Preliminary results of a program for the implementation of laparoscopic colorectal surgery in an Italian comprehensive cancer center during the COVID-19 pandemic.

Despite operative benefit and oncological non-inferiority, videolaparoscopic (VLS) colorectal surgery is still relatively underutilized. This study analyzes the results of a program for the implementation of VLS colorectal surgery started in an Italian comprehensive cancer center shortly before COVID-19 outbreak. A prospective database was reviewed. The study period was divided in four phases: Phase-1 (Open surgery), Phase-2 (Discretional phase), Phase-3 (VLS implementation phase), and Phase-4 (VLS consolidation phase). Formal surgical and perioperative protocols were adopted from Phase-3. Postoperative complications were scored by the Clavien-Dindo classification. 414 surgical procedures were performed during Phase-1, 348 during Phase-2, 360 during Phase-3, and 325 during Phase-4. In the four phases, VLS primary colorectal resections increased from 11/214 (5.1%), to 55/163 (33.7%), 85/151 (57.0%), and 109/147 (74.1%), respectively. The difference was statistically significant (P < 0.001). All-type VLS procedures were 16 (3.5%), 61 (16.2%), 103 (27.0%), and 126 (38.6%) (P < 0.001). Conversions to open surgery of attempted laparoscopic colorectal resections were 17/278 in the overall series (6.1%), and 12/207 during Phase-3 and Phase-4 (4.3%). Severe (grades IIIb-to-V) postoperative complications of VLS colorectal resections were 9.1% in Phase-1, 12.7% in Phase-2, 12.8% in Phase-3, and 5.3% in Phase-4 (P = 0.677), with no significant differences with open resections in each of the four phases: 9.4% (P = 0.976), 11.1% (P = 0.799), 13.8% (P = 1.000), and 8.3% (P = 0.729). Despite the difficulties deriving from the COVID-19 outbreak, our experience suggests that volume of laparoscopic colorectal surgery can be significantly and safely increased in a specialized surgical unit by means of strict operative protocols.

Forward modeling of pile-up events in liquid scintillator detectors for neutron emission spectroscopy.

When using liquid scintillator detectors to measure the neutron emission spectrum from fusion plasmas, the problem of pile-up distortion can be significant. Because of the large neutron rates encountered in many fusion experiments, some pile-up distortion can remain even after applying traditional pile-up elimination methods, which alters the shape of the measured light-yield spectrum and influences the spectroscopic analysis. Particularly, pile-up events appear as a high-energy tail in the measured light-yield spectrum, which obfuscates the contribution that supra-thermal ions make to the energy spectrum. It is important to understand the behavior of such "fast ions" in fusion plasmas, and it is hence desirable to be able to measure their contribution to the neutron spectrum as accurately as possible. This paper presents a technique for incorporating distortion from undetected pile-up events into the analysis of the light-yield spectrum, hence compensating for pile-up distortion. The spectral contribution from undetected pile-up events is determined using Monte Carlo methods and is included in the spectroscopic study as a pile-up component. The method is applied to data from an NE213 scintillator detector at JET and validated by comparing with results from the time-of-flight spectrometer TOFOR, which is not susceptible to pile-up distortion. Based on the results, we conclude that the suggested analysis method helps counteract the problem of pile-up effects and improves the possibilities for extracting accurate fast-ion information from the light-yield spectrum.

JET diagnostic enhancements testing and commissioning in preparation for DT scientific campaigns.

In order to optimize the scientific exploitation of JET (Joint European Torus) during the upcoming deuterium-tritium experiments, a set of diagnostic systems is being enhanced. These upgrades focus mainly on the experimental and operational conditions expected during tritium campaigns. It should be stressed that measurements relevant for burning plasmas are specifically targeted. Previously non-available capabilities, such as a current measurement system fully covering all poloidal field circuits, are described in detail. Instrument descriptions, performance prediction, testing, and initial commissioning results of these systems are presented.

Neutron emission spectroscopy of D plasmas at JET with a compact liquid scintillating neutron spectrometer.

