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Brown preadipocyte transplantation locally ameliorates obesity

  • Takaya, Kento;Matsuda, Naruhito;Asou, Toru;Kishi, Kazuo
    • Archives of Plastic Surgery
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    • v.48 no.4
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    • pp.440-447
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    • 2021
  • Background Brown adipose tissue (BAT) is a potential target for anti-obesity treatments. Previous studies have shown that BAT activation causes an acute metabolic boost and reduces adiposity. Furthermore, BAT and BAT-derived cell transplantation reportedly help treat obesity by regulating glucose and fatty acid metabolism. However, since BAT transplantation leads to whole-body weight loss, we speculated that earlier approaches cause a generalized and unnecessary fat tissue loss, including in breast and hip tissues. Methods We transplanted white adipose tissue-derived or BAT-derived preadipocytes prepared from C57BL/6 mice into one side of the inguinal fat pads of an obese mouse model (db/db mice) to examine whether it would cause fat loss at the peri-transplant site (n=5 each). The same volume of phosphate-buffered saline was injected as a control on the other side. Six weeks after transplantation, the inguinal fat pad was excised and weighed. We also measured the concentrations of glucose, triglycerides, fatty acids, and total cholesterol in the peripheral blood. Results BAT-derived preadipocytes showed abundant mitochondria and high levels of mitochondrial membrane uncoupling protein 1 expression, both in vivo and in vitro, with a remarkable reduction in weight of the inguinal fat pad after transplantation (0.17±0.12 g, P=0.043). Only free fatty acid levels tended to decrease in the BAT-transplanted group, but the difference was not significant (P=0.11). Conclusions Our results suggest that brown adipocytes drive fat degradation around the transplantation site. Thus, local transplantation of BAT-derived preadipocytes may be useful for treating obesity, as well as in cosmetic treatments.

Clinical application of RapidArc volumetric modulated arc therapy as a component in whole brain radiation therapy for poor prognostic, four or more multiple brain metastases

  • Lee, Seung-Heon;Lee, Kyu-Chan;Choi, Jin-Ho;Kim, Hye-Young;Lee, Seok-Ho;Sung, Ki-Hoon;Kim, Yun-Mi
    • Radiation Oncology Journal
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    • v.30 no.2
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    • pp.53-61
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    • 2012
  • Purpose: To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases. Materials and Methods: Nine patients with multiple (${\geq}4$) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10-12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions. Results: The median biologically effective dose to metastatic tumors was 68.1 $Gy_{10}$ and 67.2 $Gy_{10}$ and the median brain volume irradiated more than 100 $Gy_3$ were 1.9% (24 $cm^3$) and 0.8% (13 $cm^3$) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively. Conclusion: RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application.

Simultaneous Modulated Accelerated Radiation Therapy and Concurrent Weekly Paclitaxel in the Treatment of Locally Advanced Nasopharyngeal Carcinoma

  • Xie, Cong-Ying;Jin, Xian-Ce;Deng, Xia;Xue, Sheng-Liu;Jing, Zhao;Su, Hua-Fang;Wu, Shi-Xiu
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6129-6132
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    • 2012
  • Objectives: To evaluate the feasibility and efficacy of simultaneous accelerated radiation therapy (SMART) and concurrent weekly paclitaxel in the treatment of locally advanced nasopharyngeal carcinoma. Methods: Forty-one patients with pathologically confirmed nasopharyngeal carcinoma were treated by SMART with concurrent weekly paclitaxel. Daily fraction doses of 2.5 Gy and 2.0 Gy were prescribed to the gross tumor volume (GTV) and clinical target volume (CTV) to a total dose of 70 Gy and 56 Gy, respectively. Paclitaxel of $45mg/m^2$ was administered concurrently with radiation therapy every week. Adjuvant chemotherapy was given four weeks after the completion of the radiotherapy (RT) if the tumor demonstrated only a partial response (PR). Results: All patients completed the radiotherapy (RT) course. Adjuvant chemotherapy was administered to 12 patients due to PR. The CR (complete remission) rate was 82.9% three months after RT. Thirty-nine (95.1%) patients completed the concurrent weekly chemotherapy with paclitaxel, and two patients skipped their sixth course. Seven patients had a 15% dosage reduction at the fifth and sixth course due to grade 3 mucositis. The median follow-up was 30 (range, 14-42) months. The three-year overall survival (OS), metastases-free survival (MFS), and local control rates were 77.0%, 64.4%, and 97.6%, respectively. No correlation between survival rate and T or N stage was observed. Grade 3 acute mucositis and xerostomia were present in 17.1% and 7.1%, respectively. Conclusion: SMART with concurrent weekly paclitaxel is a potentially effective and toxicity tolerable approach in the treatment of locally advanced NPC.

