Laparoscopy-assisted trans gastric wedge resection: A safe treatment for gastric pyloric liposarcoma: A case report and literature review.

Background: Gastric liposarcoma (GL) is extremely rare and radical surgery has been the conventional treatment, even in small tumors. Laparoscopic wedge resection has been reported worldwide for subepithelial tumors of the stomach. Case presentation: The patient was an asymptomatic 63-year-old man presenting with a subepithelial gastric tumor. The esophagogastroduodenoscopy showed a 3 cm ulcerated soft tumor located in the posterior wall of the antrum just above the pylorus. Two preoperative biopsies were performed with a negative result for malignant neoplasm. Dynamic computerized tomography revealed 35 × 35 mm well-defined pyloric mass with fat density. Despite the difficult location of the tumor, function-preserving surgery was performed. Surgery was initiated by a laparoscopic approach with four trocars. After the dissection of the greater omentum, the greater curvature and the posterior wall of the stomach were exposed. A gastrostomy was performed in the anterior wall of the antrum. Due to the difficulty in identifying the tumor location, a mini-laparotomy was conducted. After assessing the pylorus and section parameters, the tumor was extracted by gastrostomy and resected with a linear stapler. The patient was discharged after five days with no complications. The histological diagnosis was a well-differentiated liposarcoma. Resection margins were clear. The tumor cells tested negative for MDM2. No adjuvant therapy was indicated. The patient is alive without recurrence. Conclusions: Despite its rarity, gastric liposarcoma should be respected for differential diagnosis in submucosal tumors. The main diagnostic method is histological, and surgery is the conventional treatment without yet having a consensus. Minimally invasive wedge resection might be a suitable treatment even if the location is close to the pylorus. Multicenter studies are required to obtain better results in the management of this pathology.

Real-world Nationwide Outcomes of Minimally Invasive Surgery for Advanced Gastric Cancer Based on Korean Gastric Cancer Association-Led Survey.

PURPOSE: The study aimed to investigate real-world surgical outcomes of minimally invasive surgery (MIS) for advanced gastric cancer using Korean Gastric Cancer Association (KGCA)-led nationwide data. MATERIALS AND METHODS: A nationwide survey of patients who underwent surgical treatment for gastric cancer in 2019 was conducted by the KGCA. A total of 14,076 patients from 68 institutions underwent surgery, and 4,953 patients diagnosed with pathological stages IB-III gastric cancer were included. Among them, 1,689 patients who underwent MIS (MIS group) and 1,689 who underwent the open approach (open group) were matched using propensity score in a 1:1 ratio. Surgical outcomes were compared, and multivariate analysis was performed to identify the independent factors for overall morbidity. RESULTS: The MIS group had a lower proportion of D2 lymphadenectomy, total omentectomy, and combined resection. However, the number of harvested lymph nodes was higher in the MIS group. Better surgical outcomes, including less blood loss and shorter hospital stay, were observed in the MIS group, and the overall morbidity rate was significantly lower in the MIS group (17.5% vs. 21.9%, P=0.001). The mortality rates did not differ significantly between the 2 groups. In the multivariate analysis, the minimally invasive approach was a significant protective factor against overall morbidity (odds ratio, 0.799; P=0.006). CONCLUSIONS: Based on the Korean nationwide data, MIS for stage IB-III gastric cancer had better short-term outcomes than the open approach, including lower rates of wound complications, intra-abdominal abscesses, and cardiac problems.

Feasibility of intraoperative pathologic examination for sentinel lymph nodes during sentinel node navigation surgery in early gastric cancer: results of pathologic protocol for SENORITA trial.

