Grade 3 Neuroendocrine Tumor (G3 NET) in a Background of Multiple Serotonin Cell Neoplasms of the Ileum Associated with Carcinoid Syndrome and Aggressive Behavior

Grade 3 well-differentiated neuroendocrine tumors (G3 NETs) have been characterized in the pancreas and stomach and distinguished from low-to-intermediate grade (G1–G2) NETs, as well as from highly malignant, poorly differentiated neuroendocrine carcinomas (NECs). Up to now, no G3 NET has been thoroughly described in the distal small intestine. We herein report a case of a 61-year-old man presenting with carcinoid syndrome. The surgical specimen showed, in a background of small G1 ileal NETs, a larger, grade 3 NET, which retained the nesting pattern and the expression of serotonin, chromogranin-A, and type 2A somatostatin receptors, typical of well-differentiated jejuno-ileal NETs. The patient had G3 NET metastasis to the liver and he died 14 months after surgery, due to deterioration in his clinical conditions.     

Recent updates on grading and classification of neuroendocrine tumors

Neuroendocrine tumors (NETs) are originating from neuroendocrine cells in diffuse endocrine systems. NETs are diagnosed by characteristic histologic features and immunoprofiles. Recent 2010 WHO classification for gastroenteropancreatic NETs introduced grading system based on mitotic count and Ki-67 proliferation index. Gastroenteropancreatic NETs are classified as NET grade 1, NET grade 2, and neuroendocrine carcinoma (NET grade 3). However, the carcinoid is still used in classification of NETs of the lung and uterine cervix. Some issues with grading system such as methodologies for evaluation of Ki-67 index and subclassification of neuroendocrine carcinoma (NET grade 3) are arising. The importance of Ki-67 labeling index is emerging in differential diagnosis of lung carcinoids. In this review, we focus on recent grading and classification of NETs and related issues in various organs, including gastrointestinal tract, pancreas, lung, and female reproductive organs.     

The first experience of robot assisted spleen-preserving laparoscopic distal pancreatectomy in Korea

Spleen-preservation has recently been emphasized in benign and borderline malignant pancreatic diseases requiring distal pancreatectomy. Reports to suggest that laparoscopic distal pancreatectomy is feasible and safe have been increasingly published. Robotic surgical system has been introduced and is expected to provide unique advantages in laparoscopic surgery. However, robot-assisted pancreatic surgery has not yet been performed by many surgeons. A 45-year-old female patient with abdominal discomfort was found to have pancreatic cyst in the body of the pancreas. Mucinous cystic tumor of the pancreas was the most favourable preoperative diagnosis. She underwent spleen-preserving laparoscopic distal pancreatectomy by using da Vinci surgical robot system. Splenic artery and vein were so tightly adherent to the pancreatic cyst that segmental resection of splenic vessels was required. Postoperative course was uneventful. She was able to come home in 5 days after surgery. Postoperative follow up color doppler ultrasound scan, taken on 2 weeks after surgery, showed minimal fluid collection around surgical field and no evidence of splenic infarction with good preservation of splenic perfusion. Robot-assisted spleen preserving distal pancreatectomy is thought to be feasible and safe. Several unique advantages of robotic system are expected to enhance safer and more precise surgical performance in near future. More experiences are mandatory to confirm real benefit of robot surgery in pancreatic disease.     

TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system

The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor-node-metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients.     

