Introduction

Endoscopic resection (ER) of duodenal tumors carries a high risk of intraoperative or delayed perforation because of the thin duodenal wall and exposure to bile and pancreatic juice. Delayed perforation can particularly cause serious condition due to the leakage of the digestive fluids. The detailed management and clinical course following duodenal perforation remains unclear. This study aimed to clarify the optimal management of duodenal perforation following ER.

Aims & Methods

This single-center retrospective study included cases of perforation among patients who underwent ER for duodenal tumors at our institution between April 2013 and October 2024. The study endpoint was the clinical course after perforation, including the hospitalization period after ER for duodenal tumors. Perforation was defined as the presence of extraluminal gas on computed tomography (CT) scan. Delayed perforation was defined as a perforation that was not endoscopically recognized during the procedure but was diagnosed postoperatively. In contrast, intraoperative perforation was defined as a case in which a perforation was endoscopically identified during the endoscopic procedure. Long hospitalization was defined as a hospital stay of 20 days or longer.

Results

Of the 1,475 cases with duodenal tumors underwent ER during the study period, intraoperative perforation occurred in 8 cases (0.5%) and delayed perforation in 10 cases (0.7%). The median age of patients with perforation was 62 (range: 47–80) years, and 50% (9 patients) were male. The 18 cases included 6 cases of endoscopic papillectomy (EP), 7 cases of endoscopic mucosal resection (EMR), 2 cases of endoscopic submucosal dissection, and 3 cases of endoscopic submucosal resection with a ligation device. Among the cases of intraoperative perforations, long hospitalization, 61 days of conservative treatment, was required in one case who developed a large perforation during scope insertion of single‑balloon enteroscopy for duodenal adenoma resection. The remaining 7 cases achieved successful endoscopic closure intraoperatively and hospitalization periods were within 17 days. Of the 10 delayed perforation cases, 2 occurred after EP and 8 after EMR for non-ampullary tumors. The median time from the end of endoscopic resection to the diagnosis of perforation was 24 hours (4–46 hours). The median hospitalization period of the cases with delayed perforations was 32 days (9–81 days), and significantly longer than that of intraoperative perforation (13 days) (p<0.05). Long hospitalization was required in 8 cases (80%) of delayed perforation. None of the delayed perforation cases required surgical intervention, and endoscopic nasobiliary and nasopancreatic duct drainage (ENBPD) was performed in 7 cases (70%). Ascites was observed on CT scan at the time of diagnosis of delayed perforation in 7 of the 8 patients who required long hospitalization. One case without ascites at the diagnosis of delayed perforation still required long hospitalization, possibly due to the 10-hour delay from the diagnosis to ENBPD. On the other hand, two cases who did not need long hospitalization showed no ascites at the diagnosis of delayed perforation.

Conclusion

Compared to intraoperative perforation, delayed perforation was associated with significantly prolonged hospitalization, particularly in cases with ascites. Early detection of ascites and prompt initiation of ENBPD may help mitigate the clinical burden. Establishing an emergent backup system for ENBPD is essential for the safe management of delayed perforation after duodenal ER.

Introduction

​Post-ERCP pancreatitis (PEP) is still the most common major complication of ERCP despite technical advancements and meticulous patient selection. The efficacy of the existing techniques is conflicting.

Aims & Methods

We aimed to compare the efficacy of peripapillary epinephrine injection in combination with rectal diclofenac for the prevention of PEP in high-risk patients .
Methods Between January 2023 and August 2023, a total of 378 patients were enrolled. We calculated that 189 patients in each group (rectal diclofenac – Group A and peripapillary epinephrine injection plus rectal indomethacin – Group B) would suffice based on a previous study by our group (α:0.05, 80% power). Patients with a non-naive papillae, ampulla of Vater cancer, biliary pancreatitis, altered anatomy, pregnancy, and pancreatic diseases such as chronic pancreatitis were excluded. Patients were assigned in a 1:1 simple randomized fashion. The primary outcome was the rate of PEP. Secondary outcomes were the rate of hyperamylasemia and rates of other adverse events.

