Introduction

Dyssynergic defecation (DD) is identified in approximately 30% of patients presenting with chronic constipation. Patients with DD usually poorly responded to standard laxative and biofeedback can be offered as the specific treatment. The diagnostic of DD relies on physiological tests including anorectal manometry (ARM) or defecography, which is not universally accessible. As there are lack of single predictive symptom for DD, hence, we aimed to establish a diagnostic score to help with DD diagnosis.

Aims & Methods

This is a retrospective study conducted at Siriraj Hospital. Derivation cohort included 402 refractory constipation patients who were referred to our center for ARM from 2017-2023. While validation cohort of 100 patients were recruited during 2014-2016. Clinical characteristics and results of physiological tests [ARM, balloon expulsion test (BET), and colonic transit time (CTT)] were collected. The interpretation of ARM was conducted in accordance with the London classification. Univariable and multivariable logistic regression analyses were utilized and indicative features of DD were identified. The scoring system was formulated from beta-coefficients and simplified into an integer-point format. The diagnostic performance of this score was then assessed using both cohorts.

Results

The derivation cohort had DD prevalence of 52.49%. 82.09% of this cohort were female and the average age of 52.39 years. Logistic regression analysis identified significant associations between DD and the following clinical characters: duration of symptoms less than two years (OR 1.88; 95% CI=1.02-3.49), had three or more bowel movements per week (OR 4.67; 95% CI=2.47-8.86), straining (OR 7.76; 95% CI=3.57-16.90), sensation of incomplete evacuation (OR 1.95; 95% CI=1.02-3.73), sensation of anorectal blockage (OR 3.71; 95% CI=1.75-7.88), and the use of manual maneuvers to facilitate defecation (OR 2.55; 95% CI=1.37-4.78). An 11-point diagnostic scoring system was developed: 3 points are assigned for straining during defecation; 2 points each for frequent bowel movements, the sensation of anorectal obstruction, and the use of manual maneuvers; 1 point each for a symptom duration of less than two years and the sensation of incomplete evacuation. The diagnostic performance of the score was robust, with an area under the receiver operating characteristic curve (AUROC) of 0.91 (95% CI, 0.88–0.93) in the derivation cohort and 0.88 (95% CI, 0.81–0.95) in the validation cohort. The optimal cutoff was determined to be ≥ 5 points, resulting in a sensitivity of 93.4% (95% CI = 89.1-96.3), a specificity of 72.8% (95% CI = 65.9-79.0), a positive predictive value (PPV) of 79.1% (95% CI = 73.5-84.0), and a negative predictive value (NPV) of 90.8% (95% CI = 85.1-94.9). The score also exhibited excellent calibration performance.


Univariable and multivariable analysis of clinical predictors for defecation disorder

Conclusion

We proposed the first diagnostic score for DD diagnosis. As its simplicity and excellent diagnostic performance, this can be served as a practical tool for all physicians to facilitate early identification of DD. Further diagnostic confirmation by standard physiological tests and quicken triaging patients for biofeedback therapy.

References

Carrington EV, Heinrich H, Knowles CH, et al. The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function. Neurogastroenterol Motil. 2020 Jan;32(1):e13679.

Disclosure

The authors declare that they have no conflicts of interest

Introduction

Colorectal cancer (CRC) and other bowel diseases is a significant health concern globally. In several countries, the fecal immunochemical test (FIT) is a cornerstone in CRC screening for early detection of cancer in asymptomatic individuals. Moreover, the utility of FIT extends beyond this, as it is increasingly recommended for evaluating symptomatic patients as part of the clinical pathway to render possible or rule out serious bowel pathology. Therefore, we aimed to quantify the findings of serious bowel conditions following a non-screening FIT test in the Danish population.

