2020 Vol. 11, No. 4

Editorial
Abstract:
Neuroendocrine neoplasias (NENs) are rare. Some NENs secrete hormone, thus causing hypertension of the patients. NENs are important causes of secondary hypertension, which include pheochromocytoma and paraganglioma, growth hormone-secreting pituitary adenoma, adrenocorticotropic hormone-secreting pituitary adenoma, parathyroid adenoma and carcinoma, and ectopic hormone-secreting NENs. Apart from hypertension, most NEN patients had other typical clinical features that need to be identified at early stage. In recent years, with the application of new technologies of nuclide imaging, the detection rate of these diseases has been greatly improved, and more patients can be diagnosed and treated early.
Specialist Forum
Abstract:
Multiple endocrine neoplasia (MEN) is an autosomal dominant hereditary disease involving multiple endocrine glands with two or more endocrine tumors occurring simultaneously or successively. MEN-related tumors include primary hyperparathyroidism, pheochromocytoma, medullary thyroid cancer, pancreatic neuroendocrine neoplasia, and pituitary adenoma, etc. Although the clinical characteristics and treatment of these tumors are similar to those of sporadic tumors, there are differences in some aspects. In recent years, there has been some consensus achieved on the treatment of MEN-related tumors. But there are also some controversies. The timing and scope of surgical resection are the focus of controversies.
Abstract:
Neuroendocrine neoplasm (NEN) is a heterogeneous group of tumors characterized by neuroendocrine differentiation. Most of the tumor cells show high-level expression of the somatostatin receptor (SSTR), which provides an important target for molecular imaging and peptide receptor radionuclide therapy (PRRT). This area has become a research hotspot at home and abroad in recent years. In addition, rapid progress and new breakthroughs have been made in clinical translation and application continuously. This article reviewed the new advances in SSTR-targeted nuclear molecular imaging and PRRT, and summarized their main advantages and important values in the diagnosis and treatment of NEN, in hope of giving relevant professional doctors a reference for clinical diagnosis and treatment.
Abstract:
Genomic sequencing studies have led to an increased understanding of the genotyping and molecular biology of pancreatic neuroendocrine neoplasias(pNENs). Recent studies reported that ATRX(α-thalassaemia/mental retardation syndrome X-linked)/DAXX(death-domain associated protein), ARID1A(AT-rich interactive domain-containing protein 1A, BAF250A), MUTYH(mutY homolog), and MEN-1(multiple endocrine neoplasia type 1) genes are remarkably mutated in non-functional pNENs, as well as genes encoding core components of the mammalian target of rapamycin (mTOR) signaling pathway. As a representative of functional pNENs, insulinomas had CNV amplifications and copy neutral with YY1 (Yin Yang 1) gene mutations. These mutated genes are involved in aberrations of chromatin remodeling, DNA damage repair, histone modification, and telomere maintenance, and thus might contribute to tumorigenesis and ultimately to the progression of pNENs characterized by divergent phenotypes. Differentiating genotypic subtypes of pNENs plays an important role in prognostication. Future therapies might be based on recent advances in molecular genotyping and mechanism.
Abstract:
Pancreatic neuroendocrine neoplasm (pNEN) is a relatively rare type of pancreatic tumor, and its incidence has been on the rise in recent years. The treatment of pNEN with liver metastasis needs comprehensive consideration of its pathological grade, tumor stage, liver metastasis burden, and extrahepatic metastasis, etc. On the basis of comprehensive evaluation, multidisciplinary team is needed to formulate the best diagnosis and treatment plan, and the main goals are to control tumor growth, reduce tumor burden, control excessive hormone secretion and related complications, and prolong patient survival. Surgery is an effective treatment method for pNEN with liver metastasis, which helps to improve the prognosis of patients. Based on literature review and our experiences, this article elaborated the current major issues of concern, to provide a guide for surgical treatment of pNEN with liver metastasis.
