S6K1 deficiency in tumor stroma impairs lung metastasis of melanoma in mice.

Accumulating data suggest that ribosomal protein S6 kinase 1 (S6K1), an effector in the mammalian target of rapamycin (mTOR) pathway, plays pleiotropic roles in tumor progression. However, to date, while the tumorigenic function of S6K1 in tumor cells has been well elucidated, its role in the tumor stroma remains poorly understood. We recently showed that S6K1 mediates vascular endothelial growth factor A (VEGF-A) production in macrophages, thereby supporting tumor angiogenesis and growth. As macrophage-derived VEGF-A is crucial for both tumor cell intravasation and extravasation across the vascular endothelium, our previous findings suggest that stromal S6K1 signaling is required for tumor metastatic spread. Therefore, we aimed to determine the impact of host S6K1 depletion on tumor metastasis using a murine model of pulmonary metastasis (S6k1-/- mice implanted with B16F10 melanoma). The ablation of S6K1 in the host microenvironment significantly reduced the metastasized B16F10 melanoma cells on the lung surface in both spontaneous and intravenous lung metastasis mouse models without affecting the incidence of metastasis to distant lymph nodes. In addition, stromal S6K1 loss decreased the number of tumor cells circulating in the peripheral blood of mice bearing B16F10 xenografts without affecting the vascular leakage induced by VEGF-A in vivo. These observations demonstrate that S6K1 signaling in host cells other than endothelial cells is required to modulate the host microenvironment to facilitate the metastatic spread of tumors via blood circulation, thus revealing its novel role in the tumor stroma during tumor progression.

Reliability of endoscopic ultrasonography and endoscopy in measurement of gastric subepithelial tumor size.

BACKGROUND: Subepithelial tumor (SET) size is important in determining the treatment plan; however, size estimation for gastric SETs has not been well investigated. We aimed to investigate which method predicts SET size most accurately by retrospectively analyzing surgically removed SETs. METHODS: From January 2015 through June 2020, patients who underwent surgical gastric SET removal at Asan Medical Center, Seoul, Korea, were enrolled. SET sizes measured by pathologists and endoscopists were retrospectively reviewed. The reliability of SET size measurement by endoscopic ultrasonography (EUS) and endoscopy was calculated using intraclass correlation coefficient (ICC), with pathologic size as the gold standard. RESULTS: Overall, EUS was highly reliable (ICC 0.86, P < 0.001), and endoscopy was moderately reliable (ICC 0.75, P < 0.001). When analyzed according to SET location, endoscopy was highly reliable in the lesser curvature's lower third (ICC 0.86, P = 0.014), middle third (ICC 0.88, P < 0.001), and upper third (ICC 0.90, P < 0.001); as well as the anterior wall's middle third (0.84, P < 0.001) and the posterior wall's upper third (ICC 0.80, P < 0.001). EUS (ICC 0.96, P = 0.005) and endoscopy (ICC 0.95, P = 0.008) both were most reliable for lower-third posterior wall lesions, whereas endoscopy was unreliable for middle-third greater curvature lesions (ICC 0.41, P = 0.05). CONCLUSIONS: Both EUS and endoscopy were reliable methods for measuring gastric SET size, and overall, EUS was more reliable than endoscopy. In terms of SET location, EUS was consistently reliable, whereas endoscopy showed variable reliability. When measuring SET size by endoscopy, additional size measurements with EUS should be considered in certain locations.

Clinical Outcomes of Patients with Benign Peptic Ulcer Bleeding After an Emergency Endoscopy Based on Patient Location.

