Introduction

The efficacy of Helicobacter pylori (H. pylori) eradication regimens containing a proton pump inhibitor (PPI) plus antibiotics has gradually declined in recent years due to higher rates of antimicrobial resistance and insufficient acid inhibition. Vonoprazan (VPZ) is a novel potassium-competitive acid blocker which provides a stronger and longer-lasting effect on gastric acid suppression than PPIs. Our objective was to perform a systematic review and meta-analysis evaluating the efficacy and safety of VPZ for H. pylori eradication.

Aims & Methods

We conducted bibliographical searches in PubMed, Embase and the Cochrane Library up to April 2023. Selection: studies evaluating the use of VPZ in the eradication treatment. Outcomes: Efficacy was assessed by intention-to-treat analysis. Safety was also evaluated. Results were combined by meta-analysing risk differences (RD) and were stratified by dual, triple and quadruple therapy, first-line and rescue therapy, and by the presence of clarithromycin resistance.

Results

Overall, 75 studies were included, evaluating 44,992 patients, where 22,264 had received VPZ and 22,658 a PPI-based eradication therapy. The overall eradication rate with VPZ was 88% (95%CI=87-90%, 75 studies, I²=88%). When only RCTs were considered, similar results were obtained (87%, 95%CI=85-90%, 35 studies I²=84%).
When comparing dual, triple and quadruple VPZ-containing therapies, a tendency towards better efficacy with those regimens using a greater number of antibiotics was observed: 85%, 88% and 95%, respectively. However, when we compared the eradication rates between VPZ-based dual vs. triple regimens, no significant differences were reported, either in the overall analysis (P=0.17) or in the meta-analysis of studies directly comparing these regimens (P=0.21).
The eradication rate with VPZ-based therapy in first-line was 87% (95%CI=86-89%, 55 studies, I²=89%), and 90% (95%CI=87-93%, 37 studies, I²=84%) when used as rescue therapy. Among treatment-naïve patients, a significant superiority in the VPZ vs. PPI-based regimens was reported (87% vs. 70% respectively; RD=0.12, 95%CI=0.10-0.14, P<0.00001, I²=83%). However, no significant differences were shown between VPZ and PPIs when used in rescue therapy. When focusing on RCTs only, similar results were obtained.
Among those patients with clarithromycin-resistant strains, an overall efficacy of VPZ-based therapies was 81% (95%CI=75-85%, 18 studies, I²=60%), while in those with clarithromycin-susceptible strains it was 92% (95%CI=89-95%, 18 studies, I²=87%). We found a significant superiority of VPZ vs. PPIs (75% vs. 39%; RD=0.35, 95%CI=0.27-0.42, P<0.00001, 7 studies, 797 patients) in clarithromycin-resistant patients; whereas no significant differences were found in the clarithromycin-susceptible group. RCTs subgroup analysis showed similar results.
The overall incidence of adverse events with VPZ was 18% (95%CI=15-20%, 69 studies, I²=97%). No significant differences were found between VPZ and PPIs regimens tolerability.

Conclusion

The efficacy of VPZ-based regimens was over 85% in all treatments evaluated. The advantage of triple over dual VPZ could not be demonstrated in direct comparisons. In treatment-naïve patients as well as in those cases with clarithromycin-resistant strains, VPZ-based regimens performed better than PPIs-based ones; however, in rescue therapy and in clarithromycin-susceptible patients, this advantage was not confirmed. Tolerability was similar in both VPZ and PPIs regimens.

Disclosure

Dr. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from Mayoly, Allergan, Diasorin, Gebro Pharma, and Richen. Dr. Nyssen has received research funding from Mayoly and Allergan.

Introduction

Gastrointestinal involvement is universal among patients with systemic sclerosis (SSc). Small intestinal dysfunction manifests with non-specific gastrointestinal symptoms (abdominal pain, distension, nausea, or vomiting), along with objective signs such as malnutrition, small intestinal bacterial overgrowth, and, in severe cases, chronic intestinal pseudo-obstruction. The pathogenesis of small intestinal dysmotility in SSc has been proposed to follow a sequential progression, beginning with neuropathy, progressing to myopathic damage, and ultimately culminating in fibrosis. Currently, there are no diagnostic techniques available to differentiate between stages of small intestinal involvement.

