RESUMO
BACKGROUND: The severity of oxaliplatin (L-OHP)-induced peripheral sensory neuropathy (PSN) exhibits substantial interpatient variability, and some patients suffer from long-term, persisting PSN. To identify single-nucleotide polymorphisms (SNPs) predicting L-OHP-induced PSN using a genome-wide association study (GWAS) approach. PATIENTS AND METHODS: A large prospective GWAS including 1379 patients with stage II/III colon cancer who received L-OHP-based adjuvant chemotherapy (mFOLFOX6/CAPOX) under the phase II (JOIN/JFMC41) or the phase III (ACHIVE/JFMC47) trial. Firstly, GWAS comparison of worst grade PSN (grade 0/1 versus 2/3) was carried out. Next, to minimize the impact of ambiguity in PSN grading, extreme PSN phenotypes were selected and analyzed by GWAS. SNPs that could predict time to recovery from PSN were also evaluated. In addition, SNPs associated with L-OHP-induced allergic reactions (AR) and time to disease recurrence were explored. RESULTS: No SNPs exceeded the genome-wide significance (P < 5.0 × 10-8) in either GWAS comparison of worst grade PSN, extreme PSN phenotypes, or time to recovery from PSN. An association study focusing on AR or time to disease recurrence also failed to reveal any significant SNPs. CONCLUSION: Our results highlight the challenges of utilizing SNPs for predicting susceptibility to L-OHP-induced PSN in daily clinical practice.
Assuntos
Neoplasias do Colo , Estudo de Associação Genômica Ampla , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Fluoruracila/uso terapêutico , Humanos , Recidiva Local de Neoplasia , Oxaliplatina/efeitos adversos , Estudos ProspectivosRESUMO
BACKGROUND: Oxaliplatin-based adjuvant chemotherapy may be associated with debilitating peripheral sensory neuropathy (PSN) in patients with high-risk stage II colon cancer. This open-label, multicenter, randomized phase III trial was conducted as a prospective pooled analysis to investigate the non-inferiority of 3 versus 6 months of adjuvant oxaliplatin-based chemotherapy. PATIENTS AND METHODS: From 12 February 2014 to 31 January 2017, 525 Asian patients with high-risk stage II colon cancer were randomly assigned to 3- and 6-month treatment arms. The treatment consisted of either modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine combined with oxaliplatin (CAPOX). The primary end point was disease-free survival (DFS). The secondary end points were treatment compliance and safety. RESULTS: Of the 525 randomized patients, 11 were not treated. Among the 514 participating patients (255 in the 3-month arm; 259 in the 6-month arm), 432 (84%) received CAPOX, and 184 (36%) presented with T4 as a high-risk factor for recurrence. The 3-year DFS rate was 88.2% in the 3-month arm and 87.9% in the 6-month arm [hazard ratio (HR), 1.12; 95% confidence interval (CI), 0.67-1.87]. With CAPOX, the 3-year DFS rate was 88.2% in the 3-month arm and 88.4% in the 6-month arm (HR, 1.13; 95% CI, 0.65-1.96). The discontinuation rate in the 3- and 6-month arms was 10% and 31% for mFOLFOX6 (P = 0.0193), and 15% and 35% for CAPOX (P < 0.0001), respectively. The incidence of grade ≥2 PSN was significantly lower in the 3-month arm than in the 6-month arm (16% and 43%, respectively, P < 0.0001). CONCLUSIONS: Three months of combination therapy presented significantly less grade ≥2 PSN than the respective 6-month regimen. The shortened therapy duration did not affect the 3-year DFS rate, suggesting that a 3-month course of CAPOX can be an effective treatment option. CLINICAL TRIAL INFORMATION: UMIN Clinical Trials Registry, UMIN000013036 and Japan Registry of Clinical Trials, jRCTs031180128.
Assuntos
Neoplasias do Colo , Compostos Organoplatínicos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Fluoruracila/efeitos adversos , Humanos , Japão , Leucovorina/efeitos adversos , Estadiamento de Neoplasias , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina/efeitos adversos , Estudos ProspectivosRESUMO
AIM: Rectal prolapse (RP) is usually associated with elderly women and is well recognized as having a detrimental effect on quality of life. A number of surgical procedures for RP are available, but morbidity and mortality are substantial. The Gant-Miwa-Thiersch procedure (GMT) has been frequently used for RP in Japan. However, as GMT has a high recurrence rate it is not widely used elsewhere. The aim of this study was to evaluate a modified version of GMT (mGMT) in comparison with other procedures. METHOD: mGMT was performed under spinal or local anaesthesia in 187 patients with RP. No normal mucosa was left between the tags and lateral wounds were created in the Thiersch procedure. Morbidity, mortality and recurrence rates were recorded. RESULTS: No serious postoperative complications and no operative deaths occurred after mGMT. Eight per cent of patients suffered from infection of the strings. The overall recurrence rate after mGMT was 7.5% with a median follow-up period of 13.8 years. CONCLUSION: On the basis of these results, we consider that mGMT has a number of advantages: it is minimally invasive, does not require general anaesthesia, is technically simple to perform and is associated with satisfactory outcomes and low morbidity. mGMT should be considered an option for the treatment of RP in elderly patients.