BACKGROUND: During sentinel node navigation surgery in patients with gastric cancer, intraoperative pathologic examination of sentinel nodes is crucial in determining the extent of surgery. In this study, we evaluated the feasibility and accuracy of intraoperative pathologic protocols using data from a prospective, multicenter, randomized trial. METHODS: A retrospective analysis was conducted using data from the SEntinel Node ORIented Tailored Approach trials from 2013 to 2016. All sentinel lymph nodes were evaluated during surgery with hematoxylin-eosin (HE) staining using a representative section at the largest plane for lymph nodes. For permanent histologic evaluation, sentinel basin nodes were stained with HE and cytokeratin immunohistochemistry in formalin-fixed, paraffin-embedded (FFPE) sections and examined with HE for three deeper-step sections at 200-µm intervals. The failure rate of identification by frozen section and the metastasis rate in non-sentinel basins were investigated. RESULTS: Of the 237 patients who underwent sentinel node basin dissection, 30 had lymph node metastases on permanent pathology. Thirteen patients had macrometastasis confirmed in frozen sections as well as FFPE sections (failure rate: 0%). Patients with negative sentinel nodes in frozen sections but micrometastasis in FFPE sections had no lymph node recurrence during the follow-up period (0%, 0/6). However, in cases with tumor-positive nodes in frozen sections, metastases in non-sentinel basins were detected in the paraffin blocks (8.3%, 2/24). CONCLUSIONS: The single-section HE staining method is sufficient for detecting macrometastasis via intraoperative pathological examination. If a negative frozen-section result is confirmed, sentinel basin dissection can be performed safely. Otherwise, standard surgery is required.

Real-World Compliance of Surgical Treatment According to the Korean Gastric Cancer Guideline 2018: Evaluation From the Nationwide Survey Data 2019 in Korea.

PURPOSE: This study evaluated real-world compliance with surgical treatment according to Korea's gastric cancer treatment guidelines. MATERIALS AND METHODS: The 2018 Korean Gastric Cancer Treatment Guidelines were evaluated using the 2019 national survey data for surgically treated gastric cancer based on postoperative pathological results in Korea. In addition, the changes in surgical treatments in 2019 were compared with those in the 2014 national survey data implemented before the publication of the guidelines in 2018. The compliance rate was evaluated according to the algorithm recommended in the 2018 Korean guidelines. RESULTS: The overall compliance rates in 2019 were 83% for gastric resection extent, 87% for lymph node dissection, 100% for surgical approach, and 83% for adjuvant chemotherapy, similar to 2014. Among patients with pathologic stages IB, II, and III disease who underwent total gastrectomy, the incidence of splenectomy was 8.08%, a practice not recommended by the guidelines. The survey findings revealed that 48.66% of the patients who underwent gastrectomy had pathological stage IV disease, which was not recommended by the 2019 guidelines. Compared to that in 2014, the rate of gastrectomy in stage IV patients was 54.53% in 2014. Compliance rates were similar across all regions of Korea, except for gastrectomy in patients with stage IV disease. CONCLUSIONS: Real-world compliance with gastric cancer treatment guidelines was relatively high in Korea.

Long-term Functional and Patient-reported Outcomes Between Intra-corporeal Delta-shaped Gastroduodenostomy and Gastrojejunostomy After Laparoscopic Distal Gastrectomy.

PURPOSE: This study aimed to compare the long-term functional and patient-reported outcomes between intra-corporeal delta-shaped gastroduodenostomy and gastrojejunostomy after laparoscopic distal gastrectomy for gastric cancer. MATERIALS AND METHODS: We retrospectively reviewed clinicopathological data from 616 patients who had undergone laparoscopic distal gastrectomy for stage I gastric cancer between January 2015 and September 2020. Among them, 232 patients who had undergone delta-shaped anastomosis and another 232 who had undergone Billroth II anastomosis were matched using propensity scores. Confounding variables included age, sex, body mass index, physical status classification, tumor location, and T classification. Postoperative complications, nutritional outcomes, endoscopic findings, and quality of life (QoL) were compared between the 2 groups. RESULTS: No significant differences in postoperative complications or nutritional parameters between the two groups were observed. Annual endoscopic findings revealed more residual food and less bile reflux in the delta group (P<0.001) than in the Billroth II group. Changes of QoL were significantly different regarding emotional function, insomnia, diarrhea, reflux symptoms, and dry mouth (P=0.007, P=0.002, P=0.013, P=0.001, and P=0.03, respectively). Among them, the delta group had worse insomnia, reflux symptoms, and dry mouth within three months postoperatively. CONCLUSIONS: Long-term nutritional outcomes and QoL were comparable between the delta and Billroth II groups. However, more residual food and worse short-term QoL regarding insomnia, reflux symptoms, and dry mouth were observed in the delta group. Longer fasting time before endoscopic evaluation and short-term symptom management would have been helpful for the delta group.

