New staging of endometrial carcinoma - FIGO 2023.

AIM: To review the changes in the new version of the FIGO 2023 staging system for endometrial cancer. METHODS AND RESULTS: The new FIGO 2023 endometrial cancer staging system provides key updates for the diagnosis and treatment of endometrial cancer. An important step in diagnosis is molecular classification, which allows more accurate risk stratification for recurrence and the identification of targeted therapies. The new staging system, based on the recommendations of the international societies ESGO, ESTRO and ESP, incorporates not only the description of the pathological and anatomical extent of the disease, but also the histopathological characteristics of the tumour, including the histological type and the presence of lymphovascular space invasion. In addition, the staging system uses molecular testing to classify endometrial cancers into four prognostic groups: POLEmut, MMRd, NSMP and p53abn. Each group has its own specific characteristics and prognosis. The most significant changes have occurred in stages I and II, in which the sub-staging better reflects the biological behaviour of the tumour. This update increases the accuracy of prognosis and improves individualized treatment options for patients with endometrial cancer. CONCLUSION: The updated FIGO staging of endometrial cancer for 2023 incorporates different histologic types, tumour features, and molecular classifications to better reflect the current improved understanding of the complex nature of several endometrial cancer types and their underlying bio logic behaviour. The aim of the new endometrial cancer staging system is to better define stages with similar prognosis, allowing for more precise indication of individualised adjuvant radiation or systemic treatment, including the use of immunotherapy.

A CT-based integrated model for preoperative prediction of occult lymph node metastasis in early tongue cancer.

Background: Occult lymph node metastasis (OLNM) is an essential prognostic factor for early-stage tongue cancer (cT1-2N0M0) and a determinant of treatment decisions. Therefore, accurate prediction of OLNM can significantly impact the clinical management and outcomes of patients with tongue cancer. The aim of this study was to develop and validate a multiomics-based model to predict OLNM in patients with early-stage tongue cancer. Methods: The data of 125 patients diagnosed with early-stage tongue cancer (cT1-2N0M0) who underwent primary surgical treatment and elective neck dissection were retrospectively analyzed. A total of 100 patients were randomly assigned to the training set and 25 to the test set. The preoperative contrast-enhanced computed tomography (CT) and clinical data on these patients were collected. Radiomics features were extracted from the primary tumor as the region of interest (ROI) on CT images, and correlation analysis and the least absolute shrinkage and selection operator (LASSO) method were used to identify the most relevant features. A support vector machine (SVM) classifier was constructed and compared with other machine learning algorithms. With the same method, a clinical model was built and the peri-tumoral and intra-tumoral images were selected as the input for the deep learning model. The stacking ensemble technique was used to combine the multiple models. The predictive performance of the integrated model was evaluated for accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC-ROC), and compared with expert assessment. Internal validation was performed using a stratified five-fold cross-validation approach. Results: Of the 125 patients, 41 (32.8%) showed OLNM on postoperative pathological examination. The integrated model achieved higher predictive performance compared with the individual models, with an accuracy of 84%, a sensitivity of 100%, a specificity of 76.5%, and an AUC-ROC of 0.949 (95% CI [0.870-1.000]). In addition, the performance of the integrated model surpassed that of younger doctors and was comparable to the evaluation of experienced doctors. Conclusions: The multiomics-based model can accurately predict OLNM in patients with early-stage tongue cancer, and may serve as a valuable decision-making tool to determine the appropriate treatment and avoid unnecessary neck surgery in patients without OLNM.

Identificación de las características de los ganglios evaluados en el procedimiento EBUS y su relación con el diagnóstico de malignidad en instituto de alta complejidad en cáncer / Identification of the Characteristics of the Lymph Nodes Evaluated in the EBUS Procedure and their Relationship with the Diagnosis of Malignancy in a Highly Complex Cancer Institute

