Introduction

Recent reports have evaluated the difficult biliary cannulation (DBC) during endoscopic retrograde cholangiopancreatography (ERCP) based on the shape of the papilla ¹⁾²⁾. However, it is more important to elucidate how the difficulty of biliary cannulation changes depending on the morphology of the papilla. We performed a morphological evaluation to investigate the causes of DBC during ERCP, including the relationship between the shapes of the papilla and intra-ampullary pancreaticobiliary bifurcations (IAPBs).

Aims & Methods

We prospectively established a database and retrospectively assessed the difficulty of selective biliary cannulation (SBC) with contrast-assisted cannulation (CAC) during ERCP, in which any morphological IAPBs are visualized. In all cases, both the bile and pancreatic ducts were cannulated or imaged in a naïve major duodenal papilla. The database included papilla shapes with Haraldsson's classification of Type 1-Type 3, the number of papillary orifices classified as Mono or Dual. The IAPBs were classified into four types based on their branching angle (Figure V for acute branching, Figure T for perpendicular branching, Figure X for orifice of bile duct located just above the papillary orifice inside, and​ pancreaticobiliary maljunction classified as Figure I). In addition, small intra-ampullary cysts (choledochocele, IAC) were classified into three types based on their location: the common channel (Ac) type, equivalent to Elton's dilated common channel syndrome ³⁾;, the bile duct (Ab) type, including a cyst within the papilla; and the common bile duct (CBD) type, corresponding to Alonso Lej type III. DBC was defined as cannulation longer than 5 minutes, and when guidewire placement in the pancreatic duct (P-GW) was attempted to facilitate SBC. We conducted a logistic regression analysis to investigate the association among the anatomical morphology of the papilla, the variation of IAPBs, and the presence of IAC.

Results

We analyzed a database of 1,700 consecutive cases. The shape of papilla Type 1 was found in 621 (36.5%), Type 2 in 82 (4.8%), and Type 3 in 997 cases (58.6%). Mono orifice was confirmed in 1,192 cases (70.1%), and P-GW was performed in 709 cases (41.7%). IAC was observed in 203 cases (11.9%). The odds ratio (OR) for DBC in relation to papilla morphology was analyzed with Type 1 as the reference. The OR for Type 2 was 1.9 (95% confidence interval [CI], 1.5-3.0) (p=0.07), and for Type 3, it was 1.7 (95% CI, 1.3-2.1) (p<0.01). In the analysis of the number of orifices, the OR was calculated with Dual as the reference. Mono was 2.5 (95% CI, 2.0-3.2) (p<0.01). In the analysis of IAPBs, the ORs were calculated with Dual as the reference. The ORs for Figures V, T, X and I were 1.6 (95% CI, 1.2–2.1) (p<0.01), 2.4 (95% CI, 1.7–3.2) (p<0.01), 5.1 (95% CI, 3.8–7.0) (p<0.01) and 0.6 (95% CI, 0.3–1.4) (p=0.39), respectively. In the analysis of IAC, the ORs were calculated with the absence of IAC as the reference. The ORs for Ac, Ab and CBD were 1.3 (95% CI, 0.9–2.0) (p=0.17), 1.5 (95% CI, 0.9–2.6) (p=0.14), and 0.6 (95% CI, 0.3–1.4) (p=0.23), respectively. When the shape of papilla was Type 3 and had a Mono orifice with IAPBs of Figures V, T, or X, the difficulty of SBC significantly increased.

Conclusion

Our study suggests that morphological DBC depends not only on the shape of the major duodenal papilla, but also on the number of orifices, the type of IAPBs, and the presence of IAC. Sometimes, IAPBs can exhibit unexpected bifurcations that make SBC difficult. To overcome this difficulty, it is important to perform SBC using CAC to confirm IAPBs.

References

1) Haraldsson E et al, Macroscopic appearance of the major duodenal papilla influences bile duct cannulation: a prospective multicenter study by the Scandinavian association for digestive endoscopy study group for ERCP. Gastrointest Endosc 2019;90:957–963
2) Rachid Mohamed et al, Morphology of the major papilla predicts ERCP procedural outcomes and adverse events; Surg Endosc. 2021 December ; 35(12): 6455–6465
3) E Elton et al, Dilated Common Channel Syndrome: Endoscopic Diagnosis, Treatment, and Relationship to Choledochocele Formation Gastrointest Endosc. 1998 ;47:471-8.