Aims & Methods

Aim: To assess the discriminative potential of high-resolution jejunal manometry in categorizing small intestinal dysmotility among patients with SSc.

Prospective study evaluating small intestinal motility in consecutive patients with SSc and digestive symptoms between January 2018 and July 2023 and healthy volunteers as controls. A 35-channel high-resolution manometry catheter was trans-nasally inserted into the jejunum under fluoroscopic radiological guidance. Small intestinal motility was continuously recorded for 5 h; 3 h fasting and 2 hours during continuous nutrient perfusion at 2 kcal/min. Tracings were analyzed by conventional qualitative analysis (identifying neuropathic and myopathic motility patterns) and by quantitative analysis of high-resolution parameters (measuring a motility index (MI) that integrates contractile frequency and amplitude over time, and manually counting the number of propagated contractile fronts)

Results

Twenty patients (52 ± 10 years, 95% women) with SSc and 18 healthy subjects (HS) (27 ± 6 years, 78% women) were included. By conventional visual analysis, 6 (30%) patients exhibited abnormal small intestinal motility patterns indicative of neuropathic involvement (uncoordinated bursts n=3 and postprandial minute-rhythm n=3), and 7 (35%) patients showed diminished contractile activity during fasting and after nutrient infusion (mean amplitude <20mmHg), indicative of myopathic involvement. The remaining 7 (35%) patients had apparently normal small intestinal motility.
Quantitative analysis of high-resolution parameters detected additional abnormalities in patients with SSc compared to healthy controls (table 1). A significant decrease in fasting (phase II) propagated fronts was observed in all subgroups, including those with apparently normal motility by conventional analysis. The postprandial response to nutrient infusion was reduced in 15 of 20 patients with SSc. All patients with myopathic involvement had a null response to nutrient infusion. Patients with neuropathic patterns and those with apparently normal motility by conventional analysis also exhibited a poor postprandial response, which was similarly reduced in both groups.

Table 1: Results from quantitative analysis of high-resolution jejunal manometry

Conclusion

High-resolution jejunal manometry detects abnormalities in fasting and postprandial small intestinal motility in patients with systemic sclerosis, even at early stages of intestinal involvement, when neuropathic and myopathic patterns are not evident.

References

Alcala-Gonzalez LG, Malagelada C, Galan C, Nieto A, Accarino A, Azpiroz F. Propagation patterns of jejunal motor activity measured by high-resolution water-perfused manometry. Neurogastroenterol Motil. 2021 Dec;33(12):e14240. doi: 10.1111/nmo.14240. Epub 2021 Aug 11. PMID: 34378830.

Disclosure

Nothing to declare

Clinical Case Summary

Background: Colorectal anastomotic strictures affect up to 30% of colorectal cancer surgery patients, but complete obstruction is rare. Endoscopic approaches, relying on successful guidewire passage through the stenosis followed by dilation or stent placement, may avoid surgical revision. In cases of insurmountable strictures in patients with colostomy, guidewire passage under endoscopic ultrasound (EUS) or direct endoscopic guidance, using transillumination, can be considered.
Methods: A 78-year-old underwent urgent high anterior resection with a transverse loop colostomy due to an occlusive rectal tumor. By postoperative day 8, he had anastomotic leakage, requiring reintervention. Ten months post-surgery, colonoscopy showed a complete unnegotiable anastomotic stricture. A pediatric colonoscope was inserted through the colostomy, and a therapeutic gastroscope was introduced via the rectum, both advanced to opposing sides of the stricture. Fluoroscopic confirmation of scope positions was followed by transillumination-guided puncture of the colonic side of the stricture with a 6 Fr cystotome. A guidewire was passed through the fistula and retrieved using forceps in a rendezvous manner. Balloon dilation of the fistula up to 4 mm enabled the deployment of a 16x20 mm lumen-apposing metal stent (LAMS). Contrast medium injection confirmed the correct positioning and patency of the LAMS. The patient was discharged home on the same day.
Results: At the 3-month follow-up sigmoidoscopy, the anastomosis was patent, while the stent had migrated and was removed. Colostomy reversal was successfully performed one day later. At the 6-month follow-up, the patient reported regular bowel movements without any residual symptoms.
Conclusion: Freestyle puncture of the excluded rectum using a cystotome followed by LAMS apposition during a dual endoscopic-fluoroscopic procedure seems to be a safe and effective treatment for recanalizing complete colorectal anastomotic strictures.

