Systemic versus Oral and Systemic Antibiotic Prophylaxis (SOAP) study in colorectal surgery: prospective randomized multicentre trial.

BACKGROUND: There is no consensus regarding the role of mechanical bowel preparation (MBP) and oral antibiotic prophylaxis (OABP) in reducing postoperative complications in colorectal surgery. The aim of this study was to examine the effect of OABP given in addition to MBP in the setting of a prospective randomized trial. METHODS: Patients awaiting elective colorectal surgery in four Hungarian colorectal centres were included in this multicentre, prospective, randomized, assessor-blinded study. Patients were randomized to receive MBP with or without OABP (OABP+ and OABP- groups respectively). The primary endpoints were surgical-site infection (SSI) and postoperative ileus. Secondary endpoints were anastomotic leak, mortality, and hospital readmission within 30 days. RESULTS: Of 839 patients assessed for eligibility between November 2016 and June 2018, 600 were randomized and 529 were analysed. Trial participation was discontinued owing to adverse events in seven patients in the OABP+ group (2.3 per cent). SSI occurred in eight patients (3.2 per cent) in the OABP+ and 27 (9.8 per cent) in the OABP- group (P = 0.001). The incidence of postoperative ileus did not differ between groups. Anastomotic leakage occurred in four patients (1.6 per cent) in the OABP+ and 13 (4.7 per cent) in the OABP- (P = 0.02) group. There were no differences in hospital readmission (12 (4.7 per cent) versus 10 (3.6 per cent); P = 0.25) or mortality (3 (1.2 per cent) versus 4 (1.4 per cent); P = 0.39). CONCLUSION: OABP given with MBP reduced the rate of SSI and AL after colorectal surgery with anastomosis, therefore routine use of OABP is recommended.

A prognostic model based on combining estrogen receptor expression and Ki-67 value after neoadjuvant chemotherapy predicts clinical outcome in locally advanced breast cancer: extension and analysis of a previously reported cohort of patients.

BACKGROUND: Ki-67 expression has gained attention as a breast cancer prognostic factor, however its significance in the remaining malignant cells after neoadjuvant chemotherapy (NAC) has been rarely examined. This investigation, extension and analysis of a previously reported cohort of patients, evaluates the significance of Ki-67 and estrogen receptor (ER) expression after NAC in LABC (locally advanced breast cancer). PATIENTS AND METHODS: clinical stage, tumor size, clinical and pathological lymph node involvement, Ki-67, ER, progesterone receptor (PgR), HER2 expression, grading and clinical response were evaluated before and after NAC in 110 patients with LABC. Ki-67 expression was assessed both in pre and post-therapy histological samples, using >15% positive cells as cut-off value to distinguish high from low Ki-67 expressing tumors. RESULTS: six patients (5.45%) attained pCR after NAC. A significant relationship between elevated post-CT Ki-67 and ER expression was showed at Cox multivariate analysis of disease free survival (DFS). On univariate analysis high post-chemotherapy Ki-67 and ER status were associated with worse survival; at multivariate model included these results were confirmed. Based on these two parameters, a prognostic model identified two different groups: low risk (low postchemotherapy Ki-67 and ER positive, or either high post-chemotherapy Ki-67 or ER negative), and high risk (high post-chemotherapy Ki-67 and ER negative). The low risk group showed a good prognosis (median OS still not reached), while the high risk group had a worse OS (median 41 months). CONCLUSIONS: Ki-67 value after NAC and ER status could predict a worse prognosis among LABC patients treated with NAC.

Prognostic value of estrogen receptor and Ki-67 index after neoadjuvant chemotherapy in locally advanced breast cancer expressing high levels of proliferation at diagnosis.

PURPOSE: Breast cancers expressing high levels of Ki-67, a nuclear marker of cell proliferation, are associated with worse outcome. Recent data from neoadjuvant studies indicate that a single measurement of the nuclear proliferation marker Ki-67 in breast carcinoma during neoadjuvant therapy is strongly predictive of long-term outcome. Secondly, recent literature data indicate that prognostic evaluation with Ki-67 may be better after pre-surgical therapy. A retrospective study from a prospectively maintained clinical database to compare the predictive and prognostic significance of biological markers, assessed before and after neoadjuvant chemotherapy, in locally advanced breast cancer, was performed. PATIENTS AND METHODS: The following parameters were considered before and after chemotherapy for their relationship with treatment response and disease-free survival in 64 patients with locally advanced breast cancer: clinical stage, clinical and pathological lymph node involvement, Ki-67, estrogen receptor (ER), progesterone receptor (Pgr), Her2, tumor grade, clinical response, type of surgery performed, and number of chemotherapy cycles administered. The expression of Ki-67 was assessed using immunohistochemistry in pre-therapy tru-cut and post-therapy surgical excision specimens after neoadjuvant chemotherapy; only patients with breast tumors expressing high baseline Ki-67 (≥ 15%) were included in the analysis. In addition, the correlation between pre-chemotherapy biological markers and clinical and pathological response was reported. RESULTS: Post-chemotherapy Ki-67 proliferation index decrease, pre-chemotherapy ER expression and post-chemotherapy ER expression were the only significant prognostic factors adversely influencing disease-free survival in univariate analysis. Her2 overexpression was the only factor to impact on the clinical response. CONCLUSIONS: Post-treatment Ki-67 and ER status were predictors of outcome for patients with locally advanced breast cancer and a high pre-chemotherapy proliferation index.

