Clinical Case Summary

Approximately 20% of patients with Ulcerative Colitis (UC) develop Acute Severe UC (ASUC), for which intravenous systemic steroid therapy and possibly Infliximab-based rescue therapy is generally imposed. However, there are no significant guideline recommendations on ASUC regarding Vedolizumab as an alternative to Infliximab. A 56-year-old male, non-obese, past smoker, with steroid-dependent UC on therapy with mesalazine and therapeutic-targeted azathioprine developed ASUC induced by second-line chemotherapy (for development of colitis pembrolizumab-induced by immunotherapy set in the first line) with gemcitabine plus carboplatin for treatment of recurrence of right pleomorphic lung carcinoma with lower lobe involvement as well as lymph node to hilar and paratracheal sites (primary tumor, G3, arising on the left lung and treated with left pneumectomy). Treatment with intravenous methylprednisolone was imposed; however, there was no reduction in bowel movements in the days following admission. Rescue therapy with Infliximab was contraindicated because of the oncologic history. Surgical consultation contraindicated colectomy and abdomen computerized tomography showed no megacolon. Administration of Vedolizumab 300 mg was initiated. After infusion with Vedolizumab, there was a significant reduction in bowel movements starting the day after infusion until normalization of bowel movements within three days and the concomitant normalization of inflammatory indices. Enteral feeding was reintroduced since parenteral nutrition was set up in the previous days under clinical nutritionist consultation with customized nutritional bags. The patient is currently in clinical remission and on therapy with Vedolizumab 108 mg subcutaneously every two weeks and is in oncologic follow-up for pulmonary neoplasm. This case highlights a novel potential of Vedolizumab as a possible rescue therapy in ASUC, especially in special populations, where it may offer a better safety profile.

References

- Sedano R, Quera R, Simian D, et al. An approach to acute severe ulcerative colitis. Expert Rev Gastroenterol Hepatol. 2019;13:943–955.
- Spinelli A, Bonovas S, Burisch J, Kucharzik T, Adamina M, Annese V, Bachmann O, Bettenworth D, Chaparro M, Czuber-Dochan W, Eder P, Ellul P, Fidalgo C, Fiorino G, Gionchetti P, Gisbert JP, Gordon H, Hedin C, Holubar S, Iacucci M, Karmiris K, Katsanos K, Kopylov U, Lakatos PL, Lytras T, Lyutakov I, Noor N, Pellino G, Piovani D, Savarino E, Selvaggi F, Verstockt B, Doherty G, Raine T, Panis Y. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment. J Crohns Colitis. 2022 Feb 23;16(2):179-189.
- Choy MC, Seah D, Faleck DM, et al. Systematic Review and Meta-analysis: Optimal Salvage Therapy in Acute Severe Ulcerative Colitis. Inflamm Bowel Dis. 2019;25:1169–1186.
- Bonovas S, Fiorino G, Allocca M, et al. Biologic Therapies and Risk of Infection and Malignancy in Patients With Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis. Clin Gastroenterol Hepatol. 2016;14:1385-1397.e10.

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.

Introduction

Currently, non-alcoholic liver disorder (NAFLD) is the most predominant chronic liver disorder. NAFLD has been linked to hepatic and extra-hepatic morbidities. The need for non-invasive prediction of hepatic and extra-hepatic consequences of NAFLD is a demand, due to the complexity of the disease, high burden, and the need for early intervention.

Aims & Methods

to investigate the role of serum microRNA-130b and liver stiffness [as measured by acoustic radiation force impulse (ARFI)], to non-invasively predict chronic kidney disease (CKD) in NAFLD patients.
Patients and Methods: In a case-control design, we included 40 NAFLD patients (20 NAFLD with CKD, and 20 NAFLD without CKD), and 20 healthy controls. After clinical evaluation, laboratory assessments including liver test profile, renal function test, and quantification of microRNA-130b were done. Liver stiffness was evaluated using ARFI.

