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Bartsch DK, Krasser‐Gercke N, Jesinghaus M, Görlach J, Eilsberger F, Rinke A, Maurer E. Results of Surgical Reintervention After Suboptimal Initial Resection for Locoregional Neuroendocrine Tumors of the Small Intestine. World J Surg 2025; 49:1343-1350. [PMID: 40238178 PMCID: PMC12058433 DOI: 10.1002/wjs.12582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Revised: 03/09/2025] [Accepted: 03/23/2025] [Indexed: 04/18/2025]
Abstract
BACKGROUND Complete resection is the only chance for cure in small intestine neuroendocrine neoplasms (SI-NEN). Previous ENETS guidelines proposed standards for the surgery of SI-NEN, which should be followed to provide long-term disease-free survival. AIM To analyze the results of reintervention for locoregional SI-NEN (stages I-III) after suboptimal initial resection. METHODS Perioperative characteristics of all patients who underwent surgical reintervention after suboptimal initial resection (SIR) of locoregional SI-NEN were retrieved from a prospective database. Patient characteristics, initial and redo procedures, imaging before reintervention, pathological results of SIR, and after reintervention, including missed primary tumors and lymph node metastases, were retrospectively analyzed. RESULTS During a 15 years period, 21 of 93 (22%) patients had surgical reinterventions after SIR. In 20 of 21 (95%) cases, the initial resection was performed outside an ENETS center of excellence. Ten (48%) of those cases were emergency operations because of the bowel obstruction or bowel bleeding. Seven SIR (33%) cases were performed laparoscopically, and in another 5 (24%) cases, a complete endoscopic mucosa resection was performed. Imaging before reintervention visualized residual disease in 15 of 21 (71%) patients. Surgical reintervention included either lymphadenectomy alone (LAD, n = 3) or small bowel resection plus systematic LAD (n = 12) or right hemicolectomy/ileocecal resection with systematic LAD (n = 6), respectively. In 19 of 21 (90%) patients, a R0 resection could be achieved. One patient (5%) experienced postoperative clinically relevant complications. According to pathology, in 10 (48%) patients lymph node metastases, in 6 (29%) patients additional primary tumors, and in 5 (24%) patients, both lymph nodes metastases and primary tumors were left behind in the SIR. After mean follow-up of 52 months, 16 (76%) of 21 patients were free of disease, 4 (19%) patients were alive with disease, and 1 patient deceased of an unrelated cause. CONCLUSION The proposed standards to resect locoregional SI-NEN should be followed to avoid SIR, although the prognosis after adequate surgical reintervention is good.
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Affiliation(s)
- Detlef K. Bartsch
- Department of Visceral‐, Thoracic‐ and Vascular SurgeryPhilipps‐University MarburgMarburgGermany
| | - Norman Krasser‐Gercke
- Department of Visceral‐, Thoracic‐ and Vascular SurgeryPhilipps‐University MarburgMarburgGermany
| | | | - Jannis Görlach
- Department of Diagnostic and Interventional RadiologyPhilipps‐University MarburgMarburgGermany
| | | | - Anja Rinke
- Department of Gastroenterology and EndocrinologyPhilipps‐University MarburgMarburgGermany
| | - Elisabeth Maurer
- Department of Visceral‐, Thoracic‐ and Vascular SurgeryPhilipps‐University MarburgMarburgGermany
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Spyroglou A, Violetis O, Iliakopoulos K, Vezakis A, Alexandraki K. Mesenteric Fibrosis in Neuroendocrine Neoplasms: a Systematic Review of New Thoughts on Causation and Potential Treatments. Curr Oncol Rep 2025; 27:642-655. [PMID: 40214893 DOI: 10.1007/s11912-025-01668-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/10/2025] [Indexed: 05/16/2025]
Abstract
PURPOSE OF REVIEW Mesenteric fibrosis (MF) is a hallmark of small intestinal neuroendocrine neoplasms (SI-NEN) and is frequently associated with significant morbidity due to related complications such as intestinal obstruction, ischemia, and cachexia. RECENT FINDINGS Herein we performed a systematic review to discuss the development of MF in SI-NEN. The pathophysiological mechanisms acknowledged as causative for the development of MF include the major components of the tumor microenvironment, such as fibroblasts, endothelial and immune cells and the extracellular matrix, which are involved in a complex interplay activating several signaling pathways that promote profibrotic factors and induce both a desmoplastic reaction and tumor proliferation. Surgery remains the mainstay of treatment, while several medical management options of MF complicating SI-NEN available present rather limited efficacy. MF is a frequent characteristic of SI-NEN that requires particular attention and targeted management to avoid complications.
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Affiliation(s)
- Ariadni Spyroglou
- 2nd Department of Surgery, Aretaieio Hospital, National and Kapodistrian University of Athens, Vas. Sofias 76, 11528, Athens, Greece
| | - Odysseas Violetis
- 2nd Department of Surgery, Aretaieio Hospital, National and Kapodistrian University of Athens, Vas. Sofias 76, 11528, Athens, Greece
| | - Konstantinos Iliakopoulos
- 2nd Department of Surgery, Aretaieio Hospital, National and Kapodistrian University of Athens, Vas. Sofias 76, 11528, Athens, Greece
| | - Antonios Vezakis
- 2nd Department of Surgery, Aretaieio Hospital, National and Kapodistrian University of Athens, Vas. Sofias 76, 11528, Athens, Greece
| | - Krystallenia Alexandraki
- 2nd Department of Surgery, Aretaieio Hospital, National and Kapodistrian University of Athens, Vas. Sofias 76, 11528, Athens, Greece.
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Bartsch DK, Krasser-Gercke N, Rinke A, Mahnken A, Jesinghaus M, Eilsberger F, Maurer E. Outcome of Debulking the Mesenteric Mass in Symptomatic Patients with Locally Advanced Small Intestine Neuroendocrine Tumors. Cancers (Basel) 2025; 17:1318. [PMID: 40282494 PMCID: PMC12025694 DOI: 10.3390/cancers17081318] [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: 03/02/2025] [Revised: 03/30/2025] [Accepted: 04/09/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND Approximately 10% of patients with small intestine neuroendocrine neoplasms (SI-NENs) present with locally advanced, unresectable symptomatic disease. The present study analyzed the results of debulking of the mesenteric mass in such patients. METHODS Patients operated on for locally advanced SI-NEN disease were identified from the prospective database of the ENETS Center of Excellence Marburg based on the review of imaging results and operative notes. "Locally advanced" was defined as mesenteric disease involving the mesenteric root above the level of the horizontal part of the duodenum and/or extending into the retroperitoneum. Patient characteristics, operations, and outcomes were retrospectively analyzed. RESULTS 29 of 202 (14%) operated SI-NEN patients (79% male) operated on, with a median age of 63 (46-78) years, had symptomatic locally advanced disease and presented with either abdominal pain (76%) and/or symptoms of obstruction (38%). Imaging revealed a mesenteric mass >10 mm above the level of the pars descendens duodeni in 15 (52%) patients, with tumor-related obstruction of the superior mesenteric vein in 17 (59%) patients. Fourteen (48%) patients had had previous surgery with primary tumor resection (n = 10) or diagnostic or bypass procedures (n = 4). Debulking of the mesenteric mass with (n = 26) or without (n = 2) bowel resection was performed 28 patients; the remaining patient underwent only resection of the ischemic bowel. Median operating time was 262 (156-411) minutes. Four (14%) patients had clinically relevant postoperative complications; one patient died perioperatively. A total of 27/29 (93%) patients reported improvement in preoperative abdominal symptoms. After a median follow-up of 28 (1-142) months, 21 (72%) patients were alive with disease. CONCLUSIONS Debulking of the mesenteric mass in locally advanced symptomatic SI-NENs is a challenging procedure, but most patients benefit in terms of bowel symptoms.
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Affiliation(s)
- Detlef K. Bartsch
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, 35043 Marburg, Germany; (D.K.B.); (N.K.-G.)
| | - Norman Krasser-Gercke
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, 35043 Marburg, Germany; (D.K.B.); (N.K.-G.)
| | - Anja Rinke
- Department of Gastroenterology and Endocrinology, Philipps-University Marburg, 35043 Marburg, Germany;
| | - Andreas Mahnken
- Department of Diagnostic and Interventional Radiology, Philipps-University Marburg, 35043 Marburg, Germany;
| | - Moritz Jesinghaus
- Institute of Pathology, Philipps-University Marburg, 35043 Marburg, Germany;
| | - Friederike Eilsberger
- Department of Nuclear Medicine, Philipps-University Marburg, 35043 Marburg, Germany;
| | - Elisabeth Maurer
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, 35043 Marburg, Germany; (D.K.B.); (N.K.-G.)
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Klimácek B, Åkerström T, Annebäck M, Hellman P, Norlén O, Stålberg P. Evaluation of hand-assisted laparoscopic surgery of small intestinal neuroendocrine tumours as an alternative surgical treatment to open surgery. Langenbecks Arch Surg 2025; 410:90. [PMID: 40047926 PMCID: PMC11885331 DOI: 10.1007/s00423-025-03658-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Accepted: 02/23/2025] [Indexed: 03/09/2025]
Abstract
PURPOSE Small intestinal neuroendocrine tumours (SI-NETs) are the most common malignancy of the small bowel. Curative treatment is surgical, with exploratory laparotomy considered the standard approach. This study aimed to assess the outcomes of minimally invasive surgery compared to open approach for SI-NETs at the Endocrine surgical unit at Uppsala University Hospital. METHODS This retrospective cohort study included patients who underwent surgery for SI-NET between 2013 and 2023 at Uppsala University Hospital. Variables such as operative time, length of hospital stay, use of analgesia and radicality were compared between groups of patients operated on before and after 2019, when hand-port assisted laparoscopic surgery (HALS) for SI-NETs was introduced at our unit. Outcomes were further compared between open and hand-port assisted laparoscopic approaches. The primary outcome was the rate of radicality achieved for stage II-III patients. Secondary outcomes included operative time, the length of hospital stay and the use of epidural and patient-controlled analgesia. RESULTS Of 97 patients, 58 (59.8%) underwent open surgery and 39 (40.2%) underwent hand-port assisted laparoscopic surgery. There was no significant difference in operative time (121 min [91.3-150.3] vs 108 min [83-141]), length of hospital stay, 6 days [4-7] vs 5 days [4-8]), and surgical radicality in patients with stage II-III, 85.2% vs 100%, (p = 0.079). 86.2% of patients with explorative laparotomy required epidural analgesia compared to only 23.1% with HALS (p < 0.001). CONCLUSION Hand-port assisted laparoscopic surgery of SI-NETs is a feasible approach that preserves radical resection while enhancing postoperative recovery, with a lower requirement of epidural analgesia.
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Affiliation(s)
- Branislav Klimácek
- Department of Surgical Sciences, Uppsala University Hospital, 751 85, Uppsala, Sweden.
| | - Tobias Åkerström
- Department of Surgical Sciences, Uppsala University Hospital, 751 85, Uppsala, Sweden
| | - Matilda Annebäck
- Department of Surgical Sciences, Uppsala University Hospital, 751 85, Uppsala, Sweden
| | - Per Hellman
- Department of Surgical Sciences, Uppsala University Hospital, 751 85, Uppsala, Sweden
| | - Olov Norlén
- Department of Surgical Sciences, Uppsala University Hospital, 751 85, Uppsala, Sweden
| | - Peter Stålberg
- Department of Surgical Sciences, Uppsala University Hospital, 751 85, Uppsala, Sweden
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Ritter AS, Poppinga J, Steinkraus KC, Hackert T, Nießen A. Novel Surgical Initiatives in Gastroenteropancreatic Neuroendocrine Tumours. Curr Oncol Rep 2025; 27:157-167. [PMID: 39862354 PMCID: PMC11861007 DOI: 10.1007/s11912-024-01632-4] [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] [Accepted: 12/24/2024] [Indexed: 01/27/2025]
Abstract
PURPOSE OF REVIEW Neuroendocrine tumours (NET) are rare entities arising from hormone producing cells in the gastroentero-pancreatic (GEP) tract. Surgery is the most common treatment of GEP-NETs. RECENT FINDINGS Improvements in surgical techniques allow for more locally advanced and metastasised GEP-NETs to be resected. Laparoscopic and robotically--assisted approaches are increasingly being utilised in the resection of selected GEP-NETs and are facilitated by novel intraoperative tumour localisation tools and parenchyma-sparing methods. At the same time, some authors suggest that indications for formal resections of small well differentiated non-functioning pancreatic NETs and appendiceal NETs should be more restrictive. Advancements in surgery allows for tissue-sparing resections of GEP-NETs. Indications for surgical resection and the extent of the procedure are highly dependent on GEP-NET size, localisation and grading. Robotically assisted surgeries with intraoperative ultrasound and visualisation methods as well as vessel-sparing radical retrograde lymphadenectomies for small intestinal NETs seem to be the future of GEP-NET surgery.
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Affiliation(s)
- Alina S Ritter
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg- Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany
| | - Jelte Poppinga
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg- Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany
| | - Kira C Steinkraus
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg- Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg- Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany
| | - Anna Nießen
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg- Eppendorf, Martinistraße 52, D-20246, Hamburg, Germany.
