appendectomy specimen showing LVI should prompt strong consideration of colectomy with regional lymphadenectomy even for small, typical appendiceal NETs.
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Affiliation(s)
- Andrew M Blakely
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA.
| | - Mustafa Raoof
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Philip H G Ituarte
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Gagandeep Singh
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Byrne Lee
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
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26
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Kelley KA, Tsikitis VL. Review of Colorectal Studies Using the National Cancer Database. Clin Colon Rectal Surg 2019; 32:69-74. [PMID: 30647548 DOI: 10.1055/s-0038-1673356] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The National Cancer Database (NCDB) is a large clinical oncology database developed with data collected from Commission on Cancer (CoC)-accredited facilities. The CoC is managed under the American College of Surgeons, and is a multidisciplinary team that maintains standards in cancer care delivery in health care settings. This database has been used in multiple cancer-focused studies and reports on cancer diagnosis, hospital-level, and patient-related demographics. The focus of this review is to explore and discuss the use of NCDB in colorectal surgery research. Furthermore, our aim for this review is to formulate a guide for researchers who are interested in using the NCDB to complete colorectal research.
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Affiliation(s)
- Katherine A Kelley
- Division of Gastrointestinal and General Surgery, Department of General Surgery, Oregon Health and Science University Portland, Portland, OR
| | - V Liana Tsikitis
- Division of Gastrointestinal and General Surgery, Department of General Surgery, Oregon Health and Science University Portland, Portland, OR
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27
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Appendiceal neoplasm risk associated with complicated acute appendicitis-a population based study. Int J Colorectal Dis 2019; 34:39-46. [PMID: 30242478 DOI: 10.1007/s00384-018-3156-x] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/27/2018] [Indexed: 02/04/2023]
Abstract
PURPOSE Appendiceal tumors are rare, but high neoplasm rates have been reported at interval appendectomy after periappendicular abscess. Non-operative management of uncomplicated acute appendicitis has shown promising results. The data on appendiceal tumor incidence and presentation among acute appendicitis patients is limited, especially in patient cohorts differentiating between uncomplicated and complicated acute appendicitis. Objective was to assess appendiceal tumor incidence and tumor association to appendicitis in patients with uncomplicated and complicated acute appendicitis. METHODS This nationwide population-based registry study was conducted from 2007 to 2013. The Finnish Cancer Registry and the National Institute for Health Registry were used to combine data on all appendiceal tumors and acute appendicitis diagnosis with medical reports evaluated at eight study hospitals. RESULTS Altogether, 840 appendiceal tumors were identified, and out of these, 504 patient reports were reviewed, including 472 patients in this study. Tumor was diagnosed at appendectomy for suspected acute appendicitis in 276 patients (58%). In the whole study, histologically acute appendicitis and tumor were both present in 53% (n = 250), and out of these, 41% (n = 102) were complicated and 59% (n = 148) uncomplicated acute appendicitis. The associated tumor risk was significantly higher in complicated acute appendicitis compared with uncomplicated cases (3.24% vs. 0.87%, p < 0.001). Overall tumor prevalence among acute appendicitis patients was 1.24%. CONCLUSIONS Appendiceal tumor prevalence in acute appendicitis was low. Tumor risk was significantly higher in complicated acute appendicitis compared with uncomplicated acute appendicitis. The risk of missed appendiceal tumors related to antibiotic therapy of uncomplicated acute appendicitis is very low.
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28
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Toumpanakis C, Fazio N, Tiensuu Janson E, Hörsch D, Pascher A, Reed N, O Apos Toole D, Nieveen van Dijkum E, Partelli S, Rinke A, Kos-Kudla B, Costa F, Pape UF, Grozinsky-Glasberg S, Scoazec JY. Unmet Needs in Appendiceal Neuroendocrine Neoplasms. Neuroendocrinology 2019; 108:37-44. [PMID: 30235454 DOI: 10.1159/000493894] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 09/18/2018] [Indexed: 12/13/2022]
Abstract
Appendiceal neuroendocrine neoplasms (ANEN) are mostly discovered coincidentally during appendicectomy and usually have a benign clinical course; thus, appendicectomy alone is considered curative. However, in some cases, a malignant potential is suspected, and therefore additional operations such as completion right hemicolectomy are considered. The existing European Neuroendocrine Tumour Society (ENETS) guidelines provide useful data about epidemiology and prognosis, as well as practical recommendations with regards to the risk factors for a more aggressive disease course and the indications for a secondary operation. However, these guidelines are based on heterogeneous and retrospective studies. Therefore, the evidence does not seem to be robust, and there are still unmet needs in terms of accurate epidemiology and overall prognosis, optimal diagnostic and follow-up strategy, as well as identified risk factors that would indicate a more aggressive surgical approach at the beginning and a more intense follow-up. In this review, we are adopting a critical approach of the ENETS guidelines and published series for ANEN, focusing on the above-noted "grey areas".
