Introduction

Parkinson’s disease (PD) is a neurodegenerative disorder with motor and non-motor symptoms. The gut-brain axis has emerged as a key in PD research, with fecal microbiota transplantation (FMT) proposed as a potential intervention.

Aims & Methods

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing FMT and placebo in PD to evaluate its efficacy and safety. The primary outcome was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Secondary outcomes were adverse events (AEs), Parkinson’s Disease Quality of Life Questionnaire (PDQ-39), Non-Motor Symptoms Scale for Parkinson’s Disease (NMSS), Geriatric Depression Scale (GDS), and Montreal Cognitive Assessment (MoCA). A random-effects model was used, with heterogeneity assessed via I2 statistics.

Results

Four RCTs with 157 patients were included. FMT significantly improved MDS-UPDRS part IV after 3 months (MD -0.67; 95% CI -1.09, -0.24; p < 0.01; I² = 0%) but showed no differences at 6 or 12 months. No significant improvements were observed in MDS-UPDRS total score, PDQ-39, or NMSS. GDS scores favored placebo (MD -0.83; 95% CI -2.43, 0.77; p = 0.31), and MoCA scores declined in the FMT group after 12 months (MD -0.89; 95% CI -1.19, -0.60; p < 0.01). AEs did not significantly differ between groups.

Conclusion

FMT did not significantly improve motor symptoms, quality of life, or non-motor symptoms in Parkinson's disease (PD). However, our study shows that it offers a safe intervention. Further research is needed to clarify its role in PD management.

Introduction

It is not clear whether the inverse relationship between colonoscopists’ adenoma detection rate (ADR) and post-colonoscopy colorectal cancer (PCCRC) is seamless or subject to “plateau” effect.

Aims & Methods

Aim of the study was to model the pattern of association between ADR and PCCRC. The present study is a systematic review and meta-analysis of studies published up to December 2024 providing the crude incidence rate of PCCRC according to various colonoscopists’ ADR categories. The primary outcome was calculated as the cumulative incidence of PCCRC at the lowest bound of each ADR category, starting from highest to lowest colonoscopists’ ADR. A restricted cubic spline multilevel metaregression analysis was applied to model the inverse association between ADR and cumulative PCCRC.

Results

After applying selection criteria, 7 studies published in 2020-2024, including 2,178,822 patients were included. All studies were conducted in organized CRC screening programs: 5 studies were set in primary colonoscopy screening, whereas 2 studies assessed FIT+ patients undergoing colonoscopy with two different cut-offs (20 µg Hgb/g and 47 µg Hgb/g feces). Four studies were European, and three studies were conducted in the US. Median patient age ranged from 57 to 65 years (see Table 1).
In primary colonoscopy setting (5 studies with 2,025,296 patients), adjusting for standardized follow-up and standardized CRC risk, cumulative incidence of CRC after colonoscopy showed a marked decrease for each 1-unit increase in ADR up to 27%, with a more gradual decline between 27% and 34%. In absolute numbers, assuming a 10-year follow-up period, CRC after colonoscopy ranged from 258/100,000 at 1% ADR, to 228/100,000 at 27% ADR, and 220/100,000 at 34% ADR, yielding a total decrease of 38 CRC after colonoscopy cases per 100,000 patients in 10 years. Beyond this threshold, according to model-based projections, CRC after colonoscopy would be 212/100,000 at 50% ADR, 207/100,000 at 60% ADR, and 197/100,000 at 80% ADR, yielding only an additional decrease of 8 (ADR 50%), 13 (ADR 60%), and 23 (ADR 80%) CRC after colonoscopy cases per 100,000 patients in 10 years, as compared to ADR 34%. Data remained consistent after excluding the study by Pilonis et al. [1], confirming that CRC after colonoscopy plateaus after 34% ADR. Heterogeneity was low (I²=0%) and the visual inspection of the funnel plot revealed some publication bias possibly leading to overestimate the inverse association between ADR and CRC after colonoscopy.
In the FIT-based setting (2 studies, 153,526 patients), quantitative synthesis was not performed owing to the low number of studies and different FIT thresholds (i.e., ≥20 and ≥47 µg Hb/g feces). Nonetheless, when examining the individual studies, there appears to be a more linear decline in post-colonoscopy CRC risk with increasing ADR.

Conclusion

In primary colonoscopy screening, achieving an ADR of at least 27% is essential. While increasing ADR beyond 27% continues to reduce risk, the benefit plateaus beyond ADR 34%, suggesting limited additional clinical advantage. Of note, the absolute risk reduction in CRC after colonoscopy is overall modest. Additional quality measures could provide a more comprehensive assessment of colonoscopy effectiveness.

