Kaohsiung Chang Gung Memorial Hospital Research Articles

A Shape Approximation for Medical Imaging Data.

This study proposes a shape approximation approach to portray the regions of interest (ROI) from medical imaging data. An effective algorithm to achieve an optimal approximation is proposed based on the framework of Particle Swarm Optimization. The convergence of the proposed algorithm is derived under mild assumptions on the selected family of shape equations. The issue of detecting Parkinson’s disease (PD) based on the Tc-99m TRODAT-1 brain SPECT/CT images of 634 subjects, with 305 female and an average age of 68.3 years old from Kaohsiung Chang Gung Memorial Hospital, Taiwan, is employed to demonstrate the proposed procedure by fitting optimal ellipse and cashew-shaped equations in the 2D and 3D spaces, respectively. According to the visual interpretation of 3 experienced board-certified nuclear medicine physicians, 256 subjects are determined to be abnormal, 77 subjects are potentially abnormal, 174 are normal, and 127 are nearly normal. The coefficients of the ellipse and cashew-shaped equations, together with some well-known features of PD existing in the literature, are employed to learn PD classifiers under various machine learning approaches. A repeated hold-out with 100 rounds of 5-fold cross-validation and stratified sampling scheme is adopted to investigate the classification performances of different machine learning methods and different sets of features. The empirical results reveal that our method obtains 0.88 ± 0.04 classification accuracy, 0.87 ± 0.06 sensitivity, and 0.88 ± 0.08 specificity for test data when including the coefficients of the ellipse and cashew-shaped equations. Our findings indicate that more constructive and useful features can be extracted from proper mathematical representations of the 2D and 3D shapes for a specific ROI in medical imaging data, which shows their potential for improving the accuracy of automated PD identification.

The TMPRSS6 variant (SNP rs855791) affects iron metabolism and oral iron absorption - a stable iron isotope study in Taiwanese women.

Genome wide studies have associated TMPRSS6 rs855791 (2321 C>T) with iron status and hepcidin. It is unclear whether this polymorphism affects iron absorption. We administered standardized ricebased test meals containing 4 mg of labeled 57Fe or 58Fe as FeSO4 on alternate days in non-anemic Taiwanese women (n=79, 44 TT variant, 35 CC variant). Fractional iron absorption was measured by erythrocyte incorporation of the tracers 14 days after administration. Compared to the CC variant, iron and transferrin saturation were lower (P=0.001; P<0.001, respectively) and serum hepcidin/transferrin saturation and serum hepcidin/serum iron ratios were higher (P=0.042; P=0.088, respectively) in the TT variant. Serum hepcidin did not differ between the groups (P=0.862). Geometric mean (95% Confidence Interval [CI]) fractional iron absorption, corrected to a serum ferritin of 15 μg/L, was 26.6% (95% CI: 24.0-29.5) in the CC variant and 18.5% (95% CI: 16.2-21.1) in the TT variant (P=0.002). Overall, predictors of iron absorption were: serum ferritin (P<0.001); genetic variant (P=0.032); and hepcidin (P<0.001). In the models by variant, in the CC variant the model explained 67-71% of variability in absorption and serum ferritin was the only significant predictor (P<0.001); while in the TT variant, the model explained only 35-43% of variability, and hemoglobin (P=0.032), soluble transferrin receptor (P=0.004) and hepcidin (P<0.001) were significant predictors. Women with the TMPRSS6 rs855791 (2321 C>T) polymorphism show altered iron homeostasis which affects oral iron absorption and may increase their risk for iron deficiency. The trial was registered as clinicaltrials gov. Identifier: NCT03317873, and funded by the Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, (grant CMRPG8F0721) and ETH Zurich, Switzerland.

