Comparison of prognosis between patients of pancreatic head cancer with and without obstructive jaundice at diagnosis

AbstractPurposeThe aim of this study was to elicit possible differences in prognoses and clinicopathological factors in pancreatic head cancer with and without obstructive jaundice at diagnosis.MethodsThe data from 169 patients with pancreatic head cancer were retrospectively analyzed.ResultsPatients were divided into two groups according to serum total bilirubin at diagnosis: ≥3 mg/dL for icteric group and <3 mg/dL for non-icteric group. In all cases, icteric group (n = 104) had a significantly worse prognosis than non-icteric group (n = 65) (median survival time (MST), 7.5 months (M) vs. 13.5 M, respectively; P = 0.049). In 84 resectable cases, icteric group had a significantly worse prognosis than non-icteric group (MST, 14.2 M vs. 20.9 M, respectively; P = 0.049) after almost equivalent treatment intensities. Icteric group had significantly larger T- and N-factors according to the UICC Classification compared to non-icteric group. The total number of lymph node metastases in icteric group was significantly larger than in non-icteric group (P = 0.008). The intrapancreatic nerve invasion in icteric group was significantly stronger than in non-icteric group (P = 0.016). There were no significant differences in the mortality and morbidity between icteric and non-icteric groups. In 85 unresectable cases, there was no significant difference between the survival periods of icteric and non-icteric groups (MST, 5.2 M vs. 5.3 M, respectively).ConclusionsThe presence of obstructive jaundice at diagnosis in patients with pancreatic head cancer may predict an unfavorable survival compared to such patients without obstructive jaundice

A Meta-Analysis of the Short- And Long-Term Results of Randomized Controlled Trials That Compared Laparoscopy-Assisted and Open Colectomy for Colon Cancer

Purpose: We conducted a meta-analysis to evaluate and compare the short- and long-term results of laparoscopy-assisted colectomy (LAC) and open colectomy (OC) for colon cancer

Clinical significance of the expression of connexin26 in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Connexin26 (Cx26) is one of the connexins (Cxs) family members which form gap junction channels. Cx26 is considered to be a tumor suppressor gene. However, recent studies revealed that over expression of Cx26 is associated with a poor prognosis in several human cancers. This study investigated the correlation between Cx26 expression and the clinicopathological features and P53 expression in colorectal cancer.</p> <p>Methods</p> <p>One hundred and fifty-three patients who underwent a curative resection were studied. Tissue samples were investigated by immunohistochemical staining using antibodies for Cx26 and P53. Moreover, apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining.</p> <p>Results</p> <p>Cx26 expression was found in 83 cases (54.2%) and P53 expression in 71 cases (46.4%). A correlation was observed between the Cx26 expression and recurrence, histology, and p53 expression (P < 0.05). Cx26 positive tumors had significantly longer survival than Cx26 negative tumors (P < 0.05). A multivariate Cox analysis demonstrated that Cx26 expression was an independent prognostic factor (P < 0.05). However, no significant correlation was observed between Cx26 and AI.</p> <p>Conclusion</p> <p>This study suggests that Cx26 expression is an independent prognostic factor in patients that undergo a curative resection of colorectal cancer.</p

RNA interference suppression of mucin 5AC (MUC5AC) reduces the adhesive and invasive capacity of human pancreatic cancer cells

<p>Abstract</p> <p>Background</p> <p>MUC5AC is a secretory mucin normally expressed in the surface muconous cells of stomach and bronchial tract. It has been known that MUC5AC <it>de novo </it>expression occurred in the invasive ductal carcinoma and pancreatic intraepithelial neoplasm with no detectable expression in normal pancreas, however, its function remains uncertain. Here, we report the impact of MUC5AC on the adhesive and invasive ability of pancreatic cancer cells.</p> <p>Methods</p> <p>We used two MUC5AC expressing cell lines derived from human pancreatic cancer, SW1990 and BxPC3. Small-interfering (si) RNA directed against MUC5AC were used to assess the effects of MUC5AC on invasion and adhesion of pancreas cancer cells <it>in vitro </it>and <it>in vivo</it>. We compared parental cells (SW1990 and BxPC3) with MUC5AC suppressed cells by si RNA (si-SW1990 and si-BxPC3).</p> <p>Results</p> <p>MUC5AC was found to express in more than 80% of pancreatic ductal carcinoma specimens. Next we observed that both of si-SW1990 and si-BxPC3 showed significantly lower adhesion and invasion to extracellular matrix components compared with parental cell lines. Expression of genes associated with adhesion and invasion including several integerins, matrix metalloproteinase (MMP) -3 and vascular endothelial growth factor (VEGF) were down-regulated in both MUC5AC suppressed cells. Furthermore, production of VEGF and phosphorylation of VEGFR-1 were significantly reduced by MUC5AC down regulation. Both of si-SW1990 and si-BxPC3 attenuated activation of Erk1/2. <it>In vivo</it>, si-SW1990 did not establish subcutaneous tumor in nude mice.</p> <p>Conclusions</p> <p>Knockdown of MUC5AC reduced the ability of pancreatic cancer cells to adhesion and invasion, suggesting that MUC5AC might contribute to the invasive motility of pancreatic cancer cells by enhancing the expression of integrins, MMP-3, VEGF and activating Erk pathway.</p

