Feasibility and Safety of Laparoscopic Liver Resection for Hepatocellular Carcinoma with a Tumor Size of 5–10 cm

Background

Although laparoscopic liver resection has developed rapidly and gained widespread acceptance for the treatment of benign liver diseases and hepatocellular carcinoma with a small tumor size, its usefulness for the treatment of large tumors is less clear, due to concerns about compromising oncological principles and patient safety. The purpose of this study was to explore the safety and feasibility of laparoscopic liver resection for the treatment of hepatocellular carcinoma with a tumor size of 5–10 cm.

Methods

From March 2007 to December 2011, we performed liver resection in 275 patients with hepatocellular carcinoma with a tumor size of 5–10 cm. Laparoscopic liver resection was performed in 97 patients (Lap-Hx group) and open liver resection was performed in 178 patients (Open-Hx group). Operative time, estimated intraoperative blood loss, blood transfusion rate, and length of postoperative hospital stay were compared between the two groups. Early and intermediate-term postoperative outcomes were also compared.

Results

Only one liver resection was performed for every patient with HCC in the present study.No operative deaths occurred in either group. Nine of the laparoscopic procedures were converted to open resection (conversion rate 9.28%). There were no significant differences in mean operative time (245±105 min vs 225±112 min; P = .469), mean estimated intraoperative blood loss (460±426 mL vs 454±365 mL; P = .913), or blood transfusion rate (4.6%, 4/88) vs (2.8%, 5/178)(P = .480) between the Lap-Hx and Open-Hx groups. However, postoperative hospital stay was shorter in the Lap-Hx group than the Open-Hx group (8.2±3.6 days vs 13.5±3.8 days; P = .028). There was a lower rate of postoperative complications in the Lap-Hx group than the Open-Hx group (9% vs 30%; P = .001), but there were no severe complications in either group. The median overall follow-up time was 21 months (range 2–50 months) and the median follow-up of time of survivors was 23 months. The median follow-up time was 25 months in the Lap-Hx group and 20 months in the Open-Hx group. The follow-up rate was 95% (84 patients) in the Lap-Hx group and 95% (169 patients) in the Open-Hx group, which was not a significant difference between the two groups (P = .20). Tumor recurrence occurred in 17 patients (20%) in the Lap-Hx group and 35 patients (21%) in the Open-Hx group, which was not a significant difference between the two groups (P = .876). A total of 33 patients (13%) died during the study period, including 12 patients (14%) in the Lap-Hx group and 21 patients (12%) in the Open-Hx group, which was not a significant difference between the two groups (P = .695). There were also no significant differences in the 1-year rates of overall survival (94% vs 95%; P = .942) or disease-free survival (93% vs 92%; P = .941), or the 3-year rates of overall survival (86% vs 88%; P = .879) or disease-free survival (66% vs 67%; P = .931), between the Lap-Hx and Open-Hx groups.

Conclusions

Laparoscopic liver resection is safe and feasible in patients with hepatocellular carcinoma with a tumor size of 5–10 cm. Laparoscopic liver resection can avoid some of the disadvantages of open resection, and is beneficial in selected patients based on preoperative liver function, tumor size and location.     

Timing of Hepatectomy for Resectable Synchronous Colorectal Liver Metastases: For Whom Simultaneous Resection Is More Suitable - A Meta-Analysis

Background

The optimal timing of resection for synchronous colorectal liver metastases is still controversial. Retrospective cohort studies always had baseline imbalances in comparing simultaneous resection with staged strategy. Significantly more patients with mild conditions received simultaneous resections. Previous published meta-analyses based on these studies did not correct these biases, resulting in low reliability. Our meta-analysis was conducted to compensate for this deficiency and find candidates for each surgical strategy.

Methods

A systemic search for major databases and relevant journals from January 2000 to April 2013 was performed. The primary outcomes were postoperative mortality, morbidity, overall survival and disease-free survival. Other outcomes such as number of patients need blood transfusion and length of hospital stay were also assessed. Baseline analyses were conducted to find and correct potential confounding factors.

Results

22 studies with a total of 4494 patients were finally included. After correction of baseline imbalance, simultaneous and staged resections were similar in postoperative mortality (RR = 1.14, P = 0.52), morbidity (RR = 1.02, P = 0.85), overall survival (HR = 0.96, P = 0.50) and disease-free survival (HR = 0.97, P = 0.87). Only in pulmonary complications, simultaneous resection took a significant advantage (RR = 0.23, P = 0.003). The number of liver metastases was the major factor interfering with selecting surgical strategies. With >3 metastases, simultaneous and staged strategies were almost the same in morbidity (49.4% vs. 50.9%). With ≤3 metastases, staged resection caused lower morbidity (13.8% vs. 17.2%), not statistically significant.

