Preoperative Chemotherapy for Colorectal Liver Metastases: Impact on Hepatic Histology and Postoperative Outcome

Some investigators have suggested that preoperative chemotherapy for hepatic colorectal metastases may cause hepatic injury and increase perioperative morbidity and mortality. The objective of the current study was to examine whether treatment with preoperative chemotherapy was associated with hepatic injury of the nontumorous liver and whether such injury, if present, was associated with increased morbidity or mortality after hepatic resection. Two-hundred and twelve eligible patients who underwent hepatic resection for colorectal liver metastases between January 1999 and December 2005 were identified. Data on demographics, clinicopathologic characteristics, and preoperative chemotherapy details were collected and analyzed. The majority of patients received preoperative chemotherapy (n = 153; 72.2%). Chemotherapy consisted of fluoropyrimidine-based regimens: 5-FU monotherapy, 31.6%; irinotecan, 25.9%; and oxaliplatin, 14.6%. Among those patients who received chemotherapy, the type of chemotherapy regimen predicted distinct patterns of liver injury. Oxaliplatin was associated with increased likelihood of grade 3 sinusoidal dilatation (p = 0.017). Steatosis >30% was associated with irinotecan (27.3%) compared with no chemotherapy, 5-FU monotherapy, and oxaliplatin (all p < 0.05). Irinotecan also was associated with steatohepatitis, as two of the three patients with steatohepatitis had received irinotecan preoperatively. Overall, the perioperative complication rate was similar between the no-chemotherapy group (30.5%) and the chemotherapy group (35.3%) (p = 0.79). Preoperative chemotherapy was also not associated with 60-day mortality. In patients with hepatic colorectal metastases, preoperative chemotherapy is associated with hepatic injury in about 20 to 30% of patients. Furthermore, the type of hepatic injury after preoperative chemotherapy was regimen-specific. Presented at the American Hepato-Pancreato-Biliary Association 2006 Annual Meeting, March 11, Miami, Florida.     

A prospective study of Toxoplasma-positive pregnant women in southern Brazil: a health alert

We evaluated anti-Toxoplasma gondii IgM-reactive pregnant women seen at a high-risk pregnancy outpatient clinic. From March 2005 to January 2008 in Paraná, Brazil, pregnant women seen by the Brazilian Public Health System, in any gestational period, who were anti-T. gondii IgM-positive, were followed. Clinical symptoms were noted, and tests performed including IgA, IgG avidity, ultrasonogram, and amniocentesis (PCR/inoculation in mice). Of 75 patients, 8 showed low, 3 intermediate and 31 high IgG avidity. Of those who underwent the avidity test, 31 (70.5%) were in the second trimester of pregnancy. Thirty-two (42.7%) pregnant women received specific treatment. Six received triple combination treatment; in three, tachyzoites were isolated, although only one was PCR-positive, showing changes in the cerebral sonogram, borderline IgA, and the Sabin tetrad. One fetus died, and one non-reactive IgM pregnant woman showed ocular recurrence. The municipality of residence, contact with cats during adulthood, and ingestion of unpasteurized milk were shown to be important risk factors. Congenital toxoplasmosis was observed in a pregnancy referred late for treatment. Follow-up of children born to mothers with diagnosed or suspected acute toxoplasmosis is crucial in the management of the changes that toxoplasmosis may cause.     

The development of involuntary and voluntary attention from childhood to adulthood: a combined behavioral and event-related potential study.

OBJECTIVE: This study investigated auditory involuntary and voluntary attention in children aged 6-8, 10-12 and young adults. The strength of distracting stimuli (20% and 5% pitch changes) and the amount of allocation of attention were varied. METHODS: In an auditory distraction paradigm event-related potentials (ERPs) and behavioral data were measured from subjects either performing a sound duration discrimination task or watching a silent video. RESULTS: Pitch changed sounds caused prolonged reaction times and decreased hit rates in all age groups. Larger distractors (20%) caused stronger distraction in children, but not in adults. The amplitudes of mismatch negativity (MMN), P3a, and reorienting negativity (RON) were modulated by age and by voluntary attention. P3a was additionally affected by distractor strength. Maturational changes were also observed in the amplitudes of P1 (decreasing with age) and N1 (increasing with age). P2-modulation by voluntary attention was opposite in young children and adults. CONCLUSIONS: Results suggest quantitative and qualitative changes in auditory voluntary and involuntary attention and distraction during development. The processing steps involved in distraction (pre-attentive change detection, attention switch, reorienting) are functional in children aged 6-8 but reveal characteristic differences to those of young adults. In general, distractibility as indicated by behavioral and ERP measures decreases from childhood to adulthood. SIGNIFICANCE: Behavioral and ERP markers for different processing stages involved in voluntary and involuntary attention reveal characteristic developmental changes from childhood to young adulthood.     

