Intraoperative localization of lymph node metastases with a replication-competent herpes simplex virus

ObjectivesLymph node status is the most important prognostic factor determining recurrence and survival in patients with mesothelioma and other thoracic malignancies. Accurate localization of lymph node metastases is therefore necessary to improve selection of resectable and curable patients for surgical intervention. This study investigates the potential to identify lymph node metastases intraoperatively by using herpes-guided cancer cell–specific expression of green fluorescent protein.MethodsAfter infection with NV1066, a herpes simplex virus carrying green fluorescent protein transgene, human mesothelioma cancer cell lines were assessed for cancer cell–specific infection, green fluorescent protein expression, viral replication, and cytotoxicity. Murine models of lymphatic metastasis were established by means of surgical implantation of cancer cells into the preauricular (drainage to cervical lymph nodes) and pleural (mediastinal and retroperitoneal lymph nodes) spaces of athymic mice. Fluorescent thoracoscopy, laparoscopy, and stereomicroscopy were used to localize lymph node metastases that were confirmed by means of immunohistochemistry.ResultsIn vitro NV1066 infected, replicated (5- to 17,000-fold), and expressed green fluorescent protein in all cancer cells, even when infected at a low ratio of one viral plaque-forming unit per 100 tumor cells. In vivo NV1066 injected into primary tumors was able to locate and infect lymph node metastases producing green fluorescent protein that was visualized by means of fluorescent imaging. Histology confirmed lymphatic metastases, and immunohistochemistry confirmed viral presence in regions that expressed green fluorescent protein.ConclusionsHerpes virus–guided cancer cell–specific production of green fluorescent protein can facilitate accurate localization of lymph node metastases. Fluorescent filters that detect green fluorescent protein can be incorporated into operative scopes to precisely localize and biopsy lymph node metastases

Esophageal Cancer Recurrence Patterns and Implications for Surveillance

Introduction:After definitive treatment of esophageal cancer, patients are at high risk for recurrence. Consistent follow-up is important for detection and treatment of recurrence. The optimal surveillance regimen remains undefined. We investigated posttreatment recurrence patterns and methods of detection in survivors of esophageal cancer.Methods:We retrospectively studied a cohort of patients who had undergone surgical resection for esophageal cancer at our institution between 1996 and 2010. Routine computed tomography scan and upper endoscopy were performed for surveillance.Results:In total, 1147 patients with resected esophageal adenocarcinoma or squamous cell carcinoma were included (median follow-up, 46 months). Of these, 723 patients (63%) had received neoadjuvant therapy before surgery. During follow-up, there were 595 deaths (52%) and 435 recurrences (38%) (distant [55%], locoregional [28%], or both [17%]). Half of recurrences were detected as a result of symptoms (n = 217), 45% by routine chest and abdominal computed tomography scan (n = 194), and 1% by surveillance upper endoscopy (n = 6). The recurrence rate decreased from 27 per 100 person-years in posttreatment year 1 to 4 per 100 person-years in year 6. In the first 2 years, the rate of recurrence was higher among patients who had received neoadjuvant therapy (35 per 100 person-years) than among those who had not (14 per 100 person-years) (p < 0.001).Conclusions:The incidence of recurrence is high after esophagectomy for cancer. Surveillance endoscopy has limited value for detection of asymptomatic local recurrence. The yield from follow-up scans diminishes significantly after the sixth year; surveillance scans after that point are likely unnecessary

Predictive Value of Initial PET-SUVmax in Patients with Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma

Introduction:We have previously shown that in early clinical stage esophageal adenocarcinoma, a positron emission tomography standardized uptake values (PET SUVmax) of <4.5 is associated with earlier pathologic stage and predicts better survival. In this study, we analyze the impact of the pretreatment PET SUVmax in patients with locally advanced esophageal adenocarcinoma who undergo preoperative chemoradiotherapy.Methods:We performed a retrospective analysis, selecting patients with adenocarcinoma of the esophagus who had a pretreatment PET scan and who received chemoradiotherapy before esophagectomy. Data recorded included demographics, PET SUVmax, treatment details, pathologic details, and survival data. Comparison of categorical variables was done by χ2 analysis, continuous variables by t test, survival analysis by the Kaplan-Meier method, and comparisons of survival using the log-rank test.Results:Between January 1996 and September 2007, 189 patients were appropriate for this analysis. The initial PET SUVmax was <4.5 in 28 patients and ≥4.5 in 161 patients. The two groups were similar with regards to demographics and treatment details. Patients in the low SUV group were less likely to show evidence of treatment response after chemoradiotherapy, including a higher likelihood of residual nodal disease and a lower likelihood of a pathologic complete response and estimated treatment response. However, both groups had similar survival.Conclusions:Although the initial PET SUVmax does not predict survival in patients with locally advanced esophageal adenocarcinoma who receive preoperative chemoradiotherapy, patients with a high initial SUVmax respond better to preoperative therapy. These results can be used to better select esophageal cancer patients for combined modality treatment

