Introduction

Several studies have investigated the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with chronic liver disease (CLD) and the relationship to severity and progression of disease. However, the reported rates of SIBO vary.

Aims & Methods

Against this background we conducted a systematic review and meta-analysis of case-control studies, to assess and compare the prevalence of SIBO in patients with CLD and controls and identify risk factors for SIBO in CLD. Electronic databases were searched from inception up to April 2023 for case-control studies reporting SIBO prevalence in CLD patients. Prevalence rates, odds ratios (ORs), and 95% confidence intervals (CIs) of SIBO in patients with CLD and controls were calculated utilizing a random-effects model. This study was registered with PROSPERO (CRD42022379578).

Results

We included 34 case-control studies with 2136 patients with CLD and 1240 controls. Overall, odds for SIBO prevalence in CLD patients (37.8%, 95%CI 35.7-39.8) as compared to controls (13.9%, 95%CI 12.1-16.0) was 6.1 (95%CI 4.5-8.3, p=0.0001) with moderate heterogeneity seen (I²=46.8, p=0.002).Stratified by mode of SIBO diagnosis, SIBO prevalence in CLD patients as compared to controls was highest in studies utilizing small bowel aspirate and culture (OR=11.6, 95%CI 3.6-36.6, p=0.0001), followed by glucose breath test (OR=8.1, 95%CI 3.9-16.5, p=0.0001) and lowest in those utilizing lactulose breath test (OR=5.3, 95%CI 3.6-7.7, p=0.0001).
There was no difference in the prevalence of SIBO in patients with cirrhosis (41.2% 95%CI 31.2-46.8) as compared to those without cirrhosis (39.7%, 95%CI 29.7-50.7). The odds for SIBO in patients with decompensated cirrhosis was significantly higher as compared to those with compensated cirrhosis, (OR=2.7, 95%CI 1.7-4.4, p=0.0001). Furthermore, SIBO prevalence was increased in CLD patients with portal hypertension (PHT) (49.9%, 95%CI 34.5-65.3) and in CLD patients with complications of PHT, highest in those with spontaneous bacterial peritonitis (SBP), (57.7%, 95%CI 38.8-74.5) followed by hepatic encephalopathy (41.0%, 95% CI 15.7-72.3) and variceal bleed (39.5%, 95% CI 12.1-75.6).
According to etiology of liver disease, SIBO prevalence was highest in patients with CLD due to non-alcoholic fatty liver disease (NAFLD) 41.5% (95%CI 30.9-53.0), followed by viral hepatitis 38.4% (95%CI 28.3-49.5), alcoholic liver disease 37.3% (95%CI 25.7-50.5), cryptogenic liver disease 31.9% (95%CI 13.9-57.6) and lowest in those with autoimmune liver disease 25.5% (95%CI 12.4-45.2). SIBO prevalence in CLD patients on proton pump inhibitors (PPI) (41.3%, 95%CI 30.3-52.8) was numerically higher as compared to those not on a PPI (26.5%,95%CI 19.9-34.2), but this failed significance.

Conclusion

Overall, there is a 6-fold increase in the prevalence of SIBO in patients with CLD as compared to controls. Although SIBO prevalence was similar in CLD patients with cirrhosis as compared to those without cirrhosis, patients with decompensated cirrhosis had approximately 3-fold increased SIBO prevalence as compared to those with compensated cirrhosis. Furthermore, SIBO was increased in CLD patients with PHT, particularly those with SBP. No significant difference was seen in SIBO prevalence in CLD patients according to aetiology of liver disease, with highest SIBO prevalence in patients with NAFLD. Moreover, as compared to breath tests, small bowel aspirate and culture for SIBO diagnosis yielded substantially higher SIBO prevalence rates in CLD patients and controls.

Introduction

Anal cancer accounts for 2% of malignant neoplasms of the gastrointestinal tract. Most cases are squamous cell carcinoma, and the global incidence is increasing alongside the rise in Human Papillomavirus (HPV) incidence. Individuals infected with HPV, particularly those co-infected with human immunodeficiency virus (HIV), as well as smokers, individuals with more than ten sexual partners, and those who maintain receptive anal intercourse are at increased risk of developing this cancer.