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Howe JR, Menda Y, Chandrasekharan C, Bellizzi AM, Quelle DE, O'Dorisio MS, Dillon JS. The University of Iowa Neuroendocrine Tumor Clinic. Endocr Pract 2025; 31:4-18. [PMID: 39349242 PMCID: PMC11700786 DOI: 10.1016/j.eprac.2024.09.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 09/16/2024] [Accepted: 09/23/2024] [Indexed: 10/02/2024]
Abstract
The Iowa Neuroendocrine Tumor (NET) Clinic was founded and developed by two remarkable physicians, Thomas and Sue O'Dorisio. Tom was an Endocrinologist and close friend and colleague of Aaron Vinik. Both men were pioneers in studies of gastrointestinal hormones and the management of patients with NETs. Sue was a Pediatric Oncologist and research scientist with great expertise in new drug development and clinical trials. She and Tom were leaders in bringing somatostatin analogs and somatostatin-conjugated radioligands to the clinic for the therapy and diagnosis of NETs. All three physicians received lifetime achievement awards for their contributions to the field of NETs. This is the story of how the Iowa NET Clinic developed over the years to become a model for the multidisciplinary mantagement of patients with NETs, culminating in its designation as a European Neuroendocrine Tumor Society NET Center of Excellence, and the receipt of a Specialized Project of Research Excellence (SPORE) grant for the study of NETs from the National Institutes of Health.
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Affiliation(s)
- James R Howe
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa.
| | - Yusuf Menda
- Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | | | - Andrew M Bellizzi
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - Dawn E Quelle
- Departments of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - M Sue O'Dorisio
- Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa
| | - Joseph S Dillon
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa
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7
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Butz F, Supper L, Reinhard L, Dukaczewska A, Jann H, Fehrenbach U, Müller-Debus CF, Skachko T, Pratschke J, Goretzki PE, Mogl MT, Dobrindt EM. Emergency surgery influences oncological outcome in small intestinal neuroendocrine tumors. Scand J Surg 2024; 113:303-313. [PMID: 39230104 DOI: 10.1177/14574969241271841] [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] [Indexed: 09/05/2024]
Abstract
BACKGROUND AND AIMS Patients with small intestinal neuroendocrine tumors (siNETs) frequently present emergently due to bowel ischemia or bowel obstruction. The influence of emergency surgery on the prognosis of siNET remains controversial. The aim of this study was to investigate the association between type of presentation (emergency/elective) and oncological outcome. METHODS Clinicopathological data of patients who underwent bowel resection and were treated due to siNET at the Charité - Universitätsmedizin Berlin, Germany were analyzed retrospectively. RESULTS A total of 165 patients underwent bowel resection for siNET. Of these, 22.4% (n = 37) were emergency and 77.6% (n = 128) were elective procedures. A preoperative known diagnosis was less common in patients with emergency surgery (48.6% vs 85.2%; p < 0.001) and complete resections of all tumor manifestations were performed less often (32.4% vs 50.8%; p = 0.049), while more completion operations had to be performed (24.3% vs 11.1%; p = 0.049). Overall survival (OS) and progression-free survival (PFS) of emergently operated patients were reduced (5-year OS: 85.2% vs 89.5% (p = 0.023); 5-year PFS: 26.7% versus 52.5% (p = 0.018)). In addition, emergency surgery was negatively associated with OS after multivariable regression analysis. CONCLUSION Emergency surgery in siNET patients is associated with adverse oncological outcomes including shorter OS and PFS. Prevention of emergency conditions should be emphasized in advanced disease.
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Affiliation(s)
- Frederike Butz
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
| | - Leonie Supper
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Lisa Reinhard
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Agata Dukaczewska
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Henning Jann
- Department of Hepatology and Gastroenterology, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Uli Fehrenbach
- Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Charlotte Friederike Müller-Debus
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Tatiana Skachko
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Peter E Goretzki
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Martina T Mogl
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Eva M Dobrindt
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
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8
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Maurer E, Bartsch DK. [Local resection of small intestine neuroendocrine neoplasms (SI-NEN) : Current principles]. CHIRURGIE (HEIDELBERG, GERMANY) 2024; 95:818-824. [PMID: 38771340 DOI: 10.1007/s00104-024-02102-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/24/2024] [Indexed: 05/22/2024]
Abstract
BACKGROUND Neuroendocrine tumors of the small bowel (small intestine neuroendocrine neoplasms, SI-NEN) are the most frequent tumors of the small intestine and approximately 30-40% are still surgically treatable with curative intent at the time of diagnosis. Certain surgical principles must be followed for optimal oncological outcomes and good postoperative quality of life. METHODS Based on international guidelines and own experiences, the locoregional surgical treatment of SI-NENs is presented. RESULTS Locoregional SI-NENs should always be resected if technically feasible, as only this approach can achieve a long-term cure and even small primary tumors (< 10 mm) often already show lymphatic metastasis. The resectability of SI-NENs and their difficulty depend on the extent of lymphatic metastasis, which should be assessed based on preoperative imaging of the extent around the superior mesenteric artery. Currently, the surgical gold standard for SI-NENs is open surgery with bidigital palpation of the entire small intestine followed by primary tumor resection via small bowel segment resection, right hemicolectomy or ileocecal resection and vessel-sparing, and therefore organ-preserving lymphadenectomy (≥ 8 lymph nodes). The guidelines consider that laparoscopic or robotic approaches are justified only for early stages of SI-NENs. CONCLUSION Guideline-compliant surgical treatment of locoregional SI-NEN enables recurrence-free long-term survival with good quality of life.
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Affiliation(s)
- Elisabeth Maurer
- Klinik für Visceral‑, Thorax- und Gefäßchirurgie, Philipps-Universität Marburg, Baldingerstraße, 35043, Marburg, Deutschland.
| | - Detlef K Bartsch
- Klinik für Visceral‑, Thorax- und Gefäßchirurgie, Philipps-Universität Marburg, Baldingerstraße, 35043, Marburg, Deutschland
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Lamarca A, Bartsch DK, Caplin M, Kos-Kudla B, Kjaer A, Partelli S, Rinke A, Janson ET, Thirlwell C, van Velthuysen MLF, Vullierme MP, Pavel M. European Neuroendocrine Tumor Society (ENETS) 2024 guidance paper for the management of well-differentiated small intestine neuroendocrine tumours. J Neuroendocrinol 2024; 36:e13423. [PMID: 38977327 DOI: 10.1111/jne.13423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 05/28/2024] [Accepted: 06/02/2024] [Indexed: 07/10/2024]
Abstract
Both the incidence and prevalence of well-differentiated neuroendocrine tumours from the small intestine (Si-NET) are gradually increasing. Most patients have non-functioning tumours with subtle GI symptoms and tumours are often discovered incidentally by endoscopy or at advanced disease stages by imaging depicting mesenteric lymph node and /or liver metastases while around 30% of the patients present with symptoms of the carcinoid syndrome. Adequate biochemical assessment and staging including functional imaging is crucial for treatment-related decision-making that should take place in an expert multidisciplinary team setting. Preferably, patients should be referred to specialised ENETS Centres of Excellence or centres of high expertise in the field. This guidance paper provides the current evidence and best knowledge for the management of Si-NET grade (G) 1-3 following 10 key questions of practical relevance for the diagnostic and therapeutic decision making.
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Affiliation(s)
- Angela Lamarca
- Department of Oncology - Onco Health Institute, Fundación Jiménez Díaz University Hospital, Madrid, Spain
- Department of Medical Oncology, The Christie NHS Foundation, Manchester, Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - Detlef K Bartsch
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps University Marburg, Marburg, Germany
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
| | - Beata Kos-Kudla
- Department of Endocrinology and Neuroendocrine Tumors, ENETS Center of Excellence, Department of Pathophysiology and Endocrinology, Medical University of Silesia, Katowice, Poland
| | - Andreas Kjaer
- Department of Clinical Physiology and Nuclear Medicine and Cluster for Molecular Imaging, Copenhagen University of Copenhagen-Rigshospitalet, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Stefano Partelli
- Pancreas Translational and Clinical Research Centre, Pancreatic and Transplant Surgery Unit, Vita-Salute San Raffaele University, Milan, Italy
| | - Anja Rinke
- Department of Gastroenterology, University Hospital Marburg and Philipps University Marburg, Marburg, Germany
| | - Eva Tiensuu Janson
- Department of Medical Sciences, Endocrine Oncology Unit, Uppsala University, Uppsala, Sweden
| | - Christina Thirlwell
- Department of Medical Oncology, University of Exeter Medical School, Exeter, UK
| | | | - Marie-Pierre Vullierme
- Department of Radiology, Paul Brousse University Hospital, AP-HP-University Paris Saclay, Villejuif, France
| | - Marianne Pavel
- Department of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, ENETS Center of Excellence Erlangen, CCC Erlangen- EMN, and Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany
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10
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Yogo A, Paciorek A, Kasai Y, Moon F, Hirose K, Corvera CU, Bergsland EK, Nakakura EK. Long-Term Survival Outcomes After Minimally Invasive Surgery for Ileal Neuroendocrine Tumors. Ann Surg Oncol 2024; 31:5507-5514. [PMID: 38797790 PMCID: PMC11300575 DOI: 10.1245/s10434-024-15468-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 05/01/2024] [Indexed: 05/29/2024]
Abstract
BACKGROUND Ileal neuroendocrine tumors (i-NETs) are characterized by their multifocality and bulky mesenteric mass. Having shown that minimally invasive surgery (MIS) utilizing a hand-access port device has favorable short-term outcomes and achieves the goals of surgery for i-NETs, we sought to analyze long-term survival outcomes of MIS. METHODS One hundred and sixty-eight patients who underwent resection of primary i-NETs at a single institution between January 2007 and February 2023 were retrospectively studied. Patients were categorized into the MIS or open surgery cohorts on an intention-to-treat basis. Open surgery was selected mainly based on the need for hepatectomy or bulky mesenteric mass resection. Overall survival was analyzed using log-rank tests with propensity score matching (PSM) and Cox proportional hazards regression. PSM was performed to reduce standardized mean differences of the variables to <0.2. RESULTS Overall, 129 (77%) patients underwent MIS and 39 (23%) underwent open surgery. Twenty-seven MIS patients were converted to an open procedure. The median follow-up time was 49 months (interquartile range 23-87 months). In the PSM cohorts, overall survival did not differ significantly between the MIS and open surgery cohorts {median 99 months (95% confidence interval [CI] 91-not applicable [NA]) vs. 103 months (95% CI 86-NA), p = 0.77; hazard ratio 0.87 (95% CI 0.33-2.2), p = 0.77}. CONCLUSIONS MIS is an alternative to open surgery for i-NETs, achieving similar short- and long-term oncological outcomes. Bulky mesenteric mass and a plan for concurrent liver resection are potential criteria for open surgery.
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Affiliation(s)
- Akitada Yogo
- Division of Surgical Oncology, Section of Hepatopancreaticobiliary Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA
- Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Alan Paciorek
- Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA
| | - Yosuke Kasai
- Department of Surgery, Kyoto University, Kyoto, Japan
| | - Farhana Moon
- Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Kenzo Hirose
- Division of Surgical Oncology, Section of Hepatopancreaticobiliary Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA
- Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Carlos U Corvera
- Division of Surgical Oncology, Section of Hepatopancreaticobiliary Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA
- Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Emily K Bergsland
- Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
- Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Eric K Nakakura
- Division of Surgical Oncology, Section of Hepatopancreaticobiliary Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
- Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
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11
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Holzer K, Bartsch DK. [Gastroenteropancreatic neuroendocrine neoplasms-Surgery in a multimodal concept]. CHIRURGIE (HEIDELBERG, GERMANY) 2024; 95:773-782. [PMID: 38935138 DOI: 10.1007/s00104-024-02117-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/23/2024] [Indexed: 06/28/2024]
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are mainly found in the small intestine and pancreas. The course of the disease in patients is highly variable and depends on the degree of differentiation (G1-G3) of the neoplasm. The potential for metastasis formation of GEP-NEN is high even with good differentiation (G1). Lymph node metastases and, in many cases, liver metastases are also often found. Less common are bone metastases or peritoneal carcinomas. The treatment of these GEP-NENs is surgical, whenever possible. If an R0 resection with removal of all lymph node and liver metastases is successful, the prognosis of the patients is excellent. Patients with diffuse liver or bone metastases can no longer be cured by surgery alone. The long-term survival of these patients is nowadays possible due to the availability of drugs (e.g., somatostatin analogues, tyrosine kinase inhibitors), peptide receptor radionuclide therapy (PRRT) and liver-directed procedures, with a good quality of life.
