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Objective:To investigate the clinical imaging features and prognosis of von Hippel-Lindau (VHL) syndrome associated with pancreatic lesions.Method:The retrospective case-control study was conducted. The clinicopathological data of 161 patients with VHL syndrome who were admitted to Peking University First Hospital from September 2010 to August 2022 were collected. There were 83 males and 78 females, with age of onset as 27.0(range, 8.0-66.0)years. Observation indicators: (1) imaging results of VHL syndrome associated with pancreatic lesions; (2) clinical characteristics of VHL syndrome associated with pancreatic lesions; (3) comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic cystic lesions; (4) comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic neuroendocrine neoplasms (pNENs). (5) Treatment and prognosis of patients with VHL syndrome associated with pancreatic lesions. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Results:(1) Imaging results of VHL syndrome associated with pancreatic lesions. Of the 161 patients with VHL syndrome, there were 151 patients associated with pancreatic lesions and 10 patients not associated with pancreatic lesions. Of the 151 patients with VHL syndrome associated with pancreatic lesions, there were 136 patient with pancreatic cystic lesions and 34 patients with pNENs, 22 patients with both pNENs and pancreatic cystic lesions, and the type of pancreatic lesions could not be accurately determined in 3 cases. (2) Clinical characteristics of VHL syndrome associated with pancreatic lesions. The age of onset in 151 patients with VHL syndrome associated with pancreatic lesions was 33.0(range, 14.0-68.0)years. Cases with gene site mutation of exon 1, exon 2, exon 3 and other types of gene site was 51, 16, 43 and 41, respectively. There were 116 patients of VHL type 1 and 35 patients of VHL type 2. There were 92 patients with family history of VHL syndrome and 59 patients without family history of VHL syndrome. There were 127 patients combined with renal cell carcinoma, 112 patients combined with central nervous system lesions, 46 patients combined with retinal hemangioblastoma. Patients may combined with multiple lesions. (3) Comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic cystic lesions. The age of onset, VHL syndrome type (VHL1 type, VHL2 type) and cases combined with renal cell carcinoma were 32.5(range, 14.0-68.0)years, 110, 26 and 115 in 136 patients with VHL syndrome associated with pancreatic cystic lesions, versus 22.0(range, 8.0-64.0)years, 13, 12 and 14 in 25 patients with VHL syndrome not associated with pancreatic cystic lesions, showing significant differences in the above indicators between them ( Z=-3.384, χ2=9.770, 10.815, P<0.05). (4) Comparison of clinicopathological factors in patients with VHL syndrome associated with pNENs. The age of onset, gene mutation sites (exon 1, exon 2, exon 3, other types of gene site) and VHL syndrome type (VHL1 type, VHL2 type) were 33.5(range, 14.0-64.0)years, 12, 5, 14, 3 and 18, 16 in 34 patients with VHL syndrome associated with pNENs, versus 27.0(range, 9.0-66.0)years, 41, 12, 32, 42 and 105, 22 in 127 patients with VHL syndrome not associated with pNENs, showing significant differences in the above indicators between them ( Z=-4.030, χ2=8.814, 13.152, P<0.05). (5) Treatment and prognosis of patients with VHL syndrome associated with pancreatic lesions. Of the 161 patients with VHL syndrome, 3 patients underwent surgical treatment, and the remaining patients were followed up. All 161 patients with VHL syndrome were followed up for 6 (range, 1-12)years, in which 15 patients died and 146 patients alive during the follow-up. The follow-up time of 3 patients undergoing surgical treatment was 4, 14, 9 years, respectively, and all of them were alive. Conclusions:The clinical imaging features of pancreatic lesions related to VHL syndrome are cystic lesions and pNENs, which with the characteristics of multiple lesions and benign tumors. Such patients usually do not requiring surgical treatment and have good prognosis.
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Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are neoplasms that develop from neuroendocrine cells and exhibit neuroendocrine functions. The lack of specific clinical symptoms and biological behaviors for NENs cause early misdiagnosis and missed diagnosis in a majority of cases. However, the molecular biology of GEP-NENs vary greatly in different primary sites and grades, contributing to the high heterogeneity in such type of tumors. Currently, the diagnosis of GEP-NENs mainly depends on traditional methods such as imaging and tissue biopsy, leading to imperfect diagnostics by only reflecting genetic information about the location of the biopsy sample in the overall neoplasm. With the rapid development of genome sequencing technology in recent years, the exploration of circulating biomarkers and liquid biopsy technology have compensated for the limitations of tissue biopsy, thereby creating new opportunities to improve the diagnostic rate of GEP-NENs and the realization of precise treatment. This review summarizes and compares the status of liquid biopsy applications in investigating GEP-NENs.
