Critical considerations for the management of gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms and pure neuroendocrine carcinomas

Mixed neuroendocrine non-neuroendocrine neoplasms constitute rare tumors that are located mainly in the gastrointestinal(GI)tract and have high degrees of malignancy,and the frequency of these tumors has been increasing.They consist of a neuroendocrine neoplastic component with another component of adenocarcinoma usually and have a dismal prognosis.The rare GI pure neuroendocrine carcinoma is highly aggressive and requires complex and extensive management since a genetic distinction exists between it and GI non-neuroendocrine neoplasms,which are generally slow-growing lesions.The most common GI-mixed neuroendocrine non-neuroendocrine neoplasms are colorectal,followed by gastric,mainly in the gastroesophageal junction.Current imaging modalities of nuclear medicine and radiology play important roles in the accuracy of diagnosis.Liquid biopsy may contribute to early detection and timely diagnosis.Ultrasonography,either endoscopic or abdominal,is a technique that contributes to a diagnosis;additionally,contrast-enhanced ultrasonography is very helpful in followup appointments.Histopathology establishes a definite diagnosis and stage by evaluating the cell differentiation grade and the cell proliferation index Ki67.The genetic profile can be valuable in diagnosis and gene therapy.Surgical resection with wide lymphadenectomy,whenever possible,and adjuvant chemotherapy constitute the main therapeutic management strategies.Targeted therapy and immunotherapy achieve encouraging results.

Benchmark for establishment of organoids from gastrointestinal epithelium and cancer based on available consumables and reagents

Gastrointestinal cancers are a public health problem that threatens the lives of human being. A good experimental model is a powerful tool to promote the uncovering pathogenesis and establish novel treatment methods. High-quality biomedical research requires experimental models to recapitulate the physiological and pathological states of their parental tissues as much as possible. Organoids are such experimental models. Organoids refer to small organlike cellular clusters formed by the expansion and passaging of living tissues in 3D culture medium in vitro.Organoids are highly similar to the original tissues in terms of cellular composition, cell functions, and genomic profiling. Organoids have many advantages, such as short preparation cycles, long-term storage based on cryopreservation, and reusability. In recent years, researchers carried out the establishment of organoids from gastrointestinal mucosa and cancer tissues, and accumulated valuable experiences. In order to promote effective usage and further development of organoid-related technologies in the research of gastrointestinal diseases, this study proposes a benchmark based on utilization of available experimental consumables and reagents, which are involved in the key steps such as collection and pretreatment of biospecimen, organoid construction, organoid cryopreservation and recovery, growth status evaluation, and organoid quality control. We believe that the standard for the construction and preservation of organoids derived from human gastrointestinal epithelium and cancer tissues can provide an important reference for the majority of scientific researchers.

Effects of 7.5% hypertonic saline on fluid balance after radical surgery for gastrointestinal carcinoma

AIM: To investigate the effects of 7.5% hypertonic saline on positive fluid balance and negative fluid balance, after radical surgery for gastrointestinal carcinoma. METHODS: Fifty-two patients with gastrointestinal carcinoma undergoing radical surgery were studied. The patients were assigned to receive either Ringer lactate solution following 4 mL/kg of 7.5% hypertonic saline (the experimental group, n = 26) or Ringer lactate solution (the control group, n = 26) during the early postoperative period in SICU. Fluid infusion volumes, urine outputs, fluid balance, body weight change, PaO2/FiO2 ratio, anal exhaust time as well as the incidence of complication and mortality were compared between the two groups. RESULTS: Urine outputs on the operative day and the first postoperative day in experimental group were significantly more than in control group (P<0.000001, P=0.000114). Fluid infusion volumes on the operative day and the first postoperative day were significantly less in experimental group than in control group (P= 0.000042, P= 0.000415). The volumes of the positive fluid balance on the operative day and during the first 48 h after surgery, in experimental group, were significantly less than in control group (P<0.000001). Body weight gain post-surgery was significantly lower in experimental group than in control group (P<0.000001). The body weight fall in experimental group occurred earlier than in control group (P<0.000001). PaO2/FiO2 ratio after surgery was higher in experimental group than in control group (P= 0.000111). The postoperative anal exhaust time in experimental group was earlier than in control group (P= 0.000006). The overall incidence of complications and the incidence of pulmonary infection were lower in experimental group than in control group (P= 0.0175, P= 0.0374). CONCLUSION: 7.5% hypertonic saline has an intense diuretic effect and causes mobilization of the retained fluid, which could reduce fluid infusion volumes and positive fluid balance after radical surgery for gastrointestinal carcinoma, as well as, accelerate the early appearance of negative fluid balance after the surgery, improve the oxygen diffusing capacity of the patients' alveoli, and lower the overall incidence of complications and pulmonary infection after the surgery.

