Analysis of outcome using a levator sparing technique of abdominoperineal excision of rectum and anus. Cylindrical ELAPE is not necessary in all patients

Aims

Abdominoperineal excision of rectum (APE) for cancer has a higher rate of local recurrence with a poorer outcome than stage matched anterior resection. The cylindrical excision (ELAPE) has been advocated to reduce local recurrence. However, this operation has greater morbidity and requires more post operative care. We report our outcomes from a single centre using a levator sparing dissection.

Methods

All patients undergoing APE from January 2007–June 2011 were evaluated. Case notes operation notes and pathology results were reviewed for complications and staging. Follow-up data for survival and recurrence were obtained from the cancer registry, imaging and from clinic follow up.

Results

Of all rectal cancers (n = 361), 43 had APE with curative intent. Median age was 67(IQR 59–76). Median tumour height was two centimetres from the dentate line (IQR 1–3.5 cm). Neoadjuvant chemoradiotherapy was given in 98% of APE resections with curative intent. Median post operative hospital stay was 10 days (8–15).At a median follow up of 38 months (IQR30-49) for patients undergoing curative resection, 2 patients (4.6%) had local recurrence and overall mortality was 18.6% (n = 8).

Conclusion

With adequate neoadjuvant chemoradiotherapy, a levator sparing excision of rectum remains a safe option with less morbidity and perioperative complications than has been described for ELAPE.     

VEGF and Id-1 in pancreatic adenocarcinoma: Prognostic significance and impact on angiogenesis

Objectives

The significance of vascular endothelial growth factor (VEGF) and inhibitor of differentiation/DNA synthesis (Id-1) in tumor neoangiogenesis and tumor progression in pancreatic ductal adenocarcinoma (PDAC) is still unclear. Given the central role of VEGF in cancer angiogenesis and the inconclusive results on Id-1 expression in PDAC, it is of great interest to investigate whether Id-1 and VEGF expression are associated with angiogenesis and prognosis in PDAC.

Methods

Paraffin-embedded specimens from 60 consecutive patients with PDAC were immunostained for VEGF, Id-1 and CD34 and staining quantification was assessed by Image analysis system. The correlations among the expression of individual angiogenic factors and microvessel density (MVD), clinicopathologic features and clinical prognosis were analyzed.

Results

Id-1 and VEGF Positive Activity Indices (PAIs) closely correlated with each other. MVD positively correlated with both Id-1 and VEGF expression. More advanced T and N status correlated with more intense expression of Id-1, VEGF and higher MVD. With regard to prognostic significance higher Id-1 PAI (adjusted HR = 1.69, 95%CI: 1.10–2.59, p = 0.017), higher VEGF PAI (adjusted HR = 2.66, 95%CI: 1.09–6.50, p = 0.032), and MVD (adjusted HR = 1.55, 95%CI: 1.27–1.88, p < 0.001) were associated with poorer survival.

Conclusions

VEGF and Id-1 overexpression were found to be associated with high MVD and emerged as adverse prognostic factors in terms of patient survival in PDAC. The potential of selective anti-angiogenic targeting therapy for pancreatic malignancies should prompt further validation of the present findings in studies encompassing larger samples and more elaborate techniques.     

Radiologic assessment of earliest,best, and plateau response of gastrointestinal stromal tumors to neoadjuvant imatinib prior to successful surgical resection

Background

To determine the timing of earliest, best and plateau response to neoadjuvant imatinib in patients with GIST.

Materials and methods

In this IRB-approved retrospective study, we included all 20 patients (10 women; mean age 61 years, range 30–83 years) with KIT-positive primary GIST who received neoadjuvant imatinib and underwent surgery between January 2001 and December 2012. Earliest (earliest time to partial response), best (percentage reduction in longest axial diameter [LAD] and volume correlated with RECIST 1.1 and volumetric criteria) and plateau (time point when there was <10% change in treatment response between two consecutive scans beyond best response) responses were analyzed on review of imaging.

