What is the optimal timing of surgery after short-course radiotherapy for rectal cancer?

BACKGROUND: Short-course neoadjuvant radiotherapy is a valuable tool in managing rectal cancers and has improved local recurrence rates. However, limited and conflicting data has resulted in variable usage and a lack of consensus on the optimal timing of surgery following short-course radiotherapy. This review aims to provide a contemporary summation of the available evidence regarding the optimal time interval between short-course neoadjuvant radiotherapy and surgery. METHODS: A focused literature search was undertaken using the PubMed and Embase databases from January 1980 until January 2023. Randomised control trials, large observational studies and systematic reviews focusing on the use of short-course preoperative radiotherapy for localised rectal cancers, with a focus on the timing of surgery, were included. Primary outcomes were overall survival, disease-free survival and perioperative complications. RESULTS: Five randomised control trials, two meta-analyses, and two large, population-based studies were included for their eligibility and relevance. Increased downstaging and fewer postoperative complications are demonstrated in patients receiving delayed surgery (> four weeks), but more recent data raise concerns regarding increased rates of local recurrence in this cohort. Studies directly comparing different time intervals to surgery following short-course radiotherapy have failed to demonstrate an effect on overall survival. CONCLUSIONS: This review highlights the complexities and relative shortcomings of the available data with few high-quality studies and randomised control trials directly comparing different time intervals to surgery following short-course radiotherapy. Continuing research is needed to confirm existing findings and explore gaps in the current literature.

Inguinal lymph node metastases from rectal adenocarcinoma: a systematic review.

PURPOSE: Inguinal lymph nodes are a rare but recognised site of metastasis in rectal adenocarcinoma. No guideline or consensus exists for the management of such cases. This review aims to provide a contemporary and comprehensive analysis of the published literature to aid clinical decision-making. METHODS: Systematic searches were performed using the PubMed, Embase, MEDLINE and Scopus and Cochrane CENTRAL Library databases from inception till December 2022. All studies reporting on the presentation, prognosis or management of patients with inguinal lymph node metastases (ILNM) were included. Pooled proportion meta-analyses were completed when possible and descriptive synthesis was utilised for the remaining outcomes. The Joanna Briggs Institute tool for case series was used to assess the risk of bias. RESULTS: Nineteen studies were eligible for inclusion, encompassing 18 case series and one population-based study using national registry data. A total of 487 patients were included in the primary studies. The prevalence of ILNM in rectal cancer is 0.36%. ILNM are associated with very low rectal tumours with a mean distance from the anal verge of 1.1 cm (95% CI 0.92-1.27). Invasion of the dentate line was found in 76% of cases (95% CI 59-93). In patients with isolated inguinal lymph node metastases, modern chemoradiotherapy regimens in combination with surgical excision of inguinal nodes are associated with 5-year overall survival rates of 53-78%. CONCLUSION: In specific subsets of patients with ILNM, curative-intent treatment regimens are feasible, with oncological outcomes akin to those demonstrated in locally advanced rectal cancers.

Vascularisation in Deep Endometriosis: A Systematic Review with Narrative Outcomes.

Deep endometriosis (DE) is the most severe subtype of endometriosis, with the hallmark of lesions infiltrating adjacent tissue. Abnormal vascularisation has been implicated in contributing to endometriosis lesion development in general, and how vascularisation influences the pathogenesis of DE, in particular, is of interest. This systematic review followed the PRISMA guidelines to elucidate and examine the evidence for DE-specific vascularisation. A literature search was performed using MEDLINE, Embase, PubMed, Scopus, Cochrane CENTRAL Library and Europe PubMed Central databases. The databases were searched from inception to the 13 March 2023. A total of 15 studies with 1125 patients were included in the review. The DE lesions were highly vascularised, with a higher microvessel density (MVD) than other types of endometriotic lesions, eutopic endometrium from women with endometriosis and control tissue. Vascular endothelial growth factor, its major subtype (VEGF-A) and associated receptor (VEGFR-2) were significantly increased in the DE lesions compared to superficial endometriosis, eutopic endometrium and control tissue. Progestin therapy was associated with a significant decrease in the MVD of the DE lesions, explaining their therapeutic effect. This review comprehensively summarises the available literature, reporting abnormal vascularisation to be intimately related to the pathogenesis of DE and presents potentially preferential therapeutic targets for the medical management of DE.

The immune cell profile of human fallopian tubes in health and benign pathology: a systematic review.

The fallopian tubes (FT) play a key role in fertility by facilitating the movement of gametes to promote fertilisation and, subsequently, passage of the zygote for implantation. Histologically, the FT mucosa consists of three main cell types: secretory, ciliated and peg cells. In addition, several studies have reported the presence of immune cells. This systematic review aims to present a comprehensive analysis of the immune cell populations in the human FT, both in health and benign pathology, to promote a better understanding of tubal pathologies and their influence on infertility. A comprehensive literature search was conducted across five databases and augmented with manual citation chaining. Forty-two eligible studies were selected in accordance with PRISMA guidelines. Following screening, risk of bias assessments were conducted, data extracted and the findings presented thematically. T lymphocytes, predominantly CD8+ T cells, represent the most abundant immune cell population within the healthy FT, with B lymphocytes, macrophages, NK cells and dendritic cells also localised to the tubal mucosa. There is evidence to suggest that lymphocyte and macrophage populations are susceptible to changes in the concentration of reproductive hormones. Tubal ectopic pregnancy, salpingitis, hydrosalpinx and endometriosis are all characterised by an increased population of macrophages in comparison to healthy FT. However, given the inconsistent evidence presented between studies, and the lack of studies examining all immune cell subtypes in tubal pathologies, only limited conclusions can be formulated on pathology-specific immune cell populations, and further research is required for validation.