Conclusions

The number of liver metastases was the major confounding factor for postoperative morbidity, especially in staged resections. Without baseline imbalances, simultaneous took no statistical significant advantage in safety and efficacy. Considering the inherent limitations of this meta-analysis, the results should be interpret and applied prudently.     

Salvage Liver Transplantation for Recurrent Hepatocellular Carcinoma after Liver Resection: Retrospective Study of the Milan and Hangzhou Criteria

Background

Salvage liver transplantation (SLT) has recently been proposed for recurrent hepatocellular carcinoma after liver resection; however, criteria for candidate assessment in SLT have not been thoroughly evaluated.

Methods and Findings

We retrospectively analyzed outcomes and factors affecting survival of 53 recipients who received SLT in the Liver Transplantation Center, The First Affiliated Hospital of Zhejiang University between 2004 and 2012. Thirty recipients fulfilled the Hangzhou criteria, of which 16 also fulfilled the Milan criteria, while the remaining 23 exceeded both criteria. The 1-year, 3-year and 5-year overall survival rates and tumor-free survival rates were both superior in patients fulfilling Milan or Hangzhou criteria compared with those exceeding the criteria. For recipients outside Milan criteria but within Hangzhou criteria, the 1-year, 3-year overall survival rates were 70.1%, 70.1%, similar to recipients within Milan criteria, with the 1-year, 3-year and 5-year overall survival of 93.8%%, 62.1% and 62.1% (P = 0.586). The tumor-free survival rates were also similar between these two subgroups, with 51.9% and 51.9% vs. 85.6%, 85.6% and 64.2% during the same time interval, respectively (P = 0.054). Cox regression analysis identified Hangzhou criteria (within vs. outside, hazard ratio (HR) 0.376) and diameter of the largest tumor (HR 3.523) to be independent predictors for overall survival. The only predictor for tumor-free survival was diameter of the largest tumor (HR 22.289).

Conclusions

Hangzhou criteria safely expanded the candidate pool and are feasible in assessment of candidates for SLT. This is helpful in donor liver allocation in transplant practice.     

Thoracoscopic Lobectomy versus Open Lobectomy in Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

The objective of the present meta-analysis was to evaluate the survival, recurrence rate, and complications in patients with stage I non-small cell lung cancer (NSCLC) who received video-assisted thoracoscopic surgery (VATS) or open lobectomy. A literature search was conducted on June 31, 2012 using combinations of the search terms video-assisted thoracic surgery, open thoracotomy, lobectomy, and non-small-cell lung cancer (NSCLC). Inclusion criteria were: 1) Compared video-assisted thoracic surgery (VATS) lobectomy with open lobectomy. 2) Stage I NSCLC. 2) No previous treatment for lung cancer. 4) Outcome data included 5-year survival rate, complication, and recurrence rate. Tests of heterogeneity, sensitivity, and publication bias were performed. A total of 23 studies (21 retrospective and 2 prospective) met the inclusion criteria. VATS was associated with a longer 5-year survival (odds ratio [OR] = 1.622, 95% confidence interval [CI] 1.272 to 2.069; P<0.001), higher local recurrence rate (OR = 2.152, 95% CI 1.349 to 3.434; P = 0.001), similar distant recurrence rate (OR = 0.91, 95% CI 0.33 to 2.48; P = 0.8560), and lower total complication rate (OR = 0.45, 95% CI 0.24 to 0.84; P = 0.013) compared to open lobectomy. VATS was also associated with lower rates arrhythmias, prolonged air leakage, and pneumonia but it did not show any statistical significance. Patients with stage I NSCLC undergoing VATS lobectomy had longer survival and fewer complications than those who received open lobectomy.     

Intratumoral CD8+ Cytotoxic Lymphocyte Is a Favorable Prognostic Marker in Node-Negative Breast Cancer

Background

The prognostic effect of tumor infiltrating CD8⁺ cytotoxic lymphocytes (CTLs) in breast cancer is controversial. We analyzed the association between CD8⁺ CTLs and survival of untreated node-negative breast cancer patients.

Material and Methods

CD8⁺ CTLs infiltrate was evaluated by immunostaining in a cohort of 332 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of CD8⁺ CTLs for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate analysis and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 expression and human epidermal growth factor receptor 2 (HER-2) status.

