Incidence, characteristics, and predictive factors of post-colonoscopy colorectal cancer.

BACKGROUND: Post-colonoscopy colorectal cancer (PCCRC) is colorectal cancer (CRC) diagnosed after a colonoscopy in which no cancer is found. OBJECTIVE: As PCCRC has become an important quality indicator, we determined its rates, characteristics, and index colonoscopy-related predictive factors. METHODS: We carried out a multicenter, observational, retrospective study between 2015 and 2018. Rates were calculated for PCCRC developing up to 10 years after colonoscopy. PCCRC was categorized according to the most plausible explanation using World Endoscopy Organization methodology. Our PCCRC population was compared to a control cohort without CRC matched 1:4 by sex, age, index colonoscopy date, indication, endoscopist, and hospital. RESULTS: One hundred seven PCCRC and 2508 detected CRC were diagnosed among 101,524 colonoscopy (0.1%), leading to rates of 0.4%, 2.2%, 3.1%, and 4.1% at 1, 3, 5, and 10 years, respectively. PCCRC was in right (42.4%), left (41.4%), and transverse (16.4%) colon with 31.5% at stage I, 24.7% stage II, 32.6% stage III, and 11.2% stage IV. Twenty point three percent were classified as incomplete resection, 5.4% as unresected lesions, 48.6% as missed lesions with adequate colonoscopy, and 25.7% as missed lesions with inadequate colonoscopy. The median time from colonoscopy to PCCRC was 42 months. Previous inadequate preparation (OR 3.05, 95%CI 1.73-5.36) and piecemeal polypectomy (OR 19.89, 95%CI 8.67-45.61) were independently associated with PCCRC. CONCLUSIONS: In our population, 4.1% of CRC cases were PCCRC. Most of these lesions were in right colon and attributable to lesions not visualized despite adequate bowel cleansing. Previous inadequate cleansing and piecemeal polypectomy were associated with PCCRC.

Acute effects of dipyrone on renal function in patients with cirrhosis: a randomized controlled trial.

Use of non-steroidal anti-inflammatory drugs in cirrhosis has been associated with impairment of renal function based on its ability to inhibit the renal production of prostaglandins. Renal effects of dipyrone in patients with cirrhosis have not been evaluated. We aimed to assess the renal effect of therapeutic doses of dipyrone used for short periods of time in patients with cirrhosis. Twenty-nine patients with cirrhosis were included in an observer-blind clinical trial. Patients were randomized to receive three times a day oral acetaminophen (500 mg; N = 15) or dipyrone (575 mg; N = 14) for 72 hr. Serum and urine samples were obtained at baseline, 48 and 72 hr, and cystatin C, creatinine, aldosterone, 6-keto-Prostaglandin-F1 alpha and prostaglandin E2 were measured. Cystatin C and creatinine levels remained comparable in patients treated with acetaminophen and dipyrone. Urine and serum prostaglandins concentrations were significantly decreased at 72 hr in patients treated with dipyrone regardless of the status of ascites. One patient with ascites treated with dipyrone required a paracentesis and developed renal insufficiency. We conclude that dipyrone and acetaminophen did not reduce renal function when used for short periods of time (up to 72 hr) in patients with cirrhosis. However, considering that dipyrone lowered renal vasodilator prostaglandins synthesis, acetaminophen appears as the safest choice with respect to kidney function in cirrhosis.

Proteomic evidence of bacterial peptide translocation in afebrile patients with cirrhosis and ascites.

Bacterial translocation in patients with cirrhosis induces a marked proinflammatory activity that may be different against viable bacteria or bacterial products. The aim of this study is to identify new markers of bacterial translocation by investigating bacterial-driven peptides and correlate their presence with the inflammatory response. Patients with cirrhosis and ascites were included. An analysis by two-dimensional polyacrylamide gel electrophoresis of ascitic fluid total protein from patients (n = 47) and from frequently detected bacterial strains was performed. Two-dimensional maps were digitally compared. The identification of possible markers was performed by mass spectrometry. TNF-alpha, IFN-gamma, IL-12, nitric oxide, and proteins of the complement and lipopolysaccharide-binding protein levels were measured in ascitic fluid samples of patients by enzyme-linked immunosorbent assay. Patients were distributed according to the presence (group I, n = 16) and absence (group II, n = 31) of serum and ascitic fluid bacterial DNA. Among clinical and analytical differences between groups, only mean arterial pressure was significantly higher in patients from group II. Identified bacterial peptides were associated with bacterial protection against immune defenses and included glyceraldehyde-3-phosphate dehydrogenase A, Porin OmpC, and HSP60. Eight patients from group I also showed bacterial peptides, whereas none from group II did. All studied mediators of immune activation were significantly higher in patients with bacterial DNA than in patients without bacterial DNA. TNF-alpha, IFN-gamma, and proteins of the complement were significantly increased in patients with bacterial peptides versus those without bacterial peptides. Bacterial peptide translocation is present in the ascitic fluid of a subgroup of patients with advanced cirrhosis and is associated with an increased immune response.

