Introduction

Esomeprazole and laparoscopic anti-reflux surgery have shown similar efficacy in PPI-responsive patients (1). However, a significant proportion of patients fails to respond to PPI and are the most relevant group seen by gastroenterologists and surgeons for advanced therapy, including surgery. In a highly selected subgroup of patients with PPI-refractory GERD surgery resulted in treatment success in 2/3 of patients and was superior to medical therapy (2). However, the selection of patients for surgery remains a topic of controversy and the role of pH-MII in patients with ongoing symptoms on-PPI is unknown.

Aims & Methods

Our aim was to assess whether 24h pH-impedance measurement (pH-MII) on PPI can predict outcome of anti-reflux surgery in patients with persistent typical GERD symptoms despite twice daily PPI for at least 3 months.
Patients with refractory GERD symptoms on PPI were assessed by the surgeons and selected for anti-reflux surgery based on typical GERD symptoms and the results of pH-MII off PPI. Patients underwent usual pre-operative work-up including upper endoscopy, esophageal manometry and esophago-gastro-duodenal X-ray, and underwent an additional pre-operative pH-MII on b.i.d. PPI for study purposes. Symptom questionnaires were filled out before, and at intervals after surgery. VISICK scores were used to define outcome after surgery, with grade I and II defined as treatment success, grade III or IV as failure (3).
pH-impedance monitoring (Diversatek) was analyzed using Bioview Analysis® by trained personnel. Symptom association probability (SAP) was used to describe the relation between reflux episodes and symptoms. Statistical analysis was done using GraphPad Prism.

Results

In this interim report, we analyzed 38 patients (23 female, mean age 45, BMI 26). 17 patients were SAP positive on pH-MII on PPI, 21 were SAP negative. Mean follow-up after surgery was 9 years (IQR 5.8-11).
After a mean follow-up of 9 years, 66% (25/38) of the patients in this cohort reported treatment success (VISICK I or II). Treatment success was reported by 90% (19/21) of patients with a negative SAP, 10% (2/21) were treatment failures, no patients required redo surgery. In the SAP positive group, 35% (6/17) reported treatment success, 24% (4/17) treatment failure, and 41% (7/17) required redo surgery. Indications for redo surgery were intrathoracic migration (5/7) and persisting dysphagia (2/7). The proportion of patients with treatment success, failure and redo surgery differed significantly between the SAP-based groups (χ² test; p<0.0001) (table 1), with a significantly higher success rate in the SAP negative group.

Conclusion

This interim analysis suggests that symptom association probability on pH-impedance monitoring on PPI cannot be used to select refractory GERD patients for anti-reflux surgery.

References

1. Galmiche JP, Hatlebakk J, Attwood S, et al. Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial. JAMA. 2011;305(19):1969-1977. doi:10.1001/jama.2011.626
2. Spechler SJ, Hunter JG, Jones KM, et al. Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn. N Engl J Med. 2019;381(16):1513-1523. doi:10.1056/NEJMoa1811424
3. Rijnhart-De Jong HG, Draaisma WA, Smout AJ, Broeders IA, Gooszen HG. The Visick score: a good measure for the overall effect of antireflux surgery?. Scand J Gastroenterol. 2008;43(7):787-793. doi:10.1080/00365520801935467

Introduction

The Mediterranean Diet (MedDiet) has proven to be highly beneficial to human health thanks to its balanced combination of anti-inflammatory and antioxidants nutrients. Several studies^1,2,3 have highlighted the inverse relationship between MedDiet, visceral adiposity, and chronic conditions, namely cardiovascular disease, diabetes, and cancer. The Chrono Med Diet Score (CMDS)⁴ is a recently validated, easy-to-use adherence questionnaire to the MedDiet that, differently from previously validated scores⁵, considers food, lifestyle habits and time of food consumption. Here, we evaluated the CMDS ability to predict the increased risk of gastrointestinal (GI) cancer (colorectal, liver, and stomach) development in a cohort of metabolic subjects.

