The prognostic activity of acylglycerol kinase immunohistochemical expression in colon adenocarcinoma patients.

Introduction: Adenocarcinoma of the colon and rectum (COAD) is one of the most commonly diagnosed cancers of the gastrointestinal system. Acylglycerol kinase (AGK) is a known lipid kinase producing lysophosphatidic acid (LPA) from monoacylglycerol. It is widely expressed in the heart, brain, kidney, and muscle. Moreover, AGK is a significant cancer-related gene and is upregulated in many human malignancies, e.g. prostate cancer, breast cancer, oral squamous cell carcinoma, hepatocellular carcinoma, and renal carcinoma. However, the expression pattern and clinical significance of AGK in colon adenocarcinoma patients, especially in individuals living in Europe, remain unclear. Aim: The current study investigated the expression of AGK protein in colon adenocarcinoma samples to assess its prognostic significance by correlating its immunohistochemical expression with the clinicopathological variables and survival of individuals living in Poland. Material and methods: Tissue specimens were received from 110 colon adenocarcinoma patients who underwent surgical resection at the Municipal Hospital in Jaworzno in 2013-2015. The paraffin-embedded specimens were cut into 4-µm-thick sections and incubated with rabbit polyclonal antibody to AGK (final dilution 1 : 500) (Invitrogen; cat. number PA5-28566). Results and conclusions: AGK was strongly expressed in colon adenocarcinoma tissues in comparison to non-pathological colon specimens. The high level of AGK immunoexpression was demonstrated to be clearly correlated with the malignancy-related clinicopathological factors and 5-year overall survival rate of patients.

Identification of Sliding Hiatus Hernia by High-Resolution Manometry and Upper Gastrointestinal Endoscopy in Patients with Gastro-Oesophageal Reflux Disease.

BACKGROUND/AIM: The aim of this study was to compare high-resolution manometry (HRM) and upper gastrointestinal (GI) endoscopy as diagnostic utilities in detecting a sliding hiatus hernia in patients with gastro-oesophageal reflux disease (GORD) symptoms. MATERIAL AND METHODS: For both diagnostic modalities, the data obtained from 31 patients (20 females; mean age 48.2) who qualified for Nissen fundoplication were analysed using oesophageal pressure topography in line with the Chicago Classification. Confirmation of hiatus hernia during the surgery was considered the gold standard. HRM protocol involved 10 consecutive boluses of 10 mL of water. RESULTS: Sliding hiatus hernia was confirmed intraoperatively in 29 out of 31 patients. In 14 patients, hiatus hernia was detected in HRM, while 19 patients were found to have hiatus hernia by upper GI endoscopy before surgery. No false positive results were obtained in HRM, while 15 false negative results were shown. In upper GI endoscopy, false positive data were observed in 1 patient, while false negative results were found in 10 patients. Thus, the sensitivity of HRM in detecting hiatus hernia was 48% (95%CIs: 29-67%), and sensitivity of upper GI endoscopy was 66% (95%CIs: 46-82%). It was not possible to assess the specificity of HRM or upper GI endoscopy because only 2 of 31 patients had no hiatus hernia during fundoplication (gold standard). False negative results (sensitivity) were not significantly different between compared diagnostic modalities HRM and upper GI endoscopy (52% vs. 34%, respectively, p = 0.29). CONCLUSIONS: Due to poor sensitivity, both modalities, i.e., HRM and upper GI endoscopy, are not reliable tools to diagnose sliding hiatus hernia in patients with GORD symptoms.

The clinical significance of Notch1 immunoexpression in Caucasian patients with colorectal adenocarcinoma.

