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The presence of Fusobacterium nucleatum is associated with an immunosuppressive tumor immune microenvironment (TIM) in primary colorectal cancer (CRC), contributing to tumor progression. Its persistence in CRC liver metastasis tissues raises questions about its role in modulating local and systemic immune responses and influencing recurrence patterns. This retrospective cohort study of 218 patients with CRC liver metastasis investigated the association of F. nucleatum in CRC liver metastasis tissues with systemic inflammation, TIM alterations, and the number of metastatic organs involved in recurrence. Two-step polymerase chain reaction (PCR), including digital PCR, detected F. nucleatum in 42% (92/218) of fresh-frozen specimens of CRC liver metastases. Compared with the F. nucleatum-none group, the F. nucleatum-high group showed higher C-reactive protein levels (0.82 vs. 0.22 mg/dL; Ptrend = 0.02), lower numbers of CD8+ cells (33.2 vs. 65.3 cells/mm2; Ptrend = 0.04) and FOXP3+ cells (11.3 vs. 21.7 cells/mm2; Ptrend = 0.01) in the TIM, and a greater number of metastatic organs involved in recurrence (1.6 vs. 1.1; p < 0.001). The presence of F. nucleatum in CRC liver metastasis tissues was associated with increased systemic inflammation, TIM alterations, and a greater number of metastatic organs involved in recurrence. These findings suggest a potential contribution of F. nucleatum to the metastatic propensity of CRC cells and could inform future research to enhance understanding of the interaction between tumor, host, and microbes in the metastatic process.
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BACKGROUND AND AIMS: Immunotherapy has become the standard-of-care treatment for hepatocellular carcinoma (HCC), but its efficacy remains limited. To identify immunotherapy-susceptible HCC, we profiled the molecular abnormalities and tumor immune microenvironment (TIME) of rapidly increasing nonviral HCC. APPROACHES AND RESULTS: We performed RNA-seq of tumor tissues in 113 patients with nonviral HCC and cancer genome sequencing of 69 genes with recurrent genetic alterations reported in HCC. Unsupervised hierarchical clustering classified nonviral HCCs into three molecular classes (Class I, II, III), which stratified patient prognosis. Class I, with the poorest prognosis, was associated with TP53 mutations, whereas class III, with the best prognosis, was associated with cadherin-associated protein beta 1 (CTNNB1) mutations. Thirty-eight percent of nonviral HCC was defined as an immune class characterized by a high frequency of intratumoral steatosis and a low frequency of CTNNB1 mutations. Steatotic HCC, which accounts for 23% of nonviral HCC cases, presented an immune-enriched but immune-exhausted TIME characterized by T cell exhaustion, M2 macrophage and cancer-associated fibroblast (CAF) infiltration, high PD-L1 expression, and TGF-ß signaling activation. Spatial transcriptome analysis suggested that M2 macrophages and CAFs may be in close proximity to exhausted CD8+ T cells in steatotic HCC. An in vitro study showed that palmitic acid-induced lipid accumulation in HCC cells upregulated PD-L1 expression and promoted immunosuppressive phenotypes of cocultured macrophages and fibroblasts. Patients with steatotic HCC, confirmed by chemical-shift MR imaging, had significantly longer PFS with combined immunotherapy using anti-PD-L1 and anti-VEGF antibodies. CONCLUSIONS: Multiomics stratified nonviral HCCs according to prognosis or TIME. We identified the link between intratumoral steatosis and immune-exhausted immunotherapy-susceptible TIME.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Multiómica , Pronóstico , Linfocitos T CD8-positivos , Microambiente TumoralRESUMEN
AIM: Vessels encapsulating tumor clusters (VETC) represents an adverse prognostic morphological feature of hepatocellular carcinoma (HCC), which is associated with an immunosuppressive tumor immune microenvironment (TIM). However, the underlying factors characterizing the TIM in HCC with a VETC pattern (VETC-positive HCC) remain uncertain. Oncostatin M (OSM), a pleiotropic cytokine of the interleukin-6 family, regulates various biological processes, including inflammation, proliferation, and invasiveness of tumor cells. We aimed to test a hypothesis that OSM is associated with the immunosuppressive TIM of VETC-positive HCC. METHODS: A total of 397 consecutive HCC patients with curative-intent hepatectomy were included. OSM-positive cells and inflammatory cells including CD4-, CD8-, CD163-, and FOXP3-positive cells were immunohistochemically evaluated. We compared VETC-positive and VETC-negative HCCs in terms of the number of these cells. RESULTS: We found the VETC pattern in 62 patients (15.6%). Our analysis revealed a significant decrease in the expression of arginase-1, a marker associated with mature hepatocyte differentiation, in VETC-positive HCC (p = 0.046). The number of tumor-infiltrating OSM-positive cells was significantly low in VETC-positive HCC (p = 0.0057). Notably, in VETC-positive HCC, the number of OSM-positive cells was not associated with vascular invasion, whereas in VETC-negative HCC, an increase in the number of OSM-positive cells was associated with vascular invasion (p = 0.042). CONCLUSIONS: We identified an association between a decrease in OSM-positive cells and the VETC pattern. Additionally, our findings indicate that VETC-positive HCC is characterized by low hepatocyte differentiation and OSM-independent vascular invasion. These findings highlight the potential interaction between VETC-positive HCC cells and their TIM through the reduction of OSM-expressing cells.
