Yinuo Tan

Different treatment strategies and molecular features between right-sided and left-sided colon cancers.

The colon is derived from the embryological midgut and hindgut separately, with the right colon and left colon having different features with regards to both anatomical and physiological characteristics. Cancers located in the right and left colon are referred to as right colon cancer (RCC) and left colon cancer (LCC), respectively, based on their apparent anatomical positions. Increasing evidence supports the notion that not only are there differences in treatment strategies when dealing with RCC and LCC, but molecular features also vary between them, not to mention the distinguishing clinical manifestations. Disease-free survival after radical surgery of both RCC and LCC are similar. In the treatment of RCC, the benefit gained from adjuvant FOLFIRI chemotherapy is superior, or at least similar, to LCC, but inferior to LCC if FOLFOX regimen is applied. On the other hand, metastatic LCC exhibits longer survival than that of RCC in a palliative chemotherapy setting. For KRAS wild-type cancers, LCC benefits more from cetuximab treatment than RCC. Moreover, advanced LCC shows a higher sensitivity to bevacizumab treatment in comparison with advanced RCC. Significant varieties exist at the molecular level between RCC and LCC, which may serve as the cause of all apparent differences. With respect to carcinogenesis mechanisms, RCC is associated with known gene types, such as MMR, KRAS, BRAF, and miRNA-31, while LCC is associated with CIN, p53, NRAS, miRNA-146a, miRNA-147b, and miRNA-1288. Regarding protein expression, RCC is related to GNAS, NQO1, telomerase activity, P-PDH, and annexin A10, while LCC is related to Topo I, TS, and EGFR. In addition, separated pathways dominate progression to relapse in RCC and LCC. Therefore, RCC and LCC should be regarded as two heterogeneous entities, with this heterogeneity being used to stratify patients in order for them to have the optimal, current, and novel therapeutic strategies in clinical practice. Additional research is needed to uncover further differences between RCC and LCC.

Young Patients (≤35years old) With Colorectal Cancer Have Worse Outcomes Due to More Advanced Disease: A 30-Year Retrospective Review

AbstractAn appropriate cutoff of age and the impact of age on colorectal cancer outcomes remain unclear and need to be explored, particularly in China.In total, 2460 colorectal cancer patients were studied retrospectively. All patients were divided into 6 groups according to their ages at the time of diagnosis: ⩽30, 31 to 35, 36 to 40, 41 to 45, 46 to 50, and ≥50 years. A suitable cutoff age for defining young adult colorectal cancer was explored according to the distribution of survival in each group. Clinical characteristics and prognosis between the young adult group and the older group were then compared.According to the survival curves for each group, 35 years old was considered a suitable cutoff age for defining young adult colorectal cancer. There were 140 (5.7%) and 2320 (94.3%) cases in the young adult and older groups, respectively. The proportion of stage III–IV tumors was significantly higher in the young adult group (69.3%) than in the older group (46.4%) (P = 0.000). The univariate analysis showed that the 5-year overall survival (OS) rate and the 10-year OS rate in the young adult group were 48.9% and 38.6%, respectively, whereas in the older group, they were 63.6% and 56.9%, respectively. The young adult group had a worse prognosis (P = 0.000). The multivariate analysis showed that age was not an independent prognostic factor (relative risk 0.787, P = 0.062). After adjusting for tumor stage, the hazard proportion of death in the young adult group increased by 27.6%, but this difference was not significant (P = 0.053). Stratified analyses showed that the young adults with stage IV tumors had a worse survival rate (P = 0.046).Patients ⩽35 years who were diagnosed with colorectal cancer had a worse prognosis because of a higher proportion of advanced stage tumors. When stage-to-stage analysis was performed, it was found that young adult colorectal cancer patients had a worse outcome only if they had stage IV tumors.

