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A new section on the approach to diagnostic histological interpretation, is the overture to this chapter on inherited and developmental disorders. This initial section is split chronologically into the early neonatal and infantile period and later childhood and adulthood; with the intention of reflecting clinical practice as closely and succinctly as possible. Disorders of the biliary tree, bile formation and secretion, and hepatocyte metabolism are the core of this chapter, a merger of chapters 3 and 4 of the previous edition. Considerations on the pathogenetic and/or clinical overlap between developmental, genetic and metabolic disorders were the rationale behind this change. The complexity of hepatocyte metabolism is reflected into the miriad of related pathological conditions. Recent technological advances, particularly in genomics in the last five years, have resulted in a plethora of new entities and changes in terminology, challenging the authors to balance detail and application to clinical practice. Tables and figures from previous editions have been largely kept due to their quality and contemporary relevance, whilst new ones have been added to accommodate new advances (e.g. classification of mitochondrial disorders), a compromise to bridge between the two editions for the accustomed reader. Liver involvement in immunodeficiency and miscellaneous disorders precede the final section on anatomical anomalies. Vascular anomalies are now included in the chapters on vascular disorders.

Introduction Fistula Laser Closure (FiLAC) is a method that was originally applied in the treatment of perianal fistulas. Because of promising results, diode lasers were later on used to treat pilonidal sinus disease in a method called sinus Laser Closure (SiLaC). The aim of this study is to compare between SiLaC and Limberg flap in management of pilonidal disease. Methods A prospective, nonrandomized comparative study. A short-term follow-up of 71 patients with pilonidal disease was analyzed (24 operated on using the SiLaC technique and 47 using the Limberg technique). With a primary outcome is healing rate and recurrence and a secondary outcome is other measures i.e. complications, hospital stay and postoperative pain. Results The median operative time in the SiLaC group was 26.45 ± 5.41 min (20–35 min) and in the Limberg group 58.63 ± 7.42 min (50–75 min). In the SiLaC group, the primary healing was achieved in 23 out of 24 patients (95.8%) with a total complication rate of 20.83%. There were two cases of recurrence after initial healing in each group. Conclusion Sinus laser Closure (SiLaC) is comparable to Limberg flap technique in the terms of healing rate and recurrence with better outcome regarding operative time, hospital stay and post-operative pain.

Background: Ventilation limitation has a significant adverse effects on cardiovascular function and tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease (COPD). High flow nasal cannula (HFNC) improve ventilation by washing out the anatomical dead space and providing oxygen at constant concentration. This study aimed to examine the effects of HFNC on the exercise performance and hemodynamic status in COPD patients. Methods: Fifteen patients with COPD performed two constant load exercise tests (CLET) at the 70% of maximum workload achieved at a previous incremental exercise test on arm ergometer. The CLET were performed with HFNC and with nasal cannula (NC) in random order. The hemodynamics parameters of subjects during exercises were measured by a bioelectrical impedance device. The tissue oxygenation status (oxygenated hemoglobin, deoxygenated hemoglobin (hHb), total hemoglobin) was measured by a near infrared spectrophotometer. Results: The exercise duration was longer for HFNC test than NC test (962.9 ± 281.7 s, vs 823.9 ± 184.9 s, p < 0.05). At the end of CLET, the PetCO2 was lower for HFNC than NC (29.3 ± 5.1 mmHg vs 32.1 ± 5.5 mmHg, p 0.05), stroke volume (NC:73.5 ± 21.0 vs HFNC 67.5 ± 16.3 ml, p > 0.05). The changes of hHb in muscle tissues was significantly lower in HFNC test than that in NC test (p

Background Cancer-associated venous thromboembolism (VTE) is a distinct pathological entity with much higher incidence and unique risk factors compared to general VTE. A previous study reported that cancer associated-VTE incidence in Taiwan is much lower than that reported for western countries and also lower than our anecdotal observations. To address this issue further, we initiated an investigation locally using a more detailed approach than used previously with comprehensive review of medical records to gain new insight into the incidence and risk factors for cancer-associated VTE. Methods Medical records of all adult patients with lung, pancreatic and gastric cancers, and lymphoma diagnosed from January 2011 to December 2013 in National Taiwan University Hospital indexed through the local cancer registry database were reviewed. VTE patients were identified through diagnosis coding and comprehensive medical chart review. Results Among 5620 consecutive lung, gastric and pancreatic cancer, and lymphoma patients, VTE was diagnosed in 246 (4.4%). Overall VTE incidence was 36.3 per 1000 patient-year. Multivariate analysis showed that not only high but also low body mass index (BMI) was associated with VTE risk with different cutoff levels by gender. Mildly to moderately anemic patients were at higher risk of VTE. Activated partial thromboplastin time (aPTT) had proportionally and reversely correlation to VTE risk. Conclusion We reported higher incidence of cancer associated VTE in Taiwan. Low BMI and short aPTT were found to be related to higher VTE risk that was not reported before.

Background/purpose To investigate the clinical characteristics of intraocular lymphoma and to evaluate two protocols of intravitreal methotrexate injection. Methods A retrospective chart review was conducted of newly-diagnosed intraocular lymphoma patients between January 2013 and January 2018 at National Taiwan University Hospital. Patients were divided into two groups. In Group A, intravitreal methotrexate was administered weekly for the initial 8 weeks, every 2 weeks for the following 12 weeks, and then monthly for 7 months. In Group B, intravitreal methotrexate was administered twice a week for the initial 2 weeks, weekly for the subsequent 2 weeks, once every 2 weeks for the next 1 month, and monthly for the last 10 months. Results A total of 12 patients were analyzed in the study; seven of these patients were allocated to Group A. Differences in the overall survival and progression-free survival between the two groups did not yield statistical significance. The median visual acuity was improved from LogMAR 0.46 to LogMAR 0.30 with borderline significance in Group A (p = 0.053). Two of seven patients in Group A and five of five patients in Group B developed punctate keratitis during intravitreal methotrexate injection treatment. Conclusion Intravitreal methotrexate is an effective and repeatable treatment for intraocular lymphoma. A new protocol with reduced frequency of intravitreal injections as shown in this study could potentially produce similar results without a worse prognosis, along with a decrease in the incidence of keratitis.

Background/objective Sigmoid volvulus is the most common type of volvulus. Its epidemiological features, as well as its management, differ between developed and developing countries. This work aims to analyze the epidemiological features thus allowing to compare them to the rest of the “volvulus belt’’ and assess the surgical management of sigmoid volvulus in Tunisia. Method This is a retrospective review of 64 patients with sigmoid volvulus treated in the General Surgery department of Jendouba Hospital. January 2005–December 2019. Results 64 patients were treated for acute sigmoid volvulus. The sex ratio male to female ratio was 5.4/1 with male predominance. 5.4:1 (54 males to 10 females). The mean age was 62 years. The classic triad of intestinal occlusion was reported in 56 patients. The mean duration of symptoms was 4.2 days. An accurate preoperative diagnosis was made in 58 cases. Forty patients had a viable bowel obstruction, and all of them had a resection and primary anastomosis. Sixteen patients had a gangrenous bowel obstruction, of which 6 patients had resection-primary anastomosis, and 10 had Hartmann's procedure. Out of the total five deaths reported, there were only two among patients who had resection-primary anastomosis for gangrenous bowel obstruction. The most common postoperative complication was wound infections in 5 cases. The median length of hospital stay following surgery was 8 days. No recurrences of volvulus after a median follow-up of 11 months. Conclusions Although Tunisia belongs to the volvulus belt, the epidemiologic features of sigmoid volvulus tend rather be similar to those of developed countries. The use of primary surgery, if no endoscopy is performed, is a good alternative. For patients who have contraindications for endoscopic treatment, surgical treatment is the only option.