Prestack Depth Migration for Gas Hydrate Seismic Data of the East Sea (동해 가스 하이드레이트 탄성파자료의 중합전 심도 구조보정)

  • Jang, Seong-Hyung;Suh, Sang-Yong;Go, Gin-Seok
    • Economic and Environmental Geology
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    • v.39 no.6 s.181
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    • pp.711-717
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    • 2006
  • In order to study gas hydrate, potential future energy resources, Korea Institute of Geoscience and Mineral Resources has conducted seismic reflection survey in the East Sea since 1997. one of evidence for presence of gas hydrate in seismic reflection data is a bottom simulating reflector (BSR). The BSR occurs at the interface between overlaying higher velocity, hydrate-bearing sediment and underlying lower velocity, free gas-bearing sediment. That is often characterized by large reflection coefficient and reflection polarity reverse to that of seafloor reflection. In order to apply depth migration to seismic reflection data. we need high performance computers and a parallelizing technique because of huge data volume and computation. Phase shift plus interpolation (PSPI) is a useful method for migration due to less computing time and computational efficiency. PSPI is intrinsically parallelizing characteristic in the frequency domain. We conducted conventional data processing for the gas hydrate data of the Ease Sea and then applied prestack depth migration using message-passing-interface PSPI (MPI_PSPI) that was parallelized by MPI local-area-multi-computer (MPI_LAM). Velocity model was made using the stack velocities after we had picked horizons on the stack image with in-house processing tool, Geobit. We could find the BSRs on the migrated stack section were about at SP 3555-4162 and two way travel time around 2,950 ms in time domain. In depth domain such BSRs appear at 6-17 km distance and 2.1 km depth from the seafloor. Since energy concentrated subsurface was well imaged we have to choose acquisition parameters suited for transmitting seismic energy to target area.

Surgery Alone and Surgery Plus Postoperative Radiation Therapy for Patients with pT3N0 Non-small Cell Lung Cancer Invading the Chest Wall (흉벽을 침범한 pT3N0 비소세포폐암 환자에서 수술 단독과 수술 후 방사선치료)

  • 박영제;임도훈;김관민;김진국;심영목;안용찬
    • Journal of Chest Surgery
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    • v.37 no.10
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    • pp.845-855
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    • 2004
  • Background: No general consensus has been available regarding the necessity of postoperative radiation therapy (PORT) and its optimal techniques in the patients with chest wall invasion (pT3cw) and node negative (N0) non-small cell lung cancer (NSCLC). We did retrospective analyses on the pT3cwN0 NSCLC patients who received PORT because of presumed inadequate resection margin on surgical findings. And we compared them with the pT3cwN0 NSCLC patients who did not received PORT during the same period. Material and Method: From Aug. of 1994 till June of 2002, 22 pT3cwN0 NSCLC patients received PORT-PORT (+) group- and 16 pT3cwN0 NSCLC patients had no PORT-PORT (-) group. The radiation target volume for PORT (+) group was confined to the tumor bed plus the immediate adjacent tissue only, and no regional lymphatics were included. The prognostic factors for all patients were analyzed and survival rates, failure patterns were compared with two groups. Result: Age, tumor size, depth of chest wall invasion, postoperative mobidities were greater in PORT (-) group than PORT (+) group. In PORT (-) group, four patients who were consulted for PORT did not receive the PORT because of self refusal (3 patients) and delay in the wound repair (1 patient). For all patients, overall survival (OS), disease-free survival (DFS), loco-regional recurrence-free survival (LRFS), and distant metastases-free survival (DMFS) rates at 5 years were 35.3%, 30.3%, 80.9%, 36.3%. In univariate and multivariate analysis, only PORT significantly affect the survival. The 5 year as rates were 43.3% in the PORT (+) group and 25.0% in PORT (-) group (p=0.03). DFS, LRFS, DMFS rates were 36.9%, 84.9%, 43.1 % in PORT (+) group and 18.8%, 79.4%, 21.9% in PORT(-) group respectively. Three patients in PORT (-) group died of intercurrent disease without the evidence of recurrence. Few suffered from acute and late radiation side effects, all of which were RTOG grade 2 or lower. Conclusion: The strategy of adding PORT to surgery to improve the probability not only of local control but also of survival could be justified, considering that local control was the most important component in the successful treatment of pT3cw NSCLC patients, especially when the resection margin was not adequate. Authors were successful in the marked reduction of the incidence as well as the severity of the acute and late side effects of PORT, without taking too high risk of the regional failures by eliminating the regional lymphatics from the radiation target volume.

