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Background: (Chemo)radiation may be a required treatment in young women with pelvic malignancies. Irradiation may result in ovarian and uterine failure, compromising the fertility of those patients. While ovarian transposition is an established method to move the ovaries away from the irradiation field, similar surgical procedures regarding the uterus remain investigational. The aim of this study was to carry out a systematic review of the literature on uterine displacement techniques (ventrofixation/transposition) and to simulate the radiation dose received by the uterus in different heights place after the procedures., Methods: The systematic review was performed according PRISMA guidelines. PubMed, Scopus, Web of Science and EMBASE were queried to identify included study until March 2023. Retrospectively, a dosimetric study was also performed and Volumetric Modulated Arc Therapy (VMAT) radiotherapy treatment plans were calculated, to assess the dose received by the uterus according to hypothetical different displacement positions taking the case of irradiation for rectal or anal cancer as model., Results: A total of 187 studies were included, after the screening 9 studies were selected for synthesis. Data from the dose simulation revealed that the transposition approach was the most protective with a maximum dose of about 3 and 8 Gy for anal and rectal cancer respectively. None of the simulated ventrofixation positions received a Dmean surpassing 14 Gy., Conclusion: According to the literature review and the simulation results of the present study we may conclude are feasible and safe as fertility sparing approach in young rectal/anal cancer patients., Competing Interests: Declaration of competing interest Authors declare no conflicts of interests., (© 2023 Published by Elsevier Ltd.)

Facial feminization surgery (FFS) is often the first procedure requested by patients wishing to undergo gender-affirming surgery. This study aims to evaluate the applicability and effectiveness of deep plane facelifts in FFS. The authors conducted a prospective study that included patients who requested a deep plane facelift as a standalone procedure to achieve a more feminine facial appearance as the only procedure of FFS. These patients underwent deep plane facelifts to achieve a more feminine oval face shape and increased tissue projection of the zygomatic-malar region. To assess the effectiveness of the procedure and patient satisfaction, the Face-Q scales, Face and Neck lift Objective Photo-Numerical Assessment Scale, the Satisfaction With Life Scale, and the Subjective Happiness Scale were applied preoperatively and one year after surgery. Thirty-six patients were included in the study. A statistically significant difference (p < 0.005) was observed between pre and postoperative scores. The repositioning of the malar fat pads increased the malar volume, providing a more oval overall shape of the face, which is typically feminine. No major complications were observed. Despite our encouraging results, new studies with a larger sample of patients are needed to support the benefits of the deep plane facelift as part of FFS to elevate this technique from an ancillary to a routine procedure for patients undergoing gender affirmation surgery., Competing Interests: Declaration of Competing Interest The authors have the following conflicts of interest to disclose., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: The aims of this study were to analyze the pathological response, and survival outcomes of adenocarcinoma/adenosquamous (AC/ASC) versus squamous cell carcinoma (SCC) in patients with locally advanced cervical cancer (LACC) managed by chemoradiotherapy followed by radical surgery., Methods: Retrospective, multicenter, observational study, including patients with SCC and AC/ACS LACC patients treated with preoperative CT/RT followed by tailored radical surgery (RS) between 06/2002 and 05/2017. Clinical-pathological characteristics were compared between patients with SCC versus AC/ASC. A 1:3 ratio propensity score (PS) matching was applied to remove the variables imbalance between the two groups., Results: After PS, 320 patients were included, of which 240 (75.0%) in the SCC group, and 80 (25.0%) in the AC/ASC group. Clinico-pathological and surgical baseline characteristics were balanced between the two study groups. Percentage of pathologic complete response was 47.5% in SCC patients versus 22.4% of AC/ASC ones (p < 0.001). With a median follow-up of 51 months (range:1-199), there were 54/240 (22.5%) recurrences in SCC versus 28/80 (35.0%) in AC/ASC patients (p = 0.027). AC/ASC patients experienced worse disease free (DFS), and overall survival (OS) compared to SCC patients (p = 0.019, and p = 0.048, respectively). In multivariate analysis, AC/ACS histotype, and FIGO stage were associated with worse DFS and OS., Conclusion: In LACC patients treated with CT/RT followed by RS, AC/ASC histology was associated with lower pathological complete response to CT/RT, and higher risk of recurrence and death compared with SCC patients. This highlights the need for specific therapeutic strategies based on molecular characterization to identify targets and develop novel treatments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Anterior skull base (ASB) fractures are reported in 4% of head injuries and represent 21% of all skull fractures. Cerebrospinal fluid (CSF) leaks may follow, severely exacerbating outcomes. We systematically reviewed the literature to analyze and compare the roles of endoscopic surgery, open surgery, and combined approaches in the management of CSF leak repair after posttraumatic ASB fractures., Methods: PubMed, Web of Science, and Scopus databases were searched in accordance with the PRISMA guidelines. Studies reporting clinical data of patients with CSF leaks after ASB fracture were reviewed, focusing on management strategies and posttreatment outcomes., Results: We included 29 articles comprising 888 patients. The average age at diagnosis was 34 years (range, 18-91 years), with a male predominance (54%) and a male/female ratio of 2.9:1 (647:241). Clinical data were available for 888 patients with CSF leaks after ASB fracture, reporting a median follow-up time of 33.5 months (standard deviation, ±29; range, 0.5-330.0 months). Open surgical repair was the most common approach (67.9%), followed by endoscopic surgical repair (32.1%). The endoscopy cohort showed lower rates of complications (0.7% vs. 11.1%) and fistula recurrence (2.8% vs. 5.3%) compared with open surgery., Conclusions: ASB fractures are frequently treated as late surgery, 24 hours from injury or later, especially for endoscopic surgery. Overall, the endoscopic approach is preferred, mostly because of its safety and effectiveness, offering lower failure rates than does open surgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To assess the feasibility and safety of a repeated SHort course Accelerated RadiatiON therapy (SHARON) regimen in the palliative setting of Head and Neck (H&N) cancer in older adults., Material and Methods: Patients with histological confirmed H&N cancers, age ≥ 80 years, expected survival >3 months, and Eastern Cooperative Oncology Group (ECOG) performance status of ≤3 were enrolled. Patients were treated in cohorts of six patients: a total dose of 20 Gy was delivered in 2 consecutive days with a twice-daily fractionation (5 Gy per fraction) and at least 8-h interval. If no Grade 3 toxicity was registered, a second enrollment started with another cohort of six patients to whom were administered two cycles (total dose of 40 Gy). The primary endpoint was to evaluate the feasibility of the two cycles of treatment. Secondary endpoints were evaluation of symptoms control rate, symptoms-free survival (SFS), and Quality of Life (QoL) scores., Results: Seventeen consecutive patients (median age: 85 years) were treated. Nine patients were treated with one cycle and 8 patients with two cycles. No G3 toxicity was reported in either cohort. With a median follow-up time of 4 months, 3-month SFS in the first and second cohorts was 83.3%, and 87.5%, respectively. The overall palliative response rate was 88%. Among 13 patients reporting pain, 8 (61.5%) showed an improvement or resolution of their pain., Conclusion: Repeated short course accelerated radiotherapy in a palliative setting of H&N cancers is safe and well-tolerated in older adults., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The implementation of multidisciplinary tumor board (MDTB) meetings significantly ameliorated the management of oncological diseases. However, few evidences are currently present on their impact on pancreatic cancer (PC) management. The aim of this study was to evaluate the impact of the MDTB on PC diagnosis, resectability and tumor response to oncological treatment compared with indications before discussion., Patients and Methods: All patients with a suspected or proven diagnosis of PC presented at the MDTB from 2017 to 2019 were included in the study. Changes of diagnosis, resectability and tumor response to oncological/radiation treatment between pre- and post-MDTB discussion were analyzed., Results: A total of 438 cases were included in the study: 249 (56.8%) were presented as new diagnoses, 148 (33.8%) for resectability assessment and 41 (9.4%) for tumor response evaluation to oncological treatment. MDTB discussion led to a change in diagnosis in 54/249 cases (21.7%), with a consequent treatment strategy variation in 36 cases (14.5%). Change in resectability was documented in 44/148 cases (29.7%), with the highest discrepancy for borderline lesions. The treatment strategy was thus modified in 27 patients (18.2%). The MDTB brought a modification in the tumor response assessment in 6/41 cases (14.6%), with a consequent protocol modification in four (9.8%) cases., Conclusions: MDTB discussion significantly impacts on PC management, especially in high-volume centers, with consistent variations in terms of diagnosis, resectability and tumor response assessment compared with indications before discussion., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The aim of this study was to evaluate the efficacy of preoperative intraoral ultrasonography (US) in the assessment of tumor depth of invasion (DOI) in oral squamous cell carcinoma (OSCC)., Study Design: Records of 32 patients with biopsy-proven OSCC who underwent preoperative intraoral US were retrospectively reviewed. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy as indicated by receiver operating characteristic (ROC) analysis were measured for US in the assessment of the infiltration of the tumor beyond the lamina propria into the submucosa. The correlations between US and histologic DOI, and between US DOI and US diameter of the lesion, were assessed., Results: US sensitivity, specificity, PPV, and NPV in the assessment of the infiltration of the tumor beyond the lamina propria into the submucosa were 93.1%, 100%, 100%, and 60%, respectively. The area under the ROC curve was 0.96. A significant correlation was found between the measurements of US DOI and histological DOI (r = 0.907). A moderate correlation was found between US DOI and US diameter (r = 0.591)., Conclusions: Intraoral US has potential in preoperatively determining tumor DOI and may provide additional guidance for optimal planning of therapy for OSCC patients ., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Oncotype DX (ODX) predicts breast cancer recurrence risk, guiding the choice of adjuvant treatment. In many countries, access to the test is not always available. We used correlation between phenotypical tumor characteristics, quantitative classical immunohistochemistry (IHC), and recurrence score (RS) assessed by ODX to develop a decision supporting system for clinical use., Patients and Methods: Breast cancer patients who underwent ODX testing between 2014 and 2018 were retrospectively included in the study. The data selected for analysis were age, menopausal status, and pathologic and IHC features. IHC was performed with standardized quantitative methods. The data set was split into two subsets: 70% for the training set and 30% for the internal validation set. Statistically significant features were included in logistic models to predict RS ≤ 25 or ≤ 20. Another set was used for external validation to test reproducibility of prediction models., Results: The internal set included 407 patients. Mean (range) age was 53.7 (31-80) years, and 222 patients (54.55%) were > 50 years old. ODX results showed 67 patients (16.6%) had RS between 0 and 10, 272 patients between 11 and 25 (66.8%), and 68 patients > 26 (16.6%). Logistic regression analysis showed that RS score (for threshold ≤ 25) was significantly associated with estrogen receptor (P = .004), progesterone receptor (P < .0001), and Ki-67 (P < .0001). Generalized linear regression resulted in a model that had an area under the receiver operating characteristic curve (AUC) of 92.2 (sensitivity 84.2%, specificity 80.1%) and that was well calibrated. The external validation set (183 patients) analysis confirmed the model performance, with an AUC of 82.3 and a positive predictive value of 91%. A nomogram was generated for further prospective evaluation to predict RS ≤ 25., Conclusion: RS was related to quantitative IHC in patients with RS ≤ 25, with a good performance of the statistical model in both internal and external validation. A nomogram for enhancing clinical approach in a cost-effective manner was developed. Prospective studies must test this application in clinical practice., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The aim of the present study was to analyse the consequences of masseter muscle denervation. In facial palsy surgical treatment, the masseteric nerve constitutes an important nerve source for facial reanimation due to its anatomical position and large amount of available axons. Computed tomography and/or magnetic resonance imaging were performed in 30 control subjects, and three radiologists separately measured the longitudinal diameter (LD), anteroposterior diameter (APD), transverse diameter (TD), and skeletal muscle area (SMA) of the masseter muscles as reference values. Regarding the facial palsy group, from 2009 to 2018, 11 patients (4 men and 7 women) were selected on the following inclusion criteria: diagnosis of unilateral facial paralysis, minimum follow-up of 14 months, absence of temporomandibular dysfunction, presence of complete dentition (to minimise bias of stomatognathic evaluation), complete clinical and radiological records. The mean LD, APD, TD, and SMA values of the healthy and denervated masseter muscles were obtained and compared. Stomatognathic function was clinically examined through mean mouth opening (MMO) and Maximum Bite Force (MBF). Furthermore, facial symmetry analysis (FSA) was carried out using EMOTRICS Software. Reference values obtained were as follows: mean LD = 69 ± 5.9 mm (range: 59-85 mm); mean APD = 40.2 ± 3.3 mm (range: 34-48 mm); mean TD = 15.5 ± 3.1 mm (range: 11-26 mm); and mean SMA = 43.8 ± 13.5 mm 3 (range: 26-85.8 mm 3 ). No statistically significant difference was observed between the healthy facial palsy groups's masseter muscles and reference values. As the latter, in denervated masseter muscles, no statistically significant difference was observed for APD value in contrast to LD, TD and SMA that showed statistically significant difference in comparison with control population (p < 0.05, CI 95%). Moreover fibro-adipose degeneration was consistently observed, with its degree being directly proportional to the denervation time. MMO and MBF mean values were, respectively, 54.75 mm in men, 44.4 mm in women and 705N. None of the latter showed a statistically significant difference with respect to the control population and the parameters present in the literature, indicating that masseter-facial neurorrhaphy is a safe and effective procedure for facial reanimation with good functional and aesthetic outcomes., (Copyright © 2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: The craniovertebral junction (CVJ) may be affected by several diseases. It is an anatomically complex region, involving the osteoligamentous, vascular, and nervous structures, which makes surgery challenging. In a case of ventral compression, an anterior approach is preferable, although posterior fixation is often required. Anterior transmucosal approaches are associated with high rates of complications. However, decompression and fixation by the use of retropharyngeal extramucosal approaches may be challenging., Objective: To investigate the feasibility of a single-stage, anterior, extramucosal submandibular (SM) approach modification to the CVJ for simultaneous decompression and stabilization., Materials and Methods: This was a preliminary cadaveric feasibility study on 2 injected specimens. A variation of the SM approach with a short "boomerang" incision, microsurgical decompression of the ventral CVJ, and a new hybrid construct for an anterior atlantoaxial stabilization was investigated. The surgical approach, the decompression, and the instrumentation technique have been described. In addition, intraprocedural images and radiographs and also postprocedural computed tomographic images were collected. Furthermore, surgical exposure, working corridors and angles, and decompression grade were measured., Results: The SM approach provided wide exposure of the ventral CVJ and the possibility for instrumentation and decompression by removing the anterior arch of C1 and the odontoid process., Conclusion: A single- stage anterior extramucosal SM approach for decompression and stabilization of the CVJ is feasible and could result in shorter surgical duration, avoiding the complications related to both the transmucosal approach and the prone position, although specific related risks exist. Mechanical investigation of this hybrid system and in vivo studies are needed to confirm our results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In the context of the management of the elderly patient with cancer, currently, a key topic may be expressed by sarcopenia. Sarcopenia in its various definitions and ambiguities in the older adult is always related to negative outcomes. A close correlation between sarcopenia and adverse outcomes such as treatment response or toxicity has also been shown in the patient with cancer. For these reasons, it becomes increasingly important to try to understand and therefore differentiate conditions such as the loss of muscle mass linked to normal aging, an independent pathological condition such as sarcopenia and finally a sometimes confusing pathologic condition called cachexia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Object: At present, a minimally invasive endoscopic endonasal approach is considered an efficient option for lesions affecting the anterior and middle skull base with sellar and parasellar region involvement. In this study we will retrospectively analyze the pediatric patients that we have been treating in the same medical center for the past four years, using an endoscopic approach in the skull base., Methods: We performed a retrospective chart and imaging review of pediatric patients who underwent endoscopic endonasal skull