Cytokeratin 7 is a Predictive Marker for Survival in Patients with Esophageal Squamous Cell Carcinoma

Background

Patients diagnosed with stage II and III esophageal squamous cell carcinoma (ESCC) have variable prognosis. This group would benefit greatly from the discovery of prognostic markers that are capable of identifying individuals for whom adjuvant treatment would be advantageous. The aim of this study was to investigate the impact of immunohistochemically detected cytokeratin 7 (CK7) expression on disease-free survival, overall survival (OS), or therapeutic outcome in patients with ESCC.

Methods

Immunohistochemical analysis of CK7 was performed on 225 surgically resected specimens of stage 0?CIII ESCC.

Results

In total, 20 (9%) of 225 ESCC cases were positive for CK7. In stage 0?CIII ESCC patients, CK7 expression was statistically significantly associated with OS, independent of clinical covariates, including tumor, node, metastasis system stage. In stage II and III ESCC patients (n?=?124), CK7 expression was significantly associated with poorer OS (P?=?0.0377). Furthermore, in stage II and III ESCC patients who did not receive adjuvant chemotherapy (n?=?73), CK7 expression was significantly associated with poorer OS (P?=?0.0003). CK7 expression was not associated with therapeutic outcome in patients with stage II and III ESCC who received adjuvant chemotherapy. In patients with CK7-positive ESCC (n?=?16), receipt of adjuvant chemotherapy tended to be beneficial for patients with stage II and III ESCC (P?=?0.0654).

Conclusions

Immunohistochemical analysis of CK7 will help to identify high-risk patients.     

DNA Methylation Profiling Identifies EYA4 Gene as a Prognostic Molecular Marker in Hepatocellular Carcinoma

Background

DNA hypermethylation plays important roles in carcinogenesis by silencing key genes. This study aims to identify pivotal genes in hepatocellular carcinoma (HCC) by DNA methylation microarray and to assess their prognostic values.

Materials and Methods

DNA methylation microarray was performed in 45 pairs of HCC and adjacent nontumorous tissues and six normal liver tissues to identify hypermethylated genes in HCC. Potential prognosis-related genes were selected among hypermethylated genes by analyzing influences of methylation levels on disease-free survival (DFS) and overall survival (OS) in 45 patients. Their prognostic values were validated in 154 patients with HCC (including the initial 45 patients) to determine the independent prognostic gene.

Results

Altogether, 54 CpG islands in 44 genes were hypermethylated in HCC compared with liver tissues. Among them, methylation levels of ERG and HOXA11 were inversely associated with DFS (both P < 0.050), and methylation levels of EYA4 were inversely related to DFS and OS (both P < 0.050). EYA4 expression was inversely related to tumor size (P < 0.050). Lower EYA4 expression and larger tumor size were independent predictors of both shorter DFS and OS, and higher Barcelona Clinic Liver Cancer (BCLC) staging was an independent predictor of shorter OS (all P < 0.050).

Conclusions

EYA4 functions as a prognostic molecular marker in HCC. Its aberrant hypermethylation and subsequent down-regulation may promote tumor progression.     

Body Mass Index and Survival in Esophageal Adenocarcinoma Treated with Chemoradiotherapy Followed by Esophagectomy

Background

Body mass index (BMI) has been linked with inferior outcomes in gastrointestinal malignancies. The purpose of this study is to evaluate the effect of BMI on survival in patients with esophageal adenocarcinoma.

Methods

Medical records were analyzed for patients who underwent esophagectomy after neoadjuvant chemoradiotherapy (nCRT) for adenocarcinoma from 2000 to the present. Patients were grouped into BMI ??25, >25?C30, >30?C35, and BMI >35. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan?CMeier method. Multivariate analysis (MVA) was performed using Cox proportional hazard regression model.