加速康复外科促进机器人腹腔镜胰岛素瘤摘除术术后的康复

目的比较加速康复外科(ERAS)对机器人腹腔镜胰岛素瘤摘除术术后恢复的影响。方法收集北京协和医院2013年1月至2016年3月行该手术患者的临床麻醉资料,比较在2015年采用ERAS策略前后两组患者(常规组和ERAS组)的术后恢复情况。结果68例患者纳入研究,肥胖率为69.1%。ERAS组的术中输液量较常规组明显减少(P<0.05),尿量无差异;ERAS组气道峰压最高值低于常规组(P<0.05);ERAS组的术后住院时间短于常规组(P<0.05),ERAS组术后并发症少见。结论机器人腹腔镜胰岛素瘤患者采用ERAS策略可以缩短术后住院时间,有减少术后并发症的趋势。     

腹腔镜下远端胃癌根治术中胃背系膜及系膜间隙的解剖形态特点

目的:探讨腹腔镜胃癌根治术中相关系膜及系膜间隙的镜下解剖学特点,为腹腔镜下解剖定位和操作入路提供解剖学依据。方法:通过大体解剖观察并在腹腔镜下于新鲜尸体标本上模拟进展期胃癌根治术,对胚胎期胃背系膜形成的胰腺筋膜、胃脾韧带和腹后壁筋膜间隙在腹腔镜下的解剖层次和形态特点进行观察和描述。结果:胃背系膜后层衍化形成的胃脾韧带、胰腺筋膜、胰十二指肠筋膜和横结肠系膜前叶是相互延续的一个整体;胰腺前筋膜形成的胃胰襞和肝胰襞是镜下确定胃左血管根部和肝总动脉的解剖标志;胰腺后筋膜与肾前筋膜之间的融合筋膜间隙是进行胰后淋巴结清扫的安全平面,而肾前筋膜是确保安全操作平面的后界。结论:(1)胚胎时期由于肠管旋转形成胃周广泛存在的筋膜和筋膜间隙,是腹腔镜胃癌根治术中进行解剖定位、系膜游离和淋巴结清扫的关键;(2)循筋膜间隙进行分离有助于提高腹腔镜下操作的安全性和根治的彻底性;建立腹腔镜下筋膜层次解剖的整体观念可为腹腔镜手术的设计和规范提供形态学依据。     

The Role of Robotic Surgery for Rectal Cancer: Overcoming Technical Challenges in Laparoscopic Surgery by Advanced Techniques

The conventional laparoscopic approach to rectal surgery has several limitations, and therefore many colorectal surgeons have great expectations for the robotic surgical system as an alternative modality in overcoming challenges of laparoscopic surgery and thus enhancing oncologic and functional outcomes. This review explores the possibility of robotic surgery as an alternative approach in laparoscopic surgery for rectal cancer. The da Vinci® Surgical System was developed specifically to compensate for the technical limitations of laparoscopic instruments in rectal surgery. The robotic rectal surgery is associated with comparable or better oncologic and pathologic outcomes, as well as low morbidity and mortality. The robotic surgery is generally easier to learn than laparoscopic surgery, improving the probability of autonomic nerve preservation and genitourinary function recovery. Furthermore, in very complex procedures such as intersphincteric dissections and transabdominal transections of the levator muscle, the robotic approach is associated with increased performance and safety compared to laparoscopic surgery. The robotic surgery for rectal cancer is an advanced technique that may resolve the issues associated with laparoscopic surgery. However, high cost of robotic surgery must be addressed before it can become the new standard treatment.

Graphical Abstract

相似文献   

Neutrophil proteases degrade autoepitopes of NET-associated proteins

Neutrophils can form neutrophil extracellular traps (NETs) to capture microbes and facilitate their clearance. NETs consist of decondensed chromatin decorated with anti-microbial proteins. Here, we describe the effect of neutrophil proteases on the protein content of NETs. We show that the neutrophil serine proteases degrade several neutrophil proteins associated with NETs. Interestingly, the anti-bacterial proteins associated with NETs, such as myeloperoxidase, calgranulin B and neutrophil elastase (NE), seem to be less susceptible to proteolytic degradation than other NET proteins, such as actin and MNDA. NETs have been proposed to play a role in autoimmune reactions. Our data demonstrate that a large number of the autoepitopes of NET proteins that are recognized by autoantibodies produced by systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients are also removed by the proteases. In conclusion, neutrophil serine proteases have a major impact on the NET proteome and the proteolytic changes of NET-associated proteins may counteract autoimmune reactions to NET components.     

