Clinical Outcome of Patients with Poor-Grade Aneurysmal Subarachnoid Hemorrhage with Bundled Treatments: A Propensity Score-Matched Analysis.

BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as Hunt and Hess (HH) grades IV and V, is a challenging disease because of its high mortality and poor functional outcomes. The effectiveness of bundled treatments has been demonstrated in critical diseases. Therefore, poor-grade aSAH bundled treatments have been established. This study aims to evaluate whether bundled treatments can improve long-term outcomes and mortality in patients with poor-grade aSAH. METHODS: This is a comparative study using historical control from 2008 to 2022. Bundled treatments were introduced in 2017. We compared the rate of favorable outcomes (modified Rankin Scale score 0-2) at 6 months and mortality before and after the introduction of the bundled treatments. To eliminate confounding bias, the propensity score matching method was used. RESULTS: A total of 90 consecutive patients were evaluated. Forty-three patients received bundled treatments, and 47 patients received conventional care. The proportion of patients with HH grade V was higher in the bundle treatment group (41.9% vs. 27.7%). Conversely, the proportion of patients with fixed pupils on the initial examination was higher in the conventional group (30.2% vs. 38.3%). After 1:1 propensity score matching, 31 pairs were allocated to each group. The proportion of patients with 6-month favorable functional outcomes was significantly higher in the bundled treatments group (46.4% vs. 20.7%, p = 0.04). The 6-month mortality rate was 14.3% in the bundled treatments group and 27.3% in the conventional group (p = 0.01). Bundled treatments (odd ratio 14.6 [95% confidence interval 2.1-100.0], p < 0.01) and the presence of an initial pupil reflex (odd ratio 12.0 [95% confidence interval 1.4-104.6], p = 0.02) were significantly associated with a 6-month favorable functional outcome. CONCLUSIONS: The bundled treatments improve 6-month functional outcome and mortality in patients with poor-grade aSAH.

Side-by-side placement of fully covered metal stents versus conventional 7F plastic stents in malignant hilar biliary obstruction: Prospective randomized controlled trial.

OBJECTIVES: We aimed to evaluate the efficacy and safety of metal stents compared with plastic stents when bilateral side-by-side stents were deployed for malignant hilar biliary obstruction (MHBO). METHODS: Fifty patients with unresectable advanced MHBO were randomly assigned to the metal stent (MS, n = 25) or plastic stent group (PS, n = 25). Fully covered self-expandable metal stents with 6 mm diameter and plastic stents with either 7F straight or double pigtail were used for MS and PS groups, respectively. Time to recurrent biliary obstruction (TRBO) was evaluated as the primary outcome. RESULTS: Both groups had 100% technical success rates; 88% and 76% of clinical success rates were obtained in MS and PS, respectively. Although stent migrations were more frequent in MS than PS (48% vs. 16%, P = 0.02), the mean TRBO was significantly longer in MS (190 days; 95% confidence interval [CI] 121-260 days vs. 96 days; 95% CI 50-141 days, P = 0.02). The placement of plastic stents (hazard ratio 2.42; 95% CI 1.24-4.73; P = 0.01) was the only significant risk factor associated with TRBO in multivariable analysis. The rates of adverse events were similar between the two groups (difference 0%; 95% CI -25% to 25%; P > 0.99). CONCLUSIONS: During bilateral side-by-side deployment in MHBO, the use of metal stents appears to be preferable to plastic stents in terms of TRBO, despite a higher frequency of stent migration.

