Influence of biliary stents on the diagnostic outcome of endoscopic ultrasound–guided tissue acquisition from solid pancreatic lesions: a systematic review and meta-analysis

Background/Aims This meta-analysis analyzed the effect of an indwelling biliary stent on endoscopic ultrasound (EUS)–guided tissue acquisition from pancreatic lesions. Methods A literature search was performed to identify studies published between 2000 and July 2022 comparing the diagnostic outcomes of EUS-tissue acquisition (TA) in patients with or without biliary stents. For non-strict criteria, samples reported as malignant or suspicious for malignancy were included, whereas for strict criteria, only samples reported as malignant were included in the analysis. Results Nine studies were included in this analysis. The odds of an accurate diagnosis were significantly lower in patients with indwelling stents using both non-strict (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.52–0.90) and strict criteria (OR, 0.58; 95% CI, 0.46–0.74). The pooled sensitivity with and without stents were similar (87% vs. 91%) using non-strict criteria. However, patients with stents had a lower pooled sensitivity (79% vs. 88%) when using strict criteria. The sample inadequacy rate was comparable between groups (OR, 1.12; 95% CI, 0.76–1.65). The diagnostic accuracy and sample inadequacy were comparable between plastic and metal biliary stents. Conclusions The presence of a biliary stent may negatively affect the diagnostic outcome of EUS-TA for pancreatic lesions

A prospective study of fully covered self-expandable metal stents for refractory benign pancreatic duct strictures

Background/Aims Fully covered self-expanding metal stents (FCSEMSs) are a relatively novel option for treating painful main pancreatic duct refractory strictures in patients with chronic pancreatitis. Herein, we aimed to assess the efficacy, feasibility, and safety of FCSEMSs in this patient group. Methods This prospective single-center study included patients who underwent endoscopic retrograde pancreatography with FCSEMS placement. The primary endpoints were the technical and clinical success rates. A reduction in visual analog scale pain score of >50% compared with that before stent placement was defined as clinical success. Secondary endpoints were resolution of pancreatic strictures on fluoroscopy during endoscopic retrograde pancreatography and the development of stent-related adverse events. Results Thirty-six patients were included in the analysis. The technical success rate was 100% (n=36) and the clinical success rate was 86.1% (n=31). There was a significant increase in stricture diameter from 1.7 mm to 3.5 mm (p<0.001) after stent removal. The mean visual analog scale pain score showed statistically significant improvement. At 19 months of follow-up, 55.6% of the patients were asymptomatic. Stent migration (16.7%), intolerable abdominal pain (8.3%), development of de novo strictures (8.3%), and mild pancreatitis (2.8%) were the most common adverse events. Conclusions FCSEMS placement showed good technical and clinical success rates for achieving pain relief in patients with refractory main pancreatic duct strictures

Identification of epitopes of monoclonal antibodies to porcine zona pellucida 3 β glycoprotein, a homologue of the mouse/human sperm receptor

Problem: Immunization with zona pellucida (ZP) glycoproteins leads to a block in fertility with a variable degree of ovarian dysfunction. To avoid autoimmune oophoritis, synthetic peptides corresponding to B cell epitope(s) and devoid of oophoritogenic T cell epitopes as immunogens have been proposed. The main objective of the present study is to define the epitopes recognized by monoclonal antibodies (mAbs) generated against porcine ZP3 beta, a homologue of the designated primary sperm receptor in mice and humans. Methods: A multipin synthetic peptides approach has been used to map the epitopes recognized by mAbs. Dodecapeptides with an overlap of 6 amino acids corresponding to a precursor pZP3 beta-deduced amino acid sequence (excluding the signal sequence) were synthesized on polypropylene pins and were tested for their reactivity with mAbs by enzyme-linked immunoadsorbent assay (ELISA). The ability of synthetic peptides corresponding to the identified epitopes to inhibit the binding of mAbs to pZP3 beta in a competitive inhibition ELISA was investigated to confirm the above findings. Results: Reactivity of the mAbs with the pin-bound peptides in ELISA-identified epitopes for mAb-451 to EEKLVF (166-171) and mAb-462/470 to FKAPRP (250-255) amino acid residues. mAb-30 recognized QPVWQDEGQRLR (23-34) and VICRCC (316-321) amino acid residues. Competitive inhibition with synthetic peptides encompassing the motifs corresponding to 23-34 and 316-321 for binding of mAb-30 to pZP3 beta revealed the epitopic domain to be 23-34 amino acids. Synthesis of overlapping octapeptides further identified WQDE as the minimum motif for binding of mAb-30, and the replacement of one amino acid at a time with glycine revealed tryptophan as the critical residue. Conclusions: Collectively, these results describe peptide epitopes that will help in the design of an immunocontraceptive vaccine based on synthetic peptides corresponding to pZP3 beta or its homologues in other species

