Clinical Case Summary

Introduction: Sarcoidosis is a multi-systemic disorder of unknown etiology that primarily involves the pulmonary system. Nevertheless, a diagnosis can be challenging for clinicians because of the potential for almost any organ to be affected. Hepatic granulomas occur in 50-65% of patients with systemic sarcoidosis, while isolated hepatic sarcoidosis is rare.
Aims & Methods: A 50-year-old Montenegrin female patient was consulted by a gastroenterologist due to multiple focal lesions open etiology in the liver and spleen detected on routine ultrasound examination.
Results: Laboratory results showed normal complete blood count, total bilirubin 11.1 µmol/L, aspartate-aminotransferase 35 U/L, alanine-aminotransferase 25 U/L, gamma-glutamyl transferase 247 U/L, pancreatic amylase 40 U/L, and lipase 23 U/L. Tumor markers were in range: carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, alpha fetoprotein (AFP), CA 72-4, except CA 15-3, which was slightly elevated. Increased activity of serum angiotensin-converting enzyme was shown. Viral and serological tests for hepatotropic viruses and autoimmune liver diseases were negative. Imaging methods performed were: Multi-Slice Computer Tomography (MSCT) of the lungs, abdomen and pelvis, Nuclear Magnetic Resonance of the abdomen with Magnetic Resonance Cholangiopancreatography (MRCP), mammography, upper endoscopy and colonoscopy, but these did not provide an answer to the primary cause of the focal lesion. In the end, a liver biopsy was performed, where non–caseous granulomas were described and a diagnosis of sarcoidosis was established.
Conclusion: The patient had isolated sarcoidosis of the liver and spleen, as no granulomatous abnormalities were identified in other organs. The patient showed a remarkable clinical response to corticosteroid therapy. Isolated hepatic and splenic sarcoidosis should be considered in asymptomatic patients with hepatosplenomegaly and suspected metastatic disease.

References

1. Grunewald J, Grutters JC, Arkema EV, Saketkoo LA, Moller DR, Müller-Quernheim J. Sarcoidosis. Nat Rev Dis Primers. 2019 Jul 4;5(1):45. doi: 10.1038/s41572-019-0096-x. Erratum in: Nat Rev Dis Primers. 2019;5(1):49
2. Franzen DP, Brutsche M, Nilsson J, Böni C, Daccord C, Distler O, Elsener D, Funke-Chambour M, Gruner C, Hayward-Könnecke H, Hostettler KE, Kündig T, Ribi C, Seebach JD, Seeger H, Vrugt B, Kolios AGA. Sarcoidosis - a multisystem disease. Swiss Med Wkly. 2022;152:w30049

Disclosure

This abstract was presented at the 11^th Congress of North Macedonian Society of Gastroenterohepatology with international participation held from June 9-11, 2023 in Ohrid, North Macedonia.

Clinical Case Summary

Introduction: Locally advanced pancreatic tumors can lead to both biliary and duodenal obstruction by invasion or compression. Quality of life is severely affected if obstruction occurs: jaundice, emesis and pain can become invalidating and patients become too frail for palliative chemotherapy and are sometimes declared unfit even for derivative surgery. Recently, endoscopic techniques under EUS or ERCP guidance are being used to create biliodigestive and enteral anastomoses.
Clinical case: A 75-year-old female was diagnosed with locally advanced pancreatic head adenocarcinoma in January 2024. The tumor was declared unresectable and chemotherapy was initiated. A plastic stent was inserted into the main biliary duct (MBD) to ensure biliary drainage. In May 2024, she presented with cholangitis and emesis. EGD revealed duodenal stenosis and ERCP failed due to tumor infiltration. A combined endoscopic approach was performed: EUS-guided hepatico-gastrostomy (EHG) for biliary drainage and EUS-guided gastro-enterostomy using a lumen-apposing metal stent (LAMS). In July 2024, the plastic stent was removed, and in August 2024, two fully covered 60 x 10 mm SEMS were inserted antegrade through the EHG into the MBD to improve patency. At 11 months post-intervention, the patient returned for routine reassessment, declaring good clinical performance: she remained asymptomatic, with routine blood tests, including bilirubin levels within normal range and with all stents patent and correctly positioned (confirmed radiologically and endoscopically). The patient was able to maintain oral intake and continue chemotherapy. No late adverse events were noted.
Conclusion: This case demonstrates the long-term clinical and technical success of a staged endoscopic triple bypass for the management of complex biliary and duodenal obstruction due to unresectable pancreatic cancer. The approach was minimally invasive, well tolerated and remarkably improved the patient's quality of life.

