RESUMO
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
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of localised colon cancer was published in 2020. It was decided by both the ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special virtual guidelines meeting in March 2021 to adapt the ESMO 2020 guidelines to take into account the ethnic differences associated with the treatment of localised colon cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with localised colon cancer representing the oncological societies of Japan (JSMO), China (CSCO), India (ISMPO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug availability and reimbursement situations in the different Asian countries.
Assuntos
Neoplasias do Colo , Oncologia , Ásia/epidemiologia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/terapia , Seguimentos , Humanos , República da CoreiaRESUMO
BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a well established treatment for severe obesity and type 2 diabetes. Although the gut microbiota is linked to the efficacy of LSG, the underlying mechanisms remain elusive. The effect of LSG for morbid obesity on the gut microbiota and bile acids was assessed here. METHODS: Severely obese subjects who were candidates for LSG were included and followed until 6 months after surgery. The composition and abundance of the microbiota and bile acids in faeces were assessed by 16S ribosomal RNA sequencing, quantitative PCR and liquid chromatography-mass spectrometry. RESULTS: In total, 28 patients with a mean(s.d.) BMI of 44·2(6·6) kg/m2 were enrolled. These patients had achieved excess weight loss of 53·2(19·0) per cent and showed improvement in metabolic diseases by 6 months after LSG, accompanied by an alteration in the faecal microbial community. The increase in α-diversity and abundance of specific taxa, such as Rikenellaceae and Christensenellaceae, was strongly associated with reduced faecal bile acid levels. These changes had a significant positive association with excess weight loss and metabolic alterations. However, the total number of faecal bacteria was lower in patients before (mean(s.d.) 10·26(0·36) log10 cells per g faeces) and after (10·39(0·29) log10 cells per g faeces) operation than in healthy subjects (10·83(0·27) log10 cells per g faeces). CONCLUSION: LSG is associated with a reduction in faecal bile acids and greater abundance of specific bacterial taxa and α-diversity that may contribute to the metabolic changes.
ANTECEDENTES: La gastrectomía vertical laparoscópica (laparoscopic sleeve gastrectomy, LSG) es un tratamiento bien establecido para la obesidad grave y la diabetes tipo 2. Aunque la microbiota intestinal se ha vinculado con la eficacia de LSG, los mecanismos subyacentes siguen siendo poco conocidos. En este estudio se evaluó el efecto de LSG en la obesidad mórbida sobre la microbiota del intestino y de los ácidos biliares (bile acids, BA). MÉTODOS: Tras la aprobación del Comité ético y la obtención del consentimiento informado, los sujetos con obesidad grave que eran candidatos para LSG fueron incluidos en el estudio y seguidos durante 6 meses después de la operación. Se evaluaron la composición y abundancia de la microbiota y BA en las heces mediante secuenciación del gen 16S rRNA, PCR cuantitativa y cromatografía líquida-espectrometría de masas. RESULTADOS: En total, 28 pacientes con una mediana (rango) del IMC de 43,9 kg/m2 (35,0-61,9) fueron reclutados y a los 6 meses tras una LSG, consiguieron una pérdida del exceso de peso de 47,3% (20,7-95,1) y mejoría de las enfermedades metabólicas acompañada de una alteración en la comunidad microbiana fecal. El aumento en la diversidad α y abundancia de especies taxonómicas específicas como Rikenellaceae y Christensenellaceae, se asociaba fuertemente con niveles fecales reducidos de BA. Estos cambios se asociaban de manera positiva y significativa con la pérdida del exceso de peso y las alteraciones metabólicas. Sin embargo, el número total de bacterias fecales en los pacientes fue inferior al de los sujetos sanos (10,84 log10 células/g heces (9,46-11,35)) antes de la operación (10,26 log10 células/g heces (9,44-10,91)) y después de la misma (10,42 log10 células/g heces (9,57-10,96)). CONCLUSIÓN: LSG se asoció con menos BA fecal y mayor abundancia de especies bacterianas específicas y diversidad α lo que puede contribuir a los cambios metabólicos.
