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Razzaq S, Fatima I, Moafian Z, Rahdar A, Fathi-Karkan S, Kharaba Z, Shirzad M, Khan A, Pandey S. Nanomedicine innovations in colon and rectal cancer: advances in targeted drug and gene delivery systems. Med Oncol 2025; 42:113. [PMID: 40097759 DOI: 10.1007/s12032-025-02670-z] [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: 01/01/2025] [Accepted: 03/04/2025] [Indexed: 03/19/2025]
Abstract
Nanotechnology has revolutionized cancer diagnostics and therapy, offering unprecedented possibilities to overcome the constraints of conventional treatments. This study provides a detailed overview of the current progress and difficulties in the creation of nanostructured materials, with a specific emphasis on their use in drug and gene delivery systems. The study examines tactics that attempt to improve the effectiveness and safety of chemotherapeutic drugs such as doxorubicin (Dox) by focusing on the potential of antibody-drug conjugates and functionalized nanoparticles. Moreover, it clarifies the challenges encountered in administering nanoparticles orally for gastrointestinal treatments, emphasizing the crucial physicochemical properties that affect their behavior in the gastrointestinal system. This study highlights the transformational potential of nanostructured materials in precision oncology by examining advanced breakthroughs such cell membrane-camouflaged nanoparticles and inorganic nanoparticles designed for gastrointestinal disorders. The text investigates the processes involved in the absorption of nanoparticles and their destruction in lysosomes, revealing the many methods in which enterocytes take up these particles. This study strongly supports the use of advanced nanoparticle-based methods to reduce the harmful effects on the whole body and improve the effectiveness of therapy, based on a thorough examination of current experiments on animals and humans. The main objective of this paper is to provide a fundamental comprehension that will stimulate more investigation and practical use in the field of cancer nanomedicine, advancing its boundaries.
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Affiliation(s)
- Sobia Razzaq
- School of Pharmacy, University of Management and Technology, Lahore, Punjab, Pakistan
| | - Iqra Fatima
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, 45320, Pakistan
| | - Zeinab Moafian
- Department of Chemistry and Biochemistry, University of Delaware, Newark, USA
| | - Abbas Rahdar
- Department of Physics, Faculty of Sciences, University of Zabol, Zabol, 538-98615, Iran.
| | - Sonia Fathi-Karkan
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, 94531-55166, Iran.
- Department of Advanced Sciences and Technologies in Medicine, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, 9414974877, Iran.
| | - Zelal Kharaba
- Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, UAE
| | - Maryam Shirzad
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ahmad Khan
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
| | - Sadanand Pandey
- School of Bioengineering and Food Technology, Faculty of Applied Sciences and Biotechnology, Shoolini University, Solan, 173229, Himachal Pradesh, India.
- Department of Chemistry, College of Natural Science, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk, 38541, Republic of Korea.
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Zhang Z, Liu C. EMR-C is safe and efficient for rectal neuroendocrine tumor, and easily manageable for novice endoscopists of digestive endoscopy center. Discov Oncol 2025; 16:251. [PMID: 40019663 PMCID: PMC11871194 DOI: 10.1007/s12672-025-01886-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 02/03/2025] [Indexed: 03/01/2025] Open
Abstract
OBJECTIVE The objective of this study was to evaluate the effectiveness and safety of endoscopic mucosal resection assisted by a transparent cap (EMR-C) for rectal neuroendocrine tumor (R-NET) by novice endoscopists of digestive endoscopy center. METHODS R-NET patients consulted in department of digestive endoscopy center of Guangdong Provincial Peolple's Hospital from 2022 to 2023, were recruited in this study. Novice endoscopists who had no ESD experience before were randomly to accomplish the EMR-C operation. Each novice endoscopist separately completed at least 3 cases after simple training by teachers and the operation time was counted on average. Vertical and horizontal margins of the specimens were further analyzed to determine whether radical resection was successful or not. R-NET patients were followed up at 12 months after operation. RESULTS 30 cases of R-NET patients (13 males and 17 females, (53.83 ± 13.31) y), originated from the deep or submucosal layers of the intestinal wall mucosa by ultrasound colonoscopy, were recruited in all of our study. 10 novice endoscopists (each for 3 cases) were arranged to complete EMR-C operations by 2 teachers. The average time was (8.87 ± 1.87) minutes and the sections were clean and no bleeding and further clipped by 2-4 metal clips. Pathological and immunohistochemical results were further made to confirm the diagnosis. The en bloc resection rate was 100.00% and the R0 rate was 83.33% (horizontal margins were 100.00% negative and the vertical margins were 83.33% negative). No recurrence was found during the followed up at 12 months after operation. CONCLUSIONS EMR-C is safe and efficient for R-NET, and easily manageable for novice endoscopists of digestive endoscopy center.
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Affiliation(s)
- Zefeng Zhang
- Department of Digestive Endoscopy Center, Guangdong Provincial Peolple's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan Second Road, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Chao Liu
- Department of Pathology, Guangdong Provincial Peolple's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, Guangdong, People's Republic of China.
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Wang F, Mu HF, Wang C, Tang Y, Si MY, Peng J. LncRNA PCAT6 promotes progression and metastasis of colonic neuroendocrine carcinoma via MAPK pathway. World J Gastrointest Oncol 2025; 17:96230. [PMID: 39958556 PMCID: PMC11755991 DOI: 10.4251/wjgo.v17.i2.96230] [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: 04/30/2024] [Revised: 09/18/2024] [Accepted: 12/02/2024] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND Colonic neuroendocrine carcinomas (NECs) are highly malignant and invasive with poor prognosis. Long noncoding RNAs (LncRNAs) participate in the tumorigenesis and metastasis of multiple cancers. AIM To detect the roles and mechanisms of lncRNA prostate cancer associated transcript 6 (PCAT6) in the progression of colonic NEC. METHODS Human NEC and adjacent normal samples were collected for immunohistochemistry staining of CgA and real-time quantitative polymerase chain reaction (RT-qPCR) of PCAT6 mRNA level. Subcutaneous xenograft tumor model and lung metastasis model were established in nude mice. The lung tissues were stained by hematoxylin and eosin to assess pulmonary metastasis. The expression of epithelial-mesenchymal transition (EMT)-related markers and pathway-related genes was measured by RT-qPCR and western blotting. CD56 expression was assessed by immunofluorescence staining. The biological functions of PCAT6 were examined by cell counting kit-8, colony formation assays, Transwell assays and wound healing assays. The interaction between PCAT6 and its potential downstream target was verified by luciferase reporter assays. RESULTS LncRNA PCAT6 was upregulated in human NEC samples and LCC-18 cells, and its high expression was positively correlated with poor prognosis in patients with colonic NEC. Additionally, the expression of PCAT6 was positively associated with the proliferation, migration, invasion, and EMT of LCC-18 cells. Moreover, PCAT6 facilitated tumor growth, lung metastasis and EMT in xenografts. Mechanistically, PCAT6 promoted the activation of MAPK to enhance the EMT in colonic NEC by targeting miR-326. CONCLUSION In conclusion, lncRNA PCAT6 accelerates the process of colonic NEC by activating ERK/p38 MAPK signaling through targeting miR-326. These results might provide useful information for exploring the potential therapeutic targets in colonic NEC.
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Affiliation(s)
- Fei Wang
- Department of General Surgery, Nanjing Tongren Hospital, Nanjing 211100, Jiangsu Province, China
| | - Hai-Feng Mu
- Department of General Surgery, Nanjing Tongren Hospital, Nanjing 211100, Jiangsu Province, China
| | - Chun Wang
- Department of General Surgery, Nanjing Tongren Hospital, Nanjing 211100, Jiangsu Province, China
| | - Yue Tang
- Department of General Surgery, Nanjing Tongren Hospital, Nanjing 211100, Jiangsu Province, China
| | - Ming-Yuan Si
- Department of Pathology, Nanjing Tongren Hospital, Nanjing 211100, Jiangsu Province, China
| | - Jing Peng
- Department of General Surgery, Nanjing Tongren Hospital, Nanjing 211100, Jiangsu Province, China
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Nassar M, Baraka B, Talal AH. Innovative approaches in predicting outcomes for rectal neuroendocrine tumors. World J Gastroenterol 2025; 31:100517. [PMID: 39958439 PMCID: PMC11752703 DOI: 10.3748/wjg.v31.i6.100517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 11/05/2024] [Accepted: 12/09/2024] [Indexed: 01/10/2025] Open
Abstract
Rectal neuroendocrine neoplasms pose significant challenges due to their varied presentations and prognoses. Traditional prognostic models, while useful, often fall short of accurately predicting clinical outcomes for these patients. This article discusses the development and implications of a novel prognostic tool, the GATIS score, which aims to enhance predictive accuracy and guide treatment strategies more effectively than current methods. Utilizing data from a large cohort and employing sophisticated statistical models, the GATIS score integrates clinical and pathological markers to provide a nuanced assessment of prognosis. We evaluate the potential of this score to transform clinical decision-making processes, its integration into current medical practices, and future directions for its development. The integration of genetic markers and other biomarkers could further refine its predictive power, highlighting the ongoing need for innovation in the management of rectal neuroendocrine neoplasms.
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Affiliation(s)
- Mahmoud Nassar
- Department of Internal Medicine, Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY 14221, United States
- Department of Research, American Society for Inclusion, Diversity, and Equity in Healthcare, Lewes, DE 19958, United States
| | - Bahaaeldin Baraka
- Medical Oncologist, Oncology, Nottingham University Hospitals, City Hospital, Nottingham NG5 1PB, United Kingdom
| | - Andrew H Talal
- Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY 14203, United States
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Li L, Chen Z, Zhu D, Lv Q, Zhang T, Lai J. Primary small rectal neuroendocrine tumor with pelvic lateral lymph nodes metastasis: A case report and review of literature. Int J Surg Case Rep 2025; 127:110963. [PMID: 39889652 PMCID: PMC11834123 DOI: 10.1016/j.ijscr.2025.110963] [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: 12/23/2024] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 02/03/2025] Open
Abstract
INTRODUCTION AND IMPORTANCE Neuroendocrine tumors (NETs) can occur in almost any organ of the body, and they vary in size and volume. The small tumors may be <1 cm in size, but the large ones can exceed 20 cm. The probability of developing NETs in different organs varies greatly, but rectal NETs are relatively common. Our aim is to tell the surgeon that rectal NETs metastasize to the pelvic lateral lymph nodes even in the early stages and small sizes. CASE PRESENTATION In this report, we present the case of a 47-year-old man who was asymptomatic and incidentally diagnosed with a small NET in the rectum during an enteroscopy for physical examination. The diagnosis was confirmed by pathological examination of the biopsy. The CT of the patient was performed pre-hospital for daily physical examination, but nothing could be seen in the rectum from the CT. Then, the diagnostic local resection and a wide free margin was performed on the patient, and a second operation (radical resection of rectal cancer and extensive lateral pelvic lymphadenectomy) was performed due to the post-operative pathological report and the discovery of enlarged pelvic lymph node by PET-CT (positron emission tomography CT). After the surgery, the patient is in good condition and have no other symptoms except for a slight feeling of defecating. CLINICAL DISCUSSION NETs could metastasize to the pelvic lateral lymph nodes, if so, the Total mesorectal excision (TME) should be performed, and the invasion and metastatic spread in NETs have to do with the regulatory factor named snail1 and Foxc2. We find that there is no standardized treatment approach for rectal NETs, which should be neither overtreated nor undertreated as far as possible, so the timing of surgery plays an important role, and long-term follow-up of the patients is extremely important. CONCLUSION The purpose of the presentation of this case is to highlight the potential for rectal NETs to metastasize to the pelvic lateral lymph nodes even in the early stages and small sizes, without muscular layer or neurovascular invasion, and lateral lymph node dissection were necessary, emphasizing the importance of timing for surgery.
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Affiliation(s)
- Lihong Li
- Department of Gastrointestinal surgery, Shunde Women and Children's Hospital of Guangdong Medical University (Maternal & Child Healthcare Hospital of Shunde Foshan), Foshan 528300, China
| | - Ziyue Chen
- Postgraduate of Guangdong Medical University, Zhanjiang 524002, China
| | - Dajian Zhu
- Department of Gastrointestinal surgery, Shunde Women and Children's Hospital of Guangdong Medical University (Maternal & Child Healthcare Hospital of Shunde Foshan), Foshan 528300, China.
| | - Qianbao Lv
- Department of Gynaecology, Shunde Women and Children's Hospital of Guangdong Medical University (Maternal & Child Healthcare Hospital of Shunde Foshan), Foshan 528300, China
| | - Tianpeng Zhang
- Department of Gastrointestinal surgery, Shunde Women and Children's Hospital of Guangdong Medical University (Maternal & Child Healthcare Hospital of Shunde Foshan), Foshan 528300, China
| | - Jinsong Lai
- Department of Gastrointestinal surgery, Shunde Women and Children's Hospital of Guangdong Medical University (Maternal & Child Healthcare Hospital of Shunde Foshan), Foshan 528300, China
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Lou Y, Chen H, Fei SJ, He QH, Pan Q. Ectopic corticotropin-releasing hormone syndrome caused by rectal large cell neuroendocrine carcinoma: a rare case report. Ther Adv Endocrinol Metab 2024; 15:20420188241305026. [PMID: 39669530 PMCID: PMC11635862 DOI: 10.1177/20420188241305026] [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] [Received: 04/30/2024] [Accepted: 11/18/2024] [Indexed: 12/14/2024] Open
Abstract
Ectopic corticotropin-releasing hormone (CRH) syndrome, a rare subtype of adrenocorticotropic hormone-dependent Cushing syndrome, is associated with tumors of diverse origins. Here, we present a case of a 37-year-old female diagnosed with ectopic CRH syndrome secondary to rectal large cell neuroendocrine carcinoma, a hitherto unprecedented site for CRH-secreting tumors. The patient presented with classical features of Cushing syndrome, supported by laboratory evidence of hypercortisolemia and disrupted diurnal cortisol secretion. Imaging studies ruled out a pituitary adenoma, whereas colonoscopy identified a rectal malignancy. Immunohistochemical staining confirmed the presence of ectopic CRH syndrome. Despite prompt chemotherapy initiation, the patient's condition rapidly deteriorated, highlighting the aggressive nature and dismal prognosis associated with rectal large cell neuroendocrine carcinoma linked to ectopic CRH syndrome. This case underscores the importance of early recognition and comprehensive management to optimize patient outcomes.