Assuntos
Canal Anal/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Mucosa Intestinal/cirurgia , Prolapso Retal/cirurgia , Reto/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prolapso Retal/etiologia , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: Peripheral sensory neuropathy (PSN) is a dose-limiting toxicity of oxaliplatin-based chemotherapy. Several genetic markers have been shown to predict oxaliplatin-induced PSN; however, results remain to be validated in a large-scale and prospective pharmacogenomics study. PATIENTS AND METHODS: Among 882 patients enrolled in the JFMC41-1001-C2 (JOIN trial), which was designed to investigate the tolerability of adjuvant-modified FOLFOX6 (mFOLFOX6) in Japanese Patients with stage II or III colon cancers undergoing curative resection, 465 patients were eligible for this pharmacogenomics analysis. Twelve single-nucleotide polymorphisms (SNPs) were selected based on published data. The effect of each genotype on time to PSN onset was evaluated in all patients (n = 465) using the Cox proportional hazard model. For the association analysis between severity of PSN and 12 SNP markers, 84 patients who failed to complete 12 cycles of mFOLFOX6 from grade 0/1 PSN group were excluded because the termination of the protocol treatment had been caused by reasons other than PSN. RESULTS: Comparison of grade 0/1 PSN with grade 2/3 PSN or grade 3 PSN showed no significant associations with any of the 12 SNP markers after adjustment for total dose of oxaliplatin. Time-to-onset analysis also failed to reveal any significant differences. CONCLUSIONS: Our large-scale and prospective pharmacogenomics study of Japanese patients receiving protocol treatment of adjuvant mFOLFOX6 could not verify a role for any of the 12 SNP markers reported as being significantly associated with PSN. Considering the OR observed in this study (range: 0.76-1.89), further evaluation of these 12 SNP markers in the context of L-OHP-induced PSN is unlikely to be clinically informative.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/genética , Farmacogenética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Feminino , Fluoruracila/efeitos adversos , Humanos , Japão , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/patologia , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUNDS: Preventing distant recurrence and achieving local control are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur-uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer. PATIENTS AND METHODS: The ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20-80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500-600 mg/day on days 1-5, followed by 2 days rest) or S-1 (80-120 mg/day on days 1-28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events. RESULTS: In total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61.7% [95% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63-0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm. CONCLUSION: One-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Ácido Oxônico/administração & dosagem , Neoplasias Retais/tratamento farmacológico , Tegafur/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Ácido Oxônico/efeitos adversos , Neoplasias Retais/patologia , Tegafur/efeitos adversos , Uracila/administração & dosagem , Uracila/efeitos adversosRESUMO
BACKGROUND: A targeted agent combined with chemotherapy is the standard treatment in patients with metastatic colorectal cancer (mCRC). The present phase III study was conducted to compare two doses of bevacizumab combined with irinotecan, 5-fluorouracil/leucovorin (FOLFIRI) in the second-line setting after first-line therapy with bevacizumab plus oxaliplatin-based therapy. PATIENTS AND METHODS: Patients were randomly assigned to receive FOLFIRI plus bevacizumab 5 or 10 mg/kg in 2-week cycles until disease progression. The primary end point was progression-free survival (PFS), and secondary end points included overall survival (OS), time to treatment failure (TTF), and safety. RESULTS: Three hundred and eighty-seven patients were randomized between September 2009 and January 2012 from 100 institutions in Japan. Baseline patient characteristics were well balanced between the two groups. Efficacy was evaluated in 369 patients (5 mg/kg, n = 181 and 10 mg/kg, n = 188). Safety was evaluated in 365 patients (5 mg/kg, n = 180 and 10 mg/kg, n = 185). The median PFS was 6.1 versus 6.4 months (hazard ratio, 0.95; 95% confidence interval [CI] 0.75-1.21; P = 0.676), and median TTF was 5.2 versus 5.2 months (hazard ratio, 1.01; 95% CI 0.81-1.25; P = 0.967), respectively, for the bevacizumab 5 and 10 mg/kg groups. Follow-up of OS is currently ongoing. Adverse events, including hypertension and hemorrhage, occurred at similar rates in both groups. CONCLUSION: Bevacizumab 10 mg/kg plus FOLFIRI as the second-line treatment did not prolong PFS compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC. If bevacizumab is continued after first-line therapy in mCRC, a dose of 5 mg/kg is appropriate for use as second-line treatment. CLINICAL TRIAL IDENTIFIER: UMIN000002557.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Irinotecano , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Prognóstico , Taxa de SobrevidaRESUMO
