Targetoid Primary Liver Malignancy in Chronic Liver Disease: Prediction of Postoperative Survival Using Preoperative MRI Findings and Clinical Factors

Objective@#We aimed to assess and validate the radiologic and clinical factors that were associated with recurrence and survival after curative surgery for heterogeneous targetoid primary liver malignancies in patients with chronic liver disease and to develop scoring systems for risk stratification. @*Materials and Methods@#This multicenter retrospective study included 197 consecutive patients with chronic liver disease who had a single targetoid primary liver malignancy (142 hepatocellular carcinomas, 37 cholangiocarcinomas, 17 combined hepatocellular carcinoma-cholangiocarcinomas, and one neuroendocrine carcinoma) identified on preoperative gadoxetic acid-enhanced MRI and subsequently surgically removed between 2010 and 2017. Of these, 120 patients constituted the development cohort, and 77 patients from separate institution served as an external validation cohort. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were identified using a Cox proportional hazards analysis, and risk scores were developed. The discriminatory power of the risk scores in the external validation cohort was evaluated using the Harrell C-index. The Kaplan–Meier curves were used to estimate RFS and OS for the different risk-score groups. @*Results@#In RFS model 1, which eliminated features exclusively accessible on the hepatobiliary phase (HBP), tumor size of 2–5 cm or > 5 cm, and thin-rim arterial phase hyperenhancement (APHE) were included. In RFS model 2, tumors with a size of > 5 cm, tumor in vein (TIV), and HBP hypointense nodules without APHE were included. The OS model included a tumor size of > 5 cm, thin-rim APHE, TIV, and tumor vascular involvement other than TIV. The risk scores of the models showed good discriminatory performance in the external validation set (C-index, 0.62–0.76). The scoring system categorized the patients into three risk groups: favorable, intermediate, and poor, each with a distinct survival outcome (all log-rank p < 0.05). @*Conclusion@#Risk scores based on rim arterial enhancement pattern, tumor size, HBP findings, and radiologic vascular invasion status may help predict postoperative RFS and OS in patients with targetoid primary liver malignancies.

Effectiveness and stability of robot-assisted anastomosis in minimally invasive pancreaticoduodenectomy

Purpose@#Reconstruction using robotic assistance in pancreaticoduodenectomy (PD) was expected to be an effective means to overcome the limitations of laparoscopic surgery. To our knowledge, few comparative reports exist on the outcomes of totally laparoscopic PD (TLPD) and robot-assisted laparoscopic PD (RLPD). This retrospective study aimed to analyze the surgical results of TLPD and RLPD in a high-volume pancreatic center. @*Methods@#We analyzed the surgical results of consecutive patients who underwent a minimally invasive PD for malignant or benign periampullary lesions between January 2016 and May 2020. Forty-three TLPD patients and 49 RLPD patients were enrolled. @*Results@#There were no significant differences in the demographic characteristics between the 2 groups except for tumor size, which was significantly larger in the RLPD group than in the TLPD group (mean, 3.1 cm vs. 2.5 cm; P = 0.035).The RLPD group had shorter whole operative times (mean, 400.4 minutes vs. 352.2 minutes; P = 0.003) and shorter anastomosis times than the TLPD group (mean, 94.5 minutes vs. 54.9 minutes; P < 0.001). There was no significant difference between the 2 groups in the rate of pancreatic fistulas, morbidity, and mortality. However, a significantly lower wound infection rate was found in the RLPD group relative to the TLPD group (0% vs. 9.3%, P = 0.038). @*Conclusion@#RLPD showed the advantage of reducing the operation time compared to TLPD as well as technical feasibility and safety.