Effect of Vitamin B12 Replacement Intervals on Clinical Symptoms and Laboratory Findings in Gastric Cancer Patients after Total Gastrectomy.

The management of patients with vitamin B12 deficiency after total gastrectomy (TG) remains controversial. We aimed to evaluate the effect of vitamin B12 replacement intervals on the clinical characteristics in these patients. The data from patients who received vitamin B12 supplementation after TG between 2007 and 2018 at the National Cancer Center, Korea, were retrospectively evaluated. Vitamin B12 deficiency was defined as a serum vitamin B12 level of <200 pg/mL or urine methylmalonic acid level > 3.8 mg/gCr. The patients were divided into a regular replacement group (patients received an intramuscular injection or oral medication regularly), and a lab-based replacement group (patients received vitamin B12 intermittently after checking the level). The symptoms and biochemical parameters were compared between these groups. The regular and lab-based replacement groups included 190 and 216 patients, respectively. The median vitamin B12 replacement intervals were 1 and 9 months, respectively (p < 0.001). After replacement, the regular replacement group had higher vitamin B12 levels than the lab-based replacement group (p < 0.001). However, the serum hemoglobin level showed no significant changes. After replacement, there was no significant difference in the proportion of the symptomatic patients between the groups. Replacing vitamin B12 with a lab-based protocol may be sufficient for TG patients.

Standard follow-up after curative surgery for advanced gastric cancer: secondary analysis of a multicentre randomized clinical trial (KLASS-02).

BACKGROUND: The benefit of regular follow-up after curative resection for gastric cancer is controversial as there is no evidence that it will improve survival. This study assessed whether regular follow-up leads to improved survival in patients after surgery for gastric cancer. METHODS: A secondary analysis was undertaken of patients who participated in an RCT of laparoscopic versus open distal gastrectomy for advanced gastric cancer between November 2011 and April 2015. Depending on whether patients were compliant with the initial trial follow-up protocol or not, they were analysed as having had either regular or irregular follow-up. Clinicopathological characteristics, recurrence patterns, detection, treatments, and survival were compared between the groups. RESULTS: The regular and irregular follow-up groups comprised 712 and 263 patients respectively. Disease recurrence within 36 months was more common in the regular group than in the irregular group (17.0 versus 11.4 per cent; P = 0.041). Recurrence patterns did not differ between the groups. The 3-year recurrence-free survival rate was worse in the regular than in the irregular group (81.2 versus 86.5 per cent; P = 0.031). However, the 5-year overall survival rate was comparable (84.5 versus 87.5 per cent respectively; P = 0.160). Multivariable analysis revealed that type of follow-up was not an independent factor affecting 5-year overall survival. CONCLUSION: Regular follow-up after radical gastrectomy was not associated with improved overall survival.

Cirsium Setidens Water Extracts Containing Linarin Block Estrogen Deprivation-Induced Bone Loss in Mice.

Osteoporosis is evident in postmenopausal women and is an osteolytic disease characterized by bone loss that further increases the susceptibility to bone fractures and frailty. The use of complementary therapies to alleviate postmenopausal osteoporosis is fairly widespread among women. Edible Cirsium setidens contains various polyphenols of linarin, pectolinarin, and apigenin with antioxidant and hepatoprotective effects. This study aimed to determine whether Cirsium setidens water extracts (CSEs), the component linarin, and its aglycone acacetin blocked ovariectomy (OVX)-induced bone loss. This study employed OVX C57BL/6 female mice as a model for postmenopausal osteoporosis. CSEs, acacetin, or linarin was orally administrated to OVX mice at a dose of 20 mg/kg for 8 weeks. Surgical estrogen loss in mice for 8 weeks reduced bone mineral density (BMD) of mouse femur and serum 17ß-estradiol level and enhanced the serum receptor activator of NF-κB ligand/osteoprotegerin ratio with uterine atrophy. CSEs and linarin reversed such adverse effects and enhanced femoral BMD in OVX mice. Oral administration of CSEs and linarin attenuated tartrate-resistant acid phosphate activity and the induction of αvß3 integrins and proton suppliers in resorption lacunae in femoral bone tissue of OVX mice. In addition, CSEs and linarin curtailed the bone levels of cathepsin K and matrix metalloproteinase-9 responsible for osteoclastic bone resorption. On the other hand, CSEs and linarin enhanced the formation of trabecular bones in estrogen-deficient femur with increased induction of osteocalcin and osteopontin. Further, treatment with CSEs and linarin enhanced the collagen formation-responsive propeptide levels in the circulation along with the increase in the tissue non-specific alkaline phosphatase level in bone exposed to OVX. Supplementing CSEs, acacetin, or linarin to OVX mice elevated the formation of collagen fibers in OVX trabecular bone, evidenced using Picrosirius red staining. Accordingly, CSEs and linarin were effective in retarding osteoclastic bone resorption and promoting osteoblastic bone matrix mineralization under OVX conditions. Therefore, linarin, which is abundant in CSEs, may be a natural compound for targeting postmenopausal osteoporosis and pathological osteoresorptive disorders.