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Affiliation(s)
| | - Nicola Fazio
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, Milan, Italy
| | - Eva Tiensuu Janson
- Endocrine Oncology Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Dieter Hörsch
- Center for Neuroendocrine Tumors Bad Berka, Bad Berka, Germany
| | - Andreas Pascher
- Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité University Medicine Berlin, Berlin, Germany
| | - Nicholas Reed
- Beatson Oncology Centre, Gartnavel General Hospital, Glasgow, United Kingdom
| | - Dermot O Apos Toole
- Department of Clinical Medicine, St. James's Hospital, Trinity College Dublin, Dublin, Ireland
| | - Els Nieveen van Dijkum
- Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Stefano Partelli
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy
| | - Anja Rinke
- Department of Gastroenterology, UKGM, Marburg, Marburg, Germany
| | - Beata Kos-Kudla
- Department of Endocrinology and Neuroendocrine Tumors, Department of Pathophysiology and Endocrinology, Medical University of Silesia, Katowice, Poland
| | | | - Ulrich-Frank Pape
- Division of Hepatology and Gastroenterology, Medical Department, Charité Campus Charité Mitte/Campus Virchow-Klinikum, Charité University Medicine Berlin, Berlin, Germany
| | - Simona Grozinsky-Glasberg
- Neuroendocrine Tumor Unit, Department of Endocrinology, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel
| | - Jean-Yves Scoazec
- Department of Pathology, Gustave Roussy Cancer Campus, Villejuif, France
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29
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Tsoli M, Chatzellis E, Koumarianou A, Kolomodi D, Kaltsas G. Current best practice in the management of neuroendocrine tumors. Ther Adv Endocrinol Metab 2019; 10:2042018818804698. [PMID: 30800264 PMCID: PMC6378464 DOI: 10.1177/2042018818804698] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 09/05/2018] [Indexed: 12/13/2022] Open
Abstract
Neuroendocrine neoplasms are rare tumors that display marked heterogeneity with varying natural history, biological behavior, response to therapy and prognosis. Their management is complex, particularly as a number of them may be associated with a secretory syndrome and involve a variety of options. A number of factors such as proliferation rate, degree of differentiation, functionality and extent of the disease are mostly utilized to tailor treatment accordingly, ideally in the context of a multidisciplinary team. In addition, a number of relevant scientific societies have published therapeutic guidelines in an attempt to direct and promote evidence-based treatment. Surgery remains the treatment of choice with an intention to cure while it may also be recommended in some cases of metastatic disease and difficult to control secretory syndromes. Long-acting somatostatin analogs constitute the main treatment for the majority of functioning tumors, whereas specific evolving agents such as telotristat may be used for the control of carcinoid syndrome and related sequelae. In patients with advanced disease not amenable to surgical resection, treatment options include locoregional therapies, long-acting somatostatin analogs, molecular targeted agents, radionuclides, chemotherapy and recently immunotherapy, alone or in combination. However, the ideal time of treatment initiation, sequence of administration of different therapies and identification of robust prognostic markers to select the most appropriate treatment for each individual patient still need to be defined.
