Introduction

Necrotizing pancreatitis with walled-off necrosis (WON) is associated with severe morbidity and substantial mortality. Vascular complications such as pseudoaneurysm, arterial erosion, and especially thrombosis of the splanchnic veins are all associated with acute pancreatitis (AP). However, the occurrence and clinical outcome of vascular manifestations in patients developing WON are poorly described. We aimed to describe vascular complications in a well-defined cohort of consecutive patients endoscopically treated for symptomatic WON.

Aims & Methods

Four hundred and nine patients treated endoscopically for their pancreatic fluid collection during a 10-year period were assessed for inclusion. Patients with pseudocysts, < 18 years, concomitant malignant disease and/or procedure-related bleeding were excluded. A total of 290 patients were eligible for analysis.
Vascular complications included bleeding and thromboembolic events. Thromboembolic complications were defined as confirmation of thrombus in one of the splanchnic veins on contrast-enhanced computed tomography scan (CECT). Bleeding complications were defined as clinical bleeding necessitating intervention, including embolization, surgery or transfusion.

Results

The median age was 59 years (range 18-84), and 57% were males. Gallstones were the etiology in 47%, alcohol in 20%, and post-ERCP pancreatitis in 14%. In 14% of the cases, the etiology was unknown. Infection was the main indication for intervention (92%), followed by gastric outlet obstruction (6%) and pain (2%). The average time from debut of symptoms to index procedure was 35 days (range 6-89). The average duration of hospital admission was 89 days (range 21-286). The overall in-hospital mortality was 14%, and need for admission to intensive care unit (ICU) was 35%.
In total, 87 (30%) patients developed vascular complications of which 53 (18%) were thromboembolic, 34 (12%) bleeding, and nine patients (3%) developed both thromboembolic and bleeding complications.
The portal vein was most affected (34%), followed by the splenic vein (28%) and the superior mesenteric vein (23%). Two or all three splanchnic veins were affected in 15%. The majority (81%) of thromboembolic complications occurred before the index procedure. Development of splanchnic venous thrombosis was not associated with in-hospital mortality (13% vs. 14%, p=1.0) or need for ICU admission (38% vs. 34%, p=0.64). None of the patients with splanchnic vein thrombosis developed variceal bleeding during follow-up.
The splenic artery was the most common cause of bleeding (32%), followed by the gastroduodenal artery (24%) and the left gastric artery (12%). In five cases, the source of the bleeding could not be identified. All patients received blood products, 23 patients were treated with arterial embolization and 4 patients with surgery. Seventy seven percent of the bleeding complications occurred after the index procedure. The need for ICU (59% vs. 32%, p=0.003) and in-hospital mortality (38% vs. 11%, p<0.0001) were significantly higher in patients with arterial bleedings as compared to patients without.

Conclusion

Vascular complications are common in WON patients. The timing of occurrence seems distinct, as the vast majority of thromboembolic complications occur before index endoscopic intervention, while bleeding complications mainly occur after. While arterial bleedings are linked to increased morbidity and in-hospital mortality, thromboembolic complications are not associated with a poor short- or long-term clinical outcome.

Clinical Case Summary

A 40-year-old male came to our emergency department referring worsening jaundice, mental status deterioration, epigastric pain and anorexia over the past week. Four weeks earlier he presented odynophagia, myalgias, and hand pruritus but didn’t seek medical attention.
Patient’s clinical background included cognitive impairment due to peripartum anoxia and type 2 Diabetes Mellitus. At admission, he had elevated liver enzymes (R value=2,7), coagulopathy (INR 1.3), pancreatic enzymes >3 times the upper normal level and hyperbilirubinemia (mostly conjugated).
The CT-scan revealed pancreatic tail globosity, diffuse abdominal and retroperitoneal peri-centimetric lymph nodes and excluded biliary lithiasis.
After common causes of acute hepatitis and pancreatitis were ruled out, and since patient was at risk of acute liver failure despite supportive treatment, a liver biopsy was performed. Autoimmune hepatitis, drug-induced liver injury or lymphoproliferative disease were held as potential differentials. Hepatitis E Virus (HEV) RNA was then found and genotyped in the serum (genotype 3). HEV infection was assumed as the cause for both hepatitis and pancreatitis. Histological pattern was inconclusive and epidemiological source wasn’t found.