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Pancreatic neuroendocrine neoplasms(pNENs)are the most common neuroendocrine tumors.For early local pNENs,surgery is the main therapeutic strategy and the tumor can be removed completely.But for those pNENs that cannot be surgically removed or have undergone distant metastasis,peptide receptor radionuclide therapy(PRRT)can be chosen as a first-line therapeutic strategy as pNENs overexpress somatostatin receptors.In recent years,clinical trials and studies on the use of PRRT in pNENs have been increasing rapidly.Many reports have confirmed the efficacy of 90 Y and 177 Lu-labeled somatostatin analogue in pNENs patients.
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The incidence rate of pancreatic neuroendocrine neoplasms(pNENs)is continuously increasing.Since 20% to64% of pNENs develops metastatic disease when diagnosed and functional pNENs is quite common,medical treatment is of great importance for pNENs.Somatostatin analogues(SSAs)is one of the major medical treatments for pNENs and the new generation of SSAs cannot replace the role of lanreotide autogel and octreotide long-acting repeatable(LAR)for pancreatic neuroendocrine tumor(pNET)with low proliferative index and positive expression of somatostatin receptors(SSTRs).Everolimus and sunitinib are two targeted treatments recommended for pNET.Clinical trials of other targeted treatments are gradually conducted with some of them already reached phase Ⅲ.Chemotherapy is usually applied in pNENs with high growth rate or poorly-differentiated neuroendocrine carcinoma(NEC).Most clinical trials of new chemotherapy scheme are designed for NEC.Peptide receptor radionuclide therapy(PRRT) may have important value in pNET positively expressing SSTRs.Preliminary data of immunotherapy for pNENs did not show very promising result and studies of different medical treatments combinations for pNENs are still under exploration.In general,although medical treatments for pNENs had achieved great advances,there is still a long way to go before many new treatments can be used in pNENs.
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In recent years,with the progress of imaging and diagnostic technology,the detection rate of pancreatic neuroendocrine neoplasms has increased rapidly.However,its clinical manifestations are diverse,the rate of misdiagnosis is high,the therapeutic treatments are complex,and the guidelines for diagnosis and treatment are relatively imperfect,which has caused great trouble in clinical practice.Especially in surgical treatment,it is difficult to choose between preservation of pancreatic function and standard radical resection,especially for tumors less than 2 cm.At the same time,whether lymph node resection should be performed is another open question.Because it is difficult to carry out randomized controlled studies,most of the studies on this issue are long-span retrospective studies based on public databases,which are greatly influenced by factors such as time,medical level in different regions and different surgeons.It is the confounding factors that lead to inconsistent results.
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Pancreatic neuroendocrine neoplasms(p NENs)are noted for its great variety and wide heterogeneity.The incidence is increasing gradually.Liver metastasis is not the contraindication of surgery of p NENs.Surgery is consider as a significant role in the multi-disciplinary team about treating p NENs.Although p NENs liver metastasis is relatively rare,its overall prognosis is significantly better than that of patients with pancreatic cancer liver metastasis.It is of great significance to grasp the indications and principles of surgical treatment for improving the survival of patients.Despite the relevant guidelines for diagnosis and treatment,the choice of surgical treatment options and the grasp of surgical indications for p NENs liver metastasis are still controversial.All pancreatic centers should give full play to the advantages of MDT and formulate individualized treatment plans for patients.Meanwhile,hospitals at all levels should strengthen cooperation to reduce missed diagnosis,misdiagnosis and mistreatment,and further standardize the surgical diagnosis and treatment of p NENs liver metastasis in China.
