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Cavalcoli F, Rausa E, Ferrari D, Rosa R, Maccauro M, Pusceddu S, Sabella G, Cantù P, Vitellaro M, Coppa J, Mazzaferro V. Pathological Characteristics, Management, and Prognosis of Rectal Neuroendocrine Tumors: A Retrospective Study from a Tertiary Hospital. Diagnostics (Basel) 2024; 14:1881. [PMID: 39272666 PMCID: PMC11394532 DOI: 10.3390/diagnostics14171881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/22/2024] [Accepted: 08/24/2024] [Indexed: 09/15/2024] Open
Abstract
BACKGROUND Rectal neuroendocrine tumors (rNENs) are rare, constituting 1-2% of rectal tumors, and are often asymptomatic, leading to challenges in early diagnosis. Current management guidelines recommend endoscopic resection for small lesions and surgical intervention for larger or high-risk tumors. This study aims to retrospectively analyze the pathological characteristics, management, and prognosis of rNEN patients. METHODS Data from the Neuroendocrine Tumor Registry at a tertiary hospital in Milan, Italy from 2005 to 2023 were retrospectively analyzed. Patient demographics, disease characteristics, pathology findings, treatment details, and surveillance data were collected. Statistical analyses included descriptive statistics, multivariable binary logistic regression, and Kaplan-Meier survival analysis. RESULTS Forty-five patients were included, 53.3% male with a mean age of 57.5 years. Most patients were asymptomatic, with incidental diagnosis during colonoscopy. Endoscopic excision was the primary treatment modality (77.8%), with surgical resection reserved for incomplete or inappropriate endoscopic resections. Disease progression occurred in 13 patients (28.9%), with tumor-related mortality of 22.2%. Kaplan-Meier analysis showed 5- and 10-year survival rates of 68.8% and 59.1%, respectively, with corresponding progression-free survival rates of 72.8% and 54.0%. Tumor stage was significantly associated with disease progression on multivariable analysis (OR = 7.230, p = 0.039). CONCLUSIONS This study highlights the heterogeneous presentation and prognosis of rNENs, with a substantial proportion diagnosed incidentally. Endoscopic management was predominantly utilized, aligning with current guidelines for localized tumors. Tumor stage emerged as a significant predictor of disease progression, emphasizing the importance of accurate staging for optimal management. Further research is warranted to refine management protocols and validate these findings.
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Affiliation(s)
- Federica Cavalcoli
- Gastroenterology and Gastrointestinal Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Emanuele Rausa
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
- Colorectal Surgery Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Davide Ferrari
- Colorectal Surgery Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Roberto Rosa
- Gastroenterology and Gastrointestinal Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Marco Maccauro
- Departement of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Sara Pusceddu
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Giovanna Sabella
- Department of the Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Paolo Cantù
- Gastroenterology and Gastrointestinal Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Marco Vitellaro
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
- Colorectal Surgery Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Jorgelina Coppa
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy
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Serafin M, Jabłońska B, Senderek E, Majewska K, Mrowiec S. The Clinicopathological Characteristics and Surgical Treatment of Gastrointestinal Neuroendocrine Neoplasm-A 10-Year Single-Center Experience. J Clin Med 2024; 13:4892. [PMID: 39201037 PMCID: PMC11355324 DOI: 10.3390/jcm13164892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 08/15/2024] [Accepted: 08/16/2024] [Indexed: 09/02/2024] Open
Abstract
Background: Gastrointestinal neuroendocrine neoplasms (GI-NENs) represent a diverse group of tumors, with surgical resection being the gold standard for treatment. Materials and Methods: A retrospective analysis was conducted on 63 patients (32 women, 31 men) who underwent surgery for GI-NENs at the Department of Digestive Tract Surgery from January 2013 to June 2023. Tumors were classified by stage (localized, regionally advanced, metastatic). Results: Clinical symptoms were reported by 42 (66.7%) patients, with abdominal pain being the most common symptom, affecting 28 (44.4%) patients. The majority of tumors (44, 69.8%) originated in the midgut. The most frequently performed surgery was right hemicolectomy, carried out on 33 (52.4%) patients. Radical tumor resection was performed in 35 (55.6%) patients. Postoperative complications occurred in 12 (19%) patients, with male gender identified as an independent predictive factor for complications (p = 0.04). Non-functioning tumors were more common (33, 52.4%), and most tumors were classified as grade 1 histopathologically (49, 77.8%). Distant metastases were present in 29 (46%) patients. The overall two-year survival rate was 94.9%, with a five-year survival rate also estimated at 94.9%. Conclusions: GI-NENs are often diagnosed at advanced stages, frequently with distant or lymph node metastases, and predominantly arise in the midgut. Despite low postoperative morbidity and mortality, male gender may be a predictor of postoperative complications. Overall, the prognosis for GI-NENs is favorable, reflected in high overall survival rates.
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Affiliation(s)
- Michał Serafin
- Student Scientific Society, Department of Digestive Tract Surgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland; (M.S.); (E.S.)
| | - Beata Jabłońska
- Department of Digestive Tract Surgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland; (K.M.); (S.M.)
| | - Emila Senderek
- Student Scientific Society, Department of Digestive Tract Surgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland; (M.S.); (E.S.)
| | - Karolina Majewska
- Department of Digestive Tract Surgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland; (K.M.); (S.M.)
| | - Sławomir Mrowiec
- Department of Digestive Tract Surgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 14 Medyków Street, 40-752 Katowice, Poland; (K.M.); (S.M.)
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Shannon AB, Straker RJ, Fraker DL, Miura JT, Karakousis GC. Validated Risk-Score Model Predicting Lymph Node Metastases in Patients with Non-Functional Gastroenteropancreatic Neuroendocrine Tumors. J Am Coll Surg 2022; 234:900-909. [PMID: 35426404 DOI: 10.1097/xcs.0000000000000144] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND The incidence of, and factors associated with, lymph node metastasis (LN+) in non-functional gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are not well characterized. METHODS Patients were identified from the 2010-2015 National Cancer Database who underwent surgical resection with lymphadenectomy for clinical stage I-III non-functional GEP NETs. Among a randomly selected training subset of 75% of the study population, variables associated with LN+ were identified using multivariable logistic regression analysis, and these variables were used to create a risk-score model for LN+, which was internally validated among the remaining 25% of the cohort. RESULTS Of 12,228 patients evaluated, 6,902 (56.4%) had LN+. Among the training set, variables associated with LN+ included age (70 years of age or older: odds ratio [OR] 1.12, 95% CI 1.00-1.24; ref: less than 70 years), tumor location (stomach: OR 3.72, 95% CI 2.94-4.71; small intestine: OR 19.60, 95% CI 17.31-22.19; ref: pancreas), tumor grade (moderately differentiated: OR 1.47, 95% CI 1.30-1.67; poorly differentiated/anaplastic: OR 1.53, 95% CI 1.21-1.95; ref: well-differentiated), tumor size (2-4 cm: OR 2.40, 95% CI 2.13-2.70; >4 cm: OR 5.25, 95% CI 4.47-6.17; ref: <2 cm), and lymphovascular invasion (OR 5.62, 95% CI 5.08-6.21; ref: no lymphovascular invasion). After internal validation, a risk-score model for LN+ using these variables was developed composed of low- (N = 2,779), intermediate- (N = 2,598), high- (N = 3,433), and very-high-risk (N = 3,418) groups; within each group the rate of LN+ was 8.7%, 48.6%, 64.9%, and 92.8%, respectively. CONCLUSIONS This developed risk-score model, including both patient and tumor variables, can be used to calculate the risk for LN metastases in patients with GEP NETs.