[Oncoplastic surgery for the treatment of breast cancer]. / Chirurgia oncoplastica nel trattamento dei tumori della mammella.

Surgery is still the gold standard in breast cancer. Also if the elective treatment, thanks to the adjuvant therapy, ha became more conservative than once was, breast surgery remains, in the mind of the woman affected by breast cancer, a demolitive surgery. The collaboration bet-ween the breast surgeon and the plastic surgeon has to be closer than it is, in order to obtain the total asportation of the tumor and an esthetic result that limits the psychological trauma to the woman. Oncoplastic surgery is the answer to these human and medical necessities, giving the correct approaches about breast volume, tumor volume, radicality of the treatment and esthetic outcome. This review will focus on different oncoplastic approaches, to help improving both the esthetic outcome of breast cancer resection and the likelihood of surgeons obtaining wide surgical margins in preparation for breast-conserving radiotherapy.

An extremely luminous X-ray outburst at the birth of a supernova.

Massive stars end their short lives in spectacular explosions--supernovae--that synthesize new elements and drive galaxy evolution. Historically, supernovae were discovered mainly through their 'delayed' optical light (some days after the burst of neutrinos that marks the actual event), preventing observations in the first moments following the explosion. As a result, the progenitors of some supernovae and the events leading up to their violent demise remain intensely debated. Here we report the serendipitous discovery of a supernova at the time of the explosion, marked by an extremely luminous X-ray outburst. We attribute the outburst to the 'break-out' of the supernova shock wave from the progenitor star, and show that the inferred rate of such events agrees with that of all core-collapse supernovae. We predict that future wide-field X-ray surveys will catch each year hundreds of supernovae in the act of exploding.

Cholesterol potentiates ABCG2 activity in a heterologous expression system: improved in vitro model to study function of human ABCG2.

ABCG2, a transporter of the ATP-binding cassette family, is known to play a prominent role in the absorption, distribution, metabolism, and excretion of xenobiotics. Drug-transporter interactions are commonly screened by high-throughput systems using transfected insect and/or human cell lines. The determination of ABCG2-ATPase activity is one method to identify ABCG2 substrate and inhibitors. We demonstrate that the ATPase activities of the human ABCG2 transfected Sf9 cell membranes (MXR-Sf9) and ABCG2-overexpressing human cell membranes (MXR-M) differ. Variation due to disparity in the glycosylation level of the protein had no effect on the transporter. The influence of cholesterol on ABCG2-ATPase activity was investigated because the lipid compositions of insect and human cells are largely different from each other. Differences in cholesterol content, shown by cholesterol loading and depletion experiments, conferred the difference in stimulation of basal ABCG2-ATPase of the two cell membranes. Basal ABCG2-ATPase activity could be stimulated by sulfasalazine, prazosin, and topotecan, known substrates of ABCG2 in cholesterol-loaded MXR-Sf9 and MXR-M cell membranes. In contrast, ABCG2-ATPase could not be stimulated in MXR-Sf9 or in cholesterol-depleted MXR-M membranes. Moreover, cholesterol loading significantly improved the drug transport into inside-out membrane vesicles prepared from MXR-Sf9 cells. MXR-M and cholesterol-loaded MXR-Sf9 cell membranes displayed similar ABCG2-ATPase activity and vesicular transport. Our study indicates an essential role of membrane cholesterol for the function of ABCG2.

A new gamma-ray burst classification scheme from GRB 060614.

Gamma-ray bursts (GRBs) are known to come in two duration classes, separated at approximately 2 s. Long-duration bursts originate from star-forming regions in galaxies, have accompanying supernovae when these are near enough to observe and are probably caused by massive-star collapsars. Recent observations show that short-duration bursts originate in regions within their host galaxies that have lower star-formation rates, consistent with binary neutron star or neutron star-black hole mergers. Moreover, although their hosts are predominantly nearby galaxies, no supernovae have been so far associated with short-duration GRBs. Here we report that the bright, nearby GRB 060614 does not fit into either class. Its approximately 102-s duration groups it with long-duration GRBs, while its temporal lag and peak luminosity fall entirely within the short-duration GRB subclass. Moreover, very deep optical observations exclude an accompanying supernova, similar to short-duration GRBs. This combination of a long-duration event without an accompanying supernova poses a challenge to both the collapsar and the merging-neutron-star interpretations and opens the door to a new GRB classification scheme that straddles both long- and short-duration bursts.

