Zhaolai Ma

Meta-analysis of Liver Resection Versus Nonsurgical Treatments for Pancreatic Neuroendocrine Tumors with Liver Metastases

AbstractPurpose Studies have reported limited evidence of the benefits and harms of various regimens, such as liver resection and medical therapy, for the treatment of pancreatic neuroendocrine tumors (pNETs) with liver metastases. This meta-analysis aimed to evaluate the efficacy of liver resection versus nonsurgical treatments in patients with pNET.MethodsRelevant studies published in English were retrieved from the computerized databases Medline, Embase, and Cochrane. A meta-analysis was performed to investigate the differences in the efficacy of liver resection and nonsurgical treatments based on the evaluation of 30-day mortality, symptom relief rate, median survival time, and 2-, 3-, or 5-year survival using a random-effects model. Studies were independently reviewed by two investigators. Data from eligible studies were extracted, and the meta-analysis was performed using the comprehensive meta-analysis program version 2.ResultsA total of seven studies were included in the analysis. The results demonstrated that liver resection was significantly associated with a higher rate of symptom relief, longer median survival time, higher 2- or 3-year survival rates, as well as a higher 5-year survival rate. There was no significant difference in 30-day mortality among patients with pNETs who were treated by liver resection and nonsurgical therapy or survival between functional and nonfunctional pNETs. No publication bias was detected.ConclusionsLiver resection has a favorable prognostic outcome in terms of higher postoperative symptom relief rates and longer survival rates. Further randomized, controlled trials with longer follow-up periods are required to confirm the advantages of liver resection for pNETs.

Neutrophils assist the metastasis of circulating tumor cells in pancreatic ductal adenocarcinoma: A new hypothesis and a new predictor for distant metastasis.

AbstractDuring our research on circulating tumor cells (CTCs) derived from tumor-adjacent vessels in pancreatic ductal adenocarcinoma (PDAC), we found that CTCs are sometimes surrounded by white blood cells (WBCs) in blood. We hypothesize that such interaction between WBCs and CTCs in blood is a mechanism by which WBCs assist in the metastasis of CTCs. We present our laboratory finding, with our evaluation of the association between the neutrophil-to-lymphocyte ratio (NLR, the most investigated clinical parameter of WBCs) and distant metastasis after curative surgery in PDAC. The laboratory finding was presented through immunofluorescence. In the clinical segment, we performed a retrospective study on PDAC patients with distant metastasis after curative surgery who were referred to Peking University Third Hospital between 2005 and 2014. The data on the possible clinical factors were collected by a retrospective review of the patients’ records. Immunofluorescence results showed that CTCs are surrounded by WBCs in tumor-adjacent vessels of PDAC patients. In the clinical segment, 112 (70%) of a total of 160 PDAC patients were found to have developed distant metastases after surgery; among the 112 patients, only 89 had entire data and were enrolled for further analysis (84.3% patients had liver metastasis). No significant association was found between the NLR and overall survival (hazard ratio [HR] = 1.027, 95% confidence interval [CI] 0.723–1.459, P = 0.88); however, a significant relationship between the NLR and distant metastasis after curative surgery was found on the univariate (HR = 1.641, 95% CI 1.058–2.545, P = 0.027) and multivariate analyses (HR = 2.15, 95% CI 1.279–3.615, P = 0.004). Neutrophils might assist in distant metastasis through interaction with CTCs in blood. Moreover, NLR is an effective predictor for distant metastasis after curative surgery for PDAC.

Expression profile and potential roles of EVA1A in normal and neoplastic pancreatic tissues.