Incidence of Finding Residual Disease for Incidental Gallbladder Carcinoma: Implications for Re-resection

Re-resection for gallbladder carcinoma incidentally discovered after cholecystectomy is routinely advocated. However, the incidence of finding additional disease at the time of re-resection remains poorly defined. Between 1984 and 2006, 115 patients underwent re-resection at six major hepatobiliary centers for gallbladder carcinoma incidentally discovered during cholecystectomy. Data on clinicopathologic factors, operative details, TNM tumor stage, and outcome were collected and analyzed. Data on the incidence and location of residual/additional carcinoma discovered at the time of re-resection were also recorded. On pathologic analysis, T stage was T1 7.8%, T2 67.0%, and T3 25.2%. The median time from cholecystectomy to re-resection was 52 days. At the time of re-resection, hepatic surgery most often consisted of formal segmentectomy (64.9%). Patients underwent lymphadenectomy (LND) (50.5%) or LND + common bile duct resection (43.3%). The median number of lymph nodes harvested was 3 and did not differ between LND alone (n = 3) vs LND + common duct resection (n = 3) (P = 0.35). Pathology from the re-resection specimen noted residual/additional disease in 46.4% of patients. Of those patients staged as T1, T2, or T3, 0, 10.4, and 36.4%, respectively, had residual disease within the liver (P = 0.01). T stage was also associated with the risk of metastasis to locoregional lymph nodes (lymph node metastasis: T1 12.5%; T2 31.3%, T3 45.5%; P = 0.04). Cystic duct margin status predicted residual disease in the common bile duct (negative cystic duct, 4.3% vs positive cystic duct, 42.1%) (P = 0.01). Aggressive re-resection for incidental gallbladder carcinoma is warranted as the majority of patients have residual disease. Although common duct resection does not yield a greater lymph node count, it should be performed at the time of re-resection for patients with positive cystic duct margins because over one-third will have residual disease in the common bile duct. Presented at the 48th Annual Meeting of the Society for Surgery of the Alimentary Tract at Digestive Week 2007, Plenary Session, Washington, DC, March 23, 2007.     

Impact of antibiotic-resistant pathogens colonizing the respiratory secretions of patients in an extended-care area of the emergency department.

OBJECTIVE: To determine the incidence of acquired infection, and the incidence, risk factors, and molecular typing of multidrug-resistant bacterial organisms (MROs) colonizing respiratory secretions or the oropharynx of patients in an extended-care area of the emergency department (ED) in a tertiary-care university hospital. METHODS: A case-control study was conducted regarding risk factors for colonization with MROs in ED patients from July 1996 to August 1998. The most prevalent MRO strains were determined using plasmid and genomic analysis with PFGE. RESULTS: MROs colonized 59 (25.4%) of 232 ED patients and 173 controls. The mean ED length of stay for the 59 cases was 13.9 days versus 9.8 days for the 173 controls. The mean length of stay prior to the first isolation of MROs was 9.9 days. MRO species included Acinetobacter baumannii, Staphylococcus aureus, and Pseudomonas aeruginosa. The rate of hospital-acquired infection was 32.7 per 1,000 ED patient-days. The case fatality rate was significantly higher for cases. Univariate analysis identified mechanical ventilation, nebulization, nasogastric intubation, urinary catheterization, antibiotic therapy, and number of antibiotics as risk factors for MRO colonization. Multivariate regression analysis found that mechanical ventilation and nasogastric intubation independently predicted MRO colonization. Endemic clones were identified by PFGE in ED patients and were also found in patients in other parts of the hospital. CONCLUSIONS: Prolonged stay in the ED posed a risk for colonization with MROs and for contracting nosocomial infections, both of which were associated with increased mortality. Patients colonized with antibiotic-resistant A. baumannii may serve as a reservoir for spread in this hospital.     

Defibrotide, an antithrombotic substance that preserves postsynaptic alpha- and beta-adrenergic function in post acute infarcted rabbit hearts

Defibrotide, a simple strand polydeoxyribonucleotide of mammalian origin with a molecular weight of 20,000 daltons, given intravenously to the rabbit before and after production of left ventricular infarction, prevents the alteration of the contractile response to postsynaptic adrenergic stimulation tested in isolated perfused heart preparations 3 days after coronary artery occlusion. According to the dose-response curves for isoproterenol and tyramine, left ventricular dP/dtmax was significantly depressed in infarcted hearts, whereas the dose-response curve for the inotropic effect of phenylephrine was markedly enhanced. These alterations were prevented by pretreatment of the rabbits with defibrotide (32 mg/kg/h i.v. for 6 h). In fact the potency ratios, calculated from the dose-response curves related to dP/dtmax of isoproterenol, tyramine, and phenylephrine in infarcted and control hearts excised from defibrotide treated and shamoperated rabbits, are nearly 1. The observed alterations in myocardial contractility in infarcted hearts seem to be specific for postsynaptic alpha and beta-adrenoceptors since the dose-response curve of left ventricular dP/dtmax for histamine is not different from control. The results obtained with defibrotide reflect the ability of this substance to protect the myocardial tissue from ischemic damage: this is also supported by the capacity of defibrotide (8 mg/kg/h i.v. for 6.5 h) to prevent the reduction of CPK-activity in the infarcted ventricle. Finally, we suggest that the observed beneficial effect of defibrotide in rabbit heart may also be explained by the antithrombotic effect of this substance, which is based on its profibrinolytic activity and PGI2-release.