BACKGROUND AND AIMS: In the efforts toward reducing bleeding-related mortality, it is crucial to determine the risk factors for rebleeding after endoscopic hemostasis in benign peptic ulcer (BPU). METHODS: Between 2013 and 2017, the medical records of 864 BPU patients were selected from 5076 who had undergone emergency endoscopy for suspected upper gastrointestinal bleeding. Patients who visited the emergency room or were hospitalized for other illnesses were selected. The primary end point was rebleeding within 30 days after initial endoscopy. The risk factors of rebleeding and subgroup analyses according to patient location were evaluated. RESULTS: Among 864 BPU bleeding patients, rebleeding after completion of BPU bleeding occurred in 140 (16.2%). Initial indicators of hypotension (OR 1.878, p = 0.005) and Forrest classes Ia (OR 25.53, p < 0.001), Ib (OR 27.91, p = 0.005), IIa (OR 21.41, p < 0.001), and IIb (OR 23.74, p < 0.001) were independent risk factors of rebleeding compared to Forrest class III, and being inpatients (OR 1.75, p = 0.01). Compared to the outpatients, the inpatients showed significantly higher rebleeding rates (25.6% vs 13.8%, p < 0.001), predictive bleeding scores, red blood transfusion counts, proportion of Forrest classes Ia, Ib, and IIb (p < 0.001), and overall mortality rates (68.8% vs 34.0%, p < 0.001). CONCLUSIONS: Patient location was a novel predictive factor of BPU rebleeding. Particularly, being an inpatient correlated with increased rebleeding. Furthermore, Forrest classes Ia, Ib, IIa, and IIb were predictive of rebleeding not only the included BPUs, but also in the inpatient or outpatient groups.

Prognostic significance of incorporating exercise tissue doppler mitral annular early diastolic velocity in exercise diastolic dysfunction assessment.

BACKGROUND: The existing algorithm for defining exercise-induced diastolic dysfunction incorporates resting e' velocity as a surrogate of myocardial relaxation. The additive prognostic value of incorporating post-exercise e' velocity in definition of exercise-induced diastolic dysfunction is poorly studied. AIM: To define the additive prognostic value of post-exercise e' septal velocity in the assessment of exercise-induced diastolic dysfunction compared to the traditional approach. METHODS: This retrospective study included 1409 patients undergoing exercise treadmill echocardiography with available full set of diastolic variables. Doppler measures of diastolic function included resting septal e' velocity, post-exercise septal e' velocity, post-exercise E/e' ratio, and post-exercise tricuspid regurgitant jet velocity. Approaches incorporating resting septal e' velocity and post-exercise septal e' velocity were compared in defining exercise-induced diastolic dysfunction, and for association with adverse cardiovascular outcomes. RESULTS: The mean age of study subjects was 56.3 ± 16.5 years and 791 (56%) patients were women. A total of 524 patients had disagreement between resting and post exercise septal e' velocities, and these values showed only weak agreement (kappa statistics: .28, P = .02). All categories of the traditional exercise-induced DD approach incorporating resting septal e' velocity witnessed reclassification when exercise septal e' velocity was used. When both approaches were compared, increased event rates were only evident when both approaches agreed on exercise-induced diastolic dysfunction (HR: 1.92, P < .001, 95% CI: 1.37-2.69). This association persisted after multivariable adjustment and propensity score matching for covariates. CONCLUSION: Incorporation of post-exercise e' velocity into the set of variables defining exercise-induced diastolic dysfunction can improve the prognostic utility of diastolic function assessment.

Tissue Doppler derived biphasic velocities during the pre and post-ejection phases: patterns, concordance and hemodynamic significance in health and disease.