Results

We identified 303 patients for the analysis. The only difference in patient characteristics between groups was gender. We found no difference in OS and DFS associated with BMI (p?=?0.3297 for OS; p?=?0.5950 for DFS). There were no differences in postoperative complications or mortality between BMI groups. MVA revealed that higher stage and less than a complete response to nCRT were prognostic for worse OS and DFS, while age, gender, type of surgery, year of diagnosis, and BMI were not prognostic.

Conclusions

BMI was neither associated with surgical complications nor survival in patients with esophageal adenocarcinoma treated with nCRT. BMI should not be considered a contraindication to surgical resection after nCRT.     

Value of Preoperative Inflammation-Based Prognostic Scores in Predicting Overall Survival and Disease-Free Survival in Patients with Gastric Cancer

Background

This study was designed to identify which are the best preoperative inflammation-based prognostic scores in terms of overall survival (OS) and disease-free survival (DFS) in patients with gastric cancer.

Methods

Between January 2004 and January 2013, 102 consecutive patients underwent resection for gastric cancer at S. Andrea Hospital, "La Sapienza", University of Rome. Their records were retrospectively reviewed.

Results

After a median follow up of 40.8 months (8–107 months), patients’ 1-, 3-, and 5-year OS rates were 88, 72, and 59 %, respectively. After R0 resection, the 1-, 3-, and 5-year DFS rates were 93, 74, and 56 %, respectively. A multivariate analysis of the significant variables showed that only the modified Glasgow prognostic scores (p < 0.001) and PI (p < 0.001) were independently associated with OS. Regarding DFS, multivariate analysis of the significant variables showed that the modified Glasgow prognostic score (p = 0.002) and prognostic index (p < 0.001) were independently associated with DFS.

Conclusions

The results of this study show that modified Glasgow prognostic score and prognostic index are independent predictors of OS and DFS in patients with gastric cancer.     

Resection Margin with Anatomic or Nonanatomic Hepatectomy for Liver Metastasis from Colorectal Cancer

Background

When hepatectomy is used as a primary treatment for liver metastasis from colorectal cancer (CRCLM), the balance between surgical curability and functional preservation of the remnant liver is of great importance.

Methods

A total of 108 patients who underwent initial hepatectomy for CRCLM were retrospectively analyzed with respect to tumor extent, operative method, and prognosis, including recurrence.

Results

The 1-, 2-, 3-, and 5-year overall survival rates (OS) for all patients were 90.5%, 77.8%, 63.2%, and 51.6%, respectively. Multivariate analysis indicated serum carbohydrate antigen 19-9 (CA 19-9) level after hepatectomy (<36 or ??36?mAU/mL) and presence of recurrence as independent prognostic factors of OS (P?=?0.0458 and 0.0249, respectively), and tumor depth of colorectal cancer (P?=?0.0025 and 0.00138, respectively). Neither resection margin nor type of hepatectomy (anatomic or nonanatomic) for CRCLM was a significant prognostic factor for OS or DFS or CRCLM recurrence, including intrahepatic recurrence.

Conclusions

In CRCLM, we believe that nonanatomic hepatectomy with narrow margin is indicated, and optimal treatment would include functional preservation of as much of the remnant liver as possible.     

Open Versus Thoracoscopic Esophagectomy in Patients with Esophageal Squamous Cell Carcinoma

Background

The impact of minimally invasive esophagectomy on patient prognosis, particularly disease-free survival (DFS), has not been well addressed. We compared the clinical outcomes of open and thoracoscopic esophagectomy in patients with esophageal squamous cell carcinoma (ESCC).

Methods

Sixty-three and 66 patients, nonrandomized, underwent open and thoracoscopic esophagectomies for ESCC between 2008 and 2011 were included. The clinicopathological data were reviewed retrospectively. Perioperative outcome, overall survival (OS), DFS, and the recurrence sites after open and thoracoscopic esophagectomy were compared.

