Cidan Capsule in Combination with Adjuvant Transarterial Chemoembolization Reduces Recurrence Rate after Curative Resection of Hepatocellular Carcinoma: A Multicenter, Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS: Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

Repeat hepatectomy for pediatric recurrent chemotherapy-resistant hepatoblastoma: a report of 18 cases.

BACKGROUND AND AIMS: Repeat hepatectomy for adult recurrent hepatocellular carcinoma significantly prolongs the overall survival, but repeat hepatectomy for pediatric recurrent hepatoblastoma (HB) is rarely reported, and the outcomes are warranted to be investigated. METHODS: All patients between May 2015 and December 2020 with recurrent HB after intended surgical cure were retrospectively evaluated. Clinicopathologic features, surgical details and outcomes were analyzed during a median following-up of 24 months after repeat hepatectomy. Survival analysis was performed using the Kaplan-Meier estimate. RESULTS: A total of 18 patients of recurrent HB undergoing repeat hepatectomy with radical cure intention were included. There were 11 males and 7 females. The median age was 29 months (range 5-87 months) at first hepatectomy, and the median time to the recurrence from the first hepatectomy was 7 months. The operating time of the repeat hepatectomy was 5.0 h (range 3.5-9.0 h) and the mean blood loss was 592 ml (range 50-3200 ml). Radical resection (R0) was achieved in 12 patients (66.7%), with a postoperative hospital stay of 7.9 ± 1.8 days. No serious postoperative complications or mortality occurred. The overall survival (OS) rate was 55.6% (10/18) and the event-free survival (EFS) rate was 33.3% (6/18). Those with no lung metastases, not high-risk stratification, and achieving R0 hepatectomy, anatomic hepatectomy had longer OS rate (all P < 0.05) after repeat hepatectomy. Two of three patients with re-recurrence HB undergoing salvage liver transplantation were alive with a tumor-free survival. CONCLUSIONS: Repeat hepatectomy for recurrent HB can be carried out safely. However, only a highly selected subgroup of patients might actually benefit from this procedure.

Morphological speculation of the MHPD and related clinical projections.

OBJECTIVE: The concept of mesopancreas has been brought into focus nowadays. Studies on membrane morphology of pancreas are clinically significant in determining an ideal surgical route for a "holy plane". In this paper, we aimed to observe the structure of the peripancreatic membranes and its interactions with adjacent tissues; tentatively put forward the proposition of mesohepatopancreaticoduodenum (MHPD) and explore in depth in surgical local resection. METHODS: 33 cadavers were examined in the experiment, including 30 for gross anatomy and 3 for histological observation after transection. The histological characteristics of the membrane covering the pancreas were proved by Masson and Bielschowsky silver staining and further explored in clinical application and testified in a surgical scenario. All above were carried out through traditional procedures. RESULTS: The anterior surface membrane of the pancreas was intact and the posterior portion expanding to the pancreaticoduodenum enclosed the surface of the duodenum and the pancreatic head, which could be easily isolated from the posterior abdominal wall. The posterior surface membrane around the body and tail wrapped the pancreatic parenchyma, which created a soft-tissue window for the posterior abdominal wall. Then, dense connective tissue adhesions were detected between the celiac artery and the superior mesenteric artery. CONCLUSIONS: The embryonic origin of the mesopancreas and the surgical procedures were reviewed and inspected based on the proposition of MHPD and above results. We hope that this study could stir up our interest in the advancement of imaging diagnoses and minimally invasive surgical treatment of pancreas.

LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells.

Chemotherapy is the best choice for the vast majority of hepatocellular carcinoma patients at late stage, but few effective chemotherapy drugs are available in clinic. Licochalcone A (LicA) is a new chemotherapy drug inducing apoptosis as Bcl-2 inhibitor, but few studies report on LicA­induced autophagy. This study investigated the phenomenon and mechanisms of LicA-induced autophagy looking for a targeted combination drug. Human hepatocellular carcinoma cells (HCCs) were treated with LicA, to detect markers of autophagy and to investigate the mechanisms. In order to investigate the role of reactive oxygen species (ROS) in LicA­induced autophagy, ROS, glutathione (GSH) and O2- were measured in LicA treated HCCs, and antioxidant N-Acetyl-L-cysteine (NAC) was cotreated with LicA in HCCs, then mechanisms of ROS-induced autophagy was investigated in LicA or LicA combined with NAC treated HCCs. Finally, the LicA-induced apoptosis was detected in LicA combined with NAC treated HCCs. We first report that LicA can induce autophagy through ULK1/Atg13 and ROS pathway in HCCs, suppression of LicA-induced ROS through antioxidant NAC can enhance LicA-induced apoptosis, promoting the function of LicA killing HCCs. LicA can activate the ULK1/Atg13 complex which is upstream of autophagy, additionally, LicA also can promote ROS generation, ROS trigger the expression level of TSC1/2 complex, PRAS40, CTMP, PP2A, PDK1 and Rubicon change, these molecules are upstream of autophagy. In conclusion, LicA can induce autophagy through ULK1/Atg13 and ROS pathway in HCCs, LicA combined with NAC can enhance LicA-induced apoptosis. Our results may provide a novel design for clinical hepatocellular carcinoma therapy trials.

