A randomized translational study on protein- and glucose metabolism in skeletal muscles evaluated by gene-ontology, following preoperative oral carbohydrate loading compared to overnight peripheral parenteral nutrition (PPN) before major cancer surgery.

BACKGROUND: Effects of preoperative drinks on muscle metabolism are unclear despite general recommendations. The aim of the present study was therefore to compare metabolic effects of a preoperative oral nutrition drink, recommended by protocols for enhanced recovery after surgery (ERAS), compared to overnight preoperative peripheral total parenteral nutrition (PPN) on skeletal muscle metabolism in patients aimed at major gastrointestinal cancer surgery. METHODS: Patients were randomized, based on diagnosis and clinical characteristics, to receive either a commercial carbohydrate-rich nutrition drink (Drink); or overnight (12 h) peripheral parenteral nutrition (PPN) as study regimens; compared to isotone Ringer-acetate as Control regimen. Arterial blood- and abdominal muscle tissue specimens were collected at start of surgery. Blood chemistry included substrate- and hormone concentrations. Muscle mRNA transcript analyses were performed by microarray and evaluated for changes in gene activities by Gene Ontology algorithms. RESULTS: Patient groups were comparable in all measured preoperative assessments. The Nutrition Drink had significant metabolic alterations on muscle glucose metabolism (p < 0.05), without any significant effects on amino acid- and protein metabolism. PPN showed similar significant effects on glucose metabolism as Drinks (p < 0.05), but indicated also major positive effects on amino acid- (p < 0.001) and protein anabolism (p < 0.05), particularly by inhibition of muscle protein degradation, related to both ubiquitination of proteins and autophagy/lysosome pathways (p < 0.05). CONCLUSION: Conventional overnight preoperative PPN seems effective to induce and support improved muscle protein metabolism in patients aimed at major cancer surgery while preoperative oral carbohydrate loading, according to ERAS-protocols, was ineffective to improve skeletal muscle catabolism and should therefore not be recommended before major cancer surgery. Trial registration Clinical trials.gov: NCT05080816, Registered June 10th 2021- Retrospectively registered. https://clinicaltrials.gov/study/NCT05080816.

A prospective study evaluating an optimized sentinel node algorithm in early stage cervical cancer: The PROSACC-study.

OBJECTIVE: A single center prospective non-randomized study to assess a systematically developed anatomically-based sentinel lymph node (SLN) algorithm in cervical cancer. METHODS: Consecutive women with FIGO 2009 stage 1A2-2A1 cervical cancer undergoing robotic radical hysterectomy/trachelectomy between September 2014 and January 2023 had cervically injected Indocyanine Green (ICG) as a tracer for detection of pelvic SLN. An anatomically based surgical algorithm was adhered to; defining SLNs as the juxtauterine mapped nodes within the upper and lower paracervical lymphatic pathways including separate removal of the parauterine lymphovascular tissue (PULT). A completion pelvic lymphadenectomy was performed. Ultrastaging and immunohistochemistry was performed on SLNs, including the PULT. RESULTS: 181 women were included for analysis. Median histologic tumor size was 14.0 mm (range 2-80 mm). The bilateral mapping rate was 98.3%. As per protocol an interim analysis rejected H0 and inclusion stopped at 29 node positive women, all identified by at least one metastatic ICG-defined SLN. One woman awaiting histology at study-closure was node positive and included in the analysis. Sensitivity was 100% (95% CI, 88.4%-100%) and NPV 100% (95% CI, 97.6%-100%). In node positive women, the proximal obturator position harbored 46.1% of all SLN metastases representing the only position in 40% and 10% had isolated metastases in the PULT. CONCLUSIONS: Strictly adhering to an anatomically based SLN-algorithm including identification of parallell lymphatics within major pathways, partilularly the obturator compartment, assessment of the PULT, restricting nodal dissection to the removal of SLNs accurately identifies pelvic nodal metastatic disease in early-stage cervical cancer.

A selective anatomically based lymph node sampling can replace a side specific pelvic lymphadenectomy in endometrial cancer with failed sentinel node mapping.

