FAK, CD44v6, c-Met and EGFR in colorectal cancer parameters: tumour progression, metastasis, patient survival and receptor crosstalk

Purpose

Research for reliable and patient-specific markers in colorectal cancer (CRC) is based on solid evidence that staging alone is not informative enough. Employing four cellular receptors, we embarked to identify aggressive tumour behaviour and impact of surrogate marker expression on patient prognosis.

Methods

One-hundred eighty-three CRC patients were enrolled in our investigation that focused on an array of biological markers, namely epidermal growth factor receptor (EGFR), c-Met, focal adhesion kinase (FAK) and CD44v6. Tissue samples, clinicopathological data and patient’s follow-up information were collected, and immunohistochemical assays evaluated the levels of the aforementioned molecules. All available data were correlated with tumour grade, stage, patient age, gender and survival.

Results

Expression of all receptors correlated closely with tumour stage (P?<?0.01) exhibiting a connection with cancer’s invasiveness and progress. Survival also proved to depend significantly on molecular expression (log-rank test for Kaplan–Meier; EGFR P?=?0.030, c-Met P?=?0.050, FAK P?<?0.001, CD44v6 P?<?0.001). Stage, FAK and CD44v6 emerged as independent predictors of survival in a stepwise regression analysis (FAK P?=?0.001 Exp(B)?=?2.517, 95 % confidence interval (CI)?=?1.704–5.831 and CD44v6 P?=?0.005, Exp(B)?=?2.299, 95 % CI?=?1.287–4.110). T-stage, nodal metastasis, all metastatic types (N/M) and size correlated with at least one of the receptors or their co-expression. Notably, increased staining for each receptor was followed by statistically significant expression elevation of at least one of the other markers.

Conclusions

Our results suggest that the selected cellular receptors are suitable for use as biomarkers of survival and tumour progression in CRC. Furthermore, we provide additional evidence for receptor interaction, properly clarifying their importance, which could potentially lead to more effective anti-CRC regimens.     

High CD44s expression is associated with the EMT expression profile and intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy

Background/purpose

Local ablation therapy (LAT) is a widely used treatment for hepatocellular carcinoma (HCC) because it is less invasive than hepatic resection. The precise molecular mechanism underlying local HCC recurrence after LAT is largely unknown. The CD44 standard isoform (CD44s) is involved in epithelial–mesenchymal transition (EMT) in HCC. We investigate the significance of CD44s expression and EMT expression profile in local HCC recurrence after LAT.

Methods

We studied the expression levels of CD44s, EMT expression profile (E-cadherin^low/vimentin^high expression) and their association with clinicopathological factors in 30 HCC samples from patients with locally recurrent HCCs after LAT following hepatic resection. The alterations of CD44s expression was compared with those in initial HCCs from 150 patients without prior any anticancer treatment including LAT.

Results

A high CD44s expression was significantly associated with the EMT expression profile (P = 0.002), and it was also detected with a higher frequency in the locally recurrent HCCs after LAT compared to initial HCCs (P < 0.001). In addition, high CD44s expression was associated with the intrahepatic dissemination of HCC after LAT (P = 0.006).

Conclusions

These results suggest that high CD44s expression is associated with the aggressive recurrence pattern via EMT after LAT for HCC.     

Readressing the Role of Toll-Like Receptor-4 Alleles in Inflammatory Bowel Disease: Colitis, Smoking, and Seroreactivity

Background

Toll-like receptor (TLR) polymorphisms, and especially TLR-4 Asp299Gly and TLR-4 Thr399Ile, have been linked with Crohn’s disease (CD) and to a lesser extent with ulcerative colitis (UC), CD behavior, and compromised seroreactivity to microbial antigens. Available data, however, are conflicting.

Aims

To address these issues, the distribution of TLR-4 polymorphic alleles was assessed in patients with UC, CD, and healthy controls (HC), considering patient and disease characteristics as well as related serological markers.

