RESUMO
Graft-versus-host disease (GVHD) is a physiological response of the graft to allogeneic hosts. However, the effector cells, affected organ(s), and cytokines in the GVHD remain controversially discussed, without having determined a particular cytotoxic activity of the graft against the host. After i.v. injection of C57BL/6 (H-2b) spleen cells into irradiated BDF1 (H-2b/d) mice, the hosts developed interferon-gamma (IFN-γ)-dependent bone marrow (BM) GVHD on days 5-17. When H-2DdKd transgenic H-2b lymphoma cells were i.p. inoculated into irradiated, H-2b splenocyte-transplanted H-2b/d mice, the infiltration of macrophages cytotoxic against H-2DdKd transgenic H-2b mouse skin epithelia (a GVHD activity) into the peritoneal cavity preceded several days the infiltration of interleukin (IL)-2-dependent cytotoxic T lymphocytes (CTLs) to achieve a graft-versus-leukemia (GVL) effect. In contrast, allogeneic BM transplanted alone into the irradiated mice did not induce GVHD for 44 days, whereas i.v. injection of graft anti-host macrophages or graft anti-host CTLs along with allogeneic BM, respectively, induced GVHD or promoted the GVL effect in the absence of GVHD. These results revealed that macrophage-induced GVHD and the CTL-mediated GVL effect were a set (Th1: IFN-γ/IL-2) response of the graft to allogeneic hosts and leukemia cells, respectively, and that graft T cell activation rather than inhibition skipped GVHD after BM transplantation.
Assuntos
Medula Óssea/imunologia , Doença Enxerto-Hospedeiro/imunologia , Efeito Enxerto vs Leucemia/imunologia , Macrófagos/imunologia , Linfócitos T Citotóxicos/imunologia , Animais , Transplante de Medula Óssea/métodos , Linhagem Celular Tumoral , Transplante de Células-Tronco Hematopoéticas/métodos , Interferon gama/imunologia , Interleucina-2/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBARESUMO
BACKGROUND: Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy. METHODS: The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum. RESULTS: Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age. CONCLUSIONS: The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Fluoruracila/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Combinação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/administração & dosagem , Gastrectomia , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem , Tegafur/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: Between January 2012 and June 2013, we performed laparoscopic choledocholithotomy on 10 cases of common bile duct stone disease. Laparoscopic surgery for common duct stone disease is technically demanding. Particularly, laparoscopic intracorporeal suturing and knot tying for repair of choledochotomy are the most difficult skills in this operative procedures. Barbed sutures has recently been proposed to facilitate laparoscopic suturing. This is the first report demonstrating that the barbed suture could potentially improve the efficacy of the intracorporeal repair of choledochotomy following extirpation of biliary tract stones with less time needed to suture. METHODS: Consecutive 10 patients with common bile duct stones who underwent laparoscopic choledocholithotomy were enrolled in this study. Choledochotomy was closed with V-Loc sutures (15 cm V-Loc 180 sutures) for 7 patients, and a V-20 needle (26 mm, tapered) for 3 patients. RESULTS: The mean choledochotomy closure time was significantly shorter in the V-Loc group (15.2 ± 1.6 min) than in the Vicryl group (23.5 ± 1.5 min). The unidirectional barbed sutures allowed surgeons to use both their hands effectively and to focus exclusively on the placement of the subsequent stitches, without the need to maintain tension on preceding stitches to prevent slippage. And also the unidirectional barbed sutures were able to distribute tension evenly along the suture line, allowing good tissue apposition. CONCLUSION: The knotless unidirectional barbed sutures are a safe and effective tool for choledochotomy repair during surgery for common bile duct stones.
