Prognostic significance of neutrophil-lymphocyte ratio in resectable pancreatic neuroendocrine tumors with special reference to tumor-associated macrophages.

BACKGROUND: Recent studies have shown that the systemic inflammatory response induced by cancer leads to cancer progression. Neutrophil-to-lymphocyte ratio (NLR) is the most reliable marker to detect systemic inflammation. In this study, we investigated the significance of NLR in patients with well-differentiated pancreatic neuroendocrine tumors (PanNETs) according to the World Health Organization 2017 classification. METHODS: We retrospectively collected data for patients with PanNET who underwent pancreatic resection with curative intent between January 2008 and December 2017 at six institutions. Clinicopathological factors, recurrence, and immunohistochemical staining of tumor-associated macrophages (TAMs) were analyzed in a total of 55 patients in this study. RESULTS: High NLR (>3.41) in patients was significantly associated with higher white blood cell count, higher Ki-67 index, higher mitotic count, higher grade, higher incidence of lymph node metastasis, higher incidence of lymphatic and neural invasion, massive blood loss, and a large number of CD163-expressing TAMs. Recurrence-free survival of patients with high NLR was significantly poorer than that of patients with low NLR. Multivariate analysis identified high NLR, NET Grade 2 (G2) or Grade 3 (G3), and synchronous hepatic resection as independent risk factors for recurrence after curative resection. CONCLUSIONS: NLR is a promising predictor of recurrence after pancreatectomy that needs to be further investigated and that accumulation of TAMs in the tumor could be one of the causes of NLR elevation.

Significance of Lymph Node Metastasis in Resectable Well-differentiated Pancreatic Neuroendocrine Tumor.

OBJECTIVES: Understanding the effect of lymph node metastasis (LNM) on prognosis in pancreatic neuroendocrine neoplasm is helpful for surgery and follow-up. In this study, we investigated the significance of LNM in well-differentiated pancreatic neuroendocrine tumors (PanNETs) according to the World Health Organization 2017 classification. METHODS: We retrospectively collected data for 95 consecutive patients with PanNET who underwent pancreatic resection with curative intent between January 2008 and December 2017 at 6 institutions. The clinicopathological factors were compared in patients with and without LNM, and prognostic factors were analyzed. RESULTS: Lymph node metastasis was significantly associated with malignant potential of PanNET, such as larger tumor size, higher Ki-67 index, higher tumor grade, and higher incidence of lymphatic, vessel, and neural invasion. Lymph node metastasis was also associated with disease-free but not overall survival. Multivariate analysis identified NET grade 2 (G2) and G3 as independent risk factors for recurrence after curative resection. CONCLUSIONS: World Health Organization 2017 classification was the most independent prognostic factor in patients with resectable well-differentiated PanNETs. Patients with G2 and higher-grade tumors require lymph node dissection to improve prognosis.

A Novel Clinical Factor, D-Dimer Platelet Multiplication, May Predict Postoperative Recurrence and Prognosis for Patients with Cholangiocarcinoma.

BACKGROUND: Patients with cholangiocarcinoma (CC) have a poor prognosis, and their postoperative survival depends on cancer progression and recurrence. Thus, prognostic markers are needed. The fibrin cleavage product, D-dimer, is associated with malignant progression and recurrence in various cancers, and platelets also are related to tumor progression. This study therefore evaluated a new prognostic factor, D-dimer platelet multiplication (PDM), for predicting prognosis in cases of CC. METHODS: This study retrospectively evaluated 55 cases to determine the correlations of D-dimer, platelet, and PDM levels with patient survival. The cutoff values for D-dimer, platelets, and PDM levels were determined using receiver operating characteristic curve analyses. RESULTS: The recurrence group exhibited significantly higher D-dimer (P = 0.00075) and PDM (P = 0.0000683) levels and a trend toward higher platelet levels (P = 0.117). The optimal cutoff values were 1.3 µg/mL for D-dimer levels, 245 × 104/µL for platelet levels, and 158.2 × 104 µg/mL × µL for PDM levels. Poor recurrence-free survival was associated with high D-dimer levels (P = 0.0428), high platelet levels (P = 0.0498), and high PDM levels (P = 0.00511). Poor cancer-specific survival was associated with high platelet levels (P = 0.0156) and high PDM levels (P = 0.0156). In the multivariate analysis, PDM had the greatest correlation with CC prognosis and independently predicted recurrence (P = 0.00649). CONCLUSION: High D-dimer, platelet, and PDM levels were associated with poor recurrence-free and cancer-specific survivals, with PDM exhibiting the greatest correlation with prognosis. Therefore, PDM may help to predict recurrence and prognosis for patients with CC.

[Retrospective analysis of the bevacizumab and CapeOX combination in untreated metastatic/recurrent colorectal cancer].

In recent years, there has been significant progress in systemic chemotherapy for metastatic or recurrent colorectal cancer. We investigated the clinical efficacy and feasibility of the bevacizumab and capecitabine /oxaliplatin(CapeOX)combination for untreated colorectal cancer. From October 2009 to June 2012, 38 patients were included, 18 receiving CapeOX alone and 20 receiving CapeOX plus bevacizumab. The response rate and disease-control rate were 16% and 5 0%, respectively, in the CapeOX arm, and 5 5% and 8 5%, respectively, in the CapeOX plus bevacizumab arm. Median progression-free survival was 8.0 months in the CapeOX arm and 1 2.8 months in CapeOX plus bevacizumab arm. The median overall survival was 21.6 months in the CapeOX arm and 3 4.0 months in CapeOX plus bevacizumab arm. Our results suggest that CapeOX treatment can be useful in the outpatient setting and more effective when combined with bevacizumab. Except in cases of bevacizumab intolerance, addition of bevacizumab to CapeOX treatment is considered useful as first-line therapy for metastatic or recur- rent colorectal cancer.