Methods

TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms were determined in 187 UC and 163 CD patients and 274 randomly selected HC. C reactive protein, anti-Saccharomyces cerevisiae mannan antibodies, anti-mannobioside carbohydrate antibodies, anti-laminariobioside carbohydrate antibodies IgG, and anti-chitobioside carbohydrate antibodies (ACCA) IgA levels were also assessed.

Results

UC and especially pancolitis patients carried the mutant alleles more frequently compared to CD patients and HC or UC patients with different disease extents (P = 0.002 and P < 0.0001, respectively). Involvement of the colon was more frequent in CD patients with mutant TLR-4 compared to those with wild-type alleles (P = 0.004). Levels and positivity rates of ACCA IgA were lower in inflammatory bowel disease (IBD) patients carrying the mutant compared to those with wild-type alleles (0.075 < P < 0.05). Despite the mutant TLR-4 predisposition for UC pancolitis, smoking was associated with more limited disease (P < 0.001).

Conclusions

The presence of TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms is related to UC pancolitis, involvement of the colon in CD, and lower ACCA IgA levels. Smoking reduces the extent of UC, even in the presence of mutant alleles.     

Impact of hepatic lymph node metastasis on survival of patients with synchronous resectable or unresectable liver metastases of colorectal cancer

Background

The goals of this retrospective study were to comprehensively evaluate the impact of hepatic lymph node (HLN) involvement on survival in patients with synchronous resectable or unresectable liver metastases from colorectal cancer and to highlight how to deal with such cases in the light of recent advances in chemotherapy.

Methods

The impact of HLN involvement on survival, along with various clinical, pathological, and therapeutic factors, was retrospectively evaluated in 61 patients with synchronous liver metastases from colorectal cancer (resectable, 26; unresectable, 35), undergoing resection of the primary tumor and histopathological evaluation between July 2000 and April 2008.

Results

The proportion with HLN metastasis was 11.5 % in resectable cases and 28.6 % in unresectable cases. On multivariate analysis using the Cox proportional hazards model, HLN metastasis (P < 0.001), along with non-resection of hepatic lesions (P < 0.001), larger metastatic tumor volume (P < 0.001), non-use of oxaliplatin-based chemotherapy (P < 0.001), involvement of 4 or more regional lymph nodes (P < 0.001), and excessive lymphatic invasion (P = 0.02), was identified as an independent risk factor for shorter survival.

Conclusions

To establish a new therapeutic strategy for synchronous liver metastasis of colorectal cancer, the HLNs should be examined histologically in patients undergoing resection of their primary colon and rectal cancer.     

A survey of current practices used to maintain surgically induced remission following intestinal resection for Crohn’s disease

Background and aims

Post-operative Crohn’s disease (CD) recurrence is common after intestinal resection. The European Crohn’s and Colitis Organization has issued guidelines regarding the optimal post-operative management of patients who have undergone intestinal resection for CD. The current study aims to assess the current adjuvant therapy practices of colorectal surgeons and gastroenterologists.

Methods

An electronic-based survey was sent to members of the Association of Coloproctology of Great Britain and Ireland and the Irish Society of Gastroenterology.

Results

One hundred twenty-five surgeons and gastroenterologists responded. Gastroenterologists more frequently assessed for pre-clinical recurrence with serum inflammatory markers (97 vs. 51 %, P?<?0.001), faecal calprotectin (30 vs. 10 %, P?=?0.008) and ileocolonoscopy (67 vs. 23 %, P?<?0.001), while surgeons more frequently performed a CT scan (23 vs. 6 %, P?=?0.037). The majority of respondents estimated the 1-year endoscopic recurrence to be 10–25 %, and 36 % of respondents offered prophylaxis to all post-operative patients. Budesonide (8 vs. 4 %, P?=?0.006) and azathioprine/mercaptopurine (60 vs. 33 %, P?<?0.001) were more often prescribed for high-risk patients, while imidazole antibiotics (11 vs. 5 %, P?<?0.001) and 5-ASA derivatives were more often prescribed for low-risk patients (51 vs. 14 %, P?<?0.001).

Conclusion

Currently, surgeons and gastroenterologists involved in the peri-operative care of patients with CD underestimate the risk of recurrence following intestinal resection and under-utilize ileocolonoscopy to tailor adjuvant therapy.     