Prospective validation of a noninvasive index for predicting liver fibrosis in hepatitis C virus-infected liver transplant recipients.

We previously developed a mathematical model, the Hospital Universitario La Fe (HULF) index, as an alternative to protocol liver biopsy (PLB) to estimate significant fibrosis (SF) in patients who underwent liver transplantation (LT) for liver damage caused by chronic HCV infection. In the present study, we sought to validate this noninvasive index. The commonly derived clinical and laboratory data for calculating the HULF index were prospectively collected over 2.7 years from patients undergoing LT and PLB. The sensitivity, specificity, positive and negative predictive values, and diagnostic capacity were evaluated with receiver operating characteristic curve analysis. Biopsy was performed 93 times in 86 LT patients. The prevalence of SF (F3-F4 on the Knodell scoring system) was 32%. The intraobserver and interobserver concordance was high (kappa = 0.94 and kappa = 0.75, respectively) in identifying SF in PLB. For low scores, the HULF index discarded an SF diagnosis with a sensitivity of 90% and a negative predictive value of 89%. The area under the receiver operating characteristic curve was 0.68. The precision of the HULF index did not improve with the incorporation of donor age and body mass index into the multivariate analysis. Applying the index would have prevented 24% of the biopsy procedures performed. In conclusion, the HULF index was prospectively validated with data commonly obtained in standard clinical practice. Because the index distinguishes a subgroup of HCV LT patients with a low probability of having SF, PLB would be avoided in those patients.

Norfloxacin modulates the inflammatory response and directly affects neutrophils in patients with decompensated cirrhosis.

BACKGROUND & AIMS: Patients with cirrhosis undergoing selective intestinal decontamination with norfloxacin show a reduction in serum cytokine levels, probably because of a combined effect of norfloxacin on bowel flora and neutrophils. METHODS: Thirty-one patients with cirrhosis receiving norfloxacin (400 mg/day) were included. Blood samples were collected at 0.5-4 hours (peak samples group, n = 47) and at 22-24 hours (trough samples group, n = 84) after dose. Fifty-nine ascitic fluid samples were obtained. Single doses of norfloxacin and trimethoprim/sulfamethoxazole were administered to 13 and 5 patients, respectively, (temporal profile group) and samples were collected at 0, 0.5, 1, 1.5, 2, 4, and 24 hours. Norfloxacin, trimethoprim/sulfamethoxazole, cytokines, nitric oxide, expression levels of nuclear factor (NF)-kappaB and inhibitor of NF-kappaB (IkB-alpha), neutrophil oxidative burst, and rate of apoptotic events were determined. RESULTS: All samples were bacterial DNA negative and had no significant levels of lipopolysaccharide. Serum and ascitic levels of tumor necrosis factor-alpha, interferon-gamma, interleukin-12, and nitric oxide were significantly lower in peak than in trough samples. A correlation was present between serum norfloxacins concentrations and tumor necrosis factor-alpha (r = -0.68; P < .001), interferon-gamma (r = -0.66; P < .001), interleukin-12 (r = -0.66; P < .001), and nitric oxide (r = -0.68; P < .001). Serum norfloxacin's highest concentrations (1 +/- 0.5 microg/mL) were achieved at 1-2 hours and concurred in time with the lower levels of cytokines and nitric oxide. Intracellular norfloxacin's highest levels (2 +/- 1 microg/mL/10(7) cells) were observed at 2 hours and concurred with a lower NF-kappaB expression, a reduced anion superoxide generation, and apoptotic rate in response to phorbol myristate acetate. Trimethoprim/sulfamethoxazole did not significantly modulate cytokine expression. CONCLUSIONS: Norfloxacin but not trimethoprim/sulfamethoxazole modulates inflammatory response and directly affects neutrophils in patients with cirrhosis.