Histopathological and Haemogram Features Correlate with Prognosis in Rectal Cancer Patients Receiving Neoadjuvant Chemoradiation without Pathological Complete Response.

BACKGROUND: Neoadjuvant chemoradiation therapy (NCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC); approximately 80% of patients do not achieve complete response. Identifying prognostic factors predictive of survival in these patients to guide further management is needed. The intratumoural lymphocytic response (ILR), peritumoural lymphocytic reaction (PLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PtLR) are correlated with the tumour microenvironment and cancer-related systemic inflammation. This study aimed to explore the ability of the ILR, PLR, NLR, and PtLR to predict survival in LARC patients without a complete response to NCRT. METHODS: Sixty-nine patients who underwent NCRT and surgery were retrospectively reviewed. The ILR and PLR were assessed in surgical specimens, and the NLR and PtLR were calculated using pre- and post-NCRT blood count data. The Kaplan-Meier method and Cox regression analyses were performed for survival analysis. RESULTS: A high PLR and high post-NCRT NLR and PtLR were significantly associated with better prognosis. Lymphovascular invasion (LVI), post-NCRT neutrophil count, and lymphocyte count were significant predictors of overall survival. LVI and the PLR were independent predictors of disease-free survival. CONCLUSIONS: NCRT-induced local and systemic immune responses are favourable prognostic predictors in LARC patients without complete response to NCRT.

Vacuum Brazing of Metallized YSZ and Crofer Alloy Using 72Ag-28Cu Filler Foil.

The study focused on dissimilar brazing of metallized YSZ (Yttria-Stabilized Zirconia) and Crofer alloy using BAg-8 (72Ag-28Cu, wt%) filler foil. The YSZ substrate was metallized by sequentially sputtering Ti (0.5/1 µm), Cu (1/3 µm), and Ag (1.5/5 µm) layers, and the Crofer substrate was coated with Ag layers with a thickness of 1.5 and 5 µm, respectively. The BAg-8 filler demonstrated excellent wettability on both metallized YSZ and Crofer substrates. The brazed joint primarily consisted of Ag-Cu eutectic. The metallized Ti layer dissolved into the braze melt, and the Ti preferentially reacted with YSZ and Fe from the Crofer substrate. The globular Fe2Ti intermetallic compound was observed on the YSZ side of the joint. The interfacial reaction of Ti was increased when the thickness of the metallized Ti layer was increased from 0.5 to 1 µm. Both brazed joints were crack free, and no pressure drop was detected after testing at room temperature for 24 h. In the YSZ/Ti(0.5µ)/Cu(1µ)/Ag(1.5µ)/BAg-8(50µ)/Ag(1.5µ)/Crofer joint tested at 600 °C, the pressure of helium decreased from 2.01 to 1.91 psig. In contrast, the helium pressure of the YSZ/Ti(1µ)/Cu(3µ)/Ag(5µ)/BAg-8(50µ)/Ag(5µ)/Crofer joint slightly decreased from 2.02 to 1.98 psig during the cooling cycle of the test. The greater interfacial reaction between the metallized YSZ and BAg-8 filler due to the thicker metallized Ti layer on the YSZ substrate was responsible for the improved gas-tight performance of the joint.

Rice protein prolamin promotes anti-leukemia immunity and inhibits leukemia growth in vivo.

