Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare condition caused by pancreatic neuroendocrine tumors (p-NETs). The severe hypercortisolemia that characterizes EAS is associated with a poor prognosis and survival. Mitotane is the only adrenolytic drug approved by the Food and Drug Administration and is often used to treat adrenocortical carcinoma. Combination therapy with mitotane and other adrenal steroidogenesis inhibitors is common for patients with Cushing’s syndrome (CS). Here, we describe three patients who developed EAS secondary to the liver metastasis of p-NETs. All three rapidly developed hypercortisolemia but no typical features of CS. They underwent anti-tumor and mitotane therapy, which rapidly reduced their blood cortisol concentrations and ameliorated their symptoms. Their hypercortisolemia was controlled long term using a low dose of mitotane. The principal adverse effects were a slight loss of appetite and occasional dizziness, and there were no severe adverse effects. Importantly, even when the tumor progressed, the patients’ circulating cortisol concentrations remained within the normal range. In summary, the present case series suggests that mitotane could be used to treat hypercortisolemia in patients with EAS caused by advanced p-NETs, in the absence of significant adverse effects.

Neuroendocrine neoplasms (NENs) are a group of rare tumors with strong heterogeneity. Among these tumors, well‐differentiated tumors can have a relatively good survival prognosis, while some tumors can have strong malignant potential and lead to increased mortality. Traditional Chinese medicine (TCM), which has a long history of thousands of years, has been widely used to treat tumors due to its unique advantages, such as economy, efficacy and few side effects. In recent years, the role of TCM in the treatment of NENs has gradually emerged. It can not only help prevent tumor recurrence and reduce the side effects of radiotherapy and chemotherapy but also relieve symptoms and improve quality of life. Various clinical studies have indicated that TCM has achieved good curative effects at different stages of treatment. We summarized the last 10 years of research progress on the clinical application of TCM in the treatment of NENs from four points of entry, aiming to provide a reference for the treatment of NENs.

Background: Advanced pancreatic cancer (APC) is a fatal disease with limited treatment options. This study aims to evaluate the effectiveness and safety of different Chinese herbal injections (CHIs) as adjuvants for radiotherapy (RT) in APC and compare their treatment potentials using network meta-analysis.Methods: We systematically searched three English and four Chinese databases for randomized controlled trials (RCTs) from inception to July 25, 2023. The primary outcome was the objective response rate (ORR). Secondary outcomes included Karnofsky performance status (KPS) score, overall survival (OS), and adverse events (AEs). The treatment potentials of different CHIs were ranked using the surface under the cumulative ranking curve (SUCRA). The Cochrane RoB 2 tool and CINeMA were used for quality assessment and evidence grading.Results: Eighteen RCTs involving 1199 patients were included. Five CHIs were evaluated. Compound Kushen injection (CKI) combined with RT significantly improved ORR compared to RT alone (RR 1.49, 95 % CrI 1.21- 1.86). Kanglaite (KLT) plus RT (RR 1.58, 95 % CrI 1.20-2.16) and CKI plus RT (RR 1.49, 95 % CrI 1.16-1.95) were associated with improved KPS score compared to radiation monotherapy, with KLT +RT being the highest rank (SUCRA 72.28 %). Regarding AEs, CKI plus RT was the most favorable in reducing the incidence of leukopenia (SUCRA 90.37 %) and nausea/vomiting (SUCRA 85.79 %). Conclusions: CKI may be the optimal choice of CHIs to combine with RT for APC as it may improve clinical response, quality of life, and reduce AEs. High-quality trials are necessary to establish a robust body of evidence. Protocol registration: PROSPERO, CRD42023396828.

Objective: To dig deeper into the traditional Chinese medicine treatment rules of chemotherapy-induced diarrhea with traditional Chinese medicine (TCM) inheritance computing platform system. Methods: Taking "traditional Chinese medicine", "chemotherapy" and "diarrhea" as the theme words, comprehensive search of the database of CNKI, Wanfang and VIP from its inception to November 2020 was conduct-ed. The formulas of external treatment of traditional Chinese medicine for chemotherapy-induced diarrhea were included and the association rule, clustering and factor analysis were carried out. Results: A total of 145 papers, 57 prescriptions meeting the inclusion criteria were collected, among which high-frequency drugs including Baizhu (Atractylodis macrocephalae rhizoma), Fuling (Poria), Dangshen (Codonopsisradix), Huanglian (Coptidis rhizoma), Zhigancao (Glycyrrhizae radix et rhizoma praeparata cum melle) were the most commonly used. The confidence level was set as 0.7 and the support level was set as 10, 12 core compatibility groups were obtained, and 6 categories were cluster analyzed. Conclusion: The principle of external treatment of chemotherapy-induced diarrhea is mainly "restore deficiency and benefiting qi", "benefiting water infiltration and dampness", "clearing heat" and "inducing astringency". Prescription combination and new prescription combination based on traditional Chinese medicine (TCM) inheritance computing platform system can be used as reference for clinicians and applied in primary hospitals.

