Ning-Fu Peng

Changes in ER, PR and HER2 receptors status after neoadjuvant chemotherapy in breast cancer

Previous studies have reported conflicting results regarding the impact of neoadjuvant chemotherapy (NAC) on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status in breast cancer. Our aim was to investigate whether NAC induces some selective change in the breast biomarkers. We retrospectively detected the immunohistochemical results of ER, PR and HER2 between the core biopsy and surgical excision specimens in 113 patients with NAC. As a control group, we analyzed sample pairs from 102 patients without NAC. Fourteen (12.4%) of 113 patients undergoing NAC showed the ER status modulation in the surgically removed specimen as compared with only 4 (3.9%) of 102 women without NAC (p=0.025). Eighteen (15.9%) of 113 patients given NAC appeared in the PR status alteration in the final surgical specimen, whereas only 7 (6.9%) of 102 patients without NAC did (p=0.038). The HER2 status shift was found in 17 (15.0%) of 113 patients with NAC and in 6 (5.9%) of 102 patients without NAC, respectively (p=0.030). Neoadjuvant chemotherapy does change ER, PR and HER2 status in a statistically significant manner. Retesting these biomarkers of the residual tumor should be considered to improve future tailored adjuvant therapies.

Preoperative Ratio of Neutrophils to Lymphocytes Predicts Postresection Survival in Selected Patients With Early or Intermediate Stage Hepatocellular Carcinoma.

Abstract This study aims to clarify the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) for patients with hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR). The prognostic value of the NLR for HCC patients has not been definitely reviewed by large studies, especially for those with different Barcelona Clinic Liver Cancer (BCLC) stages. A consecutive sample of 963 HCC patients who underwent potentially curative HR was classified as having low or high NLR using a cut-off value of 2.81. Overall survival (OS) and tumor recurrence were compared for patients with low or high NLR across the total population, as well as in subgroups of patients in BCLC stages 0/A, B, or C. Clinicopathological parameters, including NLR, were evaluated to identify risk factors of OS and tumor recurrence after potentially curative hepatic resection. Multivariate analyses were performed using the Cox proportional hazards model or subdistribution hazard regression model. Multivariate analyses showed that NLR (>2.81), tumor number (>3), incomplete capsule, serum albumin (⩽35 g/L), alanine transaminase activity (>40 U/L), and macrovascular invasion were risk factors for low OS, whereas NLR (>2.81), tumor size (>5 cm), alpha fetal protein concentration (>400 ng/L), and macrovascular invasion were risk factors for low tumor recurrence. NLR > 2.81 was significantly associated with poor OS and tumor recurrence in the total patient population (both P < 0.001), as well as in the subgroups of patients in BCLC stages 0/A or B (all P < 0.05). Moreover, those with high NLR were associated with low OS (P = 0.027), and also with slightly higher tumor recurrence than those with low NLR for the subgroups in BCLC stage B (P = 0.058). Neither association, however, was observed among patients with BCLC stage C disease. NLR may be an independent predictor of low OS and tumor recurrence after potentially curative HR in HCC patients in BCLC stages 0/A or B.

Prognostic Role of Nucleophosmin in Colorectal Carcinomas

AIM Recent research suggests that nucleophosmin (NPM) may be a prognostic marker in colorectal carcinomas (CRC). We here tested its use to predict the survival of CRC patients. METHODS We investigated NPM expression by immunohistochemistry in histologically normal to malignant colorectal tissues and evaluated its association with clinicopathological variables. Overall and disease-free survival after tumor removal were calculated by the Kaplan-Meier method, and differences in survival curves were analyzed by the log-rank test. The Cox proportional hazards model was used for multivariate analysis of prognostic factors. RESULTS NPM expression was found significantly upregulated in CRC compared to adjacent colorectal tissue, villous adenoma, tubular adenoma and normal colorectal mucosa (p<0.05 for all). NPM expression was statistically linked to cancer embolus, lymph node metastasis, differentiation grade, and recurrence of CRC. Overall and disease-free survival of NPM-negative CRC patients tended to be better than those for patients with NPM-positive lesions (log-rank statistic, p<0.05 for all). Multivariate analysis indicated NPM expression as an independent prognostic indicator for CRC patients (p<0.05 ). CONCLUSION Our results suggest that NPM expression can predict the survival of CRC patients. Prognosis of CRC is determined by not only many known prognostic factors but also by NPM expression.

