Randomized Controlled Trial of Hepatic Portal Reocclusion as a New Option for Detecting Bile Leakage during Hepatic Resection.

BACKGROUND/AIMS: To explore the possibility and feasibility of hepatic portal reocclusion for detecting bile leakage during hepatectomy. METHODS: Data were prospectively collected from 200 patients who underwent hepatectomy alone for removal of various benign or malignant tumors between March 2014 and November 2014. The surgical procedure used a conventional method for all patients, and one additional step (hepatic portal reocclusion) was included in group B. The postoperative outcomes of the patients in group A (subjected to the traditional procedure) and group B (subjected to hepatic portal reocclusion) were compared during the same period, and the incidence rates of postoperative bile leakage and other complications in the 2 groups were also analyzed. RESULTS: The incidence of postoperative bile leakage in group B was significantly lower than that in group A (1.0 vs. 9.2%, p = 0.009), although no significant differences in postoperative indicators of liver dysfunction and other complications were observed between the 2 groups (p > 0.05). CONCLUSIONS: Hepatic portal reocclusion effectively reduced the incidence of bile leakage compared to the traditional procedure, without significantly affecting liver function. Therefore, this method might be an alternative to other tests for bile leakage.

Sorafenib down-regulates c-IAP expression post-transcriptionally in hepatic carcinoma cells to suppress apoptosis.

Hepatocellular carcinoma (HCC) is one of leading causes of cancer-related death with a heterogeneous patient demographic and divergent pathogenic pathways. Sorafenib is the first effective drug approved for the treatment of HCC. Although it is known that sorafenib promotes apoptosis of HCC cells, the underlying mechanism remains largely obscure. Here we report that sorafenib down-regulates protein expression of the anti-apoptotic protein c-IAP1 in a time- and dose-dependent manner in HCC cells in vitro and in vivo. Furthermore, we demonstrate that sorafenib represses c-IAP1 levels without altering its transcription or protein stability. Instead, sorafenib attenuates c-IAP1 translation by targeting the internal ribosome entry site (IRES) within the c-IAP1 mRNA. Finally, ectopic expression of c-IAP1 alleviates sorafenib induced cancer cell apoptosis. In conclusion, our data highlight a previously unidentified pathway that contributes to sorafenib mediated HCC cell apoptosis and as such provide novel mechanistic insight into the rational use of sorafenib in treating HCC.

A case-control study of correlation between preoperative serum AFP and recurrence of hepatocellular carcinoma after curative hepatectomy.

BACKGROUND/AIMS: The prognostic impact of serum alpha-fetoprotein (AFP) on patients with hepatocellular carcinoma (HCC) undergoing curative resection remains unclear. We conducted a case-control study to investigate it. METHODOLOGY: A total of 196 HCC patients with negative preoperative AFP were admitted and treated by curative liver resection. During the same period, 196 patients with positive preoperative AFP were enrolled to match the TN M stages, Child-Pugh score and HBs-Ag status of the AFP-negative patients. Time to recurrence (TTR) and overall survival (OS) were prospectively studied. RESULTS: Through a median follow-up duration of 5.25 years, we found that the median TTR of patients with negative preoperative AFP was significantly longer than those with positive AFP (17.3 vs. 12.8 months, p=0.001). The median TTRs of AFP-negative and positive patients were 22.1 and 21.0 months (p=0.266), 145 and 7.4 months (p=0.005) and 3.7 and 2.9 months (p=0.197) in TNM stages I, II and IIIa, respectively. The median TTRs of TNM stage II patients with :≤20, 20-400, 400-1000 and >1000 ng/mL preoperative AFP concentration were 14.5, 13.7, 10.7 and 9.6 months (p=0.092), respectively. CONCLUSIONS: Preoperative AFP level is an independent prognostic factor affecting postoperative recurrence in HCC patients and correlated with the TTR of TNM II.

Overexpression of aspartyl-(asparaginyl)-beta-hydroxylase in hepatocellular carcinoma is associated with worse surgical outcome.