Impact of Artificial Intelligence on Colorectal Polyp Detection and Characterization

Colorectal cancer (CRC) is the third most common cancer in the world. Colonoscopy has contributed significantly to reduction of incidence and mortality of CRC. Integration of artificial intelligence (AI) into colonoscopy practice has addressed the various shortcomings of screening colonoscopies. AI-assisted colonoscopy will help in real-time recognition of type of polyp with probable histology. This will not only save time but will also help to mitigate human errors. Computer-aided detection and computer-aided characterization are two applications of AI, which are being studied extensively with a goal of improvement of polyp and adenoma detection rates. Several studies are being conducted across the globe, which either involve simple decision-making algorithms or complex patterns through neural networks, which imitate the human brain. Most data are collected retrospectively and the research is limited to single-center studies, which might have bias. Therefore, the future research on AI in colonoscopy should aim to develop more sophisticated convolutional neural network and deep learning models that will help to standardize the practice and ensure the same degree of accuracy with all the colonoscopies, irrespective of experience of performing endoscopists. In this review, we will take a closer look at the current state of AI and its integration into the field of colonoscopy

Strategies for designing an immunocontraceptive vaccine based on zona pellucida synthetic peptides and recombinant antigen

Immunization of female bonnet monkeys (Macaca radiata) with pig zona pellucida glycoprotein ZP3 using adjuvants permissible for human use leads to infertility. Fifty per cent of the animals conceived after antibody titres declined. Animals that failed to regain their fertility did not show any obvious ovarian changes. As part of the attempt to design an effective immunocontraceptive vaccine based on synthetic peptides, the epitopes recognized by monoclonal antibodies (mAb) against pig ZP3 α and ZP3 β and possessing contraceptive efficacy in vitro were mapped. These studies identified an N-blocked decapeptide from the N-terminus corresponding to 23-32 amino acids of the precursor protein of pig ZP3 β. As an alternative approach to using synthetic peptides, DNA encoding bonnet monkey ZP3 was cloned and sequenced. The deduced primary amino acid sequence revealed an overall similarity of 93.9% with human ZP3. Bonnet monkey ZP3 corresponding to an internal 975 nucleotide fragment excluding the N-terminus signal sequence and the C-terminus transmembrane domain has been expressed in Escherichia coli. These results will assist in the design of an immunocontraceptive vaccine based on either synthetic peptides or recombinant glycoproteins or proteins corresponding to ZP. Previous studies have demonstrated the efficacy, in mice, of synthetic peptides derived from zona pellucida (ZP) glycoprotein in blocking fertility without ovarian dysfunction. This study used bonnet monkeys (closely related to humans in the primate evolutionary tree and less susceptible to summer amenorrhea than rhesus monkeys) to explore the design of an immunocontraceptive vaccine based on synthetic peptides, recombinant glycoproteins, or proteins corresponding to ZP. Immunization of female monkeys with pig ZP3 glycoprotein using adjuvants permissible for human use produced infertility. Although only half the animals conceived after antibody titres declined, monkeys that failed to conceive did not show any obvious ovarian changes. Mapping of the epitopes recognized by monoclonal antibodies against ZP3 α and β and possessing contraceptive efficacy in vitro identified an N-blocked decapeptide from the N-terminus corresponding to 23-32 amino acids of the precursor protein of pig ZP3 β. When DNA encoding bonnet monkey ZP3 was cloned and sequenced, the deduced primary amino acid sequence showed a 93.9% similarity with human ZP3. Bonnet monkey ZP3 corresponding to an internal 975 nucleotide fragment excluding the N-terminus signal sequence and the C-terminus transmembrane domain has been expressed in Escherichia coli

Does a coaxial double pigtail stent reduce adverse events after lumen apposing metal stent placement for pancreatic fluid collections? A systematic review and meta-analysis