Neutron emission spectroscopy is a diagnostic technique that allows for energy measurements of neutrons born in nuclear reactions. The JET tokamak fusion experiment (Culham, UK) has a special role in this respect as advanced spectrometers for 2.5 MeV and 14 MeV neutrons have been developed here for the first time for measurements of the neutron emission spectrum from D and DT plasmas with unprecedented accuracy. Twin liquid scintillating neutron spectrometers were built and calibrated at the Physikalisch-Technische Bundesanstalt (PTB) (Braunschweig, Germany) and installed on JET in the recent years with tangential-equatorial (KM12) and vertical-radial (KM13) view lines, with the latter only recently operational. This article reports on the performance of KM12 and on the development of the data analysis methods in order to extract physics information upon D ions kinematics in JET auxiliary-heated D plasmas from 2.5 MeV neutron measurements. The comparison of these results with the correspondents from other JET neutron spectrometers is also presented: their agreement allows for JET unique capability of multi-lines of sight neutron spectroscopy and for benchmarking other 14 MeV neutron spectrometers installed on the same lines of sight in preparation for the DT experimental campaign at JET.

Extremely broadband single-shot cross-correlation frequency-resolved optical gating using a transient grating as gate and dispersive element.

A cross-correlation frequency-resolved optical gating (FROG) concept, potentially suitable for characterizing few or sub-cycle pulses in a single shot, is described in which a counter-propagating transient grating is used as both the gate and the dispersive element in a FROG spectrometer. An all-reflective setup, which can operate over the whole transmission range of the nonlinear medium, within the sensitivity range of the matrix sensor, is also proposed, and proof-of-principle experiments for the ultraviolet and visible-to-near-infrared spectral ranges are reported.

First neutron spectroscopy measurements with a pixelated diamond detector at JET.

A prototype Single crystal Diamond Detector (SDD) was installed at the Joint European Torus (JET) in 2013 along an oblique line of sight and demonstrated the possibility to carry out neutron spectroscopy measurements with good energy resolution and detector stability in discharges heated by neutral beam injection and radio-frequency waves. Starting from these positive results, within the Vertical Neutron Spectrometer project of the Joint European Torus, we have developed a pixelated instrument consisting of a matrix of 12 independent SDDs, called the Diamond Vertical Neutron Spectrometer (DVNS), which boosts the detection efficiency of a single SDD by an order of magnitude. In this paper we describe the main features of the DVNS, including the detector design, energy resolution, and data acquisition system for on-line processing. Preliminary spectroscopy measurements of 2.5 MeV neutrons from the present deuterium plasma at JET are finally presented.

JET diagnostic enhancements in preparation for DT operations.

In order to complete the exploitation of the JET ITER-like Wall and to take full benefit from deuterium-tritium experiments on JET, a set of diagnostic system refurbishments or upgrades is in progress. These diagnostic enhancements focus mainly on neutron, gamma, fast ions, instabilities, and operations support. These efforts intend to provide better spatial, temporal, and energy resolution while increasing measurement coverage. Also previously non-existing capabilities, such as Doppler reflectometry is now available for scientific exploitation. Guaranteeing diagnostic reliability and consistency during the expected DT conditions is also a critical objective of the work and systems being implemented. An overview of status and scope of the ongoing projects is presented.

Generation of three-octave-spanning transient Raman comb in hydrogen-filled hollow-core PCF.

A noise-seeded transient comb of Raman sidebands spanning three octaves from 180 to 2400 nm, is generated by pumping a hydrogen-filled hollow-core photonic crystal fiber with 26-µJ, 300-fs pulses at 800 nm. The pump pulses are spectrally broadened by both Kerr and Raman-related self-phase modulation (SPM), and the broadening is then transferred to the Raman lines. In spite of the high intensity, and in contrast to bulk gas-cell based experiments, neither SPM broadening nor ionization are detrimental to comb formation.

Contribution of germline mutations in the BRCA and PALB2 genes to pancreatic cancer in Italy.

Pancreatic adenocarcinoma (PC) is the third most common cancer associated with BRCA mutations. Most notice has been given to BRCA2, while the association between BRCA1 and PC is less widely reported. Recently, PALB2 has been implicated in both PC and breast cancer (BC) susceptibility. We selected 29 Italian PC patients from a case-control study of PC according to their personal and family history of both PC and breast/ovarian cancer (BC/OC) and tested them for presence of germline mutations in BRCA1, BRCA2 and PALB2. We identified no germline mutations or deletions in PALB2, but detected 7 BRCA mutations (4 in BRCA1 and 3 in BRCA2). These findings suggest that PALB2 does not play a major role in PC susceptibility in our population. As we found an almost equal frequency of germline mutations in BRCA1 and BRCA2, germline alterations in either of these genes may explain a subset of Italian families presenting both PC and BC/OC. Moreover, as we began the observation of these families from probands who are affected by PC, we provide here a direct assessment of the role of PALB2 and BRCA mutations in PC susceptibility.

Consensus conference on laparoscopic appendectomy: development of guidelines.