BACKGROUND: Pre-(PRE) and post-ejection (POE) velocities by mitral annular tissue Doppler (TD) are biphasic and may be related to myocardial deformations. We investigated the predominance and concordance of TD-PRE and POE velocities and their effect on myocardial functions in controls and in heart failure (HF) patients. METHODS: Retrospectively, 84 HF patients [57.6 years, 28(33%) females, NYHA: 2.3 ± 0.6, EF: 55 ± 15%, 52(62%) preserved EF, and 32(38%) reduced EF], 42 normal young controls, and 26 asymptomatic age matched controls were included. Echocardiography was done and from mitral annular tissue Doppler recordings, the biphasic PRE and POE velocity signals were identified and compared between groups. RESULTS: While controls had almost always predominantly positive PRE and negative POE, HF had more negative PRE and positive POE. Moreover, almost all controls exhibited normal concordance (positive PRE and negative POE). HF exhibited more abnormal concordance which was significantly associated with worse NYHA, and parameters of diastolic and systolic functions. Opposite PRE and POE velocities correlated significantly in all groups (PREp vs POEn: young:r = 0.52, p < 0.001, age controls:r = 0.79, p < 0.001, HFpEF: r = 0.56, p < 0.001, HFrEF: r = 0.42, p = 0.018; PREn vs POEp: young: r = 0.25,p = 0.1, age controls: r = 0.42, p = 0.04, HFpEF: r = 0.43, p = 0.004, HFrEF: r = 0.61, p < 0.001) and the ratios PRE-P/N and POE-N/P correlated significantly with E/e' in HF only. CONCLUSIONS: In physiological state, TD signals are predominantly positive during PRE and negative during POE. Opposite PRE and POE velocities corelate, representing the PRE-generation and POE-reversal of shortening-stretch relationships, the attenuation of which in HF may be related to elevated LV filling pressures. In HF, partially or completely reversed concordance of PRE and POE is associated with progressive worsening of clinical and hemodynamic profiles.

Optimal Initial Workup in Patients With Superficial Primary Gastric MALT Lymphoma.

BACKGROUND AND AIMS: The prognosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is favorable, especially in the absence of lymph node metastasis (LNM). We investigated LNM incidence and location in superficial type gastric MALT lymphoma. METHODS: We performed a retrospective analysis of 450 patients newly diagnosed with gastric MALT lymphoma with tumor infiltration confined to the mucosa or submucosa as evidenced by endoscopic ultrasonography. LNM incidence and location were evaluated. RESULTS: Of the 450 patients, most patients (434, 96.4%) were initially LNM negative as confirmed by computed tomography (CT) scanning. Sixteen patients (3.6%) were LNM positive. There was no difference in clinical characteristics between the 2 groups except for the extent of lymphoma involvement and endoscopic findings. Among 41 patients undergoing abdominal/pelvic CT (APCT) only, LNM was detected in 1 (2.4%). There were 8 LNM cases among 238 patients undergoing both APCT and chest CT (3.4%). Among 171 patients undergoing APCT, chest CT, and neck CT, 7 cases of LNM were detected (4.1%). The detection rates for each CT were as follows: abdominal CT, 13/450 (2.9%); chest CT, 6/408 (1.5%); and neck CT, 1/171 (0.6%). Among 6 patients with chest CT-positive findings, 3 showed no evidence of LNM on APCT. CONCLUSION: LNM was an infrequent finding in gastric MALT lymphoma patients with tumor infiltration confined to the mucosa or submucosa. Besides endoscopy and endoscopic ultrasonography, APCT and chest CT are considered as optimal initial workup modalities in patients with assumed primary superficial gastric MALT lymphoma.

Clinical course of duodenal mucosa-associated lymphoid tissue lymphoma: Comparison with gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND AND AIM: There are few cases of duodenal mucosa-associated lymphoid tissue (MALT) lymphoma reported in the literature, and little is known about the clinical course of this disease. Here, we aimed to characterize the clinical features of duodenal MALT lymphoma by comparison with gastric MALT lymphoma. METHODS: Thirteen patients diagnosed with duodenal MALT lymphoma at Asan Medical Center from March 1997 to February 2017 were included in this retrospective study, along with patients with gastric MALT lymphoma, matched by age and sex at a 1:10 ratio. RESULTS: Median age of patients with duodenal MALT lymphoma was 49 (range 20-72) years, and 53.8% (7/13) were male. Comparison of patient characteristics indicated that Helicobacter pylori infection (46.2% vs 90.8%, P < 0.001) and lymph node metastasis (23.1% vs 5.4%, P = 0.049) rates differed between patients with duodenal and gastric MALT lymphoma. Overall complete remission (61.5% vs 86.2%, P = 0.021) and complete remission after initial H. pylori eradication therapy (50% vs 87.7%, P = 0.037) were significantly lower in patients with duodenal than gastric MALT lymphoma. Complications including bleeding, stricture, and transformation to high-grade lymphoma occurred in a total of seven patients (4.9%), with a higher incidence in patients with duodenal than gastric MALT lymphoma (38.5% vs 1.5%, P < 0.001). CONCLUSIONS: Duodenal MALT lymphoma is very rare, and treatment outcomes appear to be inferior to those of gastric MALT lymphoma.