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Affiliation(s)
| | - Eleftherios Chatzellis
- First Department of Propaedeutic Internal
Medicine, Laiko General Hospital, National and Kapodistrian University of
Athens, Athens, Greece
| | - Anna Koumarianou
- Fourth Department of Internal Medicine, Attikon
University General Hospital, Athens, Greece
| | - Dionysia Kolomodi
- First Department of Propaedeutic Internal
Medicine, Laiko General Hospital, National and Kapodistrian University of
Athens, Athens, Greece
| | - Gregory Kaltsas
- First Department of Propaedeutic Internal
Medicine, Laiko General Hospital, National and Kapodistrian University of
Athens, Athens, Greece
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30
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Gilmore G, Jensen K, Saligram S, Sachdev TP, Arekapudi SR. Goblet cell carcinoid of the appendix - diagnostic challenges and treatment updates: a case report and review of the literature. J Med Case Rep 2018; 12:275. [PMID: 30244681 PMCID: PMC6151924 DOI: 10.1186/s13256-018-1789-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Accepted: 08/01/2018] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Goblet cell carcinoid is a rare but distinct entity of appendiceal tumors which is a hybrid or mixed tumor consisting of both epithelial (glandular) and neuroendocrine elements containing goblet cells. This entity is important to recognize and appropriately grade as it tends to be more aggressive than typical carcinoid tumors, often presenting with metastatic disease. As a result, the 5-year overall survival is 14-22% in stage III-IV disease. GCC therefore warrants more aggressive surgical and medical (chemotherapy) interventions than typical carcinoid tumors. Through this case report we give a brief update on GCC pathological features, staging, surgical management, and review the literature as a guide to indications for chemotherapy and choice of agents. CASE PRESENTATION We present the case of a 77-year-old Caucasian man with a history of stage I adenocarcinoma of transverse colon status post transverse colectomy who was incidentally found on surveillance colonoscopy to have an abnormal appendiceal orifice lesion. A biopsy revealed an appendiceal goblet cell carcinoid and he underwent a right hemicolectomy which revealed a pathologic stage III GCC for which he received eight cycles of adjuvant chemotherapy with capecitabine. CONCLUSIONS It is essential that patients who have tumors > 2 cm, are pT3 or pT4, have higher grade histology with signet ring (Tang grade B or grade C), locally advanced, or with positive surgical margins on appendectomy undergo a right hemicolectomy. Although there is no category 1 evidence, consensus recommendations are that patients with stage II (particularly Tang B and C) and stage III GCC be offered adjuvant chemotherapy with a regimen based on 5-fluorouracil, as these patients are known to have high rates of relapse.
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Affiliation(s)
- Gregory Gilmore
- Department of Medicine, Veterans Affairs Central California Health Care System, University of California San Francisco, 2615 E Clinton Ave, Fresno, CA, 93703, USA
| | - Kristin Jensen
- Department of Pathology, Veterans Affairs Palo Alto Health Care System, Stanford Hospital and Clinics, Palo Alto, CA, 94304, USA
| | - Shreyas Saligram
- Department of Medicine, Veterans Affairs Central California Health Care System, University of California San Francisco, 2615 E Clinton Ave, Fresno, CA, 93703, USA
| | - Thomas P Sachdev
- Department of Medicine, Veterans Affairs Central California Health Care System, University of California San Francisco, 2615 E Clinton Ave, Fresno, CA, 93703, USA
| | - Subramanyeswara R Arekapudi
- Department of Medicine, Veterans Affairs Central California Health Care System, University of California San Francisco, 2615 E Clinton Ave, Fresno, CA, 93703, USA.
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31
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Shibuya H, Hijioka S, Mizuno N, Kuwahara T, Okuno N, Tanaka T, Ishihara M, Hirayama Y, Oonishi S, Murakami Y, Yatabe Y, Tajika M, Niwa Y, Hara K. A Rare Case of Ampullary Goblet Cell Carcinoid. Intern Med 2018; 57:2489-2496. [PMID: 29607953 PMCID: PMC6172535 DOI: 10.2169/internalmedicine.0516-17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
An asymptomatic 70-year-old woman was referred to our hospital because of liver enzyme elevation. Enhanced abdominal computed tomography demonstrated a small, round-shaped tumor with dilation of the common bile duct and main pancreatic duct. A biopsy specimen from the papilla showed mucin-containing cells that were positive for endocrine markers on immunohistochemical staining. Endoscopic snare resection was done, and there was a positive vertical margin on pathology. Pancreaticoduodenectomy was then performed later. The final diagnosis was goblet cell carcinoid, pT2N0M0, pStage IIA [Union for International Cancer Control (UICC) 7th edition]. Ampullary goblet cell carcinoid is an extremely rare disease of which there have been no recent reports.