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

Clinical Case Summary

In advanced chronic liver disease (ACLD) patients, the endoscopic evidence of esophageal and/or gastric varices denotes the presence of clinically significant portal hypertension (CPSH), representing the main clinical consequence of portal hypertension (PH).
In this setting, although infrequently, besides typical sites (i.e., esophagus and stomach), PH-related varices can manifest even in other atypical portosystemic-shunt districts, including the vagina. CSPH-related vaginal varices bleeding can occur as a rare complication documented by limited case reports.
A 62-year-old female patient with viral (eradicated Hepatitis C Virus infection)-related- decompensated (grade 2 ascites)-ACLD, complicated by CSPH (grade F2 esophageal varices), was admitted to our Department in February 2025 for microcitic anemia. Anamnesis revealed a previous gastric cancer managed with total gastrectomy resection in 2021.
On admission, abdominal imaging showed radiological signs of ACLD/PH (coarse pattern, splenomegaly, dilated splenic-portal axis). Esophagogastroduodenoscopy ruled out active sources of bleeding, whereas colonoscopy revealed anal congestive not-bleeding varices. During the hospitalization, an episode of metrorrhagia imposed gynecologic evaluation with vaginal speculum examination. This assessment documented vaginal varices with the relative rupture as the current cause of the bleeding, suggesting this site is the further district for (CS)PH manifestation consequently to potentially occurred total gastrectomy-determined changes in abdominal vascular anatomy.
In ACLD patients receiving surgery altering abdominal vascularization, variceal bleeding represents a possible CSPH-related complication occurring even in atypical sites, such as the vagina. This scenario imposes an adequate tailored management, monitoring unusual bleeding signs, and adopting appropriate preventive strategies by including gynecologic evaluation in follow-up.

References

1. McHugh PP, Jeon H, Gedaly R, Johnston TD, Depriest PD, Ranjan D. Vaginal varices with massive hemorrhage in a patient with nonalcoholic steatohepatitis and portal hypertension: Successful treatment with liver transplantation. Liver Transpl. 2008 Oct;14(10):1538-40. doi: 10.1002/lt.21506. PMID: 18825698.
2. Kreek MJ, Raziano JV, Hardy RE, Jeffries GH. Portal hypertension with bleeding vaginal varices. Ann Intern Med. 1967 Apr;66(4):756-9. doi: 10.7326/0003-4819-66-4-756. PMID: 6067181.
3. Chan G, Taqi A, Drage M, Quan D. A case report of massive vaginal variceal hemorrhage in a patient with cirrhosis secondary to nonalcoholic steatohepatitis unresolved even after successful liver transplantation. Transplant Proc. 2013 Mar;45(2):835-7. doi: 10.1016/j.transproceed.2012.04.033. Epub 2012 Sep 19. PMID: 23267803.
4. Lebrec D, Benhamou JP. Ectopic varices in portal hypertension. Clin Gastroenterol. 1985 Jan;14(1):105-21. PMID: 3872747.
5. Nagata J, et al. Vaginal bleeding in a patient with type C liver cirrhosis without a past history of laparotomy: successful treatment with partial splenic artery embolization. Clin J Gastroenterol. 2012 Aug;5(4):275-81. doi: 10.1007/s12328-012-0316-3. Epub 2012 Jun 30. PMID: 26182393.