INTRODUCTION: Colorectal cancer (CRC) is traditionally regarded as the most commonly diagnosed gastrointestinal malignant disease. Nevertheless, despite advances in diagnosis and novel therapeutic options, the clinical outcomes of patients are still not satisfactory. AIM: To investigate the clinicopathological and prognostic roles of Notch1 expression, the immunohistochemical investigation was performed in samples of CRC tumour tissues, adjacent non-pathological mucosa, and metastatic foci in regional lymph nodes in Caucasian patients. MATERIAL AND METHODS: Paraffin-embedded adenocarcinoma samples were assessed immunohistochemically for Notch1 protein and scored according to the percentage of cells with a positive reaction combined with staining intensity. Connections between Notch1 immunoexpression and clinicopathological factors including the 5-year overall survival (OS) were evaluated. RESULTS: The level of the Notch1 immunohistochemical reactivity was correlated with the grade of the histological differentiation, size of the primary tumour, regional lymph node involvement, and perineural invasion (all p < 0.001). Kaplan-Meier survival analysis showed that the survival time for patients with a low expression of Notch1 was significantly longer than that for patients with moderate or strong level of Notch1 immunoreactivity (p < 0.001). CONCLUSIONS: The enhanced level of Notch1 immunoexpression was significantly associated with malignancy-related clinicopathological factors and reduced the 5-year overall survival in CRC patients.

Catalase immunoexpression in colorectal lesions.

INTRODUCTION: It is generally accepted that the gastrointestinal tract, and especially the colon, is constantly exposed to reactive oxygen species (ROS) that may be responsible for the appearance of genetic mutations. To keep a steady-state control over ROS production-detoxification, organisms have evolved a defensive system. Nevertheless, many reports have described decreased level of antioxidant enzymes, especially catalase (CAT), in cancer tissues. AIM: In this work we try to assess the immunohistochemical expression of CAT protein in colorectal adenoma and adenocarcinoma samples. MATERIAL AND METHODS: This study was performed on resected specimens obtained from 122 patients who had undergone surgical resection for colorectal cancer, and from 120 patients who had undergone colonoscopy. Paraffin- embedded, 4 µm-thick tissue sections were stained for rabbit polyclonal anti CAT antibody obtained from GeneTex (cat. no. GTX110704). RESULTS: In adenoma strong immunoexpression was detected mainly in infiltrating mononuclear cells within lamina propria. High expression of CAT was significantly associated with grade of dysplasia (high grade vs. low grade, p = 0.037). In adenocarcinoma samples, the high level of CAT immunoexpression was significantly correlated with histological grade of tumour (G1 vs. G2 vs. G3, p = 0.001) and depth of invasion (T1 vs. T2 vs. T3 vs. T4, p = 0.003). CONCLUSIONS: Development of colorectal cancer is associated with increased expression of CAT in the stage of adenoma and decreased expression in the stage of adenocarcinoma.

The clinical and prognostic evaluation of GRP94 immunoexpression in Caucasian patients with colorectal adenocarcinoma.

INTRODUCTION: Colorectal cancer (CRC) is traditionally regarded as the most commonly diagnosed gastrointestinal malignant disease. Nevertheless, despite advances in diagnosis and novel therapeutic options, the clinical outcomes of patients are still unsatisfactory. AIM: To investigate the clinicopathological and prognostic roles of GRP94 expression, the immunohistochemical investigation was performed on samples of CRC tumour tissues, adjacent non-pathological mucosa, and metastatic foci in regional lymph nodes in Caucasian patients. MATERIAL AND METHODS: Paraffin-embedded adenocarcinoma samples were assessed immunohistochemically for GRP94 protein and scored according to the percentage of cells with positive reaction combined with staining intensity. Connections between GRP94 immunoexpression and clinicopathological factors including the overall survival (OS) were evaluated. RESULTS: The level of the GRP94 immunohistochemical reactivity was correlated with the grade of the histological differentiation (H (2.92) = 25.906; p < 0.001), size of the primary tumour (Z = -4.010; p < 0.001), regional lymph node involvement (Z = -6.547; p < 0.001), and perineural invasion (Z = -6.235; p < 0.001). Kaplan-Meier survival analysis showed that the survival time for patients with a low expression of GRP94 was significantly longer than that for patients with a moderate or strong level of GRP94 immunoreactivity (p < 0.001). CONCLUSIONS: An enhanced level of GRP94 immunoexpression was significantly associated with malignancy-related clinicopathological factors and reduced the 5-year overall survival in CRC patients. However, a multivariate analysis demonstrated that GRP94 was not revealed as an independent risk factor for CRC prognosis.