References

Clinical Case Summary

A 65-year-old man was admitted to our emergency department presenting with intermittent abdominal distension and difficulty in defecation for over a month, and absence of passage of stool and gas for 3 days. Soft tissue masses of sigmoid colon wrapping the left ureter on abdominal CT and a large nodular neoplasm in the sigmoid colon on colonoscopy were observed. Advanced colon cancer was highly suspected. However, we made sixes times biopsy totally and found no evidence of malignancy. Histopathology only showed moderate to severe chronic mucosal inflammation. We finally performed the subtotal colectomy and the histopathology of the excised colon showed us an unexpected finding: Schistosoma japonicum ova.
According to the data published by WHO in 2020, schistosomiasis has been reported in 78 countries worldwide, resulting in an estimated 240 million deaths¹. These highlight the significance of schistosomiasis eradication. Further history taking observed that the patient swam in the Baishui River, a tributary of Yangtze River, an endemic area of schistosomiasis, in recent four years of summer vacation.
During endoscopic examinations, patients may have characteristic scattered yellow nodules, while non-specific mucosal congestion, edema, thickening, ulcers, and polyps may be commonly observed. Therefore, misdiagnosis of intestinal schistosomiasis is common, with the rate of 30.3%^2,3. As we know, we made the first report of intestinal schistosomiasis infiltrating peritoneum and ureter, mimicking advanced colon cancer or Crohn’s disease. This highlights the importance of multi-site and deep biopsies or even surgery for the diagnosis of colonic neoplasm, especially when Schistosoma ova are distributed focally in submucosal area. Moreover, Schistosoma are far from eradication. Physicians should include schistosomiasis as a common differential diagnosis of colonic neoplasm. Detailed history taking of travel and migration is necessary in these patients.

References

(1) Díaz, A. V.; Walker, M.; Webster, J. P. Reaching the World Health Organization Elimination Targets for Schistosomiasis: The Importance of a One Health Perspective. Philos Trans R Soc Lond B Biol Sci 2023, 378 (1887), 20220274. https://doi.org/10.1098/rstb.2022.0274.
(2) Yang, Y.; Wang, X.-Y.; Duan, C.; Wang, Z.-J.; Sheng, H.-Y.; Xu, X.-L.; Wang, W.-J.; Yang, J.-H. Clinicopathological Characteristics and Its Association with Digestive System Tumors of 1111 Patients with Schistosomiasis Japonica. Sci Rep 2023, 13 (1), 15115. https://doi.org/10.1038/s41598-023-42456-9.
(3) Cai, L.; Chen, Y.; Xiao, S.-Y. Clinicopathologic Features of Chronic Intestinal Schistosomiasis and Its Distinction From Crohn Disease. Am J Surg Pathol 2021, 45 (3), 430–438. https://doi.org/10.1097/PAS.0000000000001594.

Introduction

New biologics such as vedolizumab (VDZ) and ustekinumab (UST) have expanded the therapeutic armamentarium for inflammatory bowel diseases (IBD) over the past decade. Head-to-head trials comparing safety to tumor necrosis factor alpha inhibitors (anti-TNF) are limited. Data on safety of biologic sequencing remains scarce.

Aims & Methods

Aim: To assess the impact of different biologics and previous treatments on the incidence of severe adverse events (SAE) in a real-world tertiary IBD patient cohort.
Methods: A retrospective monocentric study was performed at the Ghent University Hospital. Patients starting anti-TNF, VDZ or UST from January 2018 to June 2021 with follow-up until December 2021 were included. SAE were defined as intestinal resection (IR), IBD-inflammation related hospitalization (IBD-hosp), IBD-treatment related hospitalization (e.g. infections) (treat-hosp), malignancy and death. Cox regression analysis was used to explore risk factors (RF) of SAE.