Close Observation versus Additional Surgery after Noncurative Endoscopic Resection of Esophageal Squamous Cell Carcinoma.

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.

Changes in the Expression of TBP-2 in Response to Histone Deacetylase Inhibitor Treatment in Human Endometrial Cells.

Histone deacetylase inhibitors (HDACi) induce apoptosis preferentially in cancer cells by caspase pathway activation and reactive oxygen species (ROS) accumulation. Suberoylanilide hydroxamic acid (SAHA), a HDACi, increases apoptosis via altering intracellular oxidative stress through thioredoxin (TRX) and TRX binding protein-2 (TBP-2). Because ROS accumulation, as well as the redox status determined by TBP-2 and TRX, are suggested as possible mechanisms for endometriosis, we queried whether SAHA induces apoptosis of human endometrial cells via the TRX-TBP-2 system in endometriosis. Eutopic endometrium from participants without endometriosis, and ectopic endometrium from patients with endometriosis, was obtained surgically. Human endometrial stromal cells (HESCs) and Ishikawa cells were treated with SAHA and cell proliferation was assessed using the CCK-8 assay. Real-time PCR and Western blotting were used to quantify TRX and TBP-2 mRNA and protein expression. After inducing oxidative stress, SAHA was applied. Short-interfering TRX (SiTRX) transfection was performed to see the changes after TRX inhibition. The mRNA and protein expression of TBP-2 was increased with SAHA concentrations in HESCs significantly. The mRNA TBP-2 expression was decreased after oxidative stress, upregulated by adding 2.5 µM of SAHA. The TRX/TBP-2 ratio decreased, apoptosis increased significantly, and SiTRX transfection decreased with SAHA. In conclusion, SAHA induces apoptosis by modulating the TRX/TBP-2 system, suggesting its potential as a therapeutic agent for endometriosis.

MST2 silencing induces apoptosis and inhibits tumor growth for estrogen receptor alpha-positive MCF-7 breast cancer.

Mammalian sterile 20-like kinase 1/2 (MST1/2) plays an important role in cell growth and apoptosis and functions as a tumor suppressor. Previously, we showed that MST2 overexpression activates Estrogen receptor alpha (ERα) in human breast cancer MCF-7 cells in the absence of a ligand. Here, we examined the role of MST2 in the growth of ER-positive MCF-7 cells. Cell cycle, apoptosis, and mammosphere formation assay method were implemented to detect the biological effects of MST2 ablation on the growth of MCF-7 cells in vitro. The effect of MST2-siRNA on MCF-7 cells tumor growth in vivo was studied in tumor-bearing mouse model. Kaplan-Meier plotter analysis was used to determine the effect of MST2 on overall survival in breast cancer patients. MST2 overexpression increased cell viability marginally. The ablation of MST2 using siRNA dramatically suppressed the viability of the MCF-7 cells, but not ER-negative MDA-MB-231 breast cancer cells. Furthermore, MST2 knockdown increased caspase-dependent apoptosis and led to decreased mammosphere formation. Treatment of MCF-7 tumor-bearing mice with MST2 siRNA significantly inhibited tumor growth. The tumor weight was reduced further when tamoxifen was added. Patients with ER-positive breast cancer with low MST2 expression had better overall survival than did those with high MST2 expression in Kaplan-Meier survival analyses using public datasets. Our results provide new insight into the role of MST2, a key component of the Hippo signaling pathway, in mediating breast cancer progression.

