Tunneled biopsy is an underutilised,simple,safe and efficient method for tissue acquisition from subepithelial tumours

BACKGROUND Tissue acquisition from subepithelial lesions is often attempted by endoscopic ultrasound(EUS)-sampling as conventional endoscopic biopsy usually fails to reach deeper layers of the gastrointestinal wall.AIM To investigate the utilisation,safety and diagnostic yield of an intensified“biteon-bite”tunnel biopsy technique.METHODS In this retrospective cohort study,all patients presenting with subepithelial masses in the upper gastrointestinal tract from March 2013 to July 2019 were included.Data were analysed for size and location of the subepithelial mass,use of intensified tunnel biopsy protocol(more than 10 double bite-on-bite biopsies)or superficial conventional biopsies,histology and imaging results,occurrence of readmission and adverse events after endoscopy.RESULTS Two hundred and twenty-nine patients with subepithelial lesions were included.Superficial conventional biopsies were taken in 117 patients and were diagnostic only in one lipoma(0.9%).Tunnel biopsies taken in 112/229(48.9%)patients were significantly more likely to provide histological diagnosis(53.6%;P<0.001).For lesions≥10mm the diagnostic yield of tunnel biopsies further increased to 41/67(61.2%).No immediate or delayed complications were reported.Only 8 of the 51 endoscopists(15.7%)regularly attempted tunnel biopsies.CONCLUSION Tunnel biopsy is a simple,safe and efficient but underutilised diagnostic modality for tissue acquisition in subepithelial masses.It should be routinely attempted at the initial endoscopy.

Recurrent undifferentiated embryonal sarcoma of the liver in adult patient treated by pembrolizumab: A case report

BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a neoplasm that rarely develops in adults.The main treatments for UESL are upfront gross total surgical resection and adjuvant multiagent chemotherapy.Here,we report a case of recurrent UESL in an adult treated with pembrolizumab and discuss a method to identify proper candidates for antibody of programmed cell death protein 1(anti-PD-1)treatment.CASE SUMMARY A 69-year-old woman was admitted for abdominal pain that developed for 1 wk.Computed tomography showed a 16 cm mass in the right lobe of the liver.Right hemihepatectomy and lymphadenectomy were performed,and histological diagnosis was UESL.Six months later,the patient suffered from painless obstructive jaundice,and positron emission tomography-computed tomography revealed multiple metastases.Then,percutaneous transhepatic cholangial drainage was applied to reduce jaundice,and radiofrequency ablation was used to control the lesion near the hepatic hilum.However,the patient suffered from a serious fever caused by the tumor.The patient received treatment with pembrolizumab,and the prescribed dosage was 2 mg/kg every 3 wk.After the seventh dose,positron emission tomography-computed tomography revealed that the multiple metastases had nearly disappeared.Radiologic exam was used to evaluate the disease state,and no new lesions were found.Next-generation sequencing and immunohistology were applied to determine the reason why the patient had such a favorable response to pembrolizumab.Tumor mutation burden,microsatellite instability,and programmed death ligand 1 expression can be combined to predict the effect of PD-1 antibodies. When every one of thesebiomarkers are detected in a tumor patient, the patient may be a proper candidatefor PD-1 antibodies.CONCLUSION Anti-PD-1 treatment for tumors needs further research to identify indications andproper biomarkers.

Translational pancreatic cancer research:a comparative study on patient-derived xenograft models