UNLABELLED: The association between the overexpression of aspartyl-(asparaginyl)-beta-hydroxylase (AAH) and the invasiveness of hepatocellular carcinoma (HCC) in vitro has been reported. However, the prognostic value of AAH expression in HCC remains unclear. The purpose of this study was to investigate the relationship between AAH expression, tumor recurrence, and patient survival. We identified AAH as the most overexpressed gene in HCC by way of complementary DNA microarray hybridization. A prospective study of 233 patients undergoing curative resection indicated that AAH expression was an independent factor affecting recurrence (hazard ratio [HR] 3.161, 95% confidence interval [CI] 2.115-4.724, P < 0.001) and survival (HR 2.712, 95% CI 1.734-4.241, P < 0.001). Patients with AAH overexpression had a poorer prognosis than those with AAH underexpression (P < 0.001 for both recurrence and survival). In Barcelona Clinic Liver Cancer stage A patients with AAH overexpression or underexpression, the tumor recurrence and survival rates were also statistically different (45% and 85% versus16% and 33% in 1- and 3-year cumulative recurrence rates, respectively; 73% and 37% versus 90% and 80% in 1- and 3-year survival rates, respectively; P < 0.001 for both). Furthermore, in stage A patients with tumors measuring < or =5 cm in diameter, the time to recurrence was 26.7 +/- 1.6 versus 51.9 +/- 2.8 months, and the 1- and 3- year survival rates were 97% and 52% versus 100% and 90% in AAH overexpression and underexpression patients, respectively (P < 0.001 for both). CONCLUSION: AAH overexpression in HCC is strongly correlated with worse surgical outcome, and this molecule likely provides a more precise prognostic predictor in early stage HCCs.

[Establishment and evaluation of review criteria for ADVIA 120/2120 and different series of hematology analyzers].

OBJECTIVE: To establish the suitable review criteria for ADVIA 120/2120 and those for different series of hematology analyzers. METHODS: A total of 2400 samples, including 6 blood neoplasms, were detected with ADVIA 120/2120 hematology analyzer, in which 1200 samples were detected by Sysmex XE-2100 and Beckman-Coulter LH750 hematology analyzers. In the meantime, blood smears were reviewed, and the results were analyzed statistically. The new review criteria were established by consulting and modifying the one as recommended by an international consensus group. Finally 300 samples were selected to validate the new review criteria. RESULTS: The results of 2400 samples detected by ADVIA 120/2120 hematology analyzer were analyzed statistically according to the international consensus review rules and blood smear positive criteria formulated by Chinese experts. The true positive rate was 22.1% (n = 530), false positive rate 28.1% (n = 675), true negative rate 44.3% (n = 1063), false negative rate 5.5% (n = 132), and the smear review rate 50.2% (n = 1205). The false negative rate was over the acceptable limit of 5%. The new review criteria were established by amending the blood smear positive criteria, i. e. increasing the percentage of band neutrophils, eosinophils, basophils and monocytes and adjusting the international consensus review rules. Then the results were re-analyzed. The true positive rate, false positive rate, true negative rate and false negative rate were 15.5% (n = 371), 18.7% (n = 449), 61.6% (n = 1479) and 4.2% (n = 101) respectively. The smear review rate was 34.2% (n = 821) and no specimen of blood neoplasms was missed. On that basis, the current review criteria for ADVIA 120/2120, XE-2100 and LH750 hematology analyzer were proposed by adding some specific parameters. The results of 1200 samples with three instruments were analyzed according to the current criteria. And the false negative rates were 4.3%, 4.6% and 4.6%, and false positive rate 14.7%, 17.5% and 12.7% respectively. And no specimen of blood neoplasm was missed. The false negative rates of three instruments were 3.8%, 4.3% and 4.0% in validation teses. CONCLUSION: The review criteria for three different series of hematology analyzers have been formulated for large general hospitals.

[Clinical study of 169 patients with hepatic angiomyolipoma].

OBJECTIVE: To review and investigate the optimal preoperative diagnostic means and treatment principles of hepatic angiomyolipoma (HAML). METHODS: The clinical features, treatment, prognostic and follow-up data of 169 HAML patients treated between January 1992 and May 2010 were retrospectively analyzed. The median age of the patients, including 46 male and 123 female (male/female, 1/2.7), was 45 years (range, 17 - 73 years). The mean case history was 0.54 year with a range of 2 d to 16 years. RESULTS: Among the 169 patients, 149 patients (88.2%) had a solitary tumor and 96 patients (56.8%) were detected in the right lobe. The overall preoperative diagnostic rate was 13.6% and 119 patients (70.4%) were misdiagnosed as hepatocellular carcinoma or hepatic cavernous hemangioma. The diagnostic accuracy of MRI is higher than CT in distinguishing the nature of the tumor (χ² = 5.508, P = 0.019). One hundred and sixty-eight patients received surgical resection and one received percutaneous microwave coagulation therapy. One patient occurred postoperative hemorrhage and 3 patients developed hydrothorax. The postoperative mortality and recurrence for all the patients were 0. Postoperative pathology confirmed the diagnosis of hepatic angiomyolipoma. Follow-up study showed a benign course and no signs of recurrence. CONCLUSIONS: MRI is the main diagnostic means of HAML. Treatment strategies of HAML depends largely on tumor size, location and growth rate. Surgical management is suggested to patients with the following criteria: (1) tumor size greater than 5 cm; (2) with clinical symptoms; (3) faster tumor growth; (4) the tumor located at 1, 4, 5, 8 segments of liver.

