Introduction

PuraStat is a novel hemostatic self-assembling matrix that seems promising both for the control of active bleeding and for the prevention of bleeding after operative endoscopy procedures.

Aims & Methods

The aim of this registry was to evaluate the safety and efficacy of PuraStat for the control of active bleeding and for the primary and secondary prevention of bleeding after different operative endoscopy procedures. A specific database was created and used to collect anonymous data from different Italian centers. Data on type of application (bleeding control vs prophylaxis, site and type of procedure in case of prophylaxis), amount of gel used, outcomes and safety of the application were systematically prospectively collected and analyzed.

Results

PuraStat was used on 401 patients that were treated for an active gastrointestinal bleeding or as a preventive measure after an operative endoscopy procedure in 10 Italian centers. 91 treatments for active bleeding and 310 preventive applications were included; 130 (32.4%), 44 (11%) and 227 (56.6%) were upper (ie. varices, ulcers, gastric antral vascular ectasia (GAVE), post endoscopic resection), biliopancreatic (ie. post sphincterotomy, post papillectomy, walled-off pancreatic necrosis (WOPN) drainage) and lower GI procedures (ie. post endoscopic resection, post pneumatic anastomotic dilation, radiation proctopathy) respectively. In 174/401 (43.4%) PuraStat was the primary treatment modality. The median coverage of the area treated with PuraStat was 97.9%, with difficulty in the application in 7/401 (1.7%) due to endoscope position. Hemostasis of active bleedings was achieved in 90/91 patients (98.9%). In the follow-up 7/91 patients (7.7%) in whom PuraStat was used for hemostasis had a bleeding event as compared with 12/310 patients (3.9%) after prophylactic PuraStat application. No complication related to the use of PuraStat occurred.

Conclusion

PuraStat is a safe and feasible hemostat both for bleeding control and for bleeding prevention after different operative endoscopy procedures. For the first time we explored and evaluated the use of PuraStat in upper GI and Biliopancreatic procedures, demonstrating also in these cases an excellent profile in bleeding treatments as well as in bleeding prevention. Our results show that the possible application for the use of PuraStat may be wider compared to current indications.

References

- Subramaniam S, Kandiah K, Thayalasekaran S et al. Haemostasis and prevention of bleeding related to ER: The role of a novel self-assembling peptide. United European Gastroenterol J. 2019 Feb;7(1):155-162. doi: 10.1177/2050640618811504.
- Branchi F, Klingenberg-Noftz R, Friedrich K et al. PuraStat in gastrointestinal bleeding: results of a prospective multicentre observational pilot study. Surg Endosc. 2022 May;36(5):2954-2961. doi: 10.1007/s00464-021-08589-6.

Introduction

Ozanimod (OZA), a sphingosine 1-phosphate (S1P) receptor modulator that selectively targets S1P₁ and S1P₅, is approved in the European Union, United States, and other countries for the treatment of moderately to severely active ulcerative colitis (UC). Mucosal healing (MH), a key treatment goal for patients (pts) with UC, is associated with improved long-term pt outcomes.

Aims & Methods

The goal of this analysis was to determine the rate of early MH after treatment with OZA at Week (W) 10 using stringent MH criteria (mucosal endoscopy subscore [MES] = 0 plus histologic remission [Geboes score <2.0]) and to assess the relationship between achievement of stringent MH at W10 and clinical outcomes at W52. Outcomes were compared to pts achieving MH using a standard definition (MES ≤1 plus histologic remission). This analysis included pts from True North (NCT02435992) who achieved clinical response on once-daily oral OZA 0.92 mg at W10 and continued OZA during the 42-wk maintenance period. In this post hoc analysis, we examined MH, clinical remission, and corticosteroid (CS)–free remission at W52 in pts with stringent MH vs without stringent MH at W10 and with stringent MH vs with standard MH.

