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In endometrial cancer (EC), sentinel lymph node (SLN) mapping has emerged as an alternative to systematic lymphadenectomy. Little is known about factors that might influence SLN preoperative detection. The aim of our study is to evaluate the clinical and technical variables that may influence on the success of SLN detection in preoperative lymphatic mapping in patients with intermediate and high-risk EC when performing Transvaginal Ultrasound-guided Myometrial Injection of Radiotracer (TUMIR).Between March 2006 and March 2017, we prospectively enrolled patients with histologically confirmed EC with intermediate or high-risk of lymphatic involvement. All women underwent SLN detection by using TUMIR approach. After radiotracer injection, pelvic and abdominal planar and SPECT/CT images were acquired to obtain a preoperative lymphoscintigraphic mapping. Pattern of drainage was registered and analyzed to identify the factors directly involved in drainage. Sonographer learning curves to perform TUMIR approach were created following Cumulative Sum and Wright methods. Univariate and multivariate analyses were performed using logistic regression.During study period, 123 patients were included. SLN preoperative detection rate was 70.7%. Age under 75 years at diagnosis (p0.01), radiotracer injection above 4ml -high- volume- (p0.01), and tumoral size below 2 cm (p=0.04) were associated with higher SLN preoperative detection rate. Twenty-five procedures were necessary to attain an adequate performance in TUMIR approach.The higher SLN preoperative detection rate in women with intermediate and high-risk endometrial cancer after TUMIR approach was related with younger age, smaller tumors and high-volume injection of radiotracer. Sonographers are required to perform 25 procedures before acquiring an expertise in radiotracer injection.

Background and Purpose: Mechanical thrombectomy (MT) in ischemic stroke patients with poor prestroke conditions remains controversial. We aimed to analyze the frequency of previously disabled patients treated with MT in clinical practice, the safety and clinical response to MT of patients with preexisting disability, and the disabled patient characteristics associated with a better response to MT. Methods: We studied all consecutive patients with anterior circulation occlusion treated with MT from January 2017 to December 2019 included in the Codi Ictus Catalunya registry—a government-mandated, prospective, hospital-based data set. Prestroke disability was defined as modified Rankin Scale score 2 or 3. Functional outcome at 90 days was centrally assessed by a blinded evaluator of the Catalan Stroke Program. Favorable outcome (to return at least to prestroke modified Rankin Scale at 90 days) and safety and secondary outcomes were compared with patients without previous disability. Logistic regression analysis was used to assess the association between prestroke disability and outcomes and to identify a disabled patient profile with favorable outcome after MT. Results: Of 2487 patients included in the study, 409 (17.1%) had prestroke disability (313 modified Rankin Scale score 2 and 96 modified Rankin Scale score 3). After adjustment for covariates, prestroke disability was not associated with a lower chance of achieving favorable outcome at 90 days (24% versus 30%; odds ratio, 0.79 [0.57–1.08]), whereas it was independently associated with a higher risk of symptomatic intracranial hemorrhage (5% versus 3%; odds ratio, 2.04 [1.11–3.72]) and long-term mortality (31% versus 18%; odds ratio, 1.74 [1.27–2.39]) compared with patients without disability. Prestroke disabled patients without diabetes, Alberta Stroke Program Early CT Score >8 and National Institutes of Health Stroke Scale score Conclusions: Despite a higher mortality and risk of symptomatic intracranial hemorrhage, prestroke-disabled patients return as often as independent patients to their prestroke level of function, especially those nondiabetic patients with favorable early ischemic signs profile. These data support a potential benefit of MT in patients with previous mild or moderate disability after large anterior vessel occlusion stroke.

Accurate assessment of disease extent is required to select the best primary treatment for advanced epithelial ovarian cancer patients. Estimation of tumour burden is challenging and it is usually performed by means of a surgical procedure. Imaging techniques and tumour markers can help to estimate tumour burden non-invasively. 2-[18F]FDG PET/CT allows the evaluation of the whole-body disease. This study aimed to correlate HE4 and CA125 serum concentrations with tumour burden evaluated by volumetric 2-[18F]FDG PET/CT parameters in advanced high-grade epithelial ovarian cancer. We included 66 patients who underwent 2-[18F]FDG PET/CT and serum tumour markers determination before primary treatment. Volumes of interest were delimited in every pathological uptake. Whole-body metabolic tumour volume (wb_MTV) and total lesion glycolysis (wb_TLG) were calculated summing up every VOI’s MTV value. SUVmax thresholds were set at 40% (MTV40 and TLG40) and 50% (MTV50 and TLG50). In addition, four VOI subgroups were defined: peritoneal carcinomatosis, retroperitoneal nodes, supradiaphragmatic nodes, and distant metastases. MTV and TLG were calculated for each group by adding up the corresponding MTV values. TLG was calculated likewise. wb_MTV and wb_TLG were found to be significantly correlated with serum CA125 and HE4 concentrations. The strongest correlation was observed between HE4 and wb_MTV40 (r = 0.62, p

The role of certain viruses in the etiology of some tumors is today indisputable, but there is a lack, however, of annoverview of the relationship between viruses and cancer with amultidisciplinary approach. For this reason, the Health Sciences Foundation has convened a group of professionals from different areas of knowledge to discuss the relationship between viruses and cancer, and the present document is the result of these deliberations. Although viruses cause only 10-15% of cancers, advances in oncology research are largely due to the work done during the last century on tumor viruses. The clearest cancer-inducing viruses are: HPV, HBV, HCV, EBV and, depending on the geographical area, HHV-8, HTLV-1 and HIV. HPVs, for example, are considered to be the causative agents of cervical carcinomas and, more recently, of a proportion of other cancers. Among the Herpes viruses, the association with the development of neoplasms is well established for EBV and HHV-8. Viruses can also be therapeutic agents in certain neoplasms and, thus, some oncolytic viruses with selective tropism for tumor cells have been approved for clinical use in humans. It is estimated that the prophylaxis or treatment of viral infections could prevent at least 1.5 million cancer deaths per year.

