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.     

Interaction of a plasminogen activator proteinase, LV-PA with human alpha2-macroglobulin.

Lachesis venom plasminogen activator (LV-PA) is a 33-kDa serine proteinase isolated from bushmaster (Lachesis muta muta) snake venom, which activates the fibrinolytic system in vitro. This study has examined the effect of the plasma proteinase inhibitor alpha2-macroglobulin (alpha2-M) towards LV-PA and compares it with the effect on tissue type plasminogen activator (t-PA). The proteolytic activity of LV-PA alone or previously incubated with human plasminogen (Plg) on the large molecular mass protein substrates, dimethylcasein (DMC) and fibrinogen (Fg) was completely inhibited by human alpha2-M. However, the synthetic peptides Tos-Gly-Pro-Lys-pNA and H-D-Pro-Phe-Arg-pNA (S-2302) were hydrolyzed with almost no reduction in rate. At pH 7.4 and 37 degrees C the proteinase (0.15 microM over 15 min) interacted with alpha2-M, and each mole of alpha2-M bound 2 mol of enzyme. Sodium dodecyl sulfate gel electrophoresis of reduced samples showed that the interaction of alpha2-M with either LV-PA or t-PA preincubated with Plg resulted in the formation of approximately 90 kDa fragments and high molecular mass complexes (Mr 180 kDa), generated by the incubation mixture (LV-PA or t-PA) and Plg. The data suggest that LV-PA is a direct-type PA and its fibrinolytic effect can be reduced by alpha2-M in vivo.     

Efficacy of epoetin-beta 30,000 IU/week in correcting anaemia in patients with gastrointestinal tumours subjected to concomitant chemoradiotherapy

Objective  

The aim of the project was to assess the effectiveness and safety of weekly epoetin-beta (EB) in patients with gastrointestinal cancer (GIC) subjected to concomitant chemoradiotherapy (CCTRT).     

Contribution of hypoxia-measuring molecular imaging techniques to radiotherapy planning and treatment

Hypoxia is related to poor prognosis because it is associated to chemo-and radioresistance. During recent years the evolution of imaging methods like PET/CT and MRI has meant the appearance of new perspectives with direct implications in radiation therapy. We discuss previous experiences in staging, planning and in the follow-up process with these techniques for measuring tumour hypoxia.     

On the road to automatic: dynamic aspects in the development of expertise.

One of the important steps on the road to becoming expert in a motor skill occurs when the individual can perform the movements in a seemingly effortless and automatic fashion. The authors review two lines of investigations, namely, fMRI and mathematically guided studies of the dynamics of skill acquisition, that suggest that this road to automatic involves two steps: (1) an increasing reliance on the self-regulatory aspects of the motor task, and (2) a minimization of the role of mechanisms based on intentionally directed corrective movements. The interplay between these two mechanisms implies that, at a given skill level, performance decreases whenever intention intervenes. The observation that psychological factors may be as important as mechanical repetition for the development of expertise has important implications for the design of neurorehabilitative strategies.     

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.     

Echogenic Appearance of Colorectal Liver Metastases on Intraoperative Ultrasonography is Associated with Survival After Hepatic Resection

Survival after resection of colorectal liver metastases has traditionally been associated with clinicopathologic factors. We sought to investigate whether echogenicity of colorectal liver metastasis as assessed by intraoperative ultrasound (IOUS) was a prognostic factor after hepatic resection. Prospective data on tumor IOUS appearance were collected in 84 patients who underwent hepatic resection for colorectal liver metastasis. Images were digitally recorded, blindly reviewed, and scored for echogenicity (hypo-, iso-, or hyperechoic). The median tumor number was 1 and the median tumor size was 5.0 cm. At the time of surgery, the IOUS appearance of the colorectal liver metastases were hypoechoic in 35 (41.7%) patients, isoechoic in 37 (44.0%) patients, and hyperechoic in 12 (14.3%) patients. Traditional clinicopathologic prognostic factors were similarly distributed among the three echogenicity groups (all p > 0.05). Patients with a hypoechoic lesion had a significantly shorter median survival (30.2 months) compared with patients who had either an isoechoic (53.2 months) or hyperechoic (42.3 months) lesion (p = 0.005). The 5-year survival after hepatic resection of colorectal liver metastasis was also associated with the echogenic appearance of the lesion (hypoechoic 14.4 vs isoechoic 37.4 vs hyperechoic 46.2%) (p < 0.05). Intraoperative ultrasound echogenicity should be considered a prognostic factor after hepatic resection of metastatic colorectal cancer. This study was presented at the 47th annual meeting of The Society for Surgery of the Alimentary Tract, Los Angeles, CA, USA, 22 May 2006.