RESUMO
Advances in multi-modality treatments incorporating systemic chemotherapy, endocrine therapy, and radiotherapy for the management of breast cancer have resulted in a surgical-management paradigm change toward less-aggressive surgery that combines the use of breast-conserving or -reconstruction therapy as a new standard of care with a higher emphasis on cosmesis. The implementation of skin-sparing and nipple-sparing mastectomies (SSM, NSM) has been shown to be oncologically safe, and breast reconstructive surgery is being performed increasingly for patients with breast cancer. NSM and breast reconstruction can also be performed as prophylactic or risk-reduction surgery for women with BRCA gene mutations. Compared with conventional breast construction followed by total mastectomy (TM), NSM preserving the nipple-areolar complex (NAC) with breast reconstruction provides psychosocial and aesthetic benefits, thereby improving patients' cosmetic appearance and body image. Implant-based breast reconstruction (IBBR) has been used worldwide following mastectomy as a safe and cost-effective method of breast reconstruction. We review the clinical evidence about immediate (one-stage) and delayed (two-stage) IBBR after NSM. Our results suggest that the postoperative complication rate may be higher after NSM followed by IBBR than after TM or SSM followed by IBBR.
Assuntos
Implante Mamário/métodos , Implantes de Mama , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia Segmentar/métodos , Mamilos , Tratamentos com Preservação do Órgão/métodos , Adulto , Idoso , Neoplasias da Mama/genética , Terapia Combinada , Análise Custo-Benefício , Feminino , Humanos , Mastectomia Segmentar/economia , Pessoa de Meia-Idade , Mutação , Tratamentos com Preservação do Órgão/economia , Mastectomia Profilática/economia , Mastectomia Profilática/métodos , Segurança , Resultado do Tratamento , Ubiquitina-Proteína Ligases/genéticaRESUMO
Clinical evidence has indicated that, after neo-adjuvant chemotherapy(NAC), sentinel node(SN)identification rates(IR) were lower and false-negative rates(FNR)were higher for patients(pts)with local advanced breast cancer(BC)than for pts with early stage BC who did not receive NAC. Our previous clinical trial indicated that the real-time indocyanin green (RT-ICG)fluorescence imaging technique could improve the diagnostic sensitivity and detection accuracy of sentinel node biopsy(SNB). Nine pts with histologically confirmed Stage â ¡A to â ¢B, T1-T3, N0-2, M0 BC were selected to receive NAC, and the standard surgeries were performed after NAC completion. The SNs were detected by using conventional procedures with the blue dye(indigo carmine)plus 99mTc radioisotope techniques combined with concurrent RT-ICG. Clinically positive nodes were diagnosed by the radiologists using axillary ultrasound, MRI, and/or CT scans. All pts provided written informed consent before surgery. The surgical SNB was guided via RT-ICG fluorescence under standard light conditions by using the HEMS imaging system as previously published. All pts underwent SNB followed by completion node dissection(CND). The IR and FNR were calculated by comparing the results of the SNB and the histopathology of the resection specimens obtained via CND. The IR and FNR for each procedure of SNB were, respectively, 35.3% and 41.7% when indigo carmine blue was used, 82.4% and 0 when ICG fluorescence was used, and 58.8% and 5% when RI was used. In contrast, the total calculation of the triple tracer showed that IR reached 100% and FNR was 0. These data suggest that IR and FNR of SNB might be improved in pts with BC treated with NAC by using the novel triple tracer technique.
