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Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1–2 cm in size: a retrospective, Europe-wide, pooled cohort study - 31/01/23

Doi : 10.1016/S1470-2045(22)00750-1 
Cédric Nesti, MD a, Konstantin Bräutigam, MD b, Marta Benavent, MD d, Laura Bernal, MD d, Hessa Boharoon, MD e, Johan Botling, MD f, Antonin Bouroumeau, MD h, Iva Brcic, MD j, Maximilian Brunner, MD l, Guillaume Cadiot, ProfMD m, Maria Camara, MD n, Emanuel Christ, ProfMD p, Thomas Clerici, MD q, Ashley K Clift, MBBS r, Hamish Clouston, MD s, Lorenzo Cobianchi, ProfMD t, u, Jarosław B Ćwikła, ProfMD v, Kosmas Daskalakis, ProfMD w, Andrea Frilling, ProfMD r, Rocio Garcia-Carbonero, ProfMD o, Simona Grozinsky-Glasberg, ProfMD x, Jorge Hernando, MD y, Valérie Hervieu, MD z, Johannes Hofland, MD aa, Pernille Holmager, MD ac, ad, Frediano Inzani, MD af, ah, Henning Jann, MD ai, Paula Jimenez-Fonseca, MD aj, Enes Kaçmaz, PhD ak, Daniel Kaemmerer, MD al, Gregory Kaltsas, ProfMD w, Branislav Klimacek, MD g, Ulrich Knigge, ProfMD ac, ad, ae, Agnieszka Kolasińska-Ćwikła, MD am, Walter Kolb, MD q, Beata Kos-Kudła, ProfMD an, Catarina Alisa Kunze, MD ao, Stefania Landolfi, MD ap, Stefano La Rosa, ProfMD aq, as, Carlos López López, MD at, Kerstin Lorenz, ProfMD au, Maurice Matter, ProfMD ar, Peter Mazal, ProfMD av, Claudia Mestre-Alagarda, MD aw, Patricia Morales del Burgo, MD ax, Els J M Nieveen van Dijkum, ProfMD ak, Kira Oleinikov, MD x, Lorenzo A Orci, MD i, Francesco Panzuto, MD ay, az, Marianne Pavel, ProfMD aaa, Marine Perrier, MD m, Henrik Mikael Reims, MD aab, Guido Rindi, ProfMD ag, ah, aad, Anja Rinke, MD aae, aaf, Maria Rinzivillo, MD az, Xavier Sagaert, ProfMD aag, Ilker Satiroglu au, Andreas Selberherr, MD aah, Alexander R Siebenhüner, MD aai, aaj, Margot E T Tesselaar, ProfMD aak, Michael J Thalhammer, ProfMD k, Espen Thiis-Evensen, MD aac, Christos Toumpanakis, ProfMD e, Timon Vandamme, MD aam, José G van den Berg, MD aal, Alessandro Vanoli, MD aan, aao, Marie-Louise F van Velthuysen, MD ab, Chris Verslype, ProfMD aap, Stephan A Vorburger, ProfMD aaq, Alessandro Lugli, ProfMD b, John Ramage, ProfMD aar, aas, Marcel Zwahlen, ProfPhD c, Aurel Perren, ProfMD b, *, Reto M Kaderli, MD a, *
a Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland 
b Institute of Pathology, University of Bern, Bern, Switzerland 
c Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland 
d Department of Medical Oncology, University Hospital Virgen del Rocío, Instituto de Biomedicina De Sevilla, Seville, Spain 
e Neuroendocrine Tumour Unit–ENETS Centre of Excellence, Royal Free Hospital London, London, UK 
f Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden 
g Department of Surgery, Endocrine Surgical Unit, Uppsala University, Uppsala, Sweden 
h Division of Clinical Pathology, Diagnostic Department, Geneva University Hospitals, Geneva, Switzerland 
i Division of Abdominal Surgery, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland 
j Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria 
k Department of Surgery, Division of Visceral and Transplant Surgery, Medical University of Graz, Graz, Austria 
l Department of Surgery, University Hospital of Friedrich-Alexander University Erlangen-Nuernberg, Erlangen, Germany 
m Service d’Hépato-gastroentérologie et d’Oncologie Digestive, Université Reims Champagne Ardenne, CHU de Reims, Reims, France 
n Pathology Department, Hospital Universitario 12 de Octubre, Imas12, UCM, Madrid, Spain 
o Oncology Department, Hospital Universitario 12 de Octubre, Imas12, UCM, Madrid, Spain 
p Department of Endocrinology, Diabetology and Metabolism, ENETS Center of Excellence, University Hospital of Basel, Basel, Switzerland 
q Klinik für Allgemein-, Viszeral-, Endokrin- und Transplantationschirurgie, Kantonsspital St Gallen, St Gallen, Switzerland 
r Department of Surgery and Cancer, Imperial College London, London, UK 
s Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK 
t Department of Clinical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 
u Department of General Surgery, IRCCS Policlinico San Matteo Fondazione, Pavia, Italy 
v Indywidualna Specjalistyczna Praktyka Lekarska, Warsaw, Poland 
w 1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian University of Athens, ENETS Center of Excellence, Athens, Greece 
x Neuroendocrine Tumor Unit, ENETS Center of Excellence, Department of Endocrinology and Metabolism, Hadassah Medical Organization and Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel 
y Medical Oncology Department, Vall d’Hebron University Hospital–Vall d’Hebron Institute of Oncology, Barcelona, Spain 
z Hospices Civils de Lyon, HEH, Lyon, France 
aa Department of Internal Medicine, Section of Endocrinology ENETS Center of Excellence and Erasmus Cancer Institute, Erasmus MC, Rotterdam, Netherlands 
