Wilms’ Tumor 1 Protein and Estrogen Receptor Beta Expression are Associated with Poor Outcomes in Uterine Carcinosarcoma

Background

Uterine carcinosarcoma (CS) is an aggressive malignancy. Increased expression of Wilms’ tumor 1 (WT1) protein and estrogen receptor beta (ER-β) protein is associated with worse outcomes in gynecologic cancers; therefore, we sought to assess this association in CS patients.

Methods

A retrospective analysis was conducted for women diagnosed with uterine CS from departmental databases. WT1/ER-β expression was determined by immunohistochemical staining and scoring of specimens. Univariate and multivariate models were used to correlate progression-free survival (PFS) and overall survival (OS) with WT1/ER-β expression and clinicopathologic factors.

Results

Ninety four patients had mean follow-up of 27 months. Postoperative treatments included chemotherapy for 52 (55 %) subjects and radiotherapy for 25 (27 %). Sixty-four (68 %) and 74 (79 %) tumor samples expressed WT1 and ER-β by immunohistochemistry, respectively. On univariate analysis, stage (p = .02) and lower uterine segment invasion (LUSI) (p = .001) were associated with decreased PFS. Only stage (p = .003) was linked to OS. In the total sample, increased WT1 expression was marginally associated with impaired PFS (p = .07) and OS (p = .09) but ER-β expression was not associated with PFS (p = .89) or OS (p = .30). WT1 and ER-β concurrent expression was associated with impaired OS (p = .02) and PFS (p = .02). On multivariate analysis, LUSI was a significant prognostic factor for PFS [hazard ratio (HR) 2.21, 95 % confidence interval (CI) = 1.12–4.32, p = .03] and stage for OS (HR 3.20, 95 % CI = 1.23–8.35, p = .02). Increased WT1/ER-β expression was associated with impaired OS (HR 1.31, 95 % CI = 1.02–1.69, p = .04).

Conclusions

Concurrent increased WT1 and ER-β expression impairs prognosis for women with uterine CS. Further research is warranted to define how relevant pathways interact and whether targeting these pathways improves OS.

     

Outcomes of Triple-Negative Breast Cancers (TNBC) Compared with Non-TNBC: Does the Survival Vary for All Stages?

Background

Triple-negative breast cancer (TNBC) is associated with aggressive tumor behavior and worse outcomes. In a study at a tertiary care breast unit in a developing country, clinico-pathological attributes and outcomes of patients with TNBC were compared with (c.w.) ER, PR, and/or HER2 expressing tumors (non-TNBC).

Patients and methods

Medical records of 1213 consecutive breast cancer patients managed during 2004–2010 were reviewed. An evaluable cohort of 705 patients with complete treatment and follow-up (median 36 months) information was thus identified. Patients were categorized per ER, PR & HER2 status into TNBC, and ER/PR+ and/or HER2+ groups. Clinico-pathological parameters, response to NACT, and OS & DFS were compared between TNBC and non-TNBC groups.

Results

TNBC patients (n = 249) comprised 35.3 % of the study cohort (n = 705), and were significantly younger than non-TNBC patients (mean age 49.1 ± 11.2y c.w. 51.8 ± 11.3, p = 0.02). The TNM stage at presentation was similar in the two groups (Stage I and II—37 % c.w. 44.3 %, Stage III—47.5 % c.w. 39.5 %, Stage IV—15.5 % c.w. 16.2 % in TNBC c.w. Non-TNBC; p = 0.09). Tumor size (5.7 ± 2.9 cm TNBC c.w. 5.4 ± 2.8 cm non-TNBC, p = 0.22) was similar but lymph nodal (cN) metastases were more frequent in TNBC (77.3 % c.w. 69.8 %; p = 0.03). TNBC had higher histologic grade (97.1 % gr II/III in TNBC c.w. 91.2 % non-TNBC, p = 0.01) and higher incidence of LVI (20.4 % in TNBC c.w. 13.5 %, p = 0.03). Patient groups received similar multi-disciplinary surgical, radiation, and systemic treatment. Comparable proportion of patients in 2 groups were treated with NACT (42 % c.w. 38 %), which resulted in pathological complete response (pCR) in 27.5 % TNBC patients c.w. 17.1 % non-TNBC patients (p = 0.04). Both OS (81.8 ± 4.52 c.w. 97.90 ± 3.87 months, p < 0.001) and DFS (89.2 ± 5.1 c.w. 113.8 ± 4.3 months, p < 0.001) were shorter in TNBC than non-TNBC group. On stage-wise comparison, OS differed significantly only in stage III (47.4 ± 5.3 months in TNBC c.w. 74.5 ± 4.4 in non-TNBC; p < 0.001). Univariate and multivariate analyses revealed tumor stage and IHC subtyping into TNBC c.w. non-TNBC as most important factors predictive of survival.

