• Title/Summary/Keyword: Tumor control

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NF-${\kappa}B$ Activation and cIAP Expression in Radiation-induced Cell Death of A549 Lung Cancer Cells (A549 폐암세포주의 방사선-유도성 세포사에서 NF-${\kappa}B$ 활성화 및 cIAP 발현)

  • Lee, Kye Young;Kwak, Shang-June
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.5
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    • pp.488-498
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    • 2003
  • Background : Activation of the transcription factor NF-${\kappa}B$ has been shown to protect cells from tumor necrosis factor-alpha, chemotherapy, and radiation-induced apoptosis. NF-${\kappa}B$-dependent cIAP expression is a major antiapoptotic mechanism for that. NF-${\kappa}B$ activation and cIAP expression in A549 lung cancer cells which is relatively resistant to radiation-induced cell death were investigated for the mechanism of radioresistance. Materials and methods : We used A549 lung cancer cells and Clinac 1800C linear accelerator for radiation. Cell viability test was done by MTT assay. NF-${\kappa}B$ activation was tested by luciferase reporter gene assay, Western blot for $I{\kappa}B{\alpha}$ degradation, and electromobility shift assay. For blocking ${\kappa}B$, MG132 and transfection of $I{\kappa}B{\alpha}$-superrepressor plasmid construct were used. cIAP expression was analyzed by RT-PCR and cIAP2 promoter activity was performed using luciferase assay system. Results : MTT assay showed that cytotoxicity even 48 hr after radiation in A549 cells were less than 20%. Luciferas assay demonstrated weak NF-${\kappa}B$ activation of $1.6{\pm}0.2$ fold compared to PMA-induced $3.4{\pm}0.9$ fold. Radiation-induced $I{\kappa}B{\alpha}$ degradation was observed in Western blot and NF-${\kappa}B$ DNA binding was confirmed by EMSA. However, blocking NF-${\kappa}B$ using MG132 and $I{\kappa}B{\alpha}$-superrepressor transfection did not show any sensitizing effect for radiation-induced cell death. The result of RT-PCR for cIAP1 & 2 expression was negative induction while TNF-${\alpha}$ showed strong expression for cIAP1 & 2. The cIAP2 promoter activity also did not show any change compared to positive control with TNF-${\alpha}$. Conclusion : We conclude that activation of NF-${\kappa}B$ does not determine the intrinsic radiosensitivity of cancer cells, at least for the cell lines tested in this study.

Postoperative Adjuvant Chemoradiotherapy in Rectal Cancer (직장암의 근치적 수술 후 보조 화학방사선요법)

  • Chang, Sei-Kyung;Kim, Jong-Woo;Oh, Do-Yeun;Chong, So-Young;Shin, Hyun-Soo
    • Radiation Oncology Journal
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    • v.24 no.3
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    • pp.157-163
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    • 2006
  • [ $\underline{Purpose}$ ]: To evaluate the role of postoperative adjuvant chemoradiotherapy in rectal cancer, we retrospectively analyzed the treatment outcome of patients with rectal cancer taken curative surgical resection and postoperative adjuvant chemoradiotherapy. $\underline{Materials\;and\;Methods}$: A total 46 patients with AJCC stage II and III carcinoma of rectum were treated with curative surgical resection and postoperative adjuvant chemoradiotherapy. T3 and T4 stage were 38 and 8 patients, respectively. N0, N1, and N2 stage were 12, 16, 18 patients, respectively. Forty patients received bolus infusions of 5-fluorouracil ($500\;mg/m^2/day$) with leucovorin ($20\;mg/m^2/day$), every 4 weeks interval for 6 cycles. Oral Uracil/Tegafur on a daily basis for $6{\sim}12$ months was given in 6 patients. Radiotherapy with 45 Gy was delivered to the surgical bed and regional pelvic lymph node area, followed by $5.4{\sim}9\;Gy$ boost to the surgical bed. The follow up period ranged from 8 to 75 months with a median 35 months. $\underline{Results}$: Treatment failure occurred in 17 patients (37%). Locoregional failure occurred in 4 patients (8.7%) and distant failure in 16 patients (34.8%). There was no local failure only. Five year actuarial overall survival (OS) was 51.5% and relapse free survival (RFS) was 58.7%. The OS and RFS were 100%, 100% in stage N0 patients, 53.7%, 47.6% in N1 patients, and 0%, 41.2% in N2 patients (p=0.012, p=0.009). The RFS was 55%, 78.5%, and 31.2% in upper, middle, and lower rectal cancer patients, respectively (p=0.006). Multivariate analysis showed that N stage (p=0.012) was significant prognostic factor for OS and that N stage (p=0.001) and location of tumor (p=0.006) were for RFS. Bowel complications requiring surgery occurred in 3 patients. $\underline{Conclusion}$: Postoperative adjuvant chemoradiotherapy was an effective modality for locoregional control of rectal cancer. But further investigations for reducing the distant failure rate are necessary because distant failure rate is still high.

