Heterotopic pancreas (HP) refers to the presence of ectopic pancreatic tissue located outside of the normal pancreatic location without anatomical or vascular continuity with the pancreas. HP within the gallbladder (HPGB) was first described by Otschkin in 1916. It remains an exceedingly rare pathology with few reported cases. Here we describe a case of HPGB in a 42-year-old female following laparoscopic cholecystectomy for symptoms of biliary colic. She presented with epigastric pain, elevated levels in liver function tests, and gallbladder sludge on ultrasound. Her lipase and bilirubin levels were within normal limits. Histopathological assessment of the gallbladder identified mild chronic cholecystitis and pancreatic heterotopia adjacent to the cystic duct of the gallbladder with all three elements (ducts, acini, and endocrine islets) of the pancreas, consistent with type 1 based on the classification of Gaspar Fuentes et al.HPGB is often diagnosed incidentally during histopathological examination after cholecystectomy. Preoperative diagnosis is challenging due to its rarity. It is thought to be asymptomatic. Although the clinical significance of HPGB remains uncertain, it has been hypothesized that HPGB can cause acalculous cholecystitis and also have the potential for malignant transformation. Our case supports the theory that the exocrine function of an ectopic pancreatic tissue may contribute to chronic inflammation in the gallbladder. In conclusion, although HPGB is a rare finding with unclear clinical relevance, its potential for malignancy and association with cholecystitis warrant further investigation. Given its scarcity, most knowledge about HPGB comes from case reports and case series. This report adds to the existing literature.

Heterotopic pancreas (HP) refers to the presence of ectopic pancreatic tissue located outside of the normal pancreatic location without anatomical or vascular continuity with the pancreas. HP within the gallbladder (HPGB) was first described by Otschkin in 1916. It remains an exceedingly rare pathology with few reported cases. Here we describe a case of HPGB in a 42-year-old female following laparoscopic cholecystectomy for symptoms of biliary colic. She presented with epigastric pain, elevated levels in liver function tests, and gallbladder sludge on ultrasound. Her lipase and bilirubin levels were within normal limits. Histopathological assessment of the gallbladder identified mild chronic cholecystitis and pancreatic heterotopia adjacent to the cystic duct of the gallbladder with all three elements (ducts, acini, and endocrine islets) of the pancreas, consistent with type 1 based on the classification of Gaspar Fuentes et al.HPGB is often diagnosed incidentally during histopathological examination after cholecystectomy. Preoperative diagnosis is challenging due to its rarity. It is thought to be asymptomatic. Although the clinical significance of HPGB remains uncertain, it has been hypothesized that HPGB can cause acalculous cholecystitis and also have the potential for malignant transformation. Our case supports the theory that the exocrine function of an ectopic pancreatic tissue may contribute to chronic inflammation in the gallbladder. In conclusion, although HPGB is a rare finding with unclear clinical relevance, its potential for malignancy and association with cholecystitis warrant further investigation. Given its scarcity, most knowledge about HPGB comes from case reports and case series. This report adds to the existing literature.

Heterotopic pancreas (HP) refers to the presence of ectopic pancreatic tissue located outside of the normal pancreatic location without anatomical or vascular continuity with the pancreas. HP within the gallbladder (HPGB) was first described by Otschkin in 1916. It remains an exceedingly rare pathology with few reported cases. Here we describe a case of HPGB in a 42-year-old female following laparoscopic cholecystectomy for symptoms of biliary colic. She presented with epigastric pain, elevated levels in liver function tests, and gallbladder sludge on ultrasound. Her lipase and bilirubin levels were within normal limits. Histopathological assessment of the gallbladder identified mild chronic cholecystitis and pancreatic heterotopia adjacent to the cystic duct of the gallbladder with all three elements (ducts, acini, and endocrine islets) of the pancreas, consistent with type 1 based on the classification of Gaspar Fuentes et al.HPGB is often diagnosed incidentally during histopathological examination after cholecystectomy. Preoperative diagnosis is challenging due to its rarity. It is thought to be asymptomatic. Although the clinical significance of HPGB remains uncertain, it has been hypothesized that HPGB can cause acalculous cholecystitis and also have the potential for malignant transformation. Our case supports the theory that the exocrine function of an ectopic pancreatic tissue may contribute to chronic inflammation in the gallbladder. In conclusion, although HPGB is a rare finding with unclear clinical relevance, its potential for malignancy and association with cholecystitis warrant further investigation. Given its scarcity, most knowledge about HPGB comes from case reports and case series. This report adds to the existing literature.

Background::Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance therapy for EE, but many patients still relapse. In this trial, we evaluated the noninferiority of vonoprazan vs. lansoprazole as maintenance therapy in patients with healed EE. Methods::We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, South Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded.Results::Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% [95% CI, -20.3% to-4.3%] and -13.3% [95% CI, -21.3% to -5.3%], respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group.Conclusion::Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE.Trial Registration::https://clinicaltrials.gov; NCT02388737.

Objective: The Cancer Genome Atlas study revealed an association between copy-number high (p53 abnormal) genetic mutation and poor prognosis in endometrial cancer in 2013.This retrospective study investigated outcomes in patients with abnormal p53 expression and stage I, low-grade endometrial endometrioid carcinoma (EEC). Methods: We enrolled women with stage I, grade 1 or 2 EEC who received comprehensive staging and adjuvant therapy between January 2019 and December 2022 at MacKay Memorial Hospital, Taipei, Taiwan. Pathologists interpreted immunohistochemistry stains of cancerous tissues to detect p53 mutation. We compared recurrence, survival, progressionfree survival, and overall survival between p53 abnormal and p53 normal groups. Results: Of the 115 patients included, 26 had pathologically confirmed abnormal p53 expression. Of these 26 patients, five (19.2%) experienced recurrence, and two died due to disease progression. By contrast, no patients in the normal p53 group experienced disease recurrence or died due to disease progression. Significant intergroup differences were discovered in recurrent disease status (19.4% vs. 0%, p<0.001), mortality (7.7% vs.0%, p<0.001), and progression-free survival (p<0.001). The overall survival (p=0.055) also showed powerful worse trend. Conclusion For patients with stage I, low-grade EEC, abnormal p53 expression may be used as an indicator of poor prognosis. Therefore, we suggest considering aggressive adjuvant therapies for these patients.