Association between cancer-related fatigue and traditional Chinese medicine body constitution in female patients with breast cancer

BackgroundCancer-related fatigue (CRF) is a common psychosomatic problem in breast cancer patients. Traditional Chinese medicine (TCM) has been used to address symptoms in patients with CRF. Identification of the specific constitution in TCM is essential for personalized care. AimTo explore the relationship between fatigue and specific constitutions in breast cancer. Experimental procedureWe conducted a cross-sectional study in all breast cancer patients at Kaohsiung Chang Gung Memorial Hospital in Taiwan. The severity of fatigue was determined using the Brief Fatigue Inventory-Taiwanese (BFI-T) form. TCM patterns were determined using the Body Constitution Questionnaire (BCQ). The relationship between constitution and fatigue was analyzed using logistic regression. ResultsWe recruited 110 breast cancer patients with fatigue (mean age: 55 ± 11 years). The mean duration of breast cancer was 17.4 months. The major constitution among these patients with fatigue was Yang-Qi deficiency (50%). Phlegm-Stasis syndrome was correlated with a duration of breast cancer of more than 18 months (p = 0.02). Out of all participants, 42.7% (n = 47) reported clinically significant fatigue (BFI-T score ≥4). According to logistic regression, the score of Yang-Qi deficiency [odds ratio (OR): 3.5, 95% confidence interval (CI): 1.49–8.21, p < 0.01] was also associated with clinically significant fatigue. ConclusionYang-Qi deficiency is associated with clinically significant fatigue in breast cancer patients. However, the association of Phlegm-Stasis syndrome and fatigue as disease duration increases cannot be ignored. Further studies are needed to determine whether treating both constitutions integrating TCM treatment can alleviate patients’ fatigue symptoms.

The Clinical Trend of Leprosy from 2000 to 2016 in Kaohsiung, a Major International Harbor City in Taiwan, Where Leprosy is Almost Eradicated.

Leprosy is a socially stigmatized granulomatous skin disease caused by Mycobacterium leprae. Due to improvements in medicine and hygiene in Taiwan, the incidence is very low, up to one dozen per year; however, leprosy has never been eradicated due to the increased numbers of immigrants from Southeast Asia. This study aimed to characterize the clinical and histopathological features of patients with leprosy in the context of near elimination. Fifteen cases of pathologically proven leprosy were identified from 2000 to 2016 in Kaohsiung Chang Gung Memorial Hospital. The clinical presentations, demographic details, treatment responses, and disease outcomes were reviewed. The mean age was 46 years (range: 26-73 years). Eight cases were native Taiwanese, while 6 cases and 1 case involved foreign workers from Indonesia and Thailand, respectively. The diagnosis was made 3-6 months on average after skin lesions appeared. The most common clinical subtype was lepromatous leprosy (n = 7). Ten patients were multibacillus microscopically. Three cases were deported. The remaining 12 patients received dapsone and rifampicin for 12 months without recurrence to date. In the near leprosy-eradicated country, early diagnosis and physician vigilance are critical in disease control. Immigrants from endemic countries require strict and professional dermatological examinations and regular follow-up.

Higher gestational weight gain and lower serum estradiol levels are associated with increased risk of preeclampsia after in vitro fertilization.

To assess the association of preeclampsia with serum estradiol (E2) and progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) administration during controlled ovarian hyperstimulation (COH) for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). This was a hospital-based cohort study using clinical data from the Kaohsiung Chang Gung Memorial Hospital Obstetric and Neonatal Database (KCGMHOND) from Jan 1, 2001 to December 1, 2018. A total of 622 women who had live births after fresh IVF/ICSI-ET during the study period met our inclusion criteria. Twenty-eight women (4.5%) met the diagnostic criteria for preeclampsia. However, women in the preeclampsia group had a significantly higher body weight at delivery (80.5 vs. 70.0kg, p<0.001) and gestational weight gain (19.6 vs. 13.0kg, p=0.002) and had lower use of ICSI (10.7% vs. 29.9%, p=0.021). We performed logistic regression analysis of the relationship of patient and treatment characteristics with preeclampsia. The crude ORs indicated that young female age≤34, not using ICSI, E2 on hCG day<1200pg/mL and gestational weight gain>20kg were associated with preeclampsia. After adjustment for confounding, the only factors that remained significant were E2 on hCG day<1200pg/mL (aOR=4.634, 95% CI=1.061-20.222), and gestational weight gain>20kg (aOR: 13.601, 95% CI: 3.784, 48.880). For women receiving IVF/ICSI, lower estradiol hormone levels on the day of hCG administration and higher pregnancy weight gain are related with subsequent preeclampsia.

