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1.
BMC Anesthesiol ; 23(1): 321, 2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730575

RESUMO

BACKGROUND: Proper mask ventilation is important to prevent air inflow into the stomach during induction of general anesthesia, and it is difficult to send airflow only through the trachea without gastric inflation. Changes in gastric insufflation according to mask ventilation during anesthesia induction were compared. METHODS: In this prospective, randomized, single-blind study, 230 patients were analyzed to a facemask-ventilated group (Ventilation group) or no-ventilation group (Apnea group) during anesthesia induction. After loss of consciousness, pressure-controlled ventilation at an inspiratory pressure of 15 cmH2O was performed for two minutes with a two-handed mask-hold technique for Ventilation group. For Apnea group, only the facemask was fitted to the face for one minute with no ventilation. Next, endotracheal intubation was performed. The gastric cross-sectional area (CSA, cm2) was measured using ultrasound before and after induction. After pneumoperitoneum with carbon dioxide, gastric insufflation of the surgical view was graded by the surgeon for each group. RESULTS: Increase of postinduction antral CSA on ultrasound were not significantly different between Ventilation group and Apnea group (0.04 ± 0.3 and 0.02 ± 0.28, p-value = 0.225). Additionally, there were no significant differences between the two groups in surgical grade according to surgeon's judgement. CONCLUSIONS: Pressure-controlled ventilation at an inspiratory pressure of 15 cmH2O for two minutes did not increase gastric antral CSA and insufflation of stomach by laparoscopic view. TRIAL REGISTRATION: http://cris.nih.go.kr (KCT0003620) on 13/3/2019.


Assuntos
Colecistectomia Laparoscópica , Insuflação , Humanos , Apneia , Estudos Prospectivos , Método Simples-Cego , Estômago
2.
Langenbecks Arch Surg ; 407(1): 207-212, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34240246

RESUMO

PURPOSE: Left-sided gallbladder (LSGB) is a rare congenital anomaly in the gallbladder, which is defined as a gallbladder located on the left side of the falciform ligament without situs inversus. We retrospectively analyzed 13 patients diagnosed with LSGB in a single center to confirm the safety of laparoscopic cholecystectomy (LC) and reviewed the anatomical implications in those patients. METHODS: Of the 4910 patients who underwent LC for the treatment of gallbladder disease between August 2007 and December 2019, 13 (0.26%) were diagnosed as having LSGB. We retrospectively analyzed these 13 patients for general characteristics, perioperative outcomes, and other variations through the perioperative imaging workups. RESULTS: All patients underwent LC for gallbladder disease. In all cases, the gallbladder was located on the left side of the falciform ligament. The operation was successfully performed with standard four-trocar technique, confirming "critical view of safety (CVS)" as usual without two cases (15.4%). In one case, which had an intraoperative complication and needed choledochojejunostomy because of common bile duct injury, there was an associated variation with early common bile duct bifurcation. The other patient underwent an open conversion technique because of severe fibrosis in the Calot's triangle. Furthermore, on postoperative computed tomography, abnormal intrahepatic portal venous branching was found in all cases. CONCLUSIONS: Although LSGB is usually encountered by chance during surgery, it can be successfully managed through LC with CVS. However, surgeons who find LSGB have to make efforts to be aware of the high risk of bile duct injury and possibility of associated anomalies.


Assuntos
Colecistectomia Laparoscópica , Doenças da Vesícula Biliar , Colecistectomia Laparoscópica/efeitos adversos , Vesícula Biliar/anormalidades , Doenças da Vesícula Biliar/diagnóstico por imagem , Doenças da Vesícula Biliar/cirurgia , Humanos , Estudos Retrospectivos
3.
J Korean Med Sci ; 36(28): e189, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282606

RESUMO

BACKGROUND: Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully. We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis. METHODS: We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants. RESULTS: No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions. CONCLUSION: We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer.


