Ki-67 labeling index as a prognostic marker in advanced stomach cancer

Sang Hyuk Seo,Kwang Hee Kim,Sang Hoon Oh,Yunseon Choi,Ki Jung Ahn,Ji Young Lee,Sang Min Lee,박지선,Woo Gyeong Kim 대한외과학회 2019 Annals of Surgical Treatment and Research(ASRT) Vol.96 No.1

Purpose: Proliferation marker Ki-67 is widely used in cancer prognosis prediction. We tried to investigate the role of Ki-67 as a prognostic factor in stomach cancer after surgery in this study. Methods: We retrospectively evaluated 251 patients who underwent curative resection for gastric cancer from 2010 to 2015. In pathologic examination, Ki-67 labeling index was defined as the percentage of Ki-67 antigen positive cells. Prognostic significance of Ki-67 for gastric cancer was evaluated. Disease-free survival (DFS) was assessed as a primary end-point. Results: The median follow-up period was 28.0 months. Thirty-one patients (12.4%) showed Ki-67 labeling index (LI) lower than 25%. Sixty-eight patients (26.6%) showed recurrence during follow-up period. Recurrence was associated with Ki- 67 LI level (≤25%, P = 0.016), and lymph node metastasis status (P = 0.002). High Ki-67 LI level (>25%) was also related to p53 positivity (P < 0.001) and poorly cohesive type (P = 0.002). The 3-year DFS was 69.4%. Low Ki-67 LI level (≤25%) was related with low DFS (47.6% vs. 72.6%, P = 0.016). T stage (P < 0.001), N stage (P = 0.006), lymphovascular invasion (P = 0.010), and neuronal invasion (P = 0.001) also affected the DFS. In addition, T stage (P = 0.03) and Ki-67 LI (P = 0.035) were independent prognostic factors for DFS. In patients treated with adjuvant chemotherapy (n = 239, 93.4%), low Ki-67 (≤25%) was a poor prognostic factor for DFS (P = 0.013). Conclusion: Low Ki-67 LI predicts high rate of progression and low DFS of stomach cancer. Ki-67 LI can be a predictive marker in resected stomach cancer treated with surgery and adjuvant chemotherapy.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

Comparison of controlled ovarian stimulation outcomes for fertility preservation in women with breast cancer according to KI-67, histologic grade, pathologic type, and cancer stage

( Eun Ji Oh ),( Yeon Hee Hong ),( Seul Ki Kim ),( Jung Ryeol Lee ),( Byung Chul Jee ),( Chang Suk Suh ),( Seok Hyun Kim ) 대한산부인과학회 2020 대한산부인과학회 학술대회 Vol.106 No.-

Objective: This study aims to analyze that specific prognostic factors such as Ki-67 value, histologic grade, pathology type, and cancer stage can affect controlled ovarian stimulation outcomes(COS) for fertility preservation in women with breast cancer. Methods: This retrospective cohort study included 92 patients with breast cancer aged 21-44 who underwent COS from August 2012 to April 2020, excluding patients with previous gonadotoxic therapy history. All COS cycles were conducted letrozole-combined random start GnRH antagonist protocol. COS outcomes were compared according to prognostic factors;Ki-67 (< 30% vs. ≥ 30%), histologic grade (low vs. high), and pathologic type (intraductal carcinoma(IDC) vs. triple-negative breast cancer(TNBC)), and cancer stage (early (I, II) vs. advanced (III, IV)). Multivariate analysis was also conducted to find any parameter that can impact over 10 mature oocytes acquisition. Results: Among the 92 patients, 42 were Ki-67≥30% compared to 49 of Ki-67<30%. The number of oocytes, and initial mature oocytes were comparable between Ki-67<30% and ≥30 group. The maturation rate was significantly higher in Ki-67≥30% group than Ki-67<30% group (57.4±36.8% vs. 44.8±28.3%, p=0.041). The same results were drawn when divided according to IDC or TNBC. The maturation rate was significantly higher in TNBC than the IDC group (73.0±17.6% vs. 47.0±28.1% p=0.001). However, the histologic grade or stage did not show any difference in COS outcomes between high and low grade or early and advanced stages. With multivariate analysis, age and AMH are parameters associated with the acquisition of over 10 mature oocytes (OR 0.863, 95% CI [0.755-0.987], OR 1.408, 95% CI [1.145-1.732], respectively). Conclusion: Either Ki-67 or pathologic type can be a potential reliable marker for predicting COS outcome, especially maturation rate. Further study with larger sample size with specific conditions is necessary to clarify the correlation between breast cancer prognostic factors and COS outcomes.

특발성 과호산구 증후군 환자의 치료 도중 발생한 간혈종 1례

이영태,김동기,박지훈,김윤정,김기향,박보민,권민정,김애란,이원식,주영돈,손창학 白中央醫療院 2005 仁濟醫學 Vol.26 No.1

Idiopathic hypereosinophilic syndrome is characterized by marked elevation of eosinophil count ( >1,500/㎣) in peripheral blood without explaining etiology. It shows tissue involvement in many organs such as liver, G-I tract, myocar dium, lung, skin, kidney and nerve. Some case of hypereosinophilic syndrome with hepatic involvement have been reported, but not much. We have recently experienced a case with idiopathic hypereosinophilic syndrome of a 40 year old man who presented with RUQ pain. By abdominal CT, ill- defined subcapsular hematoma was detected. Liver biopsy showed eosinophilic infiltration within the portal tract and sinusoid. Drain procedure and corticosteroid adminiiatbrought marked improvement of clinical manifestation, hematologic abnormality and radiologic abnormality.

새로운 연노출의 효과지표로서의 혈장 δ-aminolevulinic acid 측정의 유용성

이금원,황보영,김용배,리갑수,이성수,장봉기,함정오,안규동,이병국 순천향대학교 산업의학연구소 2001 순천향산업의학 Vol.7 No.1

To evaluate the usefulness of the measurement of plasma δ - aminolevulinic acid (ALAP) as a new effect indicator of lead exposure, the association of ALAP with blood lead, DMSA chelatable lead and bone lead with a special emphasis of genetic interaction of ALAD polymorphism was studied with 419 lead exposed workers and 85 non-lead exposed workers. Lead workers were recruited from storage battery industries, secondary smelting industries and other lead using industries and non-lead workers selected from electronic refrigerator manufacturing industry. Blood lead, DMSA chelatable lead and bone lead were chosen for parameters of lead exposure. Plasma and urinary ALA were selected for the effect parameter of lead intoxication. Information for age, smoking, drinking habit and body mass index were also obtained. Job duration for lead workers was also collected. The overall prevalence of the variant allele, ALAD type 1-2 or 2-2(ALAD2) in lead exposed workers was 10.0% (42 out of 419 lead workers) which was not differed from control workers (9.4% : 8 out of 85). The means blood lead and DMSA chelatable lead of lead workers with ALAD 1(ALAD type 1-1) were lower than those of lead workers with ALAD2, but the differences were not statistically significant. On the other hand, the mean of tibia lead of lead workers with ALADI was higher than that of lead workers with ALAD2, but the difference was not statistically significant. DMSA chelatable lead showed highest correlation with log transformed plasma ALA(LALAP)(r=0.682) and blood lead and tibia lead had r=0.650, r=0,402 correlation coefficient with LALAP respectively On the other hand. log transformed urinary ALA(LALAU) had lower correlation coefficient with all three parameters of lead exposure than LALAP. The equation of robustic simple linear regression of blood lead on LALAP was LALAP=2.0439+0.0165PbB in ALADI lead workers and LALAP=2.031+0.0121PbB in ALAD2 lead workers. ALAD genotype in the multiple regression analysis of blood lead with LALAP after adjusting for possible confounders(sex, ago, BMI, smoking and drinking status and job duration) showed significant main effect on LALAP resulting lower LALAP in ALAD2 lead workers than ALADI lead workers. On the other hand, effect modification of ALAD genotype was observed in the multiple regression analysis of tibia lead with LALAP after adjusting for possible confounders, but there was no significant effect of ALAD genotype in the multiple regression analysis of DMSA chelatable lead with LALAP after covariate adjustment. With above results, plasma ALA was found to be a useful effect parameter of lead exposure compared with urinary ALA. It was also observed that ALAD polymorphism made significant effect on the association of blood and tibia lead with ALAP. Thc lower plasma ALA in ALAD2 lead workers suggested supportive effect of ALAD2 in lead exposure.

Toluene, Xylene, Trichloroethylene 투여가 흰쥐의 시상하부와 뇌하수체의 GnRH, GnRH Receptor, Pit-1 유전자 발현에 미치는 영향