Aims & Methods

Our objective was to analyze the trends in anal cancer mortality rates in Brazil from 2012 to 2021, with a focus on gender and age. This descriptive study of anal cancer deaths (ICD-10 code C21) in Brazil utilized data from the Mortality Information System of the Unified Health System (DATASUS)

Results

In Brazil, from 2012 to 2021, there were a total of 5,955 deaths attributed to anal cancer, with 3,600 deaths in women and 2,355 deaths in men, and most of these deaths occurred after the age of 50. During this period, anal cancer mortality rates increased in both sexes. In 2012, the mortality rate was 0.22 deaths per 100,000 women and 0.13 deaths per 100,000 men, rising to 0.55 deaths per 100,000 women and 0.48 deaths per 100,000 men by 2021. Furthermore, the average annual percent change (AAPC) in anal cancer mortality rates was higher in males than females across all age groups except for ages 30-39. In males aged 40 and over, the AAPC of anal cancer mortality rates increased progressively with age, while in females, it remained stable across different age groups. Notably, among individuals over 80 years old, the AAPC was 11% per year among women and 44% per year among men. As a result, the mortality ratio between women and men decreased from 1.88 (2012-2016) to 1.41 (2017-2021), reaching its lowest value of 1.14 in 2021.

Conclusion

Despite its rarity, anal cancer warrants recognition due to its rising mortality rates. While initially, mortality rates from anal cancer were significantly higher among women, the accelerated increase in mortality rates among men has led to similar mortality rates between genders by the year 2021.

References

1. Roberts JR, Siekas LL, Kaz AM. Anal intraepithelial neoplasia: A review of diagnosis and management. World J Gastrointest Oncol. 2017;9(2):50-61.
2. Itarat Y, Kietpeerakool C, Jampathong N, Chumworathayi B, Kleebkaow P, Aue-Aungkul A, Nhokaew W. Sexual behavior and infection with cervical human papillomavirus types 16 and 18. Int J Womens Health. 2019;11:489-494.
3. De Vuyst H, Clifford GM, Nascimento MC, et al: Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: A meta-analysis. Int J Cancer 124:1626-1636, 2009.
4. Oliveira CR, Niu YS, Einarsdottir HM, Niccolai LM, Shapiro ED. Disparities in the Epidemiology of Anal Cancer: A Cross-Sectional Time Series. Health Equity. 2020 Sep 16;4(1):382-385.
5. Pérez-González A, Cachay E, Ocampo A, Poveda E. Update on the Epidemiological Features and Clinical Implications of Human Papillomavirus Infection (HPV) and Human Immunodeficiency Virus (HIV) Coinfection. Microorganisms. 2022;10(5):1047.
6. Kost BP, Hofmann J, Stoellnberger S, Bergauer F, Blankenstein T, Alba-Alejandre I, Stein A, Stuckart C, Weizsäcker K, Mylonas I, Mahner S, Gingelmaier A. Prevalence of human papillomavirus infection of the anal canal in women: A prospective analysis of high-risk populations. Oncol Lett. 2017;13(4):2495-2501.

Disclosure

there's no conflict of interest

Introduction

The standard treatment for T1b esophagogastric junctional adenocarcinoma (EGJAC) is surgery. However, surgery is highly invasive especially for elderly patients. Endoscopic submucosal dissection (ESD) is an alternative treatment of T1b cancer for such patients. However, the outcome and long-term prognosis of T1b EGJAC treated by ESD is unknown.

