Introduction

Systemic inflammation and nutritional parameters have been studied as possible prognostic factors in advanced pancreatic cancer (APC) treatment results predictors.

Aims & Methods

The study aimed to analyze the correlation between nutritional status parameters and indices and the number of multi-agent treatment courses received at the inpatient chemotherapy department. Pre-treatment parameters (Charlson comocrbidity index (CCI), complete blood count, total protein, albumin, bilirubin) were collected and nutritional ratios and indices (neutrophil-to-lymphocyte (NLR), platelete-to-lymphocyte (PLR), lymphocyte-to-monocyte (LMR), prognostic nutritional index (PNI), nutritional risk index (NRI), HALP (hemoglobin, albumin, lymphocyte, protein), prognostic immune nutritional index (PINI), systemic inflammation score (SIS), systemic immune-inflammation index (SII)), were calculated in 158 patients with APC. We used Kendall rank correlation coefficient test to assess the correlation between the aforementioned parameters and the amount of treatment courses received.

Results

Out of 158 patients, 72 were men (45.5%) and 89 had with metastatic disease (56.3%). Mean number of inpatient received courses was 7. Kendall rank correlation coefficient test was statistically significant for CCI (-0.15), hemoglobin (0.129), erythrocyte (0.129), total protein (0.174), and albumin levels (0.178) as well as for PNI (0.179), NRI (0.150), HALP (0.145), PINI (0.187), and SII (-0.13) (p<0.05). There was a trend to statistical significance also in neutrophil (-0.1, p=0.052) and lymphocyte counts (0.104, p=0.06) and LMR (0.101, p=0.067).

Conclusion

In advanced pancreatic cancer, nutritional and systemic inflammation indices may serve as a predictor of the number of multi-agent chemotherapy treatment courses received at the inpatient chemotherapy department.

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

Drug-induced liver injury is an adverse effect of many pharmaceutical agents. Alverine citrate, an antispasmodic agent found in the fixed-dose combination Meteospasmyl (alverine citrate and simethicone), is widely used in functional gastrointestinal disorders. To date, only three cases are published in the literature. We report a case, with strong evidence, including a rechallenge confirming the causality.
Patient Observation: A 43-year-old woman presented with biliary-type abdominal pain. Her medical history was limited to hypertension treated with bisoprolol with no alcohol use or recent medication. Abdominal ultrasound revealed uncomplicated cholelithiasis; liver tests were normal. Alverine citrate was prescribed for symptomatic relief. Within two weeks, she developed jaundice and fatigue with a normal clinical examination. Blood tests showed severe hepatocellular injury: ALT and AST were 22× and 39× ULN, bilirubin was 274 µmol/L, and GGT/ALP were mildly elevated. Viral and autoimmune panels were negative. Imaging excluded biliary obstruction. Liver biopsy revealed portal inflammation with eosinophilic infiltrates, suggestive of immunoallergic hepatitis. The discontinuation of the drug led to normalization of liver enzymes. 3 years later, the patient was inadvertently re-exposed to alverine citrate, triggering a reproducible episode of acute hepatitis, thereby confirming causality. Diagnostic probability was assessed with the RUCAM score (12, "highly probable") and Naranjo scale (8, "probable"). Only three prior cases of alverine citrate-induced hepatitis, none of which reported a confirmed rechallenge. Although liver biopsy is not routinely required in DILI, it was essential here for diagnostic clarification.
Alverine citrate should be recognized as a rare cause of acute hepatitis. This case confirms its hepatotoxic potential and underscores the importance of early recognition and drug withdrawal to prevent recurrence.

