Prognostic Significance of Intratumoral and Peritumoral Budding in Distal Extrahepatic Bile Duct Carcinoma.

INTRODUCTION: Although tumor budding (TB) has been recognized as a representative adverse prognosticator in gastrointestinal malignancies, it is not well-elucidated in distal extrahepatic bile duct carcinoma (DBDC). Herein, we investigated the prognostic significance of peritumoral (PTB) and intratumoral (ITB) budding according to the modified DBDC staging of the 8th edition of the American Joint Committee on Cancer. METHODS: PTB and ITB were independently evaluated in a cohort of DBDC patients (n = 410) based on the 2016 International Tumor Budding Consensus Conference (ITBCC). RESULTS: High levels of PTB (PTBHigh, ≥ grade-2) and ITB (ITBHigh, ≥ grade-3) were identified in 316 (77%) and 238 (58%) cases, respectively. In univariate analysis, PTBHigh and ITBHigh, larger size and sclerosing tumor growth pattern, higher histologic grade, extrapancreatic location, adenocarcinomas unrelated to intraductal papillary neoplasm of the bile duct (IPNB), pancreatic, duodenal, and lymphovascular invasion, perineural invasion, cancer involvement of the bile duct resection margin, nodal metastasis, and higher T and N categories and disease stages were associated with shorter patient overall survival (OS) times. In multivariate analysis, PTBHigh and ITBHigh remained poor independent prognostic indicators of OS in DBDC patients. Specifically, ITBHigh could predict poor prognosis in patients with stage I (T1N0) DBDC. CONCLUSIONS: Both PTBHigh and ITBHigh were strong prognostic indicators in patients with DBDC. Thus, ITB could be used to predict worse prognoses in patients with DBDC, in which PTB is difficult to assess, especially for patients with stage I (T1N0) DBDC.

Soft Tissue Chondroma of the Chin.

Soft tissue chondromas are benign tumors, generally of the hands or feet, very rarely of the head and neck region. Repeated microtrauma may be as an initiating factor. The authors describe a case of a soft tissue chondroma of the chin in a 58-year-old male who had used a continuous positive airway pressure face mask for obstructive sleep apnea for 3 years. The patient presented with a hard mass on his chin for 1 year. Computed tomography imaging showed a heterogeneous enhancing mass, with calcification in the subcutaneous layer. Intraoperatively, the mass was beneath the mentalis muscle and abutted the mental nerve, without bone involvement. The diagnosis was a soft tissue chondroma. The patient recovered fully, without recurrence. The primary cause of soft tissue chondromas is unknown. The authors consider that continuous use of a continuous positive airway pressure face mask may play a role in the etiology.

Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size.

OBJECTIVE: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown. DESIGN: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS). RESULTS: ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%). CONCLUSIONS: ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.

Clinicopathologic and Molecular Characteristics of and Diagnostic Dilemmas in Invasive Breast Carcinoma with Choriocarcinomatous Pattern apropos a New Case: A Literature Review with New Findings.

BACKGROUND: Invasive breast carcinoma with a choriocarcinomatous pattern (IBC-CP) is extremely rare, and its molecular basis is yet unclear. The choriocarcinomatous pattern is characterized by the biphasic arrangement of multinucleated syncytiotrophoblast-like cells around clusters of monotypic tumor cells in a hemorrhagic background, along with ß-human chorionic gonadotropin (ß-hCG) expression. The differentiation of IBC-CP from metastatic choriocarcinoma of the breast (MC-B) is difficult due to the histologic similarity. METHODS: Based on a literature review and our own case, the clinicopathologic differences between IBC-CP patients (n = 17) and MC-B patients (n = 8) were analyzed. Moreover, in our case of IBC-CP, next-generation sequencing (NGS) comparative analysis was conducted for both choriocarcinomatous and invasive breast carcinoma (IBC) components. RESULTS: Compared to the MC-B patients, the IBC-CP patients were older (p < 0.001) and less frequently had past histories of gestational trophoblastic disease/pregnancy/abortion (p = 0.001) and distant metastases (p = 0.005). Our case, a 49-year-old female patient, presented with masses in the right breast and axilla. Following neoadjuvant chemotherapy, a radical mastectomy found an 8.5-cm-sized tumor. Microscopically, multinucleated syncytiotrophoblast-like cells were observed around mononuclear tumor cells with hemorrhage and necrosis. Some tumor cells showed ß-hCG immunopositivity, which was compatible with IBC-CP. NGS results showed a missense mutation in exon 5 of the TP53 gene in both the choriocarcinomatous and IBC components. Meanwhile, copy number loss in the PTEN gene was only identified in the choriocarcinomatous components. CONCLUSION: The present IBC-CP case is triple-negative breast cancer with TP53 mutation. The PTEN gene may be associated with choriocarcinomatous differentiation. Obtaining a medical history is mandatory to exclude metastatic lesions.