Assuntos
Ácidos e Sais Biliares/análise , Fezes/química , Gastrectomia/métodos , Laparoscopia/estatística & dados numéricos , Obesidade Mórbida/cirurgia , Adulto , Carga Bacteriana , Biodiversidade , Diabetes Mellitus Tipo 2/microbiologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Concentração de Íons de Hidrogênio , Masculino , Obesidade Mórbida/microbiologia , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND: The objective of this randomized phase II trial was to evaluate efficacy and safety of the therapeutic sequence of regorafenib followed by cetuximab, compared with cetuximab followed by regorafenib, as the current standard sequence for metastatic colorectal cancer patients. PATIENTS AND METHODS: Patients with KRAS exon 2 wild-type metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive sequential treatment with regorafenib followed by cetuximab ± irinotecan (R-C arm), or the reverse sequence [cetuximab ± irinotecan followed by regorafenib (C-R arm)]. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) with initial treatment (PFS1), PFS with second treatment (PFS2), safety, and quality of life. Exploratory end points included serial biomarker analyses, including oncogenic alterations from circulating tumor DNA or multiple serum or plasma proteins. RESULTS: One-hundred one patients were randomized and eligible for efficacy analysis. Sequential treatment was successful in 86% patients in both arms. Median OS for R-C and C-R was 17.4 and 11.6 months, respectively (P = 0.0293), with a hazard ratio (HR) of 0.61 for OS [95% confidence interval (CI) 0.39-0.96]. The HR for PFS1 (regorafenib in R-C versus cetuximab in C-R) was 0.97 (95% CI 0.61-1.54), and PFS2 (C in R-C versus R in C-R) was 0.29 (95% CI 0.17-0.50). No unexpected safety signals were observed. The quality of life scores during the entire treatment period was not significantly different between the two arms. Circulating biomarker analyses showed emerging oncogenic alterations in RAS, BRAF, EGFR, HER2, and MET, which were more commonly detected after cetuximab than after regorafenib. CONCLUSIONS: The therapeutic sequence of regorafenib followed by cetuximab suggests a longer OS than the current standard sequence.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adenocarcinoma/secundário , Idoso , Cetuximab/administração & dosagem , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Compostos de Fenilureia/administração & dosagem , Prognóstico , Piridinas/administração & dosagem , Taxa de SobrevidaRESUMO
The predominant histological types of esophageal cancer are adenocarcinoma and squamous cell carcinoma. Since these two histological types present as different diseases in terms of their epidemiology, pathologenesis, and tumor biology, separate therapeutic approaches should be developed against each type. While surgical resection remains the dominant therapeutic intervention for patients with operable esophageal squamous cell carcinoma (ESCC), their high rates of tumor recurrence have prompted investigation of multimodality therapies that combine surgery with chemotherapy, radiotherapy, and chemoradiotherapy. In Japan, preoperative chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU) followed by radical esophagectomy has been accepted as the standard therapeutic approach for resactable clinical Stage II/III ESCC. Similarly, the CDDP and 5-FU regimen has been accepted as the first-line treatment for metastatic and unresectable ESCCs in Japan. Thus, in Japan chemotherapy is an indispensable component of therapy for both resectable and unresectable ESCCs. This review discusses the current knowledge, rationale, and available data regarding chemotherapy for resectable and unresectable ESCCs.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Quimioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Terapia Combinada , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago , Esofagectomia/métodos , Fluoruracila/administração & dosagem , Humanos , Japão , Resultado do TratamentoRESUMO
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: Recent advances in the management of lupus nephritis (LN) have also contributed to a favorable outcome in patients with pediatric-onset LN. Nevertheless, we believe that a more effective and less toxic treatment is needed to attain optimal control of pediatric-onset LN. METHODS: Seven consecutive children with biopsy-proven LN (four with class III/IV and three with class V) received multitarget induction therapy consisting of mizoribine (MZR), tacrolimus (Tac), and prednisolone (PDN). They were prospectively evaluated at three, six, and 12 months, and at the latest observation point after a mean period of 32 months. Post-treatment renal biopsy was performed in two patients with class III/IV. RESULTS: Despite gradually tapering the dose of concomitantly administered PDN, a significant improvement compared with baseline values was observed in the urinary, serological, and clinical assessment measures even at three months of treatment, and the favorable changes persisted throughout the treatment period in most of the study participants except for one. In two patients who underwent post-treatment renal biopsy, a marked histologic improvement was confirmed. No serious adverse events were observed. CONCLUSIONS: Multitarget therapy may be an attractive option for the treatment of pediatric-onset LN. Further studies involving a larger number of patients are needed.
