Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Purpose: There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC. Materials and Methods: Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients’ clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines. Results: 193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells. Conclusion Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.

BACKGROUND: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of TH2 process and increased TH1 and/or TH17 process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. METHODS: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. RESULTS: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p < 0.05 and p < 0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon γ, and tumor necrosis factor α in the CAM+DXM group than in the monotherapy group (p < 0.001, p < 0.05, and p < 0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p < 0.05). CONCLUSION Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

BACKGROUND: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of TH2 process and increased TH1 and/or TH17 process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. METHODS: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. RESULTS: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p < 0.05 and p < 0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon γ, and tumor necrosis factor α in the CAM+DXM group than in the monotherapy group (p < 0.001, p < 0.05, and p < 0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p < 0.05). CONCLUSION: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.
Adrenal Cortex Hormones ; Airway Resistance ; Animals ; Asthma ; Bronchoalveolar Lavage Fluid ; Clarithromycin ; Dexamethasone ; Eosine Yellowish-(YS) ; Female ; Hematoxylin ; Histone Deacetylase 2 ; Histone Deacetylases ; Humans ; Inflammation ; Interferons ; Interleukin-17 ; Lipopolysaccharides ; Macrolides ; Mice ; Neutrophils ; Ovalbumin ; Th17 Cells ; Tumor Necrosis Factor-alpha

In this article, the statement of ethical statement about animal experiment was omitted.

Parathyroid carcinoma is very rare in patients with primary hyperparathyroidism, only accounts for 1% to 2% of all cases. It is characterized by higher incidence of renal dysfunction, metabolic bone disease and gastrointestinal symptoms. Although the clinical manifestations of hyperparathyroidism are more severe in patients with parathyroid carcinoma when compared to those with those with parathyroid adenoma, it is difficult to differentiate carcinoma from adenoma without pathologic confirmation. To our knowledge, there have only been a few cases of hyperparathyroidism due to parathyroid carcinomas reported to date. Here, we report a case of 63-year-old woman developing osteoporosis, hypercalcemia and hypophosphatemia due to a parathyroid tumor and was diagnosed with parathyroid carcinoma postoperatively.
Adenoma ; Bone Diseases, Metabolic ; Female ; Humans ; Hypercalcemia ; Hyperparathyroidism ; Hyperparathyroidism, Primary ; Hypophosphatemia ; Incidence ; Middle Aged ; Osteoporosis ; Parathyroid Neoplasms

Parathyroid carcinoma is very rare in patients with primary hyperparathyroidism, only accounts for 1% to 2% of all cases. It is characterized by higher incidence of renal dysfunction, metabolic bone disease and gastrointestinal symptoms. Although the clinical manifestations of hyperparathyroidism are more severe in patients with parathyroid carcinoma when compared to those with those with parathyroid adenoma, it is difficult to differentiate carcinoma from adenoma without pathologic confirmation. To our knowledge, there have only been a few cases of hyperparathyroidism due to parathyroid carcinomas reported to date. Here, we report a case of 63-year-old woman developing osteoporosis, hypercalcemia and hypophosphatemia due to a parathyroid tumor and was diagnosed with parathyroid carcinoma postoperatively.
Adenoma ; Bone Diseases, Metabolic ; Female ; Humans ; Hypercalcemia ; Hyperparathyroidism ; Hyperparathyroidism, Primary ; Hypophosphatemia ; Incidence ; Middle Aged ; Osteoporosis ; Parathyroid Neoplasms

Thyrotoxic periodic paralysis (TPP) occurs in 2% of the asian patients with hyperthyroidism and is characterized by bilateral flaccid paralysis of the extremity, especially lower limbs. It is well-known that hypokalemia is usually accompanied by TPP. However, hypophosphatemia is usually mild and well neglected. Although paralysis is generally recovered without treatment, in some cases, patients with TPP may die due to cardiopulmonary complications, such as cardiac arrhythmia. Therefore, proper and rapid replacement of potassium is essential. But it should be acknowledged that replacement may cause a rebound. TPP is often unrecognized and over-treated in the emergency room due to its non-specific symptoms. This is why clinicians must be familiar with this disease and its diagnostic clues such as Echocardiography change and clinical features. This is a case report of a 29-year-old male presenting with TPP accompanied by hypokalemia, hypophosphatemia and second degree atrioventricular block, who showed rebound hyperkalemia and hyperphosphatemia after rapid replacement of electrolytes. EKG changed to the normal sinus rhythm in the end after the correction of the electrolytes.
Adult ; Arrhythmias, Cardiac ; Asian Continental Ancestry Group ; Atrioventricular Block ; Echocardiography ; Electrocardiography ; Electrolytes ; Emergencies ; Extremities ; Humans ; Hyperkalemia ; Hyperphosphatemia ; Hyperthyroidism ; Hypokalemia ; Hypophosphatemia ; Lower Extremity ; Male ; Paralysis ; Potassium

Esophageal intramural pseudodiverticulosis (EIP) is a rare benign disease that is characterized by multiple tiny flask-shaped outpouching lesions of the esophageal wall. The etiology is unknown, but the pathologic findings include dilatation of excretory ducts of submucosal glands. The predominant symptom is dysphagia, and esophageal stricture occurs frequently. Diseases such as diabetes mellitus, esophageal candidiasis, gastroesophageal reflux disease, and chronic alcoholism are often combined. Since most EIP cases are benign, the mainstream treatment is symptom relief by endoscopic dilatation or medical treatment of accompanied diseases. This report describes the case of a 68-year-old male patient who suffered from chest tightness for 2 months and was diagnosed with EIP. This symptom disappeared after 2 months of medical treatment, and the patient is now being regularly followed up.
Aged ; Alcoholism ; Candidiasis ; Deglutition Disorders ; Diabetes Mellitus ; Dilatation ; Esophageal Neoplasms ; Esophageal Stenosis ; Gastroesophageal Reflux ; Humans ; Male ; Thorax

Superwarfarin, such as brodifacoum, is a highly lethal vitamin K antagonist used as a rodenticide. Brodifacoum has a particularly long half-life in the body, which ranges to several months, and therefore requires prolonged treatment with antidotal vitamin K. We experienced a case whereby an 18-year-old male was presented to the hospital with a severe bleeding disorder. It was discovered that he had ingested brodifacoum rodenticide with intent to commit suicide. Despite continual treatment with vitamin K, the bleeding disorder persisted for several months before he recovered. We report this case with literature review.
4-Hydroxycoumarins ; Adolescent ; Half-Life ; Hemorrhage ; Humans ; Male ; Suicide ; Vitamin K ; Vitamins