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Background Pathologic complete response (pCR) of rectal cancer following neoadjuvant therapy is associated with decreased local recurrence and increased overall survival. This study utilizes a national dataset to identify predictors of pCR in patients with rectal cancer. Methods The National Cancer Database was queried for patients with nonmetastatic rectal cancer (2004–2014) who underwent neoadjuvant therapy and surgical resection. Unadjusted associations were assessed using rank-sum tests and χ 2 tests where appropriate. Backward elimination and forward selection multivariable logistic regression models were created to determine the relationship of annual surgical volume with pCR rate, adjusting for preoperative characteristics and radiation-surgery interval. Statistical tests were two-sided, with a significance level of p  ≤ 0.05. Analyses were performed using SAS version 9.4. Results A total of 27,532 patients from 1179 participating hospitals met the inclusion criteria. Generalized linear mixed models demonstrated that the odds of achieving pCR was independently associated with more recent diagnosis, female sex, private insurance, lower grade, lower clinical T classification, lower clinical N classification, increasing interval between the end of radiation and surgery, and treatment at higher-volume institutions. Conclusions pCR was associated with favorable tumor factors, insurance status, time between radiation and surgery, and institutional volume. It is not clear what is driving the higher rates of pCR at high-volume institutions. Research targeted at understanding processes that are associated with pCR in high-volume institutions is needed so that similar results can be achieved across the spectrum of facilities caring for patients in this population.

Background Current National Comprehensive Cancer Network guidelines for resectable small bowel neuroendocrine tumors (NETs) recommend regional lymphadenectomy. However, no consensus exists on the optimal nodal harvest. Methods The National Cancer Database was queried for patients with resectable small bowel NETs (1998–2013). Patients with metastatic disease and missing lymph node harvest data were excluded. We performed logistic regression of factors determining nodal positivity and multivariable survival analyses. Results Of 11,852 patients, 81.8% underwent lymphadenectomy. 79.3% were node positive (N+) and 46.9% of patients had tumors < 1 cm. Independent predictors of N+ were large tumor size, ileal location, and neuroendocrine carcinoma histology. Logistic regression found no difference between observed and expected proportions of N+ patients with lymphadenectomy greater than or equal to eight nodes. Lower metastatic node ratio predicted improved survival on multivariable analysis and is associated with high-volume institutions. Conclusion Small bowel NETs have high rates of nodal metastasis, even in patients with small tumors, and many patients do not undergo lymphadenectomy despite the clear benefit. Lymphadenectomy of eight nodes is optimal to identify N+ patients. Additionally, minimizing metastatic node ratio with complete regional lymphadenectomy is associated with improved survival in these patients.

Background Optimal nutrition after esophagectomy is challenging due to alterations in eating, both from the tumor and during surgical recovery. Enteral nutrition via feeding tube is commonly used. The impact of feeding tubes on post-esophagectomy outcomes was examined in a large national data set. Methods Patients with esophageal cancer (1998–2013) undergoing esophagectomy were extracted from the Surveillance Epidemiology and End Results-Medicare database. Chi-square and t tests were used to compare categorical and continuous variables. Time trend analyses were performed with Cochran–Armitage survival using log-rank and multivariable analysis with generalized linear modeling. Results The study examined 2495 patients. The majority had enteral feeding access (71%, n  = 1794) during the perioperative period. Mortality among the patients with feeding tubes was lower at 30 days (5.4% vs 8.4%), 60 days (9.0% vs 13.0%), and 90 days (12.2% vs 15.8%). In the multivariable analysis, the patients with feeding tubes had improved short-term survival at 30 days (odds ratio [OR], 0.65, 95% confidence interval [CI], 0.46–0.93), 60 days (OR, 0.64; 95% CI, 0.49–0.85), and 90 days (OR, 0.70; 95% CI, 0.54–0.90). The hospital stay was shorter for the patients undergoing enteral feeding tube placement (17.9 vs 19.5 days; p  = 0.04). Discharge destination (home vs health care facility) showed no difference. Conclusions Feeding tubes in patients undergoing esophagectomy were associated with an increase in short-term survival up to 90 days after surgery. Feeding tube placement was not associated with higher rates of non-home discharges and did not prolong the hospital stay.

