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Background: About 3%–5% of non‐small cell lung cancer (NSCLC) presents positive anaplastic lymphoma kinase (ALK). Recently, several target agents have been approved as a treatment for ALK‐positive NSCLC. This study aimed to analyze the real‐world efficacy and outcome when administered crizotinib, the first approved target agent for ALK‐positive NSCLC, according to first‐ or late‐line treatment. Methods: A total of 290 patients with ALK‐positive advanced NSCLC who were treated with crizotinib in 15 institutions in South Korea from January 2009 to December 2018 were enrolled. Results: The median age of patients was 57.0 years, and 50.3% were male. The median follow‐up duration was 29.3 months. Among them, 113 patients received crizotinib as first‐line therapy. The objective response rate (ORR) was 60.1% (57.0% for first‐line recipients, 61.8% for second−/later‐line). Median (95% CI) progression‐free survival (PFS) was 13.7 (11.6–17.0) months. For first‐line recipients, overall survival (OS) was 26.3 (17.6–35.0) months. No significant difference in ORR, PFS and OS, according to the setting of crizotinib initiation, was observed. In a multivariate Cox regression analysis, old age, male gender, initially metastatic, and number of metastatic organs were associated with poor PFS and OS. The most common adverse events were nausea and vomiting, and severe adverse event leading to dose adjustment was hepatotoxicity. Conclusions: ORR, PFS, OS, and adverse event profiles were comparable to previous clinical trials. Our findings could aid in the efficient management of ALK‐positive lung cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to investigate the appropriate treatment according to the operation type, margin status, complications, and adjuvant treatment for middle bile duct cancer. The age, preoperative CA19-9 level, T stage, and N stage affected the overall survival; however, the operation type, margin status, complication, or adjuvant treatment did not. There were no significant differences in the adjuvant treatment ratio according to complications and operation type (bile duct resection vs. pancreaticoduodenectomy). Patients who underwent PD with R0 resection and could not undergo chemotherapy because of complications reported better survival rates than those who underwent BDR with R1 resection after adjuvant treatment. Therefore, the surgeon should secure an R0 margin to achieve the best survival outcome. Background: Margin status is one of the most significant prognostic factors after curative surgery for middle bile duct (MBD) cancer. Bile duct resection (BDR) is commonly converted to pancreaticoduodenectomy (PD) to achieve R0 resection. Additionally, adjuvant treatment is actively performed after surgery to improve survival. However, the wider the range of surgery, the higher the chance of complications; this, in turn, makes adjuvant treatment impossible. Nevertheless, no definitive surgical strategy considers the possible complication rates and subsequent adjuvant treatment. We aimed to investigate the appropriate surgical type considering the margin status, complications, and adjuvant treatment in MBD cancer. Materials and Methods: From 2008 to 2017, 520 patients diagnosed with MBD cancer at the Samsung Medical Center were analyzed retrospectively according to the operation type, margin status, complications, and adjuvant treatment. The R1 group was defined as having a carcinoma margin. Results: The 5-year survival rate for patients who underwent R0 and R1 resection was 54.4% and 33.3%, respectively (p = 0.131). Prognostic factors affecting the overall survival were the age, preoperative CA19-9 level, T stage, and N stage, but not the operation type, margin status, complications, or adjuvant treatment. The complication rates were 11.5% and 29.8% in the BDR and PD groups, respectively (p < 0.001). We observed no significant difference in the adjuvant treatment ratio according to complications (p = 0.675). Patients with PD who underwent R0 resection and could not undergo chemotherapy because of complications reported better survival rates than those with BDR who underwent R1 resection after adjuvant treatment (p = 0.003). Conclusion: The survival outcome of patients with R1 margins who underwent BDR did not match those with R0 margins after PD, even after adjuvant treatment. Due to improvements in surgical techniques and the ability to resolve complications, surgical complications exert a marginal effect on survival. Therefore, surgeons should secure R0 margins to achieve the best survival outcomes. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the differences in characteristics, clinical stages, treatment modalities, and survival outcomes in patients with non‐small‐cell lung cancer (NSCLC) based on sex differences using Korean nationwide registry data. Methods: We analyzed the data of 8650 patients diagnosed with NSCLC between 2014 and 2017, obtained from the Korean Association for Lung Cancer Registry (KALC‐R). The Cox proportional hazard model was used to define the differences in survival based on sex. Propensity score matching was used to adjust for differences between men and women. Results: Of a total of 10 943 patients, 8650 (79.1%) were diagnosed with NSCLC, of whom 68.7% were men and 31.3% were women. For NSCLC, the median age was higher (69.0 vs. 67.0, p < 0.001) and the proportion of ever‐smokers (84.5% vs. 10.8%, p < 0.001) was higher in men. Adenocarcinoma (55.5% vs. 90.4%, p < 0.001) and stage I NSCLC (26.3% vs. 41.3%, p < 0.001) were more common in women. Survival was significantly lower in men with NSCLC (hazard ratio [HR] 1.493 [95% confidence interval, CI 1.238–1.800], p < 0.001) even after adjusting for meaningful clinical variables, and in the matched cohort (HR 1.339 [1.075–1.667], p = 0.009). Similarly, survival was significantly lower in men with stage IV adenocarcinoma after adjusting for other clinical variables (HR 1.493 [1.238–1.800], p < 0.001) and in the matched cohort (HR 1.339 [1.075–1.667]; p = 0.009). Conclusions: Male patients with NSCLC had poorer prognosis, not only after variable adjustments for prognostic factors, but also in the matched cohort. [ABSTRACT FROM AUTHOR]

