Registry-derived stage (RD-Stage) for capturing cancer stage at diagnosis for endometrial cancer.

BACKGROUND: Capture of cancer stage at diagnosis is important yet poorly reported by health services to population-based cancer registries. In this paper we describe current completeness of stage information for endometrial cancer available in Australian cancer registries; and develop and validate a set of rules to enable cancer registry medical coders to calculate stage using data available to them (registry-derived stage or 'RD-Stage'). METHODOLOGY: Rules for deriving RD-stage (Endometrial carcinoma) were developed using the American Joint Commission on Cancer (AJCC) TNM (tumour, nodes, metastasis) Staging System (8th Edition). An expert working group comprising cancer specialists responsible for delivering cancer care, epidemiologists and medical coders reviewed and endorsed the rules. Baseline completeness of data fields required to calculate RD-Stage, and calculation of the proportion of cases for whom an RD stage could be assigned, was assessed across each Australian jurisdiction. RD-Stage (Endometrial cancer) was calculated by Victorian Cancer Registry (VCR) medical coders and compared with clinical stage recorded by the patient's treating clinician and captured in the National Gynae-Oncology Registry (NGOR). RESULTS: The necessary data completeness level for calculating RD-Stage (Endometrial carcinoma) across various Australian jurisdictions varied from 0 to 89%. Three jurisdictions captured degree of spread of cancer, rendering RD-Stage unable to be calculated. RD-Stage (Endometrial carcinoma) could not be derived for 64/485 (13%) cases and was not captured for 44/485 (9%) cases in NGOR. At stage category level (I, II, III, IV), there was concordance between RD-Stage and NGOR captured stage in 393/410 (96%) of cases (95.8%, Kendall's coefficient = 0.95). CONCLUSION: A lack of consistency in data captured by, and data sources reporting to, population-based cancer registries meant that it was not possible to provide national endometrial carcinoma stage data at diagnosis. In a sample of Victorian cases, where surgical pathology was available, there was very good concordance between RD-Stage (Endometrial carcinoma) and clinician-recorded stage data available from NGOR. RD-Stage offers promise in capturing endometrial cancer stage at diagnosis for population epidemiological purposes when it is not provided by health services, but requires more extensive validation.

Correlation between physical activity, nutritional intake, and osteoporosis in postmenopausal women: a preliminary evaluation.

OBJECTIVE: Osteoporosis is a chronic metabolic syndrome associated with debilitating consequences that represents one of the major non-communicable diseases and the most common bone illness that affects both men and women. This observational study evaluates the amount of physical activity and the nutritional intake in a group of postmenopausal women who have a sedentary job. PATIENTS AND METHODS: All subjects underwent a medical evaluation, a body impedance analysis to evaluate body composition (fat mass, fat-free mass, and body cell mass), and a dual-energy X-ray absorptiometry to analyze bone mineral density. Additionally, a 3-day food record questionnaire and the International Physical Activity Questionnaire were administered respectively to evaluate patients' foods and beverages assumptions and the participants' Physical Activity levels. RESULTS: The study showed that most of the patients had a moderate activity level and inadequate calcium and vitamin D assumption compared to guidelines. CONCLUSIONS: The onset of osteoporosis seemed to be reduced at higher levels of leisure time, domestic, and transport activities, even in subjects who have a sedentary job and insufficient assumption of micronutrients.

Neuromuscular and cardiac adverse events associated with immune checkpoint inhibitors: pooled analysis of individual cases from multiple institutions and literature.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of multiple tumors, due to improved efficacy, quality of life, and safety. While most immune-related adverse events (irAEs) are mild and easily managed, in rare cases such events may be life-threatening, especially those affecting the neuromuscular and cardiac system. The management of neuromuscular/cardiac irAEs is not clear due to the lack of consistent data. Therefore, we carried out a pooled analysis of collected cases from selected Italian centers and individual data from published case reports and case series, in order to improve our understanding of these irAEs. PATIENTS AND METHODS: We collected retrospective data from patients treated in six Italian centers with ICIs (programmed cell death protein 1 or programmed death-ligand 1 and/or cytotoxic T-lymphocyte antigen 4 inhibitor) for any solid tumor who experienced neuromuscular and/or cardiovascular toxicity. Then, we carried out a search of case reports and series of neuromuscular/cardiac irAEs from ICIs with any solid tumor. RESULTS: This analysis includes cases from Italian institutions (n = 18) and the case reports identified in our systematic literature search (n = 120), for a total of 138 patients. Among these patients, 50 (36.2%) had complete resolution of their neuromuscular/cardiac irAEs, in 21 (15.2%) cases there was a clinical improvement with mild sequelae, and 53 (38.4%) patients died as a result of the irAEs. Factors significantly associated with worse outcomes were early irAE onset, within the first two cycles of ICI (Fisher P < 0.0001), clinical manifestation of both myositis and myocarditis when compared with patients who developed only myositis or myocarditis (chi-square P = 0.0045), and the development of arrhythmia (Fisher P = 0.0070). CONCLUSIONS: To the best of our knowledge, this is the largest collection of individual cases of immune-related myocarditis/myositis. Early irAE onset, concurrent development of myositis and myocarditis, as well as occurrence of arrhythmias are associated with worse outcomes and should encourage an aggressive immunomodulatory treatment.