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Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. While mitotane is the only agent approved for ACC, clinical data are scarce, especially in the Asian population. We reviewed 10 patients with ACC who received mitotane as a single agent or in combination with other agents in our institution. Patient characteristics, clinical outcomes, and toxicities were analyzed. Mitotane was administered to 2 patients as an adjuvant therapy and to 8 patients for systemic control. In the latter 8 patients, 1 patient had locally advanced disease and 1 had metastatic disease at the time of initial diagnosis, whereas the other 6 patients experienced metastatic relapse at mitotane initiation. The administered regimen was mitotane alone in 7 patients, and mitotane plus cytotoxic chemotherapy in 3 patients. The initial daily mitotane dose was 3.0 g in 2 patients, 1.5 g in 7 patients, and 1.0 g in 1 patient. The median duration of treatment was 3.7 (range, 0.7-22.1) months. In 8 systemic cases, the median overall survival from chemotherapy initiation was 7.2 months, and only 1 patient survived over 1 year. The median interval from mitotane termination to death in systemic cases was 2.8 months, and the cause was progressive disease in 4 patients and toxicity (hallucination, mycobacteriosis, or liver injury) in 3 patients. As a second-line regimen, 2 systemic cases and 1 adjuvant case were enrolled in clinical trials. Our analysis exhibited extremely poor prognosis under mitotane-based regimens, and further treatment strategies are warranted to improve outcomes.
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Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Neoplasias de la Corteza Suprarrenal/patología , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/patología , Antineoplásicos Hormonales/uso terapéutico , Humanos , Japón , Mitotano/efectos adversos , Recurrencia Local de NeoplasiaRESUMEN
Synovial sarcoma is a high-grade soft tissue sarcoma that occurs primarily in the deep soft tissue of extremities, and primary colorectal synovial sarcoma is extremely rare. In this report, we present a synovial sarcoma mostly located within the mucosa of the sigmoid colon. The patient was a man in his forties with a germline deletion in the MSH2 gene. He had experienced undifferentiated pleomorphic sarcoma of the left forearm 7 years before and adenocarcinoma of the transverse colon 6 years before, both of which were successfully treated and exhibited no recurrence to date. A surveillance colonoscopy for Lynch syndrome revealed the tumor which had a submucosal tumor-like appearance with central erosion and endoscopic resection was performed. Histologically, it was composed of monotonous proliferation of spindle cells arranged in cellular fascicles; these findings were compatible with monophasic fibrous synovial sarcoma. In the tumor cells, the presence of the SS18-SSX1 fusion gene was confirmed. Protein expression of mismatch repair genes was intact in the tumor cells, indicating the association between microsatellite instability and synovial sarcoma was weak. The present case highlights a rare primary site of synovial sarcoma in a patient with Lynch syndrome.