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Affiliation(s)
- Hitoshi Shibuya
- Departments of Gastroenterology, Aichi Cancer Center Hospital, Japan
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Japan
| | - Susumu Hijioka
- Departments of Gastroenterology, Aichi Cancer Center Hospital, Japan
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Japan
| | - Nobumasa Mizuno
- Departments of Gastroenterology, Aichi Cancer Center Hospital, Japan
| | | | - Nozomi Okuno
- Departments of Gastroenterology, Aichi Cancer Center Hospital, Japan
| | - Tsutomu Tanaka
- Departments of Endoscopy, Aichi Cancer Center Hospital, Japan
| | - Makoto Ishihara
- Departments of Endoscopy, Aichi Cancer Center Hospital, Japan
| | - Yutaka Hirayama
- Departments of Endoscopy, Aichi Cancer Center Hospital, Japan
| | - Sachiyo Oonishi
- Departments of Endoscopy, Aichi Cancer Center Hospital, Japan
| | - Yoshiko Murakami
- Departments of Pathology and Molecular Diagnosis, Aichi Cancer Center Hospital, Japan
| | - Yasushi Yatabe
- Departments of Pathology and Molecular Diagnosis, Aichi Cancer Center Hospital, Japan
| | - Masahiro Tajika
- Departments of Endoscopy, Aichi Cancer Center Hospital, Japan
| | - Yasumasa Niwa
- Departments of Endoscopy, Aichi Cancer Center Hospital, Japan
| | - Kazuo Hara
- Departments of Gastroenterology, Aichi Cancer Center Hospital, Japan
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Abstract
Appendiceal neuroendocrine neoplasms are uncommon, mostly discovered coincidentally during appendectomy. They usually show a benign clinical course and appendectomy alone is curative. However, some cases may harbor malignant potential; therefore, additional/prophylactic operations, such as right hemicolectomy, are offered. Current international guidelines are based on heterogeneous and retrospective series. Thus, there is lack of robust evidence, mainly in terms of accurate factors, that could identify patients at risk, requiring more extensive surgical treatment. In this article, we highlight controversies in the epidemiology, workup assessment, and management algorithms of appendiceal neuroendocrine neoplasms, but also to explore future developments and advances.
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Affiliation(s)
- Michail Galanopoulos
- Department of Gastroenterology, Evangelismos Hospital, 45-47 Ipsilantou Street, Athens 105 52, Greece
| | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, 8 South, Pond Street, London NW3 2QG, UK.
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Abstract
OBJECTIVES Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare but have been increasing in incidence. Limited data on the long-term outcomes of patients with these tumors are available. METHODS In this study, we used population-based data from the National Cancer Institute to assess long-term disease-specific survival (DSS) of patients who have undergone surgery for nonmetastatic disease. All patients with NETs of the stomach, small intestine, colon, rectum, appendix, and pancreas diagnosed between 1988 and 2009 were identified from the Surveillance, Epidemiology and End Results registry. Staging was derived from Surveillance, Epidemiology and End Results data using the European Neuroendocrine Tumor Society guidelines. Cases with incomplete staging data were excluded, along with those with stage IV disease, or those who did not undergo surgical resection. RESULTS Kaplan-Meier analyses were constructed to determine DSS. Analyses were further stratified according to tumor site, stage at diagnosis, and tumor grade. Overall, 13,348 patients with GEP-NETs meeting the inclusion criteria were identified. CONCLUSIONS There were excellent outcomes for most GEP-NET patients, with a 20-year DSS of greater than 75% across all sites and stages. Pancreatic tumors had the worst outcomes, but DSS remains greater than 50% at 20 years.
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34
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Clift AK, Kornasiewicz O, Drymousis P, Faiz O, Wasan HS, Kinross JM, Cecil T, Frilling A. Goblet cell carcinomas of the appendix: rare but aggressive neoplasms with challenging management. Endocr Connect 2018; 7:268-277. [PMID: 29335251 PMCID: PMC5801558 DOI: 10.1530/ec-17-0311] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 01/15/2018] [Indexed: 12/17/2022]
Abstract
Goblet cell carcinomas (GCC) are a rare, aggressive sub-type of appendiceal tumours with neuroendocrine features, and controversy exists with regards to therapeutic strategy. We undertook a retrospective review of GCC patients surgically treated at two tertiary referral centres. Clinical and histopathological data were extracted from a prospectively maintained database. Survival analyses utilised Kaplan-Meier methodology. Twenty-one patients were identified (9 females). Median age at diagnosis was 55 years (range 32-77). There were 3, 6 and 9 grade 1, 2 and 3 tumours, respectively. One, 10, 5 and 5 patients had stage I, II, III and IV disease at diagnosis, respectively. There were 8, 10 and 3 Tang class A, B and C tumours, respectively. Index operation was appendectomy (n = 12), right hemicolectomy (n = 6) or resections including appendix/right colon, omentum and the gynaecological system (n = 3). Eight patients underwent completion right hemicolectomy. Surgery for recurrence included small bowel resection (n = 2), debulking with peritonectomy and heated intraperitoneal chemotherapy, and hysterectomy and bilateral salpingo-oophorectomy (all n = 1). Median follow-up was 30 months (range 2.5-123). One-, 3- and 5-year OS was 79.4, 60 and 60%, respectively. Mean OS (1-, 3-, and 5-year OS) for Tang class A, B and C tumours were 73.1 months (85.7, 85.7, 51.4%), 83.7 months (all 66.7%) and 28.5 months (66.7, 66.7%, not reached), respectively. Chromogranin A/B and 68Ga-DOTATATE PET/CT were not useful in follow-up, but CEA, CA 19-9, CA 125 and 18F-FDG PET/CT identified tumour recurrence. GCC must be clearly discriminated from relatively indolent appendiceal neuroendocrine neoplasms. 18F-FDG PET/CT and CEA/CA19-9/CA 125 are useful in detecting recurrence of GCC.