Results

The open and thoracoscopic groups were comparable with regard to the total number of harvested lymph nodes and the percentage patients undergoing R0 resection. Fewer patients in the thoracoscopic group had pneumonia and wound complications. Intensive care unit (ICU) stay also was shorter in the thoracoscopic group. The recurrence pattern was similar in the two groups. In the open and thoracoscopic groups, the 3-year OS rates were 47.6 and 70.9 % (p = 0.031), respectively, and the 3-year DFS rates were 35 and 62.4 % (p = 0.007), respectively. However, the trends in better OS and DFS in the thoracoscopic group were not significant after stratification according to pathologic stage.

Conclusions

The perioperative benefit of thoracoscopic esophagectomy included fewer postoperative complications and shorter ICU stays. Mid-term OS and DFS associated with thoracoscopic techniques are at least equivalent to those associated with open procedures.     

Surgical Resection After Down-Staging of Locally Advanced Hepatocellular Carcinoma by Localized Concurrent Chemoradiotherapy

Background

This study evaluated the down-staging efficacy and impact on resectability of concurrent chemoradiotherapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) in locally advanced hepatocellular carcinoma, and identified prognostic factors of disease-free survival (DFS) and overall survival (OS) after curative resection.

Methods

DFS and OS were investigated using clinicopathologic variables. Functional residual liver volume (FRLV) was assessed before CCRT and again before surgery in patients with major hepatectomy. Tumor marker response was defined as elevated tumor marker levels at diagnosis but levels below cutoff values before surgery (α-fetoprotein < 20 ng/mL, protein induced by vitamin K absence or antagonist-II < 40 mAU/mL).

Results

Of 243 patients who received CCRT followed by HAIC between 2005 and 2011, 41 (16.9 %) underwent curative resection. Tumor down-staging was demonstrated in 32 (78 %) of the resected patients. FRLV significantly increased from 47.5 to 69.9 % before surgery in patients who underwent major hepatectomy. In addition, the OS of the curative resection group was significantly higher than the OS of the CCRT followed by HAIC alone group (49.6 vs. 9.8 % at 5-year survival; p < 0.001). By multivariate analysis, the poor prognostic factors for DFS after curative resection were tumor marker non-response and the presence of a satellite nodule; however, tumor marker non-response was the only independent poor prognostic factor of OS.

Conclusions

CCRT followed by HAIC increased resectability by down-staging tumors and increasing FRLV. Curative resection may provide good long-term survival in tumor marker responders who undergo CCRT followed by HAIC.     

Impact of Thoracic Recurrent Laryngeal Node Dissection: 508 Patients with Tri-Incisional Esophagectomy

Background

To evaluate the feasibility and safety of recurrent laryngeal nerve (RLN) lymph node (LN) dissection, this study compared the postoperative complications and survival between modern two-field lymphadenectomy (MTL) and modified standard two-field lymphadenectomy (MSTL) by using the propensity score matching method.

Methods

After generating propensity scores given the covariates of age, sex, tumor length, tumor location, tumor grade, and clinical stage, 254 patients with MTL were matched to 254 MSTL patients using the nearest available score matching. The LNs resected during MSTL were paraesophageal and preparatracheal LNs in the upper mediastinum, in addition to those resected during standard two-field lymphadenectomy.

Results

RLN LNs were those most commonly affected by nodal metastasis in our series (26 %). Metastasis in RLN LNs was found in around 35, 25, and 20 % of patients with cancer in the upper, middle, and lower thoracic esophagus, respectively. LN metastasis was confined to the RLN region in 49 patients. Even 35 % of patients with pT1 tumors had positive RLN LNs. MTL increased the mean number of resected LNs when compared to MSTL (29 vs.15; p?<?0.001). Recurrence was more frequent in those assigned MSTL than those assigned MTL (p?<?0.001). The 5-year overall survival (OS) and disease-free survival (DFS) rate for MTL were 50.7 and 42 % compared to 35.3 and 28.2 % for MSTL (both p?<?0.001), respectively. Postoperative complications were more frequent following MTL when compared to the MSTL. However, no statistically significant difference in postoperative complications was observed between the two groups.

