순환 종양 유전자의 정량 검출을 위한 등온 디지털 중합효소연쇄반응 플랫폼 개발

학위논문 (석사)-- 서울대학교 대학원 : 공과대학 기계항공공학부(멀티스케일 기계설계전공), 2019. 2. 전누리.Quantification of circulating tumor DNA facilitate detection of cancer without invasive detection and variables derived from characteristic of cancer patients against conventional cancer detection technique such as anti-body bio marker or tissue biopsy. For the detection and quantification of DNA biomarker, gene relate technologies are developed actively employing DNA amplification technique based on polymerase chain reaction (PCR). Especially, digital PCR specialized on quantify assay is commonly employed for research about the DNA samples which have extremely low concentration in entire liquid sample. But conventional digital PCR process generally require high cost equipment, well-trained technicians and time consuming caused by complex steps. So, the researches about microfluidic systems to substitute conventional digital PCR are on the progress in the contemporary society. In this study, a microfluidic platform that have possibility of quantification of ctDNA without high cost equipment and time consuming is through employing microfluidic systems and isothermal DNA amplification known as recombinase polymerase amplification (RPA). With isothermal DNA amplification technique, the limitations derived from conventional PCR, such as high temperature, are not remained. And also, designed microfluidic platform facilitate robust, fast and simple colony forming which is key-point of the digital PCR technics for the quantification of DNA samples. With this platform, liquid samples are easily isolated in 20,000 micro well structures with simple pressing force and generic DNAs extracted cancer cells are used to mimic actual ctDNA environment and extremely low concentration in patient blood samples. Extracted generic DNAs with mutation are detected with designed primers and probes successfully in microfluidic platform. This study provide the robust and easy-to-use microfluidic platform for quantification of ctDNA as point-of-care (POC) platform.혈액 내 순환 종양 유전자의 정량 검출은 기존의 항체 기반 바이오마커 검사나 조직 검사에 비하여 암 검출을 침습성 검사 혹은 개개인의 환자에 따라 변수가 결정되는 일 없이 가능하다. 이러한 유전자 기반 바이오마커의 검출을 위해서 많은 유전자 관련 기술들이 중합효소연쇄반응(PCR) 기술을 기반으로 활발하게 개발되었다. 특히, 디지털 중합효소연쇄반응은 정량 분석에 특화 되어있는 기술로, 전체 표본에서 농도가 매우 낮은 유전자 표본을 검출할 때 일반적으로 사용된다. 하지만 기존의 디지털 중합효소연쇄반응 과정은 일반적으로 복잡한 과정으로 인하여 높은 가격의 장비, 숙련된 기술자 그리고 많은 시간 소모를 동반한다. 이로 인해, 기존의 디지털 중합효소연쇄반응을 미세 유체 시스템을 통하여 대체하려는 연구가 현대사회에서 진행되고 있다. 이 연구에서는 미세 유체 시스템과 재조합 효소 중합효소 증폭(RPA)라고 불리는 등온 유전자 증폭 기술을 통하여 혈액 내 순환 종양 유전자의 정량 검출을 고가의 장비와 많은 시간 소모 없이 가능한 미세 유체 플랫폼을 연구하였다. 등온 유전자 증폭 기술을 통하여 고온에서 진행되는 기존의 중합효소연쇄반응의 한계점을 해결하였다. 또한 설계된 플랫폼을 통하여 디지털 중합효소연쇄반응에서 중요한 표본의 콜로니 구성을 정확하고, 빠르며, 간단하게 진행할 수 있다. 이 플랫폼에서는 간단한 압력을 가해 유체 표본을 20,000개의 미세 웰 구조에 분리해낼 수 있으며, 또한 암세포에서 추출한 유전자를 통하여 실제 환자에서의 혈액 내 순환 종양 유전자를 모사하고, 혈액 표본에서 매우 낮은 농도를 가지는 순환 종양 유전자의 환경을 유사하게 구현하였다. 추출된 변형 유전자는 설계된 프라이머, 프로브를 이용하여 미세 유체 플랫폼에서 성공적으로 검출이 가능하였다. 이 연구에서는 이를 통하여 혈액 내 순환 종양 유전자의 정량 검출이 확실하며 사용이 용이한 플랫폼을 현장현시검사(POC) 플랫폼으로 제안한다.Table of Contents Abstract........................................................................ⅰ Table of Contents...........................................................ⅳ List of figures................................................................ⅵ Chapter 1. Introduction.......................1 1.1 Study background...................................1 1.2 Purpose of Research...............................3 Chapter 2. Materials and Methods.........4 2.1 Device design and fabrication...........................4 2.2 Division of liquid sample in micro wells............6 2.3 Isothermal DNA amplification in platform.........7 2.4 Quantification of ctDNA..................................9 Chapter 3. Result.................................15 3.1 Detection of tumor DNA through digital RPA.....15 3.2 Real time detection of fluorescence signal.........16 3.3 Quantification with fluorescing micro wells.......17 Chapter 4. Discussion....................................................23 Chapter 5. Conclusion....................................................24 Bibliography Abstract (Korean)Maste