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Affiliation(s)
- K Holzer
- Klinik für Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Marburg, Baldingerstraße, Marburg, Deutschland.
| | - D K Bartsch
- Klinik für Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Marburg, Baldingerstraße, Marburg, Deutschland
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12
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Kaçmaz E, Engelsman AF, Nieveen van Dijkum EJM. Letter to the Editor: Comment on 'Surgery as a Principle and Technical Consideration for Primary Tumor Resection of Small Bowel Neuroendocrine Tumors'. Ann Surg Oncol 2024; 31:3265-3266. [PMID: 38478291 DOI: 10.1245/s10434-024-15164-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 01/30/2024] [Indexed: 04/10/2024]
Affiliation(s)
- Enes Kaçmaz
- Department of Surgery, Amsterdam Center for Endocrine and Neuroendocrine Tumours, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
| | - Anton F Engelsman
- Department of Surgery, Amsterdam Center for Endocrine and Neuroendocrine Tumours, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - E J M Nieveen van Dijkum
- Department of Surgery, Amsterdam Center for Endocrine and Neuroendocrine Tumours, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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13
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Hallet J, Clarke CN. ASO Practice Guidelines Series: Surgical Management of Gastrointestinal (Midgut) Neuroendocrine Neoplasms. Ann Surg Oncol 2024; 31:1704-1713. [PMID: 38167813 DOI: 10.1245/s10434-023-14802-8] [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: 10/17/2023] [Accepted: 12/06/2023] [Indexed: 01/05/2024]
Abstract
Gastrointestinal midgut neuroendocrine neoplasms (NENs) are a heterogeneous group of uncommon malignancies. For well-differentiated NENs, known as neuroendocrine tumors (NETs), surgery is a cornerstone of management in localized and metastatic disease. Because of heterogeneous tumor behaviour, association with endocrine syndrome, and prognosis, the management of NETs must be individualized to all these factors in addition to the primary site. With the fast pace of advancement in the field, both for therapies and understanding of tumoral etiology and behaviour, it is important for surgical oncologists to remain updated on guidelines recommendations and suggested treatment pathways. Those guidelines provide important guidance for management of NETs but are largely based on expert opinions and interpretation of retrospective evidence. This article reviews highlights of most recent practice guidelines for midgut (gastric, duodenal, small intestinal, and appendiceal) NETs.
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Affiliation(s)
- Julie Hallet
- Department of Surgery, University of Toronto, Toronto, ON, Canada.
- Susan Leslie Clinic for Neuroendocrine Tumors, Odette Cancer Centre - Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
| | - Callisia N Clarke
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
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14
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Bonomi A, Fumagalli Romario U, Funicelli L, Conti G, Realis Luc M, Ceci F, Pozzi S, Radice D, Fazio N, Bertani E. Diagnosis and staging of small intestinal neuroendocrine tumors with CT enterography and PET with Gallium-68: preoperative risk stratification protocol. Langenbecks Arch Surg 2024; 409:63. [PMID: 38363374 DOI: 10.1007/s00423-024-03254-7] [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: 10/20/2023] [Accepted: 02/07/2024] [Indexed: 02/17/2024]
Abstract
PURPOSE Pre-operative diagnosis and staging of small intestine neuroendocrine tumors (SI-NETs) remain sub-optimal, with open palpation during surgery still considered the gold standard. This limits a standardized implementation of minimally invasive surgery (MIS). The aim of this single-center retrospective study was to assess a tailored diagnostic work-up to identify candidates at low risk of undetected disease who may benefit from MIS. METHODS Patients diagnosed with SI-NETs between 2013 and 2022 who underwent contrast-enhanced computed tomography enterography (CTE) and Ga68-DOTATOC-positron emission tomography-CT (68 Ga DOTATATE PET/CT) preoperatively and subsequently underwent open surgical resection were included. Imaging studies were reassessed by two radiologists. Combined use of CTE and 68 Ga DOTATATE PET/CT in determining primary lesion disease burden (number of lesions) and LN disease stage (distal and proximal relative to superior mesenteric vessels) was assessed, using surgical reports and pathology as gold standard. RESULTS Overall, 56 patients were included. Sensitivity of CTE and 68 Ga DOTATATE PET/CT for at least one primary SI-NET was 100% and 94%, respectively. In the presence of concordance between studies, combined use of CTE and 68 Ga DOTATATE PET/CT for detection of single primary tumors improved specificity to 89% (n = 25/28) with a positive predictive value of 87.5% (n = 21/24). Distal LN disease was identified in 89.2% of cases (n = 33/37). The association of single lesion and distal LN disease was found pre-operatively in 32% of patients (n = 18). CONCLUSION Combined use of CTE and 68 Ga DOTATATE PET/CT enables identifying low-risk surgical candidates (single SI-NET lesions with distal LN disease).
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Affiliation(s)
- Alessandro Bonomi
- General Surgery Residency Program, University of Milan, Via Festa del Perdono, 7, 20122, Milan, Italy.
- Digestive Surgery, European Institute of Oncology, IRCCS, Via Ripamonti 435, Milan, Italy.
| | | | - Luigi Funicelli
- Division of Medical Imaging and Radiation Sciences, European Institute of Oncology, IEO, IRCCS, Milan, Italy
- Italian Society of Medical and Interventional Radiology, SIRM, Italian College of Computed Tomography, Milan, Italy
| | - Guglielmo Conti
- Division of Medical Imaging and Radiation Sciences, European Institute of Oncology, IEO, IRCCS, Milan, Italy
- Radiodiagnostics Residency Program, University of Milan, Via Festa del Perdono, 7, 20122, Milan, Italy
| | - Marco Realis Luc
- General Surgery Residency Program, University of Milan, Via Festa del Perdono, 7, 20122, Milan, Italy
- Digestive Surgery, European Institute of Oncology, IRCCS, Via Ripamonti 435, Milan, Italy
| | - Francesco Ceci
- Division of Nuclear Medicine, IEO European Institute of Oncology IRCCS, 20141, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, 20122, Milan, Italy
| | - Simonetta Pozzi
- Digestive Surgery, European Institute of Oncology, IRCCS, Via Ripamonti 435, Milan, Italy
| | - Davide Radice
- Division of Epidemiology and Biostatistics, IEO European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy
| | - Nicola Fazio
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO) IRCCS, Milan, Italy
| | - Emilio Bertani
- Digestive Surgery, European Institute of Oncology, IRCCS, Via Ripamonti 435, Milan, Italy
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15
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Søreide K, Stättner S, Hallet J. Surgery as a Principle and Technical Consideration for Primary Tumor Resection of Small Bowel Neuroendocrine Tumors. Ann Surg Oncol 2024; 31:1125-1137. [PMID: 38006527 PMCID: PMC10761444 DOI: 10.1245/s10434-023-14610-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 10/31/2023] [Indexed: 11/27/2023]
Abstract
Small bowel neuroendocrine tumors (SB-NETs) are increasingly identified and have become the most frequent entity among small bowel tumors. An increasing incidence, a high prevalence, and a prolonged survival with optimal modern multidisciplinary management makes SB-NETs a unique set of tumors to consider for surgical oncologists. The major goals of surgical treatment in the setting of SB-NET include control of tumor volume, control of endocrine secretion, and prevention of locoregional complications. Key considerations include assessment of multifocality and resection of mesenteric nodal masses with the use of mesenteric-sparing approaches and acceptance of R1 margins if necessary to clear disease while avoiding short bowel syndrome. A description through eight steps for consideration is presented to allow for systematic surgical planning and execution of resection. Moreover, some controversies and evolving considerations to the surgical principles and technical procedures remain. The role of primary tumor resection in the presence of (unresectable) liver metastasis is still unclear. Reports of feasibility of minimally invasive surgery are emerging, with undetermined selection criteria for appropriateness or long-term outcomes. Resection of SB-NETs should be considered in all patients fit for surgery and should follow principles to achieve surgical oncological control that is appropriate for the stage and tumor burden, considering the age and comorbidity of the individual patient.
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Affiliation(s)
- Kjetil Søreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.
- Gastrointestinal Translational Research Group, Laboratory for Molecular Medicine, Stavanger University Hospital, Stavanger, Norway.
- Department of Clinical Medicine, University of Bergen, Bergen, Norway.
| | - Stefan Stättner
- Department of General, Visceral and Vascular Surgery, Vöcklabruck, Austria
| | - Julie Hallet
- Department of Surgery, University of Toronto, Toronto, ON, Canada
- Susan Leslie Clinic for Neuroendocrine Tumors - Sunnybrook Health Sciences Centre, Toronto, ON, Canada
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16
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Kmiotek E, Lakda S, Borakati A, Ogunbiyi O, Mandair D, Caplin M, Toumpanakis C, Mirnezami R. Management Strategies and Outcomes for Small Intestinal Neuroendocrine Tumours with Involvement of the Superior Mesenteric Vessels: A Systematic Review. Curr Oncol 2023; 30:9192-9204. [PMID: 37887564 PMCID: PMC10605700 DOI: 10.3390/curroncol30100664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 09/26/2023] [Accepted: 10/14/2023] [Indexed: 10/28/2023] Open
Abstract
Small intestinal neuroendocrine tumours (SI-NETs) are the most common small intestinal tumours. A particularly challenging subset of these tumours is those that involve the superior mesenteric artery or vein for which the role and feasibility of surgery are often questioned. This systematic review aimed to identify and evaluate the management strategies used for these complex SI-NETs. The identified studies showed positive outcomes with surgery and multimodality therapy.
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Affiliation(s)
- Elizabeth Kmiotek
- Department of Colorectal Surgery, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK (O.O.)
| | - Sakina Lakda
- University College London Medical School, 74 Huntley Street, London WC1E 6DE, UK;
| | - Aditya Borakati
- Division of Surgery and Interventional Science, University College London, Royal Free Hospital Campus, 9th Floor, Pond Street, Hampstead, London NW3 2QG, UK;
| | - Olagunju Ogunbiyi
- Department of Colorectal Surgery, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK (O.O.)
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK; (D.M.); (M.C.); (C.T.)
| | - Dalvinder Mandair
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK; (D.M.); (M.C.); (C.T.)
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK; (D.M.); (M.C.); (C.T.)
| | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK; (D.M.); (M.C.); (C.T.)
| | - Reza Mirnezami
- Department of Colorectal Surgery, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK (O.O.)
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK; (D.M.); (M.C.); (C.T.)
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17
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Clift AK, Drymousis P, von Roon A, Humphries A, Goldin R, Bomanji J, Leaman S, Wasan H, Habib N, Frilling A. Management of Small Bowel Neuroendocrine Tumours: 10 Years' Experience at a Tertiary Referral Centre. Cancers (Basel) 2023; 15:4438. [PMID: 37760408 PMCID: PMC10526159 DOI: 10.3390/cancers15184438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 08/24/2023] [Accepted: 09/01/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Neuroendocrine tumours (NET) arising from the small bowel are clinically challenging and are often diagnosed at advanced stages. Disease control with surgery alone can be demanding. Multimodal treatment concepts integrating surgery and non-surgical modalities could be of benefit. METHOD Retrospective review of consecutive adult patients with SB NET treated at Imperial College Healthcare NHS Trust between 1 January 2010 and 31 December 2019. Data regarding clinicopathological characteristics, treatments, and disease trajectory were extracted and summarised. Overall and progression/recurrence-free survival were estimated at 5 and 10 years. RESULTS 154 patients were identified, with a median age of 64 years (range 33-87); 135/154 (87.7%) had stage III/IV disease at diagnosis. Surgery was used in 125 individuals (81.2%), typically with either segmental small bowel resection (60.8%) or right hemicolectomy (33.6%) and mesenteric lymphadenectomy for the primary tumour. Systemic and/or liver-directed therapies were used in 126 (81.8%); 60 (47.6%) had more than one line of non-surgical treatment. Median follow-up was 67.2 months (range 3.1-310.4); overall survival at 5 and 10 years was 91.0% (95% CI: 84.9-94.7%) and 82.5% (95% CI: 72.9-88.9%), respectively. Imaging-based median progression-free survival was 42.7 months (95% CI: 24.7 to 72.4); 5-year progression-free survival was 63.4% (95% CI: 55.0-70.6%); 10-year progression-free survival was 18.7% (95% CI: 12.4-26.1). Nineteen patients (12.3%) reached 10 years follow-up without disease recurrence and therefore were considered cured. CONCLUSIONS Most patients with SB NET present in a metastasised stage. Multimodal treatment concepts may be associated with excellent clinical outcomes. Future work should explore optimal approaches to treatment sequencing and patient selection.
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Affiliation(s)
- Ashley K. Clift
- Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0HS, UK; (A.K.C.)
- CRUK Oxford Centre, Department of Oncology, University of Oxford, Oxford OX1 2JD, UK
| | - Panagiotis Drymousis
- Department of Surgery, Ealing Hospital, London North West University Healthcare NHS Trust, London HA1 3UJ, UK
| | - Alexander von Roon
- Department of Surgery, University College London Hospitals NHS Foundation Trust London, London NW1 2BU, UK
| | - Adam Humphries
- Department of Gastroenterology, St Mark’s Hospital, London North West University Health Care NHS Trust, London HA1 3UJ, UK
| | - Robert Goldin
- Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0HS, UK; (A.K.C.)
| | - Jamshed Bomanji
- Department of Nuclear Medicine, University College London Hospitals NHS Foundation Trust London, London NW1 2BU, UK
| | - Sydney Leaman
- MRC Centre for Neurodevelopmental Disorders, King’s College London, London SE1 8WA, UK
| | - Harpreet Wasan
- Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0HS, UK; (A.K.C.)
| | - Nagy Habib
- Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0HS, UK; (A.K.C.)
| | - Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0HS, UK; (A.K.C.)
