Clinical Case Summary

Immunotherapy with checkpoint inhibitors (CPI) has transformed oncology management, achieving durable remissions. However, its widespread has also led to significant immune-mediated side effects, whose treatment is a challenge in today's medicine.
We present the case of a 59-year-old man diagnosed with non-small-cell lung cancer who started treatment with Nivolumab(anti-PD1). After 6 months, the patient was admitted for 3 weeks diarrhoea(4 liquid stools/day).
A colonoscopy was done, identifying severe pancolitis with oedema, erythema, nodularity and superficial ulcers. PA revealed diffuse non-specific colitis with CMV IHC -. Given the suspicion of immune-mediated colitis vs de novo IBD, treatment was started with iv GCC, with no improvement.
Given the contraindication of long-term use of anti-TNF in IBD patients with active malignancies, induction with IV Ustekinumab (anti-IL12/23) was decided. Ustekinumab 390 mg iv was given, after which the patient showed clinical improvement until complete resolution. He continued with Ustekinumab 90 mg/8 weeks. A follow-up colonoscopy showed pancolic scarring with pseudopolyps and no inflammatory activity. Given these findings Ustekinumab was discontinued after 1 year, with the patient remaining asymptomatic and without oncologic progression.
Immune-mediated colitis is a common side effect, being mild in most cases. When severe cases occur, CPI should be discontinued indefinitely, and high-dose iv GCC (up to 2 mg/kg) should be initiated. Up to one-third of GCC-treated patients don't respond and are candidates for immunosuppressive therapy with biologic drugs.
Although clinical guidelines recommend Infliximab/Vedolizumab for induction as 2º line treatment, the therapeutic decision should be individualized, as they are contraindicated in IBD patients with active malignancies. Therefore, in this context of complex differential diagnosis, Ustekinumab (with lower rate of oncological side effects) appears to be an effective option.

References

Photo 1: Initial colonoscopy: severe pancolitis with erythema, oedema, superficial ulcers and mucosal nodularity.
Photo 2: Abdominal CT: Diffuse thickening of the colon with increased uptake of the wall.
Photo 3: Follow-up colonoscopy: Chronic scar changes without signs of acute activity.

Clinical Case Summary

An 80-year-old man, with no history of alcohol or tobacco use, presented with a six-month history of oral mucosal erosions, odynophagia, dysphagia, dysphonia, and a significant weight loss. Physical examination revealed an abdominal mass. A CT and MRI showed a normal sized liver with regular contours and a large nodular hepatic lesion suggestive of hepatocellular carcinoma (HCC), along with two small satellite nodules and one large lymphadenopathy at the hepatic hilum. Labs showed elevated -fetoprotein levels of 190 ng/mL. He was referred to Hepatic Oncology and underwent an ultrasound-guided biopsy of the liver lesion, confirming well-differentiated HCC. The patient also developed erythematous-brown scaly plaques on the trunk and limbs. A skin biopsy was performed, and along with clinical and serological findings, confirmed the diagnosis of paraneoplastic pemphigus. High-dose Prednisolone was started and led to partial improvement. Two cycles of IVIG followed, with significant remission of skin lesions. He also began Sorafenib for HCC. After six months, follow-up imaging showed progression of the hepatic lesion, as well as tumor seeding in the thoracic wall along the needle tract of the liver biopsy. Treatment was escalated to Regorafenib, which was discontinued after two months. He died 16 months after diagnosis ,from traumatic brain injury. Paraneoplastic pemphigus is a rare autoimmune disease typically linked to hematologic cancers, with only four cases of associations with HCC described in the literature. This rare combination limits treatment options, particularly immune checkpoint inhibitors. In this case, immunosuppression may have impaired antitumor immunity, contributing to rapid tumor progression and biopsy needle tract dissemination.