base surgery (ESBS) at the Meyer Children's Hospital, (Azienda Ospedaliero Universitaria Meyer), in Florence, from January 2012 to July 2016., Results: Mean age was 12,5 years; 28 (65%) of the 44 patients were females. Skull base lesions were broadly classified as either bony abnormalities (4 cases) or skull base tumors (40 cases). The postoperative clinical follow-up duration ranged from 2 to 36 months. The two more frequently occurring diseases in our study were: craniopharyngioma and pituitary adenoma., Conclusions: After reviewing the international literature about pediatric endoscopic endonasal approach to skull base, we can affirm that our study is the world's second broadest work for number of records. While compiling this report, we have examined the first 40 consecutive pediatric patients to undergo ESBS at our institute. The appearance of postoperative complications is consistent with other international studies, confirming ESBS being feasible and safe even in the pediatric population., Level of Evidence: 4., (Copyright © 2018. Published by Elsevier Ltd.)

Aim: Male breast cancer (MBC) is a rare disease and recommendations for its clinical management are often extrapolated from those for female breast cancer, even if breast cancer (BC) has different characteristics in the two sexes. The purpose of this study was to assess the influence of several individual characteristics including clinico-pathological, lifestyle and genetic factors on overall survival (OS) of a relatively large and well characterized population-based series of 166 MBCs enrolled in Tuscany., Methods: We genotyped MBC cases at BRCA1/2 genes and at 9 candidate BC susceptibility SNPs. Kaplan-Meier method and multivariate Cox regression, adjusted for several individual characteristics were used. To reduce a possible selection bias related to the interval between diagnosis and enrolment of MBC cases into the study, we used the date of blood donation as the date of the start of observation for survival analysis., Results: Only smoking habits had a significant effect on OS at 10 years (for current smokers, HR: 3.34; 95% CI 1.45-7.68; p = 0.004), while lymph node status fell short of reaching statistical significance (for pN positive, HR: 2.07; 95% CI 0.93-4.55; p = 0.07). In the same multivariate analysis we found a significantly higher OS in cases with FGFR2 rs2981582 variant in the dominant transmission model (HR: 0.29; 95% CI: 0.13-0.62; p = 0.028). A sensitivity analysis with left truncation showed similar results., Conclusions: Our results may contribute to shed light on factors influencing MBC survival suggesting an important role for cigarette smoking and FGFR2 rs2981582 variant, and provide clues for better patient management., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the efficacy and safety of a conformal Short Course Accelerated Radiation therapy (SHARON) for symptomatic palliation of locally advanced or metastatic cancers in older patients., Materials and Methods: This is a pooled analysis on patients aged ≥80 years selected between subjects enrolled in 3 phase I-II studies on a short course palliative treatment of advanced or metastatic cancer. The primary endpoint was to evaluate the symptoms response rate produced by accelerated radiotherapy delivered in 4 total fractions in twice a day. Total dose ranged between 14 Gy and 20 Gy while dose/fraction between 3.5 and 5 Gy., Results: A total of 48 patients were included in this analysis. Twenty-six patients (54.2%) had advanced primary or metastatic head and neck tumors, 11 (22.9%) locally advanced or metastatic thoracic cancers, 11 (22.9%) complicated bone metastases. The majority of patients presented pain (60.4%). With a median follow-up time of 5.5 months, no G4 acute and late toxicities were recorded. The overall palliative response rate was 91.7% with a median duration of palliation of 4 months., Conclusion: Short course accelerated radiotherapy in locally advanced or metastatic cancers is effective in terms of symptom relief and well tolerated even in older patients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: The aim of this Phase II, non-randomized study was to assess activity and safety of neoadjuvant chemotherapy (NACT) before chemoradiation (CT/RT) followed by radical surgery (RS) in locally advanced cervical cancer (LACC) patients., Methods and Materials: The primary end point was rate of pathologic complete response (pCR). FIGO Stage IB2-IVA patients were administered NACT chemotherapy (paclitaxel 80 mg/m 2 , carboplatin AUC 2), for 6 weeks, followed by Intensity Modulated Radiotherapy plus simultaneous boost (total dose of 50.4 Gy to CTV1, and 39.6 Gy to CTV2). Clinical response was assessed according to RECIST criteria. Responsive patients were triaged to RS. The regimen would be considered active if >20 pCRs were registered in 39 patients., Results: 45 patients were enrolled into the study; 25 patients (55.5%) were FIGO stage IIB, 9 cases (20.0%) had stage III disease. At work up, pelvic lymph node involvement was documented in 38 (84.4%) patients; pCR was documented in 18 out of 40 patients (45.0%). Grade 3-4 hematological toxicity after NACT occurred in 4 patients; CT/RT associated grade 3 toxicity was found in 7 patients. Early and late postoperative complications were detected in 16, and 11 cases, respectively. Three-year PFS and OS were 66.0% and 86.0%, respectively., Conclusions: NACT followed by CT/RT by IMRT and RS, is feasible and safe; failure to achieve the primary endpoint has to be recognized; however, enrollment of a higher rate of poor prognosis patients compared to historical data used to calculate sample size, could have resulted in reduced activity., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Adjuvant chemotherapy is controversial in patients with locally advanced rectal cancer after preoperative chemoradiation. Valentini et al developed 3 nomograms (VN) to predict outcomes in these patients. The neoadjuvant rectal score (NAR) was developed after VN to predict survival. We aimed to validate these tools in a retrospective cohort at an academic institution., Patients and Methods: VN and the NAR were applied to 158 consecutive patients with locally advanced rectal cancer treated with chemoradiation followed by surgery. According to the score, they were divided into low, intermediate, or high risk of relapse or death. For statistical analysis, we performed Kaplan-Meier curves, log-rank tests, and