Assuntos
Glucocorticoides/administração & dosagem , Imunossupressores/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Prednisolona/administração & dosagem , Ribonucleosídeos/administração & dosagem , Tacrolimo/administração & dosagem , Adolescente , Criança , Quimioterapia Combinada , Feminino , Humanos , Quimioterapia de Indução , Masculino , Projetos Piloto , Estudos Prospectivos , Resultado do TratamentoRESUMO
Both internal and external oxidative stresses act on DNA and can induce carcinogenesis. 8-hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and it leads to transversion mutations and carcinogenesis. 8-OHdG is excision-repaired by 8-OHdG DNA glycosylase (OGG1). The purpose of this study is to clarify the effect of oxidative DNA damage and repair enzymes on esophageal carcinogenesis. The levels of 8-OHdG and OGG1 were immunohistochemically evaluated in resected specimens, including squamous cell carcinoma (SCC) in 97 patients with esophageal cancer. Higher levels of 8-OHdG in normal esophageal epithelium were associated with a higher smoking index (P = 0.0464). The 8-OHdG level was higher in cancerous areas than in normal epithelia (P = 0.0061), whereas OGG1 expression was weaker in cancerous areas than in normal epithelia (P < 0.0001). An increase of OGG1 expression in normal epithelium was observed as 8-OHdG levels increased (P = 0.0011). However, this correlation was not observed in cancerous areas. High OGG1 expression in the cytoplasm was related to deeper tumors (P = 0.0023), node metastasis (P = 0.0065) and stage (P = 0.0019). Oxidative DNA damage, which is attributable to smoking as well as disturbances in DNA repair systems, appears to be closely related to esophageal carcinogenesis and its progression.
Assuntos
Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Dano ao DNA , DNA Glicosilases/análise , Desoxiguanosina/análogos & derivados , Neoplasias Esofágicas/enzimologia , Neoplasias Esofágicas/patologia , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Carcinoma de Células Escamosas/genética , Enzimas Reparadoras do DNA/análise , Desoxiguanosina/análise , Epitélio/enzimologia , Neoplasias Esofágicas/genética , Esôfago/enzimologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estresse Oxidativo , FumarRESUMO
Replacing the thoracic esophagus with the colon is one mode of reconstruction after esophagectomy for esophageal cancer. There is, however, a high incidence of postoperative necrosis of the transposed colon. This study evaluated the outcomes of colon interposition with the routine use of superdrainage by microvascular surgery. Twenty-one patients underwent colon interposition from 2004 to 2009. The strategy for colon interposition was to: (i) use the right hemicolon; (ii) reconstruct via the subcutaneous route; (iii) perform a microvascular venous anastomosis for all patients; and (iv) perform a microvascular arterial anastomosis when the arterial blood flow was insufficient. The clinicopathologic features, surgical findings, and outcomes were investigated. The colon was used because of a previous gastrectomy in 18 patients (85.7%) and synchronous gastric cancer in three patients (14.3%). Eight patients (38.1%) underwent preoperative chemoradiotherapy including three (14.3%) treated with definitive chemoradiotherapy. Seven patients (33.3%) underwent microvascular arterial anastomosis to supplement the right colon blood supply. Pneumonia occurred in four patients (19.0%). Anastomotic leakage was observed in five patients (23.8%); however, no colon necrosis was observed. The 3-year and 5-year overall survival rates were both 50.6%. Colon interposition with superdrainage results in successful treatment outcomes. This technique is one option for colon interposition employing the right hemicolon.
Assuntos
Colo/transplante , Neoplasias Esofágicas/cirurgia , Esôfago/irrigação sanguínea , Microcirculação/fisiologia , Procedimentos de Cirurgia Plástica/métodos , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/métodos , Anastomose Cirúrgica/mortalidade , Estudos de Coortes , Colo/irrigação sanguínea , Drenagem , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Japão , Veias Jugulares/transplante , Masculino , Veias Mesentéricas/transplante , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/mortalidade , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Toracotomia/efeitos adversos , Toracotomia/métodos , Resultado do TratamentoRESUMO
The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer (mCRC), published in late 2022, were adapted in December 2022, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with mCRC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with mCRC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian countries. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with mCRC across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation, coupled with a disparity in the drug approvals and reimbursement strategies, between the different countries.