The roles of reactive astrocytes in cognitive function via the morphological and molecular changes in Alzheimers disease animal model

학위논문 (박사) -- 서울대학교 대학원 : 의과대학 의과학과, 2020. 8. 김혜선.Numerous roles of astrocytes have been reported in the central nervous system. Astrocytes have the potential to exist in two states, the reactive and the resting states. Reactive astrocytes have morphological features such as the increase in thickness, number of processes and volume of cell body. Molecular changes also occur, such as an increase in the expression of glial fibrillary acidic protein (GFAP). However, the morphological and molecular dynamics during the memory formation in astrocytes remain largely unknown. Moreover, the pathophysiological roles of the reactive state of astrocytes are thought to be of importance in the pathogenesis of neurodegenerative diseases, including Alzheimers disease (AD). However, the detailed mechanisms underlying the transition of astrocytes from the resting state to the reactive state during neurodegenerative disease largely remain unclear. Here, I investigated the changes in astrocytes in the hippocampus of Fvb/n mice trained with contextual fear conditioning to memory induction, and the morphological and molecular dynamics were analyzed in astrocytes. One hour after fear conditioning, type II and type III astrocytes displayed a unique status, not reactive nor resting state, with an increased the number of processes and decreased GFAP expression. In addition, the protein level of excitatory amino acid transporter 2 (EAAT 2) was increased at 1 hour to 24 hours after fear conditioning while EAAT1 did not show any changes. Connexin 43 protein expression was found to be increased at 24 hours after fear conditioning test. After L-α- aminoadipate treatment, an astrocyte-specific toxic molecule, mice showed the impairment of cognitive function. In addition, I investigated which pathways are involved in activating astrocytes from the resting state to the reactive state in an AD context such as JAK/STAT3, MAPK, NF-kB, and NFAT in primary cultured astrocytes treated with oligomeric amyloidβ peptide (oAβ) and in the hippocampus of 5XFAD mice. Treatment with oAβinduced an increase in reactive astrocytes, as assessed by the protein expression of GFAP and this increase was caused by signal transducer and activator of transcription 3 (STAT3) phosphorylation in primary cultured astrocytes. The treatment with Stattic, an inhibitor of STAT3 phosphorylation, rescued the activation of astrocytes in primary cultured astrocytes. Additionally, the systemic administration of Stattic rescued the activation of astrocytes in the hippocampus of 6-month-old 5XFAD mice as well as impairments of cognitive function. Collectively, these results demonstrated that the status of astrocytes transit into a novel state, memory induction state, by hippocampus-based contextual memory process. These astrocytes in the memory induction state are thought to be not induced in 5XFAD mice brains, because astrocytes exist in the reactive state in the hippocampus of 5XFAD mice. Reactive astrocytes in the brains of 5XFAD mice were found to be induced via STAT3 phosphorylation and the impairments in learning and memory observed in the 5XFAD mice are rescued by the inhibition of STAT3 phosphorylation, suggesting that the inhibition of STAT3 phosphorylation in astrocytes may be a novel therapeutic target for cognitive impairment in AD.중추신경계에서 성상교세포의 다양한 역할들이 보고되어 왔다. 성상교 세포는 잠재적으로 활성화 상태와 휴지기 상태의 두 가지의 상태로 변 화할 수 있는 능력이 있다. 활성화 성상교세포는 돌기의 두께와 그 수가 증가하고, 세포체 부피의 증가가 특징적으로 나타난다. 또한, 신경교 섬 유질 산성단백질 (glial fibrillary acidic protein: GFAP)과 같은 단 백질 발현의 증가나 유전자 발현의 변화가 분자적 변화로 나타난다. 하 지만, 성상교세포에서 기억을 유도하는 과정 중에 이러한 즉각적인 형태 학적, 분자적 변화는 아직 연구가 부족한 상태이다. 알츠하이머병을 포 함한 퇴행성신경계질환의 발병 기전에 있어 활성화 상태의 성상교세포 의 병리생리학적 역할은 매우 중요한 의미가 있을 것이라 생각된다. 그 러나 퇴행성신경계질환이 진행되는 동안 휴지기 상태의 성상교세포가 활성화 상태로 전환되는 구체적인 작용 원리의 이해는 여전히 명백하게 밝혀져 있지 않다. 본 연구에서는 Fvb/n 마우스 뇌내 해마에 존재하는 성상교세포를 공포 상황 조건화 실험 (contextual fear conditioning) 을 통해 기억 유도를 하였다. 이후 기억 유도한 성상교세포의 형태학적 분자적 변화를 분석 하였다. 공포 상황 조건화 실험 1시간 후, 타입 2 와 타입 3 성상교세포가 활성화와 휴지 상태의 특징이 아닌, 돌기의 수 가 증가하고, 신경교 섬유질 산성단백질의 발현이 감소되는 새로운 상태 로 관측되었다. 또한, 흥분성 아미노산 운반자 2 (excitatory amino acid transporter 2: EAAT2)의 단백질 발현이 공포 상황 조건화 후 1시간 에서 24시간까지 단백질 발현이 증가하였지만, 흥분성 아미노산 운반자 1은 변화가 없는 것이 확인되었다. 공포 상황 조건화 24시간 후 코넥신 43 (Connexin 43: Cx43) 단백질의 발현의 증가가 확인되었다. 성상교세포 특이적 독성 물질인, 엘-알파-아미노아디페이트 (L-α- aminoadipate: LAA)가 뇌내 해마에 처리된 마우스에서 인지능력의 저하가 확인되었다. 초대 배양 성상교세포에 다량체 아밀로이드 펩티드 (oAβ)를 처치하는 방법과 6개월령 알츠하이머병 동물 모델 5XFAD의 해마 부위에서 어떤 신호전달 경로가 연관되어 있는지 확인하였다. 신경 교 섬유질 산성단백질 발현의 증가를 통해서 초대 배양 성상교세포의 다량체 아밀로이드 펩티드 처치는 활성화 성상교세포의 증가의 유도함 을 확인하였다. 이러한 초대 배양 성상교세포의 활성화는 신호변환자- 전사활성자 3 (signal transducer and activator of transcription: STAT3)의 인산화를 통해 증가하였다. 초대 배양 성상교세포 활성화와 6개월령 알츠하이머동물 모델의 인지능력 저해를 신호변환자-전사활성 자 3 인산화 억제제 스테틱(Stattic)의 전신 적용이 완화시킴을 확인하 였다. 위 결과를 종합하면, 해마 기반 공포 상황 조건화 실험에 의해 기 억 유도된 성상교세포는 새로운 형태를 보이며 이를, 기억 유도 상태가 되었다. 알츠하이머병 뇌 내에서 활성화 상태의 성상교세포로 존재함으 로 이러한 기억 유도 상태 성상교세포는 정상적이지 않을 것이다. 알츠 하이머병 뇌의 활성화 성상교세포는 신호변환자-전사활성자 3 인산화를 통해서 나타나며, 학습과 기억력의 저하가 신호변환자-전사활성자 3 인 산화 억제제를 통해서 완화되었다. 이는 신호변환자-전사활성자 3 인산 화 억제제를 통한 성상교세포의 활성화 조절이 알츠하이머병의 인지능 력저하의 새로운 치료 전략으로 제시될 가능성을 보였다.Introduction 1 Introduction summary 11 Chapter 1 12 Dynamics of astrocytes during memory induction 13 Material and Methods 15 Experimental scheme 21 Results 22 Discussion 45 Graphical summary 50 Chapter 2 51 Pathophysiological role of reactive astrocyte in Alzheimers disease model Introduction 52 Material and Methods 54 Experimental scheme 62 Results 63 Discussion 119 Graphical summary 127 Conclusion 128 References 130 Abstract in Korean 139Docto

