Use of a Cytosponge biomarker panel to prioritise endoscopic Barrett's oesophagus surveillance: a cross-sectional study followed by a real-world prospective pilot.

BACKGROUND: Endoscopic surveillance is recommended for patients with Barrett's oesophagus because, although the progression risk is low, endoscopic intervention is highly effective for high-grade dysplasia and cancer. However, repeated endoscopy has associated harms and access has been limited during the COVID-19 pandemic. We aimed to evaluate the role of a non-endoscopic device (Cytosponge) coupled with laboratory biomarkers and clinical factors to prioritise endoscopy for Barrett's oesophagus. METHODS: We first conducted a retrospective, multicentre, cross-sectional study in patients older than 18 years who were having endoscopic surveillance for Barrett's oesophagus (with intestinal metaplasia confirmed by TFF3 and a minimum Barrett's segment length of 1 cm [circumferential or tongues by the Prague C and M criteria]). All patients had received the Cytosponge and confirmatory endoscopy during the BEST2 (ISRCTN12730505) and BEST3 (ISRCTN68382401) clinical trials, from July 7, 2011, to April 1, 2019 (UK Clinical Research Network Study Portfolio 9461). Participants were divided into training (n=557) and validation (n=334) cohorts to identify optimal risk groups. The biomarkers evaluated were overexpression of p53, cellular atypia, and 17 clinical demographic variables. Endoscopic biopsy diagnosis of high-grade dysplasia or cancer was the primary endpoint. Clinical feasibility of a decision tree for Cytosponge triage was evaluated in a real-world prospective cohort from Aug 27, 2020 (DELTA; ISRCTN91655550; n=223), in response to COVID-19 and the need to provide an alternative to endoscopic surveillance. FINDINGS: The prevalence of high-grade dysplasia or cancer determined by the current gold standard of endoscopic biopsy was 17% (92 of 557 patients) in the training cohort and 10% (35 of 344) in the validation cohort. From the new biomarker analysis, three risk groups were identified: high risk, defined as atypia or p53 overexpression or both on Cytosponge; moderate risk, defined by the presence of a clinical risk factor (age, sex, and segment length); and low risk, defined as Cytosponge-negative and no clinical risk factors. The risk of high-grade dysplasia or intramucosal cancer in the high-risk group was 52% (68 of 132 patients) in the training cohort and 41% (31 of 75) in the validation cohort, compared with 2% (five of 210) and 1% (two of 185) in the low-risk group, respectively. In the real-world setting, Cytosponge results prospectively identified 39 (17%) of 223 patients as high risk (atypia or p53 overexpression, or both) requiring endoscopy, among whom the positive predictive value was 31% (12 of 39 patients) for high-grade dysplasia or intramucosal cancer and 44% (17 of 39) for any grade of dysplasia. INTERPRETATION: Cytosponge atypia, p53 overexpression, and clinical risk factors (age, sex, and segment length) could be used to prioritise patients for endoscopy. Further investigation could validate their use in clinical practice and lead to a substantial reduction in endoscopy procedures compared with current surveillance pathways. FUNDING: Medical Research Council, Cancer Research UK, Innovate UK.

A phase III, randomized, open-label study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy in patients with metastatic castration-resistant prostate cancer.

Cabozantinib inhibits multiple receptor tyrosine kinases, including the TAM kinase family, and may enhance response to immune checkpoint inhibitors. One cohort of the ongoing phase Ib COSMIC-021 study (NCT03170960) evaluating cabozantinib plus the PD-L1 inhibitor atezolizumab in men with metastatic castration-resistant prostate cancer (mCRPC) that has progressed in soft tissue on/after enzalutamide and/or abiraterone treatment for metastatic disease has shown promising efficacy. Here, we describe the rationale and design of a phase III trial of cabozantinib plus atezolizumab versus a second novel hormone therapy (NHT) in patients who have previously received an NHT for mCRPC, metastatic castration-sensitive PC or nonmetastatic CRPC and have measurable visceral disease and/or extrapelvic adenopathy - a population with a significant unmet need for treatment options. Trial Registration Clinical Trial Registration: NCT04446117 (ClinicalTrials.gov) Registered on 24 June 2020.

Sleep Problems Prior to Radio-chemotherapy in Patients With Locally Advanced Cancer of the Esophagus or the Esophagogastric Junction.

