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Tumor-infiltrating lymphocytes (TILs) are associated with improved survival in patients with epithelial ovarian cancer. However, TIL evaluation has not been used in routine clinical practice because of reproducibility issues. The current study developed two convolutional neural network models to detect TILs and to determine their spatial location in whole slide images, and established a spatial assessment pipeline to objectively quantify intraepithelial and stromal TILs in patients with high-grade serous ovarian carcinoma. The predictions of the established models showed a significant positive correlation with the number of CD8+ T cells and immune gene expressions. Patients with a higher density of intraepithelial TILs had a significantly prolonged overall survival and progression-free survival in multiple cohorts. On the basis of the density of intraepithelial and stromal TILs, patients were classified into three immunophenotypes: immune inflamed, excluded, and desert. The immune-desert subgroup showed the worst prognosis. Gene expression analysis showed that the immune-desert subgroup had lower immune cytolytic activity and T-cell-inflamed gene-expression profile scores, whereas the immune-excluded subgroup had higher expression of interferon-γ and programmed death 1 receptor signaling pathway. The established evaluation method provided detailed and comprehensive quantification of intraepithelial and stromal TILs throughout hematoxylin and eosin-stained slides. It has potential for clinical application for personalized treatment of patients with ovarian cancer.
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Cistadenocarcinoma Seroso , Aprendizaje Profundo , Linfocitos Infiltrantes de Tumor , Neoplasias Ováricas , Humanos , Femenino , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Neoplasias Ováricas/genética , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/inmunología , Cistadenocarcinoma Seroso/genética , Persona de Mediana Edad , Anciano , Pronóstico , Células del Estroma/patología , Células del Estroma/inmunología , Células del Estroma/metabolismo , Linfocitos Intraepiteliales/inmunología , Linfocitos Intraepiteliales/metabolismoRESUMEN
Clonal expansion in aged normal tissues has been implicated in the development of cancer. However, the chronology and risk dependence of the expansion are poorly understood. Here we intensively sequence 682 micro-scale oesophageal samples and show, in physiologically normal oesophageal epithelia, the progressive age-related expansion of clones that carry mutations in driver genes (predominantly NOTCH1), which is substantially accelerated by alcohol consumption and by smoking. Driver-mutated clones emerge multifocally from early childhood and increase their number and size with ageing, and ultimately replace almost the entire oesophageal epithelium in the extremely elderly. Compared with mutations in oesophageal cancer, there is a marked overrepresentation of NOTCH1 and PPM1D mutations in physiologically normal oesophageal epithelia; these mutations can be acquired before late adolescence (as early as early infancy) and significantly increase in number with heavy smoking and drinking. The remodelling of the oesophageal epithelium by driver-mutated clones is an inevitable consequence of normal ageing, which-depending on lifestyle risks-may affect cancer development.
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Envejecimiento/genética , Envejecimiento/patología , Epitelio , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Mutación , Lesiones Precancerosas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/genética , Biopsia , Recuento de Células , Transformación Celular Neoplásica/genética , Niño , Preescolar , Células Clonales/metabolismo , Células Clonales/patología , Variaciones en el Número de Copia de ADN , Epitelio/metabolismo , Epitelio/patología , Evolución Molecular , Femenino , Interacción Gen-Ambiente , Genoma Humano/genética , Humanos , Lactante , Estilo de Vida , Masculino , Persona de Mediana Edad , Acumulación de Mutaciones , Proteína Fosfatasa 2C/genética , Receptor Notch1/genética , Factores de Riesgo , Análisis de Secuencia de ADN , Análisis de la Célula Individual , Fumar/genética , Adulto JovenRESUMEN
Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare, recurrent oncogenic variant that constitutively activates EGFR in non-small-cell lung cancer. Herein, we report the case of a 70-year-old man with resectable colorectal adenocarcinoma who underwent surgery followed by adjuvant therapy. He relapsed with multiple liver metastases and received standard chemotherapy until his disease became refractory. Comprehensive genomic profiling of his postoperative colorectal cancer tissue revealed EGFR-KDD. He was treated with an EGFR tyrosine kinase inhibitor (TKI), afatinib and achieved a partial response (-â 55%) after 8 weeks; however, he developed massive malignant ascites after 13 weeks. Osimertinib, another EGFR-TKI, controlled his tumors for 9 months. Patient-derived cancer organoids from his malignant ascites confirmed sensitivity to EGFR-TKIs. The findings suggest that EGFR-TKIs can be a potential treatment option for this molecular subgroup.