Assuntos
Neoplasias do Colo , Humanos , Seguimentos , Ásia , Sociedades Médicas , OncologiaRESUMO
BACKGROUND: Delta-shaped (DS) anastomosis is a new reconstruction method for totally laparoscopic distal gastrectomy (TLDG) using a linear stapler. We evaluated the feasibility of using this method for TLDG. METHODS: A retrospective analysis was performed in 114 patients who underwent TLDG with DS anastomosis. Twenty-four patients reconstructed with a Roux-en-Y (RY) anastomosis during the same period were analyzed as control subjects. RESULTS: The patient characteristics of DS and RY anastomoses were slightly different in terms of tumor location and extent of lymph node dissection, since this was not a prospective comparative study. Blood loss, postoperative complication rate and postoperative hospital stay were not different between the two groups. There was only 1 case of anastomotic leakage, and no case of anastomotic stricture after DS anastomosis. The length of the operation using DS anastomosis was significantly shorter than for RY anastomosis. The rates of body weight loss were not significantly different at 1 year after the operation. CONCLUSIONS: Although this was a small retrospective analysis, DS anastomosis was feasible, required a shorter operation time, and had no associated complications. This method can therefore be recommended as a standard procedure for TLDG.
Assuntos
Anastomose Cirúrgica/métodos , Gastrectomia/métodos , Laparoscopia , Idoso , Estudos de Viabilidade , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Estômago/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Recent advances in adjuvant chemotherapy for early colon cancer have widened physicians' recommendations on the regimen and duration (3 or 6 months) of the treatment. We conducted this prospective study to evaluate whether the 12-gene recurrence score (12-RS) assay affected physicians' recommendations on adjuvant treatment selection. PATIENTS AND METHODS: Patients with stage IIIA/IIIB or stage II colon cancer were enrolled. After the patients discussed adjuvant treatment with their treating physicians, the physicians filled in the questionnaire before assay indicating the treatment recommendation. When the 12-RS assay results were available, the physicians again filled in the questionnaire after assay. The primary endpoint was the rate of change in treatment recommendations from before to after the assay, with a threshold rate of change being 20%. Patients with stage IIIA/B to II were enrolled in a ratio of 2 : 1. RESULTS: Overall, the treatment recommendations changed in 40% of cases after obtaining 12-RS assay results. Recommendations were changed in 45% (80/178; 95% confidence interval, 37% to 53%; P < 0.001) and 30% (29/97; 95% confidence interval, 21% to 40%; P < 0.001) of patients with stage IIIA/B and II colon cancer, respectively. Patients with stage IIIA/B cancer had significantly more change than those with stage II cancer (P = 0.0148). From before to after the 12-RS assay, the percentage of patients whose physicians reported being confident in their treatment recommendations significantly increased from 54% to 81% in stage IIIA/B (P < 0.001) and from 65% to 83% in stage II (P < 0.001). CONCLUSION: Our study confirmed the usefulness of the 12-RS assay in aiding the physician-patient decision-making process for tailoring adjuvant chemotherapy for stage IIIA/B colon cancer.
Assuntos
Neoplasias do Colo , Recidiva Local de Neoplasia , Bioensaio , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Estudos ProspectivosRESUMO
BACKGROUND: Oral mucositis (OM) is an unpleasant adverse event in patients receiving chemotherapy. A prospective feasibility study showed that elemental diet (ED), an oral supplement that does not require digestion, may prevent OM. Based on this, we established a central review system for oral cavity assessment by dental oncology specialists blinded to background data. We used this system to elucidate the preventive effect of an ED against OM in patients with esophageal cancer receiving docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy. PATIENTS AND METHODS: In this phase III, multicenter, parallel-group, controlled trial, patients consuming a normal diet orally were randomly assigned (1 : 1) to receive two cycles of DCF with (group A) or without (group B) an ED (Elental® 160 g/day). We assessed the incidence of grade ≥2 OM evaluated by two reviewers, changes in body weight, prealbumin, C-reactive protein, and DCF completion rate based on ED compliance. RESULTS: Of the 117 patients randomly assigned to treatment, four failed to start treatment and were excluded from the primary analysis; thus, groups A and B comprised 55 and 58 patients, respectively. There were no significant differences in background characteristics. Grade ≥2 OM was observed in eight (15%) and 20 (34%) patients in groups A and B, respectively (P = 0.0141). Changes in body weight and prealbumin during the two DCF cycles were significantly higher in group A than B (P = 0.0022 and 0.0203, respectively). During the first cycle, changes in C-reactive protein were significantly lower in group A than B (P = 0.0338). In group A (receiving ED), the DCF completion rate was 100% in patients with 100% ED compliance and 70% in patients failing ED completion (P = 0.0046). CONCLUSIONS: The study findings demonstrate that an ED can prevent OM in patients with esophageal cancer receiving chemotherapy.
