Long-term follow-up of 5262 breast cancer patients with negative sentinel node and no axillary dissection confirms low rate of axillary disease.

AIM: It is established that axillary dissection (AD) can be safely avoided in breast cancer patients with a negative sentinel node (SN). In the present study we assessed whether the rate of axillary disease was sufficiently low on long term follow-up to consolidate the policy of AD avoidance. METHODS: We retrospectively analysed data on 5262 consecutive primary breast cancer patients with clinically negative axilla and negative SN, treated from 1996 to 2006, who did not receive AD. We used univariate and multivariate analyses to assess the influence of patient and tumour characteristics on first events and survival. The primary endpoint was the development of axillary disease as first event. RESULTS: After a median follow-up of 7.0 years (interquartile range 5.4-8.9 years) survival for the series was high (91.3%; 95% CI 90.3-92.3 at 10 years) and only 91 (1.7%) patients developed axillary disease as first event. Axillary disease was significantly more frequent in patients with the following characteristics: <35 years at diagnosis, tumour >1 cm, multifocality/multicentricity, G3, ductal histotype, Ki67 ≥ 30%, peritumoral vascular invasion, luminal B-like subtype, HER2 positivity, mastectomy, and not receiving radiotherapy. CONCLUSION: Long-term follow-up of our large series confirms that axillary metastasis is infrequent when AD is omitted in SN-negative breast cancer patients, and has low impact on overall survival.

N-acetylcysteine in pig liver transplantation from non-heart-beating donors.

Lipid peroxidation due to oxygen free radicals (OFR) seems to play a major role in loss of liver graft viability after warm ischemia, preservation, and transplantation. N-acetylcysteine (NAC) is an antioxidant that has a direct effect on OFR, and is also a glutathione precursor, another antioxidant. This study was designed to evaluate the efficacy of NAC in preventing ischemia-reperfusion damage of liver grafts harvested from non-heart-beating donors. Liver transplantation was performed on pigs divided into five groups: group 1 (control group; n=5) received livers from heart-beating donors; livers were subjected to 30 min of warm ischemia in groups 2 (n=3, no NAC) and group 3 (n=3; NAC treatment); warm ischemia time lasted 60 min in groups 4 (n=4; no NAC) and 5 (n=5; NAC treatment). Studied parameters included graft survival for more than 3 days, aspartate aminotransferase plasma levels, liver histology, and hepatic total glutathione concentrations. Graft survival was 100% in groups 1, 2, and 3, 0% in group 4, and 20% in group 5. NAC treatment did not influence initial mean aspartate aminotransferase release which was greater in warm ischemic livers than in controls. NAC treatment had no effect on liver hepatic total glutathione after reperfusion of animals receiving warm ischemic grants. Finally, no effect on liver histology was observed with NAC treatment. Our study suggests that in liver transplantation from non-heart-beating donors, NAC has no effect in both graft viability and lipid peroxidation. The role of OFR in primary dysfunction of transplanted warm ischemic livers remains controversial.

Markers of cellular dysoxia during orthotopic liver transplantation in pigs.

OBJECTIVE: To characterize global, regional, and end-organ markers of cellular dysoxia during orthotopic liver transplantation and early reperfusion in pigs. DESIGN: Descriptive study. SETTING: University hospital research laboratory. ANIMALS AND INTERVENTIONS: 7 fasted, anesthetized, and mechanically ventilated Yorkshire pigs underwent orthotopic liver transplantation. Oxygen consumption (VO2) and oxygen delivery (DO2) were both calculated using standard formulae. Gastric interstitial pH and the gastroarterial partial pressure of carbon dioxide (PCO2) gradient were measured with a gastric tonometer. The following were determined from arterial blood samples: serum lactate to pyruvate ratio, serum 3-hydroxybutyrate to acetoacetate ratio, plasma free fatty acids, and plasma free and total carnitine levels. MEASUREMENTS AND RESULTS: Data were collected 1 h after induction of anesthesia (I), at the end of the anhepatic phase (A), and 1 h after reperfusion (R), Median (range) VO2 values obtained at the specified time points were: I 318 (206-1860), A 210 (152-408), R 330 (214-424) ml/kg per min, respectively (NS); DO2 values were: I 1828 (1382-3259), A 1219 (452-2492), R 1741 (1345-12,071) ml/kg per min, respectively (NS). The lactate to pyruvate ratio, reflecting the redox potential of the cytosol, progressively increased: I 22 (9-46), A 29 (16-68), R 43 (23-55), (p < 0.05). Gastric interstitial pH, as well as the gastroarterial PCO2 gradient values at the specified time points did not reach statistical significance. Levels of ketone bodies (3-hydroxybutyrate+acetoacetate) remained lower than 0.120 mmol/l. The ketone body ratio did not significantly vary over time (NS). Plasma esterified and free carnitine concentrations and free fatty acid values remained within normal limits (NS). Among these markers, the ketone body ratio presented the largest area under the receiver operating characteristic curve as a marker of postoperative mortality, with an inflexion point at 0.9. CONCLUSION: In this study, orthotopic liver transplantation was associated with significant variations over time in the redox potential of the cytosol. Postoperative mortality was, however, related to the redox state of the liver mitochondria. Our data suggest the occurrence of abnormal tissue oxygenation during liver transplantation.

