Despite multidisciplinary treatment for patients with advanced gastric cancer, their prognosis remains poor. Therefore, the development of novel therapeutic strategies is urgently needed, and ...immunotherapy utilizing anti‐programmed death 1/‐programmed death ligand‐1 mAb is an attractive approach. However, as there is limited information on how programmed death ligand‐1 is upregulated on tumor cells within the tumor microenvironment, we examined the mechanism of programmed death ligand‐1 regulation with a particular focus on interferon gamma in an in vitro setting and in clinical samples. Our in vitro findings showed that interferon gamma upregulated programmed death ligand‐1 expression on solid tumor cells through the JAK‐signal transducer and activator of transcription pathway, and impaired the cytotoxicity of tumor antigen‐specific CTL against tumor cells. Following treatment of cells with anti‐programmed death ligand‐1 mAb after interferon gamma‐pre‐treatment, the reduced anti‐tumor CTL activity by interferon gamma reached a higher level than the non‐treatment control targets. In contrast, programmed death ligand‐1 expression on tumor cells also significantly correlated with epithelial‐mesenchymal transition phenotype in a panel of solid tumor cells. In clinical gastric cancer samples, tumor membrane programmed death ligand‐1 expression significantly positively correlated with the presence of CD8‐positive T cells in the stroma and interferon gamma expression in the tumor. The results suggest that gastric cancer patients with high CD8‐positive T‐cell infiltration may be more responsive to anti‐programmed death 1/‐programmed death ligand‐1 mAb therapy.
PD‐L1 levels significantly correlated with CD8 (stroma) levels (P = .018), but not with CD3 nor CD4 in tumor/stroma in gastric cancer. Furthermore, PD‐L1 levels also significantly positively correlated with tumor IFN‐γ levels. The results suggests that upregulation of PD‐L1 may result from increased IFN‐γ production by CTLs which migrate to the tumor during immune activation.
Recent advances in diagnostic upper endoscopy Teh, Jun-Liang; Shabbir, Asim; Yuen, Soon ...
World journal of gastroenterology,
2020-Jan-28, 2020-1-28, 20200128, Volume:
26, Issue:
4
Journal Article
Open access
Esophageo-gastro-duodenoscopy (EGD) is an important procedure used for detection and diagnosis of esophago-gastric lesions. There exists no consensus on the technique of examination.
To identify ...recent advances in diagnostic EGDs to improve diagnostic yield.
We queried the PubMed database for relevant articles published between January 2001 and August 2019 as well as hand searched references from recently published endoscopy guidelines. Keywords used included free text and MeSH terms addressing quality indicators and technological innovations in EGDs. Factors affecting diagnostic yield and EGD quality were identified and divided into the follow segments: Pre endoscopy preparation, sedation, examination schema, examination time, routine biopsy, image enhanced endoscopy and future developments.
We identified 120 relevant abstracts of which we utilized 67 of these studies in our review. Adequate pre-endoscopy preparation with simethicone and pronase increases gastric visibility. Proper sedation, especially with propofol, increases patient satisfaction after procedure and may improve detection of superficial gastrointestinal lesions. There is a movement towards mandatory picture documentation during EGD as well as dedicating sufficient time for examination improves diagnostic yield. The use of image enhanced endoscopy and magnifying endoscopy improves detection of squamous cell carcinoma and gastric neoplasm. The magnifying endoscopy simple diagnostic algorithm is useful for diagnosis of early gastric cancer.
There is a steady momentum in the past decade towards improving diagnostic yield, quality and reporting in EGDs. Other interesting innovations, such as Raman spectroscopy, endocytoscopy and artificial intelligence may have widespread endoscopic applications in the near future.
It is not clear how the duration of upper endoscopy affects the detection of cancer or premalignant lesions that increase the risk for gastric cancer. We investigated whether the length of time spent ...performing esophagogastroduodenoscopy (EGD) affects the detection of important pathologic features of the stomach.
We collected data from 837 symptomatic patients, during a 3-month period in 2010, who underwent a first diagnostic EGD at a tertiary university hospital in Singapore. Endoscopists were classified as fast or slow based on the mean amount of time it took them to perform a normal EGD examination. We used logistic regression to compare between groups the numbers of intestinal metaplasias, gastric atrophies, dysplasias, and cancers detected, using histologic analysis of biopsy samples collected during endoscopy as the standard.