Assuntos
Cisplatino , Neoplasias Esofágicas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Docetaxel/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Fluoruracila/efeitos adversos , Alimentos Formulados , Humanos , Estudos ProspectivosRESUMO
BACKGROUND: Although the efficacy of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) against metastatic colorectal cancer (mCRC) has been demonstrated, little is known about its effectiveness upon disease stratification by RAS mutations. In this phase II study, we investigated the efficacy and safety profiles of FTD/TPI in mCRC according to RAS mutation status. PATIENTS AND METHODS: Eligible patients were mCRC refractory or intolerant to all standard therapies other than FTD/TPI and regorafenib. Patients received 4-week cycles of treatment with FTD/TPI (35 mg/m2, twice daily, days 1-5 and 8-12) and bevacizumab (5 mg/kg, days 1 and 15). The primary endpoint was disease control rate (DCR). The null hypothesis of DCR in both RAS wild-type (WT) and mutant (MUT) cohorts was 44%, assuming a one-sided significance level of 5.0%. The necessary sample size was estimated to be 49 patients (target sample size: 50 patients) for each cohort. RESULTS: Between January and September 2018, 102 patients were enrolled, and 97 patients fulfilled the eligibility criteria (48 in the RAS WT cohort and 49 in the RAS MUT cohort). DCRs in the RAS WT and MUT cohort were 66.7% [90% confidence interval (CI), 53.9%-77.8%, P = 0.0013] and 55.1% (90% CI, 42.4%-67.3%, P = 0.0780), respectively. The median progression-free survival (PFS) and overall survival (OS) were 3.8 and 9.3 months, respectively, in the RAS WT cohort and 3.5 and 8.4 months, respectively, in the RAS MUT cohort. The most common grade 3 or higher adverse event in both cohorts was neutropenia (46% in the RAS WT cohort and 62% in the RAS MUT cohort), without unexpected safety signals. CONCLUSIONS: FTD/TPI plus bevacizumab showed promising activity with an acceptable safety profile for pretreated mCRC, regardless of RAS mutation status, although the efficacy outcomes tended to be better in RAS WT.
Assuntos
Neoplasias Colorretais , Trifluridina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Humanos , Mutação , Pirrolidinas , Timina , Trifluridina/uso terapêuticoRESUMO
Interferon-gamma is a potent Th1-type cytokine and a key molecule in the pathogenesis of autoimmune diseases including lupus nephritis. Retinoic acid-inducible gene-I is a putative RNA helicase that plays an important role in immune and inflammatory reactions. We previously demonstrated the increased expression of the retinoic acid-inducible gene-I protein in the kidney tissue of patients with lupus nephritis, and the presence of a significant amount of retinoic acid-inducible gene-I mRNA in the urinary sediment of patients with this inflammatory renal disease. In the present study, interferon-gamma was found to induce the expression of retinoic acid-inducible gene-I in human mesangial cells in culture. Knockdown of retinoic acid-inducible gene-I inhibited the interferon-gamma-induced upregulation of interferon regulatory factor 7, a transcriptional factor involved in immune and inflammatory reactions. These findings suggest that retinoic acid-inducible gene-I produced by mesangial cells may be involved in the pathogenesis of lupus nephritis.
