Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment o...Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.展开更多
Recent progress in the treatment of Alzheimer’s disease(AD)using antibodies against amyloid sustains amyloid generation as a key process in AD.Amyloid formation starts with two amyloidbeta(Aβ)molecules interacting(d...Recent progress in the treatment of Alzheimer’s disease(AD)using antibodies against amyloid sustains amyloid generation as a key process in AD.Amyloid formation starts with two amyloidbeta(Aβ)molecules interacting(dimer formation)followed by an accelerating build-up of socalled protofibrils,which turn into fibrils,which accumulate in the characteristic plaques.展开更多
Objective We aimed to compare perioperative and oncologic outcomes for patients undergoing robotic-assisted radical cystectomy(RARC)with intracorporeal ileal conduit(IC)and neobladder(NB)urinary diversion.Methods Pati...Objective We aimed to compare perioperative and oncologic outcomes for patients undergoing robotic-assisted radical cystectomy(RARC)with intracorporeal ileal conduit(IC)and neobladder(NB)urinary diversion.Methods Patients undergoing RARC with intracorporeal urinary diversion between January 2017 and January 2022 at the Icahn School of Medicine at Mount Sinai,New York,NY,USA were indexed.Baseline demographics,clinical characteristics,perioperative,and oncologic outcomes were analyzed.Survival was estimated with Kaplan-Meier plots.Results Of 261 patients(206[78.9%]male),190(72.8%)received IC while 71(27.2%)received NB diversion.Median age was greater in the IC group(71[interquartile range,IQR 65-78]years vs.64[IQR 59-67]years,p<0.001)and BMI was 26.6(IQR 23.2-30.4)kg/m^(2).IC group was more likely to have prior abdominal or pelvic radiation(15.8%vs.2.8%,p=0.014).American Association of Anesthesiologists scores were comparable between groups.The IC group had a higher proportion of patients with pathological tumor stage 2(pT2)tumors(34[17.9%]vs.10[14.1%],p=0.008)and pathological node stages pN2-N3(28[14.7%]vs.3[4.2%],p<0.001).The IC group had less median operative time(272[IQR 246-306]min vs.341[IQR 303-378]min,p<0.001)and estimated blood loss(250[150-500]mL vs.325[200-575]mL,p=0.002).Thirty-and 90-day complication rates were 44.4%and 50.2%,respectively,and comparable between groups.Clavien-Dindo grades 3-5 complications occurred in 27(10.3%)and 34(13.0%)patients within 30 and 90 days,respectively,with comparable rates between groups.Median follow-up was 324(IQR 167-552)days,and comparable between groups.Kaplan-Meier estimate for overall survival at 24 months was 89%for the IC cohort and 93%for the NB cohort(hazard ratio 1.23,95%confidence interval 1.05-2.42,p=0.02).Kaplan-Meier estimate for recurrence-free survival at 24 months was 74%for IC and 87%for NB(hazard ratio 1.81,95%confidence interval 0.82-4.04,p=0.10).Conclusion Patients undergoing intracorporeal IC urinary diversion had higher postoperative cancer stage,increased nodal involvement,similar complications outcomes,decreased overall survival,and similar recurrence-free survival compared to patients undergoing RARC with intracorporeal NB urinary diversion.展开更多
Background: Emergency front-of-neck airway(eFONA) is a life-saving procedure in “cannot intubate, cannot oxygenate”(CICO). The fastest and most reliable method of eFONA has not been determined. We compared two of th...Background: Emergency front-of-neck airway(eFONA) is a life-saving procedure in “cannot intubate, cannot oxygenate”(CICO). The fastest and most reliable method of eFONA has not been determined. We compared two of the most advocated approaches: surgical cricothyroidotomy and percutaneous cricothyroidotomy, in an obese, in vivo porcine hemorrhage model, designed to introduce real-time physiological feedback, relevant and high provider stress. The primary aim was to determine the fastest method to secure airway. Secondary aims were arterial saturation and partial pressure of oxygen, proxy survival and influence of experience.Methods: Twelve pigs [(60.3±4.1) kg] were anesthetized and exposed to 25%–35% total blood volume hemorrhage before extubation and randomization to Seldinger technique “percutaneous cricothyroidotomy”(n=6) or scalpelbougie-tube technique “surgical cricothyroidotomy”(n=6). Specialists in anesthesia and intensive