BACKGROUND Pancreatic neuroendocrine microtumors(PNEMTs)are small(<5 mm),nonfunctioning,well-differentiated neuroendocrine neoplasms.Although they are rare,they are not invariably benign.PNEMTs are typically discov...BACKGROUND Pancreatic neuroendocrine microtumors(PNEMTs)are small(<5 mm),nonfunctioning,well-differentiated neuroendocrine neoplasms.Although they are rare,they are not invariably benign.PNEMTs are typically discovered incidentally during autopsy.However,data regarding the occurrence of PNEMTs in the elderly population,particularly those identified incidentally in cadaveric studies,remain limited.AIM To investigate the prevalence and histopathological characteristics of PNEMTs in elderly individuals by analyzing cadaveric pancreatic tissues.METHODS We conducted a retrospective analysis of 85 pancreatic specimens(age range:58-109 years)obtained from cadavers for anatomical education and research at the Department of Life Dentistry,Nippon Dental University.Paraffin sections of the pancreatic head,body,and tail were prepared for histological and immunohistochemical analysis.RESULTS Five cases with PNEMTs(5/85,5.9%;male,n=33;female,n=52;mean age:85.8±12.1 years)were identified.The tumors were solitary,well circumscribed,and located within the pancreatic parenchyma(body:n=4;tail:n=1),and all were<5 mm(range:0.54-2.20 mm)in size.All tumors showed strong chromogranin A and synaptophysin positivity,and were predominantly glucagon(GLU)-positive.Ki-67 immunostaining indicated minimal proliferative activity;therefore,these tumors were considered non-functioning,GLU-producing,well-differentiated grade 1 PNEMTs.CONCLUSION Small,predominantly low-grade,GLU-secreting PNEMTs were present in 5.9%of elderly individuals,highlighting the prevalence of subclinical PNEMTs and the need for careful follow-up.展开更多
This study highlights the significance of considering pituitary neuroendocrine tumor volume when determining the appropriate line of therapy for patients with acromegaly.The findings suggest that,although tumor volume...This study highlights the significance of considering pituitary neuroendocrine tumor volume when determining the appropriate line of therapy for patients with acromegaly.The findings suggest that,although tumor volume may assist in predicting the need for more aggressive treatment strategies,it is not a reliable indicator of disease persistence following surgical intervention.Further research is warranted to investigate additional factors influencing acromegaly treatment outcomes to enhance patient care.展开更多
Introduction: Pituitary neuroendocrine tumor (PitNET) may present multisecreting forms. Identifying its forms helps to guide management. This management is a real challenge, given the limited resources in our regions....Introduction: Pituitary neuroendocrine tumor (PitNET) may present multisecreting forms. Identifying its forms helps to guide management. This management is a real challenge, given the limited resources in our regions. In view of advances in the management of these multisecreting pituitary neuroendocrine tumors and the lack of published data in Africa, and in Senegal particularly, this survey was carried out with the aim of describing the epidemiological, clinical and therapeutic aspects of multisecreting PitNETs. Patients and Method: It was a multicenter, retrospective, descriptive and analytical study carried out on files collected from 1st January 2008 to 31 December 2022 in the neurosurgery departments of the Fann and Principal hospitals in Dakar and the endocrinology department of the Abass Ndao hospital in Dakar. Results: Of the 242 patients treated for PitNET, 09 presented (the mean age of our patients was 41.7 ± 11 years) with bihormonal PitNET, i.e. a proportion of 3.71%. Two types of association were found: 08 tumors with GH (Growth Hormon) + PRL (prolactin) secretion and 01 PitNET with ACTH (Adreno Corticotropic Homon) + prolactin secretion. Clinically, gonadotropic insufficiency was found in all patients (100%). Dysmorphic syndrome was found in 6 patients (66.7%) and tumor syndrome in 7 patients (77.8%). Ophthalmological evaluation revealed a decrease in visual acuity in 66.6% of patients. All had macroadenomas, with extension noted in 02 patients. All patients underwent transsphenoidal surgery with complications such as transient diabetes insipidus (3 patients, 33.3%), followed by cerebrospinal fluid leaks (1 patient, 11.1%). Remission was noted in all 5 patients tested. A comparison between the different secretory forms did not reveal any significant difference in the frequency of postoperative complications. Conclusion: Despite the lack of immunohistochemistry, two types of association were found: ACTH-PRL and GH-PRL. All were macroadenomas, the majority with an associated tumor syndrome. The latter was significantly less frequent in bisecreting PitNETs compared with monosecreting and non-functional forms. However, there was no significant difference in the occurrence of post-operative complications between the three secretory forms of PitNETs.展开更多
