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

Nutritional deficiencies, including fat-soluble vitamins, water-soluble vitamins and minerals have been studied in the setting many autoimmune diseases, including those involving the digestive system. However, despite the well-known pancreatic involvement in IgG4-related diseases, nutritional deficiencies in autoimmune pancreatitis (AIP) have not been examined so far.

Aims & Methods

The aim of the present study was to determine the prevalence of micronutrient deficiencies in patients with AIP as well as to investigate their relationship with relapse. We retrospectively analysed medical records of patients followed up for AIP at our Pancreas Outpatient Clinic between January 2001 and March 2022. Demographic and clinical data were collected. The primary outcome was the prevalence of micronutrient deficiencies during AIP follow-up. The secondary outcome was the prevalence of AIP relapse, with exposure defined as micronutrient deficiency occurring at any time during follow-up. Micronutrient variables were solely described categorically as deficient or normal, according to the reference values at the time of each test. However, the cut-off value for vitamin D deficiency was set to below 25 nmol/L since levels between 25-50 nmol/L solely indicate an insufficiency.

Results

One hundred patients were included in the final analysis. The male-to-female ratio was 2.5:1; median age at diagnosis was 57 years (range 19-85). Median follow-up was 53 months, and during this time, 38% of patients suffered from at least one micronutrient deficiency. The most prevalent micronutrient deficiencies were vitamin D (16.1%) and zinc (25.5%). There were no statistically significant differences in prevalence of micronutrient deficiency stratified by AIP subtype. The prevalence of PEI and of at least one relapse were significantly higher in patients with micronutrient deficiencies than in those without (92.1% vs 69.4%, p = 0.01 for PEI, and 52.6% versus 27.4%, p = 0.02 for relapse). Interestingly, the prevalence of pancreatic enzyme replacement therapy (PERT) was also higher in patients with any micronutrient deficiency compared to in patients with no deficiencies 34 (89.5%) vs 40 (64.5%), p=0.01. Relapse was observed in 37% of the AIP patients. The odds for relapse were 2.9 (1.26-6.86, p=0.02), 2.71(1.36-5.41, p=0.006) and 3.38 (1.09-10.55, p=0.04) times higher in patients with any deficiency, zinc deficiency and vitamin D deficiency, respectively, compared to in non-deficient patients. However, after stratifying for AIP type 1 and adjusting for PEI and elevated IgG4 levels, this association ceased to be statistically significant.

Conclusion

Zinc and vitamin D deficiencies may be common in patients with AIP indicating that these micronutrients might play a role in the natural course of AIP probably as a result of delicate interplay between disease burden, disease severity and the consequent destruction of the gland. Importantly, any micronutrient deficiency may be prevalent even in the light of treated PEI which emphasizes the potential of micronutrients as an additional tool in the workup and follow-up of AIP patients. More studies are warranted to ascertain our findings.

References

Wessels I, Rink L. Micronutrients in autoimmune diseases: possible therapeutic benefits of zinc and vitamin D. J Nutr Biochem. 2020;77:108240.
Löhr JM, Vujasinovic M, Rosendahl J, Stone JH, Beuers U. IgG4-related diseases of the digestive tract. Nat Rev Gastroenterol Hepatol. 2022;19(3):185-97.
Sanna A, Firinu D, Zavattari P, Valera P. Zinc Status and Autoimmunity: A Systematic Review and Meta-Analysis. Nutrients. 2018;10(1)

Introduction

Pancreatic cancer (PC) screening can improve survival in high-risk patients by detecting preneoplastic lesions or early-stage tumors.
Surveillances is mainly based on annual magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). However, little has been described regarding the possibility of finding other morphological changes that may be also important.

Aims & Methods

The aim of the study is to evaluate all the findings described in screening test and to analyze the correlation between these two screening techniques.
Descriptive observational single-center study that includes high-risk PC patients either due to family history (familial pancreatic cancer) or because they belong to hereditary syndromes, who have been undergone pancreatic cancer screening at our center from 2015 to 2023. Demographic variables and findings described in the EUS or MRI were collected.

Results

Thirty-five patients were included, with a mean age of 57.3 ± 8.2 years and a predominance of females (65.7%). Four patients (11.4%) were smokers, two were diabetic (5.7%), and one had a history of chronic pancreatitis (2.9%). The median follow-up time was 23 months (interquartile range 8-59 months).
The most frequent hereditary syndrome was hereditary breast and ovarian cancer syndrome (n=19, 54.3%), followed by familial atypical multiple mole melanoma syndrome (n=4; 11.4%). The BRCA2 mutation was the most common identifiable genetic factor (34.8%).
Regarding screening test findings, solid tumors were detected in three patients (8.6%) (Two stage I and IV adenocarcinomas and one stage I neuroendocrine tumor). In two individuals (5.7%) branch-duct intraductal papillary mucinous neoplasm were observed. Other pancreatic abnormalities were detected in 18 patients (51.4%) that include chronic pancreatitis-like parenchymal changes (34.3%), peripancreatic lymph nodes and fatty pancreas (5.7%). Finally, in 12 patients (34.3%) the screening tests were normal.
In relation to the concordance between MRI and EUS, in ten patients (28.6%) there was no agreement between these two techniques. EUS detected more parenchymal changes (n=5), pancreatic steatosis (n=2) and one neuroendocrine tumor that were not described on MRI. In contrast, MRI detected a cystic lesion and a pseudonodular enhancement that were not found on EUS.

