Post-operative residual disease and number of cycles of neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma.

BACKGROUND: The optimal number of neoadjuvant chemotherapy cycles in patients with advanced ovarian cancer is still disputed. OBJECTIVE: To evaluate the impact of the number of neoadjuvant chemotherapy cycles and role of optimal cytoreduction on the prognosis of patients with advanced ovarian cancer. METHODS: Clinical and pathological details were examined. Patients were evaluated combining the number of cycles of neoadjuvant chemotherapy-namely, 'interval debulking surgery' after up to four neoadjuvant chemotherapy cycles, and 'delayed debulking surgery' after more than four cycles of therapy. RESULTS: A total of 286 patients were included in the study. Complete cytoreduction with no residual peritoneal disease (CC0) was achieved in 74 (74%) patients with interval debulking surgery and 124 (66.7%) patients with delayed interval debulking. Of those with residual disease, there were 26/88 (29.5%) patients in the interval debulking surgery group and 62/88 (70.5%) patients in the delayed debulking surgery group. Comparison of patients with delayed debulking-CC0 and interval debulking-CC0 showed no difference in progression-free survival (p=0.3) or overall survival (p=0.4), while significantly worse outcomes were observed in patients with interval debulking-CC1 (p=0.02 and p=0.04, respectively). Specifically, patients with interval debulking-CC1 had an approximately 67% increased risk of disease progression (p=0.04; HR=2.01 (95% CI 1.04 to 4.18)) and a 69% higher risk of death than patients with delayed debulking-CC0 (p=0.03; HR=2.34 (95% CI 1.11 to 4.67)). CONCLUSION: Increasing the number of neoadjuvant chemotherapy cycles does not worsen patient outcomes if complete resection is achieved. Nevertheless, additional prospective trials are necessary to establish the optimum number of neoadjuvant chemotherapy cycles.

Angiogenesis inhibition in lung cancer: emerging novel strategies.

PURPOSE OF REVIEW: In the current review, we will explore the molecular bases that have determined the design of clinical trials exploring the efficacy of antivascular agents in combination with chemotherapy, immune check point inhibitors and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with advanced nonsmall cell lung cancer. RECENT FINDINGS: Recent clinical trials have demonstrated the synergistic effect of antivascular agents with immune checkpoint inhibitors and EGFR-TKIs, despite no molecular marker has been identified yet to select patients. SUMMARY: Lung cancer remains one of the first causes of cancer-related death. However, thanks to the development of stratified molecular medicine and the introduction of immune checkpoint inhibitors, patients' survival has significantly improved. Due to the critical role of pro-angiogenic factors in cancer progression, antivascular agents targeting the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) have been developed. Their efficacy has been explored in combination with chemotherapy, and immune checkpoint inhibitors, with promising but not definitive conclusions about their impact on prolonging patients' survival.

Intraoperative imaging technology to maximise extent of resection for glioma: a network meta-analysis.

BACKGROUND: Multiple studies have identified the prognostic relevance of extent of resection in the management of glioma. Different intraoperative technologies have emerged in recent years with unknown comparative efficacy in optimising extent of resection. One previous Cochrane Review provided low- to very low-certainty evidence in single trial analyses and synthesis of results was not possible. The role of intraoperative technology in maximising extent of resection remains uncertain. Due to the multiple complementary technologies available, this research question is amenable to a network meta-analysis methodological approach. OBJECTIVES: To establish the comparative effectiveness and risk profile of specific intraoperative imaging technologies using a network meta-analysis and to identify cost analyses and economic evaluations as part of a brief economic commentary. SEARCH METHODS: We searched CENTRAL (2020, Issue 5), MEDLINE via Ovid to May week 2 2020, and Embase via Ovid to 2020 week 20. We performed backward searching of all identified studies. We handsearched two journals, Neuro-oncology and the Journal of Neuro-oncology from 1990 to 2019 including all conference abstracts. Finally, we contacted recognised experts in neuro-oncology to identify any additional eligible studies and acquire information on ongoing randomised controlled trials (RCTs). SELECTION CRITERIA: RCTs evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included fluorescence-guided surgery, intraoperative ultrasound, neuronavigation (with or without additional image processing, e.g. tractography), and intraoperative MRI. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma. MAIN RESULTS: We identified four RCTs, using different intraoperative imaging technologies: intraoperative magnetic resonance imaging (iMRI) (2 trials, with 58 and 14 participants); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around winter 2020. We identified no published trials for intraoperative ultrasound. Network meta-analyses or traditional meta-analyses were not appropriate due to absence of homogeneous trials across imaging technologies. Of the included trials, there was notable heterogeneity in tumour location and imaging technologies utilised in control arms. There were significant concerns regarding risk of bias in all the included studies. One trial of iMRI found increased extent of resection (risk ratio (RR) for incomplete resection was 0.13, 95% confidence interval (CI) 0.02 to 0.96; 49 participants; very low-certainty evidence) and one trial of 5-ALA (RR for incomplete resection was 0.55, 95% CI 0.42 to 0.71; 270 participants; low-certainty evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants; therefore, the trial provided very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection. Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low-certainty evidence). Overall, the proportion of reported events was low in most trials and, therefore, issues with power to detect differences in outcomes that may or may not have been present. Survival outcomes were not adequately reported, although one trial reported no evidence of improvement in overall survival with 5-ALA (hazard ratio (HR) 0.82, 95% CI 0.62 to 1.07; 270 participants; low-certainty evidence). Data for quality of life were only available for one study and there was significant attrition bias (very low-certainty evidence). AUTHORS' CONCLUSIONS: Intraoperative imaging technologies, specifically 5-ALA and iMRI, may be of benefit in maximising extent of resection in participants with high-grade glioma. However, this is based on low- to very low-certainty evidence. Therefore, the short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. Network and traditional meta-analyses were not possible due to the identified high risk of bias, heterogeneity, and small trials included in this review. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, one non-systematic review of economic studies suggested that, compared with standard surgery, use of image-guided surgery has an uncertain effect on costs and that 5-ALA was more costly. Further research, including completion of ongoing trials of ultrasound-guided surgery, is needed.

