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1
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Swafford EP, Magge DR. Acute mesenteric ischemia secondary to metastatic neuroendocrine tumor: a case analysis and review of the literature. J Surg Case Rep 2024; 2024:rjae725. [PMID: 39606039 PMCID: PMC11601975 DOI: 10.1093/jscr/rjae725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Accepted: 11/08/2024] [Indexed: 11/29/2024] Open
Abstract
Neuroendocrine tumors (NETs) are notably rare and frequently arise from the gastrointestinal tract. Generally asymptomatic, NETs uncommonly result in acute abdominal pain. We present a case of known metastatic NET manifesting as acute-on-chronic mesenteric ischemia due to the involvement of the superior mesenteric artery (SMA) and vein (SMV). A 63-year-old female with metastatic NET presented with acute-onset abdominal pain. The patient was hemodynamically stable but uncomfortable appearing with significant pain. Imaging demonstrated decreased enhancement of several small bowel loops within the right lower quadrant concerning for bowel ischemia with a mesenteric mass encasing the SMA and SMV. Surgical intervention revealed a nonviable loop of small bowel. Second-look laparotomy was performed with viable remaining bowel, and an ileocolic anastomosis was successfully created. Acute-onset abdominal pain in a patient with NET warrants urgent. Mesenteric ischemia, while rare, should not be overlooked, as timely diagnosis and intervention are imperative.
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Affiliation(s)
- Emily P Swafford
- Department of Surgery, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN 37232, United States
| | - Deepa R Magge
- Department of Surgery, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN 37232, United States
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2
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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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Park A, Martin A, Carlos R, Neychev V. Primary versus secondary nature of mesenteric neuroendocrine tumours. BMJ Case Rep 2021; 14:14/2/e239217. [PMID: 33541996 PMCID: PMC7868254 DOI: 10.1136/bcr-2020-239217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumours (NETs) are rare group of malignancy that originate from neuroendocrine cells present throughout the body. Most patients with NET first present with symptoms associated with metastasis, and up to 20% of patients have unknown primary site of tumour. Most common metastatic sites for small intestine NETs (SI-NETs) are the locoregional lymph nodes and liver. Although mesenteric metastasis through direct extension or lymphatic spread from SI-NETs is common, mesenteric extranodal involvement is extremely rare, and its biology and primary versus secondary nature are not well understood. Due to their small size and location, SI-NETs are frequently undetected on anatomical imaging or indium-111-pentetreotide single-photon emission computed tomography/CT (Octreoscan) and are difficult to be found via endoscopy. Gallium-68-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-octreotate positron emission tomography (68Ga-DOTATATE PET)/CT has been increasingly used for accurate staging, unknown primary tumour site localisation and appropriate management planning. We present a case of an incidentally found mesenteric NET with occult SI-NETs localised preoperatively by 68Ga-DOTATATE PET/CT.
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Affiliation(s)
- Ariel Park
- University of Central Florida College of Medicine, Orlando, Florida, USA
| | - Alicia Martin
- University of Central Florida College of Medicine, Orlando, Florida, USA
| | - Ramos Carlos
- Department of Pathology, Central Florida Regional Hospital, Sanford, Florida, USA
| | - Vladimir Neychev
- Department of Clinical Sciences, University of Central Florida College of Medicine, Orlando, Florida, USA
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4
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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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Voutsinas N, Patel RS, Bishay VL, Ranade M, Nowakowski FS, Kim E, Fischman AM, Divino CM, Marin ML, Lookstein RA. Pre-operative endovascular occlusion for unresectable metastatic carcinoid tumor: technique and initial results. Abdom Radiol (NY) 2020; 45:2554-2560. [PMID: 32318762 DOI: 10.1007/s00261-020-02534-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE Surgery is the only curative therapy for carcinoid patients; however, many are unresectable due to direct involvement of the superior mesenteric artery (SMA) branches. In these patients, we sought to improve surgical outcomes via arterial skeletonization of the SMA prior to surgical resection. MATERIALS AND METHODS After left radial access, the SMA was catheterized, angiography was performed, and balloon occlusion was achieved in the tumor vessel. Following balloon occlusion of the affected artery, patients were assessed for symptoms of ischemia and angiographic evidence of distal perfusion via collaterals. If patients tolerated occlusion, an endovascular plug was deployed in the affected artery; if not, the procedure was terminated. The next day, all patients underwent exploratory laparotomy and surgical resection of tumor and bowel. RESULTS The procedure was performed 15 times on 14 patients. 13 out of 15 procedures went to embolization, while the other 2 proceeded to surgery without plug deployment. One of the embolized patients had serious post-surgical complications, while both non-embolized patients developed complications including short bowel syndrome and ischemic colitis. Length of stay between embolized and non-embolized patients was equal, but re-admittance within 30 days was 7.7% in the embolized group and 100% in the non-embolized group. DISCUSSION Our initial experience demonstrates feasibility and safety of deploying plugs within branches of the SMA prior to surgical resection and improved surgical outcomes. Palpation of the plug assisted in surgical resection. We have demonstrated that pre-operative endovascular occlusion is a safe, practical procedure, which aids surgical resection of mesenteric carcinoid disease.
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Affiliation(s)
- Nicholas Voutsinas
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, 1 Gustave Levy Place, Box 1234, New York, NY, 10029, USA.
| | - Rahul S Patel
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, 1 Gustave Levy Place, Box 1234, New York, NY, 10029, USA
| | - Vivian L Bishay
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, 1 Gustave Levy Place, Box 1234, New York, NY, 10029, USA
| | - Mona Ranade
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, 1 Gustave Levy Place, Box 1234, New York, NY, 10029, USA
| | - Francis S Nowakowski
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, 1 Gustave Levy Place, Box 1234, New York, NY, 10029, USA
| | - Edward Kim
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, 1 Gustave Levy Place, Box 1234, New York, NY, 10029, USA
| | - Aaron M Fischman
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, 1 Gustave Levy Place, Box 1234, New York, NY, 10029, USA
| | - Celia M Divino
- Department of Surgery, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA
| | - Michael L Marin
- Department of Surgery, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA
| | - Robert A Lookstein
- Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, 1 Gustave Levy Place, Box 1234, New York, NY, 10029, USA
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Rajaretnam NS, Meyer-Rochow GY. Surgical Management of Primary Small Bowel NET Presenting Acutely with Obstruction or Perforation. World J Surg 2020; 45:203-207. [PMID: 32696097 DOI: 10.1007/s00268-020-05689-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/01/2020] [Indexed: 11/30/2022]
Abstract
Up to 35% of small bowel neuroendocrine tumors (SBNETs) may present with an acute intra-abdominal complication including obstruction, perforation, bleeding or ischemia and may require emergency surgical treatment in centers not normally accustomed to managing patients with neuroendocrine tumors. These patients may have a known diagnosis of SBNET, be suspected as suffering from SBNET or have SBNET diagnosed as an incidental finding on presenting radiology or postoperative pathology. Perioperative priorities include obtaining both clinical and radiological staging with cross-sectional imaging and clinical examination, screening for the presence of carcinoid syndrome and right-sided cardiac disease and assessment of prognosis. Intraoperatively careful attention should be paid to noting the presence and location of multifocal primary and metastatic disease. Ideally, surgical resection with mesenteric lymph node dissection is the treatment of choice for obstructing and perforating lesions. Extended lymphadenectomy along the SMA, SMV and behind the pancreas should be primarily considered an elective procedure. In unwell patients with advanced disease surgical bypass (jejuno or ileocolic) or proximal defunctioning should be undertaken but, given the excellent long-term survivals in patients with stage IV disease, could be considered bridging procedures to elective resection following formal staging and multidisciplinary review.
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Affiliation(s)
- N S Rajaretnam
- Department of Surgery, Waikato Hospital, Private Bag 3200, Hamilton, 3204, New Zealand
| | - G Y Meyer-Rochow
- Department of Surgery, Waikato Hospital, Private Bag 3200, Hamilton, 3204, New Zealand.
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7
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Laing E, Kiss N, Michael M, Krishnasamy M. Nutritional Complications and the Management of Patients with Gastroenteropancreatic Neuroendocrine Tumors. Neuroendocrinology 2020; 110:430-442. [PMID: 31550712 DOI: 10.1159/000503634] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 09/24/2019] [Indexed: 11/19/2022]
Abstract
Neuroendocrine tumors (NETs) have increased in incidence and prevalence over the past 2 decades and affect approximately 170,000 people in the United States alone. Gastroenteropancreatic (GEP) NETs (GEP NET) are a heterogeneous group of rare tumors that have distinct effects on the body due to their tumor location and potential to secrete hormones and peptides. Clinical practice guidelines and consensus guidelines for GEP NETs with regard to best practice for diagnosis, treatment, and medical management are available, but the supportive care needs and optimal nutritional management of patients affected by these unique tumors remain under-researched: evidence to guide clinical practice is lacking. The pathophysiology of the disease and its treatment can cause various symptoms that can have significant effects on vitamin synthesis and absorption, dietary habits, weight change, and appetite. Deficiency of fat-soluble vitamins and niacin exists amongst patients with GEP NET, particularly those on treatment with somatostatin analogs and with serotonin-secreting tumors, respectively. Malnutrition and dietary modification amongst patients with GEP NET is more prevalent than initially thought: up to 25% of inpatients with GEP NET are malnourished. Food intolerance is also reported in up to 40-90% of these patients, though its misdiagnosis is common. This review summarizes the evidence regarding the impact of GEP NET and its treatment on nutritional factors in these patients with emphasis on malnutrition, vitamin deficiencies, dietary intake, and quality of life. Recommendations for clinical practice and research approaches to address these nutritional issues are discussed.