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Affiliation(s)
- Ashley K Clift
- Department of Surgery and CancerImperial College London, London, UK
| | - Oskar Kornasiewicz
- Department of Surgery and CancerImperial College London, London, UK
- Department of SurgeryWarsaw Medical University, Warsaw, Poland
| | | | - Omar Faiz
- Department of SurgerySt Mark's Hospital, London, UK
| | - Harpreet S Wasan
- Department of Surgery and CancerImperial College London, London, UK
| | - James M Kinross
- Department of Surgery and CancerImperial College London, London, UK
| | - Thomas Cecil
- Peritoneal Malignancy UnitBasingstoke and North Hampshire Hospital, Basingstoke, UK
| | - Andrea Frilling
- Department of Surgery and CancerImperial College London, London, UK
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Carlini M, Spoletini D, Grieco M, Apa D, Appetecchia M, Lauretta R, Palazzo S, Minardi S, Severi S, lanniello A. Management of Ileal, Appendiceal and Colorectal Neuroendocrine Tumors. Updates Surg 2018. [DOI: 10.1007/978-88-470-3955-1_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Adenocarcinoma ex-goblet cell carcinoid (appendiceal-type crypt cell adenocarcinoma) is a morphologically distinct entity with highly aggressive behavior and frequent association with peritoneal/intra-abdominal dissemination: an analysis of 77 cases. Mod Pathol 2016; 29:1243-53. [PMID: 27338636 PMCID: PMC5389379 DOI: 10.1038/modpathol.2016.105] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Revised: 04/26/2016] [Accepted: 04/27/2016] [Indexed: 11/09/2022]
Abstract
High-grade versions of appendiceal goblet cell carcinoids ('adenocarcinoma ex-goblet cell carcinoids') are poorly characterized. We herein document 77 examples. Tumors occurred predominantly in females (74%), mean age 55 years (29-84), most with disseminated abdominal (77% peritoneal, 58% gynecologic tract involvement) and stage IV (65%) disease. Many presented to gynecologic oncologists, and nine had a working diagnosis of ovarian carcinoma. Metastases to liver (n=3) and lung (n=1) were uncommon and none arose in adenomatous lesions. Tumors had various histologic patterns, in variable combinations, most of which were fairly specific, making them recognizable as appendiceal in origin, even at metastatic sites: I: Ordinary goblet cell carcinoid/crypt pattern (rounded, non-luminal acini with well-oriented goblet cells), in variable amounts in all cases. II: Poorly cohesive goblet cell pattern (diffusely infiltrative cords/single files of signet ring-like/goblet cells). III: Poorly cohesive non-mucinous cell (diffuse-infiltrative growth of non-mucinous cells). IV: Microglandular (rosette-like glandular) pattern without goblet cells. V: Mixed 'other' carcinoma foci (including ordinary intestinal/mucinous). VI: goblet cell carcinoid pattern with high-grade morphology (marked nuclear atypia). VII: Solid sheet-like pattern punctuated by goblet cells/microglandular units. Ordinary nested/trabecular ('carcinoid pattern') was very uncommon. In total, 33(52%) died of disease, with median overall survival 38 months and 5-year survival 32%. On multivariate analysis perineural invasion and younger age (<55) were independently associated with worse outcome while lymph-vascular invasion, stage, and nodal status trended toward, but failed to reach, statistical significance. Worse behavior in younger patients combined with female predilection and ovarian-affinity raise the possibility of hormone-assisted tumor progression. In conclusion, 'adenocarcinoma ex-goblet cell carcinoid' is an appendix-specific, high-grade malignant neoplasm with distinctive morphology that is recognizable at metastatic sites and recapitulates crypt cells (appendiceal crypt cell adenocarcinoma). Unlike intestinal-type adenocarcinoma, it occurs predominantly in women, is disguised as gynecologic malignancy, and spreads along peritoneal surfaces with only rare hematogenous metastasis. It appears to be significantly more aggressive than appendiceal mucinous neoplasms.
