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The aim of the current study is to compare the dosimetry of 3 radiation therapy (RT) techniques used in the EORTC 22922/10925 trial for irradiating the internal mammary (IM) and medial supraclavicular nodes (MS) using a treatment planning system available nowadays for dose calculation. We performed a retrospective dosimetry analysis of anonymised data; thus, ethics approval was not required. Ten cases of left-sided breast were randomly selected for RT planning to a total dose of 50 Gy in 25 fractions. The treatment planning was done according to the trial's protocol and under the supervision of the EORTC trial's coordinators. Doses to planning target volumes (PTV) and to organs at risk (OARs) are reported. Data is presented in descriptive statistics. A total of 10 cases and 40 treatment plans (4 plans per case: standard -plan A, modified standard -plan B, individualised -plan C and breast-only –plan D). For all planning techniques, the mean dose to the PTV of the left breast (plan A-D) and the PTV-MS (plan A-C) exceeded 95% of the prescribed dose (>47.5 Gy). The individualised technique (plan C) had a lower coverage for PTV-IM, with a mean of 87% of the prescribed dose compared to ∼102% for plans A and B. The dose to OARs varied between techniques, with the mean heart dose being higher in the standard and modified standard techniques (18.3 and 16.6 Gy, respectively) compared to the individualised technique (9.5 Gy). The 3 RT techniques used in the trial varied in target coverage and OARs dose. Our results may help to understand the observed larger absolute benefit of individualised IM-MS treatment planning in terms of breast cancer outcomes. • The 3 radiation techniques used in the EORTC 22922/10925 trial to irradiate the internal mammary nodes and medial supraclavicular nodes varied in target coverage and organs at risk dose. • Variation between the 3 techniques were also per patient case. • This dosimetric study shows how radiation planning techniques can lead to significant differences dose coverage, organs at risk dose, and outcomes. • The inhomogeneity and extreme high doses in match line may explain the radiation side effects that match line fibrosis that were often observed in these patients. [ABSTRACT FROM AUTHOR]

mRNA-based vaccines symbolize a new paradigm shift in personalized medicine for the treatment of infectious and non-infectious diseases. However, the reactogenicity associated with the currently approved formulations limits their applicability in autoinflammatory disorders, such as tumour therapeutics. In this study, we present a delivery system showing controlled immunogenicity and minimal non-specific inflammation, allowing for selective delivery of mRNA to antigen presenting cells (APCs) within the medullary region of the lymph nodes. Our platform offers precise control over the trafficking of nanoparticles within the lymph nodes by optimizing stealth and targeting properties, as well as the subsequent opsonization process. By targeting specific cells, we observed a potent adaptive and humoral immune response, which holds promise for preventive and therapeutic anti-tumoral vaccines. Through spatial programming of nanoparticle distribution, we can promote robust immunization, thus improving and expanding the utilization of mRNA vaccines. This innovative approach signifies a remarkable step forward in the field of targeted nanomedicine. [Display omitted] [ABSTRACT FROM AUTHOR]

To evaluate long-term quality of life and survival in pancreatic ductal adenocarcinoma (PDAC) patients after pancreatoduodenectomy with extended lymphadenectomy (PDEL) and identify candidates. Patients with resectable PDAC with ≥1 examined lymph node (LN) during pancreatoduodenectomy (PD), and were divided into the PD with standard lymphadenectomy (PDSL) and PDEL groups. Perioperative data, long-term quality of life and survival were compared, and the prognostic effect of LNs ± in every peripancreatic station were analysed. Screening 446 PDAC patients, 237 and 126 were included in the PDSL and PDEL groups, respectively. The PDEL group showed a longer operation time, greater intraoperative blood loss, severe diarrhoea, a higher incidence of grade III complications. Notably, the PDEL patients experienced significant relief from low back pain and diarrhoea, with an obvious survival advantage (p = 0.037), especially in patients with preoperative tumor contact with vascular and pathological N0; however, LNs+ in any station (No. 8p, 12, 14, or 16) were associated with a poorer prognosis. The vascular reconstruction, T and N stage were independent risk factors for survival. PDEL can relieve symptoms and prolong the survival of PDAC patients with acceptable complications, and EL should be performed regardless of preoperative LN enlargement. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the technique of DCMRL to identify central lymphatic abnormalities in patients with primary lymphatic anomalies and discuss utility of the findings. Twenty-eight patients with primary lymphatic abnormalities underwent dynamic magnetic resonance imaging (MRI) following injection of gadolinium directly into inguinal lymph nodes at a tertiary lymphovascular referral center. Technical success was achieved in 23 patients (82.1%). Pathological imaging findings included obstructed, hypoplastic, or absent lymphatic channels with collateralization/rerouting or reflux of flow, lymphangiectasia, lymphatic pseudoaneurysms, and lymph leaks. Protocol modifications for improved imaging are highlighted including technical aspects of lymph node injection, image acquisition and MRI parameters. In two patients, imaging findings warranted embolization of the abnormal lymphatic channels with subsequent symptomatic improvement. DCMRL has been shown to be a safe, reproducible technique in patients with primary lymphatic anomalies enabling imaging of the central lymphatic system. • Central lymphatics visualized in 82.1% with dynamic contrast-enhanced intranodal magnetic resonance lymphangiography (DCMRL). • Optimizing imaging parameters and needle placement technique are critical. • DCMRL enables dynamic assessment of central lymphatics with anatomical correlation. [ABSTRACT FROM AUTHOR]

Gastric adenocarcinomas have been sporadically reported in camelids. This report describes a primary gastric adenocarcinoma and subsequent peritoneal carcinomatosis in a 20-year-old female Bactrian camel (Camelus bactrianus). Numerous metastases were present throughout the omentum, liver, abdominal lymph nodes, intestinal serosa, kidneys and lungs. The primary tumour macroscopically resembled an ulcerated crater and originated from the distal four-fifths of the C3 compartment, an anatomical region with naturally prominent gastric rugae and true glands. Moderate numbers of Helicobacter spp colonies were present within gastric pits and necrotic areas of C3. Ménetrier's disease has previously been implicated as a predisposing condition for the development of gastric adenocarcinoma in another camel, but no evidence of this premalignant disorder was found in this case. This camel also suffered from a chronic skin wound of the hump and severe degenerative joint disease of the xiphisternum, the latter of which was presumably associated with excessive pressure on the sternum. Gastric adenocarcinoma with subsequent peritoneal carcinomatosis in a Bactrian camel (Camelus bactrianus). The star in image c depicts the location of the primary tumour, which presented as an ulcerated crater in the distal C3 (image d). [Display omitted] [ABSTRACT FROM AUTHOR]

To assess toxicity and patient quality of life after stereotactic body radiotherapy (SBRT) to oligoprogressive disease (OPD) in patients with metastatic castrate-resistant prostate cancer (CRPC) on androgen receptor targeted agents (ARTA). This phase II trial enrolled patients with metastatic CRPC with ≤ 2 oligoprogressive lesions in bone, lymph node, lung, or prostate. All patients were receiving systemic treatment with abiraterone or enzalutamide at the time of oligoprogression. All patients received SBRT to the OPD site(s) and continued the current ARTA. Patients received 30 Gy in 5 fractions (alternate days) to the OPD site. The primary endpoint of the trial is to assess if SBRT to OPD sites results in progression free survival of >6 months. The primary endpoint for this toxicity analysis is the rate of grade 3 or higher adverse events at any timepoint up to 6 months after SBRT. Secondary endpoints included comparing pre- and post-SBRT patient-related outcomes reported using visual analogue scale scores and EQ-5D health questionnaire. Forty enrolled patients had at least 6 months of follow-up at the time of analysis. Grade 3 or higher toxicity from any cause recorded using common terminology criteria for adverse events and radiation therapy oncology group was found in 8/40 (20%) of patients, but only 1/40 (2.5%) was deemed possibly related to SBRT. There was no significant difference in mean EQ5D visual analogue scale score from baseline to each timepoint after SBRT (p = 0.449). In this prospective phase II clinical trial for OPD whilst on ARTA in the CRPC setting, we report low grade ≥ 3 toxicity after SBRT. There is no discernible change in patient-reported quality of life due to SBRT treatment. The final results of progression-free survival and toxicity of SBRT treatment will be reported once further follow-up is complete. • Stereotactic radiotherapy to oligoprogressive disease in metastatic prostate cancer patients on targeted agents is feasible. • Stereotactic body radiotherapy is well tolerated in patients with castrate-resistant prostate cancer. • There is minimal treatment-related effect on quality of life and patient-reported outcomes. [ABSTRACT FROM AUTHOR]