Objective: The Cancer Genome Atlas study revealed an association between copy-number high (p53 abnormal) genetic mutation and poor prognosis in endometrial cancer in 2013.This retrospective study investigated outcomes in patients with abnormal p53 expression and stage I, low-grade endometrial endometrioid carcinoma (EEC). Methods: We enrolled women with stage I, grade 1 or 2 EEC who received comprehensive staging and adjuvant therapy between January 2019 and December 2022 at MacKay Memorial Hospital, Taipei, Taiwan. Pathologists interpreted immunohistochemistry stains of cancerous tissues to detect p53 mutation. We compared recurrence, survival, progressionfree survival, and overall survival between p53 abnormal and p53 normal groups. Results: Of the 115 patients included, 26 had pathologically confirmed abnormal p53 expression. Of these 26 patients, five (19.2%) experienced recurrence, and two died due to disease progression. By contrast, no patients in the normal p53 group experienced disease recurrence or died due to disease progression. Significant intergroup differences were discovered in recurrent disease status (19.4% vs. 0%, p<0.001), mortality (7.7% vs.0%, p<0.001), and progression-free survival (p<0.001). The overall survival (p=0.055) also showed powerful worse trend. Conclusion For patients with stage I, low-grade EEC, abnormal p53 expression may be used as an indicator of poor prognosis. Therefore, we suggest considering aggressive adjuvant therapies for these patients.

Objective: The Cancer Genome Atlas study revealed an association between copy-number high (p53 abnormal) genetic mutation and poor prognosis in endometrial cancer in 2013.This retrospective study investigated outcomes in patients with abnormal p53 expression and stage I, low-grade endometrial endometrioid carcinoma (EEC). Methods: We enrolled women with stage I, grade 1 or 2 EEC who received comprehensive staging and adjuvant therapy between January 2019 and December 2022 at MacKay Memorial Hospital, Taipei, Taiwan. Pathologists interpreted immunohistochemistry stains of cancerous tissues to detect p53 mutation. We compared recurrence, survival, progressionfree survival, and overall survival between p53 abnormal and p53 normal groups. Results: Of the 115 patients included, 26 had pathologically confirmed abnormal p53 expression. Of these 26 patients, five (19.2%) experienced recurrence, and two died due to disease progression. By contrast, no patients in the normal p53 group experienced disease recurrence or died due to disease progression. Significant intergroup differences were discovered in recurrent disease status (19.4% vs. 0%, p<0.001), mortality (7.7% vs.0%, p<0.001), and progression-free survival (p<0.001). The overall survival (p=0.055) also showed powerful worse trend. Conclusion For patients with stage I, low-grade EEC, abnormal p53 expression may be used as an indicator of poor prognosis. Therefore, we suggest considering aggressive adjuvant therapies for these patients.

Mutations in genes encoding amyloid precursor protein (APP) and presenilins (PSs) cause familial forms of Alzheimer's disease (AD), a neurodegenerative disorder strongly associated with aging. It is currently unknown whether and how AD risks affect early brain development, and to what extent subtle synaptic pathology may occur prior to overt hallmark AD pathology. Transgenic mutant APP/PS1 over-expression mouse lines are key tools for studying the molecular mechanisms of AD pathogenesis. Among these lines, the 5XFAD mice rapidly develop key features of AD pathology and have proven utility in studying amyloid plaque formation and amyloid β (Aβ)-induced neurodegeneration. We reasoned that transgenic mutant APP/PS1 over-expression in 5XFAD mice may lead to neurodevelopmental defects in early cortical neurons, and performed detailed synaptic physiological characterization of layer 5 (L5) neurons from the prefrontal cortex (PFC) of 5XFAD and wild-type littermate controls. L5 PFC neurons from 5XFAD mice show early APP/Aβ immunolabeling. Whole-cell patch-clamp recording at an early post-weaning age (P22-30) revealed functional impairments; although 5XFAD PFC-L5 neurons exhibited similar membrane properties, they were intrinsically less excitable. In addition, these neurons received smaller amplitude and frequency of miniature excitatory synaptic inputs. These functional disturbances were further corroborated by decreased dendritic spine density and spine head volumes that indicated impaired synapse maturation. Slice biotinylation followed by Western blot analysis of PFC-L5 tissue revealed that 5XFAD mice showed reduced synaptic AMPA receptor subunit GluA1 and decreased synaptic NMDA receptor subunit GluN2A. Consistent with this, patch-clamp recording of the evoked L23>L5 synaptic responses revealed a reduced AMPA/NMDA receptor current ratio, and an increased level of AMPAR-lacking silent synapses. These results suggest that transgenic mutant forms of APP/PS1 overexpression in 5XFAD mice leads to early developmental defects of cortical circuits, which could contribute to the age-dependent synaptic pathology and neurodegeneration later in life.
Mice ; Animals ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Mice, Transgenic ; Neurons/metabolism* ; Receptors, AMPA/metabolism* ; Disease Models, Animal

No abstract available.
Lung Diseases, Interstitial

No abstract available.
Drug-Induced Liver Injury ; Ribavirin