Tateaki Naito

Shizuoka Cancer Center, Sizuoka, Shizuoka, Japan

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Publications (108)370.18 Total impact


  • No preview · Article · Dec 2015 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
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    ABSTRACT: Platinum-based chemoradiotherapy (CRT) is a standard front-line treatment for locally advanced non-small cell lung cancer (NSCLC). However, no clinical trials have compared the efficacy and toxicity of platinum combination and docetaxel as subsequent re-challenge chemotherapies after cancer recurrence following CRT. This study aimed to evaluate the efficacy and toxicity of platinum combination chemotherapy versus docetaxel monotherapy in NSCLC patients previously treated with platinum-based CRT. From September 2002 to December 2009, at three participating institutions, 24 patients with locally advanced NSCLC, who had previously received platinum-based CRT, were treated with platinum combination re-challenge therapy, whereas 61 received docetaxel monotherapy. We reviewed their medical charts to evaluate patient characteristics and data regarding treatment response, survival, and toxicity. The response rates were 16.7% and 6.6% in the platinum combination chemotherapy and docetaxel monotherapy groups, respectively (p = 0.09), whereas disease control rates were 58.3% and 57.4%, respectively (p = 0.82). Progression-free survival was similar between the two groups (median, 4.2 vs. 2.3 months; hazard ratio [HR] = 0.81; 95% confidence interval [CI] = 0.51–1.29; p = 0.38), as was overall survival (median, 16.5 vs. 13.0 months; HR = 0.82; 95% CI = 0.47–1.41; p = 0.47). The incidence and severity of toxicity was also similar between the two groups. Hematological toxicity, particularly leukopenia and neutropenia, was more frequent in the docetaxel group. Our results indicated that platinum combination re-challenge was equivalent to docetaxel for relapsed patients previously treated with platinum-based CRT.
    Full-text · Article · Dec 2015 · SpringerPlus
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    ABSTRACT: Background: To investigate the prognostic significance of patient characteristics and clinical laboratory test results in locally advanced non-small cell lung cancer (NSCLC), and in particular the impact of diabetes mellitus (DM) on the survival of patients who underwent chemoradiotherapy. Methods: We retrospectively reviewed 159 patients with locally advanced NSCLC with a focus on DM and other potential prognostic factors, using the log-rank test, and univariate and multivariate analyses to assess their association with survival. Result: Five significant prognostic factors were identified in univariate analysis: stage (p < 0.001), DM (p = 0.04), hemoglobin levels (p = 0.003), serum albumin (p <0.001) and lactate dehydrogenase (LDH) levels (p = 0.01). Furthermore, among the factors tested using Fisher's exact test and the Wilcoxon rank sum test, gender (p = 0.019) and plasma glucose level (p <0.001) were found to have prognostic significance. Multivariate analysis showed that stage, DM, serum albumin and LDH levels were independent prognostic factors for survival (p = 0.007, p = 0.024, p = 0.007 and p = 0.005, respectively). Conclusions: The presence of DM at the time of diagnosis was identified as an independent and significant prognostic factor for predicting negative outcome in locally advanced NSCLC patients.
    Preview · Article · Dec 2015 · BMC Cancer
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    ABSTRACT: Background: Central nervous system (CNS) metastases caused by small-cell lung cancer (SCLC) are incurable and therefore fatal. Although such metastases are usually treated with chemotherapy or radiotherapy, their sensitivity to these treatment measures is unclear. Amrubicin appears to be a promising agent for relapsed SCLC, but its effectiveness in CNS metastases originating from SCLC is unknown. Methods: Between April 2002 and December 2009, 110 SCLC patients with CNS metastasis were treated at Shizuoka Cancer Center. Of these, we retrospectively reviewed 8 consecutive cases with CNS metastases originating from relapsed SCLC that were treated with amrubicin as a second-line therapy. Results: We recorded three sensitive relapses and five refractory cases. Amrubicin yielded a CNS response rate of 50 % (2 partial responses and 2 complete response; 95 % CI, 21.5-78.5\ %) and the disease control rate for CNS lesions was 87.5 % (95 % CI, 52.9-97.8 %). All of the sensitive relapse patients achieved a partial response. The median time to progression for CNS metastases was 150.5 days (95 % CI, 9-171 days), and the median survival time from the start of amrubicin administration was 230.5 days (95 % CI, 89-619 days). We also report a dramatic improvement in one patient's radiological result of intramedullary spinal cord metastasis and alleviation of her symptoms following amrubicin monotherapy including this case series. Conclusions: The results of this study suggest that amrubicin is active in patients with CNS metastases originating from SCLC.