Aims & Methods

We enrolled 261 patients who accessed our outpatients’ clinic to assess fatty liver disease and Metabolic Syndrome and followed them for a period of 3.2 years. At first evaluation, CMDS was calculated for each patient. Fatty Liver Index (FLI) was calculated as= (e 0.953 × loge (triglycerides) + 0.139 × BMI + 0.718 × loge (GGT) + 0.053 × WC − 15.745)/(1 + e 0.953 × loge (TG) + 0.139 × BMI + 0.718 × loge (GGT) + 0.053 × WC − 15.745) × 100. ROC curves were used to identify the capability of each score to predict cancer development. T-test comparisons for CMDS values were performed for cancer (prostate, bladder, ovarian, and endometrium) and GI cancer diagnosis. P-values lower than 0.05 were considered significant. Chi-square test was used to calculate the associated Odds Ratio (OR) with 95% confidence interval (CI).

Results

A total of 47 out of 261 patients developed cancer. CMDS showed a significant discriminative power (AUC 0.7428) to predict cancer development with a cut-off of 11 (77% sensitivity, 70% specificity, p-value <0.001), while in the 26 subjects with a diagnosis of GI cancer (AUC 0.7961) the cut-off was 13 (67% sensitivity, 85% specificity). Among subjects with CMDS ≤13, those who developed GI cancer showed significantly altered metabolic markers, namely waist circumference, triglycerides, fasting glucose, HDL cholesterol, and FLI compared to patients who did not develop cancer during the follow-up period (see Table). Values of CMDS ≤13 significantly increased the risk of GI cancer with an OR of 3.41 (95% CI: 1.99-6.12). Intriguingly, CMDS was significantly lower (7.1±0.4) in subjects who were diagnosed with gastrointestinal cancer, compared to patients that developed non – gastrointestinal cancer (9.5±0.7).

Conclusion

In our cohort, adherence to the MedDiet is strongly associated to an increased risk of cancer development in metabolic subjects. This association is even stronger in patients who developed GI cancer, as demonstrated by the significant correlation between the CMDS and specific parameters of dysmetabolism, such as visceral adiposity, dyslipidemia, and liver fibrosis. Taken together, our data indicates not only that the risk of GI cancer can be identified using the CMDS as a non-invasive reference method, but also emphasize that dietary and lifestyle changes, promoting a higher adherence to the MedDiet, are significantly recommended for people affected by dysmetabolic conditions.

References

1. Bamia, C.; Lagiou, P.; Buckland, G.; Grioni, S.; Agnoli, C.; Taylor, A.J.; Dahm, C.C.; Overvad, K.; Olsen, A.; Tjønneland, A., et al. Mediterranean diet and colorectal cancer risk: results from a European cohort. European Journal of Epidemiology 2013, 28, 317-328, doi:10.1007/s10654-013-9795-x
2. Mentella, M.C.; Scaldaferri, F.; Ricci, C.; Gasbarrini, A.; Miggiano, G.A.D. Cancer and Mediterranean Diet: A Review. Nutrients 2019, 11, 2059. https://doi.org/10.3390/nu11092059
3. Crudele, L.; Piccinin, E.; Moschetta, A. Visceral Adiposity and Cancer: Role in Pathogenesis and Prognosis. Nutrients 2021, 13, 2101. https://doi.org/10.3390/nu13062101
4. De Matteis, C.; Crudele, L.; Battaglia, S.; Loconte, T.; Rotondo, A.; Ferrulli, R.; Gadaleta, R.M.; Piazzolla, G.; Suppressa, P.; Sabbà, C.; Cariello, M.; Moschetta, A. Identification of a Novel Score for Adherence to the Mediterranean Diet That Is Inversely Associated with Visceral Adiposity and Cardiovascular Risk: The Chrono Med Diet Score (CMDS). Nutrients 2023, 15, 1910. https://doi.org/10.3390/nu15081910.
5. Panagiotakos, D.B.; Pitsavos, C.; Arvaniti, F.; Stefanadis, C. Adherence to the Mediterranean food pattern predicts the prevalence of hypertension, hypercholesterolemia, diabetes and obesity, among healthy adults; the accuracy of the MedDietScore. Prev. Med. 2007, 44, 335–340. https://doi.org/10.1016/j.ypmed.2006.12.009.

