Introduction

The sex differences in the incidence of gastric cancer have been well known. However, uncertainty still exists in terms of prognosis of GC. For example, the US SEER data reports a significantly better prognosis in females than in males, but the prognosis is better in males than in females in Korean Central Cancer Registry data. Roles of molecular markers and gut microbiota as new prognostic factor are emerging recently, but few studies seem to try to reveal sex differences.

Aims & Methods

In this background, we aimed to analyze the differences in GC characteristics according to sex in Korean patients, mainly focused on survival. This was a single-center retrospective study. A total of fifteen thousand patients diagnosed with GC at the Seoul National University Bundang Hospital between 2003 and 2023 were included. Clinicopathological characteristics, histologic types, survival rates with age- and stage-stratification, and associated risk factors were analyzed. Information related to death was cross-verified using medical record review and data from the National Statistical Office.

Results

The ratio of males and females was about 2:1, and there was no differences in stage between sexes. Female patients were significantly younger than males, had more gastric body cancers and tumors with diffuse type or poorly differentiated histology. Females underwent less endoscopic treatment and more surgery, and tumors with microsatellite instability was more common in females, while mutation of p53 was less common. In histological types according to Lauren classification, diffuse type histology was more common in younger patients in both males and females. The proportion of intestinal type GC increased with age, but the proportion increased rapidly in males while increased gradually in females. In Cox multivariate regression analysis for GC-related death, older age, proximal tumor location, diffuse type histology and advanced tumor stage were risk factors. In terms of survival, overall and GC-specific survival did not show significant differences between sexes in the analysis of the total population. However, sex differences in survival reversed with age, that younger females under 50 showed survival disadvantages, but the survival became similar in 50s, and older females over 60 showed survival advantages in both overall and GC-specific survival. Furthermore, in the stratification analysis according to the stage, there were no significant differences in stages I to III. But, stage IV female patients showed significant survival disadvantages. In subgroup analysis of stage IV patients, the differences between males and females in median survival were two months, and female patients were significantly younger and had a higher proportion of diffuse type GC than male patients, which shows aggressive feature and is related to poorer survival.

		Total (N=1,924) (%)	Male (n=1,282) (%)	Female (n=642) (%)	p
Median survival (mo)		10	11	9	0.022
Age (mean±SD)		61.59±14.25	62.41±13.23	59.96±15.97	0.001
Age (in diffuse type patients, mean±SD)		54.55±14.71	56.43±14.29	52.26±14.91	0.001
Lauren classification	Intestinal	554 (48.0)	438 (56.7)	116 (30.4)	<0.001
	Diffuse	574 (49.7)	315 (40.7)	259 (68.0)
	Mixed / Indeterminate	26 (2.3)	20 (2.6)	6 (1.6)

Conclusion

Significant differences in survival between sexes were observed with stratification analysis, although sex itself was not an independent prognostic factor. These age-dependent changes are thought to suggest the effect of sex hormones. These differences should be considered in clinical practice and later research in terms of tailored medicine.

Introduction

Acute severe colitis (ASC) is an important cause of morbidity and mortality in Ulcerative Colitis (UC), requiring hospitalisation and, frequently, colectomy. Intravenous corticosteroids (CS) remain the first-line medical treatment. Approximately 40% of episodes of ASC do not respond to this treatment and require rescue therapy with ciclosporin (CIC) or infliximab (IFX)¹. In the past decades, these treatments and protocol-driven management algorithms led to reduced mortality and colectomy rates. A simple clinical scoring system (the Admission Model for the Intensification of Therapy in Acute Severe Colitis (ADMIT-ASC))³, based on CRP, albumin, and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score, was recently developed to predict the steroid response on admission.