BACKGROUND: The cranio-cervical flexion exercise and sub-occipital muscle inhibition technique have been used to improve a forward head posture among neck pain patients with straight leg raise (SLR) limitation. However, little is known about the cranio-vertebral angle (CVA) and cervical spine range of motion (CROM) after applying stretching methods to the hamstring muscle. OBJECTIVE: To compare the immediate effects of static stretching and proprioceptive neuromuscular facilitation stretching on SLR, CVA, and CROM in neck pain patients with hamstring tightness. METHODS: 64 subjects were randomly allocated to the static stretching ( n 1 = 32) or proprioceptive neuromuscular facilitation ( n 2 = 32) stretching group. The SLR test was performed to measure the hamstring muscle's flexibility and tightness between the two groups, with CROM and CVA also being measured. The paired t-test was used to compare all the variables within each group before and after the intervention. The independent t-test was used to compare the two groups before and after the stretching exercise. RESULTS: There were no between-group effects for any outcome variables (P > 0.05). However, all SLR, CVA, and CROM outcome variables were significantly improved within-group (P < 0.05). CONCLUSIONS: There were no between-group effects for any outcome variable; however, SLR, CVA, and CROM significantly improved within-group after the one-session intervention in neck pain patients with hamstring tightness. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fibromyalgia is accompanied by symptoms of fatigue, depression, sleep disorders, and physical and mental stress [1]. It is a difficult-to-treat disorder because its exact causes are unknown. OBJECTIVE: This study aimed to examine the effect of progressive muscle relaxation therapy (PMRT) on pain, fatigue, and stress in patients with fibromyalgia syndrome. METHODS: Thirty-seven patients with fibromyalgia syndrome (age: 20–65 years) were randomly allocated to the PMRT group ( n 1 = 18, 2 men and 16 women) or non-PMRT group ( n 2 = 19, 2 men and 17 women). The PMRT group received PMRT twice a week for 8 weeks and the non-PMRT group received conventional physical therapies such as electro-stimulation and heat therapies during this period. The outcome was evaluated before and after 8 week sofintervention using the Visual Analogue Scale, Multidimensional Assessment of Fatigue, Perceived Stress Scale, and measurement of the blood pressure and pulse rate. RESULTS: Pain and fatigue significantly decreased in the PMRT group compared with the non-PMRT group (both P < 0.001). In addition, perceived stress (P < 0.001), systolic blood pressure (P < 0.001), diastolic blood pressure (P < 0.05), and pulse rate (P < 0.001) significantly decreased in the PMRT group compared with the non-PMRT group. CONCLUSIONS: The findings indicate that progressive muscle relaxation therapy is a viable rehabilitative therapy for pain, fatigue, and stress symptoms in patients with fibromyalgia syndrome. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a systemic granulomatous disorder of unknown cause involving multiple organs. Its clinical presentation and prognosis vary among races. We identified the clinical characteristics and outcomes of Korean patients with sarcoidosis. Clinical data of 367 Korean patients with biopsy-proven sarcoidosis diagnosed in 2001–2017 were retrospectively analyzed. Treatment responses included improvement, stability, or progression based on changes in pulmonary sarcoidosis on chest images. The mean age was 47.4 years, and 67.3% of patients were women. The median follow-up period was 80 months. The highest prevalence was observed in individuals aged 50–59 years (30–39 years in men, 50–59 years in women), and the number of diagnoses showed an increasing trend. Lung involvement was the most common (93.5%), followed by the skin, eyes, and extrathoracic lymph nodes. Among patients with lung involvement and a follow-up period of ≥ 3 months, 66.8%, 31.0%, and 2.2% showed improvement, stability, and progression, respectively. Eleven patients (2.9%) died, and the 5-year survival rate was 99%. The number of diagnosed cases showed an increasing trend, and the mean age at diagnosis was increased compared with that in previous reports. Organ involvement was similar to that of Westerners, although the prognosis appeared better. [ABSTRACT FROM AUTHOR]

A concurrent human papilloma virus (HPV) infection potentiates the efficacy of ionizing radiation for treatment of head and neck cancer by promoting apoptosis. Studies in cell culture indicated an opposite effect for photodynamic therapy (PDT) when this leads to mitochondrial and ER photodamage. The explanation for this difference in PDT efficacy remains to be established. While apoptosis was impaired in HPV(‐) cells, such cells can be killed via photodamage directed at the ER: this leads to a nonapoptotic death pathway termed paraptosis. No differences in photosensitizer uptake or reactive oxygen species (ROS) production were observed in HPV(+) vs. HPV(‐) tumors. We now provide evidence that death pathways initiated by ER/mitochondrial photodamage leading to either paraptosis or apoptosis are impaired in an HPV(+) head and neck cell line. These results illustrate the complex determinants of PDT efficacy, a topic that has yet to be fully explored. [ABSTRACT FROM AUTHOR]