Cox regression analysis., Results: Five-year overall survival was 83%, 77%, and 67% for low-, intermediate-, and high-risk groups, respectively (P = .023), according to VN, and 84%, 71%, and 59% for low-, intermediate-, and high-risk groups, respectively (P = .004), according to NAR. When the score was considered as a continuous variable, a significant association with the risk of death was observed (NAR: hazard ratio, 1.04; P < .001; VN: hazard ratio, 1.10; P < .001)., Conclusion: We confirmed the value of these scores to stratify patients according to their individual risk when designing new trials., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To describe the current European practise on post-mastectomy radiation therapy (PMRT) in relation to breast reconstruction., Methods: A 21-item questionnaire was distributed online via Survey Monkey. Items referred to 1. general topics (country, centre, years of experience in breast cancer); 2. clinical decision making; 3. RT techniques and dosimetry; 4. dose fractionation., Results: 283 responses were received from 19 countries. Most responders worked in public health services and in academic institutions and had 5-20 years experience. Although many indicated they were consulted about the timing and type of breast reconstructive surgery, final decisions were most often made by surgeons. Immediate reconstruction with expander followed by RT and subsequently permanent reconstruction with prosthesis was recommended by 61.6% of responders. Most (48.4%) adviced a boost only when margins were close or involved with an another 17.7% recommending it in the presence of high-risk features (T3-T4, lympho-vascular involvement). Intensity modulated RT was rarely used by about two-thirds of responders, except when with 3D technique the dose constraints were not achieved or when regional lymph nodes were included. Almost 60% of responders did not use bolus/tissue equivalent material (TEM). The main indication for bolus/TEM use was skin involvement. The majority of responders used 1.8-2 Gy per fraction., Conclusions: The present survey highlighted controversial areas in clinical practise, confirming the uncertainties about the scheduling of PMRT and breast reconstruction., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Managing eutrophication remains a challenge to water managers. Currently, the manipulation of biogeochemical processes (i.e., geo-engineering) by using phosphorus-adsorptive techniques has been recognized as an appropriate tool to manage the problem. The first step in finding potential mitigating materials is conducting a sequence of upscaling studies that commence with controlled laboratory experiments. Here, the abilities of 10 possible solid-phase-sorbents (SPS) to adsorb P were examined. Four materials adsorbed P, and two of these materials were modified, i.e., a lanthanum-modified-bentonite (LMB) and an aluminum-modified-zeolite (AMZ), and had the highest adsorption capacities of 11.4 and 8.9mgPg -1 , respectively. Two natural materials, a red soil (RS) and a bauxite (BAU), were less efficient with adsorption capacities of 2.9 and 3.4mgPg -1 , respectively. Elemental composition was not related to P adsorption. Since SPS might be affected by pH and redox status, we also tested these materials at pH values of 6, 7, 8 and 9 and under anoxic condition. All tested materials experienced decreased adsorption capacities under anoxic condition, with maximum adsorptions of 5.3mgPg -1 for LMB, 5.9mgPg -1 for AMZ, 0.2mgPg -1 for RS and 0.2mgPg -1 for BAU. All materials were able to adsorb P across the range of pH values that were tested. The maximum adsorption capacities of LMB and RS were highest at pH6, AMZ was higher at a pH of 9 and BAU at a pH of 8. Thus, pH influenced P adsorption differently. Given the effects of pH and anoxia, other abiotic variables should also be considered. Considering the criteria that classify a useful SPS (i.e., effective, easy to produce, cheap and safe), only the two modified materials that were tested seem to be suitable for upscaling to enclosure studies with anoxic sediments., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Breast cancer (BC) in men is a rare disease, whose etiology appears to be associated with genetic factors. Inherited mutations in BRCA1/2 genes account for about 10-15% of all cases. FANCM, functionally linked to BRCA1/2, has been suggested as a novel BC susceptibility gene. Our aim was to test if FANCM germline mutations could further explain male BC (MBC) susceptibility., Methods: We screened the entire coding region of FANCM in 286 MBCs by a multi-gene panel analysis, and compared these data with available whole exome sequencing data from 415 men used as population controls. Moreover, we genotyped the two most frequent FANCM mutations (c.5101C>T and c.5791C>T) in 506 MBCs and 854 healthy male controls., Results: Two FANCM truncating mutations, the c.1432C>T (p.Arg478Ter) and c.1972C>T (p.Arg658Ter), were identified in two MBC cases (0.7%). When specifically considering cases at increased genetic risk for BC, FANCM mutation frequency raises up to 1%. One mutation, the c.2201&#95;2202delCT (p.Ser734Terfs), was found among controls (0.24%). Mutation frequency in cases was higher than in controls, however this difference was not statistically significant. FANCM c.5101C>T was not present in any of the cases and controls analyzed, whereas FANCM c.5791C>T was found in two controls (0.23%)., Conclusion: Rare FANCM truncating mutations, other than c.5101C>T and c.5791C>T, may have a role in MBC susceptibility. The inclusion of FANCM in gene panels for research purpose would allow for the identification of a higher number of mutation carriers, thus helping estimate BC risk associated with FANCM mutations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In treating head and neck cancer (HNC), the objectives are provided for best functional results and minimal risk of serious complications. The choice of appropriate management depends primarily on specific site and stage of primary tumor at diagnosis. Radiation therapy (RT) with or without concomitant chemotherapy represents a classical treatment option. In this review, we provide an update of recent research strategies to counteract the existing damage caused by RT and highlight clinical trials currently in progress. We discuss the challenges in the evaluation of new stage system and RT-related toxicity onset. We mainly