Aims & Methods

The aim of this study is to investigate the outcome and prognosis of T1b EGJAC treated by ESD.
Fifty lesions in 49 patients with pT1b EGJAC who underwent ESD from January 2000 to September 2019 were investigated the outcome and prognosis. The patients were divided into pT1bSM1 (n=30) and pT1bSM2 (n=20).
The patient characteristics were as follows. Male/female: 28/2, 18/2, median age: 69, 75 years old, macroscopic type (protuberance/depression): 5/25, 6/14, main histology (well differentiated (diff.)/ mixed poorly diff.): 22/8, 9/11, median diameter of resected specimen: 45, 39mm, median diameter of tumors: 22, 19mm, median follow-up period: 53, 64months, respectively. There was significant difference in only main histology (p=0.04).
EGJAC was defined as Siewert II, with T1bSM1 for ≤500 μm and T1bSM2 for >501 μm. R0 was defined as lateral and vertical margin negative, and lymph-vascular involvement negative. According to Japanese guidelines, additional treatment was recommended for all T1bSM2 cases and for SM1 lymph duct (ly)-positive and poorly diff. cases.

Results

1. Outcome of ESD
The en bloc resection rate is 100% for both T1bSM1 and T1bSM2. The R0 rate was 100% for T1bSM1 and 95% (19/20) for T1bSM2. Intraoperative perforation rate was 2% (1/50), delayed bleeding rate was 2% (1/50), and delayed perforation rate was 0%. Stenosis rate was 10% (5/50), and all of such complications were treated by endoscopy without surgery.
2. Long-term prognosis
A) T1bSM1 (n = 30)
a) One case (3%) was ly-positive. Additional surgical resection was performed, and lymph node metastasis (LNM) was observed. The patient is alive without recurrence.
b) Twenty-nine cases were ly/vascular (v) negative, and followed up without additional treatment (AT). Nineteen in 29 cases are alive without recurrence, and 10 in 29 cases died by other diseases.
c) Local recurrence rate was 0%, LNM rate was 3% (1/30), and distant metastasis (DM) rate was 0%.
B) T1bSM2 (n=20)
a) Six cases (30%) were ly and/or v positive. Additional surgical resection was performed in 3 cases, and no LNM was observed in any of the cases. Of the other 3 cases, 1 patient underwent only radiotherapy. LNM was found 14 months later, and chemotherapy was added, but treatment-related death occurred. One of the two cases who did not undergo AT had DM and multiple liver metastases 61 months after ESD, and died of the original disease despite of chemotherapy. Another patient died of other diseases.
b) Nine in 14 cases of ly/v negative underwent additional surgical resection, and no LNM was observed in any of the cases. 7 cases are alive without recurrence, and 2 cases died of other diseases. Four in 5 cases who did not undergo AT are alive without recurrence, and 1 patient died from other diseases.
c) R1 rate was 5% (1/20), local recurrence rate was 0%, LNM rate was 5% (1/20), DM rate was 5% (1/20), and mortality by primary cancer was 5% (1/20).

Conclusion

LNM and DM were not observed in the T1bSM1, ly0 group, however LNM and DM were observed in the T1bSM1,ly1 or T1bSM2 groups. Therefore, the current Japanese ESD criteria is appropriate. 　
The R0 resection rate for T1bSM2 was excellent at 95%, and local recurrence was 0%. ESD could be alternative treatment for patients with comorbidity.

References

None

Introduction

The Mediterranean diet identified as a priority because it contributes to the normalization of key metabolic parameters in patients with non-alcoholic fatty liver disease (NAFLD). However, it is necessary to take into account the possibilities of following such a diet and the nutrigenetic characteristics of patients in different regions of the world. Purpose: to study the effect of nutrigenetic parameters in patients with NAFLD on the effectiveness of non-drug treatment.

Aims & Methods

Purpose: to study the effect of nutrigenetic parameters in patients with NAFLD on the effectiveness of non-drug treatment. 105 patients (55 men and 50 women) with NAFLD were examined. In patients, the features of eating disorders (ED) were studied (DEBQ questionnaire), nutrigenetic parameters - 5 polymorphisms: Pro12Ala of the PPARG2 gene (rs1801282), 101027 of the ADRB2 gene (rs1042714) and Arg16Gly of the ADRB2 gene (1010282); (rs4994) and Thr54Ala of the FABP2 gene (rs1799883) associated with the risk of metabolic disorders.