Results

Of the 230 pts who achieved clinical response on OZA at W10 and continued OZA during the maintenance period, 44 (19.1%) achieved MH using a standard definition and 13 (5.7%) achieved stringent MH at W10. Demographic and clinical characteristics were generally balanced between OZA-treated pts with stringent MH (n=13) and without stringent MH (n=217) at W10. Notably, there were fewer male pts with stringent MH vs without stringent MH, all pts with stringent MH had moderate disease (based on endoscopy), and more pts with stringent MH vs without stringent MH had left-sided UC disease. CS use at screening and prior tumor necrosis factor inhibitor (TNFi) use were lower in those with stringent MH vs without stringent MH. Similar differences in disease severity, extent of disease, and CS and TNFi use were seen in pts with stringent MH vs standard MH. At W52, more pts treated with OZA with stringent MH at W10 vs without stringent MH at W10 had clinical remission (53.8% vs 35.9%), CS-free remission (53.8% vs 30.4%), MH (61.5% vs 27.6%), endoscopic improvement (61.5% vs 44.7), and histologic remission (61.5% vs 31.8%). Except for endoscopic improvement, a slightly higher percentage of pts with stringent MH vs standard MH at W10 achieved clinical outcomes at W52 (Table).

Conclusion

While difficult to achieve, a small proportion of pts treated with OZA experienced stringent MH by W10. Compared with pts who achieved standard MH at W10, those with stringent MH at W10 demonstrated numerically better clinical outcomes at W52 on OZA treatment. Achieving stringent MH at W10 correlated with better clinical, endoscopic, and mucosal outcomes at W52.

Disclosure

The study was funded by Bristol Myers Squibb, Princeton, NJ, USA.
WR: speaker for 4SC, Abbott Laboratories, AbbVie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Medice, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor, and Yakult; consulted for Abbott Laboratories, AbbVie, Aesca, Algernon, Amgen, AM Pharma, AMT, AOP Orphan, Arena, Astellas, AstraZeneca, Avaxia, Roland Berger GmbH, Bioclinica, Biogen IDEC, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celgene, Cellerix, Celltrion, Centocor, ChemoCentryx, Covance, Danone Austria, DSM, Elan, Eli Lilly, Ernst & Young, Falk Pharma GmbH, Ferring, Galapagos, Gatehouse Bio, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Intrinsic Imaging, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Landos, Lipid Therapeutics, LivaNova, Mallinckrodt, MedAhead, MedImmune, Millennium, Mitsubishi Tanabe Pharma, MSD, Nash Pharmaceuticals, Nestle, Nippon Kayaku, Novartis, Ocera, OMass, Otsuka, Parexel, PDL, Peri Consulting, Pharmacosmos, Philip Morris Institute, Pfizer, Procter & Gamble, Prometheus, Protagonist, Provention, Quell Therapeutics, Robarts Clinical Trial, Sandoz, Schering-Plough, Second Genome, Seres, Setpoint Medical, Sigmoid, Sublimity, Takeda, Teva, Therakos, Theravance, TiGenix, UCB, Vifor, Zealand, and Zyngenia; served as an advisory board member for 4SC, Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma, Astellas, AstraZeneca, Avaxia, Biogen IDEC, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cellerix, Celltrion, Centocor, ChemoCentryx, Danone Austria, DSM, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millennium, Mitsubishi Tanabe Pharma, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering-Plough, Second Genome, Setpoint Medical, Takeda, Therakos, TiGenix, UCB, Zealand, and Zyngenia; received research funding from Abbott Laboratories, AbbVie, Aesca, Centocor, Falk Pharma GmbH, Immundiagnostik, Janssen, MSD, Sandoz, and Takeda.
AH: Consultant, advisory board member, or speaker for AbbVie, Atlantic, Bristol-Myers Squibb, Celltrion, Falk, Ferring, Janssen, MSD, Napp Pharmaceuticals, Pfizer, Pharmacosmos, Shire, and Takeda. Global Steering Committee for Genentech.
CS: served as a speaker for AbbVie, Bristol Myers Squibb, Janssen, Pfizer, Takeda, and UCB.
RKC: consulted for AbbVie, Bristol Myers Squibb, Janssen, LabCorp, Pfizer, Samsung Bioepis, and Takeda.
HAA, AJ, HW, and MTO: employees and/or shareholders of Bristol Myers Squibb.
RL: consulted for Bristol Myers Squibb and Pfizer.
JA: received consulting fees from AbbVie, BioFire Diagnostics, Janssen, and Pfizer; received research grants from BioFire Diagnostics.