address the deficiencies and the advantages noted in the current treatment era., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: To identify a subset of cervical cancer (CC) patients administered chemoradiation (CT/RT) plus radical surgery (RS), who can be spared lymphadenectomy, and complications., Patients and Methods: 430 Stage IB2-IIB patients without LN involvement at imaging were accrued (March 1996-December 2015) at Gynecologic Oncology Unit of the Catholic University of Rome/Campobasso. CT/RT consisted of pelvic irradiation plus cisplatin based chemotherapy. Objective response was evaluated according to RECIST criteria; radical hysterectomy and pelvic ± aortic lymphadenectomy was attempted in patients achieving response or stable disease. Surgical morbidity was classified according to the Chassagne grading system., Results: 421 cases underwent RS; metastatic pelvic and aortic LNs were documented in 10.7%, and 8.8% of cases, respectively. In patients without residual tumor in the cervix, there was only 1 case (0.53%) with positive pelvic LNs, and 1 case (2.3%) with metastatic aortic LNs. Analysis of patients according to pre- and post-CT/RT imaging was able to select cases without any metastatic LNs: in patients with negative pelvic LNs at pre- and post-CT/RT imaging, none of cases without residual disease in the cervix had metastatic pelvic or aortic LNs. Of 149 early complications, 76 (51.0%) were lymphovascular. The most frequent late complications were lymphovascular (N = 25/61, 41.0%)., Conclusion: Lymphadenectomy could be avoided in stage IB2-IIB CC patients undergoing preoperative CT/RT, when a careful evaluation of pre- and post-CT/RT imaging and histological assessment of no residual disease in the cervix is made. This approach may avoid lymphadenectomy in 40% of patients with a favourable impact on lymphovascular morbidity., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: The aim of this study is to provide a prospective analysis of post-operative and oncological outcomes in patients affected by locally advanced rectal cancer (LARC), who obtained a major/complete clinical response after pre-operative radio-chemotherapy (RCT) and were treated with local excision (LE) by trans-anal endoscopic microsurgery (TEM) to confirm a pathological complete response (pCR) after to neo-adjuvant RCT., Methods: All patients with LARC treated by pre-operative RCT and full-thickness LE by TEM (2000-2014) were included in the study. If the pathological analysis confirmed near complete or pCR, intensive follow up was proposed. If the pathological response was incomplete, a radical resection with TME was proposed. Post-operative (according to Clavien's classification), functional and long-term oncological outcome were analyzed., Results: 36 patients were treated by TEM. The median post-operative hospital stay was 5 days. The post-operative morbidity was 41.6% (no grade ≥3). At pathological analysis, 23 specimens were ypT0 TRG1, and 4 were ypT1 TRG2. In 9 cases (ypT>1 and/or TRG>2), radical surgery with TME was proposed but 3 refused it. Median follow-up was 68 months. One local recurrence and 4 distant metastases occurred. The 5-yr actuarial local control, overall survival and disease-free survival were 96.0%, 92.0% and 82.8%., Conclusions: In case of major or complete clinical response of LARC after pre-operative RCT, LE by TEM can be used to confirm the pathological response. This avoids the necessity of radical surgery and, in our experience, this approach seems to guarantee oncological safety with the functional advantages of an organ-sparing procedure., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: The aim of this study was to investigate the efficacy and toxicity of volumetric modulated arc therapy (VMAT)-simultaneous integrated boost (SIB) in preoperative combined treatment of locally advanced rectal cancer., Methods: Radiation therapy was performed using the VMAT-SIB technique. The dose to mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered on GTV + 2-cm margin with a total dose of 57.5 Gy (2.3 Gy/fraction). The following concomitant chemotherapy was administered: capecitabine (825 mg/m 2 twice daily, 5 days per week) and oxaliplatin (130 mg/m 2 on days 1, 17, and 35). Efficacy was evaluated in terms of complete pathological response (pCR). Acute toxicities were evaluated according to Common Terminology Criteria for Adverse Events version 3.0 criteria., Results: A total of 18 patients (7 women; median age 62 years; clinical stage: 4 local recurrences, 6 cT4, 5 cT3, 3 cT2, 2 cN0, 7 cN1, 9 cN2) were enrolled. Sixteen patients underwent surgical resection (9 low anterior resection, 6 abdominal perineal amputations; 1 transanal excision) and 2 patients did not undergo surgery for early metastatic progression or death from acute pulmonary edema. R0 resection was achieved in all patients who underwent surgery. Overall, 4 patients had a pCR and 7 patients only a microscopic residual of disease (pT0-Tmic: 11/18 = 61.1%; 95% CI, 36.2-86.1). Acute grade ≥ 3 toxicity was as follows: 1 case of leukopenia, 1 skin toxicity, 1 genitourinary toxicity, and 5 gastrointestinal toxicities, with an overall incidence of 8 (44.4%) of 18 patients. One-, 3-, and 5-year cumulative local control was 100%, 68.6%, and 68.6%, respectively. One-, 3-, and 5-year cumulative disease-free survival was 88.9%, 66.7%, and 66.7%, respectively. One-, 3-, and 5-year cumulative overall survival was 85%, 63.8%, and 63.8%, respectively., Conclusion: The regimen used in this study showed excellent results in terms of pathologic responses. However, despite the use of the VMAT technique, more than one-third of patients had severe acute toxicity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: International guidelines strongly recommend brachytherapy as valid alternative or in addition to stenting in patients with dysphagia owing to esophageal cancer. However, for not well understood reasons, brachytherapy is definitively underused for the palliative treatment of malignant dysphagia. Aim of the current survey was to investigate the use of brachytherapy for the treatment of malignant dysphagia in Italy., Methods: A structured questionnaire was submitted to the 1510 members of the Italian Association of Radiation Oncologists (AIRO). These members refer to 177 centres of radiotherapy across Italy and in 68 (38.4%) of them brachytherapy is routinely performed., Results: Of the 1510 invited members, 