Aims & Methods

We aimed to retrospectively assess the steroid non-response during admission with ASC and the usefulness of the new prognostic clinical index ADMIT-ASC at admission to predict steroid response in a Belgian tertiary center. All patients admitted with ASC between 1^st January 2015 and 1^st April 2023 were identified from our inflammatory bowel disease database at Erasme University Hospital. Inclusion criteria were ASC patients admitted at the hospital, standard treatment with at least 3 days of intravenous CS and endoscopy evaluation upon admission. ASC was defined according to modified Truelove and Witts’ criteria as ≥6 bloody stools/day with one or more markers of systemic disturbance (tachycardia >90 beats/min, temperature >37.8°C, haemoglobin <105 g/L or CRP >30 mg/L). Steroid non-response was defined as the need for medical rescue therapy (CIC of IFX) or colectomy during the admission. ADMIT-ASC index consists of four points: CRP ≥100 mg/L (1 point), albumin ≤25 g/L (1 point) and UCEIS score ≥4 (1 point) or ≥7 (2 points).

Results

Table I Admission Demographics data (n= 84)	Steroid response (n=49)	Steroid non-response (n=35)	P value
Median disease duration (years) (IQR)	3.6 (0.3-0.9)	2.1 (0.8-5.5)	0.5
Montreal Classification	E1 : 5/49 (10%) E2 : 20/49 (41%) E3 : 24/49 (49%)	E1 : 0/35 E2 : 12/35 (34%) E3 : 23/35 (66%)	0.084
5-ASA, n (%)	22 (45%)	10 (29%)	0.13
Methotrexate or thiopurine, n (%)	6 (12%)	9 (26%)	0.11
Infliximab, n (%)	4 (8.2%)	8 (23%)	0.058
Vedolizumab, n (%)	7 (14%)	5 (14%)	>0.9
Tofacitinib, n (%)	2 (4.1%)	2 (5.7%)	>0.9
Readmission, n (%)	12 (24%)	10 (29%)	0.7
5-ASA, 5-aminosalicylate P values from Wilcoxon rank-sum test or Fisher’s exact test.

Out of 127 patients admitted with UC and treated with intravenous CS during three days, 84 (45% male, median age of 31 years old) were included in the study. Admission demographics and clinical characteristics are described in Table 1.
For 17 patients (20%), the admission was their index presentation of UC. Response to CS was seen in 49 patients (58%). Thirty-three patients (39%) received medical rescue therapy (17/33 IFX and 16/33 CIC). Colectomy rate during admission was 13% after a median duration of 18 days (IQR: 16-54). Admission C reactive protein (CRP) (p=0.036), albumin (p=0.026) and UCEIS scores (p=0.022) were significantly associated with steroid non-response. Patients scoring 0, 1, 2, 3 and 4 had steroid response rates of 90%,75%, 55%, 19% and 0%, respectively. Scoring of ≥3 was 75% (95% CI, 0.43 to 0.95) predictive of steroid failure (OR 5.08, 95%, CI 1.38 to 24.5).

Conclusion

In this tertiary referral cohort study, we confirmed that the ADMIT-ASC index is a simple clinical tool that can be used on the day of admission to predict steroid non-response in ASC with a threshold of ≥3 to identify patients who are unlikely to respond to intravenous CS and enabling timely treatment escalation or surgery.

References

1. Travis S, Satsangi J, Lémann M. Predicting the need for colectomy in severe ulcerativecolitis: a critical appraisal of clinical parameters and currently available biomarkers. Gut 2011;60:3–9.
2. Travis SP, Farrant JM, Ricketts C, et al. Predicting outcome in severe ulcerative colitis.Gut 1996;38:905–10.
3. Adams A, Gupta V, Mohsen W, et al. Gut 2023;72:433–442.