Pituitary neuroendocrine tumors(PitNETs)are pathologically characterized by dysregulation of neuroendocrine function and systemic disruption of hormonal homeostasis,yet their regulatory effects on peripheral immune ne...Pituitary neuroendocrine tumors(PitNETs)are pathologically characterized by dysregulation of neuroendocrine function and systemic disruption of hormonal homeostasis,yet their regulatory effects on peripheral immune networks remain poorly characterized.Here,we systematically analyzed bulk RNA sequencing(RNA‑seq)from 883 PitNET tumors,108 PitNET‑associated peripheral blood mononuclear cells(PBMC)samples,and 175 healthy PBMC controls,combined with 69 single‑cell RNA sequencing(scRNA-seq)samples covering tumors,normal pituitaries,as well as tumor‑derived and normal PBMCs.We identified a systemic immune disequilibrium in PitNET patients,characterized by increased circulating lymphocyte proportions,accompanied by upregulated cytokine-receptor interaction signatures.Notably,tumor resection reversed this imbalance,as supported by the normalization of monocyte and neutrophil counts,validated by flow cytometry and routine blood data from 600 samples(200 healthy controls and 200 PitNET patients with paired pre-and post-surgery follow‑up).Trajectory analysis identified terminally differentiated,secretory-specialized cell populations with lineage-specific hormone and cytokine hypersecretion.Ligand-receptor inference suggested these tumor-derived factors potentially engage circulating immune cell receptors.A random‑forest classifier based on PBMC transcriptomes distinguished PitNET subtypes,underscoring the diagnostic potential of peripheral immune signatures.Furthermore,in an estrogen-induced rat model,elevated PRL level coincided with the same peripheral immune skewing.Overall,our work provides a valuable resource and demonstrates PitNETs can be systemic immune modulators,where intrinsic hormone secretory activity and monocyte-lymphocyte imbalance collectively drive peripheral immune dysfunction.展开更多
Acromegaly,characterized by persistent hypersecretion of growth hormone(GH),is most often caused by a pituitary neuroendocrine tumor(PitNET),though,less often,ectopic GH or GH-releasing hormone secretion from various ...Acromegaly,characterized by persistent hypersecretion of growth hormone(GH),is most often caused by a pituitary neuroendocrine tumor(PitNET),though,less often,ectopic GH or GH-releasing hormone secretion from various neoplasms outside the pituitary gland could cause it.Nearly 70%of somatotroph PitNETs are macroadenomas at diagnosis.Transsphenoidal surgery,the most effective treatment modality for acromegaly,could achieve remission in 73%.However,the remission rates could reach 87%if surgery is followed by medical therapy.Due to variable therapeutic responses to surgical and medical therapy,pre-treatment awareness regarding the best therapeutic modality based on clinical,biochemical,radiological,histopathological and genetic parameters would help in accurate pretreatment decision-making.Earlier studies have identified poor prognosis markers like tumor size,tumor invasion,T2-weighted hyperintensity,granulation,and pretreatment GH and/or insulin-like growth factor 1 levels.In a recent study,published by Alvarez et al identified that preoperative PitNET volume is a good predictor of control of acromegaly following surgical treatment and the likelihood of requiring more aggressive additional therapies after surgery.They found that PitNET volume exceeding 3697 mm³was associated with poorer disease control in patients with somatotroph PitNETs.展开更多