Assuntos
Neoplasias da Mama , Biópsia de Linfonodo Sentinela , Axila , Neoplasias da Mama/terapia , Humanos , Verde de Indocianina , Linfonodos , Terapia Neoadjuvante , RadioisótoposRESUMO
BACKGROUND: The present study was aimed to evaluate the usefulness of contrast Sonazoid-enhanced ultrasonography (US) for the detection of hepatic metastases in breast cancer patients and compare the clinical efficacy and sensitivity of this technique with conventional contrast unenhanced B-mode US in follow-up examinations of breast cancer patients with liver metastasis. METHODS: We assessed a total of 84 hepatic tumors from 24 patients diagnosed with or suspected of having metastatic cancer. These hepatic nodules were diagnosed through imaging, including dynamic magnetic resonance imaging (MRI), contrast-enhanced computed tomography (CECT) scan, B-mode US or contrast Sonazoid-enhanced US (SEUS). Differences in the sensitivity between US and SEUS were compared using MR imaging, CECT, and follow-up imaging. RESULTS: A total of 79 nodules were diagnosed as metastatic tumors. The remaining nodules were diagnosed as benign tumors (hepatic hemangioma: n = 3; local fatty change: n = 2). SEUS precisely detected the presence or absence of hepatic tumors in the 24 patients examined, showing a sensitivity of 98.8 % (83 of 84 lesions) for total imaged solid liver lesions, with an accuracy of 98.7 % (78 of 79 lesions) for total metastatic breast cancer lesions. In contrast, conventional B-mode US imaging revealed hepatic tumor lesions at a sensitivity of 66.7 % (56 of 84 lesions) and an accuracy of 64.6 % (51 of 79 lesions), respectively. Furthermore, the false positive and false negative rates were, respectively, 6.33 and 29.1 % for B-mode US and 0 and 1.3 % for SEUS. Moreover, twenty-seven metastatic tumors and five benign lesions (3 hemangiomas and 2 focal fatty changes/sparings) were imaged using SEUS but not conventional B-mode US. Significant differences in diagnostic accuracy rates between contrast Sonazoid-enhanced US and conventional B-mode US were observed (Wilcoxon signed rank test: p = 0.0009). No severe adverse events occurred during SEUS after the administration of Sonazoid, except for a grade 1 skin reaction and nausea in one patient. CONCLUSION: These results suggested that Sonazoid could be safely administrated to breast cancer patients with liver metastatic disease. Thus, contrast Sonazoid-enhanced US is a feasible and more effective method than B-mode US for the detection of hepatic metastasis, particularly for small metastatic breast cancer lesions less than 14 mm in diameter, showing significant high sensitivity and accuracy.
Assuntos
Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Meios de Contraste , Compostos Férricos , Ferro , Neoplasias Hepáticas/secundário , Óxidos , Ultrassonografia Mamária/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Metástase Linfática , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Tomografia Computadorizada por Raios XRESUMO
Lung inflammation is a major adverse effect of therapy with the antitumor drug bleomycin (BLM). Transient receptor potential melastatin 2 (TRPM2) is a Ca(2+)-permeable channel that is activated by oxidative stress through the production of ADP-ribose. We herein investigated whether TRPM2 channels contributed to BLM-induced lung inflammation. The intratracheal instillation of BLM into wild-type (WT) mice increased the number of polymorphonuclear leukocytes (PMNs) and inflammatory cytokine levels in the lung. Increases in inflammatory markers in WT mice were markedly reduced in trpm2 knockout (KO) mice, which demonstrated that the activation of TRPM2 channels was involved in BLM-induced lung inflammation. The expression of TRPM2 mRNA was observed in alveolar macrophages, alveolar epithelial cells, and lung fibroblasts. Actually, TRPM2 protein was expressed in lung tissues. Of these, TRPM2 channels in epithelial cells were activated by the addition of H2O2 following a BLM pretreatment, resulting in the secretion of macrophage inflammatory protein-2 (MIP-2). The H2O2-induced activation of TRPM2 by the BLM pretreatment was blocked by the poly(ADP-ribose) polymerase (PARP) inhibitors PJ34 and 3-aminobenzamide. The accumulation of poly(ADP-ribose) in the nucleus, a marker for ADP-ribose production, was strongly induced by H2O2 following the BLM pretreatment. Furthermore, administration of PRAP inhibitors into WT mice markedly reduced recruitment of inflammatory cells and MIP-2 secretion induced by BLM instillation. These results suggest that the induction of MIP-2 secretion through the activation of TRPM2 channels in alveolar epithelial cells is an important mechanism in BLM-induced lung inflammation, and the TRPM2 activation is likely to be mediated by ADP-ribose production via PARP pathway. TRPM2 channels may be new therapeutic target for BLM-induced lung inflammation.