Assuntos
Bactérias/isolamento & purificação , Bile/metabolismo , Bile/microbiologia , Disbiose/microbiologia , Doenças da Vesícula Biliar/microbiologia , Neoplasias da Vesícula Biliar/microbiologia , Vesícula Biliar/microbiologia , Adulto , Bactérias/classificação , Estudos de Casos e Controles , Colecistite/microbiologia , Colecistite/patologia , Humanos , Metagenômica , Microbiota , Pessoa de Meia-Idade , Filogenia
4.
J Hepatol ; 70(1): 97-107, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30240598

RESUMO

BACKGROUND & AIMS: Currently, much effort is directed towards the development of new cell sources for clinical therapy using cell fate conversion by small molecules. Direct lineage reprogramming to a progenitor state has been reported in terminally differentiated rodent hepatocytes, yet remains a challenge in human hepatocytes. METHODS: Human hepatocytes were isolated from healthy and diseased donor livers and reprogrammed into progenitor cells by 2 small molecules, A83-01 and CHIR99021 (AC), in the presence of EGF and HGF. The stemness properties of human chemically derived hepatic progenitors (hCdHs) were tested by standard in vitro and in vivo assays and transcriptome profiling. RESULTS: We developed a robust culture system for generating hCdHs with therapeutic potential. The use of HGF proved to be an essential determinant of the fate conversion process. Based on functional evidence, activation of the HGF/MET signal transduction system collaborated with A83-01 and CHIR99021 to allow a rapid expansion of progenitor cells through the activation of the ERK pathway. hCdHs expressed hepatic progenitor markers and could self-renew for at least 10 passages while retaining a normal karyotype and potential to differentiate into functional hepatocytes and biliary epithelial cells in vitro. Gene expression profiling using RNAseq confirmed the transcriptional reprogramming of hCdHs towards a progenitor state and the suppression of mature hepatocyte transcripts. Upon intrasplenic transplantation in several models of therapeutic liver repopulation, hCdHs effectively repopulated the damaged parenchyma. CONCLUSION: Our study is the first report of successful reprogramming of human hepatocytes to a population of proliferating bipotent cells with regenerative potential. hCdHs may provide a novel tool that permits expansion and genetic manipulation of patient-specific progenitors to study regeneration and the repair of diseased livers. LAY SUMMARY: Human primary hepatocytes were reprogrammed towards hepatic progenitor cells by a combined treatment with 2 small molecules, A83-01 and CHIR99021, and HGF. Chemically derived hepatic progenitors exhibited a high proliferation potential and the ability to differentiate into hepatocytes and biliary epithelial cells both in vitro and in vivo. This approach enables the generation of patient-specific hepatic progenitors and provides a platform for personal and stem cell-based regenerative medicine.


Assuntos
Hepatócitos/citologia , Regeneração Hepática , Fígado/citologia , Células-Tronco/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Feminino , Quinase 3 da Glicogênio Sintase , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Animais , Pirazóis/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Tiossemicarbazonas/farmacologia
5.
Analyst ; 144(24): 7236-7241, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31674603

RESUMO

A whole-sample-covering near-infrared (NIR) spectroscopy scheme has been adopted for the simple drop-and-dry measurement of raw bile juice for the identification of gallbladder (GB) diseases of stone, polyp, and cancer. For reproducible measurement, a non-NIR absorbing polytetrafluoroethylene (PTFE) providing a hydrophobic surface was chosen as a substrate to form bile juice droplets of a consistent shape. To ensure representative spectroscopic sampling, NIR radiation illuminated the whole area of the dried sample for spectral acquisition. The NIR band shapes and relative band intensities of GB cancer differed moderately from those of GB stone and GB polyp. The composition of GB cancer samples was presumed to be dissimilar from other sample compositions. Differentiation between GB polyp and GB stone, however, was less facile; nevertheless, in the case of GB polyp samples, the obtained NIR features were informative in the identification of various pathological conditions such as adenomyomatosis (abnormal growth of epidermal tissue) and hepatitis B. To elucidate the NIR features of bile juice samples, separate NIR spectra of major bile constituents such as conjugated bile salts, lecithin, cholesterol, and albumin were analyzed. The demonstrated NIR spectroscopy scheme requiring no sample pretreatment or separation of bile juice could be useful for fast bile juice-based screening of GB diseases, especially the identification of early GB cancer.