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18
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Reinhard L, Mogl MT, Benz F, Dukaczewska A, Butz F, Dobrindt EM, Tacke F, Pratschke J, Goretzki PE, Jann H. Prognostic differences in grading and metastatic lymph node pattern in patients with small bowel neuroendocrine tumors. Langenbecks Arch Surg 2023; 408:237. [PMID: 37332044 PMCID: PMC10277262 DOI: 10.1007/s00423-023-02956-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 05/23/2023] [Indexed: 06/20/2023]
Abstract
PURPOSE Neuroendocrine tumors of the small intestine (si-NET) describe a heterogenous group of neoplasms. Based on the Ki67 proliferation index si-NET are divided into G1 (Ki67 < 2%), G2 (Ki67 3-20%) and rarely G3 (Ki67 > 20%) tumors. However, few studies evaluate the impact of tumor grading on prognosis in si-NET. Moreover, si-NET can form distinct lymphatic spread patterns to the mesenteric root, aortocaval lymph nodes, and distant organs. This study aims to identify prognostic factors within the lymphatic spread patterns and grading. METHODS Demographic, pathological, and surgical data of 208 (90 male, 118 female) individuals with si-NETs treated at Charité University Medicine Berlin between 2010 and 2020 were analyzed retrospectively. RESULTS A total of 113 (54.5%) specimens were defined as G1 and 93 (44.7%) as G2 tumors. Interestingly, splitting the G2 group in two subgroups: G2 low (Ki67 3-9%) and G2 high (Ki67 10-20%), displayed significant differences in overall survival (OS) (p = 0.008) and progression free survival (PFS) (p = 0.004) between these subgroups. Remission after surgery was less often achieved in patients with higher Ki67 index (> 10%). Lymph node metastases (N +) were present in 174 (83.6%) patients. Patients with isolated locoregional disease showed better PFS and OS in comparison to patients with additional aortocaval and distant lymph node metastases. CONCLUSION Lymphatic spread pattern influences patient outcome. In G2 tumors, low and high grading shows heterogenous outcome in OS and PFS. Differentiation within this group might impact follow-up, adjuvant treatment, and surgical strategy.
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Affiliation(s)
- Lisa Reinhard
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Martina T Mogl
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany.
| | - Fabian Benz
- Department of Hepatology and Gastroenterology, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Agata Dukaczewska
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Frederike Butz
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Eva Maria Dobrindt
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Peter E Goretzki
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Henning Jann
- Department of Hepatology and Gastroenterology, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany
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19
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Kupietzky A, Dover R, Mazeh H. Surgical aspects of small intestinal neuroendocrine tumors. World J Gastrointest Surg 2023; 15:566-577. [PMID: 37206065 PMCID: PMC10190731 DOI: 10.4240/wjgs.v15.i4.566] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/25/2023] [Accepted: 03/27/2023] [Indexed: 04/22/2023] Open
Abstract
Small intestinal neuroendocrine tumors (NETs) are a heterogeneous group of epithelial tumors with a predominant neuroendocrine differentiation. Although NETs are usually considered rare neoplasms, small intestinal NETs are the most common primary malignancy of the small bowel, with an increasing prevalence worldwide during the course of the past few decades. The indolent nature of these tumors often leads to a delayed diagnosis, resulting in over one-third of patients presenting with synchronous metastases. Primary tumor resection remains the only curative option for this type of tumor. In this review article, the various surgical aspects for the excision of small intestinal NETs are discussed.
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Affiliation(s)
- Amram Kupietzky
- Department of Surgery, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91240, Israel
| | - Roi Dover
- Department of Surgery, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91240, Israel
| | - Haggi Mazeh
- Department of Surgery, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91240, Israel
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20
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Abstract
Neuroendocrine tumors (NETs) represent a heterogeneous group of tumors, with variable presentation based on the location of origin and degree of metastatic spread. There are no randomized control trials to guide surgical management; however, surgery remains the mainstay of treatment for most gastroenteropancreatic NETs based on retrospective studies. Metastatic disease is common at the time of presentation, particularly in the liver. There is a role for cytoreduction for improvement of both symptoms and survival. Robust prospective randomized data exists to support the use of medical therapies to improve progression-free and overall survival in patients with advanced, metastatic, and unresectable NETs.
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21
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Neuroendocrine neoplasm imaging: protocols by site of origin. ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:4081-4095. [PMID: 36307597 DOI: 10.1007/s00261-022-03713-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 10/09/2022] [Accepted: 10/11/2022] [Indexed: 01/18/2023]
Abstract
With the relatively low incidence of neuroendocrine neoplasms (NEN), most radiologists are not familiar with their optimal imaging techniques. The imaging protocols for NENs should be tailored to the site of origin to accurately define local extension of NEN at time of staging. Patterns of spread and recurrence should be taken into consideration when choosing protocols for detection of recurrence and metastases. This paper will present the recommended CT and MRI imaging protocols for gastro-enteric and pancreatic NENs based on site of origin or predominant pattern of metastatic disease, and explain the rationale for MRI contrast type, contrast timing, as well as specific sequences in MRI. We will also briefly comment on PET/CT and PET/MRI imaging protocols.
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22
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Small bowel neuroendocrine neoplasm: what surgeons want to know. ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:4005-4015. [PMID: 35312820 DOI: 10.1007/s00261-022-03485-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 03/01/2022] [Accepted: 03/02/2022] [Indexed: 01/18/2023]
Abstract
Neuroendocrine neoplasms of the small bowel are a diverse group of tumors with a broad spectrum of imaging findings and clinical implications. Most tumors originate in close proximity to the ileocecal valve and most commonly metastasize to the mesentery and liver. This review will highlight the imaging findings of primary and metastatic small bowel neuroendocrine neoplasm that are most relevant to the surgical team.
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Daskalakis K, Wedin M, Tsoli M, Kogut A, Srirajaskanthan R, Sarras K, Kattiparambil S, Giovos G, Weickert MO, Kos-Kudla B, Kaltsas G. Association of lymph node metastases, grade and extent of mesenteric lymph node dissection in locoregional small intestinal neuroendocrine tumors with recurrence-free survival. J Neuroendocrinol 2022; 34:e13205. [PMID: 36385444 PMCID: PMC10078463 DOI: 10.1111/jne.13205] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 08/28/2022] [Accepted: 10/02/2022] [Indexed: 12/01/2022]
Abstract
We aimed to assess the prognostic impact of tumor- and patient-related parameters in patients with stage I-III small intestinal neuroendocrine tumors (SI-NETs), who underwent locoregional resective surgery (LRS) with curative intent. We included 229 patients with stage I-III SI-NETs diagnosed from June 15, 1993, through March 8, 2021, identified using the SI-NET databases from five European referral centers. Mean ± SD age at baseline was 62.5 ± 13.6 years; 111/229 patients were women (49.3%). All tumors were well-differentiated; 160 were grade 1 (G1) tumors, 51 were G2, two were G3 and 18 tumors were of unspecified grade (median Ki-67: 2%, range 1%-50%). One-hundred and sixty-three patients (71.2%) had lymph node (LN) involvement. The median number of retrieved lymph nodes was 10 (0-63), whereas the median number of positive LNs was 2 (0-43). After a mean ± SD follow-up of 54.1 ± 64.1 months, 60 patients experienced disease recurrence at a median (range) of 36.2 (2.5-285.1) months. The 5- and 10-year recurrence-free survival (RFS) rates were 66.6% and 49.3% respectively. In univariable analysis, there was no difference in RFS and overall survival (OS) between LN-positive and LN-negative patients (log-rank, p = .380 and .198, respectively). However, in stage IIIb patients who underwent mesenteric lymph node dissection (MLND) with a minimum of five retrieved LN (n = 125), five or more LN metastases were associated with shorter RFS (median RFS [95% CI] = 107.4 [0-229.6] vs. 73.7 [35.3-112.1] months; log-rank, p = .048). In addition, patients with G2 tumors exhibited shorter RFS compared to patients with G1 tumors (median RFS [95% confidence interval (CI)] = 46.9 [36.4-57.3] vs. 120.7 [82.7-158.8] months; log-rank, p = .001). In multivariable Cox-regression RFS analysis in stage IIIb patients, the Ki-67 proliferation index (hazard ratio = 1.08, 95% CI = 1.035-1.131; p < .0001) and the number of LN metastases (hazard ratio = 1.06, 95% CI = 1.001-1.125; p = .047) were independent prognostic factors for RFS. In conclusion, LRS with a meticulous MLND and a minimum number of five harvested LNs appears to be critical in the surgical management of SI-NET patients with locoregional disease. In patients who underwent LRS and MLND, the Ki-67 proliferation index and the LN metastases count were independent predictors of RFS.
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Affiliation(s)
- Kosmas Daskalakis
- Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
- Second Department of Surgery, "Korgialenio-Benakio", Red Cross General Hospital, Athens, Greece
| | - Maria Wedin
- Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Marina Tsoli
- Endocrine Oncology Unit, First Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Angelika Kogut
- Department of Endocrinology and Neuroendocrine Neoplasms, Department of Endocrinology and Pathophysiology, Medical University of Silesia, Katowice, Poland
| | - Raj Srirajaskanthan
- ENETS Centre of Excellence, Neuroendocrine Tumour Unit, King's College Hospital, London, UK
- Department of Gastroenterology, King's College Hospital, London, UK
| | | | | | - George Giovos
- The ARDEN NET Centre, European Neuroendocrine Tumour Society (ENETS) Centre of Excellence (CoE), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Martin O Weickert
- The ARDEN NET Centre, European Neuroendocrine Tumour Society (ENETS) Centre of Excellence (CoE), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Beata Kos-Kudla
- Department of Endocrinology and Neuroendocrine Neoplasms, Department of Endocrinology and Pathophysiology, Medical University of Silesia, Katowice, Poland
| | - Gregory Kaltsas
- Endocrine Oncology Unit, First Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Bartsch DK, Windel S, Kanngießer V, Jesinghaus M, Holzer K, Rinke A, Maurer E. Vessel-Sparing Lymphadenectomy Should Be Performed in Small Intestine Neuroendocrine Neoplasms. Cancers (Basel) 2022; 14:cancers14153610. [PMID: 35892869 PMCID: PMC9332577 DOI: 10.3390/cancers14153610] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/15/2022] [Accepted: 07/20/2022] [Indexed: 11/16/2022] Open
Abstract
Simple Summary Primary tumor resection with lymphadenectomy in small intestine neuroendocrine neoplasms potentially requires extensive small bowel resections due to central lymph node metastases and mesenteric fibrosis. Retrograde vessel-sparing lymphadenectomy (VS-LA) might be a sufficient method for avoiding local recurrence and for sparing the small bowel at the same time. We retrospectively analyzed clinical, surgical and pathological data of 50 patients with SI-NENs who exclusively underwent small bowel resections; half of them received conventional lymphadenectomy and 25 underwent VS-LA. VS-LA resulted in shorter resected bowel segments (median 40 cm vs. 65 cm, p = 0.007) with similar rates of local R0 resections (72% vs. 84%) and number of resected lymph nodes (median 13 vs. 13). Postoperative complications occurred significantly less in the vessel-sparing group. VS-LA should be the preferred surgical method in small bowel resections for SI-NENs. Abstract Introduction: The goal of primary tumor resection with lymphadenectomy (PTR) in small intestine neuroendocrine neoplasms (SI-NENs) is to avoid local recurrence while sparing as much of the small bowel as possible, even in the case of extensive mesenteric fibrosis. The results of PTR with retrograde vessel-sparing lymphadenectomy (VS-LA) were compared to those of conventional lymphadenectomy (Con-LA). Methods: Prospectively collected clinical, surgical and pathological data of consecutive patients with SI-NENs who underwent small bowel resections were retrospectively analyzed regarding the resection technique performed. Results: In a 7-year period, 50 of 102 patients with SI-NENs had only small bowel resections; of those, 25 were VS-LA and 25 were Con-LA. Patients with VS-LA had tendentially more advanced diseases with slightly higher rates of abdominal pain, mesenteric shrinkage and more level III lymph node involvement compared to patients with Con-LA. VS-LA, however, resulted in shorter resected bowel segments (median 40 cm vs. 65 cm, p = 0.007) with similar rates of local R0 resections (72% vs. 84%) and resected lymph nodes (median 13 vs. 13). Postoperative clinically relevant complications occurred in 1 of 25 (4%) in the VS-LA and in 7 of 25 (28%) patients in the Con-LA group (p = 0.02). Three months after surgery, 1 of 25 (4%) patients of the VS-LA group and 10 of 25 (40%) patients in the Con-LA group (p = 0.002) complained about abdominal pain. One of eight patients in the VS-LA group and two of thirteen patients in the Con-LA group who had completely resected stage III disease complained about diarrhea (p = 0.31). Conclusion: VS-LA seems to be oncologically safe and should be considered in small bowel resections for SI-NENs.
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Affiliation(s)
- Detlef K. Bartsch
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Baldingerstraße, 35043 Marburg, Germany; (D.K.B.); (S.W.); (V.K.); (K.H.)
| | - Sebastian Windel
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Baldingerstraße, 35043 Marburg, Germany; (D.K.B.); (S.W.); (V.K.); (K.H.)
| | - Veit Kanngießer
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Baldingerstraße, 35043 Marburg, Germany; (D.K.B.); (S.W.); (V.K.); (K.H.)
| | - Moritz Jesinghaus
- Institute of Pathology, Philipps-University Marburg, Baldingerstraße, 35043 Marburg, Germany;
| | - Katharina Holzer
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Baldingerstraße, 35043 Marburg, Germany; (D.K.B.); (S.W.); (V.K.); (K.H.)
| | - Anja Rinke
- Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Baldingerstraße, 35043 Marburg, Germany;
| | - Elisabeth Maurer
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Baldingerstraße, 35043 Marburg, Germany; (D.K.B.); (S.W.); (V.K.); (K.H.)