Potential risk of impertinent administration of methylprednisolone in lumbar spine surgery: A case report.

INTRODUCTION: Several complications of intravenous administration of Methylprednisolone in spine surgery have been reported previously. However, perioperative Addisonian crisis resulting from postoperative routine cessation of intravenous Methylprednisolone has been rarely reported. We here report a case of perioperative Addisonian crisis induced by postoperative routine cessation of intravenous Methylprednisolone. PRESENTATION OF CASE: To report a 56-year-old lady was diagnosed with Addisonian crisis on postoperative duration of lumbar spine surgery after routine cessation of intravenous Methylprednisolone on postoperative day 5. DISCUSSION: There are potential risk and medical complexity of the intravenous administration of Methylprednisolone perioperatively when patients underwent spine surgery, especially the patients with a history of adrenal insufficiency or hypothyroidism, and other endocrine diseases. The early diagnosis and effective replacement therapy after cessation of intravenous glucocorticoid to keep normal serum hormone levels can reduce risk and complication of Addisonian crisis. CONCLUSION: Addisonian crisis may be triggered by the discontinuation of exogenous glucocorticoid. Physicians need to be immediately aware of this potentially lethal complication in patients with endocrine system diseases.

Efficacy and complications of 125I seeds combined with percutaneous vertebroplasty for metastatic spinal tumors: A literature review.

To review the efficacy and complications of 125I seeds combined with percutaneous vertebroplasty for the treatment of metastatic spinal tumors. We searched PubMed/MEDLINE from its inception to November 2018 for articles on metastatic spinal tumors treated with 125I seeds combined with percutaneous vertebroplasty. A total of 273 articles were identified in PubMed/MEDLINE based on the search criteria. After deleting duplicate articles including two retrospective studies and three case control studies, five studies were included in this systematic review. In total, 161 patients aged from 49.2 to 62 years were included. The operative levels consisted of the thoracic vertebrae and lumbar vertebrae. Bone cement leakage occurred in 7 cases. None of the patients developed radiation myelopathy. Percutaneous vertebroplasty plus 125I seeds implantation is an effective palliative treatment and can alleviate back pain and enhance vertebral body strength in patients with end-stage spinal metastatic tumors. In future research, the effective dosage of 125I seeds implantation, the anchoring of seeds with safe distance, and the bone cement distribution in the vertebral body will be next research hotspot.

Long-term survival after partial hepatectomy for sub-stage patients with intermediate stage hepatocellular carcinoma.

BACKGROUND: The current study aimed to examine the long-term survival after partial hepatectomy for patients with BCLC intermediate stage hepatocellular carcinoma (HCC) stratified by the Bolondi's sub-staging model. MATERIALS AND METHODS: This cohort consisted of 360 patients with BCLC intermediate stage HCC who underwent partial hepatectomy between January 2008 and February 2010. Patients were stratified into 3 subgroups (B1-B3) based on the Bolondi's sub-staging model. The last follow-up was conducted at February 2014. RESULTS: Of these patients, 166, 171 and 23 patients had B1, B2, and B3 sub-stage HCC, respectively. The postoperative 5-year Overall survival (OS) rate for patients with these three sub-stages was 49.5%, 33.7% and 12.9%, respectively (P < 0.001). Compared with the reported survival outcomes from previous studies which used transarterial chemoembolization (TACE) as first-line treatment, hepatectomy had a better median survival than TACE in B1 and B2 patients. On multivariable analysis, presence of esophageal and gastric varices, higher NDR score, presence of microvascular invasion, differentiation grade III-IV, and patterns of AFP decreases after surgery were the independent risk factors of OS in the sub-stages B1 and B2 patients. A nomogram which integrated all these independent risk factors was developed, with a C-index of 0.71 for OS prediction. The calibration curve showed an optimal agreement between prediction by the nomogram and actual observation. CONCLUSIONS: The patients with intermediate stage HCC clarified as sub-stages B1 and B2 according to Bolondi's model had an optimal long-term survival following partial hepatectomy than TACE. Their postoperative prognosis could be accurately predicted by our proposed nomogram.

[Role of post-operative transcatheter arterial chemoembolization in hepatocellular carcinoma with different pathological characteristics].