Genetic assessment of pathogenic germline alterations in lysosomal genes among Asian patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Lysosomes are closely linked to autophagic activity, which plays a vital role in pancreatic ductal adenocarcinoma (PDAC) biology. The survival of PDAC patients is still poor, and the identification of novel genetic factors for prognosis and treatment is highly required to prevent PDAC-related deaths. This study investigated the germline variants related to lysosomal dysfunction in patients with PDAC and to analyze whether they contribute to the development of PDAC. METHODS: The germline putative pathogenic variants (PPV) in genes involved in lysosomal storage disease (LSD) was compared between patients with PDAC (n = 418) and healthy controls (n = 845) using targeted panel and whole-exome sequencing. Furthermore, pancreatic organoids from wild-type and KrasG12D mice were used to evaluate the effect of lysosomal dysfunction on PDAC development. RNA sequencing (RNA-seq) analysis was performed with established PDAC patient-derived organoids (PDOs) according to the PPV status. RESULTS: The PPV in LSD-related genes was higher in patients with PDAC than in healthy controls (8.13 vs. 4.26%, Log2 OR = 1.65, P = 3.08 × 10-3). The PPV carriers of LSD-related genes with PDAC were significantly younger than the non-carriers (mean age 61.5 vs. 65.3 years, P = 0.031). We further studied a variant of the lysosomal enzyme, galactosylceramidase (GALC), which was the most frequently detected LSD variant in our cohort. Autophagolysosomal activity was hampered when GALC was downregulated, which was accompanied by paradoxically elevated autophagic flux. Furthermore, the number of proliferating Ki-67+ cells increased significantly in pancreatic organoids derived from Galc knockout KrasG12D mice. Moreover, GALC PPV carriers tended to show drug resistance in both PDAC cell line and PDAC PDO, and RNA-seq analysis revealed that various metabolism and gene repair pathways were upregulated in PDAC PDOs harboring a GALC variant. CONCLUSIONS: Genetically defined lysosomal dysfunction is frequently observed in patients with young-onset PDAC. This might contribute to PDAC development by altering metabolism and impairing autophagolysosomal activity, which could be potentially implicated in therapeutic applications for PDAC.

Efficacy of an internal anchoring plastic stent to prevent migration of a fully covered metal stent in malignant distal biliary strictures: a randomized controlled study.

BACKGROUND: Two types of self-expandable metal stents (SEMS) are available for malignant distal biliary obstruction: fully covered SEMS (FCSEMS) and uncovered SEMS. FCSEMS can prevent stent ingrowth, but a major concern is spontaneous migration. This study aimed to determine whether the additional insertion of a double-pigtail plastic stent to anchor the FCSEMS can prevent migration. METHODS: 68 patients with unresectable, malignant, distal, biliary obstruction were included in this multicenter, randomized, superiority trial. The patients were randomly assigned to receive either the FCSEMS plus an anchoring plastic stent (n = 33) or an FCSEMS alone (n = 35). After placement of the FCSEMS, the anchoring stent was inserted inside the FCSEMS. The primary outcome was the rate of stent migration during the 6-month follow-up. The secondary outcomes were stent-related adverse events, stent patency, and survival rates. RESULTS: The baseline characteristics were similar between the two groups. The rate of stent migration at 6 months was significantly lower in patients with the FCSEMS plus anchoring stent (15 % vs. 40 %; P = 0.02). The mean stent patency was significantly longer in the FCSEMS plus anchoring group (237 days [95 % confidence interval [CI] 199 to 275] vs. 173 days [95 %CI 130 to 217]; P = 0.048). There were no significant differences in stent-related adverse events and overall survival rates at 6 months between the two groups. CONCLUSIONS: Our data suggest that the additional double-pigtail plastic stent anchored the FCSEMS to prevent migration and prolonged patency without any serious adverse events.

Optimal Biliary Drainage for Patients With Biliary Anastomotic Strictures After Right Lobe Living Donor Liver Transplantation.

Right lobe (RL) living donor liver transplantation (LDLT) usually includes 2 bile duct anastomosis sites, namely, the right anterior and the right posterior segmental ducts. This study aimed to evaluate the optimal treatment for biliary strictures following RL LDLT with respect to unilateral or bilateral drainage techniques. From January 2005 to December 2017, 883 patients at Seoul National University Hospital underwent RL LDLT. Of these, 110 patients were enrolled who had 2 duct-to-duct anastomosis sites and who were considered at risk of developing biliary anastomotic strictures. Unilateral or bilateral biliary drainage during the follow-up period was identified by endoscopic retrograde cholangiopancreatography (ERCP) and/or percutaneous transhepatic biliary drainage (PTBD). The clinical success, complication, and 180-day mortality rates were compared between the unilateral and bilateral biliary drainage groups according to the initial ERCP findings. The mean age at the time of LDLT was 54.2 ± 8.2 years. The median time from LDLT to initial biliary anastomotic strictures was 177 (interquartile range, 18-1085) days. At the initial ERCP, unilateral drainage was performed in 55 (50.0%) patients, and bilateral drainage was performed in 11 (10.0%) patients. Of the patients who underwent unilateral drainage, 35 (63.6%) patients required conversion to bilateral drainage during follow-up. Overall, 71 (64.5%) patients required bilateral drainage more than once, whereas only 27 (24.5%) patients reached a resolution with unilateral biliary drainage. In this study, most patients required bilateral biliary drainage more than once during follow-up. An active attempt should be made to drain bilaterally in patients with biliary anastomotic strictures following RL LDLT.

