Cystatin C has recently been shown to be an accurate marker of glomerular filtration rate with advantages over serum creatinine (1 , 2) . Cystatin C, a potent inhibitor of cysteine proteases, is found mainly in extracellular fluids such as blood, cerebrospinal fluid, and seminal plasma. Its low molecular weight and stable production rate indicate that the blood concentration of cystatin C is determined mainly by glomerular filtration. The production rate of cystatin C is less altered by nonrenal factors than is the production of creatinine, and it has been reported that circulating cystatin C concentrations are not affected by inflammatory conditions or malignancy …
Background.Colorectal cancer (CRC) is the third most common cancer in the world.In 75% CRC develops sporadically, in 25% hereditary or as a consequence of inflammatory bowel disease.CRC carcinogenesis develops over many years.The cause of CRC in 85% is chromosomal instability (CIN) and in 15% microsatellite instability (MSI-H), where hereditary nonpolyposis colorectal cancer (HNPCC) represents 10-20%.Microsatellite sequences (MS) are repeated sequences of short stretches of DNA all over the genome.Microsatellite stability (MSS) means MS are the same in each cell of an individual, whereas microsatellite instability (MSI-H) means MS differ in normal and cancer cells of an individual.The cause of MSI-H is a damaged mismatch repair mechanism (MMR), with the most important MMR proteins being MSH2, MLH1 and MSH6.Conclusions.MSI-H seems to be an important prognostic factor in CRC and an important predictive factor of CRC chemotherapeutic treatment efficacy.Clinical trials conducted until now have shown contradictory findings in different chemotherapeutic settings, adjuvant and palliative; therefore MSI-H is going to be the object of the future research.The future of cancer treatment is in the individualized therapy based on molecular characteristics of the tumour, such as MSI-H in CRC.
1557 Background: Epidemiological studies consistently observed an association between metformin use in diabetic patients and decreased colon cancer incidence and mortality at clinical doses (1500-2250 mg day), corresponding to plasma levels of 0.003-0.045 mM. Preclinical models report much higher doses of metformin, ranging between 1 and 40 mM for in vitro and 0.006-0.145 mM for in vivo studies. A recent trial using a low dose of metformin (250 mg/day, Higurashi T et al. Lancet 2016;17:475) showed a 40% reduction of colorectal adenoma recurrence. We performed a pilot study to measure metformin in plasma and colonic tissue of subjects with diabetes or metabolic syndrome and to explore their correlation with different tissue biomarkers, including Ki-67, pS6k, a mTOR effector protein, and EGFR expression. Methods: We used LC-MS/MS to quantify metformin in plasma and colonic tissues from 13 volunteers with diabetes or metabolic syndrome undergoing screening colonoscopy. All patients had received metformin at 1000-1850 mg/day for a median of 6.5 yrs (range 2-15), except for one who served as untreated control. Tissue quantifications were performed on specimens derived from right and left colon biopsies with or without washing to exclude a potential contamination due to lumen accumulation by the drug. Biomarker assessment was performed by standard IHC assay. Results: The mean plasma metformin was 0.025 mM/L (range 5x10 -5 -0.017), whereas the colonic tissue was ~100 fold higher in right [0.39 mM/Kg (range 0.034-1.75)] and left colon [0.46 mM/Kg (range 5x10 -3 -1.86)]. There was no significant difference between washed and unwashed biopsies. No significant correlations were detected between metformin levels in plasma/tissue and tissue biomarkers. Conclusions: Metformin can attain ~100 fold higher colonic tissue levels than in plasma. These levels are in the range of a direct antitumor effect observed in in vivo preclinical models. A two-by-two clinical trial of metformin and aspirin in colon cancer patients is underway by our group to further elucidate independent and synergistic antitumor effects.
We present a case of a 57-year-old woman with two rare concomitant diseases; sarcoidosis and collagenous colitis. Patient was admitted to our hospital with the symptoms of watery diarrhea that intermittently lasted for years because of delayed diagnosis. Despite increasing awareness of microscopic colitis, the delayed diagnosis remains an important problem. Diagnosis was quickly confirmed with flexible proctosigmoidoscopy. Rectal biopsies were sufficient for diagnosis. Symptoms improved dramatically the second day of the induction therapy with budesonide. Causal relationship between sarcoidosis and microscopic colitis is not yet confirmed, and to our knowledge, this is the first such case report.
A 27-year-old man was admitted to our department because of persistent symptoms of fever, dyspnoea, dry cough, elevated C reactive protein (CRP) (258 mg/L), leucocytosis (17×109/L), peripheral eosinophilia (29%) and elevated liver enzymes (alanine aminotransferase (ALT) 518.2 U/L; aspartate aminotransferase (AST) 192.4 U/L; total bilirubin 1.6 mg/dL direct bilirubin 0.7 mg/dL; alkaline phosphatase 115.9 U/L and gamma glutamyl transferase (GGT) 119,4 U/L). His medical history was unremarkable except for surgery that he underwent 3 weeks ago for his left radius and ulna fracture. Since the surgery, he has been taking paracetamol and sodium metamizole. Empirical antibiotic therapy was initiated.