Results

285 (85.8%) patients showed strong CD8⁺ CTLs infiltrate positive status. Univariate analysis showed that CD8⁺ CTLs had statistically significant association with DFS (P = 0.004, hazard ratio [HR] = 0.454, 95% confidence interval [CI] = 0.265–0.777) and OS (P = 0.014, HR = 0.430, 95% CI = 0.220–0.840) in the entire cohort. The significance of CD8⁺ CTLs was especially strong in ER negative, HER-2 negative and ER, PR, HER-2 triple-negative breast cancers. In Kaplan-Meier analysis, CD8⁺ CTLs had significant effect on prognosis of patients (Log-rank test: P = 0.003 for DFS and P = 0.011 for OS), independent of established clinical factors for DFS (P = 0.002, HR = 0.418, 95% CI = 0.242–0.724) as well as for OS (P = 0.009, HR = 0.401, 95% CI = 0.202–0.797).     

Prognostic Influence of Pre-Operative C-Reactive Protein in Node-Negative Breast Cancer Patients

The importance of inflammation is increasingly noticed in cancer. The aim of this study was to analyze the prognostic influence of pre-operative serum C-reactive protein (CRP) in a cohort of 148 lymph node-negative breast cancer patients. The prognostic significance of CRP level for disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS) was evaluated using univariate and multivariate Cox regression, also including information on age at diagnosis, tumor size, tumor grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, proliferation index (Ki67) and molecular subtype, as well as an assessment of the presence of necrosis and inflammation in the tumor tissue. Univariate analysis showed that CRP, as a continuous variable, was significantly associated with DFS (P = 0.002, hazard ratio [HR]  = 1.04, 95% confidence interval [CI]  = 1.02–1.07) and OS (P = 0.036, HR  = 1.03, 95% CI  = 1.00–1.06), whereas a trend was observed for MFS (P = 0.111). In the multivariate analysis, CRP retained its significance for DFS (P = 0.033, HR  = 1.01, 95% CI  = 1.00–1.07) as well as OS (P = 0.023, HR  = 1.03, 95% CI  = 1.00–1.06), independent of established prognostic factors. Furthermore, large-scale gene expression analysis by Affymetrix HG-U133A arrays was performed for 72 (48.6%) patients. The correlations between serum CRP and gene expression levels in the corresponding carcinoma of the breast were assessed using Spearman''s rank correlation, controlled for false-discovery rate. No significant correlation was observed between CRP level and gene expression indicative of an ongoing local inflammatory process. In summary, pre-operatively elevated CRP levels at the time of diagnosis were associated with shorter DFS and OS independent of established prognostic factors in node-negative breast cancer, supporting a possible link between inflammation and prognosis in breast cancer.     

Presence of CHD1L Over-Expression Is Associated with Aggressive Tumor Biology and Is a Novel Prognostic Biomarker for Patient Survival in Human Breast Cancer

Background

The chromodomain helicase/adenosine triphosphatase DNA binding protein 1–like gene (CHD1L) is a recently identified oncogene localized at 1q21. CHD1L protein over-expression in primary hepatocellular carcinoma is correlated with enhanced apoptosis inhibition, reduced chemosensitivity and shortened patient survival. However, CHD1L protein status or mRNA expression in breast cancer and its clinical significance remain obscure.

Material and Methods

In this study, immunohistochemical staining for CHD1L expression was performed on tissue microarrays containing 179 primary invasive breast cancers and 65 matched normal breast tissue specimens. Clinico-pathological features were collected and compared between different CHD1L statuses. Kaplan-Meier curves were applied to estimate disease-free survival (DFS) and overall survival (OS). Cox regression was used to identify independent prognostic factors. Also, quantitative real-time polymerase chain reaction (QRT-PCR) was employed to evaluate the mRNA level expression of CHD1L in six breast cancer cell lines.

Results

Presence of CHD1L over-expression was observed in 87 of the 179 patients (48.6%), which associated with a younger age (P = 0.011), higher grade (P = 0.004), higher Ki-67 index (P = 0.018) and HER2 over-expression/amplification (P = 0.037). After a median follow-up of 55 months, patients with presence of CHD1L over-expression had significantly poorer DFS (82.6% Vs 76.3%, P = 0.035), but not OS (87.0% Vs 94.9%, P = 0.439). In multivariate analysis, CHD1L status (HR = 2.169, [95%CI, 1.029–4.573], P = 0.042), triple negative subtype (HR = 2.809, [95%CI 1.086–7.264], P = 0.033) and HER2 positive subtype (HR = 5.221, [95%CI 1.788–15.240], P = 0.002) were identified as independent prognostic factors for DFS. In vitro study indicated that relative mRNA expression level of CHD1L was higher in breast cancer cell lines, especially in MDA-MB-231 and LM2-4175, when compared to normal breast epithelial cell line.

Conclusions

Presence of CHD1L over-expression is probably associated with aggressive tumor biology in breast cancer. CHD1L status might be a novel prognostic biomarker for patients with breast cancer.     