Conclusions

TNBC occurred at younger age and exhibited aggressive pathology as compared to non-TNBC patients. Although patients with TNBC exhibited better chemo-sensitivity, they had worse DFS and OS compared to the non-TNBC patients. The survival of Stage III TNBC patients was significantly worse compared to non-TNBC group; while in stages I, II, and IV, survival were not significantly different.

     

CD133 Expression at the Metastatic Site Predicts Patients’ Outcome in Colorectal Cancer with Synchronous Liver Metastasis

Background

CD133 is a transmembrane protein that is proposed to be a stem cell marker of colorectal cancer (CRC); however, the correlation between CD133 expression and survival of CRC patients with liver metastasis has not been fully examined.

Methods

CD133 expression was evaluated immunohistochemically, both in primary tumors and synchronous liver metastases of 88 consecutive CRC patients, as well as recurrent lesions in the remnant liver of 27 of these 88 patients. The relationship between CD133 expression and clinicopathological characteristics, recurrence-free survival, and overall survival (OS) was analyzed.

Results

CD133 expression in liver metastases (mCD133) was detected in 50 of 88 patients (56.8 %), and had significant correlation with CD133 expression in primary lesions (pCD133) (p < 0.001). CD133 expression in liver recurrent lesions (recCD133) also had a significant correlation with mCD133 (p < 0.001). mCD133+ patients had significantly longer disease-free survival (p = 0.043) and OS (p = 0.014) than mCD133? patients. In addition, mCD133+ patients had a significantly lower rate of extrahepatic recurrence (p < 0.001).

Conclusions

Patients without CD133 expression in liver metastasis had significantly shorter survival, perhaps because mCD133? patients had a significantly higher rate of extrahepatic recurrence.

     

Histopathologic risk stratification of stage IIB colorectal cancer

Purpose

To stratify stage IIB (pT4a PN0) colorectal cancer in terms of histopathologic findings.

Methods

We reviewed the medical records of 80 patients who underwent surgery for stage IIB colorectal cancer. The disease-free survival (DFS) and overall survival (OS) rates were evaluated and correlated with the presence or absence of “Tumor Necrosis”, “Crohn’s-like lymphoid reaction”, and “Perineural Invasion”.

Results

Patients with “Tumor Necrosis” had significantly lower DFS rates (p < 0.0001), those with “Crohn’s-like lymphoid reaction” had significantly higher DFS rates (p = 0.037), and those with “Perineural Invasion” had significantly lower DFS rates (p < 0.0001). Patients with “Tumor Necrosis” had significantly lower OS rates (p = 0.016), those with “Crohn’s-like lymphoid reaction” had significantly higher OS rates (p = 0.022), and those with “Perineural Invasion” had significantly lower OS rates (p = 0.003).

Conclusions

Since stage IIB colorectal cancers accompanied by the pathological findings of “Tumor Necrosis” and “Perineural Invasion”, but with the absence of “Crohn’s-like lymphoid reaction” carried a poor prognosis, the efficacy of adjuvant chemoradiation must be considered for these patients.

     

Expression of BRCA1, a factor closely associated with relapse-free survival,in patients who underwent neoadjuvant chemotherapy with docetaxel,cisplatin, and fluorouracil for squamous cell carcinoma of the esophagus

Purpose

The aim of this study was to identify the biomarkers associated with chemotherapeutic efficacy and long-term survival for patients with advanced squamous cell carcinoma of the esophagus (SCCE) who had received neoadjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil (NAC-DCF).

