Malignant gastrointestinal neuroectodermal tumor: a case report and literature review.

Introduction and importance: A malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare primary malignant mesenchymal tumor of the gastrointestinal tract characterized by EWSR1 gene rearrangement. An optimal systemic treatment strategy for advanced/recurrent GNET has not yet been identified. Case presentation: A 24-year-old male patient was hospitalized with abdominal pain and underwent two operations for a tumor in his small intestine. Immunohistochemistry (IHC) showed strong expression of S-100 protein and SOX 10. Fluorescence in situ hybridization analysis and next-generation sequencing analysis indicated that there were EWSR gene rearrangements and the presence of EWSR-ATP1 gene fusions, respectively. The diagnosis of GNET in the small intestine was confirmed by pathology. The young patient received the fifth-line of apatinib mesylate and the sixth-line of apatinib combined with temozolomide. The two apatinib-containing regimens showed stable disease and progression-free survival of 4.7 months and 3.1 months with single-agent apatinib or apatinib combined with temozolomide, respectively. Clinical discussion: To our best knowledge, this is the first report of malignant GNET treated with apatinib and temozolomide. Apatinib-containing regimens might has antineoplastic activity against GNET. The authors reviewed the relevant reports of previous GNET treatment, summarized the clinicopathological characteristics of GNET, and found that there are no reports of apatinib for backline treatment of GNET. Conclusion: Containing apatinib may provide an additional treatment option for patients with chemotherapy-resistant GNET tumors.

Observations of boundary layer wind and turbulence of a landfalling tropical cyclone.

This study investigates the atmospheric boundary layer structure based on multiple-level tower observations with a height of 350 m during the landfall of Super Typhoon Mangkhut (2018). Results show a layer of log wind profile outside of the radius of maximum wind speed with a height of 100 m or larger. The log layer height increases with the wind speed. The height of the constant flux layer reaches ~ 300 m for 10-m wind speeds less than 13 m s-1 while this height decreases with the wind speed. Momentum fluxes and turbulent kinetic energy increase with the wind speed at all vertical levels. The drag coefficient and surface roughness length estimated at the tower location have values of 7.3 × 10-3 and 0.09 m, respectively, which are independent of wind speed. The estimated vertical eddy diffusivity and mixing length increase with height up to ~ 160 m and then slowly decrease with height. The vertical eddy diffusivity increases with the wind speed while the vertical mixing length has no dependence on the wind speed. Comparing our results with previous work indicates that the vertical eddy diffusivity is larger over land than over ocean at a given wind speed range.

Recent biomedical advances enabled by HaloTag technology.

The knowledge of interactions among functional proteins helps researchers understand disease mechanisms and design potential strategies for treatment. As a general approach, the fluorescent and affinity tags were employed for exploring this field by labeling the Protein of Interest (POI). However, the autofluorescence and weak binding strength significantly reduce the accuracy and specificity of these tags. Conversely, HaloTag, a novel self-labeling enzyme (SLE) tag, could quickly form a covalent bond with its ligand, enabling fast and specific labeling of POI. These desirable features greatly increase the accuracy and specificity, making the HaloTag a valuable system for various applications ranging from imaging to immobilization of POI. Notably, the HaloTag technique has already been successfully employed in a series of studies with excellent efficiency. In this review, we summarize the development of HaloTag and recent advanced investigations associated with HaloTag, including in vitro imaging (e.g., POI imaging, cellular condition monitoring, microorganism imaging, system development), in vivo imaging, biomolecule immobilization (e.g., POI collection, protein/nuclear acid interaction and protein structure analysis), targeted degradation (e.g., L-AdPROM), and more. We also present a systematic discussion regarding the future direction and challenges of the HaloTag technique.

Surgical Treatment of Port-Site Metastases After Laparoscopic Radical Resection of Gastrointestinal Tumors.

Aim: This study was performed to investigate the feasibility of surgical treatment of port-site metastasis after laparoscopic radical resection of gastrointestinal tumors. Patients and Methods: We retrospectively analyzed the clinical data and follow-up data of 8 patients with port-site metastases after gastrointestinal cancer resection in our hospital from January 2014 to January 2018. Results: Six of port-site metastases occurred within 6 months after gastrointestinal tumor resection, one of port-site metastases occurred in 10 months after the operation, and one of port-site metastases occurred in 30 months after the operation. Any metastasis to the abdominal cavity or distant metastasis was ruled out before the surgical treatment of the port-site metastases, and all patients recovered well after the extended operation. No incisional infection or incisional hernia occurred. By December 2019, 4 patients had died (they had survived for 12, 13, 18, and 24 months, respectively) and 5 patients had survived. The follow-up duration ranged from 19 to 28 months. Conclusions: Surgical resection of port-site metastases is not difficult because of their superficial location. Surgical treatment can improve the prognosis of patients without abdominal metastasis or distant metastasis/recurrence.