References

1. Adler, Douglas G MD; Baron, Todd H MD, FACP. Endoscopic Palliation of Malignant Gastric Outlet Obstruction Using Self-Expanding Metal Stents: Experience in 36 Patients. American Journal of Gastroenterology 97(1):p 72-78, January 2002. | DOI: 10.1111/j.1572-0241.2002.05423.x
2. Giovannini, Marc. (2019). EUS-guided hepaticogastrostomy. Endoscopic Ultrasound. 8. 35. 10.4103/eus.eus_47_19.
3. Dumonceau, Jean-Marc & Tringali, Andrea & Blero, Daniel & Devière, J & Laugiers, R & Heresbach, D & Costamagna, Guido. (2012). Biliary stenting: Indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy. 44. 277-98. 10.1055/s-0031-1291633.
4. Van Der Merwe, S. W., Van Wanrooij, R. L., Bronswijk, M., Everett, S., Lakhtakia, S., Rimbas, M., ... & Van Hooft, J. E. (2022). Therapeutic endoscopic ultrasound: European society of gastrointestinal endoscopy (ESGE) guideline. Endoscopy, 54(02), 185-205. 10.1055/a-1717-1391

Introduction

In recent years, the number of early-onset CRC (EO-CRC) diagnosed at the age of less than 50 years has been increasing. Previous studies suggest that EO-CRC may have higher malignant potentials and a worse prognosis than late-onset CRC. However, the reason why EO-CRC is regarded as aggressive cancer and result in delayed diagnosis remains unclear. We thought that both the lack of appropriate opportunities for screening or medical examination and the bias that was caused owing to being analyzed altogether regarding the different clinical stages could affect worse prognosis of EO-CRC. In this study, we focused on T1 cancer to highlight the essential features of EO-CRC to minimize the bias caused by the time of diagnosis.

Aims & Methods

This study is a secondary analysis of the main JSCCR (The Japanese Society for Cancer of the Colon and Rectum) project, “International joint research on lymph node metastasis in CRC”. Utilizing 4673 T1 CRC cases treated between July 2009 and December 2016 at 27 facilities belonging to JSCCR, we divided the patients into 5 groups according to age at the diagnosis: 49 years or younger, 50‒59 years, 60‒69 years, 70‒79 years, and 80 years or older. To analyze the clinicopathological features including sex, tumor location, macroscopic type, tumor size, histology, submucosal invasion depth, lymphatic/venous invasion, tumor budding, lymph node metastasis, and treatment methods, the Spearman’s correlation test was used. The difference of disease-free survival (DFS) between early-onset and later-onset CRC was also examined using log-rank test and Kaplan–Meier method.

Results

The cases of EO-CRC were 349 (7.5%). Among age groups, the proportion of rectum (from 49 years or younger to 80 years or older;44.1%, 42.0%, 36.6%, 29.0%, and 12.0%, respectively; P <0.05), protruded type (62.2%, 59.1%, 54.9%, 48.4%, 45.9%; P <0.05), and frequency of lymph node metastasis (10.0%, 7%, 8.0%, 7.0%, 4.6%; P <0.05) were decreased as the age group increased. In terms of sex, the proportion of male tends to decrease as the age group increased (57.9%, 60.8%, 63.5%, 57.0%, 52.7%, respectively; P <0.05). No significant differences were found among the five age groups for tumor size, histology, submucosal invasion depth, vascular invasion, tumor budding, recurrence rate, and treatment. No significant difference was observed regarding DFS between the two groups (5-year DFS; 98.7% for EO-CRC and 94.3% for late-onset CRC).

Conclusion

This study showed that the frequency of lymph node metastasis of T1 CRC decreased according to the increase of age at diagnosis, suggesting that EO-CRC may have a greater biological malignant potential compared to late-onset CRC. As far as we know, this is also the first study to report that “protruded type” would be one of the features of EO-CRC. Although no difference was observed as for DFS between two groups, it was plausible considering that only T1 stage CRC was enrolled in this study. Further studies are warranted to evaluate the clinicopathological features characterizing early stage EO-CRC.

Introduction

Colorectal cancer associated to chronic colitis (CAC) has a different pathogenesis compared to sporadic or familial colorectal cancer (CRC) and represents the major complication of inflammatory bowel disease (IBD). It is now well-established that IL-33 and its receptor, ST2, are important factors in the pathogenesis of IBD. Emerging evidence also suggests its critical role in epithelial proliferation and the potential contribution to inflammation-driven tumorigenesis that can lead to CRC.

