Introduction

Linaprazan glurate (LG), a prodrug to linaprazan, is a next generation PCAB with a rapid and extensive effect on gastric pH ¹ and up to 93% 4-week healing rate in severe erosive esophagitis in phase 2 study ².
LG is formulated as tablets, initially with LG as a base. To improve the biopharmaceutical and pharmacokinetic (PK) properties, a new tablet containing LG as HCl salt has been developed. PK of LG HCl tablet was evaluated in two Phase 1 studies.

Aims & Methods

The PK of two tablet formulations were compared in a single-dose, 100 mg LG, 3-way crossover study. Additionally, the food effect on the PK of the LG HCl tablet was assessed. Repeated-dose PK for the LG HCl tablet was evaluated in a randomized, parallel-group study during 14 days of once-daily (25 mg, 50 mg, and 75 mg QD) or twice-daily (25 mg, 50 mg, and 75 mg BID) dosing. Plasma samples were collected to measure LG and linaprazan concentrations and to derive PK parameters.

Results

Healthy subjects were enrolled, with 54 and 72 evaluable for PK analysis in each study, respectively. The exposure to LG was approximately 10 times lower than that of linaprazan following both single and repeated dosing.
The bioavailability of linaprazan from LG HCl salt tablet was approximately 2-fold higher than for LG base tablet as reflected in the geometric LS mean ratio (90% CI) for linaprazan AUC_inf: 2.00 (1.83 2.16); C_max: 2.32 (2.09-2.57) with a slightly later median t_max for the LG HCl tablet (3h vs 2h).
A meal reduced mean AUC_inf by 24%, (geometric LS mean ratio (90% CI): 0.76 (0.70-0.82) and mean C_max by 55%, (geometric LS mean ratio (90% CI): 0.45 (0.41-0.50), for LG HCl tablet vs fasting intake with a later median t_max for linaprazan after fed conditions (6h vs 3h).
Linaprazan C_max and AUC increased approximately in proportion to dose, steady state was reached within 5 days, with no accumulation upon 14 days repeated QD or BID dosing of LG HCl tablet. No apparent deviation from time independent PK was seen even if exposure was slightly lower (approximately 20%) than expected for the 75 mg QD and 75 mg BID dosing groups on Day 14. Mean C_max and AUC were slightly lower (10-20%) for the QD vs first BID dose, and slightly lower (15-30%) for the second daily vs the first daily BID dose, most likely due to different conditions with respect to food intake (Table 1).

Table 1: Descriptive Statistics of linaprazan pharmacokinetic parameters

Dose Groups	Cmax (nmol/L) Mean (SD) Day 1	Cmax (nmol/L) Mean (SD) Day 14	tmax (h) Median (min-max) Day 1	tmax (h) Median (min-max) Day 14	AUC (nmol/L*h) Mean (SD) Day 1	AUC (nmol/L*h) 1) Mean (SD) Day 14
25 mg QD	527.25 (184.929)	404.75 (174.068)	5.00 (2.00-14.00)	4.00 (1.25-12.0)	5089 (1607.1)	4640 (1657.4)
50 mg QD	1066.23 (209.973)	1002.00 (538.574)	3.00 (1.00-6.00)	3.03 (1.23-6.00)	9342 (2462.3)	8626 (3571.9)
75 mg QD	1594.42 (585.525)	1044.92 (478.102)	3.50 (1.25-12.00)	3.99 (1.25-13.97)	14 614 (4601.9)	11 697 (4053.3)
25 mg BID Dose 1	658.42 (212.101)	782.92 (263.988)	1.75 (1.25-6.00)	1.50 (1.00-8.03)	4081 (1351.9)	8898 (2247.9)
25 mg BID Dose 2	520.92 (126.378)	520.83 (144.568)	4.00 (2.00-2.47)	4.99 (1.00-6.00)	3947 (939.8)
50 mg BID Dose 1	1380.18 (303.283)	1148.64 (415.251)	1.50 (1.25-4.00)	1.50 (1.00-4.00)	8084 (1400.5)	13852 (3174.1)
50 mg BID Dose 2	997.09 (363.660)	842.36 (270.396)	2.00 (1.25-11.92)	4.00 (1.00-8.00)	7107 (1917.8)
75 mg BID Dose 1	1942.00 (667.280)	1740.60 (468.197)	1.75 (0.98-6.00)	1.25 (0.85-4.00)	11814 (3181.8)	21366 (4323.8)
75 mg BID Dose 2	1283.90 (435.399)	1285.50 (443.703)	4.00 (1.50-8.08)	1.78 (0.98-8.02)	9532 (2118.1)