A Cooperative Game Approach

학위논문 (석사) -- 서울대학교 대학원 : 공과대학 산업공학과, 2021. 2. 이덕주.As machine learning thrives in both academia and industry at the moment, data plays a salient role in training and validating machines. Meanwhile, few works have been developed on the economic evaluation of the data in data exchange market. The contribution of our work is two-fold. First, we take advantage of semi-values from cooperative game theory to model revenue distribution problem. Second, we construct a model consisting of provider, firm, and market while considering the privacy and fairness of machine learning. We showed Banzhaf value could be a reliable alternative to Shapley value in calculating the contribution of each datum. Also, we formulate the firms revenue maximization problem and present numerical analysis in the case of binary classifier with classical data examples. By assuming the firm only uses high quality data, we analyze its behavior in four different scenarios varying the datas fairness and compensating cost for data providers privacy. It turned out that the Banzhaf value is more sensitive to the fairness of data than the Shapley value. We analyzed the maximum revenue proportion which the firm gives away to data providers, as well as the range of number of data the firm would acquire.기계학습이 현재 이론과 실생활 적용 모두에서 발전함에 따라 데이터는 인공지능 모델을 훈련하고 검증하는 데 중요한 역할을 하고 있다. 한편, 데이터 교환 시장에서 데이터의 경제성 평가에 대한 연구는 초기 단계이다. 본 논문의 기여는 두 가지 관점에서 접근할 수 있다. 첫째, 협동 게임 이론의 개념인 semi-value를 모델 수익 분배 문제에 활용한다. 둘째, 인공지능 모델의 공정성과 개인정보보호성을 고려한 데이터 제공자, 기업, 시장으로 구성된 모델을 제안한다. 본 연구에서 Banzhaf 값은 각 데이터의 기여도를 계산할 때 Shapley 값의 대안이 될 수 있음을 확인하였다. 또한 회사의 수익 극대화 문제를 모델링하였고, 추가적으로 데이터 예제를 사용하여 이진 분류 모델의 경우 수치 분석을 제시하였다. 이를 통해, Banzhaf 값은 Shapley 값보다 데이터의 공정성에 더 민감하다는 것을 확인하였다. 나아가 기업이 고품질 데이터만을 사용한다는 가정하에 데이터의 공정성과 데이터 제공자의 개인정보에 대한 보상비용을 달리하는 네 가지 시나리오에서 기업의 행동을 분석하였다. 기업은 데이터가 공정할수록 데이터 제공자에게 더 큰 수익을 보장해주었고, 고정비용이 작아질수록 가변비용을 통해서 데이터 제공자에게 수익을 나눠주는 것을 확인하였다.Chapter 1 Introduction 1 1.1 Research Background 1 1.2 Problem Description 2 1.3 Organization of the Thesis 3 Chapter 2 Literature Review 4 2.1 Fair Machine Learning 4 2.2 Private Machine Learning 5 2.3 Data Valuation 6 2.3.1 Dataset Price Estimation 6 2.3.2 Equitable Price Estimation 7 Chapter 3 Data Market Model 8 3.1 Basic Assumptions and Model Settings 8 3.2 Firms Profit Maximizing Problem 10 3.3 Data Valuation 12 3.4 Binary Classification Setting 14 Chapter 4 Analysis 17 4.1 Semi-value Approximation 17 4.1.1 Convergence Analysis 17 4.1.2 Group Data Calculation 20 4.2 Binary Classification 22 4.2.1 Parameter Analysis 22 4.2.2 Scenario Analysis 24 4.2.2.1 Description 24 4.2.2.2 Synthetic Data 25 4.2.2.3 Shapley Value Based Valuation 26 4.2.2.4 Banzhaf Value Based Valuation 28 4.2.2.5 Comparative Analysis 30 4.3 Data Pricing 33 Chapter 5 Conclusion 35 Bibliography 38 국문초록 43Maste

Intraoperative Transfusion is Independently Associated with a Worse Prognosis in Resected Pancreatic Cancer-a Retrospective Cohort Analysis