- Correspondence:
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25
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Immuno-histochemical correlation of fibrosis-related markers with the desmoplastic reaction of the mesentery in small intestine neuroendocrine neoplasms. J Cancer Res Clin Oncol 2022; 149:1895-1903. [PMID: 35796776 PMCID: PMC10097745 DOI: 10.1007/s00432-022-04119-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 06/07/2022] [Indexed: 10/17/2022]
Abstract
INTRODUCTION Small intestine neuroendocrine neoplasms (siNENs) will attain more importance due to their increasing incidence. Moreover, siNENs might lead to a desmoplastic reaction (DR) of the mesentery causing severe complications and deteriorating prognosis. The expression of fibrosis-related proteins appears to be the key mechanisms for the development of this desmoplastic reaction. Therefore, this study aimed to investigate the association of the desmoplastic mesentery with specific fibrosis-related protein expression levels. MATERIALS AND METHODS By immunohistochemistry, the protein expression levels of four fibrosis-related markers (APLP2, BNIP3L, CD59, DKK3) were investigated in primary tumors of 128 siNENs. The expression levels were correlated with the presence of a desmoplastic reaction and clinico-pathological parameters. RESULTS In the primary tumor, APLP2, BNIP3L, CD59 and DKK3 were highly expressed in 29.7% (n = 38), 64.9% (n = 83), 92.2% (n = 118) and 80.5% (n = 103), respectively. There was no significant correlation of a single marker or the complete marker panel to the manifestation of a desmoplastic mesentery. The desmoplastic mesentery was significantly associated with clinical symptoms, such as flushing and diarrhea. However, neither the fibrosis-related marker panel nor single marker expressions were associated with clinical symptoms. DISCUSSION The expression rates of four fibrosis-related markers in the primary tumor display a distinct pattern. However, the expression patterns are not associated with desmoplastic altered mesenteric lymph node metastases and the expression patterns did not correlate with prognosis. These findings suggest alternative mechanisms being responsible for the desmoplastic reaction.
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26
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Deguelte S, Hammoutene C, Poncet G, Brunaud L, Perrier M, Kianmanesh R, Cadiot G. Concept of reintervention with thorough lymphadenectomy after suboptimal resection of small-intestine neuroendocrine neoplasms: A multicentre preliminary study. J Neuroendocrinol 2022; 34:e13117. [PMID: 35434838 DOI: 10.1111/jne.13117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 01/09/2022] [Accepted: 02/05/2022] [Indexed: 11/26/2022]
Abstract
Complete surgical resection is the only hope to cure small intestine neuroendocrine neoplasms (SiNENs). However, inadequate lymphadenectomy or entire small bowel palpation for multiple primary tumours renders at least 20% of resections suboptimal. This study was undertaken to investigate reintervention outcomes after initial suboptimal resections (ISORs), and agreement between residual tumour identification on interval imaging and during reintervention. This retrospective, multicentre study included all patients undergoing reintervention within 18 months post ISOR. Disease-free survival (DFS) was defined as the time from reintervention resection date to recurrence or any-cause of death. The kappa coefficient assessed agreement rates between suspected residual tumour on interval imaging and its presence at reintervention. A total of 21 patients underwent reintervention for nonmetastatic SiNENs (median follow-up 2.3 [IQR 0.6-3.75] years). Residual tumour, suspected in 17/21 (81%) patients based on interval imaging, was found in 20/21 (95%) during reintervention. Interval imaging-intraoperative detection agreement was fair for residual primary tumours (kappa = 0.28, 95% CI: 0.05-0.62; p = .09) and residual lymph node metastases (kappa = 0.17, 95% CI: 0.28-0.62; p = .45). Reintervention achieved complete tumour clearance in 16/21 (76%) patients, among whom 5/16 (31%) developed liver metastases during follow-up. Median DFS was 70.6 months (IQR 39.7-not reached). Reintervention post-ISOR can obtain tumour clearance and prolonged remission. It should be systematically discussed after suspected ISOR, even when postoperative imaging does not find any residual tumour. To maximize detection of potentially resectable residual disease, imaging modalities after "curative" surgery should be redefined.
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Affiliation(s)
- Sophie Deguelte
- Department of Endocrine, Digestive and Oncological Surgery, Robert-Debré University Hospital, Reims, France
- Faculty of Medicine, UR 3797 Ageing, Frailty (VieFra), University of Reims Champagne-Ardenne, Reims, France
- Reims Medical School, University of Champagne Ardennes, Reims, France
| | - Cheryne Hammoutene
- Department of Endocrine, Digestive and Oncological Surgery, Robert-Debré University Hospital, Reims, France
| | - Gilles Poncet
- Digestive and Oncologic Surgery, Edouard-Herriot University Hospital, Claude-Bernard Lyon 1 University, Lyon, France
| | - Laurent Brunaud
- Department of Digestive, Hepato-Biliary and Endocrine Surgery, University Hospital Nancy Brabois, Vandoeuvre-les-Nancy, France
| | - Marine Perrier
- Department of Hepato-Gastro-Enterology, Robert-Debré University Hospital, Reims, France
| | - Reza Kianmanesh
- Department of Endocrine, Digestive and Oncological Surgery, Robert-Debré University Hospital, Reims, France
- Reims Medical School, University of Champagne Ardennes, Reims, France
| | - Guillaume Cadiot
- Reims Medical School, University of Champagne Ardennes, Reims, France
- Department of Hepato-Gastro-Enterology, Robert-Debré University Hospital, Reims, France
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27
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Kaçmaz E, Engelsman AF, Bemelman WA, Tanis PJ, Nieveen van Dijkum EJM. International survey on opinions and use of minimally invasive surgery in small bowel neuroendocrine neoplasms. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1251-1257. [PMID: 34823919 DOI: 10.1016/j.ejso.2021.11.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 10/25/2021] [Accepted: 11/08/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Although minimally invasive surgery is becoming the standard technique in gastrointestinal surgery, implementation for small bowel neuroendocrine neoplasms (SB-NEN) is lagging behind. The aim of this international survey was to gain insights into attitudes towards minimally invasive surgery for resection of SB-NEN and current practices. METHODS An anonymous survey was sent to surgeons between February and May 2021 via (neuro)endocrine and colorectal societies worldwide. The survey consisted of questions regarding experience of the surgeon with minimally invasive SB-NEN resection and training. RESULTS A total of 58 responses from five societies across 20 countries were included. Forty-one (71%) respondents worked at academic centers. Thirty-seven (64%) practiced colorectal surgery, 24 (41%) endocrine surgery and 45 (78%) had experience in advanced minimally invasive surgery. An open, laparoscopic or robotic approach was preferred by 23 (42%), 24 (44%), and 8 (15%) respondents, respectively. Reasons to opt for a minimally invasive approach were mainly related to peri-operative benefits, while an open approach was preferred for optimal mesenteric lymphadenectomy and tactile feedback. Additional training in minimally invasive SB-NEN resection was welcomed by 29 (52%) respondents. Forty-three (74%) respondents were interested in collaborating in future studies, with a cumulative median (IQR) annual case load of 172 (86-258). CONCLUSIONS Among respondents, 69% applies minimally invasive surgery for resection of SB-NEN. Arguments for specific operative approaches differ, and insufficient training in advanced laparoscopic techniques seems to be a barrier. Future collaborative studies can provide better insight in selection criteria and optimal technique.
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Affiliation(s)
- Enes Kaçmaz
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Center for Endocrine and Neuroendocrine Tumours, Amsterdam UMC, Amsterdam, the Netherlands.
| | - Anton F Engelsman
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Center for Endocrine and Neuroendocrine Tumours, Amsterdam UMC, Amsterdam, the Netherlands
| | - Willem A Bemelman
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Pieter J Tanis
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Center for Endocrine and Neuroendocrine Tumours, Amsterdam UMC, Amsterdam, the Netherlands
| | - Elisabeth J M Nieveen van Dijkum
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Center for Endocrine and Neuroendocrine Tumours, Amsterdam UMC, Amsterdam, the Netherlands.
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Predicting resectability of primary tumor and mesenteric lymph-node masses in patients with small-intestine neuroendocrine tumors. Updates Surg 2022; 74:1697-1704. [DOI: 10.1007/s13304-022-01251-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 01/27/2022] [Indexed: 10/19/2022]
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Maurer E, Heinzel-Gutenbrunner M, Rinke A, Rütz J, Holzer K, Figiel J, Luster M, Bartsch DK. Relevant prognostic factors in patients with stage IV small intestine neuroendocrine neoplasms. J Neuroendocrinol 2022; 34:e13076. [PMID: 34964186 DOI: 10.1111/jne.13076] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 10/10/2021] [Accepted: 11/30/2021] [Indexed: 12/13/2022]
Abstract
There are few, but controversial data on the prognostic role of upfront primary tumour resection and mesenteric lymph node dissection (PTR) in patients with diffuse metastatic small intestinal neuroendocrine neoplasia (SI-NEN). Therefore, the prognostic role of PTR and other factors was determined in this setting. This retrospective cohort study included patients with stage IV SI-NETs with unresectable distant metastases without clinical and radiological signs of acute bowel obstruction or ischaemia. Patients diagnosed from January 2002 to May 2020 were retrieved from a prospective SI-NEN database. Disease specific overall survival (OS) was analysed with regard to upfront PTR and a variety of other clinical (e.g., gender, age, Hedinger disease, carcinoid syndrome, diarrhoea, laboratory parameters, metastatic liver burden, extrahepatic and extra-abdominal metastasis) and pathological (e.g., grading, mesenteric gathering) parameters by uni- and multivariate analysis. A total of 138 patients (60 females, 43.5%) with a median age of 60 years, of whom 101 (73%) underwent PTR and 37 (27%) did not, were included in the analysis. Median OS was 106 (95% CI: 72.52-139.48) months in the PTR group and 52 (95% CI: 30.55-73.46) in the non-PTR group (p = 0.024), but the non-PTR group had more advanced metastatic disease (metastatic liver burden ≥50% 32.4% vs. 13.9%). There was no significant difference between groups regarding the rate of surgery for bowel complications during a median follow-up of 51 months (PTR group 10.9% and non-PTR group 16.2%, p = 0.403). Multivariate analysis revealed age < 60 years, normal C-reactive protein (CRP) at baseline, absence of diarrhoea, less than 50% of metastatic liver burden, and treatment with PRRT as independent positive prognostic factors, whereas PTR showed a strong tendency towards better OS, but level of significance was missed (p = 0.067). However, patients who underwent both, PTR and peptide radioreceptor therapy (PRRT) had the best survival compared to the rest (137 vs. 73 months, p = 0.013). PTR in combination with PRRT significantly prolongs survival in patients with stage IV SI-NEN. Prophylactic PTR does also not result in a lower reoperation rate compared to the non-PTR approach regarding bowel complications.
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Affiliation(s)
- Elisabeth Maurer
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Marburg, Germany
| | | | - Anja Rinke
- Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Marburg, Germany
| | - Johannes Rütz
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Marburg, Germany
| | - Katharina Holzer
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Marburg, Germany
| | - Jens Figiel
- Department of Diagnostic and Interventional Radiology, Philipps-University Marburg, Marburg, Germany
| | - Markus Luster
- Department of Nuclear Medicine, Philipps-University Marburg, Marburg, Germany
| | - Detlef Klaus Bartsch
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Marburg, Germany
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Abstract
Small bowel neuroendocrine tumors (SBNETS) are slow-growing neoplasms with a noted propensity toward metastasis and comparatively favorable prognosis. The presentation of SBNETs is varied, although abdominal pain and obstructive symptoms are the most common presenting symptoms. In patients with metastases, hypersecretion of serotonin and other bioactive amines results in diarrhea, flushing, valvular heart disease, and bronchospasm, termed carcinoid syndrome. The treatment of SBNETs is multimodal and includes surgery, liver-directed therapy, somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy.
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Steinkraus K, Andresen JR, Clift AK, Liedke MO, Frilling A. Multifocal neuroendocrine tumour of the small bowel presenting as an incarcerated incisional hernia: a surgical challenge in a high-risk patient. J Surg Case Rep 2021; 2021:rjab219. [PMID: 34150191 PMCID: PMC8208802 DOI: 10.1093/jscr/rjab219] [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: 03/25/2021] [Revised: 05/04/2021] [Accepted: 05/06/2021] [Indexed: 11/25/2022] Open
Abstract
Neuroendocrine tumours (NET) of the small bowel present significant clinical challenges, such as their rate of metastasis at initial presentation, common multifocality and understaging even with gold standard imaging. Here, we present a case of a high-risk surgical patient with a complex medical history initially presenting as an acute abdomen due to an incarcerated incisional hernia. He was found at emergency laparotomy to have three small NET deposits in a 30-cm segment of incarcerated ileum which was resected. Postoperative morphological and functional imaging and biochemical markers were unremarkable, but due to clinical suspicion for undetected residual tumour bulk given the non-systematic palpation of the entire small bowel at initial operation, underwent re-operation where a further 70 cm of ileum was found to harbour multiple tumour deposits (n = 25) and was resected. There was no surgical morbidity and the patient remains tumour-free at 9-month follow-up.