    No preview · Article · Apr 2015 · Investigational New Drugs
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    ABSTRACT: ALK rearrangement (ALKr) is known to occur in various carcinomas such as anaplastic large cell lymphoma, NSCLC, inflammatory myofibroblastic tumors (IMT), and renal medullary carcinoma. It reportedly has been proposed that tumors carrying abnormal ALK as an essential growth driver be collectively termed "ALKoma". ALKr has been documented in approximately 50% of IMTs. IMTs can occur in the retroperitoneum, mediastinum, spleen, brain, pancreas, liver, or GI tract. Surgical resection is the only effective treatment for IMTs. However, there is no standard treatment for advanced IMT.ASP-3026 is a potent and selective multi-kinase inhibitor of ALK, ROS, and ACK. Here we present, a case report of a dramatic response to ASP-3026 in a patient with highly aggressive pulmonary IMT harboring ALKr. A 57-year-old male current smoker had presented with massive right pleural effusion, and a huge mass arising in the right pleural cavity with dyspnea and chest pain. He underwent a thoracoscopic tumor biopsy. On the basis of histology and IHC findings, the pathological diagnosis was IMT. The histological and molecular profiles of the biopsy samples were reviewed and FISH analysis showed a RANBP2-ALKr which is a known aggressive variant. Curative resection was not indicated due to an insufficient pulmonary reserve. He was enrolled in a phase I study of ASP-3026 in patients with advanced solid tumors. ASP-3026 treatment (125mg q.d.) was initiated on Feb 14, 2012 as first-line treatment. After administration of ASP-3026, dramatic tumor shrinkage was revealed by computed tomography, and symptoms decreased rapidly. Furthermore, it is noteworthy that this case represents the first report of use of serum hyaluronan levels to assist in monitoring of treatment and disease progression in an IMT. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Preview · Article · Mar 2015 · Annals of Oncology
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    ABSTRACT: A recent retrospective analysis found that 23% of non-small cell lung cancer patients who acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) demonstrated "disease flare" after discontinuation of EGFR-TKIs. However, limitations of this study present the need for further investigation to elucidate this phenomenon in more detail. We reviewed the clinical records of EGFR mutated patients with advanced lung adenocarcinoma who were treated with gefitinib monotherapy in our hospital between January 2007 and December 2010. Disease flare was defined as unexpected interventions (e.g. radiation therapy or pleural drainage), hospitalization, or death attributable to disease progression after gefitinib discontinuation. Among 52 eligible patients, only two experienced disease flare (4%; 95% confidence interval: 1-13%). In both cases, interval time from gefitinib discontinuation to disease flare was 11 days, and the brain was the site of flare. Survival time after gefitinib was significantly shorter in the flare patients (78 and 97 days, respectively) compared with the no-flare patients (median 388 days). Our analysis demonstrated a lower incidence rate of disease flare after gefitinib discontinuation compared with the previous report, but the prognosis was similarly poor. Copyright © 2014 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
    No preview · Article · Mar 2015 · Annals of Oncology
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    ABSTRACT: Primary cancer of the trachea is rare and accounts for only 0.1-0.4% of all newly diagnosed respiratory tract cancers, worldwide. In the present study, a case of primary tracheal malignant melanoma, a particularly rare type of cancer, is reported. A 68-year-old male presented with a cough and bloody sputum. A chest computed tomography scan revealed a 25×20×15-mm tracheal tumor, located immediately above the carina, which reduced the cross-sectional area of the trachea by ~90%. Histopathological analysis of biopsy specimens determined a diagnosis of malignant melanoma. The patient was treated with argon plasma coagulation and chemoradiotherapy, which restored airway patency, however, metastasis was detected in the lungs. The patient refused further treatment and received palliative care. Subsequently, the patient succumbed to the disease within four months. Thus, although primary malignant melanoma of the trachea is extremeley rare, the possibility should be considered during diagnosis.
    Preview · Article · Feb 2015 · Oncology letters
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    ABSTRACT: The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC). We examined whether progression-free survival (PFS), post-progression survival (PPS), and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R(2)= 0.94), PFS was moderately correlated with OS (r = 0.58, p < 0.05, R(2)= 0.24), and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R(2)= 0.13). The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05). PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.