Therapeutic outcomes and prognostic factors in unresectable gallbladder cancer treated with gemcitabine plus cisplatin.

BACKGROUND: Gallbladder cancer (GBC) is likely to be diagnosed at progressive stages and shows a very poor prognosis. Combination therapy with gemcitabine and cisplatin (GEMCIS) has been widely used as first-line palliative chemotherapy for advanced GBC. This study was designed to investigate the efficacy of GEMCIS and identify prognostic factors in patients with unresectable GBC. METHODS: Patients with GBC who were treated with GEMCIS from January 2008 to June 2017 in a single tertiary hospital were included. All cases of GBC were diagnosed by pathologic findings and extent of the tumour was assessed by imaging tests. Combination chemotherapy consisted of cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 intravenously on days 1 and 8 every 3 weeks. To determine factors affecting prognosis, Kaplan-Meier survival analysis, log-rank test and the Cox proportional hazard regression linear model were used. All variables with P < 0.1 in univariable analysis were included in the multivariable model. RESULTS: A total of 173 patients received a median of 5.3 ± 4.4 cycles of chemotherapy over 3.8 ± 3.9 months. Most of the patients (94.8%) were stage IVB at the time of diagnosis and the most common site of metastasis was the liver (42.8%). Disease control rate was 59.5%: 2 (1.2%) patients with complete response, 26 (15.0%) patients with partial response and 75 (43.4%) patients with stable disease. Overall survival (OS) and progression-free survival were 8.1 (95% confidence interval [CI], 7.1-10.2) and 5.6 (95% CI 4.5-6.8) months, respectively. Multivariable regression model indicated that metastasis to liver (hazard ratio [HR] = 1.63, 95% CI 1.11-2.40; P = 0.013), neutrophil-to-lymphocyte ratio (NLR) ≥3 (HR 1.65, 95% CI 1.09-2.49; P = 0.017), CEA ≥ 5 ng/mL (HR 1.50, 95% CI 1.02-2.19; P = 0.038), and CA19-9 ≥ 500 U/mL (HR 1.59, 95% CI 1.01-2.50; P = 0.043) were significantly associated with OS. CONCLUSIONS: GEMCIS demonstrated a high disease control rate in patients with unresectable GBC. Factors independently related to OS were metastasis to liver, NLR ≥ 3, CEA ≥ 5 ng/mL and CA19-9 ≥ 500 U/mL.

Lymph node ratio as valuable predictor in pancreatic cancer treated with R0 resection and adjuvant treatment.

BACKGROUND: Lymph-node (LN) metastasis is an important prognostic factor in resected pancreatic cancer. In this study, the prognostic value of American Joint Committee on Cancer (AJCC) 8th edition N stage, lymph-node ratio (LNR), and log odds of positive lymph nodes (LODDS) in resected pancreatic cancer was investigated. METHODS: Between January 2005 and December 2017, there were 351 patients with pancreatic cancer treated with R0 resection and adjuvant therapy at Seoul National University Hospital. Relationships between the three LN parameters and overall survival (OS) and recurrence-free survival (RFS) were evaluated using a log-rank test and Cox proportional hazard regression model. Each multivariate-adjusted LN parameter was internally validated by bootstrap-corrected Harrell's C-index. RESULTS: The mean duration from surgery to adjuvant therapy was 47.6 ± 17.4 days. In total, the median OS and RFS was 31.7 (95% CI, 27.2-37.2) and 15.4 (95% CI, 13.5-17.7) months. The three LN classification systems were significantly correlated with OS and RFS in log-rank tests and multivariate-adjusted models (all p < 0.05). When internally validated, LNR showed the highest discrimination ability in predicting OS and RFS (each C-index = 0.65). LNR also showed the highest C-index in subgroup analysis, classified by adjuvant therapy modality. LNR and the AJCC 8th edition LN classification system were significantly associated with loco-regional recurrence (p = 0.026 and p = 0.027, respectively). CONCLUSIONS: LNR, which showed the best prognostic performance and significant relationship with loco-regional recurrence, can help further stratify the patients and establish an active treatment plan.

Safety of endoscopic ultrasound-guided ethanol ablation for pancreatic cystic lesions: A single-center experience of 214 patients.