Background Surgical management of giant and irregular pituitary neuroendocrine tumors(GIPitNETs)presents a significant challenge in neurosurgery.While endoscopic endonasal surgery(EES)is a widely used approach for Pit...Background Surgical management of giant and irregular pituitary neuroendocrine tumors(GIPitNETs)presents a significant challenge in neurosurgery.While endoscopic endonasal surgery(EES)is a widely used approach for PitNETs,GIPitNETs with extensive intracranial extension pose challenges for purely EES.We use simultaneous combined endoscopic endonasal and transcranial surgery(CECS)for the treatment of this type of tumor.Currently,there is limited research comparing CECS to EES for GIPitNETs.This study aims to compare the efficacy and short outcome of CECS and purely EES in the management of GIPitNETs to better understand the advantages and limitations of each surgical approach.Methods The data of GIPitNETs patients who underwent surgery between March 2018 and May 2023 at a single center were retrospectively reviewed.All included cases were divided into CECS and EES groups according to the treatment modality received.The baseline characteristics and tumor imaging features of patients were compared between the groups,as well as surgical results,perioperative complications,and last follow-up outcomes.Results A total of 50 patients met the inclusion criteria,with 27 undergoing CECS and 23 EES.CECS achieved a significantly higher GTR rate compared to EES(66.7%vs.13.0%,p<0.0001).CECS had longer operation times and hospital stays,but both approaches had similar rates of complications,including intracranial infection,CSF leakage,new pituitary dysfunction,postoperative diabetes insipidus,and vascular infarction.CECS reduces the risk of postoperative bleeding.Tumor recurrence and reoperation were significantly more common in the EES group.Conclusions CECS is a safe and effective surgical approach for GIPitNETs,leading to higher rates of GTR,comparable complication rates,and reduced risk of postoperative bleeding when compared to purely EES.EES was associated with more tumor recurrence.Further long-term follow-up data is needed to validate these findings.展开更多
BACKGROUND Pituitary neuroendocrine tumors(PitNETs),formerly referred to as pituitary adenomas,are prevalent intracranial neoplasms that,although often benign histologically,can demonstrate invasive growth,therapeutic...BACKGROUND Pituitary neuroendocrine tumors(PitNETs),formerly referred to as pituitary adenomas,are prevalent intracranial neoplasms that,although often benign histologically,can demonstrate invasive growth,therapeutic resistance,and recurrence.Emerging evidence supports the presence of a subpopulation of tumorinitiating cells with stem-like properties-pituitary adenoma stem cells(PASCs)-that may drive these aggressive features.This systematic review aims to critically examine the evidence on PASCs,their phenotypic and functional characteristics,and their role in PitNET pathophysiology.AIM To study the molecular markers,signaling pathways,research models,and phenotypic traits of PASCs,and to assess their potential significance for future translational and clinical applications.METHODS A comprehensive literature search was conducted in PubMed,Scopus,and Ovid MEDLINE in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Thirty-four studies were included based on predefined eligibility criteria.Data were extracted regarding PASC isolation methods(e.g.,neurosphere formation,side population sorting),marker expression[e.g.,SRY-related HMG-box transcription factor(SOX)2,octamer-binding transcription factor 4,CD133,Nestin],pathway involvement(e.g.,Wnt/betacatenin,Notch,Sonic hedgehog),and functional behaviors such as self-renewal,differentiation,tumorigenicity,and therapy resistance.RESULTS Following duplicate removal,315 unique articles were screened,with 47 full texts assessed for eligibility.Ultimately,34 studies published between 2007 and 2025 met the inclusion criteria.The majority utilized human PitNET samples(83%),with a subset employing rat-derived cell lines(28%)or murine models(15%).PASCs were identified and characterized using various in vitro and in vivo approaches.Commonly reported stemness markers included SOX2(59%),CD133(38%),Nestin(35%),and octamer-binding transcription factor 4(26%),with others such as SOX9,paired-like homeobox 1,and C-X-C chemokine receptor type 4 also frequently cited.Wnt/betacatenin(18%)and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(9%)signaling pathways were most implicated,followed by Notch,Sonic hedgehog,and janus kinase/signal transducer and activator of transcription cascades.Functional assays revealed consistent findings of tumor initiation(44%),selfrenewal(35%),and tumor progression or invasion(35%).Notably,a minority of studies explored therapeutic interventions targeting PASCs,including gamma-secretase inhibitors and possible novel combinations of molecular agents.CONCLUSION The accumulating evidence on PASCs highlights their pivotal role in PitNET tumorigenesis,progression,and therapy resistance.Their molecular and functional overlap with normal pituitary stem cells underscores the need for further lineage-tracing and in vivo validation.展开更多
基金Supported by Grant-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology of Japan,No.25K10147.