BACKGROUND: SARS-CoV-2 aerosolization during noninvasive positive-pressure ventilation may endanger health care professionals. Various circuit setups have been described to reduce virus aerosolization. However, these setups may alter ventilator performance. RESEARCH QUESTION: What are the consequences of the various suggested circuit setups on ventilator efficacy during CPAP and noninvasive ventilation (NIV)? STUDY DESIGN AND METHODS: Eight circuit setups were evaluated on a bench test model that consisted of a three-dimensional printed head and an artificial lung. Setups included a dual-limb circuit with an oronasal mask, a dual-limb circuit with a helmet interface, a single-limb circuit with a passive exhalation valve, three single-limb circuits with custom-made additional leaks, and two single-limb circuits with active exhalation valves. All setups were evaluated during NIV and CPAP. The following variables were recorded: the inspiratory flow preceding triggering of the ventilator, the inspiratory effort required to trigger the ventilator, the triggering delay, the maximal inspiratory pressure delivered by the ventilator, the tidal volume generated to the artificial lung, the total work of breathing, and the pressure-time product needed to trigger the ventilator. RESULTS: With NIV, the type of circuit setup had a significant impact on inspiratory flow preceding triggering of the ventilator (P < .0001), the inspiratory effort required to trigger the ventilator (P < .0001), the triggering delay (P < .0001), the maximal inspiratory pressure (P < .0001), the tidal volume (P = .0008), the work of breathing (P < .0001), and the pressure-time product needed to trigger the ventilator (P < .0001). Similar differences and consequences were seen with CPAP as well as with the addition of bacterial filters. Best performance was achieved with a dual-limb circuit with an oronasal mask. Worst performance was achieved with a dual-limb circuit with a helmet interface. INTERPRETATION: Ventilator performance is significantly impacted by the circuit setup. A dual-limb circuit with oronasal mask should be used preferentially.

Objective: Intraoperative magnetic resonance imaging (iMRI) can be useful for cerebral cavernous malformations (CCM) surgery. However, literature on this topic is scarce. We aim to investigate its clinical utility and propose criteria for the selection of patients who may benefit the most from iMRI. Methods: From 2017 to 2019, all patients with CCMs who required surgery assisted with iMRI were included in the study. Clinical and radiological features were analyzed. Outcome measures included the need for an immediate second-look resection and clinical course in early post-surgery-Timepoint 1(Tp1) and at the 6-to-12-month follow-up -Timepoint2-(Tp2). Results: Out of 19 patients with 20 CCMs, 89% had bleeding in the past, and in 75% the CCM affected an eloquent area. According to the iMRI results, an immediate second-look resection was needed in 16% of them. In one patient, a remnant was not seen on iMRI. The mRS worsened in the immediate postsurgical exam (median, 1; IQR, 1) with improvements on the 6-month visit (median, 1; IQR, 2), (p = 0.018). When comparing the outcome of patients with and without symptoms at baseline, the latter fared better at Tp2 (p = 0.005). Conclusions: iMRI is an intraoperative imaging tool that seems safe for CCM surgery and might reduce the risk of lesion remnants. In our series, it allowed additional revision for further resection in 16% of the patients. In our experience, iMRI may be especially useful for lesions in eloquent areas, those with a significant risk of brain shift and for large CCMs. (c) 2021 Elsevier Ltd. All rights reserved.

Resumen Los avances recientes en el campo de la biología molecular y la secuenciación del genoma se han traducido en una nueva clasificación del cáncer de mama, que busca mayor precisión y se correlaciona mejor con el riesgo de recaída de la enfermedad y la respuesta al tratamiento. Establece cuatro subtipos de cáncer de mama: luminal A, luminal B, HER 2 positivo y triple negativo, siendo el subtipo luminal A el de mejor pronóstico, y el triple negativo, el de peor pronóstico. Si combinamos la clasificación clásica histológica con la nueva molecular, nos permite encuadrar a estas pacientes de una forma más precisa en función del riesgo, definiendo así un manejo terapéutico adaptado.

Objectives The aim of this study was to evaluate the characteristics of fever of unknown origin (FUO) according to the definition with qualitative study criterion and of patients without diagnosis. Materials and methods Prospective observational study performed from 2009 to 2017 of all patients who were diagnosed with FUO according to the extended definition with qualitative study criterion. Demographic, clinical, diagnostic and evolving variables were evaluated. Results Of the 87 patients registered, 17.3% presented criteria of inflammation of unknown origin (IUO). The diagnoses were: non-infectious inflammatory diseases (NIID) in 19 patients (21.8%), infections in 15 (17.2%), miscellaneous in 14 (16.1%), malignant diseases in 13 (15%) and without diagnosis in 26 (29.9%). In 17.6% of the cases, a potentially diagnostic clue (PDC) was identified. The patients without diagnosis were characterized by a lower number of total PDC (5.9 ± 3.3 vs. 8.7 ± 3.4; P = .000), fewer clinical signs (.4 ± .6 vs. .9 ± .8; P = .001), a smaller number of tests in the previous study (2.7 ± 2.1 vs. 4.6 ± 2; P = .000), a shorter diagnostic interval (14.6 ± 7.7 days vs. 21.4 ± 9.5 days; P = .029) and less alteration of erythrocyte sedimentation rate (52.3 ± 41.3 mm/h vs. 89.8 ± 42.7 mm/h; P = .000), haemoglobin (12.9 ± 1.7 g/dl vs. 11.7 ± 1.6 g/dl; P = .003) and albumin (36.9 ± 6.4 g/l vs. 33.2 ± 7.2 g/l; P = .025). 18F-fluorodeoxyglucose positron-emission tomography combined with computed tomography (18F-FDG-PET/TC) proved to be helpful in 37% of the cases. Mortality was 6.8%. Conclusions The definition of FUO with qualitative study criterion incorporates a diagnostic protocol that provides clear benefits in terms of cost-effectiveness.