Risks and benefits of additional surgery for early gastric cancer in the upper third of the stomach meeting non-curative resection criteria after endoscopic submucosal dissection.

BACKGROUND: Additional surgery is recommended after non-curative endoscopic submucosal dissection for early gastric cancer. However, it is not easy to recommend for tumors located in the upper third of the stomach, because it would be a total or proximal gastrectomy. This study aimed to evaluate the actual risks and benefits of additional gastrectomy for upper third tumors. METHODS: We reviewed the clinicopathological data of patients who underwent total or proximal gastrectomy for early gastric cancer in the upper third of the stomach between March 2002 and January 2021. The incidence of lymph node metastasis and postoperative complications were calculated, and risk factors for lymph node metastasis were identified using logistic regression analysis. Survival rates were analyzed using the Kaplan-Meier method and log-rank test. RESULTS: A total of 523 patients underwent total or proximal gastrectomy for early gastric cancer; 379 of them had tumors meeting the non-curative resection criteria for endoscopic submucosal dissection. The overall lymph node metastasis rate was 9.5%, and lymphovascular invasion was the only significant risk factor for lymph node metastasis (p < 0.001). The most common sites of lymph node metastasis were stations 1, 3, and 7, with their rates being 3.2%, 3.7%, and 3.2%, respectively. Overall and severe (Clavien-Dindo grade III or higher) postoperative complication rates were 21.1% and 14.0%, respectively, while postoperative mortality was 0.5% (2/379). The 5-year overall survival rates for patients with and without lymph node metastasis were 96.1% and 81.1%, respectively (p = 0.076). CONCLUSIONS: Before planning an additional gastrectomy after non-curative endoscopic resection for the upper third tumor, we should consider both the benefit of the 9.5% curability for lymph node metastasis and the risks of the 21% postoperative complications and 0.5% mortality.

Epidemiology of Gastric Cancer in Korea: Trends in Incidence and Survival Based on Korea Central Cancer Registry Data (1999-2019).

This study investigated the trends of gastric cancer in Korea by adding the latest updated gastric cancer data from 2019. Gastric cancer incidence between 1999 and 2019 was reviewed using data from the Korea Central Cancer Registry. The study period was divided into 3 periods: period I (1999-2005), period II (2006-2012), and period III (2013-2019). The incidence, mortality, tumor location, histology, stage, and treatment were analyzed. Between 1999 and 2019, 577,502 patients were newly diagnosed with gastric cancer in Korea, accounting for 33.2% of patients aged ≥70 years. The age-standardized incidence rate (per 100,000) significantly decreased from 2011 (43.0) to 2019 (29.6), with an annual percent change of -4.50. Additionally, the age-standardized mortality rate (per 100,000) markedly decreased from 1999 (23.9) to 2019 (6.7). The proportions of patients with cardia and fundus cancers remained consistent. The proportion of localized stage cases increased, while those of regional and distant stages decreased. The rate of surgical treatment increased in localized and regional stages from 2006 to 2019. The overall 5-year relative survival (5YRS) rate of gastric cancer (per 100,000) increased from 55.7% in period I to 77.0% in period III. From 2013 to 2019, the 5YRS rates of patients (per 100,000) who underwent surgical treatment were 100.6% and 70.5% in the localized and regional stages, respectively. The results of this study demonstrated several changes in the epidemiology of gastric cancer in Korea. This study provides information to help understand the current trends in gastric cancer in Korea.