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Affiliation(s)
- Yuan Lou
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Huan Chen
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Si-Jia Fei
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Qing-Hua He
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Qi Pan
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 Dahua Road, Dongcheng District, Beijing 100730, China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
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Xu S, Zhai ZY, Zhou P, Xue XF, Huang ZY, Li XX, Yang GH, Bao CJ, You LJ, Cui XB, Xia GL, Ou Yang MP, Li LF, Lu L, Gong W, Pei XJ, Hu W. Whole-exome sequencing reveals novel genomic signatures and potential therapeutic targets during the progression of rectal neuroendocrine neoplasm. Cell Death Dis 2024; 15:833. [PMID: 39548061 PMCID: PMC11568169 DOI: 10.1038/s41419-024-07232-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 11/01/2024] [Accepted: 11/07/2024] [Indexed: 11/17/2024]
Abstract
Rectal neuroendocrine neoplasms (rNENs) are among the most frequent gastrointestinal neuroendocrine neoplasms and pose a serious challenge for clinical management. The size of the primary neoplasm is considered to be the most important predictor of disease progression, but the genetic alterations that occur during the progression of rNENs remain unknown. Here, we performed a comprehensive whole-exome sequencing study on 54 tumor-normal paired, formalin-fixed paraffin-embedded specimens from patients locally diagnosed with rNENs. Of these, 81.5% (n = 44) were classified as small-sized (≤2 cm) rNENs, while the remainder (18.5%, n = 10) were classified as large-sized (>2 cm) rNEN samples. Comparative analysis revealed marked disparities in the mutational landscape between small- and large-sized rNEN samples, and between large-sized rNEN samples with or without lymph node metastases. The high-confidence driver genes RHPN2, MUC16, and MUC4 were significantly mutated in both small- and large-sized rNEN specimens, whereas mutations in MAN2A1, and BAG2 were only identified in large-sized specimens diagnosed with lymph node metastases. Correspondingly, we observed that the mTOR and MAPK pathways were preferentially enriched in the large-sized rNEN specimens. Signature-based analysis revealed that mutational processes associated with defective DNA base excision repair (SBS30) significantly accumulated in large-sized rNEN samples with lymph node metastases, highlighting the important role of this mutagenic process in promoting rNEN progression. We further found that most rNEN subjects, regardless of tumor size, harbored at least one alteration with targeted therapeutic implications. Taken together, these results elucidate the genetic features associated with tumor size and lymphatic metastasis in rNEN patients, which will deepen our understanding of the genetic changes during rNEN progression and potentially directing improvements in rNEN treatment strategies.
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Affiliation(s)
- Shi Xu
- Department of Burn and Plastic Surgery, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong, China
- Department of Medical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong, China
| | - Zhi Yong Zhai
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China
| | - Ping Zhou
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China
| | - Xiu Fen Xue
- Department of Pathology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Zhao Yu Huang
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China
| | - Xia Xi Li
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Gen Hua Yang
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Chong Ju Bao
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Li Juan You
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Xiao Bing Cui
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Gui Li Xia
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Mei Ping Ou Yang
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Long Fei Li
- Institute of Chinese Medicine, State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
| | - Lan Lu
- Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, Sichuan, China
| | - Wei Gong
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China.
| | - Xiao Juan Pei
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China.
- Department of Pathology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.
| | - Wei Hu
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.
- The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China.
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Li K, Chen T, Duan B, Ji Y, Li J, Xu M. A retrospective analysis of 26 cases of duodenal neuroendocrine tumor treated by endoscopic submucosal dissection. Indian J Cancer 2024; 61:849-857. [PMID: 39960722 DOI: 10.4103/ijc.ijc_265_24] [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: 04/08/2024] [Accepted: 01/10/2025] [Indexed: 04/11/2025]
Abstract
BACKGROUND Duodenal neuroendocrine tumors (D-NETs) are rare but clinically significant tumors that can occur in various parts of the duodenum, including the duodenal papilla. Endoscopic submucosal dissection (ESD) has emerged as a minimally invasive treatment option for D-NETs, offering potential advantages in terms of tumor removal and postoperative recovery. We aimed to retrospectively analyze the clinical characteristics and prognosis of ESD for D-NETs. METHODS A total of 26 cases of duodenal neuroendocrine tumors (27 lesions), including duodenal papillary neuroendocrine tumors, were studied retrospectively. RESULTS A total of 26 patients with D-NETs (27 lesions) were pathologically diagnosed, and 27 lesions were found by chance during endoscopy. The lesions included duodenal bulbar, descending part, and duodenal papilla. Nineteen tumors were <1 cm (70.4%) in diameter, and eight tumors were 1-2 cm (29.6%) in diameter. There were five cases of duodenal papilla NETs. G1: 24 (88.8%) and G2: 3 (11.1%). Endoscopic ultrasonography showed that 27 lesions were confined to the submucosa. One case was a neuroendocrine tumor 2 mm inside a tubular adenoma at the papilla. All operations were performed by senior doctors in the department. The total resection rate was 100%, and the incidence of intraoperative bleeding and perforation was 0. Delayed bleeding and perforation were 0. The shortest operation time was 25 min, and the longest was 70 min. Burning tumor cells at the basal resection margin were noted in 11 lesions, necessitating careful pathological assessment. There were 24 cases of G1 type and 3 cases of G2 type. All 26 patients underwent abdominal CT before operation to confirm the absence of lymph node and distal metastasis. One patient with papillary lesion had positive lesion base resection and was treated with additional operation. Temporary biliary and pancreatic duct stents were placed before or after ESD in all five cases of duodenal papillary lesions, and no biliary and pancreatic complications occurred after surgery. Postoperative follow-up gastroscopy and abdominal CT confirmed no recurrence or metastasis during a follow-up period of 3 months to 4.5 years. There was no recurrence or metastasis during a follow-up period of 3 months to 4 ½ years. CONCLUSION ESD may be an effective and safe intervention for D-NETs ≤20 mm confined to the mucosa or submucosa of the duodenum, including the papilla. Clinicians should remain vigilant about potential complications during and after surgery. Duodenal ESD treatment NET has high requirements in terms of treatment technology, and clinicians should pay attention to the potential complications of ESD during operation.
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Affiliation(s)
- Kehan Li
- Endoscopy Center Department of Gastroenterology, Shanghai East Hospital, Shanghai, China
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Li R, Li X, Wang Y, Chang C, Lv W, Li X, Cao D. Risk factors for regional lymph node metastasis in rectal neuroendocrine tumors: a population-based study. Front Med (Lausanne) 2024; 11:1383047. [PMID: 39296902 PMCID: PMC11408165 DOI: 10.3389/fmed.2024.1383047] [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] [Received: 02/06/2024] [Accepted: 08/22/2024] [Indexed: 09/21/2024] Open
Abstract
Introduction The identification of risk factors for regional lymph node (r-LN) metastasis in rectal neuroendocrine tumors (R-NETs) remains challenging. Our objective was to investigate the risk factors associated with patients diagnosed with R-NETs exhibiting r-LN metastasis. Methods Patient information was obtained from the Surveillance, Epidemiology, and End Results (SEER) database, complemented by data from the West China Hospital (WCH) databases. The construction cohort comprised patients diagnosed with R-NETs from the SEER database, while cases from the WCH database were utilized as the validation cohort. A novel nomogram was developed to predict the probability of r-LN metastasis, employing a logistic regression model. Results Univariate analysis identified four independent risk factors associated with poor r-LN metastasis: age (HR = 1.027, p < 0.05), grade (HR = 0.010, p < 0.05), T stage (HR = 0.010, p < 0.05), and tumor size (HR = 0.005, p < 0.05). These factors were selected as predictors for nomogram construction. Discussion The novel nomogram serves as a reliable tool for predicting the risk of r-LN metastasis, providing clinicians with valuable assistance in identifying high-risk patients and tailoring individualized treatments.
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Affiliation(s)
- Ruizhen Li
- Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaofen Li
- Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yan Wang
- Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chen Chang
- Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wanrui Lv
- Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaoying Li
- Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Dan Cao
- Abdominal Oncology Ward, Division of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Hayasaka J, Miura Y, Yamashita S, Matsui A, Kikuchi D, Takazawa Y, Hoteya S. Traction Devices May Not Affect the Vertical Margin Distance in the Endoscopic Submucosal Dissection of Rectal Neuroendocrine Tumors. Cureus 2024; 16:e58976. [PMID: 38800345 PMCID: PMC11127712 DOI: 10.7759/cureus.58976] [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: 04/24/2024] [Indexed: 05/29/2024] Open
Abstract
Introduction The usefulness of traction devices (TDs) in endoscopic submucosal dissection (ESD) for rectal neuroendocrine tumors (NETs) has not been reported. The aim of this study was to investigate the impact of using a TD on the vertical margin (VM) distance in the ESD of rectal NETs. Methods In this single-center, retrospective study, we included patients with rectal NETs who were treated with ESD during 2013-2023. They were divided into TD and non-TD groups. One pathologist remeasured the VM distance (primary outcome) and the depth of submucosal invasion (SM depth). Secondary outcomes were margins, resection time, delayed bleeding, and perforation. First, we performed propensity score matching (PSM) to assess the usefulness of TD for VM distance. Then, we used multiple regression analysis to identify factors affecting the VM distance. Results The TD and non-TD groups comprised 24 and 117 lesions, respectively. Patients in the TD group were significantly younger than those in the non-TD group (P = 0.003). In the TD and non-TD groups, the VM distance was 150 μm and 100 μm, respectively (P = 0.70). Only resection time significantly differed between groups, shorter in the TD group (P = 0.005). Twenty-two cases in each group were matched after PSM, yielding no significant differences in VM distance. The use of a TD was not an independent predictor of VM distance (P = 0.65), but age (P < 0.001) and SM depth (P = 0.003) were. Conclusion Using a TD does not seem to affect the VM distance in ESD for rectal NETs.
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Affiliation(s)
| | | | | | - Akira Matsui
- Gastroenterology, Toranomon Hospital, Tokyo, JPN
| | | | | | - Shu Hoteya
- Gastroenterology, Toranomon Hospital, Tokyo, JPN
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Chacchi-Cahuin R, Despott EJ, Lazaridis N, Rimondi A, Fusai GK, Mandair D, Anderloni A, Sciola V, Caplin M, Toumpanakis C, Murino A. Endoscopic Management of Gastro-Entero-Pancreatic Neuroendocrine Tumours: An Overview of Proposed Resection and Ablation Techniques. Cancers (Basel) 2024; 16:352. [PMID: 38254841 PMCID: PMC10814323 DOI: 10.3390/cancers16020352] [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: 11/22/2023] [Revised: 01/06/2024] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
A literature search of MEDLINE/PUBMED was conducted with the aim to highlight current endoscopic management of localised gastro-entero-pancreatic NETs. Relevant articles were identified through a manual search, and reference lists were reviewed for additional articles. The results of the research have been displayed in a narrative fashion to illustrate the actual state-of-the-art of endoscopic techniques in the treatment of NETs. Localised NETs of the stomach, duodenum and rectum can benefit from advanced endoscopic resection techniques (e.g., modified endoscopic mucosal resection, endoscopic full thickness resection, endoscopic submucosal dissection) according to centre expertise. Radiofrequency thermal ablation can be proposed as an alternative to surgery in selected patients with localised pancreatic NETs.
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Affiliation(s)
- Rocio Chacchi-Cahuin
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
| | - Edward J. Despott
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
| | - Nikolaos Lazaridis
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
| | - Alessandro Rimondi
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
| | - Giuseppe Kito Fusai
- Department of HPB Surgery and Liver Transplant, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK
| | - Dalvinder Mandair
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London NW3 2QG, UK
| | - Andrea Anderloni
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | - Valentina Sciola
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milano, 20122 Milan, Italy;
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London NW3 2QG, UK
| | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London NW3 2QG, UK
| | - Alberto Murino
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
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Stumpo S, Formelli MG, Persano I, Parlagreco E, Lauricella E, Rodriquenz MG, Guerrera LP, Zurlo IV, Campana D, Brizzi MP, Cives M, La Salvia A, Lamberti G. Extrapulmonary Neuroendocrine Carcinomas: Current Management and Future Perspectives. J Clin Med 2023; 12:7715. [PMID: 38137784 PMCID: PMC10743506 DOI: 10.3390/jcm12247715] [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: 11/04/2023] [Revised: 12/07/2023] [Accepted: 12/12/2023] [Indexed: 12/24/2023] Open
Abstract
Neuroendocrine carcinomas (NECs) are poorly differentiated and highly aggressive epithelial neuroendocrine neoplasms. The most common primary site is the lung, but they may arise in every organ. Approximately 37% of extrapulmonary NECs (EP-NECs) occur in the gastroenteropancreatic (GEP) tract, followed by the genitourinary (GU) system and gynecological tract. As a result of their rarity, there is scant evidence to guide treatment recommendations, and a multidisciplinary approach is essential for the management of such patients. Platinum-based chemotherapy currently represents the standard of care for EP-NECs of any site, mirroring the management of small-cell lung cancer (SCLC), but further approaches are still under investigation. Indeed, ongoing trials evaluating targeted therapies, immune checkpoint inhibitors (ICIs), and radionuclide therapy could provide potentially breakthrough therapeutic options. Given the relative dearth of evidence-based literature on these orphan diseases, the aim of this review is to provide an overview of the pathology and current treatment options, as well as to shed light on the most pressing unmet needs in the field.
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Affiliation(s)
- Sara Stumpo
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum–University of Bologna, Via Zamboni 33, 40126 Bologna, Italy; (S.S.); (M.G.F.); (D.C.); (G.L.)
| | - Maria Giovanna Formelli
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum–University of Bologna, Via Zamboni 33, 40126 Bologna, Italy; (S.S.); (M.G.F.); (D.C.); (G.L.)
| | - Irene Persano
- Medical Oncology, AO S. Croce e Carle, 12100 Cuneo, Italy; (I.P.); (E.P.)
| | - Elena Parlagreco
- Medical Oncology, AO S. Croce e Carle, 12100 Cuneo, Italy; (I.P.); (E.P.)
| | - Eleonora Lauricella
- Medical Oncology Unit, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, 70124 Bari, Italy; (E.L.); (M.C.)
| | - Maria Grazia Rodriquenz
- Oncology Unit, Ospedale IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy;
| | - Luigi Pio Guerrera
- Division of Medical Oncology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
- Sarcomas and Rare Tumors Unit, Istituto Nazionale Tumori, IRCCS-Fondazione “G. Pascale”, 80131 Naples, Italy
| | | | - Davide Campana
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum–University of Bologna, Via Zamboni 33, 40126 Bologna, Italy; (S.S.); (M.G.F.); (D.C.); (G.L.)
- Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via P. Albertoni 15, 40138 Bologna, Italy
| | - Maria Pia Brizzi
- Department of Oncology, A.O.U. San Luigi Gonzaga Hospital, 10043 Orbassano, Italy;
| | - Mauro Cives
- Medical Oncology Unit, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, 70124 Bari, Italy; (E.L.); (M.C.)
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70121 Bari, Italy
| | - Anna La Salvia
- National Center for Drug Research and Evaluation, National Institute of Health (ISS), 00161 Rome, Italy
| | - Giuseppe Lamberti
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum–University of Bologna, Via Zamboni 33, 40126 Bologna, Italy; (S.S.); (M.G.F.); (D.C.); (G.L.)