The effects of tracheal occlusion and release on type II pneumocytes in fetal lambs.

UNLABELLED: Fetal tracheal occlusion (TO) has been shown to lead to lung hyperplasia in various animal models, and this procedure has already been carried out in human fetuses with congenital diaphragmatic hernia (CDH). However, the authors previously showed that TO caused a decrease in type II pneumocytes. PURPOSE: The aim of this study is to examine the effects of TO and release on type II pneumocytes. METHOD: To was carried out with a Swan Ganz or Fogarty catheter in fetal sheep at 116 to 118 days of gestation. TO was maintained for 2 weeks followed by deflation of the balloon for 1 week before delivery, in group 1; in group 2, TO was maintained for 19 days and released 2 days before delivery. Group 3 consisted of previously reported animals who had TO maintained until birth. Unoperated twins served as controls. All specimens were analyzed using the surfactant protein C (SP-C) mRNA as a specific marker for type II pneumocytes. We used Northern Blot and in situ hybridization techniques to quantify total SP-C and the density of type II cells. Electron microscopy (EM) was also used to evaluate and quantitate type II cells. RESULTS: TO resulted in significant lung growth in all groups. In situ hybridization and Northern Blot analysis showed that there was a complete recovery of type II cells in group 1 versus controls. Quantitative EM analysis confirmed these findings. In group 2 the number of type II cells was decreased but there was an increase in SP-C content per type II cell versus group 3. CONCLUSION: Lung growth after TO appears to occur at the expense of type II cell differentiation. This effect is reversible with the release of TO before birth in this animal model.

[Intrahepatic glutathione and oxidative stress in liver transplantation in the pig]. / Glutathion intra-hépatique et stress oxydatif en transplantation du foie chez le cochon.

OBJECT: To determine the loss of endogenous GSH from livers cold-stored and reperfused, using a model of liver transplantation in the pig. MATERIAL AND METHODS: Four female Yorkshire pigs weighing 19 to 40 kg received a liver allograft. Donor livers were cold-stored in the UW solution. Mean cold ischemic time was 6.5 hours. Malondialdehyde (MDA) levels were used as an index of oxidative stress. MDA plasma levels were measured following recipient laparotomy (H0), immediately (H1), and 90 minutes after liver reperfusion (H2). MDA and GSH levels in liver were measured following donor laparotomy (T0), at the end of cold ischemic period (T1), and at 90 minutes following liver reperfusion (T2). RESULTS: Three animals survived. MDA liver levels decreased of 44% between T0 and T1, then increased to 92% at T2. In contrast, in plasma, graft reperfusion was associated with an increase of MDA to 140% of the baseline values which reached 188% at H2. Intrahepatic GSH levels decreased of 49% at T1, then to 72% at T2. CONCLUSION: our study suggests that in liver transplantation: (1) Hepatic GSH is depleted to 49% during cold-storage, and an additional 23% is lost after reperfusion; (2) GSH contained in the UW solution does not prevent the loss of hepatocellular glutathione during preservation and reperfusion; (3) after short periods of cold ichemia, endogenous hepatic GSH may protect against oxydative stress in the transplanted liver.