Background: Lumen apposing metal stents (LAMSs) have a higher clinical success rate for managing pancreatic fluid collections. But they are associated with adverse events (AEs) like bleeding, migration, buried stent, occlusion, and infection. It has been hypothesized that placing a double pigtail stent (DPS) within LAMS may mitigate these AEs. The present systematic review and meta-analysis were conducted to compare the outcome and AEs associated with LAMS with or without a coaxial DPS (LAMS-DPS). Methods: A comprehensive literature search of three databases from January 2010 to August 2022 was conducted for studies comparing the outcome and AEs of LAMS alone and LAMS-DPS. Pooled incidence and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for all the dichotomous outcomes. Results: Overall, eight studies ( n  = 460) were included in the final analysis. The clinical success rate (RR 1.00, 95% CI: 0.87–1.14) and the risk of overall AEs (RR 1.60, 95% CI: 0.95–2.68) remained comparable between both groups. There was no difference in the risk of bleeding between LAMS alone and LAMS-DPS (RR 1.80, 95% CI: 0.83–3.88). Individual analysis of other AEs, including infection, stent migration, occlusion, and reintervention, showed no difference in the risk between both procedures. Conclusion: The present meta-analysis shows that coaxial DPS within LAMS may not reduce AE rates or improve clinical outcomes. Further larger studies, including patients with walled-off necrosis, are required to demonstrate the benefit of coaxial DPS within LAMS

Expression of bonnet monkey (Macaca radiata) zona pellucida-3 (ZP3) in a prokaryotic system and its immunogenicity

An internal fragment (978 bp) corresponding to the bonnet monkey (Macaca radiata) ZP3, excluding the N-terminus signal sequence and the C-terminus transmembrane-like domain, was amplified by PCR from a full-length cDNA clone. The amplified Bam HI and Sacl restricted fragment was cloned in frama downstream of the T5 promoter under lac operator control for expression in the pQE-30 vector. Recombinant ZP3 (r-ZP3) was expressed as a poly-histidine fusion protein in E. coli strains SG13009[pREP4] and BL-21(DE3). Immunoblot with a murine monoclonal antibody, MA-451 (raised against porcine ZP3β—a homologue of bonnet ZP3, and cross-reactive with bonnet zona pellucida) revealed a predominant band of 50 kDa besides degraded fragments. Optimum expression of r-ZP3 was observed at 0.5 mM IPTG. Antisera generated in monkeys against synthetic peptides from the N-(23-45 aa residues) and C-(300–322 and 324-347 aa residues) termini of the deduced bonnet monkey precursor ZP3 sequence reacted with the r-ZP3 protein in ELISA. The r-ZP3 expressed in SG13009[pREP4] was purified on Ni-NTA resin under denaturing conditions and conjugated with diphtheria toxoid (DT). Immunization of a female rabbit and six female bonnet monkeys with the r-ZP3-DT conjugate generated antibodies reactive with r-ZP3 in ELISA. Rabbit r-ZP3 antiserum reacted with porcine ZP3β and bonnet r-ZP3 but failed to react with porcine ZP3α in a Western blot. Moreover, antisera when tested by indirect immunofluorescence on bonnet monkey ovarian sections, showed positive fluorescence with zona pellucida. The availability of r-ZP3 will further help in evaluating its efficacy for fertility regulation and understanding the autoimmune oophoritis associated with ZP3 immunization in nonhuman primates

Comparison of Suction Techniques for EUS-Guided Tissue Acquisition: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Background Despite the widespread use of endoscopic ultrasound (EUS)-guided tissue acquisition, the choice of optimal suction technique remains a debate. Multiple studies have shown conflicting results with respect to the four suction techniques: Dry suction (DS), no suction (NS), stylet slow pull (SSP) and wet suction (WS). Thus, the present network meta-analysis (NMA) was conducted to compare the diagnostic yields of above suction techniques during EUS-guided tissue acquisition. Methods A comprehensive literature search from 2010 to March 2022 was done for randomized studies comparing the aspirated sample and diagnostic outcome with various suction techniques. Both pairwise and network meta-analyses were performed to analyze the outcomes: sample adequacy, moderate to high cellularity, gross bloodiness, and diagnostic accuracy. Results A total of 16 studies (n = 2048 patients) were included in the final NMA. WS was associated with a lower odd of gross bloodiness compared to DS [Odds ratio (OR) 0.50, 95% confidence interval (CI) 0.24 – 0.97). There was no significant difference between the various suction methods with respect to sample adequacy, moderate to high cellularity and diagnostic accuracy. On meta-regression, to adjust for the effect of needle type, WS was comparable to DS in terms of bloodiness when adjusted for FNA needle. Surface under the cumulative ranking analysis ranked WS as the best modality for all the outcomes. Conclusion The present NMA did not show superiority of any specific suction technique for EUS-guided tissue sampling with regard to sample quality or diagnostic accuracy, with low confidence in estimates