Comparative study on prognosis of neoadjuvant chemotherapy followed by hepatic surgery versus upfront surgery in patients with synchronous colorectal liver metastasis / 中华胃肠外科杂志

Objective: To compare the survival outcome in patients with synchronous colorectal cancer liver metastasis receiving neoadjuvant chemotherapy followed by hepatic surgery versus upfront surgery strategies. Methods: A retrospective cohort study was carried out. Data of patients undergoing surgery at the Department of Hepatopancreatobiliary Surgery Unit I of Peking University Cancer Hospital from January 2008 to December 2018 for initially resectable synchronous colorectal liver metastasis were retrospectively collected. A total of 282 cases were enrolled, including 244 in the neoadjuvant chemotherapy group, 38 in the upfront surgery first group. The overall survival (OS) and progression-free survival (PFS) of the two groups were compared. A propensity score risk adjustment was used to eliminate potential bias between groups, and the covariates including sex, age, location of primary tumor, T stage, clinical risk score (CRS), RAS gene status, adjuvant chemotherapy, and resection margin status were included for adjustment. Results: In the neoadjuvant chemotherapy group, 244 cases received 4 (1-15) cycles of chemotherapy before hepatic resection, among whom 207 cases received oxaliplatin-based regimens, 37 cases received irinotecan-based regimens, and 90 cases received combined targeted agents in the first line treatment. The median follow-up time was 30 (5-134) months, and loss of follow-up was 1%. Before adjustment, Kaplan-Meier survival analysis showed that the 1-year and 3-year OS rates in the neoadjuvant chemotherapy group (95.1% and 66.4%) were better than those in the upfront surgery first group (94.7% and 51.5%, P=0.026); 1-year and 3-year PFS rates in neoadjuvant chemotherapy group (51.0% and 23.4%) were also better than those in surgery first group (39.5% and 11.5%, P=0.039). After propensity score risk adjustment, Cox multivariate analysis indicated that neoadjuvant chemotherapy was an independent protective factor of PFS (HR=0.664, 95% CI: 0.449-0.982, P=0.040), however, neoadjuvant chemotherapy was not an independent protective factor of OS (HR=0.651, 95% CI: 0.393-1.079, P=0.096). Subgroup analysis showed that the 1-year and 3-year OS rates in the patients with response to the first line treatment (194, including complete remission, partial remission and reduction but not partial remission) (96.9% and 67.1%) were better than those in the upfront surgery group (94.7% and 51.5%, P=0.026) after adjustment. However, the 1-year and 3-year OS rates in the patients without response to the first line treatment (50, including tumor progression or enlargement) were 90.0% and 63.3%, respectively, which were not significantly different with 94.7% and 51.5% in the upfront surgery group (P=0.310) after adjustment. Conclusions: For patients with resectable synchronous colorectal cancer liver metastasis, liver resection after neoadjuvant chemotherapy can provide longer PFS than upfront surgery. Although the whole OS benefit is not significant, patients with effective neoadjuvant first-line chemotherapy have better OS than those undergoing upfront surgery.

Human U Three Protein 14a Expression is Increased in Hepatocellular Carcinoma and Associated with Poor Prognosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Human U three protein 14a (hUTP14a) promotes p53 degradation. Moreover, hUTP14a expression is upregulated in several types of tumors. However, the expression pattern of hUTP14a in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to investigate hUTP14a expression and its prognostic value in HCC.</p><p><b>METHODS</b>The hUTP14a expression was evaluated using immunohistochemistry (IHC) in HCC tissue specimens. The correlations between hUTP14a expression and clinicopathological variables were analyzed. The Kaplan-Meier method was used to analyze the association between hUTP14a expression and survival. Independent prognostic factors associated with overall survival (OS) and disease-free survival (DFS) were analyzed using the Cox proportional-hazards regression model.</p><p><b>RESULTS</b>The IHC data revealed that the hUTP14a positivity rate in HCC tissue specimens was significantly higher than that in nontumorous tissue specimens (89.9% vs. 72.7%, P < 0.05). The hUTP14a expression was detected in both the nucleolus and the cytoplasm. The positivity rate of nucleolar hUTP14a expression in HCC tissue specimens was higher than that in the nontumorous tissue specimens (29.3% vs. 10.1%, P < 0.05). No significant difference was found between HCC and nontumorous tissue specimens of cytoplasmic hUTP14a expression (60.6% vs. 62.6%, P > 0.05). In addition, no significant correlation was found between nucleolar hUTP14a expression and other clinicopathological variables. The 5-year OS and DFS rates in patients with positive nucleolar hUTP14a expression were significantly lower than those in patients with negative hUTP14a expression (P = 0.004 for OS, P = 0.003 for DFS). Multivariate analysis showed that nucleolar hUTP14a expression was an independent prognostic factor for OS (P = 0.004) and DFS (P < 0.001).</p><p><b>CONCLUSIONS</b>The positivity rate of hUTP14a expression was significantly higher in HCC specimens. Positive expression of nucleolar hUTP14a might act as a novel prognostic predictor for patients with HCC.</p>