Results

Median tumor size at baseline was 7.2 cm (range, 3.0–31.4 cm). Median duration of neoadjuvant imatinib was 32 weeks (IQR, 16–36 weeks). Partial response was noted in 16/20 patients (median interval = 16 weeks; IQR, 7–26 weeks); 4/20 had stable disease. Median time to earliest PR was 16 weeks (IQR, 7–26 weeks). At best response, median decrease in LAD and volume were 43% (IQR, 31–48%) and 83% (IQR, 63–87%), (median interval = 28 weeks; IQR, 18–37 weeks), at which point 10 tumors were resected. Plateau response (45% [IQR, 35–45%] LAD reduction) was noted in the remaining 10 patients (median interval = 34 weeks; IQR, 26–41 weeks) before resection. Tumor size, location or risk category did not correlate with best response or time to best response.

Conclusion

Best response to neoadjuvant imatinib was seen at 28 weeks irrespective of tumor size and location. Plateau response was seen at 34 weeks, beyond which further treatment may not be beneficial.     

Massive endoprosthetic replacement for bone metastases resulting from renal cell carcinoma: Factors influencing patient survival

Background

Surgery remains the main treatment of bone metastases due to renal cell carcinoma (RCC). We reviewed 135 patients treated with resection and endoprosthetic replacement (EPR) and examined clinico-pathological factors predicting survival.

Methods

Surgical and oncological outcomes were examined using a prospectively maintained database between 1976 and 2012. Survival rates were calculated by Kaplan–Meier method. Multivariate analyses were performed to investigate factors predictive of increased survival.

Results

At diagnosis, 81 patients had synchronous RCC and bone metastases and the remaining developed metachronous metastases after primary treatment for RCC. The majority were solitary tumours (75%) and 77% had ≥ one concurrent visceral metastases. The median age at surgery was 61 years old (IQR 53–69). The median follow-up was 20 months (IQR 10–43) and the overall survival was 72% at one-year. This declined to 45% and 28% at three and five-years, respectively. After adjustments for prognostic factors, there was an increased risk of death in patients with multiple skeletal metastases (HR = 2), ≥one visceral metastases (HR = 3) and local recurrence (HR = 3) (all p ≤ 0.01). Ten patients required revision (7%) and the risk of revision was 4% at one-year and remained low at 8% from two years postoperatively.

Conclusion

Patients with solitary bone lesions and no visceral metastases should be considered for bone resection and EPR. As survival beyond one-year can be expected in a majority of patients and the risk of further surgery after EPR is low, patients with multiple skeletal metastases and visceral metastases should also be considered.     

MTAP is an independent prognosis marker and the concordant loss of MTAP and p16 expression predicts short survival in non-small cell lung cancer patients

Objectives

Methylthioadenosine phosphorylase (MTAP), a ubiquitously expressed protein, plays important roles in purine biosynthesis. Locating near to each other on chromosome 9p21-22, codeletion of the MTAP and p16^Ink4A genes have been reported in non-small cell lung cancer (NSCLC). The aim of this study is to determine the respective prognostic value of MTAP and p16 by considering their correlation in NSCLC patients.

Materials and methods

We analyzed MTAP and p16 protein expression by immunohistochemical staining on 99 NSCLC tissue microarray samples. The association between MTAP and p16 expression levels and prognosis were analyzed using the Kaplan–Meier method and Cox proportional hazards model for prognosis.

Results

Patients with a low MTAP expression level had poor overall survival (P = 0.010) and disease-free survival (P = 0.002). Low p16 expression indicated a trend toward poor overall survival (P = 0.138) and disease-free survival (P = 0.199). There was a significant positive correlation between MTAP and p16 expression levels (Spearman's ρ = 0.402, P < 0.001). By multivariate analyses, the MTAP expression level retained its independent prognostic power and p16 expression loss of the correlation with prognosis. Concordant loss of MTAP and p16 expression was observed in 24 out of 99 patients (24.2%). Patients with concordant loss of MTAP and p16 expression had the worst prognosis compared to patients with high expression of both markers.

Conclusion

MTAP expression is an independent prognostic factor and has greater prognostic significance than p16 expression in NSCLC. Concordant loss of MTAP and p16 expression indicates poor outcomes in lung cancer patients.     