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Affiliation(s)
- Erin Laing
- Department of Nutrition and Speech Pathology, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia,
- Department of Nursing, School of Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia,
| | - Nicole Kiss
- Department of Nursing, School of Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia
- Department of Cancer Experiences Research, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia
| | - Michael Michael
- Department of Medical Oncology and Neuroendocrine Unit, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia
| | - Meinir Krishnasamy
- Department of Nursing, School of Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia
- Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia
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8
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Eriksson J, Norlén O, Ögren M, Garmo H, Ihre-Lundgren C, Hellman P. Primary small intestinal neuroendocrine tumors are highly prevalent and often multiple before metastatic disease develops. Scand J Surg 2019; 110:44-50. [PMID: 31587594 DOI: 10.1177/1457496919874484] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Small intestinal neuroendocrine tumors are the most common of small bowel malignancies with a clinical incidence of about 1 per 100,000 persons per year. There has been a threefold increase in the incidence of small intestinal neuroendocrine tumor during later decades, but there are no studies that clarify whether this is due to a true higher incidence or if the rise is a mere product of, for instance, improved diagnostic modalities. The aim of this study was to investigate the incidence of clinical as well as subclinical small intestinal neuroendocrine tumors found at autopsy as well as describing the frequency of concomitant malignancies in patients with small intestinal neuroendocrine tumor. MATERIALS AND METHODS An autopsy registry from the Malmö county population from 1970 to 1982 with an 87% autopsy rate was used. The clinical autopsy reports for patients coded for the existence of "carcinoid tumor" were scrutinized for the presence of small intestinal neuroendocrine tumor, metastatic disease, and concomitant malignancies. Details of patients with clinically diagnosed small intestinal neuroendocrine tumor during this time period were gathered from the Swedish Cancer Registry. RESULTS The mean annual incidence of small intestinal neuroendocrine tumor during this period was 5.33 per 100,000 individuals, and the mean annual prevalence was 581 per 100,000. The cause of death in the majority of cases was not due to small intestinal neuroendocrine tumor. In total, 48% of the people with small intestinal neuroendocrine tumor had at least one other malignancy, most commonly colorectal cancer. CONCLUSION Most small intestinal neuroendocrine tumors are subclinical, and persons living with them will often die due to other causes. There was a high rate of multiple primary tumors (40%), suggesting that multiple tumors seem to arise before the advent of metastatic disease. Moreover, a comparably high rate of associated colorectal carcinoma was found.
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Affiliation(s)
- J Eriksson
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - O Norlén
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - M Ögren
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - H Garmo
- Division of Cancer Studies, Cancer Epidemiology Group, Research Oncology, King's College London, London, UK.,Regional Oncologic Centre, Uppsala University, Uppsala, Sweden
| | - C Ihre-Lundgren
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - P Hellman
- Department of Surgical Sciences, Uppsala University Hospital, 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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10
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Tsilimigras DI, Ntanasis-Stathopoulos I, Kostakis ID, Moris D, Schizas D, Cloyd JM, Pawlik TM. Is Resection of Primary Midgut Neuroendocrine Tumors in Patients with Unresectable Metastatic Liver Disease Justified? A Systematic Review and Meta-Analysis. J Gastrointest Surg 2019; 23:1044-1054. [PMID: 30671800 DOI: 10.1007/s11605-018-04094-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Accepted: 12/28/2018] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Patients with midgut neuroendocrine tumors (MNETs) frequently present with metastatic disease at the time of diagnosis. Although combined resection of the primary MNET and liver metastases (NELM) is usually recommended for appropriate surgical candidates, primary tumor resection (PTR) in the setting of extensive, inoperable metastatic disease remains controversial. METHODS A systematic review was performed according to PRISMA guidelines utilizing Medline (PubMed), Embase, and Cochrane library-Cochrane Central Register of Controlled Trials (CENTRAL) databases until September 30, 2018. RESULTS Among patients with MNET and NELM, 1226 (68.4%; range, 35.5-85.1% per study) underwent PTR, whereas 567 (31.6%; range, 14.9-64.5%) patients did not. Median follow-up ranged from 55 to 90 months. Cytoreductive liver surgery was performed in approximately 15.7% (range, 0-34.8%) of patients. Pooled 5-year overall survival (OS) among the resected group was approximately 73.1% (range, 57-81%) versus 36.6% (range, 21-46%) for the non-resection group. For patients without liver debulking surgery, PTR remained associated with a decreased risk of death at 5 years compared with patients who did not have the primary tumor resected (HR 0.36, 95% CI 0.16 to 0.79, p = 0.01; I2 58%, p = 0.12). For patients undergoing PTR, 30-day postoperative mortality ranged from 1.43 to 2%. CONCLUSION PTR was safe with a low peri-operative risk of mortality and was associated with an improved OS for patients with MNET and unresectable NELM. Given the poor quality of evidence, however, strong evidenced-based recommendations cannot be made based on these retrospective single center-derived data. Future well-design randomized controlled trials will be critical in elucidating the optimal treatment strategies for patients with MNET and advanced metastatic disease.
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Affiliation(s)
- Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | | | - Ioannis D Kostakis
- Department of Transplantation, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Demetrios Moris
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Dimitrios Schizas
- School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA.
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Oncology, Health Services Management and Policy, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA.
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12
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The Influence of Tumor Stage on the Prognostic Value of Ki-67 Index and Mitotic Count in Small Intestinal Neuroendocrine Tumors. Am J Surg Pathol 2019; 42:247-255. [PMID: 29016403 DOI: 10.1097/pas.0000000000000968] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Tumor cell proliferation rate determined by either Ki-67 index or mitotic count (MC) has shown to be a prognostic factor for gastrointestinal neuroendocrine tumors in general, and after its incorporation in the 2010 World Health Organization tumor grading system, it has become essentially mandatory in pathology reports for all gastrointestinal neuroendocrine tumors, regardless of tumor location. Nevertheless, clinical significance for the Ki-67 index or MC has not been well demonstrated in small intestinal neuroendocrine tumor (SINET), especially those without distant metastasis, the majority of which have very low proliferation rates. We assessed the clinical behavior of 130 SINETs in relation to stage, Ki-67 index, MC, and other pathologic features. Most SINETs (86%) were grade 1 and 14% were grade 2. There were no grade 3 tumors or poorly differentiated neuroendocrine carcinomas. On multivariate analysis, age, Ki-67 index >5%, MC >10/50 high-power field, stage IV, and liver metastases were associated with increased risk of death in all patients. When both stage and grade were considered, Ki-67 index >5% was associated with a nearly 4-fold increased risk of death in stage IV cases (n=60). In contrast, Ki-67 index did not show prognostic value for patients with stages I to III disease (n=70), although MC >1/50 high-power field was significantly associated with death on multivariable analysis. Our study confirms that liver metastasis and increased tumor cell proliferation rate are independent prognostic factors for SINETs, but shows that most SINETs have a very low proliferation rate, which limits its value for predicting tumor behavior. By combining staging and grading information, we demonstrate different roles and cutoff values of Ki-67 index and MC in SINET with different stages.
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Shogbesan O, Abdulkareem A, Pappachen B, Altomare J. Primary Mesenteric Carcinoid Tumor Presenting with Carcinoid Syndrome. Case Rep Gastroenterol 2018; 12:396-401. [PMID: 30186091 PMCID: PMC6120398 DOI: 10.1159/000490522] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 05/03/2018] [Indexed: 11/19/2022] Open
Abstract
Neuroendocrine neoplasms (NENs) are a diverse group of tumors arising throughout the body with a common origin from neuroendocrine cells. Well-differentiated NENs, also known as neuroendocrine tumors (NETs), are generally indolent and are often found incidentally, while poorly differentiated tumors are more aggressive. Carcinoid tumors are NETs arising from the gastrointestinal tract and less commonly from the lungs, thymus, and kidneys. NETs in the mesentery arise from metastasis from primary tumor, and carcinoid syndrome in this setting results from concomitant metastasis to the liver. Primary mesenteric carcinoid tumors are very rare. We present a 64-year-old man with carcinoid syndrome from a mesenteric carcinoid tumor without evidence of liver metastasis or other primary tumor sites.
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Affiliation(s)
- Oluwaseun Shogbesan
- Department of Internal Medicine, Tower Health System, West Reading, Pennsylvania, USA
| | | | - Binu Pappachen
- Hospitalist Services, Department of Medicine, Tower Health System, West Reading, Pennsylvania, USA
| | - John Altomare
- Digestive Disease Associates, Wyomissing, Pennsylvania, USA
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Pirozzolo G, Cona C, Rizzo M, Shala F, Berisha S, Recordare A. Long term recurrence in primary liver neuroendocrine tumor: Report of a single case and review of literature. Ann Hepatobiliary Pancreat Surg 2018; 22:159-163. [PMID: 29896578 PMCID: PMC5981147 DOI: 10.14701/ahbps.2018.22.2.159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 12/17/2017] [Accepted: 01/14/2018] [Indexed: 11/17/2022] Open
Abstract
Primary liver neuroendocrine tumors (PLNETs) are rare tumors of the liver. They share some common characteristics with neuroendocrine tumors (NETs) of the extrahepatic bile ducts, such as slow rise, hormonal, and histological features. Nevertheless, they possess some peculiarities and the major feature is the difference in the metastatic potential between PLNETs and NETs. PLNETs have less metastatic potential compared with NETs, which is the main factor based on which differential diagnosis between the two groups is achieved. There exists few reports disease's long-term outcome, especially about the recurrences management. We report the case of a 52-year-old woman admitted to hospital for jaundice and presence of liver mass. She underwent extended right hepatectomy and subsequently, PLNET was revealed. After 9 years, a new mass was discovered in the remnant liver, far from the resection line, and was surgically removed. Histological examination confirmed a PLNET recurrence. The patient is alive and doing well after a year of surgery. We conducted a review of the literature on recurrent PLNETS. Five papers followed our inclusion criteria and included 10 patients. Clinical presentation was mostly nonspecific in included cases and no carcinoid syndrome was reported. Median overall survival and median disease-free survival periods were 22 and 5 months, respectively. The primary disease was treated with surgical resection in all the included cases and recurrent diseases were mostly treated with non-surgical techniques (mainly transarterial chemoembolization). In conclusion, more studies should be conducted in order to have significant data about this uncommon neoplasm. Finally, considering the lack of data on long-term outcome, a long and accurate follow-up should be considered.