BACKGROUND/AIM: Many patients with locally advanced cancer of the esophagus or esophagogastric junction receive definitive or neoadjuvant radiochemotherapy. Patient anticipation of this treatment can cause or aggravate distress and sleep disorders. This study aimed to identify the prevalence of sleep disorders and risk factors. PATIENTS AND METHODS: Thirty-eight patients assigned to radio-chemotherapy were retrospectively evaluated for pre-treatment sleep disorders. Investigated characteristics included age; sex; performance score; comorbidity index; previous malignancies; family history; distress score; emotional, physical or practical problems; tumor site; histology and grading; tumor stage; planned treatment; and relation to 2019 Coronavirus pandemic. RESULTS: Sleep problems were reported by 15 patients (39.5%). Significant associations were found for higher distress scores (p=0.016) and greater numbers of emotional problems (p<0.0001). A trend was observed for greater numbers of physical problems (p=0.176). CONCLUSION: The prevalence of sleep problems was high. Risk factors were found that can help identify patients requiring psychological support already prior to radio-chemotherapy.

Disparities in time to start of definitive radiation treatment for patients with locally advanced cervical cancer.

BACKGROUND: Chemoradiation or radiation therapy alone are curative standards for patients with locally advanced cervical cancer. OBJECTIVE: To investigate factors that influence time to initiation of chemoradiation or radiation and the subsequent impact of time to treatment on recurrence and survival outcomes. METHODS: Patients with locally advanced cervical cancer treated with definitive chemoradiation or radiation at our institution between November 2015 and August 2020 were retrospectively identified. Time to treatment initiation was defined as the number of days from date of diagnosis (via biopsy) to the start date of radiation. The cohort was stratified by the median time to treatment into early (<75 days) and delayed (≥75 days) cohorts. Multivariable logistic regression was conducted to examine factors associated with delayed time to treatment. RESULTS: We identified 143 patients with locally advanced cervical cancer who underwent definitive chemoradiation or radiation. Median follow-up time was 18 months (range 2-62). A total of 71 (49.7%) patients had time to treatment <75 days and 72 (50.3%) patients had time to treatment ≥75 days. The delayed cohort had a higher proportion of Hispanic patients (51.4% vs 31.0%, p=0.04). In multivariable modeling, Hispanic women were 2.71 times more likely (p=0.04) to undergo delayed time to treatment than non-Hispanic white women. Additionally, patients with stage >IIB disease were less likely to undergo delayed time to treatment (OR 0.26, p=0.02) than patients with stage

Impact of the COVID-19 Pandemic on Management of Patients with Metastatic Pancreatic Ductal Adenocarcinoma in the United States.

BACKGROUND: The purpose of this study was to understand how the COVID-19 pandemic has affected health care patterns and outcomes for patients diagnosed with metastatic pancreatic ductal adenocarcinoma (mPDAC) in 2020 compared with those diagnosed with mPDAC in 2019. PATIENTS AND METHODS: We used the Flatiron Health database to identify adults diagnosed with mPDAC from March 1 to September 30, 2019 (pre-COVID-19 cohort) and March 1 to September 30, 2020 (post-COVID-19 cohort). Between-cohort comparisons included demographic and clinical characteristics and year-over-year data for diagnosis of mPDAC, newly treated patients, time to and types of first-line therapy, and adverse events (AEs) during first-line therapy. Overall survival (OS) and milestone survival rates were evaluated. Kaplan-Meier methods were used to assess OS. RESULTS: Pre-COVID-19 (n = 923) and post-COVID-19 (n = 796) cohorts had similar baseline demographic characteristics. A smaller proportion of patients in the pre-COVID-19 cohort were initially diagnosed with stage IV disease versus the post-COVID-19 cohort (62.2% vs 69.7%). Between 2019 and 2020, there was a 13.8% decrease in diagnosis of mPDAC and a 13.0% decrease in newly treated patients. Median (interquartile range) times to first-line treatment were similar (21 [13-40] and 19 [12-32] days). Median OS (months) was significantly longer in the pre-COVID-19 cohort (8·4 [95% CI: 7·5, 9·0]) versus the post-COVID-19 cohort (6·1 [95% CI: 5·4, 6·9]; P < .001). Survival rates were higher in the pre-COVID-19 versus post-COVID-19 cohorts. CONCLUSIONS: During the pandemic, patients were initially diagnosed with PDAC at more advanced stages. While patients in both cohorts appeared to receive similar care, survival outcomes were adversely affected.

Synchronous "skip" facial metastases from colorectal adenocarcinoma: a case report and review of literature.