- Medical Oncology Unit, Vito Fazzi Hospital, 73100 Lecce, Italy;
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Wan M, Wu J, Jiang Z, Gong W, Zhou X. Risk of second primary cancers in patients with rectal neuroendocrine neoplasms: a surveillance, epidemiology, and end results analysis. Front Oncol 2023; 13:1248268. [PMID: 37790754 PMCID: PMC10543235 DOI: 10.3389/fonc.2023.1248268] [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] [Received: 08/02/2023] [Accepted: 08/21/2023] [Indexed: 10/05/2023] Open
Abstract
Background While an elevated risk of second primary cancers (SPCs) has been observed in many other cancers, risk of SPCs has not been quantified in patients with rectal neuroendocrine neoplasms (NENs). Methods Survivors of primary rectal NENs diagnosed between 2000 and 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER)-18 registries. Relative risk of SPCs was estimated as the standardized incidence ratio (SIR), which was calculated using SEER*Stat software. Results Between 2000 and 2018, a total of 15836 patients diagnosed with rectal NENs, of whom 1436 (9.1%) received diagnosis of SPCs (SIR: 1.19, 95%CI: 1.13-1.26). The majority of patients were aged 50-69 and had their first cancer diagnosed at the localized stage. Male survivors had a higher propensity for developing SPCs overall, while female survivors exhibited higher risks of specific SPCs. Age at diagnosis of rectal NENs influenced the risk of SPCs, with younger patients having greater risks. A statistically significant increase in the incidence of SPCs was observed among patients aged 30-64 years. Black patients had higher relative risks of certain SPCs, while White patients had a lower risk of subsequent melanoma. Trend analysis revealed that the highest excess burden of SPCs was observed in the years 2000 to 2002. Risk of SPCs remained elevated within the first four years post-diagnosis for survivors of rectal NENs, but diminished thereafter. Conclusion The study revealed that individuals who survived rectal NENs were at an elevated risk of developing SPCs compared to the general population. Our results hold important implications for the formulation of lifelong surveillance recommendations for cancer survivors.
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Affiliation(s)
| | | | | | | | - Xianli Zhou
- In-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Surgeons’ Hall, Harbin, Heilongjiang, China
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Vogele D, Schmidt SA, Gnutzmann D, Thaiss WM, Ettrich TJ, Kornmann M, Beer M, Juchems MS. Gastroenteropancreatic Neuroendocrine Tumors-Current Status and Advances in Diagnostic Imaging. Diagnostics (Basel) 2023; 13:2741. [PMID: 37685279 PMCID: PMC10486652 DOI: 10.3390/diagnostics13172741] [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: 07/17/2023] [Revised: 08/16/2023] [Accepted: 08/21/2023] [Indexed: 09/10/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) is a heterogeneous and complex group of tumors that are often difficult to classify due to their heterogeneity and varying locations. As standard radiological methods, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT) are available for both localization and staging of NEN. Nuclear medical imaging methods with somatostatin analogs are of great importance since radioactively labeled receptor ligands make tumors visible with high sensitivity. CT and MRI have high detection rates for GEP-NEN and have been further improved by developments such as diffusion-weighted imaging. However, nuclear medical imaging methods are superior in detection, especially in gastrointestinal NEN. It is important for radiologists to be familiar with NEN, as it can occur ubiquitously in the abdomen and should be identified as such. Since GEP-NEN is predominantly hypervascularized, a biphasic examination technique is mandatory for contrast-enhanced cross-sectional imaging. PET/CT with somatostatin analogs should be used as the subsequent method.
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Affiliation(s)
- Daniel Vogele
- Department of Diagnostic and Interventional Radiology, Ulm University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (S.A.S.); (W.M.T.); (M.B.)
| | - Stefan A. Schmidt
- Department of Diagnostic and Interventional Radiology, Ulm University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (S.A.S.); (W.M.T.); (M.B.)
| | - Daniel Gnutzmann
- Department of Diagnostic and Interventional Radiology, Konstanz Hospital, Mainaustraße 35, 78464 Konstanz, Germany; (D.G.); (M.S.J.)
| | - Wolfgang M. Thaiss
- Department of Diagnostic and Interventional Radiology, Ulm University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (S.A.S.); (W.M.T.); (M.B.)
- Department of Nuclear Medicine, Ulm University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany
| | - Thomas J. Ettrich
- Department of Internal Medicine I, Ulm University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany;
- i2SouI—Innovative Imaging in Surgical Oncology Ulm, University Hospital of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany;
| | - Marko Kornmann
- i2SouI—Innovative Imaging in Surgical Oncology Ulm, University Hospital of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany;
- Department of General and Visceral Surgery, Ulm University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany
| | - Meinrad Beer
- Department of Diagnostic and Interventional Radiology, Ulm University Medical Center, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (S.A.S.); (W.M.T.); (M.B.)
- i2SouI—Innovative Imaging in Surgical Oncology Ulm, University Hospital of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany;
| | - Markus S. Juchems
- Department of Diagnostic and Interventional Radiology, Konstanz Hospital, Mainaustraße 35, 78464 Konstanz, Germany; (D.G.); (M.S.J.)
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Zhao F, Huang L, Wang Z, Wei F, Xiao T, Liu Q. Epidemiological trends and novel prognostic evaluation approaches of patients with stage II-IV colorectal neuroendocrine neoplasms: A population-based study with external validation. Front Endocrinol (Lausanne) 2023; 14:1061187. [PMID: 36817582 PMCID: PMC9928741 DOI: 10.3389/fendo.2023.1061187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 01/16/2023] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE This study aimed to clarify the incidence trend of all-stage colorectal neuroendocrine neoplasms (CRNENs), overall survival (OS), and disease-specific survival (DSS) of patients with stage II-IV CRNENs, and to establish relevant nomograms for risk stratification. METHODS Among all patients diagnosed with CRNENs in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2019, temporal trends in incidence were assessed. Clinical data of 668 patients with stage II-IV CRNENs from 2010 to 2016 were extracted for survival analysis. Patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Univariate and multivariate cox regression analyses were utilized to identify independent prognostic factors affecting OS outcomes. Competing risk analysis was applied to investigate risk factors related to the DSS of CRNENs. Two nomograms specifically for OS and DSS were developed for patients with stage II-IV CRNENs, their prognostic capabilities were evaluated using calibration curves, receiver operating characteristic (ROC) curves, the time-dependent area under the curve (AUC), and decision-curve analysis (DCA). Our hospital's independent cohort of 62 patients with CRNENs was used as the external validation cohort. RESULTS In the period of 1975-2019, the incidence of CRNENs increased steadily with an annual percentage change (APC) of 4.50 (95% confidence interval [CI]: 3.90-5.11, P < 0.05). In total, 668 patients with stage II-IV CRNENs were included in the survival analysis from 2010 and 2016. Independent adverse prognostic factors for both OS and DSS of CRNENs prior treatment included grade III/IV (HR for OS: 4.66, 95%CI: 2.92-7.42; HR for DSS: 4.79, 95%CI: 4.27-5.31), higher TNM stage ([stage III vs stage II] HR for OS: 2.22, 95%CI: 1.25-3.94; HR for DSS: 2.69, 95%CI: 1.96-3.42. [stage IV vs stage II] HR for OS: 3.99, 95%CI: 2.03-7.83; HR for DSS: 4.96, 95%CI: 4.14-5.78), liver metastasis (HR for OS: 1.61, 95%CI: 1.03-2.51; HR for DSS: 1.86, 95%CI: 1.39-2.32), and brain metastasis (HR for OS: 4.57, 95%CI: 1.66-12.58; HR for DSS: 5.01, 95%CI: 4.15-5.87). Advanced age was also identified as a risk factor for OS (HR: 2.03, 95%CI: 1.5-2.76) but not DSS. In terms of treatment, surgery can significantly prolong OS (HR: 0.62, 95%CI: 0.44-0.86) and DSS (HR: 0.67, 95%CI: 0.29-1.05), but chemotherapy and radiation failed to show significance. The respective nomograms for OS and DSS for stage II-IV CRNENs demonstrated high accuracy and robust prediction value in predicting 1-year, 3-year, and 5-year OS and DSS outcomes in training, internal validation, and external validation cohorts. Besides, two online tools regarding OS and DSS prediction were established, facilitating nomogram score calculation, risk group determination, as well as survival prediction for each individual patient. CONCLUSION Over the past 40 years, the incidence of CRNENs presented increased steadily, along with improved survival outcomes. Grade III-IV, higher TNM stage, liver metastasis, brain metastasis, and without receiving surgery were found to be associated with worse OS and DSS. Advanced age was a risk factor for OS but not DSS. Nomograms for patients with stage II-IV stage CRNENs are capable of predicting the 1-, 3-, and 5-year OS and DSS rates with high accuracy, and realize risk stratification.
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Affiliation(s)
- Fuqiang Zhao
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liling Huang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China
| | - Zhijie Wang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fangze Wei
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tixian Xiao
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qian Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Qian Liu,
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Zhang Y, Zhang Y, Yang Y, Xu Z, Gao C, Liu M, Zhu W, Zhao H, Zhou H. Case report: Indocyanine green fluorescence-guided imaging in laparoscope, a more sensitive detection technique of lateral lymph nodes metastases from rectal neuroendocrine tumors. Front Oncol 2022; 12:1101990. [PMID: 36591455 PMCID: PMC9800599 DOI: 10.3389/fonc.2022.1101990] [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] [Received: 11/18/2022] [Accepted: 11/29/2022] [Indexed: 12/23/2022] Open
Abstract
Background The diagnosis and surgical strategy of lateral lymph node metastases of rectal neuroendocrine tumors are still controversial. At present, the major diagnostic means rely on imaging examinations, but will be affected by the size of lymph nodes leading to false negativity. We provide a new technique to determine lateral lymph node metastases during surgery. Clinical case A 68-year-old man developed abdominal pain, bloating and fever for a month. Colonoscopy revealed the mass is 2.4 cm x 2.0 cm in size, with a wide stratum, poor mobility, and a rough but intact surface mucosa. Therefore, rectal neuroendocrine tumors (R-NET) were diagnosed. Multiple imaging methods, such as CT, octreotide imaging and endoscopic ultrasonography, have not found lateral lymph node metastases from rectal neuroendocrine tumors. But indocyanine green (ICG)-enhanced near-infrared fluorescence-guided imaging during surgery found left lateral lymph nodes metastases, which was proved by postoperative pathological examination. Conclusions We believe that applying ICG-enhanced near-infrared fluorescence-guided imaging in laparoscope can improve the detection of positive LLNs in those R-NET patients who did not reveal LNM on imaging examinations.
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Affiliation(s)
- Yueyang Zhang
- Department of Colorectal Surgery, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Zhang
- Department of Pathology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Yang
- Department of Hepatobiliary Surgery, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zheng Xu
- Department of Colorectal Surgery, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Changyuan Gao
- Department of Colorectal Surgery, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Meixi Liu
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenjia Zhu
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haitao Zhou
- Department of Colorectal Surgery, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Gao X, Huang S, Wang Y, Peng Q, Li W, Zou Y, Han Z, Cai J, Luo Y, Ye Y, Li A, Bai Y, Chen Y, Liu S, Li Y. Modified Cap-Assisted Endoscopic Mucosal Resection Versus Endoscopic Submucosal Dissection for the Treatment of Rectal Neuroendocrine Tumors ≤10 mm: A Randomized Noninferiority Trial. Am J Gastroenterol 2022; 117:1982-1989. [PMID: 36455222 PMCID: PMC10508268 DOI: 10.14309/ajg.0000000000001914] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 06/06/2022] [Accepted: 06/20/2022] [Indexed: 12/04/2022]
Abstract
INTRODUCTION Although recent guidelines recommend endoscopic resection of rectal neuroendocrine tumors (NET) ≤10 mm, there is no consensus on which endoscopic modality should be performed. We aimed to compare the safety and efficacy of modified cap-assisted endoscopic mucosal resection (mEMR-C) and endoscopic submucosal dissection (ESD) methods for the treatment of rectal NET ≤10 mm. METHODS A randomized noninferiority trial comparing mEMR-C and ESD was conducted. The primary outcome was the histological complete resection rate; the secondary outcomes included en bloc resection rate, operation time, complications, and so on. Subgroup analyses and follow-up were also performed. RESULTS Ninety patients were enrolled, and 79 patients with pathologically confirmed rectal NET were finally analyzed, including 38 cases of mEMR-C and 41 cases of ESD. Histological complete resection rate was 97.4% in the mEMR-C group and 92.7% in the ESD group. The noninferiority of mEMR-C compared with that of ESD was confirmed because the absolute difference was 4.7% (2-sided 90% confidence interval, -3.3% to 12.2%; P = 0.616). En bloc resection and successful removal of rectal NET were achieved in all patients. Advantages of mEMR-C over ESD included shorter operation time (8.89 ± 4.58 vs 24.8 ± 9.14 minutes, P < 0.05) and lower hospitalization cost ($2,233.76 ± $717.70 vs $2,987.27 ± $871.81, P < 0.05). Postoperative complications were recorded in 4 patients who received mEMR-C and 2 patients in the ESD group (11.5% vs 4.9%, P = 0.509), which were all well managed using endoscopy. Similar findings were observed when subgroup analysis was performed. DISCUSSION mEMR-C is noninferior to ESD with a similar complete resection rate. In addition, mEMR-C had shorter procedure duration time and lower hospitalization costs. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03982264.
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Affiliation(s)
- Xuelian Gao
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
| | - Shaohui Huang
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
| | - Yusi Wang
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
| | - Qun Peng
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
| | - Weixin Li
- Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, USA;
| | - Yingying Zou
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
| | - Zelong Han
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
| | - Jianqun Cai
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
| | - Yuchen Luo
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
| | - Yaping Ye
- Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; and
| | - Aimin Li
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
| | - Yang Bai
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
| | - Ye Chen
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
| | - Side Liu
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
| | - Yue Li
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
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Wu ZQ, Li Y, Sun NN, Xu Q, Zhou J, Su KK, Goyal H, Xu HG. Nomogram for preoperative estimation of histologic grade in gastrointestinal neuroendocrine tumors. Front Endocrinol (Lausanne) 2022; 13:991773. [PMID: 36353229 PMCID: PMC9637831 DOI: 10.3389/fendo.2022.991773] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 10/12/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The treatment strategies and prognosis for gastroenteropancreatic neuroendocrine tumors were associated with tumor grade. Preoperative predictive grading could be of great benefit in the selection of treatment options for patients. However, there is still a lack of effective non-invasive strategies to detect gastrointestinal neuroendocrine tumors (GI-NETs) grading preoperatively. METHODS The data on 147 consecutive GI-NETs patients was retrospectively collected from January 1, 2012, to December 31, 2019. Logistic regression was used to construct a predictive model of gastrointestinal neuroendocrine tumor grading using preoperative laboratory and imaging parameters.The validity of the model was assessed by area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS The factors associated with GI-NETs grading were age, tumor size, lymph nodes, neuron-specific enolase (NSE), hemoglobin (HGB) and sex, and two models were constructed by logistic regression for prediction. Combining these 6 factors, the nomogram was constructed for model 1 to distinguish between G3 and G1/2, achieving a good AUC of 0.921 (95% CI: 0.884-0.965), and the sensitivity, specificity, accuracy were 0.9167, 0.8256, 0.8630, respectively. The model 2 was to distinguish between G1 and G2/3, and the variables were age, tumor size, lymph nodes, NSE, with an AUC of 0.847 (95% CI: 0.799-0.915), and the sensitivity, specificity, accuracy were 0.7882, 0.8710, 0.8231, respectively. Two online web servers were established on the basis of the proposed nomogram to facilitate clinical use. Both models showed an excellent calibration curve through 1000 times bootstrapped dataset and the clinical usefulness were confirmed using decision curve analysis. CONCLUSION The model served as a valuable non-invasive tool for differentiating between different grades of GI-NETs, personalizing the calculation which can lead to a rational treatment choice.