A Large Cohort Study Reveals the Association of Elevated Peripheral Blood Lymphocyte-to-Monocyte Ratio with Favorable Prognosis in Nasopharyngeal Carcinoma

Background

Nasopharyngeal carcinoma (NPC) is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20–30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients.

Methods

A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional recurrence-free survival (LRRFS), respectively.

Results

Univariate analysis revealed that higher LMR level (≥5.220) was significantly associated with superior OS, DFS and DMFS (P values <0.001). The higher lymphocyte count (≥2.145×10⁹/L) was significantly associated with better OS (P = 0.002) and DMFS (P = 0.031), respectively, while the lower monocyte count (<0.475×10⁹/L) was associated with better OS (P = 0.012), DFS (P = 0.011) and DMFS (P = 0.003), respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR  = 0.558, 95% confidence interval or 95% CI  = 0.417–0.748; P<0.001), DFS (HR  = 0.669, 95% CI  = 0.535–0.838; P<0.001) and DMFS (HR = 0.543, 95% CI  = 0.403–0.732; P<0.001), respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053) and DMFS (P = 0.080).

Conclusions

The elevated pretreatment peripheral LMR level was a significant favorable factor for NPC prognosis and this easily accessed variable may serve as a potent marker to predict the outcomes of NPC patients.     

Prognoses and Long-Term Outcomes of Nasopharyngeal Carcinoma in Han and Uyghur Patients Treated with Intensity-Modulated Radiotherapy in the Xinjiang Autonomous Region of China

Objectives

The objective of this study was to investigate the long-term outcomes and prognostic factors for nasopharyngeal carcinoma (NPC) in Han and Uyghur patients treated with intensity-modulated radiotherapy (IMRT) in the Xinjiang region of China.

Materials and Methods

One hundred twenty-one Han and 60 Uyghur patients with newly diagnosed NPC without distant metastasis received IMRT at the Affiliated Tumor Hospital of Xinjiang Medical University between 2005 and 2008. The Kaplan-Meier method was used to estimate survival rates, and the log-rank test was used to evaluate differences in survival.

Results

Comparing Han and Uyghur patients, the 5-year overall survival (OS), disease-free survival (DFS), local control (LC), regional control (RC), and distant metastasis-free survival (DMFS) rates were 81.9% vs 77.6% (P = 0.297), 72.1% vs 65.6% (P = 0.493), 88.3% vs 86.5% (P = 0.759), 95.0% vs 94.6% (P = 0.929), and 79.1% vs 75.2% (P = 0.613), respectively. Multivariate Cox proportional hazards regression identified the following independent prognostic factors in Han patients: N stage (P = 0.007) and age (P = 0.028) for OS, and age (P = 0.028) for DFS. OS differed significantly between Han and Uyghur patients >60 years old group (P = 0.036). Among Uyghur patients, the independent prognostic factors were age for OS (P = 0.033), as well as N stage (P = 0.037) and age (P = 0.021) for DFS. Additionally, Uyghur patients were less likely to experience mucositis and dermatitis than Han patients.

Conclusion

Han and Uyghur patients with NPC had statistically significant differences in age, smoking history, and N staging. There was no significant difference in overall treatment outcomes with IMRT between these 2 ethnic populations in Xinjiang, China.     

Interferon-Based Therapy Decreases Risks of Hepatocellular Carcinoma and Complications of Cirrhosis in Chronic Hepatitis C Patients

Background

Interferon-based therapy (IBT) has been the standard of care for hepatitis C virus (HCV) infection. However, conflicting results exist regarding the effects of IBT on risk of developing hepatocellular carcinoma (HCC) and cirrhosis-associated complications, and most included highly selected patients.

Methods

This 8-year cohort study was based on the Longitudinal Health Insurance Database 2000 (LHID 2000) consisting of 1,000,000 beneficiaries randomly selected from all Taiwan National Health Insurance enrollees in 2000 (>23.7 million). Patients with newly detected HCV infections (n = 11,264) were classified based on treatment and clinical outcomes. IBTs were defined as regimens that included interferon- alfa, pegylated interferon- alfa -2a, or pegylated interferon- alfa -2b for at least 3 months. The Cox proportional hazards models were used to estimate the hazard ratio (HR) and associated confidence interval (CI) of HCC and cirrhosis-associated complications for IBT.

Results

The 8-year incidence rate for HCC was 3.9% among patients who received IBT and 5.6% among those who did not. The HCC-free survival rate was significantly higher among patients receiving IBT during the 8-year period than their counterpart (adjusted HR, 0.50; 95% CI, 0.31–0.81; P = .004). Similarly, the event-free survival rates for esophageal variceal bleeding (adjusted HR, 0.45; 95% CI, 0.22–0.91; P = .026), hepatic encephalopathy (adjusted HR, 0.38; 95% CI, 0.21–0.69; P = .001), ascites (adjusted HR, 0.28; 95% CI, 0.14–0.57; P<.001), and cirrhosis (adjusted HR, 0.63; 95% CI, 0.44–0.91; P = .013) were significantly higher among patients who received IBT than those who did not, after adjustment for associated factors.