Clinical efficacy of sequential treatments in KRASG12C-mutant metastatic colorectal cancer: findings from a real-life multicenter Italian study (CRC-KR GOIM).

BACKGROUND: The presence of KRASG12C mutation in metastatic colorectal cancer (mCRC) correlates with poor outcome. Although different selective inhibitors are under clinical development, the optimal treatment remains uncertain. Thus, we conducted a retrospective analysis in a large cohort of patients with KRASG12C mCRC treated in 12 Italian oncology units. PATIENTS AND METHODS: Patients with unresectable mCRC harboring KRASG12C mutation receiving a first-line chemotherapy doublet or triplet between 2011 and 2021 were included in the study. Evaluation of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) analysis was carried out. RESULTS: A total of 256/6952 (3.7%) patients with mCRC displayed KRASG12C mutation; of these, 111 met the inclusion criteria. The ORR of first-line therapy was 38.7% (43/111). Median PFS (mPFS) was 9 months [95% confidence interval (CI) 7.5-10.5 months]. After progression, only 62% and 36% of the patients are fit to receive second or third lines of treatment, with limited clinical benefit. Median OS (mOS) was 21 months (95% CI 17.4-24.6 months). In patients receiving first-line triplet chemotherapy, ORR was 56.3% (9/16), mPFS was 13 months (95% CI 10.3-15.7 months) and mOS was 32 months (95% CI 7.7-56.3 months). For irinotecan-based doublets, ORR was 34.5 (10/29), mPFS was 9 months (95% CI 6.4-11.6 months) and mOS was 22 months (95% CI 16.0-28.0 months). With oxaliplatin-based doublets ORR was 36.4% (24/62), mPFS was 7 months (95% CI 4.6-9.4 months) and mOS was 18 months (95% CI, 13.6-22.4 months). CONCLUSION: Patients with KRASG12C-mutant mCRC had a disappointing response to standard treatments. Within the limitations of a retrospective study, these results suggest that first-line chemotherapy intensification with FOLFOXIRI is a valid option in fit patients.

Encorafenib plus cetuximab with or without binimetinib in patients with BRAF V600E-mutated metastatic colorectal cancer: real-life data from an Italian multicenter experience.

BACKGROUND: Encorafenib plus cetuximab with or without binimetinib showed increased objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared with chemotherapy plus anti-EGFR in previously treated patients with BRAF V600E-mutated (mut) metastatic colorectal cancer (mCRC). Although no formal comparison was planned, addition of binimetinib to encorafenib plus cetuximab did not provide significant efficacy advantage. PATIENTS AND METHODS: This real-life study was aimed at evaluating safety, activity, and efficacy of encorafenib plus cetuximab with or without binimetinib in patients with BRAF V600E-mut mCRC treated at 21 Italian centers within a nominal use program launched in May 2019. RESULTS: Out of 133 patients included, 97 (73%) received encorafenib plus cetuximab (targeted doublet) and 36 (27%) the same therapy plus binimetinib (targeted triplet). Most patients had Eastern Cooperative Group Performance Status (ECOG-PS) of 0 or 1 (86%), right-sided primary tumor (69%), and synchronous disease (66%). Twenty (15%) tumors were DNA mismatch repair deficiency (dMMR)/microsatellite instability (MSI)-high. As many as 44 (34%) patients had received two or more prior lines of therapy, 122 (92%) were previously exposed to oxaliplatin, and 109 (82%) to anti-vascular endothelial growth factor (anti-VEGF). Most frequent adverse events were asthenia (62%) and anti-EGFR-related skin rash (52%). Any grade nausea (P = 0.03), vomiting (P = 0.04), and diarrhea (P = 0.07) were more frequent with the triplet therapy, while melanocytic nevi were less common (P = 0.06). Overall, ORR and disease control rate (DCR) were 23% and 69%, respectively, with numerically higher rates in the triplet group (ORR 31% versus 17%, P = 0.12; DCR 78% versus 65%, P = 0.23). Median PFS and OS were 4.5 and 7.2 months, respectively. Worse ECOG-PS, peritoneal metastases, and more than one prior treatment were independent poor prognostic factors for PFS and OS. Clonality of BRAF mutation measured as adjusted mutant allele fraction in tumor tissue was not associated with clinical outcome. CONCLUSIONS: Our real-life data are consistent with those from the BEACON trial in terms of safety, activity, and efficacy. Patients in good general condition and not heavily pretreated are those more likely to derive benefit from the targeted treatment.