Background A Chinese surgical robot, Micro Hand S, was introduced for clinical use as a novel robotic platform. This study aimed to comprehensively compare the early experience of the Micro Hand S robot-assisted total mesorectal excision (TME) with conventional approaches. Methods Between May 2017 and April 2018, 99 consecutive patients who underwent open, laparoscopic and Micro Hand S robot-assisted TME (O-/L-/RTME) for rectal cancer were included. Clinical and pathological outcomes were retrospectively analyzed. Surgical success as the primary endpoint was defined as the absence of (i) conversion, (ii) incomplete TME, (iii) involved circumferential and distal resection margins (CRM/DRM), (iv) severe complications. Results The rate of surgical success was similar (89.7 vs. 86.4 vs. 84.6%, p = 0.851) in the three groups and the respective incidences were as follows: conversion (not applicable, 4.5 vs. 2.3%, p = 1.000), incomplete TME (6.9 vs. 6.8 vs. 3.8%, p = 0.980), involved CRM/DRM (0 vs. 2.3 vs. 3.8%, p = 0.592), severe complications (3.4 vs. 4.5 vs. 7.7%, p = 0.844). Compared with open and laparoscopic surgery, the robotic surgery was associated with longer operative time, less blood loss, earlier first flatus time and liquid intake time, and shorter length of hospital stay (p Conclusions The Micro Hand S assisted TME is safe and feasible, showing comparable outcomes than conventional approaches, with superiority in blood loss, recovery of bowel function, length of hospital stay, but with increased operative time.

Summary Objective The prevalence of hemorrhoids has been reported to be 7–14%. However, there have been no large-scale studies. This study aims to investigate the incidence of hemorrhoids in Korea by analyzing big data and to find the associated risk factors. Methods This was a retrospective analysis using the Health Insurance Cohort database of the National Health Insurance Corporation of Korea in 2002–2015. The study was divided into two models: the diagnostic (DM) and surgical model (SM). Socio-demographic and lifestyle behavioral characteristics were analyzed as risk factors. Results Overall, 467,567 participants were included. The incidence density of hemorrhoids was 13.9 and 5.7 per 1000 person-years in the DM and SM, respectively. Hemorrhoids occurred more frequently in men and metropolitan areas in both models. The incidence was highest in the 40s. The incidence rates were highest in the high income, smoking, alcohol and the exercise group of 1–4 times a week in both models. The adjusted hazard ratio (HR) was higher in men and decreased with increasing age. It was higher in the metropolitan area. The high-income level and alcohol consumption were risk factors in the DM and SM, respectively. The HR of the exercise group was higher than that of the non-exercise group in both models. Conclusions The diagnostic and surgical incidence density was 13.9 and 5.7 per 1000 person-years, respectively. Hemorrhoids occurred most frequently in men in their 40s. The metropolitan area, high income level and alcohol consumption were associated with an increased frequency of hemorrhoids.

Objective We aimed to discuss the underlying oncological issues in staging of mediastinal lymph node metastasis in patients with left lung cancer who underwent extended radical lymphadenectomy (ERL). Methods This multi-institutional retrospective study analyzed 116 patients with left non-small-cell lung cancer who underwent bilateral paratracheal lymph node dissection (ERL) via median sternotomy. The clinicopathological records of patients with mediastinal lymph node metastasis were examined for prognostic factors, including age, sex, histology, tumor size, cN number, preoperative data, metastatic stations (number and distribution), pT, and adjuvant chemotherapy. Results Mediastinal lymph node metastases were found in 43 patients, and right paratracheal lymph node metastases (pN3) were found in 13 patients. The 5-year overall survival rate was 25.2% in patients with pN3 tumors (n = 13) and 23.1% in patients with pN2 tumors (n = 30). The prognosis did not differ between patients with pN3 and pN2. Univariate analyses showed that histology, cN, and adjuvant chemotherapy were significant prognostic factors in patients with mediastinal lymph node metastasis. In these 43 patients, cN and adjuvant chemotherapy were significant independent prognostic factors in multivariate analysis. Conclusions The prognostic factors for left lung cancer with mediastinal lymph node metastasis were cN status and adjuvant chemotherapy, and not pN status (pN2 or pN3). We hope that the study results, which suggest that there may be no difference in prognosis between pN2 and pN3, would broaden the discussion of oncological issues in the staging of mediastinal lymph node metastasis of left lung cancer.

Background/purpose Several strategies have been reported for improving the integrity of transurethral resection of bladder tumor (TURBT). However, no standard has been established. Stratified TURBT (SR) is one of protocols for TURBT, wherein exophytic tumors are first resected and retrieved, and tumor bases are then resected. In this study, we aimed to evaluate the outcomes of SR in patients with nonmuscle invasive bladder cancer (NMIBC). Methods From January 2012 to December 2017, patients newly diagnosed as having NMIBC with a follow-up period of more than 2 years were enrolled and categorized into SR and conventional TURBT (CR) groups. Propensity score matching at a 2:1 ratio was performed. Outcomes were the detrusor muscle sampling rate, recurrence-free survival (RFS), and progression-free survival (PFS). Results In total, 205 patients were included in our study. The detrusor muscle sampling rate was higher in the SR group (P = 0.043). After propensity score matching, 162 patients were selected for outcome analysis, with 108 and 54 patients undergoing SR and CR, respectively. Compared with the CR group, the SR group showed a lower recurrence rate (P = 0.015) and better RFS in univariate (P = 0.010) and multivariate (P = 0.006) Cox proportional hazards regression. Progression rate and PFS were not significantly different between the two groups. Conclusion SR results in a higher detrusor muscle sampling rate and better disease outcomes. Our findings suggest that SR is a promising strategy for TURBT in patients with NMIBC.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disorder worldwide. Murine models of NAFLD have been widely used to explore its pathogenesis. In this study, we performed a systematic evaluation of hepatic genome-wide mRNA expression by RNA-Sequencing using three mouse models of NAFLD: leptin receptor deficient db/db mice, high-fat high-sugar diet (HSHF)-induced obese mice, and dexamethasone (DEX)-induced NAFLD mice. As a result, we found both distinct and common pathways in the regulation of lipid metabolism from transcriptomes of three mouse models. Moreover, only a total of 12 differentially expressed genes (DEGs) were commonly detected among all three mouse groups, indicating very little overlap among all three models. Therefore, our results suggest that NAFLD is a heterogeneous disease with highly variable molecular mechanisms.

Background/purpose A heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia during adolescence, then spreads to other limbs. This study investigated the frequency and clinical features of DYT1 in a Taiwanese dystonia cohort. Methods We performed targeted next generation sequencing in 318 patients with primary dystonia. We identified one DYT1 family with various types of dystonia, and we described the clinical presentations observed in this family during a 30-year follow-up. We compared the clinical characteristics to those reported in previous studies on DYT1 from 2000 to 2020. Results Among 318 patients, we identified only one DYT1 patient (0.3%) with an autosomal dominant family history of dystonia. The proband was a 43-year-old man that experienced progressive onset of focal lower limb dystonia from age 11 years. The disease spread caudal-rostrally to the upper limbs and cervical muscles. Prominent cervical dystonia was noted during follow-up, which was an atypical presentation of DYT1. Clinical assessments of other family members showed intrafamily variability. The proband's father and an affected sibling demonstrated only mild right-hand writer's cramp. A systematic review of previously reported DTY1 cases showed that Asian patients had a higher frequency of cervical dystonia (44.8%) than groups of Ashkenazi Jews (35%) and Non-Jewish Caucasians (30.5%) (P = 0.04). Conclusion Our findings revealed that DYT1 is rare in a Taiwanese dystonia cohort. The presentation of marked cervical dystonia could be the main feature of Asian patients with DYT1.