文摘BACKGROUND Pancreatic neuroendocrine microtumors(PNEMTs)are small(<5 mm),nonfunctioning,well-differentiated neuroendocrine neoplasms.Although they are rare,they are not invariably benign.PNEMTs are typically discovered incidentally during autopsy.However,data regarding the occurrence of PNEMTs in the elderly population,particularly those identified incidentally in cadaveric studies,remain limited.AIM To investigate the prevalence and histopathological characteristics of PNEMTs in elderly individuals by analyzing cadaveric pancreatic tissues.METHODS We conducted a retrospective analysis of 85 pancreatic specimens(age range:58-109 years)obtained from cadavers for anatomical education and research at the Department of Life Dentistry,Nippon Dental University.Paraffin sections of the pancreatic head,body,and tail were prepared for histological and immunohistochemical analysis.RESULTS Five cases with PNEMTs(5/85,5.9%;male,n=33;female,n=52;mean age:85.8±12.1 years)were identified.The tumors were solitary,well circumscribed,and located within the pancreatic parenchyma(body:n=4;tail:n=1),and all were<5 mm(range:0.54-2.20 mm)in size.All tumors showed strong chromogranin A and synaptophysin positivity,and were predominantly glucagon(GLU)-positive.Ki-67 immunostaining indicated minimal proliferative activity;therefore,these tumors were considered non-functioning,GLU-producing,well-differentiated grade 1 PNEMTs.CONCLUSION Small,predominantly low-grade,GLU-secreting PNEMTs were present in 5.9%of elderly individuals,highlighting the prevalence of subclinical PNEMTs and the need for careful follow-up.
文摘This study highlights the significance of considering pituitary neuroendocrine tumor volume when determining the appropriate line of therapy for patients with acromegaly.The findings suggest that,although tumor volume may assist in predicting the need for more aggressive treatment strategies,it is not a reliable indicator of disease persistence following surgical intervention.Further research is warranted to investigate additional factors influencing acromegaly treatment outcomes to enhance patient care.
文摘Introduction: Pituitary neuroendocrine tumor (PitNET) may present multisecreting forms. Identifying its forms helps to guide management. This management is a real challenge, given the limited resources in our regions. In view of advances in the management of these multisecreting pituitary neuroendocrine tumors and the lack of published data in Africa, and in Senegal particularly, this survey was carried out with the aim of describing the epidemiological, clinical and therapeutic aspects of multisecreting PitNETs. Patients and Method: It was a multicenter, retrospective, descriptive and analytical study carried out on files collected from 1st January 2008 to 31 December 2022 in the neurosurgery departments of the Fann and Principal hospitals in Dakar and the endocrinology department of the Abass Ndao hospital in Dakar. Results: Of the 242 patients treated for PitNET, 09 presented (the mean age of our patients was 41.7 ± 11 years) with bihormonal PitNET, i.e. a proportion of 3.71%. Two types of association were found: 08 tumors with GH (Growth Hormon) + PRL (prolactin) secretion and 01 PitNET with ACTH (Adreno Corticotropic Homon) + prolactin secretion. Clinically, gonadotropic insufficiency was found in all patients (100%). Dysmorphic syndrome was found in 6 patients (66.7%) and tumor syndrome in 7 patients (77.8%). Ophthalmological evaluation revealed a decrease in visual acuity in 66.6% of patients. All had macroadenomas, with extension noted in 02 patients. All patients underwent transsphenoidal surgery with complications such as transient diabetes insipidus (3 patients, 33.3%), followed by cerebrospinal fluid leaks (1 patient, 11.1%). Remission was noted in all 5 patients tested. A comparison between the different secretory forms did not reveal any significant difference in the frequency of postoperative complications. Conclusion: Despite the lack of immunohistochemistry, two types of association were found: ACTH-PRL and GH-PRL. All were macroadenomas, the majority with an associated tumor syndrome. The latter was significantly less frequent in bisecreting PitNETs compared with monosecreting and non-functional forms. However, there was no significant difference in the occurrence of post-operative complications between the three secretory forms of PitNETs.