Heat shock protein 70 as a predictive marker for platinum-based adjuvant chemotherapy in patients with resected non-small cell lung cancer

Objectives

Although adjuvant platinum-based chemotherapy improves survival in completely resected non-small cell lung cancer (NSCLC), its effect is limited. We evaluated whether the expression of heat shock protein 70 (Hsp70) is associated with clinical outcomes in patients with completely resected NSCLC who were treated with or without adjuvant platinum-based chemotherapy.

Patients and methods

Patients who underwent curative resection for NSCLC and diagnosed as stage IIA through IIIA were included. Immunohistochemical staining for Hsp70 was performed on surgical specimens and survival rates were compared by Hsp70 expression and adjuvant platinum-based chemotherapy.

Results

Of 327 enrolled patients, Hsp70 expression was positive in 220 (67.3%). For patients who did not receive adjuvant chemotherapy, Hsp70 expression did not significantly affect survival. However, for patients who received adjuvant chemotherapy, those with Hsp70-positive tumors had a longer disease-free survival outcome than cases with Hsp70-negative tumors (not reached vs. 27.3 months; P = 0.002), although there was no significant difference in overall survival (97.0 vs. 58.9 months, P = 0.080). In the adjuvant chemotherapy group, multivariate modeling showed that patients with Hsp70-postitive tumors had a lower risk of recurrence and death after adjusting for age, sex, performance status, pathologic stage, and histological type (disease-free survival: adjusted hazard ratio, 0.537; 95% CI, 0.362–0.796; P = 0.002; overall survival: adjusted hazard ratio, 0.663; 95% CI, 0.419–1.051; P = 0.080).

Conclusion

Hsp70 is a positive predictive factor in completely resected NSCLC with received platinum-based adjuvant chemotherapy.     

Prognostic impact of the mean platelet volume/platelet count ratio in terms of survival in advanced non-small cell lung cancer

Background

Mean platelet volume (MPV) is a platelet volume index. Classically, MPV was recognized as a hallmark of platelet activation. Recent studies have revealed that the MPV and MPV/platelet count (PC) ratio can predict long-term mortality in patients with ischemic cardio-vascular disease. In addition, these indices were correlated with the pathophysiological characteristics of patients with various disorders, including malignant tumors.

Patients and methods

We retrospectively analyzed various hematological indices of patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the contribution of platelet volume indices to survival in these patients.

Results

A total of 268 patients were enrolled in the study. The median age of the patients was 68 years (range: 31–87 years). We compared various hematological indices between the NSCLC group and an age- and sex-matched comparator group. MPV was significantly decreased in the NSCLC group compared to the comparator group. In contrast, the PC was significantly increased in the NSCLC group. Consequently, the MPV/PC ratio was also decreased in the NSCLC group (0.397 vs. 0.501). In receiver operating characteristics (ROC) curve analysis, the MPV/PC ratio was associated with a sensitivity of 62.3% and a specificity of 74.6% at a cutoff value of 0.408730 (area under the curve [AUC], 0.72492)]. Univariate analysis revealed that overall survival (OS) was significantly shorter in the group with a low MPV/PC ratio than in the other group (median survival time [MST]: 10.3 months vs. 14.5 months, log-rank, P = 0.0245). Multivariate analysis confirmed that a low MPV/PC ratio was an independent unfavorable predictive factor for OS (hazard ratio [HR]: 1.668, 95% confidence interval [CI]: 1.235–2.271, P = 0.0008).

Conclusion

These data clearly demonstrate that the MPV/PC ratio was closely associated with survival in patients with advanced NSCLC.     

Efficacy and safety of erlotinib in elderly patients in the phase IV POLARSTAR surveillance study of Japanese patients with non-small-cell lung cancer

Objective

More tolerable treatment options are needed for the large number of elderly patients with non-small-cell lung cancer (NSCLC). An analysis of the phase IV POLARSTAR surveillance study examined the safety and efficacy of erlotinib in elderly Japanese patients with previously treated NSCLC.