Introduction: After noncurative endoscopic submucosal dissection (ESD) of superficial esophageal squamous cell carcinoma (SESCC), additional esophagectomy is generally recommended. However, considering its high mortality and morbidity, it is uncertain if additional surgery improves the clinical outcomes. This study aimed to compare the clinical outcomes between patients who were observed without additional treatment and those who underwent radical esophagectomy. Methods: A total of 52 patients with SESCC who underwent complete but noncurative ESD from January 2008 to December 2016 at the Samsung Medical Center and Asan Medical Center in Korea were retrospectively analyzed. Clinicopathologic characteristics and oncologic outcomes were compared between the observation group (n = 23) and the additional surgery group (n = 29). Results: During a mean follow-up of 34.4 and 41.7 months, respectively, the rates of death (observation vs. surgery, 17.4 vs. 10.3%; p = 0.686), recurrence (observation vs. surgery, 13 vs. 17.2%; p = 1.000), and disease-specific death (observation vs. surgery, 4.3 vs. 6.9%; p = 1.000) did not significantly differ between the 2 groups. The 3-year overall survival was 86.3 and 96.4%, respectively (p = 0.776). The 3-year recurrence-free survival (observation vs. surgery, 85.0 vs. 88.7%; p = 0.960) and disease-specific survival (observation vs. surgery, 95.2 vs. 96.4%; p = 0.564) also did not significantly differ. Conclusions: The clinical outcomes of close observation of noncuratively resected SESCC are comparable to those of additional surgery, at least in the midterm. The wait-and-see strategy could be a feasible management option after noncurative ESD of SESCC in selected patients. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer's disease (AD). Previous studies suggested that the coculture of human MSCs with AD in an in vitro model reduced the expression of amyloid-beta 42 (Aβ42) in the medium as well as the overexpression of amyloid-beta- (Aβ-) degrading enzymes such as neprilysin (NEP). We focused on the role of primed MSCs (human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exposed to an AD cell line via a coculture system) in reducing the levels of Aβ and inhibiting cell death. We demonstrated that mouse groups treated with naïve MSCs and primed MSCs showed significant reductions in cell death, ubiquitin conjugate levels, and Aβ levels, but the effects were greater in primed MSCs. Also, mRNA sequencing data analysis indicated that high levels of TGF-β induced primed-MSCs. Furthermore, treatment with TGF-β reduced Aβ expression in an AD transgenic mouse model. These results highlighted AD environmental preconditioning is a promising strategy to reduce cell death and ubiquitin conjugate levels and maintain the stemness of MSCs. Further, these data suggest that human WJ-MSCs exposed to an AD environment may represent a promising and novel therapy for AD. [ABSTRACT FROM AUTHOR]

As patients receiving definitive chemoradiotherapy (dCRT) for oesophageal squamous cell carcinoma (ESCC) are heterogeneous, we aimed to identify prognostic factors and failure patterns after dCRT. From 2006 to 2015, 327 patients who received dCRT for ESCC were reviewed. Treatment response to dCRT was evaluated based on EORTC‐PET criteria with endoscopy and CT results. After dCRT, 296 patients (90.5%) achieved disease stabilisation, with 132 cases of complete response (CR) (40.4%), 158 of partial response (PR) (48.3%) and 6 of stable disease (SD) (1.8%); 31 patients (9.5%) had progressive disease (PD). Median overall survival (OS) from response evaluation was 24.0 months in the overall population. Post‐treatment clinical response was the most significant prognostic factor for OS in the multivariate analysis (median OS, 65.0 months for CR, 17.3 months for PR, 4.4 months for SD and 4.0 months for PD; p < 0.0001). Median progression‐free survival (PFS) in 296 patients who achieved disease stabilisation was 13.1 months, and only clinical response was a significant factor in the multivariate analysis. The median PFS of CR, PR and SD patients were 36.9, 9.2 and 2.8 months, respectively (p < 0.0001). The clinical response was also significantly associated with the predominant failure pattern (locoregional failure [81.6%] in the initial non‐PD group vs. distant metastasis [87.1%] in the initial PD group [p < 0.0001]). In conclusion, definitive chemoradiotherapy‐treated ESCC patients showed highly different prognoses after treatment especially according to the clinical response to chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background: Although chemical pleurodesis is a useful treatment option for malignant pleural effusion, little is known about the effects of intrapleural docetaxel therapy. Objectives: This study aimed to evaluate the effects of medical thoracoscopy‐guided intrapleural docetaxel therapy in patients with lung cancer. Methods: Patients with lung cancer who diagnosed malignant pleural effusion were enrolled in this single‐center prospective pilot study. The clinical response and toxicity were evaluated at two, six and 12 weeks post‐treatment. Results: Medical thoracoscopy‐guided intrapleural docetaxel therapy was conducted in four patients between June 2016 and August 2017. The control rate of malignant pleural effusion was 100% (4/4), and the progression‐free duration of effusion was 527 ± 109 days. No serious adverse events were observed, but only mild‐to‐moderate adverse events were observed and well controlled by conservative management. Although the overall quality of life assessed using questionnaires did not show significant improvement, symptom burden due to dyspnea was significantly improved. Conclusions: Intrapleural docetaxel therapy with medical thoracoscopy showed good clinical responses, relieving dyspnea symptoms and providing tolerable safety profiles in patients with non‐small cell lung cancer (NSCLC) with malignant pleural effusion. A further prospective trial is warranted to evaluate the clinical effects of intrapleural docetaxel therapy in order to compare it with other treatment modalities. [ABSTRACT FROM AUTHOR]