Expression of plasminogen activator inhibitor-2 is negatively associated with invasive potential in hepatocellular carcinoma cells / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the association between plasminogen activator inhibitor (PAI)-2 expression and invasive potential in hepatocellular carcinoma (HCC) cells.</p><p><b>METHODS</b>The HCC cell lines with high, low, and non-metastatic potentials, namely MHCC97-H, MHCC97-L, and SMMC-7721 respectively, were cultured in vitro. Matrigel invasion assay and Western blot of PAI-2 protein expression were conducted.</p><p><b>RESULTS</b>The number of invaded cells in MHCC97-L was significantly higher than that in SMMC-7721 (P=0.005), whereas that in MHCC97-H was higher than in MHCC97-L (P=0.017) and SMMC-7721 (P=0.001). Contrarily, PAI-2 protein expression was gradually reducing from SMMC-7721, MHCC97-L, to MHCC97-H (MHCC97-H vs. MHCC97-L, P<0.001; MHCC97-H vs. SMMC-7721, P=0.001; MHCC97-L vs. SMMC-7721, P=0.001). The Pearson's correlation analysis revealed a significant negative association between invaded cell number and PAI-2 expression (r=-0.892, P=0.001).</p><p><b>CONCLUSION</b>PAI-2 expression may be negatively associated with the invasive potential of HCC.</p>

Intrahepatic biliary injuries associated with radiofrequency ablation of hepatic malignancies / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Biliary injury after radiofrequency ablation can cause serious consequences including death. However, there are limited data regarding bile duct changes with or without complications associated with radiofrequency ablation of hepatic malignancies. This study aimed to assess the incidence, prognosis and risk factors of intrahepatic biliary injury associated with radiofrequency ablation.</p><p><b>METHODS</b>Between June 2001 and January 2009, 638 patients with hepatic malignancies (405 with hepatocellular carcinoma, and 233 with liver metastasis) who had 955 treatment sessions were enrolled in this study. Imaging and laboratory data, the course of treatment, and patient outcomes were reviewed retrospectively. The risk factors of biliary injury and the impact on overall survival of patients were analyzed. The chi-square test, Fisher's exact test, Kaplan-Meier curves and stepwise Logistic regression model were used for statistical analysis where appropriate.</p><p><b>RESULTS</b>Biliary injury was observed in 17 patients after 17 ablation sessions based on imaging findings. The overall incidence of biliary injury was 1.8% (17/955) with an average onset time of 12 weeks (2-36 weeks). Mild, moderate and severe complications of biliary injury were identified in 9, 6 and 2 cases, respectively. The median survival time after detection of biliary injury was 40 months. There seemed no notable difference in overall survival between patients with and those without biliary injuries. By multivariate analysis, vessel infiltration (P = 0.034) and treatment session ≥ 4 times (P = 0.025) were independent risk factors for biliary injury of hepatocellular carcinoma; while tumor located centrally was the only independent risk factor in the metastasis group (P = 0.043).</p><p><b>CONCLUSIONS</b>The incidence of biliary injury was not frequent (1.8%). Through appropriate treatment, intrahepatic bile duct injuries seemed not affect the patients' long-term survival. Additionally, risk factors may be helpful for selecting radiofrequency ablation candidates and predicting biliary complications.</p>

