Epigenetic modulation inhibits epithelial-mesenchymal transition-driven fibrogenesis and enhances characteristics of chemically-derived hepatic progenitors.

Purpose: One of the novel cell sources of cell-based liver regenerative medicine is human chemically-derived hepatic progenitors (hCdHs). We previously established this cell by direct hepatocyte reprogramming with a combination of small molecules (hepatocyte growth factor, A83-01, CHIR99021). However, there have been several issues concerning the cell's stability and maintenance, namely the occurrences of epithelial-mesenchymal transition (EMT) that develop fibrotic phenotypes, resulting in the loss of hepatic progenitor characteristics. These hepatic progenitor attributes are thought to be regulated by SOX9, a transcription factor essential for hepatic progenitor cells and cholangiocytes. Methods: To suppress the fibrotic phenotype and improve our long-term hCdHs culture technology, we utilized the epigenetic modulating drugs DNA methyltransferase inhibitor (5-azacytidine) and histone deacetylase inhibitor (sodium butyrate) that have been reported to suppress and revert hepatic fibrosis. To confirm the essential role of SOX9 to our cell, we used clustered regularly interspaced short palindromic repeats-interference (CRISPRi) to repress the SOX9 expression. Results: The treatment of only 5-azacytidine significantly reduces the fibrosis/mesenchymal marker and EMT-related transcription factor expression level in the early passages. Interestingly, this treatment also increased the hepatic progenitor markers expression, even during the reprogramming phase. Then, we confirmed the essential role of SOX9 by repressing the SOX9 expression with CRISPRi which resulted in the downregulation of several essential hepatic progenitor cell markers. Conclusion: These results highlight the capacity of 5-azacytidine to inhibit EMT-driven hepatic fibrosis and the significance of SOX9 on hepatic progenitor cell stemness properties.

Lignin-derived carbon quantum dot/PVA films for totally blocking UV and high-energy blue light.

Excessive exposure to UV and high-energy blue light (HEBL) can cause fatal eye and skin injuries. As a result, it is crucial to protect our bodies from UV and HEBL radiation. To achieve complete blocking of UV and HEBL, we developed a lignin-derived carbon quantum dot (L-CQD)/polyvinyl alcohol (PVA) film. L-CQD was synthesized from lignin, a waste woody biomass, and then blended with a PVA matrix to create a flexible L-CQD/PVA film. Thanks to simultaneous UV and HEBL absorption characteristics and bright color of L-CQD, the PVA film with 0.375 wt% L-CQD demonstrated outstanding blocking efficiency: 100 % in UV-C, UV-B, and UV-A, and at least 99.9 % in HEBL. It also exhibited a 44 % increase in lightness and a 12 % enhancement in transparency compared to lignin/PVA film. The film's ability to block UV and HEBL was further demonstrated by reducing >40 % UV-induced ROS formation in both cancerous and normal cell lines (Hs 294T, HeLa, CCD-986sk, and L929), as well as by blocking blue laser diode (LD) and LED. Since the L-CQD/PVA film is simple to produce, environmentally friendly, flexible, and thermally stable, it is suitable for use as a protective coating against sunlight and harmful emissions from IT devices.

Ex vivo kidney machine perfusion: meta-analysis of randomized clinical trials.

BACKGROUND: Machine perfusion is an organ preservation strategy used to improve function over simple storage in a cold environment. This article presents an updated systematic review and meta-analysis of machine perfusion in deceased donor kidneys. METHODS: RCTs from November 2018 to July 2023 comparing machine perfusion versus static cold storage in kidney transplantation were evaluated for systematic review. The primary outcome in meta-analysis was delayed graft function. RESULTS: A total 19 studies were included, and 16 comparing hypothermic machine perfusion with static cold storage were analysed. The risk of delayed graft function was lower with hypothermic machine perfusion (risk ratio (RR) 0.77, 95% c.i. 0.69 to 0.86), even in kidneys after circulatory death (RR 0.78, 0.68 to 0.90) or brain death (RR 0.73, 0.63 to 0.84). Full hypothermic machine perfusion decreased the risk of delayed graft function (RR 0.69, 0.60 to 0.79), whereas partial hypothermic machine perfusion did not (RR 0.92, 0.69 to 1.22). Normothermic machine perfusion or short-term oxygenated hypothermic machine perfusion preservation after static cold storage was equivalent to static cold storage in terms of delayed graft function and 1-year graft survival. CONCLUSION: Hypothermic machine perfusion reduces delayed graft function risks and normothermic approaches show promise.