Introduction

SBS-IF is a severe organ failure condition with life-long PS dependence. Glucagon-like peptide-2 (GLP-2) stimulates intestinal adaptation resulting in increased absorptive capacity of nutrients and fluids. Apraglutide (APRA) is a novel long-acting synthetic GLP-2 analog in development for SBS-IF.

Aims & Methods

We performed a pre-defined interim analysis of a phase 2 study in SBS-IF-CiC to investigate the safety and efficacy of 4W APRA treatment based on metabolic balance studies (MBS). STARS Nutrition is a 52W phase 2 study in adult patients with SBS-IF-CiC receiving once-weekly subcutaneous APRA injections. Metabolic balance studies were performed at baseline and 4w with stable PS, followed by a 48w PS adjustment period. During MBS, fluid intake was kept constant (individual predefined drinking menu). Duplicates of meals and fluids (wet weight intake), urine and feces (fecal wet weight output) were collected. Safety was the primary endpoint. Secondary endpoints included changes in fecal wet weight output, urinary output, wet weight and energy absorption. Data are presented as mean (95% CI). P-values <0.05 were considered significant (Wilcoxon matched-pairs signed rank test).

Results

Nine patients were included and comprise the full study population. APRA was well tolerated (no dose discontinuation or interruption). Fecal wet weight output decreased significantly by 253 (-437 – -68) g/day (p=0.012). Relative wet weight absorption increased by 9 (1 – 18) % (p=0.039). There was a numeric increase in urinary output (p=0.129). No significant changes in energy absorption were observed.

Conclusion

These initial short-term results of APRA in SBS-IF-CiC support safety and efficacy in increasing relative but not absolute wet weight absorption. One-year treatment outcomes are awaited to assess the full effect on wet weight, energy, and macronutrient absorption.

Disclosure

FJ has received grants/research support/honoraria or consultation fees from Baxter, Fresenius Kabi, Nestlé Health Sciences, BBraun, Theradial, Mayoli, Biocodex, mobile 3econsulting, NPS Pharmaceuticals, Shire, Takeda, Therachon, VectivBio and Zealand Pharma.
PBJ has received grants/research support/honoraria or consultation fees from Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast, Ferring, Fresenius Kabi, GLyPharma, Naia Pharma, NPS Pharmaceuticals, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectivBio and Zealand Pharma.
TV has served on the speaker bureau for Fresenius Kabi, Remedus, Takeda, and VectivBio. TV has provided clinical advice to Baxter, Shire, Takeda, VectivBio, Zealand Pharma. TV has received research grants from Takeda and VectivBio.
This research was supported by VectivBio. FB, CL and OK are employees of VectivBio.

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

Introduction

The incidence of esophageal adenocarcinoma has been increasing in Western countries, with gastroesophageal reflux (GERD) and Barrett's esophagus (BE) being important risk factos for such diagnosis. In Portugal, the current prevalence of reflux esophagitis and BE is unknown, and the aim of this study is to clarify these points.

Aims & Methods

A multicenter cross-sectional study including 13 national digestive endoscopy units, involving patients who underwent upper endoscopy from January to March 2024.