OBJECTIVE: To evaluate the efficacy of transcatheter arterial chemoembolization (TACE) on postoperative recurrence of hepatocellular carcinoma. METHODS: A total of consecutive 823 patients with hepatocellular carcinoma from October 1996 to September 2001 were included in this study. All patients underwent curative liver resection and 126 patients (15.3%) received TACE post operation. The effects of postoperative TACE on the recurrence of hepatocellular carcinoma with different pathological characteristics such as tumor size, tumor capsule, number of nodules, vascular invasion and surgical margin was analyzed. RESULTS: Postoperative TACE had not decreased the recurrence rate in patients with a tumor diameter less than 3 cm. Postoperative TACE increased the disease-free survival for patients with tumor diameter of 3 - 10 cm, positive in alpha fetoprotein (AFP), presented vascular invasion or patients with tumor diameter larger than 10 cm, positive in AFP, multi-nodular, presented vascular invasion, resection margin less than 1 cm. CONCLUSIONS: Postoperative TACE can decrease recurrence rate and prolong the survival of hepatocellular carcinoma patients with high risk factors for recurrence.

Intrahepatic splenosis mimics hepatocellular carcinoma in a patient with chronic hepatitis B: A case report and literature review.

BACKGROUND: Splenosis is a benign and relatively uncommon condition caused by trauma or splenectomy or other procedures involving splenic tissue. It is usually asymptomatic, and often diagnosed accidentally, especially misdiagnosed as malignant tumor. METHODS: A 54-year-old man with prior history of chronic hepatitis B virus infection and underwent splenectomy for traumatic splenic rupture following a traffic accident 23 years previously was admitted to our hospital and found a hepatic mass in the right upper quadrant during an imaging examination. The diagnosis of his was not clear and finally he agreed to receive a surgical treatment. RESULTS: During the operation, we found a mass in the right posterior lobe of the liver and a hard nodule on the right side of the diaphragm, both were completely resected, and postoperative histopathologic examination revealed that all excised tissues were proved to have histological structure typical for the spleen. CONCLUSIONS: The occurrence of intrahepatic splenosis is rare with only few cases previously reported in the literature. It is a benign disease and sometimes difficult to distinguish from diseases of the liver. The need for positive surgical resection of splenosis is still controversial.

A novel scoring system predicts adjuvant chemolipiodolization benefit for hepatocellular carcinoma patients after hepatectomy.

Our aim in this study was to develop a prognostic scoring system with which to identify patients most likely to benefit from adjuvant chemolipiodolization (ACL) after liver resection for hepatocellular carcinoma (HCC). Data from 1150 HCC patients who underwent liver resection between 2002 and 2008 at the Eastern Hepatobiliary Surgery Hospital were used to develop the scoring system. Patients were stratified into prognostic subgroups using the new scoring system, and the outcomes of patients who received ACL and those who did not were compared in each subgroup. Using data from 379 patients operated on between 2008 and 2010 for validation, the scoring system had a concordance index (C-index) of 0.75 for predicting post-resectional overall survival (OS). It optimally stratified patients into three prognostic subgroups with scores of 0-5, 6-9 and ≥ 10, having better, medium and worse survival outcomes, respectively. A difference in OS between ACL and non-ACL patients was only detected in the subgroup with scores ≥ 10 (1-, 3-, and 5-year OS rates: 63.9%, 22.6%, and 9.0% vs. 33.8%, 5.6%, and 2.8%, p = 0.001). Our proposed scoring system provides an effective tool for selecting the patients most likely to benefit from ACL.

Loss of function of Notch1 identifies a poor prognosis group of early stage hepatocellular carcinoma following hepatectomy.

Notch1 has previously been implicated in the carcinogenesis of hepatocellular carcinoma (HCC). The present study aimed to investigate the prognostic value of Notch1 in early stage HCC patients after hepatectomy. The differential expression of Notch1 in paired tumor and non-tumorous tissue was evaluated by RT-PCR, western blotting and immunohistochemistry. The correlation between Notch1 expression and the surgical outcome of patients at BCLC stage 0/A and its ≤5 cm subgroup was retrospectively investigated in 206 patients from the Eastern Hepatobiliary Surgery Hospital (training cohort), and prospectively validated in 185 patients from the same center and retrospectively verified in 129 patients from the Fujian Medical University (validation cohort 1 and 2, respectively). Compared with paired non-tumorous tissues, loss of Notch1 was observed in tumor tissue. Patients with normal Notch1 had better prognosis than those with loss of Notch1 in the training cohort and ≤5 cm subgroup (time to recurrence: 38.5±6.1 vs. 16.0±3.2 months, P<0.001 and 53.0±6.1 vs. 21.7±3.5 months, P=0.004; 1-, 3-, 5-year survival rates: 91, 64 and 49% vs. 73, 31 and 22%, P<0.001 and 93, 71, 57% vs. 76, 39, 24%, P<0.001). Notch1 expression was an independent factor for recurrence and survival (hazard ratio: 1.901, 2.154; 2.038 and 2.337). Moreover, Notch1 status affected early tumor recurrence, as the 2-year recurrence rate was 61.2 vs. 26.9% (P<0.001) and 51.2 vs. 21.3% (P=0.002) in tumors with reduced or increased Notch1 expression in this cohort and subgroup. These results were fully confirmed by the study in our prospective and retrospective validation cohorts. The status of Notch1 is useful for predicting the prognosis of patients with early stage HCC undergoing hepatectomy.