Materials and methods

From December 2007 to October 2009, all erlotinib-treated patients with unresectable, recurrent/advanced NSCLC in Japan were enrolled. Efficacy and safety data were stratified by age (<75 years, 75–84 years, ≥85 years). Kaplan–Meier methodology was used to estimate median progression-free survival (PFS). Safety data were collected with a focus on interstitial lung disease (ILD).

Results

A total of 9907 patients were eligible for safety assessment (<75 years, n = 7848; 75–84 years, n = 1911; ≥85 years, n = 148) and 9651 for efficacy assessment (<75 years, n = 7701; 75–84 years, n = 1815; ≥85 years, n = 135). Other baseline characteristics were balanced. The incidence of ILD (all grades) was 4.2% (<75 years), 5.1% (75–84 years), and 3.4% (≥85 years). The mortality rate due to ILD was ≤1.7% in all age groups. Other toxicities (including rash) were similar between age groups. The median PFS was 65 days (95% confidence interval [CI], 62–68) for patients aged <75 years, 74 days (95% CI, 69–82) for patients aged 75–84 years, and 72 days (95% CI, 56–93) for patients aged ≥85 years.

Conclusions

Efficacy and tolerability of erlotinib for elderly patients was not numerically inferior to that reported in younger patients. Erlotinib could be considered for elderly patients with recurrent/advanced NSCLC.     

A genetic sequence variant (GSV) at susceptibility loci of 5p15.33 (TERT-CLPTM1L) is associated with survival outcome in locally advanced and metastatic non-small-cell lung cancer (NSCLC)

Introduction

Lung cancer is a leading cause of cancer-related mortality in North America. In addition to tobacco smoking, inherited genetic factors can also influence the development of lung cancer. These genetic factors may lead to biologically distinct subsets of cancers that have different outcomes. We evaluated whether genetic sequence variants (GSVs) associated with lung cancer risk are associated with overall survival (OS) and progression-free survival (PFS) in stage-III-IV non-small-cell lung cancer (NSCLC) patients.

Methods

A total of 20 candidate GSVs in 12 genes previously reported to be associated with lung cancer risk were genotyped in 564 patients with stage-III or IV NSCLC. Multivariate Cox proportional hazard models adjusted for potential clinical prognostic factors were generated for OS and PFS.

Results

After taking into account multiple comparisons, one GSV remained significant: rs4975616 on chromosome 5p15.33, located near the TERT-CLPTM1L gene. The adjusted hazard ratio (aHR) for OS was 0.75 (0.69–0.91), p = 0.002; for PFS aHR was 0.74 (0.62–0.89), p < 0.001 for each protective variant allele. Results were similar in both Stage III (OS: aHR = 0.70; PFS: aHR = 0.71) and Stage IV patients (OS: aHR = 0.81; PFS: aHR = 0.77).

Conclusion

A GSV on 5p15.33 is not only a risk factor for lung cancer but may also be associated with survival in patients with late stage NSCLC. If validated, GSVs may define subsets of patients with different risk and prognosis of NSCLC.     

Surgical resection of primary tumour improves aerobic performance in colorectal cancer

Background

Colorectal cancer is the third most common cancer in the UK, with patients suffering declines in muscle mass and aerobic function. We hypothesised that tumour removal in non-metastatic colorectal cancer would lead to a restoration of lean muscle mass and increases in objective and subjective measures of aerobic performance.

Methods

We recruited two groups: patients with colorectal cancer (n = 30, 65.3 (51–77) y, body mass index 27.67 (4.83) kg m⁻²) and matched controls (n = 30, 64.6 (42–77) y, BMI 27.14 (3.51) kg m⁻²). Controls underwent a single study while colorectal cancer patients were studied before and 10 months after tumour resection. Aerobic performance was assessed via cardiopulmonary exercise testing and activity questionnaires. Lean muscle mass was measured via dual-energy X-ray absorptiometry.