care in a tertiary referral hospital performed the eFONA, simulating an actual CICO-situation.Results: In surgical cricothyroidotomy vs. percutaneous cricothyroidotomy, the median(interquartile range, IQR) times to secure airway were 109(IQR 71–130) s and 298(IQR 128–360) s(P=0.0152), arterial blood saturation(SaO2) were 74.7(IQR 46.6–84.2)% and 7.9(IQR 4.1–15.6)%(P=0.0167), PaO_(2) were 7.0(IQR 4.7–7.7) kPa and 2.0(IQR 1.1–2.9) kPa(P=0.0667), and times of cardiac arrest(proxy survival) were 137–233 s, 190(IQR 143–229) s, from CICO. All six animals survived surgical cricothyroidotomy, and two of six(33%) animals survived percutaneous cricothyroidotomy. Years in anesthesia, 13.5(IQR 7.5–21.3), did not influence time to secure airway.Conclusions: eFONA by surgical cricothyroidotomy was faster and had increased oxygenation and survival, when performed under stress by board certified anesthesiologists, and may be an indication of preferred method in situations with hemorrhage and CICO, in obese patients.展开更多
AIM:To assess gallbladder emptying and its association with cholecystitis and abdominal pain in patients with primary sclerosing cholangitis(PSC).METHODS:Twenty patients with PSC and ten healthy subjects were investig...AIM:To assess gallbladder emptying and its association with cholecystitis and abdominal pain in patients with primary sclerosing cholangitis(PSC).METHODS:Twenty patients with PSC and ten healthy subjects were investigated.Gallbladder fasting volume, ejection fraction and residual volume after ingestion of a test meal were compared in patients with PSC and healthy controls using magnetic resonance imaging.Symptoms, thickness and contrast enhancement of the gallbladder wall and the presence of cystic duct strictures were also assessed.RESULTS:Median fasting gallbladder volume in patients with PSC [67(19-348) mL] was twice that in healthy controls [32(16-55) mL](P < 0.05).The median postprandial gallbladder volume in patients with PSC was signiflcantly larger than that in healthy controls(P < 0.05).There was no difference in ejection fraction, gallbladder emptying volume or mean thickness of the gallbladder wall between PSC patients and controls.Contrast enhancement of the gallbladder wall in PSC patients was higher than that in controls;(69% ± 32%) and(42% ± 21%)(P < 0.05).No significant association was found between the gallbladder volumes and occurrence of abdominal pain in patients and controls.CONCLUSION:Patients with PSC have increased fasting gallbladder volume.Gallbladder Mucosal dysfunction secondary to chronic cholecystitis, may be a possible mechanism for increased gallbladder.展开更多
Non-alcoholic fatty liver disease(NAFLD) is the mostcommon liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying de...Non-alcoholic fatty liver disease(NAFLD) is the mostcommon liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis(stage F3) and cirrhosis(stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers(e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques(transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.展开更多
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 wit...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 invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5- year disease-specific survival rates reported;hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.展开更多
基金supported by the China Scholarship Council(to YW)the Swedish Research Council,No.2018-02601(to MS)+7 种基金the Alzheimer Foundation,No.AF-980695(to MS)the Stockholm County Council,No.RS2020-0731(to MS)the Foundation of Old Servants(to MS)the Gun and Bertil Stohne Foundation(to MS)the?hlén Foundation,No.233055(to MS)The Swedish Fund for Research without Animal Experiments(to MS)the Swedish Dementia Foundation(to MS)the Brain foundation,No.FO2022-0131(to MS)。
文摘Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.
基金supported by several grant agencies as stated in the full paper(to LT)。
文摘Recent progress in the treatment of Alzheimer’s disease(AD)using antibodies against amyloid sustains amyloid generation as a key process in AD.Amyloid formation starts with two amyloidbeta(Aβ)molecules interacting(dimer formation)followed by an accelerating build-up of socalled protofibrils,which turn into fibrils,which accumulate in the characteristic plaques.