Results

​Demographic characteristics, indications, and procedure-related risk factors were similar between the groups. The overall success rate of selective cannulation was 99.2% in Group A and 99.3% in Group B (p=0.997). PEP occurred in 9 of the 189 (4.8%) patients in Group A and 2 of the 189 (0.5%) patients in Group B. All cases were mild and managed conservatively. The rate of post-procedure 4th-hour hyperamylasemia was significantly higher in Group A (19% vs 5%, p<0.001). Postsphincterotomy-related bleeding developed in 5 patients in Group A (2.64%) but none of the patients had bleeding in Group B. Stapfer type-II perforation occurred in two patients in each group. No major cardiac adverse events-related to epinephrine injection were detected in Group B.

Conclusion

Compared to rectal diclofenac, peripapillary epinephrine injection significantly reduced the incidence of PEP, post-procedure hyperamylasemia, and sphincterotomy-related bleeding.

Clinical Case Summary

Aim: Abdominal Cocoon syndrome is the complete or partial wrapping of the abdominal organs with a membrane structure. Diagnosis can be made by laparoscopy. Patients mostly present with acute abdomen symptoms due to intestinal obstruction.
Case: 27-year-old male patient had recurrent abdominal pain for 12 years and was diagnosed with Behçet's disease and started on treatment. The patient’s abdominal pain increased in the last 6 months. He was followed up 4 months ago with suspected ileus, recovered with symptomatic treatments. A colonoscopy was performed and aphthous ulcers were detected in the terminal ileum and linear ulcers in the sigmoid colon. Tuberculosis,vasculitis and amyloid was excluded in the biopsies .With the preliminary diagnosis of Crohn's disease, 5-ASA and Azathioprine were started, and when no clinical response was obtained, Adalimumab was switched. The patient, who had no history of alcohol, cigarette use or any surgery, stopped all of her medications because she had not had symptomatic improvement for a long time, and was relieved by vomiting voluntarily. Her family history included rheumatoid arthritis in her sister and ulcerative colitis in her cousin. In the physical examination, there was no pathology other than widespread tenderness in the abdomen. In the ultrasonography; the small intestine walls were seem to be slightly edematous and retracted. Enteroscopy was completely normal. In the CT-Enterography, it was thought that it could be an "abdominal cocoon", so a laparotomy was performed and the diagnosis. The small intestines were freed from the fibrotic bands. The patient did not develop any post-operative complications, and her abdominal pain completely resolved after the operation.
Conclusion: Abdominal cocoon syndrome should be kept in mind as a very rare disease that can cause diagnostic confusion, remain undiagnosed for a long time, and cause unnecessary treatments, and can be fixed totally with surgical treatment.

Introduction

Bowel urgency (BU) is a bothersome symptom experienced by patients with ulcerative colitis (UC) and is associated with high clinical and quality-of-life burdens. Mirikizumab (MIRI), an anti-IL-23 antibody approved for the treatment of moderately-to-severely active UC, significantly reduced BU severity compared with placebo (PBO), and these improvements were associated with better clinical outcomes.¹ We evaluated the association between incremental improvement in BU severity at Week (W)12 and W52 with other patient-reported outcomes for MIRI-treated patients.

Aims & Methods

In LUCENT-1 (induction), patients were randomized 3:1 to intravenous MIRI 300 mg or PBO every 4 weeks (Q4W) for 12W. MIRI responders during induction were re-randomized 2:1 to subcutaneous MIRI 200 mg or PBO Q4W for 40W in LUCENT-2 (52W of continuous treatment). BU severity was measured using the Urgency Numeric Rating Scale ([UNRS] 0–10). Incremental improvement of BU severity was assessed as reduction of each single point of UNRS score from baseline (BL). The reduction of >7 points was pooled into one category due to sample size. The accumulative benefit of reducing 1 additional point of UNRS score was evaluated at W12 and W52 and was assessed for its association with mean percent improvement in inflammatory bowel disease questionnaire (IBDQ) total score, fatigue NRS, short-form (SF)-36 mental component score (MCS) and physical component score (PCS), and work productivity activity impairment (WPAI) productivity loss.

Results

Significantly greater proportions of patients receiving MIRI achieved UNRS score reduction at certain points versus PBO at W12 and W52. The reduction of each single point of UNRS score was associated with improvement in patient’s physical and mental health, fatigue, work productivity, and quality of life. At W12, fatigue and IBDQ showed greater percent improvements among all the PRO outcomes studied for each 1-point reduction of UNRS. Similar results were observed at W52 (Table 1).