Aims & Methods

The aim of our study was to characterize the precise contribution of IL-33/ST2 axis in the azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated CRC. C57/BL6 wild-type (WT), Il33^-/-, T1/St2^-/- and Nt5e^-/- mice were given a single dose of AOM (10 mg/kg) followed by two cycles of 3% DSS for 7d in drinking water. Vehicle-treated WT mice served as controls and were sacrificed at the same time points. Another group of WT followed the same protocol and received CD73 inhibitor i.p. treatment or vehicle. Disease Activity Index (DAI), as well as endoscopic, stereomicroscopic and histological evaluations of colons were performed. IHC, immunofluorescence (IF), qPCR, and ELISA were done on full-thickness colons of WT for IL-33 and ST2 localization and identification, as well as mRNA and protein expression, respectively. RNA-Seq was performed on whole tissues from AOM/DSS treated WT, Il33^-/- and T1/St2^-/-. qPCR analysis was done on isolated polyps from WT, Il33^-/- and T1/St2^-/- for Nt5e (CD73) and adenosine pathway targets.

Results

Il33, Ilrl1(ST2L), and Ilrl1(sST2) mRNA transcripts, as well as IL-33 and total ST2 proteins were dramatically elevated in AOM/DSS-treated WT mice vs. controls. IHC and IF of treated WT mice revealed localization of IL-33 to the colonic epithelium and to cells within the polyp LP morphologically consistent with stromal and mast cells. Little to no staining for IL-33 was present in controls. Using IF, IL-33 co-localized with sub-epithelial myofibroblast markers Actin and Vimentin, or with mast cell markers Tryptase and MCPT1. AOM/DSS treatment in Il33^-/- and T1/St2^-/- mice resulted in a significant decreased polyp number and size vs. WT, with colonoscopy revealing the development of protruding lesions with abnormal vascular patterns, suggesting tumorous lesions in WT mice, while all deficient mice showed their absence with a more impressive mucosal inflammation, likely due to reduced epithelial proliferation and repair caused by the deficiency of IL-33 signaling. RNA-Seq identified a significant reduction of Nt5e and adenosine pathway targets in Il33^-/- and T1/St2^-/- vs. WT. qPCR on isolated polyps confirmed this observation. AOM/DSS-treated Nt5e^-/- showed a significant decreased polyp number and size vs. controls. Therapeutic inhibition of CD73 produced similar results.

Conclusion

Our results suggest that the IL-33/ST2 axis promotes tumorigenesis in colitis-associated CRC through the activation of CD73. Further studies are underway to determine mechanisms of action that support these findings.

Introduction

Endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) with esophageal varices (EVs) is one of the most challenging endoscopic procedures due to the high risk of bleeding and fibrosis caused by prior treatment of varices. However, due to the small number of such cases, the clinical outcomes of ESD for ESCC with EVs have been reported in only a limited number of cases at single centers^​1-3.

Aims & Methods

We conducted a multicenter, retrospective, cohort study to clarify the safety and efficacy of ESD for ESCC with EVs.Eleven institutions in the Tohoku region of Japan participated in this multicenter, collaborative, retrospective study. We performed endoscopic resection for 3619 patients with esophageal carcinoma at the participating institutions during the period from January 2010 to April 2022. Among those, 30 patients who underwent ESD for ESCC with EVs were recruited for the present study.
Rates of en bloc resection and R0 resection, procedure time and adverse events were evaluated as indicators of the feasibility and safety of ESD. Additional treatment, recurrence and metastasis of the lesions were evaluated as indicators of the long-term efficacy of ESD.

Results

Portal hypertension was caused by cirrhosis, of which alcohol was the most common cause. En bloc resection was achieved in 93.3% and R0 resection in 80.0% of the patients. The median procedure time was 92 minutes. Adverse events included a case of uncontrolled intraoperative bleeding leading to discontinuation of ESD and a case of esophageal stricture due to extensive resection. During the follow-up period of a median for 42 months, a patient with local recurrence and another patient with liver metastasis were observed. One patient died of liver failure after receiving chemoradiotherapy as an additional treatment after ESD. No patient died of ESCC.

Conclusion

This multicenter, retrospective cohort study demonstrated the safety and efficacy of ESD for ESCC with EVs. Further studies are needed to establish appropriate treatment methods for EVs before ESD and additional treatments for patients with insufficient ESD.