Postoperative Complications and Their Risk Factors of Completion Total Gastrectomy for Remnant Gastric Cancer Following an Initial Gastrectomy for Cancer.

PURPOSE: Completion total gastrectomy (CTG) for remnant gastric cancer (RGC) is a technically demanding procedure and associated with increased morbidity. The present study aimed to evaluate postoperative complications and their risk factors following surgery for RGC after initial partial gastrectomy due to gastric cancer excluding peptic ulcer. MATERIALS AND METHODS: We retrospectively reviewed the data of 107 patients who had previously undergone an initial gastric cancer surgery and subsequently underwent CTG for RGC between March 2002 and December 2020. The postoperative complications were graded using the Clavien-Dindo classification. Logistic regression analyses were used to determine the risk factors for complications. RESULTS: Postoperative complications occurred in 34.6% (37/107) of the patients. Intra-abdominal abscess was the most common complication. The significant risk factors for overall complications were multi-visceral resections, longer operation time, and high estimated blood loss in the univariate analysis. The independent risk factors were multi-visceral resection (odds ratio [OR], 2.832; 95% confidence interval [CI], 1.094-7.333; P=0.032) and longer operation time (OR, 1.005; 95% CI, 1.001-1.011; P=0.036) in the multivariate analysis. Previous reconstruction type, minimally invasive approach, and current stage were not associated with the overall complications. CONCLUSIONS: Multi-visceral resection and long operation time were significant risk factors for the occurrence of complications following CTG rather than the RGC stage or surgical approach. When multi-visceral resection is required, a more meticulous surgical procedure is warranted to improve the postoperative complications during CTG for RGC after an initial gastric cancer surgery.

A Comprehensive and Comparative Review of Global Gastric Cancer Treatment Guidelines.

Countries differ in their treatment expertise and research results regarding gastric cancer; hence, treatment guidelines are diverse based on evidence and medical situations. A comprehensive and comparative review of each country's guidelines is imperative to understand the similarities and differences among countries. We reviewed and compared five gastric cancer treatment guidelines in terms of endoscopic, surgical, perioperative, and palliative systemic treatment based on evidence levels and recommendation grades, as well as the postoperative follow-up strategies for each guideline. The Korean, Chinese, and European guidelines provided evidence and grading of the recommendations. The United States guidelines suggested categories for evidence and consensus. The Japanese guidelines suggested evidence and recommendations only for systemic treatment. The Korean and Japanese guidelines described endoscopic treatment, surgery, and lymphadenectomy in detail. The Chinese, United States, and European guidelines more intensively considered perioperative chemotherapy. In particular, the indications for chemotherapy and the regimens recommended by each guideline differed slightly. Considering their medical situations, each guideline had some diversity in terms of adopting evidence, which resulted in heterogeneous recommendations. This review will help medical personnel to comprehensively understand the diversity in gastric cancer treatment guidelines for each country in terms of evidence and recommendations.

Spade-Shaped Anastomosis after Laparoscopic Proximal Gastrectomy Using Double Suture Anchoring between the Posterior Wall of the Esophagus and the Anterior Wall of the Stomach (SPADE Operation): A Case Series.

We introduced SPADE operation, a novel anastomotic method after laparoscopic proximal gastrectomy (PG). Technical modifications were performed and settled. This report aimed to demonstrate the short-term clinical outcomes after settlement. Data from 34 consecutive patients who underwent laparoscopic PG with SPADE between June 2017 and March 2020 were retrospectively reviewed. Reflux was evaluated based on the patients' symptoms and follow-up endoscopy using Los Angeles (LA) classification and RGB Classification (Residue, Gastritis, Bile). Other complications were classified using the Clavien-Dindo method. The incidence of reflux esophagitis was 2.9% (1/34). Bile reflux was observed in six patients (17.6%), and residual food was observed in 16 patients (47.1%) in the endoscopy. Twenty-eight patients had no reflux symptoms (82.4%), while five patients (14.7%) and one patient (2.9%) had mild and moderate reflux symptoms, respectively. The rates of anastomotic stricture and ileus were 14.7% (5/34) and 11.8% (4/34), respectively. No anastomotic leakage was observed. The incidence of major complications (Clavien-Dindo grade III or higher) was 14.7%. The SPADE operation following laparoscopic PG is effective in reducing gastroesophageal reflux. Its clinical usefulness should be validated using prospective clinical trials.