Indocyanine green fluorescence angiography versus standard intraoperative methods for prevention of anastomotic leak in colorectal surgery: meta-analysis.

BACKGROUND: Assessment of anastomotic blood perfusion with intraoperative indocyanine green fluorescence angiography (ICG-FA) may be effective in preventing anastomotic leak compared with standard intraoperative methods in colorectal surgery. METHODS: MEDLINE, PubMed, Cochrane Central Register of Controlled Trials and the Cochrane Library were searched for RCTs and observational studies on intraoperative ICG-FA to May 2020. Odds ratios (ORs), risk differences and mean differences (MDs) were calculated with 95 per cent c.i. based on intention-to-treat analysis. The number needed to treat for an additional beneficial outcome was also estimated. RESULTS: Twenty-five comparative studies included a total of 7735 patients. The use of intraoperative ICG fluorescence angiography was linked with a significant reduction in all grades anastomotic leak (OR 0.39 (95 per cent c.i. 0.31 to 0.49), P < 0.001; number needed to treat for an additional beneficial outcome (NNTB) 23) and length of hospital stay (MD -0.72 (95 per cent c.i. -1.22 to -0.21) days, P = 0.006). A significantly lower incidence of grade A (OR 0.33 (0.18 to 0.60), P < 0.001), grade B (OR 0.58 (0.35 to 0.97), P = 0.04) and grade C (OR 0.59 (0.38 to 0.92), P = 0.02) anastomotic leak was demonstrated in favour of ICG-FA. For low or ultra-low rectal resection, the odds of developing anastomotic leakage was 0.32 (0.23 to 0.45) (P < 0.001; NNTB 14). There were no differences in duration of surgery, and no adverse events related to ICG fluorescent injection. CONCLUSION: The use of ICG-FA instead of standard intraoperative methods to assess anastomosis blood perfusion in colorectal surgery leads to a significant reduction in anastomotic leakage and in the need for surgical reintervention for anastomotic leak, especially in patients with low or ultra-low rectal resections.

Characterization of passive dosimeters in proton pencil beam scanning - A EURADOS intercomparison for mailed dosimetry audits in proton therapy centres.

The lack of mailed dosimetry audits of proton therapy centres in Europe has encouraged researchers of EURADOS Working Group 9 (WG9) to compare response of several existing passive detector systems in therapeutic pencil beam scanning. Alanine Electron Paramagnetic Resonance dosimetry systems from 3 different institutes (ISS, Italy; UH, Belgium and IFJ PAN, Poland), natLiF:Mg, Ti (MTS-N) and natLiF:Mg, Cu, P (MCP-N) thermoluminescent dosimeters (TLDs), GD-352M radiophotoluminescent glass dosimeters (RPLGDs) and Al2O3:C optically stimulated dosimeters (OSLDs) were evaluate. Dosimeter repeatability, batch reproducibility and response in therapeutic Pencil Beam Scanning were verified for implementation as mail auditing system. Alanine detectors demonstrated the lowest linear energy transfer (LET) dependence with an agreement between measured and treatment planning system (TPS) dose below 1%. The OSLDs measured on average a 6.3% lower dose compared to TPS calculation, with no significant difference between varying modulations and ranges. Both GD-352M and MCP-N measured a lower dose than the TPS and luminescent response was dependent on the LET of the therapeutic proton beam. Thermoluminescent response of MTS-N was also found to be dependent on the LET and a higher dose than TPS was measured with the most pronounced increase of 11%. As alanine detectors are characterized by the lowest energy dependence for different parameters of therapeutic pencil beam scanning they are suitable candidates for mail auditing in proton therapy. The response of luminescence detector systems have shown promises even though more careful calibration and corrections are needed for its implementation as part of a mailed dosimetry audit system.

