An International Expert-Based Consensus on the Definition of a Clinical Near-Complete Response After Neoadjuvant (Chemo)radiotherapy for Rectal Cancer.

BACKGROUND: A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to inconsistency in clinical practice, long-term outcome, and trial enrollment. OBJECTIVE: The aim of this study was to reach expert-based consensus on the definition of a clinical near-complete response after (chemo) radiotherapy. DESIGN: A modified Delphi process, including a systematic review, 3 surveys, and 2 meetings, was performed with an international expert panel consisting of 7 surgeons and 4 radiologists. The surveys consisted of individual features, statements, and feature combinations (endoscopy, T2-weighted MRI, and diffusion-weighted MRI). SETTING: The modified Delphi process was performed in an online setting; all 3 surveys were completed online by the expert panel, and both meetings were hosted online. MAIN OUTCOME MEASURES: The main outcome was to reach consensus (80% or more agreement). RESULTS: The expert panel reached consensus on a 3-tier categorization of the near-complete response category based on the likelihood of the response to evolve into a clinical complete response after a longer waiting interval. The panelists agreed that a near-complete response is a temporary entity only to be used in the first 6 months after (chemo)radiotherapy. Furthermore, consensus was reached that the lymph node status should be considered when deciding on a near-complete response and that biopsies are not always needed when a near-complete response is found. No consensus was reached on whether primary staging characteristics have to be taken into account when deciding on a near-complete response. LIMITATIONS: This 3-tier subcategorization is expert-based; therefore, there is no supporting evidence for this subcategorization. Also, it is unclear whether this subcategorization can be generalized into clinical practice. CONCLUSIONS: Consensus was reached on the use of a 3-tier categorization of a near-complete response, which can be helpful in daily practice as guidance for treatment and to inform patients with a near-complete response on the likelihood of successful organ preservation. See Video Abstract. UN CONSENSO INTERNACIONAL BASADO EN EXPERTOS ACERCA DE LA DEFINICIN DE UNA RESPUESTA CLNICA CASI COMPLETA DESPUS DE QUIMIORADIOTERAPIA NEOADYUVANTE CONTRA EL CNCER DE RECTO: ANTECEDENTES:Actualmente, se utilizan una variedad de definiciones para una respuesta clínica casi completa después de quimioradioterapia neoadyuvante contra el cáncer de recto. Esta variedad resulta en inconsistencia en la práctica clínica, los resultados a largo plazo y la inscripción en ensayos.OBJETIVO:El objetivo de este estudio fue llegar a un consenso de expertos sobre la definición de una respuesta clínica casi completa después de quimioradioterapia.DISEÑO:Se realizó un proceso Delphi modificado que incluyó una revisión sistemática, 3 encuestas y 2 reuniones con un panel internacional de expertos compuesto por siete cirujanos y 4 radiólogos. Las encuestas consistieron en características individuales, declaraciones y combinaciones de características (endoscopía, T2W-MRI y DWI).AJUSTE:El proceso Delphi modificado se realizó en un entorno en línea; el panel de expertos completó las tres encuestas en línea y ambas reuniones se realizaron en línea.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue llegar a un consenso (≥80% de acuerdo).RESULTADOS:El panel de expertos llegó a un consenso sobre una categorización de tres niveles de la categoría de respuesta casi completa basada en la probabilidad de que la respuesta evolucione hacia una respuesta clínica completa después de un intervalo de espera más largo. Los panelistas coincidieron en que una respuesta casi completa es una entidad temporal que sólo debe utilizarse en los primeros 6 meses después de la quimioradioterapia. Además, se llegó a un consenso en que se debe considerar el estado de los nódulos linfáticos al decidir sobre una respuesta casi completa y que no siempre se necesitan biopsias cuando se encuentra una respuesta casi completa. No se llegó a un consenso sobre si se deben tener en cuenta las características primarias de estadificación al decidir una respuesta casi completa.LIMITACIONES:Esta subcategorización de 3 niveles está basada en expertos; por lo tanto, no hay evidencia que respalde esta subcategorización. Además, no está claro si esta subcategorización puede generalizarse a la práctica clínica.CONCLUSIONES:Se alcanzó consenso sobre el uso de una categorización de 3 niveles de una respuesta casi completa que puede ser útil en la práctica diaria como guía para el tratamiento y para informar a los pacientes con una respuesta casi completa sobre la probabilidad de una preservación exitosa del órgano. (Traducción - Dr. Aurian Garcia Gonzalez).

