Evaluation of neutrophil-to-lymphocyte, platelet-to-lymphocyte, and lymphocyte-to-monocyte ratios in patients with Klatskin tumors.

AIM: Our study aimed to evaluate the baseline and early follow-up evolution of three inflammatory ratios, namely neutrophil- to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and lymphocyte-to-monocyte (LMR) in patients with Klatskin tumors. MATERIAL AND METHODS: A cohort retrospective study was conducted on consecutive patients with Klatskin tumor who presented in a regional surgical department for seven years (1 January 2012 to 31 December 2018). Raw data regarding the patients' characteristics and inflammatory biomarkers were collected from the hospital database. The cohort was divided according to the received treatment as surgical resection or palliative treatment (such as surgical drainage, percutaneous biliary drainage, or endoscopic stenting), and the patterns between groups were compared. RESULTS: Fifty-seven patients, age from 39 to 79 years were evaluated. Neutrophil to lymphocyte ratio (NLR) increased significantly after both procedures (P<0.001). Lymphocytes-to-monocytes ratio (LMR) decreased significantly in the follow- up for patients with surgical resection, for Bismuth class III or IV (P=0.0037), and invasion (P<0.001). The baseline NLR (odd ratio OR=1.23, 95% CI: 1.00 to 1.52, P-value = 0.05) and PLR (OR=1.01, 95%CI: 1.00 to 1.01, P-value = 0.06) ratios could be markers for severity of the disease. CONCLUSIONS: Changes in inflammatory ratios as increases in NLR and decreases of LMR (for patients with resection, higher Bismuth class and invasion) were observed in early follow-up in patients with Klatskin tumors. Baseline NLR and PLR values are potential markers in the identification of advanced hilar cholangiocarcinoma but need further investigation. KEY WORDS: Invasive procedures, Lymphocyte-to-monocyte ratio (LMR), Neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), Klatskin tumor.

Programmed cell death ligand 1 (PD-L1, CD274) in cholangiocarcinoma - correlation with clinicopathological data and comparison of antibodies.

BACKGROUND: Cholangiocarcinoma (CCA) may arise in the intra- or extrahepatic biliary tract and is associated with a poor prognosis. Despite recent advances, to date there is still no established targeted therapeutic approach available. Non-surgical therapeutic agents are urgently needed, as most patients are non-eligible to surgical resection. Anti-PD-L1 therapy prevents cancer cells from evading the immune system and has emerged as a new treatment option in several cancer entities. Recently, PD-L1 expression has been analyzed in comparably small CCA patient cohorts. However, a systematic validation of different PD-L1 antibodies has not been performed in CCA so far. METHODS: We stained a tissue microarray consisting of 170 patients, including 72 intrahepatic cholangiocarcinomas (iCCAs), 57 perihilar cholangiocarcinomas (pCCAs) and 41 distal cholangiocarcinomas (dCCAs) by immunohistochemistry and evaluated PD-L1 positivity in tumor and stromal cells. We analyzed three different PD-L1 antibodies (clones 28-8, SP142, and SP263) that are frequently used and recommended for predictive diagnostic testing in other cancer types. RESULTS: For PD-L1 antibody clone SP263, 5% of iCCAs, 4% of pCCAs and 3% of dCCAs exhibited PD-L1 expression on tumor cells, thereby showing the highest frequencies of PD-L1 positivity. Accordingly, highest PD-L1 positivity rates of stromal cells with 31% in iCCA, 40% in pCCA and 61% in dCCA were detected for clone SP263. Agreement of PD-L1 positivity in tumor cells was moderate for clone 28-8 and SP263 (κ = 0.44) and poor between 28-8 and SP142 (κ = 0.13), as well as  SP142 and SP263 (κ = 0.11), respectively. Statistical analyses of PD-L1 expression (clone SP263) on tumor cells with clinicopathological data revealed a positive correlation with shortened overall survival in CCA patients. CONCLUSIONS: Selection of appropriate PD-L1 antibodies and careful evaluation of immunohistochemical staining patterns have a significant impact on PD-L1 testing in CCA. Clinical trials are necessary to investigate the putative beneficial effects of PD-L1 targeted immunotherapy in CCA patients.

Clinical features of isolated proximal-type immunoglobulin G4-related sclerosing cholangitis.

BACKGROUND AND AIM: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) presents as isolated proximal-type sclerosing cholangitis (i-SC). The present study sought to clarify the imaging differences between i-SC and Klatskin tumor. Differences between i-SC and IgG4-SC associated with autoimmune pancreatitis (AIP-SC) were also studied. METHODS: Differentiating factors between i-SC and Klatskin tumor were studied. Serum IgG4 level, CA19-9 level, computed tomography (CT) findings, cholangiography findings (symmetrical smooth long stricture extending into the upper bile duct [SSLS]), endosonographic features (continuous symmetrical mucosal lesion to the hilar part [CSML]), endoscopic biopsy results, treatment, relapse, and survival were also compared between patients with i-SC and those with AIP-SC. RESULTS: For a differential diagnosis between i-SC (N = 9) and Klatskin tumor (N = 47), the cut-off value of serum IgG4 level was 150 mg/dL (sensitivity, 0.857, specificity, 0.966). Logistic regression analysis indicated that serum IgG4 level, presence of SSLS, presence of CSML, and presence of swollen ampulla are independent factor for identifying i-SC. Relapse rate was significantly higher in the IgG4-SC with AIP group than in the i-SC group (log rank, P = 0.046). CONCLUSION: Isolated proximal-type sclerosing cholangitis presents as a nodular lesion with SSLS and/or CSML mimicking a Klatskin tumor. Those endoscopic features might provide a diagnostic clue for i-SC. i-SC is likely to have a more favorable prognosis than IgG4-SC with AIP.