Introducción: La EBUS ha sido el foco de numerosos estudios destinados a evaluar su utilidad y rendimiento diagnóstico en diversas patologías. Objetivo principal: Identificación de las características ganglionares evaluadas en el procedimiento de Ultrasonido Endobronquial (EBUS) y su relación con el diagnóstico de malignidad en pacientes del Instituto Nacional del Cáncer de Colombia del 1 de enero de 2017 al 31 de marzo de 2021.Métodos: Estudio analítico observacional transversal. La recopilación de datos implicó un muestreo de casos consecutivos no probabilísticos entre individuos que cumplían los criterios de inclusión.Resultados: Un total de 75 pacientes fueron sometidos a EBUS. Se identificaron 6 características ecográficas de los ganglios de la biopsia asociadas a malignidad destacándose los ganglios mayores de 1 cm, márgenes mal definidos, ecogenicidad heterogénea, ausencia de una estructura hiliar central, presencia de signos de necrosis o coagulación y presencia de conglomerado ganglionar. Conclusión: Este estudio caracterizó la frecuencia de los hallazgos en la ultrasonografía endobronquial destacando algunas características ecográficas de los ganglios mediastínicos que podrían predecir patología maligna.

Introduction: The EBUS has been the focus of numerous studies aiming to evaluate its utility and diagnostic performance across various pathologies. Objective: Identification of the node characteristics evaluated in the Endobronchial Ultrasound (EBUS) procedure and their relationship with malignancy diagnosis in patients at the National Cancer Institute of Colombia from January 1st, 2017, to March 31st, 2021. Methods: Observational cross-sectional analytical study. Data collection involved non-probabilistic consecutive case sampling among individuals meeting the inclusion criteria.Results: A total of 75 patients underwent the EBUS procedure. Our findings revealed six predictors of malignancy based on sonographic features of biopsy nodes, including nodes larger than 1 cm, poorly defined margins, heterogeneous echogenicity, absence of a central hilar structure, presence of signs indicating necrosis or coagulation, and the presence of a ganglion conglomerate. Conclusions: This study showed that endobronchial ultrasonography has several sonographic characteristics at the time of evaluating mediastinal nodes that could predict malignant and benign pathology.

The International Association for the Study of Lung Cancer Staging Project for Lung Cancer: Proposals for the Revision of the M Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

INTRODUCTION: This study analyzed all metastatic categories of the current TNM classification of NSCLC to propose modifications of the M component in the next edition (ninth) of the classification. METHODS: A database of 124,581 patients diagnosed between 2011 and 2019 was established; of these, 14,937 with NSCLC in stages IVA to IVB were available for this analysis. Overall survival was calculated using the Kaplan-Meier method, and prognosis was assessed using multivariable-adjusted Cox proportional hazards regression. RESULTS: The eighth edition M categories revealed good discrimination in the ninth edition data set. Assessments revealed that an increasing number of metastatic lesions were associated with decreasing prognosis; because this seems to be a continuum and adjustment for confounders was not possible, no specific lesion number was deemed appropriate for stage classification. Among tumors involving multiple metastases, decreasing prognosis was found with an increasing number of organ systems involved. Multiple assessments, including after adjustment for potential confounders, revealed that M1c patients who had metastases to a single extrathoracic organ system were prognostically distinct from M1c patients who had involvement of multiple extrathoracic organ systems. CONCLUSIONS: These data validate the eighth edition M1a and M1b categories, which are recommended to be maintained. We propose the M1c category be divided into M1c1 (involvement of a single extrathoracic organ system) and M1c2 (involvement of multiple extrathoracic organ systems).

Validación de técnica de ganglio centinela en cáncer de endometrio en el Hospital de Talca / Validation of sentinel lymph node technique in endometrial cancer at the Hospital de Talca

Objetivo: Validar la técnica de ganglio centinela utilizando verde de indocianina en la estadificación del cáncer de endometrio. Método: Realizamos un estudio prospectivo entre enero y diciembre de 2021. Se incluyeron todas las pacientes portadoras de cáncer de endometrio clínicamente en etapa 1, de todos los grados de diferenciación e histologías. Todas las pacientes fueron sometidas a una estadificación laparoscópica. Se inició el procedimiento con identificación de ganglio centinela utilizando verde de indocianina. Posteriormente, se completó la cirugía de estadiaje estándar en todas las pacientes. Los ganglios centinelas fueron procesados con técnica de ultraestadiaje. Resultados: Se incluyeron 33 pacientes. El 81% presentaron histología endometrioide. El 100% fueron sometida además a una linfadenectomía pelviana estándar y el 20% a una linfadenectomía paraaórtica simultáneamente. Se detectó al menos un ganglio centinela en el 100% de los casos. La detección bilateral ocurrió en el 90,9%. La localización más frecuente fue la fosa obturatriz y la arteria hipogástrica. Obtuvimos una sensibilidad del 90% para detectar enfermedad ganglionar y un valor predictivo negativo del 95,8%. Conclusiones: La técnica de ganglio centinela utilizando verde de indocianina es replicable. Los resultados de nuestra serie nos permiten realizar procedimientos menos agresivos al estadificar el cáncer de endometrio.