Postoperative Radiation Therapy in the Management of Early Cervical Cancer (초기 자궁경부암의 수술 후 방사선치료의 효과)

  • Kim, Jae-Chul
    • Radiation Oncology Journal
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    • v.24 no.3
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    • pp.164-170
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    • 2006
  • [ $\underline{Purpose}$ ]: This study identified the result of postoperative radiation therapy and the prognostic factors to affect survival rates in cancer patients. $\underline{Materials\;and\;Methods}$: One hundred and thirty three patients with cervical cancer who were treated with postoperative radiation therapy following surgery at our institution between June 1985 and November 2002 were retrospectively analyzed. One hundred and thirteen patients had stage IB disease, and 20 patients had stage IIA disease. Histological examination revealed 118 squamous cell carcinoma patients and 15 adenocarcinoma patients. Sixty seven patients were noted to have stromal invasion greater than 10 mm, and 45 patients were noted to have stromal Invasion 10 mm or less. Positive lymphovascular invasion was found in 24 patients, and positive pelvic lymph nodes were noted in 39 patients. Positive vaginal resection margin was documented in 8 patients. All of the patients were treated with external beam radiation therapy to encompass whole pelvis and primary surgical tumor bed. Intracavitary radiation therapy was added to 19 patients who had positive or close surgical margins. $\underline{Results}$: Actuarial overall and disease-free survival rates for entire group of the patients were 88% and 84% at 5 years, respectively. Five-year disease-free survival rates for patients with stromal invasion greater than 10 mm and 10 mm or less were 76% and 97%, respectively (p<0.05). Also there was a significantly lower survival in patients with positive pelvic lymph nodes compared with patients with negative pelvic lymph nodes (p<0.05). However, lymphovascular invasion, positive vaginal resection margins were not statistically significant prognostic factors. Addition of neoadjuvant chemotherapy or type of surgery did not affect disease-free survival. $\underline{Conclusion}$: Postoperative radiation therapy appears to achieve satisfactory local control with limited morbidity in cervical cancer patients with high pathologic risk factors. Distant metastasis was a dominant failure pattern to affect survival in cervical cancer patients after radical surgery and radiation and more effective systemic treatment should be investigated in these high-risk patients.

Medicinal Herb Extracts Attenuate 1-Chloro-2,4dinitrobenzene-induced Development of Atopic Dermatitis-like Skin Lesions (한약재 단일 추출물 및 복합 추출물을 이용한 아토피성 피부염 억제 효과)

  • Lee, Moon Hee;Han, Min Ho;Yoon, Jung Jeh;Song, Myung Kyu;Kim, Min Ju;Hong, Su Hyun;Choi, Byung Tae;Kim, Byung Woo;Hwang, Hye Jin;Choi, Yung Hyun
    • Journal of Life Science
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    • v.24 no.8
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    • pp.851-859
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    • 2014
  • The present study was designed to investigate whether ethanol extracts of Sophora flavescens (GS), Glycyrrhiza uralensis (GC), Dictamnus dasycarpus (BSP), and their mixtures (GGB-1, -2, -3, and -4) inhibit 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in a mouse model. DNCB was topically applied on the dorsal surface of Balb/c mice to induce AD-like skin lesions. The pathological phenotypes of AD, such as erythema, ear thickness, edema, scabs, and discharge, were significantly decreased in the GGB (DNCB + GS:GC:BSP = 3:1:1 mixture)-1-treated groups compared with the other treated groups. The weight of the spleen in immune organs was significantly decreased in the GGB-1-treated groups, whereas the weight of the liver in a control group was similar to that of the groups treated with the samples. Furthermore, toluidine blue staining analysis, a method used to specifically identify mast cells, showed that master cell infiltration into the dermis of the GGB-1-treated group was significantly decreased. The immunoglobulin E concentration was lower in the GGB-1-treated group. In addition, the levels of inflammatory cytokines (interferon-${\gamma}$, interleukin-1, 4, 5, 6, and 13, $1{\beta}$, and tumor necrosis factor-${\alpha}$) were also significantly reduced in the GGB-1-treated group. Taken together, these results suggest that a mixture of GS, GC, and BSP in a proportion of 3:1:1 (GGB-1) may contribute to the relief of AD symptoms and may be considered an excellent candidate for an AD therapeutic drug.