Aims & Methods

This study investigated use of FIT beyond the national CRC screening program in Denmark. We aimed (1) to assess utilization patterns of FIT in contexts other than screening and (2) to examine ensuing diagnoses. Our goal was to quantify the findings of CRC and other bowel diseases in symptomatic patients, thereby assessing its broader potential.
This cohort study was conducted within the Danish universal public healthcare system, delivered by five administrative regions. National CRC screening using FIT was initiated in 2014, but utilization of FIT for symptomatic patients varies between regions. The cut-off for a positive test is ≥10 µg haemoglobin/g faeces for symptomatic populations.
The study used data from the Danish Civil Registration System, the Danish National Patient Registry covering all Danish hospitals, and the Clinical Laboratory Information Register. The cohort included all patients who underwent FIT between 2014 and 2021 outside the Danish CRC screening program.
We employed descriptive statistics to examine FIT administration and demographic distributions across the Danish regions, as well as fecal haemoglobin levels among tested individuals. In addition, we estimated the cumulative incidence of CRC and inflammatory bowel disease (IBD) diagnoses following FIT, considering death as a competing risk and evaluated the proportion of diagnoses for CRC and IBD during the year following FIT.

Results

We identified 19,787 individuals who underwent FIT outside the national CRC screening program in 2014 to 2021. Of these, 4,283 (22%) individuals had a positive FIT result. Among tested individuals, 10,807 (55%) were female. Median age at testing was 64 years. Use of FIT varied across the regions, with 36% of the study cohort being from the Central Denmark Region, and 1.6% being from the Region of Southern Denmark.
Positive FIT cases had a shorter median time to CRC diagnosis (28 days) and any diagnosis (36 days) compared to negative FIT cases (711 and 58 days, respectively). Within one year of the FIT, 370 (1.9%) individuals were diagnosed with CRC, with higher occurrence for FIT positive individuals (7.9%) than for FIT negative individuals (0.2%) (risk difference: 7.7 percentage points [95% CI: -3.2, 11.1]).
Among individuals with a positive FIT result, 83 (1.9%) were diagnosed with IBD within one year, compared to 51 (0.3%) individuals with a negative FIT (risk difference: 1.6 percentage points [95% CI: -5.8, 7.3]).

Conclusion

We found that FIT used outside the national CRC screening program had over 20% positivity. A positive test indicated higher risk of CRC and IBD. Differences in diagnoses are expected due to varied follow-up procedures after positive and negative FIT results. A negative test, while not definitive, suggests a potential to rule out disease and could reduce unnecessary investigations when assessing symptomatic patients.

Introduction

Non-alcoholic steatohepatitis (NASH) is a common known risk factor for developing hepatocellular carcinoma (HCC). Many patients with NASH are given metformin, a widely prescribed medication for type 2 diabetes and obesity. Its primary mode of action involves the activation of AMP-activated protein kinase (AMPK), a central regulator of cellular energy homeostasis. Beyond its anti-hyperglycemic effects, it also exhibits pleiotropic properties that extend to modulating various cellular processes, including inflammation, metabolism, and immune response. In this similar mechanism, growing evidence indicates that metformin also has anti-cancer properties. It has shown significant synergistic effects in combination with standard chemotherapy and immune check-point inhibitors (ICI). However, its effect on advanced HCC treated with ICI (e.g. atezolizumab + bevacizumab, pembrolizumab, durvalumab) is not well understood.

Aims & Methods

This meta-analysis aims to determine the effect of metformin in the overall survival of diabetic patients with advanced HCC treated with ICIs. Major electronic databases and grey literature sources were searched up to January 2023 for studies assessing the effect of metformin in the survival of diabetic HCC patients on immunotherapy.

Results

The hazard ratios for the overall survival of metformin (experimental) vs non-metformin (control) groups were compared from the studies done by Kang 2022, Lin 2022 and Ramini 2023. Resulting I2 of 0% (p value = 0.54) implies that heterogeneity does not exist. Resulting pooled hazard ratio of 1.08, with a narrow 95% confidence interval 0.85 to 1.38, is not significant (Z = 0.65, p = 0.51), implying no significant difference between the two groups. The forest plot also shows that the diamond market intersects the 1 axis or the line of no effect, suggesting that the hazard ratio is not significant. However, eyeballing the said forest plot, all 3 studies tend toward the non-metformin or control group which signifies a worse prognosis with metformin on HCC patients on ICIs.

Conclusion

The use of metformin has no significant difference in the overall survival in diabetic HCC patients receiving immunotherapy, although trends are leading towards worse prognosis. Hence, physicians must take into consideration the diabetes status of HCC patients on immunotherapy due to its impact on their clinical outcomes and negative prognostic effect of metformin use.