Radiomics in the evaluation of ovarian masses — a systematic review

Objectives The study aim was to conduct a systematic review of the literature reporting the application of radiomics to imaging techniques in patients with ovarian lesions. Methods MEDLINE/PubMed, Web of Science, Scopus, EMBASE, Ovid and ClinicalTrials.gov were searched for relevant articles. Using PRISMA criteria, data were extracted from short-listed studies. Validity and bias were assessed independently by 2 researchers in consensus using the Quality in Prognosis Studies (QUIPS) tool. Radiomic Quality Score (RQS) was utilised to assess radiomic methodology. Results After duplicate removal, 63 articles were identified, of which 33 were eligible. Fifteen assessed lesion classifications, 10 treatment outcomes, 5 outcome predictions, 2 metastatic disease predictions and 1 classification/outcome prediction. The sample size ranged from 28 to 501 patients. Twelve studies investigated CT, 11 MRI, 4 ultrasound and 1 FDG PET-CT. Twenty-three studies (70%) incorporated 3D segmentation. Various modelling methods were used, most commonly LASSO (least absolute shrinkage and selection operator) (10/33). Five studies (15%) compared radiomic models to radiologist interpretation, all demonstrating superior performance. Only 6 studies (18%) included external validation. Five studies (15%) had a low overall risk of bias, 9 (27%) moderate, and 19 (58%) high risk of bias. The highest RQS achieved was 61.1%, and the lowest was − 16.7%. Conclusion Radiomics has the potential as a clinical diagnostic tool in patients with ovarian masses and may allow better lesion stratification, guiding more personalised patient care in the future. Standardisation of the feature extraction methodology, larger and more diverse patient cohorts and real-world evaluation is required before clinical translation. Clinical relevance statement Radiomics shows promising results in improving lesion stratification, treatment selection and outcome prediction. Modelling with larger cohorts and real-world evaluation is required before clinical translation. Key points • Radiomics is emerging as a tool for enhancing clinical decisions in patients with ovarian masses. • Radiomics shows promising results in improving lesion stratification, treatment selection and outcome prediction. • Modelling with larger cohorts and real-world evaluation is required before clinical translation

Artificial intelligence in ovarian cancer histopathology: a systematic review

This study evaluates the quality of published research using artificial intelligence (AI) for ovarian cancer diagnosis or prognosis using histopathology data. A systematic search of PubMed, Scopus, Web of Science, Cochrane CENTRAL, and WHO-ICTRP was conducted up to May 19, 2023. Inclusion criteria required that AI was used for prognostic or diagnostic inferences in human ovarian cancer histopathology images. Risk of bias was assessed using PROBAST. Information about each model was tabulated and summary statistics were reported. The study was registered on PROSPERO (CRD42022334730) and PRISMA 2020 reporting guidelines were followed. Searches identified 1573 records, of which 45 were eligible for inclusion. These studies contained 80 models of interest, including 37 diagnostic models, 22 prognostic models, and 21 other diagnostically relevant models. Common tasks included treatment response prediction (11/80), malignancy status classification (10/80), stain quantification (9/80), and histological subtyping (7/80). Models were developed using 1–1375 histopathology slides from 1–776 ovarian cancer patients. A high or unclear risk of bias was found in all studies, most frequently due to limited analysis and incomplete reporting regarding participant recruitment. Limited research has been conducted on the application of AI to histopathology images for diagnostic or prognostic purposes in ovarian cancer, and none of the models have been demonstrated to be ready for real-world implementation. Key aspects to accelerate clinical translation include transparent and comprehensive reporting of data provenance and modelling approaches, and improved quantitative evaluation using cross-validation and external validations. This work was funded by the Engineering and Physical Sciences Research Council

Combined PET-CT and MRI for response evaluation in patients with squamous cell anal carcinoma treated with curative-intent chemoradiotherapy