^{1) AUC Day 1: AUC_inf for QD and AUC_0-12h and AUC_12-24h for BID, AUC Day 14: AUC_0-24h for QD and BID
QD: All doses were taken in the evening in a non-fasted state and BID: 1st dose was taken fasted in the morning and the 2nd daily dose in the evening in a non-fasted state.}

Conclusion

An optimized linaprazan glurate HCl tablet formulation has been developed for Phase 3, with a later t_max and an approximately 2-fold higher bioavailability than the initial tablet and only a minor impact of food intake on linaprazan AUC_inf. In addition, the linaprazan glurate HCl tablet provided dose-proportional increase in linaprazan plasma exposure as reflected by AUC and C_max.

References

1. Flezar M, et al., UEG Journal, Volume12, Issue S8, Supplement: 32nd United European Gastroenterology Week 2024, October 2024
2. Sharma P, et al. Aliment Pharmacol Ther. 2025 Apr 4. doi: 10.1111/apt.70109. Epub ahead of print. PMID: 40183130.

Disclosure

Gunilla Huledal, Kajsa Larsson, Bengt Erlandsson, Kjell Andersson, Kristofer Katkits Nilsson, Elham Yektaei, are employees of Cinclus Pharma.
Peter Unge is a consultant and senior advisor at Cinclus Pharma.
Matjaž Fležar has nothing to disclose

Introduction

Laparoscopic cholecystectomy (LC) is one of the most performed surgeries worldwide. Biliary tract injuries are among the most feared complications after LC. The primary cause of biliary injuries during LC is the incorrect identification of the biliary tract anatomy. Near-infrared fluorescence (NIRF) imaging, following intravenous (IV) injection of indocyanine green (ICG), shows promise for simplifying the intraoperative visualization of biliary anatomy. This technique enables real-time identification of the cystic duct and common bile duct, potentially enhancing the outcomes of LC. This systematic review and meta-analysis aimed to investigate the effects of NIRF-ICG on LC outcomes.

Aims & Methods

This meta-analysis followed the Cochrane Handbook for Systematic Reviews of Interventions guidelines. We searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus until May 23^rd, 2024. We included randomized-controlled trials and retrospective studies comparing NIRF-ICG LC and conventional LC. Statistical analysis was performed using Review Manager 5.3 software.

Results

Fifteen studies with 1581 patients (41.1%) in the NIRF-ICG group and 2264 (58.9%) in the control group were included. The NIRF-ICG was associated with statistically significant reduced overall complications, bile leakage, and duct drainage (risk ratio (RR) = 0.62, 95% CI: [0.40, 0.95], P = 0.03; Fig 1), (RR = 0.34, 95% CI: [0.14, 0.83], P = 0.02; Fig 2), and (RR = 0.64, 95% CI: [0.44, 0.91]), P = 0.01; Fig 3), respectively. Common bile duct (CBD), cystic duct- CBD junction, and common hepatic duct visualization rates were better with the NIRF-ICG, (RR= 3.67, 95% CI: [2.62, 5.15], P < 0.001), (RR = 3.00, 95% CI: [2.03, 4.43], P < 0.001), and (RR = 2.87, 95% CI: [1.94, 4.25], P < 0.001), respectively. There was no significant difference in cystic duct visualization rate (RR = 1.40, 95% CI: [0.71, 2.78], P = 0.33).

Conclusion

NIRF following administration of ICG in LC offers better visualization of biliary tract anatomy and is associated with reduced overall complications, bile leakage, and bile duct drainage.