Incidence of interval colorectal cancer: A tertiary hospital report

AbstractColorectal cancer (CRC) remains the leading cause of death in Taiwan despite mandatory CRC screening programs for early detection. The development of CRC between periods of follow‐up remains a Taiwanese health and economic burden. This study aimed to investigate the relationship between consequent progression of polyps and interval CRC and identify potential risk factors. This retrospective chart review study reviewed 1671 CRC patients between 1 January 2002 and 31 December 2018, in Kaohsiung Chang Gung Memorial Hospital for interval CRC analysis. Interval CRC is defined as CRC diagnosed within 5 years after a negative colonoscopy. We further analyzed potential risk factors associated with interval CRC such as sex, age, underlying disease, and previous pathologic type of polyps by univariate and multivariate analyses. A total of 44 patients developed interval CRC in this study (2.63%). Ten patients were from the proctologist division and five from the gastroenterology department. Mean diagnostic interval was 919.45 ± 547.78 days in male and 897.87 ± 586.14 days in female patients. Multivariate analysis showed that right‐side colon polyp demonstrated independent risk factors for interval CRC development in our observation (P &lt; .001; hazard ratio (HR), 3.897; 95% confidence interval (CI), 1.934‐7.780). In conclusion, interval CRC prevalence in a cohort is 2.63%. Location of polyps over the right colon is relevant to interval CRC occurrence.

Live-interactive teledermatology program in Taiwan: One-year experience serving a district hospital in rural Taitung County

Population aging and unequal accessibility of health care are increasingly important in developed countries. One strategy to overcome these issues is utilizing telemedicine, which is recently made possible technologically by the advancement of internet speed, high speed zooming cameras, and the information storages. In Taiwan, the telemedicine is granted legally by the amendment for Taiwan's Physician Act in 2018. Kaohsiung Chang Gung Memorial Hospital (Kaohsiung CGMH) is the first hospital in Taiwan to provide the telemedicine service connecting to Cheng Kung Branch of Taitung Hospital since Nov 2018. Consultation services from Dermatology, ENT, and Ophthalmology have been delivered in the live-interactive and face to face module every week. Dermatology consultation comprises the majorities. In the first year, there were totally 426 dermatology consultation services. Eczema, fungal infections, and scabies infestation were the three most common diseases in the beginning. The disease diagnosis became more diverse after several months, including some ready-to-treat diseases pending correct diagnosis, such as pediculosis, psoriasis, and urticaria. Coupled with dermoscopic images, diseases such as hair loss, pediculosis capitis, skin tumor, and scabies, were diagnosed promptly. The subjective patient improvement rate was more than 75% year-round and the case closure rate was more than 85% year-round. Teledermatology is a promising approach to serve the remote medical-underprivileged regions. The teledermatology is anticipated to help underserved regions, nursing homes, prisons, and in situations with severe pandemic infections, such as COVID-19.

Planned conservative management of placenta increta and percreta with prophylactic transcatheter arterial embolization and leaving placenta in situ for women who desire fertility preservation

IntroductionThe objective of our study was to demonstrate planned conservative management of placenta increta and percreta in a single tertiary center. MethodsFrom April 2005 to July 2019, patients with placenta increta and percreta were managed conservatively at the Kaohsiung Chang Gung Memorial Hospital in Taiwan. The severity of placenta invasion was diagnosed by magnetic resonance imaging (MRI). After delivery of the neonate, prophylactic transcatheter arterial embolization (TAE) was performed immediately. The placenta was left in situ and prophylactic antibiotics were administered during hospitalization. The patient profiles, outcomes, and complications were retrospectively reviewed. ResultsBased on the MRI findings, twenty-one patients with placenta increta or percreta were included. With prophylactic TAE, the mean surgical blood loss was 854.7 ± 478.2 mL. The mean natural resorption time of residual placenta was 4.69 ± 1.65 months. Regarding maternal complications, 4 patients (19%) had delayed postpartum hemorrhage (PPH), 12 patients (57.1%) developed postpartum infections, 3 patients (14.3%) progressed to sepsis, 4 patients (19%) underwent surgical evacuation, and 4 patients (19%) underwent hysterectomy. No maternal mortality was reported. Main neonatal complications were prematurity and respiratory distress. Regarding fertility, 16 (76.1%) patients had return of menstruation, and one (4.7%) had a subsequent pregnancy resulting in a live birth. DiscussionPlanned conservative management with prophylactic TAE and leaving placenta in situ is feasible and safe for women with placenta increta or percreta who desire fertility preservation. Delayed PPH and postpartum infection are common complications after conservative treatment.

