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1.
Anticancer Res ; 44(2): 805-814, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307591

RESUMO

BACKGROUND/AIM: Uracil-tegafur+leucovorin (UFT/LV), an oral adjuvant therapy for stage II/III colorectal cancer, is non-inferior to standard weekly fluorouracil and folinate. Although polysaccharide K (PSK) has been evaluated as a postoperative adjuvant colorectal cancer drug, its efficacy remains unclear. This randomized phase II trial compared UFT/LV+PSK with UFT/LV as adjuvant chemotherapy. PATIENTS AND METHODS: Between April 2011 and August 2016, 186 patients who underwent radical resection randomly received 6 months of UFT/LV (Group A: 300 mg/m2/day UFT and 75 mg/day LV, every 35 days for five cycles), 6 months of UFT/LV+PSK (Group B: standard UFT/LV regimen and daily administration of 3 g/day of PSK), or 12 months of UFT/LV+PSK (Group C). The primary endpoint was the 3-year disease-free survival. RESULTS: Groups A, B, and C consisted of 37, 75, and 74 patients, of which treatment was completed by 33 (89.2%), 63 (84.9%), and 53 (70.4%) patients, respectively (p=0.0279). Adverse event incidence for all grades were 59.5%, 52.1%, and 59.2%, and for grade ≥3 were 13.5%, 9.6%, and 9.9%, respectively. The 3-year disease-free survival rates were 72.5%, 82.2%, and 74.2%, respectively, with no significant differences. The preoperative lymphocyte ratio did not significantly differ between groups. CONCLUSION: UFT/LV+PSK is comparable to UFT/LV therapy in terms of prognostic efficacy and reduced adverse effects. Thus, UFT/LV+PSK is a useful adjuvant chemotherapy option for patients with high-risk stage II/III colorectal cancer.


Assuntos
Quimioterapia Adjuvante , Neoplasias Colorretais , Humanos , Administração Oral , Quimioterapia Adjuvante/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Leucovorina/uso terapêutico , Levamisol/análogos & derivados , Estadiamento de Neoplasias , Tegafur/uso terapêutico , Uracila/uso terapêutico
2.
Surg Case Rep ; 6(1): 186, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737607

RESUMO

BACKGROUND: Malignant peripheral nerve sheath tumour (MPNST) is a very rare disease, and its pathogenesis is unknown. There are few reports of MPNST of the oesophagus. We report a case of an MPNST that was diagnosed and resected. CASE PRESENTATION: A 30-year-old female presented with dysphagia. She had been aware of the dysphagia approximately 6 months before presentation. The chest X-ray showed shadows in the right mediastinum. Barium fluoroscopy revealed a semicircular raised lesion in the lower oesophagus. Upper gastrointestinal endoscopy revealed a type 1 oesophageal tumour centred on the posterior wall 26-35 cm from the incisors. The surface was ulcerated, and the tumour was exposed. The affected area showed no iodine uptake. The EUS showed an isoechoic mass. The CT scan showed a mass of 71 × 61 × 55 mm in the beginning of the lower oesophagus with low density mass and swelling of the right recurrent nerve lymph node to 12 mm. On FDG-PET, the tumour showed an SUVmax of 11.05, and no abnormal accumulation was found in lymph nodes or other organs. The MRI showed a hyperintense mass on the T2WI, which had prolonged contrast enhancement, and no findings of invasion into surrounding tissue were found. The patient underwent right thoracotomy and open thoracic oesophagectomy. The affected lymph node was tumour negative by rapid pathological diagnosis during the operation. Histologically, spindle cells with different-sized nuclei were mixed throughout the tissue. Some regions showed nuclear polymorphism or a storiform pattern, and locally, there were approximately 7 mitoses/10 HPFs. The margin was relatively clear, but spindle-shaped tumour cells infiltrated the surrounding interstitium and basal myoepithelium, and the patient was diagnosed with MPNST. In this case, the postoperative course was good, and 16 months after the operation, the patient is currently under observation at the outpatient stage without recurrence. CONCLUSIONS: MPNST in the oesophagus is a relatively rare disease. Diagnosis before treatment is sometimes difficult, but the prognosis is good if radical resection is possible.