Comparison of the treatment outcomes of endoscopic and surgical resection of GI stromal tumors in the stomach: a propensity score-matched case-control study.

BACKGROUND AND AIMS: We aimed to investigate the safety and efficacy of endoscopic resection (ER) compared with surgical resection (SR) of gastric GI stromal tumors (GISTs). METHODS: This study included 51 and 403 patients who underwent ER and SR, respectively, for ≤5 cm GISTs in the stomach between June 2005 and August 2017. After propensity score matching (1:1) using age, sex, tumor size, mitotic count, and comorbidities, the oncologic outcomes were compared with 48 patients each from ER and SR groups. RESULTS: The ER group had significantly shorter hospital stay (4.4 ± 2.9 vs 6.6 ± 3.6 days, P < .001) and procedure time (38.3 ± 24.2 vs 66 ± 33.3 min, P < .001). The R0 resection rate was 62.7% in the ER group and 98.5% in the SR group. In the ER group, macroperforation occurred in 6 patients (11.8%) with a tumor located in the fundus (4/6, 66.7%) or body (2/6, 33.3%). All cases of perforation were cured with conservative treatment. In the SR group, postoperative adverse events such as stricture and leakage occurred in 7 patients (1.7%) with a tumor located in the antrum (4/7, 57.1%) or cardia (3/7, 42.9%). After matching, the overall mean follow-up period was 47.9 ± 37.8 months in the ER group and 41.3 ± 22.6 months in the SR group. No recurrence or distant metastasis occurred in either group during the follow-up period. CONCLUSIONS: ER is an effective and safe therapeutic method that might be comparable with SR for treating small-sized (≤5 cm) gastric GISTs. Selecting the resection method according to the tumor location seems appropriate.

Isolation of Helicobacter pylori using leftover tissue in the rapid urease test kit.

BACKGROUND AND AIMS: Isolation of Helicobacter pylori is considered difficult because of the requirement of the additional biopsy tissue and the effort involved in the isolation of the bacterium. We investigated whether H pylori can be cultured from tissue samples used for the rapid urease test (RUT). METHODS: Totally, 174 specimens from 87 patients referred for endoscopy were prospectively included. During endoscopy, two biopsy specimens were obtained, one each from the gastric antrum and the corpus, and were placed into a commercially available RUT kit. After detection of urease activity, H pylori was cultured using tissue leftover in the RUT, regardless of the result. RESULTS: H pylori was successfully isolated using leftover tissue in 72.4% (63/87) of the patients. In 32 patients, H pylori was isolated from both specimens, while in 31 patients, it was isolated from either antrum or corpus. Eighty-one H pylori strains were isolated from 141 specimens with positive RUT results (57.4%), whereas 14 strains were isolated from 33 specimens with negative RUT results (42.4%). The median interval between tissue acquisition and inoculation onto the isolation media was 3.6 hours (range: 0.5-27.5 hours) in cases with successful cultures, compared to 23.5 hours (range: 0.5-76.0 hours) in cases with failed cultures. Among the positive RUT tissues, 80.4% (45/56) were cultured successfully when the tissue was inoculated within 4 hours of the biopsy. CONCLUSIONS: RUT kits can be used as transport media for H pylori, and this media is most efficient when used within 4 hours of the test.

Efficacy of Endoscopic Ultrasound-Guided Fine-Needle Biopsy in Gastric Subepithelial Tumors Located in the Cardia.