AIM: Laparoscopic appendectomy (LA) is not yet unanimously considered the gold standard treatment for appendicitis, despite the increasing use of advanced laparoscopic operations and the high incidence of the disease. METHOD: Due to the results of an audit which classified LA as widespread in Italy, a Consensus Conference was organized, in order to give evidence-based answers to the most debated problems regarding the operation. After researching the literature, a panel of 20 experts were selected and interviewed on hot topics; a subsequent discussion using the Delphi methodology was utilized in the course of the consensus conference and submitted to the evaluation of an audience of surgeons. RESULTS: Checkpoint statements were formulated whenever an agreement was reached. A level of evidence was then assigned to single statements and the process revised by two external reviewers. CONCLUSION: Consensus development guidelines are herein reported and regard diagnostic pathway, diagnostic laparoscopy, indications, behaviour in case of innocent appendix, technical aspects, learning curve; however, some questions remain unsolved due to the lack of evidence.

Melanoma of the anorectal region: the experience of the National Cancer Institute of Milano.

AIMS: This study describes the experience of the National Cancer Institute of Milano in the treatment of anorectal melanoma over the last 32 years. METHODS: The influence of different surgical approaches on local care and final outcome was investigated on 40 completely evaluable patients, followed for a median follow-up time of 75 months. The analysis was carried out by calculating and comparing overall survival, disease-free survival and cumulative incidence curves of disease recurrence. RESULTS: Thirty-one patients underwent radical surgery: nine abdominoperineal resections, four total rectal resections and coloendoanal anastomosis, and 18 local excisions. The remaining nine patients received palliative treatments. Median overall survival time for patients receiving non-radical treatments was poor: only 6 months. However, even when a radical surgery was undergone, the prognosis of patients with anal melanoma remains dismal. Local relapse incidence was 45.8% for the limited surgery group, but non-existent for the extended-surgery group (p = 0.007). However, the median disease-free survival time was 7 and 9 months for patients receiving limited or major surgery (p = 0.97). Overall survival was 17 months, irrespective of the adopted surgery. CONCLUSION: Prognosis of anal melanoma remains poor. Final outcome is not influenced by modality of surgery. A limited but radical excision can be considered whenever possible while a major demolitive surgery should be applied only for therapy of advanced or bulky lesions.

Weekly epirubicin plus docetaxel as first-line treatment in metastatic breast cancer.

This study was designed to evaluate the efficacy and tolerability of a weekly schedule of epirubicin in combination with docetaxel in the first-line treatment of patients with metastatic breast cancer (MBC). A total of 43 women with MBC not previously treated with chemotherapy for metastatic disease received weekly epirubicin 25 mg m(-2) and docetaxel 25 mg m(-2) for a maximum of five cycles (total cumulative epirubicin dose of < or =900 mg m(-2)). Dose reduction was not permitted. Objective response and evaluation of toxicity profile were the primary study end points; time to progression and overall survival were secondary end points. Patients were followed for a median of 21 (4-38) months. Analysis was by intent to treat; 33 patients completed five cycles of therapy, and the median dose of epirubicin administered to the 43 patients was 23 mg m(-2). Twenty-five patients (58%) achieved a partial response and one (2%) achieved a complete response. An additional 12 patients (28%) had stable disease. The median time to progression was 11 months (95% confidence intervals (CI) 7-14) overall, and 13 months (95% CI 12-14) in the 26 patients who responded to treatment. Median overall survival was 25 months for responders and 14 months for nonresponders. Grade 3/4 neutropenia occurred in 16% of patients and in 6% of cycles. One patient developed cardiac toxicity (20% reduction in left ventricular ejection fraction). The combination of epirubicin plus docetaxel is highly active in MBC, with a manageable toxicity profile. Such a weekly schedule might provide a valuable treatment option for MBC.

Polyketone polymer: a new support for direct enzyme immobilization.

Polyketone polymer -[-CO-CH(2)-CH(2)-](n)-, obtained by copolymerization of ethene and carbon monoxide, is utilized for immobilization of three different enzymes, one peroxidase from horseradish (HRP) and two amine oxidases, from bovine serum (BSAO) and lentil seedlings (LSAO). The easy immobilization procedure is carried out in diluted buffer, at pH 7.0 and 3 degrees C, gently mixing the proteins with the polymer. No bifunctional reagents and spacer arms are required for the immobilization, which occurs exclusively via a large number of hydrogen bonds between the carbonyl groups of the polymer and the -NH groups of the polypeptidic chain. Experiments demonstrate a high linking capacity of polymer for BSAO and an extraordinary strong linkage for LSAO. Moreover, activity measurements demonstrate that immobilized LSAO totally retains the catalytic characteristics of the free enzyme, where only a limited increase of K(M) value is observed. Finally, the HRP-activated polymer is successfully used as active packed bed of an enzymatic reactor for continuous flow conversion and flow injection analysis of hydrogen peroxide containing solutions.