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Affiliation(s)
- Adrienne B Shannon
- From the Department of Surgery (Shannon, Straker), Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Richard J Straker
- From the Department of Surgery (Shannon, Straker), Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Douglas L Fraker
- Division of Endocrine and Oncologic Surgery, Department of Surgery (Fraker, Miura, Karakousis), Hospital of the University of Pennsylvania, Philadelphia, PA
| | - John T Miura
- Division of Endocrine and Oncologic Surgery, Department of Surgery (Fraker, Miura, Karakousis), Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Giorgos C Karakousis
- Division of Endocrine and Oncologic Surgery, Department of Surgery (Fraker, Miura, Karakousis), Hospital of the University of Pennsylvania, Philadelphia, PA
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Li X, Shao L, Lu X, Yang Z, Ai S, Sun F, Wang M, Guan W, Liu S. Risk factors for lymph node metastasis in gastric neuroendocrine tumor: a retrospective study. BMC Surg 2021; 21:174. [PMID: 33789664 PMCID: PMC8011070 DOI: 10.1186/s12893-021-01174-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 03/23/2021] [Indexed: 12/15/2022] Open
Abstract
Background Lymph node metastasis (LNM) plays a vital role in the determination of clinical outcomes in patients with gastric neuroendocrine tumor (G-NET). Preoperative identification of LNM is helpful for intraoperative lymphadenectomy. This study aims to investigate risk factors for LNM in patients with G-NET. Methods We performed a retrospective study involving 37 patients in non-LNM group and 82 patients in LNM group. Data of demographics, preoperative lab results, clinical–pathological results, surgical management, and postoperative situation were compared between groups. Significant parameters were subsequently entered into logistic regression for further analysis. Results Patients in LNM group exhibited older age (p = 0.011), lower preoperative albumin (ALB) (p = 0.003), higher carcinoembryonic antigen (CEA) (p = 0.020), higher International normalized ratio (p = 0.034), longer thrombin time (p = 0.018), different tumor location (p = 0.005), higher chromogranin A positive rate (p = 0.045), and higher Ki-67 expression level (p = 0.002). Logistic regression revealed ALB (p = 0.043), CEA (p = 0.032), tumor location (p = 0.013) and Ki-67 (p = 0.041) were independent risk factors for LNM in G-NET patients. Conclusions ALB, CEA, tumor location, and Ki-67 expression level correlate with the risk of LNM in patients with G-NET.
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Affiliation(s)
- Xianghui Li
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China
| | - Lihua Shao
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China
| | - Xiaofeng Lu
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China
| | - Zhengyang Yang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Shichao Ai
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China
| | - Feng Sun
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China
| | - Meng Wang
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China.
| | - Wenxian Guan
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China.
| | - Song Liu
- Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan RD, Nanjing, 210008, China.
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Watanabe A, Yip L, Hamilton TD, Loree JM, Stuart HC. Tumour grade and primary site predict patterns of recurrence and survival in patients with resected gastroenteropancreatic neuroendocrine tumors. Am J Surg 2021; 221:1141-1149. [PMID: 33795127 DOI: 10.1016/j.amjsurg.2021.03.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 02/15/2021] [Accepted: 03/13/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Patterns of recurrence help to inform surveillance of patients with resected gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS Patients with GEP-NETs in British Columbia, Canada (2004-2015) were reviewed. Associations between tumor characteristics, recurrence and survival were analyzed. RESULTS Among 759 patients, 41%, 25%, and 17% had grade 1, 2, and 3 disease, respectively. 387 patients had R0/R1 resections, of which 30% recurred (median 25 months). 5-year incidence of recurrence was 22% (grade 1), 46% (grade 2), and 59% (grade 3) (p < 0.001). Grade predicted distant recurrence (Grade 2 HR 1.89, 95% CI 1.16-3.07; p = 0.011; Grade 3 HR 3.29, 95% CI 1.81-5.99; p < 0.001). Compared to small bowel NETs, pancreas NETs had less peritoneal recurrence (OR 0.15, 95% CI 0.03-0.68, p = 0.014). No patients had isolated pulmonary recurrences. CONCLUSION Higher grade tumors and pancreatic NETs require more frequent surveillance. Evidence is limited for pulmonary surveillance.
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Affiliation(s)
- Akie Watanabe
- Vancouver General Hospital, University of British Columbia, 899 W 12th Ave, Vancouver, BC, V5Z 1M9, Canada.
| | - Lily Yip
- Vancouver General Hospital, University of British Columbia, 899 W 12th Ave, Vancouver, BC, V5Z 1M9, Canada
| | - Trevor D Hamilton
- Vancouver General Hospital, University of British Columbia, 899 W 12th Ave, Vancouver, BC, V5Z 1M9, Canada
| | - Jonathan M Loree
- British Columbia Cancer Agency, 600 W 10th Ave, Vancouver, BC, V5Z 4E6, Canada
| | - Heather C Stuart
- Vancouver General Hospital, University of British Columbia, 899 W 12th Ave, Vancouver, BC, V5Z 1M9, Canada.
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Yu YJ, Li YW, Shi Y, Zhang Z, Zheng MY, Zhang SW. Clinical and pathological characteristics and prognosis of 132 cases of rectal neuroendocrine tumors. World J Gastrointest Oncol 2020; 12:893-902. [PMID: 32879666 PMCID: PMC7443838 DOI: 10.4251/wjgo.v12.i8.893] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 05/26/2020] [Accepted: 07/19/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Neuroendocrine tumors (NETs) frequently occur in the gastrointestinal tract, lung, and pancreas, and the rectum and appendix are the sites with the highest incidence. Epidemiology statistics show that an estimated 8000 people every year in the United States are diagnosed with NETs occurring in the gastrointestinal tract, including the stomach, intestine, appendix, colon, and rectum. The pathological changes and clinical symptoms of NETs are not specific, and therefore they are frequently misdiagnosed. AIM To investigate the clinical symptoms, pathological characteristics, treatment, and prognosis of rectal neuroendocrine tumors (RNETs) by analyzing the clinical and pathological data of 132 RNET cases at our hospital. METHODS All RNETs were graded according to Ki-67 positivity and mitotic events. The tumors were staged as clinical stages I, II, III, and IV according to infiltrative depth and tumor size. COX proportional hazard model was used to assess the main risk factors for survival. RESULTS These 132 RNETs included 83 cases of G1, 21 cases of G2, and 28 cases of G3 (neuroendocrine carcinoma) disease. Immunohistochemical staining showed that 89.4% of RNETs were positive for synaptophysin and 39.4% positive for chromogranin A. There were 19, 85, 23, and 5 cases of clinical stages I, II, III, and IV, respectively. The median patient age was 52.96 years. The diameter of tumor, depth of invasion, and pathological grade were the main reference factors for the treatment of RNETs. The survival rates at 6, 12, 36, and 60 mo after operation were 98.5%, 94.6%, 90.2%, and 85.6%, respectively. Gender, tumor size, tumor grade, lymph node or distant organ metastasis, and radical resection were the main factors associated with prognosis of RNETs. Multivariate analysis showed that tumor size and grade were independent prognostic factors. CONCLUSION The clinical symptoms of RNETs are not specific, and they are easy to misdiagnose. Surgery is the main treatment method. The grade and stage of RNETs are the main indices to evaluate prognosis.
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Affiliation(s)
- Yong-Jun Yu
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Yu-Wei Li
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Yang Shi
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Zhao Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Min-Ying Zheng
- Department of Pathology, Tianjin Union Medical Center, Tianjin 300121, China
| | - Shi-Wu Zhang
- Department of Pathology, Tianjin Union Medical Center, Tianjin 300121, China
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Jiao X, Wang Z, Peng X, Zhang L, Zhou L. Effects of tumor types on treatment strategy formulation and prognostic evaluation of gastric neuroendocrine tumors. Future Oncol 2020; 16:2197-2207. [PMID: 32687408 DOI: 10.2217/fon-2020-0150] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Aim: The effects of different types of gastric neuroendocrine tumors (G-NETs) on treatment strategy formulation and prognostic evaluation still remain controversial due to their rarity. Methods: 187 patients diagnosed with G-NETs were subdivided into four types based on the pathophysiology, etiology and presentation. Results: Type I, II G-NETs >1.0 cm and type III, IV G-NETs >2.0 cm are proved with aggressive behavior (p < 0.05). Type III G-NETs with higher Ki-67 index and tumor stage showed more invasive potential than type I and II G-NETs (p < 0.05). Endoscopic resection is the primary treatment for type I, II G-NETs, while surgical combined with chemotherapy is associated with favorable outcomes for type IV G-NETs. Conclusion: The clinical classifications of G-NETs are of great significance for the choice of treatment and the evaluation of prognosis.