Conservative Surgery and Primary Radiotherapy for Early Bresst Cancer: Yonsei Cancer Center Experience (조기 유방암에서 보존적 수술후 방사선치료: 연세암센터 경험)

  • Suh Chang Ok;Lee Hy De;Lee Kyung Sik;Jung Woo Hee;Oh Ki Keun;Kim Gwi Eon
    • Radiation Oncology Journal
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    • v.12 no.3
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    • pp.337-347
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    • 1994
  • Breast conserving surgery and irradiation is now accepted as preferable treatment method for the patients with stage I and II breast cancer. Our institution activated team approach for breast conservation in 1991 and treated one hundred and fourty patients during the next three years. Purpose : To present our early experience with eligibility criteria, treatment techniques, and the morbidities of primary radiotherapy. Materials and Methods: Sixty four patients with early stage breast cancer who received breast conserving treatment between January 1991 and December 1992 were evaluated. All patients received partial mastectomy(wide excision to quadrantectomy) and axillary node dissection followed by radiotherapy. Total dose of 4500-5040 cGy in 5-5 1/2 weeks was given to entire involved breast and boost dose of 1000-2000 cGy in 1-2 weeks was given to the primary tumor site. Linac 4 MV X-ray was used for breast irradiation and electron beam was used for boost. Thirty five Patients received chemotherapy before or after radiotherapy. Patients characteristics, treatment techniques, and treatment related morbidities were analyzed. Results : Age distribution was ranged from 23 to 59 year old with median age of 40. Twenty-seven patients had T1 lesions and 34 patients had T2 lesions. In three patients, pathologic diagnosis was ductal carcinoma in situ. Thirty-seven Patients were N0 and 27 patients were Nl. There were three recurrences, one in the breast and two distant metastases during follow-up period(6-30 months, median 14 months). Only one breast recurrence occured at undetected separate lesion with microcalcifications on initial mammogram. There was no serious side reaction which interrupted treatment courses or severe late complication. Only one symptomatic radiation pneumonitis and one asymptomatic radiation pneumonitis were noted. Conclusions: Conservative surgery and primary radiotherapy for early breast cancer is Proven to be safe and comfortable treatment method without any major complication. Long-term follow up is needed to evaluate our treatment results in terms of loco-regional control rate, survival rate, and cosmetic effect.

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Analysis of Prognostic Factors in Glioblastoma Multiforme (다형성 교모세포증 환자의 예후인자 분석)

  • Chang Sei Kyung;Suh Chang Ok;Lee Sang Wook;Keum Ki Chang;Kim Gwi Eon;Kim Woo Cheol
    • Radiation Oncology Journal
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    • v.14 no.3
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    • pp.181-189
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    • 1996
  • Purpose : To find the more effective treatment methods that improving the survival of patients with glioblastoma multiforme(GBM), we analyze the prognostic factors and the outcome of therapy in patients with GBM. Materials and Methods : One hundred twently-one patients with a diagnosis of GBM treated at Severance Hospital between 1973 and 1993 were analyzed for survival with respect to patients characteristics, that is, duration of symptom, age, and Karnofsky performance status, as well as treatment related variables such as extent of surgery and radiotherapy. Results : The median survival time(MST) and 2-year overall survival rate (OSR) of the patients with GBM were 13 months and $20.8\%$, respectively. Duration of symptom, age, Karnofsky performance status(KPS), radiotherapy, and extent of surgical resection were associated with improved survial in a univariate analysis. Patients whose duration of symptom was longer than 3 months, had the 2-year OSR of $47.2\%$(p=0.0082), who were younger than age 50, $32.9\%$(p=0.0003) In patients with a KPS of 80 or higher, the 2-rear OSR was $36.9\%$(p=0.0422). Patients undergoing radiotherapy had the 2-year OSR of $22.9\%$(p=0.0030), and surgical resection of $23.3\%$ (p<0.000). A Cox regression model confirmed a significant correlation of duration of symptom, age, radiotherapy, and extent of surgical resection with survival, excluding KPS(P=0.8823). The 2-year OSR were $22.3\%$ and $19.4\%$, combined with chemotherapy or without, respectively(p=0.6028). The duration of symptom of 3 months or shorter, 50 years of age or older, and undergoing stereotactic biopsy only were considered as risk factors, then patients without any risk factors had the MST of 29 months and 2-year OSR of $53.9\%$ compared to 4 months and $0\%$ for Patients who had all 3 risk factors. Most of all treatment failures occurred in the primary tumor site($80.4\%$). Conclusion : The duration of symptom, age, radiotherapy, and extent of surgical resection were a prognostically significant indeuendent variables. To get a better survival, it seems to be reasonable that the study design which improves the local control rates is warranted.