文摘Objective We aimed to compare perioperative and oncologic outcomes for patients undergoing robotic-assisted radical cystectomy(RARC)with intracorporeal ileal conduit(IC)and neobladder(NB)urinary diversion.Methods Patients undergoing RARC with intracorporeal urinary diversion between January 2017 and January 2022 at the Icahn School of Medicine at Mount Sinai,New York,NY,USA were indexed.Baseline demographics,clinical characteristics,perioperative,and oncologic outcomes were analyzed.Survival was estimated with Kaplan-Meier plots.Results Of 261 patients(206[78.9%]male),190(72.8%)received IC while 71(27.2%)received NB diversion.Median age was greater in the IC group(71[interquartile range,IQR 65-78]years vs.64[IQR 59-67]years,p<0.001)and BMI was 26.6(IQR 23.2-30.4)kg/m^(2).IC group was more likely to have prior abdominal or pelvic radiation(15.8%vs.2.8%,p=0.014).American Association of Anesthesiologists scores were comparable between groups.The IC group had a higher proportion of patients with pathological tumor stage 2(pT2)tumors(34[17.9%]vs.10[14.1%],p=0.008)and pathological node stages pN2-N3(28[14.7%]vs.3[4.2%],p<0.001).The IC group had less median operative time(272[IQR 246-306]min vs.341[IQR 303-378]min,p<0.001)and estimated blood loss(250[150-500]mL vs.325[200-575]mL,p=0.002).Thirty-and 90-day complication rates were 44.4%and 50.2%,respectively,and comparable between groups.Clavien-Dindo grades 3-5 complications occurred in 27(10.3%)and 34(13.0%)patients within 30 and 90 days,respectively,with comparable rates between groups.Median follow-up was 324(IQR 167-552)days,and comparable between groups.Kaplan-Meier estimate for overall survival at 24 months was 89%for the IC cohort and 93%for the NB cohort(hazard ratio 1.23,95%confidence interval 1.05-2.42,p=0.02).Kaplan-Meier estimate for recurrence-free survival at 24 months was 74%for IC and 87%for NB(hazard ratio 1.81,95%confidence interval 0.82-4.04,p=0.10).Conclusion Patients undergoing intracorporeal IC urinary diversion had higher postoperative cancer stage,increased nodal involvement,similar complications outcomes,decreased overall survival,and similar recurrence-free survival compared to patients undergoing RARC with intracorporeal NB urinary diversion.
文摘Background: Emergency front-of-neck airway(eFONA) is a life-saving procedure in “cannot intubate, cannot oxygenate”(CICO). The fastest and most reliable method of eFONA has not been determined. We compared two of the most advocated approaches: surgical cricothyroidotomy and percutaneous cricothyroidotomy, in an obese, in vivo porcine hemorrhage model, designed to introduce real-time physiological feedback, relevant and high provider stress. The primary aim was to determine the fastest method to secure airway. Secondary aims were arterial saturation and partial pressure of oxygen, proxy survival and influence of experience.Methods: Twelve pigs [(60.3±4.1) kg] were anesthetized and exposed to 25%–35% total blood volume hemorrhage before extubation and randomization to Seldinger technique “percutaneous cricothyroidotomy”(n=6) or scalpelbougie-tube technique “surgical cricothyroidotomy”(n=6). Specialists in anesthesia and intensive care in a tertiary referral hospital performed the eFONA, simulating an actual CICO-situation.Results: In surgical cricothyroidotomy vs. percutaneous cricothyroidotomy, the median(interquartile range, IQR) times to secure airway were 109(IQR 71–130) s and 298(IQR 128–360) s(P=0.0152), arterial blood saturation(SaO2) were 74.7(IQR 46.6–84.2)% and 7.9(IQR 4.1–15.6)%(P=0.0167), PaO_(2) were 7.0(IQR 4.7–7.7) kPa and 2.0(IQR 1.1–2.9) kPa(P=0.0667), and times of cardiac arrest(proxy survival) were 137–233 s, 190(IQR 143–229) s, from CICO. All six animals survived surgical cricothyroidotomy, and two of six(33%) animals survived percutaneous cricothyroidotomy. Years in anesthesia, 13.5(IQR 7.5–21.3), did not influence time to secure airway.Conclusions: eFONA by surgical cricothyroidotomy was faster and had increased oxygenation and survival, when performed under stress by board certified anesthesiologists, and may be an indication of preferred method in situations with hemorrhage and CICO, in obese patients.