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Colon Sigmoide/patología , Proteína 2 Homóloga a MutS , Sarcoma Sinovial , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/metabolismo , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Mutación de Línea Germinal , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Sarcoma Sinovial/genética , Sarcoma Sinovial/metabolismo , Sarcoma Sinovial/patología , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/metabolismo , Neoplasias de los Tejidos Blandos/patologíaRESUMEN
BACKGROUND: The prognostic biomarker for patients undergoing curative liver metastasectomy for colorectal cancer (CRC) is lacking. The purpose was to investigate the prognostic role of a lack of CDX2 expression, which has been proposed as a potential biomarker for high-risk relapse in early-stage CRC, in patients undergoing curative liver metastasectomy. METHODS: A total of 396 consecutive patients with CRC liver metastasis who underwent potentially curative liver metastasectomy at a single center in Japan between 2005 and 2015 were included. For the immunohistochemical analysis of nuclear CDX2 expression, we adopted the tissue microarray approach using the resected metastatic liver CRCs. Patient subgroups were compared with respect to disease-free survival (DFS) and overall survival (OS) by applying the Kaplan-Meier curve, log-rank tests, and multivariate analyses based on the Cox proportional hazards method. OS is defined as the period from the date of curative liver resection for metastatic CRC until death. DFS is defined as the length of time from curative liver resection to either the first recurrence or death. In patients without recurrence, the latest imaging inspection date was used as the censored date. RESULTS: Thirty-six of the 396 CRCs (9.1%) reduced CDX2 expression. The reduced expression of CDX2 was associated with poor differentiation (P = 0.02). DFS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median DFS: 245 days versus 420 days; hazard ratio for disease recurrence: 1.64; 95% confidence interval: 1.08-2.38; P = 0.02). OS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median OS: 1024 days versus 3145 days; hazard ratio: 2.41; 95% confidence interval: 1.52-3.85; P < 0.001). In patients with CDX2-low CRC, both DFS and OS were similar between the with and without pre- or post-operative chemotherapy groups (median DFS: 243 versus 247 days; P = 0.73, median OS: 1016 versus 1363 days; P = 0.69). CONCLUSIONS: Reduced expression of CDX2 indicates poor DFS and OS, however, it might not represent chemosensitivity in patients undergoing curative liver metastasectomy. (339/350).
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Biomarcadores de Tumor , Factor de Transcripción CDX2/biosíntesis , Neoplasias Colorrectales , Neoplasias Hepáticas , Adulto , Anciano , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Quimioterapia , Femenino , Humanos , Japón , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Masculino , Metastasectomía , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Resultado del TratamientoRESUMEN
Inverted urothelial papilloma (IUP) is a benign neoplasm characterized by a downgrowth of the urothelium beneath the surface of morphologically normal urothelial cells; however, the molecular features of IUP and their association with clinicopathological characteristics are unclear. In this study, we aimed to investigate the mutational landscape, clinicopathological features, genotype-phenotype associations, and spread patterns of IUP. We performed targeted next-generation sequencing of 39 consecutive IUP cases, the largest series investigated to date, and identified oncogenic driver mutations in RAS family genes in 34 cases (87%). HRAS mutations were the most prevalent (28 cases), which included Q61R (15 cases), followed by KRAS (5 cases) and NRAS (1 case) mutations. Characteristic mutations observed in urothelial carcinoma, including those in FGFR3 , TP53 , or the TERT promoter, were absent. HRAS -mutated IUPs were associated with a history of smoking ( P = 0.017) and streaming morphology ( P < 0.001), corresponding to the trabecular subtype. In contrast, all KRAS -mutated IUPs occurred in never-smoking patients ( P = 0.001) and showed cystic changes in morphology ( P = 0.005), corresponding to the glandular subtype. RAS Q61R immunohistochemistry visually revealed the neoplastic nature of the overlying cells and distinct spread patterns of IUP cells within the surface, including pseudoinfiltrative spread. No recurrence or carcinoma development was observed in any of the IUP cases during the follow-up period. Thus, we confirmed the importance of RAS pathway activation in IUP pathogenesis, an association between RAS family gene mutations and IUP subtypes, and the spread patterns of IUP cells within the surface.
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Carcinoma de Células Transicionales , Papiloma Invertido , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/patología , Vejiga Urinaria/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Mutación , Papiloma Invertido/genética , Papiloma Invertido/patologíaRESUMEN
BACKGROUND: Treating rectal cancer presents challenges due to postoperative complications and reduced quality of life (QOL). Recent evidence supports the watch-and-wait (WW) approach for patients with a clinical complete response (cCR) following preoperative treatment. In this report, we discuss a case of metastatic rectal cancer with deficient mismatch repair (dMMR) treated successfully with pembrolizumab. CASE PRESENTATION: A 47-year-old male with dMMR rectal cancer and a single liver metastasis underwent treatment with pembrolizumab as neoadjuvant therapy. After 10 courses, the rectal lesion achieved cCR, prompting the selection of the WW approach. The liver metastasis showed significant shrinkage; however, the presence of a residual tumor was suspected, leading to a metastasectomy. A pathological complete response (pCR) was confirmed via histological examination. During a 24-month follow-up, there was no evidence of tumor regrowth, local recurrence, or distant metastasis. CONCLUSIONS: The WW strategy is increasingly accepted for patients achieving cCR after preoperative treatment. While pCR in dMMR rectal cancer patients treated with immune checkpoint inhibitors (ICIs) has been documented, accurately predicting pCR from imaging remains challenging. This case illustrates that integrating ICI therapy, surgical interventions, and the WW approach can effectively achieve both oncological safety and improved QOL in the treatment of dMMR metastatic rectal cancer.