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The incidence of non-functional pancreatic neuroendocrine neoplasms(NF-pNENs)constantly increases due to the development of imaging techniques and the popularity of routine medical examination.WHO classification system,ENETS and AJCC grading systems,widely used in clinical practice,are independent prognostic factors.According to the G grading system,NF-pNENs are classified into benign,low-grade malignant and high-grade malignant tumors.Operative indications and treatments are absolutely different for each subgroup.Lymph node metastasis closely correlates with the position and size of tumor,lymphovascular invasion and Ki-67 index.Pre-operative determination of the presence of lymph node metastasis provides significant instructions for the choice of surgery since it indicates early tumor relapse and metastasis.The advance of ultrasoundguide biopsy provides more sensitive indictors for preoperative pathological grade and lymph node metastasis.Both domestic and foreign guidelines consider the tumor size as the critical factors for surgery.For those NF-pNENs2 cm,even with local vascular and organs invasion,a routine pancreatic surgery is recommended(distal pancreatectomy or pancreatic duodenectomy according to the tumor position).Lymph node sampling or regional lymphadenectomy should be routinely performed during surgeries.For those with liver metastasis,surgical resection,locoregional ablative therapy or liver transplantation is suggested according to the situation of metastatic sites.
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Pancreatic neuroendocrine neoplasms(pNENs)are a group of tumors that originate from stem cells and have neuroendocrine markers and are capable of producing biologically active amines and/or polypeptide hormones with significant heterogeneity.With advances in endoscopic and imaging techniques and improved diagnostic levels,the detection rate of the pNENs has increased.But at present,there is still easy to be misdiagnosed and missed because of insufficient understanding of the pNENs.Therefore,early diagnosis which by understanding the imaging features and using the effective imaging methods has great significance for improving prognosis.
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The pathological grading diagnosis of pancreatic neuroendocrine neoplasms is the basis of clinical treatment and prognosis.The general principle guiding the classification of NEN has been evoluted several times.From the size of tumor,to the proliferation index as a key factor,and subsequently proposed distuishing between well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas.Firstly,neuroendocrine tumors and neuroendocrine carcinomas were classified according to their morphology.Then,according to mitotic image and Ki67 proliferation index,the former was classified into G1,G2 and G3 grades.
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Great progresses have been achieved in the diagnosis and treatment of pancreatic neuroendocrine tumors,especially in the close related field as radiology,medical oncology and surgery.It is difficult to accomplish high level of diagnosis and treatment of pancreatic neuroendocrine tumors if doctors only understand the progress of own specialty.The characters of pancreatic neuroendocrine tumors are complex clinical manifestation,long disease duration,and related to many clinical departments.The multidisciplinary pattern of diagnosis and treatment could significantly improve the survival and quality of life of patients while decreasing medical expense.Suergeons should emphasis the importance of multidisciplinary pattern of diagnosis and treatment in pancreatic neuroendocrine tumors.
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Pancreatic neuroendocrine neoplasms(pNENs)are a relatively rare group of heterogeneous tumors with malignant potential originating from pancreatic neuroendocrine cells.Most pNENs grow slowly with an inert biological behavior,and the surgical resection rate and longterm survivalis much better than those of pancreatic ductal adenocarcinoma.Surgery is the only curable way for treatment of pNENs.Surgical approaches should be selected based on the patient's age and physical condition,the grading classification and TNM staging of the tumor,the location of the tumor and its distance to the pancreatic duct,the invasion of surrounding organs,and distant metastasis.Even palliative resection of either the primary tumor or the metastatic lesions may be beneficial for the survival of late staged pNENs patients.
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Pancreatic neuroendocrine tumors are a group of rare neoplasms originating from the neuroendocrine cells of pancreas.They can be classified into functioning or non-functioning groups according to hormone secretion.Due to the application of high-resolution imaging techniques,the incidence of incidental non-functioning pancreatic neuroendocrine tumors has been rising for decades.Although the optimal prognosis,nonfunctioning pancreatic neuroendocrine tumor are heterogeneous,and the complication morbidity is high.So controversy still exists for the choice of treatment approach.This article aims to summarize and analyze the progress and current controversy about the treatment of incidental non-functioning pancreatic neuroendocrine tumors,and discuss about the appropriate treatment choice for patients.
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The high standard diagnosis and treatment of pancreatic neoplasms demand multidisciplinary cooperation,especially in the treatment of local advanced and metastatic pancreatic cancer.For benign borderline tumors,multidisciplinary cooperation could improve the specificity of preoperative diagnosis so that unnecessary surgery could be avoided to greatest extend.Surgeons should balance the risk and gain of patients so that rational treatment could be achieved based on evidence medicine,and the long term survival could be accomplished.