Assuntos
Procedimentos Cirúrgicos do Sistema Biliar/métodos , Coledocolitíase/cirurgia , Laparoscopia/métodos , Técnicas de Sutura/instrumentação , Suturas , Idoso , Idoso de 80 Anos ou mais , Desenho de Equipamento , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: We previously reported that S-1 plus cisplatin was feasible as adjuvant chemotherapy for stage III gastric cancer after D2 gastrectomy. Herein we evaluate the recurrence-free survival and overall survival rates as secondary endpoints based on updated follow-up data. METHODS: Patients with stage III gastric cancer who underwent D2 gastrectomy were enrolled. Treatment consisted of 3 cycles of S-1 (40 mg/m(2) PO) twice daily on days 1-21 and cisplatin (60 mg/m(2) IV) on day 8, and S-1 was given on days 1-28 every 6 weeks until 1 year after surgery. RESULTS: From August 2007 to September 2009, 63 patients were accrued. Overall, 34 and 25 patients had stage IIIA and IIIB disease, respectively. After a median follow-up of 3.9 years, 16 patients experienced recurrence and 11 patients died. The 3-year recurrence-free survival rate was 74.1 % (95 % CI: 60.8-83.5 %, IIIA 81.8 %, IIIB 64.0 %). The 3-year overall survival rate was 84.5 % (95 % CI: 72.3-91.6 %, IIIA 87.9 %, IIIB 80.0 %). Recurrence sites included the peritoneum (n = 8), hematogenous sites (n = 6), and lymph nodes (n = 4). CONCLUSION: The present results indicate that adjuvant therapy with S-1 plus 3 cycles of cisplatin may provide a survival benefit to patients with stage III gastric cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/mortalidade , Neoplasias Peritoneais/mortalidade , Neoplasias Gástricas/mortalidade , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Combinação de Medicamentos , Seguimentos , Humanos , Metástase Linfática , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Tegafur/administração & dosagemRESUMO
PURPOSE: Making a clinicopathological diagnosis of dysplasia is crucial. We herein assess the significance of the DNA methyltransferase 3b (DNMT3b) expression as a diagnostic marker of ulcerative colitis (UC)-associated neoplasia. METHODS: Thirty-one patients with long-standing and extensive UC were included in this study. The expression of DNMT3b in non-neoplastic rectal epithelium (non-dysplasia in 31 patients) and colorectal neoplasia (dysplasia in 43 patients and invasive cancer in 34 patients) was determined using immunohistochemistry. The presence of immunoreactive DNMT3b was assessed in the areas with the highest density of cells with positively staining nuclei. DNMT3b was expressed as the percentage of positive cells relative to the total number of cells counted under high power magnification. RESULTS: The DNMT3b expression in neoplastic rectal epithelium (0.76, range 0.59-0.84) was increased compared to that observed in non-neoplastic epithelium (0.32, range 0.18-0.67, P < 0.001). A ROC curve analysis confirmed 0.68 to be the best diagnostic cut-off value for the DNMT3b expression in neoplastic epithelium (area under the curve = 0.810). The sensitivity of the diagnostic test was 66.2 %, the specificity was 86.7 %, the positive predictive value was 95.7 % and the negative predictive value was 36.1 %. The positive likelihood ratio was 4.98 and the negative likelihood ratio was 0.20. The accuracy was 69.9 %. CONCLUSIONS: An immunohistochemical analysis of the DNMT3b expression was associated with significant improvements in the discrimination of UC-associated neoplastic lesions.
Assuntos
Colite Ulcerativa/diagnóstico , Neoplasias Colorretais/diagnóstico , DNA (Citosina-5-)-Metiltransferases/análise , Adulto , Biomarcadores/análise , Colite Ulcerativa/complicações , Neoplasias Colorretais/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , DNA Metiltransferase 3BRESUMO
BACKGROUND: Laparoscopic gastrectomy has recently been gaining popularity as a treatment for cancer; however, little is known about the benefits of intracorporeal (IC) gastrointestinal anastomosis with pure laparoscopic distal gastrectomy (LDG) compared with extracorporeal (EC) anastomosis with laparoscopy-assisted distal gastrectomy (LADG). METHODS: Between June 2000 and December 2011, we assessed 449 consecutive patients with early-stage gastric cancer who underwent LDG. The patients were classified into three groups according to the method of reconstruction LADG followed by EC hand-sewn anastomosis (LADG + EC) (n = 73), using any of three anastomosis methods (Billroth-I (B-I), Billroth-II (B-II) or Roux-en-Y (R-Y); LDG followed by IC B-I anastomosis (LDG + B-I) (n = 248); or LDG followed by IC R-Y anastomosis (LDG + R-Y) (n = 128)). The analyzed parameters included patient and tumor characteristics, operation details, and post-operative outcomes. RESULTS: The tumor location was significantly more proximal in the LDG + R-Y group than in the LDG + B-I group (P < 0.01). Mean operation time, intra-operative blood loss, and the length of post-operative hospital stay were all shortest in the LDG + B-I group (P < 0.05). Regarding post-operative morbidities, anastomosis-related complications occurred significantly less frequently in with the LDG + B-I group than in the LADG + EC group (P < 0.01), whereas there were no differences in the other parameters of patients' characteristics. CONCLUSIONS: Intracorporeal mechanical anastomosis by either the B-I or R-Y method following LDG has several advantages over at the LADG + EC, including small wound size, reduced invasiveness, and safe anastomosis. Although additional randomized control studies are warranted to confirm these findings, we consider that pure LDG is a useful technique for patients with early gastric cancer.