Purpose: The EORTC PET criteria (EORTC criteria) are used to assess metabolic tumor response in patients with solid tumors. We conducted this pooled study to compare tumor responses according to the RECIST and EORTC criteria.Methods: Electronic databases were searched for eligible articles with the terms of "RECIST" or "EORTC criteria". We found seven articles with the data on the comparison of tumor responses by the RECIST and EORTC criteria.Results: A total of 181 patients were recruited from the seven studies. Ninety-two patients (50.8%) received cytotoxic chemotherapy and 89 were treated with targeted agents. The agreement of tumor responses between the RECIST and EORTC criteria was moderate (k = 0.493). Of 181 patients, 66 (36.5%) showed disagreement in the tumor responses: tumor response was upgraded in 54 patients and downgraded in 12 when adopting the EORTC criteria. The estimated overall response rates were significantly different between the two criteria (52.5% by the EORTC vs. 29.8% by the RECIST, P < 0.0001). When comparing the two criteria according to the anti-cancer treatments (chemotherapy or targeted therapy), the levels of agreement in tumor responses were not excellent (k = 0.461 for chemotherapy and k = 0.524 for targeted therapy, respectively) regardless of therapeutic types.Conclusion: This pooled study indicates that the concordance of tumor responses between the RECIST and EORTC criteria is not excellent. When adopting the EORTC criteria instead of the RECIST, the overall response rate was significantly increased. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic colorectal surgery may be impeded by intraperitoneal adhesions caused by previous abdominal surgery. The aim of this study was to determine the effect of previous abdominal surgery on short- and long-term outcomes of laparoscopic colorectal surgery.Methods: We retrospectively reviewed 3188 patients with primary colorectal cancer who underwent laparoscopic colorectal surgery between January 2004 and December 2013. Patients with a history of abdominal surgery (n = 593, 18.6 %) were compared to those without such history (n = 2595, 81.4 %).Results: Patients who had undergone previous abdominal surgery exhibited acceptable intraoperative outcomes, including conversion to open surgery, operative time, estimated blood loss, and the number of harvested lymph nodes. Overall, postoperative complication rates were similar between the groups (10.8 vs. 10.6 %, p = 0.885). Subgroup analysis revealed that patients with history of major abdominal surgery (n = 165) had higher rates of conversion to open surgery (4.2 vs. 1.7 %, p = 0.033), prolonged postoperative ileus (5.5 vs. 2.0 %, p = 0.008), and wound complications (4.2 vs. 1.2 %, p = 0.006), when compared to those without prior abdominal surgery. Previous major abdominal surgery was an independent risk factor for conversion to open surgery [adjusted odds ratio = 2.740; 95 % confidence interval (CI) 1.197-6.269]. Disease-free survival [adjusted hazard ratio (HR) = 0.847; 95 % CI 0.532-1.346] and overall survival (adjusted HR = 0.846; 95 % CI 0.432-1.657) were not observed to differ between the previous major abdominal surgery group and those without previous abdominal surgery.Conclusion: Laparoscopic colorectal surgery in patients with a history of abdominal surgery exhibited acceptable short- and long-term outcomes. Patients with a history of previous abdominal surgery had relatively higher rate of conversion to open surgery as well as higher incidences of prolonged postoperative ileus and wound complications compared to patients without such history. [ABSTRACT FROM AUTHOR]

Objective: To determine the synergistic effect of parathyroid hormone (PTH) [1–34] in combination with hyperbaric oxygen (HBO) on bone graft in a rat calvarial bone defect model under impaired osteogenic conditions. Materials and Methods: Twenty‐four rats were divided into three groups. Localized radiation with a single 12 Gy dose was administered to the calvaria. Four weeks after radiation, calvarial circular defects were created in the parietal bones. All defects were filled with biphasic calcium phosphate. After the bone graft, PTH [1–34] was injected subcutaneously, and HBO was administered. At 6 weeks after the bone graft, the rats were sacrificed, and specimens were harvested. Results: Histomorphometric evaluation showed that the percentage of new bone area was higher in the PTH and PTH/HBO groups than in the control group. The percent residual material area was decreased in the PTH/HBO group compared with the control group. The percentage blood vessel number was highest in the PTH group. Micro‐CT evaluation showed that the new bone volume was highest in the PTH/HBO group. The residual material volume was lowest in the PTH/HBO group. Conclusion: Within the limitations of this study, our data indicate that PTH combined with HBO may reverse radiation‐induced impairment of bone healing. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cervical spinal instability often leads to neck pain and forward head posture (FHP). To improve neck pain and FHP, both the suboccipital muscle inhibition (SMI) technique and cranio-cervical flexion exercise (CCFE) have been used. However, little is known regarding the validity of hamstring flexibility in neck pain subjects after CCFE as a treatment index, and comparison between the SMI technique and CCFE for neck pain treatment. OBJECTIVE: This study aimed to determine the short-term effects of SMI technique and CCFE, which represent passive and active exercise programs, respectively, and whether these improve the straight leg raise (SLR) test results, popliteal angle (PA), cranio-vertebral angle (CVA), and cervical range of motion (CROM) and are equally effective in immediate enhancement of such measures in neck pain subjects. METHODS: Twenty subjects with neck pain were randomly allocated to the SMI and CCFE groups (n = 10 each). The outcomes were evaluated via clinical evaluation and SLR, PA, CVA, and CROM measurement before and after intervention. RESULTS: SLR test results, PA, CVA (sitting and standing), and CROM (flexion, extension, lateral flexion, and right and left rotations) after both interventions were significantly higher than those before the interventions (P < 0.05). The SLR test results (left), PA, and CVA (standing) after the SMI technique improved to levels similar to those observed after CCFE. CONCLUSIONS: Both the SMI technique and CCFE improve SLR test results, PA, CVA, and CROM and are equally effective in immediate enhancement of the hamstring flexibility, CVA, and CROM in subjects with neck pain. [ABSTRACT FROM AUTHOR]