Comparison of prevalence and associated factors of depressive disorder between patients with head and neck cancer and those with lung cancer at a tertiary hospital in Taiwan: a cross-sectional study

ObjectiveDepression is a common comorbidity in cancer patients. This study aimed to compare the prevalence and associated factors of depressive disorder between patients with head and neck cancer (HNC) and...

Panel-derived TMB and immune-related GEP are associated with the response to immune checkpoint inhibitors (ICIs) in urothelial cancers.

e17047 Background: Tumor mutational burden (TMB) and gene expression profile (GEP) have emerged as potential biomarkers for the prediction of response to the immune checkpoint inhibitor (ICI) treatment. An interferon-g gene signature was shown recently to predict ICI response in a pan-cancer setting. For TMB, not only did TMB-high patients experience better clinical outcome with ICI, but panel-derived TMB was also shown to be comparable to the gold standard, TMB derived from whole exome sequencing. Here, we evaluate possible correlations between panel-derived TMB, as well as immune-related GEP, with ICI response in urothelial cancers. Methods: FFPE tumor tissues from 30 patients with urothelial cancers who had previously received ICI as monotherapies or combination with chemotherapies at Kaohsiung Chang Gung Memorial Hospital were retrospectively tested for targeted next-generation sequencing (ACTOnco) and quantitative PCR-based GEP (ACTTME), for the identification of nonsynonymous variants across 440 cancer-associated genes and expression levels of &gt; 90 immune-related genes, respectively. TMB was calculated by using the sequenced regions of ACTOnco to estimate the number of somatic nonsynonymous mutations per megabase of all protein-coding genes. For ACTTME, Cq values were normalized to internal control before group analysis. RECIST criteria were used to categorize tumor response to the treatment. Results: Patients were defined as responders (CR/PR) and non-responders (SD/PD) according to the RECIST criteria. In the ICI monotherapy cohort, the responders (n = 8) had significantly higher TMB than non-responders (n = 15) (Median 16.2 muts/Mb vs. 6.5 muts/Mb, p= 0.0035). In contrast, for the cohort receiving ICI combination therapy, several genes implicated in hypoxia (HIF1A), suppressive cell types (Treg &amp; MDSC) and immune checkpoint (PD-L2) were significantly elevated ( p&lt; 0.05) in the non-responder group by 2 to 8 folds. Conclusions: Despite the fact that the cohort size is small, this study showed panel-derived TMB, as well as immune-related GEP, can potentially serve as predictive biomarkers to identify urothelial cancer patients for immune checkpoint inhibitor therapy.

Comparison of tenofovir and entecavir in the development of acute kidney injury in cirrhotic chronic hepatitis B patients with refractory ascites.