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Clinical Significance of Metastatic Lymph Nodes in the Gut of Patients with Pure and Mixed Primary Appendiceal Carcinoids. Dis Colon Rectum 2016; 59:508-12. [PMID: 27145307 DOI: 10.1097/dcr.0000000000000574] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Right hemicolectomy is indicated for primary appendiceal carcinoids with diameters greater than 2 cm because of an increased risk of metastasis to the lymph nodes of the gut. However, the natural history of positive nodes remains unknown. OBJECTIVE The aim of this study was to investigate the impact of metastatic lymph nodes on survival among patients with pure or mixed primary appendiceal carcinoids, while controlling for potential confounders such as age, sex, tumor size, surgical intervention, and lymph node rate (number of positive lymph nodes/lymph node yield). DESIGN This is a retrospective comparative study.. SETTINGS Data were retrieved from the Surveillance, Epidemiology and End Results database. PATIENTS Patients undergoing colectomy for appendiceal carcinoids between 1998 and 2009 were selected. MAIN OUTCOME MEASURES The survival curves for the 2 groups were compared to evaluate differences in prognosis. Univariate and multivariate analyses were performed. RESULTS Lymph node rates did not significantly differ between the pure and mixed carcinoid groups (p = 0.768), although overall survival was poorer among patients with mixed carcinoids (p = 0.004; HR, 0.498; 95% CI, 0.310-0.800). For pure carcinoids, surgical intervention (p = 0.029; HR, 0.241; 95% CI, 0.067-0.867), age (p < 0.001; HR, 1.083; 95% CI, 1.051-1.116), and lymph node rate (p = 0.039; HR, 5.295; 95% CI, 1.089-25.754) were independent predictors of overall survival. For mixed carcinoids, surgical intervention (p = 0.019; HR, 1.675; 95% CI, 1.088-2.578), tumor size (p < 0.001; HR, 0.442; 95% CI, 0.286-0.683), age (p < 0.001; HR, 1.041; 95% CI, 1.026-1.056), and lymph node rate (p < 0.001; HR, 17.471; 95% CI, 10.047-0.382) were significant prognostic factors. LIMITATIONS The study is limited by its retrospective nature and by the shortcomings of the Surveillance, Epidemiology and End Results database related to the availability and quality of data. CONCLUSION Based on the data retrieved from the Surveillance, Epidemiology and End Results database and adjusted for potential confounding factors, the lymph node rate of metastasis strongly impacts overall survival among patients with pure or mixed carcinoids. Nodal metastasis thus appears to be a reliable clinical hallmark of tumor aggressiveness.
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Pape UF, Niederle B, Costa F, Gross D, Kelestimur F, Kianmanesh R, Knigge U, Öberg K, Pavel M, Perren A, Toumpanakis C, O'Connor J, Krenning E, Reed N, O'Toole D. ENETS Consensus Guidelines for Neuroendocrine Neoplasms of the Appendix (Excluding Goblet Cell Carcinomas). Neuroendocrinology 2016; 103:144-52. [PMID: 26730583 DOI: 10.1159/000443165] [Citation(s) in RCA: 176] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- U-F Pape
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum, Charitx00E9; Universitx00E4;tsmedizin Berlin, Berlin, Germany
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Lamarca A, Nonaka D, Lopez Escola C, Hubner RA, O'Dwyer S, Chakrabarty B, Fulford P, Valle JW. Appendiceal Goblet Cell Carcinoids: Management Considerations from a Reference Peritoneal Tumour Service Centre and ENETS Centre of Excellence. Neuroendocrinology 2016; 103:500-17. [PMID: 26356507 DOI: 10.1159/000440725] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 08/28/2015] [Indexed: 12/24/2022]
Abstract
BACKGROUND Appendix goblet cell carcinoids are known to share histological features of adenocarcinoma and neuroendocrine tumours. Due to their low incidence, quality evidence is lacking for the management of these patients. METHODS We performed a single-centre retrospective study of patients with a confirmed diagnosis of appendiceal goblet cell carcinoid (GCC; 1996-2014). Patients were divided into curative intent (CI) and palliative intent (PI) cohorts. Our primary end point was overall survival (OS). RESULTS Seventy-four patients were eligible; 76% were treated with CI [surgery only (36%), cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC; 36%), adjuvant chemotherapy (20%) and a combination of CRS and HIPEC followed by adjuvant chemotherapy (9%)], and 23% had advanced-stage disease amenable to palliative treatment (chemotherapy or supportive care) only. Completion right hemicolectomy, performed in 64% of the CI