Downregulation of chromobox protein homolog 7 expression in multiple human cancer tissues / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between chromobox protein homolog 7 (cbx7) expression and the occurrence and development of colorectal carcinoma (CRC), gastric carcinoma (GC) and hepatocarcinoma (HCC) tissues.</p><p><b>METHODS</b>The samples of neoplastic tissues and the corresponding cutting-edge normal tissues from 22 cases of CRC, 20 cases of GC, 30 cases of HCC were surgically collected. Level of cbx7 mRNA was detected with a fluorescent quantitative RT-PCR assay, and the correlationship among expression of cbx7 mRNA, the patients' clinicopathologic features and the surviving time after surgery was analyzed.</p><p><b>RESULTS</b>The relative copy number of cbx7 mRNA in carcinomas and the normal tissues was 0.010 ± 0.015 vs 0.053 ± 0.042 for CRCs, 0.197 ± 0.195 vs 1.891 ± 1.254 for GCs, and 0.008 ± 0.008 vs 0.030 ± 0.021 for HCCs, respectively. Compared with the corresponding normal tissues, cbx7 expression was significantly downregulated in CRCs, GCs, and HCCs (t = -7.351, -5.417 and -6.680, respectively, P < 0.01). The expression of cbx7 mRNA in CRCs had significant differences not only between two age groups (the relative copy number of cbx7 mRNA in age > 55 group was 0.007 ± 0.015, but 0.017 ± 0.012 in age ≤ 55 group, t = -2.586, P = 0.022); but also between vascular embolus-positive and negative groups (the level of cbx7 mRNA in positive and negative group was 0.022 ± 0.021 vs 0.006 ± 0.011, t = -3.175, P = 0.010). The area under the receiver operating characteristics (ROC) curve is 0.769 (P = 0.033). when the Cut-off value of the relative copy number of cbx7 mRNA was 0.002 in CRCs. The values less-than 0.002 were defined as low expression. The CRC patients with low expression of cbx7 had a shorter overall survival time; whose 5 years survival rate was only 30.8% (4/13); while the rate was 77.8% (7/9) in high expression of cbx7 group. The difference had statistical significance (χ(2) = 4.329, P = 0.037). The similar differences could not be found among GC and HCC patients.</p><p><b>CONCLUSION</b>Downregulation of cbx7 expression was very common among multiple carcinomas cases, and the downregulation influenced the prognosis of CRC patients.</p>

Clinicopathological features of solid pseudopapillary tumor of the pancreas / 中国医学科学院学报

<p><b>OBJECTIVE</b>To elucidate the clinicopathological features of solid pseudopapillary tumor (SPT) of the pancreas.</p><p><b>METHODS</b>Eight patients with SPT of the pancreas admitted from August 1996 to March 2005 were retrospectively analyzed.</p><p><b>RESULTS</b>All the 8 patients were female with an average age of 25.3 (13-41) years. The primary clinical manifestations included abdominal mass (n = 3), vague abdominal pain (n = 3), and duodenal obstruction (n = 1). SPT was occasionally found in one patient during physical examination. Six tumors located at the head and the other two in the body and tail of the pancreas. Pancreaticoduodenectomies were performed in 4 patients, tumor enucleations in 2, distal pancreatectomies in 1, and palliative internal drainage with a cystoenterotomy in the other one with an unresectable huge cystic lesion. All patients were alive on an average follow-up of 37.8 (8-103) months.</p><p><b>CONCLUSION</b>SPT occurs mainly in adolescent and young females, and satisfactory outcome may be achieved with active and appropriate surgeries.</p>

Radiofrequency ablation of recurrent hepatocellular carcinoma after hepatectomy / 中华外科杂志

<p><b>OBJECTIVE</b>To assess the efficiency and safety of radiofrequency ablation (RFA) of recurrent hepatocellular carcinoma (RHCC) after hepatectomy and to investigate efficacy of RFA for patients with early and late phase recurrence, separately, setting 1 year as the cut-off between the early and late phases.</p><p><b>METHODS</b>A total of 42 patients with 77 RHCC and a history of hepatic resection for hepatocellular carcinoma (HCC) underwent ultrasound-guided percutaneous radiofrequency ablation in our department and entered this study (RHCC group). The average diameter of RHCC was (3.8 +/- 1.4) cm (range, 1.5-6.6 cm). 21 of the 42 RHCC patients had Child-Pugh class A cirrhosis 19, class B and two, class C cirrhosis. The average interval between initial surgery and the diagnosis of recurrence was 22.8 months (range, 1-96 month). 42 RHCC patients were divided into two groups as early recurrence group including 20 patients with 40 RHCC, and late recurrence group including the other 22 patients with 37 RHCC according to the recurrence interval. During the same period 148 patients with 217 primary HCC were also treated by RF ablation and regarded as primary HCC group. The average diameter of primary HCC was (4.0 +/- 1.4) cm (range, 1.2-7.0 cm). Regular follow-up with enhanced CT was performed to evaluate the treatment results. Ablation was considered a success if no contrast enhancement was detected in the treated area on 1 month CT scans.</p><p><b>RESULTS</b>The ablation success rate, local recurrence rate, new tumor incidence and mean survival in RHCC group were 90.5%, 14.3%, 38.1% and (28.0 +/- 3.5) months, respectively, which were similar to the corresponding results of 87.2%, 16.2%, 37.8% and (39.0 +/- 2.1) month in primary HCC group. However, when further comparison was performed between early recurrence group, late recurrence group and primary HCC group, there were some significant differences. The incidence of new tumors in early recurrence group was significantly higher than that in late recurrent group (60.0% vs. 18.2%, P = 0.005); early recurrence group survived shorter than primary HCC group [(15.4 +/- 2.3) vs. (39.0 +/- 2.1) months, P < 0.005]. The survival time was similar between late recurrence group and primary HCC group. One case was found haemorrhage after RFA and recovered with conservative treatment. No major complications occurred in the remaining 41 patients.</p><p><b>CONCLUSIONS</b>RF ablation is generally effective and safe in treating RHCC. And it's more effective in late recurrence than in early recurrence.</p>