Tenofovir disoproxil fumarate (TDF) and entecavir are effective antiviral medications that are recommended as first-line monotherapies for the treatment of chronic hepatitis B (CHB) infection, including decompensated liver cirrhosis with ascites. Acute kidney injury (AKI) commonly occurs in patients with cirrhosis and ascites. The aim of this study was to compare the development of AKI during TDF and entecavir treatment of CHB patients with cirrhotic refractory ascites. From January 2011 to April 2017, we identified patients who were diagnosed with cirrhosis with refractory ascites and received TDF or entecavir treatments at Kaohsiung Chang Gung Memorial Hospital. AKI was defined as an increase in serum creatinine of more than 0.3 mg/dL or 1.5-fold from baseline. All episodes of AKI were recorded and compared between those who received TDF and entecavir. A total of 111 patients were enrolled in this retrospective study, of which 22 patients were treated with TDF and 89 were treated with entecavir. Patients with AKI episodes had a higher proportion of TDF treatment (P = 0.01), male (P = 0.023), hepatocellular carcinoma (P = 0.007), admission (P = 0.045), and mortality (P = 0.018). Logistic regression analysis illustrated that TDF treatment of patients with comorbidity was an independent risk factor for the development of AKI [odds ratio (OR), 3.756; 95% confidence interval (CI), 1.293-10.912; P = 0.015] and hepatorenal syndrome (OR, 7.651; 95% CI, 1.697-34.508; P = 0.008). TDF treatment is a risk factor for AKI and HRS development in cirrhotic patients with refractory ascites in comparison with entecavir treatment, especially in patients with comorbidity.

Therapeutic hypothermia for pediatric refractory status epilepticus May Ameliorate post-status epilepticus epilepsy

BackgroundTo compare the clinical characteristics and outcomes of pediatric patients with refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) who received therapeutic hypothermia (TH) plus anticonvulsants or anticonvulsants alone. MethodsTwo-medical referral centers, retrospective cohort study. Pediatric Intensive Care Unit (PICU) at Taoyuan Chang Gung Children's hospital and Kaohsiung Chang Gung Memorial Hospital. We reviewed the medical records of 23 patients with RSE/SRSE who were admitted to PICU from January 2014 to December 2017. Of these, 11 patients received TH (TH group) and 12 patients did not (control group). ResultsThe selective endpoints were RSE/SRSE duration, length of PICU stay, and Glasgow Outcome Scale (GOS) score. We applied TH using the Artic Sun® temperature management system (target temperature, 34–35 °C; duration, 48–72 h). Of the 11 patients who received TH, 7 had febrile infection-related epilepsy syndrome (FIRSE), one had Dravet syndrome, and three had traumatic brain injury. The TH group had significantly shortern seizure durations than did the control group (hrs; median (IQR) 24(40) vs. 96(90), p < 0.05). Two patients in the TH group died of pulmonary embolism and extreme brain edema. The length of PICU stay was similar between the groups (days; median (IQR) 30(42) v.s 30.5(30.25)). The TH group had significantly better long-term outcomes than did the control group (GOS score, median (IQR) 4(2) v.s 3 (0.75), p = 0.01∗). The TH group had a significantly lower incidence of later chronic refractory epilepsy than did the control group (TH v.s non-TH, 5/11 (45%) v.s. 12/12(100%), p < 0.01). ConclusionsTH effectively reduced the seizure burden in patients with RSE/SRSE. Our findings support that for patients with RSE/SRSE, TH shortens the seizure duration, ultimately reducing the occurrence of post-status epilepticus epilepsy and improving patients’ long-term survival.

Outcome analysis of pediatric hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease associated with rapid clinical deterioration and the need for intensive care; therefore, it is essential to identify clinical parameters related to mortality and establish prognostic factors correlated with unfavorable outcome in high risk patients whose treatment may fail. Between January 2004 and December 2018, a total of 51 pediatric patients (less than 18 years old) who fulfilled the diagnostic criteria of HLH-2004 with documented results of bone marrow investigations at Kaohsiung Chang Gung Memorial Hospital were enrolled. The treatment protocol was based on hemophagocytic lymphohistiocytosis-94 (HLH-94) and HLH-2004. We retrospectively reviewed electronic medical records (EMR) including clinical features, length of intensive care unit (ICU) stay, serological tests, microscopic reports of bone marrow examination, and ultrasound examination reports at diagnosis to identify prognostic factors. The patients were divided into four groups based on etiology; these included infection associated hemophagocytic syndrome (IAHS), macrophage activation syndrome (MAS), malignancy associated hemophagocytic lymphohistiocytosis (MA-HLH), and idiopathic hemophagocytic lymphohistiocytosis (IHLH) to identify differences among the groups. Out of 51 patients enrolled, 27 patients had IAHS, 12 MAS, 8 MA-HLH, and 4 IHLH. The median age at diagnosis was 7 years. The overall mortality rate was 15.7%(there was no mortality in the MA-HLH group); the mean length of ICU stay was 6±20.8 days. Longer activated partial thromboplastin time (aPTT) (p=0.007), lower sodium concentration (p=0.0007), and higher creatinine (p=0.032) and aspartate aminotransferase (AST) (p=0.017) were significantly related to mortality. Multivariate Cox regression analysis demonstrated that aPTT (p=0.045, HR=1.03, 95% CI=1.0-1.1) was an independent risk factor for mortality. The receiver operating characteristic (ROC) curve showed that aPTT longer than 44.35s was the cutoff value predicting mortality, with a sensitivity and specificity of 72% and 66.7%, respectively. MA-HLH had the lowest mortality rate, as most children died from the underlying malignant disease and not from HLH. Impaired liver and renal functions were related to mortality. Prolonged aPTT>44.35s is a strong predictive factor for mortality.