Week 12 (N=868)	UNRS reduction	Fatigue NRS	IBDQ Total Score	MCS	PCS	WPAIa	Week 52 (N=365)	UNRS reduction	Fatigue NRS	IBDQ Total Score	MCS	PCS	WPAIb
	≤0	-11.9	16.0	6.6	9.4	4.9		≤0	8.9	35.9	18.5	21.2	23.9
	1	15.4	25.9	14.6	11.3	16.9		1	5.8	30.6	13.4	12.7	11.2
	2	28.7	31.1	13.7	14.0	20.1		2	32.4	37.5	18.8	18.6	30.1
	3	43.5	35.8	17.9	16.9	24.1		3	59.5	33.9	10.8	20.4	27.5
	4	49.8	49.1	19.7	23.5	24.2		4	62.4	55.6	17.9	33.7	42.1
	5	54.5	43.3	13.1	22.9	28.8		5	52.2	54.0	21.7	27.7	38.2
	6	59.3	55.2	22.1	24.0	36.4		6	68.9	63.0	26.0	26.5	41.9
	7	81.2	64.6	25.9	30.1	29.8		7	83.8	67.3	30.1	30.1	50.6
	>7	73.6	75.4	29.7	39.1	38.5		>7	88.1	87.6	35.0	45.4	54.8

^a Note: N=532, population was restricted to patients with baseline employment status = Yes.
^b Note: N=224, population was restricted to patients with baseline employment status = Yes.
Abbreviations: IBDQ = inflammatory bowel disease questionnaire; MCS = short-form-36 mental component score; N = number of patients in the analysis population; n = number of patients in the specified category; NRS= numeric rating scale; PBO = placebo; PCS = short-form-36 physical component score; UNRS = urgency numeric rating scale; WPAI= work productivity activity impairment productivity loss.
UNRS score was averaged from daily diary entries for a 7-day period. Data were considered as missing for that week if less than 4 days were available.

Conclusion

Incremental improvement in bowel urgency corresponded to improvements in outcomes important to patients, underscoring the importance of managing BU symptoms in improving the quality of life for patients with UC.

References

1. Dubinsky MC, et al. Crohns Colitis 360 2023;5(1):otac044.

Disclosure

MD reports consultancy fees from AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Gilead Sciences, Janssen, Pfizer, Takeda, and UCB.
ST reports grants and/or research support from AbbVie, Buhlmann Diagnostics, Celgene, Eli Lilly and Company, the International Organization for the Study of Inflammatory Bowel Disease, Janssen, the Norman Collisson Foundation, Takeda, UCB, and Vifor Pharma; consulting fees from Abacus Pharmaceuticals, AbbVie, Actial, ai4gi, Alcimed, Allergan, Amgen, Arena Pharmaceuticals, Asahi Kasei Pharma, Astellas Pharma, AstraZeneca, Atlantic Pharmaceuticals, Barco, Biocare Pharma, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Buhlmann Diagnostics, Calcico, Celgene, Cellerix, Celsius Healthcare, Cerimon Pharmaceuticals, ChemoCentryx, Cisbio, Coronado Biosciences, Cosmo Pharmaceuticals, Ducentis BioTherapeutics, Dynavax, Elan Corporation, Eli Lilly and Company, Enterome, Falk Foundation, Ferring Pharmaceuticals, FPRT Bio, Giuliani, Genentech, Genzyme, GlaxoSmithKline, Glenmark Pharmaceuticals, Grünenthal, GW Pharmaceuticals, Immunocore, Immunometabolism, Indigo Biosciences, Janssen, Lexicon Pharmaceuticals, Medarex, Merck, MSD, Neovacs, Netbiotix, Novartis, Novo Nordisk, NPS Pharma, Ocera Therapeutics, Otsuka, Palau Pharma, Pentax Medical, Pfizer, Philips, Procter & Gamble, Pronota, Proximagen, Ptima Pharma, Receptos, Resolute, Robarts Pharmaceutical, Roche, Sandoz, Santarus, Sensyne Health, Shire, Sigmoid Pharma, SynDermix, Synthon, Takeda, Theravance Biopharma, TiGenix, Tillotts Pharma, TopiVert, TxCell, UCB, Vertex, VHsquared, Vifor Pharma, Warner Chilcott, and Zeria Pharmaceutical; and speaker fees from AbbVie, Amgen, Biogen, Falk Foundation, Ferring Pharmaceuticals, GlaxoSmithKline, Janssen, Shire, Takeda, and Zeria Pharmaceutical.
TK has served as a speaker, a consultant or an advisory board member for AbbVie, Ajinomoto Pharma, Asahi Kasei Medical, Astellas, Alfresa Pharma, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen, JIMRO, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Thermo Scientific, Zeria Pharmaceutical, and received research funding from AbbVie, Alfresa Pharma, Asahi Kasei Medical, EA Pharma, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Sekisui Medical, Thermo Fisher Scientific, Zeria Pharmaceutical.
BA-B has served on advisory board for Bristol Myers Squibb, Pfizer; and reports speaker fees from AbbVie, Takeda, Bristol Myers Squibb, Janssen Pharmaceuticals.
JW, BZ, HQ, CM, SF are employees and minor shareholders of Eli Lilly and Company.
DR reports grant support from Takeda and has served as a consultant for AbbVie, AltruBio, Arena Pharmaceuticals, Bristol Myers Squibb, Eli Lilly and Company, Genentech, Gilead Sciences, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Roche, Takeda, and Techlab.