Methods

This study included 45 patients with advanced SCCE who received NAC-DCF between 2008 and 2012. The NAC-DCF was conducted as a phase II study (UMIN000007408). The expressions of excision repair cross-complementing-1 (ERCC1), class III beta-tubulin, breast cancer susceptibility gene I (BRCA1), and thymidylate synthase were investigated simultaneously in the pre-treatment endoscopic tumor biopsy samples.

Results

A multivariate logistic regression analysis indicated that pathological responses were significantly associated with tumors with low ERCC1 expression (P = 0.016) and with tumors with high BRCA1 expression (P = 0.030). The multivariate Cox proportional hazard model analysis for relapse-free survival revealed high BRCA1 expression (P = 0.031, hazards ratio 4.39) as the factor associated with survival.

Conclusions

Low ERCC1 expression and high BRCA1 expression in patients with SCCE were associative biomarkers for chemotherapeutic efficacy. High BRCA1 expression was considered the factor associated with survival. These findings may be helpful for tailoring chemotherapy.

     

Laparoscopic radical nephroureterectomy is associated with worse survival outcomes than open radical nephroureterectomy in patients with locally advanced upper tract urothelial carcinoma

Purpose

To compare survival outcomes between laparoscopic radical nephroureterectomy (LRNU) and open radical nephroureterectomy (ORNU) in upper urinary tract urothelial carcinoma (UTUC) patients.

Methods

We retrospectively analyzed the data of 371 UTUC patients who underwent ORNU (n = 271) or LRNU (n = 100) between 1992 and 2012. The survival outcomes included intravesical recurrence (IVR)-free survival, overall survival (OS), and cancer-specific survival (CSS). The Kaplan–Meier method and log-rank test were used to estimate and compare survival curves between groups. Factors associated with survival outcomes were evaluated using univariable and multivariable Cox proportional hazard models.

Results

The three-year IVR-free survival rates were similar between the ORNU and LRNU groups (59.9 and 61.7 %, p = 0.267). However, the LRNU group showed worse five-year OS (59.1 vs. 75.2 %, p = 0.027) and CSS (66.1 vs. 80.2 %, p = 0.015) rates than the ORNU group. In particular, on stratifying the study cohort by pathological stages, significant differences in OS (p = 0.007) and CSS (p = 0.005) between the surgical approaches were observed only in locally advanced disease (pT3/T4). In multivariable analysis, LRNU was an independent predictor of worse OS (p = 0.001) and CSS (p = 0.006) than ORNU. Likewise, in multivariable analysis in patients with pT3/T4 stage, LRNU was significantly associated with worse OS (hazard ratio [HR] 2.59, p = 0.001) and CSS (HR 2.50, p = 0.005).

Conclusions

Our data suggest that in UTUC patients, LRNU, compared to ORNU, is generally associated with unfavorable OS and CSS results. In particular, LRNU should be performed in locally advanced UTUC patients after careful consideration of its impact on patient survival.

     

Metaplastic Breast Cancer: Practice Patterns,Outcomes, and the Role of Radiotherapy

Purpose

Metaplastic breast cancer (MBC) is a rare, aggressive form of breast cancer with limited data to guide management. This study of a large, contemporary US database described national practice patterns and addressed the impact of radiotherapy (RT) on survival.

Methods

The National Cancer Data Base was queried (2004–2013) for women with non-metastatic MBC. Multivariable logistic regression ascertained factors associated with RT administration. Kaplan–Meier analysis evaluated overall survival (OS) between patients treated with either lumpectomy or mastectomy with or without RT, while substratifying patients into pT1–2N0 and pT3–4/N+ subcohorts. Cox proportional hazards modeling determined variables associated with OS.

Results

Of 5211 total patients, 447 (9%) had lumpectomy alone, 1831 (35%) had post-lumpectomy RT, 2020 (39%) had mastectomy alone, and 913 (18%) had post-mastectomy RT (PMRT). Most patients underwent chemotherapy (79%), and mastectomy was the most common surgical approach (56%). RT delivery was impacted by many factors, including higher nodal disease (p < 0.001), but not T classification or estrogen receptor status (p > 0.05 for both). Post-lumpectomy RT was associated with higher OS in both the pT1–2N0 and pT3–4/N+ subsets (p < 0.001 for both), while PMRT was associated with OS benefits in pT3–4/N+ cases (p < 0.001), but not in pT1–2N0 cases (p = 0.259).