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Affiliation(s)
- Zhi-Qi Wu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, Jiangsu, China
| | - Yan Li
- Academy for Advanced Interdisciplinary Studies, Peking University, Peking, China
| | - Na-Na Sun
- Department of Radiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Qin Xu
- Department of Laboratory Medicine, Jurong Hospital Affiliated to Jiangsu University, Jurong, China
| | - Jing Zhou
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, Jiangsu, China
| | - Kan-Kan Su
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, Jiangsu, China
| | - Hemant Goyal
- Department of Internal Medicine, Mercer University School of Medicine, Macon, GA, United States
| | - Hua-Guo Xu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, Jiangsu, China
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19
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Nannar J, Anciro A, Nanda AK. Collision tumor at the rectum consisting of a neuroendocrine carcinoma and adenocarcinoma: A case report. Ann Med Surg (Lond) 2022; 78:103748. [PMID: 35592827 PMCID: PMC9110971 DOI: 10.1016/j.amsu.2022.103748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 05/02/2022] [Accepted: 05/08/2022] [Indexed: 12/03/2022] Open
Abstract
Introduction and Importance Neuroendocrine carcinoma of the colon and rectum account for less than 1% of all colorectal malignancies. Here we report a case of a collision tumor at the rectum consisting of a neuroendocrine carcinoma and adenocarcinoma. Case presentation A 46-year-old asymptomatic female with severe anemia was referred by her primary care physician for admission. Initial imaging showed several innumerable heterogenous hypodense lesions within the liver. Following a colonoscopy and the excision of a rectal mass, the histopathology report revealed a Collision tumor. Clinical discussion There are no specific clinical features or imaging findings. The diagnosis is made post operatively dependent on histopathology. Conclusion It is essential to report these cases to advance a further understanding of the behaviour of these tumors, in addition to develop evidence-based guidelines and treatment strategies.
Collision tumors are rare consisting of 2 independent tumors co-existing. Diagnosis is post-operatively and dependent on histology. No current guidelines for treatment. Management focuses on the predominant tumor.
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20
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Pattarajierapan S, Khomvilai S. Recurrence after endoscopic resection of small rectal neuroendocrine tumors: a retrospective cohort study. Ann Coloproctol 2022; 38:216-222. [PMID: 34280965 PMCID: PMC9263308 DOI: 10.3393/ac.2021.00017.0002] [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] [Received: 01/06/2021] [Revised: 02/23/2021] [Accepted: 02/24/2021] [Indexed: 11/15/2022] Open
Abstract
PURPOSE According to the European Neuroendocrine Tumor Society consensus guidelines, rectal neuroendocrine tumors (NETs) up to 10 mm in size and without poor prognostic factors could be safely removed with endoscopic resection, suggesting omitting surveillance colonoscopy after complete resection. However, the benefit of surveillance colonoscopy is still unknown. In this study, we aimed to report the outcomes after endoscopic resection of small rectal NETs using our surveillance protocol. METHODS This retrospective cohort study included patients who underwent endoscopic resection for rectal NETs sized up to 10 mm from January 2013 to December 2019 at our center. We excluded patients without surveillance colonoscopy and those lost to follow-up. We strictly performed surveillance colonoscopy 1 year after endoscopic resection, and every 2 to 3 years thereafter. The primary outcomes were tumor recurrence and occurrence of metachronous tumors during followup. RESULTS Of the 54 patients who underwent endoscopic resection for rectal NETs during the study period, 46 were enrolled in this study. The complete resection rates by endoscopic mucosal resection, precutting endoscopic mucosal resection, and endoscopic submucosal dissection were 92.3% (12 of 13), 100% (21 of 21), and 100% (12 of 12), respectively. There was no local or distant recurrence during the median follow-up of 39 months. However, we found that 8.7% (4 of 46) of patients developed metachronous NETs. All metachronous lesions were treated with precutting endoscopic mucosal resection. CONCLUSION Surveillance colonoscopy is reasonable after endoscopic resection of small rectal NETs for timely detection and treatment of metachronous lesions. However, larger collaborative studies are needed to influence the guidelines.
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Affiliation(s)
- Sukit Pattarajierapan
- Surgical Endoscopy Colorectal Division, Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Supakij Khomvilai
- Surgical Endoscopy Colorectal Division, Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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21
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Papaefthymiou A, Laskaratos FM, Koffas A, Manolakis A, Gkolfakis P, Coda S, Sodergren M, Suzuki N, Toumpanakis C. State of the Art in Endoscopic Therapy for the Management of Gastroenteropancreatic Neuroendocrine Tumors. Curr Treat Options Oncol 2022; 23:1014-1034. [PMID: 35511346 DOI: 10.1007/s11864-022-00986-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/06/2022] [Indexed: 12/13/2022]
Abstract
OPINION STATEMENT Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) comprise a heterogeneous group of slow growing tumors arising from the neuroendocrine cells of the gastrointestinal (GI) tract. Although they are considered relatively rare, their incidence is rising and it is believed that the more frequent use of endoscopy and imaging studies have at least in part contributed to the increased diagnosis especially of localized neoplasms. The management of these neoplasms should be guided by a multidisciplinary NEN team following appropriate staging investigations. Localized neoplasms of the GI tract may be suitable for endoscopic therapy, while patients with pancreatic NENs, unsuitable for surgery, should be considered for endoscopic ultrasound (EUS)-guided ablation. In this review, we discuss the evidence regarding endoscopic resection of luminal NENs and EUS-guided therapy of pancreatic NENs. The efficacy, safety, and other longer-term outcomes of these techniques are summarized. In conclusion, this review of endoscopic therapies for localized NENs may be a useful guide for NEN clinicians and endoscopists who are considering these therapeutic options for the management of focal GEP NENs.
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Affiliation(s)
- Apostolis Papaefthymiou
- Department of Gastroenterology, General University Hospital of Larisa, Mezourlo, 41110, Larisa, Greece.,First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124, Thessaloniki, Macedonia, Greece
| | | | - Apostolos Koffas
- Department of Gastroenterology, General University Hospital of Larisa, Mezourlo, 41110, Larisa, Greece
| | - Anastasios Manolakis
- Department of Gastroenterology, General University Hospital of Larisa, Mezourlo, 41110, Larisa, Greece
| | - Paraskevas Gkolfakis
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, 1070, Brussels, Belgium
| | - Sergio Coda
- Digestive Diseases Centre, Barking Havering and Redbridge University Hospitals NHS Trust, London, UK
| | - Mikael Sodergren
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Noriko Suzuki
- Wolfson Unit for Endoscopy, St Mark's Hospital and Academic Institute, London, UK
| | - Christos Toumpanakis
- Neuroendocrine Tumour Unit (ENETS Centre of Excellence) Centre for Gastroenterology, Royal Free Hospital, London, UK
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22
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Feng LH, Su T, Lu Y, Ren S, Huang L, Qin X, Liao T. A model for predicting the overall survival of gastroenteropancreatic neuroendocrine neoplasms after surgery. Scand J Gastroenterol 2022; 57:581-588. [PMID: 35001789 DOI: 10.1080/00365521.2021.2024247] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND The increase in the incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NENs) and refined morphological imaging techniques have led to a rise in the number of patients undergoing surgery. However, there is still a paucity of objective, clinically reliable and personalized tools to evaluate patient prognosis. MATERIALS AND METHODS We identified patients from the Surveillance, Epidemiology, and End Results (SEER) database who underwent surgery for GEP-NEN from 1975 to 2018. The predictors associated with OS were investigated by Multivariate Cox proportional hazards (PHs) regression analysis in the primary cohort; a prognostic nomogram was then built based on the multivariate analysis results. The performance of the nomogram was assessed by Harrell's concordance index (C-index) and calibration curve and compared with the eighth edition of the American Joint Committee on Cancer (AJCC) staging system. RESULTS A total of 45,889 patients were enrolled in our study; 32,321 were included in the primary cohort, and 13,568 were included in the validation cohort. A nomogram incorporating Age, Differentiation, M staging, and AJCC staging was subsequently built based on the multivariate analysis. The C-index (0.833 for the primary cohort and 0.845 for the validation cohort) and calibration curves indicated good discriminative ability and calibration of the nomogram. Further analysis demonstrated that the nomogram had superior discriminatory ability than the AJCC staging system (C-index= 0.706). CONCLUSION The proposed nomogram showed excellent prediction with good calibration and discrimination, which can be used to make well-informed and individualized clinical decisions regarding the clinical management of GEP-NENs.
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Affiliation(s)
- Lu-Huai Feng
- Department of Comprehensive Internal Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Tingting Su
- Department of ECG Diagnostics, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Yang Lu
- Department of Comprehensive Internal Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Shuang Ren
- Department of Comprehensive Internal Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Lina Huang
- Department of Comprehensive Internal Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Xiuyu Qin
- Department of Comprehensive Internal Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Tianbao Liao
- Department of President's Office, Youjiang Medical University for Nationalities, Baise, China.,Philippine Christian University Center for International Education, Manila City, Philippine
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23
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Fu X, Wei S, Wang T, Fan H, Zhang Y, Costa CD, Brandner S, Yang G, Pan Y, He Y, Li N. Research Status of the Orphan G Protein Coupled Receptor 158 and Future Perspectives. Cells 2022; 11:cells11081334. [PMID: 35456013 PMCID: PMC9027133 DOI: 10.3390/cells11081334] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/10/2022] [Accepted: 04/11/2022] [Indexed: 02/01/2023] Open
Abstract
G-protein-coupled receptors (GPCRs) remain one of the most successful targets for therapeutic drugs approved by the US Food and Drug Administration (FDA). Many novel orphan GPCRs have been identified by human genome sequencing and considered as putative targets for refractory diseases. Of note, a series of studies have been carried out involving GPCR 158 (or GPR158) since its identification in 2005, predominantly focusing on the characterization of its roles in the progression of cancer and mental illness. However, advances towards an in-depth understanding of the biological mechanism(s) involved for clinical application of GPR158 are lacking. In this paper, we clarify the origin of the GPR158 evolution in different species and summarize the relationship between GPR158 and different diseases towards potential drug target identification, through an analysis of the sequences and substructures of GPR158. Further, we discuss how recent studies set about unraveling the fundamental features and principles, followed by future perspectives and thoughts, which may lead to prospective therapies involving GPR158.
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Affiliation(s)
- Xianan Fu
- Tomas Lindhal Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University (SYSU), No.628, Zhenyuan Rd., Guangming Dist., Shenzhen 518107, China; (X.F.); (S.W.); (T.W.); (H.F.); (Y.Z.); (Y.P.)
| | - Shoupeng Wei
- Tomas Lindhal Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University (SYSU), No.628, Zhenyuan Rd., Guangming Dist., Shenzhen 518107, China; (X.F.); (S.W.); (T.W.); (H.F.); (Y.Z.); (Y.P.)
| | - Tao Wang
- Tomas Lindhal Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University (SYSU), No.628, Zhenyuan Rd., Guangming Dist., Shenzhen 518107, China; (X.F.); (S.W.); (T.W.); (H.F.); (Y.Z.); (Y.P.)
| | - Hengxin Fan
- Tomas Lindhal Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University (SYSU), No.628, Zhenyuan Rd., Guangming Dist., Shenzhen 518107, China; (X.F.); (S.W.); (T.W.); (H.F.); (Y.Z.); (Y.P.)
| | - Ying Zhang
- Tomas Lindhal Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University (SYSU), No.628, Zhenyuan Rd., Guangming Dist., Shenzhen 518107, China; (X.F.); (S.W.); (T.W.); (H.F.); (Y.Z.); (Y.P.)
| | - Clive Da Costa
- The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK;
| | - Sebastian Brandner
- Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK;
| | - Guang Yang
- Department of Burn and Plastic Surgery, Institute of Translational Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen 518039, China;
| | - Yihang Pan
- Tomas Lindhal Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University (SYSU), No.628, Zhenyuan Rd., Guangming Dist., Shenzhen 518107, China; (X.F.); (S.W.); (T.W.); (H.F.); (Y.Z.); (Y.P.)
| | - Yulong He
- Tomas Lindhal Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University (SYSU), No.628, Zhenyuan Rd., Guangming Dist., Shenzhen 518107, China; (X.F.); (S.W.); (T.W.); (H.F.); (Y.Z.); (Y.P.)
- Center for Digestive Disease, The Seventh Affiliated Hospital of Sun Yat-sen University (SYSU), No.628, Zhenyuan Rd., Guangming Dist., Shenzhen 518107, China
- Correspondence: (Y.H.); (N.L.)
| | - Ningning Li
- Tomas Lindhal Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University (SYSU), No.628, Zhenyuan Rd., Guangming Dist., Shenzhen 518107, China; (X.F.); (S.W.); (T.W.); (H.F.); (Y.Z.); (Y.P.)
- China-UK Institute for Frontier Science, Shenzhen 518107, China
- Correspondence: (Y.H.); (N.L.)