Le cancer de la prostate est le plus fréquent chez l'homme et, au stade localisé, les schémas d'hypofractionnement de la radiothérapie sont devenus des standards, mais l'absence de risque aggravé de toxicité aiguë et tardive génito-urinaire et gastro-intestinale de l'escalade de dose reste à prouver. La population étudiée comprenait tous les patients pris en charge à l'institut Curie de février 2016 à mars 2018 pour un adénocarcinome prostatique localisé traité par irradiation externe délivrée par un accélérateur linéaire en technique conformationnelle avec modulation d'intensité guidée par l'image à la dose totale de 75 Gy en 30 fractions de 2,5 Gy dans le volume cible prévisionnel comprenant la prostate et les vésicules séminales proximales, et pouvait associer une radiothérapie prophylactique ganglionnaire de 46 Gy en 23 fractions avec la technique de boost intégré. En tout, 166 patients ont été inclus, dont 114 étaient atteints de cancer de risque au moins intermédiaire défavorable (soit 68,7 %). L'âge et le suivi médians étaient de 71,4 ans et 3,96 ans. Cent quarante-neuf patients ont reçu une radiothérapie ganglionnaire (soit 89,8 %). Cent trente et un patients ont reçu une hormonothérapie (soit 78,9 %). Une toxicité génito-urinaire de grade 2 ou plus a été notée en cours de radiothérapie, à 6 mois, 1 an et 5 ans respectivement dans 36,7 %, 8,8 %, 3,1 % et 4,7 % des cas. Deux patients ont souffert à 5 ans d'une toxicité de grade 4 (soit 1,6 %). Une toxicité gastro-intestinale de grade 2 ou plus a été notée en cours de radiothérapie, à 6 mois, 1 an et 5 ans dans respectivement 15,1 %, 1,9 %, 14,6 % et 9,3 % des cas. Parmi ces derniers, huit patients ont souffert d'une toxicité de grade 3 (soit 6,2 %). Il n'y a eu aucune toxicité de grade 4. Les analyses n'ont pas mis en évidence de facteur prédictif de toxicité. Les taux de survie globale, sans progression et spécifique à 5 ans étaient respectivement de 82,4 %, 85,7 % et 93,3 %. La concentration sérique d'antigène spécifique de la prostate et les facteurs de risque cardiovasculaires ont été retrouvés comme facteurs prédictifs d'une dégradation de la survie globale (p = 0,0028 pour les deux). La radiothérapie externe pour un cancer prostatique localisé avec notre schéma modérément hypofractionné avec escalade de dose est bien tolérée. En l'absence de toxicité tardive majorée, l'analyse des modes de rechutes à long terme sera intéressante pour déterminer l'intérêt de cette escalade de dose sur les rechutes locales et à distance. Prostate cancer is the most frequent cancer among men and radiotherapy hypofractionation regimens have become standard treatments for the localized stages, but the absence of increased risk of acute and late genitourinary or gastrointestinal toxicity of the dose escalation still must be demonstrated. The study population included all patients with localized prostatic adenocarcinoma treated at the institut Curie from February 2016 to March 2018 by external radiation delivered by a linear accelerator using an image-guided conformal intensity modulation technique at a total dose of 75 Gy in 30 fractions of 2.5 Gy in the planning target volume that included the prostate and the proximal seminal vesicles, and could be paired with a prophylactic lymph node radiotherapy at 46 Gy in 23 fractions with simultaneous integrated boost. A total of 166 patients were included. Among them, 68.6% were unfavourable intermediate or (very) high risk. The median age and follow-up were 71.4 years and 3.96 years. One hundred and forty-nine patients received prophylactic lymph node radiotherapy (89.8%). One hundred and thirty-one patients received hormonotherapy (78.9%). Genito-urinary toxicity events of grades 2 or above during radiotherapy, at 6 months, 1 year and 5 years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5 years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6 months, 1 year and 5 years were respectively 15.1%, 1.9%, 14.6% and 9.3%. Of these, eight patients had grade 3 toxicity (6.2%). There was no grade 4 toxicity. Analyses did not reveal any predictive factor for toxicity. The 5-year overall, progression-free, and specific survival rates were respectively 82.4%, 85.7%, and 93.3%. Serum prostate specific antigen concentration and cardiovascular risk factors were found to be predictive factors of deterioration in overall survival (P = 0.0028 for both). External radiotherapy for localized prostatic cancer with our moderately hypofractionated dose escalation regimen is well tolerated. In the absence of increased late toxicity, the analysis of the modes of long-term relapses will be interesting to determine the benefit of this dose escalation on local and distant relapses. [ABSTRACT FROM AUTHOR]

The identification of internal mammary lymph node metastases and the assessment of associated risk factors are crucial for adjuvant regional lymph node irradiation in patients with breast cancer. The current study aims to investigate whether tumor contact with internal mammary perforator vessels is associated with gross internal mammary lymph node involvement. We included 297 patients with primary breast cancer and gross internal mammary (IMN+) and/or axillary metastases as well as 230 patients without lymph node metastases. Based on pretreatment dynamic contrast-enhanced magnetic resonance imaging, we assessed contact of the tumor with the internal mammary perforating vessels (IMPV). A total of 59 patients had ipsilateral IMN+ (iIMN+), 10 patients had contralateral IMN+ (cIMN+), and 228 patients had ipsilateral axillary metastases without IMN; 230 patients had node-negative breast cancer. In patients with iIMN+, 100% of tumors had contact with ipsilateral IMPV, with 94.9% (n = 56) classified as major contact. In iIMN– patients, major IMPV contact was observed in only 25.3% (n = 116), and 36.2% (n = 166) had no IMPV contact at all. Receiver operating characteristic analysis revealed that "major IMPV contact" was more accurate in predicting iIMN+ (area under the curve, 0.85) compared with a multivariate model combining grade of differentiation, tumor site, size, and molecular subtype (area under the curve, 0.65). Strikingly, among patients with cIMN+, 100% of tumors had contact with a crossing contralateral IMPV, whereas in cIMN– patients, IMPVs to the contralateral side were observed in only 53.4% (iIMN+) and 24.8% (iIMN–), respectively. Tumor contact with the IMPV is highly associated with risk of gross IMN involvement. Further studies are warranted to investigate whether this identified risk factor is also associated with microscopic IMN involvement and whether it can assist in the selection of patients with breast cancer for irradiation of the internal mammary lymph nodes. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the rate of axillary node–positive disease in patients with early breast cancer who had a suspicious axillary lymph node on radiation planning computed tomography (CT). A retrospective review was conducted of the medical records of all patients with breast cancer who were referred for axillary ultrasound from the radiation unit to the breast imaging unit at the Meirav Breast Center, Sheba Medical Center, from 2012 to 2022. Ethics approval was obtained. Only the records of patients who were referred due to an abnormal axillary lymph node seen on radiation planning CT were further evaluated. During the study period, a total of 21 patients were referred to the breast imaging unit for evaluation of suspicious nodes seen on radiation planning CT. Of these, 3 cases were excluded. A total of 15 out of the 18 (83%) patients included had an abnormal lymph node in the ultrasound, and an ultrasound-guided biopsy was recommended (BI-RADS 4). Of these, 3 (out of 15, 20%) had a positive biopsy for tumor cells from the axillary lymph node. Two were cases after primary systemic therapy without complete pathologic response. Thickening of the lymph node cortex and complete loss of the central fatty hilum were associated with pathologic lymph node. Sonar had limited ability to differentiate reactive nodes from involved nodes. The presence of lymph nodes with loss of cortical-hilum differentiation on ultrasound together with clinical features are parameters that can help guide the need of further biopsy. Histopathology evaluation is important to make the diagnosis of residual axillary disease. Future studies and guidelines are needed to improve the diagnostic abilities and reduce the number of patients who are undergoing biopsy for noninvolved nodes. [ABSTRACT FROM AUTHOR]

To determine whether targeted sampling (TS), which omits biopsy of triple- normal lymph nodes (LNs) on positron emission tomography, computed tomography, and endobronchial ultrasound (EBUS), is noninferior to systematic sampling (SS) of mediastinal LNs during EBUS for staging of patients with early-stage non–small cell lung cancer (NSCLC). Patients who are clinical nodal (cN)0-N1 with suspected NSCLC eligible for EBUS based on positron emission tomography/computed tomography were enrolled in this prospective, multicenter trial. During EBUS, all patients underwent TS and then crossed over to SS, whereby at least 3 mediastinal LN stations (4R, 4L, 7) were routinely sampled. Gold standard of comparison was pathologic results. Based on the previous feasibility trial, a noninferiority margin of 6% was established for difference in missed nodal metastasis (MNM) incidence between TS and SS. The McNemar test on paired proportions was used to determine MNM incidence for each sampling method. Analysis was per-protocol using a level of significance of P <.05. Between November 2020 and April 2022, 91 patients were enrolled at 6 high-volume Canadian tertiary care centers. A total of 256 LNs underwent TS and SS. Incidence of MNM was 0.78% in SS and 2.34% in TS, with an absolute difference of 1.56% (95% confidence interval, −0.003% to 4.1%; P =.13). This falls within the noninferiority margin. A total of 6/256 LNs from 4 patients who were not sampled by TS were found to be malignant when sampled by SS. In high-volume thoracic endosonography centers, TS is not inferior to SS in nodal staging of early-stage NSCLC. This results in change of clinical management for a minority of patients. [Display omitted] [ABSTRACT FROM AUTHOR]