BACKGROUND: Skin metastases from colorectal adenocarcinoma are rare conditions that are metachronous in most of cases and may represent the first sign of a recurrence. These lesions are usually located to the abdominal wall on postoperative scars, perineum and chest due to direct spread from the tumor or to the lymphatic and venous dissemination. We describe a rare case of synchronous skin metastases in a patient affected by sigmoid adenocarcinoma with no sign of liver and lung repetitive lesions. CASE PRESENTATION: We admitted a 59 years old male, with no relevant medical history. He was evaluated by our tertiary center of colorectal surgery complaining diarrhoea and abdominal pain. The physical examination revealed a palpable mass in left flank of the abdomen. The colonoscopy showed a sub-stenosis of the sigmoid colon (G2 adenocarcinoma). No repetitive lesions were detected by the preoperative CT scan. The patient reported a rapid grow of a soft supralabial and chin nodules in the last 2 months, which he believed to be related to the use of the mask due to COVID-19 pandemic. A laparoscopic left hemicolectomy with complete mesocolic excision and a local excision of both facial nodules were performed. The histological examination revealed a poorly differentiated signet ring cell colorectal adenocarcinoma with metastases in seven pericolic lymphonodes. The excisional biopsy of the skin nodules revealed a subcutaneous metastases from primary colorectal tumour. CONCLUSIONS: As far as we know, synchronous facial metastases from colorectal cancer in the absence of any other metastases has never been described before. The onset of new skin nodules in patients affected by colorectal cancer should raise-up the clinical suspicion of metastatic lesions even when repetitive lesions are not detected in the liver or lungs.

Interlobular Septal Thickening in a Young Man With Dyspnea.

CASE PRESENTATION: A 30-year-old man with a history of childhood asthma, a 15-pack-year smoking history, and methamphetamine abuse was intubated and started on mechanical ventilation because of acute hypoxic respiratory failure after experiencing progressive dyspnea and a nonproductive cough over the previous year. During the previous 3 months, he had multiple clinic visits, with chest radiographs showing diffuse, bilateral, reticulonodular opacities and small bilateral pleural effusions and was treated for community-acquired pneumonia. Testing for COVID pneumonia was negative, and he failed to respond to antimicrobial therapy. Physical examination on admission showed diffuse fine crackles bilaterally on lung auscultation. Admission laboratory test results were unremarkable.

The Impact of Extended Delayed Surgery for Indolent Lung Cancer or Part-Solid Ground Glass Nodules.

BACKGROUND: During the COVID-19 pandemic, patients with lung cancer may experience treatment delays. The objective of this study was to evaluate the impact of extended treatment delays on survival among patients with stage I typical bronchopulmonary carcinoid (BC), lepidic predominant adenocarcinoma (LPA) or invasive adenocarcinoma with a lepidic component (ADL). METHODS: Using National Cancer Database data (2004-2015), multivariable Cox regression analysis with penalized smoothing splines was performed to examine the association between treatment delay and all-cause mortality for stage I BC, LPA, and ADL. Propensity score-matched analyses compared the overall survival of patients who received "early" vs "delayed" surgery (ie, 0-30 vs 90-120 days after diagnosis) across the different histologic subtypes. RESULTS: During the study period, patients with stage I BC (n = 4947), LPA (n = 5340), and ADL (n = 6816) underwent surgery. Cox regression analysis of these cohorts showed a gradual steady increase in the hazard ratio the longer treatment is delayed. However, in propensity score-matched analyses that created cohorts of patients who underwent early and delayed surgery that were well-balanced in patient characteristics, no significant differences in 5-year survival were found between early and delayed surgery for stage I BC (87% [95% CI:77%-93%] vs 89% [95% CI: 80%-94%]), stage I LPA (73% [95% CI: 64%-80%] vs 77% [95% CI: 68%-83%]), and stage I ADL (71% [95% CI: 64%-76%] vs 69% [95% CI: 60%-76%]). CONCLUSIONS: During the COVID-19 pandemic, for early-stage indolent lung tumors and part-solid ground glass lung nodules, a delay of surgery by 3-4 months after diagnosis can be considered.

An unusual presentation of synchronous bladder metastases from an oesophageal adenocarcinoma.

Adenocarcinoma of the bladder is a rare form of malignancy accounting for fewer than 2% of bladder tumours. It is most commonly a result of direct invasion from prostatic, rectal or gynaecological primaries and less commonly presents from distant haematological or lymphatic metastasis. We report a rare case of oesophageal carcinoma metastasising to the bladder. It involves a 71-year-old man with progressive dysphagia and diagnostic computerised tomography findings of thickening in the oesophagus, bladder and common bile duct. Subsequent endoscopic biopsies of the oesophageal and bladder abnormalities showed immunohistochemical features consistent with upper gastrointestinal malignancy. This report aims to add to current clinical evidence of this route of metastasis and also highlight some of the key markers used by pathologists in interpretation of specimens. It also emphasises the essential role of a multidisciplinary approach for the diagnosis of such rare conditions.