Resumen Objetivos Evaluar las caracteristicas de la fiebre de origen desconocida (FOD) segun la definicion con criterio de estudio cualitativo y de los pacientes sin diagnostico. Material y metodos Estudio prospectivo observacional realizado entre 2009-2017 de todos los pacientes diagnosticados de FOD segun la definicion con criterio de estudio cualitativo ampliada. Se evaluaron variables demograficas, clinicas, diagnosticas y evolutivas. Resultados De los 87 pacientes registrados el 17,3% presentaron criterios de inflamacion de origen desconocido. Los diagnosticos fueron: enfermedades inflamatorias no infecciosas en 19 pacientes (21,8%), infecciones en 15 (17,2%), miscelanea en 14 (16,1%), enfermedades malignas en 13 (15%) y sin diagnostico en 26 (29,9%). Se identifico algun indicio con potencial diagnostico (IPD) en el 17,6% de los casos. Los pacientes sin diagnostico se caracterizaron por un menor numero de IPD totales (5,9 ± 3,3 vs. 8,7 ± 3,4; p = 0,000), menos signos clinicos (0,4 ± 0,6 vs. 0,9 ± 0,8; p = 0,011), menor numero de pruebas en el estudio previo (2,7 ± 2,1 vs. 4,6 ± 2; p = 0,000), un menor intervalo diagnostico (14,6 ± 7,7 dias vs. 21,4 ± 9,5 dias; p = 0,029) y una menor alteracion de la velocidad de sedimentacion globular (52,3 ± 41,3 mm/h vs. 89,8 ± 42,7 mm/h; p = 0,000), hemoglobina (12,9 ± 1,7 g/dl vs. 11,7±1,6 g/dl; p = 0,003) y albumina (36,9 ± 6,4 g/l vs. 33,2 ± 7,2 g/l; p = 0,025). La tomografia por emision de positrones con 18F-fluorodesoxiglucosa combinada con tomografia computarizada resulto de utilidad en el 37% de los casos. La mortalidad fue del 6,8%. Conclusiones La definicion de FOD con criterio de estudio cualitativo incorpora un protocolo diagnostico que aporta evidentes beneficios en terminos de coste-eficacia.

BACKGROUND: Flow diverters (FDs) are an excellent option for the management of giant carotid artery aneurysms. However, in a nonnegligible percent of cases, the aneurysm may continue to grow despite multiple endovascular treatments and apparent occlusion on the angiogram. Due to the recent introduction of FDs, surgical experience after their failure is scarce and neurosurgeons have to face these challenging cases without much previous reference. Here we describe a giant ophthalmic-carotid aneurysm that presented with new severe mass effect 5 years after initially successful treatment with FDs and coils. We investigate the likely advantages of partial trapping versus complete trapping in this particular type of case. CASE DESCRIPTION: A 63-year-old patient with a subarachnoid hemorrhage from a 26-mm left carotid-ophthalmic aneurysm was initially embolized with coils. One year later a recanalization was observed and treated with an FD. Five years afterward, the patient's mild cognitive impairment prompted a magnetic resonance image that showed significant aneurysm growth despite apparent occlusion on angiogram. Rescue surgery consisted of partial trapping + extracranial-intracranial bypass and aneurysm debulking. The patient recovered from his deficits and remains asymptomatic 2 years later. CONCLUSIONS: In selected patients with previous long-term FDs, partial trapping may be a choice even if aneurysm debulking is needed. After years of stent placement, some endothelialization and neointimal membrane formation could have a summing effect to facilitate surgical exclusion and enable a safe thrombectomy. Classic revascularization techniques must be rethought and retested in this new FD era scenario.

According to current guidelines, patients with aneurysmal subarachnoid haemorrhage (aSAH) are mostly managed in intensive care units (ICUs) regardless of baseline severity. We aimed to assess the prognostic and economic implications of initial admission of patients with low-grade aSAH into a stroke unit (SU) compared to initial ICU admission.We reviewed prospectively registered data from consecutive aSAH patients with a World Federation of Neurosurgery Societies grade3, admitted to our Comprehensive Stroke Centre between April 2013 and September 2018. Clinical and radiological baseline traits, in-hospital complications, length of stay (LOS) and poor outcome at 90 days (modified Rankin Scale score 2) were compared between the ICU and SU groups in the whole population and in a propensity-score-matched cohort.Of 131 patients, 74 (56%) were initially admitted to the ICU and 57 (44%) to the SU. In-hospital complication rates were similar in the ICU and SU groups and included rebleeding (10% vs. 7%; P = 0.757), angiographic vasospasm (61% vs. 60%; P = 0.893), delayed cerebral ischaemia (12% vs. 12%; P = 0.984), pneumonia (6% vs. 4%; P = 0.697) and death (10% vs. 5%; P = 0.512). LOS did not differ between groups (median [interquartile range] 22 [16-30] vs. 19 [14-26] days; P = 0.160). In adjusted multivariate models, the location of initial admission was not associated with long-term poor outcome either in the whole population (odds ratio [OR] 1.16, 95% confidence interval [CI] 0.32-4.19; P = 0.825) or in the matched cohort (OR 0.98, 95% CI 0.24-4.06; P = 0.974).A dedicated SU, with care from a multidisciplinary team, might be an optimal alternative to ICU for initial admission of patients with low-risk aSAH.