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Affiliation(s)
- Xiaoxiao Jiao
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University. No. 1, East Jianshe Road, Zhengzhou 450052, PR China
| | - Zhaodi Wang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University. No. 1, East Jianshe Road, Zhengzhou 450052, PR China
| | - Xiaoqian Peng
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University. No. 1, East Jianshe Road, Zhengzhou 450052, PR China
| | - Lianfeng Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University. No. 1, East Jianshe Road, Zhengzhou 450052, PR China
| | - Lin Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University. No. 1, East Jianshe Road, Zhengzhou 450052, PR China
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SSAT State-of-the-Art Conference: Current Surgical Management of Gastric Tumors. J Gastrointest Surg 2018; 22:32-42. [PMID: 28808875 PMCID: PMC5742030 DOI: 10.1007/s11605-017-3533-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Accepted: 07/31/2017] [Indexed: 01/31/2023]
Abstract
INTRODUCTION The current era of gastric surgery is marked by low morbidity and mortality rates, innovative strategies to approach resections with a minimally invasive fashion or hyperthermic intraperitoneal chemotherapy (HIPEC), as well as improved understanding of the biology of sporadic and hereditary stromal, neuroendocrine, and epithelial malignancies. METHODS In 2017, the Society for Surgery of the Alimentary Tract convened a State-of-the-Art Conference on Current Surgical Management of Gastric Tumors with both international experts and emerging leaders in the field of gastric surgery. RESULTS Martin D. McCarter, MD of the University of Colorado discussed the current management of gastric gastrointestinal stromal tumors (GIST). Kaitlyn J. Kelly, MD of the University of California, San Diego discussed the management of gastric carcinoid tumors. Jeffrey A. Norton of Stanford University discussed recent advances in the management of gastric adenocarcinoma including a focus on hereditary diffuse gastric cancer (HDGC). Joseph Kim, MD of Stony Brook University discussed a systematic approach to minimally invasive gastrectomy for cancer. Joyce Wong, MD of Pennsylvania State University discussed the role for cytoreductive surgery (CRS) and HIPEC for gastric adenocarcinoma. CONCLUSIONS This review provides gastrointestinal surgeons with a concise update on the current surgical management of gastric tumors.
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Abstract
Gastric neuroendocrine tumors (NETs) are classified into three types. Type I gastric NETs are associated with chronic atrophic gastritis. They have a good prognosis and endoscopic resection is the mainstay of treatment. Type II gastric NETs are caused by hypergastrinemia. They have a poorer prognosis, and resection is required to control the disease. Endoscopic versus surgical resection is recommended for the gastric lesion. Type III gastric NETs are sporadic and not associated with any specific condition. They have the worst prognosis with the highest rate of metastatic disease, and oncologic resection is recommended. Medical therapies have some role.
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Affiliation(s)
- Britney Corey
- Department of Surgery, University of Alabama at Birmingham, KB 404, 1720 2nd Avenue South, Birmingham, AL 35294, USA.
| | - Herbert Chen
- Department of Surgery, UAB Hospital and Health System, UAB Comprehensive Cancer Center, University of Alabama at Birmingham, BDB 502, 1808 7th Avenue South, Birmingham, AL 35233, USA
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Maxwell JE, Howe JR. Pancreatic neuroendocrine tumors. BLUMGART'S SURGERY OF THE LIVER, BILIARY TRACT AND PANCREAS, 2-VOLUME SET 2017:997-1006.e3. [DOI: 10.1016/b978-0-323-34062-5.00065-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Mosquera C, Koutlas NJ, Fitzgerald TL. Localized high-grade gastroenteropancreatic neuroendocrine tumors: Defining prognostic and therapeutic factors for a disease of increasing clinical significance. Eur J Surg Oncol 2016; 42:1471-7. [PMID: 27528467 DOI: 10.1016/j.ejso.2016.07.137] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Revised: 07/15/2016] [Accepted: 07/26/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Due to the limited sample size in the existing series, the natural history and management of high-grade gastroenteropancreatic neuroendocrine tumors (GEP-NET) is poorly understood. In order to better understand high-grade GEP-NET, a large cohort study was undertaken. OBJECTIVE To determine the prognostic factors associated with high-grade GEP-NET. METHODS Patients diagnosed with non-metastatic high-grade GEP-NET from 1988 to 2010 were identified in SEER. RESULTS Incidence of high-grade GEP-NETs increased from 0.03 to 0.19/100,000 over the study period. The median age was 65 years, and the majority of the patients were white and females. The most common primary site was colorectal, and the most frequent T classification was T3. Surgical resection was performed in 89% of patients that varied by site (p < 0.0001). Nodal involvement was frequent and varied by site (p = 0.0002). The 5-year disease-specific survival was 63.3% and was the greatest for small bowel (p = 0.0003). Survival was associated with age, node status and surgery (p < 0.05). On multivariate analysis, the node status, surgery, and site continued to be associated with survival (p < 0.05); however, age (p = 0.08) no longer influenced the patient's survival. CONCLUSION High-grade GEP-NETs are neoplasms with exponentially increasing in incidence. Tumor location and nodal status are predictors of survival. Surgery is associated with a survival advantage and could be considered for localized disease.
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Affiliation(s)
- C Mosquera
- East Carolina University, Brody School of Medicine, Division of Surgical Oncology, Greenville, NC, USA
| | - N J Koutlas
- East Carolina University Brody School of Medicine, Greenville, NC, USA
| | - T L Fitzgerald
- East Carolina University, Brody School of Medicine, Division of Surgical Oncology, Greenville, NC, USA.
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Pruthi A, Pankaj P, Verma R, Jain A, Belho ES, Mahajan H. Ga-68 DOTANOC PET/CT imaging in detection of primary site in patients with metastatic neuroendocrine tumours of unknown origin and its impact on clinical decision making: experience from a tertiary care centre in India. J Gastrointest Oncol 2016; 7:449-61. [PMID: 27284479 DOI: 10.21037/jgo.2016.01.06] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Neuroendocrine tumours (NETs) are rare, heterogeneous group of tumours which usually originate from small, occult primary sites and are characterized by over-expression of somatostatin receptors (SSTRs). Positron emission tomography/computed tomography (PET/CT) using Ga-68-labeled-somatostatin-analogues have shown superiority over other modalities for imaging of NETs. The objective of the study was to retrospectively evaluate the efficacy of Ga-68 DOTANOC PET/CT imaging in detecting the primary site in patients with metastatic NETs of unknown origin and its impact on clinical decision making in such patients. METHODS Between December 2011 and September 2014, a total of 263 patients underwent Ga-68 DOTANOC PET/CT study in our department for various indications. Out of them, 68 patients (45 males, 23 females; mean age, 54.9±10.7 years; range, 31-78 years) with histopathologically proven metastatic NETs and unknown primary site (CUP-NET) on conventional imaging, who underwent Ga-68 DOTANOC PET/CT scan as part of their clinical work-up were included for analyses. Histopathology (wherever available) and/or follow-up imaging were taken as reference standard. Quantitative estimation of SSTR expression in the form of maximal standardized uptake value (SUVmax) of detected primary and metastatic sites was calculated. Follow-up data of individual patients was collected through careful survey of hospital medical records and telephonic interviews. RESULTS Maximum patients presented to our department with hepatic metastasis (50 out of 68 patients) and grade I NETs (>50%). Ga-68 DOTANOC PET/CT scan identified primary sites in 40 out of these 68 patients i.e., in approximately 59% patients. Identified primary sites were: small intestine [19], rectum [8], pancreas [7], stomach [4], lung [1] and one each in rare sites in kidney and prostate. In one patient, 2 primary sites were identified (one each in stomach and duodenum). Mean SUVmax of the detected primary sites was 25.1±18.0 (median: 16.25; range, 2.1-150). Significant positive correlation was found between SUVmax of detected primary site and SUVmax of the histopathologically proven sites of metastasis (r=0.662; P<0.0001). Based on the findings of the Ga-68 DOTANOC PET/CT scan, 3 out of 40 patients underwent definitive treatment for their primary tumour (1 gastric, 1 ileal and 1 prostatic tumour). One patient was being planned for resection of primary rectal lesion at the time of data-collection. Thirty-six out of 68 patients were started on long-acting somatostatin analogues or chemotherapy or targeted therapy. Two patients underwent multiple cycles of peptide receptor radionuclide therapy (PRRNT) using (90)Y and (177)Lu labeled somatostatin analogues. CONCLUSIONS Our findings indicate that Ga-68 DOTANOC PET/CT is a promising imaging modality in patients with metastatic NETs of unknown origin for detection of the primary site and in guiding their therapeutic management.