Role of nuclear receptor NR4A2 in gastrointestinal inflammation and cancers

NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with neurological disorders such as Parkinson's disease.Recently,NR4A2 has been found to play a critical role in some inflammatory diseases and cancer.NR4A2 can be efficiently trans-activated by some proinflammatory cytokines,such as tumor necrosis factor-α,interleukin-1β,and vascular endothelial growth factor(VEGF).The nuclear factor-κB signaling pathway serves as a principal regulator of inducible NR4A expression in immune cells.NR4A2 can trans-activate Foxp3,a hallmark specifically expressed in regulatory T(Treg) cells,and plays a critical role in the differentiation,maintenance,and function of Treg cells.NR4A2 in T lymphocytes is pivotal for Treg cell induction and suppression of aberrant induction of Th1 under physiological and pathological conditions.High density of Foxp3 + Treg cells is significantly associated with gastrointestinal inflammation,tumor immune escape,and disease progression.NR4A2 is produced at high levels in CD133 + colorectal carcinoma(CRC) cells and significantly upregulated by cyclooxygenase-2-derived prostaglandin E 2 in a cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)-dependent manner in CRC cells.The cAMP/PKA signaling pathway is the common pathway of NR4A2-related inflammation and cancer.NR4A2 trans-activates osteopontin,a direct target of the Wnt/β-catenin pathway associated with CRC invasion,metastasis,and poor prognosis.Knockdown of endogenous NR4A2 expression attenuates VEGF-induced endothelial cell proliferation,migration and in vivo angiogenesis.Taken together,NR4A2 emerges as an important nuclear factor linking gastrointestinal inflammation and cancer,especially CRC,and should serve as a candidate therapeutic target for inflammation-related gastrointestinal cancer.

Application of stilamin on advanced gastrointestinal carcinoma patients complicated with malignant bowel obstruction

Objective： To investigate the effectiveness of stilamin in malignant bowel obstruction （MBO） due to advanced gastrointestinal carcinoma patients. Methods： 62 patients with MBO due to gastrointestinal carcinoma were randomly divided into two groups： routine therapy group （control group 30 patients） and stilamin group （32 patients）. Stilamin group received routine therapy combined with stilamin （6 rag/d） by 24 hours continuous infusion for three to twelve days. The curative effectiveness was observed and compared between the two groups. Results： After treatment, the clinical symptoms of abdominal distention and abdominal pain were relieved significantly in stilamin group compared with the control group （84.4% vs 57.6%; P 〈 0.05）. The exhaust of anus was more earlier （62.1% vs 25.6%; P 〈 0.05）, and the average volume of gastrointestinal decompression reduced more rapidly in stilamin group compared with the control group [（216 ± 158） mL/d vs （522 ± 184） mL/d; P 〈 0.001）, smaller and less fluid-air in the intestinal and in the colon at the 81.3% of patients plain abdominal radiography were observed in stilamin group. Quality of life, evaluated with Karnofsky score （57 ±7 vs 45 ±9; P 〈 0.01）, was improved significantly. Conclusion： The administration of stilamin, in combination with routine treatment can be very effective in the management of MBO. It can effectively relieve the symptoms of MBO and improve the quality of life in patients.

Treatment of radiation-induced hemorrhagic gastritis with prednisolone:A case report

Radiation-induced gastritis is an infrequent cause of gastrointestinal bleeding.It is a serious complication arising from radiation therapy,and the standard treatment method has not been established.The initial injury is characteristically acute inflammation of gastric mucosa.We presented a 46-year-old male patient with hemorrhagic gastritis induced by external radiotherapy for metastatic retroperitoneal lymph node of hepatocellular carcinoma.The endoscopic examination showed diffuse edematous hyperemicmucosa with telangiectasias in the whole muscosa of the stomach and duodenal bulb.Multiple hemorrhagic patches with active oozing were found over the antrum.Anti-secretary therapy was initiated for hemostasis,but melena still occurred off and on.Finally,he was successfully treated by prednisolone therapy.We therefore strongly argue in favor of perdnisolone therapy to effectively treat patients with radiation-induced hemorrhagic gastritis.

Research progress on anti-tumor properties of Marsdenia tenacissima

Tongguanteng （Marsdenia tenacissima）, which is mainly distributed in the Yunnan and Guizhou provinces of China, wasfirst recorded in Diannanbencao by Lan Mao of the Ming dynasty of China. According to recent pharmacological studies,the chemical composition of Tongguanteng （Marsdenia tenacissima） is complex and contains C21 steroidal saponins,polysaccharides, alkaloids, and other molecules, which show anti-cancer effects on various tumor cell lines. It inhibitstumor cell proliferation and growth mainly by increasing the expression of apoptosis- and cell cycle-related proteins topromote apoptosis and arrest tumor cells in the G2/M or S phase. Downregulation of the expression of vascularendothelial growth factor-2/A and matrix metalloprotease-2/9 suppresses the formation of the tumor microvasculature,leading to tumor malnutrition, increased expression of interleukin-2, glutathione peroxidase, catalase, and superoxidedismutase, and decreased interleukin-10 and malondialdehyde expression, thereby enhancing immunity andantioxidation in the body. Additionally, inhibition of epidermal growth factor receptor, hepatocyte growth factor receptor,and tyrosine-protein kinase receptor activation enhances the anti-tumor efficacy of epidermal growth factorreceptor-tyrosine kinase inhibitors as well as inhibits P-glycoprotein and cytochrome P450 to increase the concentrationof anti-tumor drugs in tumor cells.