178 completed the survey (11.7%). The answers provided by the 178 participants allowed to get information on 40 out of 68 brachytherapy centres (58.8%). Seven out of 40 (17.5%) centres perform brachytherapy of the oesophagus, in 3 out of 40 (7.5%) centres brachytherapy represents the first line of treatment. The main reason why brachytherapy is not routinely performed is the lack of experience., Conclusion: Despite the strong recommendations of the international guidelines and the wide diffusion of brachytherapy centres across Italy, only very few of them routinely considered brachytherapy for the treatment of dysphagia due to esophageal cancer., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study was planned to clarify the optimal treatment for squamous cell carcinoma of the rectum, an histological entity extremely rare., Methods: Ten patients with histologically proven squamous cell carcinoma of the rectum were treated with concomitant radiochemotherapy. Radiation therapy was delivered with a 3Dconformational multiple field technique to a dose ranging from 45 to 76.5 Gy, with 6-15 MV energy photons. Chemotherapy consisted of an antimetabolite drug in association with mitomycin C or oxaliplatin. Overall survival and disease free survival were considered in months from the end of the concomitant treatment., Results: All patients completed programmed radiochemotherapy treatment but two patients were excluded to the analysis. Six patients (75%) presented negative biopsy 6 months after the end of radiochemotherapy. Seven patients (87.5%) showed a tumour regression after initial treatment. Only 1 patient underwent salvage surgery. Considering a mean follow-up of 41.75 months, 7 patients are still disease free survivors. Only 1 patient developed local recurrence at 6 months and he died 14 months after abdomino-perineal resection., Conclusion: Primary radio chemotherapy, with a curative intent, could be considered the treatment modality of choice for squamous carcinoma of the rectum., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: There is no consensus on the role of postoperative chemotherapy in patients with rectal cancer who have received preoperative radio(chemo)therapy., Materials and Methods: A systematic review and meta-analysis were performed of trials that used preoperative radio(chemo)therapy and randomized patients either between postoperative chemotherapy and observation or between a fluoropyrimidine only (FU-only) and a fluoropyrimidine with oxaliplatin (FU-OXA) as postoperative chemotherapy., Results: Five randomized studies compared postoperative chemotherapy with observation in a total of 2398 patients. None of these trials demonstrated a statistically significant benefit of chemotherapy for OS and DFS. The pooled differences in OS and DFS did not differ statistically significantly between the chemotherapy group and the observation group. The hazard ratios (HRs) and 95% confidence intervals (CIs) were 0.95 (CI: 0.82-1.10), P = 0.49 and 0.92 (CI: 0.80-1.04), P = 0.19, respectively. In the subgroup of trials in which randomization was performed after surgery (n = 753), a statistically significant positive pooled chemotherapy effect was observed for DFS (HR = 0.79, 95% CI: 0.62-1.00, P = 0.047), but not for OS (P = 0.39). Four randomized trials compared adjuvant FU-OXA with adjuvant FU-only in 2710 patients. In two trials, the difference in DFS between groups was statistically significant in favour of FU-OXA, and in the other two trials, the difference was not significant. The pooled difference in DFS between the FU-OXA group and the FU-only group was not statistically significant: HR = 0.84 (CI: 0.66-1.06), P = 0.15., Conclusion: The use of postoperative chemotherapy in patients with rectal cancer receiving preoperative radio(chemo)therapy is not based on strong scientific evidence., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: In many European countries, short-term 5 × 5 Gy radiotherapy has become the standard preoperative treatment of patients with resectable rectal cancer. Individualized risk assessment might allow a better selection of patients who will benefit from postoperative treatment and intensified follow-up., Patients and Methods: From patient's data from three European rectal cancer trials (N = 2881), we developed multivariate cox nomograms reflecting the risk for local recurrence (LR), distant metastases (DM) and overall survival (OS). Evaluated variables were age, gender, tumour distance from the anal verge, the use of radiotherapy, surgical technique (total mesorectal excision/conventional surgery), surgery type (low anterior resection/abdominoperineal resection), time from randomization to surgery, residual disease (R0 versus R1 + 2), pT-stage, pN-stage and surgical complications., Results: Pathological T- and N-status are of vital importance for an accurate prediction of LR, DM and OS. Short-course radiotherapy reduces the rate of LR. The developed nomograms are capable of predicting events with a validation c-index of 0.79 (LR), 0.76 (DM) and 0.75 (OS). The proposed stratification in risk groups allowed significant distinction between Kaplan-Meier curves for outcome., Conclusion: The developed nomograms can contribute to better individual risk prediction for LR, DM and OS for patients operated on rectal cancer. The practicality of the defined risk groups makes decision support in the consulting room feasible, assisting physicians to select patients for adjuvant therapy or intensified follow-up., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The purpose of this study was to retrospectively analyse patients with orbital floor fracture who were treated at the Department of Odontostomatology and Maxillofacial Surgery, Policlinico Umberto I, Sapienza University of Rome, Italy, between 2008 and 2013. Patients were evaluated by age, sex, aetiology, clinical findings, fracture pattern, ocular injury, treatment, complications, and sequelae. We evaluated surgical outcomes and complications with the use of different surgical approaches and various materials used to reconstruct the orbital floor. In total, there were 301 orbital fractures. Two hundred and seventeen patients were men (72.1%) and 84 were women (27.9%). The average age of the patients was 37.2 years (range, 9-90 years). The leading cause of these fractures was violent assault (27.3%). Pure blow-out fractures (50.2%) were the most represented pattern, followed by zygomatic