Assuntos
Anastomose em-Y de Roux , Gastrectomia , Trato Gastrointestinal/cirurgia , Laparoscopia , Complicações Pós-Operatórias , Neoplasias Gástricas/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Procedimentos de Cirurgia Plástica , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
BACKGROUND: As newer immunosuppressive regimens have steadily reduced in the incidence of acute rejection and have extended the life expectancy of allograft recipients, posttransplant de novo malignancies have become an important cause of death in cadaveric donor transplantation. Also, according with the recent accumulation of living donor liver transplantation (LDLT), the number of posttransplant recipients with de novo malignancy will be anticipated to increase. CASE REPORT: A 60 year-old man underwent LDLT for hepatitis C virus-related cirrhosis with hepatocellular carcinoma. Thirty months after LDLT, he was found to have gastric cancer by upper gastrointestinal endoscopy. He underwent segmental gastrectomy with lymph node dissection. Histopathological examination of the explanted stomach revealed poorly differentiated adenocarcinoma with subserosal invasion in the gastric wall and perigastric lymph node metastasis. Three years and eight months after the gastric surgery, the patient is alive with no recurrence of gastric cancer or HCC under no adjuvant chemotherapy. CONCLUSIONS: Considering that early detection is the only key in curing cancer in general, we should make effort to detect cancer in their early stage, especially in case of LDLT recipients.
Assuntos
Adenocarcinoma/diagnóstico , Transplante de Fígado , Segunda Neoplasia Primária/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Carcinoma Hepatocelular/cirurgia , Gastrectomia , Hepatite C/cirurgia , Humanos , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND/AIMS: The prognostic factor(s) of carcinoma of the ampulla of Vater were analyzed retrospectively and the significance of lymphadenectomy around the superior mesenteric artery and para-aortic region on the clinical outcome was evaluated. METHODOLOGY: From 1985 to 2008, 34 carcinomas of the ampulla of Vater patients who underwent pancreaticoduodenectomy with curative intent were analyzed with respect to tumor extent, operation method and prognosis. RESULTS: Overall 5-year survival was 52.6%. On multivariate analysis, lymph node metastasis, pancreatic invasion, venous invasion, perineural invasion and lymphadenectomy around the superior mesenteric artery were the significant prognostic factors. However, the dissection of para-aortic lymph nodes had no substantial survival benefit. Compared with the duodenal cancer, the prognosis for carcinoma of the ampulla of Vater was significantly worse although no differences in clinicopathological characteristics of patients were observed. CONCLUSIONS: Lymph node metastasis, pancreatic invasion, venous invasion, perineural invasion, and lymphadenectomy around the superior mesenteric artery are important prognostic factors. Pylorus-preserving pancreaticoduodenectomy, with lymphadenectomy around the superior mesenteric artery without dissection of para-aortic lymph nodes is recommended as optimal surgery. Though the treatment results were worse than that of duodenal cancer, curative operation should be performed, regardless of site of origin.