Clinical and seminal parameters associated with testicular microlithiasis and its severity in males from infertile couples.

STUDY QUESTION: Is there an association of testicular microlithiasis (TM) and its severity with testicular dysfunction in men from infertile couples? SUMMARY ANSWER: The presence of ≥5 testis microcalcifications per sonogram at the scrotal ultrasonography (US) of infertile males was associated with a more severe testicular dysfunction as compared to males with limited, or without, TM. WHAT IS KNOWN ALREADY: TM, representing an incidental finding in the scrotal US, is associated with male infertility and a higher risk for testicular cancer as compared to that in infertile males without TM. Still, there are unresolved questions on the relation between TM severity and testicular dysfunction in infertile men, as well as on the identification of risk factors for TM. STUDY DESIGN, SIZE, DURATION: This study was an observational, retrospective, case-control investigation involving males who underwent clinical evaluation, measurement of reproductive hormones, seminal analysis and scrotal US as part of diagnostic work-up for couple infertility at an andrology clinic, between January 2004 and December 2018. One hundred patients, out of the 2112 scored men, were found to have TM during the US evaluation. One hundred male partners from 100 infertile couples without TM, comprising the control group, were selected through a matched analysis by age and date of evaluation to reduce the confounding effect of both age and technique variability all along the long period of observation. PARTICIPANTS/MATERIALS, SETTING, METHODS: TM was defined as limited TM (LTM) or classical TM (CTM), when the maximum number of hyperecogenic spots per sonogram was <5 or ≥5, respectively. CTM, LTM and control groups were compared for clinical variables, serum levels of FSH, LH, and total testosterone, as well for semen parameters and scrotal US features. MAIN RESULTS AND THE ROLE OF CHANCE: After the exclusion of cases with testicular nodules to eliminate the possible confounding effect of testis cancer on testicular dysfunction, cases with CTM showed a lower mean testis volume (P = 0.03) and a lower sperm concentration (P = 0.03) as compared to the other two groups. A higher FSH level was observed in the CTM group compared to the LTM group (P = 0.02) and in controls (P = 0.009). The multiple logistic regression analysis showed that only a smaller testicle volume exhibited an independent significant association with a higher odds of detecting CTM (odds ratio = 0.84, 95% CI: 0.75-0.94; P = 0.02). No significant differences were observed between groups in the prevalence of risk factors for testicular cancer, or in the prevalence of conditions associated with TM. LIMITATIONS, REASONS FOR CAUTION: The retrospective design of the study did not allow conclusions to be drawn about the possible underlying links in the associations of TM with defective spermatogenesis. WIDER IMPLICATIONS OF THE FINDINGS: Males from infertile couples who exhibit a reduced testicular volume should undergo scrotal US, independent of sperm parameters, to exclude CTM and, eventually, testis cancer, although the association of CTM and current or future testis cancer risk is not yet clear. Evidence is provided here demonstrating that the presence of LTM has no clinical relevance in males from infertile couples. STUDY FUNDING/COMPETING INTEREST(S): Investigation was funded by Ministero dell'Università e della Ricerca, PRIN 2018, Italy. The authors have not declared any competing interests. TRIAL REGISTRATION NUMBER: N/A.

Frailty of the elderly in orthopaedic surgery and body composition changes: the musculoskeletal crosstalk through irisin.

In recent years, scientific interest has been developed towards irisin, a novel molecule of the family of myokines, which is directly involved in body mass composition balance, chronic diseases susceptibility and physiologic resilience to stressful events, including surgery. In the context of musculoskeletal disease, the role of this molecule has been associated to the balance of lean and fatty mass, and the production of irisin is subordinated to a healthy lifestyle and exercise. The mechanism of action of irisin on tissues is complex, and several studies described the molecular pathways in animal model and human subjects. In particular, in adipose cells, the key-role of irisin is to stimulate the differentiation of white adipose tissue to brown adipose tissue, through the action on the uncoupling protein 1. Furthermore, in the bony tissue, irisin stimulates osteogenesis through expression of Sost and Opn genes. These features make irisin a suitable molecule to use as a biomarker of the overall musculoskeletal health of the elderly, before undergoing orthopaedic surgery. Further research on this topic should be carried out to highlight the possible clinical role and predictive value of irisin in a multidisciplinary approach to the elderly before musculoskeletal surgery.

