Impact of Prospero Homeobox-1 (PROX-1) οn the Oncogenic Phenotypes of Hepatocellular Carcinoma Cells.

BACKGROUND/AIM: Transcriptional factor prospero homeobox-1 (PROX-1) is crucial for the embryonic development of various organs and cell fate specification. It exhibits either an oncogenic or tumor suppressive activity depending on cancer types. However, the relationship between PROX-1 and hepatocellular carcinoma (HCC) remains obscure. This study was conducted to investigate the effect of PROX-1 on the invasive and oncogenic phenotypes of human HCC cells. MATERIALS AND METHODS: The effect of PROX-1 on tumor cell behavior was investigated by using a pcDNA-myc vector and a small interfering RNA in HepG2 and Huh7 human HCC cell lines. Flow cytometry, migration, invasion, proliferation, and tube formation assays were performed. PROX-1 expression in human HCC cells was explored by western blotting. RESULTS: PROX-1 overexpression enhanced tumor cell proliferation and inhibited apoptosis and cell cycle arrest by modulating the activities of caspase-3, PARP, and cyclin-dependent kinase inhibitors, including p21, p27, and p57 in HCC cells. After PROX-1 overexpression, the number of migrating and invading HCC cells significantly increased, and the expression levels of N-cadherin and Snail increased in HCC cells. PROX-1 overexpression enhanced angiogenesis through increased VEGF-A and VEGF-C expression and decreased angiostatin expression. PROX-1 overexpression also increased the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and forkhead box O1 (FOXO1) in HCC cells. After PROX-1 knockdown, their phosphorylation was reversed. CONCLUSION: PROX-1 overexpression is associated with the invasive and oncogenic phenotypes of human HCC cells via GSK-3ß and FOXO1 phosphorylation.

Management of early-stage hepatocellular carcinoma: challenges and strategies for optimal outcomes.

Although hepatocellular carcinoma (HCC) is associated with a poor prognosis, management of early-stage HCC is often successful with highly efficacious treatment modalities such as liver transplantation, surgical resection, and radiofrequency ablation. However, unfavorable clinical outcomes have been observed under certain circumstances, even after efficient treatment. Factors that predict unsuitable results after treatment include tumor markers, inflammatory markers, imaging findings reflecting tumor biology, specific outcome indicators for each treatment modality, liver functional reserve, and the technical feasibility of the treatment modalities. Various strategies may overcome these challenges, including the application of reinforced treatment indication criteria with predictive markers reflecting tumor biology, compensation for technical issues with up-to-date technologies, modification of treatment modalities, downstaging with locoregional therapies (such as transarterial chemotherapy or radiotherapy), and recently introduced combination immunotherapies. In this review, we discuss the challenges to achieving optimal outcomes in the management of early-stage HCC and suggest strategies to overcome these obstacles.

A Single-center 12-year Experience of Patients with Gastrointestinal Bezoars.

Background/Aims: Gastrointestinal (GI) bezoars are relatively rare diseases with clinical characteristics and treatment modalities that depend on the location of the bezoars. This study evaluated the clinical characteristics and treatment outcomes in patients with GI bezoars. Methods: Seventy-five patients diagnosed with GI bezoars were enrolled in this study. Data were collected on the demographic and clinical characteristics and the characteristics of the bezoars, such as type, size, location, treatment modality, and clinical outcomes. Results: Among the 75 patients (mean age 71.2 years, 38 males), 32 (42.6%) had a history of intra-abdominal surgery. Hypertension (43%) and diabetes (30%) were common morbidities. The common location of the bezoars was the stomach in 33 (44%) and the small intestine in 33 (44%). Non-surgical management, including adequate hydration, chemical dissolution, and endoscopic removal, was successful in 2/2 patients with esophageal bezoars, 26/33 patients with gastric bezoars, 7/9 patients with duodenal bezoars, and 20/33 patients with small intestinal bezoars. The remaining patients had undergone surgical management. Conclusions: The management of GI bezoars requires multidisciplinary approaches, including the appropriate correction of fluid and electrolyte imbalances, chemical dissolution, and endoscopic and surgical treatments.