Pancreatic Cysts after Endoscopic Ultrasonography-Guided Ethanol and/or Paclitaxel Ablation Therapy: Another Mimic of Pancreatic Pseudocysts.

BACKGROUND: Endoscopic ultrasound-guided ablation (EUS-A) therapy is a minimally invasive procedure for pancreatic-cystic tumors in patients with preoperative comorbidities or in patients who are not indicated for surgical resection. However, histopathologic characteristics of pancreatic cysts after ablation have not been well-elucidated. METHODS: Here, we analyzed pathological findings of 12 surgically resected pancreatic cysts after EUS-A with ethanol and/or paclitaxel injection. RESULTS: Mean patient age was 49.8 ± 13.6 years with a 0.3 male/female ratio. Clinical impression before EUS-A was predominantly mucinous cystic neoplasms. Mean cyst size before and after ablation therapy was similar (3.7 ± 1.0 cm vs. 3.4 ± 1.6 cm; p = 0.139). Median duration from EUS-A to surgical resection was 18 (range, 1-59) months. Mean percentage of the residual neoplastic lining epithelial cells were 23.1 ± 37.0%. Of the resected cysts, 8 cases (67%) showed no/minimal (<5%) residual lining epithelia, while the remaining 4 cases (33%) showed a wide range of residual mucinous epithelia (20-90%). Ovarian-type stroma was noted in 5 cases (42%). Other histologic features included histiocytic aggregation (67%), stromal hyalinization (67%), diffuse egg shell-like calcification along the cystic wall (58%), and fat necrosis (8%). CONCLUSION: Above all, diffuse egg shell-like calcification along the pancreatic cystic walls with residual lining epithelia and/or ovarian-type stroma were characteristics of pancreatic cysts after EUS-A. Therefore, understanding these histologic features will be helpful for precise pathological diagnosis of pancreatic cystic tumor after EUS-A, even without knowing the patient's history of EUS-A.

Multiple KRAS mutations in the non-mucinous epithelial lining in the majority of mucinous cystic neoplasms of the pancreas.

AIMS: Mucinous cystic neoplasms (MCNs) of the pancreas are cystic neoplasms lined by mucinous lining epithelium (MLE) with associated ovarian-type stroma. Although a non-MLE (NMLE) can be observed in some MCNs, whether cystic neoplasms with ovarian-type stroma and NMLE should be classified as MCNs or separately designated is debated. METHODS AND RESULTS: To test this, NMLEs were defined as flat or cuboidal epithelial cells without intracytoplasmic mucin. A total of 112 MCNs were reviewed, and the epithelium was classified as NMLE or MLE. A total of 110 females and two males with a mean age of 46.5 ± 12.3 years were included in this study. At least focal NMLE was noted in 76.8% (86/112) of MCNs. The mean percentage of the neoplastic epithelium that was NMLE in these 86 cases was 46%. NMLE was predominant (>50%) in 38.4% (43/112) of cases. MCNs with NMLE were smaller (42 ± 21 mm) than those with MLE (60 ± 36 mm, P < 0.001), and all NMLEs had low-grade dysplasia. Twelve MCNs with NMLE or MLE were selected for KRAS mutation analysis with droplet digital polymerase chain reaction after laser capture microdissection. All 12 MCNs showed multiple types of KRAS mutation, which were detected in 92% (11/12) of NMLE foci and 89% (8/9) of MLE foci. Predominant NMLE was common in small MCNs with low-grade dysplasia. CONCLUSIONS: Clonal KRAS mutations were observed in both NMLE and MLE, supporting the hypothesis that MCNs with NMLE should be classified as MCNs.

The association of diabetes duration and glycemic control with depression in elderly men with type 2 diabetes mellitus.

