Postprogression treatment of lenvatinib plus PD-1 inhibitor in advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy.

PURPOSE: This study compares the efficacy and safety of lenvatinib and programmed cell death protein (PD)-1 versus lenvatinib alone for advanced hepatocellular carcinoma (Ad-HCC) refractory to hepatic arterial infusion chemotherapy (HAIC). METHODS: From April 2016 to September 2021, 145 patients with Ad-HCC refractory to HAIC based on modified Response Evaluation Criteria in Solid Tumors criteria were enrolled by two radiologists and classified into the HAIC-lenvatinib group (H-L, n = 87) and HAIC-lenvatinib-PD-1 group (H-L-P, n = 58). A propensity score-matching method was used to reduce selective bias. The overall survival (OS) and postprogression-free survival (PPS) rates were compared using the Kaplan-Meier method with log-rank test. Multivariable analyses of independent prognostic factors were evaluated by means of the forward stepwise Cox regression model. RESULTS: After propensity score matching 1:1, the median OS was 43.6 months in the H-L-P group and was significantly longer than that (18.9 months) of the H-L group (p = .009). The median PPS was 35.6 months in the H-L-P group and was significantly longer than that (9.4 months) of the H-L group (p = .009). Multivariate analyses showed that the factors that significantly affected the OS were α-fetoprotein (hazard ratio [HR], 2.14; 95% CI, 1.26-3.98; p = .006), early response to HAIC (HR, 0.44; 95% CI, 1.20-3.85; p = .009), and H-L treatment (HR, 0.52; 95% CI, 0.30-0.86; p = .012). Modified albumin-bilirubin grade (HR, 1.32; 95% CI, 1.03-1.70; p = .026), early response to HAIC (HR, 0.44; 95% CI, 0.25-0.77; p = .004), and H-L (HR, 0.47 ; 95% CI, 0.28-0.78; p = .003) significantly affected the PPS. CONCLUSIONS: This combination therapy of PD-1 inhibitors plus lenvatinib has promising survival benefits in the management of patients with Ad-HCC refractory to HAIC. PLAIN LANGUAGE SUMMARY: Lenvatinib plus programmed death 1 inhibitor is an effective and safe postprogression treatment and improved significantly overall survival and postprogression-free survival compared with lenvatinib alone in patients with advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy.

Consensus of Minimally Invasive and Multidisciplinary Comprehensive Treatment for Hepatocellular Carcinoma - 2020 Guangzhou Recommendations.

In China, the majority of patients with hepatocellular carcinoma (HCC) result from long-term infection of hepatitis B. Pathologically, HCC is characterized by rich blood supply, multicentric origins, early vascular invasion and intrahepatic metastasis. Therefore, HCC is not a local disease but a systemic disease at the beginning of its occurrence. For this reason, a comprehensive treatment strategy should be adopted in the management of HCC, including local treatments (such as surgical resection, radiofrequency ablation, microwave ablation, chemical ablation and cryoablation, etc.), organ-level treatments [such as transcatheter arterial infusion of chemotherapy and transcatheter arterial chemoembolization (TACE)], and systemic treatments (such as immunotherapy, antiviral therapy and molecular targeted therapy, etc.). This consensus sets forth the minimally-invasive and multidisciplinary comprehensive guideline of HCC, focusing on the following eight aspects (1) using hepaticarteriography, CT hepatic arteriography (CTHA), CT arterial portography (CTAP), lipiodol CT (Lp-CT), TACE-CT to find the intrahepatic lesion and make precise staging (2) TACE combined with ablation or ablation as the first choice of treatment for early stage or small HCC, while other therapies are considered only when ablation is not applicable (3) infiltrating HCC should be regarded as an independent subtype of HCC (4) minimally-invasive comprehensive treatment could be adopted in treating metastatic lymph nodes (5) multi-level subdivision of M-staging should be used for individualized treatment and predicting prognosis (6) HCC with severe hepatic decompensation is the only candidate criterion for liver transplantation (7) bio-immunotherapy, traditional Chinese medicine therapy, antiviral therapy, and psychosocial and psychopharmacological interventions should be advocated through the whole course of HCC treatment (8) implementation of multicenter randomized controlled trials of minimally-invasive therapy versus surgery for early and intermediate stage HCC is recommended.

Efficacy of treatment regimens for advanced hepatocellular carcinoma: A network meta-analysis of randomized controlled trials.