References

1. J. Van Den Bos et al., “Near-infrared fluorescence cholangiography assisted laparoscopic cholecystectomy (FALCON): an international multicentre randomized controlled trial,” Surg Endosc, vol. 37, no. 6, pp. 4574–4584, Jun. 2023, doi: 10.1007/s00464-023-09935-6.
2. W. H. She et al., “Routine use of ICG to enhance operative safety in emergency laparoscopic cholecystectomy: a randomized controlled trial,” Surg Endosc, vol. 36, no. 6, pp. 4442–4451, Jun. 2022, doi: 10.1007/s00464-021-08795-2.
3. J. K. Koong, G. H. Ng, K. Ramayah, P. S. Koh, and B. K. Yoong, “Early identification of the critical view of safety in laparoscopic cholecystectomy using indocyanine green fluorescence cholangiography: A randomised controlled study,” Asian Journal of Surgery, vol. 44, no. 3, pp. 537–543, Mar. 2021, doi: 10.1016/j.asjsur.2020.11.002.

Introduction

Gastric outlet obstruction (GOO) is a severe complication of unresectable gastric and pancreatic cancers. Conventional gastrojejunostomy (CGJ) is a standard surgical intervention, but it is associated with a high incidence of delayed gastric emptying (DGE). Stomach-partitioning gastrojejunostomy (SPGJ) has emerged as an alternative to improve gastric emptying and enhance clinical outcomes.

Aims & Methods

We conducted a meta-analysis comparing SPGJ and CGJ in patients with GOO due to unresectable gastric or pancreatic cancers. Electronic databases were searched up to February 8, 2025. Outcomes included DGE, major postoperative complications, need for reintervention, short-term mortality, operation time, gastric outlet obstruction scoring system (GOOS), length of hospital stay (LOS), adherence to postoperative chemotherapy, and overall survival. For continuous outcomes, mean differences (MD) with 95% confidence intervals (CI) were calculated. For dichotomous outcomes, relative risks (RR) with 95% CI were reported. Reconstructed individual patient data (IPD) from Kaplan-Meier curves was utilized for survival analysis.

Results

A total of 11 studies comprising 456 patients were included. SPGJ was associated with significantly reduced DGE (RR = 0.24, 95% CI: 0.12–0.47) and postoperative major complications (RR = 0.26, 95% CI: 0.12–0.54) compared to CGJ. No significant differences were found in the need for reintervention (RR = 0.59, 95% CI: 0.21–1.64), short-term mortality (RR = 0.99, 95% CI: 0.42–2.33), or LOS (MD = -1.47 days, 95% CI: -3.10 to 0.16). GOOS scores were comparable between groups. Overall survival was also similar between SPGJ and CGJ (HR = 1.06, 95% CI: 0.66–1.70).

Conclusion

Our meta-analysis supports SPGJ as a superior option to CGJ for managing malignant GOO, offering significant reductions in DGE and postoperative complications, similar GOOS scores, and comparable safety regarding reintervention, short-term and long-term mortality, and LOS. High-quality RCTs are needed to confirm these findings and guide clinical practice.

References

1. T. Oida, K. Mimatsu, A. Kawasaki, H. Kano, Y. Kuboi, and S. Amano, “Modified Devine Exclusion with Vertical Stomach Reconstruction for Gastric Outlet Obstruction: A Novel Technique,” Journal of Gastrointestinal Surgery, vol. 13, no. 7, pp. 1226–1232, Jul. 2009, doi: 10.1007/s11605-009-0874-y IF: 2.2 Q2 2. W. Zhang et al., “The Validation of Deep Learning-Based Grading Model for Diabetic Retinopathy,” Front. Med., vol. 9, p. 839088, May 2022, doi: 10.3389/fmed.2022.839088 IF: 3.1 Q1 .
3. R. Yildirim, “Efficacy of stomach-partitioning on gastric emptying in patients undergoing palliative gastrojejunostomy for malign gastric outlet obstruction,” Ulus Travma Acil Cerrahi Derg, 2020, doi: 10.14744/tjtes.2020.14668 IF: 0.8 Q4 .

Introduction

Esophageal Squamous Cell Carcinoma (ESCC) remains a significant global health problem with few therapeutic options and poor prognosis. Camrelizumab, an anti-PD-1 immune checkpoint inhibitor, has been shown in clinical trials to be of potential value in the treatment of advanced or metastatic ESCC as monotherapy or in combination with chemotherapy or anti-angiogenic therapy.