IMP3 combined with CD44s,a novel predictor for prognosis of patients with hepatocellular carcinoma

Purpose

Insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) is reported to be re-expressed in malignant tumors and can regulate the expression of multiple genes related to tumor invasion. CD44 standard isoform (CD44s) has been reported to play an important role in facilitating tumor invasion. In this text, we investigate the regulatory function of IMP3 on CD44s and the role of IMP3 and CD44s in predicting the outcomes of patients with hepatocellular carcinoma.

Methods

IMP3 and CD44s were measured in hepatocellular carcinoma (HCC) tissues by immunohistochemical assay, and survival analysis was conducted among 128 patients. Moreover, we studied the effect of IMP3 on the expression of CD44s and the biological functions of tumor cells in HCC cell lines.

Results

Our results showed that the expression of IMP3 was significantly correlated with CD44s expression (r = 0.505, P < 0.001), and both of them correlated with high AFP level, advanced tumor stage and grade, portal vein tumor thrombus, and early tumor recurrence or metastasis. The results of survival analysis exhibited that the 1-, 3-, 5-year disease-free and overall survival rates significantly reduced in IMP3- and CD44s-positive patients, and IMP3 combined with CD44s was an independent prognostic risk factor for HCC. In vitro assay, our results showed that IMP3 promoted HepG2 and MHCC97H cells invading and migrating via regulating CD44s expression.

Conclusions

Our findings suggest that IMP3 facilitates HCC aggressiveness through regulating CD44s expression, and IMP3 combined with CD44s can be as a new predictor for unfavorable prognosis in HCC patients.     

Multicenter study of endoscopic mucosal resection using 0.13 % hyaluronic acid solution of colorectal polyps less than 20 mm in size

Purpose

Endoscopic mucosal resection (EMR) of colorectal polyps should be curative and safe. This study aimed to determine the efficacy and safety of colorectal EMR using 0.13 % hyaluronic acid (HA) solution.

Methods

This was a single-armed multicenter prospective open trial conducted at 11 Japanese institutions. Lesion characteristics and various measures of clinical outcome, including en bloc resection, histopathologically complete resection, and postoperative bleeding were analyzed for 624 consecutive patients who underwent EMR of colorectal polyps at ≤20 mm in size from August 2010 to September 2011.

Results

En bloc and complete resection were achieved in 93.3 and 78.3 % of 624 lesions. The median EMR procedure time was 2.1?±?1.5 min. The rates of postoperative bleeding and perforation were 1.1 and 0 %. The rate of en bloc resection was higher for polyps at 5–10 mm than for polyps at 11–20 mm (95.1 vs. 85.1 %; P?<?0.001) and was higher for protruding polyps than for superficial polyps (94.5 vs. 87.1 %; P?<?0.05). The rate of en bloc resection was also higher for polyps in the left-side colon than for those in the right-side colon or rectum (96.7 vs. 91.6 vs. 90.8 %; P?<?0.05). Multivariate analysis showed that polyp at 11–20 mm in size and location not on the left-side colon was significantly independent risk factors for failure of en bloc resection.

Conclusion

EMR using 0.13 % HA of colorectal polyps less than 20 mm in size had high rates of en bloc and complete resection and few complications.     

Effect of shRNA targeting survivin on ovarian cancer

Purpose

This study investigated the effect of shRNA targeting survivin on cultured ovarian cancer cells and on a murine ovarian cancer xenograft.

Methods

An RNAi plasmid for survivin was transfected into SKOV3 cells, and the effect of shRNA targeting survivin on the expression of survivin was determined. Transmission electron microscopy (TEM), flow cytometry, and TUNEL staining were used to assess apoptosis. The MTT assay was used to measure cell growth and changes in cisplatin sensitivity. SKOV3 cells were injected into nude mice, and the effect of shRNA targeting the survivin gene on tumor growth was assessed.