Summary Background We sought to evaluate the safety and feasibility of single-stage treatment with left iliac vein stenting and saphenous stripping in patients with left iliac vein compression (LIVC) and left great saphenous vein (GSV) incompetence. Method s: We conducted a prospective cohort study of 72 patients diagnosed with LIVC and left GSV incompetence between June 2012 to Oct 2018. We evaluated the periprocedural, 30-day, and 1-year outcomes of venous clinical severity score (VCSS), Chronic Venous Insufficiency Questionnaire 2 (CIVIQ2), the success rate of stent placement, duration of intervention, length of hospital stay, duplex recurrence, and clinically visible recurrence. Results There were 43 patients in the two-staged group and 29 patients in the single-staged group. The clinical characteristics of the two groups were similar. There were no differences between the two groups in the technical success rate, perioperative mortality, and surgical morbidity. There was no significant difference in the duplex and clinically visible recurrence. The length of hospital stay was significantly lower in the single-staged group. The single-staged group was associated with a higher complication rate of ecchymosis. There was no death, pulmonary embolism, or contrast-induced nephropathy among the patients. The 1-year primary patency rate was similar. Conclusions Both treatment approaches were equally effective and had a high technical success rate. The single-staged group had a higher complication rate of ecchymosis due to heparin applying during the procedure.

Background Idiopathic (isolated) hypogonadotropic hypogonadism (IHH) is a rare disease that can be classified as Kallmann syndrome (KS) or normosmic IHH (nIHH). This study investigated the phenotype and genotype of IHH in Taiwanese patients. Methods Twenty-six unrelated IHH patients were included in this study and their clinical, hormonal, and radiological findings were analyzed retrospectively. Whole exome sequencing (WES) was performed to identify the etiology. Results The 26 patients (M:F = 19:7) were divided into a KS group (n = 11) and a nIHH group (n = 15). The diagnosis was earlier in boys than in girls. Fifteen patients were found to have pathogenic/likely pathogenic (P/LP) variants of IHH-associated genes, and the mutation detection rate was 58%. CHD7, FGFR1, and ANOS1 were the most common genetic etiologies identified in this group. Two patients with nIHH were found to have de novo SOX11 mutations and Coffin-Siris syndrome features. After treatment, the height outcomes and secondary sexual characteristics were significantly improved. There were no obvious differences between the genetically resolved (GR), variants of uncertain significance (VUS) and genetically unresolved groups (GUR). Conclusion Whole exome sequencing is useful in patients with IHH, and we identified the SOX11 gene as a causal factor in this study. We described the clinical, hormonal, and molecular characteristics, and the treatment outcomes, of Taiwanese patients with IHH, which should aid therapeutic planning and further research.

Background: With growing incidence of early gastric cancer (EGC), endoscopic submucosal dissection (ESD) is widely performed as a standard treatment for mucosal cancer. Due to the increasing application of ESD, the number of non-curative resection after ESD is also growing, leading to escalating number of patients who require additional gastrectomy with lymph node dissection after non-curative ESD. However, effects of ESD prior to surgery on technical difficulties during operation for EGC remain unclear. Therefore, this study aimed to determine the effect of non-curative ESD on short-term surgical outcomes in patients who underwent additional surgical treatment using propensity score matching method. Methods: To evaluate the effect of ESD on short-term surgical outcomes in patients who underwent additional surgical treatment after a non-curative ESD procedure, patients were divided into two groups: (1) those who underwent additional gastrectomy after non-curative resection of ESD [ESD + Surgery (ES) Group], and (2) those who underwent gastrectomy as the initial treatment [Surgery Only (SO) Group]. To minimize differences in baseline demographic features that could potentially be associated with short-term outcomes, propensity-scored matching analysis was performed. Results: After propensity-scored matching (1:1 matching), 140 patients altogether were selected and analyzed in this study. Complications were experienced by 18 (25.7%) patients in the ES group and 13 (18.6%) patients in the SO group, showing no significant (p

Background/purpose: The nature of susceptibility to condylar resorption after orthognathic surgery can be different between skeletal Class II and Class III populations, which was addressed by few in the past. The aim of the present study was to use cone-beam computed tomographic (CBCT) images to investigate the displacement and morphological changes of temporomandibular joints (TMJs) in patients received orthodontic treatment combined with orthognathic surgery. Methods: Both Class III (n = 34) and Class II (n = 17) patients were compared through overall and regional superimpositions of the initial and posttreatment CBCTs. Two-sample t-test was used to identify significance between group differences. Pearson's correlation coefficient was used to address changes of TMJ and the amount of setback or advancement. Results: The axial ramal angle increased significantly in Class III group and decreased in Class II groups after orthognathic surgery (p

Summary Objective Recent studies have shown that minimally invasive surgery (MIS) is associated with a higher recurrence rate in patients with early-stage cervical cancer. In this study, we aim to report the survival outcomes of patients with early-stage cervical cancer who received MIS, performed in a single center by the same surgeon. Methods Eligible participants included patients with early-stage cervical cancer in stage IA1 with lymphovascular space invasion (LVSI+), IA2, and IB1. The surgeries were carried out by a single surgeon and survival outcomes of the 137 patients were evaluated retrospectively. Results The median follow-up time for the 137 patients was 53 (25–94) months, with the five-year disease-free survival (DFS) rate of 96.4% and the five-year overall survival (OS) rate of 96.8%. Among them, six (4.38%) patients relapsed and four (2.92%) of whom died. The five-year DFS rate was significantly higher in patients with tumor≤2 cm in size than in those with tumor >2 cm (P = 0.013), however, with no significant difference in the five-year OS rate (P = 0.219). Conclusion According to the existing literature and the results of this study, for MIS, the proficiency levels of a surgeon may be associated with survival outcomes of cancer patients. Tumor size may also be an important factor affecting survival outcomes of cervical cancer patients.

Testis-sparing surgery (TSS) has been increasingly used for treating a variety of testicular tumors (TTs) in children. However, the indications and feasibility associated with TSS remain uncertain. This study aimed to present the clinical outcomes of TSS in children with TTs. The PubMed, Cochrane Library, and Embase databases were reviewed for relevant articles on the clinical outcomes of TSS in children. Recurrence rate, benign rate, rate of TSS and its 95% confidence interval (CI) were calculated. A total of nine relevant studies with 320 patients were included in this study. The recurrence rate was 5.8% (95% CI: 2.3%-14.1%), benign rate was 70.9% (95% CI: 56.3%-82.1%), the rate of TSS (RTSS) was 36.2% (95% CI: 26.1%-47.8%), RTSS in benign tumor was 48.4% (95% CI: 34.3%-62.9%) and rate of elevated AFP was 29.3% (95% CI: 19.7%-41.3%) in children with TTs. Regarding the distribution of TTs, 159 (49.6%) were teratomas, 74 (23.1%) were yolk sac tumors, 36 (11.3%) were epidermoid cysts, 3 (0.9%) were rhabdomyosarcomas, 7 (2.2%) were leydig cell tumor, 6 (1.8%) were sex-cord stromal tumor, 8(2.5%) were mixed malignant germ cell tumors, 3(0.9%) were hemangioma, and 4(1.3%) were adrenal rest tumors. The findings of this meta-analysis suggested that most of the TTs in children were benign, and the most common histologic subtype was teratoma. TSS should be provided to children with benign lesions. This study confirmed that very low rates of tumor recurrence were observed in children with TTs.

Background/purpose Our previous study found significantly lower serum hematinic levels and higher serum homocysteine level as well as higher frequencies of serum hematinic deficiencies and hyperhomocysteinemia in oral leukoplakia (OL) patients than in healthy control subjects. This study evaluated whether carcinoembryonic antigen (CEA)-positive or squamous cell carcinoma-antigen (SCC–Ag)-positive OL patients had significantly lower serum hematinic levels and higher serum homocysteine level as well as significantly higher frequencies of hematinic deficiencies and hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients or healthy control subjects. Methods The complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels in 184 OL patients including 85 CEA-positive, 99 CEA-negative, 25 SCC-Ag-positive, and 159 SCC-Ag-negative OL patients and in 184 age- and sex-matched healthy control subjects were measured and compared. Results We found that the 85 CEA-positive or 25 SCC-Ag-positive OL patients had a significantly lower mean serum folic acid level and a significantly higher mean serum homocysteine level as well as significantly higher frequencies of serum folic acid deficiency and hyperhomocysteinemia than 184 healthy control subjects. Moreover, the 25 SCC-Ag-positive OL patients had a significantly higher mean serum homocysteine level than the 159 SCC-Ag-negative OL patients. The 85 CEA-positive OL patients had a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than 99 CEA-negative OL patients (marginally significant, P = 0.060). Conclusion CEA-positive or SCC-Ag-positive OL patients tend to have a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients, respectively.