Conclusions

Adding the removal of RLN LNs might improve OS and DFS with acceptable morbidity for patients with ESCC.     

Preoperative Cholangitis and Metastatic Lymph Node Have a Negative Impact on Survival After Resection of Extrahepatic Bile Duct Cancer

Background

The significance of the presence of preoperative inflammation for the prognosis of patients with extrahepatic bile duct cancer (BDCA) was evaluated.

Methods

The clinical data of 84 patients who underwent surgery for BDCA from August 2003 to May 2009 were reviewed, and survival analysis was performed. The patients were classified into two groups according to the presence of preoperative cholangitis: Group A had no cholangitis (n?=?59), and group B had cholangitis (n?=?25).

Results

There were no differences in sex, mean age, TNM stage, biliary drainage, type of resection, or radicality between the two groups (p?>?0.05). The 3-year disease-specific survival (DSS) and disease-free survival (DFS) rates for the group B patients (21.5 and 11.9?%, respectively) were significantly lower than those for the group A patients (66.1 and 57.3?%, respectively; p?=?0.013 and 0.001, respectively). The multivariate analysis showed that preoperative inflammation and lymph node metastasis were the independent prognostic factors for both overall survival (OS) [p?=?0.021, relative risk (RR)?=?2.224 and p?=?0.015, RR?=?2.367, respectively] and DFS (p?=?0.014; RR?=?2.192 and p?=?0.013; RR?=?2.240, respectively). The rates of angiolymphatic and perineural invasion were higher for group B than those for group A (p?=?0.016 and 0.030, respectively).

Conclusions

The presence of preoperative inflammation is an independent poor prognostic factor for OS and DFS for patients with BDCA.     

Surgical Cytoreduction and Survival in Appendiceal Cancer Peritoneal Carcinomatosis: An Evaluation of 46 Consecutive Patients

Background

Surgical cytoreduction and intraperitoneal chemotherapy is increasingly accepted as an effective treatment modality for mucinous appendiceal neoplasm. For the majority of patients with low-grade histology, outcomes have been encouraging. The survival of patients with neoplasms of malignant character is protracted and this study was designed to evaluate the effectiveness of this surgical strategy on outcomes.

Methods

Forty-six consecutive patients with mucinous and nonmucinous appendiceal cancer with peritoneal dissemination were studied. Clinicopathological and treatment related factors were obtained from a prospective database. The study’s end points of disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method.

Results

The median DFS and OS after cytoreduction were 20.5 and 56.4 months respectively. Five-year overall survival rate was 45%. Five independent factors associated with DFS and OS were identified through a multivariate analysis: age (DFS p = 0.001, OS p = 0.002), completeness of cytoreduction (DFS p = 0.001, OS p = 0.003), previous chemotherapy treatment (DFS p = 0.021), CA 199 levels (DFS p = 0.013), and tumor grade (OS p = 0.005).

Conclusions

Cytoreductive surgery and intraperitoneal chemotherapy may achieve long-term survival in appendiceal malignancies with peritoneal dissemination for which the predictors of outcomes identified through this study may tailor the disease management to commit patients early toward this successful surgical strategy.     

Prediction of Disease-free Survival in Hepatocellular Carcinoma by Gene Expression Profiling

Background

Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis, which correlate with recurrence after surgical treatment and poor prognosis. The molecular prognostic model that could be applied to the HCC patient population in general is needed for effectively predicting disease-free survival (DFS).

Methods

A cohort of 286 HCC patients from South Korea and a second cohort of 83 patients from Hong Kong, China, were used as training and validation sets, respectively. RNA extracted from both tumor and adjacent nontumor liver tissues was subjected to microarray gene expression profiling. DFS was the primary clinical end point. Gradient lasso algorithm was used to build prognostic signatures.