Radiation Dose-escalation Trial for Glioblastomas with 3D-conformal Radiotherapy (3차원 입체조형치료에 의한 아교모세포종의 방사선 선량증가 연구)

  • Cho, Jae-Ho;Lee, Chang-Geol;Kim, Kyoung-Ju;Bak, Jin-Ho;Lee, Se-Byeoung;Cho, Sam-Ju;Shim, Su-Jung;Yoon, Dok-Hyun;Chang, Jong-Hee;Kim, Tae-Gon;Kim, Dong-Suk;Suh, Chang-Ok
    • Radiation Oncology Journal
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    • v.22 no.4
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    • pp.237-246
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    • 2004
  • Purpose: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). Materials and Methods: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received $63\~70$ Gy (Median 66 Gy, fraction size $1.8\~2$ Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. Results: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were $15{\pm}1.65$ and $11{\pm}0.95$ months, respectively. The was a significantly longer survival time for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were $21{\pm}5.03$ and $12{\pm}1.59$ months, respectively, while for Arm 2 patients they were $14{\pm}0.94$ and $10{\pm}1.63$ months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; $44.7\%$ versus $19.2\%$. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. Conclusion: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.

A Study to activate and evaluate competitive advantage on Free Trade Zone of Busan Port (부산항 관세자유지역의 경쟁력 평가 및 활성화 방안에 관한 연구)

  • Hur, Y.S.;Chung, T.W.
    • Journal of Navigation and Port Research
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    • v.28 no.1
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    • pp.59-67
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    • 2004
  • As the environment for international logistics varies according to the globalization in world economy, world-class seaports are struggling for the position as strongholds in their own block. As a new government begins its own era in Korea, they are positively implementing their strategies at the level of government for making the Korean Peninsula the logistics centre in North-eastern Asia, marking the most of its geographic advantage. As one of those strategies, it plans to foster a specific area as an international logistics base camp in Northeast Asia by activating its logistics industry through inducing multinational logistics enterprises. In reality, however, in order for Busan seaport, the late-comer, to induce investment from the world-class multinational companies, a considerably large volume of investment should be given from both central and local governments. Accordingly, the objective of this study is to assess its competitiveness and to suggest an activation plan for BSDFA(Busan Seaport Duty-Free Area), based upon the results of on-the-spot interviews in China and Japan. The survey for the respondent's preference by way of Conjoint Analysis indicated that Investment procedures and limitations get the highest 36.2% preference, so the most critical strategy to be considered for attracting enterprises into DFA(Duty-Free Area) is to solve the problems related to the investment procedures and limitations. The simulation analysis results for market share showed that UAE has the highest preference and BSDFA the lowest preference among the five countries. However, when the levels of investment procedures and limitations and production costare upgraded, the competitiveness of BSDFA was elevated next to that of UAE among the 5 countries. Thus, in order for BSDFA to obtain competitiveness, it is implied that production cost level as well as investment procedures and limitations level, should be lowered so that it could meet companies' demand.

Radiation Therapy of Intracranial Germinomas : Optimum Radiation Dose and Treatment Volume (두개내 배아종의 방사선치료:적정 방사선량 및 치료용적)

  • Chang, Sei-Kyung;Suh, Chang-Ok;Kim, Gwi-Eon
    • Radiation Oncology Journal
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    • v.17 no.4
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    • pp.269-274
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    • 1999
  • Purpose : To evaluate the Possibility of decreasing the radiation dose and to determine optimum treatment volume in intracranial germinomas. Materials and Methods : Forty five patients with pathologically-verified or presumed germinomas by a radiosensitivity test who had been treated with radiotherapy (RT) alone between 1971 and 1992 were retrospectively analyzed. The average age was 17.2 years with 68.9$\%$ of the patients being between the ages of 10$\~$20. The male and female ratio was 2.2:1. The locations of the primary tumors were at the pineal regions in 14 patients; the suprasellar regions in 12 patients; and multiple sites in 12 patients. Treatment volumes varied from a small local field (10) to the whole brain (7) or entire neuroaxis irradiation(28). All the cases after 1982 received craniospinal irradiation (CSI). Radiation doses were 41-59 Gy (median 48.5 Gy) to the primary tumor site and 19.5$\~$36 Gy (median 24 Gy) to the neuroaxis. The median follow-up period was 82 months with a range of 2$\~$260 months. Results : All the patients showed complete response after RT. Four patients sufferred from recurrence 14, 65, 76, and 170 months after RT, respectively, and two patients died with intercurrent disease. One of four recurrent cases was salvaged by re-irradiation. Therefore, a 5 and 10 year overall suNival was 95.3$\%$ and 84.7 $\%$ respectively. Five and ten year disease-free survival was 97.6 $\%$ and 88.8 $\%$ respectively. All the recurrences occurred in the patients who received local RT (3/10) or whole brain RT (1/7) with a radiation dose of 48-50 Gy. None of the patients who received CSI suffered recurrence. There was no recurrence among the 15 patients who received $\leq$45 Gy to the primary site and the 18 patients who received $\leq$24 Gy (6 patients received 19.5 Gy) to the neuroaxis. Conclusion : CSI is recommended for the treatment of intracranial germinomas. The radiation dose can be safely decreased to $\leq$45 Gy on a primay tumor site and 19.5 Gy on the spine.

