Intestinal Obstruction as Initial Presentation of Idiopathic Portal and Mesenteric Venous Thrombosis: Diagnosis, Management, and Literature Review.

It is quite common for portal vein thrombosis to occur in subjects who present predisposing conditions such as cirrhosis, hepatobiliary malignancies, infectious or inflammatory abdominal diseases, or hematologic disorders. The incidence of idiopathic portal vein thrombosis in non-cirrhotic patients remains low, and despite the intensive workup that is performed in these cases, in up to 25% of cases, there is no identifiable cause. If portal vein thrombosis is untreated, complications arise and include portal hypertension, cavernous transformation of the portal vein, gastroesophageal and even small intestinal varices, septic thrombosis, or intestinal ischemia. However, intestinal ischemia develops as a consequence of arterial thrombosis or embolism, and the thrombosis of the mesenteric vein accounts for about 10% of cases of intestinal ischemia. Although acute superior mesenteric vein thrombosis can cause acute intestinal ischemia, its chronic form is less likely to cause acute intestinal ischemia, considering the possibility of developing collateral drainage. Ileus due to mesenteric venous thrombosis is rare, and only a small number of cases have been reported to date. Most patients experience a distinct episode of acute abdominal pain due to ischemia, and in the second phase, they develop an obstruction/ileus. Acute superior mesenteric venous thrombosis is a rare condition that is still associated with a high mortality rate. The management of such cases of superior mesenteric venous thrombosis is clinically challenging due to their insidious onset and rapid development. A prompt and accurate diagnosis followed by a timely surgical treatment is important to save patient lives, improve the patient survival rate, and conserve as much of the patient's bowel as possible, thus leading to fewer sequelae.

Abilities of Pre-Treatment Inflammation Ratios as Classification or Prediction Models for Patients with Colorectal Cancer.

BACKGROUND: Systemic inflammatory status is known as an important factor of colorectal cancer prognosis. Our study aimed to evaluate the performances of inflammation biomarker ratios as classification models of seven outcomes in patients with colorectal cancer. METHODS: A retrospective cohort study was conducted on subjects with colorectal cancer over five years at a single center in Transylvania, Romania. Seven derived ratios were calculated based on laboratory data: neutrophil-to-lymphocyte (NLR), derived neutrophil-to-lymphocyte (dNLR), platelet-to-lymphocyte (PLR), lymphocyte-to-monocyte (LMR) and albumin-to-globulin (AGR) ratios, Systemic Immune Inflammation Index (SII) and Prognostic Nutritional Index (PNI). The utility of these ratios as predictors for seven outcomes was further evaluated in multivariable regression models. RESULTS: Our study shows that the evaluated ratios exhibit specific performances for individual outcomes, proving a fair ability as screening tools (NLR and dNLR for survival, T stage and M stage; NLR and SII for T stage; and PLR for M stage). A dNLR over 3.1 (OR = 2.48, 95% CI (1.421 to 4.331)) shows predictive value for survival. A value of NLR over 3.10 (OR = 1.389, 95% CI (1.061 to 1.817)) is positively associated with an advanced T stage, while LMR is negatively related to the T stage (OR = 0.919, 95% CI (0.867 to 0.975)). NLR over 4.25 (OR = 2.647, 95% CI (2.128 to 3.360)) is positively associated with, while PNI is negatively related (OR = 0.970, 95% CI (0.947 to 0.993)) to, the M stage. CONCLUSION: Each of the evaluated ratios possesses prognostic value for certain outcomes considered, but the reported models need external validation to recommend their clinical practice utilization.

Relation between serum cotinine levels and trophic lesions in patients with critical limb ischemia: a pilot study.