Objective: To validate sentinel node mapping using indocyanine green in endometrial cancer staging. Method: A prospective study was conducted between January and December 2021. All patients with clinically stage 1 endometrial cancer, of all grades and histologies were included. All patients underwent laparoscopic staging. The procedure began with identification of the sentinel node using indocyanine green. Subsequently, standard staging surgery was completed in all patients. Sentinel nodes were processed using ultrastaging technique. Results: Thirty-three patients were enrolled. 81% of cases had endometrioid histology. All patients also underwent a standard pelvic lymphadenectomy and in 20% of cases a para-aortic lymphadenectomy. At least one sentinel node was detected in 100% of the cases. Bilateral detection occurred in 90.9%. The most frequent location was obturator fossa and hypogastric artery. Sensitivity to detect lymph node disease was 90% and negative predictive value 95.8%. Conclusions: Sentinel lymph node mapping using indocyanine green is a replicable technique. Our results allows us to perform less aggressive procedures in endometrial cancer staging.

Retrospective audit: Utility of PET scan in routine preoperative rectal cancer staging.

BACKGROUND: Accurate staging for rectal cancer is pertinent with recent introduction of rectum-sparing approaches for patients showing complete clinical response on restaging. Positron emission tomography(PET) is used in detection of recurrence or metastasis, but its value in routine preoperative rectal cancer staging remains unclear. Studies report that preoperative PET altered the stage in 39% and changed the management in 17-27% of patients. Our study aims to look at the utility of PET in routine preoperative staging of rectal cancer within 2 two colorectal units, and to determine if PET did result in a change in management. METHODS: Patients in Nepean Hospital (NSW) and Peter MacCallum Cancer Centre (VIC) who were diagnosed with rectal cancer between 1 January 2017 and 31 December 2021 were included in this retrospective study. All patients who did not have a PET scan were excluded. PET scan results were then compared with MRI and CT results. RESULTS: Three hundred and fifty-seven patients were included in the study. 30.3% of the patients had Stage 3 rectal cancer. 71.7% received neoadjuvant therapy. PET scan provided additional information in 55.5% of patients when compared with CT and MRI alone; 18.2% of the PET findings resulted in an altered management for the patient. CONCLUSION: PET scan can be a valuable tool in accurate staging, especially for ambiguous or equivocal lesions on CT. Our study demonstrated that additional information from PET scan resulted in an altered management plan in 18.2% of the patients. PET/MRI as a newer modality may be more accurate with reduced radiation exposure.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: Unresolved Issues to be Addressed for the Next Ninth Edition of the TNM Classification of Malignant Tumors.

Thymic epithelial tumors are presently staged using a consistent TNM classification developed by the International Association for the Study of Lung Cancer (IASLC) and approved by the Union for International Cancer Control and the American Joint Committee on Cancer. The stage classification is incorporated in the eight edition of the TNM classification of thoracic malignancies. The IASLC Staging and Prognostic Factors Committee (SPFC)-Thymic Domain (TD) is in charge for the next (ninth) edition expected in 2024. The present article represents the midterm report of the SPFC-TD: in particular, it describes the unresolved issues identified by the group in the current stage classification which are worth being addressed and discussed for the ninth edition of the TNM classification on the basis of the available data collected in the central thymic database which will be managed and analyzed by Cancer Research And Biostatistics. These issues are grouped into issues of general importance and those specifically related to T, N, and M categories. Each issue is described in reference to the most recent reports on the subject, and the priority assigned by the IASLC SPFC-TD for the discussion of the ninth edition is provided.

PSMA PET/CT guided intensification of therapy in patients at risk of advanced prostate cancer (PATRON): a pragmatic phase III randomized controlled trial.