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Affiliation(s)
| | | | - Ashley K Clift
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Marc O Liedke
- Department of Visceral, Thoracic, and Vascular Surgery, Westkuestenkliniken, Heide Germany
| | - Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, London, UK
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Niederle B, Selberherr A, Niederle MB. How to Manage Small Intestine (Jejunal and Ileal) Neuroendocrine Neoplasms Presenting with Liver Metastases? Curr Oncol Rep 2021; 23:85. [PMID: 34018081 PMCID: PMC8137632 DOI: 10.1007/s11912-021-01074-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/31/2021] [Indexed: 11/29/2022]
Abstract
PURPOSE OF REVIEW Small intestinal neuroendocrine neoplasms (siNENs) are slowly growing tumours with a low malignant potential. However, more than half of the patients present with distant metastases (stage IV) and nearly all with locoregional lymph node (LN) metastases at the time of surgery. The value of locoregional treatment is discussed controversially. RECENT FINDINGS In stage I to III disease, locoregional surgery was currently shown to be curative prolonging survival. In stage IV disease, surgery may prolong survival in selected patients with the chance to cure locoregional disease besides radical/debulking liver surgery. It may improve the quality of life and may prevent severe local complications resulting in a state of chronic malnutrition and severe intestinal ischaemia or bowel obstruction. Locoregional tumour resection offers the opportunity to be curative or to focus therapeutically on liver metastasis, facilitating various other therapeutic modalities. Risks and benefits of the surgical intervention need to be balanced individually.
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Affiliation(s)
- Bruno Niederle
- Department of General Surgery, Divison of Visceral Surgery, Medical University of Vienna, Waehringer Gürtel 18-20, A-1090 Vienna, Austria
| | - Andreas Selberherr
- Department of General Surgery, Divison of Visceral Surgery, Medical University of Vienna, Waehringer Gürtel 18-20, A-1090 Vienna, Austria
| | - Martin B. Niederle
- Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Waehringer Gürtel 18-20, A-1090 Vienna, Austria
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Kaçmaz E, Klümpen HJ, Bemelman WA, Nieveen van Dijkum EJM, Engelsman AF, Tanis PJ. Evaluating Nationwide Application of Minimally Invasive Surgery for Treatment of Small Bowel Neuroendocrine Neoplasms. World J Surg 2021; 45:2463-2470. [PMID: 33783584 PMCID: PMC8236028 DOI: 10.1007/s00268-021-06036-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/15/2021] [Indexed: 12/22/2022]
Abstract
Aim Open resection of small bowel neuroendocrine neoplasms (SB-NEN) is still considered standard-of-care, mainly because of frequently encountered multifocality and central mesenteric masses. The aim of this study was to evaluate surgical approach for SB-NEN at a national level and determine predictors for overall survival. Methods Patients with SB-NEN who underwent resection between 2005 and 2015 were included from the Netherlands Cancer Registry. Patient and tumor characteristics were compared between laparoscopic and open approach. Overall survival was assessed by Kaplan–Meier and compared with the Log-rank test. Independent predictors were determined by Cox proportional hazards model. Results In total, 482 patients were included, of whom 342 (71%) underwent open and 140 (29%) laparoscopic resection. The open resection group had significantly more multifocal tumors resected (24% vs. 14%), pN2 lymph nodes (18% vs. 7%) and stage IV disease (36% vs. 22%). Overall survival after open resection was significantly shorter compared to laparoscopic resection (3-year: 81% vs. 89%, 5-year: 71% vs. 84%, p = 0.004). In multivariable analysis, age above 60-years (60–75, HR 3.38 (95% CI 1.84–6.23); > 75 years, HR 7.63 (95% CI 3.86–15.07)), stage IV disease (HR 1.86 (95% CI 1.18–2.94)) and a laparoscopic approach (HR 0.51 (95% CI 0.28–0.94)) were independently associated with overall survival, whereas multifocal primary tumor, grade and resection margin status were not. Conclusion Laparoscopic resection was the approach in 29% of SB-NEN at a national level with selection of the more favorable patients. Laparoscopic resection remained independently associated with better overall survival besides age and stage, but residual confounding cannot be excluded.
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Affiliation(s)
- Enes Kaçmaz
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.,Cancer Center Amsterdam, Amsterdam, The Netherlands.,Amsterdam UMC, ENETS Center of Excellence, University of Amsterdam, Amsterdam, The Netherlands
| | - Heinz-Josef Klümpen
- Cancer Center Amsterdam, Amsterdam, The Netherlands.,Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.,Amsterdam UMC, ENETS Center of Excellence, University of Amsterdam, Amsterdam, The Netherlands
| | - Willem A Bemelman
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.,Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Els J M Nieveen van Dijkum
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.,Cancer Center Amsterdam, Amsterdam, The Netherlands.,Amsterdam UMC, ENETS Center of Excellence, University of Amsterdam, Amsterdam, The Netherlands
| | - Anton F Engelsman
- Cancer Center Amsterdam, Amsterdam, The Netherlands.,Amsterdam UMC, ENETS Center of Excellence, University of Amsterdam, Amsterdam, The Netherlands.,Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Pieter J Tanis
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands. .,Cancer Center Amsterdam, Amsterdam, The Netherlands.
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Wonn SM, Ratzlaff AN, Pommier SJ, Limbach KE, Bassale S, McCully BH, Pommier RF. Evaluation of the prognosis for N2 status in patients with small bowel neuroendocrine tumors. Am J Surg 2021; 221:1135-1140. [PMID: 33785207 DOI: 10.1016/j.amjsurg.2021.03.036] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 03/11/2021] [Accepted: 03/16/2021] [Indexed: 01/16/2023]
Abstract
BACKGROUND The 8th edition AJCC Staging for small bowel neuroendocrine tumors created a novel N2 classification. This study investigates if it is independently prognostic. METHODS Records of patients from 2008 to 2019 were reviewed. Survival rates were estimated by Kaplan-Meier method and compared by log-rank. The Cox Proportional Hazards model was used to determine factors associated with overall survival (OS) via multivariate analysis. RESULTS Among 300 patients, 225 were N2 and 60 were N1. No differences were seen in pathologic markers for N1 compared to N2. N2 were more likely to have liver metastases (LM) (p = 0.048) but rates of resectability were similar. Median OS for N1 with >70% liver cytoreduction was not yet reached compared to 121 months for N2 (p = 0.005). On multivariate analysis, LM was associated with shorter survival (p = 0.028), but nodal status was not. CONCLUSIONS Unlike LM, N2 status is not independently prognostic, but a marker for aggressive LM.
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Affiliation(s)
- Sarah M Wonn
- Department of Surgery, Oregon Health & Science University, United States
| | - Anna N Ratzlaff
- Division of Surgical Oncology, Department of Surgery, Oregon Health & Science University, United States
| | - SuEllen J Pommier
- Division of Surgical Oncology, Department of Surgery, Oregon Health & Science University, United States
| | - Kristen E Limbach
- Department of Surgery, Oregon Health & Science University, United States
| | - Solange Bassale
- Knight Cancer Biostatistician, Oregon Health & Science University, United States
| | - Belinda H McCully
- Division of Surgical Oncology, Department of Surgery, Oregon Health & Science University, United States
| | - Rodney F Pommier
- Division of Surgical Oncology, Department of Surgery, Oregon Health & Science University, United States.
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Frilling A, Clift AK, Frampton AE, Bomanji J, Kaemmerer D, Al-Nahhas A, Alsafi A, Kidd M, Modlin IM, Hoersch D, Baum RP. A combination of surgery, theranostics, and liquid biopsy - a personalised oncologic approach to treatment of patients with advanced metastatic neuroendocrine neoplasms. Int J Med Sci 2021; 18:2166-2175. [PMID: 33859524 PMCID: PMC8040427 DOI: 10.7150/ijms.51740] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 01/14/2021] [Indexed: 01/29/2023] Open
Abstract
Rationale: Neuroendocrine neoplasia (NEN) of small bowel (SBNEN) frequently present with metastatic disease. Theranostics (molecular imaging followed by targeting therapy) allow for personalised medicine. Liquid biopsies enable precise identification of residual disease and real-time monitoring of therapeutic response. Our aim was to determine the clinical utility of a combination of surgery, theranostics, and a multigene blood measurement in metastasised SBNEN. Methods: Inclusion criteria were SBNEN, G1/G2 NEN, initial tumour diagnosis, stage IV NEN, positivity on 68Ga somatostatin analogue PET/CT, eligible for surgery, and 177Lu peptide receptor radionuclide therapy (PRRT). Blood samples for NETest were collected longitudinally. Progression-free survival (PFS) and overall survival (OS) were calculated. NETest results were assessed prior to surgery and during clinical follow-up. Results: A surgical cohort of 39 SBNEN patients met eligibility criteria. Thirty-two patients underwent ileal resection and 7 right hemicolectomy. The mean number of 177Lu PRRT cycles was 4. Mortality was nil. Surgical morbidity was 10.3%. Transient grade 1/2 toxicity occurred in 41% (PRRT). NETest scores (n=9 patients) decreased in 100% following treatment and correlated with diminished tumour volume and disease stabilization following surgery and PRRT. Median follow-up: 78 months. Median PFS and OS: 42.7 and 110 months, respectively. Progression-free survival at 1-, 3-, and 5-years was 79.4%, 57.1% and 40.5%, respectively. Overall survival at 1-, 3-, and 5-years was 97.4%, 97.4%, and 94.1%, respectively. Conclusions: Surgery combined with 177Lu PRRT is safe and provides favourable PFS and OS in selected patients with advanced SBNEN. Liquid biopsy (NETest) has the potential to accurately delineate disease status.
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Affiliation(s)
- Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Ashley K. Clift
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Adam E. Frampton
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Jamshed Bomanji
- Department of Nuclear Medicine, University College London Hospitals, London, UK
| | - Daniel Kaemmerer
- Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany
| | - Adil Al-Nahhas
- Department of Imaging and Nuclear Medicine, Imperial College London, London, UK
| | - Ali Alsafi
- Department of Imaging and Nuclear Medicine, Imperial College London, London, UK
| | | | - Irvin M. Modlin
- Gastroenterological and Endoscopic Surgery, Yale University School of Medicine, New Haven, USA
| | - Dieter Hoersch
- Department of Gastroenterology/Endocrinology, Zentralklinik Bad Berka, Bad Berka, Germany
| | - Richard P. Baum
- CURANOSTICUM Wiesbaden-Frankfurt at DKD Helios Klinik, Wiesbaden, Germany
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36
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Kaçmaz E, Slooter MD, Nieveen van Dijkum EJM, Tanis PJ, Engelsman AF. Fluorescence angiography guided resection of small bowel neuroendocrine neoplasms with mesenteric lymph node metastases. Eur J Surg Oncol 2021; 47:1611-1615. [PMID: 33353827 DOI: 10.1016/j.ejso.2020.12.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 11/24/2020] [Accepted: 12/13/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Surgery for small bowel neuroendocrine neoplasms (SB-NEN) might result in vascular compromise of the remaining bowel due to resection of lymph node metastases in close proximity to main mesenteric vessels. Fluorescence angiography (FA) has been described as a safe technique to assess perfusion during gastro-intestinal surgery. This study aimed to evaluate the potential value of intraoperative FA during surgery for SB-NEN. METHODS This study included patients undergoing surgery for SB-NEN of any stage. The planned level of transection was marked by the surgeon, after which FA using indocyanine green (ICG) was performed. The primary study outcome was change in management due to FA. RESULTS Ten consecutive patients with SB-NEN were included, all with metastatic lymph nodes close to main mesenteric vessels. FA use led to management changes in eight patients (80%); four patients had less bowel resected with a preserved length of 5-35 cm. The other four patients had more extended bowel resections with an additional length varying from 3 to 25 cm. The median postoperative stay was 4 days (interquartile range 4-6). No anastomotic leakage occurred. CONCLUSION This is the first known series describing preliminary results of FA during SB-NEN surgery. FA led to a management change in 80% of patients with better tailoring the extent of resection of small bowel. Structural implementation of FA to assess small bowel perfusion after dissection for small bowel NET results in change of management, either by preserving small bowel or resecting ill-perfused small bowel.
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Affiliation(s)
- E Kaçmaz
- Department of Surgery, Amsterdam UMC, University of Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - M D Slooter
- Department of Surgery, Amsterdam UMC, University of Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - E J M Nieveen van Dijkum
- Department of Surgery, Amsterdam UMC, University of Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands; ENETS Center of Excellence, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - P J Tanis
- Department of Surgery, Amsterdam UMC, University of Amsterdam, the Netherlands; Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - A F Engelsman
- Cancer Center Amsterdam, Amsterdam, the Netherlands; ENETS Center of Excellence, Amsterdam UMC, University of Amsterdam, the Netherlands; Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands.
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Tran CG, Sherman SK, Howe JR. The Landmark Series: Management of Small Bowel Neuroendocrine Tumors. Ann Surg Oncol 2021; 28:2741-2751. [PMID: 33452604 DOI: 10.1245/s10434-020-09566-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 12/20/2020] [Indexed: 12/12/2022]
Abstract
Surgical resection is the foundation for treatment of small bowel neuroendocrine tumors (SBNETs). Guidelines for surgical management of SBNETs rely on retrospective data, which suggest that primary tumor resection and cytoreduction improve symptoms, prevent future complications, and lengthen survival. In advanced NETs, improvement in progression-free survival has been reported in large, randomized, controlled trials of various medical treatments, including somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy. This review discusses important studies influencing the management of SBNETs and the limitations of current evidence regarding surgical interventions for SBNETs.