BACKGROUND: Endoscopic ultrasound-guided ethanol ablation (EUS-EA) for pancreatic cystic lesions (PCLs) has been used in recent years as a feasible treatment modality for low malignant probability PCLs or patients considered high-risk for surgery. The present study aimed to confirm the safety of EUS-EA and to find predictive factors for adverse event (AE). METHODS: A retrospective review was performed from the prospectively maintained database of patients who underwent EUS-EA for PCLs from June 2006 to April 2018 at Seoul National University Hospital. The primary outcomes of the study were the rates of AEs and severe AEs by EUS-EA. The secondary outcome was the predictive factors of AEs including acute pancreatitis and abdominal pain. RESULTS: A total of 214 patients were evaluated and the diagnoses of PCLs according to cystic fluid analysis and clinical features were as follows: serous cystic neoplasm (32.2%), mucinous cystic neoplasm (26.6%), branch duct type intraductal papillary mucinous neoplasm (BD-IPMN) (29.4%), and pseudocyst (11.7%). Three patients (1.4%) experienced severe AEs. Overall, AEs occurred in 71 (33.2%) patients. BD-IPMN (OR: 2.87; 95% CI: 1.05-7.84; P = 0.040), multilocular cysts (OR: 3.59; 95% CI: 1.09-11.85; P = 0.036), suspected ethanol leakage during procedure (OR: 10.68; 95% CI: 1.98-57.53; P = 0.006), and sticky cystic fluid (OR: 3.83; 95% CI: 1.20-12.24; P = 0.024) were predictive factors for post-procedural acute pancreatitis. PCLs of uncinate process (OR: 2.99; 95% CI: 1.22-7.35; P = 0.017) and PCLs with exophytic portion (OR: 3.70; 95% CI: 1.96-7.01; P < 0.001) were predictive factors for post-procedural abdominal pain. CONCLUSIONS: EUS-EA is a safe procedure with a very low rate of severe AEs. It seems possible to predict the AEs according to the features of the procedure and PCLs.

Low-level laser therapy with 850 nm recovers salivary function via membrane redistribution of aquaporin 5 by reducing intracellular Ca2+ overload and ER stress during hyperglycemia.

The overall goal is to study the effect of low-level laser therapy (LLLT) on membrane distribution of major water channel protein aquaporin 5 (AQP5) in salivary gland during hyperglycemia. Par C10 cells treated with high glucose (50 mM) showed a reduced membrane distribution of AQP5. The functional expression of AQP5 was downregulated due to intracellular Ca2+ overload and ER stress. This reduction in AQP5 expression impairs water permeability and therefore results in hypo-salivation. A reduced salivary flow was also observed in streptozotocin (STZ)-induced diabetic mice model and the expression of AQP5 and phospho-AQP5 was downregulated. Low-level laser treatment with 850 nm (30 mW, 10 min = 18 J/cm2) reduced ER stress and recovered AQP5 membrane distribution via serine phosphorylation in the cells. In the STZ-induced diabetic mouse, LLLT with 850 nm (60 J/cm2) increased salivary flow and upregulated of AQP5 and p-AQP5. ER stress was also reduced via downregulation of caspase 12 and CHOP. In silico analysis confirmed that the serine 156 is one of the most favorable phosphorylation sites of AQP5 and may contribute to the stability of the protein. Therefore, this study suggests high glucose inhibits phosphorylation-dependent AQP5 membrane distribution. High glucose induces intracellular Ca2+ overload and ER stress that disrupt AQP5 functional expression. Low-level laser therapy with 850 nm improves salivary function by increasing AQP5 membrane distribution in hyperglycemia-induced hyposalivation.

Stratified premedication strategy for the prevention of contrast media hypersensitivity in high-risk patients.

BACKGROUND: Although the severity of hypersensitivity reactions to iodinated contrast media varies, it is well correlated with the severity of recurrent reactions; however, prophylaxis protocols are not severity-stratified. OBJECTIVE: To assess the outcomes of tailored prophylaxis according to the severity of hypersensitivity reactions to iodinated contrast media. METHODS: Our premedication protocols were stratified based on the severity of previous reactions: (1) 4 mg of chlorpheniramine for mild reactions, (2) adding 40 mg of methylprednisolone for moderate reactions, and (3) adding multiple doses of 40 mg of methylprednisolone for severe index reactions. Cases of reexposure in patients with a history of hypersensitivity reactions were routinely monitored and mandatorily recorded. RESULTS: Among a total of 850 patients who underwent enhanced computed tomography after severity-tailored prophylaxis, breakthrough reactions occurred in 17.1%, but most breakthrough reactions (89.0%) were mild and did not require medical treatment. Additional corticosteroid use did not reduce the breakthrough reaction rate in cases with a mild index reaction (16.8% vs 17.2%, P = .70). However, underpremedication with a single dose of corticosteroid revealed significantly higher rates of breakthrough reaction than did double doses of corticosteroid in cases with a severe index reaction (55.6% vs 17.4%, P = .02). Changing the iodinated contrast media resulted in an additional reduction of the breakthrough reaction rate overall (14.9% vs 32.1%, P = .001). CONCLUSION: In a total severity-based stratified prophylaxis regimens and changing iodinated contrast media can be considered in patients with a history of previous hypersensitivity reaction to iodinated contrast media to reduce the risk of breakthrough reactions.

