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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

[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.

Radioimmunoguided surgery after primary treatment of locally advanced breast cancer.

PURPOSE: To assess the role of radioimmunoguided surgery (RIGS) using a handheld intraoperative gamma-detecting probe (GDP) to identify neoplastic disease after primary chemotherapy in locally advanced breast cancer (LABC) patients injected with iodine 125-labeled monoclonal antibodies (MAbs). PATIENTS AND METHODS: Twenty-one patients with histologically documented LABC were treated with a combined modality approach. After three courses of primary chemotherapy and before modified radical mastectomy, the 125I-radiolabeled MAbs B72.3 (anti-TAG72) and FO23C5 (anti-carcinoembryonic antigen [CEA]) were administered to 11 patients (group A) and 10 patients (group B), respectively. At surgery, a GDP was used to locate the primary tumor and to assess possible tumor multicentricity and the presence of ipsilateral axillary metastases. Routine pathologic examination was performed in neoplastic and normal tissue specimens of all 21 patients. In addition, immunohistochemical assay for TAG72 and CEA expression was performed. RESULTS: In group A patients, RIGS identified primary tumor in seven of 11 patients (63.3%) and unpalpable multicentric tumor lesions were located in two of four (50%). Positive axillary lymph nodes were histologically documented in eight of 11 patients (72.7%) and RIGS identified three of eight (37.5%). In group B, RIGS located the primary tumor lesion in four of 10 patients (40%); in two cases, the tumor was not clinically evident. Multicentricity was observed in one of two patients and lymph node involvement in three of nine (33.3%). No false-positive results were observed in either group A or B. CONCLUSION: RIGS appears to be a safe and reliable technique. However, the MAbs used in this study are not sufficiently specific. RIGS represents a technique for which the full potential for intraoperative assessment of breast cancer lesions can be reached when more specific antibodies become readily available.

Hand-foot syndrome induced by high-dose, short-term, continuous 5-fluorouracil infusion.

The aim of this study was to examine in detail the incidence and severity of hand-foot syndrome in advanced colorectal cancer patients receiving 5-fluorouracil (5-FU) and leucovorin (L-LV) chemotherapy. 70 advanced colorectal cancer patients (pts) were given weekly 24 h continuous 5-FU (2600 mg/m2) infusion plus L-LV (100 mg/m2 i.v., 50 mg orally). The toxicity, in particular HFS, was analysed, correlated to the main pts characteristics and compared to the other observed side-effects. HFS occurred in 36/70 pts (51%): grade 1 in 16 pts, grade 2 in 16 pts, grade 3 in 3 pts and grade 4 in 1 pt. It occurred after a median number of nine courses. In one case, chemotherapy was interrupted for this toxicity, and in another 5 pts drug reduction and/or treatment delay were undertaken. Changes in the therapeutic programme because of diarrhoea or mucositis were more frequent, even though these toxicities were generally mild in our series of pts. HFS was significantly correlated to previous exposure to chemotherapy (P = 0.00003). HFS was a frequent side-effect of high-dose, short-term continuous 5-FU infusion, but the impact on quality of life of pts and on the correct delivery of the planned chemotherapy was limited.

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.

Long-term femoral vein central venous access in cancer patients.

Subclavian percutaneous access with reservoir placement has been shown to be difficult or contraindicated in some patients. Of 465 cancer patients who required a port placement between January 1992 to January 1995, 41 (8.8%) had alternative percutaneous femoral access with a totally implantable port reservoir located in the abdomen because of the inaccessibility to subclavian or jugular veins and/or the presence of massive cutaneous metastases or severe radiodermitis in the upper part of the torso. Overall implant days was 9880, with an average of 241 days (range: 65-445). Ports were alternatively used for chemotherapy and nutritional purposes in 11 of 41 patients. Late morbidity causing the removal of the implanted ports was observed in two of 41 (4.9%) and 25 of 424 (5.9%) patients in the femoral and subclavian series, respectively (P = 0.86). The femoral percutaneous access for totally implantable port devices appears to be a safe alternative for cancer patients when subclavian and/or jugular vein catheterization and reservoir in the upper part of the torso is contraindicated.