To determine the indications for radiotherapy in salivary gland cancer and to specify the modalities and target radiation volumes. The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group which drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. Postoperatively, radiotherapy to the primary tumor site ± to the lymph nodes is indicated if one or more of the following adverse histoprognostic factors are present (risk > 10% of locoregional recurrence): T3–T4 category, lymph node invasion, extraglandular invasion, close or positive surgical margins, high tumor grade, perineural invasion, vascular emboli, and/or bone invasion. Intensity-modulated radiation therapy (IMRT) is the gold standard. For unresectable cancers or inoperable patients, carbon ion hadrontherapy may be considered. Radiotherapy in salivary gland cancer is indicated in postoperative situations in case of adverse histoprognostic factors and for inoperable tumors. [ABSTRACT FROM AUTHOR]

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a global concern, primarily as a cause of skin and soft tissue infections, particularly in young people. Here, we describe a case of unilateral multiple lymphadenitis caused by the CA-MRSA sequence type (ST) 834 strain. A previously healthy 15-year-old girl was referred to our hospital with fever and swollen lymph nodes in the right axillary, cubital, and groin regions. Imaging examinations revealed enlargement of the lymph nodes in these areas but no swelling in any other lymph nodes. The patient had self-destructive lymph nodes in her groin. MRSA was detected in all swollen lymph node samples. Antimicrobial susceptibility tests showed that MRSA was susceptible to clindamycin and levofloxacin, leading to the suspicion of CA-MRSA. Genetic analysis revealed that all strains were ST834 and carried the staphylococcal cassette chromosome mec IV and the toxic shock syndrome toxin-1 gene but not the Panton–Valentine leukocidin gene. The patient was treated with linezolid followed by oral clindamycin. This was a rare case of unilateral multiple lymphadenitis caused by ST834 CA-MRSA. Although ST834 strains are rarely reported, lymphadenitis has been frequently reported and is considered more likely to cause lymphadenitis than other CA-MRSA strains. [ABSTRACT FROM AUTHOR]

To study prostate specific membrane antigen – positron emission tomography (Ga68PSMA-PETCT) based patterns of relapse at biochemical failure (BCF) after prostate-only radiotherapy (PORT) in high-risk (HR) prostate cancer and its implications on pelvic contouring recommendations. Patients with clinico-radiological high-risk node-negative prostate cancer treated with curative PORT and androgen deprivation therapy (ADT), either within the POP-RT randomised trial or off trial, who underwent a Ga68PSMA-PETCT upon BCF were included. Patterns of regional and distant recurrence on Ga68PSMA-PETCT were studied. Pelvic nodal recurrences were mapped with reference to the superior border of pubic symphysis. Pelvic lymph nodal caudal border (PLN cb) recommendations in the published contouring guidelines (RTOG cb , GETUG cb , PIVOTAL cb , NRG cb , GFRU cb) were evaluated. Of the total 262 patients screened, 68 eligible patients were included (POP-RT trial 35 patients; off-trial 33 patients). Median follow-up was 91 months (IQR, 72–117) and median time to BCF was 65 months (IQR, 49–83). Regional and distant recurrence was seen in 31 (46%) and 31 (46%) patients, respectively. Of the nodal recurrences, nearly half (46%, 14/31) had no distant metastases and 64% (20/31) had a failure in the common iliac nodal region. The lower-most nodal recurrence was 20 mm cranial to the top of pubic symphysis (RTOG cb , GETUG cb , GFRU cb) and 10 mm cranial to the PIVOTAL cb. The PLN cb recommended by NRG guideline (NRG cb) had an inter-patient variability of 32 mm, ranging from 16 mm above to 16 mm below the top of pubic symphysis, and the lower most nodal recurrence ranged from 4 mm to 36 mm cranial to NRG cb. Pelvic failures accounted for a major proportion of recurrences after prostate-only radiotherapy, with the caudal most nodal recurrence being 20 mm cranial to the top of pubic symphysis. This could have implications in defining the caudal border of contouring recommendations. • Roughly half of men with localised HRCaP have pelvic failures post prostate-only RT. • Pelvic nodal lower-border definition lacks consensus across existing guidelines. • Caudal-most nodal failure was mapped 20 mm superior to the top of pubic symphysis. [ABSTRACT FROM AUTHOR]

This audit examined UK vulvar cancer practice from March 2018 to January 2019 and compared it to standards from national and international recommendations. Follow-up data collection in 2020 examined patient outcomes and toxicity. Audit standards were based on Royal College of Radiologists (RCR) guidance and published literature. A web-based questionnaire was sent to the audit leads at all cancer centres in the UK. Prospective data collection included patient demographics, tumour characteristics, radiotherapy indications, dosimetry, timelines, and follow-up data. The audit targets were 95% compliance with the RCR dose/fractionation schemes in definitive and adjuvant patients, 40% use of intensity modulated radiotherapy (IMRT), 100% of radical patients treated as category 1, and 95% use of gap compensation for category 1 patients. 34/54 UK radiotherapy centres (63%) completed data entry for 152 patients. 23 out of 34 (68%) centres submitted follow-up data for 94 patients. One indicator exceeded the audit target: 98% of radical patients received IMRT. The indicators of RCR dose/fractionation compliance for adjuvant/definitive radiotherapy were achieved by 80%/43% for the primary, 80%/86% for elective lymph nodes, and 21%/21% for pathological lymph nodes. The use of concomitant chemotherapy with radical radiotherapy in suitable patients was achieved by 71%. Other indicators demonstrated that 78% were treated as category 1 and 27% used gap compensation. Acute toxicity was mostly related to skin, gastrointestinal, and genitourinary sites. Grade 3 and Grade 4 toxicities were seen at acceptable rates within the radical and adjuvant groups. Late toxicity was mostly grade 0. This audit provides a comprehensive picture of UK practice. IMRT is widely used in the UK, and treatment-related toxicity is moderate. The dose fractionation was very heterogeneous. The designation of vulvar cancer as category 1 was not regularly followed for radical/adjuvant patients, and there was minimal gap compensation during treatment. • There is widespread use of IMRT as an RT technique for vulvar cancer in the UK with acceptable reported toxicity. • There is a considerable range of dose and fractionation used for vulvar cancer and there is no consensus regarding the minimum dose to maximize local control. • Compliance to RCR guidelines on designation of category 1 and compensation of gaps in radical treatment is below acceptable variance and should be improved. [ABSTRACT FROM AUTHOR]

The internal jugular vein (IJV) is an important vein encountered during most routine major head and neck surgeries. The IJV is known to infrequently present with anatomical variations, commonly duplication and fenestration. This report presents two cases that highlight an unusual anatomical variation of the IJV, namely the posterior tributary, which was encountered during neck dissection for papillary carcinoma of the thyroid and metastatic cervical lymph nodes. The first case was a 50-year-old woman with papillary carcinoma of the thyroid and regional metastasis, who underwent extensive neck dissection. During dissection, an anomalous posterior tributary of the IJV was discovered, originating around 3 cm above the omohyoid tendon–IJV junction. In case 2, a 40-year-old woman with a history of thyroidectomy exhibited a similar anomaly during neck dissection. In both cases, the posterior tributary was observed branching into two divisions. These cases emphasize the significance of recognizing anatomical variations to avoid inadvertent damage during surgical procedures. Anomalies like the posterior IJV tributary could have implications for surgical planning, emphasizing the importance of thorough exploration and understanding of individual variations. Awareness of such variations will help facilitate surgeons in safely performing neck dissections. [ABSTRACT FROM AUTHOR]

