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Upfront surgery of small intestinal neuroendocrine tumors. Time to reconsider?

World Journal of Gastroenterology 2018年第29期24卷 3201-3203页

作者： Kosmas Daskalakis apostolos V tsolakis Department of Surgical Sciences Uppsala University Department of Oncology and Pathology Karolinska Institute Cancer Center Karolinska Karolinska University Hospital Solna R8:04 Department of Gastrointestinal Endoscopy Karolinska University Hospital Huddinge

Small intestinal neuroendocrine tumors(SI-NETs) may demonstrate a widely variable clinical behavior but usually it is indolent. In cases with localized disease, locoregional resective surgery(LRS) is generally indicated with a curative intent. LRS of SI-NETs is also the recommended treatment when symptoms are present, regardless of the disease stage. Concerning asymptomatic patients with distant metastases, prophylactic LRS has been traditionally suggested to avoid possible future complications. Even the current European Neuroendocrine Tumor Society guidelines emphasize a possible effect of LRS in Stage IV SINETs with unresectable liver metastases. On the contrary, the 2017 National Comprehensive Cancer Network Guidelines on carcinoid tumors do not support the resection of a small, asymptomatic, relatively stable primary tumor in the presence of unresectable metastatic disease. Furthermore, a recent study revealed no survival advantage for asymptomatic patients with distant-stage disease who underwent upfront LRS. At the aforementioned paper, it was suggested that delayed surgery as needed was comparable with the upfront surgical approach in terms of postoperative morbidity and mortality, the length of the hospital stay and the rate of incisional hernia repairs but was associated with fewer reoperations for bowel obstruction. On the other hand, it is also important to note that some patients might benefit from a prophylactic surgical approach and our attention should focus on identifying this patient population.

关键词： Small intestinal neuroendocrine tumors Locoregional resective surgery

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Gastric carcinoid in a patient infected with Helicobacter pylori:A new entity?

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World Journal of Gastroenterology 2011年第25期17卷 3066-3068页

作者： Pantelis Antonodimitrakis apostolos tsolakis Staffan Welin Gordana Kozlovacki Kjell berg Dan Granberg Department of Medical Sciences Division of Endocrine OncologyUniversity Hospital of Uppsala

There are four types of gastric carcinoid tumors,classified according to their histology and malignant *** a few cases of carcinoid tumors in patients infected with Helicobacter pylori (***) have been reported so *** report a patient infected with *** presenting with a small solitary gastric carcinoid tumor with very low proliferative rate and normal gastrin *** tumor was endoscopically removed and the patient received an eradication therapy against *** signs of metastatic disease have been found so far during more than 3 year of *** with *** may cause chronic gastritis with normal or elevated gastrin levels,leading to the development of gastric carcinoids by mechanisms unrelated to ***-like cell tumors related to a chronic *** infection may be considered as a distinct type of gastric carcinoid tumors.

关键词：幽门螺旋杆菌胃泌素感染幽门螺杆菌癌实体慢性胃炎嗜铬细胞瘤

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Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis

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World Journal of Gastroenterology 2019年第35期25卷 5376-5387页

作者： apostolos V tsolakis Athanasia Ragkousi Miroslav Vujasinovic Gregory Kaltsas Kosmas Daskalakis Department of Oncology and Pathology Karolinska Institute Stockholm 17177 Sweden Cancer Centre Karolinska CCK Karolinska University Hospital Stockholm 17176 Sweden 1st Department of Propaupedic Internal Medicine Endocrine Oncology Unit Laiko Hospital National and Kapodistrian University of Athens Athens 11527 Greece Department of Digestive Diseases Karolinska University Hospital Stockholm 14186 Sweden Department of Surgical Sciences Uppsala University Uppsala 75185 Sweden

BACKGROUND To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated. AIM To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters. METHODS The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis. RESULTS We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3%(25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8;heterogeneity: P = 0.126;I2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2;95%CI: 1.8-161.1;heterogeneity: P = 0.165;I2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2;95%CI: 0.3-11.6;heterogeneity: P = 0.304;I2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3;95%CI: 0.1-1.1;heterogeneity: P = 0.173;I2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively. CONCLUSION This meta-analysis confirms that tumor size ≥ 10 mm and invasio

关键词： Gastric neuroendocrine neoplasms type 1 Meta-analysis Lymph node metastasis Tumor size Invasion Endoscopy Surgery

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Chronic pancreatitis and the heart disease:Still terra incognita?