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Packing effects on the intracavitary radiation therapy of the utaine lervix cancer ($^{192}Ir$source를 이용할 자궁경부암 강내치료시 사용하는 packing의 효과에 대한 고찰)

  • Cho, Jung-Kun;Lee, Du-Hyun;Si, Chang-Kun;Choi, Yoon-Kyung;Kim, Tae-Yoon
    • The Journal of Korean Society for Radiation Therapy
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    • v.16 no.1
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    • pp.73-77
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    • 2004
  • Purpose of the radio-therapy is maximize the radiation dose to the tumor while minimizing the dose to the critical organ. Carcinoma of the uterine cervix treatment are external irradiation or an interstitial brachtheraphy make use of isotope. Brachytherapy is a method of radiotherapy in advantage to achieve better local control with minimum radiation toxicity in comparison with external irradiation because radiation dose is distributed according to the inverse square low of gamma-ray emitted from the implanted sources. Authors make use of the patients data which 192Ir gives medical treatment intrcavity. Intracavitary radiation of the uterine cervix cancer, critical organ take $20\%$ below than exposure dose of A point in the ICRU report. None the less of the advice, Radiation proctitis and radiation cystitis are frequent and problematic early complications in patients treated with radiation for the uterine cervix cancer. In brachytherapy of uterine cervical cancer using a high dose rate remote afterloading system, it is of prime importance to deliver a accurate dose in each fractionated treatment by minimizing the difference between the pre-treatment planned and post-treatment calculated doses. Use of packing to reduce late complications intracavitary radiation of the uterine cervix cancer. Bladder and rectum changes exposure dose rate by radiotherphy make use of packing.

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Effects of Green Tea Extract on Acute Ethanol-induced Hepatotoxicity in Rats (녹차추출물이 에탄올 투여에 의한 초기 간 손상에 미치는 영향)

  • Jin, Dong-Chun;Jeong, Seung-Wook;Park, Pyoung-Sim
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.3
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    • pp.343-349
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    • 2010
  • The liver is the major target of ethanol toxicity and oxidative stress plays a role in development of alcoholic liver disease. This study was performed to investigate the effects of green tea extracts (GTE) on acute ethanol-induced hepatotoxicity in rats. Experimental animals were divided into 4 groups, control, GTE, ethanol, and GTE+ethanol treatment, with 5 rats in each group. Ethanol (6 g/kg body weight (BW)) and GTE (200 mg/kg BW) were treated by gavage. At 1 hour, 3 hours and 20 days (6 g/kg BW every 2 days for total 10 doses) after ethanol and/or GTE treatments, animals were killed; hepatic tumor necrosis factor-alpha (TNF-$\alpha$) and glutathione level, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), hepatic antioxidant enzymes (SOD, CAT, GPx) activities and hepatic thiobarbituric acid reactive substances (TBARS) were measured. At 1 hour and 3 hours, hepatic TNF-$\alpha$ levels were increased significantly in ethanol group and ethanol+GTE group but that levels was significantly lower in ethanol+GTE group compared with ethanol group. Hepatic glutathione level was decreased by ethanol treatment but GTE prevented the ethanol-induced glutathione decrement. The levels of liver marker enzymes (AST, ALT), liver antioxidant enzymes (SOD, CAT, GPx) and lipid peroxidation marker (TBARS) were not changed in rats of 1 and 3 hours after ethanol treatment. After 20 days, GTE decreased the changes of liver marker enzymes (AST, ALT) activities and TBARS level by ethanol. This study shows that GTE beneficially modulates TNF-$\alpha$ and glutathione levels in liver of ethanol administered rats. The GTE supplementation could be beneficial to liver by decreasing early changes of biomarkers of liver damage caused by ethanol.