BACKGROUND: The prevalence of depression and type 2 diabetes mellitus (T2DM) are increasing in the elderly and are reportedly related to each other. We evaluated the relationship between T2DM-related factors and the degree of depression in elderly patients with T2DM based on gender. MATERIALS AND METHODS: A total of 155 patients with T2DM (56 males and 99 females aged ≥ 65 years) from seven hospitals were included in the study. To assess the status of depressive symptoms, the short form of the Geriatric Depression Scale-Korean version (SGDS-K) was used. We evaluated DM-related factors, such as T2DM duration, hemoglobin A1c (HbA1c) levels, and T2DM complications, as well as other possible factors that could affect depression, such as cognitive function, physical function, education level, and other personal factors. RESULTS: Mean age of the participants was 71.3 years with a mean HbA1c level of 7.6%. Males in the good glycemic control group (HbA1c <7%) showed lower SGDS-K scores compared to those in the poor glycemic control group, and the mean SGDS-K score was higher in the group with a longer duration of DM (M10 years); however, no difference was observed in females. Males and females with microvascular and macrovascular complications tended to have higher SGDS-K scores than participants with no microvascular or macrovascular complications. A multiple linear regression analysis revealed that DM duration and HbA1c level were independently associated with SGDS-K scores in males. CONCLUSION: Greater depression was associated with poorer glycemic control and a longer duration of DM in elderly males with T2DM.

Establishment and characterization of 6 novel patient-derived primary pancreatic ductal adenocarcinoma cell lines from Korean pancreatic cancer patients.

BACKGROUND: Pancreatic ductal adenocarcinomas are among the most malignant neoplasms and have very poor prognosis. Our understanding of various cancers has recently improved the survival of patients with cancer, except for pancreatic cancers. Establishment of primary cancer cell lines of pancreatic ductal adenocarcinomas will be useful for understanding the molecular mechanisms of this disease. METHODS: Eighty-one surgically resected pancreatic ductal adenocarcinomas were collected. Six novel pancreatic cancer cell lines, AMCPAC01-06, were established and histogenetic characteristics were compared with their matched tissues. The clinicopathologic and molecular characteristics of the cell lines were investigated by KRAS and TP53 sequencing or SMAD4 and p53 immunohistochemistry. Xenografts using AMCPAC cell lines were established. RESULTS: From the 81 pancreatic ductal adenocarcinomas, six (7.4% success rate) patient-derived primary cell lines were established. The six AMCPAC cell lines showed various morphologies and exhibited a wide range of doubling times. AMCPAC cell lines contained mutant KRAS in codons 12, 13, or 61 and TP53 in exon 5 as well as showed aberrant p53 (5 overexpression and 1 total loss) or DPC4 (all 6 intact) expression. AMCPAC cell lines demonstrated homology for the KRAS mutation and p53 expression compared with matched primary cancer tissues, but showed heterogeneous DPC4 expression patterns. CONCLUSIONS: The novel AMCPAC01-06 cell lines established in this study may contribute to the understanding of pancreatic ductal adenocarcinomas. Trial registration Retrospectively registered.

Oncocytic type has distinct immunohistochemical and recurrence-free survival than other histologic types of the intraductal papillary neoplasm of the bile duct.

Although intraductal oncocytic papillary neoplasm (IOPN) was considered distinct from the intraductal papillary neoplasm of the pancreas, the oncocytic histologic type remained as a subtype of intraductal papillary neoplasms of the bile duct (IPNBs) with gastric, intestinal, and pancreatobiliary types based on the fifth edition of the WHO classification. To test the characteristics of the oncocytic type of IPNBs, the histopathologic, immunohistochemical (Hep Par-1 and CD117), and clinical characteristics of 13 oncocytic type were compared with 114 others (15 gastric, 39 pancreatobiliary, and 60 intestinal) IPNB types. The oncocytic type, which occupied about 9% of IPNBs, was more frequent in females (p < 0.05) and larger (mean, 5.3 vs. 3.6 cm; p < 0.002) than other IPNB types. Immunohistochemically, the oncocytic type had more frequent combined Hep Par-1 and CD117 expression than other IPNB types (all p < 0.05). The recurrence-free survival rate for patients with the oncocytic type (5-year survival, 100%) was significantly higher (p = 0.015) than for those with other histologic types (59.9%). The oncocytic type had distinct histopathologic, immunohistochemical, and survival outcomes from other IPNBs. Therefore, it can be separated from other IPNB types and classified as one independent entity, similar to IOPN of the pancreas.

