胰腺神经内分泌肿瘤的诊疗现状及研究进展

神经内分泌肿瘤属于相对罕见疾病,且无特异性临床症状,目前医学上对其研究及认识仍不足,致使该病患者的生存期近30年依赖并无明显改善。笔者结合欧洲神经内分泌肿瘤协会(ENETS),美国癌症联合会(AJCC)共识就目前胰腺神经内分泌肿瘤的诊疗现状及研究进展进行综述,以提高临床医生对胰腺神经内分泌肿瘤的认识。     

胃肠胰腺神经内分泌肿瘤诊治进展

神经内分泌肿瘤是一类源于神经内分泌细胞的肿瘤。目前,对该类疾病的术语、诊断、治疗规范发生了巨大变化。近年来,由于对该类疾病认识逐步深入,胃肠胰腺神经内分泌肿瘤发病率不断上升。本文主要结合国内两大共识,对胃肠胰腺神经内分泌肿瘤命名演进、最新诊断及主要治疗进展做一综述。     

《中国胰腺神经内分泌肿瘤诊疗指南（2020）》解读

胰腺神经内分泌肿瘤的临床决策路径复杂、诊疗难度较大，病人管理依赖多学科协调参与。为此，中华医学会外科学分会胰腺外科学组联合多领域专家，基于循证医学证据及我国现阶段医疗特点，联合制定了《中国胰腺神经内分泌肿瘤诊疗指南（2020）》，以进一步改进中国胰腺神经内分泌肿瘤病人的诊疗流程。该指南的推荐多基于临床证据充分、专家共识度高的观点。在学习现有指南的同时，应积极开展针对胰腺神经内分泌肿瘤的临床和基础研究，共同推动疾病标准化诊疗体系的建立。     

胰腺内分泌肿瘤鉴别诊断

胰腺内分泌肿瘤实质上是胃肠胰腺神经内分泌肿瘤家族成员,起源于胃肠、胰腺的神经内分泌干细胞,可分泌多种激素及胺类物质。根据肿瘤是否伴随激素相关性临床症状可分为功能性胰腺神经内分泌肿瘤、非功能性胰腺神经内分泌肿瘤。前者因有内分泌激素症状易于诊断,而后者易于胰腺癌及其他恶性肿瘤混淆,延误诊断及治疗。胰腺内分泌肿瘤的手术治疗效果好,即使是恶性胰腺内分泌肿瘤,积极治疗也可获得长期存活,但此类肿瘤容易误诊,临床上应予高度重视。近年来随着临床实践经验的积累和对胰腺内分泌肿瘤疾病本质的认识,胰腺神经内分泌肿瘤诊断率逐年增加,有关胰腺神经内分泌肿瘤的治疗手段、预后等方面的认识在不断更新。     

胰腺恶性神经内分泌肿瘤的诊断与治疗

随着对神经内分泌肿瘤认识的深入及诊断技术的提高,过去认为是罕见病的胰腺神经内分泌肿瘤发病率逐年升高。目前已成为一类严重影响人类健康的疾病。最近美国流行病学检测及最终结果数据     

胰腺神经内分泌肿瘤诊疗现状

神经内分泌肿瘤（NEN）是一种罕见的高异质性肿瘤,起源于肽能神经元和神经内分泌细胞,可发生在支气管、肺部和胃肠、胰腺等多种部位,我国以胰腺神经内分泌肿瘤（pNEN）最为多见,近几十年来发病率显著上升。笔者主要从pNEN的分级标准、诊断、治疗等方面对该疾病的最新诊疗研究现状进行介绍,以期为临床诊疗提供指导和参考。     

胰腺神经内分泌肿瘤的影像学诊断

胰腺神经内分泌肿瘤（pNENs）起源于干细胞,具有神经内分泌标记物、能够产生生物活性胺和（或）多肽激素,且具有显著异质性。随着内镜和影像学等技术的进步和诊断水平的提高,其检出率呈现升高趋势。目前临床上对pNENs的认识尚不充分,易误诊和漏诊,认识神经内分泌肿瘤的影像学特点及选择有效影像学检查手段能尽早明确诊断有利于改善病人的预后。     

