Introduction

Fecal incontinence (FI) has a strong impact on quality of life (QoL). The main treatments focus on the rehabilitation of anorectal function. In a previous study we found that sphincter dysfunctions were severe and similar in patients with or without soft stools, but their presence worsened clinical severity and QoL significantly, requiring a specific diagnostic and therapeutic approach. FI and diarrhea are strongly associated, and treatment of the latter may be an effective method to ameliorate FI. Some studies show that loperamide or fiber supplements in these patients is effective at least in the short term, although effective long-term and specific treatments aimed at the cause of diarrhea need to be identified.

Aims & Methods

To assess the impact on clinical severity and QoL of specific treatments for soft stools or diarrhea in patients with FI and diarrhea.
Quasi-experimental study. We assessed anorectal function with high-resolution anorectal manometry, fecal consistency (Bristol Stool Chart), clinical severity (Wexner Score) and QoL (FIQL/EQ5D) in women with FI, and feces with Bristol≥5; patients underwent a breath-test to detect lactose, fructose/sorbitol malabsorption and SIBO, as potential causes of diarrhea, and an empirical test using cholestyramine to assess the presence of malabsorption of bile salts. Patients with SIBO were treated with Rifaximin 1200mg/day for 15 days. Those intolerant to lactose and fructose/sorbitol were given an exclusion diet. Those who did not show intolerances were administered Resincholestyramine 4g/12 hours for 15 days. Bristol, QoL and clinical severity were re-assessed in a follow-up visit one month later.

Results

Seventy-four women with FI and soft stools completed the study; mean age was 64.92±11.70 years. Of them, 59.18% had dysfunction of the external anal sphincter, 51.02% of the internal sphincter and 15.59% of both. Rectal hypersensitivity was shown in 12% of patients and 20% had hyposensitivity. Cough reflex was altered in 41.7%. Regarding the origin of the diarrhea, 43.9% showed bile salt malabsorption, 26.6% fructose/sorbitol intolerance, 17.1% SIBO and 12.2% lactose malabsorption. After one month of specific pharmacological treatment or exclusion diet we observed that 92.9% of the patients improved fecal consistency (Bristol 3-4). Clinical severity (Wexner) was reduced by 66% (11.61±3.64 pre-treatment vs 3.89±4.05 post-treatment; p<0.001). QoL improved in all dimensions of the FIQL score (pre/post-treatment): Lifestyle (2.69±0.91/3.40±0.72 p<0.01), coping (2.32±0.88/3.03±0.78 p<0.01), depression/self-perception (2.77±0.70/3.33±0.56 p<0.01) and embarrassment (2.77±0.90/3.33±0.77 p<0.01). Health perception (EQ5D) also improved after the treatment (61.96±15.91/70±7.39 p=0.017).

Conclusion

Presence of soft stools or diarrhea is a very prevalent and important risk factor in women with IF in addition to sphincteric and anorectal alterations. Our findings suggest that specific treatment aimed at the cause of diarrhea can be highly effective in improving patient outcomes and QoL, regardless of disorders of the anorectal function. We suggest that rehabilitation strategies must start after stool assessment. This study highlights the importance of continued research in this area to help improve treatment options for this debilitating condition.

Introduction

There are three main concepts in colorectal carcinogenesis. The first is the well-known “adenoma-carcinoma sequence”, while the second is the “saw-tooth lesion pathway”. In this concept, serrated lesions transform into early carcinomas. The third concept is the “de novo” pathway, in which early carcinomas can develop even in the absence of an adenoma. In this pathway, the cancer is thought to arise directly from the normal epithelium, rather than from an adenoma, and the cancer tends to progress at a faster rate and with a higher grade of malignancy. For diagnosing colorectal cancer, magnified endoscopy, specifically the Pit pattern classification, has proved to be useful. Recently, the endoscopic examination (EC classification) has been developed, and now not only structural atypia but also cellular atypia can be observed in vivo.
In this study, we aimed to clarify the endoscopic characteristics of colorectal cancer and demonstrate the usefulness of pit pattern classification and EC classification. Our study focused mainly on colorectal cancer that is considered to arise through the "de novo" pathway.