Assuntos
Antibióticos Antineoplásicos/toxicidade , Bleomicina/toxicidade , Pneumonia/induzido quimicamente , Alvéolos Pulmonares/fisiologia , Canais de Cátion TRPM/fisiologia , Animais , Citocinas/biossíntese , Células Epiteliais/fisiologia , Peróxido de Hidrogênio/farmacologia , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Poli(ADP-Ribose) Polimerase-1 , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Poli(ADP-Ribose) Polimerases/fisiologia , Canais de Cátion TRPM/análise , Canais de Cátion TRPM/genéticaRESUMO
BACKGROUND: We investigated the efficacy and safety of metronomic chemotherapy with combined irinotecan and tegafur-gimeracil-oteracil potassium (TS-1) in patients with metastatic and recurrent breast cancer (MRBC), and the association between irinotecan metabolizing enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) gene polymorphisms and adverse events. METHODS: The study group comprised 40 patients aged 35-79 years. Irinotecan (60 mg/m(2) in 5 % dextrose) was administered by 120-min infusion on days 1, 8, and 15 every 4 weeks. TS-1 (prescribed in a standard quantity) was administered at 80 mg/m(2)/day orally on days 3-7, 10-14, and 17-21 every 4 weeks. RESULTS: Tumor response data were available for 34 patients. Median follow-up was 12 months (range 1-45 months). Response rate was 47 % (one complete and 15 partial responses). Stable disease was observed in 17 patients (50 %). One patient had disease progression (3 %). Median progression-free survival was 14 months [95 % confidence interval (CI), 10-26]. Median overall survival was 26 months (95 % CI not calculable owing to sample size), and 79.3 % of patients survived for 1 year. The most common grade 3 or 4 adverse events were neutropenia (15 %), leukopenia (12.5 %), diarrhea (7.5 %), and anemia (2.5 %). All other adverse events were grade 1 or 2. Treatment-related toxicity was generally modest and manageable. No significant correlation was observed between UGT1A1 polymorphisms and hematological or non-hematological toxicities. CONCLUSIONS: Metronomic chemotherapy with combined irinotecan and TS-1 was effective in MRBC patients. Adverse effects were mild and the regimen was safely administered without identifying UGT1A1 polymorphisms.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Administração Metronômica , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Combinação de Medicamentos , Feminino , Glucuronosiltransferase/genética , Humanos , Irinotecano , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neutropenia/induzido quimicamente , Ácido Oxônico/administração & dosagem , Polimorfismo Genético , Piridinas/administração & dosagem , Análise de Sobrevida , Tegafur/administração & dosagem , Resultado do TratamentoRESUMO
Malignant lymphomas of the breast are rare and primary breast lymphoma comprises <0.5 % of breast malignancies, within which T-cell lymphomas are an even rarer subset. We report a case of primary breast peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). Histology of the biopsied specimen revealed CD2(+), CD3(+), CD4(+), CD5(-), CD7(+), CD8(-), CD20(-), CD25(-), CD30(+), CD56(-), bcl-2(-), EBV-ISH(-), TIA-I(-), and ATLA negative. The patient was treated with six cycles of the CHOP regimen and died 17 months after the diagnosis was made, despite complete remission after conventional chemotherapy. To our knowledge, only 18 cases of primary peripheral T-cell lymphoma of the breast and just one previous case of primary PTCL-NOS of the breast have been reported in Japan.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/tratamento farmacológico , Idoso , Antígenos CD/análise , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/análise , Biópsia por Agulha Fina , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Diagnóstico por Imagem , Doxorrubicina/administração & dosagem , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Linfoma de Células T Periférico/patologia , Prednisolona/administração & dosagem , Indução de Remissão , Vincristina/administração & dosagemRESUMO
INTRODUCTION: Since treatment modalities for metastatic recurrent triple-negative breast cancer (mrTNBC) are limited, a novel treatment approach including immunotherapy is required. We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are individually selected from a pool of different peptide candidates based on the pre-existing host immunity. Herein we conducted a phase II study of PPV for metastatic recurrent breast cancer patients to investigate the feasibility of PPV for mrTNBC. METHODS: Seventy-nine patients with metastatic recurrent breast cancer who had metastases and had failed standard chemotherapy and/or hormonal therapy were enrolled. They were subgrouped as the mrTNBC group (n = 18), the luminal/human epidermal growth factor receptor 2 (HER2)-negative group (n = 41) and the HER2-positive group (n = 18), while the remaining two patients had not been investigated. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher peptide-specific immunoglobulin G (IgG) responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the four HLA-IA phenotypes (HLA-A2, -A24, or -A26 types, or HLA-A3 supertypes), and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses along with other laboratory analyses were conducted before and after vaccination. RESULTS: No severe adverse events associated with PPV were observed in any of the enrolled patients. Boosting of CTL and/or IgG responses was observed in most of the patients after vaccination, irrespective of the breast cancer subtypes. There were three complete response cases (1 mrTNBC and 2 luminal/HER2-negative types) and six partial response cases (1 mrTNBC and 5 luminal/HER2-negative types). The median progression-free survival time and median overall survival time of mrTNBC patients were 7.5 and 11.1 months, while those of luminal/HER2-negative patients were 12.2 and 26.5 months, and those of HER2-positive patients were 4.5 and 14.9 months, respectively. CONCLUSIONS: PPV could be feasible for mrTNBC patients because of the safety, immune responses, and possible clinical benefits. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000001844 (Registration Date: April 5, 2009).
Assuntos
Vacinas Anticâncer/imunologia , Peptídeos/imunologia , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/terapia , Adulto , Idoso , Antígenos de Neoplasias/química , Antígenos de Neoplasias/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/efeitos adversos , Estudos de Viabilidade , Feminino , Antígenos HLA-A/química , Antígenos HLA-A/imunologia , Humanos , Imunidade Celular , Imunidade Humoral , Imunoterapia , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Medicina de Precisão , Radiografia , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
AIMS: A prominent fibrovascular stromal core is one of the widely accepted histological features of breast papillomas, but some papillary carcinomas also show such broad fibrovascular cores, leading to confusion in diagnosis, particularly in needle biopsy specimens. We investigated the histological characteristics of papillary lesions, focusing on broad fibrovascular cores and their relationship with the architectural patterns. METHODS: Among 185 cases of needle biopsies of papillomas and papillary carcinomas, the number of cases with broad fibrovascular cores in each group was compared. The broad fibrovascular core density in the subsequently resected specimens was evaluated and compared between papillary predominant pattern (papillary structures >80% of tumours) and mixed pattern (papillary, solid, cribriform and others) within the lesions. RESULTS: Significantly more papillary carcinomas than papillomas and B3 atypical papillary lesions had broad fibrovascular cores (p=0.0091 and p=0.0164, respectively). The papillary predominant pattern was more prominent in carcinomas than in papillomas in the needle biopsies (p=0.048) and showed the same tendency in the resections (p=0.058). The broad fibrovascular core density was significantly lower in the 18 papillomas than in the 37 papillary carcinomas (p=0.0079) and was not significantly different between the papillary predominant and mixed patterns in carcinomas and papillomas. CONCLUSIONS: Broad fibrovascular cores in mammary papillary lesions are not specific for papillomas, as they are also present focally in papillary carcinomas. As the frequency of papillary carcinoma with broad fibrovascular cores is relatively high, caution in diagnosis has to be exercised, especially in needle biopsy specimens.
Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Carcinoma Papilar/patologia , Papiloma/patologia , Biópsia com Agulha de Grande Calibre , Diagnóstico Diferencial , Erros de Diagnóstico/prevenção & controle , Feminino , Fibrose , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos TestesRESUMO
PURPOSE: We compared the safety, invasiveness and cosmetic outcomes between endoscopic breast-conserving surgery (endoscopic group) and surgery under direct vision (direct vision group) for treating breast cancer. METHODS: We compared 100 cases of endoscopic surgery with 150 cases of direct vision surgery. The safety was evaluated in terms of the blood loss, length of the operation and presence or absence of complications, whereas the degree of invasiveness was assessed using preoperative and postoperative leukocyte counts, neutrophil counts, interleukin (IL-6) levels and fever. The cosmetic outcome was assessed on the basis of a breast evaluation by the medical staff and the patient's subjective satisfaction. RESULTS: In both groups, serious postoperative complications were absent. No significant differences were observed in the leukocyte counts, neutrophil counts, IL-6 level or fever between the groups. An evaluation of the cosmetic outcomes by the staff showed a more favorable breast size, breast shape and scar condition in the endoscopic group. A significantly higher level of patient satisfaction was also observed in the endoscopic group. Postoperative local recurrence was absent. CONCLUSIONS: The endoscopic approach showed comparable safety and invasiveness, and provided better postoperative cosmetic outcomes than direct vision surgery. Our results suggest that endoscopic breast-conserving surgery is a potentially useful surgical method for the treatment of breast cancer.