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Objective To assess the value of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of pancreatic neuroendocrine neoplasms (PNEN) and to analyze the factors influencing thepreoperative imaging diagnosis of PNEN.Methods From January 2016 to November 2016, patients with PNEN diagnosed by surgery and biopsy were collected. CT and MRI data of them were analyzed. The CT values or signal intensity of the lesions and the pancreatic parenchyma were measured and the contrast-to-noise ratio (CNR) of the lesion was calculated. Detecting sensitivity and diagnosis accuracy of CT and MRI were compared. Detecting sensitivity of different MRI sequences was also analyzed. Diagnosis accuracy of non-functional PNEN and functional PNEN was compared and analyzed. Lesion CNR was compared between arterial phase and portal venous phase of the contrast enhanced CT. The sensitivity, accuracy and constituent ratio were compared by nonparametric analysis. Independent sample t test and one-way analysis of variancewere performed for the quantitative parameters comparison. Results A total of 54 patients with 56 lesions of PNEN were included for two of whom had two lesions each. CT and MRI were both performed in 44 patients (46 lesions).Detecting sensitivity and diagnosis accuracy of CT were 97.8% (45/46) and87.0% (40/46), respectively. Detecting sensitivity of MRI were 97.8% (45/46) and89.1% (41/46), respectively. There was no significant difference in detecting sensitivity and diagnosis accuracy between CT and MRI (both P>0.05). The CNR of lesion in arterial phase was higher than that of portal venous phase(4.7±3.8 vs 3.4±2.5), and the difference was statistically significant (t=2.949, P<0.05). Detecting rates of T1 weighted imaging with fat suppression (T1WI-FS) image, T2 weighted imaging with fat suppression (T2WI-FS) image, diffusion weighted imagingand dynamic contrast enhanced T1WI-FS image were 90.0% (45/50), 88.0%(44/50), 86.0%(43/50), and 91.7% (44/48), respectively. There was no significant difference in detecting rate among these images sequences (Q=2.526, P=0.510). Tumor diameter in non-functional PNEN was significantly larger than that in functional PNEN ((2.9±1.6) cm vs (1.7±0.7) cm)(t=3.479,P<0.05). The overall diagnosis rate of non-functional PNEN with CT and MRI before operation was 70.8% (17/24), which was significantly lower than that of functional PNEN (100.0%, 31/31) (χ2=10.360，P=0.002).Conclusions CT and MRI are both sensitive in detectingPNEN, and they were two complementary modalities. CT image in arterial phase delineated the lesion better than that in portal venous phase. MRI images with different sequences can becomplementary and there is no significant difference in detecting sensitivity for PNEN among different sequences. CT and MRI play an equal rolein the diagnosis of PNEN before operation. Because of atypical CT and MRI findings, the diagnosis of non-functional PNEN is more difficult thanfunctional PNEN.
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The incidence of pancreatic neuroendocrine neoplasms is progressively growing.The clinical manifestation and treatment of this disease are complicated.Multi disciplinary combination therapy is needed to improve prognosis and life quality of patients.
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Objective To investigate the dynamic changes of chromogranin A in patients with pancreatic neuroendocrine neoplasms after laparoscopic surgery,and to monitor the diagnosis and prognosis of patients with real-time monitoring.Methods Forty-five patients with pancreatic neuroendocrine neoplasms were enrolled in this study from March 2013 to March 2015 in First Hospita of Yulin City.All patients were underwent laparoscopic surgery.The surgical results were observed and the levels of postoperative chromogranin A were monitored.Comparisons between groups were evaluated with the x2 test.Follow-up using telephone interview was performed to detect patients' survival and up to January 2017.Results TNM patients with benign and malignant patients in the postoperative chromogranin A examination found that the positive expression rate were 85.0％ and 53.0％,the difference between the two groups was statistically significant (P ＜ 0.01) and the corresponding synaptophysine examination were 88.0％ and 89.0％ (P ＜ 0.05).The positive expression rates of chromogranin A in patients with lymph node metastasis and non-lymph node metastasis were 47.0％ and 80.0％,respectively (P ＜ 0.01).The positive expression rates of the corresponding synaptophysin were 87.0％ and 87.0％,respectively (P ＞ 0.05).Conclusion Endoscopic surgery for pancreatic neuroendocrine neoplasms is a minimally invasive,safe surgical approach,long-term survival rate of patients with the use of chromogranin A to monitor the level of patients after surgery can effectively assess the development and prognosis of the disease,but the synaptophysine has no significance in assessing the prognosis of the patient.