Results

The median values (interquartile range “IQR”) of mRNA-130b in patients with NAFLD+CKD, patients with NAFLD without CKD, and healthy subjects were [32.10 (27.3 -37.3), 27.01 (24.8 – 31.7), and 25.36 (23.5 – 27.1), copies/µl, respectively, P <0.001]. The median (IQR) value of Liver stiffness as measured by ARFI was significantly higher among NAFLD with CKD patients compared to NAFLD without CKD [2.97 (2.87 – 3.3) vs. 2.45 (2.18 – 2.8) m/sec, P = 0.002]. The median (IQR) value of microRNA-130b was significantly higher among NAFLD with CKD patients compared to NAFLD without CKD [P = 0.032]. In the current study, ARFI readings were negatively correlated with platelet count (n = 40, rs = -0.33, P = 0.038). ARFI readings were positively correlated to serum mRNA-130b values in both groups (rs = 0.49, P = 0.02 and rs = 0.64, P = 0.002, respectively). At a cut-off value > 28.13 copies/µl, microRNA-130b could differentiate between “NAFLD with CKD” and “NAFLD without CKD” patients with a sensitivity and specificity of 75%, and 70 %, respectively (AUC = 71.9 %, P = 0.018, 95% CI: 0.56 – 0.87). Similarly, At a cut-off value > 2.81 m/sec, ARFI could differentiate between “NAFLD with CKD” and “NAFLD without CKD” patients with a sensitivity and specificity of 80% (AUC = 77.8 %, P = 0.003, 95% CI: 0.62 – 0.93).

Conclusion

MicroRNA-130b and liver stiffness measurements are suggested as potential markers for the prediction of CKD among NAFLD patients. Serum microRNA-130b, and ARFI are valuable non-invasive tools for the assessment of NAFLD severity.

Clinical Case Summary

Introduction: Demodicosis is a disease of the pilosebaceous unit, involving mainly face and head areas, caused by Demodex mites.
It can be seen in primary or secondary forms (Chen and Plewig). Secondary demodicosis is defined as skin lesions associated with an abnormal increase of Demodex mites due to skin or systemic diseases. It occurs significantly in immunosuppressed patients with leukaemia, human immunodeficiency virus infection or those being treated with topical or systemic immunosuppressants.
We report the case of a patient treated for Crohn's disease with Infliximab who developed Demodicosis.
Case report: A 26-year-old man, with 4 years history of stricturing ileo-caecal Crohn’s for which he had an ileo-caecal resection with an ileo-colic anastomosis, and perianal fistula treated by seton placement and antibiotics.
Subsequently, Infliximab treatment was initiated at a dose of 5mg/kg every 8 weeks.1 year into the treatment, the patient experienced pruritus, redness and dryness of the cheeks leading to a referral for a dermatology consultation.
Physical examination revealed skin xerosis, scaly erythematous plaques around the periphery, circinate on the forearm and facial erythema.
At polarized-light dermoscopy of the facial lesions, Demodex tails with Demodex follicular openings and telangiectasias were observed.
The diagnosis of demodicosis was made and the patient was treated with oral doxycycline (100mg/day), and a topical cream based on sertaconazole with noticeable improvement .
Conclusion: Demodicosis should be taken into account in patients treated with biological medications and presenting atypical inflammatory skin lesions.

References

1. Chen W, Plewig G. Human demodicosis: revisit and a proposed classification. Br J Dermatol 2014; 170: 1219-25.
2. CORDAN YAZICI A, Güliz İKİZOĞLU G. Demodicosis. Turkiye Klinikleri J Med Sci. 2019;39(2):231-6

Introduction

Hepatocellular Carcinoma (HCC) is a major type of primary liver cancer and one of the most frequent human malignant neoplasm. Owing to the lack of reliable clinical HCC markers, fewer than 20% of patients are diagnosed at a stage where curative treatment can be performed. It is now clear that microRNAs (miRNAs) can potentially regulate every aspect of cellular activity, including differentiation and development and proliferation; they play a role in regulating apoptotic cell death and tumorigenesis. MiRNA‑192 is hepatocyte‑specific miRNA and it is released from damaged hepatocytes early in liver injury in animal models have made miRNA‑192 an attractive biomarker for liver damage. Many studies have demonstrated that miRNA expression profiles in HCC and nontumor tissue are significantly different.

Aims & Methods

The aim is to evaluate the role of serum miRNA‑192 as potential serum marker of HCC among HCV related liver cirrhosis.
The study was carried out on 80 Egyptian patients with HCV related liver cirrhosis (Liver cirrhosis (LC) group: 40 patients with HCV related liver cirrhosis without HCC and HCC group: 40 patients with HCV related liver cirrhosis and HCC) and 20 healthy volunteers as controls from Menoufia University Hospitals (Egypt). They underwent history taking, physical examination and laboratory investigations (CBC, liver profile {ALT, AST, albumin, bilirubin, INR}, urea, creatinine, AFP, HBsAg, HCV Ab and serum miRNA‑192). Abdominal ultrasonography was done for all patients and controls. HCC is further confirmed by triphasic CT. Patients with malignancy other than HCC, received previous treatment for HCC or chronic liver disease other than HCV were excluded from the study.