ab Department of Pathology, Erasmus MC, Rotterdam, Netherlands 
ac ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark 
ad Department of Endocrinology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark 
ae Department of Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark 
af General Pathology, Department of Woman and Child Health Science and Public Health, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy 
ag Unit of Head and Neck, Lung, and Endocrine Pathology, Department of Woman and Child Health Science and Public Health, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy 
ah Roma European NeuroEndocrine Tumor Society Center of Excellence, Rome, Italy 
ai Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, Germany 
aj Department of Medical Oncology, Hospital Universitario Central de Asturias, ISPA, Oviedo, Spain 
ak Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands 
al Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany 
am The Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland 
an Department of Endocrinology and Neuroendocrine Neoplasms and Department of Endocrinology and Pathophysiology, Medical University of Silesia, Katowice, Poland 
ao Institute of Pathology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany 
ap Pathology Department, Vall d’Hebron University Hospital, Barcelona, Spain 
aq Institute of Pathology, Department of Laboratory Medicine and Pathology, University of Lausanne, Lausanne, Switzerland 
ar Department of Visceral Surgery, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland 
as Unit of Pathology, Department of Medicine and Surgery, University of Insubria, Varese, Italy 
at Medical Oncology Department, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain 
au Department of Visceral, Vascular, and Endocrine Surgery, Martin-Luther University of Halle-Wittenberg, Halle, Germany 
av Department of Clinical Pathology, Medical University of Vienna, General Hospital Vienna, Vienna, Austria 
aw Histopathology, Institute of Liver Studies, King’s College Hospital, London, UK 
ax Department of Pathology, Hospital Universitario Central de Asturias, Oviedo, Spain 
ay Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy 
az Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy 
aaa Department of Medicine 1, Friedrich Alexander University Erlangen–Nürnberg, Erlangen, Germany 
aab Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway 
aac Department of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway 
aad Section of Anatomic Pathology, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy 
aae Department of Gastroenterology and Endocrinology, UKGM, Marburg, Germany 
aaf Philipps University Marburg, Marburg, Germany 
aag Translational Cell & Tissue Research, KU Leuven, Leuven, Belgium 
aah Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria 
aai Klinik für Medizinische Onkologie und Hämatologie, Universitätsspital Zürich und Universität Zürich, Zurich, Switzerland 
aaj Departement Medizinische Onkologie, Kantonsspital Schaffhausen, Schaffhausen, Switzerland 
aak Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands 
aal Department of Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands 
aam University Hospital Antwerp, Edegem, Belgium 
aan Unit of Anatomic Pathology, Department of Molecular Medicine, University of Pavia, Pavia, Italy 
aao Unit of Anatomic Pathology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy 
aap Clinical Digestive Oncology, University Hospitals Leuven, Belgium 
aaq Surgical Department, Teaching Hospitals Emmental, Burgdorf, Switzerland 
aar University of Winchester, Winchester, UK 
aas Hampshire Hospital, Basingstoke, UK 

* Correspondence to: Dr Reto Martin Kaderli, Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland Department of Visceral Surgery and Medicine Inselspital Bern University Hospital University of Bern Bern CH-3010 Switzerland

Summary

Background

Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1–2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1–2 cm in size in patients with or without right-sided hemicolectomy.

Methods

In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1–2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693.

Findings

282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1–2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0–15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 –21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36–2·17]; p=0·71).

Interpretation

This study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1–2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort.

Funding

Swiss Cancer Research foundation.

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Vol 24 - N° 2

P. 187-194 - février 2023 Retour au numéro
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