Disclosure

VB has not disclosure.
CDT has not disclosure.
CM has not disclosure.
AC has received lecture fees from Galapagos, Abbvie, Janssen, celltrion, Pfizer, Takeda.
DF has received lecture fees from Abbvie, Astrazeneca, Dr.Falk Pharma, Ferring, Janssen, Mundipharma, MSD, Pfizer, Takeda, Amgen, and advisory board fees from Abbvie, Janssen,Takeda, Celltrion, Amgen.
CL has received consultancy fees from Janssen, Abbvie, Takeda and Galapago and speaker fees from Sandoz, Janssen, Abbvie

Introduction

Postoperative ileus, is one of the most common causes of prolonged hospital stays after abdominal surgery which cause from physiologic hypomotility of the gastrointestinal tract occurring immediately after abdominal surgery. Multi-modal approach to the resolution of postoperative ileus includes ERAS protocol such as opioid minimization, early ambulation, intake of prokinetic drug. Mosapride citrate (mosapride) is known to promote gastrointestinal motility. The objective of this study is to evaluate the effects of mosapride on postoperative ileus and postoperative gastrointestinal motility in patients undergoing elective open and laparoscopic colorectal surgery.

Aims & Methods

The study was approved by ethics committee of the Faculty of Medicine Ramathibodi Hospital Mahidol University (Ref. Number COA.MURA2021/328,ClinicalTrials.gov Identifier: NCT04905147). Forty-four colorectal cancer patients, undergoing open and laparoscopic colorectal surgery in Ramathibodi Hospital during July 2021-August 2022, were randomly assigned to a mosapride group or control group. The mosapride group received 15 mg of mosapride by enteric route with 50 ml of water three times a day, starting on postoperative day 1. The control group received 15 mg of placebo drug with 50 ml of water at the same time. Postoperative time to the first passage of flatus and the first bowel movement were evaluated by one investigator with triple blind study. Time to step diet, length of postoperative hospital stays, and adverse effects were also evaluated in secondary outcomes.

Results

All forty four patients were include, twenty-three in control group and twenty-one in mosapride group. There were no statistically significance differences between mean age and type of surgery (laparoscopic or open) in two group (P>0.05). Time to first bowel movement and time to passage of flatus after operation were significantly shorter in the mosapride group than the control group (26 vs 50 hours, P=0.004 and 40 vs 70 hours, P=0.003, respectively). Time to step diet (soft diet) was also shorter in the mosapride group (90 vs 132 hours, P=0.004). Time to defecate was less in mosapride group than control group (80 vs 120 hours, P <0.001). Length of hospital stay was significantly shorter in patients receiving mosapride (7 vs 10 days, P=0.004).

Conclusion

This study demonstrated the efficacy of mosapride when administered to patients who underwent elective colorectal surgery. Mosapride significantly enhance recovery of gastrointestinal motility and shorter length of hospital stay with no significant adverse effects.

References

1. Collins TC, Daley J, Henderson WH, Khuri SF. Risk factors for prolonged length of stay after major elective surgery. Ann Surg 1999;230:251–9
2. Vather R, O'Grady G, Bissett IP, Dinning PG. Postoperative ileus: mechanisms and future directions for research. Clin Exp Pharmacol Physiol. 2014;41(5):358-370.
3. Goldstein JL, Matuszewski KA, Delaney C, Senagore A, Chiao E, Shah M, et al. Inpatient economic burden of postoperative ileus associated with abdominal surgery in the United States. P AND T.2007;32(2):82.
4. Venara A, Neunlist M, Slim K, Barbieux J, Colas PA, Hamy A, et al. Postoperative ileus: Pathophysiology, incidence, and prevention. J Visc Surg 2016;153:439-46.
5. Luckey A, Livingston E, Taché Y. Mechanisms and Treatment of Postoperative Ileus. Arch Surg. 2003;138(2):206–214.
6. Georgiadis, G & Markantonis, Sophia & Triantafillidis, John. (2000). Prokinetic agents: Current aspects with focus on cisapride. Annals of Gastroenterology. 13.
7. Reynolds, J.C. & Putman, P.E. (1992) Prokinetic Agents, Gastroenterol Clin of North Am, Vol.21, pp.567-596.
8. Taniyama, K., Makimoto, N., Furuichi, A. et al. Functions of peripheral 5-hydroxytryptamine receptors, especially 5-hydroxytryptamine₄ receptor, in gastrointestinal motility. J Gastroenterol 35, 575–582 (2000).

