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BACKGROUND AND AIMS: In the management of ulcerative colitis (UC), histological remission is increasingly recognized as the ultimate goal. The absence of neutrophil infiltration is crucial for assessing remission. This study aimed to develop an artificial intelligence (AI) system capable of accurately quantifying and localizing neutrophils in UC biopsy specimens to facilitate histological assessment. METHODS: Our AI system, which incorporates semantic segmentation and object detection models, was developed to identify neutrophils in hematoxylin-eosin-stained whole slide images. The system assessed the presence and location of neutrophils within either the epithelium or lamina propria and predicted components of the Nancy Histological Index (NHI) and the PICaSSO Histologic Remission Index (PHRI). We evaluated the system's performance against that of experienced pathologists and validated its ability to predict future clinical relapse risk in patients with clinically remitted UC. The primary outcome measure was the clinical relapse rate, defined as a partial Mayo score of ≥3. RESULTS: The model accurately identified neutrophils, achieving a performance of 0.77, 0.81, and 0.79 for precision, recall, and F-score, respectively. The system's histological score predictions showed a positive correlation with the pathologists' diagnoses (Spearman's ρ = 0.68-0.80, P < .05). Among patients who relapsed, the mean number of neutrophils in the rectum was higher than in those who did not relapse. Furthermore, the study highlighted that higher AI-based PHRI and NHI scores were associated with hazard ratios increasing from 3.2 to 5.0 for evaluating the risk of UC relapse. CONCLUSION: The AI system's precise localization and quantification of neutrophils proved valuable for histological assessment and clinical prognosis stratification.
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BACKGROUND: For women diagnosed with hereditary breast and ovarian cancer, the clinical guidelines recommend risk-reducing salpingo-oophorectomy at age 35-40 years or after completion of childbearing. However, there is limited information regarding the current status of risk-reducing salpingo-oophorectomy in Japan. METHODS: To clarify factors influencing decision-making for risk-reducing salpingo-oophorectomy among Japanese women diagnosed with hereditary breast and ovarian cancer and their clinical outcomes, we analyzed the medical records of 157 Japanese women with germline BRCA pathogenic variants (BRCA1 n = 85, BRCA2 n = 71 and both n = 1) at our institution during 2011-21. Specimens obtained from risk-reducing salpingo-oophorectomy were histologically examined according to the sectioning and extensively examining the fimbriated end protocol. RESULTS: The risk-reducing salpingo-oophorectomy uptake rate was 42.7% (67/157). The median age at risk-reducing salpingo-oophorectomy was 47 years. Older age, married state and parity were significantly associated with risk-reducing salpingo-oophorectomy (P < 0.001, P = 0.002 and P = 0.04, respectively). History of breast cancer or family history of ovarian cancer did not reach statistical significance (P = 0.18 and P = 0.14, respectively). Multivariate analyses revealed that older age (≥45 years) and married state may be independent factors associated with risk-reducing salpingo-oophorectomy. Interestingly, the annual number of risk-reducing salpingo-oophorectomy peaked in 2016-17 and has increased again since 2020. The rate of occult cancers at risk-reducing salpingo-oophorectomy was 4.5% (3/67): ovarian cancer (n = 2) and serous tubal intraepithelial carcinoma (n = 1). CONCLUSION: Age and marital status significantly affected decision-making for risk-reducing salpingo-oophorectomy. This is the first study to suggest possible effects of Angelina Jolie's risk-reducing salpingo-oophorectomy in 2015 and the National Health Insurance introduced for risk-reducing salpingo-oophorectomy in 2020. The presence of occult cancers at risk-reducing salpingo-oophorectomy supports clinical guidelines recommending risk-reducing salpingo-oophorectomy at younger ages.