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World Journal of Gastroenterology 2019年第44期25卷 6561-6570页

作者： Sara Nikolic Ana Dugic Corinna Steiner apostolos V tsolakis Ida Marie Haugen Lofman J-Matthias Lohr Miroslav Vujasinovic Department of Medicine Huddinge Karolinska InstituteStockholm 14183Sweden Department of Gastroenterology Division of Internal MedicineUniversity Medical Centre MariborMaribor 2000Slovenia Department of Medicine Klinikum BayreuthBayreuth 95445Germany Department for Digestive Diseases Karolinska University HospitalStockholm 14186Sweden Department of Oncology and Pathology Karolinska InstituteStockholm 17176Sweden Cancer Centre Karolinska CCKKarolinska University HospitalStockholm 17176Sweden Unit of Cardiology Heart and Vascular ThemeKarolinska University Hospital HuddingeStockholm 14186Sweden Department of Medicine Solna Karolinska InstituteStockholm 17176Sweden Department of Clinical Science Interventionand Technology(CLINTEC)Karolinska InstituteStockholm 17176Sweden

BACKGROUND It has been suggested that chronic pancreatitis(CP)may be an independent risk factor for development of cardiovascular disease(CVD).At the same time,it seems that congestive heart failure(CHF)and CP share the responsibility for the development of important clinical conditions such as sarcopenia,cachexia and malnutrition due to development of cardiac cachexia and pancreatic exocrine insufficiency(PEI),*** To explore the evidence regarding the association of CP and heart disease,more specifically CVD and *** A systematic search of MEDLINE,Web of Science and Google Scholar was performed by two independent investigators to identify eligible studies where the connection between CP and CVD was *** search was limited to articles in the English *** last search was run on the 1st of May *** primary outcomes were:(1)Incidence of cardiovascular event[acute coronary syndrome(ACS),chronic coronary disease,peripheral arterial lesions]in patients with established CP;and(2)Incidence of PEI in patients with *** Out of 1166 studies,only 8 were eligible for this *** regarding PEI and CHF showed an important incidence of PEI as well as associated malabsorption of nutritional markers(vitamin D,selenium,phosphorus,zinc,folic acid,and prealbumin)in patients with ***,after substitution of pancreatic enzymes,it seems that,at least,loss of appetite was *** the other side,studies investigating cardiovascular events in patients with CP showed that,in CP cohort,there was a 2.5-fold higher incidence of *** another study,patients with alcohol–induced CP with concomitant type 3c diabetes had statistically significant higher incidence of carotid atherosclerotic plaques in comparison to patients with diabetes mellitus of other *** studies demonstrated a marked correlation between the clinical symptoms in CP and chronic coronary ***,statistically significant higher incidenc

关键词： Chronic Pancreatitis Pancreatic exocrine insufficiency Heart failure Cardiovascular diseases

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Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours

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World Journal of Gastroenterology 2015年第47期21卷 13240-13249页

作者： apostolos V tsolakis Lars Grimelius Göran Granerus Mats Stridsberg Sture E Falkmer Eva T Janson Section of Endocrine Oncology Department of Medical SciencesUppsala University Section of Genetics and Pathology Department of ImmunologyUppsala University Department of Medical and Health Sciences Linköping University Section of Biochemical Endocrinology Department of Medical SciencesUppsala University Department of Pathology Ryhov County Hospital

AIM: To study histidine decarboxylase(HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus(n = 3) and corpus(n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours(GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2(VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid(U-Me Im AA) was determined using highperformance liquid chromatography in 27 of the 64 ***: In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cellpopulation co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-Me Im AA excretion was detected, but only two of the patients exhibited related endocrine symptoms. CONCLUSION: Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Coexpression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.