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Affiliation(s)
- Catherine G Tran
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - Scott K Sherman
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - James R Howe
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
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38
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Evers M, Rinke A, Rütz J, Ramaswamy A, Maurer E, Bartsch DK. Prognostic Factors in Curative Resected Locoregional Small Intestine Neuroendocrine Neoplasms. World J Surg 2021; 45:1109-1117. [PMID: 33416940 DOI: 10.1007/s00268-020-05884-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/14/2020] [Indexed: 11/25/2022]
Abstract
BACKGROUND Small intestinal neuroendocrine neoplasms (SI-NEN) are rare, and only about 40% of patients are diagnosed without distant metastases. Aim of the study was to identify prognostic factors in patients with potentially curative resected locoregional SI-NEN. METHODS Patients with curative resected locoregional SI-NEN (ENETS stages I-III) were retrieved from a prospective data base. Demographic, surgical and pathological data of patients with and without disease recurrence were retrospectively analyzed using univariate and multivariate analysis. RESULTS In a 20-year period, 65 of 203 (32%) patients with SI-NEN were operated for stages I-III disease. Thirty-eight (58.5%) patients were men, and the median age at surgery was 59 (range 37-87) years. After median follow-up of 65 months, 14 patients experienced disease relapse median 28.5 (range 6-122) months after initial surgery, of which 2 died due to their disease. Multivariate analysis revealed age ≥ 60 years (HR = 6.41, 95% CI 1.38-29.67, p = 0.017), tumor size ≥ 2 cm (HR = 26.54, 95% CI 4.46-157.62, p < 0.001), lymph node ratio > 0.5 (HR 7.18, 95% CI 1.74-29.74, p = 0.007) and multifocal tumor growth (HR = 6.98, 95% CI 1.66-29.39, p = 0.008) as independent negative prognostic factors and right hemicolectomy compared to segmental small bowel resection (HR = 0.04, 95% CI 0.01-0.24, p < 0.001) as independent protector against recurrence. CONCLUSION Patients with locoregional SI-NEN with an age ≥ 60 years, tumor size ≥ 2 cm, lymph node ratio > 0.5 and multiple small bowel tumor foci have an increased risk for recurrence and might benefit from adjuvant treatment. In contrast, right hemicolectomy of ileal SI-NEN seems to reduce the risk of recurrence.
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Affiliation(s)
- Maximilian Evers
- Department of Visceral, Thoracic and Vascular Surgery, Philipps-University Marburg, 35043, Baldingerstrasse Marburg, Germany
| | - Anja Rinke
- Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Marburg, Germany
| | - Johannes Rütz
- Department of Visceral, Thoracic and Vascular Surgery, Philipps-University Marburg, 35043, Baldingerstrasse Marburg, Germany
| | - Annette Ramaswamy
- Department of Pathology, Philipps-University Marburg, Marburg, Germany
| | - Elisabeth Maurer
- Department of Visceral, Thoracic and Vascular Surgery, Philipps-University Marburg, 35043, Baldingerstrasse Marburg, Germany
| | - Detlef K Bartsch
- Department of Visceral, Thoracic and Vascular Surgery, Philipps-University Marburg, 35043, Baldingerstrasse Marburg, Germany.
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Gangi A, Anaya DA. Surgical Principles in the Management of Small Bowel Neuroendocrine Tumors. Curr Treat Options Oncol 2020; 21:88. [PMID: 32862334 DOI: 10.1007/s11864-020-00784-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OPINION STATEMENT Small bowel neuroendocrine tumors (SB NETs) are increasing in frequency and becoming more common in surgical practice. It is often difficult to make the diagnosis of a SB NET at an early stage, as the primary tumor tends to be small and patients are asymptomatic until there is regional or distant metastasis, when they develop abdominal pain, partial obstruction, or bleeding and/or develop carcinoid syndrome. Despite this advanced presentation at the time of diagnosis, patients with metastatic SB NETs, as compared to other gastrointestinal malignancies, have favorable survival, which can be improved by appropriate surgical interventions. With the lack of randomized studies, there is reasonable controversy surrounding the optimal management of patients with SB NETs. As such, treatment of these patients is driven primarily by physician experience and available data based predominantly on retrospective studies. Based on this, current recommendations advocate for patients with SB NETs (localized or metastatic) to be managed at experienced centers by a multidisciplinary team. Eligible patients should undergo surgical resection of primary and regional disease as outlined in this article. Additionally, patients with metastatic disease should be evaluated on a case by case basis to evaluate surgical options that may mitigate bowel symptoms (i.e., pain, intestinal angina, obstruction) and carcinoid symptoms (flushing, diarrhea, hemodynamic instability) and prolong survival. Unlike other gastrointestinal malignancies, aggressive surgical management of these patients, even in the context of unresectable metastatic disease, can improve patients' symptoms and long-term survival. The principles outlined in this article are geared to guide appropriate management of SB NET patients with improvement in quality of life and overall survival outcomes.
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Affiliation(s)
- Alexandra Gangi
- Division of Surgical Oncology, Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Daniel A Anaya
- Section of Hepatobiliary Tumors, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
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40
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Role of Primary Tumor Resection for Metastatic Small Bowel Neuroendocrine Tumors. World J Surg 2020; 45:213-218. [PMID: 32797281 DOI: 10.1007/s00268-020-05727-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/31/2020] [Indexed: 12/21/2022]
Abstract
While small bowel resection is well established as standard of care for curative-intent management of localized and loco-regional small bowel neuroendocrine tumors (SB-NETs), resection of the primary tumor in the setting of metastatic disease is debated. This review addresses the role of primary tumor resection for stage IV well-differentiated grade 1 and 2 SB-NETs. While survival benefits have been reported for primary tumor resection in the setting of metastatic disease, these studies are limited by selection bias and thus controversial. The main clinical benefits of primary tumor resection for stage IV disease involve the prevention of potentially debilitating complications associated with mesenteric fibrosis, including intestinal obstruction, mesenteric ischemia and angina, venous congestion, malabsorption, and malnutrition. Patients with metastases undergoing initial resection of the primary SB-NETs appear to have fewer episodes of care and re-intervention for loco-regional complications than those who do not undergo resection. As recommended by the NANETS and ENETS guidelines, resection of the primary tumor for stage IV SB-NETs should be strongly considered to avoid future loco-regional complications and potentially to improve survival. All patients with stage IV SB-NETs should be assessed by a surgeon experienced in the management of NETs to consider surgical therapies, including resection of the primary tumor despite metastatic disease.
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41
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Extent of Lymph Node Dissection for Small Bowel Neuroendocrine Tumors. World J Surg 2020; 45:197-202. [PMID: 32737557 DOI: 10.1007/s00268-020-05710-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/13/2020] [Indexed: 12/22/2022]
Abstract
The management of nodal disease remains controversial for small bowel neuroendocrine tumors (SB-NETs). Debates remain regarding the therapeutic role and extent of routine lymph node dissection (LND) for localized SB-NETs, as well as the need for aggressive resection of advanced loco-regional SB-NETs with mesenteric nodal masses. This review will address these questions regarding lymph node dissection for well-differentiated WHO grade 1 and 2 SB-NETs. In general, the aggressiveness and radicality of resection should be balanced against the length of bowel resected and post-operative functional outcomes. In localized SB-NETs with clinically negative lymph nodes, a nodal harvest of ≥ 8 lymph nodes provides accurate staging, but has not been shown to confer survival benefit. For loco-regional SB-NETs with clinically positive lymph nodes identified on imaging, 4 stages of nodal extent have been described: stage 1 nodes are located near to the intestinal border, stage 2 on arterial branches close to the origin of the SMA, stage 3 along the SMA itself, and stage 4 extend in the retroperitoneum under the pancreatic neck. In SB-NETs, every attempt should be made at resection of the primary tumor and the nodal mesenteric mass for curative-intent management and to prevent debilitating complications from mesenteric fibrosis. A mesenteric-sparing approach is favored to allow for resection for complex proximal nodal masses while preserving intestinal length and function. All patients with SB-NETs with nodal mesenteric mass should be assessed by a surgeon for resection; if deemed unresectable, consideration should be given to assessment in high-volume NETs centres to confirm proximal mesenteric-sparing resection is not feasible.
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Stewart JH, Blazer DG, Calderon MJG, Carter TM, Eckhoff A, Al Efishat MA, Fernando DG, Foster JM, Hayes-Jordan A, Johnston FM, Lautz TB, Levine EA, Maduekwe UN, Mangieri CW, Moaven O, Mogal H, Shen P, Votanopoulos KI. The Evolving Management of Peritoneal Surface Malignancies. Curr Probl Surg 2020; 58:100860. [PMID: 33832580 DOI: 10.1016/j.cpsurg.2020.100860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 07/04/2020] [Indexed: 02/07/2023]
Affiliation(s)
| | - Dan G Blazer
- Division of Surgical Oncology, Duke University Medical Center, Durham, NC
| | | | | | | | | | | | - Jason M Foster
- Fred and Pamela Buffet Cancer Center, University of Nebraska, Omaha, NE
| | | | - Fabian M Johnston
- Complex General Surgical Oncology Program, Johns Hopkins University, Baltimore, MD
| | - Timothy B Lautz
- Northwestern University Feinberg School of Medicine, Chicago, IL
| | | | - Ugwuji N Maduekwe
- Division of Surgical Oncology and Endocrine Surgery, University of North Carolina, Chapel Hill, NC
| | | | | | | | - Perry Shen
- Wake Forest University School of Medicine, Winston-Salem, NC
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Koumarianou A, Alexandraki KI, Wallin G, Kaltsas G, Daskalakis K. Pathogenesis and Clinical Management of Mesenteric Fibrosis in Small Intestinal Neuroendocine Neoplasms: A Systematic Review. J Clin Med 2020; 9:E1777. [PMID: 32521677 PMCID: PMC7357094 DOI: 10.3390/jcm9061777] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 06/04/2020] [Accepted: 06/04/2020] [Indexed: 02/07/2023] Open
Abstract
Mesenteric fibrosis (MF) constitutes an underrecognized sequela in patients with small intestinal neuroendocrine neoplasms (SI-NENs), often complicating the disease clinical course. The aim of the present systematic review, carried out by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, is to provide an update in evolving aspects of MF pathogenesis and its clinical management in SI-NENs. Complex and dynamic interactions are present in the microenvironment of tumor deposits in the mesentery. Serotonin, as well as the signaling pathways of certain growth factors play a pivotal, yet not fully elucidated role in the pathogenesis of MF. Clinically, MF often results in significant morbidity by causing either acute complications, such as intestinal obstruction and/or acute ischemia or more chronic conditions involving abdominal pain, venous stasis, malabsorption and malnutrition. Surgical resection in patients with locoregional disease only or symptomatic distant stage disease, as well as palliative minimally invasive interventions in advanced inoperable cases seem clinically meaningful, whereas currently available systemic and/or targeted treatments do not unequivocally affect the development of MF in SI-NENs. Increased awareness and improved understanding of the molecular pathogenesis of MF in SI-NENs may provide better diagnostic and predictive tools for its timely recognition and intervention and also facilitates the development of agents targeting MF.
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Affiliation(s)
- Anna Koumarianou
- Hematology Oncology Unit, Fourth Department of Internal Medicine, Attikon University General Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Krystallenia I. Alexandraki
- 1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, 11527 Athens, Greece; (K.I.A.); (G.K.); (K.D.)
| | - Göran Wallin
- Department of Surgery, Faculty of Medicine and Health, Örebro University, 701 85 Örebro, Sweden;
| | - Gregory Kaltsas
- 1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, 11527 Athens, Greece; (K.I.A.); (G.K.); (K.D.)
| | - Kosmas Daskalakis
- 1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, 11527 Athens, Greece; (K.I.A.); (G.K.); (K.D.)
- Department of Surgery, Faculty of Medicine and Health, Örebro University, 701 85 Örebro, Sweden;
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Kasai Y, Mahuron K, Hirose K, Corvera CU, Kim GE, Hope TA, Shih BE, Warren RS, Bergsland EK, Nakakura EK. A novel stratification of mesenteric mass involvement as a predictor of challenging mesenteric lymph node dissection by minimally invasive approach for ileal neuroendocrine tumors. J Surg Oncol 2020; 122:204-211. [PMID: 32291778 DOI: 10.1002/jso.25930] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 03/09/2020] [Accepted: 03/31/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVES We classified the extent of mesenteric mass (MM) involvement that predicts challenging mesenteric lymph node dissection (mLND) by minimally invasive surgery (MIS) for ileal neuroendocrine tumors (i-NETs). METHODS Patients who underwent surgery for i-NETs were retrospectively reviewed. MM involvement was classified as region-0: no MM; region-1: >2 cm from the origins of the ileocolic artery/vein; region-2: ≤2 cm from the origins; and region-3: more proximal superior mesenteric artery/vein. Logistic regression analysis was used to evaluate the predictive value of MM regions for gross positive mesenteric margin (mR2) and/or conversion among the MIS cohort. The open surgery cohort was used as a reference for mR2 rates. RESULTS Of 108 patients, 83 patients (77%) underwent MIS. MMs in region-2 and region-3 were independent risk factors for mR2 and/or conversion (odds ratio [95% confidence interval]: 4.25 [1.17-16.4] and 8.51 × 107 [11.0-], respectively, against regions-0 and 1]. mR2 rates of MIS and open surgery cohorts per region did not differ significantly (4% and 7% for regions-0 and 1; 17% and 25% for region-2; and 100% and 83% for region-3). CONCLUSIONS The novel stratification of MM regions was predictive of challenging mLND by MIS. Surgeons should have a low threshold for conversion for MMs in proximal regions.