BACKGROUND: This study aimed to perform a network meta-analysis to evaluate the therapeutic effect and safety of various modalities in treating advanced hepatocellular carcinoma (HCC). Typically, the modalities of interest were comprised of sorafenib, transarterial chemoembolization (TACE), sorafenib combined with TACE, TACE combined with traditional Chinese medicine (TCM), and sorafenib combined with hepatic arterial infusion chemotherapy (HAIC). METHODS: Potentially eligible studies were systemically retrieved from the electronic databases (including PubMed and Cochrane Library) up to September 2018. The overall survival (OS) associated with the 5 modalities of interest enrolled in this study was compared by means of network meta-analysis. Meanwhile, major adverse events (AEs) were also evaluated. RESULTS: The current network meta-analysis enrolled 7 published randomized controlled trials (RCTs), and the pooled results indicated that the TACE-TCM regimen displayed the highest efficacy in treating advanced HCC, followed by HAIC-sorafenib. By contrast, the TACE alone and sorafenib alone regimens had the least efficacy. Relative to other regimens of interest, the TACE-TCM regimen was associated with less incidence of treatment-associated AEs. CONCLUSION: The TACE-TCM regimen was associated with higher treatment responses in advanced HCC patients than those of the other regimens of interest.

ß-elemene increases the sensitivity of gastric cancer cells to TRAIL by promoting the formation of DISC in lipid rafts.

ß-Elemene, an anti-cancer drug extracted from traditional Chinese medicinal herb, showed anti-tumor effects on gastric cancer cells. Our previous studies reported gastric cancer cells are insensitive to TRAIL. However, whether ß-elemene could enhance anti-cancer effects of TRAIL on gastric cancer cells is unknown. In our present study, ß-elemene prevented gastric cancer cell viability in dose-dependent manner, and when combined with TRAIL, obviously inhibited proliferation and promoted apoptosis in gastric cancer cells. Compared to ß-elemene or TRAIL alone, treatment with ß-elemene and TRAIL obviously promoted DR5 clustering as well as translocation of Caspase-8, DR5 and FADD into lipid rafts. This led to cleavage of Caspase-8 and the formation of death-inducing signaling complex (DISC) in lipid rafts. The cholesterol-sequestering agent nystatin partially reversed DR5 clustering and DISC formation, preventing apoptosis triggered by the combination of ß-elemene and TRAIL. Our results suggest that ß-elemene increases the sensitivity of gastric cancer cells to TRAIL partially by promoting the formation of DISC in lipid rafts.

Transcatheter arterial chemoembolization combined with CT-guided percutaneous thermal ablation versus hepatectomy in the treatment of hepatocellular carcinoma.

INTRODUCTION: Transcatheter arterial chemoembolization (TACE) plus thermal ablation has been widely used recently in the treatment of hepatocellular carcinoma (HCC). In this study, we aimed to compare results of the combination of TACE and percutaneous thermal ablation with those of hepatectomy in patients with HCC. METHODS: The clinical data of 137 HCC patients who sequentially received TACE and computed tomography (CT)-guided percutaneous thermal ablation as an initial curative treatment (combination group) and 148 matched HCC patients who received hepatectomy (surgery group) between 2004 and 2011 were collected and analyzed. After TACE, multiphase contrast-enhanced CT was performed to identify the total number of tumors as well as lipiodol deposition in the liver. Survival was calculated by using the Kaplan-Meier method and compared by using the log-rank test. The prognostic factors were assessed with multivariate Cox proportional hazards regression analysis. RESULTS: Of all 285 patients, 225 (79.0%) had cancerous lesions≤5 cm in diameter. In preoperative contrast-enhanced CT or magnetic resonance imaging, the number of tumors was 1-4 for each patient. The 1-, 3-, and 5-year overall survival rates were 95, 74%, and 67% in the combination group and 88, 66, and 47% in the surgery group, respectively (P=0.004); the corresponding recurrence-free survival rates for the two groups were 92, 69, and 61% and 75, 58, and 44%, respectively (P=0.001). In the multivariate analysis, treatment allocation was an independent prognostic factor for survival. Only 60 patients in the combination group had sufficient imaging data, and 135 new lesions with lipiodol deposition were diagnosed as malignancies in 22 of 60 patients, whereas 20 new lesions were found in 11 of 148 patients in the surgery group. CONCLUSION: The combination of TACE and CT-guided percutaneous thermal ablation for HCC improves survival of HCC patients compared with hepatectomy.

Conventional radiological strategy of common gastrointestinal neoplasms.