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Female urethral adenocarcinoma has attracted attention as a rare tumor type based on its differential pathogenesis from its male counterpart. However, to date, our knowledge concerning its immunohistochemical and morphological characteristics remains limited due to the small number of cases studied. In this study, nine consecutive cases of female urethral adenocarcinoma were used for immunohistochemical and morphological characterization of the tumor based on semi-comprehensive immunohistochemical analysis and detailed morphological evaluations. Our immunohistochemical assay revealed two subtypes of female urethral adenocarcinoma with distinctive staining patterns: the CDX2- and PAX8-expressing subtypes. The former stained positive for other intestinal markers (e.g., HNF4α and TFF1) as well (7 of 7 cases); the latter stained negative for these intestinal markers (0 of 2 cases) but stained positive for clear cell carcinoma markers (e.g., Napsin A and HNF1ß) (2 of 2 cases). Regarding cytokeratins, the former displayed a CK7- and CK20-positive immunoprofile (7 of 7 cases); the latter exhibited a CK7-positive and CK20-negative immunoprofile (2 of 2 cases). Morphologically, CDX2- and PAX8-expressing subtypes resembled intestinal-type adenocarcinoma and clear cell carcinoma (occurring in gynecological organs), respectively. The semi-comprehensive immunoprofiling data presented in this study can potentially contribute to the correct diagnosis of this rare tumor type. Finally, our study represents an important basis for future investigations aiming to further elucidate the details and origin of female urethral adenocarcinoma, and it can potentially contribute to developing diagnostic and therapeutic strategies for treating this malignancy.
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Hepatocellular carcinomas (HCCs) with biliary/progenitor cell features frequently show increased programmed death-ligand 1 (PD-L1) expression, but their response to immunotherapy is not high. One possible explanation for this phenomenon could be the loss of major histocompatibility complex (MHC) class I expression on tumor cells, which impairs the presentation of tumor antigens to cytotoxic T cells. However, the potential correlation between MHC class I loss, biliary/progenitor cell features, and the tumor-immune microenvironment remains largely unexplored. Herein, we hypothesized that MHC class I loss could be associated with biliary/progenitor cell features and potentially impact the tumor-immune microenvironment. To evaluate this hypothesis and gain insight into the characteristics of tumor cells and the tumor-immune microenvironment in HCCs with MHC class I loss, we examined a consecutive series of 397 HCC cases. MHC class I loss was observed in 32 HCCs (8.1%). Lipid-less cytologic morphology was significantly associated with MHC class I loss (P = 0.02). CK19 expression and decreased ARG1 expression, both known as biliary/progenitor cell features, were significantly associated with MHC class I loss (P < 0.05). PD-L1 expression was irrelevant to the MHC class I status. HCCs with MHC class I loss exhibited significantly lower infiltration of CD8+, CD4+, CD20+, and FOXP3+ cells than those with intact MHC class I (all Ps < 0.01). Our study reveals an association between MHC class I loss, biliary/progenitor cell features, and a "cold" tumor-immune microenvironment in HCCs. These insights highlight the potential impact of MHC class I loss on tumor cells and the tumor-immune microenvironment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Antígeno B7-H1/metabolismo , Neoplasias Hepáticas/patología , Antígenos de Histocompatibilidad Clase I/metabolismo , Antígenos HLA , Microambiente TumoralRESUMEN