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Neoplasias de la Mama , Neoplasias Ováricas , Femenino , Humanos , Persona de Mediana Edad , Adulto , Salpingooforectomía , Pueblos del Este de Asia , Mutación , Neoplasias Ováricas/genética , Neoplasias Ováricas/prevención & control , Neoplasias Ováricas/cirugía , Neoplasias de la Mama/genética , Neoplasias de la Mama/prevención & control , Neoplasias de la Mama/cirugía , Ovariectomía , Predisposición Genética a la EnfermedadRESUMEN
A 75-year-old man who had lymphadenopathy was admitted to our hospital. Histopathological examination of cervical lymph node biopsy specimens showed diffuse proliferation of lymphoma cells with large nuclei. In immunohistochemistry, the lymphoma cells were positive for CD5, CD10, CD20, BCL2, BCL6, and MYC. The patient was diagnosed with CD5- and CD10-positive diffuse large B-cell lymphoma (DLBCL). MYD88L265P mutations have been detected in DLBCL. Partial response was achieved after six courses of R-THP-COP therapy. However, the patient died because of disease progression 18 months after the diagnosis. On autopsy, lymphoma cells were found in the lymph nodes throughout the body, central nervous system, adrenals, and skin. CD5- and CD10-positive DLBCL account for 0.5-1% of DLBCL cases and have a very poor disease prognosis. This is a rare case of CD5- and CD10-positive DLBCL with MYC and BCL2 expressions harboring MYD88L265P mutation.
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Linfoma de Células B Grandes Difuso , Factor 88 de Diferenciación Mieloide , Masculino , Humanos , Anciano , Factor 88 de Diferenciación Mieloide/genética , Linfoma de Células B Grandes Difuso/diagnóstico , Pronóstico , Mutación , Proteínas Proto-Oncogénicas c-bcl-2/genéticaRESUMEN
Microbubble testing using transcranial Doppler (TCD) is an important screening tool for diagnosing paradoxical cerebral embolism with high-risk PFO. However, little is known about the association between the microbubble test by TCD and the features of high-risk PFO evaluated by transesophageal echocardiography (TEE). We studied 101 consecutive patients at Showa University, from April 2019 to October 2020, who underwent both TCD and TEE with a sufficient Valsalva maneuver and who were strongly suspected by neurologists as cryptogenic stroke. According to the appearance of microbubbles as high-intensity transient signals (HITS), the TCD grade was stratified into three categories based on the criteria (A: none, no HITS, B: small; 1-10 HITS, and C: large; > 10 HITS, or an uncountable number of HITS). Among patients with RLS through the PFO in TEE, high-risk morphological features of PFO for cerebral embolism were evaluated as follows: (1) tunnel height, (2) tunnel length, (3) total excursion distance of the atrial septum into the right and left atrium, (4) existence of Eustachian valve or Chiari network, (5) angle of PFO from the inferior vena cava, and (6) large shunt (20 or more microbubbles). Of 101 patients (TCD grade; Group A = 49, Group B = 26, Group C = 26), RLS through PFO was detected in 37 patients (grade A = 8, grade B = 6, grade C = 23) by TEE. Among PFO-positive patients, tunnel height, length, total excursion distance into the right and left atria, angle of PFO from the inferior vena cava, and frequency of large shunt in TEE were significantly larger in grade C than in grade A and B (p < 0.05). Additionally, grade C patients had significantly more forms of high-risk PFOs than those in grades A and B when the six features of high-risk PFO were compared. A multivariate logistic regression demonstrated that the tunnel length of PFO and the presence of large shunt in TEE were independently associated with large HITS in TCD (odds ratio: 1.18 and 49.5, 95% confidence interval 1.043-1.337 and 10.05-244.3, p = 0.0086 and p < 0.0001, respectively). In conclusion, the existence of a large HITS detected by TCD may have a screening advantage in predicting the high-risk morphologies of PFO that can cause paradoxical cerebral embolism.