Of 224 normal endoscopies, the mean duration was 6.6 minutes (range, 2-32 min). When we used 7 minutes as the cut-off time, 8 endoscopists were considered to have short mean examination times (mean duration, 5.5 ± 2.1 min; referred to as fast endoscopists), and 8 endoscopists were considered to have long mean examination times (mean duration, 8.6 ± 4.2 min; referred to as slow endoscopists). Eleven cancers and 81 lesions considered to pose risks for cancer were detected in 86 patients; 1.3% were determined to be cancer, 1.0% were determined to be dysplasia, and 8.7% were determined to be intestinal metaplasia and/or gastric atrophy. Slow endoscopists were twice as likely to detect high-risk lesions as fast endoscopists (odds ratio, 2.50; 95% confidence interval, 1.52-4.12), regardless of whether they were endoscopy staff or trainees. The slow endoscopists also detected 3-fold more neoplastic lesions (cancer or dysplasia; odds ratio, 3.42; 95% confidence interval, 1.25-10.38).
Endoscopists with mean EGD examination times longer than 7 minutes identified a greater number of high-risk gastric lesions than faster endoscopists. Examination time may be a useful indicator of quality assessment for upper endoscopy. Studies are required to test these findings in different populations.
The management of thoracolumbar (TL) burst fractures remained challenging. Due to the complex nature of the fractured vertebrae and the lack of clinical and biomechanical evidence, currently, there ...was still no guideline to select the optimal posterior fixation strategy for TL burst fracture. We utilized a T10-L3 TL finite element model to simulate L1 burst fracture and four surgical constructs with one- or two-level suprajacent and infrajacent instrumentation (U1L1, U1L2, U2L1, and U2L2). This study was aimed to compare the biomechanical properties and find an optimal fixation strategy for TL burst fracture in order to minimize motion in the fractured level without exerting significant burden in the construct. Our result showed that two-level infrajacent fixation (U1L2 and U2L2) resulted in greater global motion reduction ranging from 66.0 to 87.3% compared to 32.0 to 47.3% in one-level infrajacent fixation (U1L1 and U2L1). Flexion produced the largest pathological motion in the fractured level but the differences between the constructs were small, all within 0.26 deg. Comparisons in implant stress showed that U2L1 and U2L2 had an average 25.3 and 24.8% less von Mises stress in the pedicle screws compared to U1L1 and U1L2, respectively. The construct of U2L1 had better preservation of the physiological spinal motion while providing sufficient range of motion reduction at the fractured level. We suggested that U2L1 is a good alternative to the standard long-segment fixation with better preservation of physiological motion and without an increased risk of implant failure.
Endoscopic ultrasound guided-pancreatic duct drainage (EUS- PDD) is one of the most technically challenging procedures for the interventional endoscopist. The most common indications for EUS- PDD are ...patients with main pancreatic duct obstruction who have failed conventional endoscopic retrograde pancreatography (ERP) drainage or those with surgically altered anatomy. EUS- PDD can be performed via two approaches: the EUS-rendezvous (EUS- RV) or the EUS-transmural drainage (TMD) techniques. The purpose of this review is to provide an updated review of the techniques and equipment available for EUS- PDD and the outcomes of EUS- PDD reported in the literature. Recent developments and future directions surrounding the procedure will also be discussed.
Background
Peroral endoscopic myotomy (POEM) is gaining traction as a minimally invasive treatment of achalasia. Increased reflux is reported after POEM but the incidence, type and severity of reflux ...are not fully understood. We aimed to study the prevalence and nature of reflux after POEM and correlate reflux with endoscopy and pH-impedance findings.
Methods
This is a prospective cohort study of achalasia patients undergoing POEM since 2014. Data from Eckardt and GERD symptom scores, high-resolution oesophageal manometry (HRM) and gastroscopy were performed pre-procedure and repeated at 1-year follow-up. Data from 24-h pH-impedance, if performed, were also recorded. A standardized questionnaire was used to determine the severity and frequency of heartburn symptoms and the composite score for each patient was calculated.