Mandible reconstruction with metallic endoprosthesis following Commando's operation for advanced head and neck cancer. Personal experience.

Invasion of the mandible is found in 22% to 29% of advanced (Stage III-IV) head and neck cancers; only an aggressive surgical technique, such as Commando's operation with subsequent reconstruction of tissue defects, can give a chance of cure to these patients. The reconstruction is feasible both by means of microsurgical free-tissue transfers or with alloplastic materials and myocutaneous flaps. Between 1982 and 1991, 34 patients in Stage III (n = 6; 17.7%) and IV (n = 28; 82.3%) head and neck cancers underwent Commando's operation with different types of reconstruction in 30 patients: pectoralis myocutaneous flap (n = 9), osteo-myocutaneous flap with the underlying segment of the fifth rib (n = 2), myocutaneous flap plus prosthesis (n = 17), or prosthesis alone (n = 2). Two different prostheses were implanted: the linear A-O mandibular reconstruction plate (n = 13), and the Dumbach titanium cage (n = 6). In the group of patients in which the linear A-O mandibular reconstruction plate was used there were four cases of prosthesis dislodgement and major exposure and one case of prosthesis breakage while in patients who were given the Dumbach titanium cage there were four cases of major exposure. Prosthesis removal was required in five and two patients with linear A-O and Dumbach titanium cage prosthesis, respectively. Median survival was 14 months with 28% five-year survival. In our experience, metallic prostheses with a shape and arrangement that allow a distribution of traction forces on a wider surface, with screws drilled in nonaligned points of the mandible, seem to be more reliable as they reduce the risk of dislodgement and breakage.

[Cell kinetic analysis and treatment planning in epidermoid tumors of the head and neck]. / Test di cinetica cellulare e pianificazione dei trattamenti dei tumori epidermoidali del capo e del collo.

Cell kinetic parameters were evaluated using the method based on in vivo incorporation of Bromodeoxyuridine (BrdU) and flow cytometric (FCM) analysis in 30 human epidermoid head and neck tumors from oropharynx, oral cavity, rhinopharynx, larynx and lips. BrdU was injected four/six hours before the obtainment of multiple bioptic samples from the tumor tissues. The flow cytometric method was carried out on 70% ethanol fixed cell suspensions based on established protocol for the simultaneous evaluation of DNA content and BrdU uptake using anti-BrdU monoclonal antibodies. We have evaluated the following FCM parameters: DNA ploidy, the degree of DNA aneuploidy (DNA index), Labelling Index (LI), duration of s-phase (Ts) and tumor potential doubling time (Tpot). LI values ranged from 1.5 to 20% with a median value of 10%. The median LI of DNA diploid tumors was 5.4% compared to 14% in DNA aneuploid tumors. Ts values ranged from 8 to 11, the median value being 10 hours. Tpot values ranged from 2 days to 16 days, the median Tpot being 5 days. The large heterogeneity of all these parameters indicates that these tumors may have a different degree of biologic aggressiveness (9). Tpot values did not correlate with DNA ploidy nor with lymph node metastasis status. Tpot values did not correlate in a statistically significant manner with degree of differentiation although shorter Tpot were more frequently observed in moderate or poorly differentiated tumors. Our study shows that the FCM-BrdU technique in vivo is feasible in a clinical setting to evaluate the proliferative behaviour of head and neck tumors, before any specific therapeutic decision is taken after surgery is performed. It is likely that tumors with more aggressive biological behavior, as indicated by LI > 15%, DNA aneuploidy and Tpot < 5 days, may benefit from more aggressive therapies such as accelerated regimeus of radiotherapy and/or other multimodal therapies in respect to tumors with slow growth rate (LI < 15%), DNA diploidy and Tpot > 5 days. So far, however, it still remains to be demonstrated from randomized clinical trials if the knowledge of such individualized cell Kinetic parameters really can help to choose the most effective therapy for every individual patient.

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.