International Validation of the Immunoscore Biopsy in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy.

PURPOSE: No biomarker capable of improving selection and monitoring of patients with rectal cancer managed by watch-and-wait (W&W) strategy is currently available. Prognostic performance of the Immunoscore biopsy (ISB) was recently suggested in a preliminary study. METHODS: This international validation study included 249 patients with clinical complete response (cCR) managed by W&W strategy. Intratumoral CD3+ and CD8+ T cells were quantified on pretreatment rectal biopsies by digital pathology and converted to ISB. The primary end point was time to recurrence (TTR; the time from the end of neoadjuvant treatment to the date of local regrowth or distant metastasis). Associations between ISB and outcomes were analyzed by stratified Cox regression adjusted for confounders. Immune status of tumor-draining lymph nodes (n = 161) of 17 additional patients treated by neoadjuvant chemoradiotherapy and surgery was investigated by 3'RNA-Seq and immunofluorescence. RESULTS: Recurrence-free rates at 5 years were 91.3% (82.4%-100.0%), 62.5% (53.2%-73.3%), and 53.1% (42.4%-66.5%) with ISB High, ISB Intermediate, and ISB Low, respectively (hazard ratio [HR; Low v High], 6.51; 95% CI, 1.99 to 21.28; log-rank P = .0004). ISB was also significantly associated with disease-free survival (log-rank P = .0002), and predicted both local regrowth and distant metastasis. In multivariate analysis, ISB was independent of patient age, sex, tumor location, cT stage (T, primary tumor; c, clinical), cN stage (N, regional lymph node; c, clinical), and was the strongest predictor for TTR (HR [ISB High v Low], 6.93; 95% CI, 2.08 to 23.15; P = .0017). The addition of ISB to a clinical-based model significantly improved the prediction of recurrence. Finally, B-cell proliferation and memory in draining lymph nodes was evidenced in the draining lymph nodes of patients with cCR. CONCLUSION: The ISB is validated as a biomarker to predict both local regrowth and distant metastasis, with a gradual scaling of the risk of pejorative outcome.

Analysis of the Effect of Different Physical Exercise Protocols on Depression in Adults: Systematic Review and Meta-analysis of Randomized Controlled Trials.

CONTEXT: Physical exercise (PE) is an effective treatment for depression, alone or as an adjunct. OBJECTIVE: There is a lack of indicators regarding the frequency, intensity, duration, and type of physical exercise (PE). This study aims to synthesize and analyze the dose-effect of different PE protocols in adult subjects in the treatment of depression, based on the analysis of randomized controlled trials (RCTs). DATA SOURCES: The search was conducted using Web of Science, PubMed, and Cochrane Library electronic databases. STUDY SELECTION: Studies with an exercise-based intervention published by December 31, 2021 were identified. RCTs and meta-analyses involving adults with depression were also included; 10 studies were selected, including a total of 956 subjects. STUDY DESIGN: Systematic review and meta-analysis. LEVEL OF EVIDENCE: Level 1. RESULTS: Effect sizes were summarized using standardized mean differences (95% confidence interval) by effected randomized models. The results reinforce that exercise appears to be beneficial in improving depression among adults aged 18 to 65 years. Interventions lasting above 150 minutes per week of moderate intensity and group interventions seem to have a more significant effect on reducing depression. Studies have revealed that aerobic exercise, compared with resistance or flexibility, has a more positive effect on depression. CONCLUSION: PE can be a way to reduce depression and can be used as a possible adjunctive tool for pharmacological and/or alternative treatments. Considering the findings of this study, it is important that health professionals (eg, exercise physiologists, physicians, nurses, psychologists) promote the practice of PE as a complementary alternative and act early to prevent the worsening of depression. PROSPERO REGISTRATION NUMBER: CRD42020188909.