Short and Long-Term Surgical Outcomes of Laparoscopic Total Gastrectomy Compared with Open Total Gastrectomy in Gastric Cancer Patients.

This study aimed to compare the efficacy of laparoscopic total gastrectomy (LTG) with that of open total gastrectomy (OTG) in terms of postoperative complications and long-term survival. We retrospectively reviewed the clinicopathological data of 560 patients, who underwent total gastrectomy between 2012 and 2016 at the National Cancer Center, Korea. Propensity-score matching (PSM) was performed to correct for discrepancies between the two groups. Matched variables included sex, age, body mass index, American Society of Anesthesiologists score, and pathological Tumor-Node-Metastasis stage. After PSM, 238 patients were included in this analysis. The rate of D2 lymph node dissection was significantly higher in the OTG group than in the LTG group. The estimated blood loss was significantly lower in the LTG group than in the OTG group. The overall complication rate was not significantly different between the two groups. There was no significant difference in the 3-year disease-free and 5-year overall survival rates between the two groups. LTG and OTG had comparable efficacies in gastric cancer patients regarding short- and long-term surgical outcomes. This study suggests that LTG could be an alternative approach to the OTG.

Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization.

The imbalance between bone resorption and bone formation in favor of resorption results in bone loss and deterioration of bone architecture. Osteoblast differentiation is a sequential event accompanying biogenesis of matrix vesicles and mineralization of collagen matrix with hydroxyapatite crystals. Considerable efforts have been made in developing naturally-occurring plant compounds, preventing bone pathologies, or enhancing bone regeneration. Coumarin aesculetin inhibits osteoporosis through hampering the ruffled border formation of mature osteoclasts. However, little is known regarding the effects of aesculetin on the impairment of matrix vesicle biogenesis. MC3T3-E1 cells were cultured in differentiation media with 1-10 µM aesculetin for up to 21 days. Aesculetin boosted the bone morphogenetic protein-2 expression, and alkaline phosphatase activation of differentiating MC3T3-E1 cells. The presence of aesculetin strengthened the expression of collagen type 1 and osteoprotegerin and transcription of Runt-related transcription factor 2 in differentiating osteoblasts for 9 days. When ≥1-5 µM aesculetin was added to differentiating cells for 15-18 days, the induction of non-collagenous proteins of bone sialoprotein II, osteopontin, osteocalcin, and osteonectin was markedly enhanced, facilitating the formation of hydroxyapatite crystals and mineralized collagen matrix. The induction of annexin V and PHOSPHO 1 was further augmented in ≥5 µM aesculetin-treated differentiating osteoblasts for 21 days. In addition, the levels of tissue-nonspecific alkaline phosphatase and collagen type 1 were further enhanced within the extracellular space and on matrix vesicles of mature osteoblasts treated with aesculetin, indicating matrix vesicle-mediated bone mineralization. Finally, aesculetin markedly accelerated the production of thrombospondin-1 and tenascin C in mature osteoblasts, leading to their adhesion to preformed collagen matrix. Therefore, aesculetin enhanced osteoblast differentiation, and matrix vesicle biogenesis and mineralization. These findings suggest that aesculetin may be a potential osteo-inductive agent preventing bone pathologies or enhancing bone regeneration.

Dietary Factors and Breast Cancer Prognosis among Breast Cancer Survivors: A Systematic Review and Meta-Analysis of Cohort Studies.

Few studies have summarized the association between dietary factors and breast cancer (BC) prognosis among breast cancer survivors (BCS). Therefore, we carried out a systematic review and meta-analysis to determine the associations between dietary factors and BC prognosis among BCS. We performed a literature search in PubMed and Embase to investigate the association between dietary factors and BC prognosis. We applied a random-effects model to compute the hazard ratio/relative risk and their 95% confidence intervals and heterogeneity (Higgins I2) and to generate forest plots using STATA. Among the 2279 papers identified, 63 cohort studies were included in the systematic review and meta-analysis. Our main finding was that higher consumption of beer and saturated fat negatively affected BC prognosis. However, the intake of lignans, fiber, multivitamins, and antioxidants was negatively associated with the risk of mortality. Furthermore, we performed subgroup analyses by menopausal status and dietary or supplementary micronutrient intake. Most trends were similar to the main findings; in particular, the vitamin C, vitamin D, and vitamin E supplements decreased the risk of mortality. This study's current systematic review and meta-analysis provide comprehensive dietary information for the development of dietary guidelines/recommendations to improve prognosis among BCS.