Clinical Characteristics and Predictors of Mortality in Critically Ill Influenza Adult Patients.

Severe influenza is associated with high morbidity and mortality. The aim of this study was to investigate the factors affecting the clinical outcomes of critically ill influenza patients. In this retrospective study, we enrolled critically ill adult patients with influenza at the Kaohsiung Chang Gung Memorial Hospital in Taiwan. We evaluated the demographic, clinical, and laboratory findings and examined whether any of these measurements correlated with mortality. We then created an event-based algorithm as a simple predictive tool using two variables with statistically significant associations with mortality. Between 2015 and 2018, 102 critically ill influenza patients (median age, 62 years) were assessed; among them, 41 (40.1%) patients died. Of the 94 patients who received oseltamivir therapy, 68 (72.3%) began taking oseltamivir 48 h after the onset of illness. Of the 102 patients, the major influenza-associated complications were respiratory failure (97%), pneumonia (94.1%), acute kidney injury (65.7%), adult respiratory distress syndrome (ARDS) (51%), gastrointestinal bleeding (35.3%), and bacteremia (16.7%). In the multivariate regression model, high lactate levels, ARDS, acute kidney injury, and gastrointestinal bleeding were independent predictors of mortality in critically ill influenza patients. The optimal lactate level cutoff for predicting mortality was 3.7 mmol/L with an area under curve of 0.728. We constructed an event-associated algorithm that included lactate and ARDS. Fifteen (75%) of 20 patients with lactate levels 3.7 mmol/L and ARDS died, compared with only 1 (7.7%) of 13 patients with normal lactate levels and without ARDS. We identified clinical and laboratory predictors of mortality that could aid in the care of critically ill influenza patients. Identification of these prognostic markers could be improved to prioritize key examinations that might be useful in determining patient outcomes.

Evaluation of the effect of the elective blastocyst-stage embryo transfer and freezing strategy on the abandonment of frozen embryos under the Taiwan National Assisted Reproduction Act

PurposeTo evaluate the relationship between elective blastocyst transfer, freezing strategy, and the abandonment of frozen embryos with a storage time limit of 10 years as specified in the National Assisted Reproduction Act of Taiwan.MethodsThis two-phase retrospective cohort study was conducted at a single tertiary center, Kaohsiung Chang Gung Memorial Hospital (KCGMH), in 2019. Participants were selected from a data registry containing 4167 fresh IVF cycles, including phase 1 cycles from 1999 to 2009 and phase 2 cycles from 2010 to 2014, at KCGMH.ResultsIn phase 1, embryo abandonment was associated with the production of more mature oocytes and embryos, the freezing of more embryos, young female age, blastocyst transfer, and positive pregnancy results. After adjustment for confounding factors, only positive pregnancy results (adjusted odds ratio [aOR] 4.38, 95% confidence interval [CI] 3.17, 6.04), the freezing of ≥ 2 embryos (aOR 3.68, 95% CI 3.10, 4.38), the production of ≥ 6 embryos (aOR 1.68, 95% CI 1.03, 2.73), and the use blastocyst transfer (aOR 2.46, 95% CI 1.64, 3.69) remained significantly associated with embryo abandonment. The factors associated with embryo abandonment or possible abandonment were similar in phase 2.ConclusionFor elective blastocyst stage transfer and a freezing strategy performed according to the Taiwan National Assisted Reproduction Act, a young female age ≤ 35 with positive pregnancy status due to the original IVF treatment, the production of ≥ 6 embryos, and the cryopreservation of ≥ 2 blastocysts may increase the likelihood of abandoning embryos in the future.