AIM: To evaluate the locations of metastatic pelvic sentinel nodes (SLN) and the proportion of SLNs outside and within defined typical anatomical positions along the upper paracervical lymphatic pathway (UPP). PATIENTS AND METHODS: Consecutive women with endometrial cancer (EC) of all risk groups underwent pelvic SLN-detection using cervically injected indocyanine green (ICG). A strict anatomically based algorithm and definitions of SLNs was adhered to. The positions of ICG-defined SLNs were intraoperatively depicted on an anatomical chart. All SLNs were examined using ultrastaging and immunohistochemistry. The proximal third of the obturator fossa and the interiliac area were defined as typical positions. The parauterine lymphovascular tissue (PULT) was separately removed. The proportions of metastatic SLNs, overall and isolated, typically, and atypically positioned were analyzed per woman. RESULTS: A median of two (range 1-12) SLN metastases along the UPP including the PULT were found in 162 women. 41 of 162 women (25.3 %) had isolated metastases in the obturator fossa harboring 49.1 % of all SLN metastases. Three women (1,9 %) had isolated PULT metastases. SLN metastases outside typical positions were identified in 28/162 women (17.3 %); isolated metastases were seen in seven women (4.3 %), so 95.7 % of pelvic node positive women had at least one metastatic SLN located at a typical position. CONCLUSION: A selective removal of lymph nodes at typical proximal obturator and interiliac positions and the PULT can replace a full side specific pelvic LND when SLN mapping is unsuccessful. The obturator fossa is the predominant location for metastatic disease.

Passive Infrared Sensor-Based Occupancy Monitoring in Smart Buildings: A Review of Methodologies and Machine Learning Approaches.

Buildings are rapidly becoming more digitized, largely due to developments in the internet of things (IoT). This provides both opportunities and challenges. One of the central challenges in the process of digitizing buildings is the ability to monitor these buildings' status effectively. This monitoring is essential for services that rely on information about the presence and activities of individuals within different areas of these buildings. Occupancy information (including people counting, occupancy detection, location tracking, and activity detection) plays a vital role in the management of smart buildings. In this article, we primarily focus on the use of passive infrared (PIR) sensors for gathering occupancy information. PIR sensors are among the most widely used sensors for this purpose due to their consideration of privacy concerns, cost-effectiveness, and low processing complexity compared to other sensors. Despite numerous literature reviews in the field of occupancy information, there is currently no literature review dedicated to occupancy information derived specifically from PIR sensors. Therefore, this review analyzes articles that specifically explore the application of PIR sensors for obtaining occupancy information. It provides a comprehensive literature review of PIR sensor technology from 2015 to 2023, focusing on applications in people counting, activity detection, and localization (tracking and location). It consolidates findings from articles that have explored and enhanced the capabilities of PIR sensors in these interconnected domains. This review thoroughly examines the application of various techniques, machine learning algorithms, and configurations for PIR sensors in indoor building environments, emphasizing not only the data processing aspects but also their advantages, limitations, and efficacy in producing accurate occupancy information. These developments are crucial for improving building management systems in terms of energy efficiency, security, and user comfort, among other operational aspects. The article seeks to offer a thorough analysis of the present state and potential future advancements of PIR sensor technology in efficiently monitoring and understanding occupancy information by classifying and analyzing improvements in these domains.

The Long-Term Mortality Effects Associated with Exposure to Particles and NOx in the Malmö Diet and Cancer Cohort.