Results

SKOV3 cells transfected with an RNAi plasmid against survivin had increased apoptosis and slower growth. At the molecular level, these cells also had lower expression of survivin. Nude mice inoculated with SKOV3 cells developed cancers, and treatment with shRNA targeting survivin markedly inhibited the growth of these cancers with no obvious side effects.

Conclusions

Our studies of SKOV3 cells and ovarian cancer xenografts in nude mice indicate that shRNA targeting survivin has potential for the treatment of ovarian cancer.     

Tumor-associated macrophages and angiogenesis in early stage esophageal squamous cell carcinoma

Background

The association between angiogenesis and tumor-associated macrophages (TAMs) is unclear. Mononuclear cell infiltration was reported to induce angiogenesis in early stage esophageal squamous cell carcinoma (ESCC).

Methods

The study materials included 14 samples of normal squamous epithelium, 11 samples of low-grade intraepithelial neoplasia, and 64 samples of superficial esophageal cancer (M1 and M2 cancer 27; M3 or deeper cancer 37). We assessed microvessel density (MVD) using CD34 and CD105 immunostaining and monocyte count (MC) using CD68 and CD163 immunostaining in relation to the histological type or grade of mononuclear cell infiltration, as well as the correlation between MVD and MC.

Results

MVD and MC increased in accordance with histological type, and the differences were significant (P < 0.001). MVD and MC were significantly higher in M1 and M2 lesions than in normal squamous epithelium (P < 0.05). MVD (CD34 and CD105) and MC (CD68 and CD163) were significantly correlated with the degree of mononuclear cell infiltration (P < 0.001), and there was a strong correlation between MC assessed using CD68 and MC assessed using CD163 (rS = 0.93, P < 0.001). The CD163/CD68 ratio did not differ significantly according to histological type. There was a significant correlation between MVD assessed using CD105 and MC assessed using CD68 (rS = 0.69, P < 0.001) and CD163 (rS = 0.67, P < 0.001). MVD assessed using CD34 was also significantly correlated with MC assessed using both CD68 (rS = 0.59, P < 0.001) and CD163 (rS = 0.57, P < 0.001).

Conclusion

The number of TAMs is significantly associated with the development of neovasculature in the early stage of ESCC progression.

     

The Role of Fas Expression on the Occurrence of Immunosuppression in Severe Acute Pancreatitis

Background

Severe acute pancreatitis (SAP) is a dangerous illness with high mortality where most patients do not die of excessive inflammation, but die of immunosuppression and multiple infections at a later stage. The mechanism of immunosuppression in SAP is unknown.

Aim

The purpose of this study was to analyze the role of Fas expression on the occurrence of immunosuppression in patients with SAP.

Methods

Forty-eight patients with pancreatitis were divided into two groups: 20 cases with SAP (7 cases with sepsis, 13 cases without sepsis) and 28 cases with mild acute pancreatitis (MAP). Twenty-eight healthy volunteers were selected as controls. Fas mRNA expression in peripheral blood was detected by qPCR and Fas protein of lymphocyte membranes; T lymphocyte subsets and expression of monocyte Human leukocyte antigen DR (HLA-DR) in peripheral blood were detected by flow cytometry.

Results

Compared with MAP and control groups, expression level of Fas mRNA and lymphocyte Fas protein in peripheral blood were significantly increased in the SAP group (all P < 0.01). There was a further significant increase in the SAP group with sepsis compared to those without sepsis (all P < 0.01). The CD4⁺ T cell ratio, CD4⁺/CD8⁺ ratio and monocyte HLA-DR expression in the SAP group were decreased significantly compared with MAP and control groups (all P < 0.01). Significant negative relationships were observed between Fas mRNA expression and CD4⁺ T-cell ratio, CD4⁺/CD8⁺ ratio, and monocyte HLA-DR expression in SAP patients with sepsis (all P < 0.05).

Conclusions

The results suggest that expression level of Fas is related to severity and immune status of pancreatitis. Overexpression of Fas may lead to the occurrence of immunosuppression and sepsis.     