无功能性胰腺神经内分泌肿瘤临床诊断与手术治疗的研究进展

胰腺神经内分泌肿瘤（pNEN）是一种罕见的异质性肿瘤,具有多种恶性潜能。随着横断面成像的广泛应用,无症状的无功能性胰腺神经内分泌肿瘤（NF-pNEN）被诊断的频率逐年升高,但仍存在临床确诊难度大,手术治疗不及时等诸多方面的不足。加深对NF-pNEN的认识有助于提高临床诊断率,进而采取及时有效的治疗。笔者就NF-pNEN在临床诊断与外科治疗中存在的争议问题进行综述,以期为临床提供参考。     

胰腺内分泌肿瘤

胰腺内分泌肿瘤（Pancreaticenodcrinetumor）是一种很少见的疾病，且胰腺内分泌肿瘤中各种肿瘤的发病率尚有很大的区别，有的肿瘤极罕见。各国的发病率亦有明显的差异，如胃泌素瘤在我国的发病率就明显低于西方国家，而胰岛素瘤则相对较西方国家为高。胰腺内分泌肿瘤具有共同的一些特性；①它们有共同的来源，均属于APUD系统，并具有APUD细胞产生肽及胺的特点。均含有特异的神经烯酸化酶（neu－ron－speoificenolase，NSE）、突触素（synaptophysins）、铬粒素A或C（chromograninA或C），这些物质被认为是神经内分泌细胞的标志物；…     

中国胰腺神经内分泌肿瘤诊疗指南（2020）

正神经内分泌肿瘤是一类相对少见的肿瘤,胰腺是其常见的发病部位。近年来,胰腺神经内分泌肿瘤(pancreatic neuroendocrine neoplasm,pNEN)的发病率明显上升。随着检查技术的进步和健康体检的普及,pNEN的临床检出率亦呈上升趋势。同时,学术界对疾病认识的不断深入也使得pNEN的诊疗水平显著提升。     

Pathologie neuroendokriner Neoplasien

During the last 5 years the European Neuroendocrine Tumor Society (ENETS) has developed basic recommendations for a standardized pathological diagnosis and classification of neuroendocrine neoplasms (NEN) of the gastroenteropancreatic system. These were included in the novel classification of tumors of the digestive system by the World Health Organization (WHO 2010) and the TNM classification of the union for international cancer control (2009). This review presents the pathology diagnosis regarding (1) basic diagnosis, (2) clinically relevant optional diagnosis, (3) proliferation-based grading, (4) nomenclature and (5) TNM classification. It is emphasized that a standardized diagnosis of NEN, together with clinical and radiological findings, is crucial for prognostic stratification and optimal therapy of patients with NEN. Therefore a close interdisciplinary collaboration is essential.     

Grade 2 chondrosarcoma: stage I or stage II tumor?

We analyzed chondrosarcomas of bone to assess whether Grade 2 tumors are more appropriately grouped with Grade 1 chondrosarcomas or Grade 3 and dedifferentiated chondrosarcomas (Musculoskeletal Tumor Society Stage I or Stage II). A retrospective chart review identified 109 patients who presented with nonmetastatic chondrosarcoma. Data were gathered on each tumor's histologic grade, extent (intracompartmental versus extracompartmental), resection margin status, and site (axial versus appendicular). The cohort included 60 males and 49 females with a mean age of 50 years. Forty tumors were located in the axial skeleton and the remainder were distributed throughout the appendicular skeleton. Fifty-three tumors were Grade 1, 40 tumors were Grade 2, eight tumors were Grade 3, and eight tumors were dedifferentiated. Statistical analysis established grade as the only significant variable for this group of patients; extracompartmental tumor spread also correlated with outcome, but not independent of the grade. Margin status and site were not statistically significant with respect to outcome. Chi-square analysis also established that Grade 2 tumors are grouped more appropriately with the Grade 1 chondrosarcomas as Musculoskeletal Tumor Society Stage I neoplasms. These data should be considered when developing the surgical plan, particularly for patients with Grade 2 appendicular chondrosarcomas.     