Elevated levels of serum urokinase plasminogen activator predict poor prognosis in hepatocellular carcinoma after resection

BackgroundUrokinase plasminogen activator (uPA) is an extracellular matrix-degrading protease that is involved in the invasiveness and progression of cancer. There is good evidence that uPA expression is a clinically relevant biomarker in some solid tumors, but its role in hepatocellulcar carcinoma (HCC) is uncertain. We evaluated the prognostic value of serum uPA before surgery in HCC patients receiving curative resection.MethodsSerum uPA levels were determined by enzyme-linked immunosorbent assay in 282 HCC patients who received complete liver resections at Kaohsiung Chang Gung Memorial Hospital. Overall survival (OS) curves were constructed using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional -hazards regression model was used to identify independent prognostic factors. The median follow-up time was 52 months.ResultsPatients with higher pretreatment serum uPA (≥1 ng/ml) had significantly shorter OS (p = 0.002). Patients with liver cirrhosis, hypoalbuminemia, and thrombocytopenia were significantly more likely to present with elevated uPA levels. Multivariate Cox regression analyses indicated that high pretreatment serum uPA [hazard ratio (HR), 1.848, p = 0.006], vascular invasion (HR, 2.940, p < 0.001), and pathology stage III/IV (HR, 3.517, p < 0.001) were independent prognostic factors for OS. In further stratified analyses, the combination of serum uPA and AFP had more capacity to predict OS.ConclusionsWe conclude that uPA is a clinically relevant biomarker in HCC patients receiving curative resection, with higher expression of uPA being associated with higher mortality. This also highlights the potential utility of uPA as a therapeutic target for improved treatment strategies.

The Pre- and Postoperative FIB-4 Indexes Are Good Predictors to the Outcomes of HBV-Related HCC Patients after Resection.

Background and Aim Liver fibrosis is associated with the prognosis of patients with hepatocellular carcinoma (HCC) after resection. The fibrosis-4 (FIB-4) index is an accurate and noninvasive marker to determine the degree of liver fibrosis. Here, we evaluated the effect of pre- and postoperative FIB-4 index in predicting the outcomes after resection of HCC in patients who have chronic hepatitis B (CHB) infection. Methods A total of 534 CHB patients with HCC who received curative hepatectomy between 2001 and 2016 at Kaohsiung Chang Gung Memorial Hospital, Taiwan, were enrolled in this study. The impact of the FIB-4 index (preoperative and the 1st year after operation) on overall survival (OS) and recurrence-free survival (RFS) was evaluated. Results There was a significant association between the preoperative FIB-4 index and Metavir fibrosis stage (p < 0.01). The multivariate analysis showed that preoperative FIB‐4 > 2 is an independent risk factor for RFS and OS after HCC curative resection [hazard ratio (HR), 1.902; 95% CI, 1.491–2.460; p < 0.001, and HR, 2.207; 95% CI, 1.420–3.429; p < 0.001, respectively]. Notably, preoperative FIB-4 is also an independent risk factor for RFS (HR, 1.219; p = 0.035) in noncirrhotic patients. Furthermore, patients had deteriorated FIB-4 1 year after operation [definition: the value (the 1st year FIB‐4 after operation minus preoperative FIB‐4) > 1] and had an adverse outcome in RFS and OS (p < 0.001, both). Conclusion The pre and postoperative FIB-4 indexes are useful clinical markers to predict the prognosis in HBV-HCC patients after curative hepatectomy.