Solid cancers often progress via metastasis to lymph nodes. Consequently, lymphadenectomy is central to stage cancers and eradicates disease spread. However, mounting evidence suggests that cancer immunotherapies drive antitumor immune responses within lymph nodes. This implies that immunotherapy, delivered with standard oncologic therapies, may require specific treatment sequencing to initiate immunosurveillance and affect primary tumor responses. As supported by recent preclinical and clinical studies, lymphatic-preserving strategies may offer the best promise for driving the next generation of breakthrough immunotherapy approaches. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop and prospectively validate a prediction model for superficial lymphadenopathy differentiation using Sonazoid contrast-enhanced ultrasound (CEUS) combined with ultrasound (US) and clinical data. The training cohort comprised 260 retrospectively enrolled patients with 260 pathological lymph nodes imaged between January and December 2020. Two clinical US-CEUS models were created using multivariable logistic regression analysis and compared using receiver operating characteristic curve analysis: Model 1 included clinical and US characteristics; Model 2 included all confirmed predictors, including CEUS characteristics. Feature contributions were evaluated using the SHapley Additive exPlanations (SHAP) algorithm. Data from 172 patients were prospectively collected between January and May 2021 for model validation. Age, tumor history, long-axis diameter of lymph node, blood flow distribution, echogenic hilus, and the mean postvascular phase intensity (MPI) were identified as independent predictors for malignant lymphadenopathy. The area under the curve (AUC), sensitivity, specificity, and accuracy of MPI alone was 0.858 (95% confidence interval [CI], 0.817–0.891), 86.47%, 74.55%, and 81.2%, respectively. Model 2 had an AUC of 0.919 (95% CI, 0.879–0.949) and good calibration in training and validation cohorts. The incorporation of MPI significantly enhanced diagnostic capability (p < 0.0001 and p = 0.002 for training and validation cohorts, respectively). Decision curve analysis indicated Model 2 as the superior diagnostic tool. SHAP analysis highlighted MPI as the most pivotal feature in the diagnostic process. The employment of our straightforward prediction model has the potential to enhance clinical decision-making and mitigate the need for unwarranted biopsies. [ABSTRACT FROM AUTHOR]

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A 13-year old Latino male presented with recurrent gross hematuria, 5 cm right-sided poorly defined heterogeneous mass, enlarged retrocaval lymph nodes, and 1.2 cm paratracheal lymph node. Given the need for multiple blood transfusions, robot-assisted radical nephrectomy with lymph node dissection was performed. Pathology revealed pT3a high-grade tumor, clear margins, and positive lymph node. Additionally, with multiple sickled RBCs and loss of staining of SMARCB1 in tumor specimen, and hemoglobin electrophoresis suggesting sickle cell trait, diagnosis of metastatic renal medullary carcinoma was confirmed. The patient was enrolled into COG AREN 03B2 trial, and has completed 10 cycles of carboplatin/gemcitabine/bortezomib alternating with cisplatin/gemcitabine/paclitaxel, with no evidence of recurrent disease 9 months post-surgery. [ABSTRACT FROM AUTHOR]

• FDG-PET/CTs detects a higher rate on lymph node metastasis compared with conventional CT in ovarian cancer patients. • In the literature, CT positive lymph nodes show an inverse effect on complete resection rate, PFS and OS. • In our Cohort FDG-PET/CT positive lymph node show no correlation with intra- and perioperative outcomes or the OS. Compared to conventional computed tomography (CT), fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) detects higher rates of lymph node and distant metastases in patients with ovarian cancer. However, FDG-PET/CT is not routinely performed during preoperative work-up. Therefore, we investigated the prognostic value of preoperative FDG-PET/CT in advanced epithelial ovarian cancer (EOC) and its predictive value for surgical resection in patients with no residual disease. The potential significance of PET-positive supradiaphragmatic lymph nodes (SDLNs) for these parameters was evaluated. All patients with FIGO IIA-IVB EOC diagnosed between March 2014 and January 2021 at our certified gynaecological cancer centre, who underwent FDG PET/CT before primary surgery were retrospectively included. Fifty-three consecutive patients were included in the study. Eighteen (34 %) patients had PET-positive SDLNs. We could not demonstrate a significant correlation between PET-positive SDLNs and median overall survival (OS; SDLN-positive: 58.76 months, SDLN-negative: 60.76 months; p = 0.137) or intra- or perioperative outcomes. FDG PET/CT has a higher detection rate for SDLNs in patients with ovarian cancer than CT has, as described in the literature. Moreover, PET-positive SDLNs failed to predict intraoperative outcomes or overall survival. [ABSTRACT FROM AUTHOR]

To evaluate the incidence and pattern of contralateral nodal relapse (CLNR), contralateral nodal relapse-free survival (CLNRFS) and risk factors predicting CLNR in well-lateralised oral cavity cancers (OCC) treated with unilateral surgery and adjuvant ipsilateral radiotherapy with or without concurrent chemotherapy. Consecutive patients of well-lateralised OCC treated between 2012 and 2017 were included. The primary endpoint was incidence of CLNR and CLNRFS. Univariable and multivariable analyses were carried out to identify potential factors predicting CLNR. Of the 208 eligible patients, 21 (10%) developed isolated CLNR at a median follow-up of 45 months. The incidence of CLNR was 21.3% in node-positive patients. CLNR was most common at level IB (61.9%) followed by level II. The 5-year CLNRFS and overall survival were 82.5% and 57.7%, respectively. Any positive ipsilateral lymph node (P = 0.001), two or more positive lymph nodes (P < 0.001), involvement of ipsilateral level IB (P = 0.002) or level II lymph node (P < 0.001), presence of extranodal extension (P < 0.001), lymphatic invasion (P = 0.015) and perineural invasion (P = 0.021) were significant factors for CLNR on univariable analysis. The presence of two or more positive lymph nodes (P < 0.001) was an independent prognostic factor for CLNR on multivariable analysis. CLNR increased significantly with each increasing lymph node number beyond two compared with node-negative patients. The overall incidence of isolated CLNR is low in well-lateralised OCC. Patients with two or more positive lymph nodes have a higher risk of CLNR and may be considered for elective treatment of contralateral neck. • Incidence of contralateral nodal relapse (CLNR) is low in lateralised oral cancers. • ≥2 ipsilateral positive lymph nodes are associated with higher risk of CLNR. • Nodal levels IB and II are the most common stations of contralateral relapse. • Contralateral relapse increases with increasing number of positive lymph nodes. • Elective contralateral neck treatment may be considered in case of ≥2 ipsilateral positive lymph nodes. [ABSTRACT FROM AUTHOR]

Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (T EM) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of T EM cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via T EM cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@T EM @aPD-1 holds promising potential as a future novel clinical drug delivery technique. F127@T EM @aPD-1 show unique advantages in cancer treatment. When injected subcutaneously, F127@T EM @aPD-1 can continuously supplement T EM cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN. [Display omitted] [ABSTRACT FROM AUTHOR]

Subunit vaccines are an important platform for controlling current and emerging infectious diseases. The lymph nodes are the primary site generating the humoral response and delivery of antigens to these sites is critical to effective immunization. Indeed, the duration of antigen exposure within the lymph node is correlated with the antibody response. While current licensed vaccines are typically given through the intramuscular route, injecting vaccines subcutaneously allows for direct access to lymphatic vessels and therefore can enhance the transfer of antigen to the lymph nodes. However, protein subunit antigen uptake into the lymph nodes is inefficient, and subunit vaccines require adjuvants to stimulate the initial immune response. Therefore, formulation strategies have been developed to enhance the exposure of subunit proteins and adjuvants to the lymph nodes by increasing lymphatic uptake or prolonging the retention at the injection site. Given that lymph node exposure is a crucial consideration in vaccine design, in depth analyses of the pharmacokinetics of antigens and adjuvants should be the focus of future preclinical and clinical studies. This review will provide an overview of formulation strategies for targeting the lymphatics and prolonging antigen exposure and will discuss pharmacokinetic evaluations which can be applied toward vaccine development. [ABSTRACT FROM AUTHOR]