Assuntos
Neoplasias da Mama/cirurgia , Endoscopia , Mastectomia Segmentar/métodos , Adulto , Idoso , Perda Sanguínea Cirúrgica , Feminino , Febre , Humanos , Interleucina-6/sangue , Contagem de Leucócitos , Pessoa de Meia-Idade , Duração da Cirurgia , Satisfação do Paciente , Segurança , Resultado do TratamentoRESUMO
Despite the good responses of patients (pts) with stage III breast cancer to neoadjuvant chemotherapy (NAC), most eventually relapse and have a poor prognosis. We investigated the prognostic indicators in pts with stage III breast cancer treated with NAC, using epirubicin and/or docetaxel. A total of 22 women with stage III breast cancer underwent NAC between January 2005 and May 2011. The regimens of NAC comprised ED (epirubicin 60 mg/m2 and docetaxel 60 mg/m2) in 10 cases, FEC (fluorouracil 500 mg/m2, epirubicin 75-100 mg/m2 and cyclophosphamide 500 mg/m2) in 10 cases and EC (epirubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) in two cases. Following four cycles of each regimen, a further four cycles of D (docetaxel 70 mg/m2) were undertaken in nine cases. Subsequent to the completion of NAC and surgery, we assessed the clinicopathological results and performed prognostic analyses. Statistical analyses concerning disease-free survival (DFS) or overall survival (OS) were conducted by a Cox proportional hazard model. The median survival time was 66 months and there were 12 distant metastases and two local recurrences. Multivariate analyses showed the number of metastatic axillary lymph nodes (ALNs) [hazard ratio (HR), 1.079; P=0.023] was correlated with DFS, while the Ki-67 labeling index (HR, 1.109; P=0.042) and the number of meta-static ALNs (HR, 1.087; P=0.023) were correlated with OS. In conclusion, even if pts with stage III breast cancer show good responses to NAC using epirubicin and/or docetaxel, the majority eventually relapse and have a poor prognosis. The Ki-67 labeling index and the number of involved ALNs are suggested as prognostic indicators in stage III breast cancer.
Assuntos
Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/patologia , Fator Estimulador de Colônias de Granulócitos/metabolismo , Antineoplásicos/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/metabolismo , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Evolução Fatal , Feminino , Humanos , Falência Hepática , Pessoa de Meia-Idade , GencitabinaRESUMO
Combined hepatocellular-cholangiocarcinoma comprises <1% of all liver carcinomas. The histogenesis of combined hepatocellular-cholangiocarcinoma has remained unclear for many years. However, recent advances in hepatic progenitor cell (HPC) investigations have provided new insights. The concept that combined hepatocellular-cholangiocarcinoma originates from HPCs is adopted in the chapter "combined hepatocellular-cholangiocarcinoma" of the latest World Health Organization (WHO) classification. In this study, we conducted clinicopathologic analysis of combined hepatocellular-cholangiocarcinoma according to the latest WHO classification. Fifty-four cases were included in this study. Pathologic diagnosis was made according to the WHO classification. When a tumor contained plural histologic patterns, predominant histologic pattern (≥50%) was defined. Minor histologic patterns were also appended. Immunohistochemical staining with biliary markers (CK7, CK19, and EMA), hepatocyte paraffin (HepPar)-1, HPC markers (CD56, c-kit, CD133, and EpCAM), and vimentin was performed. Forty-five and 50 patients were analyzed for progression-free survival and overall survival, respectively. Ten, 1, 32, and 11 cases were diagnosed as: combined hepatocellular-cholangiocarcinoma, classical type; combined hepatocellular-cholangiocarcinoma, stem cell features, typical subtype; combined hepatocellular-cholangiocarcinoma, stem cell features, intermediate cell subtype; and combined hepatocellular-cholangiocarcinoma, stem cell features, cholangiolocellular type, respectively. Combined hepatocellular-cholangiocarcinomas