Clinical pharmacologic aspects of immune checkpoint inhibitors in cancer therapy

김규표,정헌 대한임상약리학회 2016 Translational and Clinical Pharmacology Vol.24 No.1

During the past two years, three immune checkpoint inhibitors, ipilimumab, nivolumab and pembrolizumab, have been approved and revolutionized cancer immunotherapy. Translational and clinical pharmacology of these agents have contributed in identifying patients who will receive benefit, dose effect relationship and surrogate endpoints of clinical benefit. In addition, population pharmacokinetics/pharmacodynamics have facilitated scientific clinical development, which has led to accelerated approval of these agents. This paradigm may show how early phase studies may allow identification of subgroup of patients who can benefit and subsequent approval of drugs based on smaller patient population. This may speed the access of effective treatment for patients with life-threatening diseases.

Paired Primary and Metastatic Tumor Analysis of Somatic Mutations in Synchronous and Metachronous Colorectal Cancer

김규표,김정은,홍용상,안성민,천성민,홍승모,장세진,유창식,김진천,김태원 대한암학회 2017 Cancer Research and Treatment Vol.49 No.1

Purpose Although the mutation status of KRAS is highly concordant in primary and metastatic lesions, it has not been generalized to other major pathway genes. Materials and Methods In this study, 41 genes were evaluated and the mutational profiles were compared in 46 colorectal cancer patients with paired surgical specimens of primary and metastatic lesions: synchronous (n=27) and metachronous (n=19) lesions. A high-throughput mass spectrometry- based genotyping platform validated by orthogonal chemistry, OncoMap v.4.4, was used to evaluate the formalin-fixed, paraffin-embedded surgical specimens. The patients’ demographics, tumor characteristics, and microsatellite instability status were analyzed by a retrospective chart review. Results In this study, with OncoMap, mutations were identified in 80.4% of patients with the following frequency: KRAS (39.1%), TP53 (28.3%), APC (28.3%), PIK3CA (6.5%), BRAF (6.5%), and NRAS (4.3%). Although 19.6% (9/46) of the patients showed no gene mutations, 43.5% (20/46) and 37.0% (17/46) had mutations in one and two or more genes, respectively. The synchronous and metachronous lesions showed similar mutational profiles. Paired samples between primary and metastatic tumors differed in 7.4% (2/27) and 10.5% (2/19) for synchronous and metachronous according to OncoMap. Conclusion These findings indicate the major pathway genes, including KRAS, TP53, APC, PIK3CA, BRAF, and NRAS, are often concordant between the primary and metastatic lesions regardless of the temporal relationship of metastasis.

Oncology

김규표 대한종양외과학회 2013 대한임상종양학회 학술대회지 Vol.2013 No.10

자가면역성 만성 췌장염 17예의 임상상

김규표 ( Kim Gyu Pyo ),김명환 ( Kim Myeong Hwan ),이윤정 ( Lee Yun Jeong ),송문희 ( Song Mun Hui ),박도현 ( Park Do Hyeon ),이상수 ( Lee Sang Su ),서동완 ( Seo Dong Wan ),이성구 ( Lee Seong Gu ),민영일 ( Min Yeong Il ),송동은 ( So 대한소화기학회 2004 대한소화기학회지 Vol.43 No.2

Background/Aims: Autoimmune pancreatitis is a distinctive type of chronic pancreatitis with reversibility. We analyzed the largest number of patients with autoimmune pancreatitis among the studies carried out at a single institution in Korea. Methods: We retrospectively analyzed the clinical, radiologic, laboratory and histologic features in 17 patients who were diagnosed as autoimmune pancreatitis. Results: The patients were predominately elderly men who presented with jaundice or nonspecific gastrointestinal symptoms. In most of the patients, serum pancreatic enzymes were normal or mildly elevated with an accompanying cholestatic biochemical profile. Elevated IgG levels and detection of autoantibodies were observed in 47% (8/17) and 35% (6/17), respectively. Thirteen patients showed histologic findings of lymphoplasmacytic infiltration and fibrosis, and one patient showed predominant infiltration of eosinophils. Fifteen patients revealed radiologic images of diffuse swelling of pancreas and the sclerosing pattern on direct pancreatogram. All of the features improved in response to oral steroid therapy. Two cases showed focal narrowing with upstream duct dilatation and thus, they were diagnosed as focal type. Diabetes mellitus concurred in 13 cases and primary sclerosing cholangitis and Sjoren`s syndrome were present in 1 case, respectively. Conclusions: The recognition of autoimmune pancreatitis allows patients to avoid unnecessary surgery and recover with the administration of oral steroid. (Korean J Gastroenterol 2004; 43:112-119)