Conclusion

Treatment with interferon may reduce the 8-year risk of HCC and cirrhosis-associated complications in patients with chronic HCV infection.     

Is Hepatitis B Immunoglobulin Necessary in Prophylaxis of Hepatitis B Recurrence after Liver Transplantation? A Meta-Analysis

Background & Aims

Application of nucleoside analogues and hepatitis B immunoglobulin (HBIG) has reduced hepatitis B virus (HBV) recurrence rate after liver transplantation (LT) dramatically. Recent data suggests therapy without HBIG is also effective. We sought to evaluate the necessity of HBIG in prophylaxis of HBV recurrence after LT.

Methods

A meta-analysis was performed. PubMed/MEDLINE, Web of Knowledge and other databases were searched for eligible literatures. The major end points were recurrence rate, patient survival, and YMDD mutant. Risk difference (RD) or risk ratio (RR) was calculated to synthesize the results.

Results

Nineteen studies with a total of 1484 patients were included in this analysis. Application of HBIG was helpful to reduce HBV recurrence [P<0.001; RD = 0.16; 95% confidence interval (CI)(0.12, 0.20)] and virus mutants [P<0.001; RR = 3.13; 95%CI (1.86–5.26)], it also improved patients'' 1-year [P = 0.03; RD = 0.08; 95%CI (0.01, 0.15)] and 3-year survival rates [P = 0.005; RD = 0.17; 95%CI(0.05, 0.28)]. No significant difference was found for patients'' 5-year survival [P = 0.46; RD = −0.06; 95%CI (−0.21, 0.10)]. Sub-group analysis showed that in patients with positive pre-operative HBV DNA status, HBIG was necessary to reduce HBV recurrence rate (P<0.001; RD = 0.42; 95%CI (0.32, 0.52)). In patients with negative HBV DNA, combined therapy gained no significant advantages (P = 0.18; RD = 0.06; 95%CI (−0.03, 0.14)). Non-Lamivudine (non-LAM) antiviral drugs performed as well as combination therapy in prophylaxis of HBV recurrence after LT (P = 0.37; RD = 0.06; 95%CI (−0.02, 0.14)).

Conclusions

HBIG with nucleoside analogues is helpful to reduce HBV recurrence and virus mutants. The necessity of HBIG in prophylaxis of HBV recurrence after LT when using new potent nucleoside analogues, especially for patients with negative pre-transplant HBV DNA status remains to be evaluated.     

Prognostic Significance of E-Cadherin Expression in Hepatocellular Carcinoma: A Meta-Analysis

Backgrounds

Hepatocellular Carcinoma (HCC) is one of the most common malignancy of liver and HCC-related morbidity and mortality remains at high level. Researchers had investigated whether and how reduced E-cadherin expression impacted the prognosis of patients with HCC but the results reported by different teams remain inconclusive.

Methods

A systematic literature search was performed in all available databases to retrieve eligible studies and identify all relevant data, which could be used to evaluate the correlation between reduced E-cadherin expression and clinicopathological features and prognosis for HCC patients. A fixed or random effects model was used in this meta-analysis to calculate the pooled odds ratios (OR) and weighted mean differences (WMD) with 95% confidence intervals (CI).

Results

Total 2439 patients in thirty studies matched the selection criteria. Aggregation of the data suggested that reduced E-cadherin expression in HCC patients correlated with poor 1-, 3- and 5-year overall survival. The combined ORs were 0.50 (n = 13 studies, 95% CI: 0.37–0.67, Z = 4.49, P<0.00001), 0.39 (n = 13 studies, 95% CI: 0.28–0.56, Z = 5.12, P<0.00001), 0.40 (n = 11 studies, 95% CI: 0.25–0.64, Z = 3.82, P = 0.0001), respectively. Additionally, the pooled analysis denoted that reduced E-cadherin expression negatively impacts recurrence-free survival (RSF) with no significant heterogeneity. The pooled ORs for 1-, 3- and 5- year RSF affected by down-regulated E-cadherin were 0.73 (n = 6 studies, 95% CI: 0.54–1.00, Z = 1.95, P = 0.05), 0.70 (n = 6 studies, 95% CI: 0.52–0.95, Z = 2.32, P = 0.02), 0.66 (n = 5 studies, 95% CI: 0.48–0.90, Z = 2.64, P = 0.008). And what’s more, reduced E-cadherin expression tended to be significantly associated with metastasis (OR = 0.31, 95% CI: 0.16–0.60, Z = 3.50, P = 0.0005), vascular invasion (OR = 0.76, 95% CI: 0.59–0.98, Z = 2.14, P = 0.03), advanced differentiation grade (OR = 0.31, 95% CI: 0.21–0.45, Z = 6.04, P<0.00001) and advanced TMN stage (T3/T4 versus T1/T2) (OR = 0.61,95% CI:0.38–0.98, Z = 2.05, P = 0.04).