Conclusions

In the largest study to date evaluating MBC, practice patterns of surgery, systemic therapy, and RT are described. The addition of RT in the post-lumpectomy setting was associated with higher OS, in addition to pT3–4/N+ in the post-mastectomy setting. Although not implying causation, further work is required to corroborate the conclusions herein.

     

The feasibility of laparoscopic extended pelvic surgery for rectal cancer

Purpose

The present study aimed to assess the safety and feasibility of laparoscopic extended pelvic surgery for primary or recurrent rectal cancer.

Methods

The data on 77 patients, who underwent extended pelvic surgery between February 2008 and June 2014, were retrospectively analyzed. The patients were divided, based on their treatment history, into an open surgery (OS) group (n = 41) and a laparoscopic surgery (LS) group (n = 36).

Results

The operative time in the LS group was significantly longer than that in the OS group (766 vs. 561 min; p < 0.001). In contrast, the LS group was associated with a significantly lower volume of intraoperative blood loss (195 vs. 923 ml; p < 0.001), fluid balance (5.38 vs. 8.23 ml/kg/h; p < 0.001) and rate of complications (40.0 vs. 68.3 %; p = 0.035), and a significantly shorter postoperative hospital stay. The postoperative levels of colloid osmotic pressure and albumin were significantly higher in the LS group.

Conclusion

The operative time of the LS group was longer than that of the OS group; however, the LS group experienced less blood loss and fewer complications. Moreover, LS was associated with a reduction in intraoperative infusions and a reduced fluid balance, which maintained homeostasis.

     

Comparison of perioperative and oncologic outcomes between open and laparoscopic liver resection for intrahepatic cholangiocarcinoma

Background

Laparoscopic liver resection (LLR) has become an essential method for treating malignant liver tumors. Although the perioperative and oncologic outcomes of LLR in patients with hepatocellular carcinoma have been reported, there are few reports of LLR for intrahepatic cholangiocarcinoma (IHCC).

Methods

Patients who underwent liver resection for T1 or T2 IHCC between March 2010 and March 2015 in Gyeongsang National University Hospital were enrolled. They were divided into open (n = 23) and laparoscopic (n = 14) approaches, and the perioperative and oncologic outcomes were compared.

Results

The Pringle maneuver was less frequently used (p = 0.015) and estimated blood loss was lesser (p = 0.006) in the laparoscopic group. There were no significant differences in complication rate (p = 1.000), hospital stay (p = 0.371), tumor size (p = 0.159), lymph node metastasis (p = 0.127), and the number of retrieved lymph nodes (p = 0.553). The patients were followed up for a median of 21 months. The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 74.7 and 55.2 %, respectively. No differences were observed in the 3-year OS (75.7 vs 84.6 %, p = 0.672) and RFS (56.7 vs 76.9 %, p = 0.456) rates between the open and laparoscopic groups, even after the groups were divided into patients that received liver resection with or without lymph node dissection.

Conclusion

LLR for IHCC is a treatment modality that should be considered as an option alongside open liver resection in selected patients.

     

Overexpression of CDT1 Is a Predictor of Poor Survival in Patients with Hepatocellular Carcinoma

Background

Genomic instability is a common feature in hepatocellular carcinoma. Deregulation of replication licensing factors has been shown to trigger DNA damage response contributing to genomic instability. Overexpression of DNA replication licensing factors chromatin licensing and DNA replication factor 1 (CDT1) and minichromosome maintenance complex component 7 (MCM7) has been previously reported in several human cancers. The aim of the present study was to evaluate the expression and prognostic significance of CDT1 and MCM7 in association with DNA damage response markers and p53 in patients with hepatocellular carcinoma.

Methods

Expression of CDT1, MCM7, p-H2A histone family member X (H2AX), phospho-ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia rad3-related (ATR) substrate, and p53 was evaluated by immunohistochemistry on formalin-fixed paraffin-embedded surgical specimens from 111 patients who underwent hepatectomy for hepatocellular carcinoma. Statistical analysis was performed to evaluate associations between the studied proteins, clinicopathological parameters, and patient survival.