Effectiveness and stability of robot-assisted anastomosis in minimally invasive pancreaticoduodenectomy

Purpose@#Reconstruction using robotic assistance in pancreaticoduodenectomy (PD) was expected to be an effective means to overcome the limitations of laparoscopic surgery. To our knowledge, few comparative reports exist on the outcomes of totally laparoscopic PD (TLPD) and robot-assisted laparoscopic PD (RLPD). This retrospective study aimed to analyze the surgical results of TLPD and RLPD in a high-volume pancreatic center. @*Methods@#We analyzed the surgical results of consecutive patients who underwent a minimally invasive PD for malignant or benign periampullary lesions between January 2016 and May 2020. Forty-three TLPD patients and 49 RLPD patients were enrolled. @*Results@#There were no significant differences in the demographic characteristics between the 2 groups except for tumor size, which was significantly larger in the RLPD group than in the TLPD group (mean, 3.1 cm vs. 2.5 cm; P = 0.035).The RLPD group had shorter whole operative times (mean, 400.4 minutes vs. 352.2 minutes; P = 0.003) and shorter anastomosis times than the TLPD group (mean, 94.5 minutes vs. 54.9 minutes; P < 0.001). There was no significant difference between the 2 groups in the rate of pancreatic fistulas, morbidity, and mortality. However, a significantly lower wound infection rate was found in the RLPD group relative to the TLPD group (0% vs. 9.3%, P = 0.038). @*Conclusion@#RLPD showed the advantage of reducing the operation time compared to TLPD as well as technical feasibility and safety.

Serum level of visfatin can reflect the severity of inflammation in patients with acute cholecystitis

Purpose@#Visfatin is a key cytokine released from the pe ripheral blood mononuclear cells (PBMCs) as well as adipose tissue, and it is involved in immune response as well as inflammation. In this study, we investigated whether the serum visfatin level could be a prognostic factor for predicting the severity of inflammation in patients with acute cholecystitis. @*Methods@#We examined the blood samples and gallbladder specimens from patients who underwent laparoscopic cholecystectomy for either acute (n = 18) or chronic cholecystitis (n = 18). We determined the visfatin levels of these samples using various procedures such as real-time polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. @*Results@#The patients with acute cholecystitis exhibited higher mRNA expression of visfatin in PBMCs, higher serum levels of visfatin, and increased protein expression of visfatin in the gallbladder specimens than in patients with chronic cholecystitis. In the in vitro model of acute cholecystitis, the mRNA expression of visfatin showed the fastest increase among the other pro-inflammatory mediators studied, including interleukin (IL)-10, tumor necrosis factor-, IL-6, intracellular adhesion molecule-1, and ascular cell adhesion molecule-1. Inhibition of visfatin using siRNA abrogated the inhibitory effects of lipopolysaccharide (LPS) on the expression of ABCG1 in GBECs, suggesting that visfatin is significantly involved in the LPS-driven suppression of ABCG1. @*Conclusion@#Taken together, we concluded that visfatin is a pro-inflammatory mediators that is upregulated during acute cholecystitis and is expected to be increased within a short time after inflammation. Therefore, measuring the serum level of visfatin would be helpful in predicting the inflammatory severity in the patients with acute cholecystitis.

Serum level of visfatin can reflect the severity of inflammation in patients with acute cholecystitis

Purpose@#Visfatin is a key cytokine released from the pe ripheral blood mononuclear cells (PBMCs) as well as adipose tissue, and it is involved in immune response as well as inflammation. In this study, we investigated whether the serum visfatin level could be a prognostic factor for predicting the severity of inflammation in patients with acute cholecystitis. @*Methods@#We examined the blood samples and gallbladder specimens from patients who underwent laparoscopic cholecystectomy for either acute (n = 18) or chronic cholecystitis (n = 18). We determined the visfatin levels of these samples using various procedures such as real-time polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. @*Results@#The patients with acute cholecystitis exhibited higher mRNA expression of visfatin in PBMCs, higher serum levels of visfatin, and increased protein expression of visfatin in the gallbladder specimens than in patients with chronic cholecystitis. In the in vitro model of acute cholecystitis, the mRNA expression of visfatin showed the fastest increase among the other pro-inflammatory mediators studied, including interleukin (IL)-10, tumor necrosis factor-, IL-6, intracellular adhesion molecule-1, and ascular cell adhesion molecule-1. Inhibition of visfatin using siRNA abrogated the inhibitory effects of lipopolysaccharide (LPS) on the expression of ABCG1 in GBECs, suggesting that visfatin is significantly involved in the LPS-driven suppression of ABCG1. @*Conclusion@#Taken together, we concluded that visfatin is a pro-inflammatory mediators that is upregulated during acute cholecystitis and is expected to be increased within a short time after inflammation. Therefore, measuring the serum level of visfatin would be helpful in predicting the inflammatory severity in the patients with acute cholecystitis.

