Erlotinib in combination with bevacizumab and FOLFOX4 as second-line chemotherapy for patients with metastatic colorectal cancer.

BACKGROUND: We conducted a phase II study by combining FOLFOX4 plus bevacizumab (BV) with erlotinib (ER) as second-line chemotherapy for patients with metastatic colorectal cancer (mCRC). METHODS: Patients were divided into two groups in randomized double-blind manner. One group was given FOLFOX4 plus 5 mg/kg BV on day 1 of 2-week cycle. The other group was given 2-week-cycle of BV + FOLFOX4, and 100 mg ER every day. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), clinical response rates and adverse events (AEs). RESULTS: 66 patients received 2nd-line treatment of ER + BV+ FOLFOX4, and 65 received BV + FOLFOX4. Median PFS was 9.6 months of ER + BV + FOLFOX4 group, significantly better than 6.9 months of BV + FOLFOX4 group (P = 0.021, HR = 1.15, 95% CI = 0.88-1.39). Medium OS for ER + BV + FOLFOX4 group was 12.5 months, not statistically different than 12.1 months for BV + FOLFOX4 group (P = 00.146, HR = 0.63, 95% CI = 0.34-1.02). Combined partial response and stable disease rate was 48.5% for ER + BV + FOLFOX4 group, significantly higher than 32.2% for BV + FOLFOX4 group (P = 0.015). Patients in ER + BV + FOLFOX4 group had higher incidence rates of AEs. CONCLUSION: In second-line chemotherapy for patients with mCRC, combining erlotinib with FOLFOX4 plus bevacizumab may improve PFS, clinical response rates, but not OS. AEs, though with high incidence rates, were generally tolerable among patients receiving multiple reagents.

Efficacy and safety of SOX chemotherapy with or without surgery in AFP-producing advanced gastric cancer.

The present study investigated the clinical efficacy of S-1 plus oxaliplatin (SOX) regimen, with or without surgery in α-fetoprotein-producing gastric cancer (APGC) with liver metastasis. A total of 24 patients with APGC treated at the Liaocheng People's Hospital between January 2011 and December 2013 were retrospectively reviewed. Clinical efficacy and patient safety were compared between the two groups. The median progression-free survival (PFS) and overall survival (OS) in the SOX group were 6.5 [95% confidence interval (CI), 4.6-8.4] and 13.5 (95% CI, 8.1-18.9) months, respectively. The corresponding indicators in the SOX and surgery group were 7.0 (95% CI, 5.7-8.3) and 14 (95% CI, 11.0-17.1) months, respectively. There was no significant difference in PFS and OS between the two groups (P=0.703 and 0.710, respectively). The adverse effects of leucopenia, neutropenia, anemia and diarrhea occurred in ~10% of patients in the SOX group and in 14.3% (2/14), 7.14% (1/14), 14.3% (2/14) and 7.14% (1/14), respectively, in the surgery group. No significant difference was identified between groups in terms of overall incidence of adverse effects (P=0.17). However, severe adverse events, including gastroplegia, pancreatic fistula, pulmonary infection and refractory ascites, occurred only in the SOX plus surgery group [incidence rate for severe adverse events, 7.14% (1/14); P<0.001 between groups]. In conclusion, SOX chemotherapy is safe and effective in patients with APGC and liver metastasis. However, the addition of surgery to SOX chemotherapy may not improve the disease control rate and may increase the adverse effects.

Role of Presepsin for the Assessment of Acute Cholangitis Severity.

BACKGROUND: Presepsin is a new emerging inflammatory biomarker. The primary purpose of this study was to elucidate the predictive usability of presepsin for severity assessment in patients with acute cholangitis (AC). METHODS: A total of 119 treatment-naive patients with AC (64 males, 55 females) were enrolled in this study. Patients were classified with Grade I (mild), Grade II (moderate), or Grade III (severe) AC based on severity assessment guidelines. Presepsin concentrations were measured on admission. RESULTS: The median presepsin concentrations were 297 pg/mL (interquartile range (IQR) 234 - 386 pg/mL), 590 pg/mL (IQR 559 - 619 pg/mL), and 857 pg/mL (IQR 740 - 960 pg/mL) in patients with mild, moderate, and severe AC, respectively. Presepsin concentrations were significantly higher in patients with severe AC than in patients with moderate AC (p < 0.01), and in patients with moderate AC than in patients with mild AC (p < 0.01). With the receiver operating characteristic (ROC) analysis, the areas under the curves (AUCs) for presepsin to discriminate patients with moderate and severe AC were 0.935 (95% confidence interval (CI) 0.877 to 0.993, p < 0.001) and 0.942 (95% CI 0.885 to 0.998, p < 0.001), respectively. CONCLUSIONS: Compared with other conventional biochemical indicators such as WBC, CRP, and PCT, presepsin may be a useful parameter for the severity assessment of AC.

Less Aggressive Surgical Procedure for Treatment of Solid Pseudopapillary Tumor: Limited Experience from a Single Institute.