Gemcitabine sensitivity-related mRNA expression in endoscopic ultrasound-guided fine-needle aspiration biopsy of unresectable pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine a predictive indicator of gemcitabine (GEM) efficacy in unresectable pancreatic cancer using tissue obtained by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA).</p> <p>Methods</p> <p>mRNAs extracted from 35 pancreatic tubular adenocarcinoma tissues obtained by EUS-FNA before GEM-treatment were studied. mRNAs were amplified and applied to a Focused DNA Array, which was restricted to well-known genes, including GEM sensitivity-related genes, deoxycytidine kinase (dCK), human equilibrative nucleoside transporter 1 (hENT1), hENT2, dCMP deaminase, cytidine deaminase, 5'-nucleotidase, ribonucleotide reductase 1 (RRM1) and RRM2. mRNA levels were classified into high and low expression based on a cut-off value defined as the average expression of 35 samples. These 35 patients were divided into the following two groups. Patients with partial response and those with stable disease whose tumor markers decreased by 50% or more were classified as the effective group. The rest of patients were classified as the non-effective group. The relationship between GEM efficacy and mRNA expression was then examined by chi-squared test.</p> <p>Results</p> <p>Among these GEM sensitivity-related genes, dCK alone showed a significant correlation with GEM efficacy. Eight of 12 patients in the effective group had high dCK expression, whereas 16 of 23 patients in non-effective group had low dCK expressions (<it>P </it>= 0.0398).</p> <p>Conclusion</p> <p>dCK mRNA expression is a candidate indicator for GEM efficacy in unresectable pancreatic cancer. Quantitative mRNA measurements of dCK using EUS-FNA samples are necessary for definitive conclusions.</p

NC-6301, a polymeric micelle rationally optimized for effective release of docetaxel, is potent but is less toxic than native docetaxel in vivo

Drug release rate is an important factor in determining efficacy and toxicity of nanoscale drug delivery systems. However, optimization of the release rate in polymeric micellar nanoscale drug delivery systems has not been fully investigated. In this study NC-6301, a poly(ethylene glycol)-poly(aspartate) block copolymer with docetaxel (DTX) covalently bound via ester link, was synthesized with various numbers of DTX molecules bound to the polymer backbone. The number of DTX molecules was determined up to 14 to achieve an optimal release rate, based upon the authors’ own pharmacokinetic model using known patient data. Efficacy and toxicity of the formulation was then tested in animals. When administered three times at 4-day intervals, the maximum tolerated doses of NC-6301 and native DTX were 50 and 10 mg/kg, respectively, in nude mice. Tissue distribution studies of NC-6301 in mice at 50 mg/kg revealed prolonged release of free DTX in the tumor for at least 120 hours, thus supporting its effectiveness. Furthermore, in cynomolgus monkeys, NC-6301 at 6 mg/kg three times at 2-week intervals showed marginal toxicity, whereas native DTX, at 3 mg/kg with the same schedule, induced significant decrease of food consumption and neutrophil count. NC-6301 at 50 mg/kg in mice also regressed a xenografted tumor of MDA-MB-231 human breast cancer. Native DTX, on the other hand, produced only transient and slight regression of the same tumor xenograft. NC-6301 also significantly inhibited growth of OCUM-2MLN human scirrhous gastric carcinoma in an orthotopic mouse model. Total weight of metastatic lymph nodes was also reduced. In conclusion, NC-6301 with an optimized release rate improved the potency of DTX while reducing its toxicity

Two Cases of Long-Term Control of Metastatic Colorectal Cancer via FTD/TPI plus Bevacizumab in Elderly Patients

With advances in new cytotoxic drugs and molecular-targeted drugs, the prognosis of patients with metastatic colorectal cancer (mCRC) has improved. However, physicians often hesitate to administer intensive standard regimens to elderly patients with mCRC. Recently, first-line regimens that are effective in and well-tolerated by patients who are not eligible for intensive chemotherapy have been established. However, the therapeutic strategies to adopt after the failure of first-line treatment for patients who are not eligible for intensive chemotherapy remain unclear. We herein report two cases of long-term control of mCRC via FTD/TPI+bevacizumab (Bmab) as second- or third-line treatment in elderly patients without severe adverse events. In case 1, first-line treatment with Tegafur-Uracil, which is a prodrug of 5-FU, caused disease progression in a short period after the initiation of chemotherapy. In case 2, intensive first-line treatment caused severe adverse events, and treatment was discontinued. However, in both cases, disease control was obtained for a long time without severe adverse events by subsequent treatment with FTD/TPI+Bmab. The success in these present cases indicates that FTD/TPI+Bmab as a second- or third-line treatment is a therapeutic option for elderly patients with mCRC who are not eligible for intensive chemotherapy, even after failure of treatment with 5-FU