The association of GRB 060218 with a supernova and the evolution of the shock wave.

Although the link between long gamma-ray bursts (GRBs) and supernovae has been established, hitherto there have been no observations of the beginning of a supernova explosion and its intimate link to a GRB. In particular, we do not know how the jet that defines a gamma-ray burst emerges from the star's surface, nor how a GRB progenitor explodes. Here we report observations of the relatively nearby GRB 060218 (ref. 5) and its connection to supernova SN 2006aj (ref. 6). In addition to the classical non-thermal emission, GRB 060218 shows a thermal component in its X-ray spectrum, which cools and shifts into the optical/ultraviolet band as time passes. We interpret these features as arising from the break-out of a shock wave driven by a mildly relativistic shell into the dense wind surrounding the progenitor. We have caught a supernova in the act of exploding, directly observing the shock break-out, which indicates that the GRB progenitor was a Wolf-Rayet star.

Gamma-ray bursts: huge explosion in the early Universe.

Long gamma-ray bursts (GRBs) are bright flashes of high-energy photons that can last for tens of minutes; they are generally associated with galaxies that have a high rate of star formation and probably arise from the collapsing cores of massive stars, which produce highly relativistic jets (collapsar model). Here we describe gamma- and X-ray observations of the most distant GRB ever observed (GRB 050904): its redshift (z) of 6.29 means that this explosion happened 12.8 billion years ago, corresponding to a time when the Universe was just 890 million years old, close to the reionization era. This means that not only did stars form in this short period of time after the Big Bang, but also that enough time had elapsed for them to evolve and collapse into black holes.

An origin for short gamma-ray bursts unassociated with current star formation.

Two short (< 2 s) gamma-ray bursts (GRBs) have recently been localized and fading afterglow counterparts detected. The combination of these two results left unclear the nature of the host galaxies of the bursts, because one was a star-forming dwarf, while the other was probably an elliptical galaxy. Here we report the X-ray localization of a short burst (GRB 050724) with unusual gamma-ray and X-ray properties. The X-ray afterglow lies off the centre of an elliptical galaxy at a redshift of z = 0.258 (ref. 5), coincident with the position determined by ground-based optical and radio observations. The low level of star formation typical for elliptical galaxies makes it unlikely that the burst originated in a supernova explosion. A supernova origin was also ruled out for GRB 050709 (refs 3, 31), even though that burst took place in a galaxy with current star formation. The isotropic energy for the short bursts is 2-3 orders of magnitude lower than that for the long bursts. Our results therefore suggest that an alternative source of bursts--the coalescence of binary systems of neutron stars or a neutron star-black hole pair--are the progenitors of short bursts.

A short gamma-ray burst apparently associated with an elliptical galaxy at redshift z = 0.225.

Gamma-ray bursts (GRBs) come in two classes: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z approximately 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars. In contrast, no short GRB had been accurately (< 10'') and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from--and the localization of--the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.

Bright x-ray flares in gamma-ray burst afterglows.

Gamma-ray burst (GRB) afterglows have provided important clues to the nature of these massive explosive events, providing direct information on the nearby environment and indirect information on the central engine that powers the burst. We report the discovery of two bright x-ray flares in GRB afterglows, including a giant flare comparable in total energy to the burst itself, each peaking minutes after the burst. These strong, rapid x-ray flares imply that the central engines of the bursts have long periods of activity, with strong internal shocks continuing for hundreds of seconds after the gamma-ray emission has ended.

An unexpectedly rapid decline in the X-ray afterglow emission of long gamma-ray bursts.

'Long' gamma-ray bursts (GRBs) are commonly accepted to originate in the explosion of particularly massive stars, which give rise to highly relativistic jets. Inhomogeneities in the expanding flow result in internal shock waves that are believed to produce the gamma-rays we see. As the jet travels further outward into the surrounding circumstellar medium, 'external' shocks create the afterglow emission seen in the X-ray, optical and radio bands. Here we report observations of the early phases of the X-ray emission of five GRBs. Their X-ray light curves are characterised by a surprisingly rapid fall-off for the first few hundred seconds, followed by a less rapid decline lasting several hours. This steep decline, together with detailed spectral properties of two particular bursts, shows that violent shock interactions take place in the early jet outflows.

TeV neutrinos from successful and choked gamma-ray bursts.

Core collapse of massive stars resulting in a relativistic fireball jet which breaks through the stellar envelope is a widely discussed scenario for gamma-ray burst production. For very extended or slow rotating stars, the jet may be unable to break through the envelope. Both penetrating and choked jets will produce, by photomeson interactions of accelerated protons, a burst of greater, greater than or similar to 5 TeV neutrinos while propagating in the envelope. The predicted flux, from both penetrating and choked jets, should be easily detectable by planned 1 km(3) neutrino telescopes.