Results

In HCC group, according to BCLC classification, one patient (2.5%) at very early stage, 3 (7.5%) at early stage, 13 (32.5%) at intermediate stage, 8 (20%) at advanced stage and 15 (37.5%) at terminal stage. In HCC group, 10 patients (25%) had HCC size˂3 cm and 30 patients (75%) had HCC size˃3 cm. 65% of the patients (n=26) had single lesion, 5% (n=2) had 2 lesions and 30% (n=12) had multifocal lesions. Eleven patients (27.5%) have portal vein thrombosis (PVT). Serum miRNA‑192 ratio was significantly higher in HCC group (195.8±256.3) than LC (42.6±35.6) and control group (25.7±18.2) (P=0.001 for all) but there was no significant difference between LC and controls (P=0.06). In HCC group, miRNA‑192 ratio was higher in patients with tumor size ˃3 cm (317.9±402) than tumor size ˂3cm (170.7±254.5) (P=0.02) but there was no significant difference according to number of focal lesion or presence of PVT (P˃0.05). AFP level (ng/ml) was significantly higher in HCC group (6572±12563) than LC (28.1±35.1) and control group (14.7±13.3) (P=0.006 for both) but there was no significant difference between LC and controls (P=0.1). Serum miRNA‑192 ratio cutoff level >62.6 have 77.5% sensitivity and 82.5% specificity for detection of HCC. AFP at cutoff level >35.7 ng/ml have 70% sensitivity and 65% specificity for detection of HCC. MELD score, APRI score and FIB-4 were significantly higher in HCC group (20.5±3.5, 3.2±2.7 and 7.2±4.5 respectively) than LC group (7.9±2.2, 0.76±0.92 and 2.3±2.9 respectively) (P˂0.001 for all). In HCC and LC groups, there was a significant positive correlation between miRNA‑192 ratio and AFP (P˂0.001)

Conclusion

MiRNA‑192 could be used as a diagnostic biomarker for detection of HCC in HCV‑related cirrhosis, as it showed significant upregulation in patients with HCC in comparison with non‑HCC patients with higher sensitivity and specificity than AFP for detection of HCC.

References

1-Giordano S and Columbano A. MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma? Hepatology 2013; 57:840–847.
2-Bala S, Petrasek J, Mundkur S, Catalano D, Levin I, Ward J, et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 2012; 56:1946–1957.
3-Blanco‑Calvo M, Calvo L, Figueroa A, Haz‑Conde M, Anton‑Aparicio L, Valladares‑Ayerbes M. Circulating microRNAs: molecular microsensors in gastrointestinal cancer. Sensors 2012; 12:9349–9362.
4-Bala S, Petrasek J, Mundkur S, Catalano D, Levin I, Ward J, et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases.
Hepatology 2012; 56:1946–1957.

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

Endoscopic papillectomy (EP) has been established for the management of epithelial tumors such as adenomas and T1a carcinomas in the papilla of Vater. However, the indications and techniques for EP of submucosal lesions have not been established, and determining the appropriate treatment strategy can be challenging. Therefore, we present our experience with EP for submucosal lesions of the duodenum in this report.

Aims & Methods

The subjects were five cases of submucosal tumors of the major duodenal papilla and two cases of papillary bile duct cysts with repeated pancreatitis, out of 130 cases who underwent endoscopic papillectomy (EP) at each related facility between January 2000 and September 2019. In all cases, endoscopic ultrasonography (EUS) and intraductal ultrasound examination (IDUS) were performed to confirm that there was no invasion into the duodenal muscularis propria or progression into the bile duct or pancreatic duct, and that the size of the lesion was basically 1 cm or less for enhancing lesions. Lymph node metastasis was also ruled out before performing the resection. There were four male cases, with a median age of 72 (39-77) years, and a median tumor size of 11 (9-30) mm. The observation period was 1251 (54-2385) days.

Results

In the solid lesions, the histopathological examination showed four cases of NET-G1 and one case of paraganglioma. Complete resection was possible in all cases, with four cases having undergone complete resection and one case with unclear margins. In the cystic lesions, no clear tumor lesions were found in the resected specimens, and there was no recurrence of pancreatitis after resection. No metastasis, recurrence, or serious complications have been observed in the above cases.

Conclusion

Duodenal NETs are known to frequently occur in the duodenal papilla, and the current standard treatment is pancreaticoduodenectomy, which is a highly invasive procedure. For duodenal NETs measuring 1 cm or less, which are indicated for endoscopic resection according to the pancreatic and gastrointestinal neuroendocrine tumor guidelines, EP may be a safe and effective diagnostic treatment. EP may also be effective as a symptomatic treatment for papillary bile duct cysts with repeated pancreatitis, and further studies are necessary to accumulate cases and investigate the complete resection rate, risk of metastasis or recurrence, and risk of complications.