Tumor stage and primary treatment of hepatocellular carcinoma at a large tertiary hospital in China: A real-world study

The current clinical reality of tumor stages and primary treatments of hepatocellular carcinoma (HCC) is poorly understood. This study reviewed the distribution of tumor stages and primary treatment modalities among a large population of patients with primary HCC. Medical records of patients treated between January 2003 and October 2013 for primary HCC at our tertiary hospital in China were retrospectively reviewed. A total of 6241 patients were analyzed. The distribution of Barcelona Clinic Liver Cancer (BCLC) stages was as follows: stage 0/A, 28.9%; stage B, 16.2%; stage C, 53.6%; stage D, 1.3%. The distribution of Hong Kong Liver Cancer (HKLC) stages was as follows: stage I, 8.4%; stage IIa, 1.5%; stage IIb, 29.0%; stage IIIa, 10.0%; stage IIIb, 33.6%; stage IVa, 3.4%; stage IVb, 2.5%; stage Va, 0.2%; stage Vb, 11.4%. The most frequent therapy was hepatic resection for patients with BCLC-0/A/B disease, and transarterial chemoembolization for patients with BCLC-C disease. Both these treatments were the most frequent for patients with HKLC I to IIIb disease, while systemic chemotherapy was the most frequent first-line therapy for patients with HKLC IVa or IVb disease. The most frequent treatment for patients with HKLC Va/Vb disease was traditional Chinese medicine. In conclusion, Prevalences of BCLC-B and -C disease, and of HKLC I to IIIb disease, were relatively high in our patient population. Hepatic resection and transarterial chemoembolization were frequent first-line therapies.

Prediction of coexistent carcinomas risks by subjective EIN diagnosis and comparison with WHO classification in endometrial hyperplasias

Endometrial intraepithelial neoplasia (EIN) classification is proposed as a new diagnostic system to resolve the limitations of the World Health Organization (WHO) classification in routine practice. Our aim was to find out whether EIN classification excels the WHO classification regarding the accurate prediction of coexisting endometrial carcinomas (EC) in biopsy specimens. We retrospectively re-classified 139 WHO-classified endometrial hyperplasia (EH) cases by subjective EIN diagnosis and compared the incidence of coexisting carcinomas using two classification systems by re-evaluating biopsy and corresponding hysterectomy specimens. Of 139 WHO-classified hyperplasia cases, 36 and 103 were classified as benign and EIN cases, respectively. Forty of 93 cases with atypical EH had EC at hysterectomy as compared with 2/46 cases without atypical EH, while EC was detected in 42/103 cases with EIN, and in 0 of 36 cases without EIN. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for atypical EH vs. non-atypical EH in biopsy specimen was 95.2%, 45.4%, 43.0% and 95.7%, respectively. For EIN vs. benign, the sensitivity was 100% and the specificity was 37.1%. The incidence of coexisting carcinomas in EIN cases was similar to that in atypical EH cases. However, regarding the exclusion of coexisting carcinomas, EIN criteria of benign lesions excelled the WHO criteria of non-atypical EH/CH.

Is radioembolization or sorafenib the best option for patients with hepatocellular carcinoma and portal vein invasion

We read with interest the study by de la Torre et al. comparing survival time of Caucasian patients with hepatocellular carcinoma (HCC) and portal vein invasion (PVI) after radioembolization using yttrium-90 microspheres (n=26) or sorafenib therapy (n=47). Respective median survival time was 8.8 and 5.4 months (p=.047) after median follow-up of 6 months. Around the same time, Cho et al. reported similar median survival time for Asian patients with HCC and PVI who received radioembolization (n=32) or sorafenib (n=31) (13.8 vs 10.0 months, p=.22). These results were confirmed by propensity score analysis. We applaud those authors for examining the suitability of radioembolization for patients with HCC and PVI, who currently have few treatment options and face extremely poor prognosis. At the same time, we think that more detailed analysis is needed in order to identify the most appropriate patient subgroups who may benefit from radioembolization or sorafenib, especially in the light of strong evidence that hepatic resection can be safe and effective for certain patients with HCC and PVI. The studies by de la Torre et al. and Cho et al. did not perform subgroup analyses by PVI grade, even though the grades are associated with substantially different prognoses. A systematic review of studies involving 4389 patients with HCC and macrovascular invasion found that hepatic resection was associated with median overall survival of 50% at 1 year and 18% at 5 years. A Japanese nationwide survey of 6474 patients with HCC and PVI found hepatic resection to be associated with significantly longer median survival than other treatments (2.87 vs 1.10 years, p<.001), and the rate of postoperative 90-day mortality rate was only 3.7%. This finding was also supported by propensity score analysis. Hepatic resection survival benefit was observed regardless of patient age, HCC etiology, tumour markers or tumour number. This extensive evidence suggests that hepatic resection can be safe and effective in selected patients with PVI in the segmental or sectoral branches of the portal vein (Vp0-2). It is less clear, however, whether hepatic resection is justified in patients with PVI in the main trunk or portal bifurcation (Vp3-4). We agree with de la Torre et al. and Cho et al. that radioembolization can provide good survival in patients with HCC and PVI, but its safety and efficacy should be verified in different PVI grades. Clinicians should also consider hepatic resection as an option for selected patients with PVI limited to the first-order branch. Financial Support

Association between age and overall survival of patients with hepatocellular carcinoma after hepatic resection.