Objectives To assess the effectiveness of fluorine-18 fluorodeoxyglucose (FDG) positron-emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) for response assessment post curative-intent chemoradiotherapy (CRT) in anal squamous cell carcinoma (ASCC). Methods Consecutive ASCC patients treated with curative-intent CRT at a single centre between January 2018 and April 2020 were retrospectively identified. Clinical meta-data including progression-free survival (PFS) and overall survival (OS) outcomes were collated. Three radiologists evaluated PET-CT and MRI using qualitative response assessment criteria and agreed in consensus. Two-proportion z test was used to compare diagnostic performance metrics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy). Kaplan-Meier analysis (Mantel-Cox log-rank) was performed. Results MRI (accuracy 76%, PPV 44.8%, NPV 95.7%) and PET-CT (accuracy 69.3%, PPV 36.7%, NPV 91.1%) performance metrics were similar; when combined, there were statistically significant improvements (accuracy 94.7%, PPV 78.9%, NPV 100%). Kaplan-Meier analysis demonstrated significant differences in PFS between responders and non-responders at PET-CT (p = 0.007), MRI (p = 0.005), and consensus evaluation (p < 0.001). Cox regression analysis of PFS demonstrated a lower hazard ratio (HR) and narrower 95% confidence intervals for consensus findings (HR = 0.093, p < 0.001). Seventy-five patients, of which 52 (69.3%) were females, with median follow-up of 17.8 months (range 5–32.6) were included. Fifteen of the 75 (20%) had persistent anorectal and/or nodal disease after CRT. Three patients died, median time to death 6.2 months (range 5–18.3). Conclusion Combined PET-CT and MRI response assessment post-CRT better predicts subsequent outcome than either modality alone. This could have valuable clinical benefits by guiding personalised risk-adapted patient follow-up. Key Points • MRI and PET-CT performance metrics for assessing response following chemoradiotherapy (CRT) in patients with anal squamous cell carcinoma (ASCC) were similar. • Combined MRI and PET-CT treatment response assessment 3 months after CRT in patients with ASCC was demonstrated to be superior to either modality alone. • A combined MRI and PET-CT assessment 3 months after CRT in patients with ASCC has the potential to improve accuracy and guide optimal patient management with a greater ability to predict outcome than either modality alon

Evaluation and implications of natural product use in preoperative patients: a retrospective review

<p>Abstract</p> <p>Background</p> <p>Medication Reconciliation and Medication Safety are two themes emphasized in a variety of healthcare organizations. As a result, health care facilities have established methods for obtaining a patient's medication history. However, these methods may vary among institutions or even among the health care professionals in a single institution, and studies have shown that patients are reluctant to disclose their complementary and alternative medicine use to any health care professional. This lack of disclosure is important in surgical patients because of potential herbal interactions with medications and drugs used during the surgical procedure; and the potential for adverse reactions including effects on coagulation, blood pressure, sedation, electrolytes or diuresis. Therefore, the objectives of this study are to identify patterns of natural product use, to identify potential complications among patients scheduled for surgery, to improve existing medication reconciliation efforts, and to develop discontinuation guidelines for the use of these products prior to surgery.</p> <p>Methods</p> <p>A retrospective review of surgery patients presenting to the Anesthesia Preoperative Evaluation Clinic (APEC) at the University of Kansas Hospital was conducted to identify the prevalence of natural product use. The following data was collected: patient age; gender; allergy information; date of medication history; number of days prior to surgery; source of medication history; credentials of person obtaining the history; number and name of prescription medications, over-the-counter medications and natural products; and natural product dosage. Following the collection of data and analysis of the most common natural products used, possible complications and interactions were identified, and a protocol regarding the pre-operative use of natural products was developed and implemented.</p> <p>Results</p> <p>Approximately one-fourth of patients seen in the APEC indicated the use of natural products. Patients taking natural products were significantly older, were more likely to undergo cardiac or chest surgery, and were more likely to be taking more prescription and non-prescription medications (all p < 0.001).</p> <p>Conclusion</p> <p>Based on the results of this study, it is concluded that there is a need for established guidelines regarding discontinuation of selected natural products prior to surgery and further education is needed concerning the perioperative implications of natural products.</p

Heat stored in the Earth system 1960–2020: where does the energy go?

The Earth climate system is out of energy balance, and heat has accumulated continuously over the past decades, warming the ocean, the land, the cryosphere, and the atmosphere. According to the Sixth Assessment Report by Working Group I of the Intergovernmental Panel on Climate Change, this planetary warming over multiple decades is human-driven and results in unprecedented and committed changes to the Earth system, with adverse impacts for ecosystems and human systems. The Earth heat inventory provides a measure of the Earth energy imbalance (EEI) and allows for quantifying how much heat has accumulated in the Earth system, as well as where the heat is stored. Here we show that the Earth system has continued to accumulate heat, with 381±61 ZJ accumulated from 1971 to 2020. This is equivalent to a heating rate (i.e., the EEI) of 0.48±0.1 W m−2. The majority, about 89 %, of this heat is stored in the ocean, followed by about 6 % on land, 1 % in the atmosphere, and about 4 % available for melting the cryosphere. Over the most recent period (2006–2020), the EEI amounts to 0.76±0.2 W m−2. The Earth energy imbalance is the most fundamental global climate indicator that the scientific community and the public can use as the measure of how well the world is doing in the task of bringing anthropogenic climate change under control. Moreover, this indicator is highly complementary to other established ones like global mean surface temperature as it represents a robust measure of the rate of climate change and its future commitment. We call for an implementation of the Earth energy imbalance into the Paris Agreement's Global Stocktake based on best available science. The Earth heat inventory in this study, updated from von Schuckmann et al. (2020), is underpinned by worldwide multidisciplinary collaboration and demonstrates the critical importance of concerted international efforts for climate change monitoring and community-based recommendations and we also call for urgently needed actions for enabling continuity, archiving, rescuing, and calibrating efforts to assure improved and long-term monitoring capacity of the global climate observing system. The data for the Earth heat inventory are publicly available, and more details are provided in Table 4