BACKGROUND: In cases of subepithelial tumors (SETs) located in the cardiac area, a preoperative histologic diagnosis might be helpful in determining the requirement of surgery. AIM: To investigate the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) in gastric SETs located in the cardia. METHODS: The data of 107 patients who underwent EUS-FNB, from 2012 to 2017, for tissue sampling of gastric SETs located in the cardia were collected. The clinicopathological data, EUS-related parameters, and surgical outcomes were retrospectively reviewed. RESULTS: The EUS-FNB results were diagnostic in 86.9% (93/107) and nondiagnostic in 13.1% (14/107) of the patients. Immunostaining of the FNB specimens led to the diagnosis of gastrointestinal stromal tumor (GIST) in 25 SETs (23.4%), leiomyoma in 62 SETs (57.9%), heterotopic pancreas in 3 SETs (2.8%), and schwannoma in 2 SETs (1.9%). In the multivariate analysis, patients with GISTs showed significantly more inhomogeneous echogenicity [odds ratio (OR), 8.867], more cystic foci (OR, 26.98), and older age (OR, 1.087). In 26 patients who underwent surgical resection, the agreement between EUS-FNB and surgical pathological findings was 100% with respect to the diagnosis of GISTs (n = 20) and leiomyoma (n = 7). Among these cases, the proportion of high-risk GISTs was 20.0% (4/20), and no leiomyosarcoma was detected. CONCLUSIONS: Although a majority of the subepithelial lesions in the cardia of the stomach are benign, 20% of the cases diagnosed with GIST have a high malignant potential. Preoperative EUS-FNB might be a useful tool for decision-making regarding the ultimate management and outcomes of these lesions.

Incidence and Outcomes of Sepsis in Korea: A Nationwide Cohort Study From 2007 to 2016.

OBJECTIVES: This study aimed to estimate the incidence and clinical outcomes of sepsis in Korea from 2007 to 2016. DESIGN: Retrospective observational study. SETTING: Nationwide study with population-based healthcare reimbursement claims database. PATIENTS: Using data from the National Health Insurance Service of Korea, patients who were hospitalized with a diagnosis of sepsis from 2007 to 2016 were analyzed. The incidence of sepsis was calculated using mid-year census population and analyzed according to year, age, and sex. The Elixhauser Comorbidity Index score was calculated to adjust for the impact of comorbidities on clinical outcome. In-hospital mortality, hospital length of stay, ICU admission rates, and risk factors for in-hospital mortality were also analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The incidence of sepsis increased from 173.8 per 100,000 population in 2007 to 233.6 per 100,000 population in 2016. In-hospital mortality decreased from 30.9% in 2007 to 22.6% in 2016 (p < 0.0001). From 2007 to 2016, hospital length of stay and ICU admission rates associated with sepsis decreased from 26.0 ± 33.5 days to 21.3 ± 24.4 days (p < 0.0001) and from 16.2% to 12.7% (p < 0.0001), respectively. Male sex, age greater than 50 years, Elixhauser Comorbidity Index greater than 10, and mechanical ventilation were identified as risk factors for in-hospital mortality after adjusting for baseline characteristics. CONCLUSIONS: The incidence of sepsis in Korea increased from 2007 to 2016, while the associated in-hospital mortality, hospital length of stay, and ICU admission rates decreased.

Natural History of Gastric Cancer: Observational Study of Gastric Cancer Patients Not Treated During Follow-Up.

BACKGROUND: Understanding the natural progression of untreated gastric cancer is critical for determining the disease prognosis as well as treatment options and timing. The aim of this study is to analyze the natural history of gastric cancer. PATIENTS AND METHODS: We included patients with gastric cancer who had not received any treatment and were staged using endoscopy/endoscopic ultrasonography and computed tomography on at least two follow-up visits during intervals of nontreatment. Tumor volumes were also measured in addition to the staging. Survival of each stage at diagnosis was also analyzed. RESULTS: A total of 101 patients were included. The mean follow-up period was 35.1 ± 34.4 months. The gastric cancer doubling time was 11.8 months for T1 and 6.2 months for T4. The progression time from early gastric cancer to advanced gastric cancer was 34 months. It decreased as the stages advanced: from 34 months between tumor-nodes-metastasis stage I and II to 1.8 months between stage III and IV. No variable was identified as a risk factor for cancer progression. The 5-year survival rates of untreated patients were 46.2% in stage I and 0% in stage II, stage III, and stage IV. CONCLUSIONS: The progression and doubling times of gastric cancer shorten as the stages advance. Objective data reported in this study can be a critical factor in determining treatment timing and screening interval.