Background: Insomnia is a common sleep disorder that affects many adults either transiently or chronically. The societal cost of insomnia is on the rise, while long-term use of current drug treatments can involve adverse effects. Recently, electroacupuncture (EA) has been used to treat various conditions including insomnia. The objective of this study is to provide scientific evidence for the effect and safety of using EA to treat insomnia.Methods/design: In this multicentre, assessor-blind, three-arm, parallel-design, randomised controlled trial, 150 participants will be assigned to the EA group, the sham EA (SEA) group, or the usual care group. The EA and SEA groups will receive the specific treatments 2-3 times a week for 4 weeks, for a total of 10 sessions, whereas the usual care group will not receive EA and will continue with usual care during the same time period. The primary outcome measure will be changes in the Insomnia Severity Index 5 weeks after randomisation. The secondary outcomes will include the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, a sleep diary, the EuroQoL-5 dimension questionnaire, the levels of melatonin and cortisol, and the Patient Global Impression of Change. Safety will be assessed at each visit.Discussion: The results of this multicentre randomised controlled trial will contribute to provide rigorous clinical evidence for the effects and safety of EA for insomnia disorder.Trial Registration: Korean Clinical Trial Registry, CRIS, KCT0001685 . Registered on 2 November 2015 (retrospectively registered). Date of enrolment of the first participant to the trial 13 October 2015. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate whether the addition of radiotherapy to chemotherapy would enhance the benefits obtained with chemotherapy alone, in stage III rectal cancer in the era of preoperative chemoradiotherapy and total mesorectal excision (TME).Methods: From January 1999 to January 2008, 300 stage III rectal cancer patients who underwent TME were prospectively identified; a total of 46 patients who received preoperative chemoradiotherapy or did not receive adjuvant therapy were excluded. Patients who received postoperative chemotherapy alone (n=190) and those who received postoperative chemoradiotherapy (n=64) were compared.Results: The median follow-up period was 52 (range, 4-129) months. Patients receiving radiotherapy were younger and had a higher percentage of advanced pT category or perineural invasion than patients who did not. The estimated 5-year local recurrence-free survival rate was radiotherapy 92% with radiotherapy and 86% without. The disease-free survival rate was 55% with radiotherapy compared to 57% without and the overall survival rates were similar (63% vs. 68%, all P>0.05). In patients with a positive circumferential resection margin or insufficient distal resection margin, the local recurrence-free, disease-free, and overall survival rates were unaffected by radiotherapy.Conclusions: The addition of postoperative radiotherapy to chemotherapy did not reduce the recurrence or mortality in node-positive rectal cancer when compared with chemotherapy alone. Moreover, this approach may not compensate for a positive circumferential resection margin or insufficient distal resection margin following rectal cancer surgery. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the persistence with solifenacin therapy over a 12-month period in patients with overactive bladder (OAB).Methods: This is a 52-week long, multicenter, prospective, observational study. The subjects were individuals ≥ 18 years old with OAB symptoms for ≥ 3 months, characterised by a total OAB Symptom Score (OABSS) of ≥ 3 and OABSS urgency item score of ≥ 2. Patients were prescribed 5 mg or 10 mg of solifenacin once daily for OAB symptoms. Drug persistence, reasons for discontinuation and factors related to the persistence were evaluated.Results: A total of 1018 patients (329 men, 689 women) with a mean age of 59 years were included. The 52-week drug persistence rate was 22.1%. The drug persistence rates at 12, 24 and 36 weeks were 72.4%, 45.8% and 31.1% respectively. The three most common reasons for discontinuing therapy included symptom improvement in 30.4%, lack of efficacy in 13.4%, and a switch to another antimuscarinic agent in 10.8%. Older patients (odds ratio = 1.02, 95% CI: 1.01-1.04), and female patients (odds ratio = 1.94, 95% CI: 1.37-2.75) were more likely to continue the medication over the 12-month period than were younger, male patients. The number of nocturia episodes was negatively correlated with drug persistence (odds ratio = 0.83, 95% CI: 0.71-0.97).Conclusions: There was low persistence (22%) to solifenacin therapy for OAB symptoms over a 12-month period. Older patients, female patients and those with fewer episodes of nocturia were more persistent to therapy than were others. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the oncologic outcomes between treatment strategies for rectal cancer [radical surgery, local excision (LE), and the wait-and-see approach] in radiologic complete responders after neoadjuvant chemoradiation (nCRT). Methods: We retrospectively reviewed rectal cancer patients and included 52 radiologic complete responders after nCRT defined as no residual tumor or residual fibrosis and no suspicious metastatic lymph nodes on magnetic resonance imaging (MRI). Clinicopathologic features and oncologic outcomes were compared according to the treatment strategies. Results: The median follow-up period was 41 months (range, 6-80). Twenty-eight patients underwent radical surgery, whereas 16 underwent LE, and 8 were closely monitored without initial surgery. The pathologic complete response rate was 40.9%. Patients who underwent radical surgery showed better prognosis compared to those who underwent LE or wait-and-see (3-year disease-free survival: radical surgery 85.0% vs. LE 62.5%, wait-and-see 75.0%, p = 0.019; 3-year local recurrence-free survival: radical surgery 96.4% vs. LE 67.0%, wait-and-see 75.0%, p = 0.009). After recurrence, patients who underwent salvage surgery showed a relatively good oncologic outcome. Conclusion: Pursuing LE or the wait-and-see approach instead of radical surgery in rectal cancer patients undergoing nCRT may bring about a detrimental oncologic outcome if clinical complete response is solely determined by MRI. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives. This study investigated whether Sasang constitutional type is associated with differences in the serum levels of stress hormones and oxidative stress. Methods. A total of 236 participants (77 males and 159 females) were enrolled. The serum levels of cortisol, adrenaline, reactive oxygen species (ROS), and malondialdehyde (MDA) were analyzed. Results. The distribution of Sasang constitutional types was as follows: Taeumin, 35.6%; Soumin, 33.0%; and Soyangin, 31.4%. The serum cortisol levels of Taeumin were significantly lower than Soumin (p<0.1 in both sexes) and Soyangin (p<0.05 in males and p<0.1 in females). The adrenaline levels were also significantly lower in Taeumin than in Soumin (p<0.05 in males and p<0.1 in females) and Soyangin (p<0.1 in males). Serum ROS levels were significantly higher in Soyangin than in Taeumin and Soumin (p<0.05 in males), whereas MDA levels were significantly lower in Taeumin compared with Soumin and Soyangin (p<0.05 in males and p<0.1 in females). Conclusion. Taeumin type may tolerate psychological or oxidative stress better than other types, which suggests a biological mechanism to explain the different pathophysiological features of Sasang constitutional types. [ABSTRACT FROM AUTHOR]