Prolamin is a heat-stable storage protein of rice (Oryza sativa). This study aimed to examine the effect of prolamin on anti-tumor immune response in vitro and leukemia growth in vivo. The prolamin-enriched rice fractions were prepared to stimulate peripheral blood mononuclear cells (MNC) from mice spleen. The MNC-conditioned medium (MNC-CM) was collected to treat leukemia L1210 cells. Human MNC-CM was prepared to treat Jurkat acute T cell leukemia cells. Purified prolamin was orally administered to syngeneic L1210-bearing DBA/2 mice to assess weights of tumor, liver and spleen, liver histopathology, peripheral blood neutrophil count and cytokine levels. Prolamin-prepared MNC-CM inhibited the viability of murine leukemia L1210 cells and human leukemia Jurkat cells, indicating an immunomodulatory effect. In syngeneic L1210-bearing DBA/2 mice, oral administration of purified prolamin dose-dependently decreased the tumor weight and attenuated the leukemia-induced reduction of liver and spleen weights. Prolamin inhibited the increase of peripheral blood leukocyte count. The levels of tumor necrosis factor-α and interferon-γ in MNC-CM and mice serum were significantly increased by prolamin treatment. No significant change in body weight, serum alanine aminotransferase and creatinine levels was noted by prolamin treatment. Rice prolamin could effectively promote anti-tumor immunity and inhibit leukemia growth without significant toxicity.

Daphnoretin modulates differentiation and maturation of human dendritic cells through down-regulation of c-Jun N-terminal kinase.

Daphnoretin, an active constituent of Wikstroemia indica C.A. Meys, has been shown possessing anti-cancer activity. In this study, we examined the effect of daphnoretin on differentiation and maturation of human myeloid dendritic cells (DCs). After treatment with daphnoretin (0, 1.1, 3.3, 10 and 30µM) to initiate monocytes, the recovery rate of DCs was reduced in a dose-dependent manner. The mature DCs differentiated in the presence of daphnoretin had fewer and shorter dendrites. Daphnoretin modulated DCs differentiation and maturation in terms of lower expression of CD1a, CD40, CD83, DC-SIGN, and HLA-DR. Daphnoretin inhibited the allostimulatory activity of DCs on proliferation of naive CD4+CD45+RA+ T cell. On the mitogen-activated protein kinase, daphnoretin down-regulated the lipopolysaccharide-augmented expression of phosphorylated c-Jun N-terminal kinase (pJNK), but not p38 and extracellular signal-regulated kinase 1/2 (ERK1/2). Activation of JNK by anisomycin reversed the effect of daphnoretin on daphnoretin-inhibited pJNK expression and dendrite formation of DCs. In disease model related to maturation of DCs, daphnoretin suppressed the acute rejection of skin allografts in mice. Our results suggest that daphnoretin modulated differentiation and maturation of DCs toward a state of atypical maturation with impaired allostimulatory function and this effect may go through down-regulation of phosphorylated JNK.

Neutrophil-lymphocyte ratio and CEA level as prognostic and predictive factors in colorectal cancer: A systematic review and meta-analysis.

INTRODUCTION: There is a growing body of evidence showing the functional relationship between inflammation index like netrophil.lymphocyte ratio. (NLR) and colorectal cancer. (CRC) in both experimental and clinical situations. The serum carcinoembryonic antigen. (CEA) level is the most widely used marker and associate with poor prognosis in most studies. For these factors to be clinically useful, they should be routinely available, well standardized, and validated in different patient cohorts. AIMS: There is a growing body of evidence showing the functional relationship between inflammation index like netrophil-lymphocyte ratio. (NLR) and colorectal cancer. (CRC) in both experimental and clinical situations. The serum carcinoembryonic antigen. (CEA) level is the most widely used marker and associate with poor prognosis in most studies. For these factors to be clinically useful, they should be routinely available, well standardized, and validated in different patient cohorts. MATERIALS AND METHODS: We systemically searched PubMed, Embase, and SciVerse Scopus databases, and performed a meta.analysis by Review Manager 5.2 software. (The Cochrane Collaboration, Software Update, Oxford). Two reviewers selected studies, assessed risk of bias, and extracted data independently. Newcastle.Ottawa Scale was applied to assess the quality of included studies. RESULTS: Fifteen studies involving 7741 patients with CRC were analyzed. Patients with an NLR < 5 before treatment were significantly more likely to have 5-year overall survival (odds ratio [OR] = 2.03; 95% confidence interval [CI] = 1.56-2.63) and 5-year disease-free survival (OR = 1.67; 95% CI = 1.19-2.35). Pretreatment CEA level < 5 were significantly associated with complete tumor response and tumor downstaging after neoadjuvant treatment. The result also showed that patients with NLR > 5 were expected to have a larger tumor, poorer tumor differentiation, and higher CEA level. CONCLUSION: NLR and CEA are valuable tools for the prediction of prognosis in CRC and adjusting the treatment strategy.