Acute respiratory distress syndrome and severe pneumonitis after atezolizumab plus bevacizumab for hepatocellular carcinoma treatment: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has a high mortality. However, the treatment options for advanced HCC are limited to tyrosine kinase inhibitors, such as sorafenib and lenvatinib. Since previous regimens have an insufficient efficacy, the combination therapy of atezolizumab and bevacizumab (Ate/Bev) has been investigated, which showed an improvement in progression-free and overall survival. However, the adverse events of this combination therapy in advanced HCC have not been established. Herein, we report a novel case of an unresectable HCC and acute respiratory distress syndrome (ARDS) after a combination therapy of Ate/Bev. CASE SUMMARY: An 82-year-old male visited our outpatient clinic for an incidentally detected liver mass. Liver magnetic resonance imaging and enhanced chest computed tomography (CT) were performed, which showed arterial hyperenhancement with washout in delayed phase suggesting HCC, and a well-defined metastatic solid nodule, respectively. F-18 fluorodeoxyglucose positron emission tomography (PET)-CT exhibited multiple hypermetabolic lesions in the iliac bone, lumbar vertebrae, and femur. Because of the high burden of the intrahepatic tumor, transarterial radioembolization was initially performed; after 37 d, a combination therapy of Ate/Bev was administered. The patient visited the emergency department three days after Ate/Bev treatment complaining of dyspnea. He was diagnosed with severe pneumonitis based on CT. Despite administering oxygen via a high-flow nasal cannula, the P/F ratio was only 74; therefore, the patient was diagnosed with ARDS based on the overall examination results. Low tidal volume with high positive end-expiratory pressure, sedative agents combined with a neuromuscular blocker, and a systemic steroid were promptly applied to manage the ARDS. However, the patient did not recover from the hypoxia and expired 31 h after being admitted. CONCLUSION: Clinicians should be aware of severe pneumonitis due to the immune-related adverse events of this combination therapy, and patients should be closely monitored after therapy.

First Case of Atypical, Generalized Skin Rash after Transarterial Chemoembolization in a Patient with Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) is a widely used hepatocellular carcinoma (HCC) treatment. Some cases of supraumbilical skin rash after TACE in patients with HCC have been reported. To the best of the authors' knowledge, there are no reports on atypical, generalized rashes caused by doxorubicin systemic absorption after TACE. This paper presents the case of a 64-year-old male with HCC who developed generalized macules and patches one day after a successful TACE procedure. A histology examination of a skin biopsy of a dark reddish patch on the knee revealed severe interface dermatitis. He was treated with a topical steroid, and all skin rashes improved within a week with no side effects. This report presents this rare case with a literature review on skin rash after TACE.

Early extrahepatic recurrence as a pivotal factor for survival after hepatocellular carcinoma resection: A 15-year observational study.

BACKGROUND: Surgical resection is one of the most widely used modalities for the treatment of hepatocellular carcinoma (HCC). Early extrahepatic recurrence (EHR) of HCC after surgical resection is considered to be closely associated with poor prognosis. However, data regarding risk factors and survival outcomes of early EHR after surgical resection remain scarce. AIM: To investigate the clinical features and risk factors of early EHR and elucidate its association with survival outcomes. METHODS: From January 2004 to December 2019, we enrolled treatment-naïve patients who were ≥ 18 years and underwent surgical resection for HCC in two tertiary academic centers. After excluding patients with tumor types other than HCC and/or ineligible data, this retrospective study finally included 779 patients. Surgical resection of HCC was performed according to the physicians' decisions and the EHR was diagnosed based on contrast-enhanced computed tomography or magnetic resonance imaging, and pathologic confirmation was performed in selected patients. Multivariate Cox regression analysis was performed to identify the variables associated with EHR. RESULTS: Early EHR within 2 years after surgery was diagnosed in 9.5% of patients during a median follow-up period of 4.4 years. The recurrence-free survival period was 5.2 mo, and the median time to EHR was 8.8 mo in patients with early EHR. In 52.7% of patients with early EHR, EHR occurred as the first recurrence of HCC after surgical resection. On multivariate analysis, serum albumin < 4.0 g/dL, serum alkaline phosphatase > 100 U/L, surgical margin involvement, venous and/or lymphatic involvement, satellite nodules, tumor necrosis detected by pathology, tumor size ≥ 7 cm, and macrovascular invasion were determined as risk factors associated with early EHR. After sub-categorizing the patients according to the number of risk factors, the rates of both EHR and survival showed a significant correlation with the risk of early EHR. Furthermore, multivariate analysis revealed that early EHR was associated with substantially worse survival outcomes (Hazard ratio, 6.77; 95% confidence interval, 4.81-9.52; P < 0.001). CONCLUSION: Early EHR significantly deteriorates the survival of patients with HCC, and our identified risk factors may predict the clinical outcomes and aid in postoperative strategies for improving survival.