Clinical Case Summary

Although liver involvement is common in leukemia, acute hepatitis as its initial presentation is rare. This case highlights the diagnostic challenge of distinguishing reactive hematological changes from underlying malignancies in patients with unexplained hepatitis.
A 35-year-old woman presented in February 2024 with myalgias, fever with chills (38°C), jaundice, and right upper quadrant discomfort. Relevant history included recent intake of herbal supplements (vitamin C, zinc, echinacea, elderberry).
Initial laboratory findings showed leukocytosis, lymphocytosis (25%), monocytosis (12%), blasts (3%), thrombocytopenia (136×10⁹/L), and abnormal liver tests (AST 448 U/L, ALT 686 U/L, ALP 242 U/L, GGT 147 U/L, total bilirubin 4.14 mg/dL, direct bilirubin 2.9 mg/dL), with normal INR. Peripheral blood smear revealed mononuclear pleomorphism and lymphocytes with prominent nucleoli. Abdominal computed tomography showed moderate hepatomegaly without biliary or vascular abnormalities. Comprehensive testing for infeccious, autoimmune and metabolic causes was negative.
Liver tests improved and leukocytosis turned into leukopenia. Repeat blood smear was deemed reactive by Hematology. She was discharged and in early March re-evaluation, liver parameters normalized and leukopenia improved.
Later that month, she returned with fever, night sweats, and abdominal pain. Laboratory findings showed recurrent cytopenias and cytocholestasis. Blood smear revealed increasing blast count, and immunophenotyping suggested monoclonality. Bone marrow and liver biopsy confirmed B-cell acute lymphoblastic leukemia (ALL) with hepatic infiltration.
This case illustrates an unusual presentation of ALL as relapsing acute hepatitis. It reinforces the need to consider hematological malignancy in cryptogenic hepatitis, particularly when associated with evolving hematological changes. Serial blood smears, immunophenotyping, and timely bone marrow evaluation are essential to avoid diagnostic delay.

References

1. Hepatic biopsy: clusters of intermediate to large cells expressing TdT, CD20, PAX5, CD10, BCL6, CD43.
2. Bone marrow aspirate: 64% blasts, CD10+, CD20+ (strong homogeneous expression).
3. Bone marrow biopsy: increased cellularity due to diffuse interstitial infiltration by intermediate cells with blast-like morphology and lymphoid immunophenotype (TdT+, CD34+, MPO-, CD20+).

Clinical Case Summary

Intra-ampullary papillary tubular neoplasms (IAPNs) are rare neoplastic intraepithelial lesions that occur within the ampulla. Given their well-documented malignant potential, early recognition and intervention are paramount to prevent malignant transformation. We present a case of IAPN successfully managed via endoscopic papillectomy.
A 58-year-old male was incidentally found to have a bulky-appearing ampulla of vater during esophagogastroduodenoscopy as part of routine health screening. Endoscopic ultrasonography revealed a 20-mm hyperechoic lesion at the ampulla, with histopathological evaluation demonstrating low-grade dysplasia (indeterminate for neoplasia). Laboratory investigations, including hematological parameters, biochemical profiles, and tumor markers, were within normal limits. Contrast-enhanced abdominal CT demonstrated a well-defined, homogeneously enhancing 20-mm lesion at the ampullary region without biliary/pancreatic duct dilation.
Endoscopic papillectomy was performed using a duodenoscope with snare. Prophylactic stents were placed in both the biliary and pancreatic ducts to ensure adequate drainage. Any intraprocedural bleeding was promptly controlled with hemoclip application. Histopathological analysis confirmed high-grade IAPN, characterized by a polypoid tumor with closely packed tubular glands lined by pseudostratified columnar epithelium showing loss of polarity and moderate nuclear atypia (Ki-67 index: 50%). The postoperative course was uncomplicated, with discharge achieved on the sixth postoperative day. At six-month follow-up evaluation, surveillance endoscopic ultrasonography showed no evidence of recurrence.
IAPN represents a distinct neoplastic ampullary entity within the spectrum of ampullary tumors. While endoscopic resection demonstrates therapeutic efficacy, its implementation requires advanced endoscopic expertise in specialized centers.

References

Endoscopic ultrasonography revealed a 20-mm hyperechoic lesion at the ampulla
Endoscopic papillectomy was performed using a duodenoscope with snare. Prophylactic stents were placed in both the biliary and pancreatic ducts to ensure adequate drainage. Any intraprocedural bleeding was promptly controlled with hemoclip application.
Histopathological analysis confirmed high-grade IAPN, characterized by a polypoid tumor with closely packed tubular glands lined by pseudostratified columnar epithelium showing loss of polarity and moderate nuclear atypia (Ki-67 index: 50%).