BACKGROUND: Positron emission tomography targeting the prostate specific membrane antigen (PSMA PET/CT) has demonstrated unparalleled performance as a staging examination for prostate cancer resulting in substantial changes in management. However, the impact of altered management on patient outcomes is largely unknown. This study aims to assess the impact of intensified radiotherapy or surgery guided by PSMA PET/CT in patients at risk of advanced prostate cancer. METHODS: This pan-Canadian phase III randomized controlled trial will enroll 776 men with either untreated high risk prostate cancer (CAPRA score 6-10 or stage cN1) or biochemically recurrent prostate cancer post radical prostatectomy (PSA > 0.1 ng/mL). Patients will be randomized 1:1 to either receive conventional imaging or conventional plus PSMA PET imaging, with intensification of radiotherapy or surgery to newly identified disease sites. The primary endpoint is failure free survival at 5 years. Secondary endpoints include rates of adverse events, time to next-line therapy, as well as impact on health-related quality of life and cost effectiveness as measured by incremental cost per Quality Adjusted Life Years gained. DISCUSSION: This study will help create level 1 evidence needed to demonstrate whether or not intensification of radiotherapy or surgery based on PSMA PET findings improves outcomes of patients at risk of advanced prostate cancer in a manner that is cost-effective. TRIAL REGISTRATION: This trial was prospectively registered in ClinicalTrials.gov as NCT04557501 on September 21, 2020.

A simple additive staging system for newly diagnosed multiple myeloma.

Risk stratification in multiple myeloma is important for prognostication, patient selection for clinical trials, and comparison of treatment approaches. We developed and validated a staging system that incorporates additional FISH abnormalities not included in the R-ISS and reflects the additive effects of co-occurring high-risk disease features. We first evaluated the prognostic value of predefined cytogenetic and laboratory abnormalities in 2556 Mayo Clinic patients diagnosed between February 2004 and June 2019. We then used data from 1327 patients to develop a risk stratification model and validated this in 502 patients enrolled in the MMRF CoMMpass study. On multivariate analysis, high-risk IgH translocations [risk ratio (RR): 1.7], 1q gain/amplification (RR: 1.4), chromosome17 abnormalities (RR: 1.6), ISS III (RR: 1.7), and elevated LDH (RR: 1.3) were independently associated with decreased overall survival (OS). Among 1327 evaluable patients, OS was 11.0 (95% CI: 9.2-12.6), 7.0 (95% CI: 6.3-9.2), and 4.5 (95% CI: 3.7-5.2) years in patients with 0 (stage I), 1 (stage II), and ≥2 (stage III) high-risk factors, respectively. In the MMRF cohort, median OS was 7.8 (95% CI: NR-NR), 6.0 (95% CI: 5.7-NR), and 4.3 (95% CI: 2.7-NR) years in the 3 groups, respectively (P < 0.001). This 5-factor, 3-tier system is easy to implement in practice and improves upon the current R-ISS.

The Value of Gastric Cancer Staging by Endoscopic Ultrasonography Features in the Diagnosis of Gastroenterology.

This research was aimed at exploring the application value of endoscopic ultrasonography (EUS) in the diagnosis of gastric cancer staging and the correlation between staging and clinical features of gastric cancer. A total of 72 patients with gastric cancer were selected and randomly divided into two groups. The patients in the pathological group underwent postoperative pathological examination, while those in the EUS group received preoperative EUS examination. The results showed that the staging accuracy of EUS was 73.33% for T1, 78.57% for T2, 27% for T3, and 100% for T4, compared with the pathological staging. The accuracy of N- and N+ was 42.5% and 82.3% in EUS, respectively, and the total accuracy was 55.7%. There was no considerable difference in the accuracy of T staging between early gastric cancer and advanced gastric cancer (P > 0.05), but there was a considerable difference in N staging (P < 0.05). Lymph node metastasis affected the accuracy of N staging (P < 0.05). The number and location of metastatic lymph nodes did not affect the judgment of metastatic lymph nodes (P > 0.05). In addition, the proportion of understaging and overstaging was greatly different among different lesion sizes and histological types of gastric cancer (P < 0.05). To sum up, the accuracy of EUS for T and N staging of gastric cancer needed to be improved. The location of gastric cancer lesions affected the accuracy of T staging, while the depth of invasion and lymph node metastasis affected the accuracy of N staging.

Loss of 5-hydroxymethylcytosine as a Poor Prognostic Factor for Primary Testicular Diffuse Large B-cell Lymphoma.

