Introduction

Colorectal cancer’s (CRC) incidence above 50 years old has been decreasing globally in the last decades, but its incidence in patients below 50 years old (early-onset colorectal cancer, EO-CRC) has been increasing, for reasons not yet fully understood.

Aims & Methods

A unicentric cohort study was conducted in a tertiary centre, including all patients admitted for a first diagnosis of CRC and evaluated by the Multidisciplinary Colorectal Cancer Group from 01.01.2017 until 31.12.2018. Patients with a previous diagnosis of a Hereditary Colorectal Cancer Syndrome were excluded.

Results

A total of 438 patients were included, 58.2% males, with a mean age at diagnosis of 67.7±11.1 years old. Mean follow-up time was 41.49 months. There were 25 EO-CRC patients (5.7%), 17 males (68%), mean age 43.1±6.0 years old.
Globally, 32.4% of the patients were current or past smokers, 18.5% had previous non-colorectal cancer, 7.5% and 3.4% were previously exposed to immunosuppressive drugs or abdominal/pelvic radiotherapy, respectively. The majority presented with normal(29.7%) to high Body Max Index (39.7%), median 25.6 (IQR:22.6-28.4) Kg/m². The most common CRC location was the rectum (42.9%) and 56.1% were stage I or II (AJCC 8^th edition).
In the univariate analysis, a significant association was found between EO-CRC and: smoking status (past or current smokers 52% in EO-CRC vs. 31.2% in older cases p=0.009); lymphovascular invasion (40.0% in EO-CRC vs. 17.4% in over 50, p=0.018) No significant differences were found for histological subtype (p=0.447), perineural invasion (p=0.474), or tumor stage at diagnosis, although a relevant proportion of the younger patients had metastatic disease at diagnosis (28.0% vs. 12.8%, p=0.064).
Immunohistochemistry for mismatch-repair proteins showed loss of expression of at least one protein in 1/18 EO-CRC patients and 22/179 of older patients (p=0.728).
From the EO-CRC patients, 16 were evaluated in the Familial Cancer Clinic and 14 underwent germline mutation analysis: 13 patients had inconclusive results, one of them presented a MUTYH heterozygote mutation and another was diagnosed with MUTYH-associated Polyposis (composed heterozygote mutation).

Conclusion

Colorectal cancer showed distinctive features in the younger population, with a higher prevalence of lymphovascular invasion and, possibly, a higher incidence of metastatic disease at diagnosis. Smoking had a significant association with CRC, especially in this younger population. Whether this means there is a biological difference is not yet clear. More evidence is needed in order to clarify EO-CRC aetiology and to develop screening and improve management strategies.

References

Siegel RL, Jakubowski CD, Fedewa SA, Davis A, Azad NS. Colorectal Cancer in the Young: Epidemiology, Prevention, Management. Am Soc Clin Oncol Educ Book. 2020 Mar;40:1-14. doi: 10.1200/EDBK_279901. PMID: 32315236

Introduction

Fexuprazan, a novel potassium-competitive acid blocker (P-CAB), is currently recognized as a successful alternative to proton pump inhibitors (PPIs) for acid-related disorders. However, its experience in the global market remains limited.

Aims & Methods

This study aimed to integrate two randomized phase 3 studies (NCT03736369 in South Korea and NCT05813561 in China) investigating the efficacy and safety of fexuprazan in subjects with erosive esophagitis (EE) across Asian populations, especially those with at least moderate severity of major symptoms (≥2 days of heartburn or acid regurgitation at baseline). The Cochran-Mantel-Haenszel method was used to assess the efficacy of fexuprazan 40 mg and esomeprazole 40 mg in treating EE and relieving major symptoms, whereas the Wilcoxon signed-rank test evaluated safety by testing changes in gastrin levels within each treatment group.