Lymph node (LN) metastases are the most important prognostic factor in locally advanced cervical cancer. Paraaortic lymphadenectomy is the only method able to confirm the presence of metastasis and thereby help to determine the most adequate treatment approach. There is no standard regarding the minimal number of LNs that should be removed in paraaortic lymphadenectomy. Women with undiagnosed positive paraaortic LNs (false negatives) due to a low LN count do not receive extended-field radiation therapy, which may lead to worse survival outcomes. The aim of this study is to confirm LN metastases as poor prognosis and to assess whether in cases of locally advanced CC with negative paraaortic LN status, the number of paraaortic LN laparoscopically removed carries a prognostic value.We analyzed 78 patients with locally advanced cervical cancer that underwent complete paraaortic lymphadenectomy.Fifteen (19.2%) women had paraaortic LN metastases. The mean number of LN extracted was 11.1 (SD 7.5). Patients with paraaortic LN metastases presented a worse overall survival (127.1 months [95% CI 111.7-142.4] vs. 59.6 months [95% CI 31.2-87.9]; p0.01). Nevertheless, there were no differences regarding disease-free survival. There were no prognostic differences according to the number of LNs resected in patients with negative lymphadenectomy.Patients with locally advanced cervical cancer and paraaortic LN metastases present worse survival. In women with negative paraaortic LN, the number of LNs removed does not imply shorter survival.

Objective Paraaortic lymph node involvement is an important prognostic factor in locally advanced cervical cancer (LACC), but the anatomic limit of aortic lymphadenectomy is controversial. We assessed the impact of extraperitoneal paraaortic lymphadenectomy up to the left renal vein in patients with LACC undergoing pretherapeutic staging. Methods A retrospective, multicenter study of patients with LACC stages FIGO 2009 IB2 and IIA2-IVA treated in 10 Spanish reference hospitals in gynecological oncology between 2000 and 2016. Sites of metastatic paraaortic lymph nodes above or below the inferior mesenteric artery were evaluated. Procedural-related intraoperative and early and late complications were assessed. Results We included 634 patients undergoing paraaortic lymphadenectomy, in 616 (97.2%) of which the left renal vein was the upper limit of dissection (laparoscopy 592, robotic-assisted 24). The median surgical time was 150 min (interquartile range (IQR) 120–180), blood loss was 50 mL (range 20–80), and the length of stay was 2 days (range 2–3). Metastatic paraaortic involvement was found in 114 patients (18.5%), with infrarenal metastases in 73 (64%) of them. There were 11 patients (9.6%) with infrarenal metastases only, whereas in the remaining 62 (54.4%) patients concomitant infrarenal and inframesenteric metastases were observed. Intraoperative, early, and late postoperative complications occurred in 3.6%, 7.0%, and 4.5% of patients, respectively. Conclusions In this study of patients with LACC undergoing surgical staging, paraaortic lymphadenectomy up to the left renal vein detected skip or isolated infrarenal metastasis in 9.6% of patients, with an acceptable surgical morbidity.

The decision to treat a cervical squamous intraepithelial lesion (SIL) by loop electrosurgical excision procedure (LEEP) relies heavily on a colposcopy‐directed biopsy showing high‐grade (H)SIL. Diagnosis is often supported by p16, an immunohistochemical (IHC) biomarker of high‐risk (hr)HPV E7 gene activity. Additional potential markers include methylation of tumor suppressor genes FAM19A4/miR124‐2 in cervical cytology for advanced transforming HSIL and the IHC marker HPV E4 for productive, potentially regressing lesions. In 318 women referred for colposcopy, we investigated the relationship between staining patterns of p16 and E4 IHC in the worst biopsy, and the relation of these to FAM19A4/miR124‐2 methylation status in cytology. E4‐positive staining decreased with increasing SIL/CIN grade from 41% in LSIL to 3% in HSIL/CIN3. E4 positivity increased with grade of p16 when p16 expression was limited to the lower two third of the epithelium (r = 0.378), but fell with expression over. Loss of E4 expression in the worst lesion was associated with the methylation of FAM19A4/miR124‐2. We also examined whether these biomarkers can predict the histological outcome of the LEEP biopsy in a subgroup of 119 who underwent LEEP treatment. About 85% of women with ≥lower two third p16 staining/E4‐negative HSIL biopsies and 65% with limited p16 staining/E4‐positive HSIL biopsies had ≥HSIL in the LEEP specimen (P = .025). p16 expression in a biopsy is related both to viral production and transformation, while decreased E4 expression relates to methylation, indicating advanced HSIL. p16 expression in ≥2/3 of the epithelium and absent E4 indicate likely HSIL on a subsequent LEEP specimen., We found an inverse relation between HPV E4 expression on biopsy and hypermethylation of FAM19A4/miR124‐2 on cytology sample. p16 and hypermethylation increased with the severity of the lesion and may be used to identify premalignant transformation. The use of p16/E4 immunostaining and methylation could offer valuable information beyond current grading practice.

Aim To analyse the possible relationship between the EQD2(α/β=3Gy) at 2 cm3 of the vagina and late toxicity in vaginal-cuff-brachytherapy (VBT) after external-beam-irradiation (EBRT) for postoperative endometrial carcinoma (EC). Materials and methods From 2014 to 2016, 62 postoperative EC patients were treated with EBRT + VBT. The median EBRT dose was 45 Gy (44 Gy–50.4 Gy). VBT involved a single 7 Gy dose. Toxicity was prospectively evaluated using the RTOG score for the rectum and bladder and the objective LENT-SOMA criteria for the vagina. EQD2(α/β = 3Gy) at 2 cm3 of the most exposed part of the vagina was calculated by the sum of the EBRT + VBT dose. Statistics: Boxplot, Student’s t and Chi-square tests and ROC curves. Results Mean follow-up: 39.2 months (15–68). Late toxicity: bladder:0 patient; rectum:2 patients-G1; Vagina: 26 patients-17G1, 9G2; median EQD2(α/β=3Gy) at 2 cm3 in G0-G1 patients was 70.4 Gy(SD2.36), being 72.5 Gy(SD2.94) for G2p. The boxplot suggested a cut-point identifying the absence of G2: 100 % of G2p received >68 Gy, ROC curves showed an area under the curve of 0.72 (sensitivity of 1 and specificity of 0.15). Conclusions Doses >68 Gy EQD2(α/β=3Gy) at 2 cm3 to the most exposed area of the vagina were associated with late G2 vaginal toxicity in postoperative EC patients treated with EBRT + VBT suggesting a very good dose limit to eliminate the risk of G2 late toxicity. The specificity obtained indicates the need for prospective analyses.