Background Studies suggest that the biology of pediatric and adolescent melanoma differs from that of adult disease. We report the largest series to date examining the natural history of pediatric and adolescent melanoma. We aim to elucidate the natural history of pediatric and adolescent melanoma and to examine the appropriateness of diagnostic and therapeutic modalities developed for adults and that are currently being used in children. Methods A retrospective cohort study was conducted of patients with an index diagnosis of cutaneous non-metastatic melanoma from 1998 to 2011 using the National Cancer Data Base (NCDB; n = 420,416). Three age-based cohorts were analyzed: 1–10 years (pediatric), 11–20 years (adolescent), and ≥21 years (adult). Multivariate analyses were used to identify factors associated with overall survival (OS). Results Pediatric melanoma patients have longer OS than their adolescent (hazard ratio [HR] 0.50, 95 % CI 0.25–0.98) and adult counterparts (HR 0.11, 95 % CI 0.06–0.21). Adolescents have longer OS than adults. No difference was found in OS in pediatric patients who are node-positive versus node-negative. In pediatric patients, sentinel lymph node biopsy and completion lymph node dissection are not associated with increased OS. In adolescents, nodal positivity is a significant negative prognostic indicator (HR 4.82, 95 % CI 3.38–6.87). Conclusions Age-based differences in melanoma outcomes warrant different considerations for diagnostic and therapeutic approaches in each group in order to maximize quality of life while minimizing complications and costs. Prospective, multicenter studies should evaluate the role of diagnostic procedures for pediatric patients.

Background Esophagectomy is a complex operation in which outcomes are profoundly influenced by operative experience and volume. We report the effects of experience and innovation on outcomes in minimally invasive esophagectomy. Methods Esophageal resections for cancer from 2007 to 2016 at Levine Cancer Institute at Carolinas Medical Center (Charlotte, NC) were reviewed. During this time, three changes in technique were made to improve outcomes: vascular evaluation of the gastric conduit to improve anastomotic healing (beginning at case #63), one-stage approach to permit access to abdomen and chest through one draped surgical field (case #82), and adoption of a lung-protective anesthetic protocol (case #101). Mortality, operative time, complications, and length of stay were analyzed relative to these interventions using GLM regression. Results 200 patients underwent minimally invasive esophagectomy. There were no mortalities at 30 days, and no change in mortality rate at 60 and 90 days. Anastomotic leak decreased significantly after the introduction of intraoperative vascular evaluation of the gastric conduit (3.6 vs 19.4%). Operative time decreased with adoption of a one-stage approach (416 vs 536 min). Pulmonary complications decreased coincident with a change in anesthetic technique (pneumonia 6 vs 28%). Lymph node harvest increased over time. Length of stay was driven primarily by complications and decreased with operative experience. Conclusion s Postoperative complications, operative time, and length of stay decreased with case experience and alterations in surgical and anesthetic technique. We believe that adoption of the techniques and technology described herein can reduce complications, reduce hospital stay, and improve patient outcomes.

Introduction The standard technique for Ivor Lewis minimally invasive esophagectomy involves a two-stage approach necessitating repositioning mid-procedure. Technique We describe our technique for a one-stage hand–assisted minimally invasive esophagectomy that allows sequential access to the chest and abdomen within the same surgical field, eliminating the need for repositioning. The patient is positioned in a “corkscrew” configuration with the abdomen supine and the chest rotated to the left to allow access to the right chest. The abdomen and chest are prepped into a single operative field. This technique allows sequential access to the abdomen for gastric mobilization, chest for division of the esophagus, abdomen for construction of the gastric conduit, and chest for intrathoracic anastomosis. Conclusion This approach enables extracorporeal construction of the conduit, which helps ensure a clear distal margin on the specimen and facilitates conduit length by placing the stomach on stretch during stapling.

We report multiple lines of evidence for a stochastic signal that is correlated among 67 pulsars from the 15 yr pulsar timing data set collected by the North American Nanohertz Observatory for Gravitational Waves. The correlations follow the Hellings–Downs pattern expected for a stochastic gravitational-wave background. The presence of such a gravitational-wave background with a power-law spectrum is favored over a model with only independent pulsar noises with a Bayes factor in excess of 1014, and this same model is favored over an uncorrelated common power-law spectrum model with Bayes factors of 200–1000, depending on spectral modeling choices. We have built a statistical background distribution for the latter Bayes factors using a method that removes interpulsar correlations from our data set, finding p = 10−3 (≈3σ) for the observed Bayes factors in the null no-correlation scenario. A frequentist test statistic built directly as a weighted sum of interpulsar correlations yields p = 5 × 10−5 to 1.9 × 10−4 (≈3.5σ–4σ). Assuming a fiducial f −2/3 characteristic strain spectrum, as appropriate for an ensemble of binary supermassive black hole inspirals, the strain amplitude is 2.4−0.6+0.7×10−15 (median + 90% credible interval) at a reference frequency of 1 yr−1. The inferred gravitational-wave background amplitude and spectrum are consistent with astrophysical expectations for a signal from a population of supermassive black hole binaries, although more exotic cosmological and astrophysical sources cannot be excluded. The observation of Hellings–Downs correlations points to the gravitational-wave origin of this signal.