Results

In total 267 patients were included: 84 on VDZ, 69 UST, 60 infliximab (IFX) and 54 adalimumab (ADM). At baseline a significant difference was found between biologic groups for age (younger in IFX and ADM - P=0.001), IBD type (Crohn’s disease (CD): VDZ 51.2%, UST 73.9%, IFX 70%, ADM 77.8% - P=0.003), CRP (in mg/L, med, IQR - VDZ: 5[1.6-12.4], UST: 8.5[2.8-19.3], IFX: 13 [1.87-31.8], ADM:3.2[1-8.1] - P<0.001) and calprotectin (in µg/g, med, IQR) (VDZ: 579 [175- 1801], UST: 707 [244-2889], IFX: 652 [65-2449], ADM 200 [43.7-789] - P=0.021)). Perianal CD rate was higher in anti-TNF and UST patients (P=0.003) and prior disease duration differed significantly (VDZ: 9years, UST10y, IFX 2y,ADM 3.5y - P<0.001)). Concomitant immunomodulator (IMM) use was higher in the IFX group (81.7% vs 25% for all other groups P<0.001)) and corticosteroid (CS) use differed among treatment groups (VDZ 78.6%, UST 68.1%, IFX 70%, ADM 55.6% (P=0.041)). Number of prior biologics was higher in the UST group (P<0.001).
No significant difference in SAE rate could be found between different biologics (UST 37.7%, IFX 33.3%, VDZ 23.8%, ADM 22.2% - P=0.148). Cox regression revealed age ≥60years (aHR 2.00, 95%CI 1.11-3.60, P=0.020) and higher number of previous biologics (aHR 1.29, 95%CI 1.03-1.60, P=0.024) as independent RF for SAE. Considering SAEs types, IR rate was not significantly different between biologic groups (VDZ 4.8%, UST 15.9%, IFX 8.3%, ADM 5.6% - P=0.096). Cox regression revealed previous IMM use as an independent RF for IR (aHR 4.26, 95%CI 1.62-11.19, P=0.003). No significant difference was found between biologics considering IBD-hosp (VDZ 15.5%, UST 30.4%, IFX 21.7%, ADM 14.8% – P=0.087). Higher number of previous biologics was an independent RF for IBD-hosp (aHR 1.32, 95%CI 1.02-1.71, P=0.036). Treat-hosp rate was not significantly different between biologic groups (VDZ 7.1%, UST 10.1%, IFX 6.7%, ADM 5.6% – P=0.811). Age ≥60years was found to be an independent RF of treat-hosp (aHR 4.93, 95%CI 1.91-12.76, P=0.001). Six patients developed malignancy (3 VDZ: colorectal carcinoma, melanoma, low grade appendix neoplasia; 2 IFX: cervix CIN3, gastric adenocarcinoma; 1 ADM: basal cell carcinoma). One patient died due to progressive melanoma while on VDZ.

Conclusion

In this tertiary real-world IBD patient cohort, no influence of type of biologic on the SAE rate could be found. Elderly age (≥60 years) and higher number of previous biologics were an independent RF for SAEs.

Introduction

Hepatocellular carcinoma (HCC) is the most common primary malignant liver cancer globally and ranks as the third leading cause of cancer-related mortality. Treatment with immune checkpoint inhibitors (most commonly atezolizumab in combination with bevacizumab) is the most effective first-line systemic therapy for patients with advanced HCC. Since it is a new method of treatment, there is little clinical data on the use of this combination of drugs in practice (outside of prospective studies). This study aims to present the clinical outcomes of patients with HCC who underwent immunotherapy at our center over the past three years.

Aims & Methods

In this retrospective observational study, we included patients treated with the atezolizumab and bevacizumab combination between March 2020 and September 2023. Demographic information, general physical assesments, disease etiology, disease staging, liver cirrhosis status, portal hypertension and laboratory values (aminotransferases and total bilirubin) were collected. Adverse events were analyzed according to the Common Terminology Criteria (CTCAE). Descriptive statistics and survival analysis were performed using Statistical Package for the Social Sciences (SPSS) version 22.