Abstract:
Pancreatic neuroendocrine neoplasms (pNENs) are the most common type of gastro-entero-pancreatic neuroendocrine tumor. Over 60% of patients were detected with distant metastases after the initial diagnosis. Liver is the most common metastatic site, 65.5% of liver metastases are unresectable. The basic treatment strategy is system therapy, mainly including somatostatin analogues, target therapy, and chemotherapy with the effect of anti-hormone secretion and anti-proliferation. But the objective response ratio (ORR) of system therapy is mild. Hepatic artery direct therapies, including trans-arterial embolization (TAE), trans-arterial chemoembolization (TACE), and trans-arterial radioembolization (TARE) can reduce the hepatic tumor burden fast and safely. The ORR can be improved too. There is no significant difference in the efficacy of the three methods. TAE has the highest ORR among the three methods but no side effect of chemotherapy of TACE, so that it is widely used in clinical practice. The outcome of peptide receptor radionuclide therapy (PRRT) was proved to be satisfactory in the low-grade or intermediate grade pNENs that expressed high levels of somatostatin receptor or had a moderately metastatic hepatic tumor burden. The severe complications from PRRT are myelo-suppression and radiation nephrotoxicity. The combined therapy should be applied to the treatment of complicated pNENs with liver metastases. The general strategies are reducing the hepatic tumor burden as soon as possible by firstly applying system drugs and interventional therapy, and then the primary tumor should be resected in elective surgery.
Abstract:
Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia, which is due to excessive secretion of parathyroid hormone (PTH) from one or several parathyroid glands. With the tests of serum calcium and PTH being routinely employed, the incidence of PHPT has distinctly increased and PHPT has become a common endocrine disorder. The concept of diagnosis and treatment for PHPT has been developing continuously. Most cases of PHPT are sporadic, while 5%-10% of cases are hereditary. In this literature, we reviewed the advances in diagnosis and surgical treatment of PHPT.
Guideline Interpretation
Abstract:
Colonization of Group B streptococcus (GBS) in the reproductive tract and mother-to-child transmission is an important cause of puerperal infection and neonatal infection/death. Currently, there is no unified screening strategy in China, and most medical institutions adopt the guideline of Prevention of perinatal group B streptococcal disease that formulated by the U.S. Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists (ACOG) in 2010. The incidence of GBS related diseases has been reduced significantly. In January 2020, ACOG released a new consensus on GBS screening and intrapartum management:Prevention of Group B Streptococcal Early-Onset Disease in Newborns:ACOG Committee Opinion, Number 797, which updated issues such as timing and procedure for preterm GBS screening andintrapartum antibiotic prophylaxis. Here we present a detailed interpretation on the relevant content.
Original Contributions
Abstract:
  Objective  The aim of this study was to analyze the factors affecting the prognosis of rectal neuroendocrine neoplasia (NEN).  Methods  The clinical data were retrospectively collected in patients with rectal NEN who were diagnosed and surgically treated in the Department of General Surgery at Peking Union Medical College Hospital from May 2012 to September 2019. Patients suffering from distant organ metastases and rectal adenocarcinoma at the initial diagnosis were excluded. Kaplan-Meier analysis was used to assess the influence of general information, surgical methods, pathology, etc. on the disease-free survival.  Results  A total of 130 patients with rectal NEN were enrolled, and 102 patients had a clear WHO classification. Among them, G1, G2, and G3 had 82, 18, and 2 patients, respectively. A total of 122 patients underwent local resection and 9 patientsunderwent radical surgery. One patient underwent remedial radical surgery after local resection. Lymph node metastasis was found in 7 patients, and all of them underwent radical surgery. Follow-up was performed on 116 patients, 4 of whom had recurrence or metastasis, and 2 died of NEN metastasis. Kaplan-Meier analysis showed that patients with radical surgery, lesions ≥ 2 cm, and lymph node metastasis had a lower rate of recurrence-free survival(all P < 0.05).  Conclusions  Patients with rectal NEN who had a lesion ≥ 2 cm or metastatic lymph nodes may have a poorer prognosis. Radical surgery should be actively performed for these patients after cautious evaluation to exclude distant metastases, and a close follow-up should also be performed after surgery.
Abstract:
  Objective  The aim of this study was to evaluate the value of Huaxi emotional-distress index(HEI) on assessing the length of hospital stay, hospitalization costs, and patient satisfaction in elderly patients after surgery.  Methods  The clinical data of elderly patients in the surgery database from the Department of Anesthesiology, West China Hospital of Sichuan University during October 2015 and June 2018 were retrospectively collected, including gender, age, education, American Society of Anesthesiologists(ASA) classification, malignancy, the surgical department, Mini-cog score, Katz index, HEI classes(1-4), and adverse emotion, to analyze the correlation of HEI with length of hospital stay, hospitalization costs, and patient satisfaction.  Results  A total of 565 elderly patients meeting the inclusive and exclusive criteria were enrolled in this study. There were no statistical difference in gender, age, education, ASA classification, malignancy, the surgical department, and Mini-cog score among different HEI classes and different adverse emotion groups(all P>0.05). The patients with adverse emotion had longer length of hospital stay(P=0.003) and higheraverage daily hospitalization costs(P=0.001); and the higher the HEI rating, the longer the length of hospital stay(P=0.000). HEI and adverse emotion correlated with the 7-day patient satisfaction(all P < 0.05), the patients with adverse emotion had lower 7-day patient satisfaction.  Conclusion  HEI might predict the length of hospital stay, hospitalization costs, and patient satisfaction in elderly patients after surgery.