ANTECEDENTES: En múltiples estudios se ha identificado la importancia pronóstica del alcance de la resección en el tratamiento del glioma. En los últimos años han surgido diferentes tecnologías intraoperatorias con una eficacia comparativa desconocida para optimizar el alcance de la resección. Una revisión Cochrane anterior proporcionó evidencia de certeza baja a muy baja en los análisis de un solo ensayo y no fue posible la síntesis de los resultados. La función de la tecnología intraoperatoria para maximizar el alcance de la resección aún no está clara. Debido a las múltiples tecnologías complementarias disponibles, esta pregunta de investigación se presta a un enfoque metodológico de metanálisis en red. OBJETIVOS: Establecer el perfil comparativo de efectividad y riesgo de determinadas tecnologías de imagenología intraoperatorias mediante un metanálisis en red e identificar análisis de costos y evaluaciones económicas como parte de un breve comentario económico. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en CENTRAL (2020, número 5), MEDLINE vía Ovid hasta la semana 2 de mayo de 2020, y Embase vía Ovid hasta la semana 20 de 2020. Se realizó una búsqueda retrospectiva de todos los estudios identificados. Se hicieron búsquedas manuales en dos revistas, Neuro­oncology y Journal of Neuro­oncology, desde 1990 hasta 2019, y se incluyeron todos los resúmenes de congresos. Finalmente, se estableció contacto con expertos reconocidos en neurooncología para identificar cualquier estudio elegible adicional y obtener información sobre los ensayos controlados aleatorizados (ECA) en curso. CRITERIOS DE SELECCIÓN: ECA que evaluaron a personas de todas las edades con presuntos tumores gliales nuevos o recidivantes (de cualquier ubicación o histología) a partir del examen clínico y la imagenología (tomografía computarizada [TC] o imagenología de resonancia magnética [IRM], o ambas). Las modalidades adicionales de imagenología (p.ej., tomografía de emisión de positrones, espectroscopia de resonancia magnética) no fueron obligatorias. Las intervenciones incluyeron cirugía guiada por fluorescencia, ecografía intraoperatoria, neuronavegación (con o sin procesamiento adicional de las imágenes, p.ej., tractografía) e IRM intraoperatoria. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, evaluaron los resultados de la búsqueda en cuanto a su relevancia, realizaron la evaluación crítica según las guías conocidas y extrajeron los datos mediante un formulario predeterminado. RESULTADOS PRINCIPALES: Se identificaron cuatro ECA, que utilizaron diferentes tecnologías de imagenología intraoperatorias: la resonancia magnética (IRM) intraoperatoria (dos ensayos, con 58 y 14 participantes); la cirugía guiada por fluorescencia con ácido 5­aminolevulínico (5­ALA) (un ensayo, 322 participantes); y la neuronavegación (un ensayo, 45 participantes). Se identificó un ensayo en curso que evaluó la IRM con un tamaño de la muestra planificado de 304 participantes, del que se espera la publicación de los resultados alrededor del invierno de 2020. No se han identificado ensayos publicados sobre la ecografía intraoperatoria. Los metanálisis en red o los metanálisis tradicionales no fueron apropiados debido a la falta de ensayos homogéneos en tecnologías de imagenología. De los ensayos incluidos, hubo una notable heterogeneidad en la localización de los tumores y en las tecnologías de imagenología utilizadas en los brazos control. Hubo inquietudes significativas con respecto al riesgo de sesgo en todos los estudios incluidos. Un ensayo de IRM encontró un aumento en la extensión de la resección (razón de riesgos [RR] para la resección incompleta 0,13; intervalo de confianza [IC] del 95%: 0,02 a 0,96; 49 participantes; evidencia de certeza muy baja) y un ensayo de 5­ALA (RR para la resección incompleta 0,55; IC del 95%: 0,42 a 0,71; 270 participantes; evidencia de certeza baja). El otro ensayo que evaluó la IRM se interrumpió de forma temprana después de un análisis intermedio no planificado que incluyó 14 participantes; por lo tanto, el ensayo proporciona evidencia de calidad muy baja. El ensayo de neuronavegación no proporcionó datos suficientes para evaluar los efectos sobre el grado de resección. El informe de los eventos adversos fue incompleto e indicó la presencia de sesgo de informe significativo (evidencia de certeza muy baja). En general, la proporción de eventos informados fue baja en la mayoría de los ensayos y, por lo tanto, pueden haber estado presentes o no problemas relacionados con el poder estadístico suficiente para detectar diferencias en los desenlaces. No se informó adecuadamente sobre los desenlaces de supervivencia, aunque un ensayo no informó evidencia de mejora en la supervivencia general con 5­ALA (cociente de riesgos instantáneos [CRI] 0,82; IC del 95%: 0,62 a 1,07; 270 participantes; evidencia de certeza baja). Solo hubo datos disponibles sobre la calidad de vida de un estudio, con un sesgo de desgaste significativo (evidencia de certeza muy baja). CONCLUSIONES DE LOS AUTORES: Las tecnologías de imagenología intraoperatoria, específicamente la IRM y el 5­ALA, pueden ser beneficiosas para maximizar el grado de resección en los participantes con glioma de grado alto. Sin embargo, lo anterior se basa en evidencia de certeza baja a muy baja. Por lo tanto, los efectos neurológicos a corto y a largo plazo no están claros. No están claros los efectos de la cirugía guiada por imágenes sobre la supervivencia general, la supervivencia sin progresión ni la calidad de vida. No fue posible realizar metanálisis en red ni tradicionales debido al alto riesgo de sesgo identificado, a la heterogeneidad y a los ensayos pequeños incluidos en esta revisión. Un comentario económico breve encontró evidencia económica limitada sobre el uso equívoco de la IRM en comparación con la cirugía convencional. En cuanto a los costos, una revisión no sistemática de estudios económicos indicó que, en comparación con la cirugía estándar, el uso de la cirugía guiada por imágenes no tiene un efecto claro sobre los costos y que el ácido 5­aminolevulínico fue más costoso. Se necesitan estudios de investigación adicionales, incluida la finalización de los ensayos en curso sobre la cirugía guiada por ecografía.