진료현장에서 정밀의료의 적용

김규표 ( Kyu-pyo Kim ) 대한내과학회 2020 대한내과학회지 Vol.95 No.6

Precision medicine is the modern era version of “personalized medicine”, which integrates data from genomics and clinical information to optimize the care delivered to patients. As next generation sequencing (NGS) revolutionized the speed and cost of genomic sequencing, precision medicine entered clinical practice in 2017 via the national reimbursement of oncology and rare diseases. In parallel, the digitalization of clinical data through electronic health recording (EHR) and hospital information systems has allowed data collection and analysis. This has led to the integration of biomarkers and clinical records, which have introduced precision medicine into clinical practice. Today, many countries and medical institutes are endeavoring to create systems that will enable precision medicine to be applied to clinical practice. These data systems will benefit the patient by providing accurate data based on his/her characteristics rather than the conventional approach of using “average data”. Internal medicine will transform into a data-driven science that enables physicians to translate molecular biomarkers and big data analysis into improved clinical care. (Korean J Med 2020;95:382-386)

면역성 혈소판감소성 자반증을 동반한 크론병

김규표 ( Kyu Pyo Kim ),장혜숙 ( Hye Sook Chang ),양석균 ( Suk Kyun Yang ),명승재 ( Seung Jae Myung ),정훈용 ( Hwoon Yong Jung ),홍원선 ( Weon Seon Hong ),김진호 ( Jin Ho Kim ),민영일 ( Young Il Min ),김우건 ( Woo Kun Kim ),박찬정 대한소화기학회 2002 대한소화기학회지 Vol.40 No.5

초음파 내시경 검사가 원인진단에 크게 기여했던 급성 재발성 췌장염 1예

문성훈,김명환,김규표,김형수,송진우,형철호,박진태,양동훈,김기덕,이윤선,이상수,서동완,이성구,민영일 대한소화기내시경학회 2003 Clinical Endoscopy Vol.27 No.4

Acute recurrent pancreatitis results most commonly from gallstone disease. Although transabdominal ultrasound is a common procedure for evaluating biliary tract, it may not be effective in minilithiasis. We here report a case of acute recurrent pancreatitis, in which endoscopic ultrasonography revealed minilithiasis in the gallbladder with a review of the literature. A 57-year-old woman had suffered from idiopathic recurrent pancreatitis four times for the past 4 months. While transabdominal ultrasonography and abdominal computerized tomography revealed no evidence of bliary stones, but EUS exhibited minilithiasis in the gallbladder. After laparoscopic cholecystectomy, no further events of pancreatitis happened. (Korean J Gastrointest Endosc 2003;27:258-262) 저자들은 4개월 동안 4차례나 재발한 급성 재발성 췌장염에서 통상적인 복부 초음파 검사에서는 진단되지 않았으나 초음파 내시경으로 담낭 내 미세 담석을 발견할 수 있었다. 급성 담석성 췌장염으로 진단하여 복강경 담낭절제술을 시행하였고, 이후 1년 6개월간 췌장염이 재발하지 않았기에 성공적으로 췌장염의 원인 제거가 된 것으로 판단한다. 본 증례에서 얻는 교훈은 담낭이 있는 환자에서 임상적으로 급성 담석성 췌장염이 의심되는 경우 통상적인 복부 초음파 검사나 전산화 단층 촬영에서 담석이 발견되지 않더라도 초음파 내시경 검사의 시행을 강력히 고려해야 할 것이라는 점이다.

구연 : 소화기 ; 자가 면역성 만성 췌장염 17예의 임상상

김명환,이윤정,김규표,송문희,박도현,이상수,서동완,이성구,민영일 대한내과학회 2003 대한내과학회 추계학술대회 Vol.65 No.10

십이지장 구부로의 이소성 총수담관 개구 이상 그 임상적 의의는?

이상수,김명환,김규표,배종석,김현준,이성구,민영일,정준표,김재선,김창덕 대한내과학회 2002 대한내과학회 추계학술대회 Vol.63 No.-

췌장의 대낭성 장액성 낭종과 점액성 낭종의 감별 진단에 있어서 내시경 초음파의 유용성

정석원,이상수,김규표,송문희,한지민,김종철,최은광,주영민,서동완,이성구,김명환,장세진 대한소화기내시경학회 2006 Clinical Endoscopy Vol.32 No.2

Background/Aims: A macrocystic variant of a serous cystadenoma (M-SCA) is usually indistinguishable from a mucinous cystadenoma (MCA) as a result of their morphologic similarity on conventional imaging studies. However, a MCA requires a resection due to its malignant potential. The aim of this study was to determine the EUS morphological characteristics of a M-SCA to determine if they could be used to help differentiate it from MCA. Methods: The clinical and EUS morphologic characteristics were examined in 31 consecutive patients with M-SCA and MCA who underwent surgery. Results: Resected specimens were available from 11 M-SCAs and 20 MCAs. Significant differences were observed with regard to the age and location within the pancreas. On EUS, most of the M-SCA contained microcysts (82%) compared with only 15% of MCA cases, and a lobulated configuration of the cyst was observed more frequently in the M-SCA cases than in the MCA (91% vs. 25%). The combination of microcysts and the lobulated configuration of the cysts had a 100% specificity and positive predictive value for differentiating M-SCA from MCA. Conclusions: M-SCA tends to occur at a relatively younger age than MCA, and is located mainly in the head of the pancreas. Although there is considerable morphological similarity between M-SCA and MCA on the conventional imaging modalities, the morphological characteristics obtained from EUS including microcysts with a lobulated configuration may help to make a distinction between M-SCA and MCA. (Korean J Gastrointest Endosc 2006;32:109-115) 목적: 췌장의 장액성 낭종(seous cystadenoma, SCA)은 악성화의 가능성이 있어 절제가 필요한 점액성 낭종(mucinous cystadenoma, MCA)과 형태학적 및 임상적 중요성이 구분된다. 최근 MCA와 형태적으로 유사한 대낭성 장액성 낭종(macrocystic serous cystadenoma, M-SCA)이 많이 발견되고 있으나, M-SCA와 MCA를 수술 전에 감별 진단하는 것은 쉽지 않다. 본 연구에서는 M-SCA와 MCA의 임상적 소견과 내시경 초음파(endoscopic ultrasonography, EUS)에서의 형태학적 특징을 비교하여, 이들을 감별 진단하는 데 있어서 EUS의 유용성을 알아보고자 하였다. 대상 및 방법: 2001년 1월에서 2004년 12월까지 서울아산병원에서 췌장 낭성 병변으로 EUS를 시행받고 수술적 절제를 시행한 환자 중 M-SCA와 MCA로 진단된 환자를 대상으로 의무 기록 및 EUS 소견을 비교하였다. 결과: M-SCA와 MCA는 각각 11예와 20예가 진단되었다. 남녀비는 차이가 없었으며, 평균 연령은 44 (26~58)세와 57 (31~68)세로 MCA군의 평균 연령이 높았다(p=0.011). 낭종의 위치는 M-SCA는 췌장 두부에 많았고, MCA는 체부 및 미부에 많았다(p=0.013). 5 mm 이하의 미세 낭종은 M-SCA는 82% (9/11), MCA는 15% (3/20)로 M-SCA에서 많이 관찰되었다(p<0.001). 낭종 외연이 소엽상(lobulation)을 보이는 경우는 M-SCA에서 91% (10/11), MCA에서 25% (5/20)로 M-SCA에서 의미 있게 많았다(p=0.001). 상기 2가지 내시경적 특징을 조합하여 보았을 때, 이 두가지 낭종의 감별 진단에 있어 EUS의 예민도, 특이도, 양성 예측도, 음성 예측도는 각각 90%, 100%, 100%, 95%였다. 결론: 비록 M-SCA와 MCA 사이에 형태적인 유사점이 많지만, M-SCA는 MCA에 비해 비교적 젊은 나이에 발견되고, 주로 췌장 두부에 위치하며, EUS상 소낭의 존재 유무, 낭종 외연의 소엽상 유무가 두 낭종의 감별 진단에 도움이 된다고 생각한다.