Aims & Methods

The aim of this study is to evaluate the clinical efficacy and safety profile of Camrelizumab in patients with esophageal squamous cell carcinoma, with the main outcomes being progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events.
We conducted a comprehensive search of PubMed, Scopus, Web of Science, Embase, and Cochrane from their inception to April 2025, focusing on randomized controlled trials (RCTs) and observational studies evaluating Camrelizumab for the treatment of esophageal squamous cell carcinoma. Meta-analyses utilized a random-effects model to calculate odds ratios, mean differences, and 95% confidence intervals for adverse events and total patients.

Results

Out of 1,563 studies initially screened, 15 studies met the inclusion criteria for our meta-analysis, comprising adult patients. Meta-analysis established a median progression-free survival (PFS) of 7.60 months (95% CI: 6.00–9.19). The major pathological response rate (MPR) was 0.42 (95% CI: 0.37–0.48), and the objective response rate (ORR) was 0.53 (95% CI: 0.38–0.68). The R0 resection rate was also remarkably high at 0.98 (95% CI: 0.96–1), and the disease control rate (DCR) was 0.87 (95% CI: 0.64–1). The pathological complete response rate (pCR) was 0.31 (95% CI: 0.20–0.43).
Regarding safety, the most common treatment-related adverse events were leukopenia 0.45 (95% CI: 0.23–0.68), neutropenia 0.30 (95% CI: 0.19–0.41), anemia 0.14 (95% CI: 0.03–0.29), thrombocytopenia 0.09 (95% CI: 0.03–0.17), and elevated transaminases 0.06 (95% CI: 0.02–0.12). Pneumonia 0.17 (95% CI: 0.11-0.23) and hypertension 0.12 (95% CI: 0.06-0.19) were the other immune-related adverse events. The majority of these events were tolerable and within safe parameters.

Conclusion

Camrelizumab demonstrates promising efficacy in the treatment of esophageal squamous cell carcinoma with satisfactory rates of ORR, MPR, and R0 resection. The safety profile is acceptable with controllable adverse effects. These findings support the potential therapeutic value of camrelizumab as a significant treatment strategy in multimodal treatment of esophageal squamous cell carcinoma and the need for further research to optimize its clinical use.

Introduction

Endoscopic Retrograde Cholangio-Pancreatography (ERCP) is performed to treat pathology within the biliary system. Patients undergoing this may be on systemic anticoagulation. ERCP is classed as a high-risk bleeding procedure within BSG guidelines. This would necessitate anticoagulation interruption to prevent bleeding. It is recognised however, that resumption of antiplatelets and anticoagulants is associated with improved survival and reduced incidence of thrombotic complications. Thus, all patients should have a clear anticoagulation plan.

Aims & Methods

Attendances for ERCP over a 6-month period were analysed. Of the 132 patients, 33 (25%) were taking either an antiplatelet, warfarin or a Direct Oral Anticoagulant (DOAC). Medical records were reviewed in relation to pre-procedure management of these medications, advice from the endoscopist regarding resumption and whether these medicines were managed appropriately thereafter.
Several interventions were then made; a change to the reporting software led to a prompt relating to antiplatelet/anticoagulant medications, an education campaign for post graduate doctors in training and medication guidance summaries visible in the endoscopy department.
A second 6-month review was then undertaken to evaluate if there had been any improvement in outcomes. In this time frame, 143 patients underwent ERCP of whom 27 (16.7%) were taking antithrombotic therapy.

Results

Results are in Table 1:

	Pre-Intervention	Post Intervention
Pre-procedure appropriate management	48.5%	70.9%
Documented advice on endoscopy report	10%	30%
Post procedure appropriate prescribing	36.3%	70%

One common error was holding of anticoagulation/antiplatelet medication from admission in anticipation of ERCP. This led to long periods off anticoagulation whilst awaiting ERCP.
Documented advice was given more frequently on Endoscopy reports in cases where the patient required further procedure.
It was challenging to analyse post procedural management for inpatients, as the quality of ward round documentation and discharge letters was variable.