A Minor (<50%) Signet-Ring Cell Component Associated with Poor Prognosis in Colorectal Cancer Patients: A 26-Year Retrospective Study in China

Background We performed a retrospective study to determine the cancer-specific survival of colorectal cancer patients with a component of signet-ring cells or mucin comprising < 50% of the tumor mass. Methods A total of 2454 patients seen in our hospital from 1985 to 2011 were retrospectively studied. The patients were divided into five groups according to type of cancer: signet-ring cell carcinoma (with > 50% signet-ring cell, n = 36), partial signet-ring cell carcinoma (with < 50% signet-ring cell, n = 28), mucinous adenocarcinoma (with > 50% mucin lacking signet-ring cell, n = 267), partial mucinous adenocarcinoma (with < 50% mucin lacking signet-ring cell, n = 145), and classic adenocarcinoma (with absence of either mucin or signet-ring cell, n = 1978). Results Patients with > 50% or < 50% signet-ring cell had the lowest 5-year survival rates (35.5% and 29.7%, respectively), followed by patients with > 50% mucin (48.8%). Patients who had partial mucinous adenocarcinoma with < 50% mucin and classic adenocarcinoma patients had the highest 5-year survival rates (64.8% and 65.3%, respectively). Stratified and multivariate analysis showed that signet-ring cell carcinoma, partial signet-ring cell carcinoma and mucinous adenocarcinoma were independent predictors of decreased survival (hazard ratio 1.699, P = 0.016; hazard ratio 2.182, P = 0.005; hazard ratio 1.532, P < 0.001; respectively), and partial mucinous adenocarcinoma was not (hazard ratio 1.137, P = 0.431). Conclusions Patients with a component of signet-ring cells, regardless of the extent, had poor prognoses. Patients with mucinous adenocarcinoma containing >50% mucin had poor prognoses as well, whereas those with < 50% mucin had survival rates similar to those of classic adenocarcinoma patients. Therefore, in clinical practice, patients with a component of signet-ring cells, regardless of the extent, should be given significant clinical attention.

A Case Report of Gastrointestinal Hemorrhage and Perforation During Apatinib Treatment of Gastric Cancer.

AbstractApatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which shows good efficacy and safety in clinical trials for chemotherapy-refractory gastric cancer patients. Till now, there is no case report after apatinib came in the market.We presented a 55-year-old Chinese woman with advanced gastric cancer, who received apatinib after failure of second-line chemotherapy. On the 19th day of apatinib administration, she suffered from gastrointestinal hemorrhage. Then, her condition rapidly deteriorated to gastrointestinal perforation. Although the patient received timely medical and surgical treatment, she finally died of septic shock.Although apatinib shows exciting efficacy and good tolerance in phase II and III clinical trials, this novel targeted drug should be prescribed carefully and close clinical monitoring is needed when using it.

Hormone receptor status may impact the survival benefit of surgery in stage iv breast cancer: a population-based study.

Introduction The role of surgery in stage IV breast cancer is controversial. We used the Surveillance, Epidemiology, and End Results database to explore the impact of surgery on the survival of patients with stage IV breast cancer. Methods In total, 10,441 eligible stage IV breast cancer patients from 2004 to 2008 were included. They were divided into four groups as follows: R0 group (patients who underwent primary site and distant metastatic site resection), primary site resection group, metastases resection group, and no resection group. Results The four groups achieved a median survival time (MST) of 51, 43, 31 and 21 months, respectively, P < 0.001. The Cox proportional hazards model showed that the R0 group, primary resection group and metastases resection group had a good survival benefit, with hazard ratios of 0.558 (95% CI, 0.471-0.661), 0.566 (95% CI, 0.557-0.625) and 0.782 (95% CI, 0.693-0.883), respectively. In the hormone receptor (HR)-positive population, the R0 group (MST = 66 m, 5-year OS = 54.1%) gained an additional survival benefit compared with the primary resection group (MST = 52 m; 5-year OS = 44.9%; P < 0.001). The metastases resection group (MST = 38 m; 5-year OS = 31.7%) survived longer than the no resection group (MST = 28 m; 5-year OS = 22.0%; P < 0.001). In the HR-negative population, the R0 group and primary resection group had a similar survival (P = 0.691), and the metastases resection group had a similar outcome to that of the no resection group (P = 0.526). Conclusion Patients who underwent surgery for stage IV breast cancer showed better overall survival than the no resection group. Cytoreductive surgery could provide a survival benefit in HR+ stage IV breast cancer; however, in the HR- population, extreme caution should be exercised when considering surgery.

The clinicopathological features and prognostic factors of gastric squamous cell carcinoma.