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Affiliation(s)
- Ankur Pruthi
- Department of Nuclear Medicine & PET/CT, Mahajan Imaging Centre, Sir Ganga Ram Hospital & Research Centre, Rajendra Nagar, New Delhi 110060, India
| | - Promila Pankaj
- Department of Nuclear Medicine & PET/CT, Mahajan Imaging Centre, Sir Ganga Ram Hospital & Research Centre, Rajendra Nagar, New Delhi 110060, India
| | - Ritu Verma
- Department of Nuclear Medicine & PET/CT, Mahajan Imaging Centre, Sir Ganga Ram Hospital & Research Centre, Rajendra Nagar, New Delhi 110060, India
| | - Anjali Jain
- Department of Nuclear Medicine & PET/CT, Mahajan Imaging Centre, Sir Ganga Ram Hospital & Research Centre, Rajendra Nagar, New Delhi 110060, India
| | - Ethel S Belho
- Department of Nuclear Medicine & PET/CT, Mahajan Imaging Centre, Sir Ganga Ram Hospital & Research Centre, Rajendra Nagar, New Delhi 110060, India
| | - Harsh Mahajan
- Department of Nuclear Medicine & PET/CT, Mahajan Imaging Centre, Sir Ganga Ram Hospital & Research Centre, Rajendra Nagar, New Delhi 110060, India
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Fendrich V, Bartsch DK. Chirurgische Therapie gastroduodenaler neuroendokriner Neoplasien. Chirurg 2016; 87:280-7. [PMID: 26779647 DOI: 10.1007/s00104-015-0138-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Hauck L, Bitzer M, Malek N, Plentz RR. Subgroup analysis of patients with G2 gastroenteropancreatic neuroendocrine tumors. Scand J Gastroenterol 2016; 51:55-9. [PMID: 26137871 DOI: 10.3109/00365521.2015.1064994] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Neuroendocrine tumors (NET) are malignancies with an increasing incidence rate. NETs are graded or classified by the expression level of Ki67, a proliferation marker in Grade 1 and 2 tumors. Out of 120 patients who visited our hospital between 2003 and 2012, 40 were classified as G2 NET. This study was mainly designed to investigate a new threshold for optimising the Ki67 system. Patients were subdivided into two new groups according to Ki67 (group 1 = 3-9%, group 2 = 10-20%). Twenty-five patients were allocated to group 1 and 15 to group 2. The primary tumor originated in 46% from the foregut and 68% NET were functionally active. Patients were treated in 88 versus 60% by surgery, 48 versus 80% by somatostatin analogs, 0 versus 20% by chemotherapy, 2,5 versus 0% by Everolimus and 32 versus 47% underwent peptide receptor radionuclide therapy. Group 1 patients showed a significantly (p = 0.01) better survival compared with group 2 and also a significant difference of Chromogranin A (p = 0.03) and alkaline phosphatase (p = 0.01). In addition, all patients with elevated lactate dehydrogenase showed a significantly (p = 0.03) shorter survival. Prognostic relevance of G2 NETs may be improved by using a new boundary. Patients with Ki67 of 3-9% showed a better response to current treatment methods and significantly longer survival compared to group 2. Thus, our data clearly show that patients with higher G2 proliferation index should be treated differently. Finally, LDH has been found to be a new prognostic factor in patients with G2 NET.
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Affiliation(s)
- Lisa Hauck
- a Department of Internal Medicine I, University Hospital , Tübingen, Germany
| | - Michael Bitzer
- a Department of Internal Medicine I, University Hospital , Tübingen, Germany
| | - Nisar Malek
- a Department of Internal Medicine I, University Hospital , Tübingen, Germany
| | - Ruben R Plentz
- a Department of Internal Medicine I, University Hospital , Tübingen, Germany
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Wei JM, Zhang ZZ, Shen YY, Shen DP, Ni XZ. A rare gastric neuroendocrine carcinoma coexisting with Brunner's gland adenoma: A case report. Oncol Lett 2015; 10:1251-1254. [PMID: 26622658 DOI: 10.3892/ol.2015.3465] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Accepted: 01/22/2015] [Indexed: 11/06/2022] Open
Abstract
Gastric neuroendocrine carcinoma (G-NEC) is a rare neoplasm known for its aggressive behavior and poor prognosis. Brunner's gland adenoma (BGA) is a rare benign proliferative lesion that develops most commonly in the duodenum. To the best of our knowledge, no cases of G-NEC coexisting with BGA have previously been reported. The present study therefore reports the first case of G-NEC combined with BGA. A 67-year-old female presented with upper abdominal discomfort. No distant metastases were detected upon pre-operative abdominal computed tomography imaging. The patient underwent a radical distal gastrectomy, D2 lymphadenectomy and Billroth I gastroenterostomy. The resected masses were histologically confirmed to be G-NEC and BGA, respectively. The patient did not receive neoadjuvant or adjuvant chemotherapy or radiotherapy, and remains alive with no evidence of metastasis or recurrence at four years post-surgery.
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Affiliation(s)
- Jian-Ming Wei
- Department of General Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
| | - Zi-Zhen Zhang
- Department of General Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
| | - Yan-Ying Shen
- Department of General Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
| | - Dan-Ping Shen
- Department of General Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
| | - Xing-Zhi Ni
- Department of General Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
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Musholt TJ, Watzka FM. Neuroendokrine Neoplasien des gastroenteropankreatischen Systems. GASTROENTEROLOGE 2015. [DOI: 10.1007/s11377-015-0003-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Wang Z, Li W, Chen T, Yang J, Luo L, Zhang L, Sun B, Liang R. Retrospective analysis of the clinicopathological characteristics of gastrointestinal neuroendocrine neoplasms. Exp Ther Med 2015; 10:1084-1088. [PMID: 26622444 DOI: 10.3892/etm.2015.2634] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2014] [Accepted: 06/22/2015] [Indexed: 12/27/2022] Open
Abstract
The aim of the present study was to analyze and summarize the clinicopathological characteristics and factors affecting prognosis for patients with gastrointestinal neuroendocrine neoplasms (GINENs). Retrospective analysis was conducted on the clinicopathological data of 74 patients who were diagnosed with GINEN, and immunohistochemical methods were used to detect the expression levels of relevant markers [synaptophysin (Syn), chromogranin A (CgA) and Ki-67]. Among the 74 cases with GINEN, there were 39 males and 35 females, with an average age of 56.9 years. There were 32 neoplasms in the rectum, 29 in the stomach, 6 in the colon, 2 in the small intestine and 5 in the appendix. All 74 cases underwent surgical resection. According to the World Health Organization Classification of Tumors of the Digestive System (2010), the diagnosis of the 74 cases showed 41 cases (55.4%) of neuroendocrine tumor (NET; 25 cases of G1 and 16 cases of G2), 21 cases (28.4%) of neuroendocrine carcinoma (NEC) and 12 cases (16.2%) of mixed adenoneuroendocrine carcinoma (MANEC). Additionally, 19 cases had metastasis to lymph nodes. During 10-34 months of follow-up, 15 patients had distant metastasis and 24 patients succumbed, and the accumulative survival rate in 1 or 2 years was 87.8 and 74.3%, respectively. Six factors, namely neoplasm size, depth of invasion, lymph node metastasis, distant metastasis, pathological type and the expression or lack of expression of CgA, significantly affected the survival time of patients. Definitive diagnosis of GINEN mainly relies on pathological diagnosis. GINENs with different histopathological types and grading have different clinicopathological characteristics and prognosis: NETs are mainly early lesions with a good prognosis, whereas NECs and MANECs have high malignancy and strong invasion with a worse prognosis.