Using Psychometric Testing Procedures for Scale Validity, Reliability, and Invariance Analysis: The PRETIE-Q Portuguese Version.

This study investigated the psychometric nature of preference for and tolerance of exercise intensity in physical activity. It initially re-examined the Preference for and Tolerance of the Intensity of Exercise Questionnaire (PRETIE-Q) among Portuguese exercisers, looking at its applicability to different exercise activities and exercise experiences. Then, to investigate the applicability of the measure in different groups, its invariance was examined. The sample consisted of 1117 participants (528 male, 589 female) aged 18-81 years old (Mage = 36.81, SD = 11.89). All participants reported at baseline that they were exercising, on average, 3.93 days (SD = 1.36) per week. The exploratory structural equation modeling (ESEM) displayed the best fit. The ESEM did show invariance when tested for multigroup analysis. The conclusion of this research is that the ESEM demonstrated the best fit, displaying invariance in multigroup analysis. Furthermore, when assessing preference and tolerance in various exercise modalities, the PRETIE-Q should be primarily used as a multidimensional instrument due to the differential recognition of preference and tolerance in seemingly similar physical activity circumstances, highlighting the importance of employing context-verified measures to evaluate exercise-intensity preference and tolerance based on sample characteristics or real-time context.

Decorative Chromium Coatings on Polycarbonate Substrate for the Automotive Industry.

Metal-coated plastic parts are replacing traditional metallic materials in the automotive industry. Sputtering is an alternative technology that is more environmentally friendly than electrolytic coatings. Most metalized plastic parts are coated with a thin metal layer (~100-200 nm). In this work, the challenge is to achieve thicker films without cracking or without other defects, such as pinholes or pores. Chromium coatings with different thicknesses were deposited onto two different substrates, polycarbonate with and without a base coat, using dc magnetron sputtering in an atmosphere of Ar. Firstly, in order to improve the coating adhesion on the polymer surface, a plasma etching treatment was applied. The coatings were characterized for a wide thickness range from 800 nm to 1600 nm. As the thickness of the coatings increased, there was an increase in the specular reflectivity and roughness of the coatings and changes in morphology due to the columnar growth of the film and a progressive increase in thermal stresses. Furthermore, a decrease in the hardness and the number of pinholes was noticed. The maximum thickness achieved without forming buckling defects was 1400 nm. The tape tests confirmed that every deposited coating showed a good interface adhesion to both polymers.

Watch and wait after neoadjuvant treatment in rectal cancer: comparison of outcomes in patients with and without a complete response at first reassessment in the International Watch & Wait Database (IWWD).

BACKGROUND: In rectal cancer, watch and wait for patients with a cCR after neoadjuvant treatment has an established evidence base. However, there is a lack of consensus on the definition and management of a near-cCR. This study aimed to compare outcomes in patients who achieved a cCR at first reassessment versus later reassessment. METHODS: This registry study included patients from the International Watch & Wait Database. Patients were categorized as having a cCR at first reassessment or at later reassessment (that is near-cCR at first reassessment) based on MRI and endoscopy. Organ preservation, distant metastasis-free survival, and overall survival rates were calculated. Subgroup analyses were done for near-cCR groups based on the response evaluation according to modality. RESULTS: A total of 1010 patients were identified. At first reassessment, 608 patients had a cCR; 402 had a cCR at later reassessment. Median follow-up was 2.6 years for patients with a cCR at first reassessment and 2.9 years for those with a cCR at later reassessment. The 2-year organ preservation rate was 77.8 (95 per cent c.i. 74.2 to 81.5) and 79.3 (75.1 to 83.7) per cent respectively (P = 0.499). Similarly, no differences were found between groups in distant metastasis-free survival or overall survival rate. Subgroup analyses showed a higher organ preservation rate in the group with a near-cCR categorized exclusively by MRI. CONCLUSION: Oncological outcomes for patients with a cCR at later reassessment are no worse than those of patients with a cCR at first reassessment.