基金CAMS Innovation Fund for Medical Sciences(2021‐I2M‐1‐017),the National Natural Science Foundation of China(81970107),State Key Laboratory of Experimental Hematology Research Grant(Z22‐02)和Tianjin“131”Science Fund for Creative Research Groups(2021)基金支持Yihai Cao获得the Swed is h Research Counc i l(2016‐02215,2019‐01502,2020‐06121,2021‐06122),National Key R&D Program of China(2020YFC0846600)+6 种基金the Hong Kong Centre for Cerebro‐cardiovascular Health Engineering,the Swedish Cancer Foundation(200734PjF),the Swedish Children's Cancer Foundation(PR2018‐0107)the Strategic Research Areas(SFO)‐Stem Cell and Regenerative Medicine Foundation,the Karolinska Institute Foundation(2020‐02080)the Karolinska Institute distinguished professor award,and the Karolinska Institute Foundation(2020‐02588)基金支持Kayoko Hosaka获得the Karolinska Institute Foundation基金支持Takahiro Seki获得the Scandinavia‐Japan Sasakawa Foundation基金支持Xu Jing获得the National Natural Science Foundation of China(81801163)and Doctor Fund of Shandong Natural Science Foundation(ZR201807060846)基金支持Masahito Yoshihara获得the Japan Society for the Promotion of Science(JSPS)Overseas Research Fellowships基金支持。
基金中国国家自然科学基金(No30271272No30672042)+4 种基金瑞典Swedish Research CouncilSwedish Medical AssociationSwedish Heart-Lung and the Throne Holst FoundationsRuth and Richard Julin Foundation美国NIH(HL-49373)。
文摘AIM:To assess gallbladder emptying and its association with cholecystitis and abdominal pain in patients with primary sclerosing cholangitis(PSC).METHODS:Twenty patients with PSC and ten healthy subjects were investigated.Gallbladder fasting volume, ejection fraction and residual volume after ingestion of a test meal were compared in patients with PSC and healthy controls using magnetic resonance imaging.Symptoms, thickness and contrast enhancement of the gallbladder wall and the presence of cystic duct strictures were also assessed.RESULTS:Median fasting gallbladder volume in patients with PSC [67(19-348) mL] was twice that in healthy controls [32(16-55) mL](P < 0.05).The median postprandial gallbladder volume in patients with PSC was signiflcantly larger than that in healthy controls(P < 0.05).There was no difference in ejection fraction, gallbladder emptying volume or mean thickness of the gallbladder wall between PSC patients and controls.Contrast enhancement of the gallbladder wall in PSC patients was higher than that in controls;(69% ± 32%) and(42% ± 21%)(P < 0.05).No significant association was found between the gallbladder volumes and occurrence of abdominal pain in patients and controls.CONCLUSION:Patients with PSC have increased fasting gallbladder volume.Gallbladder Mucosal dysfunction secondary to chronic cholecystitis, may be a possible mechanism for increased gallbladder.
基金Ruth and Richard Julins Foundation,the Stockholm County Council(ALF projects No.20140329 and No.20150403)the Swedish Society of Medicine(Gastroenterology Research Fund)
文摘Non-alcoholic fatty liver disease(NAFLD) is the mostcommon liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis(stage F3) and cirrhosis(stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers(e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques(transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.
基金Supported by Swedish Society of Medicine Post Doctoral Scholarship,No.SLS-785911the Lennander Scholarship
文摘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 invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5- year disease-specific survival rates reported;hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.