Amiodarone-Induced Multi-Systemic Toxicity Involving the Liver, Lungs, Thyroid, and Eyes: A Case Report.

Objectives: Amiodarone is widely used to treat arrhythmia. However, amiodarone is known for its severe toxicity to the liver, lungs, and thyroid. Amiodarone causes liver damage ranging from asymptomatic serum aminotransferase elevation to hepatic failure requiring liver transplantation. Although amiodarone toxicity has been reported, its simultaneous multi-organ toxicity is not well-known. Here, we introduce a novel case of multi-systemic amiodarone toxicity involving the liver, lungs, thyroid, and eyes. Case Presentation: A 61-year-old woman visited the emergency room due to general weakness, nausea, visual disturbance, heat intolerance, and a non-productive cough. The patient had been using clopidogrel and amiodarone due to underlying atrial fibrillation. The total level of bilirubin was 0.71 mg/dL, aspartate aminotransferase was 358 U/L, alanine aminotransferase was 177 U/L, and prothrombin time was 27.1 s. Computed tomography showed diffuse increased liver intensity and scattered hyperattenuated nodular consolidations in both lungs. Transthoracic needle lung biopsy revealed fibrinoid interstitial inflammation with atypical change of type II pneumocytes and intra-alveolar foamy macrophages. In addition, the thyroid-stimulating hormone level was <0.008 µIU/mL, and free thyroxine was 4.67 ng/dL. The thyroid scan showed diffuse homogenous intake of technetium-99 m pertechnetate in both thyroid lobes. The ophthalmologic exam detected bilateral symmetrical corneal deposits in a vortex pattern. With these findings, we could diagnose amiodarone-induced hepatic, pulmonary, thyroid, and ophthalmologic toxicity. Liver function was restored after cessation of amiodarone, and thyroid function was normalized with methimazole administration. However, due to aggravated lung consolidations, systemic steroid treatment was administered, and improvement was seen 1 week after, at the follow-up exam. As her symptoms improved, she was discharged with a plan of steroid administration for 3 to 6 months. Conclusions: This case implies the possibility of multi-systemic amiodarone toxicity. Thus, the toxicity of amiodarone to multiple organs must be monitored. Prompt cessation of the drug should be considered upon diagnosis.

Cytomegalovirus colitis induced segmental colonic hypoganglionosis in an immunocompetent patient: A case report.

BACKGROUND: Cytomegalovirus (CMV) colitis is usually seen in immunocompromised patients with risk factors such as human immunodeficiency virus infection, solid organ transplant, inflammatory bowel disease, or malignancy. Therefore, many clinicians usually do not consider the possibility of CMV colitis in immunocompetent patients. We reported a rare case of segmental colonic hypoganglionosis associated with CMV colitis in an immunocompetent patient. CASE SUMMARY: A 48-year-old woman with no underlying disease was admitted to our hospital for severe abdominal pain and constipation. Computed tomography of the abdomen showed diffuse dilatation of the small intestine and the entire colon. Initial sigmoidoscopic findings and result of polymerase chain reaction (PCR) for CMV revealed the compatible findings of CMV colitis, the patient was treated with intravenous ganciclovir. After treatment, sigmoidoscopic findings and CMV PCR results improved. However the patient continued to suffered from constipation. Eight months after the initial admission, patient visited the emergency department with severe abdominal pain and imaging revealed aggravation of fecal impaction and bowel dilatation. We performed subtotal colectomy to control patient's symptom. Histological examination of the resected specimen showed significantly reduced number of mature ganglion cells in the sigmoid colon compared to that in the proximal colon. CONCLUSION: Our case demonstrates that CMV colitis can develop even in patients with no other underlying disease, and that CMV colitis can be one of the causes for developing colonic hypoganglionosis.

Simple parameters predicting extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma.