complex (46.5%). The most common symptom was hypoesthesia extending through the territory of the second trigeminal branch (TBH; 32.9%). Diplopia was present in 20.2% of patients followed by enophthalmos (2.3%) and extraocular movement limitation (1.7%). Ocular symptoms significantly improved following surgical repair. The most common postoperative complications included TBH in 34.2%, scarring 26%, and diplopia in 16.4% of the patients., (Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Several studies have shown remarkable differences in colorectal cancer survival across Europe. Most of these studies lacked information about stage and treatment. In this study we compared short-term survival as well as differences in tumour stage and treatment strategies between five European countries: Norway, Sweden, Denmark, Belgium, and the Netherlands. For this retrospective cohort study all patients aged 18 years or older and operated on adenocarcinoma of the rectum without distant metastases and diagnosed in 2008 and 2009 were selected in national audit registries from Norway, Sweden, Denmark, Belgium, and the Netherlands. Differences in pre-operative treatment between the countries were compared using univariable and multivariable logistic regression. One year relative survival and one year relative excess risk of death (RER) were compared between the five countries. Large variation in the use of preoperative radiotherapy and chemoradiation was found between the countries. Even though, there was little variation in relative survival between the countries, except Sweden, which had a significant better one year RER of death among the elderly patients after adjustment. The differences in survival are expected to be caused by differences in peri-operative care, selection of patients, and especially management of elderly patients. The effects of preoperative treatment are expected to be seen on long term follow-up., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: To evaluate the efficacy of preoperative low dose fractionated radiotherapy (LD-FRT) and chemotherapy in breast cancer., Materials and Methods: Patients with stage IIA-IIIA breast cancer, received LD-FRT (0.40 Gy bid, on day 1 and 2, for 6 cycles) to primary tumor volume and concurrent chemotherapy with non-pegylated liposomal anthracycline and docetaxel. Pathological response was assessed by Mandard Tumor Regression Grade (TRG). We evaluated the pathological major response rate (PMRR) as TRG1 and TRG2. The expected outcome was a PMRR of 60%. The accrual was determined by the single proportion powered analysis (α = 0.05, power = 0.8)., Results: Twentyone patients were enrolled. No grade 2-4 acute skin and hematological toxicity was observed. TRG1 was obtained in 3 patients (14.3%), TRG2 in 4 patients (19%). The PMRR was 33.3%; it does not concur with the expected result, but is similar to that of chemotherapy alone. According to molecular subtype, 2/11 luminal A patients and 4/6 luminal B patients obtained a PMRR to preoperative treatment (35.3%); 1/4 basal like patients reported TRG1 (25%)., Conclusions: LD-FRT concomitant with primary systemic treatment has a good toxicity profile. The response rate is consistent with that of chemotherapy alone, and suggests different interactions between low dose radiotherapy and molecular subtypes. Additional investigations are planned., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Colorectal cancer is one of the most common cancers in Europe. Over the past few decades, important advances have been made in screening, staging and treatment of colorectal cancer. However, considerable variation between and within European countries remains, which implies that further improvements are possible. The most important remaining question now is: when are we, health care professionals, delivering the best available care to patients with colon or rectal cancer? Currently, quality assurance is a major issue in colorectal cancer care and quality assurance awareness is developing in almost all disciplines involved in the treatment of colorectal cancer patients. Quality assurance has shown to be effective in clinical trials. For example, standardisation and quality control were introduced in the Dutch TME trial and led to marked improvements of local control and survival in rectal cancer patients. Besides, audit structures can also be very effective in monitoring cancer management and national audits showed to further improve outcome in colorectal cancer patients. To reduce the differences between European countries, an international, multidisciplinary, outcome-based quality improvement programme, European Registration of Cancer Care (EURECCA), has been initiated. In the near future, the EURECCA dataset will perform research on subgroups as elderly patients or patients with comorbidities, which are often excluded from trials. For optimal colorectal cancer care, quality assurance in guideline formation and in multidisciplinary team management is also of great importance. The aim of this review was to create greater awareness and to give an overview of quality assurance in the management of colorectal cancer., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Poor prognosis and limited therapeutic options characterize immunoglobulin light-chain (AL) amyloidosis with major heart involvement. Reliable experimental models are needed to study light-chain (LC)/heart interactions and to explore strategies for prevention of cardiac damage. We have exploited the nematode Caenorhabditis elegans as a novel tool, because its pharynx is evolutionarily related to the vertebrate heart. Our data demonstrate that the pharyngeal pumping of C elegans is significantly and selectively reduced by LCs from AL patients suffering from cardiomyopathy, but not by amyloid LCs with different organ tropism or nonamyloidogenic LCs from multiple myeloma. This functional alteration is dependent on the LC concentration and results in persistent pharyngeal dysfunction and in a significant reduction of the worms' lifespan. These manifestations are paralleled by an increase of mitochondrial reactive oxygen species and can be prevented by treatment with antioxidant agents. In conclusion, these data indicate that this nematode-based assay is a promising surrogate model for investigating the heart-specific toxicity of amyloidogenic LCs and for a rapid screening of new therapeutic strategies., (© 2014 by The American Society of Hematology.)