Introduction

Functional dyspepsia (FD) is a disorder of gut-brain interaction (DGBI) characterized by postprandial fullness, early satiation, epigastric pain or burning in the absence of a readily identifiable cause at upper endoscopy. Proton pump inhibitors (PPIs) are often used as a first-line treatment for FD, although their efficacy has not been convincingly established.

Aims & Methods

The aim was to investigate symptom patterns in FD patients with and without acid-suppressive therapy (PPI or H2-antagonist, H2RA) and to evaluate the use of these drugs in different patient groups. Ambulatory tertiary-care patients referred for upper gastrointestinal endoscopy were requested to fill out Rome IV gastro-duodenal questionnaires. Those fulfilling Rome IV FD criteria with a negative endoscopy were identified as FD patients and subdivided into patients on and off acid-suppressive therapy. The pattern of GI symptoms was compared between these two subgroups, using frequency thresholds from the Rome IV criteria. The chi-square or Fisher exact (when applicable) test was used to evaluate statistical significance (p<0.05).

Results

The Rome IV questionnaire was filled out by a total of 1002 patients (58% females, 48.5 ± 0.5 years, BMI 25.4± 0.5). Of these, 229 (23%, 73% females, 45.5 ± 1.1 years, BMI 23.9 ± 0.3) fulfilled the diagnostic criteria for FD. Organic findings at endoscopy included Barrett’s oesophagus (n=40, 4%), peptic ulcers (n=24, 2%), and reflux oesophagitis (n=352, 35%).
PPI/H2RA usage in FD patients was 60%, which was not significantly different from patients diagnosed with Barrett’s oesophagus (75%, p=0.07), peptic ulcer (50%, p=0.33), reflux oesophagitis (57%, p= 0.45) or the combined group with organic abnormality at upper endoscopy (46%, p=0.1). There was no significant difference (p=0.67) in PPI/H2RA usage between the EPS (epigastric pain syndrome, 55% usage) and PDS (postprandial distress syndrome, 50% usage) subgroups of FD.
The most prevalent symptoms in FD patients were postprandial fullness (76%), epigastric pain (67%) and bloating (62%). Patients on acid-suppressive therapy reported more nausea (41% vs 27%, p=0.04) and excessive belching (50% vs 36%, p=0.05) compared to patients without acid suppression. There was no significant difference in postprandial fullness (84% vs 73%, p=0.05), epigastric pain (75% vs 64%, p=0.08), heartburn (17% vs 28%, p=0.06) and bloating (70% vs 58%, p=0.06) between the two subgroups. Looking at the EPS and PDS subgroups of FD, there was a significant difference (p=0.03) in bloating between patients on (73%) and off (46%) acid suppression in the PDS subgroup of FD.

Conclusion

The cardinal symptom pattern in FD patients referred for upper endoscopy is similar for those on and off acid-suppressive therapy, but those on PPI/H2RA report more nausea and belching. No difference in acid-suppressive therapy use was observed between FD patients and those with organic findings at endoscopy.

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.

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

Introduction

H. pylori infection can remain after several eradication attempts. The objective of this study was to evaluate the effectiveness of the sixth-line rescue treatment in Europe.

Aims & Methods

Systematic and prospective registry on the clinical management of H. pylori infection. All cases with six eradication attempts registered in AEG-REDCap up to December 2022 were evaluated. The modified intention-to-treat (mITT) and per-protocol (PP) effectiveness was analysed.