Introduction Prader-Willi Syndrome (PWS) is a genetic disorder caused by the lack of expression of certain paternal genes located on chromosome 15q11-q13. This anomaly causes cognitive, neurological and endocrine abnormalities, among which one of the most important is hyperphagia. The aim of this study was to assess the oral health of children with PWA and to establish preventive criteria. Results Thirty patients with PWS (mean age 10.2 years) and 30 age- and gender-matched controls were included in the study. Twenty-six patients with PWS(86.6%) followed dietary treatment prescribed by their endocrinologist. Individuals with PWS had a mean caries index of 53.3% and Decayed Missing Filled teeth (DMFT) index 2.5, and 53.3% had gingivitis, in the control group the respective figures were 43.3%, 0.93, and 60%. Only the DMFT index (p 0.017) presented significant differences. Regarding stimulated salivary secretion, patients with PWS presented a mean of 0.475 ml/min with a pH of 6.15, while controls presented a mean of 0.848 ml/min with a pH of 7.53; the differences between the groups were statistically significant in both cases (p 0.032 and p 0.0001 respectively). The population with PWS presented a higher plaque index (> 2) than their healthy peers, but the differences were not significant. Conclusion Pediatric patients with Prader-Willi syndrome have an increased risk of caries and gingivitis. The children with this syndrome have a decreased salivary flow and a more acidic salivary pH. In these patients, dental care is an essential part of their multidisciplinary medical treatment.

Human papillomaviruses (HPVs) are the causative agents of carcinoma of the uterine cervix. A number of HPV genotypes have been associated with cervical cancer and almost all tumors associated with HPV show strong p16 expression. However, there is little information on the possible impact of the HPV genotype and p16 immunostaining on the clinicopathological features or their prognostic value in cervical carcinoma. We evaluated a series of 194 patients with HPV-positive cervical cancers treated at our institution, focusing on the clinicopathological features and the relationship of the HPV genotypes and p16 immunostaining with the prognosis. A single HPV type was identified in 149 (77%) tumors, multiple HPV infection was detected in 30 cases (15%), and undetermined HPV type/s were identified in 15 (8%) carcinomas. HPV 16 and/or 18 were detected in 156 (80%) tumors. p16 was positive in 186 (96%) carcinomas, but eight tumors (4%) were negative for p16 (seven squamous cell carcinomas, one adenocarcinoma); 5/8 caused by HPV 16 and/or 18. Patients with HPV 16 and/or 18 were younger (49 ± 15 vs. 57 ± 17 years, p

Frailty; Psychometrics; Feasibility Fragilitat; Psicometria; Viabilitat Fragilidad; Psicometría; Viabilidad The study aimed to assess the reliability of the scores, evidence of validity, and feasibility of the Frail-VIG index. A validation study mixing hospitalized and community-dwelling older people was designed. Intraclass correlation coefficient (ICC) was used to assess the inter-rater agreement and the reliability. The construct validity of the Frail-VIG index with respect to the Frailty Phenotype (FP) was evaluated by calculating the area under the receiver operating characteristic curve (AUC-ROC). Convergent validity with the Clinical Frailty Scale (CFS) was assessed using Pearson’s correlation coefficients. The feasibility was evaluated by calculating the average time required to administer the Frail-VIG index and the percentage of unanswered responses. A sample of 527 older people (mean age of 81.61, 56.2% female) was included. The inter-rater agreement and test–retest reliability were very strong: 0.941 (95% CI, 0.890 to 0.969) and 0.976 (95% CI, 0.958 to 0.986), respectively. Results indicated adequate convergent validity of the Frail-VIG index with respect to the FP, AUC-ROC 0.704 (95% CI, 0.622 to 0.786), and a moderate to strong positive correlation between the Frail-VIG index and CFS (r = 0.635, 95% CI, 0.54 to 0.71). The Frail-VIG index administration required an average of 5.01 min, with only 0.34% of unanswered responses. The Frail-VIG index is a reliable, feasible, and valid instrument to assess the degree of frailty in hospitalized and community-dwelling older people.

To determine whether brachytherapy with a single hypofractionated dose of 7 Gy provides the similar vaginal-cuff relapses and safety profile in terms of complications compared to schedules of 2 or 3 fractions of lower doses in patients treated previously with external beam irradiation in postoperative endometrial carcinoma. From June 2003 to December 2016, 325 patients were treated with 3 different schedules of high-dose-rate brachytherapy after external beam irradiation for postoperative endometrial carcinoma. The patients were divided into 3 groups: Group-1: 125 patients were treated with 3 fractions of 4–6 Gy per fraction (3 fractions/week) between 2003 and 2008; Group-2: 93 patients were treated with 2 consecutive daily fractions of 5–6 Gy between 2008 and 2011; Group-3: 107 patients received a single fraction of 7 Gy between 2011 and 2016. Bladder and rectum complications were assessed using RTOG scores and with the objective scores of LENT-SOMA for the vagina. Statistics: the chi-square test. The mean follow-up of Groups 1, 2 and 3 was 95, 67 and 51 months, respectively. Three patients in Group-1, 2 in Group-2, 1 in Group-3 developed vaginal-cuff relapse (p = 0.68). No differences were found in late toxicity among the three groups. One single dose of 7 Gy is safe and effective and may be the best treatment schedule with a similar incidence of vaginal-cuff relapses, complications and patient comfort with less hospital attendance.