Preventive Role of mTOR Inhibitor in Post–Kidney Transplant Urothelial Carcinoma

BackgroundThere is little evidence about whether mammalian target of rapamycin (mTOR) inhibitor could prevent post–kidney transplant (KT) urothelial carcinoma (UC) or not. The aim of this study is to analyze the role of mTOR inhibitor add-on in tacrolimus-based kidney transplant recipients. MethodThe data were obtained from the Kaohsiung Chang Gung Memorial Hospital using the Chang Gung Research Database and retrospectively reviewed from January 2000 to December 2015. Patients then were categorized into 2 groups: group FK (more than 2-year tacrolimus [FK] prescription) and group FK + mTOR inhibitor (more than 2-year tacrolimus plus at least 6-month continued sirolimus prescription). The primary end point is post-KT UC development. The secondary end point is mTOR inhibitor add-on effect on renal function deterioration episode. ResultsThere were 140 patients with tacrolimus-based immunosuppressant (group FK) and 82 patients with tacrolimus-based and add-on mTOR inhibitor regimen (group FK + mTOR inhibitor). The follow-up duration, sex distribution, and combined mycophenolate mofetil rate are similar in both groups. Younger age, lower tacrolimus trough level, lower UC incidence, and longer KT-to-UC interval were observed. Short- to intermediate-term results revealed noninferior graft outcome by creatinine level or creatinine deterioration. ConclusionsIn our preliminary result, mTOR inhibitor add-on in patients with tacrolimus-based regimen revealed less post-KT UC occurrence. In addition, noninferior graft outcome was also observed. In Taiwan, a high UC prevalence area, mTOR inhibitor add-on strategy can be considered as a preventive strategy for UC after KT.

The efficacy of limited endoscopic sphincterotomy plus endoscopic papillary large balloon dilation for removal of large bile duct stones

BackgroundThe removal of large bile duct stones (> 15 mm) by conventional endoscopic sphincterotomy (EST) and endoscopic papillary balloon dilation (EPBD) can be challenging, requiring mechanical lithotripsy (ML) in addition to EST or EPBD. The primary complication of ML is basket and stone impaction, which can lead to complications such as pancreatitis and cholangitis. The present study aims to investigate the efficacy of limited EST plus endoscopic papillary large balloon dilation (EST-EPLBD) for large bile duct stone extraction with an extent of cutting < 1/2 the length of the papillary mound.MethodsWe enrolled 185 patients with ≥15 mm bile duct stones who received EST, EPLBD and limited EST-EPLBD treatment from January 1, 2010 to February 28, 2018, at Kaohsiung Chang Gung Memorial Hospital (Kaohsiung, Taiwan). All patients were categorized into three groups: EST group (n = 31), EPLBD group (n = 96), and limited EST-EPLBD group (n = 58). The primary outcome variables were the success rate of complete stone removal and complications.ResultsThe limited EST-EPLBD group exhibited a higher success rate of the first-session treatment compared with the EST and EPLBD groups (98.3% vs. 83.9% vs. 86.5%; P = 0.032) but required a longer procedure time (32 (12–61) min vs. 23.5 (17–68) min vs. 25.0 (14–60) min; P = 0.001). The need for ML during the procedure was 4 (12.9%) in the EST group, 10 (10.4%) in the EPLBD group and 2 (3.4%) in the limited EST-EPLBD group. Post-procedure bleeding in the EST group was more common than that in the limited EST-EPLBD group (9.7% vs. 0%; P = 0.038). Furthermore, dilated bile duct was the only risk factor for bile duct stone recurrence in the limited EST-EPLBD group.ConclusionsLimited EST-EPLBD exhibits a higher success rate but requires marginally longer procedure time for the first-session treatment. Furthermore, dilated bile duct is the only risk factor for bile duct stone recurrence in patients undergoing limited EST-EPLBD.

Effect of do-not-resuscitate orders on patients with sepsis in the medical intensive care unit: a retrospective, observational and propensity score-matched study in a tertiary referral hospital in Taiwan

ObjectiveThe aim of this study was to determine whether do-not-resuscitate (DNR) orders affect outcomes in patients with sepsis admitted to intensive care unit (ICU).DesignThis is a retrospective observational study.ParticipantsWe enrolled...