Chest X-ray revealed small left and large right pleural effusion. CT was performed due …
Objectives Laryngopharyngeal reflux ( LPR ) and biliary duodenogastric reflux can cause damage to the laryngeal mucosa and voice disorders. The aim of this study was to find out whether levels of pepsin and bile acids in the saliva can serve as diagnostic markers of LPR . Setting A prospective comparative study. Participants Twenty‐eight patients with LPR proven via high‐resolution manometry and combined multichannel intraluminal impedance and 24‐h pH monitoring and 48 healthy controls without symptoms of LPR were included in the study. Main outcome measures In the patients with LPR symptoms, oesophagogastroscopy with oesophageal biopsy was performed. The levels of total pepsin, active pepsin, bile acids and the pH of the saliva were determined in all participants and compared between the groups. Reflux symptom index ( RSI ) and reflux finding score ( RFS ) were also obtained and compared. The groups differed significantly in RSI ( P = 0.00), RFS ( P = 0.00), the levels of bile acids ( P = 0.005) and total pepsin in saliva ( P = 0.023). The levels of total pepsin and bile acids were about three times higher in the patients with LPR than in the healthy controls. There was a significant correlation between the RSI and RFS score and the level of total pepsin and bile acids in the saliva. Histopathological examination of the oesophageal biopsy taken 5 cm above the lower oesophageal sphincter confirmed reflux in almost 93% of patients with symptoms. Conclusions The study results show that the levels of total pepsin and bile acids in saliva are significantly higher in patients with LPR than in the controls, thus suggesting this as a useful tool in the diagnosis of LPR and particularly biliary LPR .
The urokinase-type plasminogen activator (uPA) and its inhibitors type 1 (PAI-1) and type 2 (PAI-2) are considered to have a key role in the process of invasion and metastasis. We investigated the differences in uPA, PAI-1 and PAI-2 concentrations in primary cutaneous melanoma and normal skin and correlations with well-established melanoma prognostic factors. The study was performed on 43 patients (19 men, 24 women; mean age 57 years) with histologically confirmed primary melanomas <1.5 mm thick. The uPA concentrations were determined in 36 pairs of triton extracts, and the PAI-1 and PAI-2 concentrations in 43 pairs of cytosols prepared from the tumour and adjacent normal tissue samples (matched pairs). The uPA, PAI-1 and PAI-2 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Significantly higher concentrations of both uPA and PAI-1 were measured in melanomas than in normal surrounding skin (uPA: 1.08 vs 0.48 ng/mg total protein (mgp), p<0.001; PAI-1: 14.07 vs 2.07 ng/mgp, p<0.001). The melanoma uPA, PAI-1 and PAI-2 concentrations correlated significantly (p<0.05) with normal skin (r=0.73, 0.54, 0.38 respectively). The uPA concentrations positively correlated with those of PAI-1 measured in melanomas (r=0.45, p<0.01). PAI-1 values were significantly lower (p<0.001) in the melanomas of Breslow thickness < or =0.75 mm, Clark invasion 0.75 mm, Clark invasion of > or =II and < or =III, with microscopic ulceration and vascular invasion (22.25, 17.67, 27.67, 37.77, respectively). Determination of uPA and PAI-1 can provide significant additional prognostic information for melanoma patients.
Endoscopic retrograde cholangio-pancreatography (ERCP) in first 72 hours is a standard therapeutic procedure in patients with acute biliary pancreatitis, but it is not clear if even earlier procedure would add additional benefit. Therefore we aimed to explore if ERCP within 24 hours of admission decreases duration of hospitalization, the rate of systemic and local complications, and if this effect is limited only to patients with concomitant cholangitis.
 scale(.12937)'%3e %3csvg width='12' viewBox='-120 -190.223125 240 309.188274' height='15.459'%3e %3cpath d='m110.26-19.478l9.74-143.75a280.22 280.22 0 0 0 -240 0l9.74 143.75a155.61 155.61 0 0 0 110.26 138.45 155.61 155.61 0 0 0 110.26 -138.45' fill='%23005da4'/%3e %3cpath d='m-90 0a138.29 138.29 0 0 0 90 100.77 138.29 138.29 0 0 0 90 -100.77l-45-60-18 24-27-54-27 54-18-24-45 60' fill='%23fff'/%3e %3cg id='wave' fill='%23005da4' transform='scale(5) translate(0 5.1962)'%3e %3cpath d='m-17.196-2.1962a6 6 0 0 0 8.1962 2.1962 6 6 0 0 1 6 0 6 6 0 0 0 6 0 6 6 0 0 1 6 0 6 6 0 0 0 8.1962 -2.1962v1.732a6 6 0 0 1 -8.1962 2.1962 6 6 0 0 0 -6 0 6 6 0 0 1 -6 0 6 6 0 0 0 -6 0 6 6 0 0 1 -8.1962 -2.1962z'/%3e %3c/g%3e %3cuse xlink:href='%23wave' transform='translate(0 17.321)'/%3e %3cg id='s' transform='translate(0,-120) scale(2.25)'%3e %3cpath stroke-width='.2' d='m0-5l1 3.2679 3.3301-0.7679-2.3301 2.5 2.3301 2.5-3.3301-0.7679-1 3.2679-1-3.2679-3.3301 0.7679 2.3301-2.5-2.3301-2.5 3.3301 0.7679z' fill='%23fd0'/%3e %3c/g%3e %3cuse xlink:href='%23s' transform='translate(-33.75,-45)'/%3e %3cuse xlink:href='%23s' transform='translate(33.75,-45)'/%3e %3cpath d='m-111.58-167.05l9.96 146.99a146.95 146.95 0 0 0 101.62 129.95 146.95 146.95 0 0 0 101.62 -129.95l9.96-146.99a280.22 280.22 0 0 0 8.42 3.82l-9.74 143.75a155.61 155.61 0 0 1 -110.26 138.45 155.61 155.61 0 0 1 -110.26 -138.45l-9.74-143.75a280.22 280.22 0 0 0 8.42 -3.82' fill='%23ed1c24'/%3e %3c/svg%3e %3c/g%3e %3c/svg%3e)
