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R-(-)-TNPA, a Dopaminergic $D_2$ Receptor Agonist, Inhibits Catecholamine Release from the Rat Adrenal Medulla

  • Hong, Soon-Pyo;Seo, Hong-Joo;Lim, Dong-Yoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.5
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    • pp.273-282
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    • 2006
  • The aim of the present study was to investigate the effects of R-(-)-2,10,11-trihydroxy-N-propylnoraporphine [R-(-)-TNPA], a selective agonist of dopaminergic $D_2$ receptor and S(-)-raclopride, a selective antagonist of dopaminergic $D_2$ receptor, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused model of the rat adrenal gland, and also to establish its mechanism of action. R-(-)-TNPA $(10{\sim}100\;{\mu}M)$ perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100\;{\mu}M)$ and McN-A-343 $(100\;{\mu}M)$. R-(-)-TNPA itself did also fail to affect basal CA output. Also, in adrenal glands loaded with R-(-)-TNPA $(30\;{\mu}M)$, the CA secretory responses evoked by Bay-K-8644 $(10\;{\mu}M)$, an activator of L-type $Ca^2+$ channels and cyclopiazonic acid $(10\;{\mu}M)$, an inhibitor of cytoplasmic $Ca^{2+}-ATPase$ were also inhibited. However, S(-)-raclopride $(1{\sim}10\;{\mu}M)$, given into an adrenal vein for 60 min, enhanced the CA secretory responses evoked by ACh, high $K^+$, DMPP and McN-A-343 only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, S(-)-raclopride $(3.0\;{\mu}M)$ in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644 and cyclopiazonic acid only for the first period (4 min). However, after simultaneous perfusion of R-(-)-TNP A $(30\;{\mu}M)$ and S(-)-raclopride $(3.0\;{\mu}M)$, the inhibitory responses of R(-)-TNPA $(30\;{\mu}M)$ on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Taken together, these experimental results suggest that R-(-)-TNPA greatly inhibits the CA secretion from the perfused rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization, but S(-)-raclopride rather enhances the CA release by them. It seems that this inhibitory of R-(-)-TNPA may be mediated by stimulation of inhibitory dopaminergic $D_2$ receptors located on the rat adrenomedullary chromaffin cells, while the facilitatory effect of S(-)-raclopride is due to the blockade of dopaminergic $D_2$ receptors, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that dopaminergic $D_2$ receptors may be involved in regulation of CA release in the rat adrenal medulla.

c-fos mRNA Expression in the Vestibular System following Hypergravity Stimulation in Rats

  • Jin Guang-Shi;Lee Jae-Hyo;Lee Jae-Hee;Lee Moon-Young;Kim Min-Sun;Jin Yuan Zhe;Song Jeong-Hoon;Park Byung-Rim
    • The Korean Journal of Physiology and Pharmacology
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    • v.11 no.1
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    • pp.1-7
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    • 2007
  • Altered environmental gravity, including both hypo- and hypergravity, may result in space adaptation syndrome. To explore the characteristics of this adaptive plasticity, the expression of immediate early gene c-fos mRNA in the vestibular related tissues following an exposure to hypergravity stimulus was determined in rats. The animals were subjected to a force of 2 g (twice earth's gravity) for 1, 3, or 12 h, and were examined poststimulus at 0, 2, 6, 12, and 24 h. RT-PCR (reverse transcription polymerase chain reaction) and real-time quantitative RT-PCR were adopted to analyze temporal changes in the expression of c-fos mRNA. The hypergravity stimulus increased the expression of c-fos mRNA in the vestibular ganglion, medial vestibular nucleus, inferior vestibular nucleus, hippocampus, cerebellum, and cortex. The peak expression occurred at 0 h poststimulation in animals stimulated with hypergravity for 1 h, and at 6 h poststimulus in those stimulated for 3 h. In contrast, those stimulated for 12 h exhibited dual peaks at 0 and 12 h poststimulus. Bilateral labyrinthectomy markedly attenuated the degree of c-fos mRNA expression. Glutamate receptor antagonist also dramatically attenuated the degree of c-fos mRNA expression. These results indicate that expression of c-fos mRNA in response to hypergravity occurs in the vestibular related tissues of the central nervous system, in which peripheral vestibular receptors and glutamate receptors play an important role. The temporal pattern of c-fos mRNA expression depended on the duration of the hypergravity stimulus.