AIM To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice.METHODS This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations(intraperitoneal, subcutaneous and pancreatic). Histological analysis(haematoxylin-eosin and Masson's trichrome staining) and immunohistochemical assessment of apoptosis(TUNEL), proliferation(Ki-67), angiogenesis(CD31) and fibrogenesis(α-SMA) were performed. When a tumour xenograft reached the target size, it was reimplanted in a new nude mouse. Three sequential tumour xenograft generations were generated(F1, F2 and F3).RESULTS The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth(69.9%), followed by intraperitoneal(57.6%) and pancreatic(55%) models. Tumour development was faster in the subcutaneous model(17.7 ± 2.6 wk) compared with the pancreatic(23.1 ± 2.3 wk) and intraperitoneal(25.0 ± 2.7 wk) models(P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models(F1 28.1% vs F2 71.4% vs F3 80.9%, P < 0.001). There were no significant differences in tumour xenograft differentiation and cell proliferation between human samples and the three experimental models among the sequential generations of tumour xenografts. However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation and apoptosis was observed in the three experimental models compared with the human samples. All three pancreatic patient-derived xenograft models presented similar histological and immunohistochemical characteristics.CONCLUSION In our experience, the faster development andgreatest number of viable xenografts could make the subcutaneous model the best option for experimentation in pancreatic cancer.

Evaluation of bone remodeling in regard to the age of scaphoid non-unions

AIM: To analyse bone remodeling in regard to the age of scaphoid non-unions(SNU) with immunohistochemistry.METHODS: Thirty-six patients with symptomatic SNU underwent surgery with resection of the pseudarthrosis. The resected material was evaluated histologically after staining with hematoxylin-eosin(HE), tartrate resistant acid phosphatase(TRAP), CD 68, osteocalcin(OC) and osteopontin(OP). Histological examination was performed in a blinded fashion.RESULTS: The number of multinuclear osteoclasts in the TRAP-staining correlated with the age of the SNU and was significantly higher in younger SNU(P = 0.034; r = 0.75). A higher number of OP-immunoreactive osteoblasts significantly correlated with a higher number of OC-immunoreactive osteoblasts(P = 0.001; r = 0.55). Furthermore, a greater number of OP-immunoreactive osteoblasts correlated significantly with a higher number of OP-immunoreactive multinuclear osteoclasts(P = 0.008; r = 0.43). SNU older than 6 mo showed a signifi-cant decrease of the number of fibroblasts(P = 0.04). Smoking and the age of the patients had no influence on bone remodeling in SNU.CONCLUSION: Multinuclear osteoclasts showed a significant decrease in relation to the age of SNU. However, most of the immunhistochemical findings of bone remodeling do not correlate with the age of the SNU. This indicates a permanent imbalance of bone formation and resorption as indicated by a concurrent increase in both osteoblast and osteoclast numbers. A clear histological differentiation into phases of bone remodeling in SNU is not possible.

A Case of Huge Fibroma in the Palate

Fibroma-like lesions occur with relatively high frequency in oral soft tissues, but represent reactive proliferation against chronic irritation. True fibromas are rare. Tumor size is often seen to range from the mass of a red bean to a soybean. We encountered a case of huge fibroma in the palate with a long history of more than 30 years. The patient was a 60-year-old man who became aware of a tumor in the right palate about 30 years earlier. The mass had tended to increase in size in recent years, and was introduced to our department for the first visit. As an intraoral finding, a pedicled mass measuring 29 × 27 mm was found in the right palate. We also considered the possibility of verrucous carcinoma, and performed biopsy, obtaining a diagnosis of fibroma. Right palatectomy was performed under general anesthesia in October 2016. We performed immunohistochemical examination of the surgical specimen, obtaining a definitive diagnosis of fibroma. As of 1 year postoperatively, no recurrence has been identified and the course has been good.

Extracellular matrix-based intracortical microelectrodes:Toward a microfabricated neural interface based on natural materials

Extracellular matrix(ECM)-based implantable neural electrodes(NEs)were achieved using a microfabrication strategy on naturalsubstrate-based organic materials.The ECM-based design minimized the introduction of non-natural products into the brain.Further,it rendered the implants sufficiently rigid for penetration into the target brain region and allowed them subsequently to soften to match the elastic modulus of brain tissue upon exposure to physiological conditions,thereby reducing inflammatory strain fields in the tissue.Preliminary studies suggested that ECM-NEs produce a reduced inflammatory response compared with inorganic rigid and flexible approaches.In vivo intracortical recordings from the rat motor cortex illustrate one mode of use for these ECM-NEs.