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Most gastric cancers develop in inflamed gastric mucosa due to Helicobacter pylori infection, typically with metaplastic changes. However, the origins of gastric cancer remain unknown. Here, we present a case of intramucosal gastric carcinoma (IGC) and oxyntic gland adenoma (OGA) derived from spasmolytic polypeptide-expressing metaplasia (SPEM). Early gastric cancer adjacent to a polyp was found in the upper corpus of a 71-year-old woman without H. pylori infection and was endoscopically resected. Histological examination showed IGC and OGA, both of which had predominant MUC6 expression. Interestingly, gastric glands with enriched MUC6-positive mucous cells, referred to as SPEM, expanded between them. Whole-exome sequencing analysis revealed a truncating KRAS(G12D) mutation in IGC, OGA, and SPEM. In addition, TP53 and CDKN2A mutations and a loss of chromosome 17p were found in the IGC, whereas a GNAS mutation was observed in the OGA. These results indicated that IGC and OGA originated from the KRAS-mutated SPEM. © 2023 The Pathological Society of Great Britain and Ireland.
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Adenoma , Carcinoma , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Femenino , Humanos , Anciano , Neoplasias Gástricas/genética , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Mucosa Gástrica , Metaplasia , Adenoma/genéticaRESUMEN
AIM: Recent evidence suggests that acute liver failure (ALF) in some patients may reflect a dysregulated immune response, and that corticosteroids improve survival of the native liver in ALF patients with high serum alanine aminotransferase levels, which are an indication of liver inflammation. However, it is unclear whether steroids are effective for pediatric acute liver failure (PALF). The aim of this retrospective case-control study is to examine whether steroid therapy for PALF accompanied by immune activation improves the survival of native liver and to identify factors that predict responses to steroid treatment. METHODS: Of 38 patients with PALF treated at Kyoto University Hospital from February 2006 to August 2022, 19 receiving steroids who met the specific criteria for identifying the pathophysiology of immune activity in the liver (the "Steroid group"), and seven steroid-free patients who also met the criteria ("Nonsteroid group") were enrolled. Patients in the "Steroid group" were categorized as "responders" or "nonresponders" according to treatment outcome. Clinical and histological data were analyzed. RESULTS: Survival of the native liver in the Steroid group was significantly higher than that in the Nonsteroid group (68% vs. 0%, respectively; p = 0.0052). Nonresponders were significantly younger, with higher Model for End-stage Liver Disease and pediatric end-stage liver disease scores, higher prothrombin time - international normalized ratio, and higher serum ferritin levels than responders. Massive hepatic necrosis was more common in nonresponders. CONCLUSION: Steroid therapy is effective for PALF patients with liver inflammation; however, liver transplantation should be prioritized for young children with ALF accompanied by severe coagulopathy or massive hepatic necrosis.
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There have been no reported cases of neuroendocrine carcinoma (NEC) of the cervix with pagetoid spread (Pag-S). A 44-year-old woman came to our department because of abnormal cytology that persisted immediately after a radical hysterectomy for NEC of the cervix. A mapping biopsy in a large area from the vaginal wall to the vulva revealed that synaptophysin/Ki-67-positive tumor cells were scattered within the epithelium in multiple areas, suggesting a wide Pag-S of NEC. Because tumor cells were found beyond the vaginal wall, the anterior pelvic exenteration was performed. Since we could pathologically confirm the complete resection and no distant metastases were detected, no adjuvant therapy was performed. Four years have passed since the initial treatment without any tumor recurrence. It is known that the prognosis of NEC of the cervix that invades beyond the cervix is poor; however, if there is a Pag-S pattern, a radical surgical treatment can be considered.