References

1. Sawaguchi M, Jin M, Matsuhashi T, et al. The feasibility of endoscopic submucosal dissection for superficial esophageal cancer in patients with cirrhosis (with video). Gastrointest Endosc 2014;79:681-5.
2. Choi YK, Noh JH, Kim DH, et al. Outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms in patients with liver cirrhosis. Clin Endosc 2022;55:381-9.
3. Zhang S, Liu YD, Chai NL, et al. Endoscopic submucosal dissection for early cancers or precancerous lesions of the upper gastrointestinal tract in cirrhotic patients with esophagogastric varices: Ten-year experience from a large tertiary center in China. Gastrointest Endosc 2023 Online ahead of print.

Disclosure

The authors declare that they have no conflicts of interest.

Introduction

Gastric adenoma is recognized as a premalignant lesion.¹Much of the literature lumps all adenomas together with different classifications. These are few western reports regarding the prevalence, associated risk factors and outcomes of endoscopic management of different subtypes of gastric adenoma.

Aims & Methods

Aims: The aim of this study is to determine the prevalence, potential predictors, and outcomes of endoscopic management of the different subtypes of gastric adenoma.
Methods: Of 162 consecutive patients who underwent endoscopic resection for gastric lesions between 2017 and 2022 at our center, 79 patients were enrolled. All the hyperplastic polyps (n=37) and subepithelial lesions (n=46) were excluded. The patient clinical characteristics, endoscopic and histopathological features of gastric lesions were retrospectively collected. Patients were divided according to the histological types of gastric adenoma into 4 groups: intestinal group (n= 49), foveolar group (n= 23),pyloric group (n= 6) and oxyntic group (n=1). We statistically compared the clinical and endoscopic features of the three groups. In addition to the analysis of the outcomes of endoscopic resection of gastric adenomas.

Results

Of the 79 patients with a mean follow-up of 2622 months, 51 patients were males (65 %) and 28 patients were females (35%). Forty-nine patients (49/79,62%) had intestinal adenoma, 23 patients (29%) showed foveolar adenoma, 6 patients (8%) developed pyloric adenoma and only 1 patient (1%) had oxyntic adenoma. The mean age was significantly older in the intestinal group (71 ± 13 years vs. 64 ± 16 years vs. 58 ± 18 years, p = 0.03). Intestinal adenomas were significantly associated with family history of gastric adenocarcinoma (14% vs. 4% vs. 0%, p = 0.01) and history of statin intake (39% vs. 26% vs. 0%, p = 0.04).Foveolar adenomas were significantly associated with multiple lesions (≥3 lesions) (p < 0.001) and 0-IIa+IIc Paris classification (6/23, 26%). the size of largest polyp was significantly higher among pyloric group (28 ±15, p= 0.00). Among intestinal group, 33/49 patients (67%) had atrophic gastritis. 82% of the adenomas were resected by ESD with histologically complete resection (R0) in 72/79 patients (91%). Although the difference was not statistically significant (p = 0.4), adenocarcinoma was most frequently encountered among the intestinal adenoma group (17/49, 35%). The post endoscopic resection outcome was comparable among 3 groups with overall recurrence rate (group1:8% vs. group 2:17% vs group 3:17%, P = 0.07) with a comparable mean time to recurrence among three groups (21 ± 17 months vs. 20±17months vs. 14 months, p=0.8). Family history of gastric adenocarcinoma (HR=1.33, p< 0.001) and active helicobacter pylori infection (HR=1.14, p < 0.001) were identified as independent predictors of recurrence after endoscopic resection of different gastric adenoma. Among baseline endoscopic characteristics, polyp size ³ 30mm(HR= 2.04, p< 0.001), more than 3 polyps (HR=1.51, p<0.001), lesser curvature as lesion location (HR=1.72, p< 0.001) and morphology as Paris classification IIc are potential predictors of post resection recurrence. In addition to specimen size ³ 15mm (HR=2.19, p< 0.001) and T1b as lesion histology (HR=2.07, p< 0.001), in the histopathological examination.

Conclusion

The present study clarifies the endoscopic and histopathological characteristics of different gastric adenomas, in addition to the potential predictive factors for each subtype. Potential predictors of recurrence after endoscopic resection emphazie the importance of endoscopic follow up.

References

1. Fujiwara, Y. et al. Diagnosis of borderline adenomas of the stomach by endoscopic mucosal resection. Endoscopy 28, 425–430 (1996).