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Foramen Oval Permeable , Embolia Intracraneal , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Foramen Oval Permeable/complicaciones , Foramen Oval Permeable/diagnóstico por imagen , Embolia Intracraneal/diagnóstico por imagen , Embolia Intracraneal/etiología , Ultrasonografía Doppler Transcraneal/efectos adversos , Ecocardiografía Transesofágica , Accidente Cerebrovascular/etiologíaRESUMEN
One of the hallmarks of cancer, global gene expression alteration, is closely associated with the development and malignant characteristics associated with adult T-cell leukemia (ATL) as well as other cancers. Here, we show that aberrant overexpression of the Ellis Van Creveld (EVC) family is responsible for cellular Hedgehog (HH) activation, which provides the pro-survival ability of ATL cells. Using microarray, quantitative RT-PCR and immunohistochemistry we have demonstrated that EVC is significantly upregulated in ATL and human T-cell leukemia virus type I (HTLV-1)-infected cells. Epigenetic marks, including histone H3 acetylation and Lys4 trimethylation, are specifically accumulated at the EVC locus in ATL samples. The HTLV-1 Tax participates in the coordination of EVC expression in an epigenetic fashion. The treatment of shRNA targeting EVC, as well as the transcription factors for HH signaling, diminishes the HH activation and leads to apoptotic death in ATL cell lines. We also showed that a HH signaling inhibitor, GANT61, induces strong apoptosis in the established ATL cell lines and patient-derived primary ATL cells. Therefore, our data indicate that HH activation is involved in the regulation of leukemic cell survival. The epigenetically deregulated EVC appears to play an important role for HH activation. The possible use of EVC as a specific cell marker and a novel drug target for HTLV-1-infected T-cells is implicated by these findings. The HH inhibitors are suggested as drug candidates for ATL therapy. Our findings also suggest chromatin rearrangement associated with active histone markers in ATL.
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Epigénesis Genética , Proteínas Hedgehog/metabolismo , Leucemia de Células T/genética , Proteínas/genética , Antineoplásicos/farmacología , Secuencia de Bases , Estudios de Casos y Controles , Supervivencia Celular , Islas de CpG , Metilación de ADN , Regulación Leucémica de la Expresión Génica , Productos del Gen tax/fisiología , Células HEK293 , Humanos , Células Jurkat , Leucemia de Células T/metabolismo , Proteínas de la Membrana , Datos de Secuencia Molecular , Proteínas/metabolismo , Piridinas/farmacología , Pirimidinas/farmacología , Análisis de Secuencia de ADN , Transducción de Señal , Transcripción GenéticaRESUMEN
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy associated with a poor prognosis and limited treatment options. Although allogeneic hematopoietic stem cell transplantation or intensive chemotherapy prolongs overall survival in patients with BPDCN, intensive chemotherapy is inappropriate for older or unfit patients. Venetoclax (VEN), an oral BCL2 inhibitor, is approved for use in patients with acute myeloid leukemia (AML). BPDCN cells require BCL2 protein and are uniformly sensitive to VEN in vivo. Moreover, patients with AML who have achieved complete remission after induction therapy are reportedly considered to receive VEN monotherapy as maintenance therapy, especially older patients. However, the efficacy of VEN monotherapy as a maintenance therapy for patients with BPDCN remains controversial. Recently, BPDCN has been classified into MYC+ and MYC- subtypes, which show clinical differences. Hence, BPDCN treatment strategies based on the MYC classification may be necessary. Here, we report a case of MYC- BPDCN in an older patient in long-term complete remission after VEN monotherapy following VEN and azacitidine induction chemotherapy.