3.
Gan To Kagaku Ryoho ; 45(12): 1755-1758, 2018 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-30587735

RESUMO

A laparoscopy-assisted right hemicolectomy and D3 lymph node dissection were performed to treat a 60-year-old woman with ascending colon cancer. Microscopically, the resected specimen was diagnosed as adenocarcinoma(tub1>tub2, pSS, pN1, M0). Adjuvant chemotherapy using UFT/UZEL was administered for 6 months. Enlarged para-aortic lymph nodes were identified by follow-up CT 2 years post operation, and a para-aortic lymph node dissection was performed. Microscopic examination revealed that the #216 b1 int lymph node contained poorly differentiated metastatic adenocarcinoma. After 36 courses of FOLFOX as adjuvant chemotherapy, the chemotherapy was discontinued because of an adverse event. She has remained well without recurrence for 5 years after the second surgery. There have been reports of survival improvements by surgical resections in patients with solitary para-aorta lymph node metastases of colorectal cancer. These observations suggest that the surgical therapy may have contributed to the improved prognosis in the present case.


Assuntos
Quimioterapia Adjuvante , Colo Ascendente , Neoplasias do Colo/tratamento farmacológico , Recidiva Local de Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Pessoa de Meia-Idade
4.
Gan To Kagaku Ryoho ; 43(8): 1009-13, 2016 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-27539046

RESUMO

A 6 2-year-old woman visited our hospital with a complaint of anal bleeding and was diagnosed with rectal cancer. She underwent low anterior resection and D3 lymphadenectomy. The pathological diagnosis was shown as follows: Ra, Circ, type 2, por1, pSS, ly3, v1, pN2, pStage III b, and KRAS wild type. UFT/UZEL with polysaccharide K(PSK)was initiated as adjuvant chemotherapy after the operation. However, multiple liver metastases were found on CT after 3 courses of UFT/UZEL with PSK, and pathological reexamination revealed that the primary tumor was a neuroendocrine carcinoma. She underwent chemotherapy with CBDCA combined with CPT-11, but bone marrow suppression was observed after 4 courses of the treatment. As second-line chemotherapy, FOLFOX4 plus panitumumab(Pmab)was administered. Although the disease remained stable through 10 courses of FOLFOX4 plus Pmab, Grade 3 peripheral neuropathy was observed. Hence, FOLFIRI plus bevacizumab(Bmab)was administered as third-line chemotherapy. Twenty-eight courses of FOLFIRI plus Bmab were administered, and transcatheter arterial chemoembolization(TACE)was performed during chemotherapy. However, her general condition worsened after the therapies, and she died 2 years 3 months after the initial chemotherapy.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Adenocarcinoma/cirurgia , Terapia Combinada , Evolução Fatal , Feminino , Humanos , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia
5.
Surg Laparosc Endosc Percutan Tech ; 25(3): e101-3, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26039800

RESUMO

INTRODUCTION: We adopted the use of Penrose drains and Endo Close to secure a good surgical field during laparoscopic pancreatectomy. METHODS: We used a Penrose drain with threads ligated on both ends to suspend the stomach. We then pulled the threads out of the body from the side of the trocar or from besides the xiphisternum by using Endo Close. In most cases, 2 Penrose drains were used to retract the stomach. When the greater omentum on the left side of the cardia still blocks the surgical field, we sewed the posterior wall of the stomach onto the dome of the diaphragm. RESULTS: The use of 2 Penrose drains and Endo Close were effective to retract the stomach in most cases. However, in 3 cases, we needed to additionally sew the stomach onto the diaphragm to fully open up the field. CONCLUSION: This is a simple and effective method to ensure a good surgical field.


Assuntos
Laparoscopia/instrumentação , Pancreatectomia/instrumentação , Drenagem/instrumentação , Humanos , Laparoscopia/métodos , Pancreatectomia/métodos
6.
Asian J Endosc Surg ; 8(2): 201-4, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25913588

RESUMO

We treated a 64-year-old woman with high blood pressure. Catecholamine metabolite levels were elevated in the blood and urine. CT revealed a densely stained tumor on the right side of the descending aorta dorsal to the inferior vena cava. PET-CT revealed abnormal accumulation of (18) F-fluorodeoxyglucose, and (123) I-meta-iodo-benzylguanidine uptake was apparent on scintigraphy. The tumor was determined to be a paraganglioma located on the border between the thoracic and abdominal cavities, and laparoscopic tumorectomy was performed. The patient was placed in the left lateral position. The right lobe of the liver was turned over, and we cut the diaphragm to expose the front of the tumor. We resected the straight artery flowing in from the aorta and removed the tumor safely. Herein, we describe the removal of a paravertebral paraganglioma located in the border of the thoracic and abdominal cavities with a laparoscopic transabdominal-transdiaphragmatic approach.