Abstract:
  Objective  The aim of this study was to evaluate the rehabilitation time of parathyroid autotransplant through analyzing the changes of blood calcium in total thyroidectomy patients with four parathyroid autotransplanted during surgery.  Methods  Patients underwent total thyroidectomy with four parathyroid autotransplanted by the same surgeon group at Peking Union Medical College Hospital during the period from April, 2012 to January, 2016 were included. Serum calcium levels at 48 hours, 1 week, 1 month, 6 months and1 year after surgery were collected. The mixed linear model was established and data were analyzed by Bonferroni method after logarithm processing.  Results  A total of 37 patients who met the inclusion and exclusion criteria were included in this study, including 9 males and 28 females with a median age of 38 (33, 46)years. The levels of Serum calcium significantly decreased 48 hours after thyroidectomy (mean difference -0.099 mmol/L, 95% CI:-0.110~-0.088 mmol/L, P < 0.001). There was no significant difference in the levels of serum calcium at 1 week, 1 month, 6 months and 1 year after surgery (all P>0.05).  Conclusions  The levels of serum calcium of the 4 patients with parathyroid gland autotransplantation decreased significantly 48 h after surgery and then gradually recovered and maintained at the normal level for a long time, which suggests that the autotransplanted parathyroid begins to recover 1 week after surgery and can be maintained for a long time.
Abstract:
  Objective  The objective of this study was to analyze risk factors for pathologically negative reoperation in patients with differentiated thyroid cancer.  Methods  The clinical data of patients underwent reoperation for differentiated thyroid cancer from January 2013 to December 2017 in Peking Union Medical College Hospital were assessed retrospectively. Based on postoperative pathology, patients were further divided into pathology positive and negative groups. The demographic characteristics, operation information, pathological findings, and ultrasonography outcomes were compared between the two groups.  Results  A total of 218 patients were included. Seventy cases were males and 148 cases were females. The male to female ratio was 1:2.11. The average age was 43.7±12.7 years. All patients were diagnosed with local recurrence or metastasis before the reoperation. Twenty-seven patients had negative postoperatively pathological results, while other 191 had positive ones. Compared with the positive group, the patients of the negative group were older (49.3±12.6years vs. 42.9±12.5 years, P=0.013) and had fewer multifocal lesions (7.4% vs. 24.6%, P=0.045). The two groups had no significant difference in gender, operation information, tumor size, and ultrasonography outcomes (all P>0.05).  Conclusions  Pathologically negative reoperation for differentiated thyroid cancer is not rare. The age and multifocality of the primary surgery may be associated with negative reoperative pathology.
Reviews
Abstract:
MicroRNA-21(miRNA-21), a kind of small endogenous non-coding RNA, is widely expressed in various tissues and plays a pivotal role in the occurrence and development of many diseases. In recent years, the role of miRNA-21 in pulmonary hypertension(PH) has attracted extensive attention, and its function in subtypes of PH is not always the same or even contradictory. This review summarized recent advances of miRNA-21 in PH, encompassing pathophysiological processes mediated by miRNA-21, its roles in subtypes of PH, and insufficiency of current researches, in order to figure out the role of miRNA-21 in PH and provide a reference for future studies.
Abstract:
Pain is the main symptom of endometriosis, and about 5% to 10% of reproductive-aged women become potential patients in pain. However, to date, the mechanisms of pain associated with endometriosis are still poorly understood. Available evidence shows a lesion surrounded by aberrant nerve fibers and blood vessels, sensitization of the peripheral nerve, morphological and functional anomaly of the central nervous system are all related to pain associated with endometriosis. This review focused on the possible mechanisms of endometriosis-associated pain in the peripheral and central nervous systems, to provide a possible theoretical basis for clinical treatment.