AIM: Lateral internal sphincterotomy (LIS) remains a standard for chronic anal fissure even though other surgical techniques have shown high efficacy. Faecal incontinence is a well-documented complication of LIS. We devised modified open posterior internal sphincterotomy (m-OPIS) with sliding skin graft (SSG), which is a combined procedure of OPIS and anal advancement flap. The aim of this study is to evaluate m-OPIS+SSG. METHODS: This was a retrospective, observational, single-arm study. m-OPIS+SSG was performed for chronic anal fissure and anal stenosis. m-OPIS involved incision of the internal sphincter muscle at the posterior midline until four fingers could be passed. The incision wound was closed by anastomosis of the anoderm and skin. Then, an arcuate skin incision was created and the skin graft was advanced into the anal canal. Follow-up was conducted by clinical consultation and telephone interview. Faecal continence was assessed by Cleveland Clinic Faecal Incontinence (CCFI) score. RESULTS: m-OPIS+SSG was performed in 143 patients. The mean patient age was 50±16 years. The success and overall recurrence rates after m-OPIS+SSG were 99% and 0.7%, respectively, with a median follow-up period of 16.3 years. One patient developed incontinence with liquid stools once during the 6-month period. None of the other patients suffered permanent faecal incontinence postoperatively. The postoperative CCFI score was 0.5±0.9. CONCLUSIONS: We consider m-OPIS+SSG as one of the efficacious options of procedure for chronic anal fissure and anal stenosis, owing to its high success rate, low recurrence rate and no postoperative complication of serious faecal incontinence.
Assuntos
Incontinência Fecal , Fissura Anal , Esfincterotomia Lateral Interna , Adulto , Idoso , Canal Anal/cirurgia , Doença Crônica , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Incontinência Fecal/etiologia , Incontinência Fecal/cirurgia , Fissura Anal/complicações , Fissura Anal/cirurgia , Humanos , Esfincterotomia Lateral Interna/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Transplante de Pele/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (FOLFOX) plus panitumumab therapy is a commonly used first-line chemotherapy for metastatic colorectal cancer (mCRC). However, the long-term administration of oxaliplatin is associated with peripheral neuropathy (PN). We investigated whether the planned discontinuation of oxaliplatin after FOLFOX plus panitumumab therapy can maintain efficacy and reduce PN incidence. PATIENTS AND METHODS: Chemotherapy-naive patients with RAS wild-type mCRC, aged ≥20 years, were enrolled and received six cycles of modified FOLFOX6 (mFOLFOX6) plus panitumumab as induction therapy. Patients who completed induction therapy without progression were randomised to mFOLFOX6 plus panitumumab (group A) or to 5-FU/LV plus panitumumab (group B). The primary end-point was the progression-free survival (PFS) rate at 9 months after randomisation. The secondary end-points were PFS, overall survival (OS), time to treatment failure (TTF), response rate (RR) and safety. RESULTS: In total, 164 patients were enrolled; of whom, 113 patients were then randomised (group A, n = 56; group B, n = 57). The median follow-up after randomisation was 19.6 months. The PFS rates at 9 months and median PFS were 46.4% (80% confidence interval [CI], 38.1-54.9) and 9.1 months (95% CI, 8.6-11.1) in group A, compared with 47.4% (80% CI, 39.1-55.8) and 9.3 months (95% CI, 6.0-13.0) in group B, respectively. RR, OS and TTF were also similar in both groups. Grade ≥2 PN incidence was lower in group B (9.3%) than in group A (35.7%). CONCLUSION: Planned discontinuation of oxaliplatin after six cycles of mFOLFOX6 plus panitumumab is a potential treatment option in patients with mCRC, achieving similar efficacy while reducing oxaliplatin-associated PN compared with mFOLFOX6 plus panitumumab. TRIAL REGISTRATION NUMBER: NCT02337946.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Panitumumabe/administração & dosagem , Panitumumabe/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Resultado do TratamentoRESUMO
Nociceptin peptide-receptor system is known to be essential for the regulation of hearing ability. The mRNA for nociceptin precursor protein is highly expressed in the brainstem. We explored a detailed hybridohistochemical expression pattern of the nociceptin precursor mRNA in the mouse brainstem, and identified positive cells in several auditory brainstem nuclei. Positive cells were seen in the dorsal and ventral nuclei of the lateral lemniscus, the rostral periolivary region, the lateroventral and medioventral periolivary nuclei, the dorsal periolivary region, the superior paraolivary nucleus, and the external cortex and dorsal cortex of the inferior colliculus. Of these, the medioventral and lateroventral periolivary nuclei, the major sites of origin of olivocochlear bundle, were most populated by positive cells.