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Common extrahepatic metastasis sites of hepatocellular carcinoma (HCC) are the lungs, adrenal glands, and bones. Herein, we report a rare case of metastatic gastric, pancreatic, and renal tumors from HCC simultaneously, and review the relevant literature. A 75-year-old woman presented with right hypochondralgia, appetite loss, and weight loss. Computed tomography revealed suspected metastatic liver, lung, and renal tumors. A blood test revealed a leukocyte count of 26,210/µL and a high inflammatory reaction. As sepsis was suspected, the patient was referred to our hospital. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging revealed a hypovascular liver tumor that was suspected to be metastatic. Upper gastrointestinal endoscopy revealed two suspected metastatic gastric tumors. Liver and gastric tumor biopsies revealed poor carcinoma in both. The patient's condition gradually worsened and she died on day 8 of the illness. Based on autopsy findings, the patient was finally diagnosed with metastatic gastric and renal tumors originating from HCC. Additionally, a metastatic pancreatic tumor originating from the HCC was identified during autopsy. The pathological diagnosis of the pulmonary lesion was primary lung adenocarcinoma. In conclusion, HCC should be suspected in cases with multiple metastases of unknown primary lesions.
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Carcinoma Hepatocelular , Neoplasias Renales , Neoplasias Hepáticas , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Femenino , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/diagnóstico por imagen , Carcinoma Hepatocelular/secundario , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/diagnóstico por imagen , Anciano , Neoplasias Renales/patología , Neoplasias Gástricas/patología , Neoplasias Gástricas/secundario , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/secundario , Neoplasias Pancreáticas/diagnóstico por imagen , Resultado Fatal , Imagen por Resonancia Magnética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Tomografía Computarizada por Rayos XRESUMEN
Diffuse large B-cell lymphoma (DLBCL) exhibits clinical, genetic, and immunohistochemical heterogeneity. However, the differences between primary extranodal or nodal DLBCL and double-expressor lymphoma (DEL), which is characterized by high MYC and BCL2 expression, remain unclear. This study aimed to elucidate the clinicopathological features, response to therapy, and clinical outcomes of primary extranodal (n=61) and nodal (n=128) DLBCL. Patients with primary nodal DLBCL had higher BCL2 expression than those with extranodal DLBCL (p=0.048), with high MYC expression and DEL as poor prognostic factors. Conversely, in patients with primary extranodal DLBCL, high BCL2 expression, low BCL6 expression, non-germinal center B-cell-like type, and DEL indicated poor prognosis. DEL was significantly associated with progression free survival and overall survival in patients with primary extranodal DLBCL (p=0.014 and p=0.021, respectively) but not in patients with primary nodal DLBCL (p=0.37 and p=0.084, respectively). Our findings highlight primary extranodal DEL as a strong adverse prognostic factor in DLBCL.
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Linfoma de Células B Grandes Difuso , Proteínas Proto-Oncogénicas c-bcl-2 , Proteínas Proto-Oncogénicas c-myc , Humanos , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/genética , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Femenino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Anciano , Adulto , Pronóstico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Anciano de 80 o más Años , Adulto JovenRESUMEN
Pancreatic solid pseudopapillary neoplasm (SPN) is a low-grade malignant neoplasm with a good prognosis. Clinically aggressive SPNs have rarely been reported but have not been analyzed in detail. In this study, we referred to this highly malignant type of SPN as high-grade SPN (HG-SPN) and compared its clinicopathological and genetic characteristics with conventional SPN (C-SPN) using immunohistochemistry and gene panel analyses. Five HG-SPNs and 15 C-SPNs were evaluated in this study. HG-SPNs share many pathologic characteristics: macroscopically, solid/cystic appearances, microscopically, pseudopapillary/pseudorosette pattern (100%), tumor cell loose cohesiveness (100%), thin/delicate vasculature (100%), tumor cell cytoplasmic vacuolization (100%), immunohistochemical positivity for ß-catenin (nuclear expression) (100%), CD10 (80%), CD56 (80%), and vimentin (100%). Conversely, HG-SPNs showed distinct malignant features compared with C-SPNs: mean tumor size (11.7 vs. 2.9 cm, P <0.001); true necrosis (100% vs. 0%, P <0.001); high-grade nuclear atypia (100% vs. 0%, P <0.001); lymphatic and/or venous invasion (100% vs. 20%, P =0.004); mean mitotic count (4.38 vs. 0.05/high-power field, P <0.001); and mean Ki-67 labeling index (33.9% vs. 3.4%, P <0.001). All HG-SPN patients died of primary disease 3 to 36 months after surgery, while all C-SPN patients were alive without disease. Genetic studies have shown that all analyzed HG-SPNs have CTNNB1 mutations. Two HG-SPN cases showed RB1 mutations with altered immunohistochemical findings for RB1 and p16. Two HG-SPN cases had TP53 mutation and/or p53 overexpression. In conclusion, HG-SPNs show distinct malignant features and some genetic alterations that differ from C-SPNs, indicating the importance of differentiating between these 2 subtypes.