Evidence for a low-frequency stochastic gravitational-wave background has recently been reported based on analyses of pulsar timing array data. The most likely source of such a background is a population of supermassive black hole binaries, the loudest of which may be individually detected in these data sets. Here we present the search for individual supermassive black hole binaries in the NANOGrav 15 yr data set. We introduce several new techniques, which enhance the efficiency and modeling accuracy of the analysis. The search uncovered weak evidence for two candidate signals, one with a gravitational-wave frequency of ∼4 nHz, and another at ∼170 nHz. The significance of the low-frequency candidate was greatly diminished when Hellings–Downs correlations were included in the background model. The high-frequency candidate was discounted due to the lack of a plausible host galaxy, the unlikely astrophysical prior odds of finding such a source, and since most of its support comes from a single pulsar with a commensurate binary period. Finding no compelling evidence for signals from individual binary systems, we place upper limits on the strain amplitude of gravitational waves emitted by such systems. At our most sensitive frequency of 6 nHz, we place a sky-averaged 95% upper limit of 8 × 10−15 on the strain amplitude. We also calculate an exclusion volume and a corresponding effective radius, within which we can rule out the presence of black hole binaries emitting at a given frequency.

We present the results of a Bayesian search for gravitational wave (GW) memory in the NANOGrav 12.5 yr data set. We find no convincing evidence for any gravitational wave memory signals in this data set. We find a Bayes factor of 2.8 in favor of a model that includes a memory signal and common spatially uncorrelated red noise (CURN) compared to a model including only a CURN. However, further investigation shows that a disproportionate amount of support for the memory signal comes from three dubious pulsars. Using a more flexible red-noise model in these pulsars reduces the Bayes factor to 1.3. Having found no compelling evidence, we go on to place upper limits on the strain amplitude of GW memory events as a function of sky location and event epoch. These upper limits are computed using a signal model that assumes the existence of a common, spatially uncorrelated red noise in addition to a GW memory signal. The median strain upper limit as a function of sky position is approximately 3.3 × 10−14. We also find that there are some differences in the upper limits as a function of sky position centered around PSR J0613−0200. This suggests that this pulsar has some excess noise that can be confounded with GW memory. Finally, the upper limits as a function of burst epoch continue to improve at later epochs. This improvement is attributable to the continued growth of the pulsar timing array.

IntroductionPersistent pain after finishing breast cancer treatment is a common and disabling problem. The current state-of-the-art pain management advocates, in addition to biomedical (non-)pharmacological approaches, a biopsychosocial rehabilitation approach to address persistent pain, combining pain science education with promoting an active lifestyle through self-regulation techniques. We propose testing an innovative eHealth self-management support programme for this purpose in the breast cancer population with persistent pain after finishing cancer treatment. This delivery mode is believed to reduce barriers to pain self-management by providing timely, safe and cost-effective assistance addressing the biopsychosocial needs of patients. Utilising a chatbot format, the eHealth programme delivers pain science education and promotes physical activity (PA), personalised through decision-tree-based algorithms to support pain self-management. The programme aims to empower patients with understanding, coping skills and self-management techniques to reduce pain-related disability and enhance participation in daily life. The primary objective is to determine programme effectiveness compared with (1) usual care (superiority) and (2) a similar face-to-face pain self-management support programme (non-inferiority).Methods and analysisA pragmatic, three-arm randomised controlled trial was started in April 2024 at the University Hospitals of Antwerp and Leuven and primary care settings in Belgium. Participants are breast cancer survivors with persistent pain after finishing cancer treatment. Two hundred seventy participants will be randomised to one of three trial arms: (1) eHealth self-management support programme, (2) usual care or (3) a face-to-face self-management support programme. The ‘eHealth self-management support programme’ begins with a pain science education (PSE) module to initially convey key pain-related concepts and provide personalised pain management tips. Then, the programme progresses to daily activity planning to promote an active lifestyle. Guided by the Health Action Process Approach (HAPA) model, participants set and review daily activity goals and track progress. The eHealth self-management programme uses a chatbot and is accessible on any digital device. The ‘usual care programme’ involves sending the participants a study-specific brochure by postal mail and does not include any formal PSE and/or PA programmes. They may pursue or continue self-initiated care. In Belgium, usual care primarily involves pharmacological treatment, general advice on PA and the provision of informational brochures. The ‘face-to-face self-management support programme’ mirrors the eHealth intervention, combining PSE with PA coaching. It starts with three individual sessions with a trained physical therapist for biopsychosocial assessment and PSE, followed by six sessions on goal setting and active lifestyle coaching. The educational content is delivered both verbally and in written form. The primary outcome will be pain-related disability 6 months after baseline assessment. As a key secondary outcome, the effect on pain beliefs and attitudes will be investigated after the educational part of the eHealth and face-to-face programme (ie, at 6 weeks after baseline). Other secondary outcomes related to other dimensions of pain and physical-, psychosocial- and health-economic outcomes will be assessed at 12 weeks and 6 and 12 months after baseline as well.Ethics and disseminationThe study will be conducted in accordance with the Declaration of Helsinki (2024). The protocol has been approved by the ethical committee of the University Hospitals of Leuven and Antwerp. Results will be disseminated via peer-reviewed scientific journals and presentations at congresses. Ethical Committee of the University Hospitals Leuven and Antwerp: BUN B3002023000132.Trial registration numberClinicalTrials.gov Identifier: NCT06308029.