Results

Overall, 81 patients were included, mainly from Spain (44% of cases), Italy (26%) and the United Kingdom (17%). The mean age was 52 years, with 52% women and 1.2% of patients allergic to penicillin. Culture was performed in 26 cases (32%), of which: 13 (50%) had bacterial antibiotic resistance to clarithromycin, 12 (46%) to nitroimidazole, and 8 (31%) to quinolones. In addition, 8 (35%) patients had dual resistance (both to clarithromycin and metronidazole) and 7 (27%) triple resistance (also to levofloxacin). Twenty-two different therapeutic combinations were used, most of them prescribed for 14 days (57%) and with low doses (39%) of PPIs. The most frequent treatments were: quadruple bismuth-tetracycline-metronidazole prescribed as three-in-one single-capsule (17%), triple amoxicillin-rifabutin (15%), quadruple bismuth-furazolidone-amoxicillin (11%), triple amoxicillin-levofloxacin (7.4%), and classical quadruple bismuth-tetracycline-metronidazole (6.2%). The highest eradication rates (mITT) were achieved with the single-capsule (77%) and with the quadruple therapy with bismuth-furazolidone-amoxicillin (67%). Overall effectiveness was 53%, both by mITT and PP analyses. Additional information on effectiveness, tolerability, compliance, and prior therapies is shown in the table.

Conclusion

Sixth-line eradication treatments in Europe obtain suboptimal eradication rates. The only therapies that reach acceptable outcomes are the bismuth quadruple therapies with either tetracycline-metronidazole (single-capsule) or with furazolidone-amoxicillin.

Disclosure

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

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.

Clinical Case Summary

Introduction: Kaposi sarcoma is the most common digestive malignancy in Human Immunodeficiency Virus (HIV)-positive patients, but it can also occur in HIV-negative individuals. It is a low-grade vascular tumor associated with Human Herpes Virus-8 (HHV-8) and can appear in immunosuppressed patients. Lesions can develop on the skin, but they could also be found in internal organs and lymph nodes.
Case-report: A 61-year-old Caucasian female with alcoholic liver cirrhosis and diabetes mellitus presented in the Dermatology Department with multiple painless red-to-purple papular nodules across the thorax, cervical area, limbs, and face. Skin biopsies from the posterior cervical area and internal part of the right foot revealed a well-defined nodular dermal tumor with submucosal vascular spindle cells forming slits containing red blood cells and low mitotic activity. Immunohistochemistry confirmed CD34, CD31, HHV-8, and Ki67>30% expression, indicative of cutaneous Kaposi sarcoma. HIV serological tests were negative. Further assessments performed in the Gastroenterology Department established decompensated liver cirrhosis. Moreover, upper digestive endoscopy revealed esophageal varices, portal hypertension gastropathy, along with multiple umbilicated nodules with central ulcerations in the gastric fundus and body. Biopsy samples from these lesions described histopathological findings suggestive of Kaposi sarcoma, while immunostaining for HHV-8 and CD31 was positive. Proposed systemic chemotherapy was declined by the patient. Tumors of the gut with spindle-shaped cells such as leiomyomas, rhabdomyosarcomas, or gastrointestinal stromal tumors must be considered in the differential diagnosis of Kaposi sarcoma.
Conclusion: Kaposi sarcoma can develop in HIV-negative immunosuppressed patients, with conditions such as liver cirrhosis and HHV-8 infections, potentially affecting the digestive tract.

References

1. Xu H, Edwards JR, Espinosa O, Banerji S, Jackson DG, Athanasou NA. Expression of a lymphatic endothelial cell marker in benign and malignant vascular tumors. Hum Pathol 2004;35:857–861.
2. Rossi S, Orvieto E, Furlanetto A, Laurino L, Ninfo V, Dei Tos AP. Utility of the immunohistochemical detection of FLI-1 expression in round cell and vascular neoplasm using a monoclonal antibody. Mod Pathol 2004;17:547–552.
3. Antman K, Chang Y. Kaposi's sarcoma. N Engl J Med. 2000;342:1027–1038.
4. Huang WY, Pantanowitz L, Dezube BJ. Unusual sites of malignancies: CASE 3. AIDS-related Kaposi's sarcoma of the gastrointestinal tract. J Clin Oncol. 2005;23:2098–2099.
5. Arora M, Goldberg EM. Kaposi sarcoma involving the gastrointestinal tract. Gastroenterol Hepatol (N Y). 2010 Jul;6(7):459-62. PMID: 20827371; PMCID: PMC2933764.

Disclosure

No conflict of interest.