Assuntos
Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Carcinoma/cirurgia , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/cirurgia , Excisão de Linfonodo , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal , Vasos Sanguíneos/patologia , Feminino , Humanos , Metástase Linfática , Masculino , Mesentério , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Pâncreas/patologia , Pancreaticoduodenectomia , Estudos RetrospectivosRESUMO
Survivin is an oncogene that functions in cancer cell cytoprotection and mitosis. Here we report that differential expression in cancer cells of a C-terminal splice variant of survivin, termed survivin-ΔEx3, is tightly associated with aggressive disease and markers of unfavorable prognosis. In contrast to other survivin variants, survivin-ΔEx3 localized exclusively to nuclei in tumor cells and was phosphorylated at multiple residues by the checkpoint kinase Chk2 during DNA damage. Mutagenesis of the Chk2 phosphorylation sites enhanced the stability of survivin-ΔEx3 in tumor cells, inhibited the expression of phosphorylated H2AX (γH2AX) in response to double-strand DNA breaks, and impaired growth after DNA damage. DNA damage induced Chk2 phosphorylation, stabilization of p53, induction of the cyclin-dependent kinase inhibitor p21, and homologous recombination-induced repair were not affected. In vivo, active Chk2 was detected at the earliest stages of the colorectal adenoma-to-carcinoma transition, persisted in advanced tumors, and correlated with increased survivin expression. Together, our findings suggest that Chk2-mediated phosphorylation of survivin-ΔEx3 contributes to a DNA damage-sensing checkpoint that may affect cancer cell sensitivity to genotoxic therapies.
Assuntos
Dano ao DNA , Proteínas Inibidoras de Apoptose/metabolismo , Neoplasias/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Quinase do Ponto de Checagem 2 , Primers do DNA , Humanos , Mutagênese , Neoplasias/patologia , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Frações Subcelulares/metabolismo , SurvivinaRESUMO
Schwannoma is predominantly a benign neoplasm of the Schwann cells in the neural sheath of the peripheral nerves. Occurrence of schwannoma in parenchymatous organs, such as liver, is extremely rare. A 64-year-old man without neurofibromatosis was observed to have a space-occupying lesion of 23mm diameter in the liver during follow-up examination for a previously resected gastrointestinal stromal tumor (GIST) in the small intestine. He underwent lateral segmentectomy of the liver under a provisional diagnosis of hepatic metastatic recurrence of the GIST. Histological examination confirmed the diagnosis of a benign schwannoma, confirmed by characteristic pathological findings and positive immunoreactions with the neurogenic marker S-100 protein, but negative for c-kit, or CD34. The tumor was the smallest among the reported cases. When the primary hepatic schwannoma is small in size, preoperative clinical diagnosis is difficult. Therefore, this disease should be listed as differential diagnosis for liver tumor with clinically benign characteristics.
RESUMO
Allograft (H-2D(d)K(d))-induced macrophages (AIM) in C57BL/6 (H-2D(b)K(b)) mice exhibit major histocompatibility complex (MHC) haplotype-specific killing of allografts in a macrophage MHC receptor 1 (MMR1; for H-2D(d))- and MMR2 (for H-2K(d))-dependent manner. Recently, we showed HLA-B62 to be a ligand for the human homologue of mouse MMR2. In the present study, we isolated a cDNA encoding the human homologue of mouse MMR1 and found HLA-B44 to be the sole ligand specific for the human MMR1 by using beads that had been conjugated with 80 kinds of HLA proteins. Flow cytometric analyses revealed that HLA-B44-conjugated beads are specifically bound to HEK293T cells expressing human MMR1, that HLA-B44 tetramers are bound to the human MMR1-transfected HEK293T cells with a dissociation constant of 3.0×10(-9) M, and that the interaction was completely inhibited by the addition of R15 monoclonal antibody specific for mouse MMR1. The MMR1 cDNA (1537-bp) encoded a 473-amino acid polypeptide and was expressed at least in part in the brain and peripheral blood mononuclear cells (PBMCs) or monocytes, but not in granulocytes or lymphocytes. PBMCs from 7 non-H-2D(d) (non-self), but none from 5 H-2D(d) (self), in-bred mice expressed mouse MMR1 specific for H-2D(d). In contrast, PBMCs from none of the 16 human volunteers expressed HLA-B44; whereas those from only 3 of these 16 volunteers expressed human MMR1. These results reveal that human MMR1 on monocytes is a novel receptor specific for HLA-B44.