The prognostic significance of specific visceral sites of metastases in prostate cancer patients is not well established, as well as the interaction between visceral and nonvisceral metastatic sites. Prostate cancer patients with visceral metastases limited to lung have the best prognosis, especially if associated with concomitant nonvisceral lymph node metastases. Patients with visceral liver and/or brain metastases have invariably dismal survival, regardless the type of concomitant nonvisceral metastases. Introduction: It is unknown whether specific locations of visceral metastatic sites affect overall survival (OS) of metastatic prostate cancer (mPCa) patients. We tested the association between specific locations of visceral metastatic sites and OS in mPCa patients. Materials and Methods: Within Surveillance, Epidemiology and End Results database (2010-2016), survival analyses relied on specific locations of visceral metastases: lung only vs. liver only vs. brain only vs. ≥2 visceral sites. Kaplan-Meier plots and Cox regression models were fitted. Results: Of 1827 patients, 1044 (57%) harbored lung only visceral metastases vs. 457 (25%) liver only vs. 131 (7%) brain only vs. 195 (11%) ≥2 visceral sites. Median OS was 22 months in all patients vs. 33 months in lung only vs. 15 months in liver only vs. 16 months in brain only vs. 15 months in patients with ≥2 visceral sites. Highest OS was recorded in lung only visceral metastases patients, especially when concomitant nonvisceral metastases were located in lymph nodes only (median OS 57 months) vs. bone only (26 months) vs. lymph nodes and bone (28 months). Liver only, brain only or ≥2 visceral sites exhibited poor OS, regardless of concomitant nonvisceral metastases type (median OS from 13 to 19 months). Conclusion: In mPCa patients, lung only visceral metastases, especially when associated with lymph node only nonvisceral metastases, portend the best prognosis. Conversely, visceral metastatic sites other than lung portend poor prognosis, regardless of concomitant nonvisceral metastases type. [ABSTRACT FROM AUTHOR]

Controversy exists on how to handle central lymph nodes in papillary thyroid carcinoma, particularly regarding indications for prophylactic central neck dissection (CND). Central node metastases are more difficult to diagnose preoperatively than lateral node metastases. We enrolled 493 patients with papillary thyroid carcinoma treated at our department in the past 22 years. Metastatic lymph nodes were diagnosed preoperatively mainly by ultrasonography. In principle, CND was performed for all cases; ipsilateral CND was performed for hemithyroidectomy, and bilateral CND was performed for total thyroidectomy. Lateral neck dissection (levels II to V; LND) was performed for metastases to lateral neck lymph nodes (clinical node (cN) 1b). The cN stage was cN0 in 365 patients, cN1a in 10, and cN1b in 118. Of the 357 patients with stage cN0 who underwent CND, 42.9 % had pathologically positive nodes (pN+) in level VI, and of the 118 with stage cN1b who underwent CND, 78.0 % had pN+ in level VI. Cases with advanced T stage were significantly more common with pN+ in level VI. Level VI metastases were significantly associated with pN+ in level IV. As the total number of pN+ at each level of the lateral neck increased, the rate of patients with pN+ in level VI increased, and in patients with 3 or more pN+, about 85 % had level VI metastases. Because about half of the patients with cN0 patients had pN+ in level VI, and the rate of pN+ in level VI in each clinical T stage was 46 to 65 %, prophylactic CND should be performed, considering the various clinical benefits. Central nodes will have metastases in about 80 % of cases with lateral node metastases, requiring more accurate dissection. In lateral node metastases, there is a significant association between metastases in levels IV and VI. [ABSTRACT FROM AUTHOR]

Adipose mesenchymal stem cells (ASCs) represent a promising therapeutic approach in inflammatory neurological disorders, including multiple sclerosis (MS). Recent lines of evidence indicate that most biological activities of ASCs are mediated by the delivery of soluble factors enclosed in extracellular vesicles (EVs). Indeed, we have previously demonstrated that small EVs derived from ASCs (ASC-EVs) ameliorate experimental autoimmune encephalomyelitis (EAE), a murine model of MS. The precise mechanisms and molecular/cellular target of EVs during EAE are still unknown. To investigate the homing of ASC-EVs, we intravenously injected small EVs loaded with ultra-small superparamagnetic iron oxide nanoparticles (USPIO) at disease onset in EAE-induced C57Bl/6J mice. Histochemical analysis and transmission electron microscopy were carried out 48 h after EV treatment. Moreover, to assess the cellular target of EVs, flow cytometry on cells extracted ex vivo from EAE mouse lymph nodes was performed. Histochemical and ultrastructural analysis showed the presence of labeled EVs in lymph nodes but not in lungs and spinal cord of EAE injected mice. Moreover, we identified the cellular target of EVs in EAE lymph nodes by flow cytometry: ASC-EVs were preferentially located in macrophages, with a consistent amount also noted in dendritic cells and CD4+ T lymphocytes. This represents the first direct evidence of the privileged localization of ASC-EVs in draining lymph nodes of EAE after systemic injection. These data provide prominent information on the distribution, uptake and retention of ASC-EVs, which may help in the development of EV-based therapy in MS. [ABSTRACT FROM AUTHOR]

Les adénopathies sont une cause fréquente de consultation en médecine interne dont le diagnostic étiologique est varié. En cas de persistance, une adénopathie doit être biopsiée pour ne pas méconnaître une origine néoplasique. Nous rapportons ici le cas d'un patient de 53 ans, avec une adénopathie inguinale évoluant depuis plus d'un an. Le patient ne présentait pas de symptôme associé et avait un bilan biologique sans particularité. Devant la progression de l'adénopathie et son hypermétabolisme sur la TEP-TDM, une exérèse chirurgicale a été réalisée. L'analyse histologique retrouvait une prolifération intraganglionnaire de cellules fusiformes avec une disposition palissadique avec un marquage positif à la β-caténine et à l'actine musculaire lisse, conduisant au diagnostic de myofibroblastome palissadique intraganglionnaire, une pathologie tumorale bénigne. Le myofibroblastome palissadique intraganglionnaire est une cause bénigne rare d'adénopathie, souvent de localisation ganglionnaire inguinale, de croissance lente et sans risque de récidive après exérèse chirurgicale. Lymphadenopathies are a major cause of consultation in internal medicine, with various causes of diagnosis. Unexplained persistent lymphadenopathy must be biopsied to rule out malignant tumor. We report the case of a 53-year-old man, with inguinal lymphadenopathy evolving for more than one year. The patient had no associated symptoms and his blood tests were unremarkable. Due to the progression of the adenopathy and its hypermetabolism on PET-CT, an excisional biopsy was performed. Histological analysis revealed an intranodal proliferation of spindle cells with a palisading pattern. β-catenine and smooth muscle actin labelling were positive, leading to the diagnosis of intranodal palisaded myofibroblastoma, a benign tumour. Intranodal palisaded myofibroblastoma is a rare benign cause of adenopathy, with often inguinal lymph node localization and slow growth and without risk of recurrence after surgical removal. [ABSTRACT FROM AUTHOR]

To evaluate longitudinal patient-reported quality of life (QoL) in patients treated with stereotactic ablative radiotherapy (SABR) for oligometastases. The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases, conducted in six regional cancer centres in British Columbia, Canada from 2016 to 2020. Prospective QoL was measured using treatment site-specific QoL questionnaires at pre-treatment baseline and at 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. Patients with bone metastases were assessed with the Brief Pain Inventory (BPI). Patients with liver, adrenal and abdominopelvic lymph node metastases were assessed with the Functional Assessment of Chronic Illness Therapy-Abdominal Discomfort (FACIT-AD). Patients with lung and intrathoracic lymph node metastases were assessed with the Prospective Outcomes and Support Initiative (POSI) lung questionnaire. The two one-sided test procedure was used to assess equivalence between the worst QoL score and the baseline score of individual patients. The mean QoL at all time points was used to determine the trajectory of QoL response after SABR. The proportion of patients with 'stable', 'improved' or 'worsened' QoL was determined for all time points based on standard minimal clinically important differences (MCID; BPI worst pain = 2, BPI functional interference score [FIS] = 0.5, FACIT-AD Trial Outcome Index [TOI] = 8, POSI = 3). All enrolled patients with baseline QoL assessment and at least one follow-up assessment were analysed (n = 133). On equivalence testing, the patients' worst QoL scores were clinically different from baseline scores and met MCID (BPI worst pain mean difference: 1.8, 90% confidence interval 1.19 to 2.42]; BPI FIS mean difference: 1.68, 90% confidence interval 1.15 to 2.21; FACIT-AD TOI mean difference: –8.76, 90% confidence interval –11.29 to –6.24; POSI mean difference: –4.61, 90% confidence interval –6.09 to –3.14). However, the mean FIS transiently worsened at 9, 18 and 21 months but eventually returned to stable levels. The mean FACIT and POSI scores also worsened at 36 months, albeit with a limited number of responses (n = 4 and 8, respectively). Most patients reported stable QoL at all time points (range: BPI worst pain 71–82%, BPI FIS 45–78%, FACIT-AD TOI 50–100%, POSI 25–73%). Clinically significant stability, worsening and improvement were seen in 70%/13%/18% of patients at 3 months, 53%/28%/19% at 18 months and 63%/25%/13% at 36 months. Transient decreases in QoL that met MCID were seen between patients' worst QoL scores and baseline scores. However, most patients experienced stable QoL relative to pre-treatment levels on long-term follow-up. Further studies are needed to characterise patients at greatest risk for decreased QoL. • There are limited studies on the long-term quality of life (QoL) impact of SABR treatment to oligometastatic sites. • This was an analysis of longitudinal patient-reported QoL of the phase II SABR-5 trial using treatment site-specific tools. • Transient declines in QoL were observed, but most patients reported stable QoL on long-term follow-up. • Future clinical trials may incorporate treatment site-specific QoL measures to assess QoL in this patient population. • Further studies are needed to determine the predictors of QoL decline in the oligometastatic setting. [ABSTRACT FROM AUTHOR]