Results

Lean muscle mass was not different between groups (control: 47.82 (8.23); pre-resection: 52.41 (10.59); post-resection: 52.38 (10.52), kg). Anaerobic threshold was lower in pre-operative patients compared to controls (14.40 (3.23) vs. 19.67 (5.81) ml kg⁻¹ min⁻¹, p < 0.0001), increasing significantly post-resection (17.00 (3.56) ml kg⁻¹ min⁻¹p < 0.0001). Self reported maximal physical activity was lower after resection compared to preoperatively (pre-resection 6.0 (6.5–5 IQR), post-resection 3.75 (4–3 IQR), p < 0.0001).

Conclusion

In colorectal cancer, anaerobic threshold is reached more rapidly than in matched controls, returning toward normal with tumour resection. Self-reported measures of activity do not mirror this objective change, cardiopulmonary exercise testing may therefore allow for a more accurate evaluation of pre and postoperative performance capability. The variance between objective and subjective measures of exercise capacity may be important in determining return to normal activities.     

Preoperative plasma D-dimer levels predict survival in patients with operable non-small cell lung cancer independently of venous thromboembolism

Background and aims

D-dimer is a stable end product of fibrin degradation that is associated with advanced tumor stage and poor prognosis in lung cancer patients. Venous thromboembolism (VTE) is a frequent complication of cancer and is associated with a poor prognosis in cancer patients. The purpose of the study is to elucidate whether the increased mortality in non-small cell lung (NSCLC) patients with elevated D-dimer levels is independent of VTE.

Patients and methods

A retrospective review was conducted of 232 patients with operable NSCLC from January 2007 to June 2008. All the patients underwent a pneumonectomy, lobectomy or wedge resection. We assessed the ability of preoperative plasma D-dimer levels to predict 1-year mortality and overall survival among them, and a multivariable Cox proportional-hazard regression analysis was performed after controlling for the following potential confounding factors: age, gender, TNM stage, histology, tumor size, VTE and surgical interventions.

Results

The overall 1-year survival rate was 91.4% (95% confidence interval (CI), 82.7–94.8%), with a 76.5% survival (95% CI, 71.4–81.6%) in the high D-dimer group and a 93.9% survival (95% CI, 86.4–97.9%) in the normal D-dimer group. Comparing the high D-dimer group with the normal D-dimer group, the adjusted hazard ratio for 1-year mortality and overall survival was 3.19 (95% CI, 1.18–7.12) and 1.54 (95% CI, 1.11–2.78) respectively.

Conclusion

Our study concluded that the preoperative plasma D-dimer level is an important prognostic biomarker in patients with operable NSCLC that is independent of VTE.     

Ratio of marked and excised sentinel lymph nodes and scintigraphic appearance time in melanoma patients with negative sentinel lymph node

Aim

Metastases can occur in up to 15% of all melanoma patients with negative sentinel lymph node examination (SN –). We retrospectively investigated the number of preoperatively marked sentinel lymph nodes (SNs) with lymphoscintigraphy and effectively surgically removed SNs in SN – patients with cutaneous melanoma ≥0.5 mm. Ratio of these parameters was calculated and impact of this ratio as well as impact of scintigraphic appearance time (SAT) on disease progression was studied.

Materials and methods

Data on 122 SN – patients — 70 women (58%), mean age 56.5 years — were analyzed. Mean follow-up time was 58 months.

Results

Mean tumour thickness of all patients was 2.3 mm. In 51 patients (42%) the number of SNs marked in lymphoscintigraphy was higher than excised in surgery, in 47 patients (38%) the same number as marked was excised and in 24 patients (20%) a lower number was marked than excised. Metastases occurred in 17 patients (14%) after a mean time of 24.8 months. Mean tumour thickness (5.4 mm) was significantly higher in these patients than in the other patients (p = 0.000). Ratio of marked and excised SNs had no influence on disease progression; the only parameter influencing outcome was tumour thickness (p = 0.000). Short SAT was significantly associated with higher tumour thickness (p = 0.004).

Conclusion

Our study indicates that, in routine clinical practice, it suffices to harvest the first SN, as the ratio of marked and excised SNs has no impact on disease progression.     