Abstract:
With the rapid development of sequencing technology, a large number of clinical cases with personalized medicine have been accumulated. Abundant evidence-based medical data have promoted the rapid development of pharmacogenomics. However, it could play an important role only if it would be deployed in clinical practice. There are two strategies for the clinical deployment of pharmacogenomics:reactive strategy and preemptive strategy. Different deployment strategies require different deployment processes. The specific implementation process involves the integration of EMR, selection of gene-drug pairs, cost-effectiveness, education and training, etc. This paper reviewed the strategies and implementation workflow of pharmacogenomics clinical deployment, and discussed the challenges so as to provide guidance for the clinicaldeployment of pharmacogenomics in China.
Clinical Research and Evidence Based Medicine
Abstract:
Professor David Sackett was a physician scientist who was a critical thinker and advocated for modern medicine. He had mentored many pupils, disseminated the theory and concept of evidence-based medicine (EBM), and fully qualified the fame of Master defined by Chinese traditional culture. The primary contributions by Professor David Sackett include:(1)He pioneered to apply the methods of clinical epidemiology to clinical practice, and provided the basis and frame of EBM; (2)He established EBM centers at McMaster University and Oxford University, and cultivated a large number of talents; (3)By making EBM the reference standard for clinical research and practice, he changed modern medicine in a penetrating and powerful way. Professor David Sackett had a deep and strong relationship with Chinese scholars, and laid down the foundation for the development of clinical research and EBM in China.
Clinical Practice Guidelines
Abstract:
Patient version of guidelines(PVG) serves as a tool of health education to help patients better self-manage disease and promote shared decision-making between doctors and patients. As the number of PVG increased in recent years, their quality has gained much attention. However, there is currently no standard or guidance on how to develop PVG scientifically and rigorously. In this article, we introduce the current status, development principles, procedures and reporting standards of PVG. We also provide thoughts and suggestions on how to better develop PVG in China.
Drug Therapy for Tumors
Abstract:
The use of immune checkpoint inhibitors (ICIs) is a revolutionary breakthrough in cancer treatment, which has changed the treatment modality for many types of tumors. The elderly account for the majority of cancer cases and deaths. There are some factors that may affect the treatment of ICIs in aging patients, such as immunosenescence, high incidence of autoimmune diseases and infectious diseases, and difference of tumor mutational burden from young patients. In most clinical trials of ICIs, aging patients did not account for the due proportion of the participants. Results of subgroup analysis and meta-analysis showed that age had little effect on the efficacy of ICIs and immune-related adverse events. Clinicians can refer to the relevant trial data and administer ICIs in elderly cancer patients with good physical condition to accumulate more real-world data.
In Memory of Acadimician SHI Yi-fan
Abstract:
  Objective  The aim of this study was to summarize the etiology and clinical characteristics ofpatients with indistinguishable sellar lesions, and to explore the clinical value and safety of biopsy by endoscopic trans-sphenoidal approach.  Methods  The clinical data were retrospectively collected and analyzed in patients with indistinguishable sellar lesions who underwent biopsy by the endoscopic trans-sphenoidal approach (ETA) or endoscopic extended trans-sphenoidal approach (EETA) in Peking Union Medical College Hospital from July 1, 2011 to July 1, 2019, including the etiology, clinical manifestations, laboratory examinations, radiological features, and postoperative complications.  Results  A total of 142 patients who met the inclusive criteria were enrolled in this study. ETA biopsy was performed in 115 patients (81.0%, 115/142) and EETA in 27 patients (19.0%, 27/142). The etiology included:cystic lesions in 12 patients (8.5%, 12/142), inflammatory/infectious diseases in 30 patients (21.1%, 30/142), and tumors in 100 patients (70.4%, 100/142). The most common diseases were germ cell tumors (79 patients), Langerhans cell histiocytosis (8 patients), Rathke's cysts (8 patients), and lymphocytic hypophysitis (7 patients). The clinical manifestations of patients with this type of disease frequently lacked specificity. Among the 142 patients, the most common manifestations were those related to central diabetes insipidus. There were no patients with elevated alpha-fetoprotein in the cerebrospinal fluid and 29 patients with elevated beta-human chorionic gonadotropin in the cerebrospinal fluid. Among these 29 patients, 27 (93.1%) were germ cell tumors and 2 (6.9%) were craniopharyngiomas. Tumors and inflammatory/infectious diseases most often involved both the sella and pituitary stalk (25.0%, 33.3%), followed by the sella or protruding from the sella (21.0%, 30.0%). Cystic lesions most often involved the sella or protruding from the sella (75.0%). The disappearance of bright spots in the posterior pituitary was discovered in 97.0% of patients. Within 1 month after the biopsy, 7 patients (4.9%, 7/142) had central nervous system infection; 3 patients (2.1%, 3/142) had cerebrospinal fluid leakage with 2 of them recovered after surgical repair. Three patients (2.1%, 3/142) had worsened eye movement; 2 (1.4%, 2/142) had worsened visual acuity; 2 (1.4%, 2/142) had a decreased visual field, who have recovered basically after treatment.  Conclusions  The clinical characteristics of lesions in the sellar area frequently lack specificity. Histopathological examination is the gold standard of diagnosis. Endoscopic trans-sphenoidal biopsy in the sellar area is safe and reliable.