Dosimetric advantages and clinical outcomes of simultaneous integrated boost intensity-modulated radiotherapy for anal squamous cell carcinoma

  • Sakanaka, Katsuyuki;Itasaka, Satoshi;Ishida, Yuichi;Fujii, Kota;Horimatsu, Takahiro;Mizowaki, Takashi;Sakai, Yoshiharu;Hiraoka, Masahiro
    • Radiation Oncology Journal
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    • v.35 no.4
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    • pp.368-379
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    • 2017
  • Purpose: The purpose of this study was to explore the dosimetric difference between simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and three-dimensional conformal radiotherapy (3DCRT), and the clinical outcomes of anal squamous cell carcinoma (ASCC) chemoradiotherapy featuring SIB-IMRT. Materials and Methods: This study included ten patients with ASCC who underwent chemoradiotherapy using SIB-IMRT with 5-fluorouracil and mitomycin C. SIB-IMRT delivered 54 Gy to each primary tumor plus metastatic lymph nodes and 45 Gy to regional lymph nodes, in 30 fractions. Four patients received additional boosts to the primary tumors and metastatic lymph nodes; the median total dose was 54 Gy (range, 54 to 60 Gy). We additionally created 3DCRT plans following the Radiation Therapy Oncology Group 9811 protocol to allow dosimetric comparisons with SIB-IMRT. Locoregional control, overall survival, and toxicity were calculated for the clinical outcome evaluation. Results: Compared to 3DCRT, SIB-IMRT significantly reduced doses to the external genitalia, bladder, and intestine, delivering the doses to target and elective nodal region. At a median follow-up time of 46 months, 3-year locoregional control and overall survival rates were 88.9% and 100%, respectively. Acute toxicities were treated conservatively. All patients completed radiotherapy with brief interruptions (range, 0 to 2 days). No patient experienced ${\geq}grade$ 3 late toxicity during the follow-up period. Conclusion: The dosimetric advantages of SIB-IMRT appeared to reduce the toxicity of chemoradiotherapy for ASCC achieving high locoregional control in the extended period.

Stabilization of Short Juxta-articular Fractures Using a Circular External Skeletal Fixator System in Dogs (개에서 원형외고정장치를 이용한 관절주위 골절의 안정화)

  • Cheong, Hye-Yeon;Kim, Joo-Ho;Cha, Jae-Gwan;Seol, Jae-Won;Kim, Min-Su;Lee, Hae-Beom
    • Journal of Veterinary Clinics
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    • v.31 no.6
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    • pp.523-526
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    • 2014
  • Three dogs were admitted for repair of bone fracture. Case 1 (Maltese, 1.8 kg, intact female, 5-month-old) and case 2 (poodle, 3.0 kg, intact female, 6-month-old) had non-weight bearing lameness in the left pelvic limb, and case 3 (mixed, 3.3 kg, intact female, age unknown) had non-weight-bearing lameness in the left thoracic limb. On orthopedic examination, there was pain, crepitus, palpable instability and substantial soft tissue swelling on the affected side. No neurological deficits were identified. Radiographs revealed left proximal metaphyseal tibial and fibular fractures in cases 1 and 2, and left proximal metaphyseal radial and ulnar fractures in case 3. All cases had closed long-bone fractures with short juxta-articular fracture segments. Under fluoroscopic guidance, proper placement of the ring fixation elements was confirmed during surgery. Two or three rings were used to stabilize fractures with traditional circular external skeletal fixators (CESF). Postoperative radiographs showed acceptable alignment and apposition of the previously identified fracture. Time to radiographic union ranged from 5 to 14 weeks and there were no signs of implant failure or pin tract infection. Functional outcomes were excellent in all cases. CESF can be successfully used to reduce short juxta-articular fractures in which bone plates or external skeletal fixation cannot be applied.