Strength and microstructure characteristics of the recycled rubber tire-sand mixtures as lightweight backfill.

The disposal of scrap rubber tires has induced critical environmental issue worldwide due to the rapid increase in the number of vehicles. Recycled scrap tires as a construction material in civil engineering have significant environmental benefits from a waste management perspective. A systematic study that deals with strength and microstructure characteristics of the rubber-sand mixtures is initiated, and mechanical response of the mixtures is discussed in this investigation. Experiments were conducted to evaluate the effects of rubber fraction on the basic properties including mass density (ρ), stress-strain characteristics, shear strength, and unconfined compression strength (q u) of the rubber-sand mixtures. Additionally, scanning electron microscopy (SEM) was carried out to reveal the microstructure characteristics of the mixtures with various rubber fractions. A discussion on the micromechanics of the mixtures also was conducted. This study demonstrates that the ρ, friction angle, and q u decrease linearly with an increase in rubber fraction, whereas shear strain at peak increases. The stress-strain characteristics of the rubber-sand mixtures shift from brittle to ductile as the rubber fraction increase. These changes are attributed to remarkably lower stiffness and higher compressibility of the rubber particle compared with those of the conventional mineral aggregates. With an increase in the rubber fraction, the mechanical response of rubber-sand mixtures exhibits two types: sand-like material and rubber-like material. Rubber particle possesses the capacity to prevent the contacted sand particles from sliding at lower rubber fraction, whereas it transmits the applied loadings as the rubber fraction increased. This outcome reinforces the practicability of using recycled rubber tire-sand mixtures as a lightweight backfill in subbase/base applications.

Astaxanthin inhibits gemcitabine-resistant human pancreatic cancer progression through EMT inhibition and gemcitabine resensitization.

Pancreatic cancer rapidly acquires resistance to chemotherapy resulting in its being difficult to treat. Gemcitabine is the current clinical chemotherapy strategy; however, owing to gemcitabine resistance, it is only able to prolong the life of patients with pancreatic cancer for a limited number of months. Understanding the underlying molecular mechanisms of gemcitabine resistance and selecting a suitable combination of agents for the treatment of pancreatic cancer is required. Astaxanthin (ASX) is able to resensitize gemcitabine-resistant human pancreatic cancer cells (GR-HPCCs) to gemcitabine. ASX was identified to upregulate human equilibrative nucleoside transporter 1 (hENT1) and downregulate ribonucleoside diphosphate reductase (RRM) 1 and 2 to enhance gemcitabine-induced cell death in GR-HPCCs treated with gemcitabine, and also downregulates TWIST1 and ZEB1 to inhibit the gemcitabine-induced epithelial-mesenchymal transition (EMT) phenotype in GR-HPCCs and to mediate hENT1, RRM1 and RRM2. Furthermore, ASX acts through the hypoxia-inducible factor 1α/signal transducer and activator of transcription 3 signaling pathway to mediate TWIST1, ZEB1, hENT1, RRM1 and RRM2, regulating the gemcitabine-induced EMT phenotype and gemcitabine-induced cell death. Co-treatment with ASX and gemcitabine in a tumor xenograft model induced by GR-HPCCs supported the in vitro results. The results of the present study provide a novel therapeutic strategy for the treatment of gemcitabine-resistant pancreatic cancer.

Robotic surgery twice performed in the treatment of hilar cholangiocarcinoma with deep jaundice: delayed right hemihepatectomy following the right-hepatic vascular control.

OBJECTIVE: To explore and find a new method to treat hilar cholangiocarcinoma with deep jaundice assisted by Da Vinci robot. METHODS: A hilar cholangiocarcinoma patient of type Bismuch-Corlette IIIa was found with deep jaundice (total bilirubin: 635 µmol/L). On the first admission, we performed Da Vinci robotic surgery including drainage of left hepatic duct, dissection of right hepatic vessels (right portal vein and right hepatic artery), and placement of right-hepatic vascular control device. Three weeks later on the second admission when the jaundice disappeared we occluded right-hepatic vascular discontinuously for 6 days and then sustained later. On the third admission after 3 weeks of right-hepatic vascular control, the right hemihepatectomy was performed by Da Vinci robot for the second time. RESULTS: The future liver remnant after the right-hepatic vascular control increased from 35% to 47%. The volume of left lobe increased by 368 mL. When the total bilirubin and liver function were all normal, right hemihepatectomy was performed by Da Vinci robot 10 weeks after the first operation. The removal of atrophic right hepatic lobe with tumor in bile duct was found with no pathologic cancer remaining in the margin. The patient was followed up at our outpatient clinic every 3 months and no tumor recurrence occurs by now (1 y). CONCLUSIONS: Under the Da Vinci robotic surgical system, a programmed treatment can be achieved: first, the hepatic vessels were controlled gradually together with biliary drainage, which results in liver's partial atrophy and compensatory hypertrophy in the other part. Then a radical hepatectomy could be achieved. Such programmed hepatectomy provides a new treatment for patients of hilar cholangiocarcinoma with deep jaundice who have the possibility of radical heptolobectomy.