Aims & Methods

From April 2001 to December 2022, a total of 45,419 colorectal neoplasms, excluding advanced cancer that were resected endoscopically or surgically at Showa University Northern Yokohama Hospital. Among them, 37,098 were low-grade dysplasia, 6,802 were advanced dysplasia, and 1,519 cases were submucosal invasive carcinoma. In this study, we investigated the characteristics of depressed carcinomas with respect to Pit patterns and EC classification.

Results

Of all the T1 colorectal cancers, depressed lesions accounted for 61.4% (324/528). In contrast, flat and protruding lesions accounted for only 2.9% (575/19,578) and 2.7% (673/25,313) of T1 cancers, respectively. Flat (95.1% (18,619/19,578)) and raised (94.2% (23,844/25,313)) lesions showed mostly type IIIL and type IV pit patterns corresponding to adenomas. Among depressed lesions, 92.2% (486/528) were types IIIS, VI, and VN, corresponding to adenocarcinoma in pit pattern classification. On endoscopy, most of the flat or protruding lesions corresponded to adenomas and were classified as type EC2 in the EC classification, whereas the depressed lesions were mostly classified as EC3a and EC3b (91.2%), indicating invasive carcinoma according to the EC classification.

Conclusion

This study demonstrates that depressed colorectal cancer is prone to invade the submucosa, highlighting the need for magnifying endoscopy and endoscopy, regardless of the size of the lesion. Nonetheless, detecting this type of colorectal cancer can present a significant challenge. Thus, greater attention must be devoted to the morphological characteristics of depressed colorectal cancer during routine colonoscopy.

Introduction

The effect of analgesic modalities on short term outcomes in acute pancreatitis (AP) is unknown. Opioids are frequently used in AP but there are concerns regarding safety from preclinical models of AP. The aim of this study was to assess the effect of different analgesic modalities, in particular opioids, on the severity, morbidity, and mortality in hospitalized patients with AP.

Aims & Methods

This prospective cohort study recruited consecutive patients admitted with a first episode of AP from 1 April to 31 June 2022 with 1-month follow up. Data on aetiology of AP, clinical course, and analgesic treatment were collected. The primary outcome was the association between analgesic type and severity of AP. Statistical analysis was performed using univariate comparisons, multivariable regression, and mediation analysis.

Results

A total of 2,119 patients were recruited from 118 centers in 27 countries. The patients were 53 % male sex with median age of 55 years (IQR, 41-71). The most common aetiology of AP was gallstones (58%), followed by alcohol (21%). Pain duration prior to admission was >24 hours in 978 (47%) patients and <12 hours in 530 (25 %) patients. As for the first analgesic modality simple analgesics were administered in 1,456 (70%) patients and opioids were given in 521 (25%) patients. There were 1,383 (69%) patients who had opioid use at any time during admission. On univariate analysis, moderately severe/severe AP was associated with male sex, younger age, alcohol aetiology, predicted severe AP, higher pain scores, and opioid treatment (all p≤0.01). Also, on univariate analysis patients who received opioid treatment were at increased risk of severe AP, organ failure, necrosis, and longer length of admission (all p≤0.01). On multivariate analysis alcohol aetiology, predicted severity of AP and opioid treatment showed increased risk for moderately severe/severe AP (all p<0.001). Mediation analysis showed a significant direct effect of opioid use on AP severity (p<0.001).

Conclusion

This prospective multicentre study suggests that opioids have a direct effect on the severity and morbidity of AP. Further randomized controlled trials should be designed to test the safety of opioids in AP.