HEV infection paradigm has changed and is now considered an endemic zoonotic infection in most high-income countries (Portuguese seroprevalence is 16.3%)¹. Infection occurs due to ingestion of undercooked pig or boar meat and should be suspected in every acute hepatitis, mostly with a cholestatic pattern.
The setting of acute HEV hepatitis complicated with acute pancreatitis (AP) is uncommon². AP usually starts after a median of 10 days of jaundice onset³. Literature only reports association between AP and HEV caused by genotype 1 from Southeast Asia^{3 4}, and genotype 3 was only related to gallstone-related pancreatitis, according to current knowledge⁵. This might be the first form of HEV genotype 3 infection with hepatitis and pancreatitis.

References

1. Nascimento MSJ, Pereira SS, Teixeira J, et al. A nationwide serosurvey of hepatitis E virus antibodies in the general population of Portugal. Eur J Public Health 2018;28(4):720-24. doi: 10.1093/eurpub/ckx213 [published Online First: 2017/12/14]
2. Debnath P, Datta AK, Chakraborty U, et al. Acute viral hepatitis E complicated with acute pancreatitis in an immunocompetent adult. BMJ Case Rep 2021;14(2) doi: 10.1136/bcr-2020-239684 [published Online First: 2021/02/06]
3. Haffar S, Bazerbachi F, Garg S, et al. Frequency and prognosis of acute pancreatitis associated with acute hepatitis E: A systematic review. Pancreatology 2015;15(4):321-6. doi: 10.1016/j.pan.2015.05.460 [published Online First: 2015/06/08]
4. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol 2018;68(6):1256-71. doi: 10.1016/j.jhep.2018.03.005 [published Online First: 2018/04/04]
5. Karlsson M, Norder H, Bergstrom M, et al. Hepatitis E virus genotype 3 is associated with gallstone-related disease. Scand J Gastroenterol 2019;54(10):1269-73. doi: 10.1080/00365521.2019.1666163 [published Online First: 20190925]

Introduction

Current guidelines advise esophagectomy for submucosal esophageal adenocarcinoma (T1b EAC). However, data from retrospective studies suggest that endoscopic follow-up (FU) may be a valid alternative in patients without signs of lymph node metastases (LNM) at baseline. In this international multicenter, prospective cohort study (NCT03222635), we aim to evaluate the safety of a watchful waiting strategy with regular endoscopic FU in patients treated endoscopically for T1b EAC.

Aims & Methods

This ongoing prospective study is conducted in 19 hospitals in Europe and Australia, and aims to include 141 patients with 5-year FU. After radical endoscopic resection of T1b EAC, patients are re-staged with endoscopic ultrasound (EUS) and CT/PET. In the absence of LNM or distant metastases (N0M0), and upon consent for endoscopic FU, patients are included and undergo strict endoscopic FU with gastroscopy and EUS every 3 months during year 1 and 2, every 6 months during year 3 and 4, and at year 5. CT/PET is repeated after 1 year. We divided our cohort into two groups: ‘high-risk’ (submucosal invasion ≥500um, a/o poorly/undifferentiated tumor (G3-4), a/o lymphovascular invasion (LVI+)) and ‘low-risk’ if no high risk features are present. Primary outcome parameters are 5-year disease specific survival and overall survival; secondary outcome parameters are rate of LNM and local recurrence.

Results

Since July 2017, 134 patients (112 men, median age 69 ±10 years) were included with a median FU of 22 (IQR 11-35) months: 87 high-risk and 47 low-risk patients. 6 patients (4% [95%CI 0.2-8.8]) were diagnosed with LNM (table 1) after median FU of 8 (IQR 5-16) months. Of these 6 patients, 2/6 were referred for neoadjuvant chemo(radio)therapy with esophagectomy (ypT0N1M0, ypT0N0M0), 1/6 underwent esophagectomy only (pT0N2M0), 3/6 underwent a selective surgical resection of the tumor-positive LN.
7 patients (5% [95%CI 0.8-9.6] were diagnosed with an intra-luminal tumor recurrence not eligible for endoscopic re-treatment after median FU of 7 (IQR 6-15) months. 5 had initial ESD and 2 cap-based EMR. Of these 7 patients, 2/7 underwent esophagectomy (pT1bN0M0, pTisN0M0), 1/7 had neoadjuvant chemoradiotherapy and esophagectomy (ypT1aN0M0), 3/7 underwent (chemo)radiotherapy only, of which 1 patient eventually died as result of stenosing EAC, 1/7 refused additional treatment. No distant metastases were diagnosed during FU in both cohorts. Five patients died during FU of a cause unrelated to EAC. Five patients discontinued FU due to old age. Two patients were lost to FU.