This article summarizes the clinical characteristics and imaging features of common gastrointestinal (GI) neoplasms in terms of conventional radiological imaging methods. Barium studies are readily available for displaying primary malignancies and are minimally or not at all invasive. A neoplasm may be manifested as various imaging findings, including mucosal disruption, soft mass, ulcer, submucosal invasion and lumen stenosis on barium studies. Benign tumors typically appear as smoothly marginated intramural masses. Malignant neoplasms most often appear as irregular infiltrative lesions on barium examination. Tumor extension to adjacent GI segments may be indistinct on barium images. Cross-sectional images such as computed tomography and magnetic resonance imaging may provide more accurate details of the adjacent organ invasion, omental or peritoneal spread.

Safe temperature range for intraoperative and early postoperative continuous hyperthermic intraperitoneal perfusion in a swine model of experimental distal gastrectomy with Billroth II reconstruction.

BACKGROUND: The current study sought to investigate the safety of intraoperative and early postoperative continuous hyperthermic intraperitoneal perfusion (IEPCHIP) at different temperatures in a swine model of experimental distal gastrectomy with Billroth II reconstruction. METHODS: Thirty pigs were randomly divided into 5 groups. Two groups were used as the control groups (groups A1 and A2), and 3 groups were used as the perfusion groups (groups B, C and D). Pigs in group A1 received distal gastrectomy with Billroth II reconstruction only. Pigs in groups A2, B, C and D received the same surgery as group A1, followed by IEPCHIP at 37 ± 0.5°C, 42.5 ± 0.5°C, 43.5 ± 0.5°C or 44.5 ± 0.5°C, respectively. The perfusion time was assessed for each pig in group A2 as well as in the perfusion groups, and the perfusions were performed twice for each group. The first perfusion was conducted intraoperatively, and the second perfusion was initiated 1 day after surgery. Data concerning vital signs and hepatic and renal function were collected. Parameters concerning anastomotic healing, the pathology of the anastomotic tissue and abdominal adhesion were compared. RESULTS: The vital signs and hepatic and renal functions of the pigs in groups A1, A2, B and C were not significantly affected by this procedure. In contrast, the vital signs and hepatic and renal functions of the pigs in group D were significantly affected. Compared to the pigs in groups A1, A2 or B, the anastomotic bursting pressure, breaking strength and hydroxyproline content in group C and D pigs were significantly lower. No significant differences were observed in these parameters between groups A1, A2 and B. Abdominal adhesion was more severe in group D pigs. Collagen deposition in group A1, A2 and B pigs was dense in the anastomosis, and inflammatory cell infiltration was observed in group D. CONCLUSIONS: IEPCHIP at 42.5 ± 0.5°C was safe and caused minimal impairments. However, anastomotic healing was affected by perfusion at 43.5 ± 0.5°C and 44.5 ± 0.5°C, and abdominal adhesion was most severe in the group D animals, which were perfused at 44.5 ± 0.5°C.

One patient with metastastic colorectal cancer successfully treated by combination of targeted agents after failure of chemotherapy.

Either cetuximab or bevacizumab can improve the survival of patients with metastastic colorectal cancer (mCRC) if administered combided with cytotoxic agents. However, the effect of two or more target agents in combination is uncertain in these patients. Here, we reported a patient with mCRC successfully treated by a combination of target agents after the failure of chemotherapy. The patient received palliative resection of primary tumor followed by 9 cycles of postoperative XELOX regimen, cytokine-induced killer cell (CIK)-based biotherapy, traditional Chinese medicine, particle implantation in the lung metastatic lesions. The tumor progressed 20 months after the standard treatments. Then, the regimen cetuximab, bevacizumab and cefitinib was applied. During the treatment with targeted agents, grade IV acne-like rash and relatively severe parionychia of the toes occurred. Both of them recovered smoothly. The PET-CT reexamination at 40 days after the target treatment showed that the metabolism of mediastinal lymph nodes basically recovered to a normal level. The combination of multiple targeted agents obtained a progression-free survival(PFS) of 11 months and the patient with a good quality of life during this period.

Feasibility of (125)I brachytherapy combined with sorafenib treatment in patients with multiple lung metastases after liver transplantation for hepatocellular carcinoma.

PURPOSE: To evaluate (125)I seed brachytherapy combined with sorafenib in the treatment of patients with multiple lung metastases after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: From July 2006 to December 2009, eight patients with multiple lung metastases after OLT for HCC underwent (125)I brachytherapy combined with sorafenib, and laboratory and radiologic examinations were performed before and after the treatment. Changes in symptoms and survival time were noted at follow-up. RESULTS: The follow-up time ranged from 14 to 37 months. The local control rates of multiple lung metastases after OLT for HCC after 4, 6, 12, 18 and 24 months were 92.2, 82.4, 76.2, 73.3 and 72.2%, respectively. Four patients died (survival time 14, 15, 25 and 37 months, respectively), and four patients are alive at the time of this writing (follow-up time 18, 21, 26 and 30 months, respectively). The overall 1-, 2- and 3-year survival rates were 100, 50 and 12.5%, respectively. The median survival time was 21 months. Procedure-related complications were minimal. CONCLUSION: (125)I brachytherapy combined with sorafenib is safe, feasible and promising approach in the treatment of patients with multiple lung metastases after OLT for HCC, but large-scale randomized clinical trials are necessary for confirmation.