Keratinocyte skin cancer risks for working school teachers: Scenarios and implications of the timing of scheduled duty periods in Queensland, Australia.

Relative keratinocyte skin cancer risks attributable to lifetime occupational and casual sunlight exposures of working school teachers are assessed across the state of Queensland for 1578 schools. Relative risk modeling utilizing annual ultraviolet exposure assessments of teachers working in different geographic locations and exposed during periods of measured daily playground duty times for each school were made for local administrative education districts by considering traditional school opening and closing hours, and playground lunchtime schedules. State-wide, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) relative risk estimates varied by 24% for BCC and 45% for SCC. The highest relative risk was calculated for the state's north (sunshine) coast education district which showed that risk could increase by as much as 32% for BCC and 64% for SCC due to differences in teacher duty schedules. These results highlight the importance of playground duty scheduling as a significant risk factor contributing to the overall burden of preventable keratinocyte skin cancers in Queensland.

First-line carboplatin/nab-paclitaxel in advanced ovarian cancer patients, after hypersensitivity reaction to solvent-based taxanes: a single-institution experience.

One of the major challenges related to solvent-based taxanes administration in clinical practice is the high rate of hypersensitivity reactions (HSRs). Nab-paclitaxel is a solvent-free, albumin-bound, paclitaxel, which minimize the risk of HSR occurrence. In this single-institution, retrospective analysis, we evaluated stage IIIc-IV epithelial ovarian cancer (EOC) patients, treated with first-line carboplatin/nab-paclitaxel (± bevacizumab), after the occurrence of an HSR with solvent-based paclitaxel (and/or docetaxel). Between April 2012 and December 2018, ten patients (20.8%) received carboplatin/nab-paclitaxel (± bevacizumab) after the occurrence of an HSR to solvent-based taxanes. Among the evaluable patients, ORR was 100%. At median follow-up of 28.5 months, median PFS was 16.7 months, and median OS was 65.4 months, respectively. Median received dose intensity (DI) was 86% and 80% of the projected DI for nab-paclitaxel and carboplatin, respectively. There were no treatment-related grade 4 adverse events. Most relevant treatment-related grade 3 adverse events were: asthenia (10%), hypertransaminasemia (10%), neutropenia (20%), thrombocytopenia (20%), and anemia (10%). No HSR recurrence was observed. The high rate of HSR occurrence could limit first-line treatment options in clinical practice. Carboplatin/nab-paclitaxel association could represent a valid treatment option in this setting.

Microdosimetry at the CATANA 62 MeV proton beam with a sealed miniaturized TEPC.

A new mini-TEPC with cylindrical sensitive volume of 0.9 mm in diameter and height, and with external diameter of 2.7 mm, has been developed to work without gas flow. With such a mini counter we have measured the physical quality of the 62 MeV therapeutic proton beam of CATANA (Catania, Italy). Measurements were performed at six precise positions along the Spread-Out Bragg Peak (SOBP): 1.4, 19.4, 24.6, 29.0, 29.7 and 30.8 mm, corresponding to positions of clinical relevance (entrance, proximal, central, and distal-edge of the SOBP) or of high lineal energy transfer (LET) increment (distal-dose drop off). Without refilling the microdosimeter with new gas, the measurements were repeated at the same positions 4 months later, in order to study the stability of the response in sealed-mode operation. From the microdosimetric spectra the frequency-mean lineal energy y-F and the dose-mean lineal energy y-D were derived and compared with average LET values calculated by means of Geant4 simulations. The comparison points out, in particular, a good agreement between microdosimetric y-D and the total dose-average LET¯d, which is the average LET of the mixed radiation field, including the contribution by nuclear reactions.

A site-specific standard for comparing dynamic solar ultraviolet protection characteristics of established tree canopies.

A standardised procedure for making fair and comparable assessments of the ultraviolet protection of an established tree canopy that takes into account canopy movement and the changing position of the sun is presented for use by government, planning, and environmental health authorities. The technique utilises video image capture and replaces the need for measurement by ultraviolet radiometers for surveying shade quality characteristics of trees growing in public parks, playgrounds and urban settings. The technique improves upon tree shade assessments that may be based upon single measurements of the ultraviolet irradiance observed from a fixed point of view. The presented technique demonstrates how intelligent shade audits can be conducted without the need for specialist equipment, enabling the calculation of the Shade Protection Index (SPI) and Ultraviolet Protection Factor (UPF) for any discreet time interval and over a full calendar year. •Tree shade UPF measurements are presented using video capture analysis of moving canopies•A standard method for making accurate assessments of tree shade has been developed•Tree shade comparisons are made without the need for specialist equipment.