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Carcinoma Neuroendocrino , Neoplasias del Cuello Uterino , Femenino , Humanos , Adulto , Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Recurrencia Local de Neoplasia , Carcinoma Neuroendocrino/cirugía , Carcinoma Neuroendocrino/patología , PronósticoRESUMEN
The staging of endometrial cancer is based on the International Federation of Gynecology and Obstetrics (FIGO) staging system according to the examination of surgical specimens, and has revised in 2023, 14 years after its last revision in 2009. Molecular and histological classification has incorporated to new FIGO system reflecting the biological behavior and prognosis of endometrial cancer. Nonetheless, the basic role of imaging modalities including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography, as a preoperative assessment of the tumor extension and also the evaluation points in CT and MRI imaging are not changed, other than several point of local tumor extension. In the field of radiology, it has also undergone remarkable advancement through the rapid progress of computational technology. The application of deep learning reconstruction techniques contributes the benefits of shorter acquisition time or higher quality. Radiomics, which extract various quantitative features from the images, is also expected to have the potential for the quantitative prediction of risk factors such as histological types and lymphovascular space invasion, which is newly included in the new FIGO system. This article reviews the preoperative imaging diagnosis in new FIGO system and recent advances in imaging analysis and their clinical contributions in endometrial cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.
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OBJECTIVES: To build preoperative prediction models with and without MRI for regional lymph node metastasis (r-LNM, pelvic and/or para-aortic LNM (PENM/PANM)) and for PANM in endometrial cancer using established risk factors. METHODS: In this retrospective two-center study, 364 patients with endometrial cancer were included: 253 in the model development and 111 in the external validation. For r-LNM and PANM, respectively, best subset regression with ten-time fivefold cross validation was conducted using ten established risk factors (4 clinical and 6 imaging factors). Models with the top 10 percentile of area under the curve (AUC) and with the fewest variables in the model development were subjected to the external validation (11 and 4 candidates, respectively, for r-LNM and PANM). Then, the models with the highest AUC were selected as the final models. Models without MRI findings were developed similarly, assuming the cases where MRI was not available. RESULTS: The final r-LNM model consisted of pelvic lymph node (PEN) ≥ 6 mm, deep myometrial invasion (DMI) on MRI, CA125, para-aortic lymph node (PAN) ≥ 6 mm, and biopsy; PANM model consisted of DMI, PAN, PEN, and CA125 (in order of correlation coefficient ß values). The AUCs were 0.85 (95%CI: 0.77-0.92) and 0.86 (0.75-0.94) for the external validation, respectively. The model without MRI for r-LNM and PANM showed AUC of 0.79 (0.68-0.89) and 0.87 (0.76-0.96), respectively. CONCLUSIONS: The prediction models created by best subset regression with cross validation showed high diagnostic performance for predicting LNM in endometrial cancer, which may avoid unnecessary lymphadenectomies. CLINICAL RELEVANCE STATEMENT: The prediction risks of lymph node metastasis (LNM) and para-aortic LNM can be easily obtained for all patients with endometrial cancer by inputting the conventional clinical information into our models. They help in the decision-making for optimal lymphadenectomy and personalized treatment. KEY POINTS: â¢Diagnostic performance of lymph node metastases (LNM) in endometrial cancer is low based on size criteria and can be improved by combining with other clinical information. â¢The optimized logistic regression model for regional LNM consists of lymph node ≥ 6 mm, deep myometrial invasion, cancer antigen-125, and biopsy, showing high diagnostic performance. â¢Our model predicts the preoperative risk of LNM, which may avoid unnecessary lymphadenectomies.