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Affiliation(s)
- Zhiqiang Wang
- Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China
| | - Wenliang Li
- Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China
| | - Tianxing Chen
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, P.R. China
| | - Jun Yang
- Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China
| | - Lilin Luo
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, P.R. China
| | - Lianyu Zhang
- Department of Pathology, The Affiliated Cancer Hospital of Tianjin Medical University, Tianjin 300060, P.R. China
| | - Baocun Sun
- Department of Pathology, The Affiliated Cancer Hospital of Tianjin Medical University, Tianjin 300060, P.R. China
| | - Rui Liang
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, P.R. China
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Xourafas D, Tavakkoli A, Clancy TE, Ashley SW. Distal pancreatic resection for neuroendocrine tumors: is laparoscopic really better than open? J Gastrointest Surg 2015; 19:831-40. [PMID: 25759075 PMCID: PMC4412652 DOI: 10.1007/s11605-015-2788-1] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Accepted: 02/25/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND The latest studies on surgical and cost-analysis outcomes after laparoscopic distal pancreatectomy (LDP) highlight mixed and insufficient results. Whereas several investigators have compared surgical outcomes of LDP vs. open distal pancreatectomy (ODP) for adenocarcinomas, few similar studies have focused on pancreatic neuroendocrine tumors (PNETs). METHODS We reviewed the medical records of PNET patients undergoing distal pancreatectomy between 2004 and 2014. Patients were divided into LDP vs. ODP groups. Demographics, relevant comorbidities, oncologic variables, and cost-analysis data were assessed. Survival and Cox proportional hazards analyses were used to evaluate outcomes. RESULTS Of the 171 distal pancreatectomies for PNETs, 73 were laparoscopic, whereas 98 were open. Patients undergoing LDP demonstrated significantly lower rates of postoperative complications (P=0.028) and had significantly shorter hospital stays (P=0.008). On multivariable analysis, positive resection margins (P=0.046), G3 grade (P=0.036), advanced WHO classification (P=0.016), TNM stage (P=0.018), and readmission (P=0.019) were significantly associated with poor survival; however, method of resection (LDP vs. ODP) was not (P=0.254). The median total direct costs of LDP vs. ODP did not differ significantly. CONCLUSIONS In response to the recent considerable controversy surrounding the costs and surgical outcomes of LDP vs. ODP, our results show that LDP for PNETs is cost-neutral and significantly reduces postoperative morbidity without compromising oncologic outcomes and survival.
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Xourafas D, Tavakkoli A, Clancy TE, Ashley SW. Distal pancreatic resection for neuroendocrine tumors: is laparoscopic really better than open? J Gastrointest Surg 2015. [PMID: 25759075 DOI: 10.1007/s11605-015-2788-] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND The latest studies on surgical and cost-analysis outcomes after laparoscopic distal pancreatectomy (LDP) highlight mixed and insufficient results. Whereas several investigators have compared surgical outcomes of LDP vs. open distal pancreatectomy (ODP) for adenocarcinomas, few similar studies have focused on pancreatic neuroendocrine tumors (PNETs). METHODS We reviewed the medical records of PNET patients undergoing distal pancreatectomy between 2004 and 2014. Patients were divided into LDP vs. ODP groups. Demographics, relevant comorbidities, oncologic variables, and cost-analysis data were assessed. Survival and Cox proportional hazards analyses were used to evaluate outcomes. RESULTS Of the 171 distal pancreatectomies for PNETs, 73 were laparoscopic, whereas 98 were open. Patients undergoing LDP demonstrated significantly lower rates of postoperative complications (P=0.028) and had significantly shorter hospital stays (P=0.008). On multivariable analysis, positive resection margins (P=0.046), G3 grade (P=0.036), advanced WHO classification (P=0.016), TNM stage (P=0.018), and readmission (P=0.019) were significantly associated with poor survival; however, method of resection (LDP vs. ODP) was not (P=0.254). The median total direct costs of LDP vs. ODP did not differ significantly. CONCLUSIONS In response to the recent considerable controversy surrounding the costs and surgical outcomes of LDP vs. ODP, our results show that LDP for PNETs is cost-neutral and significantly reduces postoperative morbidity without compromising oncologic outcomes and survival.
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Abstract
Cancer is caused by the accumulation of inherited and/or acquired alterations in specific genes. The recent decline in the cost of DNA sequencing has allowed tumor sequencing to be conducted on a large scale, which, in turn, has led to an unprecedented understanding of the genetic events that drive neoplasia. This understanding, when integrated with meticulous histologic analyses and with clinical findings, has direct clinical implications. The recent sequencing of all of the major types of cystic and noncystic neoplasms of the pancreas has revealed opportunities for molecular diagnoses and for personalized treatment. This review summarizes the results from these recent studies focusing on the clinical relevance of genomic data.
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21
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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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Searching for primaries in patients with neuroendocrine tumors (NET) of unknown primary and clinically suspected NET: Evaluation of Ga-68 DOTATOC PET/CT and In-111 DTPA octreotide SPECT/CT. Radiol Oncol 2014; 48:339-47. [PMID: 25435846 PMCID: PMC4230553 DOI: 10.2478/raon-2014-0018] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Accepted: 02/23/2014] [Indexed: 12/21/2022] Open
Abstract
Background To evaluate the clinical efficacy of In-111 DTPA octreotide SPECT/CT and Ga-68 DOTATOC PET/CT for detection of primary tumors in patients with either neuroendocrine tumor of unknown primary (NETUP) or clinically suspected primary NET (SNET). Patients and methods. A total of 123 patients were included from 2006 to 2009, 52 received Ga-68 DOTATOC PET/CT (NETUP, 33; SNET, 19) and 71 underwent In-111 DTPA octreotide SPECT/CT (50; 21). The standard of reference included histopathology or clinical verification based on follow-up examinations. Results In the NETUP group Ga-68 DOTATOC detected primaries in 15 patients (45.5%) and In-111 DTPA octreotide in 4 patients (8%) (p < 0.001); in the SNET group, only 2 primaries could be detected, all by Ga-68 DOTATOC. In patients with NETUP, primary tumors could be found significantly more often than in patients with SNET (p = 0.01). Out of these 21 patients 14 patients were operated. Conclusion Ga-68 DOTATOC PET/CT is preferable to In-111 DTPA octreotide SPECT/CT when searching for primary NETs in patients with NETUP but should be used with caution in patients with SNET.
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D’Haese JG, Tosolini C, Ceyhan GO, Kong B, Esposito I, Michalski CW, Kleeff J. Update on surgical treatment of pancreatic neuroendocrine neoplasms. World J Gastroenterol 2014; 20:13893-13898. [PMID: 25320524 PMCID: PMC4194570 DOI: 10.3748/wjg.v20.i38.13893] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Revised: 05/07/2014] [Accepted: 06/23/2014] [Indexed: 02/07/2023] Open
Abstract
Pancreatic neuroendocrine neoplasms (PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential (neurendocrine tumors PNETs) or overt (neuroendocrine carcinomas PNECs) malignant, but a subset of PNETs is low-risk. Even in case of low-risk PNETs surgical resection is frequently required to treat hormone-related symptoms and to obtain an appropriate pathological diagnosis. Low-risk PNETs in the body and the tail are ideal for minimally-invasive approaches which should be tailored to the individual patient. Generally, surgeons must aim for parenchyma sparing in these cases. In high-risk and malignant PNENs, indications for tumor resection are much wider than for pancreatic adenocarcinoma, in many cases due to the relatively benign tumor biology. Thus, patients with locally advanced and metastatic PNETs may benefit from extensive resection. In experienced hands, even multi-organ resections are accomplished with acceptable perioperative morbidity and mortality rates and are associated with excellent long term survival. However, poorly differentiated neoplasms with high proliferation rates are associated with a dismal prognosis and may frequently only be treated with chemotherapy. The evidence on surgical treatment of PNENs stems from reviews of mostly single-center series and some analyses of nation-wide tumor registries. No randomized trial has been performed to compare surgical and non-surgical therapies in potentially resectable PNEN. Though such a trial would principally be desirable, ethical considerations and the heterogeneity of PNENs preclude realization of such a study. In the current review, we summarize recent advances in the surgical treatment of PNENs.