Radiologic findings as a determinant and no effect of macrolide resistance on clinical course of Mycoplasma pneumoniae pneumonia.

BACKGROUND: With the emergence of macrolide resistance, concerns about the efficacy of macrolides for the treatment of Mycoplasma pneumoniae (MP) pneumonia in children have been raised. This study aimed to determine the effect of macrolide resistance on the outcome of children who were hospitalized with MP pneumonia. METHODS: Between 2010 and 2015, we performed culture of MP from nasopharyngeal samples obtained from children who were hospitalized with pneumonia at five hospitals in Korea. Macrolide resistance was determined by the analysis of 23S rRNA gene transition and the minimal inhibitory concentrations of four macrolides. Medical records were reviewed to analyze the clinical response to treatment with macrolides. RESULTS: MP was detected in 116 (4.8%) of the 2436 children with pneumonia. MP pneumonia was prevalent in 2011 and 2015. Of the 116 patients with MP pneumonia, 82 (70.7%) were macrolide-resistant. There were no differences in the age distribution, total duration of fever, and chest x-ray patterns between the macrolide-susceptible and macrolide-resistant groups. After macrolide initiation, mean days to defervescence were longer in the macrolide-resistant group than in macrolide-susceptible group (5.7 days vs. 4.1 days, P = 0.021). However, logistic regression analysis revealed that the presence of extrapulmonary signs (P = 0.039), homogeneous lobar consolidation (P = 0.004), or parapneumonic effusion (P < 0.001) were associated with fever duration of ≥7 days after the initiation of macrolides, regardless of macrolide resistance. CONCLUSIONS: This study demonstrated that fever duration in MP pneumonia was determined by the radiologic findings of chest x-ray, not by the presence of macrolide resistance. The results highlight the need for future studies to assess therapeutic benefit from macrolides in the treatment of children with MP pneumonia.

Do we need colonoscopy following acute diverticulitis detected on computed tomography to exclude colorectal malignancy?

BACKGROUND: Although colonoscopy verification is warranted after an acute event of diverticulitis to exclude underlying malignancy, little evidence is available to support the recommendations. AIM: The aim of this study was to examine whether subsequent colonoscopy is warranted in patients with diverticulitis on computed tomography (CT). METHODS: The study was composed of patients diagnosed with acute diverticulitis on CT scan from January 2001 to March 2013. Patients who had subsequent colonoscopy within a year from the date of CT were included. For each diverticulitis case, two age- (± 5 years) and sex-matched controls were identified from healthy individuals who had received screening colonoscopy. We evaluated the diagnostic yield of advanced colonic neoplasia in colonoscopy. RESULTS: One hundred and forty-nine patients underwent subsequent colonoscopy within a year from the date of CT. Among the patients, 11 (7.4 %) had colon cancer and 5 (3.4 %) had advanced adenoma. A case-control study revealed that the odds of detecting an advanced neoplasia among patients with diverticulitis on CT were approximately 8.8 times greater than in the age- and sex-matched controls [OR 8.84; 95 % CI 2.90-26.96; p < 0.001]. On analysis of the diverticulitis group, age (≥ 50 years) is an independent risk factor for detecting advanced colonic neoplasia. CONCLUSIONS: The yield of advanced colonic neoplasia was substantially higher in patients with acute diverticulitis than in asymptomatic, average-risk individuals. Colonoscopy verification is warranted in patients with diverticulitis detected on CT, especially in those aged 50 years or older.

Long-term oncologic outcomes of endoscopic stenting as a bridge to surgery for malignant colonic obstruction: comparison with emergency surgery.