References

Pilonis ND, Spychalski P, Kalager M, et al. Adenoma Detection Rates by Physicians and Subsequent Colorectal Cancer Risk. JAMA. Published Online First: 16 December 2024.
Wisse PHA, Erler NS, de Boer SY, et al. Adenoma Detection Rate and Risk for Interval Postcolonoscopy Colorectal Cancer in Fecal Immunochemical Test-Based Screening : A Population-Based Cohort Study. Ann Intern Med. 2022;175:1366–73.
Zorzi M, Antonelli G, Barbiellini Amidei C, et al. Adenoma Detection Rate and Colorectal Cancer Risk in Fecal Immunochemical Test Screening Programs : An Observational Cohort Study. Ann Intern Med. 2023;176:303–10.
Schottinger JE, Jensen CD, Ghai NR, et al. Association of Physician Adenoma Detection Rates With Postcolonoscopy Colorectal Cancer. JAMA. 2022;327:2114–22.
Waldmann E, Penz D, Šinkovec H, et al. Interval cancer after colonoscopy in the Austrian National Screening Programme: influence of physician and patient factors. Gut. 2021;70:1309–17.
Lam AY, Li Y, Gregory DL, et al. Association between improved adenoma detection rates and interval colorectal cancer rates after a quality improvement program. Gastrointest Endosc. 2020;92:355-364.e5.
Polychronidis G, He M-M, Vithayathil M, et al. Risk of colorectal neoplasia after removal of conventional adenomas and serrated polyps: a comprehensive evaluation of risk factors and surveillance use. Gut. 2024;73:1675–83.

Introduction

Acute appendicitis is a widely encountered emergency across the globe, showcasing the resilience of modern medicine, as it is traditionally addressed through the transformative procedure of appendectomy. Endoscopic Retrograde Appendicitis Therapy (ERAT) has emerged as a minimally invasive alternative; however recurrence is a worry.

Aims & Methods

This multi-center retrospective study aimed to evaluate the long-term safety, efficacy, and recurrence-related risk factors of ERAT to guide clinical decision-making. A total of 435 patients who underwent ERAT for acute appendicitis between October 2017 and October 2024 at three Chinese medical centers were included. Appendicitis recurrence was defined as imaging-confirmed symptoms returning within one-month post-ERAT. Univariate and multivariate regression analysis identified independent recurrence risk variables.

Results

All ERAT procedures were technically successful and achieved a clinical success rate of 92.4%. Over a median follow-up period of 37 months, the overall recurrence rate was 16.1%, with the majority of recurrences (13%) observed within the first year. Independent risk factors for recurrence included recurrent appendicitis (HR=1.916), appendiceal lumen distortion (HR=7.996), absence of stent placement (HR=0.375, protective), and operator inexperience (HR=2.318). Stent implantation effectively minimizes recurrence risk, especially in complicated incidents. ERAT facilitated overseeing appendicolith elimination, which assisted in occurring appendicolith-associated appendicitis.

Conclusion

ERAT is deemed safe and effective for acute appendicitis, with the highest recurrence risk occurring within the first year. Effective stent placement and skilled operators are crucial for reducing recurrence in complex cases. The aforementioned findings put forward significant insights for enhancing ERAT and advancing therapeutic outcomes.

Clinical Case Summary

A 27-year-old male with diarrhea and rectal bleeding was diagnosed with moderate ulcerative colitis (UC) (Montreal: E3, Mayo endoscopic subscore: 2). He was started on mesalazine 4 g/day and oral prednisolone 40 mg/day, with clinical remission after 2 weeks. Prednisolone was successfully tapered off over the course of 8 weeks. He was not taking other medications. After starting therapy, the patient reported intermittent red urine discoloration, without other symptoms or association with respiratory tract infections.
Extensive investigation of hematuria was negative, including ANA, ANCA, anti-dsDNA and anti-GBM antibodies and imaging studies. Urine samples were macroscopically normal, with no red blood cells, casts or crystals. Urethrocystoscopy and urine cytology were unremarkable. Renal biopsy was considered.
The patient remained on mesalazine, with clinical, analytical and endoscopic response. During one episode, he noticed that the urine only became reddish after contact with toilet water disinfected with bleach. After stopping bleach toilet disinfection, there was no recurrence. He was diagnosed with mesalazine induced pseudohematuria and did not undergo further investigation.
Mesalazine is the first-line treatment for mild-to-moderate UC. Although uncommon, nephrotoxicity has been described and may result in urine discoloration or hematuria. Mesalazine is excreted in the urine and, when in contact with sodium hypochlorite (the active component of household bleach), oxidises, resulting in red-brown urine discoloration. Rare cases of patients reporting similar situations have been described in the literature. The role of gastroenterologists in recognizing this phenomenon is crucial, since mesalazine is a widespread efficient drug with an otherwise favorable safety profile. As our case illustrates, knowledge of this harmless reaction is desirable to avoid additional tests and potentially harmful unnecessary interventions, such as renal biopsy.

References

Figure 1 - Reaction between the urine of a patient taking mesalazine and the sodium hypochlorite present in household bleach (1A - before addition of bleach; 1B - after addition of bleach).

Disclosure

No conflict of interest to declare.