Expression of wild type and variant estrogen receptors in human hepatocellular carcinoma / 北京大学学报(医学版)

Objective:To investigate the expression of wild type estrogen receptor(wER)and the ex-on-5 deleted ER(variant ER,vER)in human hepatocellular carcinoma(HCC)samples,and thereafteranalyze the possibility of HCC treatment by endocrine therapy.Methods:The mRNA expressions of wERand vER were analysed from 28 cases of HCC by RT-PCR.The expression of ER at the protein level wasdetected by immunohistochemistry(IHC).Results:IHC results showed that 39.3% of the HCC speci-mens expressed ER.The mRNA of wER was detected in 89.3%(25/28)of the HCC specimens whilethat of vER was detected in 96.4%(27/28).Twenty four out of 28 HCC cases(85.7%)expressedboth wER and vER.One out of 28 patients(3.5%)expressed only wER whereas 3 patients out of 28(10.7%)expressed vER only.Conclusion:Ninety six percent(27/28)of the HCC patients expressedvER,which suggests that the expression of vER is an important event in the development of HCC.

Impact of spiral CT cholangiography on suspected obstructive jaundice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study spiral CT cholangiography (SCTC) before treatment in patients with obstructive jaundice due to unknown cause.</p><p><b>METHODS</b>Between October 1998 and November 2000, a total of 59 patients with obstructive jaundice of unknown cause were examined by two-phase enhanced spiral CT (eSCT). Twenty-nine of these cases were excluded because they had had T-Bil of > 34 micromol/L so that their biliary duct system could not have been visualized. The remaining 30 patients were 17 male and 13 female with an age range of 31 - 76 years (mean 56.6). Pathologically, the lesion was proven to be carcinoma of pancreatic head (n = 9), Vater's ampulla carcinoma (n = 4), extrahepatic or hilar cholangiocarcinoma (n = 13), hepatocellular carcinoma (n = 1), chronic pancreatitis (n = 1) and cholelithiasis (n = 2). SCTC was performed through intravenous injection of 20 ml 50% Cholografin within 20 min before eSCT. SCTC was undertaken with parameters of a slice thickness of 2 - 3 mm, a table feed of 3 - 5 mm, a gantry time of 0.75 sec, a reconstruction interval of 1 - 2 mm, a pitch of 1.1 - 1.2, a voltage of 120 kV, a current of 220 - 240 mA, a matrix of 512 x 512 and a scan range from the level above hepatic hilum to the third segment of duodenum within 60 - 105 min following the injection. Both reconstructed SCTC source images and later eSCT scans were considered as axial CT (ACT). Multiplanar reconstruction (MPR) was obtained immediately on the operator console. 3D imaging adopted in our study was volume rendering technology (VRT) that was processed on the Siemens 3D Virtuoso workstation within 30 min. Opacification of biliary tree (OBT) analyzed by Grades 1 to 5 and image quality (IQ) assessed by 4 scales as excellent, good, fair and poor were investigated in ACT, MPR and VRT, respectively. The correlation between total OBT, which was the highest among the 3 image methods in the same case, and T-Bil, D-Bil, ALT, severity of the biliary obstruction (SBO) as well as level of the obstruction was analyzed.</p><p><b>RESULTS</b>In OBT, no statistically significant difference was found in the five grades by the three imaging techniques (P > 0.05), the distribution of percentages being 0, 0, 13.3%, 30.0% and 56.7% in ACT, 0, 6.7%, 20.0%, 30.0% and 43.3% in MPR and 0, 0, 13.3%, 40.0% and 46.7% in VRT. The evident correlation between total OBT and D-Bil (r(s) = -0.719), ALT (r(s) = -0.544) and SBO (r(s) = 0.650) was showed. In IQ, only a statistical significance existed between ACT and MPR (P = 0.034), having the scales "excellent to poor" in percentages of 93.3%, 6.7%, 0 and 0 for ACT, 66.7%, 30.0%, 3.3% and 0 for MPR and 70.0%, 23.3%, 6.7% and 0 for VRT, respectively.</p><p><b>CONCLUSION</b>According to our study, spiral CT cholangiography is very useful for the evaluation of selected patients with suspected obstructive jaundice before treatment.</p>