BACKGROUND: Self-expandable metallic stents (SEMS) are now regarded as an effective and safe intervention for malignant colorectal obstruction (MCO). However, manipulation of the tumor might lead to the spillage of tumor cells and result in distant metastases. We aimed to compare the long-term oncologic outcomes of SEMS as a bridge to surgery with those of emergency surgery for MCO. METHODS: Between June 2005 and December 2011, 60 patients who underwent elective curative resection after endoscopic SEMS insertion were included in the "SEMS group". The SEMS group was matched to 180 patients who underwent emergency curative surgery for MCO during the same period ["Emergency surgery (ES) group"]. The clinicopathologic characteristics, recurrence-free survival (RFS), and overall survival (OS) were compared between the two groups. RESULTS: There were no significant differences in demographics, tumor stage, location, and histology between the SEMS group and the ES group. The median follow-up times were 41.4 months (IQR, 22.2-60.0 months) for the SEMS group and 45.0 months (IQR, 20.9-68.1 months) for the ES group. The proportions of patients who received postoperative adjuvant chemotherapy were comparable (SEMS group vs. ES group, 68.3 % vs. 77.8 %; P = 0.210). The long-term prognosis did not significantly differ between two groups in either the 5-year RFS rate (79.6 % vs. 70.2 %; P = 0.218) or the 5-year OS rate (97.8 % vs. 94.3 %; P = 0.469). CONCLUSIONS: Long-term oncologic outcomes of SEMS insertion as a bridge to surgery were comparable to those of primary curative surgery.

Tracking incidentally discovered pancreatic cysts smaller than 30 mm: Natural course and predictors of malignancy.

BACKGROUND AND AIMS: The aim of this study was to assess the natural course and predictors of malignancy in incidentally detected small pancreatic cysts (PCs). METHOD: We retrospectively included patients with PCs smaller than 30 mm followed up with the same cross-sectional imaging modality at least 12 months apart between January 2010 and December 2019 in three academic institutions. Cyst growth, pancreatic cancer incidence, and associated factors associated with pancreatic cancer were analyzed. RESULTS: A total of 1109 patients were followed up for a median of 34 months (range, 12‒118 months). Cyst growth and rapid cyst growth (≥ 5 mm/2 years) during follow-up were observed in 20.7% and 8.3%, respectively, both with higher rates for 15‒30 mm sized PCs. Eight patients were diagnosed with pancreatic cancer. The standardized incidence ratio for pancreatic cancer in small PCs was calculated as 5.2 [95% Confidence interval (CI): 1.3‒20.5].  The development of pancreatic cancer was associated with rapid growth [hazard ratio (HR): 8.1, 95% CI: 1.5‒43.4, p = 0.015] and newly developed worrisome features (HR: 11.7, 95% CI: 1.7‒79.6, p = 0.012) in competing risk analysis. CONCLUSIONS: One-fifth of small incidentally detected PCs increased in size. Rapid growth and newly developed worrisome features were predictors of malignancy.

Characteristics of Early Pancreatic Cancer: Comparison between Stage 1A and Stage 1B Pancreatic Cancer in Multicenter Clinical Data Warehouse Study.

BACKGROUND: Little is known about the characteristics of early pancreatic cancer. We aimed to identify the characteristics, clues for early detection, and prognostic factors for early pancreatic cancer by analyzing a large number of patients with stage 1 pancreatic cancer. METHODS: A clinical data warehouse that includes databases of all the medical records of eight academic institutions was used to select and analyze patients with pancreatic cancer that had been diagnosed from January 2010 to May 2023. RESULTS: In total, 257 stage 1 pancreatic cancer patients were included. There were 134 men (52%), and the average age was 67.2 ± 9.9 years. Compared to patients with stage 1B pancreatic cancer (2-4 cm), patients with stage 1A pancreatic cancer (≤2 cm) had more tumors in the body and tail than in the head (p = 0.028), more new-onset diabetes and less old diabetes (p = 0.010), less jaundice (p = 0.020), more follow-up of IPMN (intraductal papillary mucinous neoplasm, p = 0.029), and more histories of acute pancreatitis (p = 0.013). The pathological findings showed that stage 1A pancreatic cancer involved more IPMNs (p < 0.001) and lower pancreatic intraepithelial neoplasia (p = 0.004). IPMN was present in all 13 pancreatic tumors that were smaller than 1 cm. In multivariate analysis, positive resection margin (odds ratio [OR] 1.536, p = 0.040), venous invasion (OR 1.710, p = 0.010), and perineural invasion (OR 1.968, p = 0.002) were found to be risk factors affecting disease-free survival, while old diabetes (odds ratio [OS] 1.981, p = 0.003) and perineural invasion (OR 2.270, p = 0.003) were found to be risk factors affecting overall survival. CONCLUSIONS: IPMN is closely associated with early pancreatic cancer and may provide an opportunity for early detection. The presence of perineural invasion was a crucial prognostic factor for both overall and disease-free survival in patients with stage 1 pancreatic cancer.