Effects of a 24-Week Low-Cost Multicomponent Exercise Program on Health-Related Functional Fitness in the Community-Dwelling Aged and Older Adults.

Background and Objectives: This study aimed to examine the effects of a low-cost multicomponent exercise program on health-related functional fitness in the community-dwelling aged and older adults. As a second objective, this study compared the exercise program between aged adults (<65 years) and those considered elderly (≥65 years). Materials and Methods: Forty-eight participants were included in the exercise program, and their mean age was 64.73 years (±5.93 years). The Senior Fitness Tests were performed by each participant. A dynamometer was used to assess hand grip strength, and body composition was assessed considering the body mass index. Paired-sample t test was used to compare data at baseline and after the exercise program, considering the total sample. Afterwards, a 2 × 2 analysis of variance was used to examine differences within and between groups. Results: Statistically significant improvements in the chair stand (t = -14.06; p < 0.001; d = 0.42), arm curl (t = -12.10; p < 0.001; d = 0.58), 2 min step test (t = -9.41; p < 0.001; d = 0.24), timed up and go test (t = 5.60; p < 0.001; d = 0.19), and hand grip strength (t = -3.33; p < 0.001; d = 0.15) were observed. There were also significant differences in the back scratch (t = -6.68; p < 0.001; d = 0.18) and chair sit and reach test (t = 5.04; p < 0.001; d = 0.05), as well as body mass index (p < 0.05). No significant differences were found between groups (p > 0.05). Conclusion: This study provides evidence that a 24-week low-cost community-based exercise program can improve functional fitness in aged and in older adults. The exercise program supplied the necessary data to construct further randomized controlled trials that can be performed in the community in an environmentally sustainable fashion and applied, not only to the elderly, but also to those transitioning to this age group.

Antimicrobial Polymeric Surfaces Using Embedded Silver Nanoparticles.

Pathogens (disease-causing microorganisms) can survive up to a few days on surfaces and can propagate through surfaces in high percentages, and thus, these surfaces turn into a primary source of pathogen transmission. To prevent and mitigate pathogen transmission, antimicrobial surfaces seem to be a promising option that can be prepared by using resilient, mass-produced polymers with partly embedded antimicrobial nanoparticles (NPs) with controlled size. In the present study, a 6 nm thick Ag nanolayer was sputter deposited on polycarbonate (PC) substrate and then thermally annealed, in a first step at 120 °C (temperature below Tg) for two hours, for promoting NP diffusion and growth, and in a second step at 180 °C (temperature above Tg) for 22 h, for promoting thermal embedding of the NPs into the polymer surface. The variation in the height of NPs on the polymer surface with thermal annealing confirms the embedding of NPs. It was shown that the incorporation of silver nanoparticles (Ag NPs) had a great impact on the antibacterial capacity, as the Ag NP-embedded polymer surface presented an inhibition effect on the growth of Gram-positive and Gram-negative bacteria. The tested surface-engineering process of incorporating antimicrobial Ag NPs in a polymer surface is both cost-effective and highly scalable.

The Risk of Distant Metastases in Patients With Clinical Complete Response Managed by Watch and Wait After Neoadjuvant Therapy for Rectal Cancer: The Influence of Local Regrowth in the International Watch and Wait Database.

