Professor Lou Wenhui talks about perioperative treatment strategies for pancreatic neuroendocrine tumors, and individualized diagnosis and treatment can break the situation!

*Only for medical professionals to read and reference experts take you to see the diagnosis and treatment of pancreatic neuroendocrine tumors! Full of dry goods! Neuroendocrine tumors (NENs) are relatively rare tumors, but the incidence of NENs in China has been on the rise in recent years
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The symptoms and signs of NEN patients are different, and it is easy to be misdiagnosed clinically.
Most patients are diagnosed at an advanced stage, and only a few patients have the opportunity to undergo radical surgical resection
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At the same time, due to the heterogeneity of NEN and individual differences of patients, there are many uncertainties between clinical diagnosis and treatment behaviors and outcomes
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Different NEN patients with different grades, stages and types of metastasis have different clinical preoperative neoadjuvant therapy and postoperative adjuvant therapy strategies
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In order to clarify the surgical intervention methods for NEN patients and the individualized treatment and follow-up strategies for NEN patients, the Medical Tumor Channel invited Professor Lou Wenhui from the Pancreatic Surgery Department of Zhongshan Hospital Affiliated to Fudan University to conduct a comprehensive analysis and discussion on the above issues
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Different grades of metastatic NEN patients have great differences in surgical interventions.
NEN is a relatively rare tumor, and has gradually been known by more medical workers and patients in recent years
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NEN originates from neuroendocrine cells in the human body and can grow in any part of the human body, among which the main primary sites are the gastrointestinal tract and the pancreas
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Clinically, most NEN patients have already experienced local spread or even distant metastasis at the time of diagnosis, losing the opportunity for radical surgery
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Professor Lou Wenhui pointed out that according to statistics, about 40% to 50% of NEN patients have liver metastases at the initial diagnosis
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For such patients with metastases at the initial diagnosis, doctors need to formulate reasonable treatment strategies when performing surgical intervention
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First, doctors need to grade and classify patients according to the degree of tissue differentiation and cell proliferation activity.
The cell proliferation activity is assessed by mitotic count and Ki-67 index
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According to the 2019 World Health Organization (WHO) NEN grading standard, NENs are divided into well-differentiated NETs and poorly-differentiated NECs according to their differentiation and grading
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The key difference between NEC and G3 NET is that the latter is better differentiated
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For indistinguishable G3-grade NETs and NECs, TP53, RB1, DAXX, and ATRX chromosomes are required to assist in the differential diagnosis
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After the classification of NEN is determined, different surgical interventions need to be taken according to patients with different classifications
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Theoretically, G1/G2 NEN develops slowly and has a better prognosis.
Clinically, these patients can take more active treatment strategies, such as primary tumor resection, liver metastases resection, etc.
In addition, surgery combined with radiofrequency can also be used.
Ablation, intervention and other means of treatment
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After active treatment, most patients can achieve relatively long survival
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If the patient has many liver metastases, and the patient is younger and has a lower grade, liver transplantation is also an effective strategy.
If the patient cannot undergo surgical resection, clinical measures such as vascular embolization or intervention will be used to achieve shrinkage.
After the tumor is removed, surgical resection is performed
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For patients with grade G3 NEC liver metastases or metastases at other sites, systemic therapy is required in addition to local therapy
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At this point, clinicians choose treatment strategies individually based on the stage and grade of the patient's tumor
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Patients with pNEN need to be graded and staged to select an appropriate preoperative neoadjuvant therapy strategy.
The main purpose of neoadjuvant therapy is to achieve tumor downstaging, increase surgical resection rate and R0 resection rate, and thus improve the prognosis of patients
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Since most NEN patients have liver metastases or obvious local tumor invasion at the initial diagnosis, neoadjuvant therapy may have certain clinical significance
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Before neoadjuvant therapy, it is first necessary to comprehensively evaluate the grade, stage, functional status, and type of metastasis of the tumor to determine whether the patient can benefit from preoperative neoadjuvant therapy
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Patients with larger tumor size, more scattered distribution, and poor grades and stages may be the type for which neoadjuvant therapy should be considered clinically
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Secondly, doctors need to choose neoadjuvant treatment strategies for patients individually.
At present, the research on neoadjuvant therapy in the field of NEN is relatively limited, so the most suitable neoadjuvant therapy drugs are still inconclusive.