Background: 5-Hydroxymethylcytosine (5-hmC), a stable epigenetic marker, is closely related to tumor staging, recurrence and survival, but the prognostic value of 5-hmC in primary testicular diffuse large B-cell lymphoma (PT-DLBCL) remains unclear. This study aimed to investigate the 5-hmC expression in PT-DLBCL and evaluate its prognostic value. Methods: A total of 34 patients with PT-DLBCL treated in the Department of Hematology from August 2000 to August 2020 were included in this study. The expression of 5-hmC in PT-DLBCL tissues and normal testicular tissues were assessed by immunohistochemistry. 5-hmC staining is estimated as a percentage under every nuclear staining intensity score (0-3), 0 or 1 of which were regarded as 5-hmC reduction. The quantification of 5-hmC reduction is defined as the percentage of cells with 5-hmC staining scores of 0 and 1. According 5-hmC reduction of 80%, a 5-hmC reduction of <80% is regarded as "5-hmC high-level group", and a 5-hmC reduction of ≥80% is regarded as "5-hmC low-level group". Furthermore, Cox regression model was used to evaluate the prognostic value of all covariates. Results: The median percentage of 5-hmC reduction in the PT-DLBCL group was 77.50% (60%-90%), the median 5-hmC reduction in the normal testicular tissues was 30% (20%-50%). Compared with normal testicular tissue, 5-hmC levels in PT-DLBCL tissue were significantly decreased (p<0.05). Of the 34 PT-DLBCL patients, 17 had tumors with relatively low 5-hmC expression (5-hmC reduction of ≥80%) and 17 had tumors with relatively high 5-hmC expression (5-hmC reduction of < 80%). 5-hmC expression was negatively correlated with international prognostic index (p = 0.037), while there was no significant difference in 5-hmC decrease among different groups of age at diagnosis, lactate dehydrogenase, testicular lymphoma involvement (unilateral or bilateral), Ki-67 and tumor diameter. Relatively low 5-hmC expression indicated shorter overall survival (OS) (5-year OS 50.2% vs 81.3%, p=0.022) and progression-free survival (PFS) (5-year PFS 38.5% vs 70.7%, p=0.001). Cox multivariate analysis of IPI (2-3 vs. 0-1), intrathecal prophylaxis (No vs. Yes), and 5-hmC reduction (≥80% vs. <80%) showed that 5-hmC reduction ≥80% (hazard ratio: 7.252, p = 0.005) and not receiving intrathecal prophylaxis (hazard ratio: 7.207, p =0.001) are independent risk factors for poor prognosis of PT-DLBCL. Conclusion: Our results suggested that 5-hmC decline can be identified as a poor prognostic predictor for PT-DLBCL. It is necessary to further explore the underlying mechanism of this epigenetic marker to identify methods to re-establish 5-hmC levels and provide new targets for cancer therapy.

Predicting Factors for Pelvic Lymph Node Metastasis in Patients with Apparently Early-Stage Endometrial Cancer.

BACKGROUND: Performing lymphadenectomy in all patients with early-stage endometrial cancer (EC) is debatable because the procedure may expose patients to unnecessary risks of postoperative complications. Aim of this study was to evaluate the prevalence and risk factors of pelvic lymph node metastasis (PLNM) in patients with apparently early-stage EC. MATERIALS AND METHODS: Two hundred and two patients with apparently early-stage EC who underwent surgical staging at Thammasat University Hospital between the years 2013 and 2020 were included in this retrospective study. Clinicopathological data and preoperative laboratory results were obtained from computer-based medical records. All data were statistically analyzed to determine the prevalence of PLNM and risk factors for developing PLNM. RESULTS: PLNM was detected in 22 (10.9%) patients. Univariate analysis demonstrated that having grade 3 tumor, myometrial invasion of 50% or greater, vaginal involvement, cervical involvement, adnexal involvement, lower uterine segment involvement, lymphovascular space invasion (LVSI), and positive peritoneal cytology were associated with higher risk for developing PLNM. In addition, lower preoperative hemoglobin level and higher preoperative white blood cell count were significantly associated with PLNM. Multivariate analysis demonstrated that myometrial invasion of 50% or greater and LVSI were independent risk factors for developing PLNM (odds ratio (OR) 9.31, 95% confidence interval (CI) 2.58-33.55, p = 0.001, and OR 3.73, 95%CI 1.39-10.02, p = 0.009, respectively). CONCLUSIONS: Myometrial invasion of 50% or greater and LVSI were independent risk factors for developing PLNM in patients with apparently early-stage EC and thus lymphadenectomy in these patients should be provided.