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Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Páncreas/patología , MutaciónRESUMEN
The usefulness of the transmission electron microscope (TEM) for pathological diagnosis is apparent. However, high operating costs and other disadvantages have limited the ability to maintain and operate a TEM. In recent years, a general-purpose benchtop low-vacuum scanning electron microscope (LVSEM), which is inexpensive and easy to operate, has been developed and is expected to be applied in electron microscopic pathological diagnosis. To date, we have previously observed TEM ultrathin sections of Immunoglobulin A (IgA) nephropathy with a benchtop LVSEM using an ultra variable-pressure detector (UVD) and a newly developed holder for observing scanning transmission electron microscope (STEM) images (UVD-STEM holder) and compared the images with those obtained with typical TEM observations. We reported the results in the 53rd Annual Meeting of the Japanese Society for Clinical Molecular Morphology and the 64th Symposium of The Japanese Society of Microscopy and discussed the validity of the methods in the pathological diagnosis of IgA nephropathy and other renal diseases. As a result, we demonstrated the potential for pathological diagnosis using benchtop LVSEM. In this study, we similarly examined typical kidney diseases such as membranous nephropathy, lupus nephritis and amyloidosis. We could obtain sufficient data for the pathological diagnosis of IgA nephropathy, membranous nephropathy and lupus nephritis. However, it is difficult to detect amyloid fibres that are characteristic of amyloidosis. The development of this method is expected to expand the possibilities for pathological diagnosis using electron microscopy, including its application to other diseases.
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Glomerulonefritis por IGA , Glomerulonefritis Membranosa , Nefritis Lúpica , Humanos , Vacio , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/patología , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/patología , Microscopía Electrónica , Inmunoglobulina A , BiopsiaRESUMEN
Indocyanine green fluorescence imaging (ICG-FI)-a sensitive tool for detecting tumor localization in laparoscopic surgery-produces false positive results for benign liver tumors. This report is the first case of hepatic angiomyolipoma (HAML) treated laparoscopically with ICG-FI. We present the case of a 31-year-old woman with a liver tumor that was a 13-mm mass in the anterior superior segment. Though a benign tumor was suspected, malignant potential could not be ruled out. Therefore, minimally invasive laparoscopic resection using ICG-FI was planned. ICG, intravenously injected preoperatively, revealed the tumor's existence. Pure laparoscopic hepatectomy with ICG-FI was performed for excisional biopsy, during which the tumor was resected with adequate surgical margins, followed by histological confirmation of HAML. In conclusion, it is suggested that laparoscopic resection with ICG-FI is an effective minimal invasive surgery for tumors that are difficult to detect, such as HAML, leading to a safe surgical margin.