Objective: The criterion of two target lesions per organ in the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) is an arbitrary decision. We assumed that measuring the single largest lesion per organ (modified RECIST 1.1, hereafter referred to as mRECIST 1.1) instead of two (RECIST 1.1) might be enough to assess tumor responses. Methods: We compared tumor response using computed tomography according to the RECIST 1.1 and mRECIST 1.1 in patients with advanced gastric cancer (AGC) who received first-line chemotherapy. Results: A total of 51 patients who had at least two target lesions in any organ according to the RECIST 1.1 were included in the study. The level of concordance in the tumor response between the RECIST 1.1 and mRECIST 1.1 was excellent (k = 0.904). Only 3 patients (5.9%) showed a disagreement of tumor responses between the two criteria. The overall response rate was not significantly different between the two criteria (45.1% by RECIST 1.1 vs. 49.0% by mRECIST 1.1, p = 0.692). Conclusion: The mRECIST 1.1 showed a high concordance with the original RECIST 1.1 in the assessment of tumor response for patients with AGC. Our result suggests that it may be possible to measure the single largest target lesion per organ for assessing tumor response in clinical practice. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: The role of non-surgical treatments (NS), such as chemoradiotherapy or radiotherapy, for clinical T1N0M0 esophageal cancer (cT1N0M0 EC) has not been well delineated. The aim of this study was to evaluate and compare the feasibility and efficacy of NS and Surgical treatment (S) in cT1N0M0 EC patients. Methods: The medical records of patients who received treatment for cT1N0M0 EC at Asan Medical Center between2003 and 2012 were retrospectively reviewed. The baseline characteristics, treatment outcomes and complications, and survival were compared. Results: There were 264 S and 20 NS patients with respective median ages of 69.5 and 63.0. The main histologic finding was squamous cell carcinoma in both groups (97 and 100 %, respectively). The Eastern Cooperative Oncology Group performance status and Charlson comorbidity index score were poorer in the NS group. With a median follow-up of 49.0 months, 37 S patients (14 %) and 3 NS patients (15 %) exhibited recurrence. The first sites of recurrence for S and NS patients were locoregional (21 vs. 3 patients), distant (6 vs. 0), and both locoregional and distant (9 vs. 0), respectively. The median time-to-recurrence could not be calculated in either group (log-rank test P = 0.831). The estimated median overall survival was 64.4 months (95 % CI 37.2-91.6 months) in the NS group and could not be calculated in the S group ( P = 0.056). Conclusions: Non-surgical treatments can be an effective alternative to S for patients with cT1N0M0 EC unfit for radical surgery. The role of NS for early stage EC needs to be further verified with prospective randomized trials. [ABSTRACT FROM AUTHOR]

Introduction: This study tested the effectiveness of moxibustion on pain and function in chronic knee osteoarthritis (KOA) and evaluated safety. Methods: A multi-centre, non-blinded, parallel-group, randomised controlled trial compared moxibustion with usual care (UC) in KOA. 212 South Korean patients aged 40–70 were recruited from 2011–12, stratified by mild (Kellgren/Lawrence scale grades 0/1) and moderate-severe KOA (grades 2/3/4), and randomly allocated to moxibustion or UC for four weeks. Moxibustion involved burning mugwort devices over acupuncture and Ashi points in affected knee(s). UC was allowed. Korean Western Ontario and McMaster Universities Questionnaire (K-WOMAC), Short Form 36 Health Survey (SF-36v2), Beck Depression Inventory (BDI), physical performance test, pain numeric rating scale (NRS) and adverse events were evaluated at 5 and 13 weeks. K-WOMAC global score at 5 weeks was the primary outcome. Results: 102 patients (73 mild, 29 moderate-severe) were allocated to moxibustion, 110 (77 mild, 33 moderate-severe) to UC. K-WOMAC global score (moxibustion 25.42+/−SD 19.26, UC 33.60+/−17.91, p<0.01, effect size  = 0.0477), NRS (moxibustion 44.77+/−22.73, UC 56.23+/−17.71, p<0.01, effect size  = 0.0073) and timed-stand test (moxibustion 24.79+/−9.76, UC 25.24+/−8.84, p = 0.0486, effect size  = 0.0021) were improved by moxibustion at 5 weeks. The primary outcome improved for mild but not moderate-severe KOA. At 13 weeks, moxibustion significantly improved the K-WOMAC global score and NRS. Moxibustion improved SF-36 physical component summary (p = 0.0299), bodily pain (p = 0.0003), physical functioning (p = 0.0025) and social functioning (p = 0.0418) at 5 weeks, with no difference in mental component summary at 5 and 13 weeks. BDI showed no difference (p = 0.34) at 5 weeks. After 1158 moxibustion treatments, 121 adverse events included first (n = 6) and second degree (n = 113) burns, pruritus and fatigue (n = 2). Conclusions: Moxibustion may improve pain, function and quality of life in KOA patients, but adverse events are common. Limitations included no sham control or blinding. Trial Registration: Clinical Research Information Service (CRIS) KCT0000130 [ABSTRACT FROM AUTHOR]