Conclusion

Further education to junior staff around utility of BSG anticoagulation guidelines greatly improved pre and post procedure management and thus forms a cornerstone to improve care. Further education to more senior staff may also improve decision rationale and medication advice in ward round documentation and discharge paperwork. Human factors also need to be considered; limited advice is likely related to high endoscopy workload pressures, with sub analysis showing that advice is improved when further intervention is required or in higher risk settings, illustrating that antithrombotic decisions are considered by the endoscopist. Improved documentation at procedure with the support of upgrades to reporting software will enhance post procedure care and consequently reduce demands on the service.​

References

Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline updateVeitch AM, Radaelli F, Alikhan R, et al. Gut 2021;70:1611–1628
UEG poster: Improving documented advice regarding anticoagulants and antiplatelets in acute upper gastrointestinal bleeds. Authors: Dr Emily Creed, Dr Vanessa Theis, Dr Katie Clark, Dr Sweekriti Gurung, Dr Abdullah Motam and Dr Gregor Farrell Bins.

Introduction

Colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer-related death. Most colorectal cancers arise from benign polyps, especially dysplastic adenomas. Colonoscopy with polypectomy is the gold standard for preventing cancer by interrupting the adenoma-carcinoma sequence. This has led to the development of various techniques and devices for improved prevention and treatment. Hot snare endoscopic mucosal resection (HS-EMR), which combines submucosal injections with electrocautery, is commonly used for excising various colorectal polyps. However, it carries risks of diathermy-related complications, such as perforation, and bleeding. To address these issues, cold snare endoscopic mucosal resection (CS-EMR) has been proposed as an alternative. Concerns about residual adenoma/recurrence have been raised with CS-EMR. Therefore, we conducted this meta-analysis to compare the two techniques.

Aims & Methods

We searched electronic databases, including MEDLINE via PubMed, Scopus, Web of Science, and Cochrane, without restrictions on publication date or language. We included RCTs comparing CS-EMR and HS-EMR for colorectal polyp resection. Primary outcomes included the incidence of delayed bleeding and residual/recurrent adenoma (RRA).

Results

On Nov 5, 2024, our literature search across electronic databases retrieved a total of 1,888 records. Following a meticulous screening process, six studies met the eligibility criteria encompassing 1,449 patients and 1,947 polyps. Regarding safety, the overall effect estimates regarding delayed bleeding showed statistically significant results favoring CS-EMR group [OR 0.31, 95 % CI (0.12–0.76), P = 0.01] with no heterogeneity (P = 0.40; I² = 0 %). However, statistical superiority for CS-EMR could not be detected regarding early bleeding [OR 0.78, 95 % CI (0.31–1.97), P = 0.60]. Only two studies reported data on delayed perforation, showing a numerical difference favoring CS-EMR; however, statistical significance could not be obtained [OR 0.26, 95 % CI (0.03–2.41), P = 0.24]. Regarding efficacy, the overall effect estimates regarding complete resection and RRA did not favor either of the groups [OR 0.62, 95 % CI (0.25–1.53), P = 0.30], [OR 2.81, 95 % CI (0.43–18.47), P = 0.28] respectively.

Conclusion

Evidence obtained from this meta-analysis suggests that CS-EMR offers superior safety compared to HS-EMR for colorectal polyp resection. Current evidence remains limited due to the small number of studies included. Therefore, further high-quality randomized controlled trials with larger sample sizes are needed.

References

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

• Winawer SJ, Zauber AG, Ho MN, O'Brien MJ, Gottlieb LS, Sternberg SS, et al. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med. 1993;329(27):1977–81.

• Facciorusso A, Del Prete V, Antonino M, Buccino VR, Muscatiello N. Efficacy of endoscopic polypectomy techniques for colorectal polyps: a systematic review and network meta-analysis. Gastrointest Endosc. 2020;91(4):733–745.e9.

• Pohl H, Srivastava A, Bensen SP, Anderson P, Rothstein RI, Gordon SR, et al. Incomplete polyp resection during colonoscopy—results of the complete adenoma resection (CARE) study. Gastroenterology. 2013;144(1):74–80.e1.

• Tutticci N, Hewett DG. Cold snare polypectomy: A safe, effective technique for sessile polyps. Gastrointest Endosc Clin N Am. 2015;25(2):291–301.

• Kawamura T, Takeuchi Y, Asawa S, Yokota I, Matsuno T, Omori T, et al. A comparison of cold and hot snare polypectomy for small colorectal polyps: a randomized controlled trial. Am J Gastroenterol. 2018;113(3):403–411.