cohort, did not impact on the relapse rate or disease-free survival. FOLFOX chemotherapy was used in both the adjuvant and palliative settings; safety was as expected, and we observed a high rate (60%) of disease control in the palliative cohort. The estimated median OS (all patients), disease-free survival (CI patients) and progression-free survival (PI patients) were 52.1 (95% CI 29.4-90.3), 75.9 (26.6-not reached) and 5.3 (0.6-5.7) months, respectively. Age and stage were independent factors associated with OS in the multivariable analysis. Tang classification showed a trend for impact on OS. No benefit from specific adjuvant approach was identified; however, selection bias for treatment approach was observed. CONCLUSION Prospective trials are needed to define optimal approaches in GCC. All GCC patients should be managed by specialized centres due to their esoteric behaviour; we provide management considerations based on our experience and conclusions.
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Alexandraki KI, Kaltsas GA, Grozinsky-Glasberg S, Chatzellis E, Grossman AB. Appendiceal neuroendocrine neoplasms: diagnosis and management. Endocr Relat Cancer 2016; 23:R27-41. [PMID: 26483424 DOI: 10.1530/erc-15-0310] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/19/2015] [Indexed: 12/13/2022]
Abstract
Gastrointestinal neuroendocrine neoplasms (GI-NENs) are increasingly being recognised, while appendiceal NENs (aNENs) currently constitute the third most common GI-NEN. Appendiceal NENs are generally considered to follow an indolent course with the majority being localised at diagnosis. Thus, the initial surgical approach is not that of a planned oncological resection. Due to the localised nature of the disease in the majority of cases, subsequent biochemical and radiological assessment are not routinely recommended. Histopathological criteria (size, mesoappendiceal invasion, Ki-67 proliferation index, neuro- and angio-invasion) are mainly used to identify those patients who are also candidates for a right hemicolectomy. Goblet cell carcinoids are a distinct entity and should be treated as adenocarcinomas. Despite the absence of any substantial prospective data regarding optimal management and follow-up, recent consensus statements and guidelines have been published. The purpose of this review is to overview the published studies on the diagnosis and management of appendiceal NENs and to suggest a possible management protocol.
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Affiliation(s)
- Krystallenia I Alexandraki
- Department of PathophysiologyNational University of Athens, GreeceNeuroendocrine Tumor UnitEndocrinology and Metabolism Service, Department of Medicine, Hadassah-Hebrew University Hospital, Jerusalem, IsraelOxford Centre for DiabetesEndocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
| | - Gregory A Kaltsas
- Department of PathophysiologyNational University of Athens, GreeceNeuroendocrine Tumor UnitEndocrinology and Metabolism Service, Department of Medicine, Hadassah-Hebrew University Hospital, Jerusalem, IsraelOxford Centre for DiabetesEndocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
| | - Simona Grozinsky-Glasberg
- Department of PathophysiologyNational University of Athens, GreeceNeuroendocrine Tumor UnitEndocrinology and Metabolism Service, Department of Medicine, Hadassah-Hebrew University Hospital, Jerusalem, IsraelOxford Centre for DiabetesEndocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
| | - Eleftherios Chatzellis
- Department of PathophysiologyNational University of Athens, GreeceNeuroendocrine Tumor UnitEndocrinology and Metabolism Service, Department of Medicine, Hadassah-Hebrew University Hospital, Jerusalem, IsraelOxford Centre for DiabetesEndocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
| | - Ashley B Grossman
- Department of PathophysiologyNational University of Athens, GreeceNeuroendocrine Tumor UnitEndocrinology and Metabolism Service, Department of Medicine, Hadassah-Hebrew University Hospital, Jerusalem, IsraelOxford Centre for DiabetesEndocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
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Shaib W, Krishna K, Kim S, Goodman M, Rock J, Chen Z, Brutcher E, Staley CI, Maithel SK, Abdel-Missih S, El-Rayes BF, Bekaii-Saab T. Appendiceal Neuroendocrine, Goblet and Signet-Ring Cell Tumors: A Spectrum of Diseases with Different Patterns of Presentation and Outcome. Cancer Res Treat 2015; 48:596-604. [PMID: 26044156 PMCID: PMC4843718 DOI: 10.4143/crt.2015.029] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 04/17/2015] [Indexed: 12/16/2022] Open