Extrahepatic recurrence (EHR) after curative hepatectomy for hepatocellular carcinoma (HCC) is associated with a poor prognosis. We investigated the features of EHR and identified its predictive factors. This retrospective study included 398 treatment-naive patients who underwent curative hepatectomy for HCC at two tertiary hospitals. Multivariate Cox-regression analysis was performed to identify the variables associated with EHR. EHR was diagnosed in 94 patients (23.6%) over a median follow-up period of 5.92 years, most commonly in the lungs (42.6%). The 5-/10-year cumulative rates of HCC recurrence and EHR were 63.0%/75.6% and 18.1%/35.0%, respectively. The median time to EHR was 2.06 years. Intrahepatic HCC recurrence was not observed in 38.3% of patients on EHR diagnosis. On multivariate analysis, pathologic modified Union for International Cancer Control stage (III, IVa), surgical margin involvement, tumor necrosis, sum of tumor size > 7 cm, and macrovascular invasion were predictive factors of EHR. Four risk levels and their respective EHR rates were defined as follows: very low risk, 1-/5-year, 3.1%/11.6%; low risk, 1-/5-year, 12.0%/27.7%; intermediate risk, 1-/5-year, 36.3%/60.9%; and high risk, 1-year, 100.0%. Our predictive model clarifies the clinical course of EHR and could improve the follow-up strategy to improve outcomes.

Diagnostic yields of endoscopic ultrasound-guided fine-needle tissue acquisition according to the gastric location.

ABSTRACT: The diagnostic accuracy of endoscopic ultrasound-guided fine-needle tissue acquisition (EUS-FNTA) according to the gastric location of subepithelial tumors (SETs) has not been well established. We aimed to evaluate the efficacy of EUS-FNTA for the diagnosis of gastric SETs according to tumor location.Thirty-three patients diagnosed with gastric SETs via EUS-FNTA from January 2016 to May 2018 were analyzed retrospectively. Patient demographics, diagnostic yields, and complications were evaluated.Nineteen patients (57.6%) were female, with a mean age of 57.7 years. Endoscopic ultrasound revealed a mean longitudinal diameter of 25.6 mm. The most common location of SETs was in the gastric body (n = 18, 54.5%), followed by cardia and fundus (n = 10, 30.3%), and antrum (n = 5, 15.2%). A 20-gauge biopsy needle was most frequently used (90.9%). The diagnostic yield was obtained in 23 patients (69.7%). The most common diagnosis was gastrointestinal stromal tumor (73.9%), followed by leiomyoma (17.4%). The diagnostic yield of SETs in gastric antrum (0/5, 0%) was significantly lower than that in the gastric body and cardia (23/28, 82.1%, P = .001). A case of immediate bleeding after EUS-FNTA occurred in 1 patient (3.0%) who recovered uneventfully. According to related literature, the overall diagnostic yield of SETs in gastric antrum was significantly lower than that in the gastric body, fundus, and cardia (29.7% vs 71.4%, P < .001, n = 191).EUS-FNTA is ineffective in the diagnosis of SETs in the gastric antrum. Although EUS-FNTA is an advanced diagnostic tool for gastric SETs, it is essential to develop more effective methods for the diagnosis of antral SETs.

Endoscopic repair of delayed stomach perforation caused by penetrating trauma: A case report.

BACKGROUND: Primary endoscopic closure of a perforated gastric wall during endoscopic procedures is mostly effective and well-tolerated; however, there are very few studies on the efficacy of endoscopic management of delayed traumatic gastric perforation. Herein, we report a novel case of a patient who was successfully treated for delayed traumatic stomach perforation using an alternative endoscopic modality. CASE SUMMARY: A 39-year-old woman presented with multiple penetrating traumas in the back and left abdominal cavity. Initial imaging studies revealed left diaphragmatic disruption and peri-splenic hemorrhage without gastric perforation. An emergency primary repair of the disrupted diaphragm with omental reduction and suturing of the lacerated lung was performed; however, delayed free perforation of the gastric wall was noted on computed tomography after 3 d. Following an emergency abdominal surgery for the primary repair of the gastric wall, re-perforation was noted 15 d postoperatively. The high risk associated with re-surgery prompted an endoscopic intervention using 2 endoloops and 11 endoscopic clips using a novel modified purse-string suture technique. The free perforated gastric wall was successfully repaired without additional surgery or intervention. The patient was discharged after 46 d without any complications. CONCLUSION: Endoscopic closure with endoloops and clips can be a useful therapeutic alternative to re-surgery for delayed traumatic gastric perforation.

Underwater endoscopic mucosal resection of an incompletely resected superficial non-ampullary duodenal epithelial neoplasm using the loop-and-let-go technique: A case report.