Metachronous oligometastatic clear cell renal cell carcinoma may take many years before becoming clinically apparent. Herein we report regional lymph node recurrence of clear cell renal cell carcinoma more than two decades following radical nephrectomy. Chromosomal microarray analysis demonstrated multiple chromosomal alterations, including 3pq deletion shared by the original and recurrent tumors, and 17p deletion containing the TP53 gene present only in the latter. Sequencing of 1550 genes revealed mutations of VHL in both the primary and metastasis and BAP1 only in the metastatic lesion. These findings genetically link the original and recurrent tumors and suggest that VHL , TP53 , and BAP1 alterations played an evolutionary role in recurrence decades after initial resection. [ABSTRACT FROM AUTHOR]

Patients with breast cancer who have positive lymph nodes are currently recommended axillary node clearance (ANC) or regional nodal irradiation (RNI). ANC is associated with complications such as lymphoedema, brachial plexopathy and shoulder stiffness. The AMAROS Group showed RNI to be non-inferior to ANC with regards to survival and recurrence, and with a better quality of life. We conducted a large real-world population study to show our centre's experience with the use of RNI and to contribute to the current discussion around the management of node-positive breast cancer. We evaluated patients who received RNI as opposed to ANC between 2006 and 2009 (n = 190). Patients had a range of cancer subtypes/grades. All had positive axillary disease, identified by axillary node sampling or sentinel lymph node biopsy. Systemic therapy was given as per standard protocol. Our data were compared with those of patients who had RNI (n = 681) in AMAROS. Patients were followed up retrospectively and overall survival, breast cancer-specific survival, distant metastasis-free survival, locoregional recurrence and toxicity were recorded, including lymphoedema, brachial plexopathy and shoulder stiffness. Survival analysis was performed on R via the Kaplan–Meier method. Univariate and multivariate analyses were also performed. Toxicity data were reported as percentages. Patients meeting POSNOC trial criteria (one to two positive sentinel lymph nodes, macrometastasis, receiving adjuvant chemotherapy) including if oestrogen receptor-positive (stratified POSNOC) were identified for subgroup analysis in the regression model. Locoregional recurrence was 3.16% versus AMAROS RNI of 1.82%. Overall survival was slightly lower in our population, but cancer-specific survival was higher than AMAROS. Lymphoedema rates were 5.8% versus AMAROS 11% in RNI and 23% in ANC arms, respectively. Brachial plexopathy was 1.6% and arm/shoulder stiffness 7.4%. AMAROS conducted a quality of life survey pertaining to arm/shoulder stiffness, mobility and function, which seemed to affect about 18% in the RNI arm. Univariate analysis revealed POSNOC status, especially if also oestrogen receptor-positive, to be a low risk group with hazard ratio 0.42 (0.20–0.83, P = 0.015). Extracapsular extension of lymph node metastasis was a poor prognostic factor; hazard ratio 4.39 (1.45–14.0, P = 0.009). We support the conclusion of the AMAROS trial with survival and recurrence following RNI being non-inferior to ANC, and with similarly favourable toxicity data. We support the continuing use of RNI as a treatment option for patients with node-positive breast cancer. Further research is required to answer the key questions regarding personalised management for node-positive breast cancer, with regards to de-escalation and also intensification for the patients exhibiting adverse tumour biology. • Real world data from our centre shows similar outcomes with regards to survival and toxicity as the AMAROS Group. • We have found that the POSNOC criteria , when applied to our dataset, are a lower risk group. • We suggest de-escalation of multimodality treatment for low risk node positive breast cancer with personalisation of care. [ABSTRACT FROM AUTHOR]

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAP α) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAP α enhanced tumor cell migration, invasion, epithelial–mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAP α in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAP α -activated prodrug, inhibited CRCLNM by targeting FAP α -positive LNM-CRC cells. Our study highlights the role of FAP α in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM. FAP α exhibits selective expression in lymph node metastatic colorectal cancer cells, facilitating colorectal cancer lymph node metastasis, which can be effectively inhibited by FAP α -activated prodrug Z-GP-DAVLBH. [Display omitted] [ABSTRACT FROM AUTHOR]

Food allergen sensitization is characterized by a type 2 immune response towards a specific food protein and can adversely affect the patient after re-exposure of this food allergen. The gut, skin, and lymph nodes (including immune cells) are interconnected key organs in food allergen sensitization. Gut and skin organ-on-a-chip (OoC) devices have been developed with an immune component to recapitulate the 3D epithelial cell–immune cell crosstalk, although specialized gut–immune–skin OoC models to study food protein sensitizing allergenicity capacity are not available yet. The inclusion of compartmentalized innate and adaptive immune cells is crucial to mimic the immune cascade in the gut–immune–skin axis in a stepwise manner. Engineering a gut–immune–skin axis OoC can better evaluate food allergen sensitization in the future and advance mechanistic insight. The global population is growing, rapidly increasing the demand for sustainable, novel, and safe food proteins with minimal risks of food allergy. In vitro testing of allergy-sensitizing capacity is predominantly based on 2D assays. However, these lack the 3D environment and crosstalk between the gut, skin, and immune cells essential for allergy prediction. Organ-on-a-chip (OoC) technologies are promising to study type 2 immune activation required for sensitization, initiated in the small intestine or skin, in interlinked systems. Increasing the mechanistic understanding and, moreover, finding new strategies to study interorgan communication is of importance to recapitulate food allergen sensitization in vitro. Here, we outline recently developed OoC platforms and discuss the features needed for reliable prediction of sensitizing allergenicity of proteins. [ABSTRACT FROM AUTHOR]

Clinical target volume (CTV) delineation for pelvic lymph nodes in prostate cancer is currently based on 3 consensus guidelines with some inherent discrepancies. To improve the reproducibility in nodal delineation, the Francophone Group of Urological Radiotherapy (Groupe Francophone de Radiothérapie Urologique [GFRU]) worked toward proposing an easily applicable, reproducible, and practice-validated contouring guideline for pelvic nodal CTV. The nodal CTV data sets of a high-risk node-negative prostate cancer clinical case contoured by 86 radiation oncologists participating in a GFRU contouring workshop were analyzed. CTV volumes were defined before and after a structured presentation of literature data on lymphatic drainage pathways and patterns of nodal involvement and relapse, illustrated using a reference contour (CRef) defined by 3 GFRU experts. The consistency between the participants' contours and CRef was assessed quantitively by means of the Simultaneous Truth and Performance Level Estimation (STAPLE) method, the Dice coefficient, and the Hausdorff distance and qualitatively using a count map. These results combined with the literature review were thoroughly discussed among GFRU experts to reach a consensus. From the 86 workshop participants, the volume of the STAPLE CTV was 591 cc compared with 502 cc for CRef. The Dice coefficient of the STAPLE CTV compared with the experts' CRef was 0.736 (±0.084) before and 0.823 (±0.070) after the workshop; the standard deviation decreased from 11.5% to 8.5% over the workshop. The Hausdorff distance of the STAPLE CTV compared with the CRef was 34.5 mm (±12.4) before the workshop and 21.8 mm (±9.3) after the workshop. Four areas of significant interobserver variability were identified, and a consensus was reached. Using a robust methodology, our cooperative group proposed an easily applicable, reproducible, and practice-validated guideline for the delineation of the pelvic CTV in prostate cancer, useful for implementation in daily practice and clinical trials. [ABSTRACT FROM AUTHOR]