Results

CDT1 expression correlated with p-H2AX (p?=?0.038), while MCM7 correlated with p-H2AX and phospho-ATM/ATR substrate (p?<?0.001). Increased CDT1 expression was associated with higher tumor grade (p?=?0.006) and tumor-node-metastasis (TNM) stage (p?=?0.033). High CDT1 expression correlated significantly with reduced overall survival (60.8 and 26.5 % vs 82.8 and 53.0 %, for low CDT1 expression, at 2 and 5 years, respectively, p?=?0.012) and was identified by multivariate analysis as an independent predictor of poor overall survival (p?=?0.049).

Conclusions

Overexpression of CDT1 and MCM7 in hepatocellular carcinoma correlates with DNA damage response, and CDT1 overexpression is a significant prognostic biomarker in hepatocellular carcinoma.

     

The oncological outcomes of segmentectomy in clinical-T1b lung adenocarcinoma with a solid-dominant appearance on thin-section computed tomography

Purpose

We investigated the surgical outcomes of clinical-T1b lung adenocarcinomas patients whose tumors had a solid-dominant radiological appearance and who were treated with segmentectomy or lobectomy.

Methods

We examined 154 surgically resected clinical-T1b lung adenocarcinomas with a “solid-dominant” appearance on thin-section computed tomography (CT). The preoperative thin-section CT images of all cases were reviewed. “Solid-dominant” was defined as 0.5≤ consolidation/tumor ratio (CTR) <1.0.

Results

Pathological nodal metastasis, lymphatic invasion, vascular invasion, and pleural invasion were found in 7 (4.5 %), 27 (18 %), 21 (14 %), and 15 (10 %) patients with clinical-T1b solid-dominant lung adenocarcinoma, respectively. Lobectomy and segmentectomy were performed in 123 (80 %) and 31 (20 %) cases, respectively. The 3-year overall survival (OS) and relapse-free survival (RFS) of patients with clinical-T1b solid-dominant lung adenocarcinoma were 95.5 and 92.4 %, respectively. The 3-year RFS and OS did not differ significantly between the patients who underwent lobectomy or segmentectomy (3-year RFS, 92.3 vs. 93.4 %, p = 0.8713; 3-year OS, 95.3 vs. 96.6 %, p = 0.7603). Segmentectomy was not found to be a prognostic factor for RFS (p = 0.8714), or OS (p = 0.7613).

Conclusions

Segmentectomy can achieve acceptable oncological outcomes (both in terms of OS and RFS), which are similar to those achieved with standard lobectomy, in patients with clinical-T1b solid-dominant lung adenocarcinoma.

     

Prognostic Significance of Serum Inflammatory Markers in Gastric Cancer

Background

The aim of this study was to assess the relative prognostic value of biomarkers to measure the systemic inflammatory response (SIR) and improve prognostic modeling in a cohort of patients undergoing potentially curative surgery for gastric adenocarcinoma. The hypothesis was that a single SIR biomarker would be associated with the most prognostic value.

Methods

Consecutive 331 patients undergoing surgery for gastric cancer between 2004 and 2016 within a regional UK cancer network were identified. Serum measurements of hemoglobin, C-reactive protein, albumin, modified Glasgow Prognostic Score, and differential white cell counts were obtained before surgery, and correlated with histopathological factors (pTNM stage, differentiation, and vascular invasion) and survival. Primary outcome measures were disease-free (DFS) and overall survival (OS).

Results

Consecutive 331 patients were identified and 291 underwent potentially curative gastrectomy for adenocarcinoma. On univariable DFS analysis, female gender (p = 0.027), proximal location (p = 0.018), pT stage (p < 0.001), pN stage (p < 0.001), pTNM stage (p < 0.001), vascular invasion (p < 0.001), poor differentiation (p = 0.001), lymph node ratio (p < 0.001), R1 status (p < 0.001), platelet count (p = 0.038), and mGPS (p = 0.001) were significantly associated with poor survival. The mGPS was associated with advanced pT stage (p = 0.001), pTNM stage (p = 0.013), and poor differentiation (p = 0.030). On multivariable DFS analysis, mGPS [hazard ratio (HR) 2.51, 95% confidence interval (CI) 1.35–4.65, p = 0.011] was the only inflammatory marker to retain independent significance. Multivariable OS analysis revealed similar findings; mGPS (HR 2.75, (95% CI 1.65–4.59), p < 0.001).