HOXB7 overexpression promotes cell proliferation and correlates with poor prognosis in gastric cancer patients by inducing expression of both AKT and MARKs.

Increased expression of HOXB7 has been reported to correlate with the progression in many cancers. However, the specific mechanism by which it promotes the evolution of gastric cancer (GC) is poorly understood.In this study, we sought to investigate the role of HOXB7 in GC by assessing HOXB7 expression in patient tissue and its correlation to clinical characteristics. We found that GC tissues showed increased expression of HOXB7 and that the HOXB7 expression was significantly associated with Lauren classification, invasion depth, lymphatic metastasis and poor prognosis, and could serve as an independent prognostic factor. To further investigate the role of HOXB7 in GC, we generated stable GC cell lines and both over-expressed and knocked down HOXB7 expression. Over-expression of HOXB7 in GC cell lines enhanced cell proliferation, colony formation, migration and invasion ability, whereas the opposite trends were observed upon reduction of HOXB7 expression by knockdown. These findings were further supported by our in vivo studies which show that HOXB7 expression can affect the GC cells' subcutaneous growth and lung metastases. A Phospho-MAPK Array Kit was used to explore the possible mechanism of HOXB7-induced cell proliferation and invasion. We found that the AKT signaling pathway and the two members of the MAPK pathway, were involved in those promoting effects. In conclusion, our results showed that increased expression of HOXB7 might play an important role in promoting GC proliferation, migration and invasion by inducing both AKT and MAPK pathways, thus resulting in progression of, and poor prognosis in GC patients.

Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation.

BACKGROUND: Several somatic mutation hotspots were recently identified in the telomerase reverse transcriptase (TERT) promoter region in human cancers. Large scale studies of these mutations in multiple tumour types are limited, in particular in Asian populations. This study aimed to: analyse TERT promoter mutations in multiple tumour types in a large Chinese patient cohort, investigate novel tumour types and assess the functional significance of the mutations. METHODS: TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumour types and 799 tumour tissues from Chinese cancer patients. Thymic epithelial tumours, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), telomerase activity by the telomeric repeat amplification protocol (TRAP) assay and promoter activity by the luciferase reporter assay. RESULTS: TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%) and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in gastrointestinal stromal tumour (GIST), thymic epithelial tumours, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. CONCLUSIONS: TERT promoter mutations are frequent in multiple tumour types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumourigenesis, making them potential therapeutic targets.

[Association of SOX9 expression and prognosis in patients with gastric cancer].

OBJECTIVE: To investigate the association of SOX9 expression and clinicopathologic factors and prognosis of gastric cancer. METHODS: A retrospective cohort study including 112 gastric cancer patients admitted to the Zhejiang Provincial People's Hospital from 2004 to 2006 was performed. Immunohistochemical analysis was used to evaluate the expression of SOX9 in the 112 specimens of gastric cancer tissues and 70 non-cancerous tissues adjacent to the tumor. RESULTS: Low expression of SOX9 was seen in 5(7.1%) tissues out of 70 non-cancerous tissues adjacent to the tumor. A total of 94(83.9%) patients had varying expression of SOX9, of whom 51(45.4%) had overexpression. Univariate analysis demonstrated that the expression of SOX9 was significantly associated with Lauren classification (P<0.05), tumor invasion(P<0.01), lymph node metastasis(P<0.05), distant metastasis(P<0.05) and tumor stage(P<0.05), however there was no significant association between SOX9 expression and sex, age, histological type, histology differentiation or tumor size. Kaplan-Meier analysis showed that the 5-year survival rate of patients with SOX9 over-expression was significantly lower than that of patients with low expression(29.4% vs. 49.2%, P=0.031). Multivariate Cox regression analysis showed that histology differentiation(P=0.046), tumor invasion(P=0.001), and distant metastasis(P<0.01) were independent prognostic factors for gastric cancer, however the over-expression of SOX9 was not significant(P=0.948). CONCLUSIONS: The expression SOX9 is associated with the growth, invasion, and metastasis of gastric cancer, as well as the prognosis. However, SOX9 expression is not an independent factor for the prognosis in patients with gastric cancer.

Clinicopathological characteristics and prognosis of early gastric cancer after gastrectomy.