BACKGROUND: Nearly 30% of patients with rectal cancer develop local regrowth after initial clinical complete response managed by watch and wait. These patients might be at higher risk for distant metastases. OBJECTIVE: This study aimed to investigate risk factors for distant metastases using time-dependent analyses. DESIGN: Data from an international watch and wait database were retrospectively reviewed. Cox regression analysis was used to determine risk factors for worse distant metastases-free survival. Conditional survival modeling was used to investigate the impact of risk factors on the development of distant metastases. SETTING: Retrospective, multicenter database. PATIENTS: A total of 793 patients (47 institutions) with rectal cancer and clinical complete response to neoadjuvant treatment from the International Watch & Wait Database were included. MAIN OUTCOME MEASURES: Distant metastases-free survival. RESULTS: Of the 793 patients managed with watch and wait (median follow-up 55.2 mo)' 85 patients (10.7%) had distant metastases. Fifty-one of 85 patients (60%) had local regrowth at any time. Local regrowth was an independent factor associated with worse distant metastases-free survival in the multivariable model. Using conditional estimates, patients with local regrowth without distant metastases for 5 years (from decision to watch and wait) remained at higher risk for development of distant metastases for 1 subsequent year compared to patients without local regrowth (5-year conditional distant metastases-free survival 94.9% vs 98.4%). LIMITATIONS: Lack of information on adjuvant chemotherapy, salvage surgery for local regrowth, and heterogeneity of individual surveillance/follow-up strategies used may have affected results. CONCLUSIONS: In patients with clinical complete response managed by watch and wait, development of local regrowth at any time is a risk factor for distant metastases. The risk of distant metastases remains higher for 5 years after development of local regrowth. See Video Abstract at http://links.lww.com/DCR/C53. EL RIESGO DE METSTASIS A DISTANCIA EN PACIENTES CON RESPUESTA CLNICA COMPLETA MANEJADA POR WATCH AND WAIT DESPUS DE LA TERAPIA NEOADYUVANTE PARA EL CNCER DE RECTO LA INFLUENCIA DEL NUEVO CRECIMIENTO LOCAL EN LA BASE DE DATOS INTERNACIONAL WATCH AND WAIT: ANTECEDENTES:Casi el 30 % de los pacientes con cáncer de recto desarrollan un nuevo crecimiento local después de la respuesta clínica completa inicial manejada por watch and wait. Estos pacientes podrían tener un mayor riesgo de metástasis a distancia.OBJETIVO:Investigar los factores de riesgo de metástasis a distancia mediante análisis dependientes del tiempo.DISEÑO:Se revisó retrospectivamente los datos de la base de datos internacional de Watch and Wait. Se utilizó el análisis de regresión de Cox para determinar los factores de riesgo de peor sobrevida libre de metástasis a distancia. Se utilizó un modelo de sobrevida condicional para investigar el impacto de los factores de riesgo en el desarrollo de metástasis a distancia. El tiempo transcurrido hasta el evento se calculó utilizando la fecha de decisión para watch and wait y la fecha del nuevo crecimiento local para el diagnóstico de metástasis a distancia.ESCENARIOBase de datos multicéntrica retrospectiva.PACIENTES:Se incluyeron un total de 793 pacientes (47 instituciones) con cáncer de recto y respuesta clínica completa al tratamiento neoadyuvante de la base de datos internacional de Watch and Wait.PRINCIPALES MEDIDAS DE RESULTADO:Desarrollo de metástasis a distancia.RESULTADOS:De los 793 pacientes tratados con watch and wait (mediana de seguimiento de 55,2 meses), 85 (10,7%) tenían metástasis a distancia. 51 de 85 (60%) tuvieron recrecimiento local en algún momento. El recrecimiento local fue un factor independiente asociado a una peor supervivencia libre de metástasis a distancia en el modelo multivariable. Además, al usar estimaciones condicionales, los pacientes con recrecimiento local sin metástasis a distancia durante 5 años (desde la decisión de watch and wait) permanecieron en mayor riesgo de desarrollar metástasis a distancia durante un año subsiguiente en comparación con los pacientes sin recrecimiento local (sobrevida libre de metástasis a distancia a 5 años: recrecimiento local 94,9% frente a no recrecimiento local 98,4%).LIMITACIONES:La falta de información relacionada con el uso de quimioterapia adyuvante, las características específicas de la cirugía de rescate para el nuevo crecimient o local y la heterogeneidad de las estrategias individuales de vigilancia/seguimiento utilizadas pueden haber afectado los resultados observados.CONCLUSIONES:En pacientes con respuesta clínica completa manejados por Watch and Wait, el desarrollo de recrecimiento local en cualquier momento es un factor de riesgo para metástasis a distancia. El riesgo de metástasis a distancia sigue siendo mayor durante 5 años después del desarrollo de un nuevo crecimiento local. Consulte Video Resumen en http://links.lww.com/DCR/C53. (Traducción-Dr. Felipe Bellolio).