    No preview · Article · Jan 2015 · Annals of Thoracic Medicine
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    ABSTRACT: Purpose: The prognosis of non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) is unclear. To assess the prognosis of NSCLC patients with ILD treated with platinum-based chemotherapy, we retrospectively analyzed the clinical course of those with ILD. Methods: One hundred and four NSCLC patients with ILD treated with platinum-based chemotherapy at Shizuoka Cancer Center between August 2002 and June 2013 were retrospectively reviewed. Results: The combination of carboplatin with paclitaxel was most frequently used as the first-line treatment for NSCLC patients with ILD (61 %). The overall response rate was 38 % in 104 NSCLC patients with ILD treated with platinum-based chemotherapy. In all patients, median progression-free survival and overall survival were 4.8 and 9.9 months, respectively. During first-line platinum-based chemotherapy, 9 % of the 104 patients with ILD developed chemotherapy-related exacerbation of ILD. Multivariate analysis demonstrated that clinical stage was a significantly independent prognostic factor (hazard ratio 0.517; 95 % confidence interval 0.314-0.842, p = 0.0079). Patients with clinical stage IV or recurrence after surgical resection showed poor prognosis (median survival time 8.5 months). Conclusions: Our study suggests that the prognosis of NSCLC patients with ILD is poor. The risk of exacerbation of ILD in patients treated with platinum-based chemotherapy as the first-line treatment was slightly lower than in previous reports.
    No preview · Article · Jan 2015 · Cancer Chemotherapy and Pharmacology
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    ABSTRACT: The effects of first-line chemoradiotherapy on overall survival (OS) may be confounded by subsequent lines of therapy in patients with limited-stage disease small cell lung cancer (LD-SCLC). Therefore, we aimed to determine the relationships between progression-free survival (PFS), post-progression survival (PPS) and OS after first-line chemoradiotherapy in LD-SCLC patients. We retrospectively analyzed 71 LD-SCLC patients with performance status (PS) 0-2 who received first-line chemoradiotherapy and had disease recurrence between September 2002 and March 2013 at Shizuoka Cancer Center (Shizuoka, Japan). We determined the correlation between PFS and OS and between PPS and OS at the individual level. In addition, we performed univariate and multivariate analyses to identify significant prognostic factors of PPS. OS is more strongly correlated with PPS (Spearman’s PPS has more impact on OS than PFS in recurrent LD-SCLC patients with good PS at beginning of the treatment. Moreover, treatments administered after first-line chemoradiotherapy may affect their OS. However, larger multicenter studies are needed to validate these findings.
    No preview · Article · Jan 2015 · Radiology and Oncology
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    ABSTRACT: Background S-1, a novel oral fluoropyrimidine, has potent antitumor activity against non–small-cell lung cancer (NSCLC). Meanwhile, leucovorin enhances the efficacy of 5-fluorouracil by inhibiting thymidylate synthase. Therefore, this phase II clinical trial evaluated the safety and efficacy of S-1 plus leucovorin combination therapy for previously treated patients with NSCLC. Patients and methods Patients with stage IIIB or IV NSCLC were prospectively enrolled if they received 1 or 2 prior chemotherapy regimens. S-1 (40–60 mg) and leucovorin (25 mg) were administered together orally twice per day for 7 consecutive days followed by 7 days of rest. This 2-week cycle was repeated for a maximum of 25 cycles until the onset of disease progression or unacceptable adverse events. Endpoints included objective tumor response, progression-free survival, overall survival, and safety. Results Among 33 patients, 6 (18.2%), 14 (42.4%), and 11 (33.3%) had partial response, stable disease, and progressive disease, respectively. Median progression-free and overall survival times were 3.5 and 11.7 months, respectively. The common grade 3 toxicities included stomatitis (18.2%), anorexia (12.1%), and neutropenia (9.1%). One patient had pneumatosis cystoides intestinalis, and another experienced paralytic ileus. There were no treatment-related deaths. Conclusions S-1 plus leucovorin combination therapy demonstrated promising efficacy and an acceptable toxicity profile in previously treated patients with NSCLC (Clinical Trials Registry No.: UMIN000004568).
    No preview · Article · Dec 2014 · Lung Cancer
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    ABSTRACT: Cancer cachexia (CC) is commonly seen in advanced lung cancer patients and associated with poor prognosis. However, little is known about CC that develops during chemotherapy. We evaluated the prognostic impact of CC and skeletal muscle wasting that develops during the course of chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. The clinical data of 134 newly diagnosed NSCLC patients were retrospectively reviewed. CC was defined as a body weight loss >5 or >2 % in patients with a body mass index of <20 kg/m(2). CC was assessed at baseline (T1) and 3 months (T2), 6 months (T3), and 12 months (T4) after chemotherapy initiation. Skeletal muscle mass was assessed using the lumber skeletal muscle index (LSMI). The proportion of patients with CC at T1, T2, T3, and T4 was 45.6, 46.1, 25.5, and 26.0 %, respectively. The frequency of grade 3 chemotherapy-induced anorexia was higher in patients with CC than those without CC at T2 (15.4 vs. 0.0 %, P = 0.0044). At all time points, patients with CC had shorter survival times than those without CC. Patients with low LSMIs (men, <41 cm(2)/m(2); women, <38 cm(2)/m(2)) tended to have poor prognosis. Adjusted Cox proportional hazard ratios and corresponding confidence intervals for CC at T1, T2, T3, and T4 were 2.53 (1.33-4.88), 1.97 (1.27-3.06), 3.86 (2.14-6.81), and 1.62 (0.80-3.16), respectively. CC presence and decreased skeletal muscle mass are associated with poor prognosis in advanced NSCLC patients receiving chemotherapy.
    No preview · Article · Nov 2014 · Supportive Care Cancer
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    ABSTRACT: Background It is unclear whether there is a difference in the effect of gefitinib treatment between patients with postoperative recurrent non-small cell lung cancer (NSCLC) and those with stage IV NSCLC harboring mutations in the epidermal growth factor receptor (EGFR). Methods We retrospectively reviewed the medical records of consecutive patients with postoperative recurrent NSCLC (postoperative group) or stage IV NSCLC (stage IV group) harboring EGFR mutations who were treated with gefitinib at the Shizuoka Cancer Center between September 2002 and March 2012 to compare the effect of gefitinib on survival from treatment initiation. Results A total of 168 patients were treated with gefitinib (postoperative group, 49 patients; stage IV group, 119 patients). The response rate of gefitinib treatment in the postoperative group was similar to that in the stage IV group (58 vs. 61 %, p = 0.613). In contrast, median progression-free survival (PFS; 15.8 vs. 9.8 months, p
    No preview · Article · Oct 2014 · International Journal of Clinical Oncology
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    ABSTRACT: Background Genetic alterations in malignant pleural mesothelioma (MPM) patients are not well-understood. Patients and methods Surgical specimens and tumor biopsies from 42 patients with MPM were collected from 2003 to 2012. The samples were analyzed for mutations in EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2 and amplifications in EGFR, MET, PIK3CA, FGFR1, and FGFR2. In addition, 21 patients’ samples were analyzed using amplicon-based massively parallel sequencing for actionable mutations in 48 cancer-related genes. Results Genetic alterations were detected in 4 patients (one KRAS mutation and 3 PIK3CA amplifications). Patients harboring genetic alterations showed significantly poorer survival than patients with no genetic alterations. Moreover, significance was maintained if the patients only harbored PIK3CA amplification. A total 16 genetic mutations were identified in the 9 patients’ samples (4 TP53 mutations, 3 APC mutations, 3 PIK3CA mutations, and 2 VHL mutations, etc.) by deep sequencing. Conclusions: Genetic alterations that are potential targets for molecular targeted therapy were detected in MPM. Amplicon-based massively parallel sequencing was shown to have the advantage of more comprehensive genetic analysis. Further investigation in a larger cohort is necessary to uncover more targetable genetic alterations in MPM and to validate their clinical significance.
    No preview · Article · Oct 2014 · Lung Cancer

  • No preview · Conference Paper · Sep 2014

  • No preview · Conference Paper · Sep 2014
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    ABSTRACT: The effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with non-small cell lung cancer (NSCLC). Given the lack of research in this area, we here examined whether progression-free survival (PFS) or post-progression survival (PPS) could serve as valid surrogate endpoints for OS after second-line chemotherapy in advanced NSCLC, using individual-level data. Between April 2009 and June 2011, 39 patients with advanced non-squamous NSCLC who had received second-line chemotherapy following first-line chemotherapy treatment with cisplatin and pemetrexed were analysed. The relationships of PFS and PPS with OS were analysed at the individual level. Spearman rank correlation analyses and linear regression analyses showed that PPS was strongly associated with OS (r = 0.90, p < 0.05, R 2 = 0.85), whereas PFS only moderately correlated with OS (r = 0.76, p < 0.05, R 2 = 0.50). Best response at third-line treatment and number of regimens employed after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). Analysis of individual-level data of patients treated with second-line chemotherapy suggested that PPS may be used as a surrogate for OS in patients with advanced non-squamous NSCLC with unknown oncogenic driver mutations and therefore limited options for subsequent chemotherapy. Moreover, our findings suggest that subsequent treatment after disease progression following second-line chemotherapy may greatly influence OS. However, these results should be validated in further large-scale studies.
    No preview · Article · Aug 2014 · Medical Oncology
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    ABSTRACT: Background: Whether the mutant allele frequency (MAF) may also have predictive implications for tyrosine kinase inhibitor (TKI) therapy in patients with advanced epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (AELAd) remains unknown. Patients and methods: Based on a biobanking system in conjunction with our institution, we assessed EGFR mutation status using pyrosequencing (Py) and by outsourcing laboratory tests, such as the Cycleave (Cy) and the Scorpion ARMS (A). Results: Out of 705 patients enrolled in the Shizuoka Lung Cancer Mutation Study between July 2011 and March 2013, 102 AELAd patients were identified as carrying the L858R mutation (L858Rm) using Py to analyze histological specimens. Of these 102 patients, the EGFR mutation status was assessed using both Py and Cy in 48 patients: the median MAF of L858R (MAFLR) was 18.5% (range: 8%-82%), and 45 patients (94%) were identified as having an L858Rm using both Py and Cy. Three patients (6%) with discrepant L858Rm findings were only identified using Py. The plotting of a receiver operating characteristic curve to identify the discordance in L858Rm findings showed that the area under the curve for MAFLR was 0.967 (95% confidence interval: 0.91-1) and that an MAFLR of 9% resulted in high sensitivity (100%) and specificity (99%). Also, 29 patients with AELAd, excluding those with postoperative recurrences, had their L858R status assessed using Cy or A. The median age, 69 years (range: 47-84 years); male/female, 14 (48%)/15 (52%); smokers/never-smokers 13 (45%)/16 (55%); ECOG PS 0-1/2-3, 26 (90%)/3 (10%); stage IIIB/IV, 4 (14%)/25 (86%); median MAFLR, 18% (range: 8%-63%). Patients with an MAFLR of ≤9% had a significantly shorter progression-free survival (PFS) period after TKI therapy than those with an MAFLR of >9% (mPFS: 92 versus 284 days, P = 0.0027). Conclusion: The MAF may be a potential predictive factor of TKI treatment efficacy in patients with AELAd carrying the L858Rm.
    Preview · Article · Jul 2014 · Annals of Oncology
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    ABSTRACT: Introduction: Pleural effusion is frequently observed in patients with advanced lung cancer. Although effusion can be obtained less invasively and repeatedly, its use in multiplexed molecular profiling has not been fully investigated. Methods: Between July 2011 and April 2013, pleural effusion samples were obtained from patients with lung cancer at Shizuoka Cancer Center. They were analyzed for EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2 mutations, EGFR, MET, FGFR1, FGFR2, and PIK3CA amplifications, and ALK, ROS1, and RET fusion genes using pyrosequensing and/or capillary electrophoresis, quantitative reverse-transcriptase polymerase chain reaction, and reverse-transcriptase polymerase chain reaction, respectively. Results: One hundred and two samples from 84 patients were analyzed. Adenocarcinoma was the most common histological subtype (82%). Genetic abnormalities were detected in 42% of patients. The most common abnormality was EGFR mutation (29%), followed by EML4-ALK rearrangement (5%), KRAS mutation, and EGFR amplification (4%, each). Concordance rates between pleural effusion and matched formalin-fixed, paraffin-embedded samples were 88%. Among 11 patients who provided samples at multiple time points, changes in molecular profile over the course of treatment were observed in five patients. Conclusions: The use of pleural effusion for multiplexed molecular testing and real-time monitoring in lung cancer was demonstrated.
    No preview · Article · Jul 2014 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
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    ABSTRACT: We herein present the case of a 36-year-old woman who developed perianal metastasis of non-small cell lung cancer that was diagnosed based on the presence of symptoms mimicking a hemorrhoid. The patient initially underwent radiotherapy for a left superior sulcus tumor, then subsequently complained of a perianal mass that had prolapsed and bled. The tumor was removed via resection. Histologically, the mass was diagnosed as poorly differentiated carcinoma and considered to be a metastatic lesion arising from the primary lung cancer.
    No preview · Article · Jun 2014 · Internal Medicine