BACKGROUNDS: Investigate whether intraoperative transfusion is a negative prognostic factor for oncologic outcomes of resected pancreatic cancer. METHODS: From June 2004 to January 2014, the medical records of 305 patients were retrospectively reviewed, who underwent pancreatoduodenectomy, pylorus preserving pancreatoduodenectomy, total pancreatectomy, distal pancreatectomy for pancreatic cancer. Patients diagnosed with metastatic disease (n = 3) and locally advanced diseases (n = 15) were excluded during the analysis, and total of 287 patients were analyzed. RESULTS: The recurrence and disease-specific survival rates of the patients who received intraoperative transfusion showed poorer survival outcomes compared to those who did not (P = 0.031, P = 0.010). Through multivariate analysis, T status (HR (hazard ratio) = 2.04, [95% CI (confidence interval): 1.13-3.68], P = 0.018), N status (HR = 1.46 [95% CI: 1.00-2.12], P = 0.045), adjuvant chemotherapy (HR = 0.51, [95% CI: 0.35-0.75], P = 0.001), intraoperative transfusion (HR = 1.94 [95% CI: 1.23-3.07], P = 0.004) were independent prognostic factors of disease-specific survival after surgery. As well, adjuvant chemotherapy (HR = 0.67, [95% CI: 0.46-0.97], P = 0.035) was independently associated with tumor recurrence. Estimated blood loss was one of the most powerful factors associated with intraoperative transfusion (P < 0.001). CONCLUSIONS: Intraoperative transfusion can be considered as an independent prognostic factor of resected pancreatic cancer. As well, it can be avoided by following strict transfusion policy and using advanced surgical techniques to minimize bleeding during surgery.ope

Preoperative prognostic nutritional index as an independent prognostic factor for resected ampulla of Vater cancer

INTRODUCTION: Prognostic nutritional index (PNI) reflects the nutritional and immunologic status of the patients. The clinical application of PNI is already well-known in various kinds of solid tumors. However, there is no study investigating the relationship between PNI and oncological outcome of the resected ampulla of Vater (AoV) cancer. MATERIALS AND METHODS: From January 2005 to December 2012, the medical records of patients who underwent pancreaticoduodenectomy for pathologically confirmed AoV cancer were retrospectively reviewed. Long-term oncological outcomes were compared according to the preoperative PNI value. RESULT: A total of 118 patients were enrolled in this study. The preoperative PNI was 46.13±6.63, while the mean disease-free survival was 43.88 months and the mean disease-specific survival was 55.3 months. In the multivariate Cox analysis, initial CA19-9 (p = 0.0399), lymphovascular invasion (p = 0.0031), AJCC 8th N-stage (p = 0.0018), and preoperative PNI (p = 0.0081) were identified as significant prognostic factors for resected AoV cancer. The disease-specific survival was better in the high preoperative PNI group (≤48.85: 40.77 months vs. >48.85: 68.05 months, p = 0.0015). A highly accurate nomogram was developed based on four clinical components to predict the 1, 3, and 5-year disease-specific survival probability (C-index 0.8169, 0.8426, and 0.8233, respectively). CONCLUSION: In resected AoV cancer, preoperative PNI can play a significant role as an independent prognostic factor for predicting disease-specific survival.ope

Developing an in vivo porcine model of duct-to-mucosa pancreaticojejunostomy (Yonsei-PJDTM)

Laparoscopic pancreaticoduodenectomy (LPD) is technically feasible, but its safety is still controversial. Pancreas texture and the small size of the main pancreatic duct indicate laparoscopic pancreaticoduodenectomy (LPD) as a challenging procedure. Thus, LPD could be a risk factor for postoperative pancreatic fistula (POPF), longer hospital stay, and delayed adjuvant chemotherapy that affects long-term oncologic outcome. So, it is important to promote education on LPD especially techniques for pancreaticojejunostomy. A porcine model for duct-to-mucosa pancreaticojejunostomy (PJ) (Yonsei-PJDTM) was developed, and details of the model will be described in this report.ope

Systemic inflammation response index correlates with survival and predicts oncological outcome of resected pancreatic cancer following neoadjuvant chemotherapy

Background: The Systemic Inflammation Response Index (SIRI) has been used to predict the prognosis of various cancers. This study examined SIRI as a prognostic factor in the neoadjuvant setting and determined whether it changing after chemotherapy is related to patient prognosis. Methods: Patients who underwent pancreatic surgery following neoadjuvant chemotherapy for pancreatic cancer were retrospectively analyzed. To establish the cut-off values, SIRIpre-neoadjuvant, SIRIpost-neoadjuvant, and SIRIquotient (SIRIpost-neoadjuvant/SIRIpre-neoadjuvant) were calculated and significant SIRI values were statistically determined to examine their effects on survival rate. Results: The study included 160 patients. Values of SIRIpost-neoadjuvant ≥ 0.8710 and SIRIquotient <0.9516 affected prognosis (hazard ratio [HR], 1.948; 95% confidence interval [CI], 1.210-3.135; ∗∗P = 0.006; HR, 1.548; 95% CI, 1.041-2.302; ∗∗P = 0.031). Disease-free survival differed significantly at values of SIRIpost-neoadjuvant < 0.8710 and SIRIpost-neoadjuvant ≥ 0.8710 (P = 0.0303). Overall survival differed significantly between SIRIquotient <0.9516 and SIRIquotient ≥0.9516 (P = 0.0368). Conclusions: SIRI can predict the survival of patients with pancreatic ductal adenocarcinoma after resection and neoadjuvant chemotherapy. Preoperative SIRI value was correlated with disease-free survival, while changes in SIRI values were correlated with overall survival.ope