BACKGROUND: Assessment of lymph node metastasis (LNM) is important in early gastric cancer (EGC) and affects treatment decisions. However, the relationship between clinicopathological characteristics and LNM in EGC remains unclear. This study therefore explored favorable predictors of LNM in EGC. METHODS: A total of 716 specimens from gastric cancer patients who underwent curative gastrectomy between 1996 and 2003 at Zhejiang Provincial People's Hospital were reviewed. Forty-five cases were EGC, and clinicopathological characteristics such as gender, age, tumor size, location, gross type, differentiation, invasion depth, and vessel involvement were assessed to identify predictive factors for LNM and survival time. RESULTS: The overall cumulative 5-year survival rate of EGC patients was 88.92%. Among these, 22.4% developed LNM, which was associated with a poor 5-year survival rate of only 72.7%. Patients with tumors larger than 2 cm in diameters, with depth of tumor invasion to the submucosa, and with positive lymphatic or nerve involvement were also inclined to have poorer survival performances. EGC limited to the mucosa but poorly differentiated also had a high risk for LNM. Multivariate analysis identified lymphatic invasion and tumor size as independent prognosis factors related to survival in EGC patients. CONCLUSIONS: Careful planning is required in EGC patients at high risk of lymph node metastases. Endoscopic mucosal resection or endoscopic submucosal dissection and laparoscopic partial gastrectomy should be cautiously used in EGC, and curative gastrectomy including lymphatic dissection and postoperative adjuvant therapy might be considered to improve the prognosis.

[Clinical application of pocks embedding in duodenal stump closure after radical gastrectomy for gastric carcinoma].

OBJECTIVE: To explore the clinical effect of pockets embedding in duodenal stump closure after gastrectomy for gastric cancer. METHODS: A total of 2034 patients undergoing gastrectomy from January 1995 to December 2009 at our hospital were reviewed. Among them, Group A (n = 465) underwent pockets embedding for duodenal stump, Group B (n = 835) line-cutting stapler and hand-sewing while Group C (n = 734) double layer hand-sewing. The operation cost, processing time of duodenal stump, recent post-operative complications (within 1 month), blood loss volume and post-operative recovery status were compared between 3 groups. RESULTS: No patient died of operation. Ninety-five cases (4.7%) suffered recent post-operative complications. The most frequent complications included wound infection (36 cases, 37.9%), intra-abdominal hemorrhage (18 cases, 18.9%) and anastomotic leakage (14 cases, 14.7%). There was no significant difference in intra-abdominal bleeding, anastomotic leakage, abdominal infection, wound infection or duodenal stump leakage among 3 groups. There was no duodenal stump leakage in Group A. The difference was apparent in comparisons with Groups B (6 cases, 0.72%) and C (5 cases, 0.68%). The operation costs of Groups A [(9902 ± 312) RMB] and C [(9896 ± 281) RMB] were significantly lower than that of Group B [(13 129 ± 237) RMB, P = 0.0001]. And there was no difference between Groups A and C. The processing time of duodenal stump in Groups A [(7.1 ± 0.9) min] and B [(7.6 ± 0.8) min] were lower than that of Group C [ (11.5 ± 1.4) min, P = 0.0001]. And there was no difference between Groups A and B. There was no significant difference in blood loss volume or post-operative recovery status among 3 groups. CONCLUSION: The post-gastrotomic closure of duodenal stump with pockets embedding for gastric cancer has a short operation time, a low operation cost and a low rate of duodenal stump leakage. It is a simple, prompt, promising and safe surgical procedure for gastric neoplasms.

Application of purse-string suture for management of duodenal stump in radical gastrectomy.

BACKGROUND: Gastric cancer (GC) is the second leading cause of cancer mortality worldwide, and surgical resection is currently the only possible curative approach. Duodenal stump leakage is the most serious complication after radical gastrectomy, and optimal treatment is still lacking. METHODS: We retrospectively reviewed 2034 cases of total or subtotal gastrectomy for GC from January 1995 to December 2009, including 465 cases of duodenal stump closure using purse-string suture (group A), 835 cases of duodenal stump treated with linear cutting stapler and seromuscular layer suture (group B), and 734 cases of duodenal stump closure using full-thickness and seromuscular layer suture (group C). We evaluated the surgical cost, operative time for duodenal stump closure, short-term postoperative complications, perioperative blood loss, and postoperative recovery. RESULTS: There was no perioperative mortality in any group. Ninety-four postoperative (within 1 month) complications occurred: 18 abdominal bleeding, 14 anastomotic leakage, 15 abdominal infection, 36 wound infection, and 11 duodenal stump leakage. There was no significant difference among the groups in intra-abdominal hemorrhage, anastomotic leakage, abdominal infection and wound infection. No postoperative duodenal stump leakage occurred in group A, which had a significant difference compared with groups B and C (6 cases in group B and 5 cases in group C suffered duodenal stump leakage. P < 0.01). The surgical cost in groups A and C was significantly lower than in group B (P < 0.01), with no significant difference between groups A and C. The processing time for duodenal stump closure in groups A and B was significantly shorter than in group C (P < 0.01), with no significant difference between groups A and B. There was no significant difference in blood loss and postoperative recovery among the groups. CONCLUSIONS: Duodenal stump closure using purse-string suture seems to be a promising approach with shorter operative time, and lower cost and incidence of duodenal stump leakage in radical gastrectomy.