In this study, the long-term mortality effects associated with exposure to PM10 (particles with an aerodynamic diameter smaller than or equal to 10 µm), PM2.5 (particles with an aerodynamic diameter smaller than or equal to 2.5 µm), BC (black carbon), and NOx (nitrogen oxides) were analyzed in a cohort in southern Sweden during the period from 1991 to 2016. Participants (those residing in Malmö, Sweden, born between 1923 and 1950) were randomly recruited from 1991 to 1996. At enrollment, 30,438 participants underwent a health screening, which consisted of questionnaires about lifestyle and diet, a clinical examination, and blood sampling. Mortality data were retrieved from the Swedish National Cause of Death Register. The modeled concentrations of PM10, PM2.5, BC, and NOx at the cohort participants' home addresses were used to assess air pollution exposure. Cox proportional hazard models were used to estimate the associations between long-term exposure to PM10, PM2.5, BC, and NOx and the time until death among the participants during the period from 1991 to 2016. The hazard ratios (HRs) associated with an interquartile range (IQR) increase in each air pollutant were calculated based on the exposure lag windows of the same year (lag0), 1-5 years (lag1-5), and 6-10 years (lag6-10). Three models were used with varying adjustments for possible confounders including both single-pollutant estimates and two-pollutant estimates. With adjustments for all covariates, the HRs for PM10, PM2.5, BC, and NOx in the single-pollutant models at lag1-5 were 1.06 (95% CI: 1.02-1.11), 1.01 (95% CI: 0.95-1.08), 1.07 (95% CI: 1.04-1.11), and 1.11 (95% CI: 1.07-1.16) per IQR increase, respectively. The HRs, in most cases, decreased with the inclusion of a larger number of covariates in the models. The most robust associations were shown for NOx, with statistically significant positive HRs in all the models. An overall conclusion is that road traffic-related pollutants had a significant association with mortality in the cohort.

Some Design Considerations in Passive Indoor Positioning Systems.

User location is becoming an increasingly common and important feature for a wide range of services. Smartphone owners increasingly use location-based services, as service providers add context-enhanced functionality such as car-driving routes, COVID-19 tracking, crowdedness indicators, and suggestions for nearby points of interest. However, positioning a user indoors is still problematic due to the fading of the radio signal caused by multipath and shadowing, where both have complex dependencies on the indoor environment. Location fingerprinting is a common positioning method where Radio Signal Strength (RSS) measurements are compared to a reference database of previously stored RSS values. Due to the size of the reference databases, these are often stored in the cloud. However, server-side positioning computations make preserving the user's privacy problematic. Given the assumption that a user does not want to communicate his/her location, we pose the question of whether a passive system with client-side computations can substitute fingerprinting-based systems, which commonly use active communication with a server. We compared two passive indoor location systems based on multilateration and sensor fusion using an Unscented Kalman Filter (UKF) with fingerprinting and show how these may provide accurate indoor positioning without compromising the user's privacy in a busy office environment.

ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer - Update 2023.

In 2018, the European Society of Gynecological Oncology (ESGO) jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP) published evidence-based guidelines for the management of patients with cervical cancer. Given the large body of new evidence addressing the management of cervical cancer, the three sister societies jointly decided to update these evidence-based guidelines. The update includes new topics to provide comprehensive guidelines on all relevant issues of diagnosis and treatment in cervical cancer. To serve on the expert panel (27 experts across Europe) ESGO/ESTRO/ESP nominated practicing clinicians who are involved in managing patients with cervical cancer and have demonstrated leadership through their expertise in clinical care and research, national and international engagement, profile, and dedication to the topics addressed. To ensure the statements were evidence based, new data identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Before publication, the guidelines were reviewed by 155 independent international practitioners in cancer care delivery and patient representatives. These updated guidelines are comprehensive and cover staging, management, follow-up, long-term survivorship, quality of life and palliative care. Management includes fertility sparing treatment, early and locally advanced cervical cancer, invasive cervical cancer diagnosed on a simple hysterectomy specimen, cervical cancer in pregnancy, rare tumors, recurrent and metastatic diseases. The management algorithms and the principles of radiotherapy and pathological evaluation are also defined.

Can robotic-assisted surgery support enhanced recovery programs?

Enhanced recovery after surgery (ERAS) protocols comprise a multimodal approach to optimize patient outcome and recovery. ERAS guidelines recommend minimally invasive surgery (MIS) when possible. Key components in MIS include preoperative patient education and optimization; multimodal and narcotic-sparing analgesia; prophylactic measures regarding nausea, infection, and venous thrombosis; maintenance of euvolemia; and promotion of the early activity. ERAS protocols in MIS improve outcome mainly in terms of reduced length of stay and subsequently reduced cost. In addition, ERAS protocols in MIS reduce postoperative pain and nausea, increase patient satisfaction, and might reduce the rate of postoperative complications. Robotic surgery supports ERAS through facilitating MIS in complex procedures where laparotomy is an alternative approach.

ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer - Update 2023.

In 2018, the European Society of Gynecological Oncology (ESGO) jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP) published evidence-based guidelines for the management of patients with cervical cancer. Given the large body of new evidence addressing the management of cervical cancer, the three sister societies jointly decided to update these evidence-based guidelines. The update includes new topics to provide comprehensive guidelines on all relevant issues of diagnosis and treatment in cervical cancer.To serve on the expert panel (27 experts across Europe) ESGO/ESTRO/ESP nominated practicing clinicians who are involved in managing patients with cervical cancer and have demonstrated leadership through their expertise in clinical care and research, national and international engagement, profile, and dedication to the topics addressed. To ensure the statements were evidence based, new data identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Before publication, the guidelines were reviewed by 155 independent international practitioners in cancer care delivery and patient representatives.These updated guidelines are comprehensive and cover staging, management, follow-up, long-term survivorship, quality of life and palliative care. Management includes fertility sparing treatment, early and locally advanced cervical cancer, invasive cervical cancer diagnosed on a simple hysterectomy specimen, cervical cancer in pregnancy, rare tumors, recurrent and metastatic diseases. The management algorithms and the principles of radiotherapy and pathological evaluation are also defined.

ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer - Update 2023.

In 2018, the European Society of Gynecological Oncology (ESGO) jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP) published evidence-based guidelines for the management of patients with cervical cancer. Given the large body of new evidence addressing the management of cervical cancer, the three sister societies jointly decided to update these evidence-based guidelines. The update includes new topics to provide comprehensive guidelines on all relevant issues of diagnosis and treatment in cervical cancer.To serve on the expert panel (27 experts across Europe) ESGO/ESTRO/ESP nominated practicing clinicians who are involved in managing patients with cervical cancer and have demonstrated leadership through their expertise in clinical care and research, national and international engagement, profile, and dedication to the topics addressed. To ensure the statements were evidence based, new data identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Before publication, the guidelines were reviewed by 155 independent international practitioners in cancer care delivery and patient representatives.These updated guidelines are comprehensive and cover staging, management, follow-up, long-term survivorship, quality of life and palliative care. Management includes fertility sparing treatment, early and locally advanced cervical cancer, invasive cervical cancer diagnosed on a simple hysterectomy specimen, cervical cancer in pregnancy, rare tumors, recurrent and metastatic diseases. The management algorithms and the principles of radiotherapy and pathological evaluation are also defined.

A federated approach to identify women with early-stage cervical cancer at low risk of lymph node metastases.

OBJECTIVE: Lymph node metastases (pN+) in presumed early-stage cervical cancer negatively impact prognosis. Using federated learning, we aimed to develop a tool to identify a group of women at low risk of pN+, to guide the shared decision-making process concerning the extent of lymph node dissection. METHODS: Women with cervical cancer between 2005 and 2020 were identified retrospectively from population-based registries: the Danish Gynaecological Cancer Database, Swedish Quality Registry for Gynaecologic Cancer and Netherlands Cancer Registry. Inclusion criteria were: squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma; The International Federation of Gynecology and Obstetrics 2009 IA2, IB1 and IIA1; treatment with radical hysterectomy and pelvic lymph node assessment. We applied privacy-preserving federated logistic regression to identify risk factors of pN+. Significant factors were used to stratify the risk of pN+. RESULTS: We included 3606 women (pN+ 11%). The most important risk factors of pN+ were lymphovascular space invasion (LVSI) (odds ratio [OR] 5.16, 95% confidence interval [CI], 4.59-5.79), tumour size 21-40 mm (OR 2.14, 95% CI, 1.89-2.43) and depth of invasion>10 mm (OR 1.81, 95% CI, 1.59-2.08). A group of 1469 women (41%)-with tumours without LVSI, tumour size ≤20 mm, and depth of invasion ≤10 mm-had a very low risk of pN+ (2.4%, 95% CI, 1.7-3.3%). CONCLUSION: Early-stage cervical cancer without LVSI, a tumour size ≤20 mm and depth of invasion ≤10 mm, confers a low risk of pN+. Based on an international privacy-preserving analysis, we developed a useful tool to guide the shared decision-making process regarding lymph node dissection.