The Effects of High Dose Rate Brachytherapy in Recurrent Obstructive Bronchogenic Cancer after External Irradiation Therapy (외부 방사선 치료 조사후 재발한 기관지내 악성종양에서 고선량율 근접조사치료(High Dose Rate Brachytherapy)의 효과)

  • Cho, Jae-Youn;In, Kwang-Ho;Suh, Jung-Kyung;Kang, Sea-Yong;Shim, Jae-Jeong;Kang, Kyung-Ho;Kim, Kwang-Taak;Kim, Cheol-Yong;Yoo, Sa-Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.1
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    • pp.68-76
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    • 1998
  • Background: Patients with centrally recurred bronchogenic carcinoma make a complaint of many symptoms like hemoptysis, cough & dyspnea. At these conditions, the goal of treatment is only to relieve their symptoms. High dose rate brachytherapy(HDR-BT) is the palliative treatment modality of centrally located endobronchial tumor regardless of previous external irradiation(XRT) on the same site in symptomatic patients. Methods: We studied the effects of HDR-BT in 26 patients with symptomatic recurrent lung cancer. Patients(male: 24, mean age: 54yrs)were treated with HDR-BT underwent bronchoscopic placement of $^{192}Ir$ HDR after loading unit(Gammamed$^{(T)}$, Germany) to deliver 500cGY intraluminal irradiation at a depth of 1cm every lwk on 3 occasions. Evaluation at base line and 4wks after HDR brachytherapy included chest X-ray, bronchscopy, symptoms (Standadized Scale for dyspnea,cough,hemoptysis), and Karnofsky performance scale. Results: Endobronchial obstruction was improved in 11/26 patients(37%). Atelectasis in chest X-ray was improved in 5/15 patients(33%). Hemoptysis, dyspnea & cough were improved in 5/10 patients (50%), 5/8 patients (62%) & 10/18 patients (56%) respectively. Karnofsky performance status was changed from 76.4 scores in pretreatment to 77.6 scores after treatment. During HDR-BT, massive hemoptysis (2 patients) and pneumothorax(1 patient) were occurred as complications. Conclusion: We concluded that HDR-BT gave additional benefits for the control of symptoms and general performance and endobronchial obstruction & atelectasis. And HDR-BT will be an additional treatment for the recurrent and endobronchial obstructive lung cancer.

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MR Imaging Findings of Uterine Cervical Adenocarcinoma (자궁경부 선암종의 자기공명영상 소견)

  • 김종철
    • Investigative Magnetic Resonance Imaging
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    • v.2 no.1
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    • pp.113-119
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    • 1998
  • Purpose : Because adenocarcinomas of the uterine cervix have lower 5-year survival rate than squamous cell carcinomas due to early lymph node metastasis and local extension, scrutiny of lymph node metastasis and local extension by radiologic examination is necessary in case of clinically diagnosed or suspected adenocarcinomas. The purpose of this study is to evaluate whether there are specific findings of these tumors, compared with squamous cell carcinomas, through the analysis of magnetic resonance (MR) imaging findings. Materials and Methods : Of 21 pathologically proven cervical adenocarcinomas, MR imaging findings of 18 tumors (histologic staging : two Ib, four IIa, two IIb, one IIIa, and one IIIb) were retrospectively analyzed and compared with those of 40 wquamous cell carcinoma in consecutive patients as a control group. T1-wetighted and fast spin echo T2-weighted images were obtained on the axial and sagittal planes, using a 1.5-T MR scanner. The largest diameter, location, signal intensity and degree of contrast enhancement contour, shape and longitudinal extent of the tumor and associated findings on MR image were analyzed. Results : The largest diameters of cervical adenocarcinomas ranged from 0.8 to 4.1 cm(mean, 2.2 cm). Of 18 adenocarcinomas, nine were of endocervical type. All adenocarcinomas were isointense to surrounding cervical stroma on T1-weighted images and hyperintense(homogeneous in ten, inhomogeneous in eight) on fast spin echo T2-weighted images. Adenocarcinomas enhanced on contrast study in all patients (homogeneous in six, inhomogeneous in 12 with hyperintese enhnacing rim in two). Eight adenocarcinomas had smooth contours and ten had irregular ones. The shape of adenocarcinoma was irregular in eight patients, barrel shape in six, papillary/polypod in three, and nodular in one. All adenocarcinomas involved lower half of the uterine cervix and six tumors extended up to the upper half. Pelvic lymph nodes of more than 1.5cm in diameter in two adenocarcinomas pateints and no detectable small pelvic lymph nodes on MR imaging in one patient were pathologically positive. Hydrometra was associated in two adenocarcinomas patients, and hematometra in one patient. Compared with squamous cell carcinomas, more frequent MR findings of endocervical type and barrel shape in cervical adenocarcinomas were statistically significant. Conclusion : Cervical adenocarcinomas had more frequent MR findings of endocervical type and barrel shape, compared with wquamous cell carcinomas. Adenocarcinoma of the uterine cervix may be suspected on MR imaging, when a cervical carcinoma is of barrel shape along the endocervical canal and tends to involve lymth nodes in earlier stages.

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