Conclusion

mGPS is an important and only SIR-related prognostic biomarker independently associated with both DFS and OS in gastric cancer.

     

Collapsin Response Mediator Protein 4 Expression is Associated with Liver Metastasis and Poor Survival in Pancreatic Cancer

Background

Pancreatic cancer is an aggressive malignancy with one of the worst mortality rates of all cancers. Recently, collapsin response mediator proteins (CRMPs) were reported to be associated with proliferation, apoptosis, differentiation, and invasion in several cancers. However, CRMP expression and their role in pancreatic cancer have not been investigated. This study aimed to clarify the clinical significance of CRMPs in pancreatic cancer.

Methods

Expression of crmp genes in 11 pairs of pancreatic cancer and corresponding noncancerous pancreas tissues were examined by real-time RT-PCR. Knockdown of CRMP4 expression using siRNA was examined in pancreatic cancer cell lines to determine whether CRMP4 regulates cell proliferation and invasion in vitro. Furthermore, CRMP4 protein levels in primary tumors of pancreatic cancer (n = 53) were examined by immunohistochemistry and compared with the clinicopathological features of the tumors.

Results

Of all the CRMPs, only CRMP4 was differentially expressed in pancreatic cancer tissues (p = 0.008). CRMP4 knockdown using siRNA reduced cellular invasion, but did not affect proliferation. The expression of CRMP4 was detected immunohistochemically in 34 (64.2 %) of the 53 pancreatic cancer samples, and CRMP4 expression was correlated with severe venous invasion (p = 0.044), stage (p = 0.019), and liver metastasis (p = 0.021). Multivariate analyses suggested that venous invasion and CRMP4 overexpression were prognostic factors for survival.

Conclusions

Our results suggested that CRMP4 is significantly associated with poor prognosis by promoting liver metastasis and can serve as a novel therapeutic target for pancreatic cancer.

     

Diagnostic and Prognostic Relevance of MMP-11 Expression in the Stromal Fibroblast-Like Cells Adjacent to Invasive Ductal Carcinoma of the Breast

Background

Matrix metalloproteinase 11 (MMP-11) is a matrix degrading enzyme known to be involved in the remodeling of extracellular matrix proteins. This enzyme recently has been reported to play a key role in tumor progression and results in poor clinical outcomes for several different types of tumors.

Methods

A total of 192 patients diagnosed with invasive ductal carcinoma between 2000 and 2005 were included in this study. MMP-11 expression in tumors and stromal fibroblast-like cells was analyzed by immunohistochemical staining on a tissue microarray. Subsequently, evaluation of the associations between MMP-11 expression and clinicopathological characteristics was performed.

Results

MMP-11 expression of stromal fibroblast-like cells was correlated with prognostic factors, including tumor size, metastasis, histological grade, central tumor fibrosis, p53 expression, and luminal A subtype and was linked to therapeutic markers, such as ER and HER2 (all p < 0.05). There was a significant relationship between worse overall survival and MMP-11 expression in both tumors and stromal fibroblast-like cells (all p < 0.05). In multivariate analysis, MMP-11 expression of stromal fibroblast-like cells was still significantly associated with poor prognosis (p = 0.043).

Conclusions

MMP-11 expression was significantly related to clinicopathological parameters, which may be essential to the prediction of disease outcome in patients with invasive ductal carcinoma of the breast.

     

The prognostic role of pre-cystectomy hemoglobin levels in patients with invasive bladder cancer

Purpose

To determine whether pre-treatment hemoglobin (Hb) levels in patients with bladder cancer impact on oncological outcomes after radical cystectomy (RC).

Methods

A consecutive, contemporary series of 246 patients undergoing RC and pelvic lymph node dissection for bladder cancer. Decreased Hb level was defined as ≤12 g/dL. The Kaplan–Meier method was used to estimate recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). The Fisher exact/Chi-square test was used to investigate differences between both groups. Uni- and multivariable Cox regression analysis addressed risk factors for recurrence, cancer-specific death and overall death. The median follow-up was 30 months (2–116).