Results

High-quality gene expression profiles were obtained from 240 tumors and 193 adjacent nontumor liver tissues from the training set. Sets of 30 and 23 gene-based DFS signatures were developed from gene expression profiles of tumor and adjacent nontumor liver, respectively. DFS gene signature of tumor was significantly associated with DFS in an independent validation set of 83 tumors (P = 0.002). DFS gene signature of nontumor liver was not significantly associated with DFS in the validation set (P = 0.827). Multivariate analysis in the validation set showed that DFS gene signature of tumor was an independent predictor of shorter DFS (P = 0.018).

Conclusions

We developed and validated survival gene signatures of tumor to successfully predict the length of DFS in HCC patients after surgical resection.     

Clinical, Pathological and Surgical Characteristics of Duodenal Gastrointestinal Stromal Tumor and Their Influence on Survival: A Multi-Center Study

Background

The duodenum is a rare site of primary gastrointestinal stromal tumor (GIST). Overall (OS) and disease-free survival (DFS) after limited resection (LR) versus pancreaticoduodenectomy (PD) were studied.

Methods

All patients who underwent surgery for primary, localized duodenal GIST between 2000 and 2011 were identified from four prospective institutional databases. OS and DFS were calculated by Kaplan?CMeier method. Univariate analysis was performed.

Results

Eighty-four patients (median follow-up 42?months) underwent LR (n?=?56, 67?%) or PD (n?=?28, 33?%). Patients in the PD group had a larger median tumor size (7?cm vs. 5?cm, p?=?0.024) and higher mitotic count (39?% vs. 19?% >5/50 high-power fields, p?=?0.05). Complications were observed in five patients (9?%) in the LR group and ten patients (36?%) in the PD group. OS and DFS for the entire cohort were 89?% and 64?% at 5?years, respectively. No difference in outcome between LR and PD were observed. Eleven patients were treated with preoperative IM. A major RECIST response was obtained in nine (80?%), whereas two had stable disease. Twenty-three patients received postoperative Imatinib (IM). A trend toward a better OS in IM-treated patients could be detected only in the high-risk group.

Conclusions

Type of duodenal resection does not impact outcome. The choice should be determined by duodenal site of origin and tumor size. IM may be considered in cases at high risk of recurrence; in neoadjuvant setting, IM might facilitate resection and possibly increase the chance of preserving normal biliary and pancreatic anatomy.     

Lymph Node Harvest in Esophageal Cancer After Neoadjuvant Chemoradiotherapy

Background

This study was designed to determine the effects of lymph node (LN) harvest on survival in esophageal cancer after neoadjuvant chemoradiation (nCRT).

Methods

An analysis of surgically resected esophageal cancer patients after nCRT was performed to determine an association between the number of LNs resected and survival. Overall survival (OS) and disease-free survival (DFS) curves were calculated according to the Kaplan–Meier method and log-rank analysis. Multivariate analysis (MVA) was performed by the Cox proportional hazard model.

Results

We identified 358 patients with a mean follow-up of 27.3 months. The number of LN removed was not impacted by the type of surgical procedure. The number of LNs removed (<10 vs. ≥10, <12 vs. ≥12, and <15 vs. ≥15) did not impact OS or DFS. We found a significant difference in OS and DFS by pathologic response. The median and 5-year OS for patients with complete, partial, and no response was 65.6 months and 52.7 %, 29.7 months and 30.4 %, and 17.7 months and 25.4 % (p = 0.0002). However, the number of LN harvested did not impact OS and DFS when patients were stratified by pathologic response. MVA also revealed that the number of lymph nodes removed was not prognostic for OS or DFS. Higher age, higher stage, and less than a complete response were associated with a decreased OS. Higher stage and less than a complete response were prognostic for worse DFS.

Conclusions

The number of LNs harvested during esophagectomy does not impact survival after nCRT. Stage and pathologic response continue to be the strongest prognostic factors for survival in esophageal cancer after nCRT.     

Minimally invasive liver surgery for metastases from colorectal cancer: oncologic outcome and prognostic factors

Background

Few reports exist on long-term survival after minimally invasive liver surgery (MILS) for colorectal liver metastases (CRLM). No data are available assessing prognostic factors in the era of current modern treatment strategies.