Asaronic acid inhibits ER stress sensors and boosts functionality of ubiquitin-proteasomal degradation in 7ß-hydroxycholesterol-loaded macrophages.

BACKGROUND: Misfolded proteins are formed in the endoplasmic reticulum (ER) due to diverse stimuli including oxidant production, calcium disturbance, and inflammatory factors. Accumulation of these non-native proteins in the ER evokes cellular stress involving the activation of unfolded protein response (UPR) and the execution of ER-associated degradation (ERAD). Naturally-occurring plant compounds are known to interfere with UPR due to their antioxidant and anti-inflammatory activities, leading to inhibition of ER stress. However, there are few studies dealing with the protective effects of natural compounds on the functionality of ERAD. PURPOSE: The current study examined whether asaronic acid enhanced ubiquitin-proteasomal degradation in J774A.1 murine macrophages exposed to 7ß-hydroxycholesterol, a risk factor for atherosclerosis. Asaronic acid (2,4,5-trimethoxybenzoic acid), identified as one of purple perilla constituents, has anti-diabetic and anti-inflammatory effects. Little is known regarding the effects of asaronic acid on the ERAD process and the ubiquitin-proteasomal degradation. METHODS AND RESULTS: Murine macrophages were incubated with 28 µM 7ß-hydroxycholesterol in absence and presence of 1-20 µΜ asaronic acid for up to 24 h. Nontoxic asaronic acid in macrophage diminished the activation of the ER stress sensors of ATF6, IRE1 and PERK stimulated by 7ß-hydroxycholesterol. This methoxybenzoic acid down-regulated the oxysterol-induced expression of EDEM1, OS9, Sel1L-Hrd1 and p97/VCP1, all required for the recognition, recruitment and dislocation of misfolded proteins. On the other hand, asaronic acid enhanced the ubiquitin-proteasomal degradation of non-native proteins dislocated to the cytosol by 7ß-hydroxycholesterol, which entailed the induction of the chaperones of Hsp70 and CHIP and the increased colocalization of ubiquitin and proteasomes. Taken together, asaronic acid attenuated the induction of the UPR-associated sensors and the dislocation-linked transmembrane components in the ER. Conversely, this compound enhanced the proteasomal degradation of dislocated non-native proteins in concert with the chaperones of Hsp70 and CHIP through ubiquitination. CONCLUSION: These observations demonstrate that asaronic acid may be a potent atheroprotective agent as a natural chaperone targeting ER stress-associated macrophage injury.

Comparison between early surgical treatment and conservative treatment of appendicitis in cancer patients.

BACKGROUNDS: In cancer patients, the optimal appendicitis treatment has not been established. Therefore, we aimed to determine the ideal treatment option for appendicitis in cancer patients. METHODS: This retrospective study included 185 cancer patients with acute appendicitis who were divided into the early surgical group (n = 152) involving surgery performed within 48 h following the appendicitis diagnosis or the conservative group (n = 33) involving intravenous antibiotics. We compared the appendicitis treatment efficacy between the groups. RESULTS: In the early surgical group, the antibiotic duration [5.5 days (4.0-8.0) vs. 17.0 days (12.5-25.0), p < 0.001] and hospital stay length [7.0 days (5.0-11.75) vs. 10.0 days (8.0-32.0), p < 0.001] were significantly shorter. Regarding pathology, 16/171 (9.4%) patients who underwent surgery exhibited appendiceal tumours. During the 1-year follow-up period, one recurrence occurred in each group [1/152 (0.7%) vs. 1/33 (3.0%), p = 0.326]. The 1-year treatment success rate was higher in the early surgical group [99.3% (151/152) vs. 42.4% (14/33), p < 0.001]. CONCLUSION: Early surgical treatment yielded a significantly higher success rate than conservative treatment for appendicitis in cancer patients. Surgery for appendicitis in cancer patients should be considered not only for treatment but also for pathologic confirmation.