Results

Two polymorphisms associated with disorders of the ED gene (Pro12Ala PPARG2 and Trp64Arg ADRB3) were identified. Sex differences in the frequency of genotypes of the Pro12Ala polymorphism of the PPARG2 gene were not found (pχ2 = 0.90). 83.6% of men and 82.0% of women were carriers of the PPARG2 gene polymorphism (OR=1.10, CI=0.24-4.99) of the Pro12Pro genotype (AB=1.10, men and 16.7% of women of the genotype Pro12Ala (OR = 0.91, OR) = 0.20 - 4.13). The distribution of genotypes and allelic variants of the ADRB3 gene polymorphism had significant differences (px2 = 0.05). The Trp64Trp genotype of the ADRB3 gene polymorphism were found in 80.0% of men and 55.0% of women, the Trp64Arg genotype in 20.0% of men and 32.5% of women, the Arg64Arg genotype was found only in women. An analysis of the distribution of 64Trp and 64Arg alleles by sex using a multiplicative model showed that the significance of the association of the minor female 64Arg allele was confirmed by an odds ratio of 3.13 (CI = 1.01–9.70) versus 0.32 (CI = 0.01–9 .70). 10 - 0.99) for the minor allele. A significant association (px2 = 0.02) of the protective minor allele 12Ala with emotionally restrictive types of ED (OR = 0.11, CI = 0.10 - 0.97) was established, while the external type of oblique ED was associated with the carriage of the main allele polymorphism 12Pro of the Pro12Ala PPARG2 gene (OR = 8.71, CI = 1.03-7.66). Analysis of the distribution of 64Trp and 64Arg alleles depending on the type of EP disorder showed a significant association (px2 = 0.006) of the metabolically unfavorable minor 64Arg allele with the external type of ED disorders (OR = 5.53, CI = 1.48-20.68), while emotional and restrictive types were associated with the carrier of the main 64Trp allele (OR = 0.18, CI = 0.05-0.68). In patients with NAFLD, the external type of ED disorder prevails (p<0.05).

Conclusion

To increase the effectiveness of non-drug treatment, one should take into account nutrigenetic features - the presence of ProARA2 polymorphisms of the PPARG2 gene and Trp64Arg of the ADRB3 gene, which are associated with the peculiarities of nutrient metabolism and malnutrition in patients with NAFLD.

Disclosure

Nothing to disclose

Introduction

Emerging evidence points towards a plausible link between psoriasis, a common chronic inflammatory skin disease, and inflammatory bowel disease (IBD), as both diseases share similar inflammatory pathways(1).

Aims & Methods

Our aim was to identify patterns and potential predictors for the development of IBD in a psoriasis patients cohort.
This retrospective electronic health records-based study utilized data from the Meuhedet Health Maintenance Organization (MHMO) which contains 20 years of continuous follow-up. Patents’ data were evaluated for demographic parameters, comorbidities, auto-antibodies, and medications used.
Prevalence and incidence of IBD were measured. The association between psoriasis and IBD was evaluated using both univariate and multivariate logistic regression models, with adjustments made for possible confounding factors. The prediction model was developed to identify predictors of IBD development in psoriasis