Methods

Between October 2002 and December 2008, 274 consecutive patients were analyzed on an intention-to-treat basis. Open liver surgery (OLS) was performed in 193 patients for a total of 437 metastases, and MILS was performed in 81 patients for 176 metastases. Systemic chemotherapy was administered preoperatively in 173 and postoperatively in 174 patients. The impact of 23 potential prognostic factors on disease-free (DFS) and overall survival (OS) was evaluated using univariable and multivariable Cox regression models.

Results

Postoperative complications were observed in 54 patients after OLS and in 11 after MILS (p = 0.016). The median postoperative length of hospital stay was 9 days after OLS and 5 days after MILS (p < 0.0001). For the entire patient population, the 5 year DFS and OS rates were 29.9 and 59.5%, respectively. No differences in survival between patients treated with MILS and OLS were observed (p = 0.63). In univariable analyses, the number of liver metastases and the overall Fong’s clinical risk score (CRS) were the only two variables that predicted DFS (p ≤ 0.0035) and OS (p ≤ 0.0005). In multivariable analyses, the total CRS was the only independent predictor of both DFS (p = 0.0002) and OS (p = 0.002).

Conclusion

The long-term oncologic outcome of surgically treated patients with CRLM is determined by the Fong’s CRS. Although MILS does not influence long-term survival, it has a beneficial impact on the immediate postoperative clinical outcome.     

Prognostic Comparison Between Number and Distribution of Lymph Node Metastases in Patients with Right-Sided Colon Cancer

Background

Lymph node metastasis is the most important prognostic indicator for colon cancer patients. We compared the prognostic significance of the number of lymph node metastases (LNN) and the distribution of lymph node metastases (LND).

Methods

A total of 187 patients underwent curative resection for stage III right-sided colon cancer between 2000 and 2010. We evaluated the oncologic outcomes according to LNN (N1 1–3, N2 4–6, N3 >6) and LND (LND1 metastases in pericolic nodes, LND2 metastases along the major vessels, N3 metastases around the origin of a main artery). A Cox proportional hazards model, with backward stepwise analysis was used to determine the effects of covariates on 5-year, disease-free survival (DFS) and 5-year overall survival (OS). Akaike’s information criterion (AIC), and Harrell’s concordance index (C-index) were compared for each developed model.

Results

During the median follow-up of 42.2 months, 5-year DFS and OS were 68 and 79.3 %, respectively. Multivariate analysis showed that both LNN and LND3 were independent prognostic factor for both 5-year DFS and OS. However, the prognostic model incorporating number of LNM was more precise than that of LND, with a lower AIC (5-year DFS, 554.2 vs. 566.9; 5-year OS, 318.1 vs. 337.9) and higher C-index (5-year DFS, 0.706 vs. 0.667; 5-year OS, 0.778 vs. 0.743).

Conclusions

Our results show that the staging system incorporating LNN predicted prognosis better than LND.     

Hepatic Arterial Nodal Metastases in Pancreatic Cancer: Is This the Node of Importance?

Background

The hepatic artery lymph node (HALN) is frequently sampled during pancreaticoduodenectomy (PD). Data suggest that survival in the setting of HALN metastases is similar to that of stage IV pancreatic ductal adenocarcinoma (PDAC). The objectives of this study were to describe the prognostic significance of HALN metastases and to assess the predictive performance of HALN compared to peripancreatic lymph node status.

Methods

Patients undergoing PD for PDAC from January 2000–October 2010 were identified from a prospectively maintained database. Patients were included if during PD the HALN was submitted for pathologic evaluation. Patients were excluded if margins were macroscopically positive, if pathology was found to be consistent with a diagnosis other than PDAC. Overall (OS) and disease-free survival (DFS) were estimated by Kaplan–Meier methods.

