Clinical response to adding pyrotinib to pembrolizumab and lenvatinib for HER2-positive advanced intrahepatic cholangiocarcinoma: a case report.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly lethal hepatobiliary cancer, and very few patients can undergo surgery. The prognosis of advanced ICC is poor, especially in patients who progress after first-line chemotherapy, with a median overall survival of less than 10 months. CASE PRESENTATION: A 64-year-old male was diagnosed with advanced intrahepatic cholangiocarcinoma with ERBB2 (HER2) 3 + amplification determined by tissue-based testing and confirmed by next-generation sequencing. The patient was treated with pyrotinib added to pembrolizumab and lenvatinib after progressing with pyrotinib and tegafur and responded very well with regression of the tumor on imaging as well as normalization of tumor marker levels without serious adverse events. PET-CT after 6 months of treatment showed a partial response. The progression-free survival with second-line treatment was 17 months. For the third line of therapy, lenvatinib and pembrolizumab were used in combination with bevacizumab. Currently, he has had stable disease for approximately 6 months during third-line treatment. CONCLUSION: Adding pyrotinib to pembrolizumab and lenvatinib may represent a promising strategy for advanced ICC patients who have high levels of HER2.

Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure.

OBJECTIVE: Shortage of organ donors, a critical challenge for treatment of end-stage organ failure, has motivated the development of alternative strategies to generate organs in vitro. Here, we aim to describe the hepatorganoids, which is a liver tissue model generated by three-dimensional (3D) bioprinting of HepaRG cells and investigate its liver functions in vitro and in vivo. DESIGN: 3D bioprinted hepatorganoids (3DP-HOs) were constructed using HepaRG cells and bioink, according to specific 3D printing procedures. Liver functions of 3DP-HOs were detected after 7 days of differentiation in vitro, which were later transplanted into Fah-deficient mice. The in vivo liver functions of 3DP-HOs were evaluated by survival time and liver damage of mice, human liver function markers and human-specific debrisoquine metabolite production. RESULTS: 3DP-HOs broadly acquired liver functions, such as ALBUMIN secretion, drug metabolism and glycogen storage after 7 days of differentiation. After transplantation into abdominal cavity of Fah-/-Rag2-/- mouse model of liver injury, 3DP-HOs further matured and displayed increased synthesis of liver-specific proteins. Particularly, the mice acquired human-specific drug metabolism activities. Functional vascular systems were also formed in transplanted 3DP-HOs, further enhancing the material transport and liver functions of 3DP-HOs. Most importantly, transplantation of 3DP-HOs significantly improved the survival of mice. CONCLUSIONS: Our results demonstrated a comprehensive proof of principle, which indicated that 3DP-HO model of liver tissues possessed in vivo hepatic functions and alleviated liver failure after transplantation, suggesting that 3D bioprinting could be used to generate human liver tissues as the alternative transplantation donors for treatment of liver diseases.

Integrated analysis of serum lipid profile for predicting clinical outcomes of patients with malignant biliary tumor.

BACKGROUND: Serum lipids were reported to be the prognostic factors of various cancers, but their prognostic value in malignant biliary tumor (MBT) patients remains unclear. Thus we aim to assess and compare prognosis values of different serum lipids, and construct a novel prognostic nomogram based on serum lipids. METHODS: Patients with a confirmed diagnosis of MBT at our institute from 2003 to 2017 were retrospectively reviewed. Prognosis-related factors were identified via univariate and multivariate Cox regression analyses. Then the novel prognostic nomogram and a 3-tier staging system were constructed based on these factors and further compared to the TNM staging system. RESULTS: A total of 368 patients were included in this study. Seven optimal survival-related factors-TC/HDL >  10.08, apolipoprotein B >  0.9 g/L, lipoprotein> 72 mg/L, lymph node metastasis, radical cure, CA199 > 37 U/mL, and tumor differentiation -were included to construct the prognostic nomogram. The C-indexes in training and validation sets were 0.738 and 0.721, respectively. Besides, ROC curves, calibration plots, and decision curve analysis all suggested favorable discrimination and predictive ability. The nomogram also performed better predictive ability than the TNM system and nomogram without lipid parameters. And the staging system based on nomogram also presented better discriminative ability than TNM system (P < 0.001). CONCLUSIONS: The promising prognostic nomogram based on lipid parameters provided an intuitive method for performing survival prediction and facilitating individualized treatment and was a great complement to the TNM staging system in predicting overall survival.

Novel nomograms based on immune and stromal scores for predicting the disease-free and overall survival of patients with hepatocellular carcinoma undergoing radical surgery.

BACKGROUND: Stromal and immune cells play important roles in hepatocellular carcinoma (HCC) development and progression. However, tools for predicting the prognosis of patients with HCC based on stromal and immune scores are not well established. We aimed to develop nomograms that predicted the disease-free survival (DFS) and overall survival (OS) of patients after radical surgery. METHODS: Basic information of 251 patients were retrieved from The Cancer Genome Atlas. Multivariate Cox analyses identified variables predicting the prognosis of patients. DFS and OS nomograms were constructed based on the stromal and immune scores of the training group and verified in the well-matched test group. RESULTS: An intermediate stromal score (hazards ratio [HR] = 3.177; P < .001] was an independent risk factor for DFS. An intermediate immune score independently predicted a longer DFS (HR = 0.323; P = .002) and OS (HR = 0.305; P = .021); a high immune score predicted a longer DFS (HR = 0.289; P = .002). The concordance index (C-index) of nomograms was 0.729 for DFS and 0.696 for OS in the test group. CONCLUSION: Nomograms based on the stromal and immune scores favorably predicted the DFS and OS of patients with HCC after radical surgery.

Effects of Ambient Temperature and Forced-air Warming on Intraoperative Core Temperature: A Factorial Randomized Trial.

BACKGROUND: The effect of ambient temperature, with and without active warming, on intraoperative core temperature remains poorly characterized. The authors determined the effect of ambient temperature on core temperature changes with and without forced-air warming. METHODS: In this unblinded three-by-two factorial trial, 292 adults were randomized to ambient temperatures 19°, 21°, or 23°C, and to passive insulation or forced-air warming. The primary outcome was core temperature change between 1 and 3 h after induction. Linear mixed-effects models assessed the effects of ambient temperature, warming method, and their interaction. RESULTS: A 1°C increase in ambient temperature attenuated the negative slope of core temperature change 1 to 3 h after anesthesia induction by 0.03 (98.3% CI, 0.01 to 0.06) °Ccore/(h°Cambient) (P < 0.001), for patients who received passive insulation, but not for those warmed with forced-air (-0.01 [98.3% CI, -0.03 to 0.01] °Ccore/[h°Cambient]; P = 0.40). Final core temperature at the end of surgery increased 0.13°C (98.3% CI, 0.07 to 0.20; P < 0.01) per degree increase in ambient temperature with passive insulation, but was unaffected by ambient temperature during forced-air warming (0.02 [98.3% CI, -0.04 to 0.09] °Ccore/°Cambient; P = 0.40). After an average of 3.4 h of surgery, core temperature was 36.3° ± 0.5°C in each of the forced-air groups, and ranged from 35.6° to 36.1°C in passively insulated patients. CONCLUSIONS: Ambient intraoperative temperature has a negligible effect on core temperature when patients are warmed with forced air. The effect is larger when patients are passively insulated, but the magnitude remains small. Ambient temperature can thus be set to comfortable levels for staff in patients who are actively warmed.