Abstract:
Insulin-like growth factor-1(IGF-1) mediates the growth-promoting effect of growth hormone on peripheral tissues, which is mainly synthesized in the liver. In the circulation, most IGF-1 binds to specific binding proteins, which is more stable than growth hormone. Therefore, IGF-1 is commonly used as a diagnostic marker and treatment monitor of growth hormone deficiency and acromegaly. There are many kinds of assays that measure serum IGF-1 concentrations, including radioimmunoassay, ELISA, chemiluminescence, and mass spectrometry. Different methods have their advantages and disadvantages, so it is necessary to select the best method according to the purpose of detection. The normal reference range of IGF-1 should be established based on a random sampling of the background population. Some European and Asian countries such as Germany, Italy, Japan, and South Korea have established reference ranges of serum IGF-1 based on their own population. ZHU Hui-juan et al. from Peking Union Medical College Hospital preliminarily established the reference range of serum IGF-1 of Han Chinese adults, laying a foundation for the diagnosis and treatment of acromegaly, growth hormone deficiency, and other diseases.
MDT Case from PUMCH
Abstract:
This patient was an elderly male with poor basal multi-organ function reserve, increased eosinophils leading to acute exacerbation of chronic heart and kidney dysfunction. After treatment with hormones and immunosuppressants, eosinophils were normal and the rash subsided. However, pneumocystis carinii pneumonia appeared in the later stage, and the anti-infective treatment was not ideal. Eventually the patient died of septic shock. In this case, the basic situation of the patient was complex, the diagnosis and treatment process was twists and turns, and the multidisciplinary team participated in and discussed to solve the problems in thediagnosis and treatment decision-making of the patient step by step, which embodied the significance of multidisciplinary cooperation in the diagnosis and treatment of difficult diseases.Based on the poor prognosis of the disease, it should be recognized clinically that weakness and delirium are also risk factors for poor prognosis in elderly patients. The elderly have weak compensatory ability, poor tolerance to adverse reactions, and are prone to adverse outcomes.In clinical diagnosis and treatment, the choice of plan needs to be considered in consideration of various factors such as treatment complications, long-term benefits, and expected survival time.
Technology and Methodology
Abstract:
The diagnosis and surgical treatment of insulinoma is dependent on accurate localization with imaging modalities. Glucagon-like peptide-1 receptor (GLP-1R) imaging that targets pancreatic β cells has been highlighted for detecting insulinomas in recent years. Since the high sensitivity and specificity (se. 99%, sp. 100%) of GLP-1R imaging in localizing insulinoma, GLP-1R positron emission tomography/computed tomography (PET/CT) with 68Ga-exendin-4 is recommended to be introduced into clinical practice. This paper introduced the application of GLP-1R imaging in insulinoma, and took the GLP-1R PET/CT with 68Ga-exendin-4 as an example to elaborate the operation standard of this technique, aiming to provide a reference for clinical practice.
History of Medicine
Abstract:
In 1921, the Division of Neurology and Psychiatry was established in Peking Union Medical College Hospital(PUMCH) and there had been four foreign heads of the division before 1941. Neurology and Psychiatry in PUMCH also got developed gradually under their leadership. This paper introduces these four heads' work in the division, including academic and clinical practice, and presents their contributions during their own tenure both in PUMCH and PUMC. Moreover, it summarizes the important role they played in the development of Neurology and Psychiatry in China and provides the experience for the construction of Chinese medical disciplines and talent selection.
2020, 11(4): 500-500.
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Abstract: