Purpose: Common bile duct (CBD) stone recurrence after laparoscopic CBD exploration (LCBDE) is relatively common. No studies have been conducted evaluating the safety and feasibility of re-do LCBDE in the treatment of recurrent CBD stones. Methods: This single-center retrospective study reviewed 340 consecutive patients who underwent LCBDE for CBD stones between January 2004 and December 2020. Patients with pancreatobiliary malignancies and those who underwent other surgical procedures were excluded. Results: Of the 340 included patients, 45 experienced a recurrence after a mean follow-up period of 24.2 months. Of them, 18 underwent re-do LCBDE, 20 underwent endoscopic intervention, 2 underwent radiologic intervention, and 5 underwent observation. Re-do LCBDE and initial LCBDE showed similar surgical outcomes in terms of operative time (113.1 minutes vs. 107.5 minutes, P = 0.515), estimated blood loss (42.5 mL vs. 49.1 mL, P = 0.661), open conversion rate (2.9% vs. 0%, P = 0.461), postoperative complication (15.3% vs. 22.2%, P = 0.430), and postoperative hospital stay (6.5 days vs. 6.4 days, P = 0.921). Comparing re-do LCBDE and nonsurgical treatment (endoscopic or radiologic), no statistically significant differences were noted in posttreatment complication (22.2% vs. 13.6%, P = 0.477), hospital stay (6.4 days vs.7.3 days, P = 0.607), and recurrence (50.0% vs. 36.4%, P = 0.385). The clearance rate was higher in the re-do LCBDE group than in the nonsurgical group (100% vs. 81.8%, P = 0.057). Conclusion Compared to initial LCBDE and endoscopic or radiological treatments, re-do LCBDE for recurrent CBD stones is a treatment option worth considering in selected patients.

Background and Objectives: Electronic cigarette (e-cigarette) is a device that generate vapor by heating e-cigarettes liquid. E-cigarette damages the respiratory immune system and renders the respiratory tract vulnerable to inflammations. However, there are no studies on how the inflammatory reactions in respiratory epithelial cells caused by e-cigarette occur, and the effects of Korean red ginseng (KRG) and saponin on inflammation induced by e-cigarette are unknown. This study aimed to compare the inflammatory reactions caused by e-cigarette and lipopolysaccharide (LPS), and to investigate the effects of KRG and saponin on cytokine and mucin expression induced by e-cigarette in respiratory epithelial cells.Subjects and Method In bronchoalveolar lavage fluid and lung tissue of mice, the effects of KRG and saponin on cytokines (interleukin [IL]-1β, IL-6, IL-8) and mucin 5AC/5B (MUC5AC/5B) expression induced by e-cigarette were investigated using real-time polymerase chain reaction, enzyme linked immunosorbent assay, and immunohistochemistry staining. Results: Inflammatory cells, cytokines (IL-1β, IL-6, IL-8) and MUC5AC/5B messenger RNA expression and protein production were increased by e-cigarette, similar to LPS. KRG and saponin decreased the expression of cytokines (IL-1β, IL-6, IL-8) and MUC5AC/5B induced by e-cigarette. KRG and saponin showed effects similar to that of dexamethasone. Conclusion E-cigarette causes inflammation similar to that caused by LPS. KRG and saponin regulate the expression of cytokine and MUC5AC/5B increased by e-cigarette in respiratory epithelial cells. KRG and saponin may be an effective therapeutic option for inflammatory responses induced by e-cigarette in respiratory epithelial cells.