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24
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Kamigaichi Y, Yamashita K, Oka S, Tamari H, Shimohara Y, Nishimura T, Inagaki K, Okamoto Y, Tanaka H, Yuge R, Urabe Y, Arihiro K, Tanaka S. Clinical outcomes of endoscopic resection for rectal neuroendocrine tumors: Advantages of endoscopic submucosal resection with a ligation device compared to conventional EMR and ESD. DEN OPEN 2022; 2:e35. [PMID: 35310732 PMCID: PMC8828204 DOI: 10.1002/deo2.35] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/28/2021] [Accepted: 06/10/2021] [Indexed: 12/19/2022]
Abstract
Objectives Methods Results Conclusions
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Affiliation(s)
- Yuki Kamigaichi
- Department of Endoscopy Hiroshima University Hospital Hiroshima Japan
| | - Ken Yamashita
- Department of Endoscopy Hiroshima University Hospital Hiroshima Japan
| | - Shiro Oka
- Department of Gastroenterology and Metabolism Hiroshima University Hospital Hiroshima Japan
| | - Hirosato Tamari
- Department of Gastroenterology and Metabolism Hiroshima University Hospital Hiroshima Japan
| | - Yasutsugu Shimohara
- Department of Gastroenterology and Metabolism Hiroshima University Hospital Hiroshima Japan
| | - Tomoyuki Nishimura
- Department of Gastroenterology and Metabolism Hiroshima University Hospital Hiroshima Japan
| | - Katsuaki Inagaki
- Department of Gastroenterology and Metabolism Hiroshima University Hospital Hiroshima Japan
| | - Yuki Okamoto
- Department of Gastroenterology and Metabolism Hiroshima University Hospital Hiroshima Japan
| | - Hidenori Tanaka
- Department of Endoscopy Hiroshima University Hospital Hiroshima Japan
| | - Ryo Yuge
- Department of Endoscopy Hiroshima University Hospital Hiroshima Japan
| | - Yuji Urabe
- Division of Regeneration and Medicine Center for Translational and Clinical Research Hiroshima University Hospital Hiroshima Japan
| | - Koji Arihiro
- Department of Anatomical Pathology Hiroshima University Hospital Hiroshima Japan
| | - Shinji Tanaka
- Department of Endoscopy Hiroshima University Hospital Hiroshima Japan
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25
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Fukushima N, Furukawa K, Takano Y, Suzuki T, Yoshinobu M, Hanyu K, Kobayashi S. Multiple large cell neuroendocrine carcinomas in the rectum and descending colon presented with liver metastasis: A case report. Asian J Endosc Surg 2022; 15:405-409. [PMID: 35001529 DOI: 10.1111/ases.13025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 12/17/2021] [Accepted: 12/23/2021] [Indexed: 11/28/2022]
Abstract
Colorectal large cell neuroendocrine carcinoma (LCNEC) is rare and multiple LCNECs have not been previously reported. We encountered a case of multiple LCNECs in the rectum and the descending colon. A 66-year-old man presented with anal pain. Colonoscopy showed an ulcerated infiltrating tumor in the rectum, and 0.5 cm of erosion in the descending colon. A biopsy revealed LCNEC in both regions. Abdominal computed tomography revealed irregularly enhanced wall thickening at the rectum and hepatic metastases. Due to the diagnosis of LCNEC, laparoscopic abdominoperineal resection of the rectum was performed. Histopathological examination showed a poorly differentiated, LCNEC in both regions. Immunohistochemical examination demonstrated that the tumor cells were positive for chromogranin and synaptophysin. LCNEC was confirmed, and systemic chemotherapy with cisplatin/irinotecan was initiated. To our knowledge, this is the first case report that describes multiple LCNECs in the rectum and descending colon.
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Affiliation(s)
- Naoko Fukushima
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.,Department of Surgery, Takatsu General Hospital, Tokyo, Japan.,Department of Proctology, Clinic of Kajigaya, Tokyo, Japan
| | - Kenei Furukawa
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.,Department of Proctology, Clinic of Kajigaya, Tokyo, Japan
| | - Yuta Takano
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.,Department of Surgery, Takatsu General Hospital, Tokyo, Japan
| | - Toshiaki Suzuki
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.,Department of Surgery, Takatsu General Hospital, Tokyo, Japan
| | - Mitsuyama Yoshinobu
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.,Department of Surgery, Takatsu General Hospital, Tokyo, Japan
| | - Ken Hanyu
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.,Department of Proctology, Clinic of Kajigaya, Tokyo, Japan
| | - Susumu Kobayashi
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.,Department of Surgery, Takatsu General Hospital, Tokyo, Japan
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26
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Kohno S. Diagnosis and Surgical Treatment of Gastroenteropancreatic Neuroendocrine Neoplasms: A Literature Review. CANCER DIAGNOSIS & PROGNOSIS 2022; 2:115-125. [PMID: 35399177 PMCID: PMC8962810 DOI: 10.21873/cdp.10085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 01/31/2022] [Indexed: 06/14/2023]
Abstract
This review aimed to highlight the characteristics and surgical treatments of tumours, and answer questions regarding the assessment of gastrointestinal neuroendocrine neoplasms (NENs) and optimal therapy. NENs comprise tumours that can produce hormones and cause a secretory syndrome. The diagnostic method and accuracy differ depending on the site of occurrence; hence, the relevant scientific society has created NEN treatment guidelines for each organ. Gastroenteric pancreatic (GEP) NENs have been unified and classified together according to the 2019 World Health Organization classification. Treatment is based on complete tumour resection, and when metastatic or primary lesions cannot be completely resected, lesions and symptoms are treated. Except for surgery for NENs, chemotherapy, molecularly targeted drugs, transarterial chemoembolization, etc., have also been confirmed as treatments. GEP NEN treatment methods will continue to advance and change because of surgery and other advances in treatment and diagnostic methods.
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Affiliation(s)
- Shuzo Kohno
- Department of Surgery, The Jikei University Katsushika Medical Center, Tokyo, Japan
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27
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Shi WK, Hou R, Li YH, Qiu XY, Liu YX, Wu B, Xiao Y, Zhou JL, Lin GL. Long-term outcomes of transanal endoscopic microsurgery for the treatment of rectal neuroendocrine tumors. BMC Surg 2022; 22:43. [PMID: 35120483 PMCID: PMC8817465 DOI: 10.1186/s12893-022-01494-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 01/18/2022] [Indexed: 11/10/2022] Open
Abstract
Background Transanal endoscopic microsurgery (TEM) has been accepted worldwide for the treatment of local rectal lesions. We aimed to assess the efficacy and safety of TEM in the treatment of rectal neuroendocrine tumors (RNET). Methods A retrospective study of patients who had undergone TEM for RNET at our institution between December 2006 and June 2019 was performed. Demographic and tumor characteristics, operative and pathological details, complications, anal function questionnaires, and follow-up data were included. Results A total of 144 patients was included. TEM was performed as primary excision in 54 patients, after endoscopic forceps biopsy in 57 patients, and after incomplete resection by endoscopic excision in 33 patients. The median size of all primary tumors was 0.6 cm (range, 0.3–2.0 cm), and the negative resection margin was achieved in 142 (98.6%) patients. Postoperative complications (referring to only bleeding) occurred in 3 (2.1%) patients and was successfully managed with conservative method. After a median follow-up of 75.5 months after surgery, 3 patients died of other causes, and 2 patients suffered metastasis. An anal function questionnaire was posted 24 months after TEM. Among the results, 3 (2.1%) patients complained of major low anterior resection syndrome (LARS), including 1 (0.7%) who suffered from complete incontinence, while 6 (4.2%) patients had minor LARS. Conclusions TEM has satisfying long-term outcomes and relatively low anal function disturbance as for the treatment of small RNET. TEM also acts as a preferred salvage treatment for incomplete endoscopic excision.
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Affiliation(s)
- Wei-Kun Shi
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Shuaifuyuan 1, Beijing, 100730, China
| | - Rui Hou
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Shuaifuyuan 1, Beijing, 100730, China
| | - Yun-Hao Li
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Shuaifuyuan 1, Beijing, 100730, China
| | - Xiao-Yuan Qiu
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Shuaifuyuan 1, Beijing, 100730, China
| | - Yu-Xin Liu
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Shuaifuyuan 1, Beijing, 100730, China
| | - Bin Wu
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Shuaifuyuan 1, Beijing, 100730, China
| | - Yi Xiao
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Shuaifuyuan 1, Beijing, 100730, China
| | - Jiao-Lin Zhou
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Shuaifuyuan 1, Beijing, 100730, China
| | - Guo-Le Lin
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Shuaifuyuan 1, Beijing, 100730, China.
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28
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Ricci AD, Pusceddu S, Panzuto F, Gelsomino F, Massironi S, De Angelis CG, Modica R, Ricco G, Torchio M, Rinzivillo M, Prinzi N, Rizzi F, Lamberti G, Campana D. Assessment of the Risk of Nodal Involvement in Rectal Neuroendocrine Neoplasms: The NOVARA Score, a Multicentre Retrospective Study. J Clin Med 2022; 11:713. [PMID: 35160165 PMCID: PMC8836953 DOI: 10.3390/jcm11030713] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/25/2022] [Accepted: 01/26/2022] [Indexed: 02/05/2023] Open
Abstract
Rectal neuroendocrine tumors (r-NETs) are rare tumors with overall good prognosis after complete resection. However, there is no consensus on the extension of lymphadenectomy or regarding contraindications to extensive resection. In this study, we aim to identify predictive factors that correlate with nodal metastasis in patients affected by G1-G2 r-NETs. A retrospective analysis of G1-G2 r-NETs patients from eight tertiary Italian centers was performed. From January 1990 to January 2020, 210 patients were considered and 199 were included in the analysis. The data for nodal status were available for 159 cases. The nodal involvement rate was 9%. A receiver operating characteristic (ROC) curve analysis was performed to identify the diameter (>11.5 mm) and Ki-67 (3.5%), respectively, as cutoff values to predict nodal involvement. In a multivariate analysis, diameter > 11.5 mm and vascular infiltration were independently correlated with nodal involvement. A risk scoring system was constructed using these two predictive factors. Tumor size and vascular invasion are predictors of nodal involvement. In addition, tumor size > 11.5 mm is used as a driving parameter of better-tailored treatment during pre-operative assessment. Data from prospective studies are needed to validate these results and to guide decision-making in r-NETs patients in clinical practice.
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Affiliation(s)
- Angela Dalia Ricci
- Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi University Hospital, ENETS Center of Excellence, 40138 Bologna, Italy; (A.D.R.); (G.R.); (D.C.)
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via P. Albertoni 15, 40138 Bologna, Italy
| | - Sara Pusceddu
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori Milano, ENETS Center of Excellence, 20133 Milan, Italy; (S.P.); (M.T.); (N.P.)
| | - Francesco Panzuto
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence of Rome, 00189 Rome, Italy; (F.P.); (M.R.)
- Department of Medical Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy
| | - Fabio Gelsomino
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, 41125 Modena, Italy;
| | - Sara Massironi
- Division of Gastroenterology, Department of Medicine and Surgery, University of Milano-Bicocca, San Gerardo School of Medicine, 20900 Monza, Italy;
| | - Claudio Giovanni De Angelis
- Department of Gastroenterology and Digestive Endoscopy, AOU Città della Salute e della Scienza, University of Turin, 10126 Turin, Italy; (C.G.D.A.); (F.R.)
| | - Roberta Modica
- Endocrinology, Department of Clinical Medicine and Surgery, ENETS Center of Excellence, University “Federico II” of Naples, 80138 Naples, Italy;
| | - Gianluca Ricco
- Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi University Hospital, ENETS Center of Excellence, 40138 Bologna, Italy; (A.D.R.); (G.R.); (D.C.)
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via P. Albertoni 15, 40138 Bologna, Italy
| | - Martina Torchio
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori Milano, ENETS Center of Excellence, 20133 Milan, Italy; (S.P.); (M.T.); (N.P.)
| | - Maria Rinzivillo
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence of Rome, 00189 Rome, Italy; (F.P.); (M.R.)
| | - Natalie Prinzi
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori Milano, ENETS Center of Excellence, 20133 Milan, Italy; (S.P.); (M.T.); (N.P.)
| | - Felice Rizzi
- Department of Gastroenterology and Digestive Endoscopy, AOU Città della Salute e della Scienza, University of Turin, 10126 Turin, Italy; (C.G.D.A.); (F.R.)
| | - Giuseppe Lamberti
- Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi University Hospital, ENETS Center of Excellence, 40138 Bologna, Italy; (A.D.R.); (G.R.); (D.C.)
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via P. Albertoni 15, 40138 Bologna, Italy
| | - Davide Campana
- Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi University Hospital, ENETS Center of Excellence, 40138 Bologna, Italy; (A.D.R.); (G.R.); (D.C.)
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via P. Albertoni 15, 40138 Bologna, Italy
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Masood S, Gupta R, Jaiswal A, Bhardwaj G, Srivastav U. Neuroendocrine Carcinoma of the Colon: Emergency Presentation of a Rare Disease With Poor Biology. Cureus 2021; 13:e19582. [PMID: 34926053 PMCID: PMC8672052 DOI: 10.7759/cureus.19582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/14/2021] [Indexed: 11/05/2022] Open
Abstract
Neuroendocrine tumors (NETs) are rare entities. Most common among them are gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and pulmonary NETs. Most of them are indolent in nature. Colonic NETs are rare among GEP-NETs and mostly present with large size and with metastasis. Emergency presentation with hematochezia is rare in colonic NETs. This case report discusses a rare emergency presentation of colonic NETs and highlights their poor biological nature.
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Affiliation(s)
- Shakeel Masood
- Surgical Gastroenterology, Ram Manohar Lohia Institute of Medical Sciences, Lucknow, IND
| | - Ravi Gupta
- General Surgery, All India Institute of Medical Sciences, Gorakhpur, IND
| | - Ashish Jaiswal
- General Surgery, All India Institute of Medical Sciences, Gorakhpur, IND
| | - Gaurav Bhardwaj
- Surgical Gastroenterology, Ram Manohar Lohia Institute of Medical Sciences, Lucknow, IND
| | - Utkarsh Srivastav
- Surgical Gastroenterology, Amrita Institute of Medical Sciences, Kochi, IND
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Zheng Y, Guo K, Zeng R, Chen Z, Liu W, Zhang X, Liang W, Liu J, Chen H, Sha W. Prognosis of rectal neuroendocrine tumors after endoscopic resection: a single-center retrospective study. J Gastrointest Oncol 2021; 12:2763-2774. [PMID: 35070405 PMCID: PMC8748065 DOI: 10.21037/jgo-21-391] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 11/24/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The efficacy of endoscopic resection in patients with rectal neuroendocrine tumors (NETs) which are less than 20 mm in diameter remains unclear. This study aimed to investigate the efficacy and outcomes of different types of endoscopic resection in patients with NETs. METHODS We performed a retrospective analysis and follow-up on 98 patients who underwent endoscopic resection for rectal NETs between August 2010 and October 2019 at Guangdong Provincial People's Hospital, China. The lesions were preoperatively classified according to their endoscopic morphology and measured by endoscopic ultrasound. Patients were divided into modified endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) groups depending on the endoscopic treatment they received. The en bloc resection rate, histopathological complete resection rate, and the complication rate of the 2 groups were evaluated after the operation. The risk factors for incomplete resection were also analyzed. RESULTS The average diameter of the 98 NETs was 6.29±2.90 mm (range, 2-15 mm). The en bloc resection rate of the modified EMR and ESD treatment groups was 97.2% (35/36) and 100% (62/62), respectively. The histopathological complete resection rate was 86.1% (31/36) and 87.1% (54/62), respectively. No tumor recurrence or tumor-related death occurred. There were no statistically significant differences in the rate of histopathological complete resection, perforation, or delayed hemorrhage between the 2 groups (P>0.05). Multivariate analysis demonstrated that the depth of tumor invasion (P=0.007) and tumor diameter (P<0.001) were independent risk factors for histopathological complete resection. CONCLUSIONS Modified EMR and ESD are safe and effective endoscopic approaches for the resection of rectal NETs ≤15 mm in diameter. Endoscopic resection requires a comprehensive preoperative evaluation of risk factors including the depth of tumor invasion and tumor diameter.