Assuntos
Antígeno HLA-B44/imunologia , Monócitos/imunologia , Receptores Imunológicos/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Encéfalo/imunologia , Células HEK293 , Antígeno HLA-B44/química , Humanos , Leucócitos Mononucleares/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Receptores Imunológicos/química , Receptores Imunológicos/genéticaAssuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/diagnóstico , Proteínas de Neoplasias/análise , Proteoma , Tubulina (Proteína)/análise , Biomarcadores Tumorais/imunologia , Western Blotting , Linhagem Celular Tumoral , Neoplasias Colorretais/imunologia , Diagnóstico Precoce , Eletroforese em Gel Bidimensional , Humanos , Imuno-Histoquímica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Tubulina (Proteína)/imunologiaRESUMO
To identify the proteins involved in 5-fluorouracil (5-FU) resistance, a comparison of the total and phosphorylated proteins between the human colorectal cancer (CRC) cell line DLD-1 and its 5-FU-resistant subclone DLD-1/5-FU was performed. Using 2-DE and MALDI-TOF/TOF-based proteomics, 17 up-regulated and 19 down-regulated protein spots were identified in the 5-FU-resistant DLD-1/5-FU cells compared with the parent cell lines. In DLD-1/5-FU cells, 7 anti-apoptotic proteins (HSPB1, proteasome subunit α-5, transitional endoplasmic reticulum ATPase, 14-3-3 ß, 14-3-3 γ, 14-3-3 σ, and phosphoglycerate kinase 1) were up-regulated and 4 proapoptotic proteins (cofilin-1, pyruvate kinase M2, glyceraldehyde-3-phosphate dehydrogenase, and nucleophosmin) were down-regulated. The results show that the acquired drug resistance of DLD-1/5-FU cells is caused by the prevention of drug-induced apoptosis, in particular through the enhanced constitutive expression of HSPB1 and its phosphorylated form. Short interfering RNA knockdown of endogenous HSPB1 in DLD-1/5-FU cells restored the sensitivity to 5-FU. Furthermore, MALDI-TOF/TOF and 2-DE Western blot analysis identified the phosphorylated residues of HSPB1 as Ser-15 and Ser-82 in the main (diphosphorylated) form and Ser-15, Ser-78, and Ser-82 in the minor (triphosphorylated) form. The current findings indicate that phosphorylated HSPB1 may play an important role in 5-FU resistance.
Assuntos
Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Neoplasias/metabolismo , Proteômica , Nucleotídeos de Uracila/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico , Humanos , Chaperonas Moleculares , Proteínas de Neoplasias/genética , Fosforilação , Serina/genética , Serina/metabolismoRESUMO
BACKGROUND: Cancers are supported by a distinct type of stroma, and versican is overexpressed in the stroma of malignant tumors, including breast cancer. Versican interacts with hyaluronan and fibrillin-1 at its amino terminus (G1) and carboxyl terminus (G3), respectively. Fibrillin-1 also associates with latent transforming growth factor-ß binding protein (LTBP)-1 and -4. The detailed alteration of these molecules in breast cancer tissues is still unclear. METHODS: In 18 patients, alteration of versican, fibrillin-1 and LTBP-1 and 4 was elucidated in comparison with matched normal tissues, using real-time reverse transcriptase polymerase chain reaction, slot blotting and immunohistochemistry. The relationship between the protein expression and clinicopathological features was also investigated. RESULTS: In breast cancer tissues, mRNAs for versican V1 and V0 were upregulated, and the extracted protein levels of the versican G1 and G3 domains were increased. Meanwhile, LTBP-4 was decreased, and fibrillin-1 and LTBP-1 remained unchanged. The immunohistochemical observations were consistent with the biochemical findings, and the molecules were localized in the stromal tissue rather than in the cancer cells themselves. The expression of versican G3 and G1 domains was positively related to the Ki67 index of carcinoma cells and tumor size, respectively. CONCLUSION: The stromal alterations of versican and LTBP-4 might influence the carcinogenesis and progression of breast tumor cells and modulate their biological phenotypes.
Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Proteínas de Ligação a TGF-beta Latente/genética , Versicanas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Proteínas de Ligação a TGF-beta Latente/metabolismo , Pessoa de Meia-Idade , Estrutura Terciária de Proteína , Valores de Referência , Células Estromais/metabolismo , Regulação para Cima , Versicanas/metabolismoRESUMO
PURPOSE: Small bowel adenocarcinoma is a relatively uncommon neoplasm that accounts for approximately 0.3% to 2.4% of digestive cancers. In comparison with carcinomas of the other areas of the gastrointestinal tract, the prognosis for small bowel adenocarcinoma is generally worse. The prognostic factors of small bowel adenocarcinoma were analyzed retrospectively, and the significance of operative procedure, lymphadenectomy, and adjuvant chemotherapy was evaluated. METHODS: From 1990 to 2009, 30 patients with small bowel adenocarcinoma who underwent surgery at Osaka Medical College Hospital were analyzed with respect to tumor extent, operation method, and prognosis. RESULTS: Overall 5-year survival was 52.5%, and the median survival time was 27.0 months. On univariate and multivariate analyses, the location (duodenum vs. jejunum and ileum), size (greater or less than 70 mm), and tumor, nodes, and metastasis (TNM) stage (stage 0 + I + II vs. III + IV) of the tumor were the significant prognostic factors. No differences in survival and recurrence rates were observed between patients undergoing pancreaticoduodenectomy and those undergoing partial resection, between those undergoing mural lymphadenectomy and those undergoing extended lymphadenectomy, or between those with and without adjuvant chemotherapy. The combination of surgery and adjuvant chemotherapy did not control recurrence or improve the prognosis. CONCLUSIONS: In small bowel adenocarcinoma, location, size, and TNM stage of the tumors were the independent prognostic factors after curative resections. Partial resection with mural lymphadenectomy may be recommended as optimal surgery for small bowel adenocarcinoma.
Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Neoplasias Intestinais/mortalidade , Neoplasias Intestinais/patologia , Intestino Delgado/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Humanos , Neoplasias Intestinais/cirurgia , Intestino Delgado/cirurgia , Estimativa de Kaplan-Meier , Masculino , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: The role of laparoscopic surgery in management of transverse and descending colon cancer remains controversial. The aim of the present study is to investigate the short-term and oncologic long-term outcomes associated with laparoscopic surgery for transverse and descending colon cancer. METHODS: This cohort study analyzed 245 patients (stage II disease, n = 70; stage III disease, n = 63) who underwent resection of transverse and descending colon cancers, including 200 laparoscopic surgeries (LAC) and 45 conventional open surgeries (OC) from December 1996 to December 2010. Short-term and oncologic long-term outcomes were recorded. RESULTS: The operative time was longer in the LAC group than in the OC group. However, intraoperative blood loss was significantly lower and postoperative recovery time was significantly shorter in the LAC group than in the OC group. The 5-year overall and disease-free survival rates for patients with stage II were 84.9% and 84.9% in the OC group and 93.7% and 90.0% in the LAC group, respectively. The 5-year overall and disease-free survival rates for patients with stage III disease were 63.4% and 54.6% in the OC group and 66.7% and 56.9% in the LAC group, respectively. CONCLUSION: Use of laparoscopic surgery resulted in acceptable short-term and oncologic outcomes in patients with advanced transverse and descending colon cancer.
Assuntos
Colectomia/métodos , Colo Descendente/cirurgia , Neoplasias do Colo/cirurgia , Laparoscopia/métodos , Idoso , Perda Sanguínea Cirúrgica , Estudos de Coortes , Colectomia/mortalidade , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Laparoscopia/mortalidade , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/mortalidade , Resultado do TratamentoRESUMO
BACKGROUND: Randomized trials and cohort studies show that laparoscopic distal gastrectomy (LDG) achieves similar oncological results to open distal gastrectomy (ODG). However, studies have consistently demonstrated lower lymph node yield (LNY) for laparoscopic lymphadenectomy. Analysis of station-specific LNY may be useful in evaluating the reasons behind this difference. OBJECTIVES: Comparison of station-specific LNY, surgical, and oncological outcomes between LDG and ODG for early gastric cancer. METHODS: Patients who underwent R0 distal gastrectomy with histologically confirmed early gastric cancer were eligible for the study. All consecutive cases of LDG since the beginning of our experience with laparoscopic gastrectomy and synchronous cases of ODG with R0 resection were included in the study. Demographic, operative, histopathologic, and follow-up data were recorded in all patients. RESULTS: A total of 259 cases of LDG and 95 cases of ODG were performed between 2000 and 2009. Patients undergoing LDG had longer operations but less bleeding (P<0.05). Postoperative complications were similar in both groups. The preoperatively planned extent of lymphadenectomy was D1 (stations 1, 3, 4sb, 4d, 5, 6, and 7), D1+ (D1with stations 8a and 9), or D2 (D1+ with stations 11p and 12a). During surgery, dissection of stations 3, 4d, 5, 6, and 7 was performed in all cases of LDG and ODG. Dissection of stations 1, 4sb, 8a, 9, 11p, and 12a was performed more frequently during ODG than during LDG. Consequently, the total LNY was 26.71 and 31.43 for LDG and ODG, respectively. Station-specific LNY was significantly lower for LDG than for ODG in the common hepatic artery nodes only (P<0.05). The mean follow-up was 43.6 months. Lymph node metastases, metastatic-to-resected lymph node ratio, recurrence, and cancer-related deaths were similar for LDG and ODG. CONCLUSIONS: LDG was associated with less extensive lymph node dissection compared with ODG. Station-specific LNY was similar in all nodal stations except for the common hepatic artery nodes. In our experience, laparoscopic sub-D2 lymphadenectomy was adequate in the context of early gastric cancer and represents the future of gastric cancer resection in Japan.