References

1. Hinterhuber, G., Drach, J., Riedl, E., Böhler, K., Ferenci, P., Wolff, K., & Foedinger, D. (2003). Paraneoplastic pemphigusin associationwith hepatocellular carcinoma. Journal of the American Academy of Dermatology, 49(3), 538–540.
2. Yokokura, H., Demitsu, T., Kakurai, M., Umemoto, N. et al (2006). Paraneoplastic pemphigus mimicking erosive mucosal lichen planus associatedwith primary hepatocellular carcinoma. The Journal of dermatology, 33(12), 842–845.
3. Jang, M., Lee, K., Han, S., Park, J., Lee, J., Suh, K. (2014). Paraneoplastic Pemphigus Associated with Hepatocellular Carcinoma. Korean Journal of Dermatology,34-39.
4. Muramatsu, T., Matsumoto, H., Yamashina, Y., Shirai, T., & Sakamoto, K. (1989). Pemphigus foliaceus associated with acanthosis nigricans-like lesions and hepatocellular carcinoma. International journal of dermatology, 28(7), 462–463.
5. Schaffler-Schaden, D., Birsak, T., Zintl, R., Lorber, B., & Schaffler, G. (2020). Risk of needle tract seeding after coaxial ultrasound-guided percutaneous biopsy for primary and metastatic tumors of the liver: report of a single institution. Abdominal radiology (New York), 45(10), 3301–3306.
7. Decaens, T., Roudot-Thoraval, F., Bresson-Hadni, S., Meyer, C. et al (2006). Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma: a multicenter study of 412 patients. World journal of gastroenterology, 12(45), 7319–7325.

Introduction

Difficult biliary stones and complex bile duct anatomy often limit the efficacy of endoscopic sphincterotomy (EST) alone. Dilation-Assisted Stone Extraction (DASE), involving large balloon dilation following EST, has emerged as a complementary technique to improve stone clearance. This study aimed to evaluate the safety and effectiveness of DASE performed either after primary EST in patients with naïve papilla or as a rescue strategy following prior EST.

Aims & Methods

A retrospective review was conducted on all patients who underwent DASE between January 2018 and December 2024 at the Department of Gastroenterology and Digestive Endoscopy, Mohammed VI University Hospital, Marrakech, Morocco. Inclusion criteria comprised patients with naïve or previously treated papilla undergoing DASE for bile duct clearance. Technical success was defined as successful balloon placement across the papilla, full inflation to target diameter for >30 seconds, followed by complete stone extraction. Complications were categorized as intraprocedural, early (<24 hours), or delayed (>24 hours).

Results

A total of 57 patients were included (mean age 72.5 ± 12.1 years; 30 females [52.6%], 27 males [47.4%]). Thirty-five patients (61.4%) had a naïve papilla, and 22 (38.6%) had prior EST. Main indications for DASE included large or impacted CBD stones (63.2%), periampullary diverticulum (15.8%), difficult cannulation (12.3%), altered anatomy (5.3%), and other causes (3.5%).
Technical success was achieved in 55 patients (96.5%). Thirteen patients (22.8%) experienced complications: 7 (53.8%) intraprocedural, 4 (30.8%) early, and 2 (15.4%) delayed.
Adverse events included:

• Bleeding in 8 patients (61.5% of all complications): 4 self-limited (50%), 3 endoscopically managed (37.5%), and 1 required radiological embolization (12.5%).
• Post-ERCP pancreatitis (PEP) in 4 patients (30.8%): all mild, resolved with conservative management.
• Perforation in 1 patient (7.7%): managed successfully with endoscopic clipping and supportive care.

Conclusion

DASE following EST is a highly effective and relatively safe approach for managing difficult CBD stones, with a high technical success rate and acceptable complication profile. The results support its routine use in therapeutic endoscopy, particularly for cases refractory to EST alone. Prior EST may be associated with a higher risk of adverse events and should prompt careful intra- and post-procedural monitoring.