Aim: To evaluate if smoking, quantified by the serum cotinine levels, is related to the evolution of patients with critical limb ischemia (CLI).Method: A pilot study was conducted on CLI patients who addressed at the Second Surgery Clinic of the Emergency County Hospital, Cluj-Napoca, Romania between November 2015 and December 2016. The sample of patients was split into two groups using the threshold of 15 ng/mL for the serum level of cotinine (low cotinine level - LCL vs. high cotinine level - HCL). Furthermore, the ROC analysis was conducted to identify the threshold of cotinine level able to discriminate between CLI patients with and without trophic lesions.Results: The mean age of patients was 60.7 ± 10.5 years with a significantly higher percentage of male patients (84%). A significant association was identified between urban origin and serum cotinine level, which is related to the increased number of cigarettes smoked per day among urban participants. Excepting necrectomy and toe disarticulation, no differences were found between LCL and HCL group regarding symptoms, signs or comorbidities. In smokers with CLI (38/43), a serum cotinine cut-off of 9.765 ng/mL was observed on eight out of 10 CLI patients with necrectomy and five out of 28 patients without necrectomy.Conclusion: Our study showed higher serum cotinine levels associated with a higher number of smoked cigarettes and necrectomy in patients with CLI. The serum cotinine could be a fair screening test for necrectomy in smokers CLI patients.

Evaluation of Chitotriosidase as a Marker of Inflammatory Status in Critical Limb Ischemia.

BACKGROUND: Chitotriosidase is an enzyme secreted by activated macrophages. This study aims to investigate the usefulness of circulating chitotriosidase activity as a marker of inflammatory status in patients with critical limb ischemia (CLI). MATERIALS AND METHODS: An observational gender-matched case-control study was conducted on patients hospitalized with the primary diagnosis of CLI, as well as a control group. The control group consisted of healthy volunteers. RESULTS: Forty-three patients were included in each group. Similar demographic characteristics (median age of 60-62 years and overweight) were observed in both groups. Chitotriosidase activity ranged from 110 nmol/ml/hr to 1530 nmol/ml/hr in the CLI group and from 30 nmol/ml/hr to 440 nmol/ml/hr in the control group; demonstrating significantly elevated values in the CLI group (p<0.001). Median plasma chitotriosidase activity was significantly elevated in smokers compared with non-smokers in both groups (p<0.05). However, this activity had higher values in CLI than in control subjects. Receiver operating characteristic (ROC) analysis was then performed in order to verify the diagnostic accuracy of chitotriosidase as an inflammatory biomarker in CLI. CONCLUSION: Circulating chitotriosidase is a test which can potentially be used for the monitoring of CLI patients without other inflammatory conditions. However, the interpretation of elevated values must take into account the inflammatory response induced by tobacco exposure.

Demographic and Comorbidity Pattern of Patients with Critical Limb Ischemia.

AIM: The present study aimed at identifying the pattern of patients with critical limb ischemia (CLI) compared with those with peripheral arterial occlusive disease (PAOD). MATERIALS AND METHODS: A four-year retrospective study was conducted with patients hospitalized in the Second Surgical Clinic at the Emergency County Hospital Cluj-Napoca. The medical charts of patients with PAOD (n=466) and CLI (n=223) were reviewed and data were collected. RESULTS: The study included 689 patients; mean age 67 years for PAOD patients and 65 years for CLI patients. A significantly higher percentage of patients were male in both groups (79.25%, P < 0.0001). Most of the patients in both groups had received at least a secondary education (P < 0.0001). Most of the subjects in both groups were smokers (>71.30%) with no difference between groups (P = 0.566). No significant differences were found between the groups in comorbidities (diabetes, arterial blood hypertension, cardiac ischemia, rhythm disorders, P > 0.05). There were more CLI patients that were overweight than overweight patients with PAOD (P = 0.0004). High serum cholesterol (>200 mg/dL) and triglycerides (>150 mg/dL) levels were found in the CLI group (P < 0.05). Age was identified as a risk factors for amputation (OR = 1.03, 95%Cl [1.01-1.05], P = 0.0012). CONCLUSIONS: The profile of a patient with critical limb ischemia and peripheral arterial occlusive disease is a 65-67-year-old male smoker with at least a secondary education. The CLI patient is overweight with pathological serum levels of cholesterol and triglycerides.