Conclusions

Reduced E-cadherin expression indicates a poor prognosis for patients with HCC, and it may have predictive potential for prognosis of HCC patients.     

Immunoglobulin Kappa C Predicts Overall Survival in Node-Negative Breast Cancer

Background

Biomarkers of the immune system are currently not used as prognostic factors in breast cancer. We analyzed the association of the B cell/plasma cell marker immunoglobulin kappa C (IGKC) and survival of untreated node-negative breast cancer patients.

Material and Methods

IGKC expression was evaluated by immunostaining in a cohort of 335 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of IGKC for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 and human epidermal growth factor receptor 2 (HER-2) status.

Results

160 patients (47.7%) showed strong expression of IGKC. Univariate analysis showed that IGKC was significantly associated with DFS (P = 0.017, hazard ratio [HR] = 0.570, 95% confidence interval [CI] = 0.360–0.903) and OS (P = 0.011, HR = 0.438, 95% CI = 0.233–0.822) in the entire cohort. The significance of IGKC was especially strong in ER negative and in luminal B carcinomas. In multivariate analysis IGKC retained its significance independent of established clinical factors for DFS (P = 0.004, HR = 0.504, 95% CI = 0.315–0.804) as well as for OS (P = 0.002, HR = 0.371, 95% CI = 0.196–0.705).

Conclusion

Expression of IGKC has an independent protective impact on DFS and OS in node-negative breast cancer.     

Duration of Chemotherapy for Small Cell Lung Cancer: A Meta-Analysis

Background

Maintenance chemotherapy is widely provided to patients with small cell lung cancer (SCLC). However, the benefits of maintenance chemotherapy compared with observation are a subject of debate.

Methodology and Principal Findings

To identify relevant literature, we systematically searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases. Eligible trials included patients with SCLC who either received maintenance chemotherapy (administered according to a continuous or switch strategy) or underwent observation. The primary outcome was 1-year mortality, and secondary outcomes were 2-year mortality, overall survival (OS), and progression-free survival (PFS). Of the 665 studies found in our search, we identified 14 relevant trials, which together reported data on 1806 patients with SCLC. When compared with observation, maintenance chemotherapy had no effect on 1-year mortality (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.66–1.19; P = 0.414), 2-year mortality (OR: 0.82; 95% CI: 0.57–1.19; P = 0.302), OS (hazard ratio [HR]: 0.87; 95% CI: 0.71–1.06; P = 0.172), or PFS (HR: 0.87; 95% CI: 0.62–1.22; P = 0.432). However, subgroup analyses indicated that maintenance chemotherapy was associated with significantly longer PFS than observation in patients with extensive SCLC (HR, 0.72; 95% CI: 0.58–0.89; P = 0.003). Additionally, patients who were managed using the continuous strategy of maintenance chemotherapy appeared to be at a disadvantage in terms of PFS compared with patients who only underwent observation (HR, 1.27; 95% CI: 1.04–1.54; P = 0.018).

Conclusions/Significance

Maintenance chemotherapy failed to improve survival outcomes in patients with SCLC. However, a significant advantage in terms of PFS was observed for maintenance chemotherapy in patients with extensive disease. Additionally, our results suggest that the continuous strategy is inferior to observation; its clinical value needs to be investigated in additional trials.     

Comparison of Steroid-Free Immunosuppression and Standard Immunosuppression for Liver Transplant Patients with Hepatocellular Carcinoma