Introduction

Pancreatic steatosis (PS) has been increasingly recognized and associated with some relevant metabolic implications. However, data on its correlation with exocrine pancreatic function remain limited. We conducted a systematic review and meta-analysis to evaluate whether PS is associated with exocrine pancreatic insufficiency (EPI).

Aims & Methods

This study aimed to investigate whether imaging-detected PS is related to exocrine pancreatic dysfunction, assessed by fecal elastase-1 (FE-1) levels. We searched PubMed, EMBASE, and Cochrane Central for studies including adults with and without PS identified on imaging, and reporting FE-1 concentrations. Data were pooled using random-effects models.

Results

Three studies evaluating a total of 1,864 patients were included. Fecal elastase levels were significantly lower in patients with PS compared to controls, indicating worse exocrine pancreatic function in this group (MD -199.78; 95% CI -303.66 to -95.91; p < 0.05; I² = 97%). Moreover, PS was associated with a significantly increased risk of exocrine pancreatic insufficiency (RR 3.13; 95% CI 1.17–8.40; p = 0.023; I² = 81%), reinforcing the link between fat accumulation in the pancreas and impaired exocrine function.

Conclusion

This meta-analysis demonstrates a significant association between PS and impaired pancreatic exocrine function, compared to individuals without known pancreas disease. These findings underscore the importance of a comprehensive metabolic assessment in patients with PS, given its potential role in pancreatic dysfunction.

Introduction

Acute pancreatitis (AP) is a common cause of acute hospital admissions, with the potential for severe acute complications, progression to chronic pancreatitis and recurrent episodes. A first presentation leads to investigations to identify a cause, including serum blood tests and transabdominal ultrasound. Following these investigations, a significant minority of patients have no clear cause for pancreatitis. Endoscopic ultrasonography (EUS) can identify aetiologies of AP, and direct intervention to reduce recurrence. The goal of this study was to determine the diagnostic yield of EUS and the impact of subsequent biliary intervention on recurrence of AP.

Aims & Methods

This was a retrospective service evaluation of EUS referrals to a regional referral centre in the UK from January 2015 to December 2019. Demographics, symptoms, liver blood tests, non-invasive imaging, EUS records and outcomes were reviewed. A EUS was labelled as diagnostic if findings were identified which explained the cause for pancreatitis that had not been explained with other investigations. Symptom resolution was defined as no further episodes of acute pancreatitis or abdominal pain requiring investigation, imaging, or presentation to secondary care during the follow-up period. Statistical significance for the difference between proportions was calculated using chi-squared tests.­­­­­­­­­­

Results

Ninety-seven patients were included in the study. The median age of the cohort was 58 (range 18-88) years. 55 (57%) patients were male. 22/97 (23%) patients had previously had a cholecystectomy. 41/97 (42%) had abnormal liver blood tests at the time of referral. Three patients had no non-invasive imaging. 27/97 (28%) had one of either transabdominal ultrasound, MRCP or CT, 63/97 (65%) had two tests and 4/97 (4%) had all three. 5 (5%) patients previously had a non-diagnostic EUS.
72/97 (74%) EUS were diagnostic. Findings included gallstones (n=15), gallbladder microlithiasis/sludge (n=51), bile duct stones (n=13), bile duct microlithiasis/sludge (n=11), chronic pancreatitis (n=7) and a pancreatic mass (n=1) which was later diagnosed as a pancreatic adenocarcinoma.
65 patients had a biliary aetiology for their pancreatitis which was amenable to treatment. Of these, 12 had subsequent ERCP, 7 had ERCP and cholecystectomy, 33 had a cholecystectomy and 13 were treated conservatively. Recurrent pancreatitis occurred in 12/52 (23%) patients who had treatment for a biliary aetiology of their pancreatitis compared with 8/13 (75%; p<0.01) of patients who were managed conservatively despite a biliary aetiology for pancreatitis, 8/32 (25%; p=0.84) of patients with a diagnostic EUS with a finding not amenable to treatment or a non-diagnostic EUS experienced further episodes. One patient died from complications related to acute pancreatitis and was not included in this analysis. Median duration of follow-up was 51 months (range 32-80 months).