Development of a metabolite calculator for diagnosis of pancreatic cancer

Background: Carbohydrate antigen (CA) 19-9 is a known pancreatic cancer (PC) biomarker, but is not commonly used for general screening due to its low sensitivity and specificity. This study aimed to develop a serum metabolites-based diagnostic calculator for detecting PC with high accuracy. Methods: A targeted quantitative approach of direct flow injection-tandem mass spectrometry combined with liquid chromatography-tandem mass spectrometry was employed for metabolomic analysis of serum samples using an Absolute IDQ™ p180 kit. Integrated metabolomic analysis was performed on 241 pooled or individual serum samples collected from healthy donors and patients from nine disease groups, including chronic pancreatitis, PC, other cancers, and benign diseases. Orthogonal partial least squares discriminant analysis (OPLS-DA) based on characteristics of 116 serum metabolites distinguished patients with PC from those with other diseases. Sparse partial least squares discriminant analysis (SPLS-DA) was also performed, incorporating simultaneous dimension reduction and variable selection. Predictive performance between discrimination models was compared using a 2-by-2 contingency table of predicted probabilities obtained from the models and actual diagnoses. Results: Predictive values obtained through OPLS-DA for accuracy, sensitivity, specificity, balanced accuracy, and area under the receiver operating characteristic curve (AUC) were 0.9825, 0.9916, 0.9870, 0.9866, and 0.9870, respectively. The number of metabolite candidates was narrowed to 76 for SPLS-DA. The SPLS-DA-obtained predictive values for accuracy, sensitivity, specificity, balanced accuracy, and AUC were 0.9773, 0.9649, 0.9832, 0.9741, and 0.9741, respectively. Conclusions: We successfully developed a 76 metabolome-based diagnostic panel for detecting PC that demonstrated high diagnostic performance in differentiating PC from other diseases.ope

Pancreaticoduodenectomy with combined hepatic artery and portal vein resection after laparoscopic division of pancreaticosplenic ligament due to FOLFIRINOX-induced hepatic toxicity related secondary hypersplenism

Pancreatic cancer is one of the dismal malignant disease in gastrointestinal tract. However, since the recent literature reporting median survival of FOLFIRINOX (leucovorin clcium, fluorouracil, irinotecan hydrochloride, oxaliplatin) chemotherapy was more than 12 months in metastatic pancreatic cancer was published, the positive attitude toward the treatment of the advanced pancreatic cancer is gradually expanded among the medical and surgical oncologists. Due to multiple combination of potent chemotherapeutic agents, potential adverse side effects should be concerned when considering FOLFIRINOX. Herein, we report a 55-year old male patient with locally advanced pancreatic cancer who successfully underwent curative resection following by laparoscopic division of pancreaticosplenic ligament due to long-term preoperative use of FOLFIRINOX related hepatic toxicity associated with secondary hypersplenism. The present case suggests the extended radical PD with combined major vascular resection following laparoscopic division of pancreaticosplenic ligament containing splenic artery and vein can improve the safety of curative resection and may expand the potential indication of pancreatic cancer in well-selected long-term use of preoperative FOLFIRINOX induced hepatic toxicity associated with secondary hypersplenism.ope

Laparoscopic pancreaticoduodenectomy in pancreatic ductal adenocarcinoma

Laparoscopic pancreatoduodenectomy (LPD) in pancreatic cancer is primarily criticized for its technical and oncological safety. Although solid evidence has not yet been established, many institutions are performing LPD for pancreatic cancer patients, with continuous efforts to ensure oncologic safety. In this video, we demonstrated a case of standard LPD combined with vascular resection in pancreatic cancer.ope