Conclusion

Pancreatic cancer screening in high-risk individuals, detects neoplastic and preneoplastic lesions at a high rate.
Other findings, such as chronic pancreatitis-like parenchymal changes, peripancreatic lymph nodes or fatty pancreas, were also common in these patients
MRI and EUS have a good correlation, but EUS detects more parenchymal changes.

References

1. Goggins M, Overbeek KA, Brand R et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut 2020; 69 (1): 7-17
2. Bogdanski AM, van Hooft JE, Boekestijn B, Bonsing BA, Wasser MNJM, Klatte DCF, van Leerdam ME. Aspects and outcomes of surveillance for individuals at high‑risk of pancreatic cancer. Fam Cancer 2024; 23(3):323-339.
3. Blackford AL, Canto MI, Dbouk M, Hruban RH, Katona BW, Chak A et al. Pancreatic Cancer Surveillance and Survival of High-Risk Individuals. JAMA Oncol. 2024;10(8):1087-1096.
4. Maurer E, Lehman B, Matthäi E, Denzer U, Figiel J, Jseinghaus M et al. Pancreatic cancer screening is effective in individuals at risk with predisposing germline gene variants, but not in gene variant‐negative familial pancreatic cancer families. United European Gastroenterol J 2024; 12 (9): 1211-1221

Introduction

Lynch syndrome (LS) represents the most prevalent hereditary colorectal cancer (CRC) syndrome, with approximately one in 279 individuals in the general population believed to carry a pathogenic variant. This autosomal dominant condition results from germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM). In addition to colorectal cancer, LS encompasses various extracolonic malignancies, such as gastric carcinoma (lifetime risk of 13%) and small bowel cancer (lifetime risk of 8%). Both German and current NCCN guidelines advise upper GI screening using esophagogastroduodenoscopy (EGD) every 2-4 years. However, standard EGD screening often misses lesions in the jejunum, where up to one third of small bowel cancers occur. Consequently, we sought to determine the frequency of jejunal lesion detection with push enteroscopy employing a colonoscope and whether this method maintains the overall diagnostic quality.

Aims & Methods

Patients with a proven pathogenic mutation in a DNA mismatch repair gene were included in a surveillance program at our National Center of Hereditary Tumor Syndromes, where all patients are followed prospectively after signing an informed consent. We assessed endoscopic findings using standard esophagogastroduodenoscopy (EGD) compared to push enteroscopy using a pediatric colonoscope at our center. We implemented the routine use of push enteroscopy in August 2022. The same endoscope was used for the following colonoscopy. Results of endoscopy, histopathology, affected gene were compared.

Results

Between April 2013 and July 2022, a total number of 445 EGDs were performed in 187 patients (range 1-7; 108 (58%) female; median age at endoscopy 48 years), all carrying a pathogenic MMR gene variant (66 MLH1 (35.5%); 86 MSH2 (46%); 25 MSH6 (13%); 9 PMS2 (5%); 1 Epcam (0.05%)).
Between August 2023 and April 2023, a total number of 103 push enteroscopies using a colonoscope were performed in 103 carriers of a pathogenic MMR gene variant (54 (52%) female; median age at endoscopy 48 years; 38 MLH1 (37%); 46 MSH2 (45%); 11 MSH6 (11%); 4 PMS2 (4%); 1 Epcam (1%); 3 MLH1 and MSH2 (3%)).
Using standard EGD, Barrett esophagus was detected in 23 (5%) patients, with three patients exhibiting high-grade dysplasia, whereas push enteroscopy identified Barrett's esophagus in 4 (4%) patients and revealed one case of eosinophilic esophagitis. Helicobacter pylori infection was found in 21 (5%) and 4 (4%) cases, respectively. Intestinal metaplasia was detected in 49 (11%) patients with standard EGD and 23 (22%) patients with push enteroscopy, both revealing one case (MLH1) with dysplasia. Neoplastic and preneoplastic lesions observed included gastric cancer (5; 1%), gastric adenomas (7; 1.6%), duodenal cancer (3 duodenal, 2 ampullary cancers; 1%), and duodenal adenomas (8; 1.8%) with standard EGD, while no neoplastic lesions were found using push enteroscopy. However, push enteroscopy enabled the detection of three jejunal adenomas, including two advanced adenomas.

Conclusion

This prospective endoscopic study demonstrates that monitoring the upper gastrointestinal (GI) tract in Lynch syndrome (LS) patients yields clinically significant findings for a considerable proportion of individuals. The application of push enteroscopy does not impede the identification of pertinent lesions. Notably, we observed an increased detection rate of gastric intestinal metaplasia using this technique.