Results

6320 patients were included (57% female, mean age 58). Reflux esophagitis was identified in 1105 patients (17% of the exams, 54% male, mean age 57) (Los Angeles Grade A 10.1%; B 5.6%; C 1.1%; D 0.4%) and 46 with BE (0.7% (95%CI 0.05-1%), 67.4% male, mean age 59 years), with only 4 (0.06% of the total) having 3 cm or more of extension. The prevalence of BE was higher in the Lisbon region (1.35% vs 0.5%, p<0.05), with no difference in the prevalence of reflux esophagitis. Among patients who underwent endoscopy for GERD symptoms, 38% had erosive esophagitis (p<0.05 vs the rest of the population). Among patients with esophagitis and BE, 27% and 39%, respectively, underwent endoscopy for symptoms and/or surveillance related to GERD (vs 11.6% of the rest of the population, p<0.05), with a prevalence of BE in patients with GERD of 2.3% (95%CI 2.1-2.5%, p<0.05 vs the rest of the population). Male gender was a risk factor for grade C/D esophagitis and BE (p<0.05).

Conclusion

Erosive esophagitis is common in Portugal, particularly in patients undergoing endoscopy for GERD symptoms. However, the prevalence of BE, particularly long segment BE, remains low compared to other Western countries, despite similar values of reflux esophagitis. This trend may be reversing in Lisbon with a higher prevalence of BE. Further studies are necessary to better understand these differences.

Introduction

Gastric cancer continues to be one of the main challenges worldwide, with a predictable increase in the number of new cases in the coming decades. Staging systems for gastric precancerous lesions: Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia (OLGIM) are considered to be the best predictors for gastric cancer development. Only OLGA/OLGIM stages III-IV are considered high-risk lesions with a significant potential of progressing towards gastric cancer.

Aims & Methods

The purpose of this study was to evaluate the predictive role of OLGA and OLGIM staging in gastric cancer development.
We conducted a retrospective cohort study by matching gastric adenocarcinoma cases registered in the Latvian Cancer Registry between 2005 and 2022 to the pathology reports in the database of Academic Histology Laboratory from upper endoscopies performed in the Digestive Diseases Centre GASTRO, Jurmala hospital and Riga 1^st hospital. Only cases with antral and corpus biopsies (as the minimum) available from the index endoscopy allowing OLGA / OLGIM staging were included in the study. If data from several endoscopies were available for the same patient, the case with the highest OLGA/OLGIM stage was used as the index endoscopy; if OLGA/OLGIM staging was identical across several endoscopies, the first endoscopy was used as the index case. The presence of dysplasia in any of the previous pathology reports was also considered. Patients with suspected cancer at the enrolment or having been recorded in the cancer registry less than 6 months after the index endoscopy were excluded from the study.

Results

Altogether 54 patients were available for the analysis; 38.9% were male. The mean age at the time gastric cancer detection 69.2 years, range 40-90. The median time between the index endoscopy and gastric cancer diagnosis was 1403.5 days (IQR: 826.5-2793.3). Forty-one patients (75.9%) had one endoscopy, eleven (20.4%) had two, one (1.9%) had four and one (1.85%) – 8 endoscopies. Biopsies from incisura angularis of the stomach were available for 43 patients (79.6%).
Altogether 16 patients (29.6%) had dysplasia reported at one of the preceding endoscopies, of those 14 were low grade, 2 – high grade. Patient distribution per OLGA and OLGIM stages at the index endoscopy is shown in Table 1. Among patients ultimately diagnosed with gastric cancer, only 11 (20.4%) had OLGA III-IV stages and 10 (18.6%) had OLGIM III-IV stages at the time of the index endoscopy. Excluding cases with dysplasia reported during any of the preceding endoscopies did not make a substantial change in the OLGA and OLGIM stage distribution at the index endoscopy.

Table 1. OLGA and OLGIM stages at the time of the index upper endoscopy in patients having developed gastric cancer thereafter.

Conclusion

The majority of patients having undergone upper endoscopy before the diagnosis of gastric cancer were in low-risk OLGA and OLGIM stages. Continued research is warranted to identify the best approach for risk stratification of gastric precancerous lesions. Yet, the current study demonstrates that the assessment should not be solely based on OLGA or OLGIM staging.