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Abstract
INTRODUCTION AND PURPOSE Despite being technically challenging, minimally-invasive pancreatic surgery is increasingly being used to treat pancreatic diseases. Therefore, the evaluation of its oncological safety and its advantages arebecoming increasingly more important. This review focuses on these questions based on the currently available literature. MATERIAL AND METHODS The technically less demanding laparoscopic distal pancreatectomy has been evaluated in numerous meta-analyses. Minimally invasive pancreaticoduodenectomy has only been reported from a few centers worldwide. RESULTS AND CONCLUSION Minimally invasive pancreatic surgery, in particular laparoscopic distal pancreatectomy, is increasingly being used to treat pancreatic tumors. The advantages of laparoscopy, such as less intraoperative blood loss, reduced postoperative pain and a shorter length of stay have all been demonstrated in large trials. However, a sufficient oncological treatment was only assessed via indirect surrogate parameters, such as the number of lymph nodes obtained and R0 resection rates; therefore, larger prospective trials are needed to prove adequate oncological treatment. To date, minimally invasive techniques should only be employed in trials on treatment of pancreatic malignancies.
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Haugvik SP, Gorunova L, Haugom L, Eibak AM, Gladhaug IP, Heim S, Micci F. Loss of 11p11 is a frequent and early event in sporadic nonfunctioning pancreatic neuroendocrine neoplasms. Oncol Rep 2014; 32:906-12. [PMID: 25018013 PMCID: PMC4121415 DOI: 10.3892/or.2014.3328] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Accepted: 05/20/2014] [Indexed: 02/07/2023] Open
Abstract
The pathogenesis of sporadic pancreatic neuroendocrine neoplasms (PNENs) is poorly understood. To gain insight into the genetic mechanisms underlying this tumor entity, we performed genome-wide screening of 16 surgical specimens from 15 patients with sporadic PNEN, combining G-band karyotyping and high resolution comparative genomic hybridization (HR-CGH). G-banding revealed abnormal karyotypes in 2 of 10 tumor samples analyzed. DNA copy number changes were detected in 13 samples, whereas three tumors showed a balanced genome. Gains were more frequent than losses in the nonfunctioning tumors (n=13). Common gains were scored at 5p12–13, 4q13–24, 5p15, 5q11–31, and 9q21–22. Common losses were scored at 11p11, 11p14–15, 11q23, 11p12–13, and 11q22. The average number of copy aberrations (ANCA index) was 12 for 13 nonfunctioning primary tumors, 4.8 for the nonfunctioning tumors with low Ki-67 (≥5%), 21.2 for the tumors with high Ki-67 (<5%), 2.5 for small tumors (<3.5 cm), and 17.8 for large tumors (≥3.5 cm). There was a statistically significant difference in the ANCA index between the groups defined by Ki-67 and tumor size. Nonfunctioning tumors with low Ki-67, no distant metastasis and small size had few aberrations detected by HR-CGH, but frequent loss of material from chromosomal band 11p11. The present study indicates the existence of distinct cytogenetic patterns in sporadic nonfunctioning PNEN. Loss of chromosomal band 11p11 might indicate a primary pathogenetic event in these tumors.
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Affiliation(s)
- Sven-Petter Haugvik
- Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, 0372 Oslo, Norway
| | - Ludmila Gorunova
- Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, 0372 Oslo, Norway
| | - Lisbeth Haugom
- Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, 0372 Oslo, Norway
| | - Anne Mette Eibak
- Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, 0372 Oslo, Norway
| | - Ivar Prydz Gladhaug
- Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, 0372 Oslo, Norway
| | - Sverre Heim
- Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway
| | - Francesca Micci
- Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, 0372 Oslo, Norway
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Al-Kurd A, Chapchay K, Grozinsky-Glasberg S, Mazeh H. Laparoscopic resection of pancreatic neuroendocrine tumors. World J Gastroenterol 2014; 20:4908-4916. [PMID: 24803802 PMCID: PMC4009522 DOI: 10.3748/wjg.v20.i17.4908] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 12/06/2013] [Accepted: 01/05/2014] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are a rare heterogeneous group of endocrine neoplasms. Surgery remains the best curative option for this type of tumor. Over the past two decades, with the development of laparoscopic pancreatic surgery, an increasingly larger number of PNET resections are being performed by these minimally-invasive techniques. In this review article, the various laparoscopic surgical options for the excision of PNETs are discussed. In addition, a summary of the literature describing the outcome of these treatment modalities is presented.
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Woodbridge LR, Murtagh BM, Yu DFQC, Planche KL. Midgut Neuroendocrine Tumors: Imaging Assessment for Surgical Resection. Radiographics 2014; 34:413-26. [DOI: 10.1148/rg.342135504] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Abstract
PURPOSE OF REVIEW To review the recent advances and current controversies in patients with Zollinger-Ellison syndrome (ZES). RECENT FINDINGS Recent advances in the management of ZES include: improved understanding of the pathogenesis of gastrinoma and pancreatic neuroendocrine tumors, new prognostic classification systems, new diagnostic algorithms, more sensitive localization studies, new treatment strategies including improved control of gastric acid secretion and role for surgery, and new approaches to patients with advanced disease. Controversies include: the best approach to a patient with hypergastrinemia suspected of possibly having ZES, the appropriate gastrin assay to use, the role of surgery in patients with ZES, especially those with multiple endocrine neoplasia type 1, and the precise order of therapeutic modalities in the treatment of patients with advanced disease. SUMMARY This review updates clinicians regarding important advances and controversies required to optimally diagnose and manage patients with ZES.
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Affiliation(s)
- Tetsuhide Ito
- aDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan bDigestive Diseases Branch, NIDDK, NIH, Bethesda, Maryland, USA
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Uygun A, Kadayifci A, Polat Z, Yilmaz K, Gunal A, Demir H, Bagci S. Long-term results of endoscopic resection for type I gastric neuroendocrine tumors. J Surg Oncol 2013; 109:71-4. [PMID: 24165913 DOI: 10.1002/jso.23477] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2013] [Accepted: 10/03/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND A number of different therapies, including endoscopic resection, have been suggested for the treatment of Type 1 gastric neuroendocrine tumors (NETs). The current study aimed to determine the long-term efficacy of endoscopic resection for Type 1 gastric NETs. METHODS Twenty-two patients (from 1999 to 2012) with Type 1 gastric NETs were included in the study. All patients were treated with endoscopic resection and received regular followed-up appointments at a tertiary referral center. RESULTS All patients were initially diagnosed with hypergastrinemia, atrophic gastritis and intestinal metaplasia. Polyps' diameters were >1 cm in 4 patients, and between 0.5 and 1 cm in 18 patients. All detectable lesions were successfully resected. One patient required surgery due to gastric perforation during endoscopic mucosal resection. Recurrence was detected in four patients (18%) and endoscopic resection was performed again. Local or distant metastasis was not observed in any patient during follow-up. Median follow-up time was 7 years, with a maximum of 14 years. Seventeen patients (78%) completed a 5-year follow-up period, and overall disease-free survival rate was 100%. CONCLUSIONS Long-term follow-ups with 22 patients suggest that endoscopic resection of Type 1 gastric NETs is a safe and effective treatment option with a relatively low recurrence rate.