Comparison of efficacy of enucleation and pancreaticoduodenectomy for small (<3 cm) branch duct type intraductal papillary mucinous neoplasm located at the head of pancreas and the uncinate process

Purpose

Accurate indications and the extent of surgery for branch duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas are still debatable. In particular, small tumor is located at the head portion of pancreas presents a dilemma. The purpose of this study is to compare the efficacy of enucleation (EN) with that of pancreaticoduodenectomy (PD) in patients with small (2 cmMaterials and MethodsAmong 155 patients who underwent pancreatic surgery due to pancreatic cystic tumors between January 2000 and December 2007 at Yonsei University Health System in Seoul, Korea, 14 patients with small (2 cmp-values less than 0.05 were considered significant.

Results

The average age was 62.21 years (±6.71 years) and consisted of 8 men and 6 women. The mean operation time and blood loss were significantly lower in EN group. There were no significant differences in other surgical morbidities.

Conclusion

The result suggests that enucleation for small branch duct IPMN located at the head of pancreas or uncinate process is feasible and as safe as PD, despite a high rate of minor complications.     

Solid pseudopapillary tumor: an invasive case report of primary ovarian origin and review of the literature

Solid pseudopapillary neoplasm occurring as a primary tumor outside the pancreas is a rare event. We report a case of an ovarian primary occurring with an ill-defined cystic mass in a 39-year-old woman. The morphologic and immunohistochemical features of the ovarian neoplasm described in this report are compatible with those of solid pseudopapillary neoplasm of the pancreas. Histologically, the tumor cells of the case we report infiltrate into the ovarian parenchyma. Because of the diagnosis is not clear before surgery, the patient had a reoccurrence two months after the operation in which laparoscopic simple ovarian cystectomy and part ovarian tissue removal, followed by the right salpingo-oophorectomy. The case herein confirms that solid pseudopapillary neoplasm of the ovary belongs to the class of low-grade malignant tumor with certain invasiveness. The diagnosis should be taken into serious consideration in order to avoid missed diagnosis and delay treatment. Through this case we have a better understanding of the biological behavior of solid pseudopapillary neoplasm of the ovary.     

PCSK2 expression in neuroendocrine tumors points to a midgut,pulmonary, or pheochromocytoma–paraganglioma origin

Neuroendocrine tumors (NETs) are often diagnosed from the metastases of an unknown primary tumor. Specific immunohistochemical (IHC) markers indicating the location of a primary tumor are needed. The proprotein convertase subtilisin/kexin type 2 (PCSK2) is found in normal neural and neuroendocrine cells, and known to express in NETs. We investigated the tissue microarray (TMA) of 86 primary tumors from 13 different organs and 9 metastatic NETs, including primary tumor-metastasis pairs, for PCSK2 expression with polymer-based IHC. PCSK2 was strongly positive in all small intestine and appendiceal NETs, the so-called midgut NETs, in most pheochromocytomas and paragangliomas, and in some of the typical and atypical pulmonary carcinoid tumors. NETs showing strong positivity were re-evaluated in larger tumor cohorts confirming the primary observation. In the metastases, the expression of PCSK2 mirrored that of the corresponding primary tumors. We found negative or weak staining in NETs from the thymus, gastric mucosa, pancreas, rectum, thyroid, and parathyroid. PCSK2 expression did not correlate with Ki-67 in well-differentiated NETs. Our data suggest that PCSK2 positivity can indicate the location of the primary tumor. Thus, PCSK2 could function in the IHC panel determined from screening metastatic NET biopsies of unknown primary origins.     