RATIONALE: Endoscopic resection of superficial non-ampullary duodenal epithelial neoplasm (SNADEN) is a challenging procedure owing to the high recurrence rate and considerable incidence rate of adverse events. PATIENT CONCERNS: SNADEN accidentally found during a medical examination in a 56-year-old man. DIAGNOSIS: The patient was diagnosed as having a 20-mm-sized flat elevated SNADEN at the superior duodenal angle. INTERVENTIONS: First, we tried to perform conventional EMR (CEMR). However, the submucosal injection interrupted the endoscopic view and did not provide enough space for CEMR because of its angulated location. Therefore, we chose to perform endoscopic resection using the "loop-and-let-go" technique. Follow-up duodenoscopy after 2 days revealed post CEMR ulcer with suspicious remnant lesion. Underwater endoscopic mucosal resection (UEMR) was successfully performed 3 months after the first session of endoscopic resection. OUTCOMES: Complete endoscopic en bloc resection and histological complete resection were achieved with UEMR. Follow-up duodenoscopy revealed no recurrence. LESSONS: Step-by-step endoscopic treatment with UEMR following loop-and-let-go technique may be a good strategy for SNADEN over 20-mm in diameter.

Underwater endoscopic mucosal resection for neoplasms in the pyloric ring of the stomach: Four case reports.

BACKGROUND: Tumors located in the pylorus are technically more complex to resect by endoscopic resection, as the anatomical characteristics of this region can affect the adequate assessment of margins and performance of the procedure. We reported the results of underwater endoscopic mucosal resection (UEMR) of benign mucosal neoplasms located in the pyloric ring. CASE SUMMARY: This case series describes 4 patients with 4 mucosal neoplasms located in the pyloric ring. The diameter of each neoplasm was less than 15 mm. We performed UEMR for the lesions. Water immersion enabled slight floating of the lesions, resulting in easy identification. We achieved en bloc resection with a snare and electrosurgical unit. All procedure were performed within 3 min without adverse events. Pathologic examination showed low-grade dysplasia with clear resection margins in one case and hyperplastic polyps in three cases. CONCLUSION: UEMR can be an effective and safe treatment method for neoplasms in the gastric pyloric ring.

Association between Charlson comorbidity index and complications of endoscopic resection of gastric neoplasms in elderly patients.

BACKGROUND: Although endoscopic resection is safe and effective for gastric epithelial neoplasms, information is limited on its efficacy and safety in extremely elderly patients who have various comorbidities. Further, the relationship between comorbidities and complications of endoscopic resection is not well established. Therefore, we aimed to evaluate the efficacy and safety of endoscopic resection of gastric epithelial neoplasms in extremely elderly patients. METHODS: From October 2008 to December 2017, 4475 consecutive patients underwent endoscopic resection of gastric epithelial neoplasms. Among them, 242 were 75 years or older. We assessed Charlson comorbidity index (CCI) scores, procedural outcomes, and procedure- and sedation-related complications related to endoscopic resection. RESULTS: Mean patient age was 78.7 ± 3.2 years. Of the 242 patients, 124 (51.2%) had low-grade dysplasia and 112 (46.3%) had adenocarcinoma. The most common comorbidity was hypertension (55.4%), followed by diabetes (23.1%). The mean CCI score was 1.67 ± 1.43. Sixty patients (24.8%) had a CCI score ≥ 3. During the procedure, 10 (4.1%) patients had desaturation that recovered by flumazenil use with mask (n = 2) or Ambu bag (n = 3) ventilation. During subsequent admission, atelectasis or pneumonia occurred in 45 (18.6%) patients, post-procedural bleeding in 12 (5.0%), and perforation in 3 (1.2%). Respiratory complications were more common in patients with a CCI score ≥ 3 (20/60, 33.3%) than in those with a CCI score < 3 (25/182, 13.7%, P = 0.002). CONCLUSIONS: CCI score is related to respiratory complications of endoscopic resection in extremely elderly patients. Endoscopic resection must be performed cautiously, particularly in elderly patients with a high CCI score, to prevent respiratory complications.

Endoscopic and Endosonographic Features of Histologically Proven Gastric Ectopic Pancreas by Endoscopic Resection.