Introduction

Fibrosis constitute an important complication of CD. MicroRNAs (miRNAs), which are small RNA molecules that regulate gene expression, have been shown to participate in the molecular interactions of both inflammation and fibrosis. Lower levels of miR-378a-3p have been reported associated to murine liver fibrosis [1] and we analyze here the relevance of miR-378a-3p on intestinal fibrosis.

Aims & Methods

B57BL/6 mice were intravenously injected with 2,5mg/kg of negative control (NC) or mm-miR-378a-3p mimic, twice a week and received vehicle or Dextran Sulfate Sodium (DSS) for 2 cycles (7 days drinking DSS 2% in water solution followed by 10 days drinking water). Body weight and DAI score was obtained every day and the colon was collected after sacrifice. Sirius and hematoxylin-eosin dyes were employed to determine the fibrosis and structural state in 5µm slides of intestinal tissue. Gene expression and miRNA profiles were analyzed by RT-qPCR. Human small intestinal fibroblasts (HSIF; P10760, Innoprot, Spain) were transfected with 20nM of NC or hsa-miR-378a-3p mimic during 24h.

Results

No significant changes in body weight, DAI score, and colon length were detected between mice receiving NC and those receiving mimic, all along the two DSS cycles. Colon of mice treated with DSS, exhibited a significant diminution in the mRNA expression of mm-miR-378a-3p compared with naïve samples. In DSS-treated mice, the iv administration of the mimic compared with the NC: a) significantly increased levels of miR-378a-3p in the colon; b) increased the number of neutrophils, and heightened changes in the glandular epithelia and architectural distortion C) decreased the number of lymphoid follicles; d) slightly increased collagen deposition, as analyzed by sirius red and e) significantly increased the mRNA expression of Tgfb1, Il1b, and Mmp2. Treatment of human intestinal fibroblasts with hsa-miR-378a-3p mimic did not significant modify the mRNA expression of markers of fibrosis but it significantly increased the mRNA expression of two antiapoptotic molecules BCL2 and MCL1.

Conclusion

Levels of mm-miR-378a-3p are diminished in a murine model of intestinal fibrosis; The exogenous administration of miR-378a-3p, increased the acute inflammatory response and the expression of fibrosis markers in murine fibrotic colon and the expression of antiapoptotic molecules in human intestinal fibroblasts.

References

1. Hyun, J.; Wang, S.; Kim, J.; Rao, K.M.; Park, S.Y.; Chung, I.; Ha, C.S.; Kim, S.W.; Yun, Y.H.; Jung, Y. MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression. Nat Commun 2016, 7, 10993, doi:10.1038/ncomms10993.

Introduction

Rigid surgical instruments used for conventional laparoscopic surgery provide limited movement, and it is difficult to perform skillful surgery due to their long, jointless straight features. Articulated instruments could have the same advantages seen in robotic surgery, such as excellent control in smaller spaces, restoration of more intuitive and ergonomic movements, and the ability to overcome obstacles on a direct visual line. The aim of this study was to evaluate the surgical performance and clinical outcomes of patients following laparoscopic colorectal surgery with multijoint laparoscopic instruments, ArtiSential® (LivsMed, Seongnam, Korea), compared with those using conventional instruments.

Aims & Methods

Patients aged 19–80 years undergoing elective laparoscopic surgery for colorectal disease between December 2021 and November 2022, were consecutively enrolled. The first 20 cases underwent conventional laparoscopic surgery, and the latter 50 cases underwent laparoscopic surgery using ArtiSential®. Unedited operative videos were submitted to the Crowd-Sourced Assessment of Technical Skills (C-SATS) platform for evaluation using the Global Operative Assessment of Laparoscopic Skills (GOALS), which is a validated tool for technical proficiency. Each of GOALS’ four domains (bimanual dexterity, depth perception, efficiency, and tissue handling) was scored on a Likert scale between 1 and 5, scoring anchor, with a total score ranging from 4 to 20. The learning curve analysis was performed using the cumulative sum control chart (CUSUM) for GOALS grades (Registration number: KCT0006798).