High-security closed devices are efficient and safe to protect human oocytes from potential risk of viral contamination during vitrification and storage especially in the COVID-19 pandemic.

PURPOSE: The main purpose and research question of the study are to compare the efficacy of high-security closed versus open devices for human oocytes' vitrification. METHODS: A prospective randomized study was conducted. A total of 737 patients attending the Infertility and IVF Unit at S.Orsola University Hospital (Italy) between October 2015 and April 2020 were randomly assigned to two groups. A total of 368 patients were assigned to group 1 (High-Security Vitrification™ - HSV) and 369 to group 2 (Cryotop® open system). Oocyte survival, fertilization, cleavage, pregnancy, implantation, and miscarriage rate were compared between the two groups. RESULTS: No statistically significant differences were observed on survival rate (70.3% vs. 73.3%), fertilization rate (70.8% vs. 74.9%), cleavage rate (90.6% vs. 90.3%), pregnancy/transfer ratio (32.0% vs. 31.8%), implantation rate (19.7% vs. 19.9%), nor miscarriage rates (22.1% vs. 21.5%) between the two groups. Women's mean age in group 1 (36.18 ± 3.92) and group 2 (35.88 ± 3.88) was not significantly different (P = .297). A total of 4029 oocytes were vitrified (1980 and 2049 in groups 1 and 2 respectively). A total of 2564 were warmed (1469 and 1095 in groups 1 and 2 respectively). A total of 1386 morphologically eligible oocytes were inseminated by intracytoplasmic sperm injection (792 and 594 respectively, P = .304). CONCLUSIONS: The present study shows that the replacement of the open vitrification system by a closed one has no impact on in vitro and in vivo survival, development, pregnancy and implantation rate. Furthermore, to ensure safety, especially during the current COVID-19 pandemic, the use of the closed device eliminates the potential samples' contamination during vitrification and storage.

VITOM® 3D in Arterio-Venous Fistulas: Single Centre Preliminary Surgical Experience.

