Nesti Cédric, Bräutigam Konstantin, Benavent Marta, Bernal Laura, Boharoon Hessa, Botling Johan, Bouroumeau Antonin, Brcic Iva, Brunner Maximilian, Cadiot Guillaume, Camara Maria, Christ Emanuel, Clerici Thomas, Clift Ashley K, Clouston Hamish, Cobianchi Lorenzo, Ćwikła Jarosław B, Daskalakis Kosmas, Frilling Andrea, Garcia-Carbonero Rocio, Grozinsky-Glasberg Simona, Hernando Jorge, Hervieu Valérie, Hofland Johannes, Holmager Pernille, Inzani Frediano, Jann Henning, Jimenez-Fonseca Paula, Kaçmaz Enes, Kaemmerer Daniel, Kaltsas Gregory, Klimacek Branislav, Knigge Ulrich, Kolasińska-Ćwikła Agnieszka, Kolb Walter, Kos-Kudła Beata, Kunze Catarina Alisa, Landolfi Stefania, La Rosa Stefano, López Carlos López, Lorenz Kerstin, Matter Maurice, Mazal Peter, Mestre-Alagarda Claudia, Del Burgo Patricia Morales, van Dijkum Els J M Nieveen, Oleinikov Kira, Orci Lorenzo A, Panzuto Francesco, Pavel Marianne, Perrier Marine, Reims Henrik Mikael, Rindi Guido, Rinke Anja, Rinzivillo Maria, Sagaert Xavier, Satiroglu Ilker, Selberherr Andreas, Siebenhüner Alexander R, Tesselaar Margot E T, Thalhammer Michael J, Thiis-Evensen Espen, Toumpanakis Christos, Vandamme Timon, van den Berg José G, Vanoli Alessandro, van Velthuysen Marie-Louise F, Verslype Chris, Vorburger Stephan A, Lugli Alessandro, Ramage John, Zwahlen Marcel, Perren Aurel, Kaderli Reto M
Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Institute of Pathology, University of Bern, Bern, Switzerland.
Lancet Oncol. 2023 Feb;24(2):187-194. doi: 10.1016/S1470-2045(22)00750-1. Epub 2023 Jan 11.
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.
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.
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).
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.
Swiss Cancer Research foundation.
人们越来越意识到，对1-2厘米大小的阑尾神经内分泌肿瘤（NET）患者进行肿瘤切除可能存在全球范围内过度治疗的情况，但这种肿瘤的罕见性阻碍了至今明确的治疗建议的制定。我们旨在评估在接受或未接受右侧半结肠切除术的患者中，1-2厘米大小的阑尾NET的恶性潜能。
在这项回顾性队列研究中，我们汇总了来自15个欧洲国家40家医院的数据，这些数据涉及任何年龄且东部肿瘤协作组体能状态的患者，他们经组织病理学确诊为1-2厘米大小的阑尾NET，并且在2000年1月1日至2010年12月31日期间对原发性肿瘤进行了完整切除。患者要么仅接受阑尾切除术，要么接受阑尾切除并进行肿瘤学上的右侧半结肠切除术或回盲部切除术。预定义的主要结局是远处转移的频率和肿瘤相关死亡率。次要结局包括区域淋巴结转移的频率、区域淋巴结转移与组织病理学危险因素之间的关联，以及接受或未接受右侧半结肠切除术的总生存期。采用Cox比例风险回归来估计与单纯阑尾切除术相比，右侧半结肠切除术相关的相对全因死亡风险。本研究已在ClinicalTrials.gov注册，注册号为NCT03852693。
共识别出282例疑似阑尾肿瘤患者，其中278例为1-2厘米大小的阑尾NET患者被纳入研究。163例（59%）接受了阑尾切除术，115例（41%）接受了右侧半结肠切除术，110例（40%）为男性，168例（60%）为女性，初次手术时的平均年龄为36.0岁（标准差18.2）。中位随访时间为13.0年（四分位间距11.0-15.6）。经过集中的组织病理学检查，在278例有远处腹膜转移的患者中有2例（1%）以及在278例有肝脏远处转移的患者中有2例（1%），阑尾NET被分类为可能或很可能的原发性肿瘤。所有转移均为同步诊断，随访期间无肿瘤相关死亡。在有可用数据的112例接受右侧半结肠切除术的患者中，有22例（20%）发现区域淋巴结转移。根据组织病理学危险因素，我们估计接受阑尾切除术的患者中12.8%（95%置信区间6.5-21.1）可能有残留的区域淋巴结转移。阑尾切除术患者和右侧半结肠切除术患者的总生存期相似（调整后风险比0.88[95%置信区间0.36-2.17]；p=0.71）。
本研究提供的证据表明，对于1-2厘米大小的阑尾NET，在通过阑尾切除术完整切除后，无需进行右侧半结肠切除术；阑尾NET的区域淋巴结转移在临床上无关紧要；并且所呈现的结果不支持术后额外排除转移以及对危险因素进行组织病理学评估。这些发现应为该患者群体的共识最佳实践指南提供参考。
瑞士癌症研究基金会。