References

1. RUCAM Scale: https://clincasequest.hospital/rucam-scale/
2. Naranjo Scale: https://proeurodilinet.eu/wp-content/uploads/2019/03/Causality-assessment-training-course-15-MARCH-.pdf
3. Couzigou P et al. Hepatitis and Alverine Citrate. J Hepatol. 1997. https://www.sciencedirect.com/science/article/abs/pii/S0168827897801870
4. Turkish case report. Turk J Gastroenterol. 2004. https://pubmed.ncbi.nlm.nih.gov/15259090/
5. Korean case report. Korean J Hepatol. 2010. https://pubmed.ncbi.nlm.nih.gov/20375645/
6. Simethicone safety review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033443/
7. Zhang X et al. Histopathologic Manifestations of Drug-induced Hepatotoxicity. Clin Liver Dis. 2013.

Introduction

Despite the progress in advanced therapies (AT) for ulcerative colitis (UC), selecting a second-line treatment after failure remains challenging. Recent guidelines recommend Ustekinumab (UST), Tofacitinib (TOFA), or Upadacitinib (UPA) as high-efficacy options after prior AT failure. However, no real-world studies have compared all three therapies.

Aims & Methods

Retrospective multicenter study (8 centers) of UC patients who failed ≥1 advanced therapy. Patients were stratified into UST, TOFA, or UPA groups and assessed at 16 and 52 weeks. The primary outcome was steroid-free clinical remission (SFCR) based on the Patient Reported Outcomes-2. Secondary outcomes included biochemical remission (fecal calprotectin ≤ 250 µg/g) and endoscopic remission (Mayo Endoscopic Subscore=0). Time to remission was assessed using Cox regression analysis. A subanalysis was performed including only second-line use after anti-TNF failure. Multivariate analysis was performed, adjusted for duration of disease, extent and number of prior therapies.

Results

We evaluated 259 cases [54.4% (n=141) female; diagnostic age 32.3 ± 15.1 years] who initiated UST (n=105; 40.5%), UPA (n=87; 33.6%) or TOFA (n=67; 25.9%). The groups were similar in disease duration (UST: 11.6 ± 8.0; UPA: 9.8 ± 6.4; TOFA: 10.4 ± 5.4 years) and 49.8% (n=129) had failed ≥2 previous AT
At week 16, UPA showed higher SFCR compared to UST (OR 2.1; p=0.014) and TOFA (OR 2.1; p=0.040), with no difference at week 52. Biochemical remission was higher with UPA at week 16 vs UST (OR 2.3; p=0.015) and TOFA (OR 2.1; p=0.039) and at week 52 vs UST (OR 4.7; p=0.010) and TOFA (OR 4.6; p=0.013). At week 16, endoscopic remission was higher with UST (OR 3.5; p=0.036) and UPA (OR 3.1; p=0.041) compared to TOFA; and at week 52, UPA was associated with higher endoscopic remission vs UST (OR 3.6; p=0.036).
In Cox regression, UPA achieved earlier biochemical remission than UST (HR 1.9; p<0.001) and TOFA (HR 1.8; p=0.011). JAK inhibitors led to earlier endoscopic remission than UST (vs UPA: HR 3.2; p<0.001; vs TOFA: HR 1.4; p=0.002).
In the subanalysis, UPA as second-line therapy demonstrated higher SFCR than TOFA (OR 3.6; p=0.035) and higher endoscopic remission at week 52 than TOFA (OR 12.0; p=0.017), and trend-wise compared to UST (OR 4.5; p=0.090).

Conclusion

Even though all three medication demonstrated high efficacy in bio-exposed UC patients, UPA achieved better results in this real world study.

References

Singh, Siddharth, et al. "AGA living clinical practice guideline on pharmacological management of moderate-to-severe ulcerative colitis." Gastroenterology 167.7 (2024): 1307-1343.