Validation of a functional evaluation system in patients with musculoskeletal tumors

The validity and reliability of the Musculoskeletal Tumor Society functional evaluation system were evaluated using the Nottingham Health Profile, the Short Form-36, and the EuroQol protocol to measure the quality of life of patients with malignant musculoskeletal tumors. Forty-nine patients were assessed and osteosarcoma around the knee was the most common type of tumor. Prosthetic reconstructions had been done in 55.1% of patients. In a content validity analysis, neither social nor psychologic domain was identified in the Musculoskeletal Tumor Society system. All items of the lower extremity were related to the same function-walking ability. The Musculoskeletal Tumor Society system had a strong correlation with other quality of life measures in the construct validity and the reliability, but each domain of the system was so comprehensive that it could not represent the quality of life properly. Furthermore, the preoperative and postoperative status of patients could not be compared using this system. The overall validity and reliability of the Musculoskeletal Tumor Society system seemed to be acceptable. However, this system may require additional development of the appropriate domains for evaluating the quality of life in patients with musculoskeletal tumors.     

Neuroendocrine tumors of the gastroenteropancreatic system--reevaluation using the Capella classification

INTRODUCTION: Neuroendocrine tumors of the gastroenteropancreatic system (GEP) are heterogeneous regarding hormone production, localisation and biological behaviour making the prognostic evaluation of these rare tumors difficult. Capella et al. proposed a new classification that combines for the first time both biological and prognostic characteristics. This study aimed to evaluate the prognostic value of Capella's classification in the patients treated at our hospital. METHODS: 86 from 1975-1999 surgically treated and histologically confirmed neuroendocrine tumors were retrospectively classified as benign (B), uncertain behavior (UB), low grade malignant (LG) or high grade malignant (HG) following the Capella classification. These data were correlated with the long-term outcome of the patients 8.5 (range: 1-24) years after surgery. RESULTS: 43 % of tumors were localised in the pancreas, the others were equally distributed in the remaining GEP. Most tumors were classified as B (42 %) or LG (41 %), few were UB (10 %) or HG (7 %). 61 patients survived free of disease, 25 patients died, 13 of them not tumor related. Tumor related deaths were only observed in 6 patients with inoperable LG- and 6 patients with HG-neuroendocrine tumors within 3 years after surgery. CONCLUSION: The Capella classification reliably reflects the heterogeneity and the biological behaviour of GEP-neuroendocrine tumors and can therefore be recommended for clinical use.     

Iliofemoral arthrodesis and pseudarthrosis: a long-term functional outcome evaluation

Reconstruction after the resection of pelvic tumors is a major challenge. It depends on many factors such as age, activity level, type of tumor, its adjuvant treatment, and the extent of the disease. The purpose of the current study was to analyze the functional and oncologic outcomes of patients who had an iliofemoral arthrodesis after resection of a pelvic sarcoma. Between 1981 and 1999, 20 males and 12 females with a mean age of 39.9 years (range, 10-71 years) had an iliofemoral arthrodesis, either as a solid fusion or primary pseudarthrosis, at one institution. The functional outcome was evaluated using the Musculoskeletal Tumor Society and the Toronto Extremity Salvage scores. At a mean followup of 97 months (range, 14-226 months), 15 of 32 patients were alive, all without disease. The radiographic union rate was 86%. The mean overall Musculoskeletal Tumor Society and Toronto Extremity Salvage scores were 64% and 48%, respectively. Patients with a primary solid fusion did functionally better compared with patients who had pseudarthrosis (Toronto Extremity Salvage Score, 76%; Musculoskeletal Tumor Society Score, 71% versus Toronto Extremity Salvage Score, 52%; Musculoskeletal Tumor Society Score, 25%). Biomechanical analysis showed that the loss of motion in the hip is well-compensated. The authors conclude from this series that iliofemoral reconstruction after resection of a pelvic sarcoma provides acceptable and durable long-term results, not only from the oncologic, but also from the functional perspective.     

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??The presentation of 14th annual European neuroendocrine tumor society conference LYU Yang??LOU Wen-hui. Department of Genaral Surgery, Zhongshan hospital??Fudan University??Shanghai 200032??China
Corresponding author??LOU Wen-hui??E-mail: lou.wenhui@
zs-hospital.sh.cn
Abstract The 14th annual European Neuroendocrine Tumor Society (ENETS) Conference were held in Barcelona??Spain from 08-03-2017 to 10-03-2017??the Conference aims to explore the diagnosis and treatment of neuroendocrine neoplasms from both the clinical and basic perspective. In this conference??the genome sequencing results of pNETs and the upcoming new WHO pathology classification of the gastroenteropancreatic NENs are worthy of attention. Overall??recently the disease terminology??diagnosis and treatment norms have undergone tremendous changes in the field of NENs??more and more research are being carried out.     