Superior clinical outcomes of peroral endoscopic myotomy compared with balloon dilation in all achalasia subtypes.

BACKGROUND AND AIM: Optimal treatment modalities for each of the three subtypes of achalasia are still under debate. Differences in prognosis and long-term outcomes between peroral endoscopic myotomy (POEM) and balloon dilation (BD) are also unclear. We aimed to compare the treatment outcomes of BD and POEM in each subtype of achalasia by using information from the manometry database of a tertiary referral center in Korea. METHODS: Data from 5207 esophageal manometry procedures performed between 1989 and 2016 were analyzed. The medical records and results of esophagography and esophagogastroduodenoscopy were also reviewed. RESULTS: We identified 264 patients (116 men and 148 women) with diagnosis of achalasia during the study period. POEM and BD were carried out on 64 and 177 patients, respectively. There was a significant difference in the time to relapse between the POEM group and the BD group (P = 0.002). At the 24-month follow-up, the clinical success rates of POEM and BD were 91.8% and 68.0%, respectively. The hazard ratio of symptom return was 6.54 for BD compared with POEM (95% confidence interval 2.12-20.22, P = 0.001). After a follow-up period of 24 months, the success rate of POEM was significantly higher than that of BD for all subtypes of achalasia. However, only that of types I and II was statistically significant (type 1: 92.0% vs 51.1%, P = 0.004; type 2: 92.3% vs 59.8%, P = 0.007; and type3: 91.7% vs 55.6%, P = 0.051). CONCLUSIONS: Peroral endoscopic myotomy was more effective than BD in providing mid-long-term remission in patients with all manometric subtypes of achalasia.

Effect of Institutional Kidney Transplantation Case-Volume on Post-Transplant Graft Failure: a Retrospective Cohort Study.

BACKGROUND: The impact of institutional case volume to graft failure rate after adult kidney transplantation is relatively unclear compared to other solid organ transplantations. METHODS: A retrospective cohort study of 13,872 adult kidney transplantations in Korea was performed. Institutions were divided into low- (< 24 cases/year), medium- (24-60 cases/year), and high- (> 60 cases/year) volume centers depending on the annual case volume. One-year graft failure rate was defined as the proportion of patients who required dialysis or re-transplantation at one year after transplantation. Postoperative in-hospital mortality and long-term graft survival were also measured. RESULTS: After adjustment, one year graft failure was higher in low-volume centers significantly (adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.26-1.78; P < 0.001) and medium-volume centers (aOR, 1.87; 95% CI, 1.57-2.23; P < 0.001) compared to high-volume centers. Low-volume centers had significantly higher mortality (aOR, 1.75; 95% CI, 1.15-2.66; P = 0.01) than that of high-volume centers after adjustment. Long-term graft survival of up to 9 years was superior in high-volume centers compared to low- and medium-volume centers (P < 0.001). CONCLUSION: Higher-case volume centers were associated with lower one-year graft failure rate, lower in-hospital mortality, and higher long-term graft survival after kidney transplantation.

Perioperative red blood cell transfusion and mortality following heart transplantation: A retrospective nationwide population-based study between 2007 and 2016 in Korea.