Assuntos
Bile/química , Doenças da Vesícula Biliar/diagnóstico , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Estudos de Viabilidade , Humanos , Interações Hidrofóbicas e Hidrofílicas , Politetrafluoretileno/química , Análise de Componente Principal , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação
6.
World J Surg ; 41(2): 552-558, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27730351

RESUMO

BACKGROUND: Stomach cancer is the second most commonly diagnosed cancer in Korea. Although the long-term survival outcome has improved, secondary primary tumors from periampullary regions are increasing inevitably and pancreaticoduodenectomy (PD) following gastrectomy is challenging. This study evaluates the surgical outcomes of PD following gastrectomy and suggests the optimum method for reconstruction. METHODS: Patients who underwent curative PD with a history of gastric resection between 2005 and 2015 were assessed retrospectively. PD was performed according to the standard fashion, with the aim of creating a new pancreaticobiliary limb with sufficient length (40-50 cm). Different reconstructive methods were employed during PD according to the previous gastrectomy type. RESULTS: A total of 3064 patients underwent PD, 39 of whom had previous gastrectomies including 12 with Billroth I gastrectomy, 20 with Billroth II gastrectomy, and seven patients with total gastrectomy (TG). In patients with Billroth I gastrectomy, all of the previous gastroduodenostomy site was resected for specimen retrieval. All previous esophagojejunostomy site was preserved in seven patients who had TG. In the Billroth II patients, the gastrojejunostomy site was preserved in 17 patients. Re-operation after PD was required in two patients, and 14 patients (36 %) developed pancreatic fistula and five (13 %) of grade B or higher. CONCLUSIONS: Our study has been the largest report so far of PD following gastric resection, and we were able to confirm the safety and the feasibility of PD procedure. We therefore suggest standardizing the reconstruction method for PD following gastrectomy based on the type of previous gastrectomy.


Assuntos
Gastrectomia/métodos , Gastroenterostomia , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/métodos , Procedimentos de Cirurgia Plástica/métodos , Neoplasias Gástricas/cirurgia , Idoso , Esôfago/cirurgia , Feminino , Humanos , Jejuno/cirurgia , Masculino , Pessoa de Meia-Idade , Pancreaticoduodenectomia/efeitos adversos , Reoperação , República da Coreia , Estudos Retrospectivos
7.
World J Surg ; 40(6): 1412-21, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26796885

RESUMO

BACKGROUND: Cholecystectomy might contribute to the development of hepatic steatosis through metabolic changes. The biologic alteration of the enterohepatic circulation of bile acids and the alteration of the metabolic activity of bile acid that follows cholecystectomy may contribute to hepatic steatosis. This prospective study was conducted to clarify the possibility of steatosis development after cholecystectomy. METHODS: From October 2013 to July 2014, 82 consecutive patients with a presumptive diagnosis of gallbladder disease were cholecystectomized. Liver parenchymal steatosis was measured using ultrasound and the hepatic steatosis index. RESULTS: In all 82 patients, the hepatic steatosis index was found to be significantly correlated with the US fatty liver grade (Spearman's correlation r (2) = 0.331, P < 0.001). A total of 62 patients were followed up for 3 months. Comparison with the initial grade showed that 12 (18.5 %) patients had worsened from normal to mild (n = 10), from mild to moderate (n = 1), and from mild to severe (n = 1). The other patients stayed at their initial grade except one patient who improved (from moderated to mild). Analysis of laboratory findings showed that white blood cell count, aspartate transaminase, alanine transaminase level, and total bilirubin level were decreased. However, serum albumin and high-density lipoprotein cholesterol levels significantly increased. CONCLUSIONS: Hepatic steatosis significantly developed 3 months after cholecystectomy. Therefore, cholecystectomy might be considered a risk factor for hepatic steatosis, but the relationship should be confirmed with long-term follow-up from a large group of patients.