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BACKGROUND: Ovarian serous borderline tumors (SBT) are typically unilateral and are primarily treated using hysterectomy and bilateral salpingooophorectomy (SO). However, most young patients prefer fertility-sparing surgeries (FSS) with tumorectomy or unilateral SO. Micropapillary morphology and invasive implants have been designated as histopathological risk indicators for recurrence or metastasis, but their clinical impact remains controversial because of limitations like diagnostic inconsistency and incomplete surgical staging. METHODS: A nationwide multi-institutional population-based retrospective surveillance was conducted with a thorough central pathology review to reveal the clinical features of SBT. Of 313 SBT patients enrolled in the Japanese Society of Clinical Oncology's Surveillance of Gynecologic Rare Tumors, 289 patient records were reviewed for clinical outcomes. The glass slides of patients at stage II-IV or with recurrence or death were re-evaluated by three gynecological pathologists. RESULT: The 10-year overall and progression-free survival (PFS) rates were 98.6% and 92.3%. The median recurrence period was 40 months and 77.0% was observed in the contralateral ovary within 60 months. Patients aged ≤ 35 years underwent FSS more frequently and relapsed more (p < .001). A clinic-pathological analysis revealed diagnosis during pregnancy, FSS, and treatment at non-university institutes as well as advanced stage and large diameter were independent risk factors of recurrence. Among patients having pathologically confirmed SBTs, PFS was not influenced by the presence of micropapillary pattern or invasive implants. CONCLUSION: The recurrence rate was lower in this cohort than previous reports, but the clinical impacts of incomplete resection and misclassification of the tumor were still significant on the treatment of SBT.
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BACKGROUND: Tubulointerstitial nephritis with IgM-positive plasma cells (IgMPC-TIN) is a newer disease about which there are many unclear points. Glucocorticoid therapy is effective in many cases of IgMPC-TIN; however, relapse during glucocorticoid tapering has been reported. Relapse and its treatment are poorly defined. CASE PRESENTATION: Case 1 was a 61-year-old man with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. He was diagnosed with IgMPC-TIN accompanied by Fanconi syndrome and distal renal tubular acidosis (d-RTA). Prednisolone (PSL; 30 mg daily, 0.45 mg/kg/day) treatment was highly effective, and PSL was gradually tapered and discontinued after 1 year. However, 1 month after PSL discontinuation, therapeutic markers were elevated. Therefore, PSL (10 mg daily, 0.15 mg/kg/day) was administered, and the markers indicated improvement. Case 2 was a 43-year-old woman referred for renal dysfunction and proteinuria. Laboratory data revealed that she had primary biliary cholangitis (PBC), d-RTA, and Fanconi syndrome. A renal biopsy showed accumulation of IgM-positive plasma cells in the tubulointerstitium without any glomerular changes. A diagnosis of IgMPC-TIN was made and the patient was started on PSL (35 mg daily, 0.6 mg/kg/day). Therapeutic markers decreased immediately and PSL was discontinued after 1 year. Three months later, the proteinuria and Fanconi syndrome worsened. PSL treatment was restarted (20 mg daily, 0.35 mg/kg/day) and markers indicated improvement. Case 3 was a 45-year-old woman with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. The patient had PBC, Sjögren syndrome, d-RTA, and Fanconi syndrome, and the diagnosis of IgMPC-TIN was made. The patient was started on PSL (30 mg daily, 0.4 mg/kg/day) and disease markers decreased immediately. However, when PSL was tapered to 15 mg daily (0.2 mg/kg/day), the patient's serum IgM levels increased; therefore, we maintained the PSL at 15 mg daily (0.2 mg/kg/day). CONCLUSION: We report three cases of relapsed IgMPC-TIN associated with reduction or discontinuation of glucocorticoid therapy. In these cases, elevation of serum IgM preceded that of other markers such as urinary ß2-microglobulin, proteinuria, and glycosuria. We recommend monitoring serum IgM levels while tapering glucocorticoids; a maintenance dose of glucocorticoid should be considered if relapse is suspected or anticipated.