Results

53 HCC patients received atezolizumab and bevacizumab in studied time period, 8 (15.1%) females and 45 (84.9%) males. The median age at the initiation of immunotherapy was 68 years (range 41 – 84 years). Thirteen patients (24.5%) had esophageal varices prior to immunotherapy, with three (5.6%) requiring ligation. The majority of patients had liver cirrhosis A 27 (50.9%) according to Child Pugh criteria, a minority B (9.4%), and 21 patients (39.6%) were without cirrhosis. The primary causes of the disease were alcohol (51.6%), metabolic dysfunction-associated steatotic liver disease (MASLD) (16.1%), hepatitis C virus (12.9%), hepatitis B virus (6.5%), and hemochromatosis (3.2%). Stage C HCC, according to The Barcelona Clinic Liver Cancer, World Health Organization (WHO) performance status 0, and absence of macrovascular invasion and extrahepatic spread were predominant at treatment initiation. Grade I or II adverse events occurred in almost all patients (98.1%). Severe adverse events were present in 36 patients (67.9%). Due to severe side effects, 8 (15.1%) patients discontinued treatment, 2 (3.8%) died due to treatment related complications (encephalitis and bleeding from esophageal varices). Treatment was modified in 21 (39.6%) patients due to adverse events. The estimated median survival was 15.7 months.

Conclusion

The majority of patients with unresectable HCC, treated with a combination of atezolizumab and bevacizumab immunotherapy, experienced adverse events, primarily grades I-II. The immunotherapy combination proved to be more effective in patients with viral etiology of liver cirrhosis. The estimated median survival was 15.7 months. This combination of immunotherapy has been demonstrated to be a safe and effective treatment method. Currently, there is limited data regarding the utilization of this treatment in standard clinical practice and our data aligns reasonably well with the findings of the registration study.

References

1. McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of Hepatocellular Carcinoma. Hepatology. 2021 Jan;73 Suppl 1(Suppl 1):4–13.
2. Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022 Mar;76(3):681–93.
3. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894–905.
4. Lee YC, Huang WT, Lee MY, Tsao CJ, Feng YH. Bevacizumab and Atezolizumab for Unresectable Hepatocellular Carcinoma: Real-world Data in Taiwan-Tainan Medical Oncology Group H01 Trial. In Vivo. 2023;37(1):454–60.
5. Himmelsbach V, Pinter M, Scheiner B, Venerito M, Sinner F, Zimpel C, et al. Efficacy and Safety of Atezolizumab and Bevacizumab in the Real-World Treatment of Advanced Hepatocellular Carcinoma: Experience from Four Tertiary Centers. Cancers (Basel). 2022 Mar 28;14(7):1722.
6. de Castro T, Jochheim LS, Bathon M, Welland S, Scheiner B, Shmanko K, et al. Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience. Ther Adv Med Oncol. 2022;14:17588359221080298.

Introduction

Systemic sclerosis (SSc) is a rare autoimmune disease of the connective tissue that can affect multiple organs. The esophagus is the most affected gastrointestinal tract, while interstitial lung disease (ILD) is a main feature associated with SSc.

Aims & Methods

The aim of the present study was to evaluate the association and prognostic implication between motor esophageal disorders and pulmonary involvement in SSc patients. We retrospectively assessed patients with SSc who underwent both the high resolution manometry with the new Chicago Classification 4.0 and pulmonary evaluation comprehensive of function tests and high-resolution computer tomography (HrCT) with the use of Warrick score. A total Warrick score≥7 was considered predictive of ILD, while a score≥10 in a HrCT acquired prospectively from baseline evaluation was considered to establish significant interstitial involvement.

Results

Forty-two patients were included. We found a score≥7 in 11 patients with aperistalsis, in 6 subjects with ineffective esophageal motility and in 6 patients with a normal manometry. Otherwise, a Warrick score<7 was observed in 3 patients with aperistalsis, and in 2 and 14 patients with ineffective esophageal motility disorder and with a normal contractility, respectively. Higher scores were observed in subjects with absent contractility or ineffective esophageal motility than subjects with normal motility, indeed DCI and HrCT score were inversely correlated in linear and logarithmic regression analysis. Prospectively, lower baseline pressure of lower esophageal sphincter and greater HrCT scores at follow-up evaluation were significantly associated.

Conclusion

This study shows an association between motor esophageal disorder and pulmonary involvement in SSc patients: more severe is the esophageal involvement, more critical is the pulmonary disease.