Recommendations for the optimal management of peritoneal metastases in patients with colorectal cancer: a TTD and GECOP-SEOQ expert consensus statement.

Peritoneal metastases (PM) occur when cancer cells spread inside the abdominal cavity and entail an advanced stage of colorectal cancer (CRC). Prognosis, which is poor, correlates highly with tumour burden, as measured by the peritoneal cancer index (PCI). Cytoreductive surgery (CRS) in specialized centres should be offered especially to patients with a low to moderate PCI when complete resection is expected. The presence of resectable metastatic disease in other organs is not a contraindication in well-selected patients. Although several retrospective and small prospective studies have suggested a survival benefit of adding hyperthermic intraperitoneal chemotherapy (HIPEC) to CRS, the recently published phase III studies PRODIGE-7 in CRC patients with PM, and COLOPEC and PROPHYLOCHIP in resected CRC with high-risk of PM, failed to show any survival advantage of this strategy using oxaliplatin in a 30-min perfusion. Final results from ongoing randomized phase III trials testing CRS plus HIPEC based on mitomycin C (MMC) are awaited with interest. In this article, a group of experts selected by the Spanish Group for the Treatment of Digestive Tumours (TTD) and the Spanish Group of Peritoneal Oncologic Surgery (GECOP), which is part of the Spanish Society of Surgical Oncology (SEOQ), reviewed the role of HIPEC plus CRS in CRC patients with PM. As a result, a series of recommendations to optimize the management of these patients is proposed.

GECOP-MMC: phase IV randomized clinical trial to evaluate the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) with mytomicin-C after complete surgical cytoreduction in patients with colon cancer peritoneal metastases.

BACKGROUND: The French PRODIGE 7 trial, published on January 2021, has raised doubts about the specific survival benefit provided by HIPEC with oxaliplatin 460 mg/m2 (30 minutes) for the treatment of peritoneal metastases from colorectal cancer. However, several methodological flaws have been identified in PRODIGE 7, specially the HIPEC protocol or the choice of overall survival as the main endpoint, so its results have not been assumed as definitive, emphasizing the need for further research on HIPEC. It seems that the HIPEC protocol with high-dose mytomicin-C (35 mg/m2) is the preferred regime to evaluate in future clinical studies. METHODS: GECOP-MMC is a prospective, open-label, randomized, multicenter phase IV clinical trial that aims to evaluate the effectiveness of HIPEC with high-dose mytomicin-C in preventing the development of peritoneal recurrence in patients with limited peritoneal metastasis from colon cancer (not rectal), after complete surgical cytoreduction. This study will be performed in 31 Spanish HIPEC centres, starting in March 2022. Additional international recruiting centres are under consideration. Two hundred sixteen patients with PCI ≤ 20, in which complete cytoreduction (CCS 0) has been obtained, will be randomized intraoperatively to arm 1 (with HIPEC) or arm 2 (without HIPEC). We will stratified randomization by surgical PCI (1-10; 11-15; 16-20). Patients in both arms will be treated with personalized systemic chemotherapy. Primary endpoint is peritoneal recurrence-free survival at 3 years. An ancillary study will evaluate the correlation between surgical and pathological PCI, comparing their respective prognostic values. DISCUSSION: HIPEC with high-dose mytomicin-C, in patients with limited (PCI ≤ 20) and completely resected (CCS 0) peritoneal metastases, is assumed to reduce the expected risk of peritoneal recurrence from 50 to 30% at 3 years. TRIAL REGISTRATION: EudraCT number: 2019-004679-37; Clinicaltrials.gov: NCT05250648 (registration date 02/22/2022, ).

The Landmark Series: Surgical Treatment of Colorectal Cancer Peritoneal Metastases.