Research Progress of Heavy Ion Radiotherapy for Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) has a high incidence and poses a serious threat to human health. However, the treatment outcomes of concurrent chemoradiotherapy for non-small-cell lung cancer are still unsatisfactory, especially for high grade lesions. As a new cancer treatment, heavy ion radiotherapy has shown promising efficacy and safety in the treatment of non-small-cell lung cancer. This article discusses the clinical progress of heavy ion radiotherapy in the treatment of non-small-cell lung cancer mainly from the different cancer stages, the different doses of heavy ion beams, and the patient's individual factors, and explores the deficiency of heavy ion radiotherapy in the treatment of non-small-cell lung cancer and the directions of future research, in order to provide reference for the wider and better application of heavy ion radiotherapy in the future.

Imaging Prostate Cancer: Clinical Utility of Prostate-Specific Membrane Antigen.

PURPOSE: Our goal was to review the pathway and pertinent materials leading to approval of prostate-specific membrane antigen (PSMA) scanning by the U.S. Food and Drug Administration (FDA). MATERIALS AND METHODS: Beginning with the pivotal trials and working backward, we summarize the evolution of PSMA scanning, beginning with the discovery of the molecule, the mechanism of action to identify prostate cancer, the route to the present-day test and some of the major publications leading to each step of the sequence. From the thousands of PSMA articles listed on PubMed®, the present review is focused on the 4 large U.S. trials incorporating university studies of the gallium-68 compound and commercial studies of the fluorine-18 compound. The review further focuses on the role of PSMA scanning for both initial staging of prostate cancer and diagnosis of recurrent prostate cancer. RESULTS: PSMA is a transmembrane-bound glycoprotein which is overexpressed by 100-1,000-fold in prostate cancer cells. Preclinical PSMA studies at Cornell and Johns Hopkins in the 1990s were followed by early human studies in Germany in the early 2010s, then pivotal clinical trials at University of California, Los Angeles and University of California, San Francisco, leading to the first FDA approval in December 2020 (68Ga-PSMA-11). In January 2021, a commercially available product (18F-DCFPyL) was approved on the basis of multisite registration trials (CONDOR and OSPREY). Sensitivity and specificity of PSMA scanning exceeds that of any other imaging method currently available for initial staging of prostate cancer and diagnosis of recurrent disease. The accuracy of PSMA scanning is attributed to the great image contrast (high signal-to-noise ratio), a property deriving from the high PSMA tracer uptake by prostate cancer cells. That property can be estimated quantitatively by a metric, the standardized uptake value. A follow-on PSMA compound, the theranostic lutetium-177, is currently pending FDA approval for treatment of metastases. CONCLUSIONS: PSMA scanning is a disruptive technology that promises to transform the way prostate cancer is initially staged, recurrence is diagnosed and some advanced cases are treated.

The blood level of thioredoxin 1 as a supporting biomarker in the detection of breast cancer.

BACKGROUND: There is a long-time unmet need for a means to detect breast cancer (BC) using blood. Although mammography is accepted as the gold standard for screening, a blood-based diagnostic can complement mammography and assist in the accurate detection of BC in the diagnostic process period of early diagnosis. We have previously reported the possible use of thioredoxin 1 (Trx1) in serum as a novel means to detect BC. In the present study, we validated the clinical utility of Trx1 to identify BC by testing sera from biopsy-confirmed cancer patients and women without cancer. METHODS: We have generated monoclonal antibodies against Trx1 and developed an ELISA kit that can quantitate Trx1 in sera. The level of Trx1 was determined in each serum from women without cancer (n = 114), as well as in serum from patients with BC (n = 106) and other types of cancers (n = 74), including cervical, lung, stomach, colorectal, and thyroid cancer. The sera from BC patients were collected and classified by the subjects' age and cancer stage. In addition to the Trx1 levels of BC patients, several pathological and molecular aspects of BC were analyzed. Test results were retrospectively compared to those from mammography. Each test was duplicated, and test results were analyzed by ROC analysis, one-way ANOVA tests, and unpaired t-tests. RESULTS: The mean level of Trx1 from women without cancer was 5.45 ± 4.16 (±SD) ng/ml, that of the other malignant cancer patient group was 2.70 ± 2.01 ng/ml, and that from the BC group was 21.96 ± 6.79 ng/ml. The difference among these values was large enough to distinguish BC sera from non-BC control sera with a sensitivity of 97.17% and specificity of 94.15% (AUC 0.990, p < 0.0001). Most Trx1 levels from BC patients' sera were higher than the cut-off value of 11.4 ng/ml regardless of age, stage, histological grade, type, and specific receptors' expression profile of BC. The level of Trx1 could rescue women from most cases of misread or incomplete mammography diagnoses. CONCLUSION: These results indicated that the blood level of Trx1 could be an effective and accurate means to assist the detection of BC during the early diagnosis period.