Isolation of Secretome with Enhanced Antifibrotic Properties from miR-214-Transfected Adipose-Derived Stem Cells

BACKGROUND: Secretome refers to the total set of molecules secreted or surface-shed by stem cells. The limitations of stem cell research have led numerous investigators to turn their attention to the use of secretome instead of stem cells. In this study, we intended to reinforce antifibrotic properties of the secretome released from adipose-derived stem cells (ASCs) transfected with miR-214. METHODS: We generated miR-214-transfected ASCs, and extracted the secretome (miR214-secretome) from conditioned media of the transfected ASCs through a series of ultrafiltrations. Subsequently, we intravenously injected the miR-214-secretome into mice with liver fibrosis, and determined the effects of miR-214-secretome on liver fibrosis. RESULTS: Compared with that by naïve secretome, liver fibrosis was ameliorated by intravenous infusion of miR-214-secretome into mice with liver fibrosis, which was demonstrated by significantly lower expression of fibrosis-related markers (alpha-smooth muscle actin, transforming growth factor-β, and metalloproteinases-2) in the livers as well as lower fibrotic scores in the special stained livers compared with naïve secretome. The infusion of miR-214-secretome also led to lesser local and systemic inflammation, higher expression of an antioxidant enzyme (superoxide dismutase), and higher liver proliferative and synthetic function. CONCLUSION: MicroRNA-214 transfection stimulates ASCs to release the secretome with higher antifibrotic and anti-inflammatory properties. miR-214-secretome is thus expected to be one of the prominent ways of overcoming liver fibrosis, if further studies consistently validate its safety and efficiency.

Antioxidant action of hypoxic conditioned media from adipose-derived stem cells in the hepatic injury of expressing higher reactive oxygen species

PURPOSE: Almost all liver diseases are known to be accompanied by increased levels of reactive oxygen species (ROS), regardless of the cause of the liver disorder. However, little is known about the role of hypoxic conditioned media (HCM) in the view of pro-oxidative/antioxidative balance. METHODS: Normoxic conditioned media (NCM) and HCM were obtained after culturing adipose-derived stem cells in 20% O₂ or 1% O₂ for 24 hours, respectively. Their effects on the expression of various markers reflecting pro-oxidative/antioxidative balance were investigated in both in vitro (thioacetamide-treated AML12 cells) and in vivo (partially hepatectomized mice) models of liver injury, respectively. RESULTS: HCM treatment induced the higher expression of antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase than did NCM in the in vitro model of liver injury. We also found that HCM increased the expression of nuclear factor erythroid 2-related factor (NRF2). The in vivo models of liver injury consistently validated the phenomenon of upregulated expression of antioxidant enzymes by HCM. CONCLUSION: We thus could conclude that HCM provides protection against ROS-related toxicity by increasing the expression of antioxidant enzymes, in part by releasing NRF2 in the injured liver.

Laparoscopic end-to-end biliary reconstruction with T-tube for transected bile duct injury during laparoscopic cholecystectomy

PURPOSE: This report describes the laparoscopic end-to-end biliary reconstruction with T-tube for transected bile duct injury (BDI) during laparoscopic cholecystectomy. METHODS: We performed a retrospective descriptive analysis for all patients with a transected BDI at a single institution. We collected and analyzed data for injury site and type, reconstruction methods, conversion rate, previous intervention, and outcomes. RESULTS: Between January 2014 and December 2017, 2,901 patients underwent laparoscopic cholecystectomy at a single institution. Among them, 8 patients experienced a transected BDI during laparoscopic cholecystectomy, so the surgeon performed laparoscopic end-to-end biliary reconstruction with T-tube. Our patient series consisted of 6 women (75%) and 2 men (25%) with a mean age of 48.3 years (median, 49 years; range, 29–77 years). Two cases were converted to open surgery. The most common injured site was the common bile duct (5 of 8, 62.5%). The most common injury type, using Bismuth's classification system, was type I (3 of 8, 37.5%). The mean operating time was 136.8 minutes (median, 135.0 minutes; range, 0–180.0 minutes). The mean hospital stay was 7.0 days (median, 4.5 days, range: 3.0–21.0 days). The mean follow-up was 36.4 months (median, 34.0 months; range, 16.0–63.0 months). We observed one postoperative complication during the follow-up period. The patient had an anastomosis site leakage and was cured after reoperation. CONCLUSION: Laparoscopic end-to-end biliary reconstruction with T-tube for transected BDI during laparoscopic cholecystectomy seems to be safe and feasible in selected patients. However, long-term follow-up to identify complications from bile duct stricture remains important.