In general, such patients are generally discussed and treated individually
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For patients with NEC with a high degree of malignancy, chemotherapy is often selected clinically.
For patients with NET, long-acting somatostatin analogs combined with targeted therapy or combined interventional and radiofrequency ablation are preferred
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For NEN neoadjuvant therapy, relevant clinical studies are being carried out in China, including the exploration of targeted therapy drugs.
It is believed that with the passage of time, more drugs or treatments will be applied to NEN neoadjuvant therapy in the future, benefiting domestic of NEN patients
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Pancreatic cancer and pNEN are two different types of tumors.
Pancreatic cancer and pNEN have significant differences in terms of cell origin, biological characteristics and prognosis.
Regarding the relationship between pancreatic cancer and pNEN, Professor Lou Wenhui pointed out: First, The pathological origins of the two are different.
Pancreatic cancer is derived from cells with exocrine function, including ductal adenocarcinoma, cystadenocarcinoma, and acinar cell carcinoma.
pNEN is derived from neuroendocrine cells
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Secondly, the different origins of the two lead to different clinical manifestations.
Pancreatic cancer is a type of highly malignant tumor.
Most patients have already metastasized at the time of diagnosis.
Even if they undergo surgery, the prognosis is not satisfactory.
Two or three years later Recurrence and metastasis may occur, which seriously affects the survival of patients
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Pancreatic cancer patients are often accompanied by weight loss, obstructive jaundice, pain and fatigue, while pNEN grows slowly and is a low-grade malignant tumor, and most patients do not experience obvious symptoms
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Finally, the treatment strategies of the two are completely different.
In clinical practice, surgical resection is the first choice for patients with pancreatic cancer, and most patients who cannot undergo surgical resection also choose more aggressive treatment strategies, such as concurrent chemoradiotherapy, in order to achieve a short time Control tumors
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For tumors that develop relatively slowly, such as NEN, there is often enough time to adjust the patient's treatment plan and prolong the patient's survival time
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In addition, compared with pancreatic cancer, pNEN has more treatment methods, and the application of long-acting somatostatin analogs, targeted drugs, chemotherapy drugs, immunotherapy, and radioisotopes in terms of drugs is also currently being explored.

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Targeted selection of postoperative adjuvant therapy strategies can effectively reduce the risk of recurrence.
The Chinese Guidelines for the Diagnosis and Treatment of Pancreatic Neuroendocrine Tumors (2020) pointed out that the biological behavior of most pancreatic neuroendocrine tumors (pNETs) is relatively indolent, but some research results show that, The overall recurrence and metastasis rate after pNET can be as high as 13.
7% to 36.
2%
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It is currently believed that higher tumor burden, higher tumor stage or grade (especially higher Ki-67 index), combined lymph node metastasis and vascular invasion are all risk factors for postoperative recurrence and poor prognosis of patients
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Although there is currently no unified postoperative adjuvant treatment standard and scheme, since radical resection alone cannot achieve satisfactory results in patients with high-grade pNET and pancreatic neuroendocrine carcinoma (pNEC), surgery is still recommended for such patients in principle.
Post-adjuvant therapy [1]
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Professor Lou Wenhui emphasized that radical surgery is usually effective in the treatment of patients with grades G1 and G2 pNET.
Currently, such patients are not routinely recommended for postoperative adjuvant therapy, but there are risk factors for postoperative recurrence, especially for grade G2 pNET.
The patient is recommended for adjuvant therapy
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If the patient has grade G3 p-NET, the domestic expert consensus suggests that such patients can be empirically treated with capecitabine combined with temozolomide (CAPTEM) regimen.
For pNEC patients, carboplatin/cisplatin combined with etopo is currently used.
Adjuvant therapy with glycoside (EP/EC) regimen [1]
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G1 or G2 pNEN patients with distant metastases such as liver metastasis or lung metastasis, on the premise of ensuring the safety of surgery, if both the primary tumor and the metastatic tumor can be radically removed, surgical resection is performed.
High-risk recurrence risk factors are also evaluated clinically.
If the patient has high-risk recurrence risk factors, long-acting somatostatin analogs or targeted drug therapy are selected according to the specific conditions of the patient
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Professor Lou Wenhui emphasized that the drugs used in clinical practice to prevent the recurrence of pNEN should firstly have controllable adverse reactions, and secondly, have definite curative effect
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At present, long-acting somatostatin analogs are the preferred drugs in clinical practice, and targeted therapy drugs may also be considered in the future.