Treatment Result and Prognostic Factors in Pateints with Esophageal Cancer (식도암의 근치적 치료성적 및 예후인자)

  • Chung, Weon-Kuu;Kim, Soo-Kon;Kim, Min-Chul;Jang, Myoung;Moon, Sun-Rock
    • Radiation Oncology Journal
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    • v.13 no.3
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    • pp.233-241
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    • 1995
  • Purpose : To analyse clinical outcome and prognostic factors according to treatment modality, this paper report our experience of retrospective study of patients with esophageal cancer Materials and Methods : One hundred and ten patients with primary esophageal cancer who were treated in Presbyterian Medical Center from May 1985 to December 1992. We analysed these patients retrospectively with median follow up time of 28 months, one hundred and four patients($95{\%}$) were followed up from 15 to 69 months. In methods, twenty-eight patients were treated with median radiation dose irradiated 54.3Gy only. Fifty-six patients were treated with combined chemoradiotherapy. Sixteen cases of these patients were treated with concurrent chemoradiation and the other patients(forty cases) were treated sequential chemoradiotherapy. In concurrent chemoradiotherapy group, patients received 5-FU continuous IV infusion for 4 days. Cisplatin IV bolus. and concurrent esophageal irradiation to 30 Gy. After that patients received 5-FU continuous IV, Cisplatin bolus injection and Mitomycin-C bolus IV, Bleomycin continuous IV, and irradiation to 20 Gy. In sequential chemoradiotherapy group, the chemotherapy consisted of 5-FU 1,000mg/$m^2$ administered as a continuous 24 hour intravenous infusion during five days and Cisplatin 80-100mg/$m^2$ bolus injected, or Bleomycin, Vinblastine, Cisplatin, Methotrexate were used of 1 or 2 cycles. After preoperative concurrentm chemoradiation twenty-six patients underwent radical esophagectomy. Results : Ninety-three patients could be examined for response assessment, By treatment modality, response rates were $85.1{\%}$ for radiation alone group and $86.3{\%}$ for combined chemoradiation group. But in operation group, after one cycle of concurrent chemoradiation treatment, response rate was $61.9{\%}$. The pathologic complete response were $15.4{\%}$ in operation group. Overall median survival was II months and actuarial 5-year survival rate was $8{\%}$. The median survival interval was 6 months for radiation alone group, 11 months for combined chemoradiation group and 19 months for operation group. And also median survival was 19 months for complete responder group that 8 months for noncomplete responder group. In univariative analysis, statistically significant prognostic factors were tumor size, clinical stage, tumor response, and operation. In multivariative analysis, significantly better survival was associated with clinical stage, tumor response, radiation dose, and operation. Conclusion : Compared with radiotherapy alone, combined multimodality may improve the median survival in patients with localized carcinoma of the esophagus and toxicity is acceptable.

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Slit Ventricle Syndrome in Children : Clinical Presentation and Treatment (소아에서 틈새뇌실 증후군 : 임상 양상 및 치료)

  • Shin, Beom-Sik;Yang, Kook-Hee;Kim, Dong-Seok;Choi, Joong-Uhn
    • Journal of Korean Neurosurgical Society
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    • v.30 no.sup2
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    • pp.309-315
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    • 2001
  • The term slit ventricle syndrome(SVS) refers to an episodic occurrence of headache, vomiting, and possibly some degree of impaired consciousness in shunted hydrocephalic children in whom slit-like ventricles are seen on CT scan or MRI. Authors present 6 cases with SVS who were treated at our institute for last 10 years. From 1986 to 1996, 821 patients underwent shunt surgery for hydrocephalus. The etiology of hydrocephalus included brain tumor(140 patients), post-hemorrhagic(62 patients), idiopathic normotensive hydrocephalus(64 patients), post-meningitic( 58 patients), post-traumatic(54 patients), congenital(48 patients), neurocysticercosis(31 patients), and unknown etiology(364 patients). During the mean follow-up duration of 68 months, 232 shunt revisions were performed by a revision rate of 1.28 per patient. The incidence of SVS was 0.7%(6 patients). Most of them have been operated on in infancy. Time interval from the first operation to the development of slit-ventricle syndrome ranged from 4 to 8 years, the mean was 6 years. Shuntogram showed patent shunt in all patients. Two patients with less severe clinical symptoms improved with conservative treatment. These patients were not measured ICP because of good hospital course. One patient showed high ICP and needed only revision with same pressure valve as previous shunt. Low ICP was noted in 3 patients. Pressure augmentation using an anti-siphon device(ASD) or upgrading valve system were necessary in these patients. The authors stress that determining type of SVS is the first step in treatment planning and that the best treatment is a strategy aimed at resolving the specific type of SVS responsible for the symptoms.