Objectives: The antifatigue effect of indirect moxibustion and its antioxidant properties were investigated. Subjects and design: A randomized, double-blind, controlled clinical trial was performed with 44 patients who had idiopathic chronic fatigue. The subjects were treated with a placebo or moxibustion (indirect moxibustion on CV4 and CV8 3 times per week for 4 weeks), and their fatigue severity was monitored using a self-rating numeric scale (NRS) and a visual analog scale (VAS). Serum level of reactive oxygen species and malondialdehyde (MDA), total antioxidant capacity, the activity of catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase and total glutathione content, were determined before initial moxibustion therapy and after the 12th moxibustion treatment. Results: The moxibustion group had a significantly lower fatigue severity score compared to the control for both the NRS ( p<0.05) and VAS scores ( p<0.01). The level of serum MDA was significantly lower in the moxibustion group than in the placebo group ( p<0.05), whereas glutathione reductase activity and total glutathione content increased significantly following moxibustion ( p<0.05). Conclusions: The results provide clinical evidence for an antifatigue effect of indirect moxibustion at CV4 and CV8 and suggest that the effect is due to the antioxidant properties of moxibustion. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to evaluate the impact of resection for primary colorectal cancer on oncologic outcomes in patients with synchronous colorectal liver metastases.Methods: A retrospective analysis was performed on 91 consecutive patients with synchronous colorectal liver metastases who underwent resection of the primary colorectal cancer between December 1999 and December 2007. Of the 91 patients, 54 (59.3%) also underwent complete (R0) resection for liver metastases, and 84 (92.3%) received postoperative chemotherapy. The oncologic outcomes and prognostic factors were analyzed.Results: Operative mortality was 1.1%, and morbidity was 37.4%. The 3- and 5-year overall survival rates were 44.5% and 26.8%, respectively. A multivariate analysis revealed that residual disease after surgery (non-R0 resection; p = 0.003), lymph node metastasis of the primary tumor (p = 0.015), and no postoperative chemotherapy (p = 0.001) were independent prognostic factors for poor survival. Independent predictors of an inability to achieve a complete resection were the presence of three or more liver metastases and the presence of extrahepatic disease at exploration. Significant differences in survival existed among the three risk stratification groups (no-, low-, and high-risk groups; p < 0.001).Conclusions: The inability to safely render the liver and colon microscopically free of disease should cause a surgeon to reconsider synchronous colectomy and hepatectomy. A multidisciplinary approach that combines both complete resection of synchronous colorectal liver metastases and postoperative chemotherapy may achieve improved survival in patients with synchronous colorectal liver metastases. [ABSTRACT FROM AUTHOR]

For locally advanced esophageal cancer, concurrent chemoradiotherapy (CRT) followed by surgery has been a standard treatment, while clinical studies showed comparable survival outcomes between definitive CRT and neoadjuvant CRT followed by surgery in patients responding to CRT. Thus, biomarkers are required to predict treatment outcomes and benefit of adding surgery after CRT. This prospective biomarker study examined the role of cell-free DNA (cfDNA) fragmentation profiles and genomic copy number variations (CNVs) in predicting treatment outcomes in esophageal squamous cell carcinoma patients treated with neoadjuvant or definitive CRT. The clinical response was evaluated after induction chemotherapy and after CRT. Fragment Ratio (FR)-score and I-score were calculated from plasma cfDNA reflecting fragment lengths and CNV of cfDNA, respectively. The association between indices of cfDNA (cfDNA concentration, FR-score, and I-score) and treatment outcomes (clinical response, time to progression [TTP], and overall survival [OS]) were evaluated. Sixty-one patients were included. Thirty patients received neoadjuvant CRT followed by surgery, whereas 31 received definitive CRT. Low baseline, post-induction chemotherapy, and post-CRT FR-scores and low post-induction I-score were significantly associated with improved treatment response (P < 0.05). Additionally, patients with surgery after CRT showed significantly longer survival than patients without surgery in the FR-score-high group (median TTP, 12.7 vs 3.4 months; P = 0.011; OS, not reached vs 12.9 months; P = 0.02), while there was no survival benefit with surgery in the FR-score-low group. FR-score may be a new biomarker to predict treatment response, residual tumor burden after CRT, and consequently, survival benefit of adding morbid surgery after CRT. FR-score has strength in a relatively simple and inexpensive methodology compared to deep sequencing, resulting in high availability and accessibility, despite limited sensitivity. [ABSTRACT FROM AUTHOR]

We aimed to assess the survival benefits of primary tumor resection (PTR) followed by chemotherapy in patients with asymptomatic stage IV colorectal cancer with asymptomatic, synchronous, unresectable metastases compared to those of upfront chemotherapy alone. This was an open-label, prospective, randomized controlled trial (ClnicalTrials.gov Identifier: NCT01978249). From May 2013 to April 2016, 48 patients (PTR, n = 26; upfront chemotherapy, n = 22) diagnosed with asymptomatic colorectal cancer with unresectable metastases in 12 tertiary hospitals were randomized (1:1). The primary endpoint was two-year overall survival. The secondary endpoints were primary tumor-related complications, PTR-related complications, and rate of conversion to resectable status. The two-year cancer-specific survival was significantly higher in the PTR group than in the upfront chemotherapy group (72.3% vs. 47.1%; p = 0.049). However, the two-year overall survival rate was not significantly different between the PTR and upfront chemotherapy groups (69.5% vs. 44.8%, p = 0.058). The primary tumor-related complication rate was 22.7%. The PTR-related complication rate was 19.2%, with a major complication rate of 3.8%. The rates of conversion to resectable status were 15.3% and 18.2% in the PTR and upfront chemotherapy groups. While PTR followed by chemotherapy resulted in better two-year cancer-specific survival than upfront chemotherapy, the improvement in the two-year overall survival was not significant. [ABSTRACT FROM AUTHOR]