Dietary Collagen Hydrolysates Ameliorate Furrowed and Parched Skin Caused by Photoaging in Hairless Mice.

Collagen hydrolysates have been suggested as a favorable antiaging modality in skin photoaged by persistent exposure to ultraviolet radiation (UV). The current study evaluated the beneficial effect of collagen hydrolysates (fsCH) extracted from Pangasius hypophthalmus fish skin on wrinkle formation and moisture preservation in dorsal skin of hairless mice challenged with UV-B. Inter-comparative experiments were conducted for anti-photoaging among fsCH, retinoic acid (RA), N-acetyl-D-glucosamine (NAG), and glycine-proline-hydroxyproline (GPH). Treating human HaCaT keratinocytes with 100-200 µg/mL fsCH reciprocally ameliorated the expression of aquaporin 3 (AQP3) and CD44 deranged by UV-B. The UV-B-induced deep furrows and skin thickening were improved in parched dorsal skin of mice supplemented with 206-412 mg/kg fsCH as well as RA and GPH. The UV-B irradiation enhanced collagen fiber loss in the dorsal dermis, which was attenuated by fsCH through enhancing procollagen conversion to collagen. The matrix metalloproteinase expression by UV-B in dorsal skin was diminished by fsCH, similar to RA and GPH, via blockade of collagen degradation. Supplementing fsCH to UV-B-irradiated mice decreased transepidermal water loss in dorsal skin with reduced AQP3 level and restored keratinocyte expression of filaggrin. The expression of hyaluronic acid synthase 2 and hyaluronidase 1 by UV-B was remarkably ameliorated with increased production of hyaluronic acid by treating fsCH to photoaged mice. Taken together, fsCH attenuated photoaging typical of deep wrinkles, epidermal thickening, and skin water loss, like NAG, RA, or GPH, through inhibiting collagen destruction and epidermal barrier impairment.

Asaronic Acid Inhibited Glucose-Triggered M2-Phenotype Shift Through Disrupting the Formation of Coordinated Signaling of IL-4Rα-Tyk2-STAT6 and GLUT1-Akt-mTOR-AMPK.

Macrophage polarization has been implicated in the pathogenesis of metabolic diseases such as obesity, diabetes, and atherosclerosis. Macrophages responsiveness to polarizing signals can result in their functional phenotype shifts. This study examined whether high glucose induced the functional transition of M2 macrophages, which was inhibited by asaronic acid, one of purple perilla constituents. J774A.1 murine macrophages were incubated with 40 ng/mL interleukin (IL)-4 or exposed to 33 mM glucose in the presence of 1-20 µΜ asaronic acid. In macrophages treated with IL-4 for 48 h, asaronic acid further accelerated cellular induction of the M2 markers of IL-10, arginase-1, CD163, and PPARγ via increased IL-4-IL-4Rα interaction and activated Tyk2-STAT6 pathway. Asaronic acid promoted angiogenic and proliferative capacity of M2-polarized macrophages, through increasing expression of VEGF, PDGF, and TGF-ß. In glucose-loaded macrophages, there was cellular induction of IL-4, IL-4 Rα, arginase-1, and CD163, indicating that high glucose skewed naïve macrophages toward M2 phenotypes via an IL-4-IL-4Rα interaction. However, asaronic acid inhibited M2 polarization in diabetic macrophages in parallel with inactivation of Tyk2-STAT6 pathway and blockade of GLUT1-mediated metabolic pathway of Akt-mTOR-AMPKα. Consequently, asaronic acid deterred functional induction of COX-2, CTGF, α-SMA, SR-A, SR-B1, and ABCG1 in diabetic macrophages with M2 phenotype polarity. These results demonstrated that asaronic acid allayed glucose-activated M2-phenotype shift through disrupting coordinated signaling of IL-4Rα-Tyk2-STAT6 in parallel with GLUT1-Akt-mTOR-AMPK pathway. Thus, asaronic acid has therapeutic potential in combating diabetes-associated inflammation, fibrosis, and atherogenesis through inhibiting glucose-evoked M2 polarization.