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Affiliation(s)
- Giovanni Pirozzolo
- General and Emergency Surgery Department, Angelo Hospital, Venice, Italy
| | - Camilla Cona
- General and Emergency Surgery Department, Angelo Hospital, Venice, Italy.,University of Padua, Padova, Italy
| | - Maurizio Rizzo
- General and Emergency Surgery Department, Angelo Hospital, Venice, Italy
| | - Fazli Shala
- General Surgery Department, Regional Hospital Peja, Peja, Kosovo
| | - Sadri Berisha
- General Surgery Department, Regional Hospital Peja, Peja, Kosovo
| | - Alfonso Recordare
- General and Emergency Surgery Department, Angelo Hospital, Venice, Italy
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Eriksson J, Garmo JEH, Ihre-Lundgren C, Hellman P. Prognostic factors for death after surgery for small intestinal neuroendocrine tumours. BJS Open 2018; 2:345-352. [PMID: 30263986 PMCID: PMC6156160 DOI: 10.1002/bjs5.76] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 03/23/2018] [Indexed: 01/01/2023] Open
Abstract
Background Neuroendocrine tumours of the small intestine (SI-NETs) are rare gastrointestinal neoplasms with an annual incidence of about one per 100 000. Patients with apparently similar tumours have variable outcomes. The aim of this study was to identify postoperative prognostic factors identifiable after initial surgery. Methods This was a nested case-control study of patients with SI-NETs who were treated between 1961 and 2001. Data were retrieved from the Swedish Cancer Registry. Patients who died from the SI-NET and corresponding controls (who outlived cases by at least 1 month), matched by age at diagnosis and calendar period, were included. Sex, postoperative symptoms, postoperative 5-hydroxyindoleacetic acid (5-HIAA) values, European Neuroendocrine Tumor Society (ENETS) stage, insufficiency of the tricuspid valve, radical secondary surgery and secondary malignancy were studied as potential prognostic factors. Results In total, 1122 patients were included (561 cases, 561 controls). Postoperative factors of prognostic importance included hormone-related symptoms, stage IV disease, raised levels of 5-HIAA, insufficiency of the tricuspid valve, secondary surgery not being macroscopically radical and a second malignancy. Conclusion Stage and symptomatic disease are important prognostic factors in SI-NET.
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Affiliation(s)
- J Eriksson
- Department of Surgical Sciences Uppsala University Uppsala Sweden
| | - J E H Garmo
- Regional Oncological Centre Uppsala University Uppsala Sweden.,Cancer Epidemiology Unit, Division of Cancer Studies King's College London London UK
| | - C Ihre-Lundgren
- Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden
| | - P Hellman
- Department of Surgical Sciences Uppsala University Uppsala Sweden
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Manguso N, Gangi A, Johnson J, Harit A, Nissen N, Jamil L, Lo S, Wachsman A, Hendifar A, Amersi F. The role of pre-operative imaging and double balloon enteroscopy in the surgical management of small bowel neuroendocrine tumors: Is it necessary? J Surg Oncol 2017; 117:207-212. [PMID: 28940412 DOI: 10.1002/jso.24825] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Accepted: 08/11/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVES Pre-operative localization of small bowel neuroendocrine tumors (SBNET) is important for operative planning. The aim was to determine the effectiveness of pre-operative imaging and double-balloon enteroscopy (DBE) in identifying extent of disease. METHODS Database review identified 85 patients with primary SBNET between 2006 and 2013. Analysis included patients who underwent imaging, endoscopy, and surgery at our institution. RESULTS Average age was 60.7 years. Sixty-six (77.1%) patients had a primary NET in the ileum. Seventy-two patients (67.3%) underwent CT, 47 (46.7%) had MRI, 44 (46.7%) had somatostatin receptor imaging (SRI), and 41 (39.3%) underwent DBE. The sensitivity of each in identifying the NET was 59.7% for CT, 54% for MRI, 56% for SRI, and 88.1% for DBE. Eighteen (21.2%) patients had primary tumors not identified on imaging. Of these 18, 13 underwent DBE, and 12 of 13 (92.3%) DBEs identified the primary lesion. DBE was significantly better at identifying the primary NET than CT, MRI or SRI (P = 0.004, 0.007, and 0.012). CONCLUSIONS Most SBNETs are identified with a combination of imaging modalities. In those with unidentified primary tumors after imaging, DBE should be considered as it may provide valuable information as to the location of the primary tumor.
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Affiliation(s)
- Nicholas Manguso
- Department of Surgery, Division of Surgical Oncology and Hepatobiliary Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Alexandra Gangi
- Department of Surgery, Division of Surgical Oncology and Hepatobiliary Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Jeffrey Johnson
- Department of Surgery, Division of Surgical Oncology and Hepatobiliary Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Attiya Harit
- Department of Surgery, Division of Surgical Oncology and Hepatobiliary Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Nicholas Nissen
- Department of Surgery, Division of Surgical Oncology and Hepatobiliary Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Laith Jamil
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Simon Lo
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Ashley Wachsman
- Department of Radiology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Andrew Hendifar
- Department of Internal Medicine, Division of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Farin Amersi
- Department of Surgery, Division of Surgical Oncology and Hepatobiliary Surgery, Cedars-Sinai Medical Center, Los Angeles, California
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Howe JR, Cardona K, Fraker DL, Kebebew E, Untch BR, Wang YZ, Law CH, Liu EH, Kim MK, Menda Y, Morse BG, Bergsland EK, Strosberg JR, Nakakura EK, Pommier RF. The Surgical Management of Small Bowel Neuroendocrine Tumors: Consensus Guidelines of the North American Neuroendocrine Tumor Society. Pancreas 2017; 46:715-731. [PMID: 28609357 PMCID: PMC5502737 DOI: 10.1097/mpa.0000000000000846] [Citation(s) in RCA: 264] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Small bowel neuroendocrine tumors (SBNETs) have been increasing in frequency over the past decades, and are now the most common type of small bowel tumor. Consequently, general surgeons and surgical oncologists are seeing more patients with SBNETs in their practices than ever before. The management of these patients is often complex, owing to their secretion of hormones, frequent presentation with advanced disease, and difficulties with making the diagnosis of SBNETs. Despite these issues, even patients with advanced disease can have long-term survival. There are a number of scenarios which commonly arise in SBNET patients where it is difficult to determine the optimal management from the published data. To address these challenges for clinicians, a consensus conference was held assembling experts in the field to review and discuss the available literature and patterns of practice pertaining to specific management issues. This paper summarizes the important elements from these studies and the recommendations of the group for these questions regarding the management of SBNET patients.
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Affiliation(s)
- James R Howe
- From the *Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA; †Department of Surgery, Winship Cancer Institute of Emory University, Atlanta, GA; ‡Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA; §Endocrine Oncology Branch, National Cancer Institute, Bethesda, MD; ∥Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, NY; ¶Department of Surgery, LSU Health Sciences Center, New Orleans, LA; #Department of Surgery, University of Toronto, Sunnybrook Health Sciences Center, Toronto, Canada; **Rocky Mountain Cancer Center, Denver, CO; ††Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; ‡‡Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, IA; §§Department of Radiology, H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL; ∥∥Department of Medicine, University of California San Francisco, San Francisco, CA; ¶¶Department of Medicine, H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL; ##Department of Surgery, University of California San Francisco, San Francisco, CA; and ***Department of Surgery, Oregon Health & Science University, Portland, OR
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Peker A, Çiçek O, Soydal Ç, Küçük NÖ, Bilgiç S. Radioembolization with yttrium-90 resin microspheres for neuroendocrine tumor liver metastases. Diagn Interv Radiol 2016; 21:54-9. [PMID: 25430526 DOI: 10.5152/dir.2014.14036] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE We aimed to evaluate the effectiveness and safety of radioembolization with yttrium-90 (90Y) microspheres in cases with unresectable neuroendocrine tumor liver metastases (NETLMs). METHODS Thirty patients (mean age, 55 years) underwent resin-based 90Y radioembolization for unresectable NETLM at a single institution between April 2008 and June 2013. Post-treatment tumor response was assessed by cross-sectional imaging using the Response Evaluation Criteria in Solid Tumors (RECIST). Prognostic variables that affected survival were determined. RESULTS The mean follow-up was 23.0±19.4 months and the median overall survival was 39 months (95% CI, 12.6-65.4 months), with one- and two-year survival rates of 71% and 45%, respectively. Imaging follow-up using RECIST at three-month intervals demonstrated partial response in 43%, complete remission in 3%, stable disease in 37%, and progressive disease in 17% of patients. Extent of tumor involvement was found to have a statistically significant influence on overall survival (P = 0.03). The existence of extrahepatic disease at the time of radioembolization, radiographic response, age, and primary neuroendocrine tumor site were not significant prognostic factors. CONCLUSION The current study demonstrates the effectiveness and safety of radioembolization for the treatment of unresectable NETLMs. We identified that the extent of tumor involvement has a significant effect on overall survival. The use of imaging methods reflecting metabolic activity or cellularity such as scintigraphy or diffusion-weighted MRI would be more appropriate, for the response evaluation of liver metastases after radioembolization.
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Affiliation(s)
- Ahmet Peker
- Department of Radiology, Ankara University Medical School, Ankara, Turkey.