基金supported by the National Research Center for Translational Medicine under grant number NRCTM(SH)2023-15(to Z-B.W.)Fundamental Research Funds for the Central Universities(No.YG2023ZD06 to Z-B.W.)+3 种基金National Natural Science Foundation of China(82472640 to Z-B.W.,82373131 and 82573142 to S-J.L.,82200153 to Y-T.D.,82500265 to S-S.Y.)Health care leader of Shanghai Municipal Health Commission(No.2022LJ006 to Z-B.W.)the Natural Science Foundation of Shanghai,China(25ZR1402349 to S-S.Y.)the Innovative Research Team of HighLevel Local Universities in Shanghai.
文摘Pituitary neuroendocrine tumors(PitNETs)are pathologically characterized by dysregulation of neuroendocrine function and systemic disruption of hormonal homeostasis,yet their regulatory effects on peripheral immune networks remain poorly characterized.Here,we systematically analyzed bulk RNA sequencing(RNA‑seq)from 883 PitNET tumors,108 PitNET‑associated peripheral blood mononuclear cells(PBMC)samples,and 175 healthy PBMC controls,combined with 69 single‑cell RNA sequencing(scRNA-seq)samples covering tumors,normal pituitaries,as well as tumor‑derived and normal PBMCs.We identified a systemic immune disequilibrium in PitNET patients,characterized by increased circulating lymphocyte proportions,accompanied by upregulated cytokine-receptor interaction signatures.Notably,tumor resection reversed this imbalance,as supported by the normalization of monocyte and neutrophil counts,validated by flow cytometry and routine blood data from 600 samples(200 healthy controls and 200 PitNET patients with paired pre-and post-surgery follow‑up).Trajectory analysis identified terminally differentiated,secretory-specialized cell populations with lineage-specific hormone and cytokine hypersecretion.Ligand-receptor inference suggested these tumor-derived factors potentially engage circulating immune cell receptors.A random‑forest classifier based on PBMC transcriptomes distinguished PitNET subtypes,underscoring the diagnostic potential of peripheral immune signatures.Furthermore,in an estrogen-induced rat model,elevated PRL level coincided with the same peripheral immune skewing.Overall,our work provides a valuable resource and demonstrates PitNETs can be systemic immune modulators,where intrinsic hormone secretory activity and monocyte-lymphocyte imbalance collectively drive peripheral immune dysfunction.
文摘Acromegaly,characterized by persistent hypersecretion of growth hormone(GH),is most often caused by a pituitary neuroendocrine tumor(PitNET),though,less often,ectopic GH or GH-releasing hormone secretion from various neoplasms outside the pituitary gland could cause it.Nearly 70%of somatotroph PitNETs are macroadenomas at diagnosis.Transsphenoidal surgery,the most effective treatment modality for acromegaly,could achieve remission in 73%.However,the remission rates could reach 87%if surgery is followed by medical therapy.Due to variable therapeutic responses to surgical and medical therapy,pre-treatment awareness regarding the best therapeutic modality based on clinical,biochemical,radiological,histopathological and genetic parameters would help in accurate pretreatment decision-making.Earlier studies have identified poor prognosis markers like tumor size,tumor invasion,T2-weighted hyperintensity,granulation,and pretreatment GH and/or insulin-like growth factor 1 levels.In a recent study,published by Alvarez et al identified that preoperative PitNET volume is a good predictor of control of acromegaly following surgical treatment and the likelihood of requiring more aggressive additional therapies after surgery.They found that PitNET volume exceeding 3697 mm³was associated with poorer disease control in patients with somatotroph PitNETs.
基金sponsored by Joint Funds for Innovation of Science and Technology,Fujian Province(No.2021Y9089)University-Industry Research Joint Innovation Project of Science and Technology,Fujian Province(No.2023Y4018)+1 种基金Fujian Province Finance Project(No.BPB-2022YXR)scientific research,Fujian Medical University(grant number 2022QH1098).
