Applying the 2011 St Gallen panel of prognostic markers on a large single hospital cohort of consecutively treated primary operable breast cancers.

BACKGROUND: Many easily measurable and readily available factors are now established as being prognostic in primary operable breast cancer. We here applied the 2011 St Gallen surrogate definition for breast cancer subclassification using tumor grade instead of Ki67. PATIENTS AND METHODS: Four thousand three hundred and eighteen consecutive patients who had surgery for primary operable breast cancer (1 January 2000 and 31 December 2009) in UZ Leuven excluding primary metastastic male breast cancers and those receiving neoadjuvant therapy. Five different surrogate phenotypes were created using the combined expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 together with tumor grade. Disease-free interval (DFI), distant metastastis-free interval (DMFI), locoregional relapse-free interval (LRRFI), breast cancer-specific survival (BCSS) and overall survival (OS) were calculated. RESULTS: Surrogate phenotypes present with significant differences in DFI, DMFI, LRRFI, BCSS and OS. 'Luminal A' tumors presented with the best outcome parameters but the effect weakened at longer follow-up. CONCLUSIONS: The four surrogate markers, agreed upon by the 2011 St Gallen consensus, defined five prognostic surrogate phenotypes in a large series of consecutively treated breast cancer patients. Their prognostic value changed with longer follow-up. The added value of gene expression profile over classical pathological assessment remains to be defined.

Optimization of the coherence measurement computed by means of the Welch averaged periodogram method for assessment of impaired cerebral autoregulation.

The coherence method (COH) has been widely used to study the concordance between continuously measured signals intervening in the assessment of cerebral autoregulation in neonates. Several research groups have applied this method to mean arterial blood pressure (MABP) combined with cerebral signals such as the intravascular oxygenation (HbD), cerebral tissue oxygenation (TOI), and regional oxygen saturation (rSO(2)) measured by near-infrared spectroscopy (NIRS). All groups contributed in a particular way to the fine-tuning of the application of COH with the Welch averaged periodogram (WAP) method. We have made a comparative study of all published results coupled with an optimization of the use of the WAP method within COH. We have also proposed a pre-processing algorithm to remove signal artefacts, and defined a new critical score value (CSV) for COH to distinguish infants with impaired autoregulation from those without.

The partial coherence method for assessment of impaired cerebral autoregulation using near-infrared spectroscopy: potential and limitations.

The most important forms of brain injury in premature infants are partly caused by disturbances in cerebral autoregulation. As changes in cerebral intravascular oxygenation (HbD), regional cerebral oxygen saturation (rSO(2)), and cerebral tissue oxygenation (TOI) reflect changes in cerebral blood flow (CBF), impaired autoregulation can be measured by studying the concordance between HbD/rSO(2)/TOI and the mean arterial blood pressure (MABP), assuming no changes in oxygen consumption, arterial oxygen saturation (SaO(2)), and in blood volume. We investigated the performance of the partial coherence (PCOH) method, and compared it with the coherence method (COH). The PCOH method allows the elimination of the influence of SaO(2) on HbD/rSO(2)/TOI in a linear way. We started from long-term recordings measured in the first days of life simultaneously in 30 infants from three medical centres. We then compared the COH and PCOH results with patient clinical characteristics and outcomes, and concluded that PCOH might be a better method for assessing impaired autoregulation.

Surgical closure of the patent ductus arteriosus and its effect on the cerebral tissue oxygenation.

AIM: Surgical patent ductus arteriosus (PDA) ligation is considered after failure or contraindication of medical treatment. Till now ligation of the PDA has been associated with low morbidity and mortality although recently concerns have been raised about the possible association of ductal clipping and neurodevelopmental abnormalities later in life. By means of near-infrared spectroscopy (NIRS), we analysed the changes in the cerebral tissue oxygenation index (TOI) and fractional tissue oxygen extraction (FTOE) at the time of clipping as well as after clipping. METHOD: Ten preterm infants with a symptomatic PDA who underwent surgical ligation were continuously monitored for heart rate (HR), mean arterial blood pressure (MABP), peripheral oxygen saturation (SaO(2)) and TOI from 1 h before up to 1 h after clipping. FTOE and haemoglobin difference (HbD) were calculated. Changes in parameters at 5 min after ligation represent the effect of the clipping itself whereas changes up to 1 h-post-clipping represent the post-clipping effect. RESULTS: At the exact time of clipping, over the entire group, we found a significant increase in TOI of 2.9% (p = 0.037), in HbD of 12.5 micromol/l (p = 0.047) and in HR of 6.5 bpm (p = 0.012). FTOE significantly decreased by 0.02% (p = 0.013). One hour post-clipping, the cerebral and peripheral parameters were not significantly different from the control values before clipping. CONCLUSION: The ductal clipping in se has no negative effect on the cerebral oxygenation.

Use of the liver tissue oxygenation index as a noninvasive parameter of intestinal ischemia in rabbits.