Neuroendocrine "silent" tumors of the pancreas

Neuroendocrine tumors are the rare pathology. They are characterized by slow growth and favorable prognosis for life. From 1985 to 2000 fifty-two patients with "silent" neuroendocrine tumors were treated. Clinical symptoms in 60% patients were associated with squeezing of the surrounding organs and tissues (gastroduodenal obstruction or cholestasis), in 20% patients tumors were diagnosed within the framework of syndrome of multiple endocrine metaplasia and in 16% cases tumors were revealed accidentally. Fifty-two percent of the tumors located in the head of the pancreas, 23 and 25% - in the corpus and tail of the pancreas respectively. All the patients underwent surgery. Neuroendocrine nature of the tumors was verified during morphologic study. Five-year survival was 51.8, 41.6 and 54.5% when tumor located in the head, corpus and tail of the pancreas, respectively.     

Liver Transplantation for Unresectable Neuroendocrine Tumor Liver Metastases

Background

Liver transplantation (LT) is performed in selected patients with neuroendocrine hepatic metastases. Survival benefit and the risk of tumor recurrence after LT, also exacerbated by immunosuppressive therapy, remain important clinical issues. Whether patients with particular types of neuroendocrine tumors (NET) benefit more than others is unclear.

Methods

Bibliographical searches were performed in PubMed for the terms “liver transplantation and neuroendocrine tumors,” “liver transplant and neuroendocrine tumors,” “liver transplantation and immunosuppressive therapy,” “tumor recurrence.”

Results

Promising results have been reported for LT for NET metastases with 5-year survival of up to 90 % in patients with well-differentiated gastroenteropancreatic NETs, but only few patients are free of tumor 5 years after LT. Better outcomes have been reported for gastrointestinal tumors than for pancreatic NETs for both survival and risk or recurrence after LT. Selection criteria for LT are limited and include the 2007 Milan Criteria and the 2012 European Neuroendocrine Tumor Society guidelines, including: well-differentiated NET (Ki-67 <10 %), age <55 years, absence of extrahepatic disease, primary tumor removed before transplantation, stable disease for at least 6 months before LT, and <50 % liver involvement.

Conclusions

LT might be considered in carefully selected patients. The risk of tumor recurrence remains a significant clinical problem after LT, but data focused on immunosuppression issue are lacking, and there are no currently approved strategies for prevention of recurrence or follow-up protocols. Further studies are needed to define universally accepted inclusion criteria, reliable predictors of better outcome, and optimal timing for LT.     

Malignant bone tumors of the hand

Primary malignant tumors of the bone are among the most rare tissue type and more rare in the acral parts. The authors recommend the use of the Musculoskeletal Tumor Society Grading System for standardization of these rare tumors in the hand.     

Functional outcome of endoprosthetic proximal femoral replacement

Endoprosthetic proximal femur replacement is a well-accepted method for treatment of primary bone tumors; however the functional results of treatment are not well documented. To evaluate functional outcomes, we recorded the Toronto Extremity Salvage Score and Musculoskeletal Tumor Society 1987 and 1993 scores in 29 patients, and also recorded Musculoskeletal Tumor Society scores alone in four more patients treated with endoprosthetic proximal femur replacement. The mean followup was 3 years. Twelve patients had a total hip endoprosthetic proximal femur replacement, and 21 had a bipolar hip endoprosthetic proximal femur replacement. In nine patients, the greater trochanter was attached to the femoral prosthesis. Sixteen patients had an abductor soft tissue repair, and in eight patients, no abductor repair was possible. The mean Musculoskeletal Tumor Society 1987 score was 23.2 +/- 4.1 points of 35 points. The mean Musculoskeletal Tumor Society 1993 score was 67.7 +/- 12.0%. The Toronto Extremity Salvage Score mean was 76.2 +/- 16.2 points of 100 points. Functional scores did not differ significantly between abductor repair types. There was a trend toward less disability in patients with abductor soft tissue repair compared with patients with no abductor repair. Functional results were similar in patients receiving bipolar and total hip replacements.