Results

Of the 246 patients, 182 (74 %) had normal (>12 g/dL) and 64 decreased (≤12 g/dL) preoperative Hb (26 %). In univariable analysis, decreased Hb was associated with increased age, extravesical disease, hydronephrosis (all p < 0.001), node-positive disease and positive resection margins (both p = 0.01). Subanalyzed for patients with organ-confined disease (defined as ≤pT2bN0R0; N = 109), the 3-year RFS, CSS and OS was significantly lower in patients with decreased (34.9, 35.5 and 19.8 %) compared to normal Hb level (69.7, 86.3 and 77.6 %; p = 0.01/p = 0.002/p < 0.001). In multivariable analysis, RFS, CSS and OS were significantly lower in patients with decreased Hb (p = 0.007, p = 0.001 and p = 0.002), pathologically locally advanced tumor (≥pT3a; p = 0.023, p = 0.036 and p = 0.065) and nodal stage (p < 0.001, p = 0.006 and p = 0.001) and positive soft tissue surgical margins (p = 0.040, p = 0.004 and 0.012).

Conclusions

Pre-cystectomy Hb levels are associated with adverse histopathologic characteristics and provide additional prognostic information especially for patients with pathologically localized bladder cancer.

     

Impact of smoking status on survival after cytoreductive nephrectomy for metastatic renal cell carcinoma

Objective

To assess the association of smoking status with standard clinicopathological features and overall survival (OS) in a large multi-institutional cohort of patients with metastatic renal cell carcinoma (mRCC) treated with cytoreductive nephrectomy (CNT).

Methods

A total of 613 patients with mRCC treated with CNT in US and Europe institutions between 1990 and 2013 were included. Smoking history comprised smoking status, smoking duration in years, number of cigarettes per day and years since smoking cessation. Cumulative smoking exposure was categorized as light short term, heavy long term and moderate. Association between smoking history and OS was assessed by Cox regression logistic analysis.

Results

One hundred and seventy-one patients (27.9 %) never smoked, 193 (31.5 %) were former smokers and 249 (40.6 %) were current smokers. Smoking status was associated with a higher number of metastases (p < 0.001) and an abnormal preoperative corrected calcium level (p = 0.01). Median follow-up was 16 (IQR 7–24) months. Current smokers had a shorter OS than never and former smokers (log rank, p = 0.004). Smoking status was significantly associated with OS in univariable analysis (HR 1.45; 95 % CI 1.16–1.82; p < 0.001), and in multivariable analysis that adjusted for established prognostic factors (HR 1.46; 95 % CI 1.16–1.84; p = 0.002). Daily consumption of more than 20 cigarettes, more than 20 years of smoking exposure and heavy long exposure were all independent prognosticators of worse OS.

Conclusions

Current smoking and a higher cumulative smoking exposure are associated with a higher risk of death in patients with mRCC treated with CNT. Even at this stage, smoking negatively affects kidney cancer outcomes.

     

The Significance of MMP-9 Over MMP-2 in HCC Invasiveness and Recurrence of Hepatocellular Carcinoma After Curative Resection

Background

The extracellular matrix metalloproteases MMP-9 and MMP-2 are critical for the invasive potential of tumors. However, it is not clear which of the two plays the predominant role in tumor invasion and progression. In the present study, we compared the clinical efficacy of MMP-9 and MMP-2 overexpression for predicting tumor recurrence and survival after surgical resection in HCC patients.

Materials and Methods

MMP-9 and MMP-2 expression in HCC cell lines and in vitro HCC invasion model were detected by quantitative RT-PCR and immunofluorescence. The expression levels of MMP-9 and MMP-2 were assessed by immunohistochemistry in HCC tissue microarrays from HCC patients (study set) who underwent curative resection. The clinicopathological data were retrospectively analyzed. The results were further verified in an independent cohort of 92 HCC patients (validation set).