Conclusion

In our cohort of patients referred for EUS for unexplained acute pancreatitis, EUS had a high diagnostic yield. A lower proportion of patients had a biliary aetiology for their pancreatitis that was amenable to intervention with either ERCP, cholecystectomy or both procedures; these patients experienced fewer episodes of recurrent acute pancreatitis than those managed conservatively. This supports the use of EUS in patients with acute pancreatitis with no cause identified with non-invasive imaging.

Introduction

The adenoma detection rate (ADR) is widely recognized as a quality indicator in colonoscopy based colorectal cancer (CRC) screening. ADR has been shown to be inversely associated with the risk of post colonoscopy colorectal cancer (PCCRC).^1,2
A wide variation on the ADR among endoscopy units has been observed in the Danish fecal immunochemical based colonoscopy screening programme since the initiation in 2014. The ADR varied from 39% to 67% among endoscopist units from 2014-2017.³

Aims & Methods

To investigate the association between ADR and the risk of PCCRC using multivariable Poisson regression. Endoscopy units were grouped in quartiles based on the ADR. PCCRC was defined as a colorectal occurred 6-36 months after the initial screening colonoscopy. The Danish colorectal cancer screening registry (from 2014-2017) and the Danish Cancer registry (from 2014-2020) were used to identify colonoscopies, screening detected CRCs and PCCRCs.

Results

The study covered 80,374 colonoscopies (performed at 20 endoscopy units), 4,829 screening detected CRCs and 356 PCCRCs. Mean ADR in quartile 1 (lowest) was 41.0%, range [38.8-44.3], quartile 2: 48.3% [46.2-50.0], quartile 3: 52.2% [50.2-53.6] and quartile 4: 60.0% [54.1-67.0]. The proportion of PCCRCs (of all CRC) declined from 8.8% in quartile 1 to 4.8% in quartile 4.
Results from the multivariable Poisson regression analysis (outcome = PCCRC, predictors = age, sex, ADR) are shown in Table 1. The analysis found increased risk for PCCRC among females and a falling risk of PCCRC with higher ADR quartile.


Table 1: Multivariable poisson regression analysis for PCCRC*

Conclusion

PCCRC is an important colonoscopy quality performance indicator, however the need for years of follow-up and large-scale data limits the use as an indicator for current colonoscopy performance. ADR is a viable alternative. The latest Danish colonoscopy screening report from 2021 still shows a wide variation in ADR highlighting the need for attention to colonoscopy performance in order to increase the efficacy of the CRC screening program.⁴

References

1) Corley DA, Jensen CD, Marks AR, et al. Adenoma Detection Rate and Risk of Colorectal Cancer and Death. N Engl J Med 2014; 370: 1298–1306
2) Kaminski MF, Wieszczy P, Rupinski M, et al. Increased Rate of Adenoma Detection Associates With Reduced Risk of Colorectal Cancer and Death. Gastroenterology 2017; 153: 98–105
3) Regionernes Kliniske Kvalitetsudviklingsprogram. Dansk tarmkræftscreeningsdatabase Årsrapport 2017. 2018; 1–105. https://www.regionshospitalet-randers.dk/siteassets/afdelinger/afdeling-for-folkeundersogelser/pdf-episerver/retningslinjer/dts_arsrapport-2017_final.pdf. Accessed the 28th of April 2023.
4) Regionernes Kliniske Kvalitetsudviklingsprogram. Dansk tarmkræftscreeningsdatabase Årsrapport 2021. 2022; 1–102. https://www.sundhed.dk/content/cms/45/61245_dts_aarsrapport2021_til-offentliggrelse_13122022.pdf. Accessed the 28th of April 2023.

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