Assuntos
Colecistectomia/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/etiologia , Adulto , Idoso , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Biópsia , Progressão da Doença , Feminino , Seguimentos , Humanos , Lipoproteínas HDL/sangue , Fígado/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Estudos Prospectivos , Albumina Sérica/metabolismo , Índice de Gravidade de Doença , Ultrassonografia/métodos
8.
J Korean Med Sci ; 30(9): 1253-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26339164

RESUMO

Despite a low risk of liver failure and preserved liver function, non-cirrhotic hepatocellular carcinoma (HCC) has a poor prognosis. In the current study, we evaluated an active regulator of SIRT1 (AROS) as a prognostic biomarker in non-cirrhotic HCC. mRNA levels of AROS were measured in tumor and non-tumor tissues obtained from 283 non-cirrhotic HCC patients. AROS expression was exclusively up-regulated in recurrent tissues from the non-cirrhotic HCC patients (P = 0.015) and also in tumor tissues irrespective of tumor stage (P < 0.001) or BCLC stage (P < 0.001). High mRNA levels of AROS were statistically significantly associated with tumor stage (P < 0.001), BCLC stage (P = 0.007), alpha fetoprotein (AFP) level (P = 0.013), microvascular invasion (P = 0.001), tumor size (P = 0.036), and portal vein invasion (P = 0.005). Kaplan-Meir curve analysis demonstrated that HCC patients with higher AROS levels had shorter disease-free survival (DFS) in both the short-term (P < 0.001) and long-term (P = 0.005) compared to those with low AROS. Cox regression analysis demonstrated that AROS is a significant predictor for DFS along with large tumor size, tumor multiplicity, vascular invasion, and poor tumor differentiation, which are the known prognostic factors. In conclusion, AROS is a significant biomarker for tumor aggressiveness in non-cirrhotic hepatocellular carcinoma.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Distribuição por Idade , Idoso , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prevalência , Reprodutibilidade dos Testes , República da Coreia/epidemiologia , Fatores de Risco , Sensibilidade e Especificidade , Distribuição por Sexo , Adulto Jovem
9.
Hepatogastroenterology ; 61(130): 304-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24901129

RESUMO

BACKGROUND/AIMS: T-stage is currently the only factor determining the extent of surgery of gallbladder cancer (GBCA). We hypothesized that perineural invasion could be another predictive factor determining the extent of surgery because it is very powerful prognostic factor for GBCA. METHODOLOGY: A retrospective analysis was carried out of patients who underwent operation for gallbladder cancer between February 1991 and November 2011. The data were retrospectively analyzed and reviewed and the microscopic findings were checked by a pathologist. RESULT: Simple and extended cholecystectomy was performed in 82 patients during the study period. In univariate analysis, CA 19-9 level, gross type, depth of invasion, lymph node metastasis, distant metastasis, perineural invasion, lymphatic invasion and vascular invasion were associated with survival (P < 0.05). In multivariate analysis, perineural invasion and vascular invasion had an impact on survival (P < 0.05). CONCLUSIONS: T and N stage are powerful prognostic factor for GBCA, but perineural invasion and vascular invasion are also significant prognostic factors. To improve survival radical resection should be considered in early GBCA with perineural and vascular invasion.


Assuntos
Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias do Sistema Nervoso Periférico/secundário , Estudos Retrospectivos
10.
Surg Endosc ; 27(10): 3776-80, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23644836

RESUMO

PURPOSE: With the accumulating experience in laparoscopic surgery, early laparoscopic cholecystectomy (LC) is increasingly offered for acute cholecystitis. However, early LC without percutaneous transhepatic gallbladder drainage (PTGBD) for gallbladder empyema is still believed to be unsafe. The purpose of this study was to determine the optimal time for LC in gallbladder empyema. METHODS: A retrospective analysis was carried out of patients who underwent LC without PTGBD for gallbladder empyema between August 2007 and December 2010. All cases were confirmed by biopsy. The patients were divided into two groups on the basis of a cutoff of 72 h. RESULTS: LC for gallbladder empyema was performed without PTGBD in 61 patients during the study period. The overall conversion rate was 6.6 %. Based on the 72 h cutoff, there were 33 patients in the early group and 28 in the delayed group. There were no significant differences between early and late patients with respect to operation duration (75.5 vs. 71.4 min, p = 0.537), postoperative hospital stay (4.2 vs. 3.3 days, p = 0.109), conversion rate (12.1 vs. 0 %, p = 0.118), and complication rate (12.1 vs. 3.6 %, p = 0.363). However, the early group had a significantly shorter total hospital stay (5.3 vs. 8.7 days, p = 0.001). CONCLUSIONS: Early LC without PTGBD is safe and feasible for gallbladder empyema and is associated with a low conversion rate. Delayed LC for gallbladder empyema has no advantages and results in longer total hospital stays. LC should be performed as soon as possible within 72 h after admission to decrease length of hospital stay.


Assuntos
Colecistectomia Laparoscópica/métodos , Colecistite/cirurgia , Fatores de Tempo , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Colecistite/patologia , Drenagem/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Humanos , Laparotomia/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Supuração , Procedimentos Desnecessários
11.
Hepatogastroenterology ; 60(126): 1488-91, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23933943

RESUMO

BACKGROUND/AIMS: Pancreaticoduodenectomy is associated with a high incidence of postoperative morbidity, and pancreatic fistulas are the most important complication. We therefore designed a modified method of pancreaticojejunostomy using reinforcing suture on the pancreatic stump. METHODOLOGY: The procedure is performed as follow: first, insert a soft rubber catheter into the pancreatic duct, then make reinforcing sutures with 3-0 vicryl. These sutures are parallel to the cut edge of the pancreatic stump, and 5mm from the cut edge. The whole layer of jejunum is sewed to the pancreas including the reinforcing sutures. RESULTS: Between July 2002 and November 2011, 52 consecutive cases of pancreaticoduodenectomy were performed using this method. We used The International Study Group for Pancreatic Surgery (ISGPS) severity grading for postoperative pancreatic fistula (POPF) and delayed gastric emptying (DGE). There was 1 grade A fistula (1.9%), 16 grade B fistulas (30.8%), and 2 grade C fistulas (3.8%). CONCLUSIONS: This method of one layer anastomosis is straightforward and practicable; hence it saves operative time, and is not much affected by lack of familiarity with the surgical technique. Even if it does not actually prevent pancreatic fistula formation, it does prevent the life-threatening complete breakdown of the pancreaticojejunostomy.


Assuntos
Pancreaticojejunostomia/métodos , Suturas , Adulto , Idoso , Feminino , Esvaziamento Gástrico , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Pancreaticojejunostomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Índice de Gravidade de Doença
12.
Ann Surg Treat Res ; 105(6): 404-416, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38076606

RESUMO

Purpose: This study aimed to determine the blood transfusion rates during liver resection by country to prepare a basis for patient blood management policy. Methods: Relevant articles from January 2020 to December 2022 were identified through an electronic database search. Meta-analyses were performed using fixed- or random-effects models. Study heterogeneity was assessed using the Q-test and I2 test. Publication bias was evaluated using funnel plots and Egger's and Begg's tests. Results: Of 104 studies (103,778 participants), the mean transfusion rate was 16.20%. Korea's rate (9.72%) was lower than Western (14.97%) and other Eastern nations (18.61%). Although open surgery rates were alike (approximately 25%) globally, Korea's minimally invasive surgery rate was lower (6.28% vs. ≥10%). Odds ratios (ORs) indicated a higher transfusion risk in open surgeries than minimally invasive surgery, especially in Korea (8.82; 95% confidence interval [CI], 5.55-14.02) compared to other Eastern (OR, 2.57) and Western countries (OR, 2.20). For liver resections due to hepatocellular carcinoma and benign diseases, Korea's rates (10.86% and 15.62%) were less than in Eastern (18.90% and 29.81%) and Western countries (20.15% and 25.22%). Conclusion: Korea showed a lower transfusion rate during liver resection than other countries. In addition to the patient's characteristics, including diagnosis and surgical methods, differences in the medical environment affect blood transfusion rates during liver resection.