The validity and safety of multispectral light emitting diode (LED) treatment on grade 2 pressure ulcer: Double-blinded, randomized controlled clinical trial.

PURPOSE: The management of pressure ulcers (PUs) poses challenges due to their chronic nature and the lack of established conservative treatment methods. In this clinical trial, our objective was to examine the validity and safety of using a light-emitting diode device contained four wavelengths in the treatment of grade 2 sacral PUs. METHOD: A total of 38 patients were randomly assigned to two groups: sham device (Sham) and experimental device (LED) group. The treatment sessions were conducted over a period of four weeks, with a frequency of three times per week. The study was conducted in a double-blinded manner. The study assessed the primary validity by measuring wound size and re-epithelialization after 0 and 4 weeks. Secondary evaluations included epidermal regeneration, collagen density, and immunological markers. Safety was evaluated by monitoring adverse reactions throughout the trial. RESULT: The presence of eschar was found to have a significant impact on wound healing. Sham consisted of 15 wounds without eschar, while LED had nine. After treatment in without eschar situation, the post-treatment size of wounds in Sham was 13.80 ± 20.29%, while it was 3.52 ± 6.68% in LED. However, there was no significant difference (p = 0.070). And analysis of epidermal thickness showed a significant increase in LED (495.62 ± 327.09 µm) compared to Sham (195.36 ± 263.04 µm) (p < 0.0001). CONCLUSION: While LED treatment had a potential for wound reduction in PUs without eschar, we could not uncover evidence to support the efficacy of LED treatment in grade 2 PUs.

Current Diagnosis and Treatment of Acute Pancreatitis in Korea: A Nationwide Survey.

Background/Aims: : Acute pancreatitis (AP) is a leading cause of emergency hospitalization. We present the current diagnostic and therapeutic status of AP as revealed by analysis of a large multicenter dataset. Methods: : The medical records of patients diagnosed with AP between 2018 and 2019 in 12 tertiary medical centers in Korea were retrospectively reviewed. Results: : In total, 676 patients were included; of these, were 388 (57.4%) males, and the mean age of all patients was 58.6 years. There were 355 (52.5%), 301 (44.5%), and 20 (3.0%) patients with mild, moderate, and severe AP, respectively, as assessed by the revised Atlanta classification. The most common etiologies of AP were biliary issues (41.6%) and alcohol consumption (24.6%), followed by hypertriglyceridemia (6.8%). The etiology was not identified in 111 (16.4%) patients at the time of initial admission. The overall mortality rate was 3.3%, increasing up to 45.0% among patients with severe AP. Notably, 70.0% (14/20) of patients with severe AP and 81.5% (154/189) of patients with systemic inflammatory response syndrome had received <4 L per day during the initial 24 hours of admission. Only 23.8% (67/281) of acute biliary pancreatitis patients underwent cholecystectomy during their initial admission. In total, 17.8% of patients experienced recurrent attacks during follow-up. However, none of the patients with acute biliary pancreatitis experienced recurrent attacks if they had undergone cholecystectomy during their initial admission. Conclusions: : This study provides insights into the current status of AP in Korea, including its etiology, severity, and management. Results: reveal disparities between clinical guidelines and their practical implementation for AP treatment.

Hypertriglyceridaemic waist phenotype and waist circumference triglyceride index are associated with higher incidence of acute pancreatitis: a nationwide population-based retrospective cohort study.