Assuntos
Neoplasias Abdominais/cirurgia , Laparoscopia/métodos , Paraganglioma/cirurgia , Neoplasias Torácicas/cirurgia , Cavidade Abdominal , Neoplasias Abdominais/diagnóstico , Diafragma/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Paraganglioma/diagnóstico , Cavidade Torácica , Neoplasias Torácicas/diagnóstico
8.
Artigo em Inglês | MEDLINE | ID: mdl-25462983

RESUMO

INTRODUCTION: We present a widely applicable technique of the modified Pringle maneuver to reduce blood loss for laparoscopic hepatectomy. METHODS: We use a drip-infusion tube and wrap it around the hepatoduodenal ligament. In the modified Pringle maneuver ① (m-Pringle ①), we use a 60 cm long tube. Both ends of the tube are led out from the side of the umbilical port, then pulled and clipped with Pean forceps to interrupt blood flow. In the modified Pringle maneuver ② (m-Pringle ②), we use a 20 cm long tube with silk threads tied at both ends. The threads were led extraperitoneally in the same manner. RESULTS: Although blood flow was sufficiently interrupted, CO2 leak occurred in 14 of 60 cases in m-Pringle ①. Blood flow was interrupted and intra-abdominal pressure was kept in all 10 patients in m-Pringle ②. CONCLUSIONS: These maneuvers require no extra port, and tube pulling and releasing is readily performed from outside the body.

9.
Gan To Kagaku Ryoho ; 41(6): 737-41, 2014 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-25129085

RESUMO

In recent years, there has been significant progress in systemic chemotherapy for metastatic or recurrent colorectal cancer. We investigated the clinical efficacy and feasibility of the bevacizumab and capecitabine /oxaliplatin(CapeOX)combination for untreated colorectal cancer. From October 2009 to June 2012, 38 patients were included, 18 receiving CapeOX alone and 20 receiving CapeOX plus bevacizumab. The response rate and disease-control rate were 16% and 5 0%, respectively, in the CapeOX arm, and 5 5% and 8 5%, respectively, in the CapeOX plus bevacizumab arm. Median progression-free survival was 8.0 months in the CapeOX arm and 1 2.8 months in CapeOX plus bevacizumab arm. The median overall survival was 21.6 months in the CapeOX arm and 3 4.0 months in CapeOX plus bevacizumab arm. Our results suggest that CapeOX treatment can be useful in the outpatient setting and more effective when combined with bevacizumab. Except in cases of bevacizumab intolerance, addition of bevacizumab to CapeOX treatment is considered useful as first-line therapy for metastatic or recur- rent colorectal cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab , Capecitabina , Neoplasias Colorretais/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
10.
Biomed Rep ; 2(5): 719-724, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25054017

RESUMO

Murine double minute 2 (MDM2) is a negative regulator of p53. A single-nucleotide polymorphism (SNP) (rs2279744: c.309T>G) in the promoter region of the MDM2 gene has been shown to result in higher levels of MDM2 RNA and protein. Regarding the contribution of c.309T>G in the MDM2 gene to the lung cancer risk, previous studies are conflicting. In order to evaluate the association between c.309T>G and the lung cancer risk, a case-control study was performed. The MDM2 genotypes were determined in 762 lung cancer patients and in 700 cancer-free control subjects using the Smart Amplification Process. Statistical adjustment was performed for gender, age and pack-years of smoking. The distributions of c.309T>G (T/T, T/G, G/G) were 20.1, 49.7, 30.2% in the case group and 21.7, 47.9, 30.4% in the healthy-control group. There were no overall associations between the MDM2 genotypes and the risk of lung cancer [T/G genotype: Adjusted odds ratio (AOR), 1.30; 95% confidence interval (CI), 0.88-1.93; and G/G genotype: AOR, 1.18; 95% CI, 0.78-1.80]. The subgroup analysis of gender, histology, smoking status and epidermal growth factor receptor mutation status also indicated that there was no association with lung cancer. Additionally, the genotypes did not have an effect on the age at the time of diagnosis of lung cancer (P=0.25). In conclusion, the G allele frequency in the lung cancer cases was 0.551, which was similar to other studies. The results of the present study suggest that the c.309T>G is not significantly associated with lung cancer.

