Background Insertion–deletion mutations (indels) may generate more tumour-specific neoantigens with high affinity to major histocompatibility complex class I. A high indel ratio is also related to a good response to programmed death-1 (PD-1) checkpoint blockade in melanoma and renal cell carcinoma. However, the correlation between a high indel ratio and the immunotherapy response in intrahepatic cholangiocarcinoma (ICC) is unknown. Case presentation Two patients with relapsed ICC at stage IIIb were treated with PD-1 blockade combined with chemotherapy. After 7 and 4 months of chemotherapy and PD-1 blockade (3 and 15 cycles, and 5 and 6 cycles, respectively), magnetic resonance imaging and positron emission tomography with computed tomography imaging showed that both patients achieved a complete response (CR), which has lasted up to nearly 16 and 13 months to date, respectively. Whole-exome sequencing and immunohistochemistry analysis showed that both patients had cancers with microsatellite stability (MSS) and mismatch repair (MMR) proficiency, weak PD-L1 expression, and a tumour mutation burden (TMB) of 2.95 and 7.09 mutations/Mb, respectively. Patient 2 had mutations of TP53 and PTEN that are known to confer sensitivity to immunotherapy, and the immunotherapy-resistant mutation JAK2 , whereas patient 1 had no known immunotherapy response-related mutations. However, the indel ratios of the two patients (48 and 66.87%) were higher than the median of 12.77% determined in a study of 71 ICC patients. Moreover, comparison to six additional ICC patients who showed a partial response, stable disease, or progressive disease after PD-1 blockade treatment alone or in combination with chemotherapy demonstrated no difference in PD-L1 expression, TMB, MSI, and MMR status from those of the two CR patients, whereas the indel frequency was significantly higher in the CR patients. Conclusions These two cases suggest that indels might be a new predictor of PD-1 blockade response for ICC patients beside PD-L1 expression, TMB, MSI, and dMMR, warranting further clinical investigation. Electronic supplementary material The online version of this article (10.1186/s40425-019-0596-y) contains supplementary material, which is available to authorized users.

Purpose As we all know, curative resection remains the only effective treatment for hepatocellular cancer (HCC). However, systemic inflammatory response syndrome always correlates with surgery, which may impose an impact on the clinical outcome of HCC patients who had undergone curative treatment. The present study is aimed at exploring the correlation between perioperative inflammatory mediators and recurrence risk of HCC. Methods This study retrospectively included 157 histologically confirmed single HCC patients (88 patients developed HCC again) who had received radical hepatectomy between January 2016 and May 2018 at the Department of Hepatobiliary Surgery, the People's Liberation Army General Hospital (PLAGH), China. The cut-off values for predicting recurrence were determined by receiver operating characteristic (ROC) curve analysis with estimation of the Youden index. Recurrence-free survival (RFS) was assessed using the Kaplan-Meier method, and the difference was compared between groups by the log-rank test. Univariate/multivariate analysis was performed to identify independent risk factors of postoperative tumor recurrence. Results The perioperative serum IL1, IL2, and IL10 levels showed no difference between groups, whereas the serum IL6, IL8, and TNF-α levels showed significant differences between groups. High preoperative serum IL6, IL8, and TNF-α levels were significantly associated with shorter RFS. Multivariate analysis revealed that preoperative serum IL6 > 8.45 pg/ml, preoperative serum IL8 > 68 pg/ml, preoperative serum TNF − α > 14.9 pg/ml, microvascular invasion (MVI), and maximum tumor size > 6 cm were independent predictors of RFS. Conclusions The present study confirmed that high preoperative serum IL6, IL8, and TNF-α levels were distinctly correlated with the postoperative tumor recurrence risk of HCC patients.

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BackgroundMatricellular proteins of the extracellular matrix (ECM) include tenascin-C (TNC) and cellular communication network factor 3 (CCN3). This study aimed to investigate the role of TNC and CCN3 as prognostic factors for post hepatectomy liver failure (PHLF) in a rat model of partial hepatectomy and 50 patients following partial hepatectomy.Material/MethodsSprague-Dawley rats underwent 85% (n=53) or 90% hepatectomy (n=53) in the partial hepatectomy (PHx) model. TNC and CCN3 mRNA expression in residual liver tissue was evaluated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and enzyme-linked immunoassay (ELISA) determined the serum levels of TNC and CCN3. In 50 patients who underwent partial hepatectomy, TNC and CCN3 serum levels were measured on postoperative day 1 and day 3.ResultsIn the rat partial hepatectomy model, mRNA and serum levels of TNC and CCN3 were significantly increased within the first 24 h, and were higher in the 90% PHx group compared with the 85% PHx group. Fifty patients who underwent partial hepatectomy, included patients with PHLF (n=12) and patients without PHLF (n=38). Multivariate analysis confirmed that serum levels on postoperative day 3 TNChigh+CCN3high was a significant predictor of PHLF, which was associated with more than twice the risk of severe morbidity when compared with the low-risk patients (80% vs. 30%) and a significantly longer hospital stay (17 days vs. 8 days).ConclusionsFurther studies are needed to evaluate the potential role of the matricellular proteins, TNC and CCN3 as early clinical predictors for PHLF.