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Affiliation(s)
- Ahmet Uygun
- Division of Gastroenterology, Gulhane Military Medical Academy, Ankara, Turkey
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31
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Laparoscopic pancreatic resections. Langenbecks Arch Surg 2013; 398:939-45. [PMID: 24006117 DOI: 10.1007/s00423-013-1108-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2013] [Accepted: 08/22/2013] [Indexed: 02/06/2023]
Abstract
PURPOSE Pancreatic surgery is technically complex and requires considerable expertise. Laparoscopic pancreatic surgery adds the need for considerable experience with advanced laparoscopic techniques. Despite the technical difficulties, an increasing number of centers propagate the use of laparoscopy in pancreatic surgery over the last decade. METHODS In this review, we provide an overview of the literature regarding the advantages and disadvantages of laparoscopic pancreatic surgery. Larger prospective randomized studies have emerged in the subset of laparoscopic or retroperitoneoscopic surgery for acute pancreatitis, considerable single center experience has been reported for laparoscopic pancreatic tail resection, and laparoscopic pancreatic head resection, however, is still restricted to a few experienced centers worldwide. RESULTS AND CONCLUSIONS Laparoscopic pancreatic surgery is becoming more and more established, in particular for the treatment of benign and premalignant lesions of the pancreatic body and tail. It has been shown to decrease postoperative pain, narcotic use, and length of hospital stay in larger single center experience. However, prospective trials are needed in laparoscopic resective pancreatic surgery to evaluate its advantages, safety, and efficacy in the treatment of pancreatic neoplasms and in particular in malignant pancreatic tumors.
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Haugvik SP, Marangos IP, Røsok BI, Pomianowska E, Gladhaug IP, Mathisen O, Edwin B. Long-term outcome of laparoscopic surgery for pancreatic neuroendocrine tumors. World J Surg 2013; 37:582-90. [PMID: 23263686 DOI: 10.1007/s00268-012-1893-5] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND As most pancreatic neuroendocrine tumors (PNET) are relatively small and solitary, they may be considered well suited for removal by a minimally invasive approach. There are few large series that describe laparoscopic surgery for PNET. The primary aim of this study was to describe the feasibility, outcome, and histopathology associated with laparoscopic pancreatic surgery (LS) of PNET in a large series. METHODS All patients with PNET who underwent LS at a single hospital from March 1997 to April 2011 were included retrospectively in the study. RESULTS A total of 72 patients with PNET underwent 75 laparoscopic procedures, out of which 65 were laparoscopic resections or enucleations. The median operative time of all patients who underwent resections or enucleations was 175 (60-520) min, the median blood loss was 300 (5-2700) ml, and the median length of hospital stay was 7 (2-27) days. The overall morbidity rate was 42%, with a surgical morbidity rate of 21% and postoperative pancreatic fistula (POPF) formation in 21%. Laparoscopic enucleations were associated with a higher rate of POPF than were laparoscopic resections. Five-year disease-specific survival rate was 90%. The T stage, R stage, and a Ki-67 cutoff value of 5% significantly predicted 5-year survival. CONCLUSION LS of PNET is feasible with acceptable morbidity and a good overall disease-specific long-term prognosis.
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Affiliation(s)
- Sven-Petter Haugvik
- Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, Sognsvannsveien 20, 0372, Oslo, Norway.
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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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Abstract
Pancreatic neuroendocrine tumors account for 1% to 2% of pancreatic neoplasms and may occur sporadically or as part of a hereditary syndrome. Patients may present with symptoms related to hormone secretion by functional tumors or to locally advanced or metastatic nonfunctional tumors. Asymptomatic pancreatic neuroendocrine tumors are increasingly detected incidentally during abdominal imaging performed for other reasons. The management of localized pancreatic neuroendocrine tumors is surgical resection. Hepatic metastases are common and their management involves a variety of liver-directed therapies, which should be tailored according to extent of disease, symptoms, presence of extrahepatic metastases, and patient performance status.
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Affiliation(s)
- Paxton V Dickson
- Division of Surgical Oncology, Department of Surgery, University of Tennessee Health Science Center, 910 Madison Avenue, Suite 208, Memphis, TN 38163, USA
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Kim MJ, Choi DW, Choi SH, Heo JS, Park HJ, Choi KK, Jang KT, Sung JY. Surgical strategies for non-functioning pancreatic neuroendocrine tumours. Br J Surg 2012; 99:1562-8. [PMID: 23027073 DOI: 10.1002/bjs.8892] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND The purpose of this study was to identify management strategies for non-functioning pancreatic neuroendocrine tumours (NF-PNETs) by analysis of surgical outcomes at a single institution. METHODS Archived records of patients with NF-PNETs who underwent surgery between 1994 and 2010 were reviewed. RESULTS Among 125 patients, the median tumour size was 2·5 (range 0·15-20·5) cm. Of the 51 NF-PNETs with a diameter of no more than 2 cm, 12 (24 per cent) were diagnosed as carcinoma. Overall 20 patients (16·0 per cent) had metastases to the lymph nodes. The minimum size of the tumour with lymph node metastasis was 1·2 cm. Having a NF-PNET of 2 cm or larger significantly increased the probability of a poorly differentiated carcinoma (P = 0·006), and having a NF-PNET of at least 2·5 cm significantly increased the probability of lymph node metastasis (P = 0·048). The 5-year cumulative survival rate after curative resection was 89·7 per cent. During a median follow-up of 31·5 months, there were 27 recurrences (23·1 per cent) and 13 disease-specific deaths (11·1 per cent) among the 117 patients who had an R0 resection. All patients who underwent repeat operations were alive without additional recurrence after a mean(s.d.) follow-up of 27·1(18·0) months. CONCLUSION Curative surgery should be performed for control of primary NF-PNETs. Lymph node dissection for NF-PNETs of 2·5 cm or larger and at least node sampling for tumours with a diameter of 1 cm or more are recommended. Debulking surgery should be considered for advanced tumours.
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Affiliation(s)
- M J Kim
- Department of Surgery, Jeju National University Hospital, School of Medicine, Jeju National University, Jeju, Korea
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Heverhagen AE, Dietzel K, Waldmann J, Langer P, Fendrich V, Bartsch DK. Harmonic scalpel versus conventional dissection technique in pylorus-preserving partial duodenopancreatectomy. Dig Surg 2012; 29:420-5. [PMID: 23234869 DOI: 10.1159/000345581] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2012] [Accepted: 10/25/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIMS Pancreatic head resection is performed with low mortality, but morbidity remains high. Extensive preparation, long operating times, intraoperative blood loss and the need for blood transfusions are risk factors for postoperative morbidity. The aim of our study was to evaluate the feasibility and safety of the ultrasonic dissection device in pylorus-preserving duodenopancreatectomy (PPPD). METHODS Fifty consecutive patients who underwent PPPD with an ultrasonic dissection device (group 1) were compared with a match-controlled group of 50 consecutive patients who underwent PPPD with conventional dissection techniques (group 2). Duration of surgery, intraoperative blood loss, blood units, complications, mortality and duration of hospital stay were analyzed. RESULTS There was no difference in age, gender or BMI between groups. In group 1, mean blood loss (446 ± 281.8 ml, p = 0.008) and number of blood units (0.32 ± 0.86, p = 0.001) were significantly lower than in group 2 (819 ± 915.4 ml; 1.36 ± 2.83 units). Duration of surgery was shorter in group 1 (345.6 vs. 373 min, p = 0.28). The rate of postoperative complications, mortality and hospital stay were not significantly different. CONCLUSIONS Use of an ultrasonic dissection device in PPPD might significantly reduce intraoperative blood loss and the need for blood transfusions. These results should be verified in a prospective randomized controlled trial.
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Affiliation(s)
- A E Heverhagen
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany.
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Knigge U, Hansen CP. Surgery for GEP-NETs. Best Pract Res Clin Gastroenterol 2012; 26:819-31. [PMID: 23582921 DOI: 10.1016/j.bpg.2012.12.005] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2012] [Accepted: 12/27/2012] [Indexed: 01/31/2023]
Abstract
Surgery is the only treatment that may cure the patient with gastroentero-pancreatic (GEP) neuroendocrine tumours (NET) and neuroendocrine carcinomas (NEC) and should always be considered as first line treatment if R0/R1 resection can be achieved. The surgical and interventional procedures for GEP-NET are accordingly described below. Life-long follow-up should be performed in almost all patients at a specialized NET center.