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Acidosis Tubular Renal , Síndrome de Fanconi , Glucocorticoides , Nefritis Intersticial , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Acidosis Tubular Renal/diagnóstico , Síndrome de Fanconi/complicaciones , Glucocorticoides/uso terapéutico , Inmunoglobulina M/sangre , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/tratamiento farmacológico , Nefritis Intersticial/complicaciones , Células Plasmáticas , Proteinuria/tratamiento farmacológico , RecurrenciaRESUMEN
BACKGROUND: Early identification of placental insufficiency can lead to appropriate treatment selections and can improve neonates' outcomes. Possible contributions of magnetic resonance imaging (MRI) have been suggested. PURPOSE: To evaluate the prognostic capabilities of placental intravoxel incoherent motion (IVIM) parameters and T2-relaxation time, and their correlation with fetal growth and adverse outcomes, comparing umbilical artery (UmA) pulsatility index (PI). MATERIAL AND METHODS: A total of 68 singleton pregnancies at 24-40 weeks of gestation underwent placental MRI and were reviewed retrospectively. UmA-PI was measured using Doppler ultrasound by obstetricians. IVIM parameters (Dfast, Dslow, and f) were calculated with a Bayesian model fitting. First, the associations between gestational age (GA) with placental IVIM parameters, T2-relaxation time, and placental thickness (PT) were evaluated. Second, IVIM parameters, T2 value (Z-score), PT (Z-score), and UmA-PI (Z-score) were compared between ( 1) those delivering small for gestational age (SGA) and appropriate for gestational age (AGA) neonates, ( 2) emergency cesarean section (ECS), and non-ECS, and ( 3) preterm birth and full-term birth. RESULTS: Low birth weight was observed in 15/68 cases (22%). GA was significantly associated only with T2-relaxation time and PT. SGA was significantly associated with T2 value (Z-score), f, and UmA-PI (Z-score). In the ECS groups, T2 value (Z-score), f, and Dfast were significantly lower than those in non-ECS groups. All IVIM parameters and T2 values (Z-score) showed significantly lower scores in the preterm birth group. CONCLUSION: Placental f and T2 value (Z-score) had significant associations with low birth weight and clinical adverse outcomes and could be potential imaging biomarkers of placental insufficiency.
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Insuficiencia Placentaria , Nacimiento Prematuro , Embarazo , Recién Nacido , Humanos , Femenino , Placenta/diagnóstico por imagen , Insuficiencia Placentaria/diagnóstico por imagen , Estudios Retrospectivos , Arterias Umbilicales/diagnóstico por imagen , Teorema de Bayes , Cesárea , Imagen por Resonancia Magnética/métodos , Movimiento (Física) , Ultrasonografía Doppler , Imagen de Difusión por Resonancia MagnéticaRESUMEN
Mesonephric-like carcinoma histologically resembles mesonephric adenocarcinoma (MA) of the cervix. MA arises from mesonephric duct remnants. However, the origin of mesonephric-like carcinoma is not extensively studied because of its rarity. Here, we present a case of synchronous ovarian and uterine mesonephric-like carcinoma that potentially arose from endometrioid adenofibroma. A 69-year-old woman presented with an abdominal mass with no genital bleeding. She underwent simple total abdominal hysterectomy and bilateral adnexal resection. Histological and immunohistochemical analyses were consistent with mesonephric-like carcinoma involving both ovaries and the uterus. Endometrioid adenofibroma was present in both ovaries, while adenomyosis was observed in the uterus. The glandular duct of the endometrioid adenofibroma in the right ovary had areas suggestive of precursor lesions of mesonephric-like carcinoma. All tumors exhibited the KRAS G12D mutation. These findings suggest that the origin of the mesonephric-like carcinoma was the Müllerian duct, and that the ovarian and uterine tumors were monoclonal.
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Adenocarcinoma , Adenofibroma , Carcinoma Endometrioide , Carcinoma , Femenino , Humanos , Anciano , Ovario/patología , Adenocarcinoma/patología , Útero/patología , Carcinoma Endometrioide/patologíaRESUMEN
BACKGROUND: Tuft cells are chemosensory epithelial cells playing a role in innate immunity. Recent studies revealed cancers with a tuft cell-like gene expression signature in the thorax. We wondered whether this signature might also occur in extrathoracic cancers. METHODS: We examined mRNA expression of tuft cell markers (POU2F3, GFI1B, TRPM5, SOX9, CHAT, and AVIL) in 19 different types of cancers in multiple extrathoracic organs with The Cancer Genome Atlas (TCGA) (N = 6322). Four different extrathoracic cancers in our local archives (N = 909) were analysed by immunohistochemistry. RESULTS: Twenty-two (0.35%) extrathoracic tumours with co-expression of POU2F3 and other tuft cell markers were identified in various TCGA datasets. Twelve of the 22 "tuft cell-like tumours" shared poor differentiation and a gene expression pattern, including KIT, anti-apoptotic BCL2, and ionocyte-associated genes. In our archival cases, eleven (1.21%) tumours co-expressing POU2F3, KIT, and BCL2 on immunohistochemistry, i.e., were presumable tuft cell-like cancers. In three among five TCGA cohorts, the tuft cell-like cancer subsets expressed SLFN11, a promising biomarker of PARP inhibitor susceptibility. CONCLUSIONS: Tuft cell-like carcinomas form distinct subsets in cancers of many organs. It appears warranted to investigate their shared gene expression signature as a predictive biomarker for novel therapeutic strategies.