Beneficial effects of fresh and fermented kimchi in prediabetic individuals.

BACKGROUND: With the increased incidence of diabetes mellitus, the importance of early intervention in prediabetes has been emphasized. We previously reported that fermented kimchi, a traditional Korean food, reduced body weight and improved metabolic factors in overweight participants. We hypothesized that kimchi and its fermented form would have beneficial effects on glucose metabolism in patients with prediabetes. METHODS: A total of 21 participants with prediabetes were enrolled. During the first 8 weeks, they consumed either fresh (1-day-old) or fermented (10-day-old) kimchi. After a 4-week washout period, they switched to the other type of kimchi for the next 8 weeks. RESULTS: Consumption of both types of kimchi significantly decreased body weight, body mass index, and waist circumference. Fermented kimchi decreased insulin resistance, and increased insulin sensitivity, QUICKI and disposition index values (p = 0.004 and 0.028, respectively). Systolic and diastolic blood pressure (BP) decreased significantly in the fermented kimchi group. The percentages of participants who showed improved glucose tolerance were 9.5 and 33.3% in the fresh and fermented kimchi groups, respectively. CONCLUSIONS: Consumption of kimchi had beneficial effects on glucose metabolism-related and anthropometric factors in participants with prediabetes. Fermented kimchi had additional effects on BP and insulin resistance/sensitivity. The percentage of participants who showed improvement in glucose tolerance was high in the fermented kimchi group.

An unusual presentation of diabetic ketoacidosis in familial hajdu-cheney syndrome: a case report.

A 21-year-old man with diabetic ketoacidosis (DKA) displayed short and clubbed fingers and marked eyebrow, which are typical of Hajdu-Cheney Syndrome (HCS). Laboratory findings confirmed type 1 diabetes mellitus (DM). After conservative care with hydration and insulin supply, metabolic impairment was improved. Examinations of bone and metabolism revealed osteoporosis and craniofacial abnormalities. The mutation (c.6443T>G) of the NOTCH2 gene was found. The patient was diagnosed with HCS and DM. There may be a relationship between HCS and DM, with development of pancreatic symptoms related to the NOTCH2 gene mutation.

Sleep duration and glycemic control in patients with diabetes mellitus: Korea National Health and Nutrition Examination Survey 2007-2010.

Short sleep duration has been reported to increase the risk of diabetes. However, the influence of sleep duration on glycemic control in diabetic patients has not been clarified. In this study we evaluated the association between sleep duration and glycemic control in diabetic patients. We analyzed the data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2007-2010. Sleep duration was classified into five groups: <6, 6, 7, 8, and ≥9 h/day. Fasting blood glucose and HbA1c showed a U-shaped trend according to sleep duration. Sleep duration of 7 h/day had the lowest HbA1c (7.26%) among the subjects (P=0.026). In the older age group (≥65 yr), a sleep duration of 6 h/day was associated with the lowest HbA1c (7.26%). The adjusted odds ratio (OR) with a 95% confidence interval (CI) of worse glycemic control (HbA1c ≥7.0%) in group of sleep duration of ≥9 h/day was 1.48 (1.04-2.13) compared with the group of 7 h/day. This relationship disappeared after adjusting duration of diabetes (OR, 1.38; 95% CI, 0.93-2.03). Our results suggest that sleep duration and glycemic control in diabetic patients has U-shaped relationship which was mainly affected by duration of diabetes.

Diagnostic Value of Nestin Expression in Adult Gliomas.

Introduction. Nestin, a type VI intermediate filament, is expressed in neuroepithelial cells during embryogenesis and has been expressed in various human tumors. Recent studies reported that the expression was associated with poor prognosis in brain tumors, but the results were inconclusive. In this study, we evaluated usefulness of nestin expression as a prognostic biomarker in consideration of IDH mutation and the World Health Organization (WHO) classification fifth edition. Methods. To investigate nestin expression, immunohistochemistry was performed on 92 adult brain gliomas using tissue microarrays. We analyzed the clinical characteristics and survival outcomes according to nestin expression and examined whether nestin expression alone affects the prognosis, independent of IDH mutation. Results. Sixty patients (65.2%) were nestin-positive (weak and strong). Nestin expression and intensity were significantly correlated with pathologic diagnosis and IDH mutation. The patients with high-grade gliomas showed a higher frequency and stronger intensity of nestin expression than those with low-grade gliomas (P < .001). The majority (93.6%) of gliomas with IDH mutation showed no expression or weak positivity. Multivariate Cox proportional hazard regression analysis for overall survival demonstrated that nestin expression (weak, hazard ratio [HR] 5.39, P = .036; strong, HR 8.43, P = .007) was an independent prognostic factor. Moreover, patients with nestin-expressing glioma showed shorter survival (P < .001). Conclusions. Nestin seems to be strongly expressed in the vast majority of glioblastomas, IDH-wildtype and rarely in IDH-mutant gliomas. Clear correlation between nestin expression and pathologic diagnosis makes an accurate patient diagnosis. Expression and intensity of nestin were significantly correlated with worse survival.

Tumor Microenvironment Prognostic Risk and Its Association With MUC5AC in Ampullary Carcinoma.

CONTEXT.­: The tumor-host interaction in the tumor microenvironment (TME) affects the prognosis of patients with malignant tumors. TME assessed via tumor budding (BD) and tumor-infiltrating lymphocyte (TIL) had a prognostic impact in patients with nonampullary small intestinal and colorectal carcinomas. In ampullary carcinoma (AC), MUC5AC was recently revealed as a significant prognosticator, but studies about the TME have not been conducted. OBJECTIVE.­: To assess TME-based prognostic risk in AC. DESIGN.­: We generated a collective TME risk index based on high-grade BD at the invasive front (BD3) and high density of stromal-TIL (>5%) in 64 surgically resected ACs. We evaluated its predictive values for overall survival (OS) and recurrence-free survival (RFS). We also investigated the relationship of TME to MUC5AC expression. RESULTS.­: TME prognostic risk index was classified into low-risk (BDLow/TILHigh; 26 of 64; 41%), intermediate-risk (BDLow/TILLow or BDHigh/TILHigh; 23; 36%), and high-risk (BDHigh/TILLow; 15; 23%) groups. Higher TME prognostic risk was associated with higher tumor grade (P = .03), lymphovascular invasion (P = .05), and MUC5AC immunopositivity (P = .02). TME prognostic risk index displayed better predictive ability for both OS (53.9 versus 46.1 versus 42.2) and RFS (24.8 versus 16.9 versus 15.3) than BD or TIL alone. In multivariate analysis, TME prognostic risk index was an independent prognosticator for OS (P = .003) and RFS (P = .03). CONCLUSIONS.­: TME risk index in combination with BD and TIL was a stronger predictor of prognostic risk stratification than either BD or TIL alone for both OS and RFS in patients with AC. MUC5AC may modulate the interaction between tumor cells and immunity toward enhancing invasiveness in TME.

In-vitro cell tests using doxorubicin-loaded polymeric TiO2 nanotubes used for cancer photothermotherapy.

To determine the appropriate surfactant to be added to TiO(2) nanotubes (TNTs) for use in cancer photothermotherapy, this study measured the increase in temperature and examined the size distribution of TNT particles loaded with different surfactants during near-infrared irradiation. In addition, in-vitro cell (fluorescein isothiocyanate and MTT assay) tests were carried out to examine the cytotoxic effect of doxorubicin-loaded and polyvinyl alcohol-added TNTs (pTNTs). The mean particle size of the pTNTs was 151.8 nm with a particle size variation of less than 3 nm, which is low enough to flow through blood vessels without causing a blockage. The temperature of the pTNTs was ∼47°C, which is high enough to destroy cancer cells. Doxorubicin-loaded TNTs and pTNTs in combination with a near-infrared laser showed a cell viability of 4.5% - a sufficiently high cytotoxic effect.

Psychomotor Speed Predicts Outcome in Patients with Acute Meningitis and Encephalitis: A Prospective Observational Study.