Background Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are rare, accounting for ~1/100,000 of NECs, aggressive neoplasms and poor prognosis. Sometimes, a non-neuroendocrine component is also accompanying these EP-NECs. Curative surgery is suggested for early stage patients while system chemotherapy and locoregional radiotherapy are considered for advanced inoperable disease. Nonetheless, there was lack of standard second-line treatment strategy. Herein, we report a case of NEC involving a large cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma of the gallbladder treated with a surufatinib-containing regimen in the second-line treatment setting and establish the efficacy of this regimen in the treatment of EP-NECs. Case Description A 58-year-old male presented with symptoms such as distension in the upper right abdomen and a palpable mass. The abdominal magnetic resonance imaging (MRI) scan showed a giant soft tissue mass in the left lobe of the liver, and liver biopsy suggested LCNEC with a non-neuroendocrine (NNE) component. Based on the available literature, a first-line therapy of oxaliplatin + gemcitabine + camrelizumab + apatinib was started initially; however, there was rapid tumor progression. Thus, a second line of treatment was started, where apatinib was replaced with surufatinib, which was given along with oxaliplatin and camrelizumab and continued for seven complete cycles. The patient was re-examined with MRI, which showed a significant decrease in tumor size. And a partial response was achieved. Main adverse events included hand and foot numbness, hypertension, proteinuria, hematuria, and hyperthyroidism. The patient underwent surgery after the second line of treatment and the post-operative pathology report revealed the presence of LCNEC and adenocarcinoma of the gallbladder. Two months later, re-examination result showed no tumor recurrence. Conclusions As yet, the criteria strategy for unresectable EP-NECs to improve survival outcomes is scarce. EP-NECs are badly in need of effective second-line therapy to carry out survival benefits after resistance to first-line regimen. The case report demonstrated that a surufatinib-containing regimen including oxaliplatin and camrelizumab could be an effective treatment strategy for the second-line treatment of EP-NECs. Furthermore, this strategy is well tolerated and treatment-related toxicity are manageable. More clinical trials are warranted to further confirm the efficacy.

Autoimmune atrophic gastritis （AAG） is an organ-specific autoimmune disease limited to the gastric fundus and corpus mucosa,which can be combined with various diseases,including type 1 gastric neuroendocrine tumors （g-NETs）.Type 1 g-NETs is a rare malignant tumor that grows slowly but is prone to recurrence,which is caused by the proliferation of enterochromaffin-like cells on the basis of AAG.In recent years,due to the improvement of diagnostic technology and raising of awareness of the diseases,the incidence of these diseases has been increasing gradually which has been paid attention by clinicians.In this article,a comprehensive review on the etiopathogenesis,diagnosis and treatment for AAG and type 1 g-NETs and the relations between the two kinds of diseases was carried out,in order to provide references for clinical practice.

目的 挖掘中医治疗恶性肿瘤放化疗性口腔黏膜炎的用药规律.方法 通过检索中国知网、万方数据库、维普网自建库至2019年7月中医治疗放化疗性口腔黏膜炎的文献,使用Excel、R-studio、SPSS 20.0等工具,对纳入药物进行关联规则分析及因子分析.结果 符合纳入标准的方剂共75首,中药155味,使用频数≥10的药物共11味,以苦寒、甘寒药为主;对这11味中药进行关联规则分析发现提升度较高组合有14对,对去除甘草的频数≥10的10味中药进行关联规则分析,发现提升度均较高;因子分析提取4个公因子.结论 中医治疗放化疗性口腔黏膜炎用药以清热解毒、养阴生津、活血生肌止痛为主.

Dysfunction of the blood-brain barrier (BBB) is a prerequisite for the pathogenesis of many cerebral diseases. Oxidative stress and inflammation are well-known factors accounting for BBB injury. Panax notoginseng saponins (PNS), a clinical commonly used drug against cerebrovascular disease, possess efficient antioxidant and anti-inflammatory activity. In the present study, the protective effects of PNS on lipopolysaccharide (LPS)-insulted cerebral microvascular endothelial cells (bEnd.3) were assessed and the underlying mechanisms were investigated. The results showed that PNS mitigated the decrease of Trans-Endothelial Electrical Resistance, increase of paracellular permeability, and loss of tight junction proteins in bEnd.3 BBB model. Meanwhile, PNS suppressed the THP-1 monocytes adhesion on bEnd.3 monolayer. Moreover, PNS prevented the pro-inflammatory cytokines secretion and reactive oxygen species generation in bEnd.3 cells stimulated with LPS. Mechanism investigations suggested that PNS promoted the Akt phosphorylation, activated Nrf2 antioxidant signaling, and inhibited the NF-kappa B activation. All the effects of PNS could be abolished by PI3K inhibition at different levels. Taken together, these observations suggest that PNS may act as an extrinsic regulator that activates Nrf2 antioxidant defense system depending on PI3K/Akt and inhibits NF-kappa B inflammatory signaling to attenuate LPS-induced BBB disruption and monocytes adhesion on cerebral endothelial cells in vitro.