Introduction

Mirikizumab (MIRI) is an anti-IL-23p19 antibody with demonstrated efficacy compared to placebo (PBO) in the treatment of moderately-to-severely active ulcerative colitis (UC) (LUCENT-1: NCT03518086; LUCENT-2: NCT03524092).¹ Prevention of IBD-related surgery and hospitalizations is a goal in disease-modification trials for preventing disease progression.² We described the rates of these events in the LUCENT-1 and -2 trials.

Aims & Methods

Patients were randomized to intravenous MIRI 300 mg or PBO every 4 weeks (Q4W) for induction in LUCENT-1. Patients randomized to MIRI induction and achieving clinical response at Week (W)12 were re-randomized 2:1 in LUCENT-2 to subcutaneous MIRI 200 mg Q4W or PBO (MIRI withdrawal) for maintenance (W12-52). Descriptive statistics were used for proportion of patients in LUCENT-1 and -2 who had hospitalization and/or surgery by treatment group and the exposure-adjusted incident rate (IR). For LUCENT-1, hospitalizations in the induction period and surgeries during the induction and 16-week follow-up period were included. For LUCENT-2, all events were from the on-treatment period. Only hospitalizations associated with an adverse event with ≥24-hour stay (for any causes) were recorded.

Results

MIRI-treated patients had significantly lower IR of overall hospitalization, UC-related hospitalization, and overall surgery vs PBO-treated patients in LUCENT-1 (IR ratio MIRI vs PBO: 0.4, 0.1, 0.4, respectively). IR of UC-related surgery was 1.3 per 100 patient-years in MIRI-treated patients vs 2.6 per 100 patient-years in PBO group (Table). Mean time to first surgery or hospitalization from randomization was 30.5 days for PBO and 58.7 days for MIRI. Additional analyses revealed that patients on MIRI who had surgery/hospitalization in LUCENT-1 or -2 tended to have prior biologic failure and longer duration of disease. Similarly, in LUCENT-2, MIRI-treated patients had significantly lower IR of all-cause hospitalization and similar all-cause surgery vs PBO. No UC-related hospitalization and surgery were reported in the MIRI group while 2 UC-related hospitalizations (1.8 per 100 person-years) were reported from PBO.