BACKGROUND: Peritoneal metastases (PM) are a form of metastatic spread affecting approximately 5-15% of colon cancer patients. The attitude towards management of peritoneal metastases has evolved from therapeutic nihilism towards a more comprehensive and multidisciplinary approach, in large part due to the development of cytoreductive surgery (CRS), usually coupled with heated intraperitoneal chemotherapy (HIPEC), along with the constant improvement of systemic chemotherapy of colorectal cancer. Several landmark studies, including 5 randomized controlled trials have marked the development and refinement of surgical approaches to treating colorectal cancer peritoneal metastases. METHODS: This review article focuses on these landmark studies and their influence in 4 key areas: the evidence supporting surgical resection of peritoneal metastases, the identification and standardization of important prognostic variables influencing patient selection, the role of surgery and intraperitoneal chemotherapy in prevention of colorectal PM and the role of intraperitoneal chemotherapy as an adjuvant to surgical resection. RESULTS: These landmark studies indicate that surgical resection of colorectal PM should be considered as a therapeutic option in appropriately selected patients and when adequate surgical expertise is available. Standardized prognostic variables including the Peritoneal Cancer Index and the Completeness of Cytoreduction Score should be used for evaluating both indications and outcomes. CONCLUSIONS: Current evidence does not support the use of second look surgery with oxaliplatin HIPEC or prophylactic oxaliplatin HIPEC in patients with high risk colon cancer nor the use of oxaliplatin HIPEC with CRS of colorectal PM.

A Near-Zero Anastomotic Leak Rate in Cytoreductive Surgery with Heated Intraperitoneal Chemotherapy is Achievable.

Gastrointestinal complications are the main source of severe morbidity after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), mainly in the form of anastomotic leak. Reducing the rate of anastomotic leaks is of paramount importance and should be approached both through risk factor understanding and reduction, as well as optimization of surgical team performance. We performed a study that describes the details of a technical protocol for the creation of anastomoses after colorectal resections in CRS and HIPEC and the anastomotic outcomes associated with its systematic application in a high-volume peritoneal surface malignancy center. An extremely low, near-zero anastomotic leak rate (0.85% in colorectal anastomoses, 1% in ileo-colic anastomoses, and 0% in ileo-rectal anastomoses) was observed among 1172 patients. Extremely low, near-zero rates of anastomotic leak after colorectal resections in CRS and HIPEC could be achievable in high-volume peritoneal malignancy centers. The described techniques could be adopted and validated in other high-volume peritoneal malignancy centers.

LNDb challenge on automatic lung cancer patient management.

Lung cancer is the deadliest type of cancer worldwide and late detection is the major factor for the low survival rate of patients. Low dose computed tomography has been suggested as a potential screening tool but manual screening is costly and time-consuming. This has fuelled the development of automatic methods for the detection, segmentation and characterisation of pulmonary nodules. In spite of promising results, the application of automatic methods to clinical routine is not straightforward and only a limited number of studies have addressed the problem in a holistic way. With the goal of advancing the state of the art, the Lung Nodule Database (LNDb) Challenge on automatic lung cancer patient management was organized. The LNDb Challenge addressed lung nodule detection, segmentation and characterization as well as prediction of patient follow-up according to the 2017 Fleischner society pulmonary nodule guidelines. 294 CT scans were thus collected retrospectively at the Centro Hospitalar e Universitrio de So Joo in Porto, Portugal and each CT was annotated by at least one radiologist. Annotations comprised nodule centroids, segmentations and subjective characterization. 58 CTs and the corresponding annotations were withheld as a separate test set. A total of 947 users registered for the challenge and 11 successful submissions for at least one of the sub-challenges were received. For patient follow-up prediction, a maximum quadratic weighted Cohen's kappa of 0.580 was obtained. In terms of nodule detection, a sensitivity below 0.4 (and 0.7) at 1 false positive per scan was obtained for nodules identified by at least one (and two) radiologist(s). For nodule segmentation, a maximum Jaccard score of 0.567 was obtained, surpassing the interobserver variability. In terms of nodule texture characterization, a maximum quadratic weighted Cohen's kappa of 0.733 was obtained, with part solid nodules being particularly challenging to classify correctly. Detailed analysis of the proposed methods and the differences in performance allow to identify the major challenges remaining and future directions - data collection, augmentation/generation and evaluation of under-represented classes, the incorporation of scan-level information for better decision-making and the development of tools and challenges with clinical-oriented goals. The LNDb Challenge and associated data remain publicly available so that future methods can be tested and benchmarked, promoting the development of new algorithms in lung cancer medical image analysis and patient follow-up recommendation.

Comprehensive Perspective for Lung Cancer Characterisation Based on AI Solutions Using CT Images.