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Angiomiolipoma , Neoplasias Gastrointestinales , Laparoscopía , Neoplasias Hepáticas , Femenino , Humanos , Adulto , Verde de Indocianina , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Angiomiolipoma/diagnóstico por imagen , Angiomiolipoma/cirugía , Hepatectomía/métodos , Imagen Óptica/métodos , Neoplasias Gastrointestinales/cirugía , Laparoscopía/métodosRESUMEN
Background: Cancer of unknown primary (CUP) is a malignant tumor without a known primary lesion with a frequency of 3-5%. It can be divided into favorable and unfavorable prognosis subsets. While recommended treatments are available for the former group, there is no established treatment for the latter. Here, we report the effective treatment of a 32-year-old woman with p16-positive squamous cell CUP with pembrolizumab plus 5-fluorouracil and cisplatin therapy. Case presentation: A 32-year-old woman presented with metastatic lesions in the liver, lung, bone, cervical region, abdominal region, and pelvic lymph nodes. She was diagnosed with p16-positive squamous cell carcinoma of unknown primary origin. The patient received pembrolizumab plus 5-fluorouracil and cisplatin therapy, which markedly reduced the metastasis and improved her Eastern Cooperative Oncology Group performance status after two courses. Conclusion: This case report highlights the potential of pembrolizumab plus 5-fluorouracil and cisplatin therapy for treating CUP with an unfavorable prognosis. p16 positivity is worth examining for squamous cell carcinoma of unknown primary origin, and if present, this therapy should be considered a promising treatment option.
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BACKGROUND: Hormone receptor (HR)-positive breast cancer is a disease for which no immune checkpoint inhibitors have shown promise as effective therapies. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors synergistically increased the effectiveness of antiprogrammed cell death protein-1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) antibodies in preclinical studies. METHODS: This non-randomized, multicohort, phase II study evaluated the efficacy and safety of the anti-PD-1 antibody nivolumab 240 mg administered every 2 weeks in combination with the CDK4/6 inhibitor abemaciclib 150 mg twice daily and either fulvestrant (FUL) or letrozole (LET) as a first-line or second-line treatment for HR-positive HER2-negative metastatic breast cancer. The primary end point was the objective response rate (ORR), and secondary end points were toxicity, progression-free survival, and overall survival. Blood, tissue, and fecal samples were collected at multiple points for correlative studies to evaluate immunity biomarkers. RESULTS: From June 2019 to early study termination due to safety concerns on July 2020, 17 patients were enrolled (FUL: n=12, LET: n=5). One patient with a prior treatment history in the FUL cohort was excluded. ORRs were 54.5% (6/11) and 40.0% (2/5) in the FUL and LET cohorts, respectively. Treatment-emergent (TE) adverse events (AEs) of grade ≥3 occurred in 11 (92%) and 5 (100%) patients in the FUL and LET cohorts, respectively. The most common grade ≥3 TEAEs were neutropenia (7 (58.3%) and 3 (60.0%) in the FUL and LET cohorts, respectively), followed by alanine aminotransferase elevation (5 (41.6%) and 4 (80.0%)). One treatment-related death from interstitial lung disease occurred in the LET cohort. Ten patients developed liver-related grade ≥3 AEs. Liver biopsy specimens from 3 patients showed hepatitis characterized by focal necrosis with predominant CD8+ lymphocyte infiltration. Marked elevation of tumor necrosis factor-related cytokines and interleukin-11, and a decrease in peripheral regulatory T cells (Tregs), were observed in patients with hepatotoxicity. These findings suggest that treatment-related toxicities were immune-related AEs likely caused by proinflammatory cytokine production and suppression of Treg proliferation due to the addition of abemaciclib to nivolumab therapy. CONCLUSIONS: Although the combination of nivolumab and abemaciclib was active, it caused severe and prolonged immune-related AEs. TRIAL REGISTRATION NUMBER: JapicCTI-194782, jRCT2080224706, UMIN000036970.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Nivolumab/uso terapéutico , Aminopiridinas/uso terapéutico , Bencimidazoles/uso terapéutico , Letrozol , AnticuerposRESUMEN