AbstractPrimary gastric squamous cell carcinoma (SCC) is an exceedingly rare disease. We increased the understanding of gastric SCC and evaluated prognostic factors of gastric SCC.In this large-population cohort study, we retrospectively collected 163 primary gastric SCC and 66,209 primary gastric adenocarcinoma cases from the surveillance, epidemiology, and end results program (SEER) database from 1988 to 2012. The Chi-squared test demonstrated the distributed differences. Cox proportional hazards regression model was used to evaluate the prognostic factors.Gastric SCC accounted for 0.2% of all the primary gastric cancer cases. The mean age of patients with gastric SCC was 69.6 years old, and the man-to-woman ratio was 2.3:1. The proportion of black was higher in gastric SCC than gastric adenocarcinoma (P < 0.001). Almost half of the gastric SCCs were diagnosed in stage IV and more than half were poorly differentiated. In gastric SCC, the median survival was 8.0 months and the 5-year overall survival (OS) was 32.7%; in gastric adenocarcinoma the median survival rate was 19.0 months and the 5-year OS was 35.4%. The multivariate analysis showed that number of primary lesions, tumor location, grade, and stage were independent prognostic factors in gastric SCC. The tumor stage was the most important prognostic factor.Primary gastric SCC is exceedingly rare. Compared with gastric adenocarcinoma, gastric SCC was more frequent in black patients and was usually diagnosed when it was poorly differentiated and at a later stage. On the whole, gastric SCC has a poorer outcome. Disease stage is likely a key determinant in survival.

Left-sided primary tumor is a favorable prognostic factor for metastatic colorectal cancer patients receiving surgery

Objective The role of surgery in metastatic colorectal cancer (mCRC) remains controversial. This study was performed to assess the impact of surgery on survival in metastatic colorectal cancer. Materials and Methods Information of mCRC patients diagnosed between January 1, 2004, and December 31, 2013, was retrieved from the Surveillance, Epidemiology, and End Results Program database. Patients were classified in three groups: patients undergoing resection of both primary and distant metastatic tumors (group ‘PMTR’), patients receiving primary tumor resection alone (group ‘PTR’) and patients not undergoing any surgery (group ‘No resection’). Kaplan-Meier method and multivariate Cox proportional hazard regression analysis were applied to estimate disease specific survival time (DSS) and determine prognostic factors. Results A total of 38,591 mCRC patients were eligible. Overall, median DSS of group ‘PMTR’ was significantly longer compared with group ‘PTR’ and group ‘No resection’ (28.0 vs 21.0 vs 11.0 months, P < 0.001). Stratified analysis observed that primary tumor in left-sided colorectal cancer (LCRC) was a favorable prognostic factor compared with right-sided colorectal cancer (RCRC) (median DSS of LCRC: PMTR, 34 months, PTR, 25 months, No resection, 13 months; median DSS of RCRC: PMTR, 20 months, PTR, 16 months, No resection, 8 months; P < 0.001). Multivariate analysis demonstrated that surgery was an independent prognostic factor for better survival (PMTR, HR = 0.403, 95% CI 0.384–0.423, P < 0.001; PTR, HR = 0.515, 95% CI 0.496–0.534, P < 0.001). Furthermore, in patients undergoing surgery, patients with younger age, female, married status, LCRC and lower CEA level were prone to receiving PMTR. Conclusions This analysis demonstrated that surgery was an independent prognostic factor for improved survival in mCRC. Patients with LCRC had better survival than patients with RCRC after surgery.

Clinicopathological Features and Prognostic Factors of Colorectal Neuroendocrine Neoplasms

Background. Limited research is available regarding colorectal NENs and the prognostic factors remain controversial. Materials and Methods. A total of 68 patients with colorectal NENs were studied retrospectively. Clinical characteristics and prognosis between colonic and rectal NENs were compared. The Cox regression models were used to evaluate the predictive capacity. Results. Of the 68 colorectal NENs patients, 43 (63.2%) had rectal NENs, and 25 (36.8%) had colonic NENs. Compared with rectal NENs, colonic NENs more frequently exhibited larger tumor size (P < 0.0001) and distant metastasis (P < 0.0001). Colonic NENs had a worse prognosis (P = 0.027), with 5-year overall survival rates of 66.7% versus 88.1%. NET, NEC, and MANEC were noted in 61.8%, 23.5%, and 14.7% of patients, respectively. Multivariate analyses revealed that tumor location was not an independent prognostic factor (P = 0.081), but tumor size (P = 0.037) and pathological classification (P = 0.012) were independent prognostic factors. Conclusion. Significant differences exist between colonic and rectal NENs. Multivariate analysis indicated that tumor size and pathological classification were associated with prognosis. Tumor location was not an independent factor. The worse outcome of colonic NENs observed in clinical practice might be due not only to the biological differences, but also to larger tumor size in colonic NENs caused by the delayed diagnosis.