A systematic review and meta-analysis of blood transfusion rates during liver resection by country.

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.

Gastric insufflation and surgical view according to mask ventilation method for laparoscopic cholecystectomy: a randomized controlled study.

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.

Enhancing generation efficiency of liver organoids in a collagen scaffold using human chemically derived hepatic progenitors.

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.

Human chemically-derived hepatic progenitors (hCdHs) as a source of liver organoid generation: Application in regenerative medicine, disease modeling, and toxicology testing.

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.

Dual-signal optical detection of Lead(II) ions (Pb2+) using galloyl group-functionalized polydiacetylene.

In this study, we developed a novel galloyl group-functionalized polydiacetylene (Galloyl-PDA) sensor for colorimetric and fluorescent detection of Pb2+. Among three types of Galloyl-PDA vesicles prepared by changing the ratio of newly synthesized galloyl group-conjugated 10,12-pentacosadiynoic acid (Galloyl-PCDA) and matrix 10,12-tricosadinoic acid (TCDA), the blue Galloyl-PDA vesicles with 1:9 molar ratio of Galloyl-PCDA:TCDA showed the most dramatic color transitions to red with colorimetric response (CR) value of 46.66 ± 1.373% within 5 min upon addition of 50 µM Pb2+. However, they didn't exhibit any color change upon interaction with other heavy metals. Since the terminal galloyl moieties of the Galloyl-PDA vesicles could form coordination bonds with Pb2+, the Galloyl-PDA vesicles were stressed and showed obvious blue-to-red chromatic transitions. Besides, because the Galloyl-PDA vesicles exhibited nonfluorescent-to-fluorescent transitions, a linear response in colorimetric and fluorescent signals was observed in the range of 0-10 µM and 0.025-1 µM, respectively. From the colorimetric and fluorescent results, the limit of detection (LOD) was determined to be 1.329 µM and 0.068 µM, which is 8-fold and 12-fold better sensitivity than those of previously reported methods, respectively. Furthermore, the capability of our PDA sensor for detection of Pb2+ in tap water, river water, and human serum was validated with excellent precision and recovery rates of 97.14-100.0%, 99.05-103.3%, and 100.7-106.7%, respectively. As our PDA dual-signal sensor for Pb2+ is rapid, sensitive, specific, and detectable by the naked eye, this approach holds great promise for application in point-of-care testing (POCT).

Non-Renal Risk Factors for Chronic Kidney Disease in Liver Recipients with Functionally Intact Kidneys at 1 Month.

Chronic kidney disease (CKD) is a critical complication of liver transplants, of which non-renal risk factors are not fully understood yet. This study aimed to reveal pre- and post-transplant risk factors for CKD (<60 mL/min/1.73 m2), examining liver recipients with functionally intact kidneys one month after grafting using nationwide cohort data. Baseline risk factors were analyzed with multivariable Cox regression analyses and post-transplant risk factors were investigated with the time-dependent Cox model and matched analyses of time-conditional propensity scores. Of the 2274 recipients with a one-month eGFR ≥ 60 mL/min/1.73 m2, 494 (22.3%) developed CKD during a mean follow-up of 36.6 ± 14.4 months. Age, female sex, lower body mass index, pre-transplant diabetes mellitus, and lower performance status emerged as baseline risk factors for CKD. Time-dependent Cox analyses revealed that recurrent hepatocellular carcinoma (HR = 1.93, 95% CI 1.06−3.53) and infection (HR = 1.44, 95% CI 1.12−1.60) were significant post-transplant risk factors for CKD. Patients who experienced one of those factors showed a significantly higher risk of subsequent CKD compared with the matched controls who lacked these features (p = 0.013 for recurrent hepatocellular carcinoma, and p = 0.003 for infection, respectively). This study clarifies pre- and post-transplant non-renal risk factors, which lead to renal impairment after LT independently from patients' renal functional reserve.

Therapeutic applications of gene editing in chronic liver diseases: an update.