Nuclear and cytoplasmic cellular distribution of survivin as survival predictor in resected non-small-cell lung cancer

Aim

Survivin is a member of the inhibitors of apoptosis (IAP) gene family that acts through pathways different from those involving the bcl-2 family. Largely undetectable in normal adult tissues, survivin is deregulated in most human cancers including non-small-cell lung cancer (NSCLC) and may represent a tumor marker with prognostic and therapeutic implications. Aim of our study was to determine the prognostic role of survivin as an apoptosis-related biomarker in a series of resected NSCLC patients.

Methods

A retrospective series of resected NSCLC patients were retrieved from the files of the Regina Elena National Cancer Institute. Survivin was detected by immunohistochemistry (IHC) using a polyclonal antibody. Survivin displayed two kinds of immunoreactivity: (i) a diffuse cytoplasmic staining and (ii) a distinct nuclear staining. A score-scale to distinguish positive (score 1–2) vs. negative (score 0) pattern was applied. Clinical and biological (nuclear and cytoplasmic survivin staining) covariables were screened for a prognostic relationship with overall survival (OS) and disease-free survival (DFS) into the univariate and multivariate analyses.

Results

Data referring to 116 NSCLC patients who underwent surgery for stage I–IIIA NSCLC were collected. Multivariate analyses identified tumor size, nodal status and nuclear, but not cytoplasmic, expression of survivin as significant independent predictors of OS, with a hazard ratio of 2.40 (95% CI 1.44, 3.99, p = 0.001), 2.03 (95% CI 1.26, 3.26, p = 0.003) and 1.83 (95% CI 1.01, 3.30, p = 0.044), respectively. Median OS for nuclear survivin positive (score 1–2) and negative (score 0) patients were 23 months (95% CI 15, 31) and 36 months (95% CI 1, 76), respectively (p = 0.01); five-year survival for score 1–2 and score 0 patients were 20% and 44.5%, respectively. Conversely, no significant impact on survival is found when patients are stratified according to cytoplasmic survivin expression.

Conclusions

Data presented herein open the issue that prognosis of stage I–IIIA NSCLC can be linked to the cellular pattern of distribution of survivin.     

Is primary tumor resection associated with a longer survival in colon cancer and unresectable synchronous metastases? A 4-year multicentre experience

Aim

To explore the survival impact of primary tumor resection (PTR) in patients with metastatic colon cancer (mCC) and unresectable metastases.

Methods

We retrospectively studied a multicenter cohort of consecutive mCC patients with unresectable metastases receiving first-line chemotherapy. A weighted Cox proportional regression model was used to balance for clinical variables associated with the probability of undergoing PTR, using inverse probability of treatment weighting (IPTW) based on a propensity score.

Results

Ninety-six patients were included. PTR was performed in 69 (72%). The rates of secondary resection of metastases (p = 0.02) and bevacizumab administration (p = 0.02) were higher in the PTR group. Raw median overall survival (OS) was 23.1 months (95%CI[14.6–27.8]) in the PTR group and 22.1 months (95%CI[12.3–23.7]) in the non-PTR group (p = 0.11). After adjustment on IPTW, OS was 23.1 months (95%CI[17.0–28.7]) in the PTR group and 17.2 months (95%CI[13.5–22.2]) in the non-PTR group (HR 0.68; 95%CI[0.50–0.93]; p = 0.016). This result remained significant on multivariate analysis (HR 0.71; 95%CI[0.50–1.00]; p = 0.05).

Conclusion

In mCC patients with unresectable metastases receiving chemotherapy, up-front PTR was independently associated with prolonged OS. Patients eligible for secondary metastases resection and/or bevacizumab may benefit the most from PTR. Randomized controlled trials are mandatory.     

Video-assisted thoracoscopic surgery lobectomy versus open lobectomy in patients with clinical stage Ⅰ non-small cell lung cancer: A meta-analysis

Aims

Video-assisted thoracoscopic surgery (VATS) lobectomy for early lung cancer has been shown to be technically feasible. Weather VATS lobectomy has equivalent or better clinical effect compared with open lobectomy for early lung cancer patients remains controversial. The purpose is to assess the value of VATS compared with thoracotomy for stage Ⅰ non-small cell lung cancer (NSCLC) by meta-analysis.