文摘Background Surgical management of giant and irregular pituitary neuroendocrine tumors(GIPitNETs)presents a significant challenge in neurosurgery.While endoscopic endonasal surgery(EES)is a widely used approach for PitNETs,GIPitNETs with extensive intracranial extension pose challenges for purely EES.We use simultaneous combined endoscopic endonasal and transcranial surgery(CECS)for the treatment of this type of tumor.Currently,there is limited research comparing CECS to EES for GIPitNETs.This study aims to compare the efficacy and short outcome of CECS and purely EES in the management of GIPitNETs to better understand the advantages and limitations of each surgical approach.Methods The data of GIPitNETs patients who underwent surgery between March 2018 and May 2023 at a single center were retrospectively reviewed.All included cases were divided into CECS and EES groups according to the treatment modality received.The baseline characteristics and tumor imaging features of patients were compared between the groups,as well as surgical results,perioperative complications,and last follow-up outcomes.Results A total of 50 patients met the inclusion criteria,with 27 undergoing CECS and 23 EES.CECS achieved a significantly higher GTR rate compared to EES(66.7%vs.13.0%,p<0.0001).CECS had longer operation times and hospital stays,but both approaches had similar rates of complications,including intracranial infection,CSF leakage,new pituitary dysfunction,postoperative diabetes insipidus,and vascular infarction.CECS reduces the risk of postoperative bleeding.Tumor recurrence and reoperation were significantly more common in the EES group.Conclusions CECS is a safe and effective surgical approach for GIPitNETs,leading to higher rates of GTR,comparable complication rates,and reduced risk of postoperative bleeding when compared to purely EES.EES was associated with more tumor recurrence.Further long-term follow-up data is needed to validate these findings.
文摘BACKGROUND Pituitary neuroendocrine tumors(PitNETs),formerly referred to as pituitary adenomas,are prevalent intracranial neoplasms that,although often benign histologically,can demonstrate invasive growth,therapeutic resistance,and recurrence.Emerging evidence supports the presence of a subpopulation of tumorinitiating cells with stem-like properties-pituitary adenoma stem cells(PASCs)-that may drive these aggressive features.This systematic review aims to critically examine the evidence on PASCs,their phenotypic and functional characteristics,and their role in PitNET pathophysiology.AIM To study the molecular markers,signaling pathways,research models,and phenotypic traits of PASCs,and to assess their potential significance for future translational and clinical applications.METHODS A comprehensive literature search was conducted in PubMed,Scopus,and Ovid MEDLINE in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Thirty-four studies were included based on predefined eligibility criteria.Data were extracted regarding PASC isolation methods(e.g.,neurosphere formation,side population sorting),marker expression[e.g.,SRY-related HMG-box transcription factor(SOX)2,octamer-binding transcription factor 4,CD133,Nestin],pathway involvement(e.g.,Wnt/betacatenin,Notch,Sonic hedgehog),and functional behaviors such as self-renewal,differentiation,tumorigenicity,and therapy resistance.RESULTS Following duplicate removal,315 unique articles were screened,with 47 full texts assessed for eligibility.Ultimately,34 studies published between 2007 and 2025 met the inclusion criteria.The majority utilized human PitNET samples(83%),with a subset employing rat-derived cell lines(28%)or murine models(15%).PASCs were identified and characterized using various in vitro and in vivo approaches.Commonly reported stemness markers included SOX2(59%),CD133(38%),Nestin(35%),and octamer-binding transcription factor 4(26%),with others such as SOX9,paired-like homeobox 1,and C-X-C chemokine receptor type 4 also frequently cited.Wnt/betacatenin(18%)and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(9%)signaling pathways were most implicated,followed by Notch,Sonic hedgehog,and janus kinase/signal transducer and activator of transcription cascades.Functional assays revealed consistent findings of tumor initiation(44%),selfrenewal(35%),and tumor progression or invasion(35%).Notably,a minority of studies explored therapeutic interventions targeting PASCs,including gamma-secretase inhibitors and possible novel combinations of molecular agents.CONCLUSION The accumulating evidence on PASCs highlights their pivotal role in PitNET tumorigenesis,progression,and therapy resistance.Their molecular and functional overlap with normal pituitary stem cells underscores the need for further lineage-tracing and in vivo validation.