The incidence of non-alcoholic non-virus-related hepatocellular carcinoma (NANV-HCC) is increasing along with the growing prevalence of metabolic disorders. In this subset, few useful biomarkers are available to narrow down the high-risk group for recurrence. This study aimed to evaluate the prognostic impact of decreased ARG1 (arginase-1), which is pathologically known as a marker reflecting hepatocyte differentiation, in NANV-HCC. Besides, its relationship with biliary/progenitor cell markers, whose expressions are associated with poor prognosis, was also assessed. To reveal the clinicopathological association of decreased ARG1 expression in NANV-HCC, we investigated 99 patients who underwent curative-intent hepatectomy for NANV-HCC. Tissue microarrays were employed for immunohistochemical analysis. A total of 21 NANV-HCC cases (21%; 21/99) showed decreased ARG1 expression. Decreased ARG1 expression was an independent prognostic factor for both poor DFS (hazard ratio 2.17; 95% confidence interval 1.15-4.09; p = 0.02) and OS (hazard ratio 4.09; 95% confidence interval 1.71-9.80; p = 0.002). In addition, decreased ARG1 expression was significantly associated with expressions of biliary/progenitor cell markers, CK19 and CD56 (p < 0.01). As cytologic features of tumor cells, decreased ARG1 expression was significantly associated with lipid-less cytologic morphology (p = 0.045). These findings indicate that decreased ARG1 expression is a predictive phenotype of postoperative recurrence with poor prognosis in patients with NANV-HCC. Decreased ARG1 expression may be a precursor or overlapping feature with biliary/progenitor cell marker expressions in NANV-HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores de Tumor , Carcinoma Hepatocelular/patología , Hepatectomía , Humanos , Neoplasias Hepáticas/patología , Fenotipo , PronósticoRESUMEN
ABSTRACT: Nonalcoholic non-virus-related hepatocellular carcinoma (NANV-HCC) is considered to occur in steatotic livers; however, emerging evidence indicates that a subset of NANV-HCC occurs in nonsteatotic livers. Currently, little information is available regarding this subset. This study sought to provide the clinical and pathological features of NANV-HCC in nonsteatotic livers.We retrospectively investigated the clinicopathological features of 101 consecutive patients with NANV-HCC treated with a curative-intent hepatectomy. A background liver with <5% steatosis by area was regarded as a nonsteatotic liver. Survivals of patient subgroups were estimated using the Kaplan-Meier method, and log-rank tests were conducted to assess the survival difference. Multivariate analysis was performed with the Cox proportional hazards method.Overall, 34 of 101 patients with NANV-HCC were found to have a nonsteatotic liver. Vascular invasion of the tumor was more frequently observed in patients with a nonsteatotic liver than in those with a steatotic liver (Pâ=â.03). The extent of lobular inflammation and fibrosis did not differ between patients with and without steatosis in the liver. NANV-HCC with a nonsteatotic liver was independently associated with a shorter disease-free survival (DFS) (hazard ratio [HR] 2.14; 95% confidence interval [CI] 1.21-3.80; Pâ=â.009) and a shorter overall survival (OS) (HR 2.79; 95% CI 1.27-6.16; Pâ=â.01) than NANV-HCC with a steatotic liver.The absence of steatosis in the liver is independently associated with shorter DFS and OS in patients with NANV-HCC. Our findings indicate that nonsteatotic liver can be a surrogate phenotype of aggressive NANV-HCC.
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Carcinoma Hepatocelular , Hígado Graso , Neoplasias Hepáticas , Alcoholismo , Carcinoma Hepatocelular/cirugía , Supervivencia sin Enfermedad , Hígado Graso/complicaciones , Hígado Graso/epidemiología , Hepatectomía , Humanos , Neoplasias Hepáticas/cirugía , Pronóstico , Estudios Retrospectivos , VirosisRESUMEN
A 67-year-old man presented with hemorrhagic shock due to the rupture of hepatic tumor and underwent emergency partial resection of the right liver. Pathological examination revealed hepatic angiosarcoma with involvement in its surgical margin. Six months after the operation, disease recurrence was detected, and he was referred to our hospital for second opinion. CT revealed tumors at the liver cut surface and left lateral segment. The tumor at the liver cut surface abutted to the common bile duct and the portal vein. The tumor was deemed unresectable, and systemic chemotherapy with 4 courses of weekly paclitaxel was given with excellent response. Then, we performed partial liver resection of S4 and S1 with remnant right liver and middle hepatic vein, and wedge resection for the metastatic lesion of segment 3 as a conversion surgery. He developed a grade B bile leakage postoperatively and was discharged on postoperative day 28. He remained disease free for 8 months after the operation.