BACKGROUND EVA1A (eva-1 homolog A) is a novel gene that regulates programmed cell death through autophagy and apoptosis. Our objective was to investigate the expression profiles and potential role of EVA1A in normal and neoplastic human pancreatic tissues. MATERIALS AND METHODS The expression pattern of EVA1A in normal pancreatic tissue was examined by indirect immunofluorescence and confocal microscopy. Protein levels in paraffin-embedded specimens from normal and diseased pancreatic and matched non-tumor tissues were evaluated by immunohistochemistry. RESULTS EVA1A colocalized with glucagon but not with insulin, demonstrating production in islet alpha cells. Itwas strongly expressed in chronic pancreatitis, moderately or weakly expressed in the plasma membrane and cytoplasm in pancreatic acinar cell carcinoma, and absent in normal pancreatic acinar cells. Although the tissue architecture was deformed, EVA1A was absent in the alpha cells of pancreatic ductal adenocarcinomas, intraductal papillary mucinous neoplasms, mucinous cystadenomas, solid papillary tumors and pancreatic neuroendocrine tumors. CONCLUSIONS EVA1A protein is specifically expressed in islet alpha cells, suggesting it may play an important role in regulating alpha-cell function. The ectopic expression of EVA1A in pancreatic neoplasms may contribute to their pathogenesis and warrants further investigation.

Simultaneous laparoscopic splenectomy and right hemihepatectomy for littoral cell angiosarcoma accompanied with liver metastases

Despite the wide acceptance of laparoscopic resection for treatment of abdominal tumors, only few cases of simultaneous laparoscopic removal of the spleen and the right liver have been reported to date. Littoral cell angiosarcoma (LCAS), which arises from the littoral cells lining the sinus channels of the splenic red pulp, is a rare condition, and there is limited literature on littoral cell angiosarcoma with liver metastases. We present the case of a 28-year-old woman with postoperative pathologically-proven LCAS with right liver metastases. The patient’s surgery was safely performed, and her postoperative course was uneventful until now. This case suggests that concomitant laparoscopic splenectomy (LS) and right hemihepatectomy is a suitable surgical option for selected patients.

G-CSF associates with neurogenesis and predicts prognosis and sensitivity to chemotherapy in pancreatic ductal adenocarcinoma

Background Recent studies demonstrated that granulocyte colony-stimulating factor (G-CSF), regularly used for the prevention of neutropenia, is engaged in cancer progression. However, the role of G-CSF in pancreatic ductal adenocarcinoma (PDAC) is not clear. The aim of the present study was to investigate the expression and prognostic value of G-CSF in patients with PDAC. Materials and methods The localization and expression of G-CSF in PDAC were examined by immunohistochemistry (IHC). The analysis of the levels of G-CSF in plasma was evaluated using ELISA kit. The correlation between G-CSF expression and patients’ survival was assessed by Kaplan–Meier analysis. Results In IHC specimens, G-CSF was discovered predominantly in the cell cytoplasm and expressed in most of PDAC, while in plasma, the systemic level of G-CSF is no different between normal patients and pancreatic cancer patients. In 100 PDAC cases with IHC, patients with grades 2 and 3 were defined as the high expression group (41 patients, 41%), and those with grades 0 and 1 as the low expression group (59 patients, 59%). Significant correlation was noted between high G-CSF expression and neural invasion (P = 0.042) or early recurrence (P < 0.001). G-CSF appeared to be an independent adverse prognostic factor (hazard ratio = 1.774, 95% confidence interval 1.150–2.737, P = 0.010) in addition to N stage (P = 0.002). Specifically, adjuvant chemotherapy consisting of gemcitabine prolongs survival of patients with high G-CSF expression (median survival time 14 months vs 7.5 months). Morphologically, high G-CSF expression cells demonstrate the association with neurogenesis. Conclusion High expression of G-CSF is a prognostic marker and an indicator to chemotherapy response in PDAC.