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Eriksson J, Garmo H, Hellman P, Ihre-Lundgren C. The Influence of Preoperative Symptoms on the Death of Patients with Small Intestinal Neuroendocrine Tumors. Ann Surg Oncol 2016; 24:1214-1220. [PMID: 27904972 PMCID: PMC5374169 DOI: 10.1245/s10434-016-5703-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Indexed: 12/24/2022]
Abstract
Background Small intestinal neuroendocrine tumors (SI-NETs) are uncommon tumors with an annual incidence of about 1 per 100,000. Usually, SI-NETs have a slow progression, and patients often present with generalized disease. Many patients do well, and the disease has a relatively favorable 5-year survival rate. Some SI-NETs, however, have a more negative prognosis. This study aimed to establish prognostic factors for death identifiable at primary surgery. Methods A nested case-control study investigated 1150 patients from the cohort of all patients with a diagnosis of SI-NETs in Sweden between 1961 and 2001. The study cases consisted of all patients who died of SI-NETs during the study period. Each case was assigned a control subject matched by age at diagnosis and calendar period. Possible prognostic factors [gender, degree of symptoms, indication for surgery, World Health Organization (WHO) stage] were evaluated in uni- and multivariable analyses. Results The patients with symptomatic disease had an increased risk of dying. The indication for primary surgery influenced survival, showing a more negative prognosis for elective surgery. The WHO stage influenced survival, and stage 4 patients had an almost threefold risk of dying compared with stages 1 to 3b patients. Conclusions This study showed that preoperative symptoms are important in prognostication for SI-NETs. Hormonal symptoms generally signify a patient with a more advanced disease stage and a worse prognosis. Including symptomatic disease together with the WHO stage and grade could possibly increase the accuracy of prognostication.
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Affiliation(s)
- John Eriksson
- Department of Surgical Sciences, Faculty of Medicine, Uppsala University, Uppsala, Sweden.
| | - Hans Garmo
- Division of Cancer Studies, Cancer Epidemiology Group, Research Oncology, King's College London, UK/Regional Oncologic Center, Uppsala University, Uppsala, Sweden
| | - Per Hellman
- Department of Surgical Sciences, Faculty of Medicine, Uppsala University, Uppsala, Sweden
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Watzka FM, Fottner C, Miederer M, Weber MM, Schad A, Lang H, Musholt TJ. Surgical Treatment of NEN of Small Bowel: A Retrospective Analysis. World J Surg 2016; 40:749-58. [PMID: 26822157 DOI: 10.1007/s00268-016-3432-2] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Neuroendocrine Neoplasms of the small intestine have been noticed more frequently over the past 35 years. They constitute about 25% of all NENs and 29% of all tumors of the small intestine. Due to the predominantly indolent nature and overall good prognosis, the benefit of surgical treatment is still debated. METHODS In a retrospective study, data of 83 surgically treated patients with neuroendocrine neoplasms of the small intestine, 48 males and 35 females with a median age of 62 years (range 25-86 years) were analyzed. Patient data were documented in the MaDoc database for neuroendocrine tumors of the University Medical Center of Mainz. IBM SPSS Statistics 20 was used for statistical analysis. Kaplan-Meier survival curves and Log-Rank tests, censoring patients at the time of last follow-up, were used to compare the overall survival depending on potential prognostic factors (stage, grade, surgical treatment). RESULTS At the time of diagnoses, the most common clinical symptoms were abdominal pain (n = 31, 37.3%), bowel obstruction (n = 11, 13.3%), bowel perforation and peritonitis (n = 3, 3.6%), gastrointestinal bleeding (n = 9, 10.8%), weight loss (n = 11, 13.3%), and carcinoid syndrome (n = 27, 32.5%). 65 patients (78.3%) had lymph node metastasis and in 58 patients (69.9%) distant metastasis were present. Segmental bowel resection (44) was the most common surgical procedure, followed by right hemi-colectomy (32) and explorative laparotomy (7). In most patients (78.9%), lymphadenectomy (systematic/selective) was performed. The 5-year survival of patients who underwent a systematic or a selective lymphadenectomy differed significantly (82.2 vs. 40.0%). The overall 3-, 5-, and 10-year survival rates were 88.2, 80.3, and 71.0%, respectively. CONCLUSION Mesenteric lymph node metastases are almost invariably present and have significant impact on patients' prognosis. Systematic lymphadenectomy prevents complications and improves the survival. Early surgical treatment should be the goal in order to prevent complications.
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Affiliation(s)
- F M Watzka
- Clinic of General, Visceral- and Transplantation Surgery, University Medicine Mainz, Langenbeckstr. 1, 55131, Mainz, Germany
| | - C Fottner
- Endocrinology and Metabolic Diseases, University Medicine Mainz, Langenbeckstr. 1, 55131, Mainz, Germany
| | - M Miederer
- Clinic of Nuclear Medicine, University Medicine Mainz, Langenbeckstr. 1, 55131, Mainz, Germany
| | - M M Weber
- Endocrinology and Metabolic Diseases, University Medicine Mainz, Langenbeckstr. 1, 55131, Mainz, Germany
| | - A Schad
- Institute of Pathology, University Medicine Mainz, Langenbeckstr. 1, 55131, Mainz, Germany
| | - H Lang
- Clinic of General, Visceral- and Transplantation Surgery, University Medicine Mainz, Langenbeckstr. 1, 55131, Mainz, Germany
| | - T J Musholt
- Clinic of General, Visceral- and Transplantation Surgery, University Medicine Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.
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Vitamin D and vitamin B12 deficiencies are common in patients with midgut carcinoid (SI-NET). Eur J Clin Nutr 2016; 70:990-4. [PMID: 27026421 DOI: 10.1038/ejcn.2016.40] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 02/03/2016] [Accepted: 02/10/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND/OBJECTIVES Patients with small intestinal neuroendocrine tumours (SI-NET) often have diarrhoea from hormonal overproduction, surgery and medical treatment, leading to malabsorption of bile salts, fats, vitamin B12 and fat-souble vitamins. This could lead to malnutrition. SUBJECTS/METHODS We assessed nutritional status in 50 consecutive out patients with disseminated SI-NET, 25 patients in each cohort. The first cohort was descriptive and the second cohort supplemented with vitamin D, B12 and calcium. Vitamin D deficiency was defined as <50 nmol/l. All patients were assessed by clinical chemistry and dual-energy X-ray absorptiometry (DXA) and interviewed about weight changes, appetite, gastrointestinal disorders, sunhabits and the use of supplements. RESULTS In the first cohort, 29% of the patients were severely and 17% moderately vitamin D deficient. In patients without prior substitution, 32% had subnormal vitamin B12 levels. Seventy-six percent had low bone density. In the second cohort with vitamin and mineral supplementation, none had severe vitamin D deficiency, but 28% had moderate deficiency. No patient had subnormal vitamin B12 levels. Sixty percent had low bone density. The serum levels of vitamin D and B12 were higher and parathyroid hormone (PTH) lower in the second cohort compared with the first cohort (P⩽0,022). Vitamin D and PTH were negatively correlated, r=-30, P=⩽0.036. CONCLUSIONS Low serum levels of vitamin D and vitamin B12, and low bone density are common in patients with disseminated SI-NET. Supplementation of vitamin D, B12 and calcium resulted in higher serum levels of vitamins, lower PTH levels and diminished severe vitamin D deficiency and is thus recommended as standard care.
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Barral M, Dohan A, Allez M, Boudiaf M, Camus M, Laurent V, Hoeffel C, Soyer P. Gastrointestinal cancers in inflammatory bowel disease: An update with emphasis on imaging findings. Crit Rev Oncol Hematol 2016; 97:30-46. [DOI: 10.1016/j.critrevonc.2015.08.005] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2014] [Revised: 06/15/2015] [Accepted: 08/04/2015] [Indexed: 12/20/2022] Open
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Retrograde Stenting Under Transmesenteric Angiographic Guidance of an Occluded Superior Mesenteric Vein to Treat Life-Threatening Hemorrhage. Ann Vasc Surg 2015; 31:209.e11-5. [PMID: 26657192 DOI: 10.1016/j.avsg.2015.09.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Revised: 09/02/2015] [Accepted: 09/05/2015] [Indexed: 02/04/2023]
Abstract
Midgut carcinoid tumors (MCTs) are responsible for a range of mesenteric vascular complications and may rarely manifest with gastrointestinal (GI) hemorrhage. Endovascular approaches are particularly useful for this population, as surgery is often technically difficult. We report a case of life-threatening upper GI bleeding in a 50-year-old man previously diagnosed with an MCT in the small bowel mesentery. Computed tomography angiogram revealed an MCT obstructing the superior mesenteric vein (SMV) associated with multiple large collateral vessels. The patient underwent retrograde stenting of the obstructed SMV using a combined open and endovascular approach to successfully terminate the persistent GI bleeding.
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Farley HA, Pommier RF. Surgical Treatment of Small Bowel Neuroendocrine Tumors. Hematol Oncol Clin North Am 2015; 30:49-61. [PMID: 26614368 DOI: 10.1016/j.hoc.2015.09.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Neuroendocrine tumors of the small bowel are rare, slow-growing malignancies that commonly metastasize to nodes at the root of the mesentery and the liver. Liver metastases are associated with carcinoid syndrome. Mesenteric nodal masses can cause bowel obstruction, intestinal angina, or variceal hemorrhage. Patients die of liver failure or bowel obstruction. Primary resection is associated with improved survival rates. Selected patients may benefit from liver debulking operations. Liver resection has excellent survival rates even in the event of an incomplete resection, as well as improvement in hormonal symptoms. Radiofrequency ablation can help to preserve hepatic parenchyma during resection.
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Affiliation(s)
- Heather A Farley
- Department of Surgery, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Mail Code L 619, Portland, OR 97329, USA
| | - Rodney F Pommier
- Division of Surgical Oncology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Mail Code L 619, Portland, OR 97329, USA.