OBJECTIVES: The hypertriglyceridaemic waist (HTGW) phenotype, an indicator to assess metabolic syndrome, could be a useful predictive marker for the risk of acute pancreatitis. This study aimed to evaluate the association between the HTGW phenotype and the risk of acute pancreatitis with a nationwide population-based cohort. DESIGN: A retrospective, nationwide cohort study. SETTING: Registry of health check-up result from Korean National Health Insurance Service. PARTICIPANTS: A total of 3 912 551 adults who underwent health checkups under the National Health Insurance Service in 2009 were enrolled in this study. INTERVENTIONS: Subjects with both increased waist circumference (WC) and elevated blood triglyceride concentrations were defined as the HTGW phenotype. The participants were divided into four groups, classified as NWNT (normal WC-normal triglycerides), EWNT (elevated WC-normal triglycerides), NWET (normal WC-elevated triglycerides) and HTGW. The WC triglyceride index (WTI) is a quantitative indicator of the HTGW phenotype which is calculated by multiplying WC (cm) by triglyceride levels (mmol/L). PRIMARY OUTCOME MEASURE: The subjects were followed until 31 December 2018. The adjusted HRs of acute pancreatitis in each group were estimated. RESULTS: During the follow-up, there were a total of 8933 of acute pancreatitis occurrences. The incidence of acute pancreatitis in all subjects was 0.278 per 1000 person-year. The HTGW group had the highest incidence (0.444), followed by the NWET (0.381), and EWNT (0.316) groups. The HTGW group had a significant higher incidence of acute pancreatitis than the NWNT groups (HR 1.364 (95% CI 1.279 to 1.454)). The risk of acute pancreatitis steadily increased as the WTI increased (HR 1.847 (95% CI 1.657 to 2.058) in 10th decile). CONCLUSIONS: The HTGW phenotype is confirmed to be an independent risk factor that increases the risk of acute pancreatitis.

Effects of Scalp Nerve Block on the Quality of Recovery after Minicraniotomy for Clipping of Unruptured Intracranial Aneurysms : A Randomized Controlled Trial.

OBJECTIVE: This study compared the quality of recovery (QoR) after minicraniotomy for clipping of unruptured intracranial aneurysms (UIAs) between patients with and without scalp nerve block (SNB). METHODS: Patients were randomly assigned to the SNB (SNB using ropivacaine with epinephrine, n=27) and control (SNB using normal saline, n=25) groups. SNB was performed at the end of surgery. To assess postoperative QoR, the QoR-40, a patient-reported questionnaire, was used. The QoR-40 scores were measured preoperatively, 1-3 days postoperatively, at hospital discharge, and 1 month postoperatively. Pain and intravenous patient-controlled analgesia (IV-PCA) consumption were evaluated 3, 6, 9, and 12 hours and 1-3 days postoperatively. RESULTS: All QoR-40 scores, including those measured 1 day postoperatively (primary outcome measure; 155.0 [141.0-176.0] vs. 161.0 [140.5-179.5], p=0.464), did not significantly differ between the SNB and control groups. The SNB group had significantly less severe pain 3 (numeric rating scale [NRS]; 3.0 [2.0-4.0] vs. 5.0 [3.5-5.5], p=0.029), 9 (NRS; 3.0 [2.0-4.0] vs. 4.0 [3.0-5.0], p=0.048), and 12 (NRS; 3.0 [2.0-4.0] vs. 4.0 [3.0-5.0], p=0.035) hours postoperatively. The total amount of IV-PCA consumed was significantly less 3 hours postoperatively in the SNB group (2.0 [1.0-4.0] vs. 4.0 [2.0-5.0] mL, p=0.044). CONCLUSION: After minicraniotomy for clipping of UIAs, SNB reduced pain and IV-PCA consumption in the early postoperative period but did not improve the QoR-40 scores.

Flavokawain B Inhibits Growth of Cholangiocarcinoma Cells by Suppressing the Akt Pathway.

BACKGROUND/AIM: Cholangiocarcinoma is a devastating malignancy with limited treatment options and poor prognosis. Natural products have gained considerable attention for showing antitumor effects with less toxicities. Flavokawain B (FKB), a natural product, has been studied for its antitumor effects on various cancer cells. However, the anti-tumor effect of FKB on cholangiocarcinoma cells remains unknown. This study aimed at investigating the antitumor effect of FKB on cholangiocarcinoma cells in vitro and in vivo. MATERIALS AND METHODS: SNU-478, a human cholangiocarcinoma cell line, was used in this study. Effects of FKB on cell growth inhibition and apoptosis were investigated. The synergistic anti-tumor effect of FKB and cisplatin in combination was also evaluated. Western blotting was performed to examine the underlying molecular mechanisms of the effect of FKB. A xenograft mouse model study was performed to investigate the effect of FKB in vivo. RESULTS: FKB inhibited cell proliferation of cholangiocarcinoma cells in a concentration- and time-dependent manner. FKB also induced cellular apoptosis additively in combination with cisplatin. Akt pathway was suppressed by FKB either alone or in combination with cisplatin. In the xenograft model, FKB treatment in combination with cisplatin/gemcitabine significantly inhibited tumor growth of SNU-478 cells. CONCLUSION: FKB showed an antitumor effect through the induction of apoptosis, which was mediated by suppressing the Akt pathway in cholangiocarcinoma cells. However, the synergistic effect of FKB and cisplatin was not definite.