Establishment and Characterization of a Human Neuroendocrine Tumor Xenograft

Neuroendocrine tumors (NETs) are increasing in incidence yet the cause of these tumors remains unknown. Familial associations have shed light on the genetic basis of some of these tumors, but sporadic tumors seem to have primarily epigenetic dysregulation. The rarity of cell lines and animal models has been a barrier to studies of treatment modalities. We set out to develop a xenograft model of gastrointestinal NETs. Primary human NETs were collected at the time of surgery under sterile conditions and xenografted into the flanks of immunodeficient mice. Tumor growth was measured and when tumors reached 1500 mm³, they were excised and half was re-xenografted through multiple generations. The other half was bisected; a part was frozen and a part was fixed for morphologic and immunohistochemical characterization as well as molecular validation of fidelity of a successful xenograft. Of 106 human NETs, seven were successfully engrafted of which only one tumor was successfully propagated for eight passages. Two years later, the tumor retains its neuroendocrine features and similarity to the original primary human tumor. It has retained expression of keratin as well as chromogranin A reactivity. The establishment of a NET xenograft provides a model for further study of the biological behavior of these tumors and can be used to examine the in vivo effects of various medical and targeted radiotherapeutic agents on tumor growth.     

中性粒细胞胞外诱捕网及其在相关疾病中的作用

中性粒细胞胞外诱捕网(NETs)是由激活的中性粒细胞释放到胞外的一种网状结构,不但可以包裹病原体,也具有很强的细胞毒性,与多种疾病的发病及进展密切相关.随着近年来对其代谢过程和影响因素的研究逐渐深入,NETs有望成为多种疾病诊断和治疗的新靶点.     

Surgical management of pancreatico-duodenal tumors in multiple endocrine neoplasia syndrome type 1

Pancreatico-duodenal tumors are the second most common endocrinopathy in multiple endocrine neoplasia syndrome type 1, and have a pronounced effect on life expectancy as the principal cause of disease-related death. Previous discussions about surgical management have focused mainly on syndromes of hormone excess and, in particular, the management of multiple endocrine neoplasia syndrome type 1-related Zollinger-Ellison syndrome. Since hormonal syndromes tend to occur late and indicate the presence of metastases, screening with biochemical markers and endoscopic ultrasound is recommended for early detection of pancreatico-duodenal tumors, and with early surgery before metastases have developed. Surgery is recommended in patients with or without hormonal syndromes in the absence of disseminated liver metastases. The suggested operation includes distal 80% subtotal pancreatic resection together with enucleation of tumors in the head of the pancreas, and in cases with Zollinger-Ellison syndrome, excision of duodenal gastrinomas together with clearance of regional lymph node metastases. This strategy, with early and aggressive surgery before metastases have developed, is believed to reduce the risks for tumor recurrence and malignant progression.     

腹腔镜下手术治疗卵巢巧克力囊肿研究

腹腔镜手术近年来已经成为临床妇科手术治疗的一个重要的发展方向,传统的手术治疗模式正在被其逐步的取代。与临床以往应用的传统开腹手术方式相比较,腹腔镜手术主要具有对机体造成创伤,术后的恢复速度快,不会对美观造成妨碍等几大基本的优点,目前在临床上已经成为对妇科疾病特别是卵巢囊肿进行治疗的首选。本文主要通过卵巢巧克力囊肿概述、腹腔镜治疗适应症、手术方式选择等几个方面,对腹腔镜下手术治疗卵巢巧克力囊肿的研究情况进行综述。     