usually have high expression of biliary markers. CD56, c-kit, and EpCAM were expressed to various degrees in all combined hepatocellular-cholangiocarcinomas apart from the hepatocellular carcinoma component of combined hepatocellular-cholangiocarcinoma, classical type. The expression of CD133 and vimentin was observed only in combined hepatocellular-cholangiocarcinoma, stem cell features of intermediate cell subtype and cholangiolocellular subtype. The expression of CD133, EpCAM, and vimentin was significantly high in combined hepatocellular-cholangiocarcinoma, subtypes with stem cell features, especially cholangiolocellular subtype. Minor histologic patterns were significantly frequent in combined hepatocellular-cholangiocarcinoma, subtypes with stem cell features, compared with combined hepatocellular-cholangiocarcinoma, classical type. There was no significant difference in clinical outcome between each subtype. Combined hepatocellular-cholangiocarcinoma has wide histologic diversity and shows immunophenotypic expression of not only biliary markers but also HPC markers to various degrees, suggesting that the histogenesis of combined hepatocellular-cholangiocarcinoma could be strongly associated with HPCs. Our results pathologically validate the latest WHO classification of combined hepatocellular-cholangiocarcinoma. However, the complex mixture of histologic subtypes has presented a challenge to the classification of combined hepatocellular-cholangiocarcinoma. Further study should be conducted using a large cohort to support this classification.
Assuntos
Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/patologia , Neoplasias Hepáticas/patologia , Idoso , Neoplasias dos Ductos Biliares/classificação , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/mortalidade , Ductos Biliares Intra-Hepáticos/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/classificação , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Colangiocarcinoma/classificação , Colangiocarcinoma/metabolismo , Colangiocarcinoma/mortalidade , Feminino , Humanos , Japão/epidemiologia , Neoplasias Hepáticas/classificação , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas , Taxa de Sobrevida , Organização Mundial da SaúdeRESUMO
The forkhead box protein 3 (FOXP3) transcription factor is highly expressed in tumor cells as well as in regulatory T cells (Tregs). It plays a tumor-enhancing role in Tregs and suppresses carcinogenesis as a potent repressor of several oncogenes. The clinical prognostic value of FOXP3 expression has not yet been elucidated. In this study, immunohistochemistry was used to investigate the prognostic significance of FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes (TILs) in breast cancer patients. Of the 100 tumor specimens obtained from primary invasive breast carcinoma, 63 and 57% were evaluated as FOXP3+ tumor cells and as being highly infiltrated by FOXP3+ lymphocytes, respectively. Although FOXP3 expression in tumor cells was of no prognostic significance, FOXP3+ lymphocytes were significantly associated with poor overall survival (OS) (n=98, log-rank test P=0.008). FOXP3 exhibited a heterogeneous subcellular localization in tumor cells (cytoplasm, 31%; nucleus, 26%; both, 6%) and, although cytoplasmic FOXP3 was associated with poor OS (P= 0.058), nuclear FOXP3 demonstrated a significant association with improved OS (P=0.016). Furthermore, when patients were grouped according to their expression of tumor cytoplasmic FOXP3 and lymphocyte FOXP3, there were notable differences in the Kaplan-Meier curves for OS (P<0.001), with a high infiltration of FOXP3+ lymphocytes accompanied by a cytoplasmic FOXP3+ tumor being the most detrimental phenotype. These findings indicated that FOXP3 expression in lymphocytes as well as in tumor cells may be a prognostic marker for breast cancer. FOXP3 in tumor cells may have distinct biological activities and prognostic values according to its localization, which may help establish appropriate cancer treatments.
