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.

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e16173 Background: The combination of lenvatinib and PD-1 inhibitor has shown to be a promising regimen for advanced hepatocellular carcinoma (HCC). We aimed to assess the feasibility of conversion therapy by lenvatinib combined with PD-1 inhibitor in unresectable HCC in a non-randomized phase IV study (ChiCTR1900023914). Methods: Eligible patients had histologically or cytologically confirmed unresectable HCC (AASLD); BCLC B or C; an ECOG status of 0 or 1 and Child-Pugh A-B. Patients received lenvatinib (8-12mg, oral QD) and PD-1 inhibitor (IV Q3W) until disease progression, unacceptable toxicity or satisfied for curative surgery. Surgical patients received maintenance therapy based on the pathological evaluation (pCR: PD-1 inhibitor 6-12m, pPR: combination therapy 6-12m, pPD: personalized). The primary endpoint was conversion rate for surgery based on radiological assessment. The secondary endpoints were objective response rate (ORR), disease control rate (DCR), relapse-free survival (RFS) and overall survival (OS) by modified RECIST. Tumor tissue samples were collected at diagnosis and surgery. Immune cell subsets (CD8+ T cell, macrophage, NK cell) in tumor and stromal were measured by multiplex fluorescent immunohistochemistry. Whole exosome sequencing was performed with tumor samples and matched white blood cells. Results: and received the combination therapy. 49 patients were evaluated for the efficacy, 51.0% patients (5 CR, 17 PR and 3 SD) were conversed successfully based on their radiological evaluation after 3-7 cycles of combination therapy, among whom 15 patients (30.6%) actually received curative surgery upon comprehensive evaluation and patient preference. The median duration of follow-up was 271 days. The ORR was 53.1% (26/49, 5 CR and 21 PR) and the DCR was 69.4% (34/49). The median RFS and median OS of the 15 surgical patients were unreached. The 12-month OS was 74.1% and the 12-month RFS was 61.1%. Treatment-related adverse events occurred in 46.9% (23/49) of patients (grade ≥ 3, 6.1%). In both pre- and post-therapy tumor tissues, more CD8+ T cells (pre: p = 0.083, post: p = 0.007) and M1 macrophages (pre: p = 0.127, post: p = 0.120) were present in responders compared with non-responders. The conversion therapy could promote macrophage differentiating into M1 type in treatment-sensitive patients, as post-therapy tumoral M1/M2 ratio were higher in responders than non-responders (p = 0.073). Higher frequency of KMT2C mutation (missense and splicing, p = 0.040) were observed in response group. Conclusions: Combination of PD-1 inhibitor with lenvatinib as conversion therapy could benefit unresectable advanced HCC patients to achieve curative surgery. Tumor microenvironment and genomic characteristics may explain the potential mechanism of the clinical response. Clinical trial information: ChiCTR1900023914.

Background Various minimally invasive approaches have been described for infected necrotizing pancreatitis. This article describes a modified minimal‐access retroperitoneal pancreatic necrosectomy (MARPN) procedure assisted by gas insufflation. Methods This retrospective, observational study documented patients who had undergone a step‐up MARPN between 1 January 2010 and 31 December 2016. A minimum follow‐up of 1 year was required for inclusion. The step‐up approach involved percutaneous catheter drainage followed by the modified MARPN and necrosectomy. If more than one access site was needed it was categorized as complex MARPN. Results Of 212 patients with infected necrotizing pancreatitis, 164 (77·4 per cent) underwent a step‐up approach. The median number of percutaneous catheter drains and MARPN procedures was 3 (range 1–7) and 1 (1–6) respectively. Ninety patients (54·9 per cent) underwent complex MARPN. For residual necrosis after MARPN, three patients (1·8 per cent) underwent sinus tract gastroscopy, and 11 (6·7 per cent) had sinography combined with a tube change. However, operations in 13 patients (7·9 per cent) required conversion to open surgery. Postoperative complications developed in 103 patients (62·8 per cent). The mortality rate was 6·1 per cent (10 deaths). Conclusion A step‐up approach using a modified MARPN for infected necrotizing pancreatitis is a reasonable option.

AIMTo explore the value of three-dimensional (3D) visualization technology in the minimally invasive treatment for infected necrotizing pancreatitis (INP).METHODSClinical data of 18 patients with INP, who were admitted to the PLA General Hospital in 2017, were retrospectively analyzed. Two-dimensional images of computed tomography were converted into 3D images based on 3D visualization technology. The size, number, shape and position of lesions and their relationship with major abdominal vasculature were well displayed. Also, percutaneous catheter drainage (PCD) number and puncture paths were designed through virtual surgery (percutaneous nephroscopic necrosectomy) based on the principle of maximum removal of infected necrosis conveniently.RESULTSAbdominal 3D visualization images of all the patients were well reconstructed, and the optimal PCD puncture paths were well designed. Infected necrosis was conveniently removed in abundance using a nephroscope during the following surgery, and the median operation time was 102 (102 ± 20.7) min. Only 1 patient underwent endoscopic necrosectomy because of residual necrosis.CONCLUSIONThe 3D visualization technology could optimize the PCD puncture paths, improving the drainage effect in patients with INP. Moreover, it significantly increased the efficiency of necrosectomy through the rigid nephroscope. As a result, it decreased operation times and improved the prognosis.