OBJECTIVES: To evaluate the clinical characteristics and radiological features of solid pseudopapillary tumor (SPT) and assess surgical therapy strategy. METHODS: A retrospective review was performed in 62 patients pathologically confirmed of SPT treated between 2003 and 2014. The clinical features, radiological examinations and surgical strategies were analyzed. RESULTS: 56 females and 6 males were included in this study, mean age was 26 years old (range: 8-66 years old) with mean size of the tumor was 7.2 cm (range: 3-15 cm), and most tumor were commonly located in the head of pancreas (n = 29). Among all the cases, 3 patients had liver metastasis and underwent resection of SPT and liver metastasis. Furthermore, we performed 29 cases of local tumor excision; other patients underwent pancreaticoduodenectomy, middle pancreatectomy, middle pancreatectomy with splenectomy, distal pancreatectomy with spleen preservation, distal pancreatectomy with splenectomy and duodenum-preserving pancreatic head resection. No patient suffered from lymph node metastases. After median follow-up of 46 months (range: 2-135 months), no mortality or local recurrence or distant metastasis was found. CONCLUSIONS: Solid pseudopapillary tumor is a latent malignant tumor with excellent prognosis. If feasible, less aggressive resection without regular lymphadenectomy is recommended for treatment of patients with SPT.

Overexpression of Klotho suppresses liver cancer progression and induces cell apoptosis by negatively regulating wnt/ß-catenin signaling pathway.

BACKGROUND: Klotho is a discovered aging suppressor gene, and its overexpression in mice extends the life span of the animal. Recently, Klotho is also identified as a tumor suppressor gene in variety of tumors; however, the potential role and the antitumor mechanism remain unclarified in liver cancers. METHODS: RT-PCR and western blotting analysis were used to detect the expression of Klotho, ß-catenin, C-myc, and Cyclin D1. MTT assay was used to detect the survival rates of HepG2 and SMMC-7721 cells. Colony formation assay was used to test the proliferation ability in Klotho transfected cells. FACS was used to detect the cell apoptosis rate in different groups. RESULTS: The results showed that lower expression of Klotho were found in liver cancer cell lines than the immortalized liver cell L02. Also, MTT assay results found that overexpression or recombinant Klotho administration suppressed the proliferation of liver cancer cells HepG2 and SMMC-7721. Moreover, the colony formation assay results showed that the number of colonies was significantly lower in the cells with transfection with pCMV-Klotho than the controls. Thus, functional analysis demonstrated that Klotho expression inhibited the proliferation of liver cancer cells and Klotho worked as an important antitumor gene in tumor progression. Next, the mechanism was partly clarified that Klotho expression induced cell apoptosis in HepG2 and SMMC-7721 cells, and this phenomenon was mainly involved in the Wnt/ß-catenin signaling pathway. The western blotting analysis revealed that overexpression or recombinant administration of Klotho obviously decreased the expression levels of ß-catenin, C-myc, and Cyclin D1 in HepG2 cells. Most importantly, the antitumor mechanism for Klotho due to that overexpression of Klotho not only decreased the endogenous ß-catenin levels but also inhibited the nuclear translocation of ß-catenin to delay the cell cycle progression. CONCLUSIONS: Klotho was a tumor suppressor gene, and overexpression of Klotho suppressed the proliferation of liver cancer cells partly due to negative regulation of Wnt/ß-catenin signaling pathway. So, Klotho might be used as a potential target, and the study will contribute to treatment for therapy of liver cancer patients.

Radical lymph node dissection and assessment: Impact on gallbladder cancer prognosis.

AIM: To investigate the lymph node metastasis patterns of gallbladder cancer (GBC) and evaluate the optimal categorization of nodal status as a critical prognostic factor. METHODS: From May 1995 to December 2010, a total of 78 consecutive patients with GBC underwent a radical resection at Liaocheng People's Hospital. A radical resection was defined as removing both the primary tumor and the regional lymph nodes of the gallbladder. Demographic, operative and pathologic data were recorded. The lymph nodes retrieved were examined histologically for metastases routinely from each node. The positive lymph node count (PLNC) as well as the total lymph node count (TLNC) was recorded for each patient. Then the metastatic to examined lymph nodes ratio (LNR) was calculated. Disease-specific survival (DSS) and predictors of outcome were analyzed. RESULTS: With a median follow-up time of 26.50 mo (range, 2-132 mo), median DSS was 29.00 ± 3.92 mo (5-year survival rate, 20.51%). Nodal disease was found in 37 patients (47.44%). DSS of node-negative patients was significantly better than that of node-positive patients (median DSS, 40 mo vs 17 mo, χ² = 14.814, P < 0.001), while there was no significant difference between N1 patients and N2 patients (median DSS, 18 mo vs 13 mo, χ² = 0.741, P = 0.389). Optimal TLNC was determined to be four. When node-negative patients were divided according to TLNC, there was no difference in DSS between TLNC < 4 subgroup and TLNC ≥ 4 subgroup (median DSS, 37 mo vs 54 mo, χ² = 0.715, P = 0.398). For node-positive patients, DSS of TLNC < 4 subgroup was worse than that of TLNC ≥ 4 subgroup (median DSS, 13 mo vs 21 mo, χ² = 11.035, P < 0.001). Moreover, for node-positive patients, a new cut-off value of six nodes was identified for the number of TLNC that clearly stratified them into 2 separate survival groups (< 6 or ≥ 6, respectively; median DSS, 15 mo vs 33 mo, χ² = 11.820, P < 0.001). DSS progressively worsened with increasing PLNC and LNR, but no definite cut-off value could be identified. Multivariate analysis revealed histological grade, tumor node metastasis staging, TNLC and LNR to be independent predictors of DSS. Neither location of positive lymph nodes nor PNLC were identified as an independent variable by multivariate analysis. CONCLUSION: Both TLNC and LNR are strong predictors of outcome after curative resection for GBC. The retrieval and examination of at least 6 nodes can influence staging quality and DSS, especially in node-positive patients.