ABO Incompatible Living Donor Liver Transplantation: A Single Center Experience / 대한이식학회지

BACKGROUND: This study examined the outcomes of ABO incompatible living donor liver transplantation (LDLT). The changes in the immunologic factors that might help predict the long term outcomes were also studied. METHODS: Twenty-three patients, who underwent ABO incompatible LDLT from 2010 to 2015, were reviewed retrospectively. The protocol was the same as for ABO compatible LDLT except for the administration of rituximab and plasma exchange. The clinical outcomes and immunologic factors, such as isoagglutinin titer and cluster of differentiation 20+ (CD20+) lymphocyte levels were reviewed. RESULTS: The center showed a 3-year survival of 64% with no case of antibody-mediated rejection. When transplantation-unrelated mortalities (for example, traffic accidents and myocardial infarction) were removed from statistical analysis, the 3-year survival was 77.8%. Although isoagglutinin titers continued to remain at low levels, the CD20+ lymphocyte levels recovered to the pre-Rituximab levels at postoperative one year. CONCLUSIONS: As donor shortages continue, ABO incompatible liver transplantation is a feasible method to expand the donor pool. On the other hand, caution is still needed until more long-term outcomes are reported. Because CD20+ lymphocytes are recovered with time, more immunologic studies will be needed in the future.

Clinical outcome of 1,000 consecutive cases of liver transplantation: a single center experience

PURPOSE: The aim of this study was to analyze survival outcomes in 1,000 consecutive liver transplantations (LTs) performed at a single institution from 1993 to April 2017. METHODS: The study population was divided into 2 groups based on donor type: deceased donor LT (DDLT; n = 181, 18.1%) and living donor LT (LDLT; n = 819; 81.9%), and into 3 periods based on the number of cases (first 300 cases, middle 300 cases, last 400 cases). RESULTS: Infection was the most common cause of death, accounting for 34.8% (95 of 273). Mortality due to hepatocellular carcinoma recurrence occurred most frequently between 1 and 5 years after transplantation. Mortality rate by graft rejection was highest between 5 and 10 years after transplantation. And mortality by de novo malignancy occurred most frequently after 10 years after transplantation. The patient survival rates for the entire population at 5 and 10 years were 74.7%, and 68.6%, respectively. There was no difference in survival rate between the LDLT and DDLT groups (P = 0.188). Cause of disease, disease severity, case period, and retransplantation had a significant association with patient survival (P = 0.002, P = 0.031, P = 0.003, and P = 0.024, respectively). CONCLUSION: Surgical techniques and perioperative management for transplant patients have improved and undergone standardization. Controlling perioperative infection and managing patients with HCC as LT candidates will result in better outcomes.

Prognostic factors after curative resection hepatocellular carcinoma and the surgeon's role

PURPOSE: Patient, surgical, and tumor factors affect the outcome after surgical resection for hepatocellular carcinoma (HCC). The surgical factors are only modifiable by the surgeon. We reviewed our experience with curative resection for HCC in terms of surgical factors. METHODS: After analyses of the prospectively collected clinical data of 256 consecutive patients undergoing surgical resection for HCC, prognostic factors for disease-free survival (DFS) and overall survival (OS) were identified; all patients were stratified by tumor diameters > or 5 cm. CONCLUSION: Tumor recurrence after liver resection for HCC depends on tumor status, bleeding, and transfusions, which subsequently lead to poor patient survival. Surgeons can help improve the prognosis of patients by minimizing blood loss and transfusion, particularly in patients with larger tumors.

Recurrence of Multiple Focal Nodular Hyperplasia in a Young Male Patient / 대한소화기학회지

Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor that is usually found in women. Diagnosis of FNH mainly depends on imaging studies such as color Doppler flow imaging, computed tomography, and magnetic resonance imaging. It is characterized by the presence of stellate central scar and is nowadays incidentally diagnosed with increasing frequency due to advances in radiologic imaging technique. FNH typically presents as a single lesion in 70% of cases and generally does not progress to malignancy or recur after resection. Herein, we report a case of a young male patient with recurrent multiple FNH who underwent surgical resection for presumed hepatic adenoma on computed tomography.