References

Papadakos SP, et al. The Emerging Role of Metformin in the Treatment of Hepatocellular Carcinoma: Is There Any Value in Repurposing Metformin for HCC Immunotherapy? Cancers (Basel). 2023 Jun 13;15(12):3161. doi: 10.3390/cancers15123161

Hua, Y., Zheng, Y., Yao, Y. et al. Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing. J Transl Med 21, 403 (2023). https://doi.org/10.1186/s12967-023-04263-8

Disclosure

No conflict of interest

Clinical Case Summary

Up to 5% of patients with newly diagnosed Celiac disease, have negative serology. Although seronegative celiac, is the most common cause for villous atrophy, there are other differential diagnoses (D.D) that should be ruled out when we find villous blunting without positive serology for Celiac disease. The etiologies are usually divided to 5 categories: immune-mediated, infectious, iatrogenic, inflammatory and infiltrative.
We hereby report a case of 39 years old male, with end-stage renal failure and pancreatic insufficiency. He was treated with peritoneal dialysis and was candidate for combined kidney-pancreas transplantation. Hyperphosphatemia is a common complication in patients with end-stage renal disease. In order to reduce his serum phosphate levels, he was treated with high dose of Lanthanum Carbonate, one of the most effective and safe noncalcium-based phosphate binders.
During weight loss investigation, he underwent gastroscopy that demonstrated duodenal denudated mucosa with villous blunting (1). Biopsy showed complete villous atrophy and accumulation of foreign material in mucosal histiocytes (2). Von Kossa staining, that was performed, emphasized the depositions of the foreign material that has been identified as Lanthanum (3). Consequently, the treatment with Lanthanum has been stopped and replaced by another phosphate binder.
This case illustrates a rare differential diagnosis of villous atrophy typical for end-stage renal disease patients, that can be categorized as iatrogenic and infiltrative etiology for villous atrophy.
Since the long-term consequences of lanthanum deposition in tissue are unknown, this case also emphasizes the need for multidisciplinary approach for treating dialysis patients, in order to understand which phosphate binder has been given.
Points to discuss:

1. D.D of villous atrophy
2. Seronegative celiac – definition & diagnosis
3. The impact of Lanthanum deposits in human body tissues
4. The need for cooperation of multi-disciplinary team

References

1. Endoscopic picture of duodenal villous atrophy
2. H&E staining that demonstrates complete duodenal atrophy with foreign material in the mucosal histiocytes
3. Von Kossa staining emphasizes the deposits of the foreign material

Disclosure

No conflict of interest to declare

Introduction

ESPGHAN aims to develop evidence-based guidelines and practice recommendations in pediatric gastroenterology, hepatology, and nutrition (PGHN). The Quality of Care Task Force of ESPGHAN was set up to evaluate the implementation of such standards in routine practice. Here, we report the findings of our first initiative on documentation of anthropometric measurements in routine clinical practice in paediatric hospitals across Europe.

Aims & Methods

Pediatric hospitals from 28 European countries provided pseudonymized data through an online survey. Standards of nutritional care and anthropometric measurements were collected in the first survey using a questionnaire composed through consensus from members of the Quality of Care group. Hospitals reviewed medical notes of eight current and eight discharged patients, retrospectively, to retrieve additional data on anthropometric assessment and documentation in clinical routine. Differences between perceived (as estimated by physicians) compared with actual reports of anthropometric measurements in discharge letters were obtained by using the Friedman paired test. The second survey is ongoing and relates to diagnostic work-up and management of celiac disease.

Results

By 04/2023, 109 hospitals participated (68% academic, 62% certified for PGHN training, 92% with at least one pediatric gastroenterologist). Of these, 9% had no nutritionist/dietician available. Lack of standard policy for weight and height assessments was reported in 15% of hospitals, and absent training for nursing staff on anthropometric measurements in 15%. A wall-mounted stadiometer to measure standing height was unavailable in 10%, equipment for sitting weight in 33%. Measuring infant length was performed in 50% of hospitals by one but not two healthcare professionals. 14% routinely used measuring tape instead of a rigid length measuring board. When we compared physician-reported estimates (0 – 100%) against collected data from patient notes on documentation of weight, height, weight percentiles, and height percentiles, physicians overestimated performance for most items in both patients with PGHN-disorders and other diseases (Table 1).