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Affiliation(s)
- Yue Zheng
- Department of Gastroenterology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Kehang Guo
- Department of Gastroenterology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Ruijie Zeng
- Department of Gastroenterology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
| | - Zhendao Chen
- Department of Gastroenterology, Huazhou People’s Hospital, Maoming, China
| | - Wanwei Liu
- Department of Gastroenterology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Xiaoguang Zhang
- Department of Gastroenterology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Weimin Liang
- Department of Gastroenterology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Jianhua Liu
- Department of Oncology, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Hao Chen
- Department of Gastroenterology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Weihong Sha
- Department of Gastroenterology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
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Somatostatin and Its Receptor System in Colorectal Cancer. Biomedicines 2021; 9:biomedicines9111743. [PMID: 34829972 PMCID: PMC8615525 DOI: 10.3390/biomedicines9111743] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 11/19/2021] [Accepted: 11/20/2021] [Indexed: 12/14/2022] Open
Abstract
Somatostatin (SST)/somatotropin release-inhibiting factor (SRIF) is a well-known neuropeptide, widely distributed in the central and peripheral nervous systems, that regulates the endocrine system and affects neurotransmission via interaction with five SST receptors (SST1-5). In the gastrointestinal tract, the main SST-producing cells include intestinal enteroendocrine cells (EECs) restricted to the mucosa, and neurons of the submucosal and myenteric plexuses. The action of the SRIF system is based on the inhibition of endocrine and exocrine secretion, as well as the proliferative responses of target cells. The SST1–5 share common signaling pathways, and are not only widely expressed on normal tissues, but also frequently overexpressed by several tumors, particularly neuroendocrine neoplasms (NENs). Furthermore, the SRIF system represents the only peptide/G protein-coupled receptor (GPCR) system with multiple approved clinical applications for the diagnosis and treatment of several NENs. The role of the SRIF system in the histogenesis of colorectal cancer (CRC) subtypes (e.g., adenocarcinoma and signet ring-cell carcinoma), as well as diagnosis and prognosis of mixed adenoneuroendocrine carcinoma (MANEC) and pure adenocarcinoma, is poorly understood. Moreover, the impact of the SRIF system signaling on CRC cell proliferation and its potential role in the progression of this cancer remains unknown. Therefore, this review summarizes the recent collective knowledge and understanding of the clinical significance of the SRIF system signaling in CRC, aiming to evaluate the potential role of its components in CRC histogenesis, diagnosis, and potential therapy.
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Tziatzios G, Gkolfakis P, Papadopoulos V, Papanikolaou IS, Fuccio L, Facciorusso A, Ebigbo A, Gölder SK, Probst A, Messmann H, Triantafyllou K. Modified endoscopic mucosal resection techniques for treating precancerous colorectal lesions. Ann Gastroenterol 2021; 34:757-769. [PMID: 34815641 PMCID: PMC8596214 DOI: 10.20524/aog.2021.0647] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 04/24/2021] [Indexed: 11/13/2022] Open
Abstract
Endoscopic mucosal resection (EMR) is a technique allowing efficacious and minimally invasive resection of precancerous lesions across the entire gastrointestinal tract. However, conventional EMR, involving injection of fluid into the submucosal space, is imperfect, given the high rate of recurrence of post-endoscopic resection adenoma, especially after piecemeal resection. In light of these observations, modifications of the technique have been proposed to overcome the weakness of conventional EMR. Some of them were designed to maximize the chance of en bloc resection-cap-assisted EMR, underwater EMR, tip-in EMR, precutting, assisted by ligation device-while others were designed to minimize the complications (cold EMR). In this review, we present their modes of action and summarize the evidence regarding their efficacy and safety.
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Affiliation(s)
- Georgios Tziatzios
- Hepatogastroenterology Unit, Second Department of Internal Medicine-Propaedeutic, Medical School, National and Kapodistrian University of Athens, “Attikon” University General Hospital, Athens, Greece (Georgios Tziatzios, Ioannis S. Papanikolaou, Konstantinos Triantafyllou)
| | - Paraskevas Gkolfakis
- Department of Gastroenterology Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium (Paraskevas Gkolfakis)
| | - Vasilios Papadopoulos
- Department of Gastroenterology, Koutlimbaneio & Triantafylleio General Hospital, Larissa, Greece (Vasilios Papadopoulos)
| | - Ioannis S. Papanikolaou
- Hepatogastroenterology Unit, Second Department of Internal Medicine-Propaedeutic, Medical School, National and Kapodistrian University of Athens, “Attikon” University General Hospital, Athens, Greece (Georgios Tziatzios, Ioannis S. Papanikolaou, Konstantinos Triantafyllou)
| | - Lorenzo Fuccio
- Gastroenterology Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy (Lorenzo Fuccio)
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Surgical and Medical Sciences, University of Foggia, Italy (Antonio Facciorusso)
| | - Alanna Ebigbo
- Department of Gastroenterology, University Hospital Augsburg, Augsburg, Germany (Alanna Ebigbo, Stefan Karl Gölder, Andreas Probst, Helmut Messmann)
| | - Stefan Karl Gölder
- Department of Gastroenterology, University Hospital Augsburg, Augsburg, Germany (Alanna Ebigbo, Stefan Karl Gölder, Andreas Probst, Helmut Messmann)
| | - Andreas Probst
- Department of Gastroenterology, University Hospital Augsburg, Augsburg, Germany (Alanna Ebigbo, Stefan Karl Gölder, Andreas Probst, Helmut Messmann)
| | - Helmut Messmann
- Department of Gastroenterology, University Hospital Augsburg, Augsburg, Germany (Alanna Ebigbo, Stefan Karl Gölder, Andreas Probst, Helmut Messmann)
| | - Konstantinos Triantafyllou
- Hepatogastroenterology Unit, Second Department of Internal Medicine-Propaedeutic, Medical School, National and Kapodistrian University of Athens, “Attikon” University General Hospital, Athens, Greece (Georgios Tziatzios, Ioannis S. Papanikolaou, Konstantinos Triantafyllou)
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Yozgat A, Kekilli M, Altay M. Time to give up traditional methods for the management of gastrointestinal neuroendocrine tumours. World J Clin Cases 2021; 9:8627-8646. [PMID: 34734042 PMCID: PMC8546836 DOI: 10.12998/wjcc.v9.i29.8627] [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: 02/20/2021] [Revised: 05/19/2021] [Accepted: 08/24/2021] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumors (NETs) are a rare and heterogeneous disease group and constitute 0.5% of all malignancies. The annual incidence of NETs is increasing worldwide. The reason for the increase in the incidence of NETs is the detection of benign lesions, incidental detection due to the highest use of endoscopic and imaging procedures, and higher recognition rates of pathologists. There have been exciting developments regarding NET biology in recent years. Among these, first of all, somatostatin receptors and downstream pathways in neuroendocrine cells have been found to be important regulatory mechanisms for protein synthesis, hormone secretion, and proliferation. Subsequently, activation of the mammalian target of rapamycin pathway was found to be an important mechanism in angiogenesis and tumor survival and cell metabolism. Finally, the importance of proangiogenic factors (platelet-derived growth factor, vascular endothelial growth factor, fibroblastic growth factor, angiopoietin, and semaphorins) in the progression of NET has been determined. Using the combination of biomarkers and imaging methods allows early evaluation of the appropriateness of treatment and response to treatment.
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Affiliation(s)
- Ahmet Yozgat
- Department of Gastroenterology, Ufuk University, Ankara, 06510, Turkey
| | - Murat Kekilli
- Department of Gastroenterology, Gazi University, Ankara 06560, Turkey
| | - Mustafa Altay
- Department of Endocrinology and Metabolism, University of Health Sciences Turkey, Keçiören Health Administration and Research Center, Ankara 06190, Turkey
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Waked B, De Maeyer F, Carton S, Pieter-Jan CUYLE, Vandamme T, Verslype C, Demetter P, Borbath I, Van Eycken L, Hoorens A, Geboes K, Van Damme N, Ribeiro S. Quality of pathology reporting and adherence to guidelines in rectal neuroendocrine neoplasms: a Belgian national study. Acta Clin Belg 2021; 77:823-831. [PMID: 34607538 DOI: 10.1080/17843286.2021.1985806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
The incidence of neuroendocrine neoplasms (NEN) in the rectum is rising since the introduction of colonoscopy screening programs. Guidelines, such as the European NeuroEndocrine Tumor Society (ENETS) algorithm, are mainly based on expert opinion. The goal of this nationwide study is to gain a better insight into the evolution in pathology reporting and adherence to the ENETS guidelines in Belgium. In Belgium, all NENs have to be reported to the Belgian Cancer Registry. We thoroughly reviewed all available pathology reports, coded as rectal NEN between 2004 and 2015, and reclassified according to World Health Organisation (WHO) classification 2019. To evaluate the adherence to the ENETS guidelines, population-based cancer registry data were linked with the medical procedures of the Belgian Health Insurance database. A total of 670 rectal NEN were retained and 16% of the cases needed reclassification. Annual incidence between 2004 and 2015 tripled from 0,20 to 0,61 per 100.000 inhabitants. Reporting of Ki67 proliferation index ameliorated most, while reporting of tumor size, lymphovascular and perineural invasion remained disappointing. Endoscopic ultrasound was performed in only 36.6% of the cases, while the mostly recommended mode of treatment (endoscopic/surgical/no resection) was followed in the majority of the cases. Incidence of rectal NEN in Belgium increased throughout the years and quality of pathology reporting improved especially after the WHO classification update in 2010. The growing awareness and knowledge among clinicians and pathologists in the community counters the need for centralization.
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Affiliation(s)
- Bruno Waked
- Ghent University Hospital, Department of Gastroenterology. Ghent, Belgium
| | - Filip De Maeyer
- Az Sint-Elisabeth Zottegem, Department of Gastroenterology. Godveerdegemstraat 69, Zottegem, Belgium
| | - Saskia Carton
- Imeldaziekenhuis, Bonheiden, Department of Gastroenterology. Bonheiden, Belgium
| | - CUYLE Pieter-Jan
- Imeldaziekenhuis, Bonheiden, Department of Gastroenterology. Bonheiden, Belgium
| | - Timon Vandamme
- Ziekenhuis Netwerk Antwerpen, Department of Gastroenterology. Antwerp, Belgium
| | - Chris Verslype
- University Hospital Gasthuisberg Leuven, Department of Gastroenterology. Leuven, Belgium
| | - Pieter Demetter
- Institute Jules Bordet, Department of Gastroenterology. Brussels, Belgium
| | - Ivan Borbath
- Cliniques Universitaires Saint-Luc, Department of Gastro-enterology. Brussels, Belgium
| | | | - Anne Hoorens
- Ghent University Hospital, Department of Pathology. Ghent, Belgium
| | - Karen Geboes
- Ghent University Hospital, Department of Gastroenterology. Ghent, Belgium
| | | | - Suzane Ribeiro
- Ghent University Hospital, Department of Gastroenterology. Ghent, Belgium
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Depiction of the genomic and genetic landscape identifies CCL5 as a protective factor in colorectal neuroendocrine carcinoma. Br J Cancer 2021; 125:994-1002. [PMID: 34331023 PMCID: PMC8476633 DOI: 10.1038/s41416-021-01501-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 06/20/2021] [Accepted: 07/16/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal neuroendocrine carcinomas (CRNECs) are highly aggressive tumours with poor prognosis and low incidence. To date, the genomic landscape and molecular pathway alterations have not been elucidated. METHODS Tissue sections and clinical information of CRNEC (n = 35) and CR neuroendocrine tumours (CRNETs) (n = 25) were collected as an in-house cohort (2010-2020). Comprehensive genomic and expression panels (AmoyDx® Master Panel) were applied to identify the genomic and genetic alterations of CRNEC. Through the depiction of the genomic landscape and transcriptome profile, we compared the difference between CRNEC and CRNET. Reverse transcription-polymerase chain reaction and immunofluorescence staining were performed to confirm the genetic alterations. RESULTS High tumour mutation load was observed in CRNEC compared with CRNET. CRNECs showed a "cold" immune landscape and increased endothelial cell activity compared with NETs. Importantly, PAX5 was aberrantly expressed in CRNEC and predicted a poor prognosis of CRNECs. CCL5, a factor that is considered an immunosuppressive factor in several tumour types, was strongly expressed in CRNEC patients with long-term survival and correlated with high CD8+ T cell infiltration. CONCLUSION Through the depiction of the genomic landscape and transcriptome profile, we demonstrated alterations in molecular pathways and potential targets for immunotherapy in CRNEC.
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Nam SJ, Kim BC, Chang HJ, Jeon HH, Kim J, Kim SY. Risk Factors for Lymph Node Metastasis and Oncologic Outcomes in Small Rectal Neuroendocrine Tumors with Lymphovascular Invasion. Gut Liver 2021; 16:228-235. [PMID: 34552040 PMCID: PMC8924811 DOI: 10.5009/gnl20364] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 03/31/2021] [Accepted: 04/20/2021] [Indexed: 11/08/2022] Open
Abstract
Background/Aims Small rectal neuroendocrine tumors (NETs) are often managed with local resection (endoscopic or transanal excision) owing to their low risk of metastasis and recurrence. However, the clinical significance of lymphovascular invasion in resected specimens remains controversial. In this study, we aimed to analyze the frequency of and risk factors for lymph node metastasis proven by histopathologic examination after radical resection. Methods We retrospectively reviewed the records of 750 patients diagnosed with a rectal NET at four academic medical centers in South Korea between 2001 and 2019. The frequency of histopathologically proven lymph node metastasis and the associated risk factors were analyzed for small tumors (≤1.5 cm) with lymphovascular invasion. Results Among 750 patients, 75 had a small tumor (≤1.5 cm) with lymphovascular invasion, of whom 31 patients underwent endoscopic resection only and 44 patients underwent additional radical surgery. Among the 41 patients who underwent surgery and had available data, the rate of regional lymph node metastasis was 48.8% (20/41). In multivariate analysis, the Ki-67 index (odds ratio, 6.279; 95% confidence interval, 1.212 to 32.528; p=0.029) was an independent risk factor for lymph node metastasis. During the mean follow-up period of 37.7 months, only one case of recurrence was detected in the surgery group. The overall survival was not significantly different between radical resection and local resection (p=0.332). Conclusions Rectal NETs with lymphovascular invasion showed a significantly high rate of regional lymph node metastasis despite their small size (≤1.5 cm).