Conclusion

The preliminary analysis from our ongoing prospective study suggest that in patients with radically removed high- or low-risk T1b EAC, without LNM at baseline, a strict endoscopic follow-up protocol is feasible and the window for curative therapy remains open for those patients who develop LNM (4%) or a local intra-luminal recurrence (5%) during FU. Most patients demonstrate uneventful FU.

Disclosure

No conflict of interests.

Introduction

Diverticular disease of the colon is one of the most common diseases in Western world. Despite in the natural history in most of cases diverticulosis remains asymptomatic or manifests with mild abdominal pain, complications may occur. Bleeding from diverticula is one of the most common complications and, despite it is usually a self-limiting event, it may lead to anemia or shock. Among the endoscopic interventions for active bleeding, direct or indirect clipping of the diverticulum is the most diffuse one. However, it has been hypothesized that endoscopic band ligation (EBL) may be more effective, since it may improve the chance to close the bleeding vessel, with a better outcome on long term. Therefore we performed a meta-analysis comparing clipping versus EBL for diverticular bleeding.

Aims & Methods

Literature search on main databases (PubMed, Web of science, SCOPUS, EMBASE) was performed in November 2022. Studies comparing clip versus EBL for acute diverticular bleeding were selected. We excluded case series, abstract and articles not written in English. The following outcomes were analysed: short term effectiveness, early rebleeding, tardive rebleeding and need for surgery or radiologic embolization. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculate according to Mantel-Haenszel method. Heterogeneity was estimated by I² statistic with chi square test, and, if present, a random effect model was used, otherwise a fixed one was adopted.

Results

Seven studies were selected, overall enrolling 2322 patients (979 in EBL and 1343 in clip groups). Immediate haemostasis was achieved in the EBL and clipping group respectively in the 96.8% and 96.5% (OR=0.94, 95% CI 0.59-4.19, p=0.79). Early rebleeding was observed more frequently in the clipping (25.0%) than in the EBL group (11.8%), with an OR=0.40 (95% CI 0.32-0.51, p<0.001). Similarly, tardive rebleeding was more common in the clipping arm (37.4%) than in the EBL (24.5%), OR=0.39, 95% CI 0.22-0.68, p=0.0001. Patients receiving clipping needed more frequently salvage surgery or embolization than EBL (1.48% versus 0.53%, OR=0.40, 95% CI 0.17-0.93, p=0.03).

Conclusion

Despite EBL and clip have similar effectiveness in achieving immediate haemostasis, EBL showed better effectiveness in maintaining it on longer interval times, with less probable need for major surgical/radiologic interventions.

Clinical Case Summary

75 years old female reporting vomiting, chronic diarrhea, epigastric pain and weight loss since 2021. She was initially investigated with Esophagogastroduodenoscopy and biochemical exams (both negative). Computed Tomography (CT) showed enlarged mesenteric lymph nodes in right iliac fossa, mesenterial fibrous distortion, venous vessels stenosis, wall thickening in distal ileal tract and mucosal hyperemia. Several differential diagnoses were proposed: ileal Neuroendocrine Tumor (NET) with mesenteric metastases, small bowel neoplasia/ileal lymphoma, inflammatory bowel disease, vascular disruption/ischemia, infections (i.e. tuberculosis). NET markers were negative, as well as Positron Emission Tomogaphy (PET) with Gallium. Total body FDG PET showed hypermetabolism in terminal ileum. Ileocolonoscopy showed sub stenosis, with a serpiginous ulcer of 8 mm located 15 cm from the ileocecal valve and mucosal edema. Histology was nonspecific. The patient underwent ileal resection and right hemicolectomy. Surgical specimen histopatology with immunohistochemical staining (for S100, CD117, Bcl-2 and Calretinin) diagnosed sporadic diffuse ganglioneuromatosis. Post-operative follow up was regular. The differential diagnosis was indeed challenging. The symptoms were confusing, i.e. the presence of diarrhea and the absence of anemia, and the endoscopic appearence was nonspecific. The lesion was hard to sample endoscopically, so surgical specimen evaluation was needed. Video capsule or device-assisted enteroscopy could have been attempted, but with caveats related to luminal stenosis. Multiple neuroendocrine neoplasia (MEN) IIB had to be ruled out since the patient had multiple thyroid nodules, to exclude medullary carcinoma. Subsequent follow up has yet to be established.

References

1. Endoscopic image showing ileal ulcer and stenosis
2. CT scan with mesenterial distortion and lymph nodes enlargment
3. CT scan showing ileal wall thickening and corresponding FDG PET uptake