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Hemangiosarcoma , Neoplasias Hepáticas , Anciano , Hemangiosarcoma/tratamiento farmacológico , Hemangiosarcoma/cirugía , Hepatectomía , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/cirugía , PaclitaxelRESUMEN
BACKGROUND: Prostate cancer spans a broad spectrum from indolent to deadly disease. In the management of prostate cancer, diagnostic biopsy specimens are important sources of data that inform the selection of treatment. B7-H3 (CD276), an immune checkpoint molecule, has emerged as a promising immunotherapy target. B7-H3 expression is related to adverse clinical outcomes in various types of cancer; however, little is known concerning the association between tumor B7-H3 expression in diagnostic biopsy specimens and clinical outcome in patients with metastatic prostate cancer. METHODS: We evaluated tumor B7-H3 expression levels in diagnostic biopsy specimens from 135 patients with metastatic prostate cancer and 113 patients with localized prostate cancer. RESULTS: High B7-H3 expression was more frequently observed in patients with metastatic cancer than in those with localized cancer (31 vs. 12%; p = 0.0003). In patients with localized cancer, the B7-H3 expression status was not associated with biochemical recurrence-free survival. However, among patients with metastatic cancer, high B7-H3 expression was independently associated with high disease-specific mortality (multivariable hazard ratio [HR] = 2.72; p = 0.047) and overall mortality rates (multivariable HR = 2.04; p = 0.025). CONCLUSIONS: Tumor B7-H3 expression in diagnostic biopsy specimens may be a useful biomarker for identifying highly aggressive metastatic prostate cancer. Given the potential utility of anti-B7-H3 immunotherapy, this information may aid in stratifying prostate cancer based on its responsiveness to B7-H3-targeted treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígenos B7/metabolismo , Biomarcadores de Tumor/metabolismo , Recurrencia Local de Neoplasia/mortalidad , Neoplasias de la Próstata/mortalidad , Anciano , Estudios de Seguimiento , Humanos , Masculino , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Pronóstico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To identify specific ultrasonographic features that differentiate hepatic angiomyolipoma (HAML) from hepatocellular carcinoma (HCC). METHODS: Twelve patients with HAML and 73 patients with HCC, whose diagnosis were pathologically confirmed at a single center in Japan between 2006 and 2016, were included in this study. The HAML and HCC cases were histologically evaluated and their histological growth patterns were compared. Using ultrasonographic data, we evaluated the imaging features representing the distinct histological differences. Ultrasonographic findings, reviewed by two examiners, were compared via interobserver variability analysis. This retrospective study was approved by the institutional ethics committee at our institute (No. 2017-1004). RESULTS: The enrolled patients were carefully divided into two case sets: discovery case set (6 HAML patients and 37 HCC patients) and validation case set (6 HAML patients and 36 HCC patients). In the discovery case set, half of the HAML cases had intratumoral regions showing a reticular growth pattern. None of the HCC cases appeared as a region with the reticular growth pattern. The regions with the reticular growth pattern present as an intratumoral hyper echoic foci on ultrasound images. The presence of the intratumoral hyper echoic foci was significantly associated with HAML (Pâ¯<â¯.01). In the validation case set, the intratumoral hyper echoic foci predicted HAML at a specificity of 100% and a sensitivity of 50%. CONCLUSIONS: Intratumoral hyper echoic foci, representing reticular growth pattern, can be a promising ultrasonographic finding to help differentiate HAML from HCC.
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Angiomiolipoma/diagnóstico por imagen , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Ultrasonografía/métodos , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Japón , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
A 69-year-old man was diagnosed with cT1aN2M0-stage IIIA lung adenocarcinoma. Chemoradiotherapy, the standard treatment for cN2, stage IIIA adenocarcinoma, was considered impossible due to his renal functional impairment. So surgery was the only radical treatment option and therefore planned. However, a preoperative chest computed tomography (CT) scan performed three months after the first scanning revealed apparent shrinking of the pulmonary nodule. We performed left upper lobectomy and mediastinal lymph node dissection. Pathologically, we confirmed no adenocarcinoma cells in the resected lung specimen. Alternatively, a foreign body granuloma composed of foamy macrophages and cholesterol clefts was observed among fibrous tissue, suggesting a trace of lost tumor after some treatment, whereas viable adenocarcinoma cells remained in the lymph nodes. Six weeks after surgery, the patient developed hypothyroidism as a side effect and confessed to having undergone a preoperative treatment with nivolumab 20 mg per body twice before surgery. Unexpected preoperative nivolumab treatment was effective only on the primary lesion possibly due to intratumoral heterogeneity or insufficient dosage. We present an extremely rare case with unique pathological findings of lung adenocarcinoma after unexpected preoperative nivolumab treatment that was followed by surgery. We histologically confirmed the tumor cells disappearing only at the primary site and remaining at the lymph node. This case report may provide a clue to the future development of induction therapy using nivolumab and surgery.