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Affiliation(s)
- Seung-Joo Nam
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Byung Chang Kim
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Hee Jin Chang
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.,Department of Pathology, Research Institute and Hospital, National Cancer Center, Goyang, Korea.,Precision Medicine, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Han Ho Jeon
- Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Junho Kim
- Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Su Young Kim
- Divison of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
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de Castro JSL, da Rocha ECV, do Vale VA, Mendonça P, Jr. OWM, Taglieri E, Koyama FSC, Filho CAMC, Nakagawa WT. Risk Factors for Development of Rectal Neuroendocrine Tumors Longer Than 9 mm: Retrospective Cohort. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2021; 32:616-621. [PMID: 34528874 PMCID: PMC8975358 DOI: 10.5152/tjg.2021.19910] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 01/13/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Rectal neuroendocrine tumors (R-NET) represent the most frequent of gastroenteropancreatic neuroendocrine neoplasms (NEN-GEP) according to the United States Surveillance, Epidemiology, and End Results database. With an annual percentage of occurrence increasing to 8.2% of all rectal neoplasms, R-NET affect less than 2% and are reported in only 0.05% to 0.07% of patients undergoing colorectal cancer (CRC) screening. The primary objective of this study was to assess the risk factors associated with R-NET greater than 10 mm. As a secondary objective, it was also aimed to evaluate the response to endoscopic treatment. METHODS This was a retrospective study, using data collected through the analysis of medical records of colonoscopies performed from January 2008 to December 2014. Records of polypectomies were identified, and the results were searched for pathological findings of R-NET. We also gathered epidemiological data and outcomes as risk factors for lesions greater than or equal to 10 mm, with local and distant recurrence. RESULTS During the study period, 18 218 colonoscopies were performed and 10 865 polypoid lesions were detected and removed, 20 with R-NET anatomopathology. The detection rate was 0.1%. The risk factors associated with major lesions were Japanese ethnicity, the lack of previous cancer diagnosis, and a Ki67 index > 2%. The mean follow-up was 56.6 months, and there was no local lymph node recurrence or distant relapse. CONCLUSION This study concludes that endoscopic resection is a good and effective method for treatment of Grade 1 rectal NET smaller than 11 mm, with high cure rates and low rates of local or distant relapse.
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Affiliation(s)
| | | | - Vanessa Assis do Vale
- Department of Gastrointestinal Endoscopy, A.C. Camargo Cancer Center, São Paulo (SP), Brazil
| | - Paula Mendonça
- Department of Gastrointestinal Endoscopy, A.C. Camargo Cancer Center, São Paulo (SP), Brazil
| | | | - Eloy Taglieri
- Department of Gastrointestinal Endoscopy, A.C. Camargo Cancer Center, São Paulo (SP), Brazil
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Della Torre S, de Nucci G, Lombardi PM, Grandi S, Manes G, Bollina R. Long-term complete response in metastatic poorly-differentiated neuroendocrine rectal carcinoma with a multimodal approach: A case report. World J Clin Oncol 2021; 12:500-506. [PMID: 34189072 PMCID: PMC8223717 DOI: 10.5306/wjco.v12.i6.500] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 12/24/2020] [Accepted: 03/03/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neuroendocrine gastrointestinal tumors (NETs) are rare and have different natural behaviors. Surgery is the gold standard treatment for local disease while radiotherapy has been demonstrated to be ineffective. Poorly differentiated neuroendocrine carcinomas (NECs) represent only 5%-10% of digestive NETS. Due to aggressive growth and rapid metastatic diffusion, early diagnosis and a multidisciplinary approach are mandatory. The role of surgery and radiotherapy in this setting is still debated, and chemotherapy remains the treatment of choice.
CASE SUMMARY A 42-year-old male with an ulcerated bleeding rectal lesion was diagnosed with a NEC G3 (Ki67 index > 90%) on May 2015 and initially treated with 3 cycles of first-line chemotherapy, but showed early local progressive disease at 3 mo and underwent sphincter-sparing open anterior low rectal resection. In September 2015, the first post-surgery total-body computed tomography (CT) scan showed an early pelvic disease relapse. Therefore, systemic chemotherapy with FOLFIRI was started and the patient obtained only a partial response. This was followed by pelvic radiotherapy (50 Gy). On April 2016, a CT scan and 18F-fluorodeoxyglucose positron emission tomography imaging showed a complete response (CR) of the pelvic lesion, but pathological abdominal inter-aortocaval lymph nodes were observed. Due to disease progression of abdominal malignant nodes, the patient received radiotherapy at 45 Gy, and finally obtained a CR. As of January 2021, the patient has no symptoms of relapse and no late toxicity after chemotherapy or radiotherapy.
CONCLUSION This case demonstrates how a multimodal approach can be successful in obtaining long-term CR in metastatic sites in patients with high grade digestive NECs.
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Affiliation(s)
| | - Germana de Nucci
- Department of Gastroenterology, Garbagnate Milanese Hospital, ASST Rhodense, Garbagnate Milanese 20024, Italy
| | | | - Samuele Grandi
- Robotic and Emergency Surgery, General Surgery Division, Manzoni Hospital, Lecco 23900, Italy
| | - Gianpiero Manes
- Gastroenterology Unit, ASST Rhodense-Garbagnate Milanese, Garbagnate Milanese 20054, Italy
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Redondo De Oro K, Redondo Bermúdez C, Mendoza Durán LD, Marrugo Padilla V, Otero Urda MS. Tumor neuroendocrino en recto simulando una neoplasia benigna: reporte de caso y revisión de la literatura. REVISTA COLOMBIANA DE CIRUGÍA 2021. [DOI: 10.30944/20117582.813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Los tumores neuroendocrinos se definen como un grupo heterogéneo de neoplasias de origen epitelial, provenientes de células enterocromafines diseminadas por todo el organismo, y representan alrededor del 1 al 4 % de todas las neoplasias. Su mayor distribución se encuentra en el tracto gastrointestinal, donde se localiza el 75 % de los tumores neuroendocrinos, siendo los ubicados en el recto, el 27 % de todos los que afectan el tracto gastrointestinal. A propósito de esta revisión de tema, presentamos el caso de un paciente de 71 años de edad, que consultó por sangrado rectal rojo rutilante, sin otra sintomatología asociada, y se le diagnosticó un tumor neuroendocrino grado 1, que se comportaba como una lesión benigna del recto.
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Toriyama K, Yamamura T, Nakamura M, Maeda K, Sawada T, Mizutani Y, Ishikawa E, Furukawa K, Ishikawa T, Ohno E, Kawashima H, Fujishiro M. An evaluation of resectability among endoscopic treatment methods for rectal neuroendocrine tumors <10 mm. Arab J Gastroenterol 2021; 22:104-110. [PMID: 34053887 DOI: 10.1016/j.ajg.2021.05.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 04/23/2021] [Accepted: 05/10/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND STUDY AIMS With respect to rectal neuroendocrine tumor (NET) resection, it remains unclear which of the following methods is the most effective: conventional endoscopic mucosal resection (cEMR), EMR using a fitted cap (EMR-C), EMR with a ligation band device (EMR-L), or endoscopic submucosal dissection (ESD). Thus, in this study, we aim to retrospectively evaluate the most effective endoscopic resection for rectal NETs < 10 mm. PATIENTS AND METHODS In total, 61 consecutive patients with primary rectal NETs < 10 mm in diameter were included in this study; they were then divided into three groups: those with cEMR; those with modified EMR (mEMR) involving EMR-C and EMR-L; and those with ESD. The primary endpoint was to evaluate the difference in the complete en bloc resection rate. The secondary endpoint was to investigate differences in procedure time and complications. RESULTS Among the three groups, a significant difference was found in procedure time (cEMR vs ESD, P < .01; mEMR vs ESD, P < .01), en bloc resection rate (cEMR vs mEMR, P = .015), tumor size (mEMR vs ESD, P < .01), percentage of tumor diameter ≥ 5 mm (mEMR vs ESD, P < .01), and complete en bloc resection rate (cEMR vs mEMR, P = .014). Meanwhile, no significant difference was noted in terms of complication rate among the three groups. CONCLUSION The mEMR was the most suitable resection method for rectal NETs < 10 mm with respect to the risks and benefits from procedure-related factors, such as complete en bloc resection rate, procedure time, and complication rate.
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Affiliation(s)
- Kazuhiro Toriyama
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Takeshi Yamamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Keiko Maeda
- Department of Endoscopy, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8560, Japan
| | - Tsunaki Sawada
- Department of Endoscopy, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8560, Japan
| | - Yasuyuki Mizutani
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Eri Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Kazuhiro Furukawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Hiroki Kawashima
- Department of Endoscopy, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8560, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
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Park BS, Cho SH, Son GM, Kim HS, Kim SJ, Park SB, Choi CW, Kim HW, Shin DH. Tumor grade 2 as the independent predictor for lymph node metastasis in 10-20 mm sized rectal neuroendocrine tumor. KOREAN JOURNAL OF CLINICAL ONCOLOGY 2021; 17:37-43. [PMID: 36945210 PMCID: PMC9942737 DOI: 10.14216/kjco.21006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 06/17/2021] [Accepted: 06/23/2021] [Indexed: 11/07/2022]
Abstract
Purpose Rectal neuroendocrine tumors (NETs) <10 mm are endoscopically resected, while those ≥20 mm are treated with radical surgical resection. The choice of treatment for 10-20 mm sized rectal NETs remains controversial. This study aimed to verify factors predicting lymph node metastasis (LNM) of 10-20 mm sized rectal NET and utilize them to decide upon the treatment strategy. Methods Twenty-eight patients with 10-20 mm sized rectal NETs treated at Pusan National University Yangsan Hospital from January 2009 to September 2020 were divided into LNM (+) and LNM (-) groups, and their respective data were analyzed. Results Seven patients (25%) had LNM while 21 patients (75%) did not. Endorectal ultrasound findings showed tumor size was significantly larger in the LNM (+) than in the LNM (-) group (15 mm vs. 10 mm, P=0.018); however, pathologically, there was no significant difference in tumor size (13 mm vs. 11 mm, P=0.109). The mitotic count (P=0.011), Ki-67 index (P=0.008), and proportion of tumor grade 2 patients (5 cases, 71% vs. 1 case, 5%; P=0.001) were significantly higher in the LNM (+) group. In multivariate analysis, tumor grade 2 was the independent factor predicting LNM (odds ratio, 61.32; 95% confidence interval, 3.17-1,188.64; P=0.010). Conclusion Tumor grade 2 was the independent factor predicting LNM in 10-20 mm sized rectal NETs. Therefore, it could be considered as the meaningful factor in determining whether radical resection is necessary.
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Affiliation(s)
- Byung-Soo Park
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Sung Hwan Cho
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Gyung Mo Son
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Hyun Sung Kim
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Su Jin Kim
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Su Bum Park
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Cheol Woong Choi
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Hyung Wook Kim
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Dong Hoon Shin
- Department of Pathology, Pusan National University Yangsan Hospital, Yangsan, Korea
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Chung HG, Goh MJ, Kim ER, Hong SN, Kim TJ, Chang DK, Kim YH. Recurrence pattern and surveillance strategy for rectal neuroendocrine tumors after endoscopic resection. J Gastroenterol Hepatol 2021; 36:968-973. [PMID: 32864790 DOI: 10.1111/jgh.15231] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 08/06/2020] [Accepted: 08/21/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIM Endoscopic resection is highly effective treatment option for rectal neuroendocrine tumors (NETs) as they usually present as small localized tumors. However, there are no well-established surveillance strategies following endoscopic resection. We established our own protocol for the surveillance of rectal NETs after endoscopic resection since 2013. This study aimed to assess the outcome and to optimize the surveillance strategies after endoscopic resection. METHODS We retrospectively analyzed the data of patients with endoscopically treated rectal NETs between January 2013 and April 2018 at Samsung Medical Center. We analyzed 337 patients with a median follow-up duration of 35.0 months (min-max: 12.0-88.3). RESULTS A total of 329 (97.6%) patients had tumors ≤ 1 cm in size, and eight (2.4%) patients had tumors > 1 cm in diameter. Synchronous rectal NETs were diagnosed in nine (2.7%) patients. Thirteen (3.9%) patients were identified as having positive resection margins. Regardless of the salvage treatment, none of these patients developed recurrence. Metachronous rectal NETs were diagnosed in nine (2.7%) patients. Metachronous lesions were associated with the number of synchronous lesions at initial diagnosis (P < 0.001, hazard ratio = 1.75, 95% confidence interval = 1.38-2.23). Extracolonic metastasis was not detected in this study. CONCLUSION Although initial screening for detecting metastatic lesions using computed tomography is recommended, repeated imaging for detecting extracolonic recurrence was not necessary for small non-metastatic rectal NETs. However, regular endoscopic follow-up seems reasonable, especially in case of synchronous rectal NETs, for detecting metachronous rectal NETs.
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Affiliation(s)
- Hye Gyo Chung
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Myung Ji Goh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Eun Ran Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sung Noh Hong
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Tae Jun Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Dong Kyung Chang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Young-Ho Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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La Rosa S, Uccella S, Rindi G. Neuroendocrine Neoplasms of the Gut. THE SPECTRUM OF NEUROENDOCRINE NEOPLASIA 2021:207-244. [DOI: 10.1007/978-3-030-54391-4_10] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Zhou Z, Wang Z, Zhang B, Wu Y, Li G, Wang Z. Comparison of 68Ga-DOTANOC and 18F-FDG PET-CT Scans in the Evaluation of Primary Tumors and Lymph Node Metastasis in Patients With Rectal Neuroendocrine Tumors. Front Endocrinol (Lausanne) 2021; 12:727327. [PMID: 34539577 PMCID: PMC8440966 DOI: 10.3389/fendo.2021.727327] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 08/16/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Lymph node metastasis of rectal neuroendocrine tumors (RNETs) predicts poor prognosis. However, the assessment of lymph node metastasis remains a challenge. It has been reported that 68Ga-DOTANOC and 18F-FDG PET-CT scans could be employed in the work-up of rectal neuroendocrine tumors (RNETs). This study aimed to assess both tracers' ability to identify primary tumors and lymph node (LN) metastasis in RNETs. METHODS A total of 537 patients with RNETs were enrolled from January 2014 to January 2021. Both 68Ga-DOTANOC and 18F-FDG PET-CT scans were used to evaluate primary tumors and LN group metastasis. PET images were evaluated through visual and semiquantitative assessment. Receiver Operating Characteristics (ROC) curve analysis was used to investigate the performance of SUVmax of 68Ga-DOTANOC and 18F-FDG PET in predicting LN group metastasis. RESULTS Fifty-two patients with preoperative 68Ga-DOTANOC with 18F-FDG PET-CT scans underwent endoscopic biopsy or dissection of the primary tumor, while 11 patients underwent rectal surgery together with regional LN dissection. For primary tumors, 68Ga-DOTANOC had a sensitivity of 89.58% and a positive predictive value (PPV) of 95.56% through visual assessment, while 18F-FDG PET-CT showed 77.08% sensitivity and 97.37% PPV. For the prediction of LN group metastasis, 68Ga-DOTANOC PET-CT had 77.78% sensitivity and 91.67% specificity, while 18F-FDG PET-CT had 38.89% sensitivity and 100% specificity according to visual assessment. The area under the ROC curves (AUC) for 68Ga-DOTANOC PET/CT was 0.852 (95%CI:0.723-0.981) with an optimal SUVmax cut-off value of 2.25, while the AUC for 18F-FDG PET were 0.664 (95%CI:0.415-0.799) with an optimal SUVmax cut-off value of 1.05. CONCLUSIONS This study showed that 68Ga-DOTANOC PET-CT was a promising tool for detecting LN metastasis in RNETs with high sensitivity and specificity in visual assessment and semiquantitative assessment, which was better than 18F-FDG PET-CT.