Phase II Adjuvant Cancer-specific Vaccine Therapy for Esophageal Cancer Patients Curatively Resected After Preoperative Therapy With Pathologically Positive Nodes; Possible Significance of Tumor Immune Microenvironment in its Clinical Effects.

OBJECTIVES: To elucidate the efficacy of adjuvant vaccine monotherapy using 3 Human Leukocyte Antigen (HLA)-A∗24-restricted tumor-specific peptide antigens for ESCC, upregulated lung cancer 10, cell division cycle associated 1, and KH domain-containing protein overexpressed in cancer 1. SUMMARY OF BACKGROUND DATA: ESCC patients with pathologically positive nodes (pN(+)) have a high risk for postoperative recurrence, despite curative resection after preoperative therapy. Subclinical micrometastases are an appropriate target for cancer vaccine. METHODS: This is a non-randomized prospective phase II clinical trial (UMIN000003557). ESCC patients curatively resected after preoperative therapy with pN(+) were allocated into the control and vaccine groups (CG and VG) according to the HLA-A status. One mg each of three epitope peptides was postoperatively injected 10 times weekly followed by 10 times biweekly to the VG. The primary and secondary endpoints were relapse-free survival (RFS) and esophageal cancer-specific survival (ECSS), respectively. RESULTS: Thirty were in the CG and 33 in the VG. No significant difference was observed in RFS between the CG and VG (5-year RFS: 32.5% vs 45.3%), but the recurrence rate significantly decreased with the number of peptides which induced antigen-specific cytotoxic T lymphocytes. The VG showed a significantly higher 5-year ECSS than the CG (60.0% vs 32.4%, P = 0.045) and this difference was more prominent in patients with CD8+ and programmed death-ligand 1 double negative tumor (68.0% vs 17.7%, P = 0.010). CONCLUSIONS: Our cancer peptide vaccine might improve the survival of ESCC patients, which is warranted to be verified in the phase III randomized controlled study.

Historical and Contemporary Management of Infantile Hepatic Hemangioma: A 30-year Single-center Experience.

OBJECTIVE: To describe outcome of infants with hemangioma(s) of the liver. SUMMARY OF BACKGROUND DATA: Infantile hepatic hemangiomas exhibit a diverse phenotype. We report our 30-year experience and describe optimal management based on precise radiological classification. METHODS: Retrospective review of 124 infants (66 female) 1986-2016. Categorical analysis with Chi2 and nonparametric comparison. Data expressed as median (range) and P < 0.05 considered significant. RESULTS: Lesions classified as focal (n = 70, 56%); multifocal (n = 47, 38%) or diffuse (n = 7, 6%) and of these 80(65%) were symptomatic (eg, cardiac failure n = 39, 31%; thrombocytopenia n = 12, 10%).Increased hepatic artery velocity was seen in 63 (56%). Median hepatic artery velocity was greatest in diffuse lesions [245 (175-376) cm/s vs focal 120 (34-242) cm/s vs multifocal 93 (36-313) cm/s; P = 0.0001]. Expectant management alone was followed in 55 (44%). Medical therapy was utilised in 57(46%) and sufficient for symptom control in 29/57 (51%). Propranolol therapy (from 2008) was sufficient for symptom control in 22/28 (79%). Surgery (hepatic artery ligation n = 26; resection n = 13; embolization n = 1) was required in 40 (32%). Median maximal lesion diameter was 3 (0.5-17.1) cm and greater in those requiring surgery (7 cm vs 4.9 cm; P = 0.04). The proportion requiring surgery decreased markedly in the propranolol era [pre-propranolol 25/48 (52%) vs post-propranolol 16/76 (21%) (P = 0.0003)]. Systematic follow-up with ultrasound to a median of 2.6 (0.02-16) years. CONCLUSIONS: A proportion of infantile hepatic hemangiomas remain asymptomatic permitting observation until resolution but the majority require complex multi-modal therapy. First-line pharmacotherapy with propranolol has reduced but not abolished the need for surgery.