기노석,이종태,강대성,김대환,이채관,이헌,전진호,김정호,이채언 大韓産業醫學會 1998 대한직업환경의학회지 Vol.10 No.2

The workplace exposure of chemicals has steadily increased, therefore the concern for subsequent effect on reproductive outcome has been an important issue in occupational medicine. In previous studies, higher rates of spontaneous abortion, reduced fertility and menstrual disorder among women, and an impairement of sperm quantity and quality among men have been associated with a wide variety of chemical agents. This study was conducted to evaluate the effects of toluene, xylene and trichloroethylene(TCE) injection on the mRNA levels of GnRH, GnRH receptor and Pit-1 genes in male rats hypothalamus and pituitary and the effects on the plasma levels of FSH, LH, prolactin and testosterone. Sprague-Dawley male rats were divided into five groups of five each according to concentration of toluene, xylene and TCE. The rats were injected subcutaneously to 0, 50, 100, 200, 400 mg/kg body weight/day of toluene, xylene and TCE, respectively for 6 days. Rat brains were excised and hypothalamus and pituitary were separated. Reverse transcription-polymerase chain reaction (RT-PCR) and RNase protection assay(RPA) were used to evaluate the GnRH, GnRH receptor and Pit-1 mRNA levels. Plasma concentrations of FSH, LH, prolactin and testosterone were assayed by radioimmunoassay(RIA). The results were as follows; 1. GnRH, GnRH receptor and Pit-1 mRNA levels in toluene and xylene injected groups, and GnRH receptor mRNA levels in TCE injected group were lowered dose-dependently. Especially, GnRH receptor and Pit-1 mRNA levels in 200mg/kg of toluene injected group, and GnRH, GnRH receptor and Pit-1 mRNA levels in 400mg/kg of toluene injected group were significantly lower than control group (p<0.05). GnRH receptor and Pit-1 mRNA levels in 400mg/kg of xylene injected group, and GnRH receptor mRNA levels in 400mg/kg of TCE injected group were significantly lower than control group(p<0.05). 2. The plasma levels of prolactin and testosterone in 400mg/kg of toluene injected group, and LH in 100, 200 and 400mg/kg of xylene injected group, and testosterone in 400 mg/kg of TCE injected group were significantly lower than control group(p<0.05). In conclusion, we speculated that toluene and xylene affected reproductive system secondarily through hypothalamus-pituitary axis, and TCE affected directly through steroidogenesis. And we recommended that further study for assessment of the reproductive toxicity of mixed organic solvent exposures should be conducted.

개에서 발생한 수컷 가성 반음양 1례

이기찬,손정민,윤기영,최호정,박성준,이영원,정성목,신상태,조종기 忠南大學校 獸醫科大學 附設 動物醫科學硏究所 2006 動物醫科學硏究誌 Vol.14 No.-

In this report, we present a case of the male pseudohermaphrodite in a beagle dog. The animal was subjected for examination due to enlargement of clitoris that was shown as reddish finger-like structure protruding from the vulva. Visual examination of the internal genitalia revealed that the animal possessed both testes and uterus. Based on the findings of physical examination and exploratory laparotomy, it was tentatively diagnosed as male pseudohermaphrodite. Internal genitalia and enlarged clitoris were removed for the prevention of pyometra and Sertoli cell tumor.

P196 : Effects of different electrical parameter settings on hair growth: the changes of dermal papilla cell in vitro and at microscopic level in animal tissue

( Ki Min Sohn ),( Kwan Ho Jeong ),( Joo Hyun Lee ),( Jung Eun Kim ),( Hoon Kang ) 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: Frequency electrical stimulation is clinically being used in variable skin therapeutic conditions such as skin rejuvenation and hair disorder. There have been several clinical studies demonstrating the positive effect of electrical stimuli on hair regrowth. However, its exact mechanism is yet to be clarified. Objectives: The objective of this study is to investigate effects of different electrical parameter settings on hair growth by revealing the changes of dermal papilla cell in vitro and at microscopic level in animal tissue. Methods: Cultured dermal papilla cells (DPCs) and dorsal skin of rabbit were electrically stimulated with different parameter settings at alternating-current to find the optimal condition for hair growth. Cell viability and proliferation were measured by MTT. In addition, Ki67, proliferation marker, expression was measured by immunofluorescence. Hair growth-related gene expression in DPCs and the skin of rabbit were measured by RT-PCR. Results: At certain electrical settings, DPCs responded well and their proliferation was successfully induced. Wnt/β -catenin, Ki67, p-ERK and p-AKT expressions in DPCs increased at certain frequency settings. Dermal thickness and hair related genes (PDGF, VEGF, SOX9 and KGF) expressions in the skin of rabbit also significantly increased. Conclusion: These data suggest that electrical stimulations at certain electrical settings, may give more effective therapeutic outcomes for hair growth.

Effects of Streptozotocin-Induced Type 1 Diabetes on Cell Proliferation and Neuronal Differentiation in the Dentate Gyrus : Correlation with Memory Impairment

Jung Hoon Choi,In Koo Hwang,Sun Shin Yi,Ki-Yeon Yoo,Choong Hyun Lee,Hyung-Cheul Shin,Yeo Sung Yoon,Moo-Ho Won 대한해부학회 2009 Anatomy & Cell Biology Vol.42 No.1