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Relationship Between Death Orientation of First Care Giver and Quality of Life of Hospice Patients (호스피스환자 주 수발자의 죽음에 대한 인식과 호스피스 환자의 삶과 질과의 관계)

  • Choe, Yeong-Sun
    • Korean Journal of Hospice Care
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    • v.6 no.2
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    • pp.55-68
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    • 2006
  • In Korea, there are constantly increasing number of cancer patients with reaching 65,000 deaths and it was 26.3% of the total number of death in 2004. Many cancer patients suffer from surgery, chemotherapy, and radiotherapy after being diagnosed as cancer. And many of them are facing fear of death because they can't be perfectly cured. Due to patients' physical, psychological, and spiritual pain, quality of life drops dramatically. Patients' families also suffer from huge medical expenses while they have to take care of patients's suffering from pain. At the same time, family's attitude can influence on the quality of patients' life. The purpose of this study is to investigate the relationship between the death orientation of first care giver and the quality of life of hospice patient. The subjects of the study were 80 hospice patients registered at ten hospice institutions with hospice team and medical practitioners in six cities including Seoul as well as their first care givers. This study used 13 questions for the hospice patients and nine questions for the first care givers to recognize general characteristic. To measure death orientation of the first care giver the tool developed by Noh, Soon-hee (2003) was used. And to measure quality of life of the hospice patients Yoo, Seung-yeon's structured tool was used. The data were collected for a month through interview method. SPSS win 12.0 was used to analyze the data by using frequency, percentage, t-test, Pearson correlation. The study result is as follows. In relationship between general characteristic of hospice patient and quality of life, the highest suffering was pain (60%) and the second suffering was anorexia (23.8%). There was no significant relationship between physical pain and general characteristics of hospice patient. In psychological aspects, religion (p=.044) showed significant difference (p<.05). In existential aspects, age (p=.035) showed significant difference (p<.05). There was no significant difference variable in support aspects. And religion (p=.000) was statistically significant variable in spiritual aspects (p<.001). Age (p=0.025) and religion (p=.050) were the variable showed significant difference according to general characteristics of first care giver's death orientation. Although the relation between death orientation of first care giver and quality of life of hospice patient was not statistically significant correlation. In conclusion, while death orientation of first care giver and hospice patient's quality of life are not statistically significant in correlation analysis.

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The Evaluation of Therapeutic Control with Warfarin in Patients with Mechanical Heart Valve Prostheses (인공심장판막 환자를 대상으로 한 Warfarin 치료의 적정성 평가)

  • Im, Young Sun;Chang, Byung Chul;Suh, Ok Kyung;Lee, Suk Hyang;Shin, Hyun Taek
    • Korean Journal of Clinical Pharmacy
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    • v.9 no.1
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    • pp.27-34
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    • 1999
  • The goal of oral anticoagulation therapy with warfarin is to maintain INR values within the therapeutic range in order to prevent complications such as bleeding and thrombosis. The purposes of this study were to investigate the current level of anticoagulation control using INR values, to investigate the incidences of thromboembolism and bleeding complications, and to compare the effect of low intensity INR regimen with therapeutic range recommended by ACCP (American College of Chest Physician). Two hundred three patients with mechanical heart valve replacement done at Yonsei University Cardiovascular Center between January 1994 and December 1996 were selected and reviewed retrospectively. The target INR ranges of $2.5\sim3.5$ (ACCP standard) and low intensity INR of $2.0\sim3.5$ were used for evaluation. According to ACCP standard, $51.2\%$ of patients and $31.1\%$ of INR values were within the therapeutic range when average INR and cumulative INR were used, respectively. Applying low intensity INR values of $2.0\sim3.5$, the therapeutic control was achieved in $57.4\%\;and\;90.1\%$, using average INR and total INR, respectively. The incidences of major and minor bleedings were $0.5\%\;and\;26.6\%$, respectively. The incidence of thromboembolism was $0.5\%$. There was no significant difference in terms of complication incidences between INR $2.0\sim2.5\;and\;INR\;2.5\sim3.5$ groups. However, INR values at the time of bleeding were generally high. In conclusion, the evaluation of patients with mechanical heart valve replacement showed low level of therapeutic control with warfarin therapy. This is partially explained by the fact that the physicians at Yonsei University Cardiovascular Center were using lower intensity INR values as a goal than recommended INR. Also, in the near future, systematic anticoagulation service should be implemented at various hospitals in Korea so that patients on anticoagulant therapy can be more closely monitored to be within the recommended INR by ACCP.