13.
Ann Hepatobiliary Pancreat Surg ; 27(4): 342-349, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37661098

RESUMO

Backgrounds/Aims: Liver organoids have emerged as a powerful tool for studying liver biology and disease and for developing new therapies and regenerative medicine approaches. For organoid culture, Matrigel, a type of extracellular matrix, is the most commonly used material. However, Matrigel cannot be used for clinical applications due to the presence of unknown proteins that can cause immune rejection, batch-to-batch variability, and angiogenesis. Methods: To obtain human primary hepatocytes (hPHs), we performed 2 steps collagenase liver perfusion protocol. We treated three small molecules cocktails (A83-01, CHIR99021, and HGF) for reprogramming the hPHs into human chemically derived hepatic progenitors (hCdHs) and used hCdHs to generate liver organoids. Results: In this study, we report the generation of liver organoids in a collagen scaffold using hCdHs. In comparison with adult liver (or primary hepatocyte)-derived organoids with collagen scaffold (hALO_C), hCdH-derived organoids in a collagen scaffold (hCdHO_C) showed a 10-fold increase in organoid generation efficiency with higher expression of liver- or liver progenitor-specific markers. Moreover, we demonstrated that hCdHO_C could differentiate into hepatic organoids (hCdHO_C_DM), indicating the potential of these organoids as a platform for drug screening. Conclusions: Overall, our study highlights the potential of hCdHO_C as a tool for liver research and presents a new approach for generating liver organoids using hCdHs with a collagen scaffold.

14.
Biomaterials ; 303: 122360, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38465578

RESUMO

BACKGROUND & AIMS: Several types of human stem cells from embryonic (ESCs) and induced pluripotent (iPSCs) to adult tissue-specific stem cells are commonly used to generate 3D liver organoids for modeling tissue physiology and disease. We have recently established a protocol for direct conversion of primary human hepatocytes (hPHs) from healthy donor livers into bipotent progenitor cells (hCdHs). Here we extended this culture system to generate hCdH-derived liver organoids for diverse biomedical applications. METHODS: To obtain hCdHs, hPHs were cultured in reprogramming medium containing A83-01 and CHIR99021 for 7 days. Liver organoids were established from hCdHs (hCdHOs) and human liver cells (hLOs) using the same donor livers for direct comparison, as well as from hiPSCs. Organoid properties were analyzed by standard in vitro assays. Molecular changes were determined by RT-qPCR and RNA-seq. Clinical relevance was evaluated by transplantation into FRG mice, modeling of alcohol-related liver disease (ARLD), and in vitro drug-toxicity tests. RESULTS: hCdHs were clonally expanded as organoid cultures with low variability between starting hCdH lines. Similar to the hLOs, hCdHOs stably maintained stem cell phenotype based on accepted criteria. However, hCdHOs had an advantage over hLOs in terms of EpCAM expression, efficiency of organoid generation and capacity for directed hepatic differentiation as judged by molecular profiling, albumin secretion, glycogen accumulation, and CYP450 activities. Accordingly, FRG mice transplanted with hCdHOs survived longer than mice injected with hLOs. When exposed to ethanol, hCdHOs developed stronger ARLD phenotype than hLOs as evidenced by transcriptional profiling, lipid accumulation and mitochondrial dysfunction. In drug-induced injury assays in vitro, hCdHOs showed a similar or higher sensitivity response than hPHs. CONCLUSION: hCdHOs provide a novel patient-specific stem cell-based platform for regenerative medicine, toxicology testing and modeling liver diseases.


Assuntos
Células-Tronco Pluripotentes Induzidas , Medicina Regenerativa , Adulto , Humanos , Animais , Camundongos , Células Cultivadas , Fígado/metabolismo , Organoides , Diferenciação Celular
15.
Pathol Int ; 61(8): 449-55, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21790858

RESUMO

To date, protein profiles for hepatocellular carcinomas and cholangiocarcinomas have not been systematically evaluated and compared with each other in an unbiased way. Thirty-six hepatocellular carcinomas and adjacent normal tissue samples were analyzed using histology-directed, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Four cholangiocarcinomas and adjacent normal tissue samples were also evaluated. Tissue samples were sectioned at 10 µm, with 1-3 sections thaw-mounted on a conductive indium tin oxide-coated glass slide. Sinapinic acid was manually deposited on areas of each tissue section enriched by epithelial cells, either tumor or normal, and mass spectra were acquired using a MALDI-time of flight instrument. According to class prediction analysis, average prediction accuracy in test sets (composed of 18 hepatocellular carcinoma-normal pairs) ranged from 93.0 to 95.8%. Cholangiocarcinomas and hepatocellular carcinomas had different protein profiles, as evidenced by average prediction accuracy of >95% in the test set for all classifiers. Permutation P-values for 0.632 + bootstrap cross validated misclassification rates (at feature selection P < 0.001) were less than 0.05 for predicting p53 immunostaining status. We conclude that MALDI MS profiles may be useful in assisting with the diagnosis and the differential diagnosis of primary liver cancers.