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Affiliation(s)
- Zhihao Zhou
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhixiong Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Bing Zhang
- Department of Nuclear Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yanzhang Wu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Guanghua Li
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- *Correspondence: Zhao Wang, ; Guanghua Li,
| | - Zhao Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- *Correspondence: Zhao Wang, ; Guanghua Li,
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Wang Z, An K, Li R, Liu Q. Tumor Macroscopic Morphology Is an Important Prognostic Factor in Predicting Chemotherapeutic Efficacy and Clinical Outcomes of Patients With Colorectal Neuroendocrine Neoplasms, One Multicenter Retrospective Cohort Study. Front Endocrinol (Lausanne) 2021; 12:801741. [PMID: 34987482 PMCID: PMC8721845 DOI: 10.3389/fendo.2021.801741] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 11/22/2021] [Indexed: 12/07/2022] Open
Abstract
BACKGROUND AND AIMS Locally advanced and metastatic colorectal neuroendocrine neoplasm (NEN) is a rare disease with a dismal prognosis. We aimed to explore the value of the macroscopic morphology of NENs in the management of TNM stage II-IV colorectal NENs, which has not been fully elucidated in previous reports. METHODS We retrospectively enrolled 125 eligible patients with TNM stage II-IV colorectal NENs who were diagnosed between 2000 and 2020 from three Chinese hospitals. All were categorized into either protruding or ulcerative NEN groups through endoscopic evaluation of their macroscopic morphology. Clinicopathological data were collected and compared between the two groups. Survival analysis was performed to assess the survival outcomes between the two groups. RESULTS A total of 77 and 48 patients had protruding and ulcerative NENs, respectively. Patients with ulcerative NENs had a larger median tumor size (P<0.001) and higher median Ki-67 index (P<0.001), and a larger proportion of these patients had grade G3 disease (P=0.001) and poorly differentiated neoplasms (P=0.001), as well as higher frequencies of T3 and T4 tumors (P=0.006) than patients with protruding NENs. In addition, patients with ulcerative NENs showed a much lower response to first-line chemotherapy [50% (95% CI: 27.3% - 72.7%) versus 20% (95% CI: 3.1% - 36.9%), P=0.03] and a worse 3-year progression-free survival (PFS) rate [19.7% (95% CI: 7.2% - 32.2%) versus 49.5% (95% CI: 37.5% - 61.5%), P=0.001] and 3-year overall survival (OS) rate [30.7% (95% CI: 15.6% - 45.8%) versus 76.9% (95% CI: 66.5% - 87.3%), P<0.001] than those with protruding NENs. The multivariate analysis results indicated that the macroscopic shape of NENs was an independent prognostic factor affecting both PFS (HR = 1.760, 95% CI: 1.024 - 3.026, P = 0.04) and OS (HR = 2.280, 95% CI: 1.123 - 4.628, P = 0.02). CONCLUSIONS Ulcerative NENs were more malignant and chemotherapy resistant than protruding NENs. Tumor macroscopic morphology is a valuable prognostic factor for stage II-IV colorectal NENs.
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Affiliation(s)
- Zhijie Wang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ke An
- Department of General Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Rui Li
- Department of General Surgery, Beijing Hospital, Beijing, China
| | - Qian Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Qian Liu,
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Panzuto F, Massironi S, Partelli S, Campana D, Rinzivillo M, Invernizzi P, Andreasi V, Lamberti G, Falconi M. Gastro-entero-pancreatic neuroendocrine neoplasia: The rules for non-operative management. Surg Oncol 2020; 35:141-148. [PMID: 32877883 DOI: 10.1016/j.suronc.2020.08.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 07/26/2020] [Accepted: 08/17/2020] [Indexed: 02/05/2023]
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with favorable pathological and clinical features may be considered as indolent lesions, and therefore be amenable to conservative management. According to the primary tumor site, different non-aggressive approaches, based on endoscopic resection or simple active surveillance, can be proposed to selected patients fulfilling specific criteria. Tumor size, Ki67 proliferative index and depth of invasion are markers that can be used in order to identify these subjects. Patients with type I gastric NENs <1 cm as well as those with non-ampullary duodenal NENs <1 cm with no associated syndrome can be safely managed by endoscopic resection. On the other hand, an active surveillance approach is preferred over surgery for patients with asymptomatic, non-functioning pancreatic NENs ≤2 cm without dilation of the main pancreatic duct or bile duct. As far as NENs of the appendix are concerned, appendectomy should be considered as curative when a R0 resection has been achieved in the presence of a tumor ≤1.5 cm, graded as G1 and without lymphovascular invasion. Finally, G1 rectal NENs ≤1 cm without invasion of the muscular layer can be safely treated by endoscopic resection. Therefore, surgeons should be aware of the existence of indolent GEP-NENs, in order to avoid unnecessary operations with associated postoperative complications.
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Affiliation(s)
- Francesco Panzuto
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy.
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Stefano Partelli
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute - Vita-Salute San Raffaele University, Milan, Italy
| | - Davide Campana
- Division of Oncology, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Valentina Andreasi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute - Vita-Salute San Raffaele University, Milan, Italy
| | - Giuseppe Lamberti
- Division of Oncology, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Massimo Falconi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute - Vita-Salute San Raffaele University, Milan, Italy
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Lee HS, Moon HS, Kwon IS, Park JH, Kim JS, Kang SH, Lee ES, Kim SH, Sung JK, Lee BS, Jeong HY. Comparison of conventional and modified endoscopic mucosal resection methods for the treatment of rectal neuroendocrine tumors. Surg Endosc 2020; 35:6055-6065. [PMID: 33094828 DOI: 10.1007/s00464-020-08097-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 10/13/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIM Small rectal neuroendocrine tumors (NETs) confined to the submucosa are endoscopically resectable. Because most rectal NETs are submucosal tumors, conventional endoscopic mucosal resection (cEMR) may not result in a complete resection. This study investigated whether modified EMRs, namely endoscopic submucosal resection with ligation (ESMR-L), EMR with precutting (EMR-P), and strip biopsy are superior to cEMR for achieving histologically complete resection (HCR) of rectal NETs. METHODS Medical records of 215 patients who were treated with endoscopic resections for rectal NETs between January 2011 and July 2019 were retrospectively enrolled. Of the patients, 110, 33, 29, and 43 underwent cEMR, ESMR-L, EMR-P, and strip biopsy, respectively. For each method, HCR and en bloc resection rates, procedure times, and complication rates were measured. RESULTS HCR was achieved with cEMR, EMR-P, ESMR-L, and strip biopsies for 74.5%, 90.9%, 93.1%, and 90.7% of cases, respectively. The HCR rate for cEMR was inferior to those of the modified EMRs (p = 0.045 for cEMR vs. EMR-P; p = 0.031 for cEMR vs. ESMR-L; p = 0.027 for cEMR vs. strip biopsy). Among the three modified EMRs, there was no significant difference in achieving HCR (p = 1.000). En bloc resection (p = 0.096) and complication rates (p = 0.071) were not significantly different among the four EMR methods, although EMR-P required the longest procedure time (p = 0.000). CONCLUSIONS All three modified EMRs are superior to cEMR and are equally effective for achieving HCR of rectal NETs.
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Affiliation(s)
- Hee Sung Lee
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University College of Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea
| | - Hee Seok Moon
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University College of Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea.
| | - In Sun Kwon
- Clinical Trials Center, Chungnam National University Hospital, Daejeon, 35015, South Korea
| | - Jae Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University College of Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea
| | - Ju Seok Kim
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University College of Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea
| | - Sun Hyung Kang
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University College of Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea
| | - Eaum Seok Lee
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University College of Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea
| | - Seok Hyun Kim
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University College of Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea
| | - Jae Kyu Sung
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University College of Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea
| | - Byung Seok Lee
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University College of Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea
| | - Hyun Yong Jeong
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University College of Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon, 35015, South Korea
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Rindi G, Wiedenmann B. Neuroendocrine neoplasia of the gastrointestinal tract revisited: towards precision medicine. Nat Rev Endocrinol 2020; 16:590-607. [PMID: 32839579 DOI: 10.1038/s41574-020-0391-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/03/2020] [Indexed: 02/06/2023]
Abstract
Over the past 5 years, a number of notable research advances have been made in the field of neuroendocrine cancer, specifically with regard to neuroendocrine cancer of the gastrointestinal tract. The aim of this Review is to provide an update on current knowledge that has proven effective for the clinical management of patients with these tumours. For example, for the first time in the tubular gastrointestinal tract, well-differentiated high-grade (grade 3) tumours and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are defined in the WHO classification. This novel classification enables efficient identification of the most aggressive well-differentiated neuroendocrine tumours and helps in defining the degree of aggressiveness of MiNENs. The Review also discusses updates to epidemiology, cell biology (including vesicle-specific components) and the as-yet-unresolved complex genetic background that varies according to site and differentiation status. The Review summarizes novel diagnostic instruments, including molecules associated with the secretory machinery, novel radiological approaches (including pattern recognition techniques), novel PET tracers and liquid biopsy combined with DNA or RNA assays. Surgery remains the treatment mainstay; however, peptide receptor radionuclide therapy with novel radioligands and new emerging medical therapies (including vaccination and immunotherapy) are evolving and being tested in clinical trials, which are summarized and critically reviewed here.
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Affiliation(s)
- Guido Rindi
- Università Cattolica del Sacro Cuore, Rome, Italy.
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
| | - Bertram Wiedenmann
- Charité, Campus Virchow Klinikum and Charité Mitte, University Medicine Berlin, Berlin, Germany
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Chida K, Watanabe J, Hirasawa K, Inayama Y, Misumi T, Kunisaki C, Endo I. A novel risk-scoring system for predicting lymph node metastasis of rectal neuroendocrine tumors. Ann Gastroenterol Surg 2020; 4:562-570. [PMID: 33005851 PMCID: PMC7511567 DOI: 10.1002/ags3.12355] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 05/11/2020] [Accepted: 05/14/2020] [Indexed: 01/02/2023] Open
Abstract
AIM Although rectal neuroendocrine tumors (NETs) are considered to be rare low-grade malignancies when lymph node metastasis (LNM) is present, their degree of malignancy is comparable to that of colorectal cancer (CRC). However, it remains unclear as to which patients require radical lymph node dissection. The aim of this study was to elucidate the risk factors for LNM and develop a risk-scoring system for LNM to help determine appropriate therapeutic approaches. METHODS In this study, we examined 103 patients with rectal NETs who underwent local resection (n = 55) or radical resection with LN dissection (n = 48). We evaluated each pathological feature, including the depth of submucosal invasion (SM depth) and tumor budding grade. RESULTS According to our univariate analyses and previous reports, the significant five risk factors for LNM were weighted with point values: 2 points for tumor size ≥ 15 mm and muscularis invasion, and 1 point each for SM depth ≥ 2000 µm, positive lymphovascular invasion, budding grade 3, and vertical margin. The area under the receiver operating curve for the scoring system was 0.899 (95% CI: 0.843-0.955). When a score of 2 was used as the cut-off value, the sensitivity and specificity for the prediction of LNM were 100% and 72.1%, respectively. CONCLUSIONS The risk-scoring system for LNM of rectal NETs showed high diagnostic performance. Using this risk-scoring system, it is possible to predict the risk of LNM and thereby potentially avoid unnecessary surgery. Further prospective external validation studies should be performed. The study was registered in the Japanese Clinical Trials Registry as UMIN000036658.
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Affiliation(s)
- Keigo Chida
- Department of Gastroenterological SurgeryYokohama City University Graduate School of MedicineYokohamaJapan
| | - Jun Watanabe
- Department of SurgeryGastroenterological CenterYokohama City University Medical CenterYokohamaJapan
| | - Kingo Hirasawa
- Division of EndoscopyYokohama City University Medical CenterYokohamaJapan
| | - Yoshiaki Inayama
- Department of PathologyYokohama City University Medical CenterYokohamaJapan
| | - Toshihiro Misumi
- Department of BiostatisticsYokohama City University School of MedicineYokohamaJapan
| | - Chikara Kunisaki
- Department of SurgeryGastroenterological CenterYokohama City University Medical CenterYokohamaJapan
| | - Itaru Endo
- Department of Gastroenterological SurgeryYokohama City University Graduate School of MedicineYokohamaJapan
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Juhlin CC, Falhammar H, Kjellman M, Åhlén J, Welin S, Calissendorff J. Highly proliferative anal neuroendocrine carcinoma: molecular and clinical features of a rare, recurrent case in complete remission. BMC Gastroenterol 2020; 20:290. [PMID: 32854635 PMCID: PMC7457256 DOI: 10.1186/s12876-020-01433-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 08/20/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Poorly differentiated anal neuroendocrine carcinomas (ANECs) are rare lesions with poor prognosis, and the molecular etiology is only partially understood. CASE PRESENTATION At our institution, we have treated and followed a patient with such a rare ANEC. He had primarily surgery followed by three rounds of repeated surgery for loco-regional recurrences. He also received three different combinations of chemotherapy and external beam radiation. At last follow-up 13 years since the primary diagnosis, the patient had been in complete remission for nine years. The patient's medical files were re-examined, including laboratory, radiology and clinical examinations. Histopathology was re-assessed, and expanded immunohistochemistry was performed from tissue specimens from the four surgical procedures. In addition, the molecular genetic status was evaluated through next-generation sequencing. The initial tumor was consistent with a 59 mm small cell neuroendocrine cancer with a Ki-67 index of 80%. Regional lymph node metastases were evident, and immunohistochemistry supported a neuroendocrine origin. A PCR screening detected human papilloma virus type 45 DNA (high-risk subtype), and focused next-generation sequencing found a missense mutation in the Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) gene. In tissues representing subsequent recurrences, the Chromogranin A expression was lost, and the Ki-67 index increased to 90%. CONCLUSIONS For the first time, we report the detection of HPV45 in a case of ANEC. To our belief, PIK3CA mutations have also not been previously demonstrated in this tumor entity. In highly malignant ANECs, cure can in rare cases be achieved. Although speculative, expression of HPV45 and/or the PIK3CA mutation may have contributed to the favorable outcome.
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Affiliation(s)
- Carl Christofer Juhlin
- Department of Oncology-Pathology, BioClinicum J6:20, Karolinska Institutet, Stockholm, Solna, Sweden. .,Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden.
| | - Henrik Falhammar
- Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.,Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Magnus Kjellman
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Jan Åhlén
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Staffan Welin
- Institution of Medical Sciences, Uppsala Akademiska Hospital, Uppsala, Sweden.,Department of Endocrine Oncology, Uppsala Akademiska Hospital, Uppsala, Sweden
| | - Jan Calissendorff
- Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden. .,Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
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