Overexpression of CK20, MAP3K8 and EIF5A correlates with poor prognosis in early-onset colorectal cancer patients

Purpose

Due to ethnic, genetic and environmental factors, the clinical and molecular characteristics of Turkish colorectal cancer (CRC) patients are different from those of Western populations. The aim of this study was to clarify the relevant alterations of gene expression associated with colorectal carcinogenesis in early-onset patients and to identify specific biomarkers that could provide novel therapeutic molecular targets in this population.

Methods

The expression profiles of 114 different genes were evaluated using mRNA PCR arrays in 39 tumors and 20 surgical margin tissue samples from 39 sporadic CRC patients diagnosed at less than 50 years of age.

Results

The expression levels of IMPDH2, CK20, MAP3K8 and EIF5A were strongly up-regulated in CRC tissues compared with normal colorectal tissues (p < 0.05). The highly significant expression ratios of CK20, MAP3K8 and EIF5A observed in the colorectal tumors of patients predicted recurrence (p < 0.05). The expression of IMPDH2, CK20, MAP3K8 and EIF5A was significantly higher in the tumors of patients with short median survival (log-rank p value < 0.05). Progression-free survival was also significantly increased in patients with low expression of the EIF5A gene compared with those who exhibited high expression of this gene (log-rank p value < 0.05).

Conclusion

We demonstrated that high CK20, MAP3K8 and EIF5A expression levels were significant prognostic factors for poor overall survival in CRC patients. Further studies and validations are required; these genes may provide novel therapeutic molecular targets for CRC treatment, as well as new directions for the development of anticancer drugs.     

Genetic association of osteopontin (OPN) and its receptor CD44 genes with susceptibility to Chinese gastric cancer patients

Purpose

(1) To investigate associations between single nucleotide polymorphisms (SNPs) in osteopontin (OPN) and its receptor—cluster of differentiation 44 (CD44) genes and gastric cancer susceptibility. (2) To explore the correlation of OPN and CD44 expression of gastric cancer.

Methods

We detected 26 SNPs of the genes in gastric cancer patients from the Chinese Han population by Sequenom technique and performed expression of OPN in combination with CD44 in 243 tissues samples of the cases by tissue microarray and immunohistochemistry (IHC).

Results

We found that the minor alleles of OPN rs4754C>T and OPN rs9138C>A remained strongly associated with decreased gastric cancer risk (P = 1.53 × 10^?4, odds ratio (OR) 0.642, 95 % confidence interval (CI) 0.511–0.808 and P = 1.59 × 10^?4, OR 0.642, 95 %CI 0.510–0.809). OPN variant rs1126772A>G and CD44 variant rs353639A>C significantly contributed to elevated risk of gastric cancer (P = 0.042, OR 1.279, 95 % CI 1.008–1.622 and P = 0.047, OR 1.334, 95 % CI 1.003–1.772). Haplotypes of OPN and CD44 variants significantly influenced risk of gastric cancer. Clinical data indicated that rs4754 and rs9138 of OPN were significantly associated with smoking (P = 0.029, OR 0.343, 95 % CI 0.127–0.926 and P = 0.029, OR 0.343, 95 %CI 0.127–0.926) and OPN rs1126772 revealed associations with tumor–node–metastasis (TNM) stage (P = 0.025, OR 1.765, 95 % CI 1.073–2.905) and tumor differentiation (P = 0.031, OR 1.722, 95 % CI 1.049–2.825). OPN expression was observed in 133 of the 243 cases (54.7 %) by IHC and was correlated with serosa invasion (P = 0.013), TNM stage (P = 0.003) and lymph node metastasis (P = 0.002). CD44 expression was found in 92 of the 243 cases (37.9 %) and was associated with tumor size (P = 0.005) and lymph node metastasis (P = 0.023), respectively. The OPN expression displayed a positive association with CD44 (P = 0.01, r _s = 0.164).

Conclusions

We found that the polymorphisms rs4754, rs9138 and rs1126772 of OPN gene and rs353639 of CD44 gene were significantly associated with gastric cancer. Our IHC data indicated that interaction of OPN and CD44 protein would promote progression and metastasis of gastric cancer.     