Treatment of adnexal torsion using operative laparoscopy

The aim of this work was to clarify the value and applicationof operative laparoscopic treatment for adnexa] torsion. Weincluded in our study all patients (n = 27) who presented withan intra-operative diagnosis of torsion of the adnexa betweenJanuary 1989 and May 1995. A total of 28 adnexal torsions weretreated. Treatment was carried out by laparoscopic surgery in75% of cases (21 torsions); in one-half of the cases (14 torsions)it was possible to achieve conservative laparoscopic treatmentThe nature of the lesions and the experience of the surgeonsare two factors which closely govern the outcome of surgicaltreatment For those patients presenting a benign pathology,laparoscopic surgery was used to treat 84% of cases in the series.All the patients presenting a benign pathology and operatedupon since 1993 have received laparoscopic surgical treatmentNo major complications (peritonitis, thrombotic emboli, coagulationproblems) were observed after conservative laparoscopic surgery.These results demonstrate that, provided the surgeons are sufficientlyexperienced, treatment by conservative laparoscopic surgeryfor adnexal torsion is both safe and reliable. In the yearsto come more work must be done to assess the vitality of theadnexa so that as many patients as possible can benefit fromconservative treatment.     

Lymphovascular invasion as a prognostic value in small rectal neuroendocrine tumor treated by local excision: A systematic review and meta-analysis

Because rectal neuroendocrine tumors (NETs) are usually small-sized despite of malignant potential, endoscopic resection techniques are recommended. It is unclear whether the lymphovascular invasion (LVI) in the endoscopic resected specimens of small rectal NETs should be indicated for completion surgery. We performed a systematic review and meta-analysis for the incidence of LVI in small rectal NETs (≤20 mm) treated by endoscopic resection and its prognostic impacts.We searched the relevant literature published before January 2019. A total of 21 publications including 1816 patients were enrolled.Overall prevalence of LVI in small rectal NETs was 21.8%. Immunohistochemical method significantly increased the detection rate of LVI up to 35.8% compared than H&E staining only (13.2%). Tumor size more than 5 mm was a risk factor for LVI in small rectal NET, whereas tumor grade did not influence the risk. The LVI in the endoscopic resected specimens was a risk factor for subsequent lymph node metastasis. Separately analyzed in detail, the vascular invasion had a stronger impact on lymph node metastasis than the lymphatic invasion. The prognosis of endoscopically treated rectal NET with LVI was excellent with only 0.3% of recurrence rate during the 5-year follow-up period.LVI is highly prevalent and a risk factor for lymph node metastasis in the small rectal NETs. Endoscopically treated small rectal NETs had excellent short-term prognoses despite of LVI. Immediate completion radical surgery is not absolutely necessary for the LVI-positive small rectal NETs. However, long-term follow-up is recommended for any delayed recurrence.     

吲哚菁绿荧光成像技术在胆道外科的应用进展

吲哚菁绿（ICG）荧光成像技术在胆道外科的临床应用逐渐凸显其作用。ICG荧光胆道成像在腹腔镜胆囊切除术、腹腔镜胆总管探查再次手术和肝胆管结石、肝内胆管癌、肝门部胆管癌、胆囊癌等胆道外科疾病行肝切除术,以及淋巴结清扫手术、肝移植术和防治胆管损伤、胆漏等方面均具有积极作用。本文主要阐述ICG荧光成像在上述胆道外科的应用进展。     

Neuroendokrine Neoplasien der Appendix und des Kolorektums

Appropriate diagnosis and treatment of neuroendocrine neoplasms (NENs) of the appendix and colorectum requires a detailed knowledge of their proper classification according to the updated WHO and TNM systems. The WHO classification distinguishes well differentiated NEN, the neuroendocrine tumors (G1 and G2 NETs), from the poorly differentiated carcinomas (G3 NECs). While NETs are common in the appendix and rectum, NECs occur predominantly in the colon. G1 appendiceal and rectal NETs of 1?cm in size or below that do not invade either the muscular wall or vessels bear almost no metastatic risk and can be treated by appendectomy or endoscopic resection. G2 appendiceal and rectal NETs larger than 1?cm in size in combination with other risk factors have an increased risk of metastasis and need to be treated more aggressively. NECs of the colon usually require chemotherapy in addition to resection. Today, most patients with NETs of the appendix and rectum have an excellent prognosis when these diagnostic and therapeutic guidelines are borne in mind.