Gamma-Ray bursts: accumulating afterglow implications, progenitor clues, and prospects.

Gamma-ray bursts (GRBs) are sudden, intense flashes of gamma rays that, for a few blinding seconds, light up in an otherwise fairly dark gamma-ray sky. They are detected at the rate of about once a day, and while they are on, they outshine every other gamma-ray source in the sky, including the sun. Major advances have been made in the last 3 or 4 years, including the discovery of slowly fading x-ray, optical, and radio afterglows of GRBs, the identification of host galaxies at cosmological distances, and evidence showing that many GRBs are associated with star-forming regions and possibly supernovae. Progress has been made in understanding how the GRB and afterglow radiation arises in terms of a relativistic fireball shock model. These advances have opened new vistas and questions on the nature of the central engine, the identity of their progenitors, the effects of the environment, and their possible gravitational wave, cosmic ray, and neutrino luminosity. The debates on these issues indicate that GRBs remain among the most mysterious puzzles in astrophysics.

Observation of X-ray lines from a gamma-ray burst (GRB991216): evidence of moving ejecta from the progenitor.

We report on the discovery of two emission features observed in the x-ray spectrum of the afterglow of the gamma-ray burst (GRB) of 16 December 1999 by the Chandra X-ray Observatory. These features are identified with the Ly(alpha) line and the narrow recombination continuum by hydrogenic ions of iron at a redshift z = 1.00 +/- 0.02, providing an unambiguous measurement of the distance of a GRB. Line width and intensity imply that the progenitor of the GRB was a massive star system that ejected, before the GRB event, a quantity of iron approximately 0.01 of the mass of the sun at a velocity approximately 0.1 of the speed of light, probably by a supernova explosion.

5-10 GeV neutrinos from gamma-Ray burst fireballs

A gamma-ray burst fireball is likely to contain an admixture of neutrons. Inelastic collisions between differentially streaming protons and neutrons in the fireball produce nu(&mgr;) (nu;(&mgr;)) of approximately 10 GeV as well as nu(e) (nu;(e)) of approximately 5 GeV, which could produce approximately 7 events/year in km(3) detectors, if the neutron abundance is comparable to that of protons. Photons of approximately 10 GeV from pi(0) decay and approximately 100 MeV nu;(e) from neutron decay are also produced, but will be difficult to detect. Photons with energies less, similar1 MeV from shocks following neutron decay produce a characteristic signal which may be distinguishable from the proton-related MeV photons.

Impulsive and Varying Injection in Gamma-Ray Burst Afterglows.

The standard model of gamma-ray burst afterglows is based on synchrotron radiation from a blast wave produced when the relativistic ejecta encounters the surrounding medium. We reanalyze the refreshed shock scenario, in which slower material catches up with the decelerating ejecta and reenergizes it. This energization can be done either continuously or in discrete episodes. We show that such a scenario has two important implications. First, there is an additional component coming from the reverse shock that goes into the energizing ejecta. This persists for as long as the reenergization itself, which could extend for up to days or longer. We find that during this time the overall spectral peak is found at the characteristic frequency of the reverse shock. Second, if the injection is continuous, the dynamics will be different from that in constant energy evolution and will cause a slower decline of the observed fluxes. A simple test of the continuously refreshed scenario is that it predicts a spectral maximum in the far-infrared or millimeter range after a few days.

Radioimmunoguided surgery with different iodine-125 radiolabeled monoclonal antibodies in recurrent colorectal cancer.

Sixty-four patients with recurrent or metastatic colorectal cancer underwent radioimmunoguided surgery (RIGS). Thirty patients (Group A) were preoperatively injected with radiolabeled monoclonal antibody (MAb) B72.3, a whole IgG1 that reacts with tumor-associated glycoprotein (TAG-72) antigen. Thirty-four patients (Group B) were given monoclonal antibody FO23C5, an F(ab')2 which reacts with the carcinoembryonic antigen (CEA). The use of F(ab')2 antibodies ensured a lower time interval from the preoperative injection of the radiolabeled MAb to surgery. This interval was 22.7 days for Group A patients and 10.9 days for Group B patients. The correct RIGS identification of tumor sites occurred in 80.4% of Group A patients and in 92.6% of Group B patients. Additional information capable of modifying surgical strategy was obtained in 23.3% of Group A patients and in 8.8% of Group B patients. This difference was due to the different patterns of biodistribution and pharmacokinetics of the two MAbs. Although FO23C5 yields an improved diagnostic resolution for macroscopic tumor sites, we believe that B72.3 or other whole IgG1 should be the first choice for RIGS in recurrent or metastatic colorectal cancer patients.