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Refractive Error Induced by Combined Phacotrabeculectomy (섬유주절제술과 백내장 병합수술 후 굴절력 오차의 분석)

  • Lee, Jun Seok;Lee, Chong Eun;Park, Ji Hae;Seo, Sam;Lee, Kyoo Won
    • Journal of The Korean Ophthalmological Society
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    • v.59 no.12
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    • pp.1173-1180
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    • 2018
  • Purpose: We evaluated the postoperative accuracy of intraocular lens power prediction for patients undergoing phacotrabeculectomy and identified preoperative factors associated with refractive outcome in those with primary open-angle glaucoma (POAG). Methods: We retrospectively reviewed the medical records of 27 patients who underwent phacotrabeculectomy to treat POAG. We recorded all discrepancies between predicted and actual postoperative refractions. We compared the data to those of an age- and sex-matched control group that underwent uncomplicated cataract surgery during the same time period. Preoperative factors associated with the mean absolute error (MAE) were identified via multivariate regression analyses. Results: The mean refractive error of the 27 eyes that underwent phacotrabeculectomy was comparable to that of the 27 eyes treated via phacoemulsification (+0.02 vs. -0.01 D, p = 0.802). The phacotrabeculectomy group exhibited a significantly higher MAE (0.65 vs. 0.35 D, p = 0.035) and more postoperative astigmatism (-1.07 vs. -0.66 D, p = 0.020) than the phacoemulsification group. The preoperative anterior chamber depth (ACD) and the changes in the postoperative intraocular pressure (IOP) were significantly associated with a greater MAE after phacotrabeculectomy. Conclusions: POAG treatment via combined phacoemulsification/trabeculectomy was associated with greater error in terms of final refraction prediction, and more postoperative astigmatism. As both a shallow preoperative ACD and a greater postoperative change in IOP appear to increase the predictive error, these two factors should be considered when planning phacotrabeculectomy.

Partial versus Radical Nephrectomy for T1-T2 Renal Cell Carcinoma in Patients with Chronic Kidney Disease Stage III: a Multiinstitutional Analysis of Kidney Function and Survival Rate

  • Chung, Jae-Seung;Son, Nak Hoon;Lee, Sang Eun;Hong, Sung Kyu;Jeong, Chang Wook;Kwak, Cheol;Kim, Hyeon Hoe;Hong, Sung Hoo;Kim, Yong June;Kang, Seok Ho;Chung, Jinsoo;Kwon, Tae Gyun;Hwang, Eu Chang;Byun, Seok-Soo
    • Journal of Korean Medical Science
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    • v.33 no.43
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    • pp.277.1-277.10
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    • 2018
  • Background: To examine survival rates and renal function after partial nephrectomy (PN) and radical nephrectomy (RN) in patients with chronic kidney disease (CKD). Methods: We studied 4,332 patients who underwent PN or RN for pathological T1a-T2N0M0 renal cell carcinoma from 1988 to 2014. Patients were divided into two subgroups of CKD stage I-II and stage III. Kidney function, and survival outcomes were compared between groups. Results: We included 1,756 patients with CKD I-II and 276 patients with CKD III in the final pair-matched analysis. Kidney function was significantly better preserved in the PN than in the RN group among all patients. However, the beneficial effect of PN on kidney function gradually disappeared over time in CKD III patients. The 5-year overall survival (OS) rates after PN and RN differed in patients with CKD I-II disease (99.4% vs. 96.5%, respectively, P = 0.015). The 5-year OS rates after surgery were not affected by mode of nephrectomy in CKD III patients (97.8% vs. 93.5%, P = 0.103). The 5-year cancer-specific survival rates did not differ between treatment groups in all CKD stage. Cox hazard analysis showed that the operative method was a significant factor for OS in CKD I-II patients (hazard ratio [HR], 0.320; confidence interval [CI], 0.122-0.840; P = 0.021). However, PN was not beneficial in terms of OS in CKD III patients (HR, 0.395; CI, 0.086-1.172; P = 0.117). Conclusion: PN is associated with a higher OS rate and better kidney function in patients with preoperative CKD stage I and II, but not in those with CKD stage III.