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Hughes MS, Azoury SC, Assadipour Y, Straughan DM, Trivedi AN, Lim RM, Joy G, Voellinger MT, Tang DM, Venkatesan AM, Chen CC, Louie A, Quezado MM, Forbes J, Wank SA. Prospective evaluation and treatment of familial carcinoid small intestine neuroendocrine tumors (SI-NETs). Surgery 2015; 159:350-6. [PMID: 26454678 DOI: 10.1016/j.surg.2015.05.041] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Revised: 04/22/2015] [Accepted: 05/13/2015] [Indexed: 01/17/2023]
Abstract
BACKGROUND The aim of this study was to prospectively screen patients with a positive family history of carcinoid small intestine neuroendocrine tumors (SI-NETs) to elucidate the benefits of early detection and operative intervention. METHODS A single-center, prospective trial was conducted from 2008 to 2014 that evaluated patients with 2 or more blood relatives with carcinoid SI-NETs. All eligible patients were screened with urine/serum biochemistries and various imaging modalities. Operative intervention was elected in patients found to have at least 1 positive diagnostic study. RESULTS Twenty-nine patients from 13 families had occult carcinoid SI-NETs (15 female, 14 male). Twenty-four of the 29 patients (83%) had multifocal disease found in either the distal jejunum or ileum. On average, 75.9 cm (range, 13-195) of bowel was resected in 1 segment. Three patients were found to have stage IV disease at operation. All stage I-IIIB patients who had R0 resections have remained disease-free, with a median follow-up of 35 months. CONCLUSION Familial carcinoid SI-NETs often are asymptomatic and can be diagnosed with aggressive screening. With early detection, there may be a window of opportunity for operative resection to change the natural history of this disease and even prove to be curative.
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Affiliation(s)
- Marybeth S Hughes
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
| | - Saïd C Azoury
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Yasmine Assadipour
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - David M Straughan
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Apurva N Trivedi
- Digestive Diseases Branch, National Institute of Diabetes, Kidney and Digestive Diseases, National Institutes of Health, Bethesda, MD
| | - Ramona M Lim
- Digestive Diseases Branch, National Institute of Diabetes, Kidney and Digestive Diseases, National Institutes of Health, Bethesda, MD
| | - Grishma Joy
- Digestive Diseases Branch, National Institute of Diabetes, Kidney and Digestive Diseases, National Institutes of Health, Bethesda, MD
| | - Mark T Voellinger
- Digestive Diseases Branch, National Institute of Diabetes, Kidney and Digestive Diseases, National Institutes of Health, Bethesda, MD
| | - Derek M Tang
- Digestive Diseases Branch, National Institute of Diabetes, Kidney and Digestive Diseases, National Institutes of Health, Bethesda, MD
| | | | - Clara C Chen
- Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD
| | - Adeline Louie
- Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD
| | - Martha M Quezado
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Joanne Forbes
- Digestive Diseases Branch, National Institute of Diabetes, Kidney and Digestive Diseases, National Institutes of Health, Bethesda, MD
| | - Stephen A Wank
- Digestive Diseases Branch, National Institute of Diabetes, Kidney and Digestive Diseases, National Institutes of Health, Bethesda, MD
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Geis C, Fendrich V, Rexin P, Di Fazio P, Bartsch DK, Ocker M, Quint K, Heverhagen AE. Ileal neuroendocrine tumors show elevated activation of mammalian target of rapamycin complex. J Surg Res 2015; 194:388-393. [PMID: 25439321 DOI: 10.1016/j.jss.2014.10.052] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2014] [Revised: 10/24/2014] [Accepted: 10/30/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Neuroendocrine tumors (NETs) of the ileum are sporadic tumors derived from submucosal gastrointestinal stem cells. They often show clinical symptoms only after hepatic metastasation when curative therapy is limited or impossible. In this study, we analyzed the expression of the candidate genes mammalian target of rapamycin (mTOR), alpha thalassemia/mental retardation syndrome X-linked (ATRX), and death domain-associated protein (DAXX) to investigate the specific oncogenetics and potential therapeutic options for ileal NETs. METHODS In a prospective database, all patients who underwent surgical removal of a NET of the ileum between 2001 and 2011 were specified. Expression analysis was performed for mTOR, ATRX, and DAXX by immunohistochemistry of paraffin-embedded tumor samples. To evaluate the results the immunoreactive score was applied. Normal tissue and tumor tissue were analyzed for the comparison of gene expression levels using quantitative-real-time polymerase chain reaction for ATRX and mTOR genes. Results were correlated under pathologic and clinical aspects. RESULTS A total of 69 patients were admitted to the study. Positive cytosolic expression of the potential oncogene mTOR was immunohistochemically detected in 76.2% of the human probes. A loss of nuclear ATRX expression was detected in 13.0% of the samples. A nonexpression of the DAXX-protein in cell nuclei was not found (0%). Gene transcript levels did not show a significant alteration in ileal NETs in comparison with normal tissue. CONCLUSIONS mTOR is overexpressed in ileal NETs. Additionally, the loss of ATRX expression was registered, thus underlying a tumorigenic role in a subgroup of these tumors. To enable potential therapeutic application of mTOR inhibitors, further trials with larger study groups are needed.
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Affiliation(s)
- Christian Geis
- Department of Visceral-, Thoracic- and Vascular-Surgery, Philipps-University Marburg, Marburg, Germany; Institute for Surgical Research, Philipps-University Marburg, Marburg, Germany
| | - Volker Fendrich
- Department of Visceral-, Thoracic- and Vascular-Surgery, Philipps-University Marburg, Marburg, Germany
| | - Peter Rexin
- Department of Pathology, Philipps-University Marburg, Marburg, Germany
| | - Pietro Di Fazio
- Department of Visceral-, Thoracic- and Vascular-Surgery, Philipps-University Marburg, Marburg, Germany
| | - Detlef K Bartsch
- Department of Visceral-, Thoracic- and Vascular-Surgery, Philipps-University Marburg, Marburg, Germany
| | - Matthias Ocker
- Institute for Surgical Research, Philipps-University Marburg, Marburg, Germany
| | - Karl Quint
- Institute for Surgical Research, Philipps-University Marburg, Marburg, Germany
| | - Anna E Heverhagen
- Department of Visceral-, Thoracic- and Vascular-Surgery, Philipps-University Marburg, Marburg, Germany.
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Shamiyeh A, Gabriel M. Laparoscopic resection of gastrointestinal neuroendocrine tumors with special contribution of radionuclide imaging. World J Gastroenterol 2014; 20:15608-15. [PMID: 25400444 PMCID: PMC4229525 DOI: 10.3748/wjg.v20.i42.15608] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Revised: 03/22/2014] [Accepted: 05/23/2014] [Indexed: 02/06/2023] Open
Abstract
The surgical treatment of neuroendocrine tumors (NETs) draws on experience and guidelines more than on prospective randomized trials. The incidence of NET is increasing in all parts of the gastrointestinal tract. A variety of classifications introduced over the last decade may have led to difficulties in judging clinical relevance and determining the right surgical strategy. The North American Neuroendocrine Tumor Society and the European Neuroendocrine Tumor Society have developed usable guidelines from the available literature. For more than 20 years laparoscopy has developed as the gold standard for various surgical indications. Nevertheless, few trials have compared open and laparoscopic surgery with regard to NET. This review summarizes the recent literature on surgery for NET and incorporates the evidence on laparoscopy for cancer which might be also applied for NET.
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Partelli S, Maurizi A, Tamburrino D, Baldoni A, Polenta V, Crippa S, Falconi M. GEP-NETS update: a review on surgery of gastro-entero-pancreatic neuroendocrine tumors. Eur J Endocrinol 2014; 171:R153-62. [PMID: 24920289 DOI: 10.1530/eje-14-0173] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The incidence of neuroendocrine tumors (NETs) has increased in the last decades. Surgical treatment encompasses a panel of approaches ranging from conservative procedures to extended surgical resection. Tumor size and localization usually represent the main drivers in the choice of the most appropriate surgical resection. In the presence of small (<2 cm) and asymptomatic nonfunctioning NETs, a conservative treatment is usually recommended. For localized NETs measuring above 2 cm, surgical resection represents the cornerstone in the management of these tumors. As they are relatively biologically indolent, an extended resection is often justified also in the presence of advanced NETs. Surgical options for NET liver metastases range from limited resection up to liver transplantation. Surgical choices for metastatic NETs need to consider the extent of disease, the grade of tumor, and the presence of extra-abdominal disease. Any surgical procedures should always be balanced with the benefit of survival or relieving symptoms and patients' comorbidities.