A Comprehensive Review and Bifactor Modeling Analysis of the Brief COPE.

The Brief COPE is a measure of coping strategies that contains 14 factors. The purpose of this research was twofold: (a) examine the psychometric proprieties of the Brief Cope in previous studies; and (b) perform Confirmatory Factor Analyses (CFA) with second-order model and bifactor model specifications that could be used to assess the best model that represents the 14 coping strategies inherent to the instrument. In order to meet the first objective, a bibliographic review of published peer-reviewed studies between 1997 and 2021 was conducted. Results from the review identified 50 studies, of which 21 used exploratory factor analysis, 28 CFA and one study test-retest analysis. Seventeen studies used the entire correlated 14-factor structure. However, only 11 studies conducted a CFA. For the second objective, a sample of 472 working class individuals (female = 278) with a mean work experience of 19.06 years (SD = 11,92) were recruited. We tested several model specifications, convergent and discriminant validity analysis. We found the correlated 14-factor structure of the Brief COPE to have good psychometric properties. The second-order and bifactor model specifications displayed poor fit or did not converge, respectively. The measure showed good convergent and discriminant validity, and the subscales showed adequate internal consistency. We provide further validity and reliability of the correlated 14-factor structure, evidencing that this measure can assess coping mechanisms. Second-order model specifications need further testing and empirical evidence to support such hierarchical categorization.

Data Driven decision support during COVID.

This paper outlines the development and use of a tool suite developed by the NCI Agency to provide situational awareness and decision support during the current Covid-19. The tool suite was developed to understand how Covid-19 could impact the provision of communication and information services (CIS) to NATO, and so understand where risks to NATO operational functions might occur. The tool suite combines open source data on instances of Covid-19 globally along with internal information about the impact of Covid-19 on NCI Agency staff and the services they deliver to the NATO enterprise. It supports business impact assessments due to Covid-19; showing trends, age demographics, and providing early indications of critical services that may be affected, sites that may be affected, etc. The tool suite is an example of data science techniques supporting data driven decision making within a military organization.

Laparoscopic Complete Mesocolic Excision Without Routine Gastro-Pancreatico-Colic Trunk Dissection: Survival Outcomes and Morbidity for 567 Cases.

Purpose: It is unclear whether the principles of open complete mesocolic excision (CME) can be safely applied to laparoscopic surgery. Furthermore, definitions vary over how radical optimal CME surgery should be. We report morbidity and oncological outcomes for laparoscopic CME without routine gastro-pancreatico-colic trunk (GPCT) dissection. Materials and Methods: An observational study with consecutive data for patients with Union for International Cancer Control (UICC) stage I-III colon adenocarcinoma who underwent elective laparoscopic resection between 2006 and 2015. Data were retrieved for demographics, tumor characteristics, treatment, and histology from prospectively maintained databases. Standardized, routinely video recorded, laparoscopic resections were performed in two United Kingdom centers from The National Training Programme for Laparoscopic Colorectal Surgery. Overall survival and disease-free survival (DFS) were reported using Kaplan-Meier curves and Cox regression. Results: Laparoscopic CME was performed in 567 patients, 52.7% (288/546) women, median (interquartile range [IQR]) age 73 (65-80) years. Median (IQR) length of stay was 4 (3-5) days with 4.0 (2.2-5.7)-year follow-up. Significant DFS predictors (hazard ratio [HR]) by multivariable Cox regression were age >80 years (1.9), American Society of Anesthesiologists (ASA) 3 and 4 (HR = 1.1), right colon cancer (1.7), UICC stage III (3.4), and intramesocolic grade (2.2). Overall 4-year DFS (95% confidence interval) was 81.3% (77-85). Four-year DFS by UICC grades I, II, and III was 94.6% (89-99), 83.4% (77-88), and 72.2% (66-78), respectively (log-rank P = .001). Morbidity by Clavien-Dindo grade was III 18 (3.2%), IV 4 (0.7%) and V 7 (1.2%). Conclusion: This large series suggests standardized laparoscopic CME without routine GPCT dissection has a low morbidity and achieves equivalent outcomes to the most radical open CME techniques.