A Modern Assessment of Cancer Risk in Adrenal Incidentalomas: Analysis of 2219 Patients.

OBJECTIVE: The aim of this study was to analyze the incidence of and risk factors for adrenocortical carcinoma (ACC) in adrenal incidentaloma (AI). SUMMARY OF BACKGROUND DATA: AI guidelines are based on data obtained with old-generation imaging and predominantly use tumor size to stratify risk for ACC. There is a need to analyze the incidence and risk factors from a contemporary series. METHODS: This is a retrospective review of 2219 AIs that were either surgically removed or nonoperatively monitored for ≥12 months between 2000 and 2017. Multivariate logistic regression was performed to define risk factors. ROC curves constructed to determine optimal size and attenuation cut-offs for ACC. RESULTS: 16.8% of AIs underwent upfront surgery and rest initial nonoperative management. Of conservatively managed patients, an additional 7.7% subsequently required adrenalectomy. Overall, ACC incidence in AI was 1.7%. ACC rates by size were 0.1%, 2.4%, and 19.5% for AIs of <4, 4 to 6, and >6 cm, respectively. The optimal size cut-off for ACC in AI was 4.6 cm. ACC risks by Hounsfield density were 0%, 0.5%, and 6.3% for lesions of <10, 10 to 20, and >20 HU, with an optimal cut-off of 20 HU to diagnose ACC. 15.5% of all AIs and 19.2% of ACCs were hormonally active. Male sex, large tumor size, high Hounsfield density, and >0.6 cm/year growth were independent risk factors for ACC. CONCLUSION: This contemporary analysis demonstrates that ACC risk per size in AI is less than previously reported. Given these findings, modern management of AIs should not be based just on size, but a combination of thorough hormonal evaluation and imaging characteristics.

The prognostic value of Kirsten rat sarcoma viral oncogene homolog mutations in resected lung adenocarcinoma differs according to clinical features.

BACKGROUND: The ninth edition of lung cancer staging system recommends that specific driver mutations should be considered as prognostic factors in survival models. This study comprehensively investigated the prognostic value of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in patients with resected lung adenocarcinomas according to different clinicopathologic and radiologic characteristics. METHODS: In total, 1464 patients with completely resected primary lung adenocarcinomas were examined for KRAS mutations from November 2008 to March 2015. Age, sex, smoking status, performance status, tumor-node-metastasis stage, radiologic features, and histologic subtypes were collected. Competing risk model was used to estimate the cumulative incidence rate of recurrence. Cox regression multivariable analyses on recurrence-free survival (RFS) and overall survival (OS) were performed. RESULTS: KRAS mutations were more frequent in male subjects (P < .001), current/former smokers (P < .001), invasive mucinous adenocarcinoma (P < .001), and solid tumors (P < .001). In general, KRAS-mutated patients had greater cumulative recurrence rate (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.23-3.08; P < .001) and worse overall survival (OS; HR, 1.88; 95% CI, 1.23-2.87; P < .001) than KRAS wild-type patients. The OS (P < .001) of patients harboring KRAS-G12C/V mutations was shorter than that of other KRAS-mutated patients. Cox multivariable analyses demonstrated that KRAS mutations were independently associated with worse RFS (HR, 5.34; 95% CI, 2.53-11.89; P = .001) and OS (HR, 2.63; 95% CI, 1.03-6.76; P = .044) in part-solid lung adenocarcinomas. For stage I patients, Cox multivariable analyses revealed that KRAS mutation was an independent risk factor for RFS (HR, 2.05; 95% CI, 1.19-3.56; P = .010) and OS (HR, 2.38; 95% CI, 1.29-4.40; P = .005). CONCLUSIONS: In this study, we revealed that KRAS mutations was an independent prognostic factor in part-solid tumors and in stage I lung adenocarcinomas. These findings may contribute to the ninth edition of lung cancer staging project.