Introduction

Irritable bowel syndrome (IBS) is a chronic gut-brain disorder that can be responsabil for a variety of uncomfortable gastrointestinal symptoms (laid out in the Rome Criteria) that can reduce quality of life. Although the precise mechanism remains unknown, recent research suggests that an imbalance in intestinal microbiota and a dysfunctional gut-brain axis may be involved in the development of IBS. Because of this, methods to restore the microbiota have been explored as treatment for this condition.

Aims & Methods

Randomized placebo controlled trial 180 patients: active group (probiotic formula, 3g/day- 92, placebo group – 88. men and women aged 24 to 75 who met the Rome IV criteria. One sachet probiotic (3 g) contains 7.5 billion bacteria: Lactobacillus casei W56, Lactococcus lactis W19, Lactobacillus acidophilus W22, Bifidobacterium lactis W52, Lactobacillus paracasei W20 Lactobacillus plantarum W62, Bifidobacterium lactis W51, Bifidobacterium bifidum W23, Lactobacillus salivarius W24. Assessments were made at 4, 8, 12 weeks. All patients agreed to maintain their lifestyle behaviors during their participation in the study. Exclusion criteria: chronic gastrointestinal condition (other than IBS), including inflammatory bowel disease, lactose intolerance, celiac disease, diabetes, neoplasms.Patients have complete weekly data on stool frequency and consistency (Boston scale) and intensity of IBS symptoms (abdominal pain/discomfort, bloating, flatulence/borborygmi, and difficulty defecating) on a Likert scale of 0 (absent) to 7 (severe). Participants completed an IBS-specific quality of life questionnaire (IBS-QoL) at randomization (V1), fallow-up (V2) and at the end of the intervention (V3). Primary endpoint was mean weekly scores of gastrointestinal symptoms. Responders of abdominal pain were defined as subjects who experienced a reduction of at least 30% of the mean daily abdominal score reported at baseline (week 0). Secondary endpoints were the total AUC (W0-W12) of abdominal symptoms (abdominal pain, bloating and flatulence/borborygmi).

Results

​There is a significant reduction in abdominal pain and bloating scores trough all 12 weeks of supplementation versus placebo. A higher overall IBS-QOL score, indicative of better QOL was reported at the end of the intervention (specially for interference with activity P=0.05, body image P=0.040, food avoidance P=0.03)

Conclusion

​The probiotic treatment provides statistically significant and clinically relevant benefits for individuals with IBS. Improves gastrointestinal symptoms and quality of life in IBS patient

References

Rome IV criteria-Rome Foundation

Introduction

Fusobacterium nucleatum (Fn) and other species typical of the oral cavity are implicated in colorectal oncogenesis. The pathogenesis of serrated polyposis syndrome (SPS), the most common polyposis syndrome, remains unknown, and to date, the oral and gut microbiota of these patients has not been characterized.

Aims & Methods

The primary objective of this study was to describe and compare the composition of the oral and gut microbiota in individuals with SPS versus individuals without polyps, with sporadic serrated polyps, and with adenomas.
A prospective, observational, and bicentric study was conducted. Clinical and endoscopic data were collected, along with information obtained from a questionnaire on diet and dental health. Additionally, saliva and stool samples were obtained from 126 individuals divided into four groups: SPS (n=32), serrated (n=30), adenoma (n=32), and control (n=32). The microbiota was analyzed using 16S rRNA amplicon sequencing, and qPCR was performed for the detection of Fn.

Results

The main clinical, dietary, and dental health characteristics of the groups are presented in Table 1. Regarding the oral microbiota, no differences were observed in alpha diversity (species variety) among the groups. However, the composition of the oral microbiota in the SPS group showed significant differences compared to the other groups, as evidenced by a greater unweighted UniFrac distance (differences in bacterial taxonomy) (p<0.001). In the gut microbiota, the adenoma group exhibited lower species richness than the control group, according to the Chao1 index (p=0.03), while no differences were found in the other groups. Statistically significant differences in beta diversity, measured using unweighted UniFrac distance, were observed between the SPS group and the adenoma and control groups (p<0.001).
Regarding taxonomy, Porphyromonas gingivalis, an oral bacterium associated with colorectal cancer (CRC) development and progression, showed higher oral abundance in the SPS group compared to the control and adenoma groups (p<0.05; FDR p=0.104). Treponema denticola and Prevotella intermedia, two oral bacteria related to CRC, were more abundant in the SPS group than in the control group (p<0.05; FDR p=0.09). Additionally, Peptoanaerobacter stomatis, an oral bacterium linked to CRC via the serrated pathway, was more prevalent in the SPS group compared to the serrated and adenoma groups (p<0.05; FDR p=0.26).
No differences in the abundance of Fn were found among the groups, either in saliva or stool samples.

Conclusion

The oral and gut microbiota of individuals with SPS exhibit a distinct bacterial composition compared to individuals without polyps and those with adenomas. Furthermore, certain oral bacteria associated with colorectal carcinogenesis are increased in SPS patients.

Disclosure

There are no conflicts of interest to declare.