Background and Purpose. Although acute meningitis and encephalitis are known to cause cognitive dysfunction, the prognostic values of neuropsychological and neurophysiological tests in predicting clinical outcomes are seldom studied. We investigated specific neurocognitive dysfunction and event-related potentials (ERPs), which can predict functional outcomes in patients with acute meningitis and encephalitis. Methods. We enrolled consecutive adult patients with acute meningitis and encephalitis and performed neuropsychological tests and ERP studies using a passive auditory oddball paradigm at enrollment. Patient functional outcomes were assessed using the Glasgow Outcome Scale at 6 (GOS6) months after discharge. Results. Twenty-two patients were included in the study. Among 21 patients who performed neuropsychological tests, Korean-Trail Making Test-Elderly's version, Part A time (TMT-A time) correlated with GOS6, which remained significant even after controlling for age. We identified a significant association between TMT-A time and P3a latency. Post-hoc analysis showed that patients with longer TMT-A time (≥23 s) tended to have longer P3a latency than those with shorter TMT-A time. Conclusions. Decreased psychomotor speed predicted poor clinical outcomes. Because TMT-A time can be performed at the bedside in a relatively short time, this might be a useful neuropsychological biomarker to predict or monitor clinical outcomes. Furthermore, passive oddball P3a may be useful in patients with more severe disease who are unable to perform the TMT task.

Preclinical Evidence of Curcuma longa and Its Noncurcuminoid Constituents against Hepatobiliary Diseases: A Review.

Hepatobiliary disease currently serves as an important public health issue due to the fact that it is one of the major causes of death among economically active individuals and can easily progress to chronic diseases. Despite the development of vaccines and numerous drugs, a definite treatment remains lacking owing to different stages of the disease itself, its intricate pathogenesis, an effect uncertainty for long-term use, resistance, and side effects. Curcuma longa (C. longa), which belongs to the family Zingiberaceae and the genus Curcuma, has long been used not only as spice for curry or dye but also as a constituent of herbal formula for the treatment of different diseases due to its bioactive activities. Recently, many studies on the experimental results of C. longa have been published relative to hepatobiliary diseases such as fatty liver, hepatitis, cirrhosis, and tumors. Therefore, in this review, we aimed to summarize the pharmacological effects and underlying molecular mechanisms of C. longa and its four compounds, ß-elemene, germacrone, ar-turmerone, and bisacurone, against hepatobiliary diseases. C. longa exhibited antioxidant, hepatoprotective, antisteatotic, anti-inflammatory, antifibrotic, antitumor, and cholagogic effects by regulating apoptosis, CYP2E1, Nrf, lipid metabolism-related factors, TGF-ß, NF-κB, CYP7A1, and so on. In particular, ß-elemene could be an attractive compound owing to its remarkable hepatoprotective, anti-inflammatory, antifibrotic, and antitumor activities. Altogether, the present review provides a preclinical basis for the efficacy of C. longa as an effective therapeutic agent for the prevention and treatment of hepatobiliary diseases, despite the need for further studies to establish the extraction conditions and separation of active constituents with high bioavailability, and warrants further evaluation in clinical trials.

Efficacy and Safety of an mHealth App and Wearable Device in Physical Performance for Patients With Hepatocellular Carcinoma: Development and Usability Study.

BACKGROUND: Exercise is predicted to have a positive effect among hepatocellular carcinoma (HCC) patients. However, these patients are hesitant to start and build up an exercise program for one major reason: the vague fear of developing hepatic decompensation, a potentially fatal condition that can lead to death. Integrating mobile health (mHealth) with individualized exercise programs could be a possible option for promoting physical capacity among HCC patients. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of rehabilitation exercises, which have been individually prescribed via an mHealth app, on physical fitness, body composition, biochemical profile, and quality of life among HCC patients. METHODS: A total of 37 HCC patients were enrolled in a 12-week course with an mHealth app program targeted to HCC patients. The wearable wristband device Neofit (Partron Co) was provided to participants, and recorded daily physical data, such as the number of steps, calorie expenditure, exercise time, and heart rate. Each participant was given an individualized rehabilitation exercise program that was prescribed and adjusted at the 6-week midintervention period based on the assessment results. At baseline, 6-week, and 12-week sessions, participants' physical fitness levels (ie, 6-minute walk test, grip strength test, and 30-second chair stand test) were measured. Physical activity levels, as measured by the International Physical Activity Questionnaire-Short Form (IPAQ-SF); body composition (ie, body mass index, body fat percentage, and muscle mass); biochemical profiles; and quality of life, as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C30, were assessed at baseline and at the end point. At the 6-week midpoint, exercise intensity was individually adjusted. RESULTS: Of the 37 patients, 31 (84%) completed the 12-week intervention. Grip strength improved significantly after 12 weeks of the intervention. The 30-second chair stand test and the 6-minute walk test showed significant improvement from 0 to 6 weeks, from 0 to 12 weeks, and from 6 to 12 weeks. Muscle mass and the IPAQ-SF score increased significantly after 12 weeks of the intervention without biochemical deterioration. CONCLUSIONS: Following 12 weeks of mHealth care, including an individually prescribed rehabilitation exercise program, we saw significant improvements in physical fitness, body composition, and physical activity without any complication or biochemical deterioration among compensated HCC patients who had completed therapy.

Clinicopathological significance of olfactomedin-4 in extrahepatic bile duct carcinoma.

The clinicopathological and prognostic significance of olfactomedin-4 (OLFM4) expression has not yet been elucidated in extrahepatic bile duct carcinomas (EBDCs). Immunohistochemical analysis of OLFM4 expression in 31 normal biliary epithelia, 33 biliary intraepithelial neoplasias (BilINs), and 180 surgically resected EBDCs (54 perihilar and 126 distal) was performed and was used to analyze clinicopathological variables including patient survival. The expression of OLFM4 showed a progressive increase from normal biliary epithelia (0.2 ±â€¯0.4) to BilINs (2.8 ±â€¯3.2) to EBDCs (4.6 ±â€¯4.2; P < 0.001). OLFM4 was highly expressed in 26.1% (47/180) of the EBDC cases, and high OLFM4 levels were more frequently observed in tumors with nodular growth (P = 0.029), well differentiation (P = 0.011), and lower T-category (P = 0.025) and stage grouping (P = 0.013). Patients with EBDC having high expression of OLFM4 had better survival than those with low expression of OLFM4 (median, 43.3 vs. 29.2 months; P = 0.037). OLFM4 might play an important role in carcinogenesis and in the progression from BilINs to EBDCs. High OLFM4 expression predicted less aggressive clinical behavior in patients with EBDC.

Mechanical Properties of Muscles around the Shoulder in Breast Cancer Patients: Intra-rater and Inter-rater Reliability of the MyotonPRO.

BACKGROUND: Patients with breast cancer typically experience changes in the properties of muscles around the shoulder. However, there is no appropriate evaluation tool for these changes. OBJECTIVE: The primary objective was to investigate the inter-rater and intra-rater reliability of muscle-related parameters measured by the MyotonPRO, a myotonometer device. The secondary objective was to investigate differences in properties of muscle around the shoulder between the mastectomy side and the other side. DESIGN: Cross-sectional reliability study. SETTING: Outpatient clinic in a tertiary care university-affiliated hospital. PARTICIPANTS: Twenty-two patients with breast cancer who underwent mastectomy. METHODS: Muscle tone, stiffness, and elasticity of the pectoralis major (PM), sternocleidomastoid (SCM), and upper trapezius (UT) were measured using the MyotonPRO. Rater 1 performed two sets of measurements with a time interval of 30 minutes to determine intra-rater reliability. Rater 2 performed measurements during the interval between the two sets of rater 1. Reliability was assessed using intraclass correlation coefficients (ICCs) and Bland-Altman analysis. A paired t-test was used to compare muscle properties between the affected and unaffected sides. MAIN OUTCOME MEASUREMENTS: Frequency (tone, Hz), stiffness (N/m), and decrement (elasticity). RESULTS: Intra-rater reliability was excellent (ICC > 0.75, 0.85-0.98) for all parameters of the PM, SCM, and UT in the affected and unaffected upper limbs of patients with breast cancer. Inter-rater reliability was fair to excellent for all parameters except unaffected PM elasticity (ICC = 0.34). There were significant differences in all parameters of the PM between the affected and unaffected sides. There were no significant differences in the parameters of the SCM and UT between the two sides. CONCLUSIONS: Our findings indicate that the MyotonPRO device is a feasible tool to quantify PM, UT, and SCM muscle properties (stiffness, tone, and elasticity) in patients with breast cancer. LEVEL OF EVIDENCE: III.