References

- Zhang Q, Shen H, Zhang Y, Ding Y, Zhang X, Wang L.
Dilation-assisted stone extraction versus mechanical lithotripsy for large bile duct stones: a systematic review and meta-analysis. Endoscopy. 2021;53(5):454–463.
- Liao WC, Angsuwatcharakon P, Isayama H, Dhir V, Devereaux B, Khor CJL, et al.
International consensus recommendations for difficult biliary access.
Gastrointest Endosc. 2017;85(2):295–304.
- Tringali A, Familiari P, Perri V, Boskoski I, Mutignani M, Costamagna G.
Endoscopic papillary large balloon dilation with sphincterotomy for the treatment of difficult common bile duct stones: outcomes, complications, and rates of stone recurrence.
Surg Endosc. 2020;34(11):4912–4920.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the most common neoplastic disease of the pancreas with a high mortality rate due to late diagnosis at an advanced stage for its asymptomatic progression. Chronic pancreatitis, one of the risk factors for the development of PDAC, complicates the diagnostic process as both conditions sometimes share overlapping clinical and pathological features. Identifying individuals at higher risk of developing the disease and detecting pancreatic cancer at an early, curable stage is critical to improving overall patient outcomes. This study investigates the potential of relative telomere length (RTL) in peripheral blood and microbiome composition as biomarkers for PDAC. These biomarkers could support a minimally invasive liquid biopsy approach for early diagnosis of PDAC, differentiation from chronic pancreatitis, and screening of high-risk individuals.

Aims & Methods

A total of 239 participants were enrolled in the study and were divided into four groups: patients with PDAC (n = 36), chronic pancreatitis (n = 60), type II diabetes mellitus (n = 91) and cancer-free individuals (n = 52). Peripheral blood samples were collected to estimate relative telomere length using the multiplex monochrome qPCR method. Stool samples from a subset comprising chronic pancreatitis patients (n = 13), PDAC patients (n = 12), and healthy controls (n = 7) were analysed using 16S rRNA sequencing for metataxonomic analysis of the gut microbiome.

Results

Microbiome analysis revealed dysbiosis in a subset of patients, with an overrepresentation of bacterial species such as Prevotella copri and Akkermansia muciniphila in chronic pancreatitis and PDAC patients. A trend towards reduced microbial diversity was observed in PDAC patients, with changes in bacterial composition already detectable in chronic pancreatitis patients. No significant differences were found in RTL between the PDAC and cancer-free patient groups, and the only risk factors associated with changes were age, gender and smoking.

Conclusion

The pilot findings suggest a general trend towards reduced microbial diversity in PDAC patients, with alterations in bacterial proportions already observed in individuals diagnosed with chronic pancreatitis. These data ptovide a basis for the development of non-invasive diagnostic strategies to improve early detection and clinical outcomes for patients with PDAC. However, relative telomere length has not been shown to be a reliable biomarker.

References

Wu H, Zou WB, Zhou DZ, Gu YT, Liao Z, Li ZS. Longer Leukocyte Telomere Length is Associated With an Increased Risk of Chronic Pancreatitis. Pancreas. 2017;46(8):e65-e66. doi:10.1097/MPA.0000000000000887
Riquelme E, Zhang Y, Zhang L, et al. Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell. 2019;178(4):795-806.e12. doi:10.1016/j.cell.2019.07.008
Antwi SO, Petersen GM. Leukocyte Telomere Length and Pancreatic Cancer Risk: Updated Epidemiologic Review. Pancreas. 2018;47(3):265-271. doi:10.1097/MPA.0000000000000995
Campa D, Felici A, Corradi C, et al. Long or short? Telomere length and pancreatic cancer and its precursor lesions, a narrative review. Mutagenesis. 2025;40(1):39-47. doi:10.1093/mutage/gead034
Sexton RE, Uddin MH, Bannoura S, et al. Connecting the Human Microbiome and Pancreatic Cancer [published correction appears in Cancer Metastasis Rev. 2022 Jun;41(2):333. doi: 10.1007/s10555-022-10037-3.]. Cancer Metastasis Rev. 2022;41(2):317-331. doi:10.1007/s10555-022-10022-w