OBJECTIVEReliable tools are lacking to predict shunt-dependent hydrocephalus (SDHC) development after aneurysmal subarachnoid hemorrhage (aSAH). Quantitative volumetric measurement of hemorrhagic blood is a good predictor of SDHC but might be impractical in the clinical setting. Qualitative assessment performed using scales such as the modified Fisher scale (mFisher) and the original Graeb scale (oGraeb) is easier to conduct but provides limited predictive power. In between, the modified Graeb scale (mGraeb) keeps the simplicity of the qualitative scales yet adds assessment of acute hydrocephalus, which might improve SDHC-predicting capabilities. In this study the authors investigated the likely capabilities of the mGraeb and compared them with previously validated methods. This research also aimed to define a tailored mGraeb cutoff point for SDHC prediction.METHODSThe authors performed retrospective analysis of patients admitted to their institution with the diagnosis of aSAH between May 2013 and April 2016. Out of 168 patients, 78 were included for analysis after the application of predefined exclusion criteria. Univariate and multivariate analyses were conducted to evaluate the use of all 4 methods (quantitative volumetric assessment and the mFisher, oGraeb, and mGraeb scales) to predict the likelihood of SDHC development based on clinical data and blood amount assessment on initial CT scans.RESULTSThe mGraeb scale was demonstrated to be the most robust predictor of SDHC, with an area under the curve (AUC) of 0.848 (95% CI 0.763–0.933). According to the AUC results, the performance of the mGraeb scale was significantly better than that of the oGraeb scale (χ2 = 4.49; p = 0.034) and mFisher scale (χ2 = 7.21; p = 0.007). No statistical difference was found between the AUCs of the mGraeb and the quantitative volumetric measurement models (χ2 = 12.76; p = 0.23), but mGraeb proved to be the simplest model since it showed the lowest Akaike information criterion (66.4), the lowest Bayesian information criterion (71.2), and the highest R2Nagelkerke coefficient (39.7%). The initial mGraeb showed more than 85% specificity for predicting the development of SDHC in patients presenting with a score of 12 or more points.CONCLUSIONSAccording to the authors’ data, the mGraeb scale is the simplest model that correlates well with SDHC development. Due to limited scientific evidence of treatments aimed at SDHC prevention, we propose an mGraeb score higher than 12 to identify patients at risk with high specificity. This mGraeb cutoff point might also serve as a useful prognostic tool since patients with SDHC after aSAH have worse functional outcomes.

Introduction/Background* The combination of improved survival and delaying child bearing increases the trend of early cervical cancer diagnosis in women without a fulfilled gestational wish. Fertility preservation surgery (FSS) becomes a necessary treatment option for young women. The aim of this study is to analyze the impact of tumor size on surgical and oncological outcomes of FSS in early cervical cancer in Spain. Methodology A multicenter, retrospective cohort study of early cervical cancer (IA2- IB1, FIGO 2009) patients with gestational desire who underwent FSS was carried out at the departments of gynecology of 12 tertiary care hospitals between 01/2005 and 01/2019 throughout Spain. The data were registered in an on-line database. All analyses were performed using STATA 15 statistical software Result(s)* A total of 111 patients who underwent trachelectomy were included, 82 (73.9%) of them with tumors Median follow-up was 55.7 months in patients group Cox regression was performed to identify different predictor factor for recurrence. Only tumor size ( Conclusion* This study shows a real world data of a large number of trachelectomies performed in patients with early cervical cancer after negative lymphnode assessment. Selection criteria should be rigorous especially for patients with tumor ≥ 2 cm due to its worse oncological outcomes. Options may be discussed with the patient to reach a balance between the risk of recurrence and the best fertility results

Introduction/Background* Molecular landscape and carcinogenesis of vulvar squamous cell carcinoma (VSCC) have been poorly explored and lack a biomarker-driven targeted therapy. In this non-systematic review we aimed to summarize findings of studies exploring molecular landscape of VSCC. Methodology Key word search was conducted (PubMed, Scopus) in January 2021, using the terms (“vulvar” and “cancer” or “carcinoma”) and (“molecular” or “genomic” or “mutation”). Observational studies evaluating molecular alterations in VSCC were deemed eligible. Pre-specified data were extracted from the selected articles, including the number of samples analyzed, DNA sequencing technique, number and frequency of identified mutations, HPV prevalence and prognostic data. Result(s)* Fourteen studies published between 2005 and 2020 were identified, including a total of 747 VSCC samples. Selected studies were highly heterogeneous in terms of DNA sequencing and HPV testing strategies and included small samples. Twelve studies performed next generation sequencing (NGS), nine of whom used targeted approach, two used whole exome sequencing and one used whole genome sequencing. The two remaining studies used multiplex ligation-dependent probe amplification assay and Sanger sequencing. The most frequently studies and mutated genes were TP53 and CDKN2A, followed by PIK3CA, HRAS and PTEN (table 1). Evidence on genomic differences between HPV-associated and -independent VSCC is particularly scarce and variable between studies. Only a single, targeted NGS study showed notorious differences in molecular profiles based on HPV status. Accumulated evidence indicates that in HPV-associated VSCC more frequently involves PI3K/AKT/mTOR pathway, involving HRAS, KRAS, PIK3CA, KMT2D, PTEN and FBXW7 mutations. On the other hand, HPV-independent VSCC involve alterations in TP53, CDKN2A, CCND1. The prognostic role of molecular alterations in VSCC was assessed in seven articles, with discordant results. Some articles suggest that TP53 alterations are associated to worse prognosis in patients with VSCC, particularly when combined with PIK3CA, HRAS or CDKN2A. Conclusion* Limitations and heterogeneity of available molecular series contribute to a limited view of the molecular landscape of VSCC. Prognostic or therapeutic roles of identified mutations and pathways in VSCC remain to be elucidated. Large-scale, genome or exome-wide studies with robust HPV testing are necessary to expand the knowledge on molecular landscape in VSCC.