Assuntos
Vias Auditivas/metabolismo , Percepção Auditiva/fisiologia , Tronco Encefálico/metabolismo , Expressão Gênica/fisiologia , Neurônios/metabolismo , Peptídeos Opioides/genética , RNA Mensageiro/metabolismo , Animais , Vias Auditivas/citologia , Tronco Encefálico/citologia , Cóclea/fisiologia , Vias Eferentes/citologia , Vias Eferentes/metabolismo , Hibridização In Situ , Colículos Inferiores/citologia , Colículos Inferiores/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Inibição Neural/fisiologia , Neurônios/citologia , Núcleo Olivar/citologia , Núcleo Olivar/metabolismo , Transmissão Sináptica/fisiologia , NociceptinaRESUMO
There is considerable evidence that the N-methyl-D-aspartate receptor (NMDAR) is a component of excitatory amino acid synapses in the ascending auditory pathway. The availability of mice that are defective in NMDAR epsilon 1 or NMDAR epsilon 4 subunit paves the way for investigations on the role of this receptor in auditory function. Non-radioactive in situ hybridization was used in the parent C57/6J wild strain to determine if these subunits are normally expressed in cochlear nucleus (CN) and superior olivary complex (SOC) and to confirm their absence in the respective mutant mice. Evoked auditory brainstem response (ABR) to normal acoustic stimulation was investigated to assess function. In situ hybridization revealed the expression of NMDAR epsilon 1 and epsilon 4 subunits mRNAs in major neuronal types in the CN and SOC of the wild type mice while epsilon 1 and epsilon 4 expression were absent in their respective mutant mice. The ABR threshold for the epsilon 1 mutant mice was similar to that of wild type mice however the threshold for the epsilon 4 mutant mice was significantly elevated. These results suggest a role for the NMDAR epsilon 4 in normal auditory functions while the NMDAR epsilon 1 may have a less critical function under normal conditions.
Assuntos
Vias Auditivas/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Receptores de N-Metil-D-Aspartato/deficiência , Animais , Núcleo Coclear/química , Feminino , Hibridização In Situ , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , RNA Mensageiro/análise , Receptores de N-Metil-D-Aspartato/biossíntese , Receptores de N-Metil-D-Aspartato/genéticaRESUMO
In our hospital, 83 patients with colorectal cancer underwent the immunologic fecal occult blood test (IFOBT). The positive rate for IFOBT in all patients was 87%. Colon cancers more proximal than the transverse colon were 100% positive. Carcinomas of the ulcerative type showed a significantly higher positive rate than those of the non-ulcerative type (94% vs 73%). Carcinomas penetrating the muscularis or beyond showed a significantly higher positive rate, of 96% (52/54 cases) compared to carcinomas confined to the mucosa or submucosa, which gave positive rates of 64% and 60%, respectively. In the investigation of the 7 patients with colorectal cancer who showed negative results on the IFOBT, IFOBT had been performed only once in of these patients. Accordingly, it was considered necessary to perform IFOBT more than once. The cancers in 5 of these 7 patients were found to be carcinomas confined to the mucosa. This result suggests the advisability of annual IFOBTs. It is also considered necessary to manage patients who show undefinable but possibly positive (+/-) results with caution.