RESUMO
We present a case of a 57-year-old woman with a giant malignant phyllodes tumor (PT) in her right breast, with maximum diameter of 20 cm. The core-needle and excisional biopsy specimens were diagnosed as suspicious for low-grade myofibroblastic sarcoma (LGMS). The subsequent total mastectomy with partial resection of the pectoral muscles showed predominance of stromal hypercellularity without an epithelial component. However, we diagnosed this as a malignant PT because focal areas showed a leaf-like pattern. In the case of large malignant PTs that exhibit stromal predominance, it can be difficult to distinguish between a pure sarcoma and malignant PT. It is important to thoroughly examine multiple sections from the view point of residual epithelial structure in morphological diagnosis.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Tumor Filoide/diagnóstico , Tumor Filoide/cirurgia , Biópsia por Agulha , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Feminino , Humanos , Mastectomia Simples , Pessoa de Meia-Idade , Tumor Filoide/patologia , Sarcoma/diagnóstico , Resultado do TratamentoRESUMO
A 52-year-old woman underwent modified radical mastectomy and axillary lymph node resection for right breast cancer (stage IIB). Afterwards FEC therapy (5-FU 500 mg/m/2, epirubicin 75 mg/m2, cyclophosphamide 500 mg/m2) x 4, docetaxel therapy (60 mg/m2) x 4 and radiation of the illness side collarbone, upper and lower lymph nodes were enforced for adjuvant therapy after the operation. Furthermore, administration of aromatase inhibitor (anastrozole) and trastuzumab was started due to the postoperative pathological diagnosis of hormone receptor-positive and HER2 (score 3+). This became an urgent hospital admission because of the sudden escape power from impaired consciousness due to the articulation disorders and limb weakness when trastuzumab was administered nine times. It was diagnosed by MRI examination and the cerebrospinal fluid cytology as meningeal carcinomatosis of breast cancer, and she died on the 31st recurrence of disease. A serious relapse may be caused in a case of fast-progressing breast cancer like this while being administered trastuzumab as an adjuvant treatment.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinomatose Meníngea/secundário , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Progressão da Doença , Evolução Fatal , Feminino , Humanos , Carcinomatose Meníngea/tratamento farmacológico , Pessoa de Meia-Idade , TrastuzumabRESUMO
Angiosarcoma of the breast is a rare non-epithelial tumor and that accounts for less than 0.1% of primary malignancies of the breast. The disease has a relatively higher occurrence among young people, and its prognosis (3-year-survival of only 38%) is extremely poor compared to breast cancer. Here we present a case of an 87-year-old woman who had undergone bilateral breast augmentation with silicone injections in her youth. Although she became aware of a tumor in her right breast, she waited 8 years before seeking treatment. She felt the tumor growing and experienced swelling and pain, but she ended up declining therapy at that time. Two years later she was brought to our hospital by ambulance for continuous bleeding from the same tumor of the breast, which by that time was over 11 cm in diameter. We performed emergency mastectomy. The histological diagnosis was angiosarcoma of the breast with silicone granuloma.
Assuntos
Implante Mamário/efeitos adversos , Neoplasias da Mama/etiologia , Hemangiossarcoma/etiologia , Géis de Silicone/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Granuloma/etiologia , Hemangiossarcoma/patologia , Hemangiossarcoma/cirurgia , HumanosRESUMO
There are no reports comparing the efficacy of 3 selective 5-HT(3) receptor antagonists (Granisetron, Ondansetron, and Ramosetron). We designed a prospective study to compare the efficacy of Granisetron, Ondansetron, and Ramosetron. Thirteen patients gave informed consent to participate in the study. We assigned them to groups taking Granisetron, Ondansetron, or Ramosetron before the high-dose chemotherapy. They themselves reported the extent of their nausea and how many times they vomited per day from the first to the sixth day of chemotherapy. We evaluated their report with PLS (Partial Least Squares) and Welch's t-test. From the results of PLS, it was suggested that CDDP contributed the most and Ramosetron the least to the extent of nausea, while Doxorubicin (ADM)/CDDP contributed the most and Ramosetron the least to the frequency of vomiting. Then we compared the antiemetic effect of the agents regarding the types of chemotherapy. It was concluded that Ramosetron might have been the most effective of the three agents in reducing nausea and vomiting, but with no significant difference.