Hospitalization and Surgery Rates in LUCENT-1 and LUCENT-2
Note: * represent p<0.05. IR = incidence rate; IRR = incidence rate ratio; MIRI = mirikizumab; N = number of patients in the analysis population; n = number of patients within each specific category; N/A= not applicable; PBO = placebo; PYE = patient years of exposure; PYR = patient years at risk; UC = ulcerative colitis. a The IR and IRR confidence intervals and the p-values are based on a Poisson distribution b UC-related surgeries are total colectomy, partial colectomy, and proctocolectomy.
LUCENT-1								LUCENT-2
	MIRI 300mg (N=868, PYE=201.0)			PBO (N=294, PYE=65.8)			MIRI vs. PBO	MIRI 200mg (N=365, PYE=267.9)			PBO (N=179, PYE=111.0)			MIRI vs. PBO
	Events, n(%)	PYR	Incidence rate, per-100 py (95%CI)a	Events, n(%)	PYR	Incidence rate, per-100 py (95%CI)a	IRR (95% CI)	Events, n(%)	PYR	Incidence rate, per-100 py (95%CI)a	Events, n(%)	PYR	Incidence rate, per-100 py (95%CI)a	IRR (95% CI)
Overall hospitalization	21 (2.4)	199.7	10.5 (6.5, 16.1)	16 (5.4)	64.6	24.8 (14.1, 40.2)	0.4 (0.2, 0.8)*	10 (2.7)	264.9	3.8 (1.8, 6.9)	11 (6.1)	109.0	10.0 (5.0, 17.9)	0.4 (0.2, 0.9)*
UC-related hospitalization	3 (0.3)	200.9	1.5 (0.3, 4.4)	10 (3.4)	65.2	15.3 (7.4, 28.2)	0.1 (0.0,0.4)*	0	267.9	0 (0.0, 1.4)	2 (1.1)	110.7	1.8 (0.2, 6.5)	0
Overall surgery	11 (1.3)	227.9	4.8 (2.4, 8.6)	9 (3.1)	75.8	11.9 (5.4, 22.5)	0.4 (0.2,1.0)*	13 (3.6)	263.2	4.9 (2.6, 8.4)	5 (2.8)	109.5	4.6 (1.5, 10.7)	1.1 (0.4, 3.0)
UC-related surgeryb	3 (0.3)	228.6	1.3 (0.3, 3.8)	2 (0.7)	76.8	2.6 (0.3, 9.4)	0.5 (0.1, 3.0)	0	267.9	0 (0.0, 1.4)	0	111.0	0 (0.0, 3.3)	N/A

Conclusion

Lower rates of UC-related hospitalizations and UC-related surgery were observed in patients treated with MIRI compared to those treated with PBO during the 12W induction LUCENT-1, and that impact continued through the 40W of maintenance LUCENT-2 with no UC-related hospitalizations or UC-related surgery reported in MIRI-treated patients.

References

1. D’Haens G, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. New England Journal of Medicine 2023;388(26):2444-2455.
2. Le Berre C, Peyrin-Biroulet L. Selecting End Points for Disease-Modification Trials in Inflammatory Bowel Disease: the SPIRIT Consensus From the IOIBD. Gastroenterology 2021;160(5):1452-1460.e21.

Disclosure

MR serves as a consultant and on advisory boards for AbbVie, Janssen, Bristol-Myers Squibb, UCB, Takeda, Pfizer, Prometheus Laboratories, Lilly, Celgene, and Amgen.
LPB has served as a consultant for AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax; he received grants from Takeda, Fresenius Kabi, Celltrion; he served as a speaker for Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, Medac; he also declares support travel by Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Gossamer Bio, Sandoz, MSD, Amgen, Lilly, Gilead, Thermo Fisher, Medac, CONNECT Biopharm; he declares stock options of Clinical trials Mobile Application.
JW, BZ, IR, KT, CO are employees and minor shareholders of Eli Lilly and Company.
SN has served on advisory board and speaker for Eli Lilly and Company, Pfizer and advisory board for madrigal and speaker for Janssen
TK has served as a paid consultant for Abbvie, Amgen, Biogen, Mundipharma, Hospira, Gilead, Janssen, Pfizer, MSD Sharp & Dome GmbH, and Novartis. He has received reimbursement of meeting participation fees and of travel and accommodation expenses from Abbvie, Janssen, MSD, and Takeda. He has received honoraria for preparing continuing medical education events from Abbvie, Falk, Janssen, MSD, Takeda, and Ferring Arzneimittel GmbH.
LM reports educational grants from Abbvie, Janssen, Pfizer and Takeda; advisory boards: AbbVie, Bristol Myers Squibb, Janssen, and Celltrion; consultant for Abbvie, Pfizer and Pharmacosmos.
FM has served as a speaker and received honoraria from Merck Sharp & Dohme, Abbvie, Vifor, Falk, Laboratorios Vitoria, Ferring, Hospira, and Biogen.