BACKGROUND: Patients undergoing heart transplantation (HT) frequently receive perioperative red blood cell (RBC) transfusions, but the impact of perioperative transfusion on clinical outcomes after HT remains unclear. METHODS: All adult HTs performed in Korea between 2007 and 2016 were analyzed using data from the National Health Insurance Service. Patients were classified into four groups based on the number of RBC units transfused during hospital admission for HT: 0, 1 to 2, 3 to 5, and greater than or equal to 6 units. In-hospital and long-term mortality rates were compared among the groups. RESULTS: In total, 833 adults HTs were included in the study. The overall in-hospital mortality rate was 8.4% (70 of 833), with no mortality occurring in patients who received no transfusion. The in-hospital mortality rate was higher in patients requiring greater than or equal to 6 units (25.1%) than in patients who received 1 to 2 units (0.3%) and 3 to 5 units (2.7%; P < .001). Patients who received greater than or equal to 6 units of RBCs had a significantly higher risk of all-cause mortality after HT compared to patients who received no transfusion (hazard ratio [95% confidence interval], 5.99 [1.46-24.56]; P = .012). Long-term survival rate was also lower in patients who received transfusions of greater than or equal to 6 units of RBCs than in patients who received no transfusion (P < .001). CONCLUSIONS: Perioperative transfusion of greater than or equal to 6 units of RBCs may be associated with an increased risk of in-hospital and long-term mortality after HT.

Zr-89 Immuno-PET Targeting Ectopic ATP Synthase Enables In-Vivo Imaging of Tumor Angiogenesis.

In this study, we synthesized a Zr-89-labeled anti-adenosine triphosphate synthase monoclonal antibody (ATPS mAb) for applications in immuno-positron emission tomography (PET) and evaluated its feasibility for angiogenesis imaging. The cellular uptake of Zr-89 ATPS mAb was measured after treatment of cancer cell lines in vitro, and its biodistribution was evaluated at 4, 24 and 48 h in vivo in mice bearing xenografts. PET images were acquired at 4, 24, 48, and 96 h after Zr-89 ATPS mAb administration. Tumor angiogenesis was analyzed using anti-CD31 immunofluorescence staining. The cellular uptake of Zr-89 ATPS mAb increased over time in MDA-MB-231 breast cancer cells but did not increase in PC3 prostate cancer cells. The tumor uptake of Zr-89 ATPS mAb at 24 h was 9.4 ± 0.9% ID/g for MDA-Mb-231 cells and was 3.8 ± 0.6% ID/g for PC3 cells (p = 0.004). Zr-89 ATPS mAb uptake in MDA-MB-231 xenografts was inhibited by the administration of cold ATPS mAb (4.4 ± 0.5% ID/g, p = 0.011). Zr-89 ATPS mAb uptake could be visualized by PET for up to 96 h in MDA-MB-231 tumors. In contrast, there was no distinct tumor uptake detected by PET in the PC3 xenograft model. CD31-positive tumor vessels were abundant in MDA-MB-231 tumors, whereas they were scarcely detected in PC3 tumors. In conclusion, ATPS mAb was successfully labeled with Zr-89, which could be used for immuno-PET imaging targeting tumor angiogenesis.

Institutional Case-Volume and Mortality After Heart Transplantation.

The relationship between lower institutional case-volume and higher mortality after complex high-risk procedures has been shown. The aim of this study is to examine the effect of institutional volume on patient outcome after heart transplantation (HT) in the entire Korean population.We analyzed all adult HTs performed in Korea between 2007 and 2016 using data from the National Health Insurance Service. The association between case-volume and in-hospital mortality after HT was analyzed after categorizing hospitals performing HT into low-, medium-, or high-volume centers depending on the number of HTs performed. The effect of case-volume on long-term mortality was also assessed.A total of 833 adult HTs were performed in 17 centers. In-hospital mortality was 3.7% (13/356), 10.1% (38/375), and 18.6% (19/102) in high-, medium-, and low-volume centers, respectively. Medium-, and low-volume centers showed increased risk of in-hospital mortality (odds ratio [95% confidence interval]; 2.11 [1.42-3.13] and 3.68 [2.16-2.27], respectively.). Long-term survival of up to 10 years was worse in lower-volume centers compared to high-volume centers (P < 0.001).In conclusion, lower case-volume was associated with increased in-hospital mortality and long-term mortality after HT. A minimum case-volume mandate may be required for hospitals performing HT to ensure the best patient outcome and effective resource allocation.