OBJECTIVE: The tissue oxygenation index (TOI), measured by spatially resolved spectroscopy (SRS), reflects the ratio between oxygenated and deoxygenated tissue hemoglobin. We investigated whether liver TOI is a noninvasive parameter for early detection of intestinal ischemia. METHODS: In seven adult New Zealand rabbits the superior mesenteric artery (SMA) and vein were exposed by laparotomy. The SRS probe was attached at the skin above the liver to calculate the TOI. The bowel (SbO(2)) and peripheral (SpO(2)) oxygen saturation were continuously measured. The SMA was occluded, creating small bowel ischemia for 90 minutes. Then reperfusion was started for 1 hour. The median TOI and interquartile range (IQR) of the TOI were calculated. A paired Wilcoxon test was used to evaluate changes in the liver TOI and SpO(2) during ischemia and reperfusion. RESULTS: The median TOI was 54.3% (IQR 8) at the start of ischemia, 54.9% (IQR 9) after 30 minutes, 51% (IQR 11) after 60 minutes, and 50.3% (IQR 10) after 90 minutes. The median TOI values were 46.3% (IQR 5) after 30 minutes of reperfusion and 41.2% (IQR 5) after 60 minutes. The decrease in TOI became significant (p < 0.05) after 90 minutes of ischemia. The SpO(2) was stable during the experiment. DISCUSSION: A significant decrease in liver TOI was seen after 90 minutes of occlusion of the SMA and is likely to be the consequence of bowel ischemia. The further decrease after reperfusion might reflect reperfusion injury. Liver TOI may be a new tool for noninvasive early detection of intestinal ischemia and reperfusion. Further study is needed to confirm these findings.

Delayed maturation of the interstitial cells of Cajal: a new diagnosis for transient neonatal pseudoobstruction. Report of two cases.

The case histories of two neonates presenting with intestinal pseudoobstruction are presented. One boy infant was premature and the girl infant was full term. Both patients needed a defunctioning ileostomy, and biopsy findings of the intestine in both patients showed a lack of interstitial cells of Cajal (ICC). At the time of closure of the ileostomies to restore intestinal continuity, repeat biopsy results showed a normal pattern of distribution of ICC. Delay in the development of ICC in the gastrointestinal tract may be a cause of intestinal pseudoobstruction in the newborn.

RDC8 codes for an adenosine A2 receptor with physiological constitutive activity.

The cDNA of an unidentified recently cloned G protein-coupled receptor, RDC8, has been expressed in Y1 adrenal cells, in dog thyrocytes in primary culture and in Xenopus oocytes. In all these systems this resulted in the activation of adenylyl cyclase and of the cyclic AMP cascade in the absence of any added external signal. However, this physiologically constitutive activator was inhibited by adenosine deaminase and by inhibitors of the adenosine A2 receptor. Cos 7 cells transfected with RDC8 cDNA constructs acquired binding characteristics of an adenosine A2 receptor. Moreover, RDC8 mRNA and adenosine A2 receptors display a very similar distribution in the brain. RDC8 therefore codes for an A2 adenosine receptor. Whether the physiologically constitutive activation of this receptor is entirely explained by endogeneously produced adenosine is as yet unknown.

Intracisternal administration of cholecystokinin-8 counteracts the central cardiovascular effects of adrenaline and NPY. A study based on the coexistence of cholecystokinin, phenylethanolamine N-methyltransferase and neuropeptide Y immunoreactivity in neurons of the nucleus tractus solitarius.

(1) In the present study the occlusion method was employed to evaluate the overall coexistence of neuropeptide Y and phenylethanolamine-N-methyl transferase, neuropeptide Y and tyrosine hydroxylase as well as cholecystokinin and phenylethanolamine-N-methyl transferase immunoreactivity in nerve cell bodies of the dorsal subnuclei of the nucleus tractus solitarius of the male rat. A high degree of coexistence was established for neuropeptide Y/phenylethanolamine-N-methyl transferase, cholecystokinin/phenylethanolamine-N-methyl transferase and for tyrosine hydroxylase/neuropeptide Y immunoreactivity. (2) Sulfated [(12)I]cholecystokinin-8 was used as radioligand to study the densities of cholecystokinin-8 binding sites in the dorsal medulla oblongata by means of quantitative receptor autoradiography. High densities of binding sites were observed in parts of the nucleus tractus solitarius and in the area postrema. Labeling was also observed in the dorsal motor nucleus of the vagus. (3) In the physiological studies adrenaline (0.15-1.0 nmol), neuropeptide Y (0.075-0.75 nmol) and sulfated cholecystokinin-8 (0.3-3.0 nmol) were administered alone or in combination with neuropeptide Y or adrenaline intracisternally into ?-chloralose anaesthetized male rats. Especially the hypotensive and bradycardic responses of adrenaline were counteracted in the adrenaline/cholecystokinin co-treated animals, whereas the cardiovascular effects of neuropeptide Y when co-administered with cholecystokinin-8 (0.3 nmol) appeared to be more resistant to the antagonistic effect of cholecystokinin 8. In addition, cholecystokinin-8 further enhanced the neuropeptide Y-induced bradynpnea and increase in the tidal volume. The present results indicate the existence of neuropeptide Y, adrenaline and cholecystokinin-8 immunoreactivity in the same neurons of the dorsal subnuclei of the nucleus tractus solitarius. Furthermore, binding sites for cholecystokinin-8 seem to at least partly co-distribute with ?-2 adrenergic and neuropeptide Y binding sites in the nucleus tractus solitarius. In the functional analysis, an antagonistic interaction between cholecystokinin-8 and adrenaline as well as between cholecystokinin and neuropeptide Y is demonstrated opening up the possibility that cholecystokinin peptides act as intrinsic modulators in the putative cholecystokinin/neuropeptide Y/adrenaline synapses in the nucleus tractus solitarius.