Abstract
PURPOSE Appendiceal tumors are a heterogeneous group of diseases that include typical neuroendocrine tumors (TNET), goblet cell carcinoids (GCC), and atypical GCC. Atypical GCC are classified into signet-ring cell cancers (SRCC) and poorly differentiated appendiceal adenocarcinoids. The prognosis and management of these diseases is unclear because there are no prospective studies. The aim of this study is to assess the characteristics and outcome of appendiceal TNET, GCC, and SRCC patients. MATERIALS AND METHODS Appendiceal TNET, GCC, and SRCC patients diagnosed between 1973 and 2011 were identified in the Surveillance Epidemiology and End Results (SEER) database. Demographics, type of surgery, and clinicopathologic characteristics were collected. Survival functions were estimated by the Kaplan-Meier method, and log-rank test was used to assess the difference in overall survival (OS) among the three histologies. RESULTS The SEER database yielded 1,021 TNET patients, 1,582 with GCC, and 534 SRCC patients. TNET presented at a younger age (p < 0.001). Patients with SRCC presented with advanced stage disease (p < 0.001). The median OS (mOS) for GCC and TNET patients was not reached; mOS for SRCC was 24 months. Multivariate analysis stratified for stage revealed significantly longer survival for TNET and GCC than SRCC (p < 0.001). CONCLUSION This is the largest report to date for appendiceal neuroendocrine tumor patients, suggesting a spectrum of diseases with different characteristics and outcomes. In this report, we present a treatment approach for this complex spectrum of disease, based on the experience of Ohio State and Emory Universities investigators.
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Affiliation(s)
- Walid Shaib
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Kavya Krishna
- Division of Hematology Oncology, The Ohio State University, Columbus, OH, USA
| | - Sungjin Kim
- Department of Biostatistics, Emory University, Atlanta, GA, USA
| | | | - Jonathan Rock
- Department of Pathology, The Ohio State University, Columbus, OH, USA
| | - Zhengjia Chen
- Department of Biostatistics, Emory University, Atlanta, GA, USA
| | - Edith Brutcher
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Charles Iii Staley
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Samih Abdel-Missih
- Department of Surgical Oncology, The Ohio State University, Columbus, OH, USA
| | - Bassel F El-Rayes
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Tanios Bekaii-Saab
- Division of Hematology Oncology, The Ohio State University, Columbus, OH, USA
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Carcinoid Tumors. Surg Oncol 2015. [DOI: 10.1007/978-1-4939-1423-4_26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Abstract
BACKGROUND Neuroendocrine tumours (NETs) of the appendix are slow-growing tumours and, although rare, they are the most common gastrointestinal epithelial tumours in childhood and adolescence. The treatment and the follow-up screenings have not been standardised. In addition to this, although tumour size is considered the main prognostic variable to define the aggressiveness of approach, a precise cutoff needs to be established. METHODS A total of 113 patients younger than 18 years with a diagnosis of appendiceal NETs were registered as of January 1, 2000, until May 30, 2013, within the Rare Tumors in Pediatric Age (TREP) project, an Italian multi-institutional network dedicated to rare tumours in children and adolescents. The recommendations of the Rare Tumors in Pediatric Age study included imaging and laboratory investigations. The treatment after appendectomy was decided on the basis of histology, tumour size, and imaging; primary reexcision (PRE) was not recommended in completely excised tumours, regardless of tumour size and invasiveness. RESULTS A total of 113 of 113 patients had a diagnosis of well-differentiated NETs; in 108 of 113 the tumour was smaller than 2 cm and in 5, larger than 2 cm. Excision margins were free in 111 of 113 patients. In 3 of 113 a PRE was performed, and in 1 residual tumour was detected. All 113 of 113 patients are alive in complete remission (median follow-up of 41 months). CONCLUSIONS Reported data and our experience showed that no relapse or death occurred in children and adolescents affected by appendiceal NETs. Appendectomy alone should be considered curative for most patients, and a more aggressive surgical approach is warranted in the cases with incompletely excised tumours.
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