Introduction/Background* The aim of this study was to correlate the serum concentrations of tumor markers HE4 and CA125 with the tumor burden evaluated through the volumetric parameters of FDG-PET/CT FDG in patients with advanced epithelial ovarian cancer (EOC) before primary treatment. Methodology Sixty-six patients with advanced stage high grade serous ovarian carcinoma (HGSOC) or undifferentiated carcinoma (UOC) were included. Serum HE4, serum CA125 and FDG PET/CT were performed before primary treatment. Volumes of interest (VOIs) were delimited on every pathological uptake in PET images. Whole-body metabolic tumor volume (wbMTV) and total lesion glycolysis (wbTLG) were calculated as the sum of every single VOI value. SUVmax thresholds were set at 40% and 50%. Four VOIs subgroups were defined for analysis: carcinomatosis, retroperitoneal, supradiaphragmatic and metastases. MTV and TLG values were calculated for each of them. The associations between these parameters and serum tumor markers were assessed through Pearson and Spearman tests. Result(s)* When correlating wbMTV and wbTLG with both CA125 and HE4, significant associations were found. The strongest correlation was observed between HE4 and wbMTV40% (r=0.61, p Conclusion* Peritoneal tumor burden measured by FDG PET/CT volumetric parameters correlates better with HE4 than with CA125 in patients with advanced epithelial ovarian cancer. These results support the increasing utility of HE4 to improve the stratification of these patients in clinical practice

Introduction/Background* Systematic pelvic and paraortic lymphadenectomy is part of the initial epithelial ovarian cancer (EOC) staging surgery but this procedure is associated with potential severe morbidity. Moreover, there is no evidence suggesting a possible therapeutic value. The detection of the sentinel lymph node (SLN) in the early stage of EOC is in the experimental phase and there is little literature about it. This study evaluates the lymphatic mapping with radiotracer and indocyanine green (ICG)) and the detection of ovarian SLN. Methodology Prospective cohort study in ovarian masses suspected of malignancy or re-staging surgery after confirmed malignancy. Albumin [99mTc] Tc-nanocolloid was injected into the utero-ovarian and infundibulo-pelvic ligaments. After 15 minutes, intraoperative images were acquired with a portable gammacamera. Subsequently, the adnexectomy and intraoperative pathological analysis were performed. In the cases in which malignancy was confirmed, ICG was injected proximally to the sectioned area of the ligaments and the lymphatic chains were traced with the fluorescence camera prior to the pelvic and paraortic lymphadenectomy. Ultrastaging of the SLN was done. The follow-up for possible adverse events lasted 30 days after surgery. Result(s)* 20 patients were included between September-2020 and May-2021. Ovarian carcinoma was confirmed in 8 (40%) cases. In all cases gamma probe was used, in 60% the gamma camera and 40% the fluorescence camera. Some SLN was detected in 18/20 cases (90%) with exclusive paraortic drainage in 5/18 (28%), pelvic in 1/18 (6%) and in both territories in 12/18 (66%). Overall para-aortic drainage was observed in 17/18 (94%) patients (35% supramesenteric, 30% at the level of the inferior mesenteric artery, and 35% inframesenteric). 100% of aortic SLNs were detected with a gamma probe after being visualized with the gamma camera. In the 8 patients who underwent lymphadenectomy, 1 case had positive nodes diagnosed by ultrastaging and the rest of the lymph nodes were negative. No complications related to the technique were observed. Conclusion* The SLN technique is feasible and safe. The intraoperative gamma camera shows the lymphatic map and is especially useful in the paraortic region.

Introduction/Background* In patients with early-stage, grade 1-2, endometrioid endometrial cancer, preoperative assessment of myometrial invasion is essential to define the need of pelvic and paraaortic lymph node dissection. Our aim was to evaluate the role of three-dimensional transvaginal ultrasound (3D-TVUS) and diffusion-weighted magnetic resonance imaging (DW-RMI) for the assessment of myometrial infiltration in patients with well-differentiated (G1) or moderately differentiated (G2) endometrioid endometrial carcinoma (EC). Methodology We performed a retrospective observational study. Myometrial infiltration was assessed by 3D-TVUS and DW-MRI in 152 women with G1 or G2 endometroid EC who underwent surgical treatment in a tertiary referral center between 2012 and 2019. Sensitivity, specificity, predictive values and accuracy for the two techniques and for a combination of both were computed. Definitive histopathological data in the surgical specimen regarding myometrial infiltration was used as ‘Gold Standard’. Result(s)* One hundred and fifty-two patients were included, 120 (79%) patients presented myometrial infiltration 50%). 3D-TVUS and DW-MRI showed an agreement of 78.9% with a kappa index of 0.44 for the detection of deep myometrial infiltration. Sensitivity, specificity and accuracy of 3D-TVUS for the detection of deep myometrial infiltration were 71.0%, 80.5% and 78.5% respectively. Evaluation of myometrial infiltration with DW-MRI had a sensitivity, specificity and accuracy of 76.2%, 84.4% and 82.9% respectively. Association of both techniques increased sensitivity and specificity up to 84.6% and 93.2% and provided a low false negative rate (2.3%). Conclusion* The combination of 3D-TVUS and DW-RMI offers a high sensitivity and specificity to identify deep myometrial infiltration in patients with endometrioid G1 or G2 EC, thus these patients might benefit from performance of both techniques in preoperative evaluation.