BACKGROUND/OBJECTIVES: This study aimed to use plasma metabolites to identify clusters of breast cancer survivors and to compare their dietary characteristics and health-related factors across the clusters using unsupervised machine learning. SUBJECTS/METHODS: A total of 419 breast cancer survivors were included in this crosssectional study. We considered 30 plasma metabolites, quantified by high-throughput nuclear magnetic resonance metabolomics. Clusters were obtained based on metabolites using 4 different unsupervised clustering methods: k-means (KM), partitioning around medoids (PAM), self-organizing maps (SOM), and hierarchical agglomerative clustering (HAC). The t-test, χ2 test, and Fisher’s exact test were used to compare sociodemographic, lifestyle, clinical, and dietary characteristics across the clusters. P-values were adjusted through a false discovery rate (FDR). RESULTS: Two clusters were identified using the 4 methods. Participants in cluster 2 had lower concentrations of apolipoprotein A1 and large high-density lipoprotein (HDL) particles and smaller HDL particle sizes, but higher concentrations of chylomicrons and extremely large very-low-density-lipoprotein (VLDL) particles and glycoprotein acetyls, a higher ratio of monounsaturated fatty acids to total fatty acids, and larger VLDL particle sizes compared with cluster 1. Body mass index was significantly higher in cluster 2 compared with cluster 1 (FDR adjusted-PKM < 0.001; PPAM = 0.001; PSOM < 0.001; and PHAC = 0.043). CONCLUSION The breast cancer survivors clustered on the basis of plasma metabolites had distinct characteristics. Further prospective studies are needed to investigate the associations between metabolites, obesity, dietary factors, and breast cancer prognosis.

BACKGROUND/OBJECTIVES: Isoflavones are estrogen-like compounds found in plants and their health effects remain equivocal. We investigated dietary isoflavone intake and its associated factors in Korean breast cancer survivors, with a comparison to cancer-free women. SUBJECTS/METHODS: The usual dietary intake of breast cancer survivors (n = 981, mean age 52 yrs) in 9 hospitals between 2012 and 2019 was assessed using 3-day food records or food frequency questionnaires (FFQs). They were age-matched to 2,943 cancer-free women who completed FFQs as part of a nationwide study conducted between 2012 and 2016. We used the flavonoid database of common Korean foods and the Phenol-Explorer database to estimate isoflavone intake. The contribution of each food or food group to the total isoflavone intake was calculated. The adjusted least-squares means of dietary isoflavone intake according to lifestyle and clinical factors were calculated using generalized linear models. RESULTS: Breast cancer survivors had a higher mean dietary isoflavone intake (23.59 mg/day) than cancer-free women (17.81 mg/day). Major food sources, including tofu, soybeans, and doenjang, contributed to over 70% of the isoflavone intake in both groups. When we estimated dietary isoflavone intake according to lifestyle characteristics, isoflavone intake increased with higher scores of adherence to the American Cancer Society dietary guidelines but decreased with increasing body mass index in both groups. Among cancer-free women, dietary isoflavone intake was higher among those who had never smoked and among dietary supplement users. Among breast cancer survivors, dietary isoflavone intakes did not vary with clinical characteristics, including time since surgery and estrogen receptor status. CONCLUSION Breast cancer survivors were more likely to consume isoflavones than agematched cancer-free women. Dietary isoflavone intake was associated with healthy lifestyle characteristics in women both with and without breast cancer. Further research is needed to understand the role of the higher isoflavone intake among breast cancer survivors compared to cancer-free women on their prognosis.

Primary cholangiocarcinoma is a rare bile duct epithelial neoplasm that can present with atypical clinical manifestations, complicating its diagnosis. A 62-year-old male showed symptoms suggestive of a complicated hepatic cyst that was later identified as intrahepatic cholangiocarcinoma. The patient presented with abdominal discomfort without fever. Imaging revealed a large cystic lesion in the liver. Despite the initial treatment for a presumed abscess, a biopsy confirmed cholangiocarcinoma. This case highlights the diagnostic challenge of distinguishing between benign complicated hepatic cysts and malignancies, particularly when typical markers of infection are absent. Early biopsy and vigilant assessments are crucial in such presentations to avoid a delayed diagnosis and initiate appropriate treatment.

Hepatic tuberculosis, typically associated with miliary tuberculosis, can occasionally present as localized liver lesions. This case report describes a 77-year-old male presenting with persistent abdominal pain and fever, following an endoscopic retrograde cholangiopancreatography for bile duct sludge removal. Subsequent computed tomography revealed focal liver lesions. Despite initial treatment with antibiotics for a suspected inflammatory liver abscess, his condition did not improve. A liver biopsy was performed, revealing caseous granulomas, and the tuberculosis polymerase chain reaction result was positive. The patient was diagnosed with primary hepatic tuberculosis, which later disseminated. Oral anti-tuberculosis therapy was initiated and is currently being closely monitored. This case emphasizes the importance of considering hepatic tuberculosis in the differential diagnosis of liver lesions, particularly in cases involving cholestatic liver function tests, and persistent symptoms unresponsive to conventional antibiotics.