Results

Of the 671 patients who underwent PD for PDAC, HALN status was analyzed for 147 patients. HALN was positive in 23 patients (16 %), 38 were peripancreatic lymph node (PPLN) and HALN negative, and 86 were PPLN+/HALN?. Median follow-up for survivors was 10 months. In a multivariable model, lymph node status and tumor differentiation predicted OS and DFS. Hazard of death and relapse/death were highest among the HALN+ patients (hazard ratio [HR] 2.94; p?=?0.017 and HR 2.66; p?=?0.011, respectively). Kaplan–Meier analysis revealed significant differences in OS (p?=?0.017) and DFS (p?=?0.013) based on lymph node status.

Conclusions

OS and DFS are significantly reduced in patients with a positive HALN. Differentiation and lymph node status were predictors of OS and DFS. In the multivariate models, differentiation and lymph node status remain independent predictors of OS and DFS.     

Complete Pathologic Response after Combined Modality Treatment for Rectal Cancer and Long-Term Survival: A Meta-Analysis

Background

Complete pathologic response (CPR) after neoadjuvant chemoradiotherapy (combined modality treatment, CMT) for rectal cancer seems associated with improved survival compared to partial or no response (NPR). However, previous reports have been limited by small sample size and single-institution design.

Methods

A systematic literature review was conducted to detect studies comparing long-term results of patients with CPR and NPR after CMT for rectal cancer. Variables were pooled only if evaluated by 3 or more studies. Study end points included rates of CPR, local recurrence (LR), distant recurrence (DR), 5-year overall survival (OS), and disease-free survival (DFS).

Results

Twelve studies (1,913 patients) with rectal cancer treated with CMT were included. CPR was observed in 300 patients (15.6%). CPR and NPR patient groups were similar with respect to age, sex, tumor size, distance of tumor from the anus, and stage of disease before treatment. Median follow-up ranged from 23 to 46?months. CPR patients had lower rates of LR [0.7% vs. 2.6%; odds ratio (OR) 0.45, 95% confidence interval (CI) 0.22?C0.90, P?=?0.03], DR (5.3% vs. 24.1%; OR 0.15, 95% CI 0.07?C0.31, P?=?0.0001), and simultaneous LR?+?DR (0.7% vs. 4.8%; OR 0.32, 95% CI 0.13?C0.79, P?=?0.01). OS was 92.9% for CPR versus 73.4% for NPR (OR 3.6, 95% CI 1.84?C7.22, P?=?0.002), and DFS was 86.9% versus 63.9% (OR 3.53, 95% CI 1.62?C7.72, P?=?0.002).

Conclusions

CPR after CMT for rectal cancer is associated with improved local and distal control as well as better OS and DFS.     

Tobacco Use Is Associated with Increased Recurrence and Death from Gastric Cancer

Background

Tobacco use increases the risk of developing gastric cancer. We examined the hypothesis that gastric cancer developing in patients with a history of tobacco use may be associated with increased risk of cancer-specific death after curative surgical resection.

Methods

From the Memorial Sloan-Kettering Cancer Center Gastric Cancer prospective surgical database, we collected baseline demographic data and tumor characteristics from all patients who had undergone curative resection for gastric cancer between 1995 and 2009 and who had not received pre- or postoperative chemo- or radiotherapy. A smoking history was defined as >100 cigarettes?? lifetime use. The primary end point was gastric cancer disease-specific survival (DSS); secondary end points were 5-year disease-free survival (DFS) and overall survival (OS). Gastric cancer?Cspecific hazard was modeled by Cox regression.

Results

A total of 699 eligible patients were identified with a median age of 70?years (range 25?C96?years); 410 (59%) were current or previous smokers. Smoking was associated with gastroesophageal junction/cardia tumors and white non-Hispanic ethnicity. Multivariate analysis included the following variables: tumor stage, age, performance status, diabetes mellitus, gender, and tumor location. In this analysis, the hazard ratio for gastric cancer DSS in smokers was 1.43 (95% confidence interval 1.08?C1.91, P?=?0.01). Smoking was also an independent significant risk factor for worse 5-year DFS (hazard ratio 1.46, P?=?0.007) and OS (hazard ratio 1.48, P?=?0.003). Among 516 patients for whom tobacco pack-year usage was available, both heavy (???20 pack-years) and light (<20 pack-years) tobacco use was significantly associated with DSS, DFS, and OS.