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Affiliation(s)
- Stefano Partelli
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
| | - Angela Maurizi
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
| | - Domenico Tamburrino
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
| | - Andrea Baldoni
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
| | - Vanessa Polenta
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
| | - Stefano Crippa
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
| | - Massimo Falconi
- Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy
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Ezhapilli SR, Moreno CC, Small WC, Hanley K, Kitajima HD, Mittal PK. Mesenteric masses: Approach to differential diagnosis at MRI with histopathologic correlation. J Magn Reson Imaging 2014; 40:753-69. [DOI: 10.1002/jmri.24690] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Accepted: 06/09/2014] [Indexed: 12/15/2022] Open
Affiliation(s)
- Sajeev R. Ezhapilli
- Department of Radiology & Imaging Sciences; Emory University School of Medicine; Atlanta Georgia USA
| | - Courtney Coursey Moreno
- Department of Radiology & Imaging Sciences; Emory University School of Medicine; Atlanta Georgia USA
| | - William C. Small
- Department of Radiology & Imaging Sciences; Emory University School of Medicine; Atlanta Georgia USA
| | - Krisztina Hanley
- Department of Pathology; Emory University School of Medicine; Atlanta Georgia USA
| | - Hiroumi D. Kitajima
- Department of Radiology & Imaging Sciences; Emory University School of Medicine; Atlanta Georgia USA
| | - Pardeep K. Mittal
- Department of Radiology & Imaging Sciences; Emory University School of Medicine; Atlanta Georgia USA
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Heverhagen AE, Geis C, Fendrich V, Ramaswamy A, Montalbano R, Di Fazio P, Bartsch DK, Ocker M, Quint K. Embryonic transcription factors CDX2 and Oct4 are overexpressed in neuroendocrine tumors of the ileum: a pilot study. Eur Surg Res 2013; 51:14-20. [PMID: 23887079 DOI: 10.1159/000353612] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2012] [Accepted: 06/11/2013] [Indexed: 02/05/2023]
Abstract
BACKGROUND Neuroendocrine tumors (NETs) of the ileum are rare submucosal tumors that are often diagnosed at advanced stages with metastatic spread to the liver causing a carcinoid syndrome. They present as solitary or multiple tumors. In NETs, loss of sequences on chromosomes 11, 16, 18 and 22 or gain of sequences on chromosomes 17 and 19 has been described. In this study we explored the expression of two novel candidate genes, CDX2 and Oct4, in NETs of the ileum and analyzed whether the molecular expression pattern correlates with the clinical phenotype (solitary/multiple tumors). METHODS Data from all patients who underwent surgery for a NET of the ileum between 2000 and 2010 were retrieved from a prospective database. For each patient, frozen normal and tumor tissue was used for the comparison of gene expression levels of two putative cancer stem cell markers, CDX2 and Oct4, using real-time PCR (rtPCR). Serial slides from paraffin blocks were used for immunohistochemistry. Gene expression was compared between normal and tumor tissue as well as between solitary and multiple tumors. RESULTS 78 patients were identified. In rtPCR, a statistically significant higher expression of CDX2 in tumor tissue (p < 0.001) compared to normal tissue was found. The expression of Oct4 was elevated in the tumors, but did not reach the level of significance (p = 0.155). The expression of both candidate genes was confirmed immunohistochemically and showed a nuclear expression pattern. There was no difference in expression between solitary and multiple tumors or between tumors that had already spread to the liver. CONCLUSION CDX2 is overexpressed in ileum NETs, thus playing a role in the tumorigenesis of these rare tumors. Since expression does not correlate with clinical stage or phenotype, it might be an early event in tumor development.
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Affiliation(s)
- A E Heverhagen
- Department of Visceral, Thoracic and Vascular Surgery, Philipp University of Marburg, Marburg, Germany
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Gedde-Dahl M, Thiis-Evensen E, Tjølsen AM, Mordal KS, Vatn M, Bergestuen DS. Comparison of 24-h and overnight samples of urinary 5-hydroxyindoleacetic acid in patients with intestinal neuroendocrine tumors. Endocr Connect 2013; 2:50-4. [PMID: 23781318 PMCID: PMC3680961 DOI: 10.1530/ec-12-0077] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2012] [Accepted: 12/14/2012] [Indexed: 01/19/2023]
Abstract
Neuroendocrine tumors (NETs) arising in the small intestine are known to produce vasoactive substances, including serotonin, that may result in the carcinoid syndrome (flushing, diarrhea, bronchoconstriction, and carcinoid heart disease). Measurement of the serotonin breakdown product 5-hydroxyindoleacetic acid (5-HIAA) in urine is important in diagnosing and monitoring of patients with intestinal NETs. Our aim was to compare 5-HIAA measurement in 24-h urine sampling with overnight (∼8-h) sampling in patients with known NETs, or at follow-up of patients potentially cured for their NETs. Twenty-four-hour and overnight urine samples were collected from 34 patients and analyzed for urinary 5-HIAA (U5-HIAA) using HPLC. Comparison of the overnight sampling values with the 24-h values showed no difference, P=0.45, and there was a significant direct correlation between the two samples using linear regression (R=0.97, P<0.001). U5-HIAA sample collection during a nightly interval of ∼8 h appears to have the same accuracy as the 24-h collection in this group of patients.
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Park IS, Kye BH, Kim HS, Kim HJ, Cho HM, Yoo C, Hwang SS. Primary mesenteric carcinoid tumor. JOURNAL OF THE KOREAN SURGICAL SOCIETY 2013; 84:114-7. [PMID: 23397044 PMCID: PMC3566469 DOI: 10.4174/jkss.2013.84.2.114] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2012] [Revised: 10/16/2012] [Accepted: 10/26/2012] [Indexed: 12/20/2022]
Abstract
Primary mesenteric carcinoid tumor is very rare, although secondary mesenteric involvement is common, reported as 40% to 80%. And distant metastasis rate reported as 80% to 90%, when the size is larger than 2 cm. We present a case of very rare primary mesenteric carcinoid tumor showing benign character though large size. The patient visited St. Vincent's Hospital, The Catholic University of Korea with increasing palpable abdominal mass. At laparotomy, a well encapsulated mass arising from the mesentery near the ligament of Treitz was found without any adjacent organ invasion or distant metastasis. The mass was measured as 8.2 × 7.3 cm and histopathologically benign character. At 11 months of follow up, the patient was recurrence free.
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Affiliation(s)
- In-Soo Park
- Department of Surgery, St. Vincent's Hospital, The Catholic University of Korea College of Medicine, Suwon, Korea
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33
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Simion NI, Muntean V, Fabian O. Current state of knowledge on neuroendocrine small bowel tumours: non-systematic review of the literature based on one case. BMJ Case Rep 2013; 2013:bcr-2012-007217. [PMID: 23329706 DOI: 10.1136/bcr-2012-007217] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
More than 60% of neuroendocrine tumours, also called carcinoids, are localised within the gastrointestinal tract. Small bowel neuroendocrine tumours have been diagnosed with increasing frequency over the past 35 years, being the second most frequent tumours of the small intestine. Ileal neuroendocrine tumours diagnosis is late because patients have non-specific symptoms. We have proposed to illustrate as an example the case of a patient, and on its basis, to make a brief review of the literature on small bowel neuroendocrine tumours, resuming several recent changes in the field, concerning classification criteria of these tumours and new recommendations and current advances in diagnosis and treatment. This patient came to our emergency department with a complete bowel obstruction, along with a 2-year history of peristaltic abdominal pain, vomits and diarrhoea episodes. During emergency laparotomy, an ileal stricture was observed, that showed to be a neuroendocrine tumour of the small bowel.
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Severe intestinal ischemia as a presenting feature of metastatic ileal carcinoid tumor: role of MDCT with coronal reformation in the early diagnosis. ACTA ACUST UNITED AC 2013; 37:558-60. [PMID: 22052449 DOI: 10.1007/s00261-011-9815-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Intestinal ischemia is a rare but potentially fatal complication of mesenteric metastasis of intestinal carcinoid tumor and its mechanism isn't entirely clear. We present a case of intestinal ischemia secondary to metastatic ileal carcinoid tumor diagnosed by CT that showed a small mesenteric mass with an extensive desmoplastic reaction causing an intense involvement of the small bowel. Improvements in CT technology with the use of MDCT scanners and advanced reformatting capabilities play an important role in the early diagnosis and accurate recognition of this entity and its need for immediate treatment.
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Habbe N, Fendrich V, Heverhagen A, Ramaswamy A, Bartsch DK. Outcome of surgery for ileojejunal neuroendocrine tumors. Surg Today 2012; 43:1168-74. [PMID: 23143168 DOI: 10.1007/s00595-012-0408-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2012] [Accepted: 07/30/2012] [Indexed: 01/17/2023]
Abstract
PURPOSE Neuroendocrine tumors (NET) of the ileum/jejunum are rare and may require different treatment options to provide long-term survival. The purpose of the study was to evaluate the outcome of surgery for ileojejunal NET. METHODS A database of patients that underwent surgery for ileojejunal NETs between 1999 and 2010 was retrospectively analyzed regarding the clinical characteristics, surgical therapy, survival and prognostic factors. RESULTS Only six of 97 patients with ileojejunal NET who underwent surgery had localized tumors (stage I/II), 29 had lymph node involvement (stage III) and 62 had distant metastases (stage IV) at the initial presentation. All stage I/II tumors were cured, in comparison to 69% of stage III and 0% of stage IV tumors (p = 0.01). Palliative surgery in combination with sequential multimodal treatment regimens resulted in a 5-year survival rate of 63% in patients with stage IV tumors. A multivariate analysis showed that incomplete resection (HR 2.87; CI 1.18-6.98; p = 0.04) and distant metastases (HR 5.39; 95% CI 1.23-23.57; p = 0.02) were associated with worse disease-specific survival. CONCLUSIONS Localized and regionally restricted ileojejunal NETs have an excellent prognosis after surgical treatment. Although stage IV tumors cannot be cured, an aggressive surgical approach in combination with medical or interventional treatment can provide long-term survival.
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Affiliation(s)
- Nils Habbe
- Department of Surgery, University Hospital Marburg, Baldingerstraße, 35043, Marburg, Germany
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36
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Capurso G, Rinzivillo M, Bettini R, Boninsegna L, Delle Fave G, Falconi M. Systematic review of resection of primary midgut carcinoid tumour in patients with unresectable liver metastases. Br J Surg 2012; 99:1480-1486. [PMID: 22972490 DOI: 10.1002/bjs.8842] [Citation(s) in RCA: 110] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/08/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Surgery for small intestinal neuroendocrine tumours (SI-NETs) is limited by metastatic disease in most patients. However, resection of the primary lesion alone has been advocated in patients with unresectable liver metastases. The present systematic review investigated the value of surgical resection of the primary lesion in patients with unresectable metastatic disease. METHODS MEDLINE was searched for studies reporting the outcome of patients with SI-NETs and unresectable liver metastases where there was an explicit comparison between resection of the primary lesion alone and no resection. The primary outcome was overall survival. Secondary outcomes were progression-free survival, treatment-related mortality and relief of symptoms. RESULTS Meta-analysis was not possible, but six studies were analysed qualitatively to highlight useful information. Possible confounders in these studies were the inclusion of patients with other primary tumour sites, unknown primary tumour or non-metastatic disease. Bearing in mind these limitations, there was a clear trend towards longer survival in patients who underwent surgical resection in all studies; their median overall survival ranged from 75 to 139 months compared with 50-88 months in patients who did not have resection. The difference between the two groups was statistically significant in three studies. Data on symptomatic improvement were scarce and did not suggest a clear benefit of surgery. Surgery-related mortality seemed low. CONCLUSION Available data suggest a possible benefit of resection of the primary lesion in patients with unresectable liver metastases, but the studies have several limitations and the results should therefore be considered with caution.
