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1.
Anticancer Res ; 44(2): 805-814, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38307591

ABSTRACT

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.


Subject(s)
Chemotherapy, Adjuvant , Colorectal Neoplasms , Humans , Administration, Oral , Chemotherapy, Adjuvant/adverse effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Leucovorin/therapeutic use , Levamisole/analogs & derivatives , Neoplasm Staging , Tegafur/therapeutic use , Uracil/therapeutic use
2.
Surg Case Rep ; 6(1): 186, 2020 Jul 31.
Article in English | MEDLINE | ID: mdl-32737607

ABSTRACT

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.
Article in Japanese | MEDLINE | ID: mdl-30587735

ABSTRACT

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.


Subject(s)
Chemotherapy, Adjuvant , Colon, Ascending , Colonic Neoplasms/drug therapy , Neoplasm Recurrence, Local , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Lymph Node Excision , Lymph Nodes , Lymphatic Metastasis , Middle Aged
4.
Gan To Kagaku Ryoho ; 43(8): 1009-13, 2016 Aug.
Article in Japanese | MEDLINE | ID: mdl-27539046

ABSTRACT

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.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Liver Neoplasms/drug therapy , Rectal Neoplasms/drug therapy , Adenocarcinoma/surgery , Combined Modality Therapy , Fatal Outcome , Female , Humans , Liver Neoplasms/secondary , Middle Aged , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery
5.
Surg Laparosc Endosc Percutan Tech ; 25(3): e101-3, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26039800

ABSTRACT

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.


Subject(s)
Laparoscopy/instrumentation , Pancreatectomy/instrumentation , Drainage/instrumentation , Humans , Laparoscopy/methods , Pancreatectomy/methods
6.
Asian J Endosc Surg ; 8(2): 201-4, 2015 May.
Article in English | MEDLINE | ID: mdl-25913588

ABSTRACT

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.


Subject(s)
Abdominal Neoplasms/surgery , Laparoscopy/methods , Paraganglioma/surgery , Thoracic Neoplasms/surgery , Abdominal Cavity , Abdominal Neoplasms/diagnosis , Diaphragm/surgery , Female , Humans , Middle Aged , Paraganglioma/diagnosis , Thoracic Cavity , Thoracic Neoplasms/diagnosis
8.
Article in English | MEDLINE | ID: mdl-25462983

ABSTRACT

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.
Article in Japanese | MEDLINE | ID: mdl-25129085

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bevacizumab , Capecitabine , Colorectal Neoplasms/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/analogs & derivatives , Humans , Male , Middle Aged , Neoplasm Metastasis , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Oxaliplatin , Recurrence , Retrospective Studies , Treatment Outcome
10.
Biomed Rep ; 2(5): 719-724, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25054017

ABSTRACT

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.
Article in English | MEDLINE | ID: mdl-24300932

ABSTRACT

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.


Subject(s)
Colonic Neoplasms/blood supply , Colonic Neoplasms/surgery , Imaging, Three-Dimensional , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Colonic Neoplasms/diagnostic imaging , Female , Humans , Male , Mesenteric Artery, Superior/anatomy & histology , Mesenteric Veins/anatomy & histology , Middle Aged
12.
PLoS One ; 8(4): e60151, 2013.
Article in English | MEDLINE | ID: mdl-23565197

ABSTRACT

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.


Subject(s)
Nucleic Acid Amplification Techniques , Polymorphism, Single Nucleotide , Proto-Oncogene Proteins c-mdm2 , Aged , Alleles , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Neoplasms/genetics , Neoplasms/pathology , Nucleic Acid Amplification Techniques/methods , Polymerase Chain Reaction/methods , Polymorphism, Restriction Fragment Length , Reproducibility of Results , Sensitivity and Specificity
13.
Gan To Kagaku Ryoho ; 40(1): 91-3, 2013 Jan.
Article in Japanese | MEDLINE | ID: mdl-23306926

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Liver Neoplasms/drug therapy , Stomach Neoplasms/drug therapy , Aged , Cisplatin/administration & dosage , Combined Modality Therapy , Drug Combinations , Female , Humans , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Oxonic Acid/administration & dosage , Remission Induction , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Tegafur/administration & dosage
14.
Oncol Rep ; 26(5): 1205-11, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21811765

ABSTRACT

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.