Innovative genome editing techniques developed in recent decades have revolutionized the biomedical research field. Liver is the most favored target organ for genome editing owing to its ability to regenerate. The regenerative capacity of the liver enables ex vivo gene editing in which the mutated gene in hepatocytes isolated from the animal model of genetic disease is repaired. The edited hepatocytes are injected back into the animal to mitigate the disease. Furthermore, the liver is considered as the easiest target organ for gene editing as it absorbs almost all foreign molecules. The mRNA vaccines, which have been developed to manage the COVID-19 pandemic, have provided a novel gene editing strategy using Cas mRNA. A single injection of gene editing components with Cas mRNA is reported to be efficient in the treatment of patients with genetic liver diseases. In this review, we first discuss previously reported gene editing tools and cases managed using them, as well as liver diseases caused by genetic mutations. Next, we summarize the recent successes of ex vivo and in vivo gene editing approaches in ameliorating liver diseases in animals and humans. [BMB Reports 2022; 55(6): 251-258].

Elimination of Reprogramming Transgenes Facilitates the Differentiation of Induced Pluripotent Stem Cells into Hepatocyte-like Cells and Hepatic Organoids.

Hepatocytes and hepatic organoids (HOs) derived from human induced pluripotent stem cells (hiPSCs) are promising cell-based therapies for liver diseases. The removal of reprogramming transgenes can affect hiPSC differentiation potential into the three germ layers but not into hepatocytes and hepatic organoids in the late developmental stage. Herein, we generated hiPSCs from normal human fibroblasts using an excisable polycistronic lentiviral vector based on the Cre recombinase-mediated removal of the loxP-flanked reprogramming cassette. Comparing the properties of transgene-carrying and transgene-free hiPSCs with the same genetic background, the pluripotent states of all hiPSCs were quite similar, as indicated by the expression of pluripotent markers, embryonic body formation, and tri-lineage differentiation in vitro. However, after in vitro differentiation into hepatocytes, transgene-free hiPSCs were superior to the transgene-residual hiPSCs. Interestingly, the generation and hepatic differentiation of human hepatic organoids (hHOs) were significantly enhanced by transgene elimination from hiPSCs, as observed by the upregulated fetal liver (CK19, SOX9, and ITGA6) and functional hepatocyte (albumin, ASGR1, HNF4α, CYP1A2, CYP3A4, and AAT) markers upon culture in differentiation media. Thus, the elimination of reprogramming transgenes facilitates hiPSC differentiation into hepatocyte-like cells and hepatic organoids with properties of liver progenitor cells. Our findings thus provide significant insights into the characteristics of iPSC-derived hepatic organoids.

Laparoscopic cholecystectomy for left-sided gallbladder.

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.

Association of Microbial Dysbiosis with Gallbladder Diseases Identified by Bile Microbiome Profiling.

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.

Antioxidant and anti-aging carbon quantum dots using tannic acid.

Overexpression of collagenase, elastase, and tyrosinase is caused by external factors such as ultraviolet (UV) radiation and stress, resulting in wrinkle formation and freckles through the loss of skin elasticity and skin pigmentation. In this study, we developed novel carbon quantum dots (CQDs) with antioxidant and anti-aging properties using tannic acid as a carbon source through a simple microwave-assisted pyrolysis method. The synthesized tannic acid-derived CQDs (T-CQDs) showed bright blue fluorescence (QY = 28.2 ± 4.0%), exhibiting maximum emission at 430 nm under 350 nm excitation. Even though small amount of the T-CQDs (3µg ml-1) was used, they exhibited excellent free radical scavenging ability (82.8 ± 4.3%). Also, the T-CQDs (10µg ml-1) revealed remarkable inhibitory activity against skin aging-related collagenase (77.6 ± 4.8%), elastase (52.6 ± 1.0%), and tyrosinase (44.2 ± 1.3%), demonstrating their antioxidant and anti-aging effects. Furthermore, their antioxidant and anti-aging properties were superior to those of tannic acid, L-ascorbic acid, and quercetin used as positive controls. Finally, the T-CQDs effectively suppressed UV-induced reactive oxygen species generation by 30% at the cellular levels and showed high cell viability (99.7 ± 0.8%) even at 500µg ml-1. These results demonstrate that the T-CQDs with superior antioxidant, anti-aging properties, and low cytotoxicity can be utilized as novel anti-aging materials in cosmetic and nanomedicine fields.

Glutathione-decorated fluorescent carbon quantum dots for sensitive and selective detection of levodopa.