Methods

We searched databases of EMBASE, PubMed, and ScienceDirect for relevant articles published between January 1990 and January 2013. Eligible studies were randomized controlled trials (RCTs) or comparative studies of VATS lobectomy and open lobectomy for clinical stage Ⅰ NSCLC. Data on operation time, intra-operative blood loss, length of chest tube drainage and hospital stay, complications incidence and 5 year survival rate were meta-analyzed using Review Manager 5.0.

Results

20 studies with 3457 clinical stage Ⅰ NSCLC patients were included. There was no difference in operation time between the two groups (P = 0.14), but distinct advantages in terms of intra-operative blood loss, chest drainage time, hospital stay and complication incidence were found in the VATS group (P < 0.01). Moreover, the 5 year survival rate of VATS group was significantly higher than thoracotomy group (OR 1.82, 95% CI, 1.43–2.31, P < 0.01).

Conclusion

Compared with thoracotomy group, VATS achieved better surgical and oncological outcomes and was a more favorable treatment for stage Ⅰ NSCLC patients.     

Prognostic impact of pERK in advanced hepatocellular carcinoma patients treated with sorafenib

Background

Sorafenib represents the standard of care targeted therapy for patients with advanced hepatocellular carcinoma (HCC). However, biomolecules that predict a patient's response to sorafenib treatment for HCC remain largely unknown. Thus, this study was designed to investigate whether phosphorylated ERK (pERK) and members of the sorafenib target or PI3K/Akt/mTOR signaling pathway predict the efficacy of sorafenib in advanced HCC patients.

Methodology

From December 2008 to October 2011, pathological specimens from 54 advanced HCC patients received sorafenib treatment were obtained. Clinicopathological variables, treatment response, survival and time to progression (TTP) were recorded. Immunophenotypical analysis was carried out using antibodies against pERK, phosphorylated S6K (pS6K), VEGFR2 and PTEN.

Results

The median overall survival (OS) and TTP were 14.2 and 3.4 months, respectively, and the disease control rate (DCR) was 59.3%. Better Eastern Cooperative Oncology Group Performance Status (ECOG PS) (95% CI: 3.27–4.93 m vs. 1.15–2.85 m, p = 0.01), Child–Pugh class A score (95% CI: 3.47–4.53 vs. 1.14–2.06 m, p < 0.01), and higher pERK (3.34–6.66 m vs. 1.33–2.67 m, p = 0.03) and VEGFR2 (3.49–6.52 m vs. 2.15–2.73 m, p = 0.04) immunohistochemical staining score were associated with increased TTP by univariate analysis. The ECOG PS (p = 0.022), Child–Pugh class (p = 0.045) and pERK staining score (p = 0.012) were found to be associated with TTP using multivariate analysis.

Conclusion

Sorafenib treatment outcome is favorable in advanced HCC patients who received tumor resection and who have a good ECOG PS and Child–Pugh class A liver function. The pERK immunohistological staining score, ECOG PS and Child–Pugh class may be helpful in determining patients most likely to benefit from sorafenib therapy.     

The prognostic value of P-cadherin in non-muscle-invasive bladder cancer

Objectives

This research aims to specify the prognostic value of P-cadherin on recurrence and progression in non-muscle-invasive bladder cancers (NMIBC).

Methods

A total of 110 NMIBC cases were collected and P-cadherin protein was assessed by immunohistochemical test in these samples. Correlations between P-cadherin expression and clinicopathologic features were analyzed. For recurrence-free and progression-free survival, Kaplan–Meier log-rank test was used. Then Cox univariate and multivariate analyses were further performed.

Results

P-cadherin high expression correlated with tumor progression (P = 0.031). Kaplan–Meier results showed that patients with high P-cadherin expression had worse progression-free survival (P = 0.034) but not recurrence-free survival (P = 0.133) than low-expression patients. Cox regression results showed P-cadherin expression was an independent predictor for progression (P = 0.042) but not recurrence (P = 0.139) in NMIBC.

Conclusions

Our results demonstrated that P-cadherin expression correlated with tumor progression and could be taken as an independent predictor for progression in NMIBC.