Subject(s)
Adenocarcinoma/diagnostic imaging , Adenocarcinoma/genetics , ErbB Receptors/genetics , Genes, ras , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/genetics , Mutation , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Adult , Aged , Aged, 80 and over , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Tomography, X-Ray Computed
15.
Oncol Rep ; 26(5): 1213-9, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21769434

ABSTRACT

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.


Subject(s)
Adenocarcinoma/genetics , ErbB Receptors/genetics , Exons , Lung Neoplasms/genetics , Mutation , Adenocarcinoma/enzymology , Adenocarcinoma of Lung , Base Sequence , Cell Line, Tumor , DNA Mutational Analysis/methods , Humans , Lung Neoplasms/enzymology , Molecular Sequence Data , Peptide Nucleic Acids/genetics , Polymerase Chain Reaction/methods
16.
Cancer ; 117(18): 4257-66, 2011 Sep 15.
Article in English | MEDLINE | ID: mdl-21387273

ABSTRACT

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.


Subject(s)
Adenocarcinoma/genetics , Lung Neoplasms/genetics , ras Proteins/genetics , Adenocarcinoma of Lung , Adenocarcinoma, Bronchiolo-Alveolar/genetics , Adenocarcinoma, Mucinous/genetics , Adolescent , Adult , Aged, 80 and over , ErbB Receptors/genetics , Female , Humans , Male , Middle Aged , Mutation , Prognosis , Smoking/genetics
17.
Oncol Rep ; 25(4): 921-8, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21318227

ABSTRACT

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.


Subject(s)
Adenocarcinoma/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Squamous Cell/genetics , ErbB Receptors/genetics , Germ-Line Mutation/genetics , Lung Neoplasms/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Female , Humans , Immunoenzyme Techniques , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Middle Aged , Prognosis , Transcription Factors/metabolism , Tumor Suppressor Proteins/metabolism
18.
J Mol Diagn ; 12(2): 257-64, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20093389

ABSTRACT

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.


Subject(s)
ErbB Receptors/genetics , Formaldehyde/chemistry , Lung Neoplasms/genetics , Mutation , Nucleic Acid Amplification Techniques/methods , Paraffin Embedding/methods , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Antineoplastic Agents/therapeutic use , ErbB Receptors/antagonists & inhibitors , Fixatives/chemistry , Gefitinib , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Proto-Oncogene Proteins p21(ras) , Quinazolines/therapeutic use , Sequence Analysis, DNA/methods , Tissue Fixation/methods
19.
J Mol Diagn ; 12(1): 118-24, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20007840

ABSTRACT

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.


Subject(s)
Adenocarcinoma/genetics , DNA Mutational Analysis/methods , Lung Neoplasms/genetics , Mutation , Polymerase Chain Reaction/methods , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Adenocarcinoma/diagnosis , Cell Line, Tumor , DNA Mutational Analysis/economics , Humans , Lung Neoplasms/diagnosis , Polymerase Chain Reaction/economics , Proto-Oncogene Proteins p21(ras) , Sensitivity and Specificity , Sequence Analysis, DNA , Time Factors
20.
Intern Med ; 45(2): 87-91, 2006.
Article in English | MEDLINE | ID: mdl-16484745

ABSTRACT

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.


Subject(s)
Colectomy , Colitis, Ulcerative/complications , Colitis, Ulcerative/surgery , Purpura, Thrombocytopenic, Idiopathic/immunology , Acute Disease , Adult , Anti-Inflammatory Agents/therapeutic use , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/immunology , Glucocorticoids/therapeutic use , Humans , Male , Megacolon, Toxic/etiology , Pancreatitis/etiology , Purpura, Thrombocytopenic, Idiopathic/etiology , Sulfasalazine/therapeutic use
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