Blood taken immediately after fatal resuscitation attempts yields higher quality DNA for genetic studies as compared to autopsy samples.

BACKGROUND: The out-of-hospital cardiac arrest (OHCA) in the young may be associated with a genetic predisposition which is relevant even for genetic counseling of relatives. The identification of genetic variants depends on the availability of intact genomic DNA. DNA from autopsy may be not available due to low autopsy frequencies or not suitable for high-throughput DNA sequencing (NGS). The emergency medical service (EMS) plays an important role to save biomaterial for subsequent molecular autopsy. It is not known whether the DNA integrity of samples collected by the EMS is better suited for NGS than autopsy specimens. MATERIAL AND METHODS: DNA integrity was analyzed by standardized protocols. Fourteen blood samples collected by the EMS and biomaterials from autopsy were compared. We collected 172 autopsy samples from different tissues and blood with postmortem intervals of 14-168 h. For comparison, DNA integrity derived from blood stored under experimental conditions was checked against autopsy blood after different time intervals. RESULTS: DNA integrity and extraction yield were higher in EMS blood compared to any autopsy tissue. DNA stability in autopsy specimens was highly variable and had unpredictable quality. In contrast, collecting blood samples by the EMS is feasible and delivered comparably the highest DNA integrity. CONCLUSIONS: Isolation yield and DNA integrity from blood samples collected by the EMS is superior in comparison to autopsy specimens. DNA from blood samples collected by the EMS on scene is stable at room temperature or even for days at 4 °C. We conclude that the EMS personnel should always save a blood sample of young fatal OHCA cases died on scene to enable subsequent genetic analysis.

22nd meeting of the European Society of Gynaecological Oncology (ESGO 2021) report.

This is a report from the 22nd Meeting of the European Society of Gynaecological Oncology, held October 23-25, 2021. The 3-day event offered an educational experience covering the major scientific and clinical advances in gynecological oncology. The Congress program included different session formats, including guidelines updates and state-of-the-art lectures. This article provides an overview of the main Congress activities as well as of the most important studies that were presented at the event for the first time.

Increase in protandry over time in a long-distance migratory bird.

Protandry is a widespread life-history phenomenon describing how males precede females at the site or state of reproduction. In migratory birds, protandry has an important influence on individual fitness, the migratory syndrome, and phenological response to climate change. Despite its significance, accurate analyses on the dynamics of protandry using data sets collected at the breeding site, are lacking. Basing our study on records collected during two time periods, 1979 to 1988 and 2006 to 2016, we aim to investigate protandry dynamics over 38 years in a breeding population of willow warblers (Phylloscopus trochilus). Change in the timing of arrival was analyzed in males and females, and protandry (number of days between male and female arrival) was investigated both at population level and within breeding pairs. Our results show advancement in the arrival time at the breeding site in both sexes, but male arrival has advanced to a greater extent, leading to an increase in protandry both at the population level and within breeding pairs. We did not observe any change in sex ratio that could explain the protandry increase, but pronounced temperature change has occurred and been reported in the breeding area and along the migratory route. Typically, natural selection opposes too early arrival in males, but given warmer springs, this counteracting force may be relaxing, enabling an increase in protandry. We discuss whether our results suggest that climate change has induced sex-specific effects, if these could be evolutionary and whether the timing of important life-history stages such as arrival at the breeding site may change at different rates in males and females following environmental shifts.

Sonification enables continuous surveillance of the ST segment in the electrocardiogram.