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Effects of Fractionated Stereotactic Radiotherapy for Primary Hepatocellular Carcinoma (원발성 간암의 분할 정위방사선치료 효과)

  • Choi Byeong Ock;Kang Ki Mun;Jang Hong Seok;Lee Snag-wook;Kang Young Nam;Chai Gyu Young;Choi Ihl Bhong
    • Radiation Oncology Journal
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    • v.23 no.2
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    • pp.92-97
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    • 2005
  • Purpose : Reports on the outcome of curative radiotherapy for the primary hepatocellular carcinoma (HCC) are rarely encountered in the literature. in this study, we report our experience of a clinical trial where fractionated stereotactic radiotherapy (SRT) was used in treating a primary HCC. Materials and Methods : A retrospective analysis was peformed on 20 patients who had been histologically diagnosed as HCC and treated by fractionated SRT. The long diameter of tumor measured by CT was $2\~6.5$ cm (average: 3.8 cm). A single dose of radiation used in fractionated SRT was S or 10 Gy: each dose was prescribed based on the planning target volume and normalized to $85\~99\%$ isocenter dose. Patients were treated $3\~5$ times per week for 2 weeks, with each receiving a total dose of 50 Gy (the median dose: 50 Gy). The follow up period was $\~55$ months (the median follow up period: 23 months). Results : The response rate was $50\%$ (12 patients), with 4 patients showing complete response ($20%$), 8 patients showing partial response ($40\%$), and 8 patients showing stable disease ($40\%$). The 1-year and 2-year survival rates were $70.0\%$ and $43.1\%$, respectively, and the median survival time was 20 months. The 1-year and 2-year disease free survival rates were $65\%$ and $32.5\%$, respectively, and the median disease-free survival rate was 19 months. Some acute complications of the treatment were noted as follows: dyspepsia in 12 patients ($60\%$), nausea/emesis in 8 patients ($40\%$), and transient liver function impairment in 6 patients ($30\%$). However, there was no treatment related death. Conclusion : The study indicates that fractionated SRT is a relatively safe and effective method for treating primary HCC. Thus, fractionated SRT may be suggested as a local treatment for HCC of small lesion and containing a single lesion, when the patients are inoperable or operation is refused by the patients. We thought that fractionated SRT is a challenging treatment modality for the HCC.

The Outcome of Postoperative Radiation Therapy for Patients with Stage II Pancreatic Cancer (T3 or N1 Disease) (2기(T3 또는 N1) 췌장암 환자들의 수술 후 방사선치료의 성적 및 고찰)

  • Kim, Sang-Won;Kim, Myung-Wook;Kim, Wook-Hwan;Kang, Seok-Yun;Kang, Seung-Hee;Oh, Young-Taek;Lee, Sun-Young;Yang, Ju-No;Chun, Mi-Sun
    • Radiation Oncology Journal
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    • v.25 no.4
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    • pp.213-218
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    • 2007
  • Purpose: To analyze retrospectively the outcome of postoperative radiation therapy with or without concurrent chemotherapy for curatively resected stage II pancreatic cancer with T3 or N1 disease. Materials and Methods: Between January 1996 and December 2005, twenty-eight patients completed adjuvant radiation therapy at Ajou University Hospital. The patients had either pathologic T3 stage or N1 stage. The radiation target volume encompassed the initial tumor bed identified preoperatively, resection margin area and celiac nodal area. In the case of N1 patients, the radiation field extended to the lower margin of the L3 vertebra for covering both para-aortic lymph nodes bearing area. The median total radiation dose was 50 Gy. Ten patients received concurrent chemotherapy. Results: Thirteen patients (46%) showed loco-regional recurrences. The celiac axis nodal area was the most frequent site (4 patients). Five patients showed both loco-regional recurrence and a distant metastasis. Patients with positive lymph nodes had a relatively high probability of a distant metastasis (57.1%). Patients that had a positive resection margin showed a relatively high local failure rate (57.1%). The median disease-free survival period of all patients was 6 months and the 1-and 2-year disease free survival rates were 27.4% and 8.2%, respectively. The median overall survival period was 9 months. The 2-and 3-year overall survival rates were 31.6% and 15.8%, respectively. Conclusion: The pancreatic cancer patients with stage II had a high risk of local failure and a high risk of a distant metastasis. We suggest the concurrent use of an effective radiation-sensitizing chemotherapeutic drug and adjuvant chemotherapy after postoperative radiation therapy for the treatment of patients with stage II pancreatic cancer.