Anti-Saccharomyces cerevisiae Antibodies Associate with Phenotypes and Higher Risk for Surgery in Crohn’s Disease: A Meta-Analysis

Background

Recent studies suggested that anti-Saccharomyces cerevisiae antibody (ASCA) status was associated with diagnostic findings, stratified classification phenotypes, disease activity and clinical course of Crohn’s disease (CD). However, the relationship between ASCA status and phenotypes of CD remains controversial in these studies.

Aims

The purpose of this study was to evaluate whether ASCA status is associated with the phenotypes and the risk of surgery in diverse populations in CD.

Methods

We conducted a meta-analysis of studies assessing the association of ASCA status with phenotypes and risk of surgery in CD. Three independent reviewers undertook data extraction. We pooled odds ratios separately for the cohort and case–control studies.

Results

We identified ten cohort studies (n = 2,365) and 14 case–control studies (n = 1,887) that investigated the association of ASCA status with phenotypes and risk of surgery in CD. The meta-analysis of the cohort studies showed significant association between the ASCA-positive status and higher risk of early-onset age (OR 2.25, 95 % CI 1.41–3.57, P < 0.001), ileal involvement disease (1.70, 1.05–2.77, P = 0.03), complicated disease behavior (2.09, 1.71–2.57, P < 0.001), perianal disease (1.49, 1.14–1.94, P = 0.004), and risk for surgery (1.61, 1.29–2.01, P < 0.001). Meta-analysis of the case–control studies also showed a significantly higher risk in ileal involvement disease (1.77, 1.25–2.49, P = 0.001), complicated disease behavior (2.13, 1.70–2.68, P < 0.001), perianal disease (1.96, 1.38–2.78, P < 0.001), and risk for surgery (1.71, 1.17–2.49, P = 0.005), except for the early-onset age (1.16, 0.80–1.69, P = 0.44).

Conclusions

This meta-analysis indicated that positive ASCA status is a risk factor for early-onset age, ileal involvement, complicated behavior, perianal disease and requirement for surgery in CD.     

Positive Expression of LSD1 and Negative Expression of E-cadherin Correlate with Metastasis and Poor Prognosis of Colon Cancer

Background

The first identified lysine-specific demethylase, LSD1, plays an important role in the metastatic progression of several types of cancer.

Aims

The aim of this study was to investigate LSD1, E-cadherin, and N-cadherin expression in colon cancer specimens and their clinical significance.

Methods

The expression of LSD1, E-cadherin, and N-cadherin in colon cancer specimens was determined by immunohistochemistry, and the relationship between the expression of the respective molecules and clinicopathological characteristics was analyzed.

Results

The positive expression rates of LSD1, E-cadherin, and N-cadherin in colon cancer specimens were 66.7 % (72/108), 85.2 % (92/108), and 41.7 % (45/108), respectively. LSD1 was significantly more highly expressed in colon cancer specimens classified as high TNM stage lesions and with distant metastasis (P < 0.05). Further analysis demonstrated that LSD1 expression was positively correlated with lymph node and distant metastases (P < 0.05). However, E-cadherin expression was significantly downregulated in colon cancer specimens classified as high TNM stage lesions and with distant metastasis (P < 0.05), whereas the expression of N-cadherin did not differ significantly according to clinical and pathological characteristics (P > 0.05). Correlation analysis revealed that LSD1 expression was negatively correlated with E-cadherin expression (r _s = ?0.318, P = 0.001), but not evidently correlated with N-cadherin expression (r _s = 0.182, P = 0.06). Colon cancer specimens with positive LSD1 expression and negative E-cadherin expression were correlated with significantly lower overall survival.

Conclusions

LSD1 showed a significantly higher expression, in contrast to the significantly lower expression of E-cadherin, in colon cancer specimens classified as high TNM stage lesions and with distant metastasis. Positive expression of LSD1 and negative expression of E-cadherin may be predictors of a worse colon cancer prognosis.     