Surgical Delay and Pathological Outcomes for Clinically Localized High-Risk Prostate Cancer.

Importance: There is a lack of data evaluating the association of surgical delay time (SDT) with outcomes in patients with localized, high-risk prostate cancer. Objective: To investigate the association of SDT of radical prostatectomy and final pathological and survival outcomes. Design, Setting, and Participants: This cohort study used data from the US National Cancer Database (NCDB) and identified all patients with clinically localized (cT1-2cN0cM0) high-risk prostate adenocarcinoma diagnosed between 2006 and 2016 who underwent radical prostatectomy. Data analyses were performed from April 1 to April 12, 2020. Exposures: SDT was defined as the number of days between the initial cancer diagnosis and radical prostatectomy. SDT was categorized into 5 groups: 31 to 60, 61 to 90, 91 to 120, 121 to 150, and 151 to 180 days. Main Outcomes and Measures: The primary outcomes were predetermined as adverse pathological outcomes after radical prostatectomy, including pT3-T4 disease, pN-positive disease, and positive surgical margin. The adverse pathological score (APS) was defined as an accumulated score of the 3 outcomes (0-3). An APS of 2 or higher was considered a separate outcome to capture cases with more aggressive pathological features. The secondary outcome was overall survival. Results: Of the 32 184 patients included in the study, the median (interquartile range) age was 64 (59-68) years, and 25 548 (79.4%) were non-Hispanic White. Compared with an SDT of 31 to 60 days, longer SDTs were not associated with higher risks of having any adverse pathological outcomes (odds ratio [OR], 0.95; 95% CI, 0.80-1.12; P = .53), pT3-T4 disease (OR, 0.99; 95% CI, 0.83-1.17; P = .87), pN-positive disease (OR, 0.79; 95% CI, 0.59-1.06; P = .12), positive surgical margin (OR, 0.88; 95% CI, 0.74-1.05; P = .17), or APS greater than or equal to 2 (OR, 0.90; 95% CI, 0.74-1.05; P = .17). Longer SDT was also not associated with worse overall survival (for SDT of 151-180 days, hazard ratio, 1.12; 95% CI, 0.79-1.59, P = .53). Subgroup analyses performed for patients with very high-risk disease (primary Gleason score 5) and sensitivity analyses with SDT considered as a continuous variable yielded similar results. Conclusions and Relevance: In this cohort study of patients who underwent radical prostatectomy within 180 days of diagnosis for high-risk prostate cancer, radical prostatectomy for high-risk prostate cancer could be safely delayed up to 6 months after diagnosis.

Clinical Course of Three Postoperative Symptomatic COVID-19 Cases in Patients After Lung Lobectomy.

The novel coronavirus disease 2019 is a highly contagious viral infection caused by the severe acute respiratory syndrome coronavirus 2 virus. Its rapid spread and severe clinical presentation influence patient management in all specialties including thoracic surgery. We report 3 cases of coronavirus disease 2019 occurring in patients shortly after thoracotomy and thoracoscopy procedures, illustrating the imminent threat of severe acute respiratory syndrome coronavirus 2 infection for thoracic surgery patients.

Early histologic findings of pulmonary SARS-CoV-2 infection detected in a surgical specimen.

Despite the current pandemic season, reports on pathologic features of coronavirus disease 19 (Covid-19) are exceedingly rare at the present time. Here we describe the pathologic features of early lung involvement by Covid-19 in a surgical sample resected for carcinoma from a patient who developed SARS-CoV-2 infection soon after surgery. The main histologic findings observed were pneumocyte damage, alveolar hemorrhages with clustering of macrophages, prominent and diffuse neutrophilic margination within septal vessels, and interstitial inflammatory infiltrates, mainly represented by CD8+ T lymphocytes. These features are similar to those previously described in SARS-CoV-1 infection. Subtle histologic changes suggestive pulmonary involvement by Covid-19 may be accidentally encountered in routine pathology practice, especially when extensive sampling is performed for histology. These findings should be carefully interpreted in light of the clinical context of the patient and could prompt a pharyngeal swab PCR test to rule out the possibility of SARS-CoV-2 infection in asymptomatic patients.