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Objective To study the diagnosis,treatment and prognostic factors of pancreatic neuroendocrine neoplasms (pNENs).Methods The clinical,pathological and follow-up data of 44 patients with pNENs treated at the Peking University First Hospital from Jan.2007 to Dec.2016 were retrospectively studied.Survival analysis was performed with the Kaplan-Meier method.Results There were 21 male and 23 female patients.The mean age was (54.8 ± 14.0) years.25 patients had non-functional,while 19 had functional pNENs.Curative resection was performed in 40 patients.Neural invasion and intravascular cancer emboli were found in 7 and 5 patients,respectively.The pathologic data showed that the number of patients with G1,G2,G3 were 23 (52.3 ％),15 (34.1％),6 (13.6％),respectively.The number of patients with stage Ⅰ,Ⅱ,Ⅲ,and Ⅳ were 23 (52.3 ％),16 (36.4％),2 (4.5 ％) and 3 (6.8 ％),respectively.The predictive factors on prognosis included curative resection or not,WHO grade,TNM staging,lymph node metastasis and distant metastasis (P ＜ 0.05).Conclusions Curative surgical resection is the first choice of treatment for pNENs.WHO grade,TNM staging,lymph node metastasis and distant metastasis were significantly related to the prognosis of pNENs.
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This study investigated the accuracy of MRI features in differentiating the pathological grades of pancreatic neuroendocrine neoplasms (PNENs).A total of 31 PNENs patients were retrospectively evaluated,including 19 cases in grade 1,5 in grade 2,and 7 in grade 3.Plain and contrastenhanced MRI was performed on all patients.MRI features including tumor size,margin,signal intensity,enhancement patterns,degenerative changes,duct dilatation and metastasis were analyzed.Chi square tests,Fisher's exact tests,one-way ANOVA and ROC analysis were conducted to assess the associations between MRI features and different tumor grades.It was found that patients with older age,tumors with higher TNM stage and without hormonal syndrome had higher grade of PNETs (all P＜0.05).Tumor size,shape,margin and growth pattern,tumor pattern,pancreatic and bile duct dilatation and presence of lymphatic and distant metastasis as well as MR enhancement pattern and tumor-topancreas contrast during arterial phase were the key features differentiating tumors of all grades (all P＜0.05).ROC analysis revealed that the tumor size with threshold of 2.8 cm,irregular shape,pancreatic duct dilatation and lymphadenopathy showed satisfactory sensitivity and specificity in distinguishing grade 3 from grade 1 and grade 2 tumors.Features ofperipancreatic tissue or vascular invasion,and distant metastasis showed high specificity but relatively low sensitivity.In conclusion,larger size,poorlydefined margin,heterogeneous enhanced pattern during arterial phase,duct dilatation and the presence of metastases are common features of higher grade PNENs.Plain and contrast-enhanced MRI provides the ability to differentiate tumors with different pathological grades.
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Background and purpose:The symptoms of pancreatic neuroendocrine neoplasms (PNENs) are complicated, that might lead to misdiagnosis. This study aimed to detect the expression level of DJ-1 in PNENs and explore the clinical significance of DJ-1 in PNENs.Methods:DJ-1 protien levels in the serum of 16 cases of PNENs patients and 25 cases of healthy persons were detected by ELISA analysis; The expressions of DJ-1 in 78 cases of PNENs tissues were detected by immunohistochemical staining.Results:The DJ-1 level in the serum of PNENs patients was signiifcantly higher than healthy persons (36.19±6.71vs 24.68±5.94 ng/mL;P<0.001);53.8% (42/78) cases of PNENs tissues showed DJ-1 positive staining; DJ-1 expression level in PNENs tissues had signiifcantly positive correlation with lymph node metastasis (P=0.033), distant metastasis (P=0.017), TNM stage (P=0.012), and pathology grade (P=0.049); As a dependent risk factor, DJ-1 expression was signiifcantly associated with shorter OS (P=0.003) and DFS (P=0.018) of PNENs patients.Conclusion:High expression of DJ-1 protein correlated with invasion and metastasis, disease progression, and poor prognosis in PNEN.