Introduction

Gastroesophageal varices are present in approximately 50% of cirrhotic patients¹. The cirrhosis-related age-standardized mortality is high². Gastroesophageal variceal bleeding is a medical emergency with a mortality rate of approximately 10-20% at six weeks¹, and rebleeding incidence ranged from 32% to 84%³, and even higher, around 90%, in patients receiving no antiviral therapy⁴. Endoscopic variceal ligation (EVL) and endoscopic variceal obliteration (EVO) with cyanoacrylate are recommended for patients with acute variceal bleeding⁵, but both treatments have no impact on portal pressure⁶. Portal hypertension is the primary pathophysiological mechanism underlying gastroesophageal varices. Non-selective beta-blockers (NSBBs) induce vasodilation by targeting beta-receptors on blood vessels and the heart, reduce cardiac output through negative inotropic effects, thereby reducing portal blood flow and associated portal pressure^{7, 8}. Gastroesophageal varices type 1 (GOV1) and type 2 (GOV2) are varices in direct continuity from the esophagus to the stomach (lesser and greater curvatures, respectively)⁹. We chose EVL after EVO for treatment of GOV1 and GOV2, which tended to have a better secondary prophylactic effect according to our clinical experience. However, no prior research has evaluated the effect of additional NSBB under these circumstances. It remains unclear whether the addition of NSBB provides further benefit after combined use of tissue adhesive and endoscopic variceal ligation for bleeding gastroesophageal varices.

Aims & Methods

We retrospectively analyzed cirrhotic patients (mainly due to hepatitis B and C) who received endoscopic combined treatment of gastroesophageal varices and were assigned or not to NSBB treatment as a second prophylaxis. Subanalysis was done for ascites, portal vein thrombosis, splenectomy, and Child-Pugh grade. 5-year overall survival and rebleeding rates were compared between treatment groups.

Results

A total of 490 patients were analyzed, and 130 patients received additional NSBB treatment. Although the additional NSBB treatment did not lead to a statistically significant difference in overall 5-year survival (Log-rank test, p = 0.133), it did reduce the 5-year rebleeding rate from 45.7% to 30.64% (Log-rank test, p = 0.002, univariate COX analysis, HR 0.57, 95% CI 0.39-0.82), consistent with the comparison after propensity score matching. Neither overall survival nor bleeding differed significantly between propranolol and carvedilol. NSBB (HR 0.54, 95% CI 0.37-0.79, p = 0.001) and splenectomy (HR 0.65, 95% CI 0.44-0.96, p = 0.030) were independent factors in reducing rebleeding, rather than improving survival, in cirrhotic patients who received combined endoscopic treatment. In patients without splenectomy, NSBB treatment improved overall survival (Log-rank test, p = 0.019, univariate COX analysis, HR 0.43, 95% CI 0.21-0.89) and reduced rebleeding rates (Log-rank test, p = 0.001, univariate COX analysis, HR 0.52, 95% CI 0.34-0.78).

Conclusion

We show for the first time that adding NSBB to combined endoscopic therapy significantly reduced recurrent variceal bleeding (GOV1 & GOV2) in cirrhotic patients, yet did not improve overall survival, except for patients without splenectomy. The addition of NSBB for patients receiving combined endoscopic treatment of gastroesophageal varices provides benefits but does not prolong overall survival.

References

1. Jakab SS, Garcia-Tsao G. Evaluation and Management of Esophageal and Gastric Varices in Patients with Cirrhosis. Clin Liver Dis 2020;24:335-50.
2. Collaborators GBDC. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2020;5:245-66.
3. de Franchis R, Primignani M. Natural history of portal hypertension in patients with cirrhosis. Clin Liver Dis 2001;5:645-63.
4. He L, Ye X, Ma J, et al. Antiviral therapy reduces rebleeding rate in patients with hepatitis B-related cirrhosis with acute variceal bleeding after endotherapy. BMC Gastroenterol 2019;19:101.
5. de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII - Renewing consensus in portal hypertension. J Hepatol 2022;76:959-74.
6. European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018;69:406-60.
7. Baiges A, Hernández-Gea V, Bosch J. Pharmacologic prevention of variceal bleeding and rebleeding. Hepatol Int 2018;12:68-80.
8. Reiberger T, Mandorfer M. Beta adrenergic blockade and decompensated cirrhosis. J Hepatol 2017;66:849-59.
9. Alqahtani SA, Jang S. Pathophysiology and Management of Variceal Bleeding. Drugs 2021;81:647-67.