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Carcinoma , Transcriptoma , Humanos , Células Epiteliales/patología , Carcinoma/patología , Biomarcadores/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Nucleares/metabolismoRESUMEN
A 39-year-old man had an intracranial tumour without infiltration into the surrounding cerebral tissue. The tumour recurred seven times in 11 years but maintained a well-demarcated character. Histopathological examination of the 4th surgical specimens showed nests of tumour cells surrounding small blood vessels. The tumour cells harboured amphophilic cytoplasm and small round nuclei with fine chromatin, and perinuclear haloes and clear borders were frequently observed, which was unclassifiable histology. By the Deutsches Krebsforschungszentrum methylation classifier, the tumour was not classified into any of the methylation classes. mRNA sequencing identified a novel SREBF1::NACC1 gene fusion. This intracranial tumour could be a novel tumour entity with NACC1 rearrangement showing characteristic histological and diagnostic imaging findings.
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Neoplasias Encefálicas , Fusión Génica , Masculino , Humanos , Adulto , Proteína 1 de Unión a los Elementos Reguladores de Esteroles , Proteínas de Neoplasias , Proteínas RepresorasRESUMEN
BACKGROUND: Diagnosis of fetal growth restriction (FGR) entails difficulties with differentiating fetuses not fulfilling their growth potential because of pathologic conditions, such as placental insufficiency, from constitutionally small fetuses. The feasibility of placental MRI for risk stratification among pregnancies diagnosed with FGR remains unexplored. PURPOSE: To explore quantitative MRI features useful to identify pregnancies with unfavorable outcomes and to assess the diagnostic performance of visual analysis of MRI to detect pregnancies with unfavorable outcomes, among pregnancies diagnosed with FGR. STUDY TYPE: Retrospective. POPULATION: Thirteen pregnancies with unfavorable outcomes (preterm emergency cesarean section or intrauterine fetal death) and 11 pregnancies with favorable outcomes performed MRI at gestational weeks 21-36. FIELD STRENGTH/SEQUENCE: A 5-T, half-Fourier-acquired single-shot turbo spin echo (HASTE), spin-echo echo-planar imaging (SE-EPI) and T2 map derived from SE-EPI. ASSESSMENT: Placental size on HASTE sequences and T2 mapping-based histogram features were extracted. Three radiologists qualitatively evaluated the visibility of maternal cotyledon on HASTE and SE-EPI sequences with echo times (TEs) = 60, 90, and 120 msec using 3-point Likert scales: 0, absent; 1, equivocal; and 2, present. STATISTICAL TESTS: Welch's t-test or Mann-Whitney U test for quantitative features between the favorable and unfavorable outcome groups. Areas under the receiver operating curves (AUCs) of the three readers' visual analyses to detect pregnancies with unfavorable outcomes. A P value of <0.05 was inferred as statistically significant. RESULTS: Placental size (major and minor axis, estimated area of placental bed, and volume of placenta) and T2 mapping-based histogram features (mean, skewness, and kurtosis) were statistically significantly different between the two groups. Visual analysis of HASTE and SE-EPI with TE = 60 msec showed AUCs of 0.80-0.86 to detect pregnancies with unfavorable outcomes. DATA CONCLUSION: Placental size, histogram features, and visual analysis of placental MRI may allow for risk stratification regarding outcomes among pregnancies diagnosed with FGR. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.