Development and validation of a staging system for gastric adenocarcinoma after neoadjuvant chemotherapy and gastrectomy with D2 lymphadenectomy.

BACKGROUND: Neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy is commonly used for patients with locally advanced gastric adenocarcinoma. The eighth AJCC ypTNM staging system was validated based on patients undergoing more limited lymphadenectomy (less than D2). The aim of this study was to develop a system for accurate staging of patients with locally advanced gastric adenocarcinoma who receive neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy. METHODS: A modified system of ypTNM was developed, based on overall survival (OS) of patients receiving neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy at Memorial Sloan Kettering Cancer Center, and validated using data from an international cohort of patients who had similar treatment. RESULTS: Of 325 patients in the derivation cohort, 33 (10·2 per cent) had ypT0 N0/+ tumours, which are not classifiable under the AJCC system. The 5-year OS rate for modified ypTNM stages I, II, IIIA and IIIB was 89, 71, 42·3 and 10 per cent respectively, compared with 82, 65·2 and 24·1 for AJCC stages I, II and III respectively. The concordance index (0·730 versus 0·709), estimated area under the curve (0·765 versus 0·740) and time-dependent receiver operating characteristic (ROC) curve throughout the observation period were all superior for modified ypTNM staging. For the validation cohort of 186 patients, the modified system was again better at separating patients into prognostic groups for OS. CONCLUSION: The modified ypTNM staging system improves the accuracy of OS prediction for patients treated with neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy.

Enhanced recovery pathways in colorectal surgery: a consensus paper by the Associazione Chirurghi Ospedalieri Italiani (ACOI) and the PeriOperative Italian Society (POIS).

Enhanced Recovery After Surgery (ERAS) pathway is a multi-disciplinary, patient-centered protocol relying on the implementation of the best evidence-based perioperative practice. In the field of colorectal surgery, the application of ERAS programs is associated with up to 50% reduction of morbidity rates and up to 2.5 days reduction of postoperative hospital stay. However, widespread adoption of ERAS pathways is still yet to come, mainly because of the lack of proper information and communication. Purpose of this paper is to support the diffusion of ERAS pathways through a critical review of the existing evidence by members of the two national societies dealing with ERAS pathways in Italy, the PeriOperative Italian Society (POIS) and the Associazione Italiana Chirurghi Ospedalieri (ACOI), showing the results of a consensus development conference held at Matera, Italy, during the national ACOI Congress on June 10, 2019.

SOI microdosimetry and modified MKM for evaluation of relative biological effectiveness for a passive proton therapy radiation field.

With more patients receiving external beam radiation therapy with protons, it becomes increasingly important to refine the clinical understanding of the relative biological effectiveness (RBE) for dose delivered during treatment. Treatment planning systems used in clinics typically implement a constant RBE of 1.1 for proton fields irrespective of their highly heterogeneous linear energy transfer (LET). Quality assurance tools that can measure beam characteristics and quantify or be indicative of biological outcomes become necessary in the transition towards more sophisticated RBE weighted treatment planning and for verification of the Monte Carlo and analytical based models they use. In this study the RBE for the CHO-K1 cell line in a passively delivered clinical proton spread out Bragg peak (SOBP) is determined both in vitro and using a silicon-on-insulator (SOI) microdosimetry method paired with the modified microdosimetric kinetic model. The RBE along the central axis of a SOBP with 2 Gy delivered at the middle of the treatment field was found to vary between 1.11-1.98 and the RBE for 10% cell survival between 1.07-1.58 with a 250 kVp x-ray reference radiation and between 1.19-2.34 and 0.95-1.41, respectively, for a Co60 reference. Good agreement was found between RBE values calculated from the SOI-microdosimetry-MKM approach and in vitro. A strong correlation between proton lineal energy and RBE was observed particularly in the distal end and falloff of the SOBP.

MICRODOSIMETRIC MEASUREMENT OF SECONDARY RADIATION IN THE PASSIVE SCATTERED PROTON THERAPY ROOM OF iTHEMBA LABS USING A TISSUE-EQUIVALENT PROPORTIONAL COUNTER.