11.
Surg Laparosc Endosc Percutan Tech ; 23(6): 536-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24300932

RESUMO

BACKGROUND: The mesenteric vessels have many branching patterns. This study clarified the anatomic relationship between the superior mesenteric vein (SMV), the right colic artery (RCA), and the ileocolic artery (ICA) using 3-dimensional computed tomography (3D-CT). The relationship between the RCA and the right colic vein (RCV) was also examined. METHODS: Between April 2006 and July 2011, all patients with colorectal cancer underwent multidetector computed tomography (MDCT) before laparoscopic surgery. The 100 most recent consecutive cases were analyzed. 3D-CT images were made by combining arterial angiography, venous angiography, colonography, tumor, lymph node, and duodenal images. RESULTS: The RCA branched from the SMA in 37 cases (37%); of these, 21 had an ICA that crossed anterior to the SMV and 16 had an ICA that crossed posterior. When the ICA crossed anterior to the SMV, all had an RCA that crossed anterior to the SMV, and no posterior RCA was seen. Furthermore, the RCV joined the SMV in 10 cases (27%) and the gastrocolic trunk in 27 cases (73%). CONCLUSIONS: Our study clarified the anatomic variety of the vessels in right-sided colon cancer. Preoperative 3D-CT is useful for understanding the anatomy to ensure a safe, precise operation.


Assuntos
Neoplasias do Colo/irrigação sanguínea , Neoplasias do Colo/cirurgia , Imageamento Tridimensional , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/diagnóstico por imagem , Feminino , Humanos , Masculino , Artéria Mesentérica Superior/anatomia & histologia , Veias Mesentéricas/anatomia & histologia , Pessoa de Meia-Idade
12.
PLoS One ; 8(4): e60151, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23565197

RESUMO

BACKGROUND: Genetic polymorphisms in the human MDM2 gene are suggested to be a tumor susceptibility marker and a prognostic factor for cancer. It has been reported that a single nucleotide polymorphism (SNP) c.309T>G in the MDM2 gene attenuates the tumor suppressor activity of p53 and accelerates tumor formation in humans. METHODOLOGY: In this study, to detect the SNP c.309T>G in the MDM2 gene, we have developed a new SNP detection method, named "Duplex SmartAmp," which enabled us to simultaneously detect both 309T and 309G alleles in one tube. To develop this new method, we introduced new primers i.e., nBP and oBPs, as well as two different fluorescent dyes that separately detect those genetic polymorphisms. RESULTS AND CONCLUSIONS: By the Duplex SmartAmp method, the genetic polymorphisms of the MDM2 gene were detected directly from a small amount of genomic DNA or blood samples. We used 96 genomic DNA and 24 blood samples to validate the Duplex SmartAmp by comparison with results of the conventional PCR-RFLP method; consequently, the Duplex SmartAmp results agreed totally with those of the PCR-RFLP method. Thus, the new SNP detection method is considered useful for detecting the SNP c.309T>G in the MDM2 gene so as to judge cancer susceptibility against some cellular stress in the clinical setting, and also to handle a large number of samples and enable rapid clinical diagnosis.


Assuntos
Técnicas de Amplificação de Ácido Nucleico , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-mdm2 , Idoso , Alelos , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/patologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
13.
Gan To Kagaku Ryoho ; 40(1): 91-3, 2013 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-23306926

RESUMO

A 70-year-old female presented with epigastralgia. Gastrointestinal endoscopic examination showed advanced gastric cancer type 2. Computed tomography(CT)showed a liver tumor of 37mm in segment 6. She was treated with oral S-1, 80 mg/body for 14 days, followed by a 7-day rest, and CDDP 20mg/m2(day 1 and 8). After ten courses of treatment, CT showed reduction of the primary cancer, the liver tumor, and the affected lymph nodes. Then, distal gastrectomy, lymph node dissection, and partial liver resection were performed. The histological diagnosis was no viable cancer cells found in stomach, liver or lymph nodes. One year and 1 month postoperatively, the patient is alive without recurrence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Idoso , Cisplatino/administração & dosagem , Terapia Combinada , Combinação de Medicamentos , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Ácido Oxônico/administração & dosagem , Indução de Remissão , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem
14.
Oncol Rep ; 26(5): 1205-11, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21811765