Results

Of the 595 randomized subjects, 513 (256 in the fexuprazan group and 257 in the esomeprazole group) were included in the efficacy analysis set (per-protocol set, PPS). In the PPS, the healing rates of EE in the fexuprazan and esomeprazole groups at weeks 4 and 8 were 86.90% and 84.00% (95% confidence interval [CI] = -2.80, 9.23) and 98.05% and 98.44% (95% CI = -2.30, 2.02), respectively. In the subgroup analysis of patients with at least a moderate severity of major symptoms (205 in the fexuprazan group and 197 in the esomeprazole group), the healing rates of EE did not differ between the two groups (week 4, 85.57% vs. 83.33% [95% CI = -4.70, 9.28]; week 8, 97.56% vs. 97.97% [95% CI = -2.84, 2.61]). However, the proportion of subjects without symptoms in the first 3 days in both full day and nighttime in the fexuprazan group was significantly higher than that in the esomeprazole group (20.44% vs. 11.90%, p = 0.0212 and 32.04% vs. 22.02%, p = 0.0387, respectively). In the safety set, serum gastrin levels at the final visit significantly increased by 87.23 pg/ml and 61.99 pg/ml from baseline serum gastrin levels in both fexuprazan and esomeprazole groups, respectively. However, the mean gastrin levels at the final visit in both groups did not increase to the clinically significant levels (121.89 pg/ml vs. 96.40 pg/ml, respectively). None of the observed increases in gastrin levels resulted in discontinuation of the study, and no significant safety risks were identified in either group.

Conclusion

The efficacy of fexuprazan in treating EE was not inferior to that of esomeprazole in Asian populations. In subjects with at least a moderate severity of major symptoms, symptom relief in the fexuprazan group was higher in the first 3 days, regardless of full-day or nighttime. In terms of safety, serum gastrin level was tolerable in both groups, and no serious adverse events occurred in the fexuprazan group.

Introduction

Hypertriglyceridemia is a well-established cause of acute pancreatitis, representing up to 35% of all etiologies. The risk of developing acute pancreatitis increases progressively with serum triglyceride (TG) levels over 500 mg/dL. The degree of TG elevation is also associated to the severity of hypertriglyceridemia-induced pancreatitis (HTGP). Besides general measures, it has been suggested from observation studies that, in selected patients, insulin and plasmapheresis may have a role in the management of this condition.

Aims & Methods

We present an observational retrospective study of patients diagnosed with severe HTGP treated with plasmapheresis (PX) in an Intensive Care Unit (ICU) between January 2013 and March 2023.

Results

Of the 19 patients included in this study, 89% were men (n=17) and the mean age of presentation was 41 ± 7 years. Around 90% of patients were obese with a mean body mass index (BMI) of 29 ± 3 kg/m². The average APACHE II score was 9±7 and most patients did not require organ support (n=16, 84%). All the selected patients had severe hypertriglyceridemia at admission (1225 to 4700 mg/dL) and underwent PX within 48h of ICU admission. Levels of TG were measured before and after each plasmapheresis. 68% of patients needed only one treatment to reduce TG to a value below 500 mg/dL (n=13), 26% needed two treatments (n=5) and 5% needed four (n=1). A total of 27 PX were conducted. The average decrease in TG levels per treatment was 67% and 74% with the first treatment. The mean volume exchanged was 3683 mL ± 859 mL, and the most used replacement solutions were albumin/crystalloid (n=12, 44%) and albumin alone (n=11, 41%). The technique was interrupted mainly due to elevated transmembrane pressure (n=11, 40%). There were no PX interruptions due to complications related to the patient. Although heparin was used in all patients for anticoagulation, no hemorrhagic complications were associated to the technique. Hypotension occurred in 7% of plasmapheresis and was solved with crystalloid administration . The mean ICU length of stay was 7+11 days and the mean hospital length of stay was 17+21 days. The hospital mortality was 5% (n=1).

Conclusion

PX proved to be successful in lowering TG levels in HTGP. One to two plasma exchanges effectively reduced the serum TG level. There was a low rate of procedure-related complications. However, having no comparison with standard treatments, the impact of this technique on the patients’ clinical outcomes is still uncertain. Further prospective randomized clinical studies are needed to outline an efficient treatment for the management of HTGP.

References

Padmanabhan, A et al, “Guidelines on the Use of Therapeutic Apheresis in Clinical Practice”, J Clin Apher. 2019;34:171–354.
Banks PA, “Practice guidelines in acute pancreatitis.”, Am J Gastroenterol. 2006;101(10):2379)
Rawla, P. “Hypertriglyceridemia-induced pancreatitis: updated review of current treatment and preventive strategies”, Clin J Gastroenterol. 2018 Dec;11(6):441-448.
Faria, R. et al, “Therapeutic Plasmapheresis: Seven Year Experience of an Intensive Care Unit in Portugal”, Acta Med Port 2022 Mar;35(3):176-183
Stefanutti, C. et al, “Severe Hypertriglyceridemia-Related Acute Pancreatitis”, Therapeutic Apheresis and Dialysis 2013; 17(2):130–137