BACKGROUND: Arteriovenous fistula (AVF) is the vascular access of choice for hemodialysis patients. A correct microsurgical vascular anastomoses is essential to the optimal care of patients. Loupes can help surgeons perform such procedures, but often cause neck or back pain and fatigue. AIM: This study aimed to evaluate whether a video telescopic operating microscope (VITOM®; Karl Storz Endoscopy GmbH, Tuttlingen, Germany) could be used as a substitute for loupes to create microsurgical vascular anastomoses. METHODS: We evaluated microsurgical anastomoses with VITOM® in 10 patients (6 male, 4 female) from January 2019 to December 2019. The created anastomoses were 7 side-to-side, 2 side-to-end and 1 end-to-end. RESULTS: A valid thrill was always present on palpation. Surgical procedures had an average time of 87.6 min, ranging from 49 to 110 min. Eight patients had AVF maturation; in the remaining 2, one had a thrombosis after 25 days and one couldn't be dialyzed due to low flow in AVF. CONCLUSIONS: The VITOM® system makes it possible to carry out anastomosis in difficult cases. It is both safe and useful for the training of young surgeons.

Impact of BRCA1 and BRCA2 mutations on ovarian reserve and fertility preservation outcomes in young women with breast cancer.

PURPOSE: To determine the impact of BRCA1 and BRCA2 mutations on ovarian reserve and fertility preservation outcome. The main purpose and research question of the study is to determine the impact of BRCA1 and BRCA2 mutations on ovarian reserve and fertility preservation outcomes. METHODS: Prospective study: 67 breast cancer patients between 18 and 40 years old, undergoing a fertility preservation by means of oocyte storage were considered. Inclusions criteria for the study were age between 18 and 40 years old, BMI between 18 and 28, breast cancer neoplasm stage I and II according to American Joint Committee on Cancer classification (2017) and no metastasis. EXCLUSION CRITERIA: age over 40 years old, BMI < 18 and > 28, breast cancer neoplasm stage III and IV and do not performed the BRCA test. A total of 21 patients had not performed the test and were excluded. Patients were divided into four groups: Group A was composed by 11 breast cancer patients with BRCA 1 mutations, Group B was composed by 11 breast cancer patients with BRCA 2 mutations, Group C was composed by 24 women with breast cancer without BRCA mutations, and Group D (control) was composed by 181 normal women. RESULTS: Group A showed significant lower AMH levels compared to Group C and D (1.2 ± 1.1 vs 4.5 ± 4.1 p < 0.05 and 1.2 ± 1.1 vs 3.8 ± 2.5 p < 0.05). BRCA1 mutated patients showed a significant lower rate of mature oocytes (MII) compared to Group C (3.1 ± 2.3 vs 7.2 ± 4.4 p < 0,05) and Group D (3.1 ± 2.3 vs 7.3 ± 3.4; p < 0,05). Breast cancer patients needed a higher dose of gonadotropins compared to controls (Group A 2206 ± 1392 Group B2047.5 ± 829.9 Group C 2106 ± 1336 Group D 1597 ± 709 p < 0,05). No significant differences were found among the groups considering basal FSH levels, duration of stimulation, number of developed follicles, and number of total retrieved oocytes. Regarding BRCA2 mutation, no effect on fertility was shown in this study. CONCLUSIONS: The study showed that BRCA1 patients had a higher risk of premature ovarian insufficiency (POI) confirmed by a diminished ovarian reserve and a lower number of mature oocytes suitable for cryopreservation.

Intraoperative imaging technology to maximise extent of resection for glioma.

BACKGROUND: Extent of resection is considered to be a prognostic factor in neuro-oncology. Intraoperative imaging technologies are designed to help achieve this goal. It is not clear whether any of these sometimes very expensive tools (or their combination) should be recommended as standard care for people with brain tumours. We set out to determine if intraoperative imaging technology offers any advantage in terms of extent of resection over standard surgery and if any one technology was more effective than another. OBJECTIVES: To establish the overall effectiveness and safety of intraoperative imaging technology in resection of glioma. To supplement this review of effects, we also wished to identify cost analyses and economic evaluations as part of a Brief Economic Commentary (BEC). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 7, 2017), MEDLINE (1946 to June, week 4, 2017), and Embase (1980 to 2017, week 27). We searched the reference lists of all identified studies. We handsearched two journals, the Journal of Neuro-Oncology and Neuro-oncology, from 1991 to 2017, including all conference abstracts. We contacted neuro-oncologists, trial authors, and manufacturers regarding ongoing and unpublished trials. SELECTION CRITERIA: Randomised controlled trials evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included intraoperative MRI (iMRI), fluorescence-guided surgery, ultrasound, and neuronavigation (with or without additional image processing, e.g. tractography). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma. MAIN RESULTS: We identified four randomised controlled trials, using different intraoperative imaging technologies: iMRI (2 trials including 58 and 14 participants, respectively); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around autumn 2018. We identified no trials for ultrasound.Meta-analysis was not appropriate due to differences in the tumours included (eloquent versus non-eloquent locations) and variations in the image guidance tools used in the control arms (usually selective utilisation of neuronavigation). There were significant concerns regarding risk of bias in all the included studies. All studies included people with high-grade glioma only.Extent of resection was increased in one trial of iMRI (risk ratio (RR) of incomplete resection 0.13, 95% confidence interval (CI) 0.02 to 0.96; 1 study, 49 participants; very low-quality evidence) and in the trial of 5-ALA (RR of incomplete resection 0.55, 95% CI 0.42 to 0.71; 1 study, 270 participants; low-quality evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants, therefore the trial provides very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection.Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low-quality evidence). Overall, reported events were low in most trials. There was no clear evidence of improvement in overall survival with 5-ALA (hazard ratio 0.83, 95% CI 0.62 to 1.07; 1 study, 270 participants; low-quality evidence). Progression-free survival data were not available in an appropriate format for analysis. Data for quality of life were only available for one study and suffered from significant attrition bias (very low-quality evidence). AUTHORS' CONCLUSIONS: Intra-operative imaging technologies, specifically iMRI and 5-ALA, may be of benefit in maximising extent of resection in participants with high grade glioma. However, this is based on low to very low quality evidence, and is therefore very uncertain. The short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, a non-systematic review of economic studies suggested that compared with standard surgery use of image-guided surgery has an uncertain effect on costs and that 5-aminolevulinic acid was more costly. Further research, including studies of ultrasound-guided surgery, is needed.