Serum thioredoxin is a diagnostic marker for hepatocellular carcinoma.

Here we found that serum levels of thioredoxin were increased in patients with hepatocellular carcinoma (HCC). The optimum diagnostic cutoff for thioredoxin was 20.5 ng/mL (area under curve [AUC] 0.946 [95% CI 0.923-0.969] in the training cohort; 0.941 [0.918-0.963] in the validation cohort). High serum concentrations of thioredoxin differentiated HCC from chronic liver diseases and cirrhosis (0.901 [0.875-0.923] in the training cohort; 0.906 [0.870-0.925] in the validation cohort). Furthermore, a higher proportion of patients with very early HCC had positive results for thioredoxin than for alpha-Fetoprotein (AFP) (73.7% VS.31.6%; P < 0.0001). Among AFP-negative patients with very early HCC, 18 (69.2%) of 26 had positive thioredoxin results. Our results indicate that serum thioredoxin complements measurement of AFP in the diagnosis of HCC, especially in very early disease. Combined model (thioredoxin and AFP) showed a significantly greater discriminatory ability as compared with those markers alone.

Relationship between the imaging features and pathologic alteration in hepatoma of rats.

AIM: The imaging features of MRI and DSA, using the models of implanted and induced hepatoma, were investigated in rats. METHODS: CBRH3 cancer cells were implanted for different liver site of rat liver and the diethylnitrosoamine was given orally to rats in order to induce liver cancer. Both experimental groups were detected by magnetic resonance imaging (MRI), digital subtraction angiography (DSA) and morphologic assay. RESULTS: Hypointensity on T1WI and homogenous high signal intensity on T2WI in MRI, and ring-like abnormal stain on DSA were found in implanted cancer. Induced cancers appeared as homogeneous or heterogeneous hypointensity on T1WI (10 cases), and equal or slight high intensity on T2WI (8 cases), but some as hypointensity on T2WI (2 cases). CONCLUSION: The imaging features of implanted cancers were similar to that of human liver metastases. Therefore, it could serve as an experimental model of human liver metastatic tumor. The imaging feature of induced cancers, whereas, were similar to that of human primary liver cancer. It could be use as an experimental model of human primary liver cancer.

Treatment of portal vein tumor thrombus of hepatocellular carcinoma with percutaneous laser ablation.

BACKGROUND: Portal vein tumor thrombus (PVTT) is a common complication of hepatocellular carcinoma (HCC), and is associated with extremely poor prognosis. PATIENTS AND METHODS: In this retrospective study, we first evaluate the application of percutaneous laser ablation as a treatment for PVTT due to advanced hepatocellular carcinoma. 108 patients (2002.7-2005.12) that have adequate liver function and be in reasonably good general condition were enrolled at Eastern hepatobiliary surgery hospital. The thrombus was ablated via an optic fiber placed in the guide needle with the guiding of ultrasound. In the follow-ups, the serial imaging and laboratory routines were examined and the overall clinical progress was measured at regular intervals until time of death. In the clinical assessment, survival time and factors affecting survival time were analyzed. The changes of laboratory test (alanine transaminase and alpha fetoprotein) and clinical manifestation (ascites and diarrhea) of the PVTT patients before and after laser ablation were observed. RESULTS: Patency of the tumor-occluded portal vein branch is the only factor that affect the survival time, the longer the patency time, the longer the survival time. The long-term survivals of patients in our study are 55.56, 33.58 and 22.38% at 1, 2 and 3 years, respectively. Both laboratory test and clinical presentations were improved. Alphalpha fetoprotein in the positive patients decreased and alanine transaminase in the abnormal patients normalized at 1 month after the treatment. Ascites disappeared in 44.00% patients (11/25), and diarrhea ameliorated in 57.14% (12/21). CONCLUSION: Laser ablation might be a novel and effective treatment for PVTT associated with advanced HCC.