关键词： Enterochromaffin-like cells High performance liquid chromatography Gastric neuroendocrine tumours Histidine decarboxylase Immunohistochemistry Urinary excretion of the main histamine metabolite methylimidazoleacetic acid Vesicular monoamine transporter 2

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Metastatic type 1 gastric carcinoid:A real threat or just a myth?

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World Journal of Gastroenterology 2013年第46期19卷 8687-8695页

作者： Simona Grozinsky-Glasberg Dimitrios Thomas Jonathan R Strosberg Ulrich-Frank Pape Stephan Felder apostolos V tsolakis Krystallenia I Alexandraki Merav Fraenkel Leonard Saiegh Petachia Reissman Gregory Kaltsas David J Gross Neuroendocrine Tumor Unit Endocrinology and Metabolism ServiceDepartment of MedicineHadassah-Hebrew University Medical Center Endocrine Unit Department of PathophysiologyNational University of Athens Moffitt Cancer Center Tampa Department of Internal Medicine Division of HepatologyGastroenterologyEndocrinology and MetabolismCharité Universit tsmedizin Department of Medical Sciences Section of Endocrine OncologyUppsala University Institute of Endocrinology Soroka Ben Gurion University Hospital Department of Surgery Shaare-Zedek Medical CenterThe Hebrew University School of Medicine

AIM:To describe disease characteristics and treatment modalities in a group of rare patients with metastatic gastric carcinoid type 1(GCA1).METHODS:Information on clinical,biochemical,radiological,histopathological findings,the extent of the disease,as well as the use of different therapeutic modalities and the long-term outcome were ***’data were assessed at presentation,and thereafter at 6 to 12 monthly intervals both clinically and biochemically,but also endoscopically and *** were evaluated for the presence of specific symptoms;the presence of autoimmune disorders and the presence of other gastrointestinal malignancies in other family members were also *** evaluation of response to treatment was defined using established WHO ***:We studied twenty consecutive patients with a mean age of 55.1 *** mean follow-up period was 83 *** patients had regional lymph node metastases and 8 patients had liver *** primary tumor mean diameter was 20.13±10.83mm(mean±SD).The mean Ki-67 index was 6.8%±11.2%.All but one patient underwent endoscopic or surgical excision of the *** disease was stable in all but 3 patients who had progressive liver *** patients remained alive during the follow-up ***:Metastatic GCA1 carries a good overall prognosis,being related to a tumor size of≥1 cm,an elevated Ki-67 index and high serum gastrin levels.

关键词： Metastatic gastric carcinoids Gastrin Chro-mogranin A Somatostatin analogues Stomach neuro-endocrine tumor

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Obstructive ileus due to a giant fibroepithelial polyp of the anus

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World Journal of Gastroenterology 2009年第29期15卷 3687-3690页

作者： Ioannis Galanis Dimitrios Dragoumis Michail tsolakis Konstantinos Zarampoukas Thomas Zarampoukas Konstantinos Atmatzidis 2nd Surgical Clinic Aristotle University of Thessaloniki "G. Gennimatas" District Hospital Ethnikis Aminis 41 Thessaloniki 54 635 Greece

Fibroepithelial polyps or hypertrophied anal papillae are essentially skin tags that project up from the dentate line and the junction between the skin and the epithelial lining of the anus. They are usually small in size, but sometimes they become enlarged, causing unexpected medical conditions. An extremely rare case of a giant hypertrophied anal papilla complicated by obstructive ileus is reported. Fibroepithelial anal polyp, despite its size, should be included in the differential diagnosis of a smooth mass located near the anal verge, especially in a patient with a history of chronic anal irritation or infection.