A Comparison between Endoscopic Thyroidectomy Performed by the Axillary Approach and by a Conventional Thyroidectomy / 대한내분비외과학회지

PURPOSE: Endoscopic thyroidectomy has not become a widespread procedure because of limited advantages to its use. We have performed endoscopic thyroidectomies by use of the axillary approach. The purpose of this study was to determine the efficacy of this surgical procedure. METHODS: Between June of 2002 and December of 2002, 17 patients underwent an endoscopic thyroidectomy by use of the axillary approach while 11 patients underwent a conventional thyroidectomy. Each procedure was performed by one surgeon under general anesthesia. Patients with thyroid carcinoma at the preoperative diagnosis or who received a bilateral thyroidectomy were excluded. We compared the age, size of the tumor, postoperative pain (48 hours after surgery), surgical time, cosmetic result, length of hospital stay, and paresthesia. Statistical analysis was determined by use of the Mann-Whitney test and the chi-square test using SPSS software. RESULTS: The mean age of the patients was 46.6 years who received a conventional thyroiodectomy and 32.9 years who underwent the axillary approach. The size of the tumor was 3.1 cm for patients who received conventional thyroiodectomy and 3.3 cm for patients who underwent the axillary approach. The operation time was 80.91±16.1 (65~100) minutes for the conventional thyroiodectomy and 135.3± 34.6 (80~210) minutes for the axillary approach. The difference between the two approaches in regards to parameters such as postoperative pain, parethesia, and total hospital days was negligible. The degree of satisfaction was 2.7±0.8 for the conventional thyroiodectomy and 1.1±0.3 for the axillary approach. CONCLUSION: While conventional thyroidectomy still offers an advantage in terms of surgical time, performance of endoscopic thyroidectomy by the axillary approach has an advantage in producing better cosmetic results. Although a multitude of patients will be necessary to follow in further studies, the use of endoscopic thyroidectomy by the axillary approach could become the procedure of choice by offering better cosmetic results to young patients who present with thyroid nodules.

Laparoscopic Management for Intestinal Obstruction Caused by Meckel's Diverticulum

Meckel's diverticulum is the most frequent congenital anomaly of the gastrointestinal tract with an incidence of 2% for the general population, and it is one of the frequent causes of small bowel obstruction in young population. A 30-year-old male and a 20-year-old female presented with a short history of wide spread abdominal pain and distension. Radiologic studies revealed severe partial small bowel obstruction. Diagnostic laparoscopy was performed and the small bowel obstruction was observed to result from Meckel's diverticulum. The adhesive bands between Meckel's diverticulum and the mesentery of the ileum were lysed and the diverticulum was resected with an Endo-GIA stapler. The patients were discharged without complications and they tolerated a regular diet. Laparoscopy is a useful diagnostic and therapeutic tool for the younger patients showing small bowel obstruction with an unclear etiology.

Sigmoid Colon Cancer with Isolated Metastasis to the Left Kidney

We report the case of a 63-year-old female with sigmoid colon cancer and isolated metastasis to the left kidney at the time of initial diagnosis. An anterior resection of the sigmoid colon and a left nephrectomy were performed. Three cycles of adjuvant chemotherapy consisting of oxaliplatin, 5-fluorouracil, and leucovorin were given, but two months after the surgery, multiple metastases of the liver were detected on a CT scan. The patient refused further treatment and died 5 months after the discovery of an isolated metastasis. An isolated metastasis to the kidney is very rare in clinical practice. A nephrectomy for kidney metastasis has no effect on survival and quality of life, and a nephrectomy may also compromise the choice of chemotherapy agents that require renal clearance; thus, a careful evaluation of renal function is necessary before a nephrectomy. At present, kidney metastasis should be regarded as an advanced metastatic disease, and aggressive chemotherapy, including target therapy, should prolong survival and improve the quality of life. However, when a synchronous or a metachronous renal tumor is suspected, a nephrectomy should be performed for accurate diagnosis and treatment.