Clinical and microbiological analysis of adult perianal abscess.

BACKGROUND: In Taiwan, Klebsiella pneumoniae is the predominant pathogen causing pyogenic liver abscess in patients with diabetes mellitus (DM). The purpose of our hospital-based study was to determine the predominant bacterial species causing perianal abscess in hospitalized patients with and without DM in Taiwan. METHODS: Data on patients admitted and then operated on for perianal abscess during the period of March 2001 to December 2008 were reviewed. Information extracted from medical records included clinical information and laboratory data as well as culture and antibiotic sensitivity results. RESULTS: A total of 183 patients underwent surgery for perianal abscess. The most common pathogen causing perianal abscess in non-DM patients was Escherichia coli (67.1%), and the most common pathogen isolated in DM patients was K pneumoniae (60%; p=0.009). Among the 25 patients with DM, incident DM was diagnosed in 24.0% (6 of 25). In addition, five patients had transient hyperglycemia. CONCLUSIONS: Escherichia coli was the predominant pathogen isolated from perianal abscesses in patients without DM. Klebsiella pneumoniae, however, was the predominant pathogen isolated in DM patients. In both DM and non-DM patients, more than 90% of K pneumoniae isolates showed in vitro sensitivity to first-generation cephalosporins.

Massive bleeding from a ruptured artery in jejunal diverticulosis without pre-existing mucosal inflammation or ulceration.

A case of massive bleeding from a ruptured artery in jejunal diverticulosis without pre-existing mucosal inflammation or ulceration is presented. A 75-year-old bed-ridden man had massive gastrointestinal bleeding and deteriorated to a state of shock rapidly. Panendoscopy, selective abdominal angiography, and radionuclide scanning were performed, but none of these studies revealed the exact bleeding point. Emergent operation revealed a segment of jejunal diverticulosis with bleeding, and it was resected. Pathologic examination revealed tortuous veins in the submucosa of diverticula and a ruptured artery with evidence of active bleeding in a large diverticulum. No pre-existing mucosal inflammation or ulceration was seen. The bleeding cause is thought to be acquired false diverticular wall tearing of a submucosal artery by bowel distension or unknown moving content.

Post-operative concurrent chemoradiation therapy using oral uracil-tegafur versus weekly intravenous fluorouracil for locally advanced rectal cancer.

BACKGROUND: This prospective, nonrandomized study was conducted to compare the efficacy and toxicity of post-operative concurrent chemoradiation therapy (CCRT) using daily oral uracil-tegafur plus leucovorin (UFUR/LV) vs. weekly intravenous fluorouracil plus leucovorin (5-FU/LV) in patients with locally advanced rectal cancer. MATERIALS AND METHODS: From November 1996 through December 2004, 30 patients with stage II or III rectal cancer were enrolled. Either 5-FU (400 to 450 mg/m2) plus LV (80 to 100 mg/m2) weekly or oral UFUR (250 to 300 mg/m2/d) plus oral LV (30 to 45 mg/m2/d) were given during radiotherapy. Radiation (50.4 to 60.4 Gy) was delivered to the tumor bed in 28-33 fractions. RESULTS: The mean survival, 2-year overall survival and disease-free survival were 36 months vs. 30 months, 68% vs. 66% and 55% vs. 50%, (p > 0.05), in the UFUR/LV and 5-FU/LV groups, respectively. There were no treatment-related deaths or grade 4 toxicity in either group. Grade 3 dermatitis, gastrointestinal and hematologic toxicity were noted in the 5-FU/LV group. CONCLUSION: Because of a similar survival rate and lower toxicity, oral UFUR/LV is suggested as an alternative regimen to intravenous 5-FU/LV in post-operative CCRT of locally advanced rectal cancer.