Lung cancer is still the leading cause of cancer death in the world. For this reason, novel approaches for early and more accurate diagnosis are needed. Computer-aided decision (CAD) can be an interesting option for a noninvasive tumour characterisation based on thoracic computed tomography (CT) image analysis. Until now, radiomics have been focused on tumour features analysis, and have not considered the information on other lung structures that can have relevant features for tumour genotype classification, especially for epidermal growth factor receptor (EGFR), which is the mutation with the most successful targeted therapies. With this perspective paper, we aim to explore a comprehensive analysis of the need to combine the information from tumours with other lung structures for the next generation of CADs, which could create a high impact on targeted therapies and personalised medicine. The forthcoming artificial intelligence (AI)-based approaches for lung cancer assessment should be able to make a holistic analysis, capturing information from pathological processes involved in cancer development. The powerful and interpretable AI models allow us to identify novel biomarkers of cancer development, contributing to new insights about the pathological processes, and making a more accurate diagnosis to help in the treatment plan selection.

La vitamina D durante la gestación / Vitamin D during gestation

OBJETIVO: Describir la relevancia del déficit de vitamina D durante la gestación, así como sus consecuencias y sus factores de riesgo, y evaluar la necesidad de administración de suplementos para su tratamiento. METODOLOGÍA: Revisión bibliográfica de las bases de datos Turning Research Into Practice, Evidence-Based Nursing, Joanna Briggs Institute, Biblioteca Cochrane Plus, guías de la National Institute of Health and Care Excellence, PubMed, Índice Médico Español (IME), Cumulative Index to Nursing and Allied Health Literature (CINAHL), en inglés y español, y de la disponibilidad en la biblioteca desde la cual se hacía la consulta. La última búsqueda se efectuó en diciembre de 2017. RESULTADOS: Se obtuvo un total de 127 referencias bibliográficas, de las que 30 cumplían los criterios de selección. Se seleccionaron 26 artículos: 15 artículos originales, 5 revisiones bibliográficas y 6 guías de práctica clínica y protocolos de actuación. CONCLUSIONES: La vitamina D es fundamental en todas las etapas de la vida de la mujer. El déficit de vitamina D en las gestantes es un hecho constatado en los estudios internacionales actuales. Se describe la necesidad de optimizar los niveles de vitamina D durante la gestación, dado que su déficit está relacionado con complicaciones importantes que pueden afectar tanto a la madre como al recién nacido, e incluso a la vida futura de ambos. No obstante, la necesidad, la seguridad y la eficacia de los suplementos de vitamina D administrados de manera sistemática y preventiva durante el embarazo es un tema no exento de controversia entre los profesionales, dado su potencial efecto tóxico. No se dispone de estudios que demuestren el beneficio de los suplementos de vitamina D a corto y largo plazo. Cabe destacar que no parecen tener un efecto teratogénico ni ser potencialmente nocivos para la gestante

AIM: To describe the relevance of vitamin D deficiency during pregnancy, as well as its consequences and risk factors, and to evaluate the need for supplementation for its treatment. METHODOLOGY: Bibliographic review of Turning Research Into Practice databases, Evidence-Based Nursing, Joanna Briggs Institute, Cochrane Plus Library, guides of the National Institute of Health and Care Excellence, PubMed, Spanish Medical Index (IME), Cumulative Index to Nursing and Allied Health Literature (CINAHL) in English and Spanish and availability in the library from which the consultation was made. Last search December of 2017. RESULTS: A total of 127 bibliographical references were obtained, of which 30 met the selection criteria. After reading the abstracts and checking if there was documentary duplication from the different databases, a total of 26 articles were selected. Of these, 15 are original articles, 5 are a bibliographic review and 6 are action guides. CONCLUSIONS: Vitamin D is essential in all stages of a woman's life. The deficit of Vitamin D in pregnant women is a fact described in the current studies worldwide. The need to optimize vitamin D levels during pregnancy is described, because its deficit is related to important complications that can affect the mother and the newborn and even the future life of both. However, the need, safety and efficacy of vitamin D supplements administered routinely and preventively during pregnancy is a controversial issue among professionals, given its potential toxic effect. There are no studies that demonstrate its short and long-term benefit. It should be noted that it does not seem to have a teratogenic effect nor does it seem to be potentially harmful for the pregnant woman