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Affiliation(s)
- G Capurso
- Digestive and Liver Disease Unit, II Medical School, University Sapienza, S. Andrea Hospital, Rome, Italy
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Dronamraju SS, Joypaul VB. Management of gastrointestinal carcinoid tumours - 10 years experience at a district general hospital. J Gastrointest Oncol 2012; 3:120-9. [PMID: 22811879 DOI: 10.3978/j.issn.2078-6891.2011.039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2011] [Accepted: 08/13/2011] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND There is paucity of guidelines regarding management of gastrointestinal carcinoid tumours in district hospitals. METHODS This study was undertaken at a district hospital to analyse the management pathway of gastrointestinal carcinoid tumours. RESULTS Over a period of 10 years there were 35 patients, with an estimated annual incidence of 2.5 per 100,000 population. After a median follow up of 24 months, 22 (63%) patients were alive and disease free. Only 56% patients were referred to the regional neuro-endocrine multidisciplinary team. CONCLUSIONS Management of patients with carcinoid tumours in district hospitals needs streamling with increased utilisation of regional neuroendocrine multidisciplinary teams.
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Affiliation(s)
- Shridhar S Dronamraju
- Department of General Surgery, South Tyneside District General Hospital, Harton Lane, South Shields, UK
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Abstract
Neuroendocrine tumors of the small intestine have been diagnosed with increasing frequency over the past 35 years and presently account for approximately 2% of all gastrointestinal neoplasms. While most of these tumors are discovered incidentally during emergency laparotomy or in the clinical setting of unknown primary cancer with hepatic metastases, the growing awareness of this rare entity and improved diagnostic methods promote earlier diagnosis. The classical carcinoid syndrome with flush, diarrhea and cardiac strain is observed only in 20-30% of patients. The clinical symptoms necessitate a special preoperative preparation of the patient including evaluation of cardiac function.Prospective studies assessing the efficacy of surgical treatment strategies for neuroendocrine neoplasms of the small intestine do not exist. However, retrospective studies have demonstrated that curative as well as palliative resection of the primary tumor improves the prognosis and the quality of life of patients. Besides limited resection of the small bowel in order to avoid postoperative short bowel syndrome an effective clearance of the regional lymph nodes is essential. A primary tumor site in the terminal ileum requires dissection of the lymph nodes on the right side of the ileocolic artery which usually implies an additional resection of the right colon. In cases of a primary tumor site located in the lower ileum up to the distal jejunum, a cone-shaped resection of the mesenterium of the small bowel with extension of lymphadenectomy into adjacent segments with preservation of vascularization is performed.
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Affiliation(s)
- T J Musholt
- Endokrine Chirurgie, Klinik für Allgemein- und Abdominalchirurgie, Universitätsmedizin der Johannes Gutenberg Universität Mainz, Langenbeckstrasse 1, Mainz, Germany.
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Relapse factors for ileal neuroendocrine tumours after curative surgery: a retrospective French multicentre study. Dig Liver Dis 2011; 43:828-33. [PMID: 21641888 DOI: 10.1016/j.dld.2011.04.021] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2010] [Revised: 03/31/2011] [Accepted: 04/28/2011] [Indexed: 12/11/2022]
Abstract
AIM To evaluate the characteristics of postoperative relapse, predictive factors and time to relapse after curative surgery for well-differentiated neuroendocrine tumours of the ileum, without hepatic or other distant metastases. METHODS Clinical data of patients entered into the Groupe d'étude des Tumeurs Endocrines database were collected and analysed retrospectively to identify factors predictive of relapse. RESULTS Among 100 patients followed for a median of 56.5 (range 1-290) months, 42 relapsed after a median follow-up of 57.5 (range 6-176) months, with liver lesions in 27 (64.3%). Median disease-free survival (Kaplan-Meier) was 88 months (95% confidence interval 72-115). Disease-free survival was shorter for emergency surgery patients (p<0.01), patients with distant mesenteric lymph-node metastases (p<0.01), with fortuitous diagnosis (p=0.02), with tumour diameter >20mm (p=0.02), and those with multiple tumours (p=0.07). Multivariate analysis retained emergency surgery (odds-ratio 4.04 [95% confidence interval 2.01-8.11]), distant mesenteric lymph-node metastases (odds-ratio 2.53 [95% confidence interval 1.22-5.25]), and multiple tumours (odds-ratio 2.14 [95% confidence interval 1.01-4.50]), as being significantly associated with relapse. CONCLUSION Patients who underwent emergency surgery, with distant mesenteric lymph-node metastases or with multiple ileal tumours relapsed earlier. Closer monitoring for the patients with these risk factors may be required.
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Paprottka PM, Hoffmann RT, Haug A, Sommer WH, Raessler F, Trumm CG, Schmidt GP, Ashoori N, Reiser MF, Jakobs TF. Radioembolization of symptomatic, unresectable neuroendocrine hepatic metastases using yttrium-90 microspheres. Cardiovasc Intervent Radiol 2011; 35:334-42. [PMID: 21847708 DOI: 10.1007/s00270-011-0248-1] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2010] [Accepted: 07/20/2011] [Indexed: 12/29/2022]
Abstract
PURPOSE To evaluate safety, efficacy, and symptom-control of radioembolization in patients with unresectable liver metastases from neuroendocrine tumors (NETLMs). MATERIALS AND METHODS Forty-two patients (mean age of 62 years) with treatment-refractory NETLMs underwent radioembolization using yttrium-90 ((90)Y) resin microspheres. Posttreatment tumor response was assessed by cross-sectional imaging using the Response Evaluation Criteria in Solid Tumors (RECIST) and tumor-marker levels. Laboratory and clinical toxicities and clinical symptoms were monitored. RESULTS The median activity delivered was 1.63 GBq (range 0.63-2.36). Imaging follow-up using RECIST at 3-month follow-up demonstrated partial response, stable disease, and progressive disease in 22.5, 75.0, and 2.5% of patients, respectively. In 97.5% of patients, the liver lesions appeared hypovascular or partially necrotic. The mean follow-up was 16.2 months with 40 patients (95.2%) remaining alive. The median decrease in tumor-marker levels at 3 months was 54.8% (chromogranin A) and 37.3% (serotonin), respectively. There were no acute or delayed toxicities greater than grade 2 according to Common Terminology Criteria for Adverse Events [CTCAE (v3.0)]. No radiation-induced liver disease was noted. Improvement of clinical symptoms 3 months after treatment was observed in 36 of 38 symptomatic patients. CONCLUSION Radioembolization with (90)Y-microspheres is a safe and effective treatment option in patients with otherwise treatment-refractory NETLMs. Antitumoral effect is supported by good local tumor control, decreased tumor-marker levels, and improved clinical symptoms. Further investigation is warranted to define the role of radioembolization in the treatment paradigm for NETLMs.
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Affiliation(s)
- Philipp M Paprottka
- Department of Clinical Radiology, Ludwig-Maximilians-University of Munich, 81377 Munich, Germany.
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Fendrich V, Bartsch DK. Surgical treatment of gastrointestinal neuroendocrine tumors. Langenbecks Arch Surg 2011; 396:299-311. [PMID: 21279821 DOI: 10.1007/s00423-011-0741-7] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2011] [Accepted: 01/17/2011] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are uncommon but clinically challenging and fascinating tumors. GEP-NETs present as either functional or as nonfunctional tumors. Functional tumors are commonly associated with a specific hormonal syndrome directly related to a hormone secreted by the tumor, like gastrinomas with a Zollinger-Ellison syndrome or carcinoid syndrome in patients with neuroendocrine tumors (NET) of the ileum. Nonfunctional tumors do not secrete a hormone resulting in a clinical syndrome. METHODS The natural course of GEP-NETs is highly variable. Small, benign neoplasms such as 90% of all insulinomas or gastric endocrine tumors type 1 are readily curable by surgical resection; however, most other GEP-NETs have a much less favorable prognosis. Patients with completely resected tumors generally have a good prognosis, and an aggressive surgical approach in patients with advanced disease may also prolong survival. CONCLUSIONS This review focuses on the current standards of surgical treatment of gastric endocrine tumors, NETs of the pancreas (PNET) and NETs of the ileum. Although the evidence level is low in many instances due to the lack of randomized controlled trials, important treatment recommendations can be given.
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Affiliation(s)
- Volker Fendrich
- Department of Surgery, Philipps University Marburg, Baldingerstrasse, Marburg, Germany.
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Kitchens WH, Elias N, Blaszkowsky LS, Cosimi AB, Hertl M. Partial abdominal evisceration and intestinal autotransplantation to resect a mesenteric carcinoid tumor. World J Surg Oncol 2011; 9:11. [PMID: 21281518 PMCID: PMC3038967 DOI: 10.1186/1477-7819-9-11] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2010] [Accepted: 01/31/2011] [Indexed: 11/17/2022] Open
Abstract
Background Midgut carcinoids are neuroendocrine tumors that commonly metastasize to the intestinal mesentery, where they predispose to intestinal obstruction, ischemia and/or congestion. Because of their location, many mesenteric carcinoid tumors are deemed unresectable due to the risk of uncontrollable bleeding and prolonged intestinal ischemia. Case Presentation We report the case of a 60-year-old male with a mesenteric carcinoid tumor obstructing his superior mesenteric vein, resulting in intestinal varices and severe recurrent GI bleeds. While his tumor was thought to be unresectable by conventional techniques, it was successfully resected using intestinal autotransplantation to safely gain access to the tumor. This case is the first described application of this technique to carcinoid tumors. Conclusions Intestinal autotransplantation can be utilized to safely resect mesenteric carcinoid tumors from patients who were not previously thought to be surgical candidates. We review the literature concerning both carcinoid metastases to the intestinal mesentery and the use of intestinal autotransplantation to treat lesions involving the mesenteric root.