Measurements of the dose equivalent at different distances from the isocenter of the proton therapy center at iThemba LABS were previously performed with a tissue-equivalent proportional counter (TEPC). These measurements showed that the scattered radiation levels were one or two orders of magnitude higher in comparison to other passive scattering delivery systems. In order to reduce these radiation levels, additional shielding was installed shortly after the measurements were done. Therefore, the aim of this work is to quantify and assess the reduction of the secondary doses delivered in the proton therapy room at iThemba LABS after the installation of the additional shielding. This has been performed by measuring microdosimetric spectra with a TEPC at 11 locations around the isocenter when a clinical modulated beam of 200 MeV proton was impinging onto a water phantom placed at the isocenter.

Management of Fournier's gangrene non-healing wounds by autologous skin micrograft biotechnology: a new technique.

Fournier's gangrene is an acute bacterial infection producing necrosis of the perineum and external genitalia that generally affects elderly men. Although skin grafts and flaps are the standard procedure for reconstruction, sometimes wounds can become chronic. Rigenera Protocol is a new technique based on autologous skin micrografts that reactivates and supports wound healing. A 40-year-old male with Fournier's gangrene, due to a rectal microperforation following diarrhoea, was treated with surgical debridement, negative pressure wound therapy and subsequently coverage with skin grafts. He developed non-healing wounds treated by Rigenera protocol after two months of advanced wound dressings. This technique is based on skin micrografts obtained by mechanical dermal disgregation to provide mesenchymal stem cells and extracellular matrix to the wound. The suspension injected into the wound triggers reactivation of healing without significant residual scarring on both donor site and treated area. Non-healing wounds were reduced by 15% at day 7 and by 50% after 30 days. Wounds completely healed after seventy days. The regenerated tissue appeared closer to skin graft than to scar tissue. This report shows how the use of skin micrografts through Rigenera protocol can be a useful method to reactivate wound healing resulting from Fournier's gangrene, with no discomfort for patient in a practical, safe and easy way.

Concurrent evaluation of personal damaging and beneficial UV exposures over an extended period.

Personal exposure to solar ultraviolet radiation (UVR) is acknowledged as having both positive and negative effects on human health. This study aimed to measure concurrently the personal erythemal UV, UVA and vitamin D effective exposures of participants in each season of a year. Participants were all indoor office workers located at two different sites less than 6.5 km apart at the sub-tropical location of Toowoomba (27°33'S 151°55'E). The subjects wore a combined dosimeter badge horizontally on the shoulder for a minimum of one week in each season; this badge used 8-methoxypsoralen film to record the UVA waveband and polyphenylene oxide film for the erythemal and the vitamin D effective UV wavebands. The results show that median erythemal exposure was highest during the spring and lowest during winter, as was the vitamin D effective exposure. Median UVA exposures were at a similar level in winter and summer, autumn was higher (double) and spring at a lower level. The duration and time of day participants spent outdoors changed in each season; in winter, participants spent an average of 101 minutes outdoors between 10:00-14:00 h over the week, whereas in summer this fell to 79 minutes even though they were outdoors more often. The daily UVA/UVB ratio is lowest between 10:00-14:00 h and also changes with the season resulting in the differences between the distributions of exposure for each of the wavebands. Each category of exposures must be assessed individually as each season and each waveband has different distributions. The results also demonstrate that the dual film dosimeter developed and characterized with a calibration to three different biological responses, is an effective device for the concurrent measurement of erythemal UV, UVA and vitamin D effective UV exposures for periods of up to seven days.

A rare case of perforation of the subhepatic appendix by a toothpick in a patient with intestinal malrotation: laparoscopic approach.

Foreign body ingestion is not an uncommon problem in clinical practice. While most ingested foreign bodies pass uneventfully through the gastrointestinal tract, sharp foreign bodies such as toothpicks should cause intestinal perforation. We reported the case of a perforation of the appendix caused by a toothpick, which also pierced the liver without hepatic damages, in a male with an intestinal malrotation and subhepatic appendix. The patient was admitted to our hospital for abdominal pain in the right upper quadrant. An abdominal computed tomography scan revealed the anomalous position of the first portion of the large intestine with inflamed appendix. A laparoscopic appendicectomy and the exploration of the abdominal cavity was performed using minimally invasive technique.