OneShot-M: A New Device for Close Laparoscopy Pneumoperitoneum.

INTRODUCTION: The induction of pneumoperitoneum is the first and most critical phase of laparoscopy, due to the significant risk of serious vascular and visceral complications. The closed technique for the creation of pneumoperitoneum could lead to several surgical complications. The present study aimed to overcome the complications associated with the insertion of Veress needle, improving its use, and facilitating the rapid creation of pneumoperitoneum. METHODS: Thirty large white female pigs were enrolled in our study. A common plunger was modified in order to allow the passage of a 15-cm long Veress needle. This method was applied to 26 laparoscopic procedures (26 pigs) of several specialist branches. RESULTS: OneShot-M close laparoscopy pneumoperitoneum creation device allowed us to obtain pneumoperitoneum quickly in all attempts, without any intraoperative and postoperative complications related to the use of the Veress needle. CONCLUSION: The use of the proposed device showed an induction time as quick as the standard laparoscopic closed abdominal entry. The patented device is cheap and allows a safe abdominal entry. In addition, abdominal entry is much faster than the classic open technique.

Methodological shortcomings in the literature evaluating the role and applications of 3D training for surgical trainees.

AIM: There has been an increased interest in the use of three-dimensional (3D) technology in surgical training. We wish to appraise the methodological rigor applied to evaluating the role and applications of 3D technology in surgical training, in particular, on the validity of these models and assessment methods in simulated surgical training. METHODS: Literature search was performed using MEDLINE with the following terms: "3D"; "surgery"; and "training". Only studies evaluating the role of 3D technology in surgical training were eligible for inclusion and assessed for the level of evidence, validity of the simulation model, and assessment method used. RESULTS: A total of 93 studies were analyzed, and majority of reviewed articles focused on 3D displays (36) and 3D printing (35). Most of these studies were case series, the most common assessment was subjective (69), with objective assessment used by 57 studies. Very few studies provided evidence for validity of the model or the assessment methods used. CONCLUSIONS: 3D technology has a great potential in simulated surgical training. However, the validity of this technology and strong evidence for its beneficial effects in surgical training is lacking. Further work on validation of 3D technology and assessment tools is needed.

Short versus long-segment posterior fixation in the treatment of thoracolumbar junction fractures: a comparison of outcomes.

PURPOSE: To compare clinical and radiological outcomes between short (SSPF) and long-segment (LSPF) posterior fixation for thoracolumbar junction (TLJ) fractures. MATERIALS AND METHODS: Retrospective review of adult patients, with single-level, TLJ (T11-L2) fractures, treated with posterior fixation between 2007 and 2014 at a regional spinal centre. SSPF and LSPF were defined as transpedicular screw fixation at one and two levels above and below the fractured vertebra, respectively. Construct failure was defined as instrument breakage or screw pull-out requiring operative intervention. Two independent assessors measured the kyphotic Cobb angle at up to six months. RESULTS: A total of 28 patients were included with a median age of 38 years (range 20-76 years) and median follow-up period of 14 months (4-41 months). All patients sustained traumatic fractures and the male to female ratio was 19:9. AO fracture classes were: A (29%), B (50%) and C (21%). SSPF and LSPF were performed in 17 (61%) and 11 (39%) patients, respectively. There was no significant difference in age (Fisher's exact, p > 0.99), AO fracture class (chi-squared, p = 0.510), preop TLICS score (independent t-test, p = 0.668) and length of stay (independent t-test, p = 0.106) between the groups. Construct failure occurred in three SSPF cases (3-14 months postop) and was associated with an increased mean loss of correction. By six months, the Cobb angle had increased significantly in the SSPF group (paired t-test, p = 0.049), but not the LSPF group (paired t-test, p = 0.157). CONCLUSIONS: Our data identified a trend towards better clinical and radiological outcomes in the LSPF, compared to the SSPF group. Although supported by some studies, these findings should be evaluated in future clinical trials.