Management of bleeding gastric varices in patients with sinistral portal hypertension.

BACKGROUND AND AIM: Sinistral portal hypertension (SPH) is a rare cause of upper gastrointestinal hemorrhage. Besides splenectomy, there is no consensus on the role of sclerotherapy and splenic embolization for bleeding gastric varices (GVs). This retrospective study summarizes our experience in managing GV bleeding from SPH in patients with pancreatic diseases. METHODS: Patients with pancreatic diseases who had bleeding GVs from SPH in two tertiary hospitals were reviewed from January 2001 to December 2011. The etiology, clinical manifestations, diagnostic and therapeutic modalities were analyzed. RESULTS: Twenty-one patients (15.2 %) complicating bleeding GVs among 139 patients with SPH secondary to pancreatic diseases were enrolled. The etiologies were acute pancreatitis in one patient, chronic pancreatitis in seven patients, and pancreatic tumors in 13 patients. Emergent endoscopic sclerotherapy was initially performed in five patients, and succeeded in two patients, while one patient died of massive hemorrhage. Initial transcatheter artery embolization using Gianturco coils was successfully performed in six patients. Splenectomy combined with other surgical procedures was undertaken for 15 patients. The patients undergoing artery embolization or splencetomy achieved hemostasis. The survivors had no recurrent bleeding during a median 72-month follow-up period. CONCLUSIONS: The incidence of bleeding GVs from SPH is relatively rare. Splenic artery embolization could be selected as a first-line choice for bleeding SPH, especially for patients in poor conditions, and sclerotherapy may not be preferentially recommended. Further studies are required to evaluate the optimum treatment algorithm for bleeding GVs from SPH.

Da Vinci robot-assisted anatomic left hemihepatectomy and biliary reconstruction.

BACKGROUND: Since the introduction of Da Vinci robotic surgery, more and more complicated surgeries can now be performed robotically, yet there have been very few on robotic hepatectomy, especially when billiary reconstruction is involved. The video shows our initial experience with an anatomic hepatectomy using Da Vinci surgical robot. In this case, we also conducted billiary reconstruction due to the anatomic abnormality of bile duct, while applying the choledochoscopy. The preoperative diagnosis is primary liver carcinoma, tumor thrombi in bile duct, and hepatitis B. METHODS: First, the gallbladder was resected, and cystic artery and duct were identified. After opening of the common bile duct above the junction, the choledochoscopy was performed. Tumor thrombi were found in common bile duct and left hepatic duct, and they were all removed. Left branches hepatic artery and portal vein were dissected, ligated, and divided. Thrombi in the left hepatic duct were removed also. After marking the cutting line along the ischemic boarder, liver parenchyma was transected using robotic harmonic scalpel. Branches of ducts were encountered and managed by either direct coagulating or dividing after clipping. The left hepatic vein was visualized, exposed, and divided during hepatectomy. Two T tubes were placed into common hepatic duct and the proximal cutting end of right anterior bile duct which was found to join the left hepatic duct, respectively. RESULTS: The operation went on successfully. The operation time was 410 minutes, the blood loss was 200 mL. The pathologic diagnosis was introductal papillary adenocarcinoma of left hepatic duct. The patient went on well postoperatively and was followed up for 22 months till now. Postoperative computed tomography examination showed no recurrence. CONCLUSIONS: Da Vinci-assisted robotic hepatectomy can be performed safely in the hands of experienced hepatobilliary surgeons, and choledochoscopy can be combined for bile duct exploration. With the advantages of Da Vinci robot system, complicated billiary reconstruction can be performed (http://links.lww.com/SLE/A74).

XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma risk in the Chinese Han population: a meta-analysis.

PURPOSE: Numerous studies have evaluated the association between XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma risk in the Chinese Han population. However, the results have been inconsistent. We therefore here examined whether the XRCC1 Arg399Gln gene polymorphism confers hepatocellular carcinoma risk by conducting a meta-analysis. METHODS: PubMed, Google scholar and China National Knowledge Infrastructure databases were searched for eligible articles in English and Chinese that were published before April 2012. RESULTS: 6 studies involving 1,246 patients with hepatocellular carcinoma and 1,953 controls were included. The association between XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma in the Chinese Han population was significant under GG vs AA (OR = 1.48, 95% CI = 1.13 to 1.94). Limiting the analysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust. CONCLUSIONS: In the Chinese Han population, the XRCC1 Arg399Gln gene polymorphism is associated with an increased hepatocellular carcinoma risk.