Table 1: Anthropometrics routinely reported in discharge letter, perceived (as estimated by physicians) compared with actual reports

Conclusion

The survey identified several gaps in fundamental aspects of nutritional care of pediatric patients, including reporting of anthropometric data. The long-term Quality of Care initiative will survey two topics per year on PGHN with re-assessment after providing educational material and feedback for benchmarking. To assess improvement over time, the surveys will be repeated after one to three years. Hospitals in Europe caring for PGHN patients are invited to join this initiative.

Introduction

Gluten-related disorders include Celiac Disease (CD), Wheat Allergy (WA) and Non-Celiac Gluten Sensitivity (NCGS). NCGS is a syndrome characterized by the onset of intestinal and/or extra-intestinal symptoms after the ingestion of gluten-containing foods. Diagnosis is, firstly, based on the exclusion of CD and WA and on clinical response to a gluten-free diet (GFD). Furthermore, a single- or double-blind placebo-controlled gluten challenge is needed in order to limit placebo/nocebo effects. However, food challenges are time consuming and require dedicated health-professionals, but, according to Salerno Criteria, they are necessary to make a correct diagnosis of NCGS.

Aims & Methods

Our aim was to evaluate the efficacy of Test33, a new test, in NCGS diagnosis and to simplify the diagnostic procedure through its use in daily clinical practice. It is a self-administered commercially-available kit containing undistinguishable gluten and placebo capsules, identifiable through a unique code. The patients downloaded a mobile app, which guided them through the administration of the capsules during the blind challenge. Furthermore, the app allowed the self-assessment of symptoms by means of 33 10cm visual analogue scales (VAS), 10 for gastrointestinal symptoms and 23 for extraintestinal symptoms. After an initial three-week-long phase on a GFD, responsive patients were randomly assigned to the blind challenge. The challenge consisted of three different phases: gluten (5.6 g/day) or placebo capsules for seven days, followed by a one-week-long washout period (on GFD) and, finally, seven days of crossover period. We made a “Initial NCGS Diagnosis” after the GFD phase and a “Confirmed NCGS Diagnosis” after the challenge, following two different criteria, the second one less stringent. The primary endpoint was the worsening of symptoms (VAS increase ≥ 3 cm) during blind gluten ingestion compared to placebo.

Results

107 persons (88 females, 38.5 ± 15.6 years of age) agreed to participate. 97 (91%) completed the GFD period, while 88 (82%) completed the entire challenge. After 3 weeks on a GFD, 96.9% of participants reported significantly improved gastrointestinal (p<0.006) and extra-intestinal symptoms and higher general well-being (p<0.00001), resulting as responsive to GFD. During the blind challenge, general well-being score was significantly lower in the gluten group (p<0.027). Among gastrointestinal symptoms, abdominal pain (3.17 ± 0.32 vs 2.37 ± 0.30), constipation (3.27 ± 0.35 vs 2.38 ± 0.30), meteorism (5.40 ± 0.35 vs 3.68 ± 0.33), bloating (4.43 ± 0.31 vs 2.90 ± 0.30) and fullness (4.14 ± 0.36 vs 3.12 ± 0.33) were all worsened by blinded gluten ingestion (all p<0.039), while, regarding extra-intestinal symptoms, 13 out of 22 were significantly worsened after blind gluten ingestion (all p<0.04). None of the symptoms (both gastrointestinal and extra-intestinal) worsened during placebo assumption. The “Initial NCGS diagnosis” was made in 54.6% of the 97 participants who completed the GFD period, while the “Confirmed NCGS Diagnosis” was made only in 8 out of 88 patients (9.1%) who completed gluten challenge, following the more stringent criterion 1.

Conclusion

This self-administered blind gluten challenge supported by a dedicated app diagnosed NCGS among patients reporting symptoms after gluten intake. Therefore, Test33 may be a useful strategy for the assessment of symptoms (intestinal and extra-intestinal) strictly related to the blind gluten ingestion with less time and staff-consuming.
Its use may simplify NCGS diagnostic procedure in daily clinical practice.