Immunosuppression therapy following liver transplantation often includes steroids. However, extended corticosteroid therapy is associated with numerous complications. This study evaluated the efficacy and safety of using basiliximab in place of a corticosteroid for immunosuppression following liver transplantation for hepatocellular carcinoma (HCC) in Chinese patients. The records of 178 patients with HCC who underwent orthotopic liver transplantation from January 2003 to December 2009 were retrospectively reviewed. All patients received immunosuppression therapy that contained either basiliximab (n = 78) or steroids (n = 100) in addition to tacrolimus and mycophenolate mofetil. Assessments included complications related to liver transplantation, occurrence of steroid side effects, recurrence of HCC, and patient and graft survival. A smaller proportion of patients receiving basiliximab compared with steroids experienced de novo diabetes (38.7% vs. 91.0%, respectively) or long-term de novo diabetes mellitus (7.7% vs. 38.0%, respectively) (both, P<0.0001). The median overall and disease free survival was similar between basiliximab (50.8 months and 19.6 months, respectively) and steroid treated patients (64.2 months and 23.8 months, respectively). The 5-year overall survival and disease free survival rates was also similar between the basiliximab (42.5% and 38.9%, respectively) and steroid (50.5% and 39.2%) groups (all, P>0.730). However, in patients who met the Milan criteria basiliximab was associated with greater 5-year overall survival rate as compared with steroid therapy (88.9% vs. 57.4%, respectively, P = 0.022). These findings provide further evidence of the negative impact of steroids as a part of immunosuppression therapy following liver transplantation for HCC.     

Prognostic Value of Metastatic Axillary Lymph Node Ratio for Chinese Breast Cancer Patients

Objective

The prevalence of breast cancer varies among countries and regions. This retrospective study investigated the prognostic value of the lymph node ratio (LNR) compared with the number of positive lymph nodes (pN) in Chinese breast cancer patients.

Methods

The medical records of female breast cancer patients (N = 2591) were retrospectively evaluated. The association of LNR and TMN staging system were compared with respect to overall, disease-free, and distant metastasis-free survival.

Results

Out of 2591 patients, 2495 underwent modified radical surgery and 96 received breast conserving surgery. All patients had adjuvant chemotherapy following surgery. The median follow up period 66.9 months (range 5–168 months). The 5-year and 10-year overall survival rates were 89.3% and 78.8%, respectively, and 5-year disease-free survival and distant metastasis-free survival rates were 81.6% and 83.5%, respectively. Univariate analysis indicated that in general T, pN, LNR, as well as tumor expression of the estrogen receptor, progesterone receptor, and HER2 were associated with overall, disease-free, and distant metastasis-free survival (all P-values <0.05). Mutlivariate analysis found pN stage and LNR were independent predictors of overall, disease-free, and distant metastasis-free survival (all P-values <0.001). If pN stage and LNR were both included in a multivariate analysis, LNR was still an independent prognostic factor for overall, disease-free, and distant metastasis-free survival (all P-values <0.001).

Conclusion

Our findings support the use of LNR as a predictor of survival in Chinese patients with breast cancer, and that LNR is superior to pN stage in determining disease prognosis.     

Using SCC Antigen and CRP Levels as Prognostic Biomarkers in Recurrent Oral Cavity Squamous Cell Carcinoma

Squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) levels have been successfully used to stratify risk groups in primary oral squamous cell carcinoma (OSCC) patients; however, related biomarkers have rarely been investigated in recurrent OSCC. The purpose of the present study was to analyze the relationships of SCC-Ag and CRP levels at the time of recurrence with clinical factors and prognosis. We retrospectively recruited patients with recurrence in a cohort of 534 OSCC patients between March 2001 and July 2013. One hundred patients had recurrence. The serum SCC-Ag and CRP levels were measured at the time of cancer diagnosis, 3 to 6 months after treatment with clinical disease-free, and at the time of recurrence. The SCC-Ag levels were significantly lowered after treatment (paired t-test: p = 0.001) and re-elevated at the time of recurrence (paired t-test: p = 0.027). An SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L at the time of recurrence were significantly associated with recurrent tumor status (P<0.001), recurrent nodal metastasis (χ² trend test: P = 0.020), distant metastasis (P<0.001), and overall survival (P<0.001). Moreover, the influence of both elevated SCC-Ag and CRP levels on overall survival (P<0.001, H.R. [95% CI]: 5.406 [2.210–13.222]) still existed after adjusting for the recurrent tumor stage and patient age. The present study demonstrates that concurrent high levels of both SCC-Ag and CRP at the diagnosis of recurrence acts as a predictor of recurrent tumor status, recurrent advanced tumor stage, distant metastasis, and survival after the diagnosis of recurrence. This study expands the applicability of these two markers in the risk stratification in recurrent OSCC.     