Assuntos
Carcinoma Hepatocelular/secundário , Colangiocarcinoma/secundário , Técnicas Histológicas/métodos , Neoplasias Hepáticas/patologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Proteína Supressora de Tumor p53/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/metabolismo , Colangiocarcinoma/química , Colangiocarcinoma/metabolismo , Feminino , Humanos , Fígado/química , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/química , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Proteômica/métodos , Estudos Retrospectivos , Proteína Supressora de Tumor p53/análise
16.
Am Surg ; 77(3): 322-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21375845

RESUMO

The aims of this study were to clarify the distribution and spread pattern of metastatic nodes and to evaluate the importance of the number, ratio, and location of positive nodes in ampullary adenocarcinoma. We analyzed the clinicopathologic data and survival of 52 patients who received curative pancreatoduodenectomy for ampullary adenocarcinoma between June 1994 and May 2009. Metastatic lymph nodes were found in 32 (61.5%) patients. The median number of evaluated nodes and positive nodes were 26 (range 10-60) and two (range 1-15), respectively. The most commonly involved nodes were the posterior pancreaticoduodenal nodes (26 patients) followed by the anterior pancreaticoduodenal nodes (11 patients). No positive hepatoduodenal and common hepatic artery nodes were found. In univariate analysis, number of positive nodes, and their ratio and location were significantly associated with survival. Only the factor of three or more metastatic nodes had the independent power in predicting a poor outcome in multivariate analysis (P < 0.001). Ampullary adenocarcinoma first spreads to the posterior pancreaticoduodenal nodes and then the anterior nodes. The number of positive lymph nodes, rather than their ratio and location, independently affects survival after curative resection in patients with ampullary carcinoma.


Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Ampola Hepatopancreática , Neoplasias do Ducto Colédoco/mortalidade , Neoplasias do Ducto Colédoco/patologia , Metástase Linfática/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias do Ducto Colédoco/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Pancreaticoduodenectomia , Estudos Retrospectivos , Taxa de Sobrevida
17.
Surg Today ; 41(3): 430-5, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21365432

RESUMO

Carcinoid tumors located in the biliary tree are exceedingly rare, accounting for 0.2%-2% of all gastrointestinal carcinoids. This study describes four cases of carcinoid tumors of the extrahepatic biliary tract. Four carcinoid tumors arising in the common bile duct (Case 1, 59-year-old man), gallbladder (Case 2, 49-year-old man; Case 3, 65-year-old man), and ampulla of Vater (Case 4, 52-year-old woman) were studied. All of the cases were misdiagnosed before surgery as proximal bile duct cancer, stomach cancer with liver metastasis, gallbladder cancer, and adenocarcinoma of ampulla of Vater, respectively. The clinicopathological characteristics and clinical course were reviewed. Treatment depends on the location of the tumor and the extent of the disease. Aggressive surgical therapy with a curative intention therefore offers the only chance for cure and has to be considered whenever possible.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares Extra-Hepáticos , Tumor Carcinoide/diagnóstico , Colecistectomia/métodos , Idoso , Neoplasias dos Ductos Biliares/cirurgia , Tumor Carcinoide/cirurgia , Diagnóstico Diferencial , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
18.
Asian J Surg ; 44(1): 286-291, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32773202

RESUMO

BACKGROUND: Discussions about pancreaticojejunostomy (PJ), which can reduce the incidence of postoperative pancreatic fistula (POPF) in pancreaticoduodenectomy (PD), are ongoing. Here we introduce the surgical technique of PJ performed at our hospital and analyze its safety and advantages. METHODS: We retrospectively analyzed 122 patients who underwent one-layer PJ using reinforcing sutures in PD. PJ was performed with reinforcing sutures on the pancreatic stump, including the insertion of a soft silastic catheter for internal drainage followed by suturing of the pancreas and jejunum with one layer. RESULTS: Of the 122 patients who underwent PJ with this technique, 62 (50.8%) developed POPF. However, 37 (30.3%) had grade A that did not affect the hospital course. Critical POPF occurred in 25 patients: grade B in 20 (16.4%) and grade C in 5 (4.1%). There was no significant difference in the critical POPF patient group according to the pancreas related disease related to pancreatic texture. CONCLUSION: Although this technique cannot prevent POPF, we noted no significant difference in POPF versus other surgical techniques. In addition, this technique, which was designed to increase pancreatic texture, is practical and simple for PJ. Therefore, the inexperienced hepatobiliary and pancreatic surgeon can perform it without major complications.