The "Immunoscore" in rectal cancer: could we search quality beyond quantity of life?

Because of the function and anatomical environment of the rectum, therapeutic strategies for local advanced rectal cancer (LARC) must deal with two challenging stressors that are a high-risk of local and distal recurrences and a high-risk of poor quality of life (QoL). Over the last three decades, advances in screening tests, therapies, and combined-modality treatment options and strategies have improved the prognosis of patients with LARC. However, owing to the heterogeneous nature of LARC and genetic status, the patient may not respond to a specific therapy and may be at increased risk of side-effects without the life-prolonging benefit. Indeed, each therapy can cause its own side-effects, which may worsen by a combination of treatments resulting in long-term poor QoL. In LARC, QoL has become even more essential with the increasing incidence of rectal cancer in young individuals. Herein, we analyzed the value of the Immunoscore-Biopsy (performed on tumor biopsy at diagnosis) in predicting outcomes, alone or in association with clinical and imaging data, for each therapy used in LARC.

Spotlight on laparoscopy in the surgical resection of locally advanced rectal cancer: multicenter propensity score match study.

PURPOSE: This study was aimed to assess the feasibility of laparoscopic rectal surgery, comparing quality of surgical specimen, morbidity, and mortality. METHODS: Prospectively acquired data from consecutive patients undergoing laparoscopic surgery for rectal cancer, at 2 minimally invasive colorectal units, operated by the same team was included. Locally advanced rectal tumors were identified as T3B or T4 with preoperative magnetic resonance imaging scans. All the patients were operated on by the same team. The 1:1 propensity score matching was performed to create a perfect match in terms of tumor height. RESULTS: Total of 418 laparoscopic resections were performed, out of which 109 patients had locally advanced rectal cancer (LARC) and were propensity score matched with non-LARC (NLARC) patients. Median operation time was higher for the LARC group (270 minutes vs. 250 minutes, P=0.011). However, conversion to open surgery was done in 5 vs. 2 patients (P=0.445), reoperation in 8 vs. 7 (P=0.789), clinical anastomotic leak was found in 3 vs. 2 (P=0.670), and 30-day mortality rates was 2 vs. 1 (P>0.999) between LARC and NLARC, respectively. Readmission rate was higher in the NLARC group (33 patients vs. 19 patients, P=0.026), due to stoma-related issues. There was no statistically significant difference in the R0 resection between the 2 groups (99 patients in LARC vs. 104 patients in NLARC, P=0.284). CONCLUSION: This study demonstrates that standardized approach to laparoscopy is safe and feasible in LARC. Comparable postoperative short-term clinical and pathological outcomes were seen between LARC and NLARC groups.

Watch and wait after a clinical complete response in rectal cancer patients younger than 50 years.

BACKGROUND: Young-onset rectal cancer, in patients less than 50 years, is expected to increase in the coming years. A watch-and-wait strategy is nowadays increasingly practised in patients with a clinical complete response (cCR) after neoadjuvant treatment. Nevertheless, there may be reluctance to offer organ preservation treatment to young patients owing to a potentially higher oncological risk. This study compared patients aged less than 50 years with those aged 50 years or more to identify possible differences in oncological outcomes of watch and wait. METHODS: The study analysed data from patients with a cCR after neoadjuvant therapy in whom surgery was omitted, registered in the retrospective-prospective, multicentre International Watch & Wait Database (IWWD). RESULTS: In the IWWD, 1552 patients met the inclusion criteria, of whom 199 (12.8 per cent) were aged less than 50 years. Patients younger than 50 years had a higher T category of disease at diagnosis (P = 0.011). The disease-specific survival rate at 3 years was 98 (95 per cent c.i. 93 to 99) per cent in this group, compared with 97 (95 to 98) per cent in patients aged over 50 years (hazard ratio (HR) 1.67, 95 per cent c.i. 0.76 to 3.64; P = 0.199). The cumulative probability of local regrowth at 3 years was 24 (95 per cent c.i. 18 to 31) per cent in patients less than 50 years and 26 (23 to 29) per cent among those aged 50 years or more (HR 1.09, 0.79 to 1.49; P = 0.603). Both groups had a cumulative probability of distant metastases of 10 per cent at 3 years (HR 1.00, 0.62 to 1.62; P = 0.998). CONCLUSION: There is no additional oncological risk in young patients compared with their older counterparts when following a watch-and-wait strategy after a cCR. In light of a shared decision-making process, watch and wait should be also be discussed with young patients who have a cCR after neoadjuvant treatment.