Clinical Case Summary

The ubiquitous availability of digital media does not only have advantages. Inexperienced mushroom pickers increasingly frequently use APPs for mushroom identification and consume forest mushrooms with false security. Currently, for example, life-threatening Amanita phalloides poisoning is becoming more frequent.
A 65-year-old patient presented with a latency period of approximately 40 hours after consumption of the mushrooms. Nausea and vomiting, as well as loss of strength and cramps in arms and legs, had already been present for about 24 hours. Laboratory tests revealed coagulation failure and markedly elevated transaminases (INR 2.1, GOT 2590 U/l, GPT 3119 U/l). The Meld Score was 33. Only when asked explicitly the patient reported eating wild mushrooms he had collected. The vomit and mushroom debris were recovered and immediately examined by a mushroom expert. Immediately after admission to our intensive care unit, liver protective therapy with Silibinin and N-Acetylcysteine was initiated.
Analysis by a fungal expert revealed evidence of Amanita phalloides. At an INR of 3.3 with massive diffuse skin hemorrhages and rising transaminases (GOT 4825U/l, GPT 4104U/l), repeated therapeutic plasma exchange (exchange of 1.3 times the plasma volume) was performed to control the complications of liver failure. In the course, transaminases and coagulation parameters stabilized, and liver transplantation was not necessary. The patient is now in excellent general health.
Our patient case shows that early diagnosis, as well as therapy, are crucial to reducing the lethality of tuberous leaf fungus poisoning. Patients are often unaware of the danger, so if they have symptoms, they should be asked explicitly about consuming collected mushrooms. As a bridging therapy for the stabilization and regeneration of liver function, therapeutic plasma exchange is an excellent option.

Disclosure

No conflicts of interests

Clinical Case Summary

A 31-year-old woman presented to her physician with painful abdominal mass in the left hypochondrium since an episode of abdominal trauma. An abdominal computed tomography (CT) scan showed a voluminous cystic mass measuring 142 mm in its greatest axis, located between the left hepatic lobe and the stomach. She was referred to a General Surgery hospital consultation. An endoscopic ultrasound was performed, which revealed a cystic lesion measuring at least 12x10 cm, with an irregular hyperechoic wall, a lumen with multiple foci and hyperechoic sediment, without an evident solid component, in the pancreas area, consistent with a pancreatic pseudocyst. Endoscopic transgastric drainage was decided upon by a multidisciplinary group consultation. During the procedure, a puncture was performed with aspiration of transparent content and placement of a 10x15 mm Hot Axios stent under endoscopic and endoscopic ultrasound control, with immediate intra-cystic migration observed. A new 10x15 mm Axios stent was placed with appropriate final positioning. The stent was dilated with a TTS balloon up to 12 mm, and a 3 cm x 10 Fr. double pigtail plastic stent was placed. Biochemical analysis of the aspirated fluid showed CEA 24084 ng/mL; glucose <4 mg/dL; amylase <20 U/L, consistent with a mucinous cystic pancreatic neoplasm. The patient underwent distal pancreatectomy without immediate complications. The pathological analysis showed a histology consistent with a mucinous cystic pancreatic neoplasm with low-grade dysplasia. She remains under follow-up in an outpatient General Surgery consultation.
This is a case of a mucinous cystic pancreatic neoplasm with atypical presentation, mimicking a pseudocyst. Aspiration puncture and biochemical analysis of the aspirated fluid allowed for a directed approach, proving to be fundamental for differential diagnosis and treatment.