Renal Transplantation by Automatic Anastomotic Device in a Porcine Model.

Automatic vascular staplers for vascular anastomoses in kidney transplantation may dramatically reduce the operative time and, in particular, warm ischemia time, thus increasing the outcome of transplantation. Ten pigs underwent kidney auto-transplantation by automatic anastomotic device. Kidneys were collected by laparotomy with selective ligations at the renal hilum and perfused with cold storage solution. To overcome the shortage in length of renal hilum, a tract of the internal jugular vein was harvested to increase the length of the vessels. The anastomoses were totally performed by the use of the anastomotic device. On 10 kidney transplants, nine were successful and no complications occurred. Renal resistive indexes showed a slight increase in the immediate postoperative period returning normal at 10 days of follow-up. We demonstrated the possibility to perform renal vascular anastomoses by means of an automatic anastomotic device. This instrument developed for coronary bypass surgery by virtue of the small caliber of the vessels could be adopted on a larger scale for renal transplantation. The reduced warm ischemia time needed for anastomosis may help to achieve a better outcome for the graft and expand the pool of marginal donors in renal transplantation.

Survival rate and neurodevelopmental outcome of extremely premature babies: an 8-year experience of an Italian single neonatal tertiary care center.

Extremely preterm babies are at major risk for adverse neurodevelopmental outcome, being the gestational age (GA) the main determinant for a good-quality survival. Aim of this retrospective study was to investigate the neurodevelopmental outcome in a population of extremely preterm babies admitted to a single neonatal tertiary care unit over an 8-year period. All babies born between 23+0 and 25+6 weeks of GA from January 2003 until December 2010 were retrospectively enrolled. Perinatal and neonatal variables were recorded. Motor and cognitive development was assessed using the neurofunctional scale (NFS) and the Griffith's scales at 2 years. Fifty-five out of 122 infants survived to discharge. Survival rates doubled for each additional gestational week from 23 to 25: 16%, 38% and 74% at 23, 24 and 25 weeks GA respectively. Forty-six infants were evaluated at 2 years. A poor cognitive and motor outcome was observed in all babies born at 23 weeks. Griffith's general quotient (GQ) was ≥76 in 62% and ≥88 in 33% of babies born between 24 and 25 weeks. No severe motor disabilities were found in 81% of babies born between 24 and 25 weeks. Preterm premature rupture of membranes, absence of prenatal steroids, intrauterine growth restriction, male, lower GA and major brain abnormalities at magnetic resonance imaging (MRI) were significantly associated with worse NFS and lower mean GQ at 2 years of age. GA, gender and abnormal MRI findings remained significantly associated with impaired NFS at the multivariate analysis. Survival rates and neurodevelopmental outcome improved with each week of GA. These results are relevant for clinicians counselling families facing an unavoidable extremely preterm birth.

Image guided surgery for the resection of brain tumours.