RESUMO

We examined the correlation between computed tomography (CT) findings and the incidence of epidermal growth factor receptor (EGFR) and KRAS mutations in lung adenocarcinoma. We analyzed the tumors of 136 patients with surgically resected primary lung adenocarcinoma. CT scans were evaluated for the presence of ground grass opacity (GGO), spiculation and the maximum diameter of the tumor was measured. SMart Amplification Process (ver. 2) was used to detect the presence of EGFR and KRAS mutations. EGFR and KRAS mutations were found in 56 (41.1%) and 25 (18.4%) of the 136 cases, respectively. Although no significant association was found between GGO and EGFR mutations (p=0.07), the EGFR mutation occurred more frequently in male patients with GGO than in those without GGO (p=0.04). The KRAS mutation occurred more frequently in patients whose tumor diameter was ≥ 31 mm than in those whose tumor diameter was <30 mm (p=0.003). Evaluation of CT findings may be helpful for determining the presence of EGFR and KRAS mutations, particularly when it is not possible to obtain a tumor specimen.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/genética , Receptores ErbB/genética , Genes ras , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Mutação , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
15.
Oncol Rep ; 26(5): 1213-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21769434

RESUMO

The presence of EGFR mutations is correlated with a positive therapeutic response to tyrosine kinase inhibitors; therefore, the accurate detection of EGFR mutations is crucial when deciding appropriate therapeutic strategies. Recently, the rapid and sensitive assay smart amplification process version 2 (SmartAmp2) was developed. However, this method can only detect one type of mutation in EGFR exon 19; therefore, we applied the PNA technology to the SmartAmp2 assay to develop PNA-clamp SmartAmp2 for the detection of many types of deletions in EGFR exon 19, in a single reaction. This new assay was evaluated using 172 clinical samples. Thirty-nine (22.7%) samples were found to have deletions by PNA-clamp SmartAmp2; whereas 30 (17.4%) and 38 (22.1%) tumors were found to have deletions by direct sequencing and PNA-enriched sequencing, respectively. Three cases, in which we detected mutations with PNA-clamp SmartAmp2, but not with direct sequencing, were treated with gefitinib, and all cases showed a partial therapeutic response. Using clinical samples, we demonstrated that PNA-clamp SmartAmp2 can detect various types of mutations in EGFR exon 19 in a relatively short time and with high sensitivity. This method detected small amounts of mutant DNA and identified patients for whom clinical information was previously unavailable from other tests. This test may contribute to the administration of efficient therapeutic strategies.


Assuntos
Adenocarcinoma/genética , Receptores ErbB/genética , Éxons , Neoplasias Pulmonares/genética , Mutação , Adenocarcinoma/enzimologia , Adenocarcinoma de Pulmão , Sequência de Bases , Linhagem Celular Tumoral , Análise Mutacional de DNA/métodos , Humanos , Neoplasias Pulmonares/enzimologia , Dados de Sequência Molecular , Ácidos Nucleicos Peptídicos/genética , Reação em Cadeia da Polimerase/métodos
16.
Cancer ; 117(18): 4257-66, 2011 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-21387273