Levodopa has been a standard drug for treating Parkinson's disease since the 1960s, but it has caused many side effects such as wearing-off, motor fluctuation, and dystonia. In this work, we developed glutathione-conjugated carbon quantum dots (GSH-CQDs) as a novel fluorescent sensor for sensitive and selective detection of levodopa. The GSH-CQDs were prepared by EDC/NHS coupling reaction of glutathione (GSH) with amine-functionalized CQDs (N-CQDs) synthesized using meta-phenylenediamine and ethylenediamine. The synthesized GSH-CQDs emitted bright green fluorescence with a high quantum yield (QY) of 22.42 ± 6.88%. However, upon the addition of levodopa to GSH-CQDs under alkaline conditions, the fluorescence of GSH-CQDs was quenched. Since levodopa is converted to dopaquinone in an alkaline environment, it is presumed that thiol groups of GHS-CQDs form covalent bonds with dopaquinone, causing fluorescence quenching through photoinduced electron transfer. Therefore, as the concentration of levodopa increased, the fluorescence intensity of GSH-CQDs was gradually decreased. Under optimal conditions, a linear response was observed in the range of 0.05-1 µM, and limit of detection (LOD) was determined to be 0.057 µM. The GSH-CQDs exhibited high specificity to levodopa over other non-target biological substances, quinone derivatives, and Parkinson's medications. Furthermore, the capability of this GSH-CQDs sensor for monitoring levodopa in human serum were validated with excellent precision and recovery rates of 100.20-103.33%.

De Novo Cancer Incidence after Cholecystectomy in Korean Population.

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.

Transduodenal ampullectomy for ampullary tumor.

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.

Folic Acid Functionalized Carbon Dot/Polypyrrole Nanoparticles for Specific Bioimaging and Photothermal Therapy.

Polypyrrole nanoparticles (PPy-NPs) with excellent near-infrared absorption are commonly used as photothermal therapy (PTT) agents; however, PTT using PPy-NPs has a limitation in that it is difficult to maximize their therapeutic effect because of the lack of specific targeting. In this study, to overcome the difficulty of targeting, folic acid functionalized carbon dots (FA-CDs) with bright green fluorescence properties were combined with carboxylated PPy-NPs via the EDC/NHS coupling reaction to yield a PTT imaging agent. The synthesized FA-CD/PPy-NPs with excellent photostability performed folate receptor (FR) positive HeLa cancer cell imaging by green fluorescence signals of FA-CDs and exhibited high cell viability (above 90%) even at 500 µg/mL. The viability of HeLa cells incubated with 200 µg/mL FA-CD/PPy-NPs was dramatically decreased to 25.02 ± 1.85% by NIR laser irradiation, through photothermal therapeutic effects of FA-CD/PPy-NPs with high photothermal conversion efficiency (η = 40.80 ± 1.54%). The cancer cell death by FA-CD/PPy-NPs was confirmed by fluorescence imaging of FA-CDs as well as live/dead cell staining assay (calcein-AM/PI). These results demonstrate that the FA-CD/PPy-NPs can be utilized as multifunctional theranostic agents for specific bioimaging and treatment of FR-positive cancer cells.

One-layer pancreaticojejunostomy using reinforcing sutures in pancreaticoduodenectomy: A single surgeon's experience with 122 cases.

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.

Preoperative CT anthropometric measurements and pancreatic pathology increase risk for postoperative pancreatic fistula in patients following pancreaticoduodenectomy.

Postoperative pancreatic fistula (POPF) is a common complication following pancreaticoduodenectomy (PD). However, risk factors for this complication remain controversial. We conducted a retrospective analysis of 107 patients who underwent PD. POPF was diagnosed in strict accordance with the definition of the 2016 update of pancreatic fistula from the International Study Group on Pancreatic Fistula (ISGPF). Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for POPF. A total of 19 (17.8%) subjects of pancreatic fistula occurred after PD, including 15 (14.1%) with grade B POPF and 4 (3.7%) with grade C POPF. There were 33 (30.8%) patients with biochemical leak. Risk factors for POPF (grade B and C) were larger area of visceral fat (odds ratio [OR], 1.40; p = 0.040) and pathology other than pancreatic adenocarcinoma or pancreatitis (OR, 12.45; p = 0.017) in the multivariate regression analysis. This result could assist the surgeon to identify patients at a high risk of developing POPF.