BACKGROUND: Extent of resection is believed to be a key prognostic factor in neuro-oncology. Image guided surgery uses a variety of tools or technologies to help achieve this goal. It is not clear whether any of these, sometimes very expensive, tools (or their combination) should be recommended as part of standard care for patient with brain tumours. We set out to determine if image guided surgery offers any advantage in terms of extent of resection over surgery without any image guidance and if any one tool or technology was more effective. OBJECTIVES: To compare image guided surgery with surgery either not using any image guidance or to compare surgery using two different forms of image guidance. The primary outcome criteria was extent of resection and adverse events. Other outcome criteria were overall survival; progression free survival; and quality of life (QoL). SEARCH METHODS: The following databases were searched, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2013), MEDLINE (1948 to March, week 10, 2013) and EMBASE (1970 to 2013, week 10). Reference lists of all identified studies were searched. Two journals, the Journal of Neuro-Oncology and Neuro-oncology, were handsearched from 1991 to 2013, including all conference abstracts. Neuro-oncologists, trial authors and manufacturers were contacted regarding ongoing and unpublished trials. SELECTION CRITERIA: Study participants included patients of all ages with a presumed new or recurrent brain tumour (any location or histology) from clinical examination and imaging (computed tomography (CT), magnetic resonance imaging (MRI) or both). Image guidance interventions included intra-operative MRI (iMRI); fluorescence guided surgery; neuronavigation including diffusion tensor imaging (DTI); and ultrasonography. Included studies had to be randomised controlled trials (RCTs) with comparisons made either with patients having surgery without the image guidance tool in question or with another type of image guidance tool. Subgroups were to include high grade glioma; low grade glioma; brain metastasis; skull base meningiomas; and sellar or parasellar tumours. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a pre-specified pro forma. MAIN RESULTS: Four RCTs were identified, each using a different image guided technique: 1. iMRI (58 patients), 2. 5-aminolevulinic acid (5-ALA) fluorescence guided surgery (322 patients), 3. neuronavigation (45 patients) and 4. DTI-neuronavigation (238 patients). Meta-analysis was not appropriate due to differences in the tumours included (eloquent versus non-eloquent locations) and variations in the image guidance tools used in the control arms (usually selective utilisation of neuronavigation). There were significant concerns regarding risk of bias in all the included studies, especially for the study using DTI-neuronavigation. All studies included patients with high grade glioma, with one study also including patients with low grade glioma. The extent of resection was increased with iMRI (risk ratio (RR) (incomplete resection) 0.13, 95% CI 0.02 to 0.96, low quality evidence), 5-ALA (RR 0.55, 95% CI 0.42 to 0.71) and DTI-neuronavigation (RR 0.35, 95% CI 0.20 to 0.63, very low quality evidence). Insufficient data were available to evaluate the effects of neuronavigation on extent of resection. Reporting of adverse events was incomplete, with a suggestion of significant reporting bias. Overall, reported events were low in most studies, but there was concern that surgical resection using 5-ALA may lead to more frequent early neurological deficits. There was no clear evidence of improvement in overall survival (OS) with 5-ALA (hazard ratio (HR) 0.82, 95% CI 0.62 to 1.07) or DTI-neuronavigation (HR 0.57, 95% CI 0.32 to 1.00) in patients with high grade glioma. Progression-free survival (PFS) data were not available in the appropriate format for analysis.Data for quality of life (QoL) were only available for one study and suffered from significant attrition bias. AUTHORS' CONCLUSIONS: There is low to very low quality evidence (according to GRADE criteria) that image guided surgery using iMRI, 5-ALA or DTI-neuronavigation increases the proportion of patients with high grade glioma that have a complete tumour resection on post-operative MRI. There is a theoretical concern that maximising the extent of resection may lead to more frequent adverse events but this was poorly reported in the included studies. Effects of image guided surgery on survival and QoL are unclear. Further research, including studies of ultrasound guided surgery, is needed.

Alternative cost-effective method to record 3D intra-operative images: a technical note.

The educational value of stereoscopic imaging in neurosurgical training has increasingly been appreciated and its use increased during the last decade. We describe a technique that we developed to acquire and reproduce intra-operative stereoscopic images.

LIM-domain-only 4 (LMO4) enhances CD8+ T-cell stemness and tumor rejection by boosting IL-21-STAT3 signaling.

High frequencies of stem-like memory T cells in infusion products correlate with superior patient outcomes across multiple T cell therapy trials. Herein, we analyzed a published CRISPR activation screening to identify transcriptional regulators that could be harnessed to augment stem-like behavior in CD8+ T cells. Using IFN-γ production as a proxy for CD8+ T cell terminal differentiation, LMO4 emerged among the top hits inhibiting the development of effectors cells. Consistently, we found that Lmo4 was downregulated upon CD8+ T cell activation but maintained under culture conditions facilitating the formation of stem-like T cells. By employing a synthetic biology approach to ectopically express LMO4 in antitumor CD8+ T cells, we enabled selective expansion and enhanced persistence of transduced cells, while limiting their terminal differentiation and senescence. LMO4 overexpression promoted transcriptional programs regulating stemness, increasing the numbers of stem-like CD8+ memory T cells and enhancing their polyfunctionality and recall capacity. When tested in syngeneic and xenograft tumor models, LMO4 overexpression boosted CD8+ T cell antitumor immunity, resulting in enhanced tumor regression. Rather than directly modulating gene transcription, LMO4 bound to JAK1 and potentiated STAT3 signaling in response to IL-21, inducing the expression of target genes (Tcf7, Socs3, Junb, and Zfp36) crucial for memory responses. CRISPR/Cas9-deletion of Stat3 nullified the enhanced memory signature conferred by LMO4, thereby abrogating the therapeutic benefit of LMO4 overexpression. These results establish LMO4 overexpression as an effective strategy to boost CD8+ T cell stemness, providing a new synthetic biology tool to bolster the efficacy of T cell-based immunotherapies.

Renal cell carcinoma with venous neoplastic thrombosis: a ten years review.