Immune checkpoint inhibitors (ICIs) are among the most notable advances in cancer immunotherapy; however, reliable biomarkers for the efficacy of ICIs are yet to be reported. Programmed death (PD)-ligand 1 (L1)-expressing CD14+ monocytes are associated with shorter overall survival (OS) time in patients with cancer treated with anti-PD-1 antibodies. The present study focused on the classification of monocytes into three subsets: Classical, intermediate and non-classical. A total of 44 patients with different types of cancer treated with anti-PD-1 monotherapy (pembrolizumab or nivolumab) were enrolled in the present study. The percentage of each monocyte subset was investigated, and the percentage of cells expressing PD-L1 or PD-1 within each of the three subsets was further analyzed. Higher pretreatment classical monocyte percentages were correlated with shorter OS (r=-0.32; P=0.032), whereas higher non-classical monocyte percentages were correlated with a favorable OS (r=0.39; P=0.0083). PD-L1-expressing classical monocytes accounted for a higher percentage of the total monocytes than non-classical monocytes with PD-L1 expression. In patients with non-small cell lung cancer (NSCLC), a higher percentage of PD-L1-expressing classical monocytes was correlated with shorter OS (r=-0.60; P=0.012), which is similar to the observation for the whole patient cohort. Comparatively, higher percentages of non-classical monocytes expressing PD-L1 were significantly associated with better OS, especially in patients with NSCLC (r=0.60; P=0.010). Moreover, a higher percentage of non-classical monocytes contributed to prolonged progression-free survival in patients with NSCLC (r=0.50; P=0.042), with similar results for PD-L1-expressing non-classical monocytes. The results suggested that the percentage of monocyte subsets in patients with cancer before anti-PD-1 monotherapy may predict the treatment efficacy and prognosis. Furthermore, more classical monocytes and fewer non-classical monocytes, especially those expressing PD-L1, are involved in shortening OS time, which may indicate the poor efficiency of anti-PD-1 treatment approaches.
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Introduction: Programmed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method. Methods: In total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression. Results: PD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group. Conclusion: Quantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antígeno B7-H1/metabolismo , Reproducibilidad de los Resultados , Recurrencia Local de Neoplasia/tratamiento farmacológicoRESUMEN
BACKGROUND: Mucin depletion is one of the histological indicators of clinical relapse among patients with ulcerative colitis (UC). Mucin depletion is evaluated semiquantitatively by pathologists using histological images. Therefore, the interobserver concordance is not extremely high, and an objective evaluation method is needed. This study was conducted to demonstrate that our automated quantitative method using a deep learning-based model is useful in predicting the prognosis of patients with UC. METHODS: Deep learning-based models were trained to detect goblet cell mucus area from whole slide images of biopsy specimens. This study involved 114 patients with UC in endoscopic remission with a partial Mayo score of ≤ 1. Biopsy specimens were collected during colonoscopy, and the ratio of goblet cell mucus area to the epithelial cell and goblet cell mucus area was calculated as goblet cell ratio (GCR). The follow-up time was 12 months, and the primary outcome was the relapse rate. Clinical relapse was defined as partial Mayo score of ≥ 3. RESULTS: Sixteen patients (14%) experienced clinical relapse. In the relapsed group, the GCRs of specimens obtained from the cecum, ascending colon, and rectum were significantly lower than those of specimens in the relapse-free group (p = 0.010, p = 0.027, p < 0.01). In the rectum, patients with a GCR of ≤ 12% had a significantly higher relapse rate than those with a GCR of > 12% (45% [10/22] vs. 6.5% [6/92]; p < 0.01). CONCLUSIONS: Quantifying goblet cell mucus areas using a deep learning-based model is useful in predicting the clinical relapse in patients with UC in clinical and endoscopic remission.