2D and 3D in vitro models can be used to assess human immune responses to vaccination. Human whole-blood assays can be used as 2D in vitro tools to assess human innate and adaptive immune responses. 3D tissue models can recreate the complexity of lymph nodes. Tonsils can be used to model peripheral lymphoid organs and organoids. Skin tissue and capillary vein models can be used to investigate human immunity in vitro. High-density cell in vitro models can facilitate lymph node follicle formation. Human in vitro modeling is an emerging approach for preclinical evaluation of candidate vaccines with certain key advantages over animal models in accounting for species specificity and enabling direct benchmarking in the same study participant, while accounting for demographic variables such as age, sex, and comorbidity. 2D models offering simplicity and practicality and microphysiological 3D models that consider tissue architecture can model innate and adaptive immune responses and can accelerate and de-risk vaccine discovery and development. The human immune system is a complex network of coordinated components that are crucial for health and disease. Animal models, commonly used to study immunomodulatory agents, are limited by species-specific differences, low throughput, and ethical concerns. In contrast, in vitro modeling of human immune responses can enable species- and population-specific mechanistic studies and translational development within the same study participant. Translational accuracy of in vitro models is enhanced by accounting for genetic, epigenetic, and demographic features such as age, sex, and comorbidity. This review explores various human in vitro immune models, considers evidence that they may resemble human in vivo responses, and assesses their potential to accelerate and de-risk vaccine discovery and development. The human immune system is a complex network of coordinated components that are crucial for health and disease. Animal models, commonly used to study immunomodulatory agents, are limited by species-specific differences, low throughput, and ethical concerns. By contrast, in vitro modeling of human immune responses can enable species- and population-specific mechanistic studies and translational development within the same study participant. Translational accuracy of in vitro models is enhanced by accounting for genetic, epigenetic, and demographic features such as age, sex, and comorbidity. This review explores various human in vitro immune models, considers evidence that they may resemble human in vivo responses, and assesses their potential to accelerate and de-risk vaccine discovery and development. [ABSTRACT FROM AUTHOR]

To present the preliminary results on the clinical utilisation of an online daily adaptive magnetic resonance-guided radiation therapy (MRgRT) for various gynaecological cancers. Twelve patients treated between September 2018 and June 2022 were included. Six patients (50%) were treated with pelvic radiation therapy followed by MRgRT boost as brachytherapy boost was ineligible or unavailable, three patients (25%) were treated with pelvic MRgRT followed by high dose rate brachytherapy, two patients (16.7%) were treated with only MRgRT, one patient (8.3%) was treated with linear accelerator-based radiation therapy followed by MRgRT boost for bulky iliac lymph nodes. The median age was 56.5 years (range 31–86 years). Eight patients (66.7%) had a complete response, three patients (25%) had a partial response and one patient (8.3%) died due to acute renal failure. The mean follow-up time was 11.2 months (range 3.1–42.6 months). The estimated 1-year overall survival was 88.9%. The median treatment time was 47 days (range 10–87 days). During external beam radiation therapy, 10 (83.3%) patients had concomitant chemoradiotherapy. Pelvic external beam radiation therapy doses for all cohorts were 45–50.4 Gy with a fraction dose of 1.8 Gy. The median magnetic resonance-guided boost dose was 32 Gy (range 20–50 Gy) and fraction doses ranged between 4 and 10 Gy. Three patients were treated with intracavitary high dose rate brachytherapy (26–28 Gy in four to five fractions). None of the patients had grade >3 late genitourinary toxicities. MRgRT is reliable and clinically feasible for treating patients with gynaecological cancers alone or in combination with brachytherapy with an acceptable toxicity and outcome. MRgRT boost could be an option when brachytherapy is not available or ineligible. • MRgRT represents a new method for delivering radiotherapy for gynaecological cancers. • MRgRT is a markerless method providing online adaptive planning and real-time tracking. • MRgRT boost could be an option when brachytherapy is not available or is ineligible. [ABSTRACT FROM AUTHOR]

Background : Lymphatic spread of intrahepatic cholangiocarcinoma (iCCA) is common and negatively impacts survival. However, the precise role of lymph node dissection (LND) in oncologic outcomes for patients with intrahepatic cholangiocarcinoma remains to be established. Methods: Updated evidence on the preoperative diagnosis and prognostic value of lymph node metastasis is reviewed, as well as the potential benefit of LND in patients with iCCA. Results: The ability to accurately determine nodal status for iCCA with current imaging modalities is equivocal. LND has prognostic value for both survival and disease recurrence. However, execution rates of LND are highly varied in the literature, ranging from 26.9 to 100%. At least 6 lymph nodes should be examined from nodal stations of the hepatoduodenal ligament and hepatic artery as well as based on the location of the primary tumor. Neoadjuvant therapies may be beneficial if lymph node metastases at diagnosis are suspected. Surgeons performing a minimally invasive approach should focus on increasing LND rates and harvesting ≥ 6 lymph nodes. Lymph node negativity is required in patients with iCCA being considered for liver transplantation under investigational protocols. Conclusion: Despite an upward trend in the LND rate, the reality is that only 10% of patients with iCCA receive an adequate LND. This review underscores the importance of routinely increasing the rate of adequate LND in these patients in order to achieve accurate staging, appropriately select patients for adjuvant therapy, and improve the prognosis of clinical outcomes. While prospective data is lacking, the therapeutic impact of LND remains unknown. [ABSTRACT FROM AUTHOR]

Lymph nodes (LNs) are frequent sites of metastasis and serve as a source of tumor-specific immune tolerance. It is unclear whether LN dissection improves the prognosis for many solid organ malignancies. LNs are crucial sites of immune education and activation in response to immunotherapy. Therapeutic approaches aimed at reprogramming immune responses in LNs may prove more efficacious than lymphadenectomy. Metastasis to lymph nodes (LNs) is a common feature of disease progression in most solid organ malignancies. Consequently, LN biopsy and lymphadenectomy are common clinical practices, not only because of their diagnostic utility but also as a means of deterring further metastatic spread. LN metastases have the potential to seed additional tissues and can induce metastatic tolerance, a process by which tumor-specific immune tolerance in LNs promotes further disease progression. Nonetheless, phylogenetic studies have revealed that distant metastases are not necessarily derived from nodal metastases. Furthermore, immunotherapy efficacy is increasingly being attributed to initiation of systemic immune responses within LNs. We argue that lymphadenectomy and nodal irradiation should be approached with caution, particularly in patients receiving immunotherapy. [ABSTRACT FROM AUTHOR]

It is not clear whether cancer specific mortality (CSM) differences exist in radical prostatectomy (RP) treated prostate cancer (PCa) patients with specimen-confined (pT2) stage according to presence of lymph node invasion (LNI). Overall, 32,258 patients with pT2 PCa at RP + LND were identified. Of these, 448 (1.4%) patients harbored LNI. In multivariable Cox-regression models pN1 independently predicted higher CSM (HR: 4.4, P < .001). In sensitivity analyses addressing pT2 pN1 patients, 5-year CSM-free estimates were 99.3, 100 and 84.4% for ISUP GG 1-3 vs. 4 vs. 5, respectively (P < .001). These findings might be of value for clinical decision making, as well as for individual patient counseling. Purpose: To test cancer-specific mortality (CSM) differences in specimen-confined (pT2) prostate cancer (PCa) at radical prostatectomy (RP) with lymph node dissection (LND) according to lymph node invasion (LNI). Methods: RP + LND pT2 PCa patients were identified (surveillance, epidemiology, and end results 2010-2015). CSM-FS rates were tested in Kaplan-Meier plots and multivariable Cox-regression (MCR) models. Sensitivity analyses respectively addressing patients with 6 or more lymph nodes analyzed and pT2 pN1 patients were performed. Results: Overall, 32,258 patients with pT2 PCa at RP + LND were identified. Of these, 448 (1.4%) patients harbored LNI. Five-year CSM-1free estimates were 99.6% for pN0 vs. 96.4% for pN1 (P < .001). In MCR models, pN1 (HR: 3.4, P < .001) independently predicted higher CSM. In sensitivity analyses addressing patients with 6 or more lymph nodes analyzed (n = 15,437), 328 (2.1%) pN1 patients were identified. In this subgroup, 5-year CSM-free estimates were 99.6% for pN0 vs. 96.3% for pN1 (P < .001) and, in MCR models, pN1 independently predicted higher CSM (HR: 4.4, P < .001). In sensitivity analyses addressing pT2 pN1 patients, 5-year CSM-free estimates were 99.3, 100 and 84.8% for ISUP GG 1-3 vs. 4 vs. 5, respectively (P < .001). Conclusions: In patients with pT2 PCa a small proportion harbor LNI (1.4%-2.1%). In such patients, CSM rate is higher (HR 3.4-4.4, P < .001). This higher CSM risk seems to virtually exclusively apply to ISUP GG5 patients (84.8% 5-year CSM-free rate). [ABSTRACT FROM AUTHOR]