Results

There was no significant difference between group with regards to type of operation, hospital stay, and 30-day postoperative complication. The GOALS’ grades were similar between the two groups (15.7 ± 0.7 vs. 15.9 ± 0.5, P = 0.190), but the scores in two domains (depth perception and tissue handling) were significantly higher in the ArtiSential® group (3.9 ± 0.3 vs. 4.0 ± 0.2, P = 0.014 and 3.9 ± 0.2 vs. 4.1 ± 0.2, P = 0.048, respectively) compared with those in the conventional group. In addition, patients in the ArtiSential® group experienced a shorter operation time (122.3 ± 58.9 vs. 88.1 ± 35.1, P = 0.022) and less intraoperative blood loss (56.5 ± 69.9 vs. 29.8 ± 1.4, P = 0.002) than those in the conventional group. According to the CUSUM learning curve analysis, the first 10 cases using ArtiSential® were in the inexperienced phase, and the remaining 40 cases were in the experienced phase. The GOALS’ score in the experienced phase of ArtiSential® was improved compared with that in the conventional group (16.0 ± 0.5 vs. 15.7 ± 0.7, P = 0.037).

Conclusion

A plateau in the learning curve of laparoscopic colorectal surgery performed with an articulated instrument was observed in approximately 10 cases, and it can be expected that surgical proficiency in the experienced phase increases without deterioration of clinical outcome as compared to that in conventional surgery.

References

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Disclosure

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grantnumber: HI20C2092).

Introduction

There are no established treatments for esophageal anastomotic stricture refractory to endoscopic balloon dilation (EBD). Patients experience a reduced quality of life and suffer a financial burden after surgery until the strictures are relieved. New treatments for refractory anastomotic stricture are clearly needed. Local steroid injection is reported to improve the effects of EBD. In addition, EBD with local steroid injection is a current community standard treatment for patients with refractory anastomotic stricture after esophagectomy, although the effect is limited. A new endoscopic treatment for such strictures is radial incision and cutting (RIC), which improves strictures by cutting through scar tissue at the stricture site with an electrocautery knife and removing any fibrous tissue that may cause re-stricture. However, the evidence for its effectiveness is limited to retrospective studies and small case series.

Aims & Methods

The aim of this multicenter, randomized, open-label, phaseⅡ/Ⅲ trial was to investigate the safety and the superiority of RIC with steroid injection compared with EBD with steroid injection for patients with refractory anastomotic stricture after esophagectomy for thoracic esophageal cancer. This is the first randomized controlled trial in the world for patients with refractory esophageal anastomotic strictures. Patients with Dysphagia Score ≥2 (able to swallow only semisolid foods or liquids) who had strictures through which a conventional endoscope (diameter, 9.6–10.4 mm) did not pass despite three or more EBDs or bougienage dilations were eligible for this trial. The primary endpoint in the phase II part was proportion of hemorrhages, post-operative esophageal perforations, esophageal hemorrhages, pneumothorax, lung or mediastinum infections or other unexpected adverse events. Co-primary endpoints in the phase III part were re-stricture-free survival and number of dilations for 24 weeks after treatment. This study was registered with the Japan Registry of Clinical Trials jRCTs031180177.