Treatment with Sildenafil and Donepezil Improves Angiogenesis in Experimentally Induced Critical Limb Ischemia.

Objectives. In this study, we aimed to demonstrate the role of sildenafil (an antagonist of phosphodiesterase type 5 (PDE-5)) and donepezil (a specific and reversible inhibitor of acetylcholinesterase (Ach)) in increasing ischemia-induced angiogenesis. Method. Critical limb ischemia was induced by ligation of the common femoral artery followed by ligation of the common iliac artery. The operated animals were divided into 3 groups: receiving sildenafil, receiving donepezil, and surgery alone; the contralateral lower limb was used as a negative control. The results were controlled based on clinical score and Doppler ultrasound. Gastrocnemius muscle samples were taken from all animals, both from the ischemic and nonischemic limb and were used for histopathological and immunohistochemical examination for the evaluation of the number of nuclei/field, endothelial cells (CD31), dividing cells (Ki-67), and vascular endothelial growth factor (VEGFR-3). Results. An increasing tendency of the number of nuclei/field with time was observed both in the case of sildenafil and donepezil treatment. The formation of new capillaries (the angiogenesis process) was more strongly influenced by donepezil treatment compared to sildenafil or no treatment. This treatment significantly influenced the capillary/fiber ratio, which was increased compared to untreated ligated animals. Sildenafil treatment led to a gradual increase in the number of dividing cells, which was significantly compared to the negative control group and compared to the ligation control group. The same effect (increase in the number of Ki-67 positive cells) was more obvious in the case of donepezil treatment. Conclusion. Donepezil treatment has a better effect in ligation-induced ischemia compared to sildenafil, promoting angiogenesis in the first place, and also arteriogenesis.

Association of atherosclerotic peripheral arterial disease with adiponectin genes SNP+45 and SNP+276: a case-control study.

OBJECTIVES: We hypothesized that adiponectin gene SNP+45 (rs2241766) and SNP+276 (rs1501299) would be associated with atherosclerotic peripheral arterial disease (PAD). Furthermore, the association between circulating adiponectin levels, fetuin-A, and tumoral necrosis factor-alpha (TNF-α) in patients with atherosclerotic peripheral arterial disease was investigated. METHOD: Several blood parameters (such as adiponectin, fetuin-A, and TNF-α) were measured in 346 patients, 226 with atherosclerotic peripheral arterial disease (PAD) and 120 without symptomatic PAD (non-PAD). Two common SNPs of the ADIPOQ gene represented by +45T/G 2 and +276G/T were also investigated. RESULTS: Adiponectin concentrations showed lower circulating levels in the PAD patients compared to non-PAD patients (P < 0.001). Decreasing adiponectin concentration was associated with increasing serum levels of fetuin-A in the PAD patients. None of the investigated adiponectin SNPs proved to be associated with the subjects' susceptibility to PAD (P > 0.05). CONCLUSION: The results of our study demonstrated that neither adiponectin SNP+45 nor SNP+276 is associated with the risk of PAD.

Epigallocatechin-3-Gallate (EGCG) inhibits cell proliferation and migratory behaviour of triple negative breast cancer cells.

Previous studies indicate that green tea extract may inhibit breast cancer progression by blocking angiogenesis, although the molecular mechanisms are not well defined. Epigallocatechin-3-gallate (EGCG) is the major biologically active component of green tea. In this study we evaluated the cell proliferation and relative gene expression of vascular endothelial growth factor (VEGF) expression on Hs578T human breast cancer cell line at 24, 48 and 72 hours after 10 microM of EGCG treatment. Also, we evaluated the effect of this natural compound on the cell migratory behaviour based on real-time XCELLigence data. Cell proliferation becomes significantly low at 72 hours. EGCG had a dual effect on the VEGF gene expression timeline: after a first increase at 24 hours, it started to decrease at 48 and 72 hours. The inhibition of cell proliferation at 72 hours suggests a possible reactivation of apoptosis. The dual effect on VEGF expression in the presence of EGCG suggests the complexity of the angiogenic switch leading to the modulation of the cell migration processes. It also emphasizes the importance of the metabolite products in the modulation of these effects. Our findings have shown that EGCG suppresses the growth, migration and invasion of human breast cancer cells by inhibiting VEGF expression. A better understanding of this mechanism may lead to an improved strategy for tumor therapy based on the inhibition of angiogenesis.