Backgrounds/Aims: Distinguishing gastric ectopic pancreas (GEP) from malignant tumors is relatively difficult. This study evaluated the endosonography findings of pathologically proven GEP. Methods: Thirty-one patients diagnosed with GEP based on a histopathological analysis from January 2004 to July 2018 were enrolled in this study. All patients underwent EUS and an endoscopic resection. Results: Seventeen patients were female, and the median age was 41.1 years (range, 14-74). The lesions were localized most commonly in the antrum. The mean size of the GEP was 10.6 mm (range, 7-15). Superficial type lesions, lesions with heterogeneous echogenicity, mixed pattern lesions, and lesions with indistinct borders were commonly observed on EUS. Calcification, anechoic duct-like structures, and thickening of the muscularis propria were observed in some patients. Endoscopic mucosal resection (41.9%) and endoscopic submucosal dissection (58.1%) were performed. The mean procedure time was 22.5 minutes. Complete resection was achieved for 71% of patients. No statistically significant results between the endosonography findings and complete resection rates were obtained. The mean follow-up esophagogastroduodenoscopy duration was 4.5 months. None of the patients presented with residual lesions on subsequent endoscopy. Conclusions: EUS can help identify the features of GEP. Careful observations of the EUS findings can avoid unnecessary removal of GEP.

Minimally invasive surgical strategy for refractory hepatic hydrothorax.

OBJECTIVES: Treatment of refractory hepatic hydrothorax, a complication of liver cirrhosis, is complex. We aimed to investigate the usefulness of the '4-step approach', which is a minimally invasive surgical strategy combining 4 therapeutic modalities: (i) pneumoperitoneum to localize diaphragmatic defects; (ii) thoracoscopic pleurodesis; (iii) postoperative positive-pressure ventilation; and (iv) peritoneal drainage for abdominal decompression. METHODS: We retrospectively analysed the medical records of 12 patients with hepatic hydrothorax who underwent surgical treatment using the 4-step approach from January 2013 to December 2017. Nine of them (75.0%) were Child C cases; the median model for end-stage liver disease score was 20.5. The diaphragmatic defects localized after forming a pneumoperitoneum were treated with primary closure followed by thoracoscopic pleurodesis, postoperative positive-pressure ventilation and peritoneal drainage. RESULTS: Diaphragmatic defects were localized in all patients except one. The median postoperative positive-pressure ventilation duration was 20.1 h. Peritoneal drainage was performed for a median duration of 5 days; the peritoneal drains were removed at a median of 8 postoperative days. The median duration of postoperative hospital stay until discharge/transfer was 9.5 days. No operative mortalities occurred. The median duration of follow-up was 10.9 months. Eight deaths (66.7%) occurred during the follow-up period; however, no deaths were surgery-associated. Ipsilateral pleural effusion recurred in 3 patients (25%), among whom reoperation was performed in 1 without recurrence at the 13-month follow-up. CONCLUSIONS: The 4-step approach seems to be a safe and effective minimally invasive surgical strategy for treating refractory hepatic hydrothorax.

A Review of Hepatocellular Carcinoma in Elderly Patients Focused on Management and Outcomes.

Recent studies report a significant age-specific increase in hepatocellular carcinoma (HCC) development among persons over 75 years old. Therefore, there is an urgent need to determine the optimal treatment strategy in elderly patients with HCC. This systemic review examines the clinical characteristics, efficacy, and safety of first-line treatment modalities. The literature was searched regarding epidemiology and clinical outcomes in elderly patients (age ≥75 years) undergoing first-line treatment for HCC. Causative or comorbid conditions of HCC in elderly patients differed from those in younger patients. Radiofrequency ablation may be effective and safe in early stages. Surgical resection may also be feasible in the early stages for selected patients. Transarterial chemoembolization may be safe and effective for intermediate HCC, and sorafenib may be feasible in elderly patients with advanced HCC. Prospective randomized trials are needed to establish the treatment strategy for elderly patients with HCC.

Various Treatment Modalities in Hepatic Hydrothorax: What Is Safe and Effective?

PURPOSE: Hepatic hydrothorax is a complication of decompensated liver cirrhosis that is difficult and complex to manage. Data concerning the optimal treatment method, other than liver transplantation, are limited. This study aimed to compare the clinical features and outcomes of patients treated with various modalities, while focusing on surgical management and pigtail drainage. MATERIALS AND METHODS: Forty-one patients diagnosed with refractory hepatic hydrothorax between January 2013 and December 2017 were enrolled. RESULTS: The mean Child-Turcotte-Pugh and model for end stage liver disease scores of the enrolled patients were 10.1 and 19.7, respectively. The patients underwent four modalities: serial thoracentesis (n=11, 26.8%), pigtail drainage (n=16, 39.0%), surgery (n=10, 24.4%), and liver transplantation (n=4, 9.8%); 12-month mortality rate/median survival duration was 18.2%/868 days, 87.5%/79 days, 70%/179 days, and 0%/601.5 days, respectively. Regarding the management of refractory hepatic hydrothorax, surgery group required less frequent needle puncture (23.5 times in pigtail group vs. 9.3 times in surgery group), had a lower occurrence of hepatorenal syndrome (50% vs. 30%), and had a non-inferior cumulative overall survival (402.1 days vs. 221.7 days) compared to pigtail group. On multivariate analysis for poor survival, body mass index <19 kg/m², refractory hepatic hydrothorax not managed with liver transplantation, Child-Turcotte-Pugh score >10, and history of severe encephalopathy (grade >2) were associated with poor survival. CONCLUSION: Serial thoracentesis may be recommended for management of hepatic hydrothorax and surgical management can be a useful option in patients with refractory hepatic hydrothorax, alternative to pigtail drainage.

Association Between Gastric Emptying Time and Incidence of Cardiovascular Diseases in Subjects With Diabetes.

BACKGROUND/AIMS: Delayed gastric emptying (GE) is associated with high morbidity and mortality in subjects with diabetes. The aim of this study is to investigate associations between GE time and the major cardiovascular events (coronary heart diseases and ischemic stroke) in diabetic subjects with upper gastrointestinal (UGI) symptoms. METHODS: Among 259 subjects with chronic UGI symptoms who underwent gastric emptying study (GES) over 13 years, 122 diabetic subjects without gastric surgery and/or rapid GE were enrolled in this study. We also gathered data about baseline demographics, clinical characteristics, estimated GE half-time (GE T½) and incidence of cardiovascular events following GES. RESULTS: The mean age of subjects was 64.0 ± 17.4 years. There were 86 women and 104 subjects with type 2 diabetes. There were 52 (42.6%) subjects with normal GE, 50 (41.0.%) subjects with mild delayed GE, and 20 (16.4%) subjects with marked delayed GE. During follow-up (median, 207 weeks), cardiovascular events occurred in 7 (13.5%) subjects with normal GE, 4 (8.0%) subjects with mild delayed GE and 7 (35.0%) subjects with marked GE ( P = 0.015). Univariate analysis showed that GE T½ was significantly associated with incidence of cardiovascular events (crude OR, 1.74; 95% CI, 1.12-2.69; P = 0.014). In a multivariate model, association between GE T½ and incidence of cardiovascular events remained statistically significant after adjustment for baseline characteristics and comorbidities (adjusted OR, 1.94; 95% CI, 1.21-3.12; P = 0.006). CONCLUSION: A delay of GE was associated with an increased incidence of cardiovascular events in diabetic subjects with chronic UGI symptoms.

Characteristics and Outcomes of Extreme Elderly Patients With Hepatocellular Carcinoma in South Korea.

BACKGROUND/AIM: The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) has been increasing. But there is no proper management based on age stratification in elderly patients. Therefore, we evaluated the clinical characteristics and outcomes of elderly HCC patients more than 75 years old in South Korea. PATIENTS AND METHODS: Five hundred and fifty elderly patients with HCC were enrolled and divided into the oldest-old (age ≥85 years), middle-old (age between 80 and 85 years), and young-old groups (age between 75 and 80 years). RESULTS: Fifty-one, 153, and 346 patients were included in the oldest-old (mean age: 87 years), middle-old (mean age: 82 years), and young-old groups (mean age: 77 years), respectively. There was a significantly lower rate of alcohol-related and hepatitis B virus-related diseases in the oldest-old group than in the other groups, whereas there was no significant difference in other characteristics. With increasing age, conservative treatment was predominantly performed. Transarterial chemoembolization was the main modality of active treatment in all groups. In multivariate analysis, the performance score, model for end-stage liver disease score, modified Union for International Cancer Control staging, Barcelona Clinic Liver Cancer staging, presence of portal vein tumor thrombosis, ruptured HCC, and active treatment were risk factors of overall survival. CONCLUSION: When the therapeutic approach is used in elderly patients with HCC, the patient's performance status, liver function, and stage of cancer should be considered, and its use should not be restricted to those of advanced age.