RESUMO

BACKGROUND: KRAS and epidermal growth factor receptor (EGFR) mutations are thought to play an important role in the carcinogenesis of lung adenocarcinoma. However, clinicopathological findings of KRAS mutated adenocarcinoma cases have not yet been fully clarified. The authors analyzed the relationship between the KRAS mutation and corresponding clinicopathological findings, focusing on nonmucinous and mucinous bronchioloalveolar elements. METHODS: EGFR and KRAS mutations were detected in DNA samples extracted from 182 surgically resected tissues of lung adenocarcinomas by the Smart Amplification Process. The relations between gene mutation status and clinicopathological features were analyzed. All adenocarcinoma cases were divided into bronchioloalveolar carcinoma (BAC), adenocarcinoma with bronchioloalveolar features, and adenocarcinoma without BAC components (non-BAC). BAC/adenocarcinoma with bronchioloalveolar features tumors were further assessed for the presence of mucinous features. RESULTS: EGFR and KRAS mutations were found in 76 and 30 cases, respectively. In the KRAS mutant group, BAC/adenocarcinoma with bronchioloalveolar features was found in 22 cases, which included 10 nonmucinous and 12 mucinous tumors. Of 19 cases with mucinous BAC/adenocarcinoma with bronchioloalveolar features, KRAS mutations were detected in 12, but no EGFR mutation was detected. In the KRAS mutant group, BAC/adenocarcinoma with bronchioloalveolar features had significantly earlier pathological stages and more favorable prognoses than did non-BAC. Mucinous BAC/adenocarcinoma with bronchioloalveolar features showed less smoking history than did nonmucinous BAC/adenocarcinoma with bronchioloalveolar features and non-BAC. Furthermore, transversion type KRAS mutations were more common in non-BAC. CONCLUSIONS: KRAS mutated adenocarcinomas can be divided into BAC/adenocarcinoma with bronchioloalveolar features and non-BAC types. Non-BAC adenocarcinoma is related to smoking history and has a poor prognosis. BAC/adenocarcinoma with bronchioloalveolar features adenocarcinoma, however, has a more favorable prognosis, and mucinous BAC/adenocarcinoma with bronchioloalveolar features has little relationship to smoking history.


Assuntos
Adenocarcinoma/genética , Neoplasias Pulmonares/genética , Proteínas ras/genética , Adenocarcinoma de Pulmão , Adenocarcinoma Bronquioloalveolar/genética , Adenocarcinoma Mucinoso/genética , Adolescente , Adulto , Idoso de 80 Anos ou mais , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Fumar/genética
17.
Oncol Rep ; 25(4): 921-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21318227

RESUMO

Epidermal growth factor receptor (EGFR) gene mutations have been reported to be clinically significant in non-small cell lung cancer (NSCLC). However, because most previous studies focused only on adenocarcinomas, EGFR mutations in other histotypes are poorly investigated. We evaluated the frequency of EGFR gene mutations in squamous cell carcinoma (SCC) and its clinicopathological features. In total, 89 frozen tumor specimens that had been first diagnosed as SCCs, were examined for EGFR mutations in exons 19 and 21 using direct sequencing, PNA-enriched sequencing and SmartAmp2. Additionally, pathological investigation, including immunostaining for p63 and TTF-1, alcian blue staining and EGFR mutation-specific immunohistochemistry in mutation-positive samples was also performed. The frequency of EGFR mutations was 5.6% (5/89); all mutations were deletions in EGFR exon 19. Immunohistological investigation of these samples revealed that two of five were positive for p63 and TTF-1 staining, and showed production of mucin, as evidenced by alcian blue staining. Consequently, three of the samples were considered to be true SCC at final pathological diagnosis, while the remaining two samples were revised to adenosquamous carcinoma and adenocarcinoma. The final frequency of the EGFR mutations in true SCC was 3.4% (3/87). In conclusion, EGFR mutations were found in a small, but significant, number of SCC tumor samples and thus EGFR mutational analysis was useful in the accurate diagnosis of SCC. Our data demonstrate that EGFR mutational analysis should be performed not only in adenocarcinoma, but also in SCC to allow accurate diagnosis and treatment.


Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Receptores ErbB/genética , Mutação em Linhagem Germinativa/genética , Neoplasias Pulmonares/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo
18.
J Mol Diagn ; 12(2): 257-64, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20093389

RESUMO

Recent evidence indicates that the presence of epidermal growth factor receptor (EGFR) or KRAS mutations in non-small cell lung cancer (NSCLC) can predict the response of the tumor to gefinitib. However, it is difficult to detect these mutations using formalin-fixed, paraffin-embedded (FFPE) tissues because the fixation process and aging can damage the DNA. In this study, we describe our work in adapting the Smart Amplification Process version 2 (SmartAmp2) to detect EGFR or KRAS mutations in DNA extracted from FFPE tissues. We were able to detect these mutations in 37 (97%) of 38 FFPE lung cancer tissue samples within 60 minutes with the SmartAmp2 assay and to confirm the correlation between EGFR mutations in FFPE tissues and gefitinib responsiveness. All mutations had previously been confirmed in the 38 samples using DNA extracted from frozen tissues. Electrophoresis results indicated that PCR analysis was not reliable for DNA extracted from FFPE tissue when primers with a long amplicon (>300 bp) were used. This study confirms that the SmartAmp2 assay is suitable for use with DNA extracted from FFPE as well as frozen tissues.


Assuntos
Receptores ErbB/genética , Formaldeído/química , Neoplasias Pulmonares/genética , Mutação , Técnicas de Amplificação de Ácido Nucleico/métodos , Inclusão em Parafina/métodos , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Antineoplásicos/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Fixadores/química , Gefitinibe , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas p21(ras) , Quinazolinas/uso terapêutico , Análise de Sequência de DNA/métodos , Fixação de Tecidos/métodos
19.
J Mol Diagn ; 12(1): 118-24, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20007840

RESUMO

KRAS is an oncogene that can be activated by mutations. Patients with non-small cell lung cancer who have KRAS mutations do not respond to tyrosine kinase inhibitors; therefore, accurate detection of KRAS mutations is important for deciding therapeutic strategies. Although sequencing-related techniques have been frequently used, they are usually too complex, have low sensitivity, and are time-consuming for routine screening in clinical situations. We evaluated peptide nucleic acid (PNA)-clamp smart amplification process version 2 (SmartAmp2) as a detection method for KRAS codon 12 mutations in patient specimens compared with traditional sequencing and polymerase chain reaction-related methods. Among 172 lung adenocarcinoma samples, direct sequencing, enzyme-enriched sequencing, and PNA-enriched sequencing showed that 16 (9.3%), 26 (15.7%), and 28 (16.3%) tumors, respectively, contained KRAS mutations in codon 12. Using PNA-clamp SmartAmp2, we could identify 31 (18.0%) tumors that had KRAS mutations in codon 12 within 60 minutes, three of which were undetected by polymerase chain reaction-related methods. On the other hand, we examined 30 nonmalignant peripheral lung tissue specimens and found no mutations in any of the samples using PNA-clamp SmartAmp2. In this study, we confirmed that PNA-clamp SmartAmp2 has high sensitivity and accuracy and is suitable for the clinical diagnosis of KRAS codon 12 mutations.


Assuntos
Adenocarcinoma/genética , Análise Mutacional de DNA/métodos , Neoplasias Pulmonares/genética , Mutação , Reação em Cadeia da Polimerase/métodos , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adenocarcinoma/diagnóstico , Linhagem Celular Tumoral , Análise Mutacional de DNA/economia , Humanos , Neoplasias Pulmonares/diagnóstico , Reação em Cadeia da Polimerase/economia , Proteínas Proto-Oncogênicas p21(ras) , Sensibilidade e Especificidade , Análise de Sequência de DNA , Fatores de Tempo
20.
Intern Med ; 45(2): 87-91, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16484745

RESUMO

We report a case of successfully treated acute thrombocytopenia associated with preexisting ulcerative colitis (UC). The patient had typical symptoms of UC, and colonoscopy showed pancolitis. During treatment with sulfasalazopyridine (SASP) and steroids, thrombocytopenia was observed. Despite the cessation of drugs, severe thrombocytopenia was noted. Immune thrombocytopenic purpura (ITP) was suspected based on a normal bone marrow megakaryocyte count, positive autoantibody to platelet membrane antigen, and the absence of splenomegaly. Medical treatment, including increased dosage of steroids, failed to control UC and acute thrombocytopenia in this patient. Moreover, acute severe pancreatitis developed and abdominal computed tomography showed toxic megacolon. Platelet count recovered after urgent total colectomy without splenectomy. When patients with UC develop thrombocytopenia, particularly in the presence of extensive and significant colonic inflammation, a diagnosis of ITP should be considered. In such patients, preexisting UC might be involved in the immunological causal mechanism of ITP. In this situation, colectomy might cure both UC and resistant thrombocytopenia. Steroid-refractory and life-threatening UC complicated by thrombocytopenia presumably caused by ITP is therefore a possible indication for colectomy.


Assuntos
Colectomia , Colite Ulcerativa/complicações , Colite Ulcerativa/cirurgia , Púrpura Trombocitopênica Idiopática/imunologia , Doença Aguda , Adulto , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/imunologia , Glucocorticoides/uso terapêutico , Humanos , Masculino , Megacolo Tóxico/etiologia , Pancreatite/etiologia , Púrpura Trombocitopênica Idiopática/etiologia , Sulfassalazina/uso terapêutico
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