Epirubicin, cisplatin and docetaxel combination therapy for metastatic gastric cancer.

BACKGROUND: Docetaxel is a new agent with activity in metastatic gastric cancer. This phase II study was designed to evaluate the activity and safety of an epirubicin, cisplatin and docetaxel combination in patients with this disease. PATIENTS AND METHODS: Forty-six patients with gastric adenocarcinoma with measurable distant metastasis were eligible for the study. Patients received epirubicin 50 mg/m(2) and docetaxel 60 mg/m(2), on day 1, and cisplatin 60 mg/m(2) on day 2. Granulocyte colony-stimulating factor 300 mug/day subcutaneously was given on days 5 and 6. Cycles were repeated every 3 weeks for a maximum of eight courses. RESULTS: All patients were evaluable for response and toxicity. Two complete and 21 partial responses were observed, with an overall response rate of 50% [95% confidence interval (CI) 36% to 64%]. Stable disease was observed in 13 patients (28%) and progressive disease in 10 patients (22%). The median time to progression was 6 months (95% CI 5-7) and the median overall survival was 11.2 months (95% CI 8.5-13.9). Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 46%, 7% and 13% of patients, respectively. There were five episodes of febrile neutropenia in four patients. Other grade 3 toxicities included mucositis in three patients (6.5%), vomiting in four patients (8.7%) and diarrhea in one patient (2%). There were no cardiac toxicity, severe neurotoxicity or treatment-related deaths. CONCLUSIONS: The epirubicin, cisplatin and docetaxel combination is an active and well tolerated novel chemotherapy regimen for treating metastatic gastric cancer and deserves further evaluation in randomized studies.

The biological functions of polyamine oxidation products by amine oxidases: perspectives of clinical applications.

The polyamines spermine, spermidine and putrescine are ubiquitous cell components. If they accumulate excessively within the cells, due either to very high extracellular concentrations or to deregulation of the systems which control polyamine homeostasis, they can induce toxic effects. These molecules are substrates of a class of enzymes that includes monoamine oxidases, diamine oxidases, polyamine oxidases and copper containing amine oxidases. Polyamine concentrations are high in growing tissues such as tumors. Amine oxidases are important because they contribute to regulate levels of mono- and polyamines. These enzymes catalyze the oxidative deamination of biogenic amines and polyamines to generate the reaction products H2O2 and aldehyde(s) that are able to induce cell death in several cultured human tumor cell lines. H2O2 generated by the oxidation reaction is able to cross the inner membrane of mitochondria and directly interact with endogenous molecules and structures, inducing an intense oxidative stress. Since amine oxidases are involved in many crucial physiopathological processes, investigations on their involvement in human diseases offer great opportunities to enter novel classes of therapeutic agents.

Effects of heavy ions on visual function and electrophysiology of rodents: the ALTEA-MICE project.

ALTEA-MICE will supplement the ALTEA project on astronauts and provide information on the functional visual impairment possibly induced by heavy ions during prolonged operations in microgravity. Goals of ALTEA-MICE are: (1) to investigate the effects of heavy ions on the visual system of normal and mutant mice with retinal defects; (2) to define reliable experimental conditions for space research; and (3) to develop animal models to study the physiological consequences of space travels on humans. Remotely controlled mouse setup, applied electrophysiological recording methods, remote particle monitoring, and experimental procedures were developed and tested. The project has proved feasible under laboratory-controlled conditions comparable in important aspects to those of astronauts' exposure to particle in space. Experiments are performed at the Brookhaven National Laboratories [BNL] (Upton, NY, USA) and the Gesellschaft für Schwerionenforschung mbH [GSI]/Biophysik (Darmstadt, FRG) to identify possible electrophysiological changes and/or activation of protective mechanisms in response to pulsed radiation. Offline data analyses are in progress and observations are still anecdotal. Electrophysiological changes after pulsed radiation are within the limits of spontaneous variability under anesthesia, with only indirect evidence of possible retinal/cortical responses. Immunostaining showed changes (e.g. increased expression of FGF2 protein in the outer nuclear layer) suggesting a retinal stress reaction to high-energy particles of potential relevance in space.