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Colitis Ulcerosa , Aprendizaje Profundo , Células Caliciformes , Mucinas , Humanos , Colitis Ulcerosa/diagnóstico por imagen , Colitis Ulcerosa/patología , Colonoscopía , Células Caliciformes/patología , Mucosa Intestinal/diagnóstico por imagen , Mucosa Intestinal/patología , Mucinas/deficiencia , Moco , Recurrencia , Inducción de Remisión , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Patients with metastatic urothelial carcinoma have poor prognosis and limited treatment options. CASE PRESENTATION: The patient was a 60-year-old male with bladder cancer and multiple lung metastases. He underwent three courses of gemcitabine and cisplatin chemotherapy, despite left femoral bone metastases. Tumor resection and bone replacement surgery was performed. Following the administration of four courses of pembrolizumab, lung metastasis completely resolved. However, after nine courses, right femoral neck bone metastasis was observed; therefore, tumor resection and bone replacement surgery were repeated. Pathologically, PD-L1 expression was low in lung biopsy tissue and bone metastases. Pembrolizumab treatment continued for up to 20 courses; cancer recurrence and adverse events were not observed upon follow-up examination after 1 year. CONCLUSION: Patients responding well to systemic therapy may have resectable metastatic sites, and long-term survival might be achieved with adjunctive metastasectomy. The effect of pembrolizumab was not associated with positive PD-L1 expression.
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Background: We explored the histologic patterns of and age-related changes in atrial and ventricular myocardial contiguity at the left and right atrioventricular (AV) junction that could be a target site for catheter ablation. MethodsâandâResults: Twenty-three structurally normal adult hearts obtained at autopsy were studied. The 2 AV annuli were divided into 13 clinically recognized portions in which we measured distance between the atrial and ventricular myocardium at the AV junction. Overall, measured distance was less on the right than left side (mean [±SD] 0.74±0.59 vs. 1.15±0.78 mm, respectively), and distance increased gradually with age. The gap was smallest at the anterolateral portion on the right side and posterolateral portion on the left side. Three specific features were noted, namely extension of the ventricular myocardium (coarse trabeculae) towards the atrium on the right side of the AV junction, extension of the atrial myocardium onto the AV valve leaflets, and a collection of small myocardial cells, perhaps including specialized cells, in the right anterolateral portion. No concealed AV muscular connections were found. Conclusions: Contiguity and separation of the myocardium at the AV junction have specific patterns, and myocardial proximity is influenced by age. These histologic features of the AV junction may prove to be informative for catheter ablation of tachyarrhythmias related to the AV junction.
RESUMEN
There are few case reports of hepatocellular carcinoma (HCC) metastasis to the skeletal muscle. A 78-year-old man developed a mass in the right shoulder. Washout of contrast medium during contrast-enhanced ultrasonography (CEUS) in both the primary HCC and the metastatic site was detected. Several nodules were scattered throughout the liver on an autopsy. In addition, the moderately differentiated HCC had metastasized to the right teres major muscle. Rare muscular metastasis should be considered if a hepatic tumor is moderately or poorly differentiated HCC. Early washout during CEUS is consistent with a pathological diagnosis of moderately or poorly differentiated HCC.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Anciano , Carcinoma Hepatocelular/diagnóstico por imagen , Medios de Contraste , Humanos , Aumento de la Imagen , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , UltrasonografíaRESUMEN
BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) can visualize microscopic structures at high resolution but has not yet yielded definitive diagnostic features of gallbladder malignancy, as opposed to benign changes. PATIENTS AND METHODS: A total of 73 patients had their gallbladder evaluated with pCLE performed on resected benign and malignant gallbladder surgical specimens, which were sprayed with fluorescein. Malignant and benign features of pCLE findings were identified on the basis of Miami and Paris Classifications. Standard histopathological diagnoses and individual patient pCLE findings of gallbladder lesions were correlated. RESULTS: Of the 73 consecutive patients that had their gallbladder evaluated ex vivo with pCLE, 11 were identified with gallbladder malignancy. pCLE identified features of gallbladders examined ex vivo, including the presence of thick dark bands and dark clumps, which together correlated with histopathologically-determined biliary malignancy at 100% sensitivity. Thick white bands and visualized epithelium, also identified with pCLE, together correlated with histopathologically-determined malignancy at 100% specificity. CONCLUSION: pCLE can be used for real-time differentiation of cancerous/non-cancerous regions in the gallbladder using the diagnostic criteria identified in the present study.