Healthcare Utilization and Clinical Outcomes after Catheter Ablation of Atrial Flutter

Atrial flutter ablation is associated with a high rate of acute procedural success and symptom improvement. The relationship between ablation and other clinical outcomes has been limited to small studies primarily conducted at academic centers. We sought to determine if catheter ablation of atrial flutter is associated with reductions in healthcare utilization, atrial fibrillation, or stroke in a large, real world population. California Healthcare Cost and Utilization Project databases were used to identify patients undergoing atrial flutter ablation between 2005 and 2009. The adjusted association between atrial flutter ablation and healthcare utilization, atrial fibrillation, or stroke was investigated using Cox proportional hazards models. Among 33,004 patients with a diagnosis of atrial flutter observed for a median of 2.1 years, 2,733 (8.2%) underwent catheter ablation. Atrial flutter ablation significantly lowered the adjusted risk of inpatient hospitalization (HR 0.88, 95% CI 0.84–0.92, p<0.001), emergency department visits (HR 0.60, 95% CI 0.54–0.65, p<0.001), and overall hospital-based healthcare utilization (HR 0.94, 95% CI 0.90–0.98, p = 0.001). Atrial flutter ablation was also associated with a statistically significant 11% reduction in the adjusted hazard of atrial fibrillation (HR 0.89, 95% CI 0.81–0.97, p = 0.01). Risk of acute stroke was not significantly reduced after ablation (HR 1.09, 95% CI 0.81–1.45, p = 0.57). In a large, real world population, atrial flutter ablation was associated with significant reductions in hospital-based healthcare utilization and a reduced risk of atrial fibrillation. These findings support the early use of catheter ablation for the treatment of atrial flutter.     

Expression of THOP1 and Its Relationship to Prognosis in Non-Small Cell Lung Cancer

Background

The study was designed to detect the expression level of thimet oligopeptidase (THOP1) protein in non-small cell lung cancer (NSCLC) and investigate its correlation with clinicopathologic features and prognosis.

Methods

Immunohistochemical staining was used to determine the expression of THOP1 protein in 120 NSCLC specimens and 53 distant normal lung tissues. Quantitative real-time PCR and western blotting were employed to measure the expression of THOP1 in 16 pairs of primary NSCLC and corresponding normal tissues.

Results

Analysis of immunohistochemical staining suggested low THOP1 expression was found in 71 (59.2%) of the 120 NSCLC specimens and significantly correlated with positive lymph node metastasis (P = 0.048). However, low THOP1 expression was found in 22 (41.5%) of the 53 normal lung tissues. Chi-square test suggested that the expression of THOP1 was significantly higher in the normal lung tissues than that in the NSCLC specimens (P = 0.032). Real-Time PCR and western blotting showed that NSCLC specimens had decreased THOP1 mRNA and protein expression compared to corresponding normal tissues. Univariate analysis demonstrated that low THOP1 expression significantly predicted decreased 5-year disease-free survival (P = 0.038) and overall survival (P = 0.017). In addition, positive lymph node metastasis (P = 0.025) and advanced TNM stage (P = 0.009) significantly predicted decreased 5-year overall survival. However, multivariate Cox regression analysis showed that only low THOP1 expression retained its significance as an independent prognostic factor for unfavorable 5-year disease-free survival (P = 0.046) and overall survival (P = 0.021).

Conclusions

THOP1 may have clinical potentials to be employed as a promising biomarker to identify individuals with better prognosis and a novel antitumor agent for therapy of patients with NSCLC.     

Analysis of the Relationships between Clinicopathologic Factors and Survival in Gallbladder Cancer following Surgical Resection with Curative Intent

Background

This study elucidated the relationships between various clinicopathologic factors and the outcome of patients with gallbladder cancer (GBC) treated by surgical resection with curative intent.

Methods

Between January 2003 and January 2011, 76 patients with GBC underwent surgical resection with curative intent at our department. We then conducted a retrospective analysis of clinicopathologic data. Fourteen clinicopathological variables were selected for univariate and multivariate analysis to evaluate their influence on the outcome.

Results

The actuarial 1-, 3-, and 5-year survival rates in the 76 resected cases were 56.6%, 32.7%, and 23.8%, respectively. The univariate analysis revealed that curative resection (P<0.001), lymph node metastasis (P<0.001), AJCC stage (P = 0.030), tumor location (P = 0.008), histologic differentiation (P = 0.028), intraoperative blood loss (P = 0.011), and preoperative jaundice (P = 0.012) were significant risk factors for survival. Multivariate analysis revealed that noncurative resection and tumor location on gallbladder neck were significant risk factors for poor outcome. Among jaundiced patients, we discovered that gallbladder carcinoma with tumor thrombus in common bile duct (CBD) was very rare but with relatively special clinical manifestation and characteristic radiography manifestation. The prognosis of gallbladder carcinoma with tumor thrombus in CBD after surgical procedure was apparently better than gallbladder carcinoma with invasion of hilar tissues.

Conclusions

Curative surgical resection remains the only effective approach to the treatment of GBC. This series confirm that jaundice is a poor prognostic factor. However, the presence of jaundice does not preclude resection, especially in highly selected patients (when R0 resection is achievable). Gallbladder carcinoma with tumor thrombus in CBD has special clinical characteristics, which need to be awared by radiologists and clinicians.