Its application in the adjuvant therapy of other solid tumors has also played a good role in the exploration of the adjuvant therapy mode of pNEN
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The follow-up strategy needs to be adjusted individually after operation, and long-term follow-up is required.
Malignant tumors need regular follow-up after operation.
The progression of pNEN is relatively slow, and the interval between postoperative recurrence is mostly long.
Therefore, it needs to be individually formulated according to the situation of different patients.
follow-up strategy
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The follow-up content of pNEN patients is mainly based on imaging examinations, including abdominal contrast-enhanced CT or magnetic resonance imaging, and chest imaging examinations are not routinely recommended
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For patients with non-functional pNEN, chromophein A (CgA) has important value as a tumor marker, but because the detection of this marker has not been standardized in domestic clinical practice, it is not recommended as a routine
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For functional tumors, hormones such as insulin and glucagon can be used as follow-up detection indicators
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Regarding the recommended follow-up time for pNEN patients, Professor Lou Wenhui suggested that all pNEN patients should be followed up for no less than 10 years.
If the patient has high-risk recurrence risk factors or is receiving postoperative adjuvant therapy, it is recommended to follow up every 6 months.
Follow-up for at least 3 years
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If the patient had no sign of recurrence after 3 years, the follow-up was adjusted to once a year until 10 years
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Some patients develop recurrence and metastasis 15 years after surgery, so extending the follow-up time to 15-20 years can also effectively prevent recurrence
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In addition, it is recommended that patients with grade G1 pNEN be reexamined once a year, with a maximum interval of no more than 2 years
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Many patients ignore the importance of follow-up after 5 or 10 years of follow-up without recurrence and metastasis.
After symptoms appear, the tumor often recurs and metastasizes, thus losing the opportunity for early treatment
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Expert Profile Lou Wenhui Professor Director of Pancreatic Surgery, Deputy Director of General Surgery, and Director of the Surgery Center Laboratory, Zhongshan Hospital Affiliated to Fudan University
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Doctor of Medicine, Chief Physician, Professor, Doctoral Supervisor
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He has long been engaged in the diagnosis and treatment of pancreatic tumors, gastrointestinal tumors and gastroenteropancreatic neuroendocrine tumors
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Outstanding academic leader in Shanghai, former chairman of the General Surgery Branch of Shanghai Medical Association
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He is currently the deputy director of the Surgery Branch of the Shanghai Medical Association, the national member of the 18th Surgical Committee of the Chinese Medical Association, the deputy head of the Pancreatic Surgery Group of the Surgery Branch of the Chinese Medical Association, the vice chairman of the Pancreatic Disease Branch of the Chinese Research Hospital Association, and a Chinese physician.
National member of the Surgical Branch of the Association, member of the Standing Committee of the Pancreatic Disease Professional Committee of the Chinese Medical Doctor Association, member of the Standing Committee of the MDT Professional Committee; Chairman of the Neuroendocrine Tumor Sub-Committee; Vice-Chairman of the Neuroendocrine Tumor Branch, the Fast Recovery Committee, and the Weight Loss and Metabolic Surgery Branch of the China Medical Association Chairman; Chairman of the Basic Equipment Special Committee of the Surgical Equipment Branch of the China Medical Equipment Association
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"Journal of Digestive Disease", "Annual of Surgery" (Chinese version), "Chinese Journal of Practical Surgery", "Chinese Journal of Hepatobiliary Surgery", "Chinese Journal of Medicine", "Chinese Journal of Surgery", "Chinese Journal of Digestive Surgery" Editorial Board and Correspondence Editorial Board
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In recent years, as the first author and corresponding author, he has published more than 100 articles in domestic core journals and foreign journals, including more than 60 SCI papers
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He has undertaken a number of national, provincial and municipal research projects including the National Natural Science Foundation of China, the "863" Project, and the National Major R&D Program
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In 2020, he won the second prize of Shanghai Medicine, and successively won the titles of "National Famous Doctor" (2019), Shanghai Outstanding Specialist Physician (2020)
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References: [1] Chinese Guidelines for the Diagnosis and Treatment of Pancreatic Neuroendocrine Tumors (2020) MCC No.
SAN22031818 Valid on 2023-03-16, the data is expired and will be considered invalid
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*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform