PURPOSE: The serum carcinoembryonic antigen (CEA) level has been recognized as a prognostic factor in colorectal cancer, and associated with response of rectal cancer to radiotherapy. This study aimed to identify CEA-interacting proteins in colon cancer cells and observe post-irradiation changes in their expression. MATERIALS AND METHODS: CEA expression in colon cancer cells was examined by Western blot analysis. Using an anti-CEA antibody or IgG as a negative control, immunoprecipitation was performed in colon cancer cell lysates. CEA and IgG immunoprecipitates were used for liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis. Proteins identified in the CEA immunoprecipitates but not in the IgG immunoprecipitates were selected as CEA-interacting proteins. After radiation treatment, changes in expression of CEA-interacting proteins were monitored by Western blot analysis. RESULTS: CEA expression was higher in SNU-81 cells compared with LoVo cells. The membrane localization of CEA limited the immunoprecipitation results and thus the number of CEA-interacting proteins identified. Only the Ras-related protein Rab-6B and lysozyme C were identified as CEA-interacting proteins in LoVo and SNU-81 cells, respectively. Lysozyme C was detected only in SNU-81, and CEA expression was differently regulated in two cell lines; it was down-regulated in LoVo but up-regulated in SNU-81 in radiation dosage-dependent manner. CONCLUSION: CEA-mediated radiation response appears to vary, depending on the characteristics of individual cancer cells. The lysozyme C and Rab subfamily proteins may play a role in the link between CEA and tumor response to radiation, although further studies are needed to clarify functional roles of the identified proteins.
Blotting, Western ; Carcinoembryonic Antigen ; Cell Line ; Colon* ; Colonic Neoplasms* ; Colorectal Neoplasms ; Immunoglobulin G ; Immunoprecipitation ; Mass Spectrometry ; Membranes ; Muramidase ; Radiotherapy ; Rectal Neoplasms

PURPOSE: The serum carcinoembryonic antigen (CEA) level has been recognized as a prognostic factor in colorectal cancer, and associated with response of rectal cancer to radiotherapy. This study aimed to identify CEA-interacting proteins in colon cancer cells and observe post-irradiation changes in their expression. MATERIALS AND METHODS: CEA expression in colon cancer cells was examined by Western blot analysis. Using an anti-CEA antibody or IgG as a negative control, immunoprecipitation was performed in colon cancer cell lysates. CEA and IgG immunoprecipitates were used for liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis. Proteins identified in the CEA immunoprecipitates but not in the IgG immunoprecipitates were selected as CEA-interacting proteins. After radiation treatment, changes in expression of CEA-interacting proteins were monitored by Western blot analysis. RESULTS: CEA expression was higher in SNU-81 cells compared with LoVo cells. The membrane localization of CEA limited the immunoprecipitation results and thus the number of CEA-interacting proteins identified. Only the Ras-related protein Rab-6B and lysozyme C were identified as CEA-interacting proteins in LoVo and SNU-81 cells, respectively. Lysozyme C was detected only in SNU-81, and CEA expression was differently regulated in two cell lines; it was down-regulated in LoVo but up-regulated in SNU-81 in radiation dosage-dependent manner. CONCLUSION: CEA-mediated radiation response appears to vary, depending on the characteristics of individual cancer cells. The lysozyme C and Rab subfamily proteins may play a role in the link between CEA and tumor response to radiation, although further studies are needed to clarify functional roles of the identified proteins.
Blotting, Western ; Carcinoembryonic Antigen ; Cell Line ; Colon* ; Colonic Neoplasms* ; Colorectal Neoplasms ; Immunoglobulin G ; Immunoprecipitation ; Mass Spectrometry ; Membranes ; Muramidase ; Radiotherapy ; Rectal Neoplasms

Even in patients undergoing an optimal surgical technique (e.g., total mesorectal excision), radiotherapy provides a significant benefit in the local control of rectal cancer. Compared with postoperative treatment, chemoradiotherapy given preoperatively has been shown to decrease local recurrence rates and toxicity. Additionally, preoperative chemoradiotherapy permits the early identification of tumor responses to this cytotoxic treatment by surgical pathology. Pathological parameters reflecting the tumor response to chemoradiotherapy have been shown to be surrogate markers for long-term clinical outcomes. Post-chemoradiotherapy downstaging from cStage II-III to ypStage 0-I indicates a favorable prognosis, with no difference between ypStage 0 and ypStage I. Research is ongoing to develop useful tools (clinical, molecular, and radiological) for clinical determination of the pathologic chemoradiotherapeutic response before surgery, and possibly even before preoperative treatment. In the future, risk-adapted strategies, including intensification of preoperative therapy, conservative surgery, or the selective administration of postoperative chemotherapy, will be realized for locally-advanced rectal cancer patients based on their response to preoperative chemoradiotherapy.
Biomarkers ; Chemoradiotherapy ; Humans ; Pathology, Surgical ; Prognosis ; Rectal Neoplasms ; Recurrence

Personalized medicine for rectal cancer patients includes nonoperative management. This strategy is appropriate for select patients who exhibit a clinical complete response (cCR) to neoadjuvant chemoradiotherapy (nCRT). This study presents the case of a 70-year-old female with locally advanced rectal cancer. She received standard nCRT, consisting of 50.4 Gy pelvic radiotherapy and concurrent 5-fluorouracil chemotherapy. The response to nCRT was evaluated at 11 weeks after nCRT completion. Colonoscopy and computed tomography indicated cCR, but a partial residual tumor was suspected based on magnetic resonance imaging. Low anterior resection was performed with the creation of a protective colostomy. The pathological examination of the surgical specimen revealed only a fibrotic mass, no viable tumor cells. The stoma was maintained for 10 months until reversal after adjuvant chemotherapy ended. The patient remains alive with no evidence of disease 4 years later; however, the utility of this radical major surgery was questionable for this patient. Development of a risk-adapted strategy based on the nCRT response would avoid overtreatment, improving functional outcomes and quality of life while also retaining good oncological outcomes.

PURPOSE: Patients show variable responses to chemoradiotherapy (CRT), which is generally administered before surgery for locally advanced rectal cancer (LARC). The aim of this study was to identify molecular markers predictive of CRT responses by analysis of low-mass ions (LMIs) in serum of LARC patients. MATERIALS AND METHODS: LMIs (< 1,000 m/z) in serum obtained before CRT from 73 LARC (cT3-4) patients were profiled using matrix-assisted laser desorption/ionization mass spectrometry. LMIs with higher weighting factors in discriminating CRT responses were selected using principal components analysis and discriminant analysis. Selected LMIs were identified using the Human Metabolome Database. The concentrations of identified LMIs were determined by colorimetric enzyme assay, and compared according to post-CRT pathological stage (ypStage) or Dworak's tumor regression grade (TRG). RESULTS: The nine highest-ranking LMIs were selected. Among them, two LMIs with 137.08 and 169.04 m/z were identified as hypoxanthine (HX) and phosphoenolpyruvic acid (PEP), respectively. Higher HX concentration was observed in patients with ypStage 0-1 compared to ypStage 2-4 (p=0.034) or ypStage 3-4 (p=0.030); a similar difference was observed between TRG 4-3 and TRG 1 (p=0.035). HX > 16.0 muM showed significant association with ypStage 0-1 or TRG 4-3 than ypStage 3-4 (p=0.009) or TRG 1 (p=0.024), respectively. In contrast, a significantly lower concentration of PEP was observed in TRG 4-3 compared with TRG 2-1 (p=0.012). CONCLUSION: Findings of this study demonstrated that serum concentrations of HX and PEP, identified using LMI profiling, may be useful for predicting the CRT response of LARC patients before treatment.
Biological Markers* ; Chemoradiotherapy* ; Enzyme Assays ; Humans ; Hypoxanthine* ; Ions ; Mass Spectrometry ; Metabolome ; Phosphoenolpyruvate ; Rectal Neoplasms*

PURPOSE: This study aimed to investigate efficient approaches for determining internal target volume (ITV) from four-dimensional computed tomography (4D CT) images used in stereotactic body radiotherapy (SBRT) for patients with early-stage non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: 4D CT images were analyzed for 15 patients who received SBRT for stage I NSCLC. Three different ITVs were determined as follows: combining clinical target volume (CTV) from all 10 respiratory phases (ITV10Phases); combining CTV from four respiratory phases, including two extreme phases (0% and 50%) plus two intermediate phases (20% and 70%) (ITV4Phases); and combining CTV from two extreme phases (ITV2Phases). The matching index (MI) of ITV4Phases and ITV2Phases was defined as the ratio of ITV4Phases and ITV2Phases, respectively, to the ITV10Phases. The tumor motion index (TMI) was defined as the ratio of ITV10Phases to CTVmean, which was the mean of 10 CTVs delineated on 10 respiratory phases. RESULTS: The ITVs were significantly different in the order of ITV10Phases, ITV4Phases, and ITV2Phases (all p < 0.05). The MI of ITV4Phases was significantly higher than that of ITV2Phases (p < 0.001). The MI of ITV4Phases was inversely related to TMI (r = -0.569, p = 0.034). In a subgroup with low TMI (n = 7), ITV4Phases was not statistically different from ITV10Phases (p = 0.192) and its MI was significantly higher than that of ITV2Phases (p = 0.016). CONCLUSION: The ITV4Phases may be an efficient approach alternative to optimal ITV10Phases in SBRT for early-stage NSCLC with less tumor motion.
Carcinoma, Non-Small-Cell Lung ; Four-Dimensional Computed Tomography ; Humans ; Lung Neoplasms* ; Lung* ; Radiosurgery ; Radiotherapy*

PURPOSE: To evaluate the treatment outcomes of the three-dimensional conformal radiotherapy (3D-CRT), in conjunction with induction chemotherapy, for the treatment of stage III non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between November 1998 and March 2003, 22 patients with histologically proven, clinical stage III NSCLC, treated with induction chemotherapy, followed by 3D-CRT, were retrospectively analyzed. There were 21 males (96%) and 1 female (4%), with a median age of 68.5 (range, 42~79). The clinical cancer stages were IIIA and IIIB in 41 and 59%, respectively. The histologies were squamous cell carcinoma, adenocarcinoma and others in 73, 18 and 9%, respectively. Twenty patients (91%) received induction chemotherapy before radiation therapy. The majority of the chemotherapy regimen consisted of cisplatin and gemcitabine. Radiation was delivered with conventional anteroposterior/ posteroanterior fields for 36 Gy, and then 3D-CRT was performed. The total radiation dose was 70.2 Gy. The median follow-up period was 17 months (range, 4~59 months). RESULTS: The median overall survival was 19 months. The two and four-year overall survival rates were 37.9 and 30.3%, respectively. The median progression-free survival was 21 months. The two and four-year progression-free survival rates were 42.1 and 21%, respectively. The prognostic factors for overall survival by a univariate analysis were age, histology and T stage (p<0.05). Acute radiation toxicities, as evaluated by the RTOG toxicity criteria, included two cases of grade 3 lung toxicity and one case of grade 2 esophagus toxicity. CONCLUSIONS: The radiation dose could be increased without a significant increment in the acute toxicities when using 3D-CRT. It also seems to be a safe, well- tolerated and effective treatment modality for stage III NSCLC.
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Chemoradiotherapy ; Cisplatin ; Disease-Free Survival ; Drug Therapy ; Esophagus ; Female ; Follow-Up Studies ; Humans ; Induction Chemotherapy ; Lung ; Male ; Radiotherapy, Conformal* ; Retrospective Studies ; Survival Rate

BACKGROUND AND OBJECTIVES: Auricular masses are growths on the outer ear that have not been well characterized clinically. We assessed the clinical nature and treatment of auricular benign masses in patients at our institution. SUBJECTS AND METHODS: We retrospectively identified 63 patients with auricular benign masses who underwent excision and biopsy from May 1970 to April 2011. We determined the site, cause, size, pathology and postoperative results of these auricular masses. RESULTS: Auricular benign masses occurred most commonly on the lobule (44.4%), followed by the tragus (20.6%), crus of helix (11.1%), triangular fossa (6.3%), crus of antihelix-antitragus (3.1%) and scapha (1.5%). Pathologically, the most common type of auricular mass was epidermal cysts (25.3%), followed by hypertrophic scar (12.6%), fibrous tissue-accessory ear (9.5%), chronic inflammation-nevus (7.9%), keloid (6.3%), hemangioma (4.7%), and skin tag-seborrheic keratosis (3.1%). CONCLUSIONS: The most common site of auricular benign masses is the lobule and most common pathology is an epidermal cyst.
Biopsy ; Cicatrix, Hypertrophic ; Ear ; Ear, External ; Epidermal Cyst ; Hemangioma ; Humans ; Keloid ; Keratosis ; Retrospective Studies ; Skin

PURPOSE: A retrospective study was performed to evaluate the efficiency and feasibility of twice daily radiation therapy plus concurrent chemotherapy for limited-stage small cell lung cancer in terms of treatment response, survival, patterns of failure, and acute toxicities. MATERIALS AND METHODS: Between February 1993 and October 2002, 76 patients of histologically proven limited-stage small cell lung cancer (LS-SCLC) were treated with twice daily radiation therapy and concurrent chemotherapy. Male was in 84% (64/76), and median age was 57 years (range, 32~75 years). Thoracic radiation therapy consisted of 120 or 150 cGy per fraction, twice a day at least 6 hours apart, 5 days a week. Median total dose was 50.4 Gy (range, 45~51 Gy). Concurrent chemotherapy consisted of CAV (cytoxan 1000 mg/m2, adriamycin 40 mg/m2, vincristine 1 mg/m2) alternating with PE (cisplatin 60 mg/m2, etoposide 100 mg/m2) or PE alone, every 3 weeks. The median cycle of chemotherapy was six (range, 1~9 cycle). Prophylactic cranial irradiation (PCI) was recommended to the patients who achieved a complete response (CR). PCI scheme was 25 Gy/ 10 fractions. Median follow up was 18 months (range, 1~136 months). RESULTS: Overall response rate was 86%; complete response in 39 (52%) and partial response in 26 (34%) patients. The median overall survival was 23 months. One, two, and three year overall survival rate was 72%, 50% and 30%, respectively. In univariate analysis, the treatment response was revealed as a significant favorable prognostic factor for survival (p<0.001). Grade 3 or worse acute toxicities were leukopenia in 46 (61%), anemia in 5 (6%), thrombocytopenia in 10 (13%), esophagitis in 5 (6%), and pulmonary toxicity in 2 (2%) patients. Of 73 evaluable patients, 40 (55%) patients subsequently had disease progression. The most frequent first site of distant metastasis was brain. CONCLUSION: Twice daily radiation therapy plus concurrent chemotherapy produced favorable response and survival for LS-SCLC patients with tolerable toxicities. To improve the treatment response, which proved as a significant prognostic factor for survival, there should be further investigations about fractionation scheme, chemotherapy regimens and compatible chemoradiotherapy schedule.
Anemia ; Appointments and Schedules ; Brain ; Chemoradiotherapy ; Cranial Irradiation ; Disease Progression ; Doxorubicin ; Drug Therapy* ; Esophagitis ; Etoposide ; Follow-Up Studies ; Humans ; Leukopenia ; Male ; Neoplasm Metastasis ; Retrospective Studies ; Small Cell Lung Carcinoma* ; Survival Rate ; Thrombocytopenia ; Vincristine

The correlation between facial pain and/or headache in patients with chronic sinusitis and localized findings on paranasal sinus omputed tomography (CT) are poorly understood. So we prospectively evaluated the relationship of paranasal sinus pain symptoms with CT imaging. Fifty eight patients with headache and/or facial pain rated their pain in 9 areas at the time of CT scanning and 2 months after endoscopic sinus surgery (ESS). We scored the degree of air-fluid level, mucosal thickening, and mucus retention cysts using a grade scale of severity. The ostiomeatal unit, middle meatus and nasofrontal duct were also evaluated for patency. Bivariate analysis was performed to evaluate the relationship between patients' pain, that was improved after ESS and CT findings. Among 58 patients who had facial pain and/or headache at the time of CT scan, the pain improved in 51 patients after ESS. Bivariate analysis failed to show any relationship between pain symptoms and CT findings in 51 patients. This study suggests that findings on CT do not routinely correlate with the patients' symptoms of facial pain or headache. CT should therefore be reserved for delineating the anatomy and degree of sinus disease before surgical intervention.
Facial Pain ; Headache ; Humans ; Korea* ; Mucus ; Prospective Studies ; Sinusitis ; Tomography, X-Ray Computed