Results

Data between psoriasis patients (n=61,003) and age and gender-matched controls (n=244,012) was compared.
Among psoriasis patients, 2.5% were diagnosed with IBD, compared to 1.6% of controls (OR 1.57, 95%CI 1.48-1.67). The adjusted OR was 1.47 (95% CI 1.37-1.56), p<0.001. IBD was diagnosed before the onset of psoriasis in 51.9% and within 1 year of psoriasis onset in 7.2%. Predictors of IBD development in psoriasis patients were: older age (OR 1.01, 95%CI 1.01-1.02), male gender (OR 1.22, 95%CI 1.03-1.45), axial spondyloarthropathies (OR 1.78, 95%CI 1.29-2.45), severe psoriasis (OR 16.03, 95%CI 11.02-23.34), uveitis (OR 3.13, 95%CI 2.08-4.71), ASCA positivity (OR 10.71, 95%CI 7.38-15.55), and P-ANCA positivity (OR 7.71, 95%CI 2.04-29.04). The specific risk for IBD among psoriasis patients according to disease severity is shown in Table 1.
Decreased risk for IBD in psoriasis patients was observed in patients with obesity (OR 0.76, 95%CI 0.62-0.94), psoriatic arthritis (OR 0.49, 95%CI 0.34-0.72), phototherapy (OR 0.09, 95%CI 0.06-0.15), and methotrexate use (OR 0.13, 95%CI 0.08-0.21). The presence of ANA antibodies was not significantly associated with the risk of IBD within the psoriasis cohort.

Conclusion

Our study provides evidence for a significant association between psoriasis and IBD and identifies several predictors for the development of IBD in psoriasis patients. These findings may improve clinical decision-making and patients’ outcomes.

References

Li, Y., Guo, J., Cao, Z., & Wu, J. (2022). Causal Association Between Inflammatory Bowel Disease and Psoriasis: A Two-Sample Bidirectional Mendelian Randomization Study. Frontiers in immunology, 13, 916645. https://doi.org/10.3389/fimmu.2022.916645

Disclosure

None

Introduction

​Volatile Organic Compounds (VOC’s) are produced in response to endogenous metabolic processes within the body and as a result of functional activation of the trillions of microbes within the gut (exogenous VOC’s). VOC’s pass from the gut lumen into the blood stream and can be detected on exhaled breath. To date, microbiome research has mainly relied on stool collection and analysis which has both spatial and temporal limitations in that stool represents the end of the metabolic process and sampling is mostly constrained to spontaneous bowel movements. Breath can be assessed repeatedly in real time and, following ingestion of carbohydrate probes, samples can be taken during periods when the microbiome is known to be functionally active. In this study we used state of the art collection and detection technology to fully characterise both endogenous and exogenously produced VOC’s in healthy subjects for the first time.

Aims & Methods

In 45 healthy subjects, baseline breath samples were taken after a 24-hour low fermentable diet and overnight fast. Subjects then ingested 10g of lactulose mixed with 200ml water and subsequent breath samples were taken at 45, 90 and 180-mins following ingestion. VOC breath samples were acquired using the Breath Biopsy ® collection system over 10-minutes whilst subjects breathed filtered air and VOC’s were collected onto sorbent tubes which concentrated the compounds for later analysis. Analysis was then performed using Gas Chromatography Mass Spectrometry (GC-MS).
The exhaled breath samples were evaluated in targeted (i.e. absolute amounts of 42 compounds of interest) and untargeted manner (i.e. gathering as many compounds in the sample as possible).

Results

600 distinct VOC’s were detected at baseline and these represent the endogenous healthy human VOCome. Targeted analysis indicated that levels of isoprene, 3-methylthiophene, phenol and propionic acid showed differences in exhaled breath between baseline and post-lactulose challenged individuals (p < 0.05). Moreover, the untargeted analysis identified 14 additional compounds in exhaled breath with significant increases following lactulose ingestion (p-value<0.05). All those compounds were reliably measured only on breath and appeared in at least 85% of individuals.

Conclusion

This study provides the first comparative profile of the entire healthy human VOCome in relation to endogenous and exogenously (microbiome related) VOC’s. We identified several changes in the composition of exhaled breath during functional activation of the microbiome following ingestion of a carbohydrate probe. This fundamental work describes a unique experimental model and provides normative reference ranges that will form the foundation for future novel microbiome, nutritional and gut biomarker research.

Disclosure

A Hobson is a shareholder in the Functional Gut Clinic
S Bloor is an employee of he Functional Gut Clinic
N Nagalingam, A Somlinska, B O'Brien, R Stollard, T Woodland, A Tawfike, M Allsworth and B Boyle are employees of Owlstone Medical