Results

From May 2014 to March 2022, 130 patients were enrolled from 32 institutions participating Gastrointestinal Endoscopy Study Group of the Japan Clinical Oncology Group and 65 patients each were randomized to EBD arm and RIC arm. The median number of dilations before registration was five in each arm. Dysphagia Score represented grade 2 (able to swallow semisolid foods) in 104 (80.0%) patients, grade 3 (able to swallow liquids only) in 25 (19.2%) patients, and grade 4 (unable to swallow liquids) in 1 (0.8%) patient in whole of study. Grade 3/4 pre-defined adverse events occurred in 1 (1.5%) patient in each arm. Median re-stricture-free survival in EBD arm was 10.6 weeks (95% CI: 6.9-20.1 weeks) and 8.7 weeks (95% CI: 7.1-10.9 weeks) in RIC arm (hazard ratio 1.22, 90% CI 0.85-1.74, one-sided p=0.82). The median number of dilations for 24 weeks after initial treatment was once (IQR: 0-2) in EBD arm and twice (IQR: 0-4) in RIC arm (one-sided p=0.99). The proportion of patients with anastomotic diameter >10 mm at 8 weeks after treatment was 27.7% (95% CI: 17.3-40.2%) in EBD arm and 24.6% (95% CI: 14.8-36.9%) in RIC arm.

Conclusion

RIC with steroid injection was not superior to repeated EBD with steroid injection for refractory anastomotic stricture after esophagectomy. EBD combined with steroid injection remains the standard of care for refractory anastomotic stricture after esophagectomy.

Introduction

Stenosis after esophageal Endoscopic Submucosal Dissection (ESD) has a high incidence of ranks, and muscular injury might be an important risk factor for esophageal stenosis.

Aims & Methods

Our study aimed to classify muscular injury degree and investigate its association with postoperative stenosis. This retrospective study included 1,033 patients with esophageal mucosal lesions treated by ESD between August 2015 and March 2021. Demographic and clinical parameters were analyzed, and stenosis risk factors were identified using multivariate logistic regression. A novel muscular injury classification system was proposed and further used to investigate the association between the different degrees of muscular injury and postoperative stenosis. Finally, a scoring system was established for the prediction of muscular injury.

Results

Of 1,033 patients, 118 (11.4%) had esophageal stenosis. The multivariate analysis demonstrated that the history of endoscopic esophageal treatment, circumferential range, and muscular injury were significant risk factors for esophageal stenosis. Patients with Type II muscular injuries tended to develop complex stenosis (n = 13, 36.1%, p < 0.05). Moreover, Type II muscular injuries were more likely to predispose patients to severe stenosis than Type I (73.3 and 92.3%, respectively). According to the scoring system for predicting muscular injury, patients with high scores (3-6) were more likely to suffer muscular injury. The score model presented good discriminatory power in the internal validation (AUC: 0.706; 95% CI: 0.645-0.767) and goodness-of-fit in the Hosmer-Lemeshow test (p = 0.865).

Conclusion

Muscular injury was an independent risk factor for esophageal stenosis. The scoring system demonstrated good performance in predicting muscular injury during ESD.

References

1. Yang D, Othman M, Draganov PV. Endoscopic Mucosal Resection vs Endoscopic Submucosal Dissection For Barrett's Esophagus and Colorectal Neoplasia. Clin Gastroenterol Hepatol. 2019;17:1019-28.
2. Chen M, Dang Y, Ding C, et al. Lesion size and circumferential range identified as independent risk factors for esophageal stricture after endoscopic submucosal dissection. Surg Endosc. 2020;34:4065-71.
3. Ishihara R, Arima M, Iizuka T, et al. Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer. Dig Endosc. 2020;32:452-93.
4. Zhang BZ, Zhang Y, Wang YD, et al. Stent placement to prevent strictures after esophageal endoscopic submucosal dissection: a systematic review and meta-analysis. Dis Esophagus. 2021;34.
5. Wu QN, Xu XY, Zhang XC, et al. Submucosal fibrosis in achalasia patients is a rare cause of aborted peroral endoscopic myotomy procedures. Endoscopy. 2017;49:736-44.
6. Nagami Y, Ominami M, Shiba M, et al. Prediction of esophageal stricture in patients given locoregional triamcinolone injections immediately after endoscopic submucosal dissection. Dig Endosc. 2018;30:198-205.
7. Xu Y, Lin Z, Zhong S, et al. Muscular injury was identified the risk factor of post-operative stenosis after large area but non-circumferential esophageal endoscopic submucosal dissection. Scand J Gastroenterol. 2022:1-8.