Correlation study of GAPDH, Bcl-2, and Bax protein immunoexpression in patients with colorectal adenocarcinoma.

INTRODUCTION: Colorectal cancer (CRC) is the third and second most commonly diagnosed cancer worldwide in males and females, respectively. Despite prominent progress in diagnosis and treatment, the recurrence rates are still high. A tumour hypoxic environment leads to an increase in glycolytic metabolism. The crucial intermediate component of glycolysis, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), could play a significant role in cancer progression. An increased level of GAPDH has been described in oncogene-induced transformation and anti-apoptotic function. In other studies, GAPDH has been involved in apoptosis induction. AIM: We examined colorectal adenocarcinoma samples to assess the immunoexpression of GAPDH protein. We also evaluated the correlation between the expression of GAPDH protein and apoptotic parameters including expression of Bcl2 and Bax. MATERIAL AND METHODS: Paraffin sections were incubated for 60 min with primary antibody against GAPDH, Bcl-2, and Bax. RESULTS: Results of our study have shown that GAPDH expression in colorectal cancer is upregulated. We revealed significant positive correlation between expression of this protein and grade and size of tumour, and regional lymph node involvement. In the case of apoptosis-associated proteins, e.g. Bcl-2 and Bax, we found negative correlations between expression of these proteins and grade and size of tumour, lymphovascular invasion, and regional lymph node involvement. Finally, we demonstrated that GAPDH up-regulation is connected with down-regulation in Bcl-2 and Bax. CONCLUSIONS: Up-regulation of GAPDH protein and down-regulation of Bcl-2 and Bax may result in increased of cancer.

Absorbable sutures in general surgery - review, available materials, and optimum choices.

Sutures are the most versatile materials used in surgery. Despite recent technological advances and availability of novel materials such as tissue cements, it appears that surgical sutures will continue to be used for many years to come. The objective of this study was to provide an overview of the most common absorbable sutures used in general surgery. The appropriate suture choice for a particular procedure is of key importance for the success of that procedure.

Notch and its oncogenic activity in human malignancies.

BACKGROUND: Increasing evidence has demonstrated that Notch signaling is deregulated in human hematological malignancies and solid tumors. This signaling has a protumorigenic effect but may also act as a tumor suppressor. How induction of a single pathway gives rise to the opposite effects in different cell types is still unknown. METHODS: This review article includes available data from peer-reviewed publications associated with the role of Notch signaling during cancer pathogenesis. RESULTS: Numerous reports have indicated that alterations in Notch signaling and its oncogenic activity were originally associated with the pathogenesis of T­cell acute lymphoblastic leukemia/lymphoma (T-ALL), an aggressive hematologic tumor affecting children and adolescents. The possibility that Notch could play a significant role in human breast cancer development comes from studies on mouse mammary tumor virus-induced cancer. Numerous findings over the past several years have indicated that alterations in Notch signaling are also responsible for ovarian cancer development. Mention should also be made of the connection between expression of Notch 3 and increased resistance to chemotherapy, which remains a major obstacle to successful treatment. Notch as an oncogenic factor is also involved in the development of colon cancer, lung carcinoma and Kaposi's sarcoma. CONCLUSION: Notch is a binary cell fate determinant and its overexpression has been described as oncogenic in a wide array of human malignancies. This finding led to interest in therapeutically targeting this pathway, especially by the use of gamma-secretase inhibitors (GSIs) blocking the cleavage of Notch receptors at the cell membrane by the inhibition of Notch intracellular domain (NICD) releasing. Preclinical cancer models have revealed that GSIs suppress the growth of cancers such as pancreatic, breast and lung cancer.