Background/Purpose: Stereotactic ablative radiotherapy (SABR) is the treatment of choice for medically inoperable, early-stage non-small cell lung cancer (ES-NSCLC). The influence of oncogenic driver alterations and comorbidities are not well known. Here we present treatment outcomes based on clinicopathologic features and molecular profiles. Methods: We retrospectively analyzed patients treated with SABR for inoperable ES-NSCLC. Molecular features of oncogenic driver alterations included EGFR, ALK, and ROS1. Comorbidities were assessed using the age-adjusted Charlson Comorbidity Index (ACCI). Survival was calculated using the Kaplan–Meier method. The Cox regression model was performed for univariate and multivariate analyses of prognostic factors. Competing risk analysis was used to evaluate the cumulative incidence of disease progression. Results: From 2008 to 2020, 100 patients (median age: 82 years) were enrolled. The majority of patients were male (64%), ever-smokers (60%), and had adenocarcinoma (65%). With a median follow-up of 21.5 months, the median overall survival (OS) and real-world progression-free survival were 37.7 and 25.1 months, respectively. The competing-risk-adjusted 3-year cumulative incidences of local, regional, and disseminated failure were 8.2%, 14.5%, and 31.2%, respectively. An ACCI ≥7 was independently associated with inferior OS (hazard ratio [HR] 2.45, p = 0.03). Tumor size ≥4 cm (HR 4.16, p

Background Nonintubated thoracoscopic lobectomy has been described as a feasible surgical treatment for early-stage lung cancer since 2011. Despite promising perioperative results, studies on tumor recurrence and long-term survival are very limited. This study was aimed to compare outcomes after thoracoscopic lobectomy with versus without intubation for stage I non-small cell lung cancer. Methods A retrospective data set including 115 and 155 patients who underwent nonintubated and intubated thoracoscopic lobectomy, respectively, between January 2011 and December 2013 was used to identify matched nonintubated and intubated cohorts (n = 97 per group) using a propensity score matching algorithm that accounted for confounding effects of preoperative patient variables. Primary outcome variables included freedom from recurrence and overall survival. Factors affecting survival were assessed using Cox regression analysis and Kaplan–Meier survival estimates. Results No perioperative mortality occurred in both groups. At an average follow-up of 74 months, comparing nonintubated thoracoscopic lobectomy with intubated procedure, no differences were observed in recurrence rates (14.4% vs. 25.8%, respectively; p = .057). Furthermore, no significant differences were noted in overall survival (97.9% vs. 93.8%, respectively; p = .144). Nonintubated thoracoscopic lobectomy was not found to be an independent predictor of recurrence (hazard ratio, .53; 95% confidence interval [CI], .28–1.02) or overall survival (hazard ratio, .33; 95% CI, .07–1.61). Conclusions In this propensity-matched comparison, nonintubated thoracoscopic lobectomy was not associated with an increased risk for recurrence and overall survival during the 5-year follow-up. However, more randomized trials should be conducted for further validation of these results.

Objective This study was designed to assess the demographic characteristics of patients with Crohn's perianal fistula (CPF) who were treated at a tertiary referral institution. Surgical outcomes were compared in groups of patients who underwent seton placement, fistulotomy, and stem cell therapy. Methods Patients who underwent surgery for CPF between 2015 and 2017 at Asan Medical Center, Seoul, Korea, were retrospectively evaluated. Patients were divided into groups who underwent seton placement, fistulotomy, and stem cell therapy. Their clinical variables and closure rates were compared. Results This study included 156 patients who underwent a total of 209 operations. More than half of the operations consisted of seton placement (67%), followed by stem cell therapy (18%) and fistulotomy (15%) patients. Of the 209 fistulas, 153 (73%) were complex, with an overall closure rate of 38% during a median follow-up of 29 months. Closure rates following fistulotomy, stem cell therapy, and seton placement were 90%, 70%, and 18%. Seton placement was more significantly frequently used than the other procedures in patients with complex fistula and those with abscesses. Of the 79 fistulas that achieved complete closure, 11 (14%) recurred. The recurrence rates did not differ among the various techniques. Conclusion Surgical treatment of CPF is dependent on lesion type. Seton placement was the primary draining procedure for complex fistulas and abscesses, resulting in low closure rates. Fistulotomy was the definite procedure for low type and simple fistula. Stem cell therapy showed high closure rates as definitive treatment, even for complex fistulas.

Background Management of comorbidities of people living with HIV (PLHIV) involves different care models, including providing diabetes care and HIV care by the same infectious diseases physician (IDP) (“consolidated care”) or providing diabetes care by the physicians other than IDP (“shared care”). The impact of diabetes care model on PLHIV with diabetes mellitus (DM) has not been well-evaluated. Methods A nationwide cross-sectional sample in the Taiwan National Health Insurance Research Database was used to compare the performance rates of seven guideline-recommended tests provided by the different subspecialists. Results Of 523 PLHIV with DM, there were 54.88% (n = 287) in the consolidated care group and 45.12% (n = 236) in the shared care group. More patients in the consolidated care group received the tests of lipid profile (92.33% vs. 79.24%), creatinine (Cr) (93.73% vs. 78.39%), and alanine transaminase (ALT) (91.99% vs. 75.42%), but fewer received urine protein test (35.54% vs. 51.69%) and fundoscopic examination (8.01% vs. 33.90%). The two groups did not differ in the performance rates of serum fasting glucose and HbA1c. After controlling for demographic factors and diabetic severity, the consolidated group was less likely to miss the serum tests of lipid profile (odds ratio [OR]: 0.30), Cr (OR: 0.19), and ALT (OR: 0.23), but more often missed urine protein test (OR: 1.56) and fundoscopic examination (OR: 4.97). Conclusion These findings suggest the need to focus on different process indicators of diabetes cares in different care models to enhance the diabetes care for PLHIV.

Background/Purpose: Lacto-vegetarians (LVs) tend to have vitamin B12 deficiency (B12D). This study assessed whether 140 female LVs, including 16 B12D/LVs and 124 non-B12D/LVs, had significantly higher frequencies of microcytosis, macrocytosis, and of blood hemoglobin (Hb), red blood cell (RBC), and serum vitamin B12 deficiencies than 140 healthy control subjects (HCSs). Methods: The complete blood count and serum vitamin B12 level in 140 female LVs and 140 female HCSs were measured and compared. Results: We found that 8.6%, 4.3%, 22.9%, 20.0%, and 11.4% of 140 LVs had microcytosis, macrocytosis, and blood Hb, RBC, and serum vitamin B12 deficiencies, respectively. The 140 LVs, 16 B12D/LVs, and 124 non-B12D/LVs had significantly higher frequencies of microcytosis as well as blood Hb and RBC deficiencies than 140 HCSs (all P-values

Background: To explore the expression of microribonucleic acid-340 (miR-340) and cyclin D1 (CCND1) in lung cancer (LC) tissues and its relationship with the clinicopathological characteristics and prognosis of LC. Methods: Cancer tissues and paracancerous normal lung tissues of 65 patients with LC admitted to our hospital from January 2014 to March 2015 were included as the LC group, and the paracancerous group, respectively. Results: The relative expression levels of miR-340 mRNA and miR-340 protein in the LC group were lower than those in the paracancerous group, while the relative expression levels of CCND1 mRNA and CCND1 protein in the LC group were higher than those in the paracancerous group (P

Background/Purpose Bisphosphonates (BPs) impact on the survival and cardiovascular safety of osteoporosis patients after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) was evaluated. Methods A nationwide epidemiological study was conducted using the Taiwan National Health Insurance Research Database from 2000 to 2010. From the 1456 osteoporosis patients with previous ACS or AIS, mortality and cardiovascular safety was compared between 464 patients who used BPs and 464 patients who did not. Primary outcomes included all-cause mortality, and major adverse cardiovascular events. Results The BPs group had a lower risk of all-cause mortality than the control group after the 8-year follow-up (HR, 0.64; 95% CI, 0.46–0.88; P = 0.006). The risks of myocardial infarction, ischemic stroke, cardiovascular death, hospitalization for heart failure or other causes of mortality were similar across groups. However, there was a higher risk of hospitalization for atrial fibrillation in the BPs group than the control group (HR, 1.76; 95% CI, 1.26–2.46; P = 0.001). Conclusion Among osteoporosis patients after ACS or AIS, BPs use was associated with a reduced risk of all-cause mortality. However, patients with previous cardiovascular disease who received BP treatment should be careful about the risk of atrial fibrillation.