• The landscape of treating cN+ seminoma is changing. • Up to 22% of patients may have pN0 disease after RPLND. • This finding indicates likely historical overtreatment. • Smaller lymph nodes and solitary lymph node enlargement is associated with pN0. • Efforts to predict pN0 histology such as with miRNA-371, can decrease overtreatment. Retroperitoneal lymph node dissection (RPLND) for testicular seminoma with enlarged retroperitoneal lymph nodes has received increased consideration and exposed a new clinical entity: pN0 disease. Enlarged, nonmetastatic retroperitoneal lymph nodes provide insight into the natural history of seminoma while offering a benchmark for improving the accuracy of staging. The purpose of this systematic review was to report the pN0 rates, describe risk factors associated with it, and discuss emerging research that may reduce its incidence. We performed a systemic review of published literature on PubMed, Embase, Web of Science, as well as oncology meeting abstracts evaluating histology of lymph nodes in patients with testicular seminoma treated primarily with retroperitoneal lymph node dissection. Studies were excluded if histology was not reported. A total of 15 publications and abstracts were included. Although study designs were heterogeneous, there was a minimal risk of bias. Overall, the reported pN0 rates were 0% to 22%. In prospective clinical trials it was 9% to 16%. The presence of pN0 was associated with preoperative smaller lymph nodes, a solitary enlarged lymph node, or negative serum miRNA-371. The incidence of pN0 seminoma is concerning as it points to a potential historical overtreatment; however, it also represents an important inflection for testicular cancer research as quantifiable improvements in clinical staging will translate to clear benefits to patients. [ABSTRACT FROM AUTHOR]

After primary radiotherapy, biochemical recurrence is defined according to the Phoenix criteria as a prostate-specific antigen (PSA) value >2 ng/ml relative to the nadir. Several studies have shown that prostate-specific membrane antigen (PSMA)-ligand positron emission tomography/computed tomography (PET/CT) can help in detecting recurrence in patients with low PSA values. This study aimed to assess the detection rate and patterns of PSMA-ligand PET/CT uptake in patients with suspected biochemical recurrence after primary radiotherapy and with PSA levels below the Phoenix threshold. The meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Articles providing data on patients with suspected prostate cancer recurrence after primary radiotherapy with a PSA value below the Phoenix threshold and who underwent PSMA-ligand PET/CT were included. Quality assessment was carried out using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). In total, five studies were included, recruiting 909 patients (202 with PSA ≤2 ng/ml). The PSMA-ligand detection rate in the patients with ≤2 ng/ml ranged from 66 to 83%. The most frequent source of PSMA-ligand PET/CT uptake was local recurrence, followed by lymph node metastasis and bone metastasis. PSMA-ligand PET/CT uptake due to local-only recurrence was more likely in patients with PSA ≤2 ng/ml compared with PSA > 2 ng/ml: risk ratio 0.72 (95% confidence interval 0.58–0.89), P = 0.003. No significant differences were observed in the detection of PSMA-ligand uptake in other areas. Limitations include a lack of biopsy confirmation, cohort reports with small sample sizes and a potentially high risk of bias. A significant detection of PSMA-ligand-avid disease was observed in patients with PSA levels below the Phoenix threshold. There was a higher likelihood of detecting local-only uptake when the PSA value was ≤2 ng/ml. The findings suggest that a critical review of the Phoenix criteria may be warranted in the era of PSMA-ligand PET/CT and highlight the need for further prospective trials. • PSMA-ligand PET/CT detects PSMA-avid disease (up to 80%) in patients with PSA below Phoenix threshold. • The likelihood of detecting local-only uptake was higher when the PSA ≤2 ng/ml. • A critical review of the Phoenix criteria may be warranted in the era of PSMA-ligand PET/CT. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the impact of deep inspiration breath hold (DIBH) on the positioning of thoracic structures and provide treatment planning recommendations for internal mammary chain (IMC) irradiation in breast cancer patients. Thirty-two breast cancer patients from our database underwent both DIBH and free breathing (FB) treatment planning. Contouring of the axillary lymph node clinical target volumes (CTVs: level I, II, III, IV, and IMC according to ESTRO), the internal mammary artery (IMA), the heart, and the left anterior descending artery (LAD) was performed. The following were then analyzed: the distance between the IMA and the heart, the craniocaudal distance in which IMC-CTV and heart coexist, the craniocaudal distance between the lower end of the of level III and IV and the upper end of the heart. Several significant geometric differences were observed between DIBH and FB that explain the efficacy of the DIBH for regional nodal irradiation. In >80% of patients the cranial origin of the LAD lies below the lower edge of the IMC-CTV in DIBH. In addition the slices in which the heart/LAD and IMC-CTV coexist decrease during DIBH. The IMA-heart distance is significantly larger in DIBH. Also the craniocaudal distance between the lower border of the CTV level III and IV and the upper border of the heart is larger in DIBH. The observed mechanisms during DIBH contribute significantly to the dose reduction in regional nodal irradiation. To further enhance the benefits of DIBH for the irradiation of the IMC-CTV, it is recommended to implement steep dose gradients in the caudal plane. [ABSTRACT FROM AUTHOR]

Background: Transhiatal esophagectomy (THE) is an accepted approach for distal esophageal (DE) and gastroesophageal junction (GEJ) cancers. Its reported weaknesses are limited loco-regional resection and high anastomotic leak rates. We have used laparoscopic assistance to perform a THE (LapTHE) as our preferred method of resection for GEJ and DE cancers for over 20 years. Our unique approach and experience may provide technical insights and perhaps superior outcomes. Methods: We reviewed all patients who underwent LapTHE for DE and GEJ malignancy over 10 years (2011–2020). We included 6 principles in our approach: (1) minimize dissection trauma using laparoscopy; (2) routine Kocher maneuver; (3) division of lesser sac adhesions exposing the entire gastroepiploic arcade; (4) gaining excess conduit mobility, allowing resection of proximal stomach, and performing the anastomosis with a well perfused stomach; (5) stapled side-to-side anastomosis; and (6) routine feeding jejunostomy and early oral diet. Results: One hundred and forty-seven patients were included in the analysis. The median number of lymph nodes procured was 19 (range 5–49). Negative margins were achieved in all cases (95% confidence interval [CI] 98–100%). Median hospital stay was 7 days. Overall major complication rate was 24% (17–32%), 90-day mortality was 2.0% (0.4–5.8%), and reoperation was 5.4% (2.4–10%). Three patients (2.0%, 0.4–5.8%) developed anastomotic leaks. Median follow-up was 901 days (range 52–5240). Nine patients (6.1%, 2.8–11%) developed anastomotic strictures. Conclusions: Routine use of LapTHE for DE and GEJ cancers and inclusion of these six operative principles allow for a low rate of anastomotic complications relative to national benchmarks. [ABSTRACT FROM AUTHOR]

This article examines the controversy surrounding the classification system for Siewert type II adenocarcinoma of the esophagogastric junction (AEG) and the optimal number of total examined lymph nodes (TLN) for AEG. The study collected data from 1,819 patients with Siewert type II AEG and found that dissecting at least 13 lymph nodes is necessary for accurate staging of AEG. The study also developed a predictive model for patients with inadequate TLN and a web application for the model. However, the study acknowledged limitations, such as excluding patients who received neoadjuvant chemotherapy. [Extracted from the article]

• SLRPs, released from a remodeling ECM or synthesized de novo by activated fibroblasts, are more communicative with immune cells than collagen-associated SLRPs in mature ECMs. • SLRPs interact with toll-like receptor-mediated innate immune signals in macrophages and dendritic cells. • Transcriptomic studies identify stromal cell subsets that express SLRPs in lymph nodes and their functional implications. In this review we highlight emerging immune regulatory functions of lumican, keratocan, fibromodulin, biglycan and decorin, which are members of the small leucine-rich proteoglycans (SLRP) of the extracellular matrix (ECM). These SLRPs have been studied extensively as collagen-fibril regulatory structural components of the skin, cornea, bone and cartilage in homeostasis. However, SLRPs released from a remodeling ECM, or synthesized by activated fibroblasts and immune cells contribute to an ECM-free pool in tissues and circulation, that may have a significant, but poorly understood foot print in inflammation and disease. Their molecular interactions and the signaling networks they influence also require investigations. Here we present studies on the leucine-rich repeat (LRR) motifs of SLRP core proteins, their evolutionary and functional relationships with other LRR pathogen recognition receptors, such as the toll-like receptors (TLRs) to bring some molecular clarity in the immune regulatory functions of SLRPs. We discuss molecular interactions of fragments and intact SLRPs, and how some of these interactions are likely modulated by glycosaminoglycan side chains. We integrate findings on molecular interactions of these SLRPs together with what is known about their presence in circulation and lymph nodes (LN), which are important sites of immune cell regulation. Recent bulk and single cell RNA sequencing studies have identified subsets of stromal reticular cells that express these SLRPs within LNs. An understanding of the cellular source, molecular interactions and signaling consequences will lead to a fundamental understanding of how SLRPs modulate immune responses, and to therapeutic tools based on these SLRPs in the future. [ABSTRACT FROM AUTHOR]