Tissue hemostasis is shifted toward thrombogenesis in the psoriatic plaques.

BACKGROUND: Psoriasis is a common autoimmune disease of unknown etiology. Recently, much attention has been paid to evidence that a local hypercoagulable state is an important contributing factor to the development of inflammatory skin diseases. Thus, the aim of this study was to characterize the local hemostasis in the affected skin of patients with psoriasis. METHODS: Skin biopsies of psoriatic plaques were obtained from 73 consecutive patients (48M, 25F, average age 45 years) with at least a one year history of the disease. The studied patients had not received any specific systemic treatment for at least 4 weeks before the biopsy was done. As a control, normal skin biopsies were obtained from 16 healthy subjects. For immunohistological study, the En-Vision method (DAKO EnVision Kit ®/Alkaline Phosphatase detection system), and monoclonal antibodies anti-tissue factor (TF), anti-thrombomodulin (TM) and anti-von Willebrand Factor (vWF) were used. All these molecules were assessed semi-quantitatively in the frozen sections. RESULTS: Clinically, the Body Surface Area index ranged between 1-90% and the Psoriasis Area Severity Index score ranged from 1.6 to 47. Immunohistochemistry revealed redistribution of TF antigens from the upper to lower layers of the epidermis as compared to the control. It was collaborated with the number of TF-positive cells in the psoriatic skin sections (78.3%) as compared with the healthy subjects (34.4%; P<0.001). In addition, TF was uniformly and moderately expressed on capillary endothelial cells of the plaque sections in 43 out of 73 patients (58.9%). As far as the thrombomodulin is concerned, TM was clearly down-regulated and localized mainly in the upper layers of the psoriatic epidermis. It was collaborated with the number of TM positive cells in the psoriatic skin sections (38.9%) as compared with the healthy subjects (66.7%; P<0.001). All capillary vessels found in the biopsy sections were positive for TM and vWF staining, with similar expression (≥2+) in both groups. In the current study, no relationship was found between the TF, TM and vWF expression and the PASI and BAS (NS). CONCLUSIONS: A local procoagulable state found in psoriatic plaques suggests a significant role of local tissue hemostasis in pathogenesis of the disease. These findings indicate another potential target for a therapeutic approach in patients with psoriasis, although further research would help elucidate the exact mechanisms.

High-resolution Manometry in Patients with Gastroesophageal Reflux Disease Before and After Fundoplication.

BACKGROUND/AIMS: The study aimed to determine pre- and post-fundoplication esophagogastric junction (EGJ) pressure and esophageal peristalsis by high-resolution manometry (HRM) in patients with gastroesophageal reflux disease (GERD). METHODS: Pre-operative and post-operative HRM data from 25 patients with GERD were analyzed using ManoView version 2.0.1. with updated software for Chicago classification and pressure topography. The study involved swallowing water boluses of 10 mL in the upright position. RESULTS: Significant increase of mean basal EGJ pressure and minimal basal EGJ pressure was found in post-operative as compared with pre-operative patients (P < 0.05 and P < 0.001, respectively). Integrated relaxation pressure (IRP) reached higher values in post-operative patients than in pre-operative patients (P < 0.001). Intra-bolus pressure (IBP) was significantly higher (P < 0.05) and contractile front velocity (CFV) was slower (P < 0.01) in post-operative patients than in pre-operative patients. Moreover significant increase of distal contractile integral (DCI) was found in post-operative patients (P < 0.05). Hiatal hernia was detected by HRM in 11 pre-operative patients. Fifteen out of 25 post-operative patients complained of dysphagia. CONCLUSIONS: Fundoplication restores the antireflux barrier by reinforcing EGJ basal pressures, repairing hiatal hernias, and enhances peristaltic function of the esophagus by increasing DCI. However slight IRP elevation found in post-fundoplication patients may result in bolus pressurization and motility disorders.