PURPOSE: To review the 10-year experience of our urological unit in the surgical management of renal cell carcinoma (RCC) with neoplastic tumor thrombosis focusing on postoperative survival. MATERIALS AND METHODS: We underwent a retrospective analysis of the patients treated for this pathology during the last decade 2002-2012, stratifying them by tumor thrombus level and histological subtype. Kaplan-Meyer curves were used to assess survival. RESULTS: Overall, 67 patients underwent surgery for RCC with neoplastic tumoral thrombosis in the period under review. 60 were clear cell RCC, 4 were urothelial papillary tumors of the renal pelvis and 3 were rare histotypes, as a nefroblastoma, a spinocellular tumor of the renal pelvis and an unclassifiable renal carcinoma. Thrombus level was I in 40 cases, II in 17, III in 2 and IV in 8 patients. We report the main postoperative complications and our survival data, with mean follow up of 36 months. Tumor stage is the most important variable in predicting survival. Patients with N0M0 disease had 70% survival at 36 months, instead of 20% for those with primitive metastatic tumor. CONCLUSION: Our survival results fit with the main reports in literature and our surgical management was completely in keeping with international guidelines. We did not observe relevany post-operative complications, except of hemorrhagic ones that occurred in 6 patients (9% of total) and were always successfully managed. Eighteen patients (26.87% of total) underwent caval filter positioning, without evidence of complications during its positioning or removal. Life expectancy was particularly low for the cases of RCC without clear cell histotype (7 cases in our series, 10.4% of total) that always was less than one year from surgery.

Reproductive health in Turner's syndrome: from puberty to pregnancy.

Turner syndrome (TS) is a genetic pathology that affects about 1/2500 newborn females. Turner's syndrome is characterized by highly variable genetic anomalies that consist in a partial or complete deletion of the X sexual chromosome; it can be present as a monosomy or as a mosaicism with two o three different cellular lines. 50% of the patients with Turner's syndrome has a 45 XO karyotype while the remaining cases have karyotypes with mosaicism or X isochromosome or with partial or whole Y chromosome. This pathology is characterized by multiple anomalies that involve physical and cognitive development and in particular endocrine, cardiovascular, reproductive, auditive and visual systems. Integrity of the X chromosome in essential for fertility. In TS is accelerated germ cells apoptosis. About 30% of TS girls have some pubertal development, 10-20% undergo menarche and 2-8% go through spontaneous pregnancy. Women with TS should be informed about the risk of premature menopause and should be referred, if possible, to a specialist evaluation with a doctor expert in assisted reproductive techniques. In adolescents and in adults, Premature Ovarian Insufficiency (POI) can be evaluated clinically and biochemically with the classic combination of amenorrhea and elevated FSH concentrations (hypergonadotropic hypogonadism). However, in postpubertal adolescents and adult women, reproductive hormones may remain within the normal range before POI is clinically evident, despite significant depletion of the ovarian reserve. Today, reproductive medicine offers the opportunity of fertility preservation in women with premature ovarian insufficiency (POI). Two techniques have been suggested such as ovarian cortex cryopreservation and oocytes cryopreservation.

Sex dimorphism and cancer immunotherapy: May pregnancy solve the puzzle?

In the immunoncology era, growing evidence has shown a clear sex dimorphism in antitumor immune response with a potential impact on outcomes upon immunecheckpoint blockade (ICI) in patients with cancer. Sex dimorphism could affect tumor microenvironment composition and systemic anticancer immunity; however, the modifications induced by sex are heterogeneous. From a clinical perspective, six metanalyses have explored the role of sex in cancer patients receiving ICI with conflicting results. Environmental and reproductive factors may further jeopardize the sex-related heterogeneity in anticancer immune response. In particular, pregnancy is characterized by orchestrated changes in the immune system, some of which could be long lasting. A persistence of memory T-cells with a potential fetal-antigen specificity has been reported both in human and mice, suggesting that a previous pregnancy may positively impact cancer development or response to ICI, in case of fetal-antigen sharing from tumor cells. On the other hand, a previous pregnancy may also be associated with a regulatory memory characterized by increased tolerance and anergy towards cancer-fetal common antigens. Finally, fetal-maternal microchimerism could represent an additional source of chronic exposure to fetal antigens and may have important immunological implications on cancer development and ICI activity. So far, the role of pregnancy dimorphism (nulliparous vs parous) in women and the impact of pregnancy-related variables remain largely underexplored in cancer patients. In this review, we summarize the evidence regarding sex and pregnancy dimorphism in the context of immune response and anticancer immunotherapy and advocate the importance of analyzing pregnancy variables on ICIs clinical trials.

An unexpected surprise at the end of a "quiet" cholecystectomy. A case report and review of the literature.

BACKGROUND: Anatomic unexpected variations in biliary tree may be discovered during laparoscopic cholecystectomy. CASE REPORT: A 57-year-old man was admitted for abdominal pain, vomiting and mild jaundice. Abdominal ultrasonography revealed a gallbladder containing multiple stones and biliary sludge. All pre-operative investigations showed no anatomical variations in extrahepatic biliary tree. During surgical intervention an accessory extrahepatic duct, connecting the IV segment of the liver to the fundus of gallbladder, was discovered. CONCLUSIONS: Pre-operative routine investigations for gall stones diseases may not reveal anatomic variations of biliary tree.