Results
58 patients underwent POEM between January 2014 and October 2018. The efficacy of POEM at 1 year was 93.0%. We observed reduction of median Integrated Relaxation Pressure (IRP) from 23.5 ± 33.1 mmHg to 13.4 ± 7.71 mmHg (
p
= 0.005) and mean Eckardt score improved from 6.09 ± 2.43 points to 1.16 ± 1.70 points (
p
< 0.001). At 1 year, 43.1% (
n
= 25) had symptomatic reflux. Of the 40 patients who underwent repeated gastroscopy, 60.0% (
n
= 24) had endoscopic evidence of oesophagitis with seven patients (18%) diagnosed with Grade C or D oesophagitis. 43.1% (
n
= 25) of patients had pH-impedance done post-POEM off PPIs. 14 patients (56%) had increased acid exposure. Sixteen percent of reflux episodes were acidic and 77.3% were weakly acidic
.
Conclusion
POEM was an effective treatment for achalasia. However, GERD was common after POEM with incidence of 43% on symptom score, 60% on endoscopy and 56% on pH-impedance test. Post-POEM reflux appeared to be predominantly acidic in nature. Routine surveillance for GERD after POEM is recommended.
Management of upper gastrointestinal (UGI) tract gastrointestinal stromal tumor (GIST) has evolved significantly over the past two decades. For GIST size smaller than 5 cm, laparoscopic resection has ...become the current standard. To avoid postoperative gastric deformity and preserve gastric function, laparoscopic endoscopic cooperative surgery (LECS) was developed and various modifications have been reported and utilized successfully. Pure endoscopic resection techniques have also been reported at a similar period of time, which further push the boundary of incisionless surgery in managing these lesions. Both tunneling and nontunneling exposed type endoscopic full thickness resection are well described procedures for resection of small UGI GIST. In this review, a summary of these procedures is provided, and the pros and cons of each technique from the perspective of a surgical endoscopist are discussed in detail. LECS and endoscopic resection are complementary to each other. The choice of technique should be tailored to the location, morphology, and size of the target lesions, taking into account the experience of the laparoscopic surgeons and endoscopists.
Background
Bleeding of the gastrointestinal tract (BGIT) is a common gastrointestinal emergency. There is no consensus whether this condition should be admitted to medical or surgical discipline. ...Timing of presentation may also impact patient outcomes due to differences in healthcare resource availability. This study thus aims to investigate the impact of admitting discipline and timing of admission on patient outcomes in BGIT.
Methods
A 2‐year tertiary institution database was retrospectively reviewed. Outcome measures included 30‐day mortality, 30‐day readmissions and rebleeding requiring repeat endoscopic, angiographic or surgical interventions. Secondary outcome measures included time to endoscopy, percutaneous angiographic interventions and surgery. The effect of admission discipline (medical versus surgical) and time of admission (office‐hours versus after office‐hours) were analysed using a propensity‐score‐adjusted estimate.
Results
A total of 1384 patients were included for analysis, medical (n = 853), surgical (n = 530); during office‐hours (n = 785) and after office‐hours (n = 595). After propensity‐score‐adjusted analysis, no significant differences in mortality or readmissions were noted between medical or surgical admissions. Patients admitted under surgery were less likely to sustain rebleeding (P = 0.004) for lower BGIT and had an earlier time to endoscopy for upper BGIT (P = 0.04). Patients admitted after office‐hours had similar outcomes with those admitted during office hours apart from a delay in time to endoscopy (P = 0.02).
Conclusion
For BGIT patients, admission to a surgical discipline compared to a medical discipline appeared to have at least equivalent patient outcomes. Patients presenting with BGIT after office‐hours were more likely to experience a delay to endoscopy, although it did not affect patient mortality.
Surgeons trained in therapeutic endoscopy can manage gastrointestinal bleeding patients with at least equivalent, if not better, outcomes as physicians. In addition, for all patients presenting with gastrointestinal bleeding, although there might be a delay to endoscopy for patients who presented after office‐hours, it did not significantly impact patient outcomes.
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