• This is the first RCT of Chunggan extract (CGX) in patients with liver fibrosis. • The end point was the changed value of liver stiffness measurement using Fibroscan. • CGX effectively ameliorated hepatic fibrosis in patients with chronic liver disease. • No significant adverse event was observed during the trial. Chunggan extract (CGX) is an herbal formula used for the treatment of chronic liver disease in traditional Korean medicine. Many preclinical studies have suggested its therapeutic or preventive effects on liver fibrosis. To evaluate the efficacy and safety of CGX, we conducted a randomized controlled clinical trial of CGX in patients with liver fibrosis diagnosed by Fibroscan. We enrolled 67 subjects at two hospitals with chronic liver disorders with a 5.5 ≤ liver stiffness measurement (LSM) score ≤ 16 kPa. Subjects were randomly assigned at a 1:1:1 ratio with stratification (with/without concomitant use of antivirals) and orally administered CGX (1 g or 2 g) or placebo twice daily for 24 weeks. The end point was the change in instantaneous elasticity of the liver assessed by Fibroscan before and after treatment. LSM scores were significantly decreased in both the CGX1 g (2.5 ± 1.7 kPa, p < 0.01) and CGX2 g (1.9 ± 2.0 kPa, p < 0.05) groups compared to the placebo (0.6 ± 1.6 kPa) group. The change was also significant in 35 subjects without concomitant use of antiviral agents in the CGX1 g group (placebo 0.1 ± 1.4 kPa vs. 2.7 ± 1.6 kPa, p < 0.01) but not in those with concomitant antiviral use (p > 0.05). No notable adverse events were present. CGX appeared to have a pharmacological effect against liver fibrosis. Further studies to confirm the results are needed in the future using a larger sample size. [ABSTRACT FROM AUTHOR]

RIPK3 is a key regulator of necroptosis, which plays a double-edged sword role in tumor progression. CHIP is an E3 ubiquitin ligase that regulates necroptosis by degrading RIPK3. Here, we investigated the prognostic value of RIPK3 and CHIP expression in 404 patients with non-small cell lung cancer (NSCLC). Expressions of CHIP and RIPK3 showed opposite correlations with survival. CHIP expression was associated with the longer overall survival (OS), whereas RIPK3 expression was associated with the shorter OS. RIPK3 positivity showed marginal association with shorter OS and disease-free survival (DFS) in adjuvant radiotherapy recipients but not in non-recipients, suggesting that necroptosis may induce radioresistance. In multivariate analysis, CHIP expression was associated with longer OS. Compared with other patients, CHIP(−)/RIPK3(+) patients had shorter OS and DFS. In summary, in patients with NSCLC, the expression of CHIP was an independent favorable prognostic factor while that of RIPK3 was an adverse prognostic factor. [ABSTRACT FROM AUTHOR]

Chlorogenic acid (CGA) is a major component of green coffee beans. Surfactin, a cyclic lipopeptide, is produced and secreted by Bacillus subtilis strains. In this study, bioactivities of fermented green coffee bean extract (FGCBE) and the individual compounds, CGA and surfactin. were compared in HepG2 cells. The concentration of surfactin and CGA in the FGCBE and non-fermented green coffee bean extract (NFGCBE) were determined to be 9.2 and 7.33 and 0.72 and 0.53 mg·mL−1, respectively. The FGCBE contained about 20% and 26% more CGA and surfactin than the NFGCBE. Although CGA and surfactin exhibited cytotoxicity at concentrations more than 100 and 20 μg respectively, the FGCBE 50 containing CGA (460 μg·mL−1) and surfactin (720 μg·mL−1) effectively prevented cell death by oxidative stress and also strongly activated the proliferation of cells incubated with under 50 μM H2O2. The CGA and surfactin in FGCBE were 9.2 and 72 times higher than the CGA and surfactin compounds (50 and 10 μg·mL−1). The relative proliferation of the FGCBE-treated cells also was 3.3 and 8.8 times higher than the CGA and surfactin compounds treated the oxidative stressed cells with 50 μM H2O2. These results suggest that the single compounds such as CGA and surfactin generally have cytotoxicity at low concentration of them but FGCBE contained them acted as strong antioxidants, activators of cell proliferation, inhibitors of cell apoptosis. Various bioactive compounds in fermented coffee bean also seem to help cell proliferation and decreasing of cytotoxicity by CGA and surfactin in coffee bean. [ABSTRACT FROM AUTHOR]

This study is to compare clinical outcomes including survivals between two generally used neoadjuvant chemotherapies, gemcitabine and FOLFIRINOX, for the patients with BRPC. Clinical outcomes included survival, curative resectability, and recurrence pattern survival according to chemotherapeutic regimens. B Conclusion: b FOLFIRINOX, compared to the gemcitabine regimen, provided better clinical outcomes like 2-YSR, R0 resection rate, and recur rate. [Extracted from the article]