Introduction

The Kimura-Takemoto's (KT) classification, the endoscopic assessment for the extent of gastric atrophy, has been recommended to useful risk marker of gastric cancer (GC) in Japan. In Western countries, recent studies suggest the endoscopic findings with narrow band imaging (NBI) according to the classification of endoscopic grading of gastric intestinal metaplasia (EGGIM) are useful markers for GC risk. However we reported that both KT and EGGIM are useful stratification method for the GC in Japanese, the association between KT and EGGIM is unknown.

Aims & Methods

This study is a post-hoc analysis of a multicenter prospective study for a histological and endoscopic risk for GC in 10 Japanese facilities (UMIN00027023). We assessed the KT classification with white-light endoscopy and EGGIM score with NBI endoscopy in all subjects. We also evaluated the histological findings using biopsy specimens according to the operative link for gastritis assessment (OLGA) and the operative link for gastric intestinal metaplasia (OLGIM). The biopsy specimens were taken randomly according to the updated Sydney system, not guided target biopsy with NBI. We evaluated the association between KT and EGGIM. We also analyzed the diagnostic ability for histological findings (OLGA/OLGIM) using receiver operating characteristic (ROC) analysis. In OLGA, OLGIM and EGGIM analysis, We assessed four points (lesser and greater curvatures of antrum and corpus), not included angularis because of a questionable diagnostic benefit.

Results

The 380 subjects (115 GC and 265 non-GC) were analyzed. The white-light endoscopy revealed that 99 patients were non to mild atrophy (C-0, C-1; low risk for GC), 104 were moderate atrophy (C-2,C-3; moderate risk) and 177 were extent atrophy (O-1, O-2, O-3; high risk) in KT classification. The NBI findings showed that 109 were low risk (score 0), 158 were moderate risk (score 1 to 4), 113 were high risk (score 5-8) in EGGIM score. The high risk group in KT classification had significant association with that of EGGIM score (odds ratio (OR) 4.3 [95% confidence interval (CI) 2.6-6.8]). The high risk group in KT classification showed significant relationship not only high risk group of histological atrophy (OLGA stage III/IV) with OR 5.5 [3.4-8.8], and also that of histological IM (OGIM stage III/IV) with OR 8.5 [4.5-16.0]. The area under the ROC curve of diagnostic ability for OLGA III/IV were 0.786 in KT and 0.769 in EGGIM. Also those of OLGIM IIII/IV were 0.761in KT and 0.734 in EGGIM.

Conclusion

Endoscopic assessments according to the Japanese traditional method (KT) and Western method (EGGIM) showed significant association. The KT classification associated with not only extent of histological atrophy but also extent of histological IM.

References

1. Kawamura M, Uedo N, Koike T,et al : Kyoto classification risk scoring system and endoscopic grading of gastric intestinal metaplasia for gastric cancer: Multicenter observation study in Japan. Dig Endosc 2022; 34: 508-516.
2. Kimura K, Takemoto T. An endoscopic recognition of the atrophic border and its significance in chronic gastritis. Endoscopy 1969; 1: 87–97.
3. Pimentel-Nunes P, Libânio D, Lage J et al. A multicenter prospective study of the real-time use of narrow-band imaging in the diagnosis of premalignant gastric conditions and lesions. Endoscopy 2016; 48 :723-730.
4. Esposito G, Pimentel-Nunes P, Angeletti S et al. Endoscopic grading of gastric intestinal metaplasia (EGGIM): a multicenter validation study. Endoscopy 2019; 51: 515-521.
5. Marcos, P.; Brito-Gonçalves, G.; Libânio, D.; Pita, I.; Castro, R.; Sá, I.; Dinis-Ribeiro, M.; Pimentel-Nunes, P. Endoscopic grading of gastric intestinal metaplasia on risk assessment for early gastric neoplasia: Can we replace histology assessment also in the West? Gut 2020; 69: 1762–1768.

Disclosure

All authors disclose no financial relationships relevant to this study