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Retardo del Crecimiento Fetal , Placenta , Recién Nacido , Humanos , Femenino , Embarazo , Retardo del Crecimiento Fetal/diagnóstico por imagen , Placenta/diagnóstico por imagen , Estudios Retrospectivos , Cesárea , Imagen por Resonancia Magnética/métodos , Medición de RiesgoRESUMEN
BACKGROUND: The European Society for Medical Oncology Precision Medicine Working Group (ESMO-PMWG) published recommendations regarding confirmatory germline testing for presumed germline pathogenic variants (PGPVs) in tumor-only comprehensive genomic profiling (CGP). However, the clinical validity of these recommendations has not been investigated in a real-world practice. METHODS: Medical records of 180 consecutive patients who obtained the results of a tumor-only CGP (FoundationOne® CDx, Foundation Medicine, Inc, Cambridge, MA, USA) between October 2018 and March 2020, were retrospectively reviewed. After excluding patients with no reported variants in 45 actionable genes (n = 6), or no archived germline DNA samples (n = 31), 143 patients were investigated. The PGPVs were selected from the CGP report and germline sequencing were performed using DNA samples archived in Clinical Bioresource Center in Kyoto University Hospital (Kyoto, Japan). RESULTS: A total of 195 variants were classified as PGPV based on the conventional criteria. Germline sequencing disclosed that 12 variants (6.2%) were of germline origin. In contrast, after filtering these 195 variants through the ESMO-PMWG recommendation criteria for confirmatory germline testing, following seven PGPVs, BRCA2 (n = 2), BRIP1 (n = 1), BAP1 (n = 1), PMS2 (n = 1), MSH2 (n = 1), and SDHB (n = 1) remained and six variants (85.7%) were confirmed to be of germline origin. CONCLUSION: Our current data suggested that the application of ESMO-PMWG criteria is helpful in selecting PGPVs with a high likelihood of germline origin in a tumor-only CGP in daily clinical practice.
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Mutación de Línea Germinal , Neoplasias , Genómica/métodos , Células Germinativas/patología , Mutación de Línea Germinal/genética , Humanos , Neoplasias/genética , Neoplasias/patología , Estudios RetrospectivosRESUMEN
Comprehensive genomic profiling (CGP) testing by next-generation sequencing has been introduced into clinical practice as part of precision cancer medicine to select effective targeted therapies. However, whether CGP testing at the time of first-line chemotherapy could be clinically useful is not clear. We conducted this single-center, prospective, observational study to investigate the feasibility of CGP testing for chemotherapy-naïve patients with stage III/IV gastrointestinal cancer, rare cancer, and cancer of unknown primary, using the FoundationOne® companion diagnostic (F1CDx) assay. The primary outcome was the detection rate of at least one actionable/druggable cancer genomic alteration. Actionable/druggable cancer genomic alterations were determined by the F1CDx report. An institutional molecular tumor board determined the molecular-based recommended therapies. A total of 197 patients were enrolled from October 2018 to June 2019. CGP success rate was 76.6% (151 of 197 patients), and median turnaround time was 19 days (range: 10-329 days). Actionable and druggable cancer genomic alterations were reported in 145 (73.6%) and 124 (62.9%) patients, respectively. The highest detection rate of druggable genomic alterations in gastrointestinal cancers was 80% in colorectal cancer (48 of 60 patients). Molecular-based recommended therapies were determined in 46 patients (23.4%). CGP testing would be a useful tool for the identification of a potentially effective first-line chemotherapy.
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Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Terapia Molecular Dirigida/métodos , Neoplasias/genética , Medicina de Precisión/métodos , Análisis de Secuencia de ADN/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Recently, several malignant peritoneal mesotheliomas (MPMs), occurring in young women without asbestos exposure and with fusion genes such as anaplastic lymphoma kinase (ALK) and Ewing sarcoma breakpoint region 1, have been reported. In the present case, we encountered MPM with STRN-ALK fusion in a 17-year-old female adolescent. The case did not respond to chemotherapy and is currently in a clinical trial of alectinib. This is the fourth reported case of MPM with STRN-ALK fusion. Of the 45 cancer cases with STRN-ALK fusion in which the fusion partners were examined, all cases except for the current case showed fusion of exon 3 of STRN and exon 20 of ALK. This is the first case with fusion of exon 2 of STRN and exon 20 of ALK. Further advances in cancer genomic medicine may help clarify the clinical significance of this new fusion. KEY POINTS: Malignant peritoneal mesotheliomas (MPMs) can occur in young women without asbestos exposure and show fusion genes that activate anaplastic lymphoma kinase (ALK) by gene rearrangement. ALK rearrangement and the fusion partner can be detected by companion diagnostics and by next generation sequencing. Patients with MPMs with ALK rearrangement may benefit from target therapy.