Introduction/Background* The SENTIX is a prospective cohort international study on sentinel lymph node (SLN) biopsy without pelvic lymph node dissection (PLND) in patients with early-stage cervical cancer. The primary end point is a recurrence rate at 24 months´ follow-up after the surgery. Either magnetic resonance imaging (MRI) or expert ultrasound (EUS) was mandatory as a preoperative staging method. The aim of this study is to report the accuracy of preoperative local staging. Methodology Forty-seven sites from 18 countries participated in the study. Patients with stages T1a1/LVSI+ – T1b1 (FIGO 2009), common histological types and no suspicious lymph nodes on imaging were eligible. Patients were excluded from further study if SLN were not detected on both sides and if SLN was positive on frozen section histological evaluation. Compared were results from preoperative imaging with final pathology reports. Result(s)* From May 2016 to October 2020, 733 registered patients underwent surgery, 132 were excluded intraoperatively, data from 708 were analysed in this study. Patients’ characteristics are in table 1. Out of 90 patients clinically staged as 1A tumours, 42 (46.7%) were upstaged to IB1 (86% ≤ 2 cm, 14% 2-4cm, 0% > 4cm); 76.3% had conisation as diagnostic procedure. Fourteen out of 547 preoperatively IB1 tumours (2.6%) were upstaged to IB2 > 4cm. Analogously 33 patients (6%) with IB tumours were downstaged to IA. Preoperatively unrecognized parametrial involvement was found by pathology only in 22 out of 637 patients (3.5%). EUS and MRI were used equally in the study (53.5% vs 56.1%), both were comparable in the accuracy of tumour size measurement (2 cm size categories shift in stage IB) (p=1.000) and in the failure to detect parametrial involvement (2.9% vs 4.0%) (p=0.535). Chart 1. Conclusion* Clinical staging with EUS and MRI failed to detect positive parametria only in 3.5% of patients in the Sentix trial. Upstaging from IA tumours was frequent, mostly after previous conization. Only 2.6% of patients were upstaged to IB2 tumours >4 cm (IB3 FIGO 2018). Both EUS and MRI were equally reliable in tumour size and parametrial involvement assessment.

Introduction/Background* Lower-limb lymphedema (LLL) is a well-recognized adverse outcome of the surgical management of cervical cancer. Recently, sentinel lymph node (SLN) biopsy has emerged as an alternative procedure to systematic pelvic lymphadenectomy (PLND) aiming to decrease the risk of complications, especially LLL development. Our study represents the first prospective analysis of LLL incidence in cervical cancer patients after a uterine procedure with SLN biopsy, without systematic PLND. Methodology In a prospective international multicenter trial SENTIX, the group of 150 patients with stage IA1–IB2 cervical cancer treated by uterine surgery with bilateral SLN biopsy was prospectively evaluated using both objective LLL assessments, based on limb volume increase (LVI) between pre- and postoperative measurements, and subjective patient-perceived swelling were conducted in six-month periods over 24-months post-surgery. The characteristics of the patients are summarized in table 1. Result(s)* The cumulative incidence of LLL at 24 months was 17.3% for mild LLL (LVI 10-19%), 9.2% for moderate LLL (LVI 20-39%), while only one patient (0.7%) developed severe LLL (LVI >40%). The median interval to LLL onset was nine months (figure 1). A transient edema resolving without intervention within six months was reported in an additional 22% of patients. Subjective LLL was reported by 10.7% of patients, though only a weak and partial correlation between subjective-report and objective-LVI was found. No risk factor directly related to LLL development was identified. Conclusion* Contrary to the expectations, the replacement of standard PLND by bilateral SLN biopsy in the surgical treatment of cervical cancer does not eliminate the risk of mild to moderate LLL, which develops irrespective of the number of SLN removed. Trial registration ClinicalTrials.gov: NCT02494063 Funding This work was supported by Charles University in Prague (UNCE 204065 and PROGRES Q28/LF1) and by a grant from the Czech Health Research Council (NV19-03-00023). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Conflicts of Interest The authors declare no conflict of interest.

Purpose The feasibility and effects of multimodal prehabilitation in patients with advanced ovarian cancer (AOC) undergoing a cytoreductive surgery are unknown. We aimed to evaluate the feasibility of a multimodal prehabilitation program in patients with AOC and its impact on postoperative outcomes.Methods We prospectively compared 15 patients with AOC stage scheduled to undergo a citorreductive surgery between December 2019 and January 2021 after a multimodal prehabilitation program consisting of supervised exercise training, nutritional optimization and psychological preparation versus a control cohort of 19 patients matched according to clinical and surgical characteristics who underwent surgery without prehabilitation between January 2018 and November 2019. In both groups, the enhanced recovery after surgery guidelines were followed. We analyzed adherence to the program, comprehensive complication index (CCI), hospital length of stay, and time to starting chemotherapy. Results Overall adherence to the multimodal prehabilitation program was 80%, with 86.7% adherence to exercise training, 100% adherence to nutritional optimization, and 80% adherence to psychological preparation. Median hospital stay was shorter in the prehabilitation cohort [5 days (IQR, 4-6) vs. 7 days (IQR,5-9) in the control cohort, p=0.04]. CCI score in the prehabilitation cohort was 9.3 (SD 12.12) vs. 16.61 (SD 16.89) in the control cohort, p=0.2. Median time to starting chemotherapy was shorter in the prehabilitation cohort compared to control cohort [25 days (IQR, 23-25) vs. 35 days (IQR 28-45), p=0.03]. Conclusion Multimodal prehabilitation is feasible and safe in patients with AOC. This study found significantly shorter hospital stays and time to starting chemotherapy in the multimodal prehabilitation cohort.