TNF-α gene knockout in triple negative breast cancer cell line induces apoptosis.

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in the promotion and progression of cancer, including triple negative breast cancer cells. Thus, there is significant interest in understanding the molecular signaling pathways that connect TNF-α with the survival of tumor cells. In our experiments, we used as an in vitro model for triple negative breast cancer the cell line Hs578T. The purpose of this study is to determine the gene expression profiling of apoptotic signaling networks after blocking TNF-α formation by using specially designed siRNA molecules to target TNF-α messenger RNA. Knockdown of TNF-α gene was associated with cell proliferation inhibition and apoptosis, as observed by monitoring the cell index using the xCELLigence RTCA System and flow cytometry. PCR array technology was used to examine the transcript levels of 84 genes involved in apoptosis. 15 genes were found to be relevant after comparing the treated group with the untreated one of which 3 were down-regulated and 12 up-regulated. The down-regulated genes are all involved in cell survival, whereas the up-regulated ones are involved in and interact with pro-apoptotic pathways. The results described here indicate that the direct target of TNF-α in the Hs578T breast cancer cell line increases the level of certain pro-apoptotic factors that modulate different cellular networks that direct the cells towards death.

Evaluation of serum adipokines in peripheral arterial occlusive disease.

AIM: Out study aimed to assess the serum levels of adipokines in patients with peripheral arterial occlusive disease (PAOD) caused by atherosclerosis. METHODS: Serum samples were obtained from 221 patients. One hundred and forty patients, (26 females and 114 males) met the inclusion criteria and were assigned into the case group. Eighty one patients (17 females and 64 males), were included in the control group. Circulating plasma levels of adiponectin, leptin, resistin, and TNF-α were measured using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Significant lower levels of adiponectin were present (P = 0.0061) in PAOD patients (2380.23 ± 1634.42 pg/mL) compared to the control group (3065.06 ± 1901.2 pg/mL). The mean value of leptin (2844.42 ± 3301.08 pg/mL) and resistin (2047.81±3301.08 pg/mL) patients included in the PAOD group was higher, as compared to the control group. Statistically significant difference was found between the two groups for leptin (P = 0.0332) and for resistin (P = 0.0352). No statistically significant difference for TNF-α was found between the two groups (P > 0.05). CONCLUSION: The markers of inflammation secreted by the adipose tissue (adiponectin, leptin, resistin) showed significant differences in patients from the case group (with PAOD) compared to the control group.

Epithelioid hemangioendothelioma of the forearm with radius involvement. Case report.

Epithelioid hemangioendothelioma (EHE) is a rare, well-differentiated endothelial tumor with intermediate malignancy which develops more frequently from the peripheral veins, generally in the lower limb. Bone EHE comprises less than 1% of the bone neoplasms. We present the case of a young man, 24-year-old, with EHE of the forearm with secondary involvement of the distal radius. The location and the extension of the tumor allowed a wide excision, without the reconstruction of radius, followed by adjuvant radiotherapy, with a subsequent favorable evolution. Based on the clinical, radiographic, and pathological features of the EHE review, we concluded that it is difficult to adopt a standardized therapeutic approach due to the extremely low incidence of the bone involvement in EHE and the variable tendencies towards malignancy of this tumor. To our knowledge this is the third case of EHE with the involvement of the radius.