Assuntos
Pâncreas/cirurgia , Pancreaticoduodenectomia/métodos , Pancreaticojejunostomia/métodos , Técnicas de Sutura , Suturas , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/cirurgia , Cateteres de Demora , Drenagem/métodos , Neoplasias Duodenais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/prevenção & controle , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/prevenção & controle , República da Coreia , Estudos Retrospectivos , Resultado do Tratamento
19.
Asian J Surg ; 44(5): 723-729, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33485767

RESUMO

BACKGROUND: Transduodenal ampullectiomy (TDA) is a surgical local excision method that can be performed in patients with ampullary tumors, but it has not been widely used clinically. Recently, TDA is considered as a good alternative surgical technique in patients who are unable to perform the endoscopic ampullectomy (EA) or pancreaticoduodenectomy (PD) for various reasons. The purpose of this study is to evaluate the surgical outcomes of TDA and the clinicopathological significance of pathologic findings in TDA. METHODS: We reviewed the medical records of 31 patients diagnosed as ampullary tumor and underwent TDA from March 2004 to December 2019 in a single center. RESULTS: All 31 patients were planned to perform TDA, and 4 of them were converted to PPPD due to the marginal status results of frozen biopsy. Of the 31 patients, 19 were diagnosed with malignancy and 12 were diagnosed with benign. Of the 18 patients who were diagnosed as malignancy in final biopsy, only 9 patients (50%) were diagnosed with malignancy on the preoperative endoscopic biopsy. In 15 patients who underwent only TDA for malignancy, there was no recurrence during the follow-up period (mean: 51.1 months, range: 19-137). CONCLUSIONS: In benign ampullary tumor, TDA is a choice of treatment for patients who are unsuitable for endoscopic ampullectomy. TDA may be considered as an alternative operation in highly selective patients with early ampullary cancer (Tis and T1). Further studies on consensus of TDA indication for ampullary tumor will be needed in the future.


Assuntos
Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Ampola Hepatopancreática/cirurgia , Neoplasias do Ducto Colédoco/cirurgia , Humanos , Recidiva Local de Neoplasia/cirurgia , Pancreaticoduodenectomia , Estudos Retrospectivos , Resultado do Tratamento
20.
J Clin Med ; 10(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916209

RESUMO

Background: Cancer development after cholecystectomy remains debatable. We estimated the major cancer incidence rates after cholecystectomy stratified by age and sex. Methods: The records of 408,769 subjects aged >20 years were extracted from the National Health Insurance database from 2008 to 2016. The risks of major cancers were compared between the cholecystectomy and general populations using standardised incidence ratios (SIR). Results: The overall cancer incidence was comparable between cholecystectomy patients and the general population. However, patients aged <65 years who underwent cholecystectomy had a higher cancer risk than those aged ≥65 years and the general population (SIR 2.62; 95% confidence interval [CI] 2.15-3.08; SIR 1.36, 95% CI 1.32-1.40; and SIR 0.90, 95% CI 0.87-0.92 in men and SIR 1.91; 95% CI 1.71-2.10; SIR 1.07; 95% CI 1.03-1.10; and SIR 0.90; 95% CI 0.87-0.94 in women aged 20-34, 35-64, and ≥65 years at cholecystectomy). Colorectal and liver cancer incidences after cholecystectomy were higher than those in the general population regardless of age group and sex (SIR, 1.55 for colorectal cancer in men and women; SIR, 1.25 and 1.51 for liver cancer in men and women, respectively). However, for other major cancers, the risk was higher in patients who underwent cholecystectomy at a younger age than in those who underwent cholecystectomy at an age ≥65 years. Conclusion: Patients with cholecystectomy, especially those undergoing cholecystectomy at a younger age, need preventive strategies based on the cancer type.

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