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Scherübl H, Jensen RT, Cadiot G, Stölzel U, Klöppel G. Neuroendocrine tumors of the small bowels are on the rise: Early aspects and management. World J Gastrointest Endosc 2010; 2:325-34. [PMID: 21160582 PMCID: PMC2998818 DOI: 10.4253/wjge.v2.i10.325] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2010] [Revised: 08/02/2010] [Accepted: 08/09/2010] [Indexed: 02/05/2023] Open
Abstract
Neuroendocrine tumors of the small bowel are on the rise. In the US they have increased by 300%-500% in the last 35 years. At the same time their prognosis is much improved. Today, most neuroendocrine tumors (NETs) of the duodenum are detected "incidentally" and therefore recognized at an early stage. Duodenal NETs which are well differentiated, not larger than 10 mm and limited to the mucosa/submucosa can be endoscopically resected. The management of duodenal NETs ranging between 10 and 20 mm needs an interdisciplinary discussion. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. Surgery is recommended for well-differentiated duodenal NET tumors greater than 20 mm, for localized sporadic gastrinomas (of any size) and for localized poorly differentiated NE cancers. Surgery is recommended for any ileal NET. Advanced ileal NETs with a carcinoid syndrome are treated with long-acting somatostatin analogs. This treatment significantly improves (progression-free) survival in patients with metastatic NETs of the ileum. For optimal NET management, tumor biology, type, localization and stage of the neoplasm, as well as the patient's individual circumstances have to be taken into account.
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Affiliation(s)
- Hans Scherübl
- Hans Scherübl, Departments of Gastroenterology and Gastrointestinal Oncology, Vivantes Klinikum Am Urban, Berlin 10967, Germany
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Røsok BI, Marangos IP, Kazaryan AM, Rosseland AR, Buanes T, Mathisen O, Edwin B. Single-centre experience of laparoscopic pancreatic surgery. Br J Surg 2010; 97:902-909. [PMID: 20474000 DOI: 10.1002/bjs.7020] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Laparoscopic resection is regarded as safe and feasible in selected patients with benign pancreatic tumours. Few data exist on laparoscopic surgery for malignant lesions and larger neoplasms in unselected patients. METHODS The study included all patients admitted to Oslo University Hospital, Rikshospitalet, from March 1997 to March 2009 for surgery of lesions in the body and tail of the pancreas, and selected patients with lesions in the pancreatic head, who underwent surgery by a laparoscopic approach with curative intent. RESULTS A total of 166 patients had 170 operations, including 138 pancreatic resections, 18 explorations, nine resections of peripancreatic tissue and five other therapeutic procedures. Four patients had repeat procedures. There were 53 endocrine tumours (31.0 per cent), 28 pancreatic carcinomas (16.4 per cent), five cases of metastases (2.9 per cent), 48 cystic tumours (28.1 per cent) and 37 other lesions (21.6 per cent). The total morbidity rate was 16.5 per cent. Fistula was the most common complication (10.0 per cent). Three patients needed reoperation for complications. There were three hospital deaths (1.8 per cent). Median hospital stay following surgery was 4 days. CONCLUSION Laparoscopic resection of lesions in the body and tail of the pancreas in an unselected patient series was safe and feasible, and should be the method of choice for this patient group in specialized centres.
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Affiliation(s)
- B I Røsok
- Division of Surgery, Section for Gastrointestinal Surgery, Oslo University Hospital (OUH), Rikshospitalet, 0027 Oslo, Norway
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Stenting of the Superior Mesenteric Vein in Midgut Carcinoid Disease with Large Mesenteric Masses. World J Surg 2010; 34:1373-9. [DOI: 10.1007/s00268-009-0361-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Slim K, Blay JY, Brouquet A, Chatelain D, Comy M, Delpero JR, Denet C, Elias D, Fléjou JF, Fourquier P, Fuks D, Glehen O, Karoui M, Kohneh-Shahri N, Lesurtel M, Mariette C, Mauvais F, Nicolet J, Perniceni T, Piessen G, Regimbeau JM, Rouanet P, sauvanet A, Schmitt G, Vons C, Lasser P, Belghiti J, Berdah S, Champault G, Chiche L, Chipponi J, Chollet P, De Baère T, Déchelotte P, Garcier JM, Gayet B, Gouillat C, Kianmanesh R, Laurent C, Meyer C, Millat B, Msika S, Nordlinger B, Paraf F, Partensky C, Peschaud F, Pocard M, Sastre B, Scoazec JY, Scotté M, Triboulet JP, Trillaud H, Valleur P. [Digestive oncology: surgical practices]. ACTA ACUST UNITED AC 2009; 146 Suppl 2:S11-80. [PMID: 19435621 DOI: 10.1016/s0021-7697(09)72398-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- K Slim
- Chirurgien Clermont-Ferrand.
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Vikman S, Sommaggio R, De La Torre M, Öberg K, Essand M, Giandomenico V, Loskog A, Tötterman TH. Midgut carcinoid patients display increased numbers of regulatory T cells in peripheral blood with infiltration into tumor tissue. Acta Oncol 2009; 48:391-400. [PMID: 18855160 DOI: 10.1080/02841860802438495] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
INTRODUCTION Our aim was to investigate the immune status of midgut carcinoid patients. Cancer patients generally display suppressed Th1-type immunity that disables mounting of an efficient anti-tumor response. However, little is known about patients with neuroendocrine midgut carcinoids. MATERIAL AND METHODS Circulating regulatory T cells were determined in patient blood by staining for CD4, CD25 and FoxP3 in flow cytometric analysis. T cell proliferation was measured by Alamar Blue in response to polyclonal activation and the regulatory phenotype of patient CD25+ cells was validated by allogeneic stimulation of CFSE labelled responders. Cytokine levels in patient peripheral blood were measured by ELISA and CBA. Tumor infiltrating T cells were analyzed by immunohistochemistry and immunofluorescence. RESULTS The results demonstrate that midgut carcinoid patients exhibit increased frequencies of circulating Tregs and patient T cells have a decreased proliferative capacity compared to healthy donors. Systemic Th1-promoting cytokines are reduced. Midgut carcinoid tumors display CD4+ and CD8+ T cell infiltration, always in the presence of regulatory CD4+FoxP3+ cells. DISCUSSION Midgut carcinoid patients display elevated T regulatory cell numbers and T cell dysfunction. Therapeutic strategies to overcome tumor-induced Th1 immunosuppression are required in combination with anti-tumor vaccinations.
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Povoski SP, Neff RL, Mojzisik CM, O'Malley DM, Hinkle GH, Hall NC, Murrey DA, Knopp MV, Martin EW. A comprehensive overview of radioguided surgery using gamma detection probe technology. World J Surg Oncol 2009; 7:11. [PMID: 19173715 PMCID: PMC2653072 DOI: 10.1186/1477-7819-7-11] [Citation(s) in RCA: 141] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2008] [Accepted: 01/27/2009] [Indexed: 02/08/2023] Open
Abstract
The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology.
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Affiliation(s)
- Stephen P Povoski
- Division of Surgical Oncology, Department of Surgery, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
| | - Ryan L Neff
- Division of Surgical Oncology, Department of Surgery, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
| | - Cathy M Mojzisik
- Division of Surgical Oncology, Department of Surgery, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
- Department of Radiology, The Ohio State University, Columbus, OH, 43210, USA
| | - David M O'Malley
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
| | - George H Hinkle
- Department of Radiology, The Ohio State University, Columbus, OH, 43210, USA
- College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA
| | - Nathan C Hall
- Department of Radiology, The Ohio State University, Columbus, OH, 43210, USA
| | - Douglas A Murrey
- Department of Radiology, The Ohio State University, Columbus, OH, 43210, USA
| | - Michael V Knopp
- Department of Radiology, The Ohio State University, Columbus, OH, 43210, USA
| | - Edward W Martin
- Division of Surgical Oncology, Department of Surgery, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
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Landry CS, Brock G, Scoggins CR, McMasters KM, Martin RCG. A proposed staging system for small bowel carcinoid tumors based on an analysis of 6,380 patients. Am J Surg 2009; 196:896-903; discussion 903. [PMID: 19095106 DOI: 10.1016/j.amjsurg.2008.07.042] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2008] [Revised: 05/15/2008] [Accepted: 07/08/2008] [Indexed: 01/13/2023]
Abstract
BACKGROUND Little is known about the long-term prognosis of small bowel carcinoids because currently no staging system exists. METHODS A search of the Surveillance, Epidemiology and End Results (SEER) database identified 6,380 patients with small bowel carcinoid tumors from 1977 to 2004. Patients were analyzed according to various clinicopathologic factors and a tumor (T1, T2, T3), lymph node (N0, N1), and metastasis (M0, M1) staging system was created according to these parameters. RESULTS Among the 6,380 patients, 2,985 women and 3,395 men, with a median age of 66 years (range 14-98), the median tumor size was 1.9 cm (range .1-30 cm). Multivariate analysis demonstrated that age, size of the primary tumor, and depth of invasion were significant factors. Four stages were created according to statistically significant prognostic factors: 13% of patients were classified into stage I, 31% into stage II, 16% into stage III, and 40% into stage IV. Five-year survival rates were 96%, 87%, 74%, and 43% for stages I through IV, respectively. CONCLUSIONS The newly developed TNM staging system accurately discriminates prognosis for small bowel carcinoid tumors.
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Affiliation(s)
- Christine S Landry
- Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville, School of Medicine, Louisville, KY, USA
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Jin K, Hwang E, Han S, Park S, Kim H, Kwon K, Kim H, Cho W, Kwak J, Ahn K. Rectal Carcinoid Tumor in a Renal Transplant Patient. Transplant Proc 2008; 40:2433-4. [DOI: 10.1016/j.transproceed.2008.07.066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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