Conclusions

Smoking history appears to be an independent risk factor for death from gastric cancer in patients who have undergone curative surgical resection.     

High Serum Levels of Vascular Endothelial Growth Factor-A and Transforming Growth Factor-β1 Before Neoadjuvant Chemoradiotherapy Predict Poor Outcomes in Patients with Esophageal Squamous Cell Carcinoma Receiving Combined Modality Therapy

Background and Purpose

This study was aimed at using proximity ligation assay (PLA) followed by enzyme-linked immunosorbent assay (ELISA) to identify serum biomarkers that predict treatment response and survival for patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant concurrent chemoradiotherapy (CCRT) followed by esophagectomy.

Methods

Seventy-nine patients with ESCC receiving CCRT of taxane-based/5-fluorouracil-based chemotherapy and 40 Gy followed by surgery were enrolled. Serum samples were collected before and <1 month after CCRT. Fifteen biomarkers were analyzed using PLA. Biomarkers significantly correlating with pathological response/survival were verified by ELISA. Associations of the serum level of biomarkers and clinical factors with pathological response, disease-free survival (DFS), and overall survival (OS) were evaluated by analysis of variance and log-rank tests.

Results

Thirty patients had complete response (38 %), 37 had microscopic residual disease (47 %), and 12 had macroscopic residual disease (15 %). With a median follow-up of 52.8 months, the median DFS was 43 months. Among the 15 biomarkers screened by PLA, vascular endothelial growth factor (VEGF)-A and transforming growth factor (TGF)-β1 were significantly associated with pathological response and/or DFS. These biomarkers were further analyzed by ELISA to confirm initial biomarker findings by PLA. After ELISA of these two markers, only VEGF-A levels were significantly correlated with pathological response. On multivariate analysis, patients with combined high pre-CCRT VEGF-A and TGF-β1 levels (greater than or equal to the median), independent of pathological response, had significantly worse DFS (11 months vs. median not reached; p = 0.007) and OS (16 vs. 46 months; p = 0.07).

Conclusions

Pre-CCRT serum VEGF-A and TGF-β1 levels may be used to predict pathological response and survivals for ESCC patients receiving combined-modality therapy.     

The Impact of the Lymph Node Ratio is Greater than Traditional Lymph Node Status in Stage III Colorectal Cancer Patients

Background

The prognostic value of nodal status in colorectal cancer (CRC) patients may be influenced by the total number of lymph nodes (LNs) harvested. This study evaluates the impact of LN ratio (LNR) on CRC patients’ outcome.

Methods

A total of 612 stage III CRC patients who underwent curative-intent surgery between 2004 and 2008 were enrolled. The measured end point was postoperative disease-free survival (DFS) and overall survival (OS).

Results

The metastatic LN numbers were significantly higher in patients with more than 12 LN harvested (4.6 ± 5.81 vs. 2.7 ± 1.97, P < 0.001). The mean LNR was 22.9 ± 20 % (range = 2–100 %, median = 16.7 %). As the cutoff value of LNR was set above 17 %, the impact of the LNR on 5-year DFS became statistically significant. In univariate analysis, the 5-year DFS and OS for patients with high-LNR tumors was 54.4 and 57.3 %, respectively, significantly lower than those for patients with low-LNR tumors (72.8 and 76.4 %; P < 0.001). In multivariate analysis, the independent factors affecting the 5-year DFS and OS were tumor depth, carcinoembryonic antigen level, and LNR.

Conclusion

The LNR, set at the median value or 17 %, could be an independent prognostic factor for stage III CRC patients.