Assuntos
Carcinoma/diagnóstico , Neoplasias Colorretais/diagnóstico , Sangue Oculto , Humanos , Técnicas Imunológicas , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Sixteen cases of gastric cancer with liver metastases (H2 less than) as group A, fifteen with distant peritoneal metastases (P2 less than) as group B, twenty-five with distant lymph nodes metastases (N3 less than) as group C, twenty-eight with two prognostic factors as group D, and seven with three factors as group E were treated. A1, B1, C1, D1 and E1 groups were treated with mitomycin C (MMC) (4 mg) + tegafur (FT) (400 mg) (i.v.-weekly) and A2, B2, and C2 group with FT (600 mg) (p.o.-daily). Partial response in the evaluable cases was found in 7 cases and a total response rate was 11.7%. The 50% survival interval was as follows; 8.5 months (M) in A1 group, 10.0 M in A2, 7.2 M in B1, 2.3 M in B2, 10.4 M in C1, 14.2 M in C2, 5.2 M-7.2 M in D1, and 3.1 M in E1. In the cases with H2 less than or N3 less than, FT (p.o.) and with P2 less than, MMC + FT (i.v.) were effective respectively. Chemotherapeutic effect was better in A1 and A2 group from the aspects of prognostic factors and in the cases of poorly differentiated adenocarcinoma from histological types than in B1 and B2 group and well or moderately differentiated adenocarcinoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mitomicinas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Administração Oral , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Mitomicina , Tegafur/administração & dosagemRESUMO
Pre-operative chemotherapy for 7 days with 5'-DFUR (p.o.) were carried out in the patients with gastric, breast, thyroid and colon cancers. The concentration of 5-fluorouracil (5-FU) in tumor cells was higher than that in the normal tissue. In case of breast cancer, it was 10 times higher than normal tissue. The concentration of 5-FU at the metastatic lymph nodes in gastric cancer was considerably high. The pattern of DNA histogram changed when chemotherapy was applied, and we observed the G2 and M phase block.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Floxuridina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Antineoplásicos/administração & dosagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Ciclo Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/cirurgia , Terapia Combinada , Feminino , Floxuridina/administração & dosagem , Floxuridina/farmacocinética , Fluoruracila/farmacocinética , Humanos , Linfonodos/enzimologia , Linfonodos/metabolismo , Pentosiltransferases/metabolismo , Cuidados Pré-Operatórios , Pirimidina Fosforilases , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirurgia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/cirurgia , Distribuição TecidualRESUMO
To clarify the pathogenetic mechanisms in acute gastric lesions induced by vibration (VIB), the effects of VIB (3.0 G, 10 Hz, 90 min) on changes in gastric mucosal blood flow (GMBF), plasma corticosterone (COR) and catecholamines (CA) as well as ulcer formation were compared with those of forced water immersion stress (FWI). While the VIB increased the GMBF during the exposure, the FWI decreased it during and after the stress. No difference in the severity of ulcer formation between the VIB groups was seen. Although both VIB and FWI increased the COR and CA, the degree of increased in the COR by the VIB tended to be less than that by the FWI. The truncal vagotomy inhibited the reduction of the GMBF and ulcer formation by the FWI, but promoted the reduction of the GMBF by the VIB. These results suggest that ulceration induced by VIB is caused primarily by its direct, mechanical and specific actions and not through the central nerve system.
Assuntos
Úlcera Gástrica/etiologia , Estresse Fisiológico/fisiopatologia , Vibração/efeitos adversos , Animais , Mucosa Gástrica/irrigação sanguínea , Imersão/efeitos adversos , Masculino , Ratos , Ratos Endogâmicos , Fluxo Sanguíneo Regional , Úlcera Gástrica/fisiopatologiaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Cisplatino/administração & dosagem , Esquema de Medicação , Neoplasias Esofágicas/tratamento farmacológico , Fluoruracila/administração & dosagem , HumanosRESUMO
Discussed is a case of a giant cell carcinoma that presented a high value of serum thyroglobulin. Histopathologically, this tumor had been diagnosed as being an anaplastic carcinoma that had transformed from a differentiated carcinoma, with calcification that was thought to have occurred from a preceding adenoma. To study the possibility of a malignant transformation, an immunohistochemical study of a specimen confirmed the production of thyroglobulin and vimentin, though the specimen stained negatively for keratin.
Assuntos
Carcinoma/patologia , Neoplasias da Glândula Tireoide/patologia , Idoso , Calcinose/patologia , Carcinoma/sangue , Carcinoma/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Tireoglobulina/biossíntese , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/metabolismo , Vimentina/biossínteseRESUMO
PURPOSE: In conventional endoscopic snare polypectomy, bleeding and perforation are the principal concerns. To prevent these complications, we employ an endoscopic clipping technique using the HX-3L clipping apparatus. METHODS: With this method, clips are used to clamp the base of a polyp. A snare is hung peripheral to the clips. The polyp is then resected by coagulating and cutting with an electric current. RESULTS: Neither bleeding nor perforation during or after polypectomy has occurred, nor have complications related to the use of clips developed. Gigantic polyps were not resected piecemeal, but rather were resected en bloc facilitating a clear determination of cancer on the surface of the resected site. Endoscopic clipping permitted site marking for colonoscopic surveillance. CONCLUSION: We conclude that the clipping method has many advantages and is a useful technique in colonoscopic polypectomy.