Background: In Taiwan, carbapenem-resistant Klebsiella pneumoniae (CRKP) now became a leading cause of difficult-to-treat healthcare-associated infection, for which there are a lack of recent hospital epidemiological studies on risk factors, mortality, and antimicrobial susceptibility. Methods: We prospectively enrolled patients with healthcare-associated CRKP monomicrobial bloodstream infection (mBSI) and matched patients with carbapenem susceptible K. pneumoniae (CSKP) mBSI at National Taiwan University Hospital (Taipei, Taiwan) from October 2017 through December 2019 in a 1:2 ratio. Multivariable logistic regression and Kaplan–Meier analyses were applied to identify factors associated with CRKP mBSI and to compare the 14-day survival curves, respectively. We detected the presence of blaKPC and blaNDM gene among the included CRKP strains, and performed antimicrobial susceptibility testing (including susceptibility to colistin, aminoglycoside, tigecycline, and ceftazidime/avibactam). Results: A total of 36 CRKP cases and 72 CSKP controls were enrolled. Patients with CRKP mBSI were more likely to have liver cirrhosis (adjusted odds ratio [aOR], 5.61; P = 0.024), length of hospital stay over the previous 14 days (aOR, 1.23; P = 0.001) and prior use of carbapenems in the previous 14 days (aOR, 6.07; P = 0.004) than patients with CSKP mBSI. The 14-day survival was significantly worse for patients with CRKP mBSI than those with CSKP mBSI (all CRKP cases: 50.0% vs. 87.5%; P

Background/Purpose Concurrent sexually transmitted infections (STIs) are not uncommon in at-risk populations, for which control requires integrated testing, treatment and prevention. Methods From May, 2019 to February, 2020, multiplex real-time PCR assays were prospectively performed to detect Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) in the urine and rectal/vaginal swab specimens collected from HIV-positive patients with a history of STIs or symptoms suggestive of STIs. Patients confirmed to have acquired STIs were treated according to treatment guidelines. Results During the study period, 430 participants (99.1% men who have sex with men and median age 37 years) were included. The overall prevalence of CT, NG, and/or TV infection was 30.0%, including 24.7%, 12.1%, and 0.2% for CT, NG, and TV infection, respectively. The factors associated with CT, NG, and/or TV infection were hepatitis B surface antigen (HBsAg) seropositivity (AOR, 2.76; 95% CI, 1.22–6.26), recently acquired hepatitis C virus (HCV) infection (AOR, 5.62; 95% CI, 1.99–15.88), using mobile dating application (AOR, 2.08; 95% CI, 1.13–3.83), and oral sex (AOR, 2.12; 95% CI, 1.04–4.32). The rates of CT, NG, and/or TV infection were 50.0% in participants with recent HCV infection, 44.2% in those with HBsAg positivity, and 35.9% in those with incident syphilis. Among participants completing test-of-cure visits, the microbiological cure rate was 91.7% and 90.0% for chlamydia and gonorrhea, respectively. Conclusion HIV-positive participants had a high prevalence of CT and/or NG, especially those coinfected with viral hepatitis and syphilis. Our results strongly support integrated STI services in the population.

Background/Purpose Heavy metals impair renal function, causing chronic kidney disease (CKD), and the petrochemical industry is one of the major environmental metal emission sources. This study aimed to investigate the relationship between renal function and metal exposure among the Taiwanese residents living near a petrochemical industry site. Methods We recruited residents near the No. 6 Naphtha Cracking Complex, and they were categorized into a high-exposure (HE) group (N = 190) in Taisi Village and a low-exposure (LE) group (N = 1184) in other villages of Dacheng Township in Changhua County of Taiwan. The urinary nickel, chromium, and vanadium levels of the study subjects were measured and the levels were standardized by urine creatinine, and the estimated glomerular filtration rates (eGFRs) were calculated to estimate renal function by one-time health data. Linear regression models were applied to illustrate the correlations between the distance to the complex and urinary metal levels and renal function; linear and logistic regression models were applied to evaluate the associations between urinary metal levels and renal function indicators. Results The study subjects living closer to the petrochemical complex had significantly higher urinary nickel, chromium, and vanadium levels and worse renal function than study subjects living farther away. The urinary nickel and chromium levels of the study subjects were associated with their renal function indicators. When the subject's urinary nickel level increased 1-fold, the eGFR level significantly decreased by 0.820 ml/min/1.73 m2. Conclusion Residents living closer to the petrochemical industry were exposed to higher metal levels and had worse renal function, and the nickel exposure of residents was potentially related to their decline in renal function.

Background/purpose The aim of this study was to systematically review all COVID-19 publications to summarize the clinical features, assess comorbidities, prevalence, and disease outcomes. Methods Included were all COVID-19 published studies between January 1 to July 20, 2020. The random effect model was used to calculate the pooled prevalence and corresponding 95% confidence interval (CI). Publication bias was assessed using the funnel plot for the standard error by logit event. Results The mean age of the patients was 46.8 years (95% CI, 41.0–52.6) and males comprised 54.0% (95% CI, 51.3–56.7). Total co-morbidities prevalence was 29.5% (95% CI, 19.0–36.6), with diabetes mellitus being the most prevalent 13.8% (95% CI, 8.7–21.1), followed by hypertension 11.7% (95% CI, 5.7–22.6), and cardiovascular disease 9.7% (95% CI, 6.5–14.2). The most common clinical manifestations were fever, 82.0% (95% CI, 67.7–90.8), cough 54.3% (95% CI, 45.5–62.9), fatigue 30.2% (95% CI, 23.3–38.1), sputum 28.5% (95% CI, 21.2–37.2), sore throat 21.7% (95% CI, 14.6–31.0), and headache 11.0% (95% CI, 7.9–15.2). The most common COVID-19 serious complications were RNA Anemia 98.2% (95% CI, 96.2–99.2), hospitalization 83.7% (95% CI, 76.0–89.3), bilateral pneumonia 70.9% (95% CI, 58.2–81.0); of those hospitalized 43.5% (95% CI, 24.9–64.2) were discharged. Fatality accounted for 10.5% (95% CI 6.8–16.1). Conclusion Patients infected with COVID-19 coronavirus showed a wide range of clinical presentation with non-specific symptoms.