INTRODUCTION: ST segment elevation myocardial infarction is a common reason for out-of-hospital cardiac arrest in adult patients. The surveillance of the ST segment in the electrocardiogram is limited to visual presentation. However, the ST segment can change during the course of treatment. If ST elevation is present immediate coronary revascularization is needed, therefore detecting ST elevation changes the treatment fundamentally. Sonification of the ST segment is a new method which enables the emergency team to detect intermediate changes of the ST segment. MATERIAL AND METHODS: We have chosen two sonification designs which were introduced to two groups, medical students and computer science students. Twenty-one participants took part in the study. The sonification was designed for evaluation of the ST segment. The user was supposed to become empowered to distinguish between no, medium-low, medium-high or extreme ST elevation by listening to the sonification. The two groups were asked to evaluate the sounds for possible ST elevation as well as for aesthetics and usability. In a second study twenty-five medical students were taking part in a medical scenario in which sonification was played during a simulated case. The patient was suffering from a myocardial infarction, ST elevation was transient and sonification sounds were changing appropriately. The students were supposed to detect these changes and act accordingly by modifying the treatment. RESULTS: Both groups were able to classify ST segment elevation by listening to the sonification samples. The higher the ST segment, the better was the detection rate overall. In all of the three categories (pleasantness, informativeness and long-term listening) the Water Ambience sonification was rated higher compared to the Polarity sonification. Moreover, in the two groups that took part in the study, we found a significant difference when comparing classification performance using both sonification designs. For the group of medical students as t(20) = 4.31, p = 3.44 × 10-4, p < 0.01 and for the computer science students as t(19) = 3.40, p = 9.39 × 10-6, p < 0.01. In the simulated medical scenario participants indicated that 96% detected the ST elevation. 60% stated that sonification played a role whereas for 32% it did not play a role for the detection of ST elevation. CONCLUSIONS: Sonification has the potential to play an important role as a new supporting tool for the surveillance of the ST segment during the care of patients with suspicion of myocardial infarction. It can be helpful to differentiate between ST segment elevation myocardial infarction and non-ST segment myocardial infarction especially if ST elevation is transient. Furthermore, sonification is viewed as pleasant to listen to and might not contribute to alarm fatigue.

Similar distribution of pelvic sentinel lymph nodes and nodal metastases in cervical and endometrial cancer. A prospective study based on lymphatic anatomy.

OBJECTIVE: Comparing the anatomical distribution of metastatic and non-metastatic pelvic sentinel lymph nodes (SLN) in cervical and endometrial cancer. METHODS: Detailed SLN mapping results were prospectively retrieved in cervical (n = 145) or high-risk endometrial cancer (n = 201) patients undergoing a robotic staging procedure. Cervically injected Indocyanine Green (ICG), allowing for reinjection in case of inadequate mapping, was used as tracer. An anatomically based definition of SLNs was adhered to evaluating the upper (UPP) and lower (LPP) paracervical lymphatic pathways. The positions of SLNs were intraoperatively depicted on an anatomical chart. A completory pelvic lymphadenectomy was performed. Mapping rates and anatomical distribution of SLNs and the location of pelvic nodal metastases were compared between groups. RESULTS: The bilateral mapping rate was 97.9% and 95.0% for cervical and endometrial cancer respectively (p = .16). The proportion of typically positioned (interiliac and proximal obturator fossa) SLNs along the UPP was similar between groups (78.1% vs 82.1%, p = .09), and the rate of metastatic SLNs in the obturator fossa was 54.1% and 48.6% respectively (p = .45). All pelvic node positive women (cervical cancer n = 19, endometrial cancer n = 37) had at least one metastatic SLN. Anatomically typical positions could not be defined along the LPP. CONCLUSION: The anatomical location of SLNs and SLN metastases are similar in cervical and endometrial cancer suggesting that sensitivity results for an SLN concept in endometrial cancer and cervical cancer can be accumulated.

Detection of Early-Stage Pancreatic Ductal Adenocarcinoma From Blood Samples: Results of a Multiplex Biomarker Signature Validation Study.