Radiofrequency ablation as a treatment for hilar cholangiocarcinoma.

AIM: To explore the role of radio-frequency ablation (RFA) as a treatment for hilar cholangiocarcinoma. METHODS: Eleven patients with obstructive cholestasis underwent Computed Tomography (CT) examination, occupying lesions were observed in the hepatic hilar region in each patient. All lesions were confirmed as cholangioadenocarcinoma by biopsy and were classified as type III or IV by percutaneous transhepatic cholangiography. Patients were treated with multiple electrodes RFA combined with other adjuvant therapy. The survival rate, change of CT attenuation coefficient of the tumor and tumor size were studied in these patients after RFA. RESULTS: In a follow-up CT scan one month after RFA, a size reduction of about 30% was observed in six masses, and two masses were reduced by about 20% in size, three of the eleven masses remained unchanged. In a follow-up CT scan 6 mo after RFA, all the masses were reduced in size (overall 35%), in which the most significant size reduction was 60%. The survival follow-up among these eleven cases was 18 mo in average. Ongoing follow-up showed that the longest survival case was 30 mo and the shortest case was 10 mo. CONCLUSION: RFA is a microinvasive and effective treatment for hilar cholangiocarcinoma.

Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine.

CONTEXT: Berberine, a natural plant alkaloid, is usually used as an antibiotic drug. The potential glucose-lowering effect of berberine was noted when it was used for diarrhea in diabetic patients. In vitro and in vivo studies have then showed its effects on hyperglycemia and dyslipidemia. OBJECTIVE: The objective of the study was to evaluate the efficacy and safety of berberine in the treatment of type 2 diabetic patients with dyslipidemia. DESIGN: One hundred sixteen patients with type 2 diabetes and dyslipidemia were randomly allocated to receive berberine (1.0 g daily) and the placebo for 3 months. The primary outcomes were changes in plasma glucose and serum lipid concentrations. Glucose disposal rate (GDR) was measured using a hyperinsulinemic euglycemic clamp to assess insulin sensitivity. RESULTS: In the berberine group, fasting and postload plasma glucose decreased from 7.0 +/- 0.8 to 5.6 +/- 0.9 and from 12.0 +/- 2.7 to 8.9 +/- 2.8 mm/liter, HbA1c from 7.5 +/- 1.0% to 6.6 +/- 0.7%, triglyceride from 2.51 +/- 2.04 to 1.61 +/- 1.10 mm/liter, total cholesterol from 5.31 +/- 0.98 to 4.35 +/- 0.96 mm/liter, and low-density lipoprotein-cholesterol from 3.23 +/- 0.81 to 2.55 +/- 0.77 mm/liter, with all parameters differing from placebo significantly (P < 0.0001, P < 0.0001, P < 0.0001, P = 0.001, P < 0.0001, and P <0.0001, respectively). The glucose disposal rate was increased after berberine treatment (P = 0.037), although no significant change was found between berberine and placebo groups (P = 0.063). Mild to moderate constipation was observed in five participants in the berberine group. CONCLUSIONS: Berberine is effective and safe in the treatment of type 2 diabetes and dyslipidemia.

[Study on primary hepatocellular carcinoma associated with hypersplenism treated by partial splenic embolization combined with hepatic arterial chemoembolization].

BACKGROUND & OBJECTIVE: 70-90% of patients of primary hepatocellular carcinoma (PHC) are associated with liver cirrhosis, portal hypertension and hypersplenism. The treatment of PHC is usually hampered by low or slow recovery of blood cell counts. This study was to investigate the effect of partial splenic embolization (PSE) combined with transcatheter hepatic arterial chemoembolization (TACE) for the treatment of PHC with portal hypertension and hypersplenism. METHODS: Efficacy of 26 patients with PSE combined with TACE and 26 patients with single TACE was observed. RESULTS: Satisfactory effects were achieved in PSE combined with TACE group in terms of correction of blood cell counts compared with cases treated with TACE alone. CONCLUSION: PSE associated with TACE is safe and effective for the treatment of patients with PHC associated with liver cirrhosis, portal hypertension and hypersplenism.