Background: Taiwan is a rapidly aging society. The elderly with mild cognitive impairment (MCI) have increased risk of dementia, and this is a population-based report using standard neuropsychological tests and expert consensus diagnosis to assess the MCI prevalence and its associated factors in Taiwan. Method: The Epidemiology of Mild Cognitive Impairment study in Taiwan (EMCIT) is a community-based, prospective cohort study. Independently-living individuals aged ≧60 years in a rural area (n = 122) and in an urban area (n = 348) of New Taipei City, Taiwan, completed detailed neuropsychological tests at the cohort baseline. Diagnosis of MCI was ascertained through expert consensus based on 2011 NIA-AA criteria. Results: Of 470 participants recruited between 2017 and 2019 (mean age 71.2 ± 5.4 years), the prevalence of MCI was higher in the rural area than in the urban area (25.1% vs. 10.8%, p

Background The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is complex, and the modality of treatment is surgery and targeted medication. Patients with CTEPH could have a poor prognosis if their diagnosis or treatment is delayed. The incidence of CTEPH and its clinical features are largely unknown in Taiwan, even among other Asian populations. In this study, we aimed to investigate the geodemographics of CTEPH in Taiwan and describe the practical management and treatment outcomes in patients with CTEPH. Methods This study retrospectively enrolled patients in the Taiwan cohort – Registry of CTEPH. The study was conducted over 2 years inclusive of follow-up. The enrolment criteria depended on the current global guideline. Results From January 2018 to March 2020, 107 CTEPH patients enrolled in the Taiwan registry. All patients received right heart catheterisation examinations. The overall median age was 61.4 ± 16.5 years, and the cohort was dominated by female patients (75/107). Risk factors included pulmonary embolism (81.3%), deep vein thrombosis (22.4%), and previous major surgery (20.6%). Twenty-one (19.6%) patients underwent pulmonary endarterectomy operation alone, and 38 (35.5%) patients underwent balloon pulmonary angioplasty alone. Conclusion To our knowledge, this is the first national cohort study that demonstrated the raw CTEPH incidence in Taiwan. It also showed the CTEPH incidence between male and female patients in the Asian population was different from the Caucasian population.

Background: There is an increasing demand for minimally invasive aortic valve replacement. This study aimed to investigate the safety and feasibility of minimally invasive aortic valve replacement through a right parasternal second intercostal transverse incision. Methods: This was a retrospective study, and we collected information from 111 patients who underwent isolated aortic valve replacement surgery performed by the same surgeon from January 2018 to December 2019. According to the operative approach, the patients were divided into a sternotomy aortic valve replacement (SAVR) group (n = 62) and a minimally invasive aortic valve replacement (Mini-AVR) group (n = 49). We compared the intraoperative and postoperative data between the two groups. Result: There was no difference in preoperative data between the Mini-AVR and SAVR. The postoperative ventilator-assisted time, CSICU time and postoperative hospital stay of the Mini-AVR were shorter than those of the SAVR [(15.45 ± 5.75) VS (18.51 ± 6.71) h; (1.77 ± 0.31) VS (2.04 ± 0.63) d; (8.69 ± 2.75) VS (10.77 ± 2.94) d], and the difference was statistically significant (P

Background/purpose Anti-resorptive agents are commonly used in cancer patients with bone metastasis or multiple myeloma (MM). An adverse event termed medication-related osteonecrosis of the jaws (MRONJ) was discovered in patients using these agents but relatively little attention has been paid to its prognosis. Our aims were to find out the treatment outcomes and prognostic indicators of MRONJ in cancer patients who received zoledronic acid as antiresorptive therapy. Methods We retrospectively surveyed a cohort of 133 cancer patients who received zoledronic acid. A total of 150 MRONJ lesions were included for investigation. Cumulative complete response rate after treatment was calculated with the Kaplan–Meier method, and significance was examined with the log-rank tests. Cox regression was used for univariate and multivariate analyses of prognostic factors. Results The cumulative complete response rate of all patients at 24 months was 53.2%, and those of patients with MM, breast cancer and prostate cancer were 27.8%, 60.7% and 68.0%, respectively. Having MM was identified as an independent prognostic factor in a multivariate analysis with adjusted hazard ratios of 0.28 (95% confidence interval, 0.09–0.83). Conclusion For cancer patients with ONJ related to zoledronic acid, patients with MM endure a worse treatment outcome.

Background Isolated sphenoid sinus disease (ISSD) is a rare clinical entity with potentially serious complications. The etiological distribution of ISSD varies among different areas and ethnicities. We aimed to investigate the clinical features of patients with endoscopic treated ISSD. Methods We retrospectively reviewed all patients with ISSD who had undergone endoscopic surgery between April 2013 and May 2019. The patient records were reviewed for demographic data, clinical presentations, endoscopic and imaging study findings, surgical outcomes and complications. Results A total of 37 patients with ISSD who underwent surgery were recruited. We divided patients into three groups according to etiology, including inflammatory diseases (78.4%), neoplasms (13.5%) and spontaneous cerebrospinal fluid (CSF) leaks (8.1%); fungal ball (62.2%) constituted the major cause of ISSD. Overall, the most common presenting symptom was headache or facial pain (65.5%). The endoscopic findings of bloody discharge and tumor lesions were mainly from the neoplasm group. Bony defects were more obvious on computed tomography in the neoplasm and CSF leak groups. Magnetic resonance imaging revealed a higher rate of involvement of the cavernous sinus (40.0%) and intracranial extensions (40.0%) in the neoplasm group. To summarize the surgical outcomes, the success rate was 97.1%, and the major complication rate was 5.4%. Conclusion ISSD represents a variety of etiologies, mostly comprising fungal ball in our area, while there is still a considerable proportion of ISSDs attributed to neoplasm and CSF leak. Untreated ISSD can result in serious complications. We recommend early surgical intervention for all patients with ISSD.

Hereditary angioedema (HAE) is an autosomal dominant disease characterized clinically by recurrent episodes of swelling in the tissues of the extremities, face, abdomen, and respiratory tract. It is most often caused by C1 esterase inhibitor (C1 INH) gene mutation. This swelling may lead to bradykinin release, resulting in recurrent, paroxysmal, painful angioedema. Blister formation is an uncommon cutaneous manifestation of HAE. Herein, we report a case of a patient with HAE who developed linear wrist blisters on her skin, with swelling, as a rare complication of HAE. She was treated with attenuated androgens (Danazol) for two weeks at our clinic, after which the blisters showed dramatic improvement. To date, only a few HAE cases have been reported across the world. Therefore, it is important to focus on and recognize the development of edema blisters as a flare of HAE, which could consequently avoid unnecessary dermatological diagnostic workup and treatment.

Toxocariasis is a zoonosis disease with high sero-prevalence in Southeast Asian. Neurotoxocariasis has never been reported in Taiwan. Herein, we presented 2 cases of neurotoxocariasis. The first case is a 48-year-old man with febrile headache, rapid progressive cognitive problems and later thoracic myelitis. Meningeal enhancements on the corresponding sites were found on magnetic resonance imaging (MRI). Eosinophilic pleocytosis was present in peripheral blood and cerebrospinal fluid (CSF). A positive Toxocara canis larval excretory-secretory antigen (TcES)-based immunoblotting test for CSF confirmed the diagnosis. The second case is a 42-year-old woman of progressive headache with features of increased intracranial pressure. CSF analysis showed lymphocytic pleocytosis initially and eosinophilic pleocytosis later. Her brain MRI was normal. The diagnosis was confirmed by the presence of anti-TcES IgG in CSF. The two cases were soonly cured by mebendazole. Neurotoxocariasis presented a broad spectrum of neurological symptoms and the CSF profile can be non-eosinophilic pleocytosis. The prevalence of neurotoxocariasis may be seriously underestimated due to low awareness of physicians and lack of standard conventional diagnostic test in Taiwan. The two cases of neurotoxocariasis firstly reported in Taiwan will raise physician's awareness in recognizing this curable disease particularly in managing patients with aseptic meningitis or meningoencephalitis of undetermined pathogen.