Surgical resection of a primary tumor improves survival of metastatic pancreatic cancer: a population-based study

Introduction Pancreatic cancer is a lethal disease with a very poor prognosis. This study investigates survival of patients diagnosed with metastatic pancreatic cancer (mPC) based on local treatment of the primary tumor. Methods Patients diagnosed with stage IV mPC between 2004 and 2013 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Cancer-specific survival (CSS) and overall survival (OS) were examined. CSS and OS were examined by using the Kaplan–Meier method with the log-rank test. Multivariable survival analyses of CSS and OS were conducted using the Cox proportional hazard model. Results A total of 28918 patients with mPC were included in this analysis. There were 467 patients who received surgical resection (1.6%) and 28451 patients who did not (98.4%). Patients who were younger than 70 years (odds ratio [OR]=1.45, 95% CI=1.04–2.03, p=0.03), diagnosed from 2004 to 2008 (OR=1.49, 95% CI=1.25–1.80, p<0.001), female (OR=1.31, 95% CI=1.08–1.58, p<0.001), married (OR=1.56, 95% CI=1.27–1.90, p<0.001), at T3 stage (OR=3.53, 95% CI=1.10–11.37, p=0.035), at N1 stage (OR=2.05, 95% CI=1.68–2.50, p<0.001), presenting histological types other than adenocarcinoma (OR=2.04, 95% CI=1.43–2.94, p<0.001), and with tumor of the pancreatic head (OR=1.90, 95% CI=1.27–2.82, p=0.002) were more likely to be treated with surgical resection. The results of multivariate analysis showed that surgical resection of the primary tumor was associated with CSS (hazard ratio [HR]=0.58, 95% CI=0.52–0.64, p<0.001) and OS (HR=0.59, 95% CI=0.53–0.65, p<0.001) benefits. In addition, not receiving chemotherapy (HR=2.33, 95% CI=2.27–2.39, p<0.001), age >50 years (HR=1.25, 95% CI=1.09–1.42, p=0.001), male (HR=1.121, 95% CI=1.09–1.15, p<0.001), black ethnicity (HR=1.11, 95% CI=1.1–1.15, p<0.001), unmarried (HR=1.20, 95% CI=1.17–1.23, p<0.001), histological type of adenocarcinoma (HR=1.18, 95% CI=1.14–1.22, p<0.001), and primary site other than the pancreatic head (HR=1.08, 95% CI=1.05–1.11, p<0.001) are factors associated with poor survival. Conclusion This study reveals that local treatment has the primary benefit of both CSS and OS in patients with mPC. These results may guide the management of this patient population.

Pure Laparoscopic Liver Resection for Malignant Liver Tumor: Anatomic Resection Versus Nonanatomic Resection

Background:Laparoscopic liver resection (LLR) has been considered to be safe and feasible. However, few studies focused on the comparison between the anatomic and nonanatomic LLR. Therefore, the purpose of this study was to compare the perioperative factors and outcomes of the anatomic and nonanatomic LLR, especially the area of liver parenchymal transection and blood loss per unit area. Methods:In this study, surgical and oncological data of patients underwent pure LLR procedures for malignant liver tumor were prospectively collected. Blood loss per unit area of liver parenchymal transection was measured and considered as an important parameter. All procedures were conducted by a single surgeon. Results:During nearly 5 years, 84 patients with malignant liver tumor received a pure LLR procedure were included. Among them, 34 patients received anatomic LLR and 50 received nonanatomic LLR, respectively. Patients of the two groups were similar in terms of demographic features and tumor characteristics, despite the tumor size was significantly larger in the anatomic LLR group than that in the nonanatomic LLR group (4.77 ± 2.57 vs. 2.87 ± 2.10 cm, P = 0.001). Patients who underwent anatomic resection had longer operation time (364.09 ± 131.22 vs. 252.00 ± 135.21 min, P < 0.001) but less blood loss per unit area (7.85 ± 7.17 vs. 14.17 ± 10.43 ml/cm2, P = 0.018). Nonanatomic LLR was associated with more blood loss when the area of parenchymal transection was equal to the anatomic LLR. No mortality occurred during the hospital stay and 30 days after the operation. Moreover, there was no difference in the incidence of postoperative complications. The disease-free and overall survival rates showed no significant differences between the anatomic LLR and nonanatomic LLR groups. Conclusions:Both anatomic and nonanatomic pure LLR are safe and feasible. Measuring the area of parenchymal transection is a simple and effective method to estimate the outcomes of the liver resection surgery. Blood loss per unit area is an important parameter which is comparable between the anatomic LLR and nonanatomic LLR groups.