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Mesotelioma Maligno , Neoplasias Peritoneales , Adolescente , Quinasa de Linfoma Anaplásico/genética , Proteínas de Unión a Calmodulina/genética , Exones/genética , Femenino , Reordenamiento Génico , Humanos , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Proteínas de Fusión Oncogénica/genética , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/genéticaRESUMEN
BACKGROUND: Mutations in driver genes such as IDH and BRAF have been identified in gliomas. Meanwhile, dysregulations in the p53, RB1, and MAPK and/or PI3K pathways are involved in the molecular pathogenesis of glioblastoma. RAS family genes activate MAPK through activation of RAF and PI3K to promote cell proliferation. RAS mutations are a well-known driver of mutation in many types of cancers, but knowledge of their significance for glioma is insufficient. The purpose of this study was to reveal the frequency and the clinical phenotype of RAS mutant in gliomas. METHODS: This study analysed RAS mutations and their clinical significance in 242 gliomas that were stored as unfixed or cryopreserved specimens removed at Kyoto University and Osaka National Hospital between May 2006 and October 2017. The hot spots mutation of IDH1/2, H3F3A, HIST1H3B, and TERT promoter and exon 2 and exon 3 of KRAS, HRAS, and NRAS were analysed with Sanger sequencing method, and 1p/19q codeletion was analysed with multiplex ligation-dependent probe amplification. DNA methylation array was performed in some RAS mutant tumours to improve accuracy of diagnosis. RESULTS: RAS mutations were identified in four gliomas with three KRAS mutations and one NRAS mutation in one anaplastic oligodendroglioma, two anaplastic astrocytomas (IDH wild-type in each), and one ganglioglioma. RAS-mutant gliomas were identified with various types of glioma histology. CONCLUSION: RAS mutation appears infrequent, and it is not associated with any specific histological phenotype of glioma.
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Neoplasias Encefálicas/genética , Genes ras/genética , Glioma/genética , Mutación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Astrocitoma/genética , Neoplasias Encefálicas/patología , Niño , Preescolar , Metilación de ADN , Metilasas de Modificación del ADN/metabolismo , Análisis Mutacional de ADN/métodos , Enzimas Reparadoras del ADN/metabolismo , Exones/genética , Femenino , Glioblastoma/genética , Glioma/patología , Histonas/genética , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Persona de Mediana Edad , Oligodendroglioma/genética , Fenotipo , Regiones Promotoras Genéticas , Telomerasa/genética , Proteínas Supresoras de Tumor/metabolismo , Adulto JovenRESUMEN
BACKGROUND : Accurate preoperative assessment of the longitudinal extension of perihilar cholangiocarcinoma (PHCC) is essential for treatment planning. Mapping biopsies for PHCC remain challenging owing to technical difficulties and insufficient sample amounts. The aim of this study was to investigate the usefulness of a novel technique for mapping biopsies of PHCC. METHODS : Our novel method focused on a biliary stent delivery system for mapping biopsies. Fifty patients with PHCC undergoing endoscopic transpapillary mapping biopsy using the novel method were reviewed from August 2015 to June 2019. RESULTS : The median number of biopsy samples was six (range 1â-â17), and the rate of adequate sampling was 91.4â% (266â/291). Biopsy from the intrahepatic bile duct was possible in 82.0â% of patients (41â/50), and negative margins were confirmed in the resected specimens from 34â/39 patients who underwent surgery (87.2â%). None of the patients had post-endoscopic retrograde cholangiopancreatography pancreatitis. CONCLUSIONS : With our novel method, accurate assessment of the longitudinal extension of PHCC might be expected with minimal trauma to the duodenal papilla.