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Affiliation(s)
- Ulrich Knigge
- Department of Gastrointestinal Surgery C, Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
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Feldmann G, Bisht S, Schütte U, Haarmann J, Brossart P. Everolimus for the treatment of pancreatic neuroendocrine tumors. Expert Opin Pharmacother 2012; 13:2073-84. [DOI: 10.1517/14656566.2012.713348] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Goretzki PE, Starke A, Akca A, Lammers BJ. [Surgery for neuroendocrine tumors of the gastroenteropancreatic system (GEP-NET)]. Internist (Berl) 2012; 53:152-60. [PMID: 22290318 DOI: 10.1007/s00108-011-2917-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Surgical treatment is still the only curative treatment proven for patients with neuroendocrine tumors (NET) of the gastroenteropancreatic system. In addition to the therapy of incidental findings, the treatment of NET with variable aggressiveness and often good long-term prognosis requires a thorough preoperative assessment and a surgical procedure that is based on each individual case. Treatment can be surgery alone (if the disease is locally confined) or can be combined with other therapies. Early NET of the stomach and rectum can be cured endoscopically without further diagnostics, while early findings of the appendix can be treated by an appendectomy. Functionally active pancreatic NET and NET of the small intestine are often preoperatively diagnosed based on symptoms. Thus, it is possible to refer the patient to a NET center, if necessary. Stratification of the necessary treatment combination can be made early. An alternative to radical surgical treatment is the operative reduction of the tumor size and hormone production in metastasized NET, which can lead to improved life expectancy and quality of life. Combination with other treatment forms is absolutely necessary in these patients. It has been proven useful to divide the large group of NET based on the different tumor locations, hormone activity, and the degree of differentiation of the tumor. Early forms, locoregionally limited tumor stages, and tumor stages with distant metastases are considered separately.
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Affiliation(s)
- P E Goretzki
- Chirurgische Klinik I, Lukaskrankenhaus GmbH Neuss und Insulinoma und GEP-NET Tumorzentrum Neuss–Düsseldorf, Preussenstrasse 84, Neuss.
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Markinez Gordobil I, Ruiz Montesinos I, Arteaga Martín X, Medrano Gómez MÁ, Beguiristain Gómez A. [Autologous cephalic duodenopancreatectomy with superior mesenteric vein dissection and reconstruction using the renal vein]. Cir Esp 2012; 91:269-71. [PMID: 22541452 DOI: 10.1016/j.ciresp.2011.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2011] [Accepted: 08/26/2011] [Indexed: 10/28/2022]
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de Wilde RF, Edil BH, Hruban RH, Maitra A. Well-differentiated pancreatic neuroendocrine tumors: from genetics to therapy. Nat Rev Gastroenterol Hepatol 2012; 9:199-208. [PMID: 22310917 PMCID: PMC3544293 DOI: 10.1038/nrgastro.2012.9] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Well-differentiated pancreatic neuroendocrine tumors (PanNETs) comprise ∼1-3% of pancreatic neoplasms. Although long considered as reasonably benign lesions, PanNETs have considerable malignant potential, with a 5-year survival of ∼65% and a 10-year survival of 45% for resected lesions. As PanNETs have a low incidence, they have been understudied, with few advances made until the completion of their exomic sequencing in the past year. In this Review, we summarize some of the latest insights into the genetics of PanNETs, and their probable implications in the context of prognosis and therapy. In particular, we discuss two genes (DAXX and ATRX) that have collectively been identified as mutated in >40% of PanNETs, and the biological and prognostic implications of these novel mutations. The identification of recurrent somatic mutations within the mTOR signaling pathway and the therapeutic implications for personalized therapy in patients with PanNETs are also discussed. Finally, this Review outlines state-of-the-art advances in the biology of PanNETs that are of emerging translational importance.
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Abstract
PURPOSE OF REVIEW Pancreatic neuroendocrine tumors (PNETs) are rare tumors, with an incidence of one per 100, 000 individuals per year, and they account for 1-2% of all pancreatic neoplasms. PNETs are a heterogeneous group with varying clinical presentation, tumor biology and prognosis. This article reviews the current diagnostic strategy and treatment armamentarium for PNETs. Special attention is paid to recent and ongoing developments in treatment, particularly with regards to multimodality treatment and newer systemic therapies for unresectable disease. RECENT FINDINGS There has been significant progress in the genetic understanding of hereditary syndromes in regards to PNETs, as well as in the diagnosis and treatment of resectable and nonresectable PNETs. Whereas surgical therapy remains the most advisable therapy for resectable neuroendocrine tumors of the pancreas, there have been significant recent advances in systemic therapy for those with unresectable disease. Results from recent clinical trials examining mammalian target of rapamycin inhibitors and tyrosine kinase inhibitors for unresectable disease are promising in expanding treatment options for metastatic PNETs. SUMMARY Neuroendocrine tumors of the pancreas are a heterogeneous group of tumors with varying clinical presentation, tumor biology and prognosis. Clinicians must be aware of the variety of manifestations of this disease, as well as the role of systemic chemotherapy in treatment of unresectable disease.
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Fischer L, Mehrabi A, Büchler MW. [Neuroendocrine tumors of the duodenum and pancreas. Surgical strategy]. Chirurg 2012; 82:583-90. [PMID: 21656305 DOI: 10.1007/s00104-011-2069-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The incidence of neuroendocrine tumors (NET) has increased worldwide by 3-5 times over the last decades. This is mainly based on the broad use of imaging modalities such as computed tomography (CT) and endoscopic approaches. As a consequence many duodenal and pancreatic tumors are detected in an early stage resulting in an improved prognosis of these patients. Besides the measurement of serum chromogranin A and 5-hydroxy indolic acid measured in 24 h urine collection, CT, endosonographic ultrasound (EUS) and endoscopy are important diagnostic tools. About 20% of all patients with pancreatic and duodenal NETs are diagnosed because of specific symptoms. More than 95% of diagnosed NETs are sporadic tumors. Whenever possible these patients should be treated by resection. Benign neuroendocrine duodenal tumors up to 1 cm in size can be removed endoscopically. The endoscopic resection of larger tumors should be performed surgically. The therapy of hereditary NETs of the duodenum and the pancreas should be decided after interdisciplinary discussion. However, even these patients seem to benefit from resection. In case of metastatic disease debulking surgery should be considered if more than 90% of the tumor mass can be resected. In patients with extensive liver metastases but resectable primary NET, liver transplantation is a reasonable option. There is no consensus about adjuvant or neoadjuvant treatment of duodenal or pancreatic NETs. The therapy with everolimus or sunitinib in advanced tumor stages has shown promising results. The administration of somatostatin analogues or antacids is appropriate for symptom reduction.
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Affiliation(s)
- L Fischer
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 110, Heidelberg, Germany
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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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Pavlidis TE, Psarras K, Symeonidis NG, Pavlidis ET, Sakantamis AK. Current surgical management of pancreatic endocrine tumor liver metastases. Hepatobiliary Pancreat Dis Int 2011; 10:243-247. [PMID: 21669565 DOI: 10.1016/s1499-3872(11)60040-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The management of metastatic disease in pancreatic endocrine tumors (PETs) demands a multidisciplinary approach and the cooperation of several medical specialties. The role of surgery is critical, even when a radical excision cannot always be achieved. DATA SOURCES A PubMed search of relevant articles published up to February 2011 was performed to identify current information about PET liver metastases regarding diagnosis and management, with an emphasis on surgery. RESULTS The early diagnosis of metastases and their accurate localization, most commonly in the liver, is very important. Surgical options include radical excision, and palliative excision to relieve symptoms in case of failure of medical treatment. The goal of the radical excision is to remove the primary tumor bulk and all liver metastases at the same time, but unfortunately it is not feasible in most cases. Palliative excisions include aggressive tumor debulking surgeries in well-differentiated carcinomas, trying to remove at least 90% of the tumor mass, combined with other additional destructive techniques such as hepatic artery embolization or chemoembolization to treat metastases or chemoembolization to relieve symptoms in cases of rapidly growing tumors. The combination of chemoembolization and systemic chemotherapy results in better response and survival rates. Other local destructive techniques include ethanol injection, cryotherapy and radiofrequency ablation. CONCLUSION It seems that the current management of PETs can achieve important improvements, even in advanced cases.
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Affiliation(s)
- Theodoros E Pavlidis
- Second Surgical Propedeutical Department, Hippocration Hospital, Medical School, Aristotle University of Thessaloniki, Konstantinopoulos 49, 54642 Thessaloniki, Greece.
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