INTRODUCTION: The IMMray PanCan-d test combines an 8-plex biomarker signature with CA19-9 in a proprietary algorithm to detect pancreatic ductal adenocarcinoma (PDAC) in serum samples. This study aimed to validate the clinical performance of the IMMray PanCan-d test and to better understand test performance in Lewis-null (le/le) individuals who cannot express CA19-9. METHODS: Serum samples from 586 individuals were analyzed with the IMMray PanCan-d biomarker signature and CA19-9 assay, including 167 PDAC samples, 203 individuals at high risk of familial/hereditary PDAC, and 216 healthy controls. Samples were collected at 11 sites in the United States and Europe. The study was performed by Immunovia, Inc (Marlborough, MA), and sample identity was blinded throughout the study. Test results were automatically generated using validated custom software with a locked algorithm and predefined decision value cutoffs for sample classification. RESULTS: The IMMray PanCan-d test distinguished PDAC stages I and II (n = 56) vs high-risk individuals with 98% specificity and 85% sensitivity and distinguished PDAC stages I-IV vs high-risk individuals with 98% specificity and 87% sensitivity. We identified samples with a CA19-9 value of 2.5 U/mL or less as probable Lewis-null (le/le) individuals. Excluding these 55 samples from the analysis increased the IMMray PanCan-d test sensitivity to 92% for PDAC stages I-IV (n = 157) vs controls (n = 379) while maintaining specificity at 99%; test sensitivity for PDAC stages I and II increased from 85% to 89%. DISCUSSION: These results demonstrate the IMMray PanCan-d blood test can detect PDAC with high specificity (99%) and sensitivity (92%).

Long term oncologic and reproductive outcomes after robot-assisted radical trachelectomy for early-stage cervical cancer. An international multicenter study.

OBJECTIVES: Long term outcomes following fertility sparing robot-assisted radical trachelectomy (RRT). METHODS: A retrospective study of consecutive women selected for RRT between 2007 and 2019 at five referral centres. Generally used selection criteria for fertility-sparing surgery were applied. Oncologic, reproductive and long-term clinical data were analysed. RESULTS: Of the 166 included women, 149 completed a RRT. Median tumor size was 9 mm (range 3-20 mm), 111 women (75%) had FIGO 2009 stage IB1 cancer and 4.8% were node positive. At a median follow up of 58 months, 12 of all women (7.2%) and 9 of 149 women (6%) who underwent completed RRT with fertility preservation had recurred and two had died. 70 of 88 women (80%) who attempted to conceive succeeded, resulting in 81 pregnancies that progressed beyond the first trimester and 76 live births of which 54 (70%) were delivered at term and 65 (86%) delivered after gestational week 32. A short postoperative cervical length was associated with impaired fertility. A late secondary hysterectomy was necessary in four women due to persistent bleeding (n = 2), hematometra due to a cervical stenosis (n = 1) and recurrent dysplasia (n = 1). CONCLUSION: In this long-term follow-up of RRT the recurrence rate is comparable to larger individual studies of minimally invasive or vaginal radical trachelectomy with similar risk profile and follow up. The high pregnancy rate and low rate of premature delivery before 32 weeks GA may promote the use of robot-assisted approach.

Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

Resectable, borderline, and locally advanced pancreatic cancer-"the good, the bad, and the ugly" candidates for surgery?

The possibility of surgical resection strongly overrules medical oncologic treatment and is the only modality, causa sine qua non, long-term survival can be achieved in patients with pancreatic cancer. For this reason, the clinical classification of local resectability, subdividing tumors into resectable, borderline resectable, and locally advanced cancer, that is very technical in nature, is the one most widely used and accepted. As multimodality treatment with potent agents, particularly in the neoadjuvant setting, seems to be stepping forward as the new standard of treatment of pancreatic cancer, the established technical surgical landmarks tend to get challenged. This review aims to highlight the grey zones in the current classifications for local tumor involvement with respect to the observed patient outcome in the current multimodality treatment era. It summarizes the latest reported series on the outcome of resected primary resectable, borderline and locally advanced pancreatic cancer, and particularly vascular resections during pancreatectomy, in the background of different types of neoadjuvant therapy. It also hints what the new horizons of cancer biology tend to reveal whenever the technical hinders start being pushed aside. The current calls for the necessity of re-classification of the clinical categories of pancreatic cancer, from technically oriented to biology-focused individualized approach, are being elucidated.