The Suppression Effects of Thalidomide on Human Lung Fibroblasts: Cell Proliferation, Vascular Endothelial Growth Factor Release, and Collagen Production

Background

Expression of transforming growth factor (TGF)-β₁ and increases in angiogenesis and deposition of extracellular matrix are the key features of tracheal granulation formation. The aim of this study was to investigate the potential role of thalidomide in preventing granulation tissue formation from the aspect of cellular effects in vitro, including fibroblast proliferation, vascular endothelial growth factor (VEGF) release, and collagen production.

Methods

Human lung fibroblasts were obtained from bronchus and cultured. The effects of thalidomide on cell proliferation, migration, TGF-β₁-induced VEGF, and signal pathway were investigated.

Results

Thalidomide (20 μM) not only inhibited cell proliferation after 24 h [fold increase of cell number, 0.85 ± 0.09 vs. 1.47 ± 0.14 (treatment vs. control group); P < 0.01] and 48 h of incubation (0.85 ± 0.10 vs. 1.97 ± 0.12; P < 0.001), it also inhibited cell migration and slowed wound closure at 24 h (P < 0.001). Thalidomide significantly attenuated TGF-β₁-induced VEGF expression at both the mRNA and protein levels. Incubation of thalidomide with cells stimulated with TGF-β₁ significantly inhibited their production of collagen. Thalidomide inhibited Smad3, STAT3, and subsequent p44/42 kinase phosphorylation.

Conclusion

Thalidomide may inhibit human fibroblast proliferation and it is worthy of further in vivo investigation.     

Effect of a mixture of diosmin,coumarin glycosides,and triterpenes on bleeding,thrombosis, and pain after stapled anopexy: a prospective,randomized, placebo-controlled clinical trial

Purpose

We evaluated the efficacy of oral administration of a mixture of diosmin, coumarin glycosides, and Centella asiatica (Venoplant®) in preventing bleeding, pain, and thrombosis of internal and external hemorrhoids after stapled anopexy (SA).

Methods

SA was conducted in 182 patients with third-degree hemorrhoids. Preoperatively, patients were randomized evenly into two groups. Group A patients were administered Venoplant for 30 days post-SA, and group B received a placebo for 30 days post-SA. Patients received paracetamol for postoperative pain. Visit (v)1, v2, and v3 took place 7, 15, and 30 days postoperatively, respectively; bleeding (clinical examination), visual analog scale (VAS), thrombosis (clinical examination), and pain (paracetamol dosage, VAS) were evaluated.

Results

At v1, v2, and v3, the numbers of patients with bleeding in groups A and B were 21 and 46, 3 and 25, and 1 and 5, respectively (p < 0.05). At v1, v2, and v3, the numbers of patients in groups A and B with thrombosed internal hemorrhoids were 3 and 13, 2 and 11, and 1 and 8, respectively (p < 0.05). The number of patients who took at least one paracetamol tablet was similar in both groups at v1 but was significantly greater in group B than group A at v2 and v3 (p < 0.05); pain VAS scores were equivalent at v1 and significantly greater in group B than group A at v2 and v3 (p < 0.05).

Conclusions

Venoplant effectively reduced bleeding after SA, decreased the incidence of thrombosed internal hemorrhoids, and decreased postoperative pain.

     

Perioperative change in white blood cell count predicts outcome of hepatic resection for hepatocellular carcinoma

Background

In spite of improvements in surgical management, hepatocellular carcinoma (HCC) still recurs after operation in 60–70% of patients. Therefore, we investigated the relation between perioperative change in white blood cell count (WBC) and tumor recurrence as well as survival in patients with HCC after hepatic resection.

Methods

Subjects were 53 patients who underwent elective hepatic resection for HCC. We retrospectively examined the relation between perioperative change in WBC and recurrence of HCC as well as overall survival.

Results

Advanced tumor stage and increasing of WBC on postoperative day (POD) 1 were positively associated with worse disease-free survival rate on both univariate and multivariate analysis (P < 0.05). Advanced tumor stage, increasing of WBC on POD 1, and blood transfusion were positively associated with worse overall survival rate on univariate analysis (P < 0.05), while change in WBC was the only independent factor on multivariate analysis (P < 0.05).

Conclusions

Perioperative change in WBC after elective hepatic resection for HCC is positively associated with recurrence and worse survival.