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

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

Effect of a helium gas atmosphere on the mechanical properties of Ti-6Al-4V alloy built with laser powder bed fusion: A comparative study with argon gas

In metal additive manufacturing, the microstructures and associated mechanical properties of metal specimens can be controlled over a wide range. Although process parameters are considered important in the fabrication of functional parts, the effect of atmospheric gas has not been comprehensively documented. In laser powder bed fusion (LPBF), gas flow is used to eliminate fumes generated by laser irradiation. Simultaneously, the gas removes heat from the laser-irradiated part, which is exposed to high temperature. In this study, we investigated the capacity of helium as an alternative to argon, which is conventionally used as the LPBF atmosphere gas. He has a higher thermal conductivity and lower gas density than Ar, which may result in enhanced heat removal from the Ti-6Al-4V alloy during fabrication. Numerical simulations suggest a greater cooling rate under He flow. Further, the material built under He flow contained finer α' martensite grains and showed improved mechanical properties compared to those fabricated under Ar flow, despite the identical laser irradiation conditions. Thus, He gas is advantageous in LPBF for fabricating products with superior mechanical performance through microstructural refinement, and this is a result of its capacity for cooling and fume generation inhibition. Therefore, this study reveals the importance of the choice of atmospheric gas because of its effects on the characteristics of metallic specimens fabricated using LPBF.Amano H., Ishimoto T., Suganuma R., et al. Effect of a helium gas atmosphere on the mechanical properties of Ti-6Al-4V alloy built with laser powder bed fusion: A comparative study with argon gas. Additive Manufacturing, 48, 102444. https://doi.org/10.1016/j.addma.2021.102444

Tumor-Infiltrating Lymphocytes and Macrophages as a Significant Prognostic Factor in Biliary Tract Cancer

Background: The impact of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) on the prognosis of biliary tract cancer (BTC) is not completely understood. Therefore, in our study, we investigated the effects of the various immune cells infiltration in tumor microenvironment (TME). Methods: A total of 130 patients with BTC who underwent surgical treatment at our institution were enrolled in this study. We retrospectively evaluated TILs and TAMs with immunohistochemical staining. Results: With CD8-high, CD4-high, FOXP3-high, and CD68-low in TME as one factor, we calculated Immunoscore according to the number of factors. The high Immunoscore group showed significantly superior overall survival (OS) and recurrence-free survival (RFS) than the low Immunoscore group (median OS, 60.8 vs. 26.4 months, p = 0.001; median RFS not reached vs. 17.2 months, p \u3c 0.001). Also, high Immunoscore was an independent good prognostic factor for OS and RFS (hazards ratio 2.05 and 2.41 and p = 0.01 and p = 0.001, respectively). Conclusions: High Immunoscore group had significantly superior OS and RFS and was an independent good prognostic factor for OS and RFS

Plasma pharmacokinetics after combined therapy of gemcitabine and oral S-1 for unresectable pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>The combination of gemcitabine (GEM) and S-1, an oral 5-fluorouracil (5-FU) derivative, has been shown to be a promising regimen for patients with unresectable pancreatic cancer.</p> <p>Methods</p> <p>Six patients with advanced pancreatic cancer were enrolled in this pharmacokinetics (PK) study. These patients were treated by oral administration of S-1 30 mg/m²twice daily for 28 consecutive days, followed by a 14-day rest period and intravenous administration of GEM 800 mg/m²on days 1, 15 and 29 of each course. The PK parameters of GEM and/or 5-FU after GEM single-administration, S-1 single-administration, and co-administration of GEM with pre-administration of S-1 at 2-h intervals were analyzed.</p> <p>Results</p> <p>The maximum concentration (Cmax), the area under the curve from the drug administration to the infinite time (AUCinf), and the elimination half-life (T1/2) of GEM were not significantly different between GEM administration with and without S-1. The Cmax, AUCinf, T1/2, and the time required to reach Cmax (Tmax) were not significantly different between S-1 administration with and without GEM.</p> <p>Conclusion</p> <p>There were no interactions between GEM and S-1 regarding plasma PK of GEM and 5-FU.</p

Identification of a high incidence region for retroviral vector integration near exon 1 of the LMO2 locus

Therapeutic retroviral vector integration near the oncogene LMO2 is thought to be a cause of leukemia in X-SCID gene therapy trials. However, no published studies have evaluated the frequency of vector integrations near exon 1 of the LMO2 locus. We identified a high incidence region (HIR) of vector integration using PCR techniques in the upstream region close to the LMO2 transcription start site in the TPA-Mat T cell line. The integration frequency of the HIR was one per 4.46 × 10(4 )cells. This HIR was also found in Jurkat T cells but was absent from HeLa cells. Furthermore, using human cord blood-derived CD34(+ )cells we identified a HIR in a similar region as the TPA-Mat T cell line. One of the X-linked severe combined immunodeficiency (X-SCID) patients that developed leukemia after gene therapy had a vector integration site in this HIR. Therefore, the descriptions of the location and the integration frequency of the HIR presented here may help us to better understand vector-induced leukemogenesis

Degenerative changes in the appendicular joints of ancient human populations from the Japan Islands

Degenerative changes in six major limb joints were investigated to compare their prevalence among five ancient skeletal populations from the Japan Islands. The populations assessed in this study consisted of the farmers in the northern Kyushu/Yamaguchi area and the foragers from the northwestern Kyushu area from the Yayoi period (5th century BC to 3rd century AD); the Okhotsk (5th to 12th centuries AD) foragers from Hokkaido and Sakhalin; the common people from medieval Kamakura (12th to 14th centuries AD) in Kanto, central Japan; and the early-modern farmers (17th to 19th centuries AD) from Kumejima, in the southernmost island chain (Ryukyu Islands). Crude prevalence comparisons showed that the shoulder and hip joints were principally affected in early-modern Kumejima and medieval Kamakura, which contrasted with the high prevalence of elbow and knee joint changes in the Okhotsk people. The heavy dependence on marine mammals and fish for dietary protein intake probably required flexion and extension movements of the most severely degenerated joints in the Okhotsk people. The northern Kyushu/Yamaguchi and northwestern Kyushu Yayoi peoples were more affected by degeneration in the wrist joints than others, possibly due to their use of innovative tools such as stone or shell knives and harpoons. A multivariate logistic regression analysis, adjusted for age, region, and sex as the predictor variables for degenerative changes in joints, was applied to only the two samples from Kumejima and Kamakura (including previously reported spine data) because of their better preservation. This revealed differences in the prevalence of changes in some joints; for example, age-related changes were recognized. The Kumejima people were more commonly affected by hip and knee joint changes, whereas the Kamakura people were more commonly affected by changes to apophyseal joints. Because a stable isotope analysis indicated that the trophic levels of the two populations were almost the same, the pattern of degenerative changes would have reflected differences in their specific workloads, such as wet rice cultivation using a peculiar hoe by the Kumejima people. This study, combining multivariate logistic regression analysis of degenerative joint changes and stable isotope analyses, uses large skeletal populations to add clarity to the actual rigors of ancient life. © 2015 Elsevier Ltd and INQUA