Results

Univariate analysis demonstrated that high expression of MMP-9 was associated with both time to recurrence (TTR, P = .015) and overall survival (OS, P = .024), whereas high expression of MMP-2 was only correlated with TTR (P = .041). Multivariate analysis confirmed that MMP-9 expression was an independent predictor of TTR and OS. The coindex of MMP-9 and preoperative serum AFP levels was significantly correlated with TTR and OS (P = .036 and P = .040), but the coindex of MMP-2 and AFP did not show prognostic significance for either TTR or OS (P = .067 and P = .053). The prognostic value of MMP-9 overexpression was validated in the independent data set.

Conclusion

MMP-9 is superior to MMP-2 for the prediction of tumor recurrence and survival in HCC patients after surgical resection.

     

Common Hepatic Artery Abutment or Encasement Is an Adverse Prognostic Factor in Patients with Borderline and Unresectable Pancreatic Cancer

Background

Localized and unresectable pancreatic ductal adenocarcinoma (PDA) comprises one third of new diagnoses and includes borderline resectable (BR) and locally advanced (LA) unresectable disease. In a cohort of patients who were treated and followed at a single institution, we assessed clinical and radiographic predictors of outcome.

Methods

The study included 69 consecutive patients with BR or LA PDA. Serial imaging studies were reviewed by both a pancreatic surgeon and a radiologist for vascular abutment or encasement by cancer, and they were recorded.

Results

The cohort included 25 patients with BR and 44 patients with LA PDA, with median overall survivals (OS) of 15 and 14 months, respectively (p = 0.802). Fifteen patients were resected (22%), with a median OS of 21 months from diagnosis (HR 2.50, p = 0.006) and 13 months from resection. Median OS from diagnosis was 33 months in patients without lymph node metastases at resection (n = 10), but just 17 months with lymph node metastases (n = 5, HR = 8.95, p = 0.011). There were 12 two-year survivors in the total cohort (17%), and seven of them never underwent resection. First-line treatments consisted of gemcitabine (n = 13), modern first-line combinations (FOLFIRNOX or gemcitabine/nab-paclitaxel, n = 24), or alternative multi-agent therapies (n = 32); there were no statistical differences between treatment subgroups (OS of 10, 13, and 16 months, respectively). Common hepatic artery (CHA) abutment or encasement at diagnosis was associated with poor survival (adjusted hazard ratio, CHA abutment = 2.47 (p = 0.015) and CHA encasement = 2.16 (p = 0.036)).

Conclusion

In this cohort, common hepatic arterial abutment or encasement and residual lymph node disease at resection portended a particularly poor outcome in patients with localized, unresectable PDA.

     

Impact of Sarcopenia on Unplanned Readmission and Survival After Esophagectomy in Patients with Esophageal Cancer

Background

Although sarcopenia increases postoperative complications following esophagectomy, its effects on prognosis remain unclear. This study was performed to identify the effect of sarcopenia on 90-day unplanned readmission and overall survival (OS) after esophagectomy.

Methods

Ninety-eight patients with esophageal cancer who underwent esophagectomy were enrolled in this study. Unplanned readmission was defined as any emergent hospitalization within 90 days after discharge. Sarcopenia, defined as low muscle mass plus low muscle strength and/or low physical performance according to the Asian consensus definition, was assessed prior to esophagectomy. Multivariate logistic regression analysis was performed to identify factors that contributed to 90-day unplanned readmission. OS was estimated using the Kaplan–Meier method, and a Cox proportional hazards model was used to assess the relationship between sarcopenia and OS.

Results

Thirty-one patients (31.6%) were diagnosed with sarcopenia. The 90-day unplanned readmission rate was significantly higher in patients with sarcopenia than those without (42.9% vs. 16.4%, respectively; p = 0.01). Multivariable logistic regression analysis showed that sarcopenia was an independent predictor of 90-day unplanned readmission [odds ratio 3.71, 95% confidence interval (CI) 1.29–11.05; p = 0.02], and the log-rank test showed that sarcopenia was associated with OS (p = 0.01). Moreover, sarcopenia was a significant predictor of OS after adjustment for age, sex, and pathological stage (hazard ratio 2.35, 95% CI 1.21–4.54; p = 0.01).

Conclusions

Sarcopenia is a risk factor for 90-day unplanned readmission and OS following esophagectomy. Assessment of sarcopenia could help to identify patients at higher risk of a poor prognosis after esophagectomy.