Dry eye disease (DED) is a complicated disorder that impacts ocular surface and tear-film stability. Inflammation has recently been reported as the core mechanism and main therapeutic target of DED. Although anti-inflammatory drugs have been developed, they still have limited efficacy and various side effects. Recent reports have suggested that kinase inhibitors are beneficial for relieving inflammation. Therefore, this study aimed to investigate the anti-inflammatory effects of LCB 03-0110, a multi-tyrosine kinase inhibitor, on representative cell-based models (HCE-2 and Th17 cells) of DED. While tacrolimus and tofacitinib, two different anti-inflammatory drugs that have entered clinical trials for DED treatment, did not induce any anti-inflammatory responses in HCE-2 cells, LCB 03-0110 significantly suppressed the phosphorylation of P38 and ERK and reduced the expression levels of IL-6 and IL-8 in HCE-2 cells treated with either LPS or poly(I:C). Moreover, LCB 03-0110 notably decreased the expression level of IL-17A in Th17 cells in a dose-dependent manner, whereas tofacitinib promoted IL-17A production at low concentrations but inhibited its expression at concentrations greater than 1 μM. In addition, LCB 03-0110 was found to be non-toxic to both HCE-2 and Th17 cells. In conclusion, these results suggest that LCB 03-0110 would be a promising drug candidate for the treatment of DED because of its advantages over tacrolimus and tofacitinib.

Background and Objectives: Electronic cigarette (e-cigarette) is a device that generate vapor by heating e-cigarettes liquid. E-cigarette damages the respiratory immune system and renders the respiratory tract vulnerable to inflammations. However, there are no studies on how the inflammatory reactions in respiratory epithelial cells caused by e-cigarette occur, and the effects of Korean red ginseng (KRG) and saponin on inflammation induced by e-cigarette are unknown. This study aimed to compare the inflammatory reactions caused by e-cigarette and lipopolysaccharide (LPS), and to investigate the effects of KRG and saponin on cytokine and mucin expression induced by e-cigarette in respiratory epithelial cells.Subjects and Method In bronchoalveolar lavage fluid and lung tissue of mice, the effects of KRG and saponin on cytokines (interleukin [IL]-1β, IL-6, IL-8) and mucin 5AC/5B (MUC5AC/5B) expression induced by e-cigarette were investigated using real-time polymerase chain reaction, enzyme linked immunosorbent assay, and immunohistochemistry staining. Results: Inflammatory cells, cytokines (IL-1β, IL-6, IL-8) and MUC5AC/5B messenger RNA expression and protein production were increased by e-cigarette, similar to LPS. KRG and saponin decreased the expression of cytokines (IL-1β, IL-6, IL-8) and MUC5AC/5B induced by e-cigarette. KRG and saponin showed effects similar to that of dexamethasone. Conclusion E-cigarette causes inflammation similar to that caused by LPS. KRG and saponin regulate the expression of cytokine and MUC5AC/5B increased by e-cigarette in respiratory epithelial cells. KRG and saponin may be an effective therapeutic option for inflammatory responses induced by e-cigarette in respiratory epithelial cells.

Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

Primary cholangiocarcinoma is a rare bile duct epithelial neoplasm that can present with atypical clinical manifestations, complicating its diagnosis. A 62-year-old male showed symptoms suggestive of a complicated hepatic cyst that was later identified as intrahepatic cholangiocarcinoma. The patient presented with abdominal discomfort without fever. Imaging revealed a large cystic lesion in the liver. Despite the initial treatment for a presumed abscess, a biopsy confirmed cholangiocarcinoma. This case highlights the diagnostic challenge of distinguishing between benign complicated hepatic cysts and malignancies, particularly when typical markers of infection are absent. Early biopsy and vigilant assessments are crucial in such presentations to avoid a delayed diagnosis and initiate appropriate treatment.