The suitability of hepatic resection for older patients remains controversial. This study aimed to investigate whether age influences overall survival of patients with hepatocellular carcinoma (HCC) after resection.

Prognostic factors of regression and relapse of complex atypical hyperplasia and well-differentiated endometrioid carcinoma with conservative treatment.

OBJECTIVE To evaluate possible prognostic factors regarding regression and relapse of complex atypical hyperplasia (CAH) and well-differentiated endometrioid adenocarcinoma (WDC) treated with conservative treatment. METHODS The retrospective study reviewed clinicopathologic, treatment, regression and relapse data from patients diagnosed with CAH or WDC who were treated with conservative treatment at 4 institutions. Potential factor evaluation was performed. SPSS 16 was used for statistical analyses. RESULTS Eighty-eight patients were included (51 had WDC, and 37 had CAH). Regression was evaluated in 88 patients, with a median follow-up of 61 (range 15-95) months. Seventy-seven (87.5%) patients regressed, and 11 (12.5%) had persistent or progressive disease. Univariate and multivariate analyses showed no factors associated with regression. Relapse was evaluated in 71 patients, with median follow-up of 54 (range 8-86) months. Twenty-five/71 (35.2%) patients experienced relapse. On univariate analysis, body mass index (BMI) 30 or higher (p=0.001), WCD at initial biopsy (p=0.017) and positive expression of post-treatment ki67 (p=0.033) were associated to a higher relapse probability. However, only BMI 30 or higher was significant on multivariate analysis (p=0.012). The Kaplan-Meier analysis revealed a higher relapse probability in the patients with BMI 30 or higher (p=0.001). CONCLUSION Obesity seems to be a risk factor for relapse of CAH or WDC with conservative treatment.

Relationship between GSTT1 gene polymorphism and hepatocellular carcinoma in patients from China.

OBJECTIVE The results from studies on associations of the glutathione S-transferase T1 (GSTT1) gene polymorphism and hepatocellular carcinoma (HCC) risk in Chinese populations are still conflicting. This meta- analysis was performed to evaluate the relationship in detail. METHODS Eligible reports were recruited into this meta-analysis from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database). Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. RESULTS Eighteen investigations were identified for the analysis of association between polymorphic deletion of GSTT1 and HCC, consisting of 2,693 patients with HCC and 4,696 controls. Null genotype of GSTT1 was associated with HCC susceptibility in Chinese (OR=1.53, 95%CI: 1.28-1.82; P<0.00001). CONCLUSION The GSTT1 null genotype is associated with HCC susceptibility in Chinese.

Combination of 5-fluorouracil and 2-morphilino-8-phenyl-4H-chromen-4-one may inhibit liver cancer stem cell activity

This work aims to evaluate the impact of 2-morpholino-8-phenyl-4H-chromen-4-one (LY294002) combined 5-fluorouracil (5-FU) for the activity of CD90+ liver cancer cells derived from the human liver cancer cell line MHCC97H. MHCC97H sphere-forming cells (MSFCs) were amplified in serum-free medium and CD90+ cells were isolated from bulk MSFCs using flow cytometry. The phenotype of these CD90+ cells which show liver cancer stem cells (LCSCs) behavior was validated in vitro and in a xenograft model in nude mice. MSFCs, CD90+ liver cancer cells (CD90+ LCCs), and parental MHCC97H cells were treated with no drug, LY294002 alone, 5-FU alone, or both drugs together and then compared in terms of stem cell-related gene expression, proliferation, and invasion. Stem cell phenotype increased with increasing proportion of CD90+ cells, in ascending order: parental MHCC97H cells, MSFCs, and CD90+ liver cancer cells. LY294002 reduced the expression of CD90, Nanog, SALL4, and SHP2 in a concentration-dependent manner in CD90+ LCCs and MSFCs, but not in parental cells. LY294002 blocked AKT phosphorylation via the PI3K/AKT signaling pathway and inhibited CD90+ LCCs proliferation and tumorigenicity in vitro and in vivo. CD90+ liver cancer cells can express liver cancer stem cell phenotype. LY294002 inhibits the proliferation and invasion of MHCC97H-derived CD90+ LCCs and sensitized CD90+ LCCs-derived tumors to 5-FU in the current study which may provide insight into the association between the LY294002 combined 5-FU and liver cancer stem cell (LCSCs).