Assuntos
Gastrectomia/métodos , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Tempo de Internação/estatística & dados numéricos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
Hepatocellular carcinoma (HCC) with a tumor thrombus (TT) extending into the right atrium is generally regarded as a terminal-stage condition. We report a case of long-term survival following treatment of this complication with en bloc hepatectomy and resection of the thrombus under cardiopulmonary bypass. Our review of 19 similar cases reported in the literature found the following: that lung metastasis, the most critical prognostic factor, occurred in only 5 (27.8%) patients; that postoperative survival ranged from 18 days to 56 months, with a median survival of 11 months; and that 7 (38.9%) patients showed no signs of recurrence, with 4 (21.1%) surviving longer than 2 years. Thus, to prevent sudden death and extend the survival of patients with HCC and TT extending into the right atrium, we advocate simultaneous en bloc resection performed under cardiopulmonary bypass, provided distant metastasis and recurrence in the remnant liver are controlled.
Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Trombose Coronária/etiologia , Trombose Coronária/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Idoso , Trombose Coronária/diagnóstico , Átrios do Coração , Hepatectomia , Humanos , MasculinoRESUMO
PURPOSE: To investigate the diagnostic performance and clinical feasibility of diffusion-weighted magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph nodes (ALNs) in patients with breast cancer. MATERIALS AND METHODS: Sixteen patients with known breast cancer underwent 1.5 T MRI. Axial diffusion-weighted images (DWIs) and conventional T1- and T2*-weighted images (CIs) were acquired before and 24-36 hours after intravenous administration of USPIO. Detection of ALNs was evaluated on DWIs in comparison with CIs. The apparent diffusion coefficient values (ADCvs) of the nonmetastatic and metastatic nodes in precontrast DWIs were determined. The diagnostic performance of DWI using USPIO was compared with that of CIs using USPIO with pathological correlation. RESULTS: Out of a total of 286 ALNs, 216/286 (76%) nodes were detected on DWIs and 238/286 (83%) on CIs. The differences in the ADCvs between metastatic and nonmetastatic nodes were not significant (P = 0.06). Sensitivity of CIs and DWIs using USPIO were respectively 70% and 83%, specificity 98% and 98%, and overall accuracy 93% and 95%. CONCLUSION: Although the detection on DWIs of ALNs in patients with breast cancer was inferior compared to CIs, the sensitivity and accuracy of DWIs using USPIO were superior in the diagnosis of ALNs metastasis.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/secundário , Dextranos , Nanopartículas de Magnetita , Adulto , Axila/patologia , Carcinoma , Meios de Contraste , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Projetos Piloto , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
Laparoscopic colorectal resection has been applied to advanced colorectal cancer. Synchronous liver metastasis of colorectal cancer would be treated safely and effectively by simultaneous laparoscopic colorectal and hepatic resection. Seven patients with colorectal cancer and synchronous liver metastasis treated by simultaneous laparoscopic resection were analyzed retrospectively. Three patients received a hybrid operation using a small skin incision, 2 patients underwent hand-assisted laparoscopic surgery using a small incision produced for colonic anastomosis, and 2 patients were treated with pure laparoscopic resection. The mean total operation duration was 407 minutes, and mean blood loss was 207 mL. Negative surgical margins were achieved in all cases. Mean postoperative hospital stay was 16.4 days. No recurrence at the surgical margin was observed in the liver. For selected patients with synchronous liver metastasis of colorectal cancer, simultaneous laparoscopic resection is useful for minimizing operative invasiveness while maintaining safety and curability, with satisfying short- and long-term results.