关键词：纤维上皮息肉肛门皮肤治疗方法

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外周动脉闭塞患者的交感神经皮肤反应

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世界核心医学期刊文摘（神经病学分册） 2006年第6期2卷 25-26页

作者： Argyriou A.A. tsolakis I. Papadoulas S. E. Chroni 袁海峰 Laboratory of Clinical Neurophysiology Department of Neurology University of Patras Medical School P.O. Box 1045 26504 Rion-Patras Greece

Objective: The current study aimed to assess the viability of sympathetic sudomotor fibers in patients suffering from mild peripheral arterial occlusive disease (PAD). Methods: Sympathetic skin response (SSR) from the hand (electrical stimulation) and sole (electrical and magnetic stimulation) of 25 patients with PAD (19 males and 6 females with mean age 62.7±10.2 years) was recorded unilaterally depending on the side of the affected limb (18 right side, 7 left side). Electrophysiological data were also collected and correlated with the SSR results. Twenty-five, age-and gender-matched healthy volunteers served as controls. Results: No evidence of nerve conduction abnormalities was recorded from the group of patients. Intact SSR recordings were obtained from the upper limb of patients. Nine patients (36%) had absent SSR in the lower limb following electrical stimulation, whilst the same 9 patients had absent SSR following magnetic stimulation. Significant differences occurred between groups in the SSR latency scores recorded from the lower limb. Following electrical stimulation the mean SSR latency in patients was significantly prolonged, compared to that of controls (P=0.000), whilst the same applied following magnetic stimulation (P=0.000). There was no correlation between SSR abnormalities and nerve conduction measurements. The manifestation of intermittent claudication at a walking distance of 250 m was strongly correlated w ith absent lower limb SSR (r=0.71, P=0.035). Conclusions: SSR abnormalities appe ared to be an early and independent finding of neural impairment in our patients . Significance: SSR study, performed at an early stage of PAD may prove useful i n differentiating PAD-induced neuropathy from other neuropathic processes.

关键词：交感神经皮肤反应外周动脉闭塞 AD患者交感神经纤维传导异常神经传导检测神经系统损害病程早期电生理资料

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颈动脉内膜剥离术对经颅磁刺激所致运动诱发电位的影响

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世界核心医学期刊文摘(神经病学分册) 2006年第1期 19-20页

作者： Katsoulas G. tsolakis I. Argyriou A.A. E. Chroni 李一明 Dept. of Neurology University of Patras Medical School P. O. Box 1045 26504 Rion Greece

Purpose: To investigate the within 3 days effects of carotid endarterectomy (CEA) on functional status of the central motor system in patients with carotid stenosis by means of transcranial magnetic stimulation (TMS). Patients and method: We studied 30 consecutive patients, 20 males and 10 females with a mean age of 69.2 ±7.1 years, who underwent CEA for symptomatic carotid stenosis. All patients had suffered an ischemic attack 6 months prior to the operation. Two TMS studies, one before and one shortly after CEA were performed on both sides in each of the patients. Resting motor threshold, motor evoked potentials (MEP) amplitude at rest, MEP latency at rest and during contraction and silent period duration (SPD) were recorded and analyzed. Two groups of data were collected. Group 1 consisted of data from the operated side in all 30 patients. Group 2 consisted of data from the contralateral side and served as a control. Results: Motor resting thresholds were similar in the two groups. Intragroup pre and post CEA comparisons showed no difference in the operated group and significant increased threshold after CEA on the non-operated side. There was no significant difference of TMS intensity for maximal MEP in either side before or after CEA. Latency at rest and during voluntary contraction and amplitude at rest showed no significant differences between or within groups’comparisons. In group 1 SPD showed a statistically significant increase after CEA as opposed to baseline. In group 2 SPD showed a non significant increase after CEA. Conclusion: In the absence of other MEP changes, our finding of prolonged SPD post-operativ-ely suggests preferential influence of the inhibitory cortical circuits. The potential favorable effect of CEA in patients with hyperexcitability such as disabling spasticity after stroke should be further studied.

关键词：颈动脉内膜磁刺激经颅诱发电位剥离术

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