Targeting Neoepitopes to Treat Solid Malignancies: Immunosurgery.

Successful outcome of immune checkpoint blockade in patients with solid cancers is in part associated with a high tumor mutational burden (TMB) and the recognition of private neoantigens by T-cells. The quality and quantity of target recognition is determined by the repertoire of 'neoepitope'-specific T-cell receptors (TCRs) in tumor-infiltrating lymphocytes (TIL), or peripheral T-cells. Interferon gamma (IFN-γ), produced by T-cells and other immune cells, is essential for controlling proliferation of transformed cells, induction of apoptosis and enhancing human leukocyte antigen (HLA) expression, thereby increasing immunogenicity of cancer cells. TCR αß-dependent therapies should account for tumor heterogeneity and availability of the TCR repertoire capable of reacting to neoepitopes and functional HLA pathways. Immunogenic epitopes in the tumor-stroma may also be targeted to achieve tumor-containment by changing the immune-contexture in the tumor microenvironment (TME). Non protein-coding regions of the tumor-cell genome may also contain many aberrantly expressed, non-mutated tumor-associated antigens (TAAs) capable of eliciting productive anti-tumor immune responses. Whole-exome sequencing (WES) and/or RNA sequencing (RNA-Seq) of cancer tissue, combined with several layers of bioinformatic analysis is commonly used to predict possible neoepitopes present in clinical samples. At the ImmunoSurgery Unit of the Champalimaud Centre for the Unknown (CCU), a pipeline combining several tools is used for predicting private mutations from WES and RNA-Seq data followed by the construction of synthetic peptides tailored for immunological response assessment reflecting the patient's tumor mutations, guided by MHC typing. Subsequent immunoassays allow the detection of differential IFN-γ production patterns associated with (intra-tumoral) spatiotemporal differences in TIL or peripheral T-cells versus TIL. These bioinformatics tools, in addition to histopathological assessment, immunological readouts from functional bioassays and deep T-cell 'adaptome' analyses, are expected to advance discovery and development of next-generation personalized precision medicine strategies to improve clinical outcomes in cancer in the context of i) anti-tumor vaccination strategies, ii) gauging mutation-reactive T-cell responses in biological therapies and iii) expansion of tumor-reactive T-cells for the cellular treatment of patients with cancer.

Re-staging and follow-up of rectal cancer patients with MR imaging when "Watch-and-Wait" is an option: a practical guide.

In the past nearly 20 years, organ-sparing when no apparent viable tumour is present after neoadjuvant therapy has taken an increasingly relevant role in the therapeutic management of locally-advanced rectal cancer patients. The decision to include a patient or not in a "Watch-and-Wait" program relies mainly on endoscopic assessment by skilled surgeons, and MR imaging by experienced radiologists. Strict surveillance using the same modalities is required, given the chance of a local regrowth is of approximately 25-30%, almost always surgically salvageable if caught early. Local regrowths occur at the endoluminal aspect of the primary tumour bed in almost 90% of patients, but the rest are deep within it or outside the rectal wall, in which case detection relies solely on MR Imaging. In this educational review, we provide a practical guide for radiologists who are, or intend to be, involved in the re-staging and follow-up of rectal cancer patients in institutions with an established "Watch-and-Wait" program. First, we discuss patient preparation and MR imaging acquisition technique. Second, we focus on the re-staging MR imaging examination and review the imaging findings that allow us to assess response. Third, we focus on follow-up assessments of patients who defer surgery and confer about the early signs that may indicate a sustained/non-sustained complete response, a rectal/extra-rectal regrowth, and the particular prognosis of the "near-complete" responders. Finally, we discuss our proposed report template.