How young is too young in breast cancer? -Young breast cancer is not a unique biological subtype

Micro‐Abstract “How young is very young for breast cancer” has long been a controversial topic. We first used the X‐tile program to determine and proposed that the age of 40 years is a reasonable cutoff value to define “young.” However, the gene expression profiles from the Cancer Genome Atlas proved that young breast cancer might not be a unique biological entity. Background: There is no uniformly adopted cutoff value to define “young patients” with breast cancer. This study was designed to determine an optimal cutoff value, to investigate prognostic factors and to explore gene expression profiles of young female breast cancer. Materials and Methods: The Surveillance, Epidemiology, and End Results database was examined to identify cases of female breast cancer diagnosed between 2000 and 2007. The optimal cutoff value for young age was determined using the X‐tile program (Yale University, version 3.6.1). Age‐specific gene expression profiles were explored using RNA sequence data from the Cancer Genome Atlas database. Results: The age of 40 years was determined as the optimal cutoff value. Among 94,087 patients, 12,755 were aged 40 years or younger (younger group), and 81,332 were older (older group). The 5‐ and 10‐year cancer‐specific survival rates in younger and older groups were 88.74% and 80.65%, respectively, and 93.22% and 88.43%, respectively (P < .001). Univariate and multivariate analyses indicated younger patients had worse prognosis. Subgroup analysis according to estrogen receptor (ER) showed the risk for cancer‐specific death of ER‐positive (ER+) younger patients increased by approximately 2 times (hazard ratio, 1.96) compared with ER+ older patients. We failed to find any age‐related gene in 509 patients after adjusting according to subtype (50‐gene prediction analysis of a microarray) and histological type. Conclusion: The age of 40 years is a reasonable cutoff value for defining “young.” Young patients with breast cancer, especially those in the ER+ subgroup, have worse prognosis. However, we found that young breast cancer is not a unique biological entity, and therefore, a lack of new potential targets.

Surgical Intervention Improves Survival for Metastatic Non-Small Cell Lung Cancer Patients

AbstractSurgical intervention for stage IV non-small cell lung cancer (NSCLC) is still controversial. This study sought to evaluate the clinical effects of surgical intervention on survival in patients with stage IV NSCLCs and to identify the cohort benefitting the most from surgery.A retrospective study from the Surveillance, Epidemiology, and End Results database was performed to compare the survival of stage IV NSCLC patients who had undergone surgery with those who did not undergo surgery. Overall survival (OS) was evaluated using the Kaplan–Meier method and the log-rank test. The Cox proportional hazards model was used for multivariate analysis.The total number of eligible patients was 43,538, including 16.8% in the M1a stage and 83.2% in the M1b stage. The percentages of patients with no surgery (NONE), only metastatic tumor resection (MTR), only primary tumor resection (PTR), and both primary and metastatic tumor resection (PMTR) were 89.0%, 6.7%, 3.5%, and 0.8%, respectively; the corresponding 5-year survival rates were 2.0%, 4.0%, 13.0%, and 20.0%, respectively (P < 0.001); and the corresponding OS rates were 11.1 months, 14.7 months, 29.4 months, and 34.9 months, respectively (P < 0.001). Notably, the pairwise comparisons of 5-year survival rate and OS among the subgroups were all statistically significant. The multivariate analysis showed that surgical intervention was correlated with longer survival in patients with stage IV NSCLC. The stratified analysis showed significant differences in the OS on strata of the M1a stage and strata of the M1b stage. In the M1a stage, patients with PTR had significantly better OS than those with NONE (P < 0.001) or MTR (P < 0.001) but showed no significant differences compared with those with PMTR (P = 0.174); patients with MTR did not have prolonged survival compared with patients with NONE (P = 0.185), and they also did not have prolonged survival compared with patients with PMTR (P = 0.052). In the M1b stage, pairwise comparisons of OS were all statistically significant among the subgroups (P < 0.001).Surgical intervention can prolong survival to different degrees according to the modalities of surgery in stage IV NSCLC.