We examined the effects of steptozotocin (STZ)-induced type 1 diabetes on cell proliferation and neuroblasts in the subgranular zone of the hippocampal dentate gyrus (SZDG) of male Wistar rats. Change in memory function was also investigated using the passive avoidance test. In the SZDG, Ki67 (a marker for cell proliferation) positive nuclei were significantly decreased at 2 and 3 weeks and slightly decreased at 4 weeks after STZ treatment. Doublecortin (DCX, a marker for neuronal differentiation)-immunoreactive (+) neuroblasts with tertiary dendrites were significantly decreased in the STZ-treated group compared to those in the vehicle-treated group. However, DCX+ neuroblasts without tertiary dendrites were abundant at 4 weeks after STZ treatment. In addition, retention latency time in STZ-treated group was similar to that of vehicle-treated group at 2 and 3 weeks after STZ treatment. However, the retention latency time was significantly decreased at 4 weeks after STZ treatment. These results suggest that STZ significantly reduced cell proliferation and neuroblasts at 2~3 weeks after STZ treatment, but not at 4 weeks after STZ treatment although memory impairment was detected at 4 weeks after STZ treatment. The gradual reduction of DCX+ neuroblasts with tertiary dendrites may be associated with the impairment of hippocampus-related memory function.

관상동맥 시술 도중 발생한 좌주간부 관상동맥 박리에 대한 스텐트 삽입 치료의 단장기 임상 결과 : acute and long-term results

이세환,이승환,홍명기,김영학,이철환,한기훈,송종민,강덕현,송재관,김재중,박성욱,박승정 대한내과학회 2004 대한내과학회지 Vol.66 No.6

목적 : 심도자 사용 시술과 관련된 좌주간부 관상동맥박리에 대한 적절한 치료는 아직 확실히 정립되지 않은 상태이다. 이에 본 연구는 좌주간부 관상동맥 박리에 대한 스텐트 삽입술의 단장기 임상결과를 후향적으로 분석하였다. 방법 : 좌주간부 관상동맥 박리에 대한 치료로 즉각적인 스텐트 삽입술을 시행하는 것이 안전하고 효과적인 방법임을 가설하였고, 이러한 즉각적인 스텐트 삽입을 시행한 10명의 환자를 대상으로 단장기적 임상경과를 의무기록 고찰과 전화 면담을 통해서 평가하였다. 결과 : 전체 환자 모두 처음부터 좌주간부 관상동맥에 유의한 협착을 가진 환자는 없었으며, 8명의 환자는 심도자의 조작으로 인한 박리가 발생한 경우였고(진단적 혈관 조영술 중에 3명, 유도 도자 조작 중에 5명), 나머지 2명은 다른 병변에 스텐트 삽입시술을 하는 중에 박리가 발생하였다. 이 10명의 환자에서 모두 즉각적인 스텐트 삽입술이 시행되었고, 4명의 환자에서 시술 도중 혈압 저하로 Intra-aortic Ballon Pump (IABP)를 장착하였다. 모든 환자에서 성공적으로 스텐트가 삽입되었고, 병원내 사망은 1명도 없었다. 6개월 추적 관상동맥 조영술은 8명의 환자에서 시행되었다. 혈관 조영상의 재협착(직경 협착 50% 이상)은 8명 모두에게서 관찰되지 않았으며, 퇴원 후 평균 31±25개월의 추적관찰 결과 주요 심장사건은 1건도 발생하지 않았다. 결론 : 비록 대상 환자가 적은 연구였지만 좌주간부 관상동맥 박리에 대한 스텐트 삽입술은 기술적으로 안전하고 빠르게 시행 할 수 있으며, 훌륭한 단장기적인 치료 효과를 보여준다. Background : The optimal treatment of patients with left main coronary artery (LMCA) dissection during catheter-based procedure remains uncertain. We retrospectively analyzed the acute and long-term results of bail-out stenting for LMCA dissection. Methods : In cases with significant LMCA dissection occurring during catheter-based procedure, prompt stent implantation may be safe and associated with favorable clinical outcome. We evaluated the acute and long-term results of bail-out stenting for LMCA dissection occurring during catheter-bases procedure in 1- patients. Results : Initially, there was significant stenosis of LMCA segment in these patients. Catheter-induced dissection occurred in 8 patients (during diagnostic angiography in 3 patients and guiding catheter manipulation in 5 patients). Two patients suffered dissection in the setting of stent deployment in other vessels. Therefore, bail-out stenting LMCA dissection was performed in a total of 10 patients. In 4 patients, hypotension developed and intra-aortic balloon pump was placed during procedure. Stents were successfully deployed in all patients. There was no in-hospital mortality. Six-month angiographic follow-up was performed in 8 patients. Angiographic restenosis(diameter stenosis 50%) was not observed in all patients at follow-up study. During a mean follow-up of 31±25 months after hospital discharge, there was no major adverse cardiac event (death, myocardial infarction, and target lesion revascularization). Conclusion : Bail-out LMCA stenting is technically feasible, and showed good acute and long-term results in a small series of patients.