Background: Excellent success rates with short-term outcomes are noted for laparoscopic ureteral reconstruction (LUR) for iatrogenic ureteral injury. This multi-institutional study assessed the medium-term (>1 year) outcomes and compared three surgical techniques of LUR. Methods: Patients who underwent LUR at five tertiary hospitals between January 2007 and June 2016 were retrospectively analyzed. Patients with active abdominopelvic inflammatory disease, history of urothelial cancer, and tumor recurrence and those who received adjuvant chemotherapy or radiotherapy were excluded. Results: The success rates of LUR for 61 patients at 3 months postoperatively and at the last follow-up (at least 12 months postoperatively) were 100% and 95.1%, respectively. No significant difference was noted in the success rates of the three types of LUR. LUR was mainly performed in response to the demands of the primary surgeon responsible for the iatrogenic injury (33 of 45 cases, 73.3%). The vesicoureteral reflux (VUR) incidence was higher in the refluxing laparoscopic ureteroneocystostomy (LUN) group (40%) than in the anti-refluxing LUN group (15%, odds ratio: 1.5, p = 0.252). None of the patients in the LUN groups received treatment for VUR during the follow-up. The laparoscopic end-to-end ureteroureterostomy (LEEU) group had shorter operative time (p

Summary Background The treatment of primary spontaneous pneumothorax (PSP) remains controversial. We aimed to examine the role of chest computed tomography (CT), the advantages of pigtail catheter versus chest tube regarding duration of drainage or hospitalization period, and the impact of small PSP and surgical treatment on recurrence rate. Methods We retrospectively reviewed the medical records of 109 children with PSP (20 years’ period). Patients with recurrent and those with non-recurrent PSP were compared. Results We recorded 183 episodes of PSP (45% recurrences), 89 patients (97%) were male, and the median age at presentation was 16 years. There were no significant differences between recurrence and non-recurrence PSP regarding age, gender, medical background, presentation symptoms, type of chest drain, median hospitalization length and median follow-up period. Recurrences were less frequent among patients who presented with small PSP and were treated conservatively (P = 0.029). PSP was almost always unilateral and the recurrence was observed ipsilateral in almost 80% of the cases. CT was more frequently used and blebs/bullae were more frequently found among patients with recurrent PSP. Pigtail use had no advantage in reducing hospitalization period and surgical procedures prevented recurrences. Conclusion The size of pneumothorax at presentation helps to predict recurrences. There are no differences regarding duration of drainage or hospitalization period in the use of pigtail compared to chest tube. CT helps evaluate findings in the lungs in recurrent cases of PSP and surgery prevents recurrences effectively.

Background: Identification and treatment for latent tuberculosis infection (LTBI) are of great epidemiological importance of controlling tuberculosis (TB) worldwide. Identification in high-risk population on dialysis and treatment with 12-week weekly rifapentine plus isoniazid (3HP) help improve prevention outcomes effectively. Methods: We conducted a single-center, nonrandomized follow-up study on end-stage renal disease patients on hemodialysis. The interferon-gamma release assay (IGRA) was used for the diagnosis of LTBI. Participants were treated with 3HP, and treatment responses were recorded and analyzed. Results: A total of 123 of the 641 patients showed positive IGRA results. The male sex, age >60 years, low serum albumin level ( 10.2 mg/dL) were associated with IGRA positivity. Seventy-five patients were treated with 3HP, with a completion rate of 66.67%. The male sex, albumin level >4.0 g/dL, and absence of adverse drug reaction were associated with increased completion rates. Adverse drug reactions included dizziness, fatigue, nausea and vomiting, fever, and hypertension. Conclusion: Risk factors for LTBI in dialysis patients were identified to prioritize LTBI screening and initiate early treatment. The completion rate in dialysis patients were approximately 2 of 3 patients with mild adverse drug reaction, leading to discontinuation of the treatment.

Summary 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.

Background & Aims Epithelial cells form a monolayer at mucosal surface that functions as a highly selective barrier. Lysophosphatidic acid (LPA) is a bioactive lipid that elicits a broad range of biological effects via cognate G protein-coupled receptors. LPA receptor 5 (LPA5) is highly expressed in intestinal epithelial cells, but its role in the intestine is not well-known. Here we determined the role of LPA5 in regulation of intestinal epithelial barrier. Methods Epithelial barrier integrity was determined in mice with intestinal epithelial cell (IEC)-specific LPA5 deletion, Lpar5ΔIEC. LPA was orally administered to mice, and intestinal permeability was measured. Dextran sulfate sodium (DSS) was used to induce colitis. Human colonic epithelial cell lines were used to determine the LPA5-mediated signaling pathways that regulate epithelial barrier. Results We observed increased epithelial permeability in Lpar5ΔIEC mice with reduced claudin-4 expression. Oral administration of LPA decreased intestinal permeability in wild-type mice, but the effect was greatly mitigated in Lpar5ΔIEC mice. Serum lipopolysaccharide level and bacterial loads in the intestine and liver were elevated in Lpar5ΔIEC mice. Lpar5ΔIEC mice developed more severe colitis induced with DSS. LPA5 transcriptionally regulated claudin-4, and this regulation was dependent on transactivation of the epidermal growth factor receptor, which induced localization of Rac1 at the cell membrane. LPA induced the translocation of Stat3 to the cell membrane and promoted the interaction between Rac1 and Stat3. Inhibition of Stat3 ablated LPA-mediated regulation of claudin-4. Conclusions This study identifies LPA5 as a regulator of the intestinal barrier. LPA5 promotes claudin-4 expression in IECs through activation of Rac1 and Stat3., Graphical abstract

Background/purpose Radiofrequency ablation (RFA) is increasingly being used instead of surgical resection for the treatment of hepatocellular carcinoma (HCC) tumor measuring ≦2 cm. However, the long-term outcomes of RFA, especially in comparison to surgical resection, are still debated. We compared the outcomes of surgical resection and RFA in patients with a solitary HCC tumor measuring ≦2 cm from a 10-year cohort study. Methods From Jan 2006 to Dec 2016, 156 patients with a resectable HCC measuring ≦2 cm who underwent surgical resection (n = 83) or RFA (n = 73) at the Buddhist Tzu Chi Medical Foundation were enrolled. Patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were retrospectively examined, and comparisons were made between the two groups and through subgroup analyses. Results The 1-year, 3-year, 5-year, and 7-year OS outcomes were comparable between the surgical resection group and the RFA group (P = 0.193), but the surgical resection group had significantly higher 1-year, 3-year, 5-year, 7-year, and 10-year RFS than the RFA group (P = 0.018). Multivariate analysis revealed that patients with lower age, Child–Turcotte-Pugh score, or albumin–bilirubin score before treatment had better OS, and patients with an HCV infection or receiving RFA treatment had higher HCC recurrence rates. Conclusion The liver reserve determined the long-term OS of patients with an HCC tumor ≦ 2 cm, and surgical resection offered better RFS than RFA ( ClinicalTrials.gov number, NCT04525833.).

Background/Purpose: The HCV core antigen (HCV Ag) assay displays high sensitivity and strong correlation with HCV RNA. However, the feasibility of anti-HCV reflex HCV Ag screening in a community-wide setting is rarely discussed. Methods: We performed a two-phase community-based hepatitis C screen in an HCV-prone area of central Taiwan. During the training phase, all participants were test for anti-HCV, HCV Ag and HCV RNA to validate sensitivity, specificity, and accuracy of HCV Ag. During the validation phase, an anti-HCV reflex HCV Ag screen was conducted based on the results of training phase. Outcomes of the study were presented as positive and negative predictive values (PPV and NPV). Results: Of 935 training phase participants, the rate of positive anti-HCV and HCV Ag were 175 (18.7%) and 78 (8.3%), respectively. Test sensitivity, specificity, and accuracy of HCV Ag were 97.1%, 98.6%, and 97.8%, respectively. During validation phase, only anti-HCV-positive serum samples were tested for HCV Ag. Of 1932 participant, 285 (14.8%) were anti-HCV-positive. 133 (46.7%) of the 285 anti-HCV-positive samples were HCV Ag-positive. PPV and NPV were 98.4% and 99.3%, respectively. Across the entire participant sample, a significant linear correlation between HCV Ag and HCV RNA concentration was noted (r2 = 0.93, p-value

Summary: Background: The aim of this study was to assess the safety of several modified Nuss procedures for severe pectus excavatum (PE). Methods: Thirty-four patients with severe PE underwent the Nuss procedure: 10 underwent slanting-directed bar insertion (group A); 11 underwent standard Nuss procedure (group B); and 13 underwent Nuss procedure with subxiphoid assistance (group C). All the patients met the criteria of having a Haller index greater than 4.5, assessed from chest computed tomography. Besides, the transverse length of the most depressed point and the 2-intercostal left slant length between the heart and the anterior chest wall were measured. Results: All patients were followed up for 6–45 months (mean 31.4 ± 11.38 months). None of the patients suffered from injuries to the pericardium, heart or lungs. There were no significant differences in age, Haller’s index, operation time and postoperative stay among the three groups. However, two patients in group B experienced bar rotation and subsequently required reoperation vs the other two groups (p