Assuntos
RNA Helicases DEAD-box/genética , Regulação da Expressão Gênica , Interferon gama/metabolismo , Células Mesangiais/metabolismo , Células Cultivadas , Proteína DEAD-box 58 , Humanos , Inflamação/genética , Inflamação/fisiopatologia , Fator Regulador 7 de Interferon/genética , Nefrite Lúpica/genética , Nefrite Lúpica/fisiopatologia , Receptores Imunológicos , Regulação para CimaRESUMO
Head-and-neck cancer is frequently associated with esophageal cancer. Because the operative procedures for these synchronous double cancers are too invasive, definitive chemoradiotherapy tends to be applied as an initial treatment. A salvage esophagectomy for either recurrent or residual disease after definitive chemoradiotherapy in patients with such double cancer has never been reported. We reviewed 21 patients with esophageal cancer who underwent a salvage esophagectomy after definitive chemoradiotherapy. Among them, the treatment course of five patients who underwent a salvage esophagectomy for patients with synchronous double cancers of the esophagus and head-and-neck region was analyzed. Because head-and-neck cancer was well controlled after chemoradiotherapy in all five patients, a salvage esophagectomy was indicated for either recurrent or residual esophageal cancer after definitive chemoradiotherapy. Anastomotic leakage developed in four patients; however, no other complications including pulmonary complications were recognized. All of them were discharged to home and three of them are still alive without any recurrence for 20-43 months. A salvage esophagectomy should be considered as a treatment option for either recurrent or residual esophageal cancer with well-controlled head-and-neck cancer after definitive chemoradiotherapy when complete resection of the esophagus is expected.
Assuntos
Neoplasias Esofágicas/terapia , Esofagectomia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Primárias Múltiplas/patologia , Terapia de Salvação , Idoso , Carcinoma de Células Escamosas/terapia , Quimioterapia Adjuvante , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasia Residual/cirurgia , Neoplasias Primárias Múltiplas/terapia , Radioterapia AdjuvanteRESUMO
AIMS: Studies on immunosuppressive treatment with tacrolimus (Tac) in subjects with lupus nephritis (LN) are limited. Here, we report our experience with Tac administered daily as a single-dose for maintenance therapy in young patients with pediatric-onset, long-standing LN. METHODS: Eleven consecutive patients with long-standing biopsy-proven LN were recruited for at least 6 months or longer (6 - 24 months) as part of an open-label trial for the single-daily-dose administration of Tac (3 mg/day, 0.04 - 0.075 mg/kg) without dose increases of concomitantly administered prednisolone (PDN). Tac treatment was started at the time of the most recent flare. Data on clinical parameters and serologic lupus activity were collected prospectively. RESULTS: The baseline characteristics of the patients were as follows: mean age, 18 years; urinary protein/creatinine ratio (Up/cr), 0.74 +/- 1.49; serum C3 level, 69.5 +/- 26.5 mg/dl (normal 79 - 152 mg/dl); serum complement hemolytic activity (CH50), 23.0 +/- 8.9 U/ml (normal 23 - 46 U/ml); serum anti-dsDNA antibody titer, 58.9 +/- 54.2 IU/ml (normal < 12.0 IU/ml); serum creatinine, 0.54 +/- 0.13 mg/dl; and European Consensus Lupus Activity Measurement (ECLAM) index, 4.4 +/- 2.2. Despite the gradual tapering of the PDN dose, a marked improvement, compared with the baseline values was observed in the ECLAM index even at 1 month and in the serological parameters at 3 months after the start of treatment. These favorable results persisted until the end of the study. The Up/cre ratio gradually decreased and had dropped significantly at 24 months after the start of treatment. After a mean of 18 months of treatment, complete responses were achieved in 8 patients (73%) and a partial response was achieved in 2 patients. The remaining one patient showed no response. No serious adverse effects were observed. CONCLUSION: These data suggest that low-dose Tac treatment, administered once daily, is an effective and safe method for managing selected young patients with pediatric-onset, long-standing LN. However, further studies involving a larger number of patients are needed to confirm these results.
Assuntos
Imunossupressores/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Tacrolimo/administração & dosagem , Adolescente , Adulto , Anticorpos Antinucleares/sangue , Biópsia , Complemento C3/metabolismo , Ensaio de Atividade Hemolítica de Complemento , DNA/imunologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Masculino , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Acute lung injury (ALI) is one of most serious complications to occur after an esophagectomy for esophageal cancer. However, the pathogenesis of ALI is still unclear. The cytokine levels of pleural drainage fluid as well as peripheral blood were measured in 27 patients who had undergone an extended radical esophagectomy. Both the clinical factors and cytokine levels were compared between 11 patients with (group I) and 16 without ALI (group II). ALI occurred more frequently in patients who underwent colon interposition than in those who received a gastric tube reconstruction (86%vs 25%, P = 0.009). The operation time of group I was significantly longer than that of group II. A logistic regression analysis revealed colon interposition to be an independent factor associated with the ALI (P < 0.05). Postoperative anastomotic leakage and systemic inflammatory response syndrome (SIRS) occurred more frequently in group I than in group II (P < 0.01). Both the serum interleukin-6 (IL-6) and IL-8 levels of group I were significantly higher than those of group II. IL-1beta and tumor necrosis factor-alpha were undetectable in the peripheral blood, whereas they were detectable in the pleural effusion. The IL-1beta of pleural effusion was higher in group I than group II. In conclusion, greater surgical stress, such as a longer operative time, is thus considered to be associated with the first attack of ALI. The adverse events developing in the extra-thoracic site, such as necrosis and local infection around anastomosis may therefore be the second attack. Furthermore, ALI may cause not only SIRS but also other complications such as anastomotic leakage.
Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia , Complicações Pós-Operatórias , Síndrome do Desconforto Respiratório/etiologia , Idoso , Anastomose Cirúrgica/efeitos adversos , Carcinoma de Células Escamosas/cirurgia , Colo/transplante , Citocinas/análise , Esofagectomia/métodos , Esofagoplastia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/química , Respiração Artificial , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Fatores de TempoRESUMO
Analyzing microsatellite instability (MI) in malignant tumors is thought to be useful for screening cancer patients to identify those patients with a higher risk of developing second malignant tumors. In this paper, we report a new, accurate, and efficient method of detecting MI using an automated fluorescent DNA sequencer and a computer that automatically calculates the size, height, and area of each fluorescent product, making it possible to assess MI more accurately and more rapidly. The primers for amplification of each microsatellite locus are labeled by two different fluorescent dyes, rox (red) and fam (blue). The rox-labeled primer was used for the tumor, whereas the fam-labeled primer was used for the corresponding normal tissue. Two amplified products from both the tumor and the normal tissue were co-loaded into a single lane of the sequencing gel and were analyzed. MI could be detected based on the presence of different waving patterns. Furthermore, several loci could also be analyzed simultaneously for MI in a single lane. Using this method, we examined the frequency of MI in gastric cancer. The results showed that 5 of 22 (22.7 %) gastric cancers were MI-positive, which corresponds to the findings of previous reports that used the radioisotopic method. The improved method may open up the possibility of performing routine examination of MI in many cancer patients and offers hope for the potential clinical application of Ml analysis as a follow-up evaluation of cancer patients.
Assuntos
Aberrações Cromossômicas/diagnóstico , DNA de Neoplasias/análise , DNA Satélite/análise , Diagnóstico por Computador , Repetições de Microssatélites , Análise de Sequência de DNA/métodos , Neoplasias Gástricas/genética , Transtornos Cromossômicos , Eletroforese em Gel de Poliacrilamida , Feminino , Corantes Fluorescentes , Humanos , Masculino , Segunda Neoplasia Primária/genética , Reação em Cadeia da Polimerase , Análise de Sequência de DNA/instrumentação , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND/AIM: The Kyushu Study Group of Clinical Cancer (KSCC) previously reported the safety and efficacy of neoadjuvant chemotherapy with mFOLFOX6 + bevacizumab for H2/H3 liver metastases of colorectal cancer. The aim of the current study was to evaluate the resectability of these metastases before and after chemotherapy as determined by independent liver surgeons. METHODS: Between May 2008 and April 2010, 40 patients were registered in a multicenter phase 2 trial of neoadjuvant chemotherapy (KSCC 0802). In Study 1, 5 independent liver surgeons from five different KSCC centers evaluated the resectability of liver metastases of colorectal cancer based on imaging studies performed before and after chemotherapy. Each surgeon was blinded to the other surgeons' evaluations. In addition, no information about the patients' characteristics was provided. In Study 2, 3 surgeons evaluated the resectability of these lesions based on imaging studies with discussion with each other, with the surgeons being provided with information on the patients' characteristics. RESULTS: In Study 1, 13 patients (36.1%) were evaluated to be resectable at baseline, whereas 17 patients (47.2%) were evaluated to be resectable after chemotherapy. In Study 2, 4 patients (11.1%) were evaluated to be resectable at baseline, compared to 23 patients (63.9%) after chemotherapy. CONCLUSION: Neoadjuvant chemotherapy with mFOLFOX6 + bevacizumab was confirmed to increase the resectability of non-resectable liver metastases of colorectal cancer according to the independent assessments of surgeons.