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Affiliation(s)
- Yosuke Kasai
- Department of Surgery, University of California, San Francisco, San Francisco, California.,UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
| | - Kelly Mahuron
- Department of Surgery, University of California, San Francisco, San Francisco, California
| | - Kenzo Hirose
- Department of Surgery, University of California, San Francisco, San Francisco, California.,UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
| | - Carlos U Corvera
- Department of Surgery, University of California, San Francisco, San Francisco, California.,UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
| | - Grace E Kim
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.,Department of Pathology, University of California, San Francisco, San Francisco, California
| | - Thomas A Hope
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.,Department of Radiology and Biomedical Imaging, University of California, San Francisco, California
| | - Brandon E Shih
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
| | - Robert S Warren
- Department of Surgery, University of California, San Francisco, San Francisco, California.,UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
| | - Emily K Bergsland
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.,Department of Medicine, University of CFACS, California, San Francisco, San Francisco, California
| | - Eric K Nakakura
- Department of Surgery, University of California, San Francisco, San Francisco, California.,UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California
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Wang YZ, Chauhan A, Ramirez RA, Beyer DT, Stevens MA, Woltering EA, Boudreaux JP, Anthony L. Does the addition of adjuvant intraoperative tumor bed chemotherapy during midgut neuroendocrine tumor debulking procedures benefit patients? J Gastrointest Oncol 2019; 10:928-934. [PMID: 31602331 DOI: 10.21037/jgo.2019.07.05] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Background Midgut neuroendocrine tumor (NET) patients are often diagnosed at advanced stages with extensive mesenteric nodal and hepatic metastasis. The only potentially curative treatment is surgical tumor eradication. Despite an aggressive resection, macro and microscopic residual disease still may remain in the resection bed. We hypothesize that the application of 5-fluorouracil (5-FU) within the tumor bed will help eliminate microscopic residual disease. Methods Records of 189 patients who underwent extensive cytoreductive surgeries during 2003-2012 for advanced, midgut NETs with extensive mesenteric lymphadenopathy were reviewed. Eighty-six patients (46%) who had 5-FU saturated gel foam strips secured into their mesenteric resection sites served as the study group and a matching 103 patients (54%) who did not have such an intra-operative chemotherapy served as controls. Survival from the time of diagnosis and post-operative complications between the two groups were compared. Results Mortality rates at 30, 60 and 90 days post-operatively were 4%, 0%, 0% versus 2%, 0%, 2% for study and control groups, respectively. Major complications (Grades III & IV) at the same intervals were 0, 0, 1 versus 2, 3, 2 for study and control groups, respectively. Median survival was 236 months versus 148 months for the study and control groups, respectively 24 (P=0.15). Conclusions Intraoperative tumor resection bed chemotherapy is a safe adjuvant without discernible toxicity. This procedure may provide survival benefits to midgut NET patients with extensive mesenteric lymphadenopathy undergoing extensive cytoreductive surgery. Further study in prospective trials must be conducted to determine definitive benefit to the NET patient.
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Affiliation(s)
- Yi-Zarn Wang
- Department of Surgery, Baylor University Medical Center, Dallas, TX, USA
| | - Aman Chauhan
- Division of Medical Oncology, University of Kentucky, Markey Cancer Center, Lexington, KY, USA
| | - Robert A Ramirez
- Department of Hematology and Oncology, Ochsner Medical Center, New Orleans, LA, USA
| | - David T Beyer
- Department of Surgery, Baylor University Medical Center, Dallas, TX, USA
| | - Melissa A Stevens
- Department of Surgery, Baylor University Medical Center, Dallas, TX, USA
| | - Eugene A Woltering
- Department of Surgery, Baylor University Medical Center, Dallas, TX, USA
| | - J Philip Boudreaux
- Department of Surgery, Baylor University Medical Center, Dallas, TX, USA
| | - Lowell Anthony
- Division of Medical Oncology, University of Kentucky, Markey Cancer Center, Lexington, KY, USA
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Daskalakis K, Karakatsanis A, Hessman O, Stuart HC, Welin S, Tiensuu Janson E, Öberg K, Hellman P, Norlén O, Stålberg P. Association of a Prophylactic Surgical Approach to Stage IV Small Intestinal Neuroendocrine Tumors With Survival. JAMA Oncol 2019; 4:183-189. [PMID: 29049611 DOI: 10.1001/jamaoncol.2017.3326] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Importance Primary tumor resection and mesenteric lymph node dissection in asymptomatic patients with stage IV small intestinal neuroendocrine tumors (SI-NETs) are controversial. Objective To determine the association of locoregional surgery (LRS) performed at diagnosis with outcomes in patients with asymptomatic SI-NETs and distant metastases. Design, Setting, and Participants This cohort study included asymptomatic patients with stage IV SI-NETs diagnosed from January 1, 1985, through December 31, 2015, and identified using the prospective database of SI-NETs from Uppsala University Hospital, Uppsala, Sweden. Patients included were treated at a tertiary referral center and followed up until May 31, 2016, with data from the Swedish National Patient Register. The 363 patients with stage IV SI-NETs without abdominal symptoms were divided between those who underwent prophylactic up-front surgery within 6 months from diagnosis combined with oncologic treatment (hereafter referred to as LRS group [n = 161]) and those who underwent nonsurgical treatment or delayed surgery as needed combined with oncologic treatment (hereafer referred to as delayed LRS group [n = 202]). Exposures Prophylactic up-front surgery within 6 months from diagnosis combined with oncologic treatment vs nonsurgical treatment or delayed surgery as needed combined with oncologic treatment. Main Outcomes and Measures Overall survival (OS), length of hospital stay (LOS), postoperative morbidity and mortality, and reoperation rates measured from baseline. Propensity score matching was performed between the 2 groups. Results The 363 patients included 173 women (47.7%) and 190 men (52.3%), with a mean (SD) age at diagnosis of 62.4 (11.1) years. Two isonumerical groups with 91 patients in each resulted after propensity score matching. The LRS and delayed LRS groups were comparable in median OS (7.9 years [range, 5.1-10.7 years] vs 7.6 years [range, 5.8-9.5 years]; hazard ratio [HR], 0.98; 95% CI, 0.70-1.37; log-rank P = .93) and cancer-specific survival (7.7 years [range, 4.5-10.8 years] vs 7.6 years [range, 5.6-9.7 years]; HR, 0.99; 95% CI, 0.71-1.40; log-rank P = .99). No difference was found in 30-day mortality (0 patients in both matched groups) or postoperative morbidity (2 [2.2%] vs 1 [1.1%]; P > .99), median LOS (73 days [range, 2-270 days] vs 76 days [range, 0-339 days]; P = .64) or LOS due to local tumor-related symptoms (7.0 days [range, 0-90 days] vs 11.5 days [range, 0-69 days]; P = .81), or incisional hernia repairs (4 patients [4.4%] in both groups; P > .99). Patients in the LRS group underwent more reoperative procedures (13 [14.3%]) compared with those in the delayed LRS group (3 [3.3%]) owing to intestinal obstruction (P < .001). Conclusions and Relevance Prophylactic up-front LRS conferred no survival advantage in asymptomatic patients with stage IV SI-NETs. Delayed surgery as needed was comparable in all examined outcomes and was associated with fewer reoperations for intestinal obstruction. The value of a priori LRS in the presence of distant metastases is challenged and needs to be elucidated in a randomized clinical study.
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Affiliation(s)
- Kosmas Daskalakis
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | | | - Ola Hessman
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Heather C Stuart
- Division of Surgical Oncology, University of Miami, Miami, Florida
| | - Staffan Welin
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | | | - Kjell Öberg
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Per Hellman
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Olov Norlén
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Peter Stålberg
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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Horwitz JK, Marin ML, Warner RRP, Lookstein RA, Divino CM. EndoVascular Occlusion and Tumor Excision (EVOTE): a Hybrid Approach to Small-Bowel Neuroendocrine Tumors with Mesenteric Metastases. J Gastrointest Surg 2019; 23:1911-1916. [PMID: 31090038 DOI: 10.1007/s11605-019-04232-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 04/12/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Mesenteric metastases from small-bowel neuroendocrine tumors (SBNETs) present a surgical challenge due to encasement of mesenteric vessels. In this study, we evaluate the feasibility and safety of a new, hybrid surgical approach to these mesenteric masses, EndoVascular Occlusion and Tumor Excision (EVOTE). METHODS From 2014 to 2018, 13 patients underwent the EVOTE procedure after being referred to our institution for primary SBNETs with "unresectable" mesenteric metastases. During stage 1 of the hybrid EVOTE procedure, angiographic evaluation of the mesenteric mass is performed. If adequate collateralization is demonstrated, the encased mesenteric vessel(s) is embolized. Mass excision is performed the following day during stage 2 of the EVOTE procedure. RESULTS Preoperative embolization was successful in 86% of cases; 2 cases were aborted for persistent abdominal pain following occlusion testing. Complete surgical excision of the mesenteric mass was achieved in 86% of cases. The 30-day overall morbidity and mortality rate was 29% and 0%, respectively. There was one local recurrence at 31.8 months post-op; this patient underwent a repeat EVOTE procedure with successful complete excision. DISCUSSION EVOTE represents a new technique that aids in preoperative planning and surgical resection of SBNETs with mesenteric metastases.
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Affiliation(s)
- Julian K Horwitz
- Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA
| | - Michael L Marin
- Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA
| | - Richard R P Warner
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Robert A Lookstein
- Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Celia M Divino
- Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
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Barry L, McFadden DW. Gastrointestinal Carcinoid Tumors. SHACKELFORD'S SURGERY OF THE ALIMENTARY TRACT, 2 VOLUME SET 2019:939-950. [DOI: 10.1016/b978-0-323-40232-3.00080-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Surgery Provides Long-Term Survival in Patients with Metastatic Neuroendocrine Tumors Undergoing Resection for Non-Hormonal Symptoms. J Gastrointest Surg 2019; 23:122-134. [PMID: 30334178 PMCID: PMC10183101 DOI: 10.1007/s11605-018-3986-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Accepted: 09/20/2018] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Patients with metastatic neuroendocrine tumor (NET) often have an indolent disease course yet the outcomes for patients with metastatic NET undergoing surgery for non-hormonal (NH) symptoms of GI obstruction, bleeding, or pain is not known. METHODS We identified patients with metastatic gastroenteropancreatic NET who underwent resection from 2000 to 2016 at 8 academic institutions who participated in the US Neuroendocrine Tumor Study Group. RESULTS Of 581 patients with metastatic NET to liver (61.3%), lymph nodes (24.1%), lung (2.1%), and bone (2.5%), 332 (57.1%) presented with NH symptoms of pain (n = 223, 67.4%), GI bleeding (n = 54, 16.3%), GI obstruction (n = 49, 14.8%), and biliary obstruction (n = 22, 6.7%). Most patients were undergoing their first operation (85.4%) within 4 weeks of diagnosis. The median overall survival was 110.4 months, and operative intent predicted survival (p < 0.001) with 66.3% undergoing curative resection. Removal of all metastatic disease was associated with the longest median survival (112.5 months) compared to debulking (89.2 months), or palliative resection (50.0 months; p < 0.001). The 1-, 3-, and 12-month mortality was 3.0%, 4.5%, and 9.0%, respectively. Factors associated with 1-year mortality included palliative operations (OR 6.54, p = 0.006), foregut NET (5.62, p = 0.042), major complication (4.91, p = 0.001), and high tumor grade (11.2, p < 0.001). The conditional survival for patients who lived past 1 year was 119 months. CONCLUSIONS Patients with metastatic NET and NH symptoms that necessitate surgery have long-term survival, and goals of care should focus on both oncologic and quality of life impact. Surgical intervention remains a critical component of multidisciplinary care of symptomatic patients.
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Neuroendocrine tumors of the small intestine causing a desmoplastic reaction of the mesentery are a more aggressive cohort. Surgery 2018; 164:1093-1099. [PMID: 30076029 DOI: 10.1016/j.surg.2018.06.026] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Revised: 05/28/2018] [Accepted: 06/18/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND Desmoplastic reaction of the mesentery is commonly seen in patients with neuroendocrine tumors of the small intestine. However, it is not clear whether desmoplastic reaction is associated with tumor-specific characteristics and diminished prognosis. Therefore, the aim of this study was to investigate whether the presence of a desmoplastic reaction correlates with prognostic and molecular markers of neuroendocrine tumors of the small intestine. METHODS Patients with neuroendocrine tumors of the small intestine operated at our department from 2000 to 2016 were analyzed. Patient and tumor characteristics were evaluated. Kaplan-Meier and multivariate analyses were performed. RESULTS In total, 148 patients underwent surgery, and preoperative imaging was available in 113 patients. A total of 45 patients showed desmoplastic reaction of the mesentery and progression-free survival was significantly impaired (26 months versus 65.4 months) compared with patients without desmoplastic reaction. These patients had significantly more often distant metastases (84.4% vs 39.7%), lymphatic vessel (68.9% vs 44.1%), and perineural tissue infiltration (57.8% vs 17.6%) compared with patients without desmoplastic reaction. However, proliferation index (positive desmoplastic reaction 4.1% versus negative desmoplastic reaction 3.3%) and tumor size (positive desmoplastic reaction 2 cm versus negative desmoplastic reaction 1.9 cm) were not diverging significantly. CONCLUSION This study revealed that tumors leading to desmoplastic reaction are more aggressive, despite similar Ki67 indices.
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