Background & Aims HCV-infected patients with cirrhosis achieve high sustained virological response (SVR) rates with direct-acting antivirals (DAAs) even after hepatic decompensation. We aimed to assess the clinical outcome following DAAs among patients with compensated and decompensated cirrhosis in relation to SVR and changes in model for end-stage liver disease (MELD) score. Methods Consecutive DAA-treated chronic HCV-infected patients with cirrhosis from 4 hepatology clinics were included. The primary endpoint in survival analyses was clinical disease progression, defined as liver failure, hepatocellular carcinoma, liver transplantation or death. Results In total, 868 patients were included with a median age of 59 (IQR 54–65) years; 719 (83%) with Child-Pugh A cirrhosis and 149 (17%) with Child-Pugh B/C cirrhosis. SVR was attained by 647 (90%) Child-Pugh A patients and 120 (81%) Child-Pugh B/C patients. During a median follow-up of 28 (IQR 20–36) months, 102 (14%) Child-Pugh A patients and 96 (64%) Child-Pugh B/C patients experienced clinical disease progression. SVR was independently associated with an improved event-free survival in patients with Child-Pugh A cirrhosis (adjusted hazard ratio [HR] 0.47; 95% CI 0.27–0.82, p = 0.007), but not in patients with Child-Pugh B/C cirrhosis (adjusted HR 1.23; 95% CI 0.67–2.26; p = 0.51). Twelve weeks post-DAAs, 28 (19%) patients with Child-Pugh B/C cirrhosis had ≥2-point MELD decline, but their 2-year event-free survival did not differ from those with a stable MELD (47.9%; 95% CI 28.7–67.1 vs. 48.9%; 95% CI 38.1–59.7, respectively, p = 0.99). Conclusions Among patients with chronic HCV infection, DAA-induced SVR was associated with a reduced risk of clinical disease progression in patients with Child-Pugh A cirrhosis but not in patients with Child-Pugh B/C cirrhosis. In Child-Pugh B/C cirrhosis, a ≥2-point MELD decline did not translate into improved clinical outcome. Lay summary Chronic HCV infection can be cured with antiviral therapy. In this study, we evaluated the long-term effects of antiviral therapy on liver-related complications in patients with cirrhosis. Our results suggest that patients with compensated cirrhosis who were cured of their HCV infection have a lower rate of complications. In contrast, the rate of complications was not related to virological cure among those with decompensated cirrhosis. While these patients seem to remain in need of liver transplantation, antiviral therapy may lower their priority on the liver transplantation waiting list.

Background and Aims The Cancer Genome Atlas (TCGA) project has identified HER2 mutations or amplification in 7% of colon cancers. In addition to HER2 mutations, colon cancer patients also possess co-occurring mutations in genes such as APC. Here, we investigated the role of HER2 and APC mutations on the crypt-villus architecture of the intestinal epithelium, localization of secretory cells, and expression of intestinal stem cell markers. Methods We generated a HER2 transgenic mouse (HER2V777L Tg) possessing an activating mutation commonly found in colorectal cancer patients, HER2V777L, using transcription activator-like effector nucleases–based gene editing technology. We expressed the HER2V777L transgene in mouse small intestine and colon using Lgr5-Cre and Villin-Cre recombinases. In addition, we analyzed Lgr5-Cre; APCmin; HER2V777L Tg mice by morphologic and gene expression assays on intestinal sections and organoids derived from the epithelium. Results HER2V777L expression resulted in hypertrophic crypt formation with expanded zones of proliferation. Proximal intestinal villi showed increased abundance of multiple differentiated lineages including extensive intermediate cell differentiation, as evidenced by MUC2/MMP7 co-immunofluorescence and transmission electron microscopy. HER2V777L expression in the context of APC loss resulted in further enhancement and expansion of the proliferative crypt compartment. Conclusions We established an epithelial intrinsic role for HER2V777L on enhanced cellular proliferation. Additionally, we determined that HER2 and APC mutations, when combined, promote enhanced proliferation of intestinal crypts., Graphical abstract Model of HER2 and APC mutations on the intestinal epithelium. HER2V777L expression conferred hypertrophic crypt formation characterized by increased intestinal stem cells and promoted intermediate cells formation along the villus. HER2V777L expression, in the context of APC loss, induced hyperproliferation of the crypt compartment.

Background/objective: This study’s goal is to describe wound outcomes at 2 years following intervention for atherosclerotic femoropopliteal lesions in patients with ischemic tissue loss. Methods: A retrospective review of 135 first-time endovascular procedures for chronic femoropopliteal atherosclerotic lesions related to ischemic tissue loss was performed. The final wound outcomes were categorized according to the initial wound healing, recurrence and the need of major/minor amputation. Results: At 2-years of follow up, 76 limbs (56.3%) showed complete wound healing without recurrence, however, wound development occurred at other sites on the same foot following complete primary healing in 11 limbs (8.1%). Tolerable wounds persisted or wounds recurred at the same site in 30 limbs (22.2%), and 18 limbs (13.3%) needed major amputations. Independent factors that prevented wound healing without recurrence at 2 years were renal insufficiency (HR = 0.225, 95% C.I. = 0.091–0.556, p = 0.001), ankle pressure < 50 mmHg or flat forefoot PVR (HR = 0.328, 95% C.I. = 0.124–0.867, p = 0.025) and functional performance < 4 metabolic equivalents (MET) (HR = 0.150, 95% C.I. = 0.063–0.360, p

Background and Aims Recent data support a role for endoscopic radiofrequency ablation (RFA) in unresectable cholangiocarcinoma by improving stent patency and overall survival. Methods We describe 3 patients with inoperable cholangiocarcinoma with jaundice and cholestasis who were recommended palliative chemotherapy. They underwent endoscopic retrograde cholangiopancreatography with single-operator cholangioscope and intraductal RFA. Results The procedures were performed without adverse events in all patients, with clinical and analytical improvement 1 month later. Conclusions RFA is a promising and safe palliative treatment in patients with unresectable cholangiocarcinoma.

Background/purpose Oral submucous fibrosis (OSF) is an irreversible fibrosis disease and a potentially malignant disorder in the oral cavity. Various studies have shown that miR-21 was implicated in the fibrogenesis and carcinogenesis, but its functional role in the development of OSF has not been investigated. Methods The expression levels of miR-21 in arecoline-stimulated normal buccal mucosal fibroblasts (BMFs) and OSF specimens were determined by qRT-PCR. Exogenous administration of TGF-β and its inhibitor (SB431542) were utilized to examine the involvement of TGF-β signaling in miR-21 alteration. Collagen gel contraction, transwell migration, and invasion assays were used to assess the myofibroblast activities. The relationship between α-SMA and miR-21 was calculated using the Pearson correlation coefficient. Results MiR-21 expression was induced in BMFs by arecoline treatment in a dose-dependent manner. Our results showed that this upregulation was mediated by TGF-β signaling. Subsequently, we demonstrated that the administration of the miR-21 inhibitor suppressed the arecoline-induced myofibroblast characteristics, including a higher collagen gel contractility and cell motility, in normal BMFs. Furthermore, inhibition of miR-21 was sufficient to attenuate the myofibroblast features in fibrotic BMFs. Besides, we showed that the expression of miR-21 was aberrantly upregulated in the OSF tissues and there was a positive correlation between miR-21 and myofibroblast marker, α-SMA. Conclusion MiR-21 overexpression in OSF may be due to the stimulation of areca nut, which was mediated by the TGF-β pathway. Our data suggested that the repression of miR-21 was a promising direction to palliate the development and progression of OSF.