Completion Total Mesorectal Excision After Transanal Local Excision of Early Rectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Completion total mesorectal excision is recommended when local excision of early rectal cancers demonstrates high-risk histopathological features. Concerns regarding the quality of completion resections and the impact on oncological safety remain unanswered. OBJECTIVE: This study aims to summarize and analyze the outcomes associated with completion surgery and undertake a comparative analysis with primary rectal resections. DATA SOURCES: Data sources included PubMed, Cochrane library, MEDLINE, and Embase databases up to April 2021. STUDY SELECTION: All studies reporting any outcome of completion surgery after transanal local excision of an early rectal cancer were selected. Case reports, studies of benign lesions, and studies using flexible endoscopic techniques were not included. INTERVENTION: The intervention was completion total mesorectal excision after transanal local excision of early rectal cancers. MAIN OUTCOME MEASURES: Primary outcome measures included histopathological and long-term oncological outcomes of completion total mesorectal excision. Secondary outcome measures included short-term perioperative outcomes. RESULTS: Twenty-three studies including 646 patients met the eligibility criteria, and 8 studies were included in the meta-analyses. Patients undergoing completion surgery have longer operative times (standardized mean difference, 0.49; 95% CI, 0.23-0.75; p = 0.0002) and higher intraoperative blood loss (standardized mean difference, 0.25; 95% CI, 0.01-0.5; p = 0.04) compared with primary resections, but perioperative morbidity is comparable (risk ratio, 1.26; 95% CI, 0.98-1.62; p = 0.08). Completion surgery is associated with higher rates of incomplete mesorectal specimens (risk ratio, 3.06; 95% CI, 1.41-6.62; p = 0.005) and lower lymph node yields (standardized mean difference, -0.26; 95% CI, -0.47 to 0.06; p = 0.01). Comparative analysis on long-term outcomes is limited, but no evidence of inferior recurrence or survival rates is found. LIMITATIONS: Only small retrospective cohort and case-control studies are published on this topic, with considerable heterogeneity limiting the effectiveness of meta-analysis. CONCLUSIONS: This review provides the strongest evidence to date that completion surgery is associated with an inferior histopathological grade of the mesorectum and finds insufficient long-term results to satisfy concerns regarding oncological safety. International collaborative research is required to demonstrate noninferiority. REGISTRATION NO: CRD42021245101.

Novel microarchitecture of human endometrial glands: implications in endometrial regeneration and pathologies.

BACKGROUND: Human endometrium remains a poorly understood tissue of the female reproductive tract. The superficial endometrial functionalis, the site of embryo implantation, is repeatedly shed with menstruation, and the stem cell-rich deeper basalis is postulated to be responsible for the regeneration of the functionalis. Two recent manuscripts have demonstrated the 3D architecture of endometrial glands. These manuscripts have challenged and replaced the prevailing concept that these glands end in blind pouches in the basalis layer that contain stem cells in crypts, as in the intestinal mucosa, providing a new paradigm for endometrial glandular anatomy. This necessitates re-evaluation of the available evidence on human endometrial regeneration in both health and disease in the context of this previously unknown endometrial glandular arrangement. OBJECTIVE AND RATIONALE: The aim of this review is to determine if the recently discovered glandular arrangement provides plausible explanations for previously unanswered questions related to human endometrial biology. Specifically, it will focus on re-appraising the theories related to endometrial regeneration, location of stem/progenitor cells and endometrial pathologies in the context of this recently unravelled endometrial glandular organization. SEARCH METHODS: An extensive literature search was conducted from inception to April 2021 using multiple databases, including PubMed/Web of Science/EMBASE/Scopus, to select studies using keywords applied to endometrial glandular anatomy and regeneration, and the references included in selected publications were also screened. All relevant publications were included. OUTCOMES: The human endometrial glands have a unique and complex architecture; branched basalis glands proceed in a horizontal course adjacent to the myometrium, as opposed to the non-branching, vertically coiled functionalis glands, which run parallel to each other as is observed in intestinal crypts. This complex network of mycelium-like, interconnected basalis glands is demonstrated to contain endometrial epithelial stem cells giving rise to single, non-branching functionalis glands. Several previous studies that have tried to confirm the existence of epithelial stem cells have used methodologies that prevent sampling of the stem cell-rich basalis. More recent findings have provided insight into the efficient regeneration of the human endometrium, which is preferentially evolved in humans and menstruating upper-order primates. WIDER IMPLICATIONS: The unique physiological organization of the human endometrial glandular element, its relevance to stem cell activity and scarless endometrial regeneration will inform reproductive biologists and clinicians to direct their future research to determine disease-specific alterations in glandular anatomy in a variety of endometrial pathological conditions.