The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Hypoplastic left heart syndrome with prenatally diagnosed foramen ovale restriction: diagnosis, management and outcome

Objective: Despite advances in prenatal diagnosis and postnatal intervention/surgery methods, patients with Hypoplastic Left Heart Syndrome (HLHS) and coexisting foramen oval restriction still achieve high mortality rates. Our objective was to determine survival predictors and to find answers to, why restriction develops in some, but not others.Methods: We performed a retrospective analysis of prenatal history and postnatal sequel of 22 patients with HLHS and foramen ovale restriction between 2008 and 2017.Results: There were 11 survivors and 11 nonsurvivors. The most significant difference between the two groups pertained to the average time of foramen ovale restriction diagnosis which was 33 weeks for survivors and 28 weeks for nonsurvivors (p = .0416) and the duration of in-utero restriction (9 versus 5 weeks, p = .0213). Twenty patients (20/22) exhibited possible signs of infection.Conclusions: (1) Earlier development and longer presence of foramen ovale restriction in the setting of HLHS is associated with higher short-term mortality regardless of the degree of restriction. (2) Ratio of forward pulmonary vein flow to reverse flow (f/r) expressed as a velocity-time integral (VTI) is a good emergent intervention predictor, but it does not correlate with foramen ovale size and maximal velocity, nor does it influence survival rates. (3) Ultrasonographic signs of possible infection of the fetus is a potential risk factor of foramen ovale restriction development in patients with HLHS

Evaluating the Significance of Paleophylogeographic Species Distribution Models in Reconstructing Quaternary Range-Shifts of Nearctic Chelonians

<div><p>The climatic cycles of the Quaternary, during which global mean annual temperatures have regularly changed by 5–10°C, provide a special opportunity for studying the rate, magnitude, and effects of geographic responses to changing climates. During the Quaternary, high- and mid-latitude species were extirpated from regions that were covered by ice or otherwise became unsuitable, persisting in refugial retreats where the environment was compatible with their tolerances. In this study we combine modern geographic range data, phylogeny, Pleistocene paleoclimatic models, and isotopic records of changes in global mean annual temperature, to produce a temporally continuous model of geographic changes in potential habitat for 59 species of North American turtles over the past 320 Ka (three full glacial-interglacial cycles). These paleophylogeographic models indicate the areas where past climates were compatible with the modern ranges of the species and serve as hypotheses for how their geographic ranges would have changed in response to Quaternary climate cycles. We test these hypotheses against physiological, genetic, taxonomic and fossil evidence, and we then use them to measure the effects of Quaternary climate cycles on species distributions. Patterns of range expansion, contraction, and fragmentation in the models are strongly congruent with (i) phylogeographic differentiation; (ii) morphological variation; (iii) physiological tolerances; and (iv) intraspecific genetic variability. Modern species with significant interspecific differentiation have geographic ranges that strongly fluctuated and repeatedly fragmented throughout the Quaternary. Modern species with low genetic diversity have geographic distributions that were highly variable and at times exceedingly small in the past. Our results reveal the potential for paleophylogeographic models to (i) reconstruct past geographic range modifications, (ii) identify geographic processes that result in genetic bottlenecks; and (iii) predict threats due to anthropogenic climate change in the future.</p></div

Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study

Background: Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods: This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index &lt;20), moderate lockdowns (20–60), and full lockdowns (&gt;60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926. Findings: Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p&lt;0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p&lt;0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p&lt;0·001), and full lockdowns (0·57, 0·54–0·60; p&lt;0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation: Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services. Funding: National Institute for Health Research Global Health Research Unit, Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, Medtronic, Sarcoma UK, The Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research