Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Progesterone hypersensitivity is mediated by type I, III, and IV hypersensitivity reactions to endogenous or exogenous progesterone, involving autoimmune mechanisms in females of reproductive age. It presents with a range of dermatologic manifestations, most commonly urticaria, angioedema, eczema, and maculopapular rashes. Systemic and severe symptoms, such as generalized erythema multiforme or lesions resembling severe cutaneous adverse reactions, have rarely been reported. We describe a case of a 42-year-old woman who developed drug reaction with eosinophilia and systemic symptoms (DRESS) following exogenous progesterone therapy administered for assisted reproduction. She received high-dose subcutaneous progesterone and vaginal tablets. Despite this being her first procedure, she achieved pregnancy. However, at 8 weeks of gestation and during the third month of progesterone treatment, she developed generalized erythema multiforme, pruritus, and high-grade fever. Her laboratory findings showed increased blood eosinophil counts and inflammatory markers. After oral corticosteroid (OCS) treatment for several weeks, her skin lesions were partially improved. However, after tapering of OCS, her skin lesions were aggravated with increased blood eosinophil counts. Despite daily OCS (prednisolone, 12.5–60 mg/day) treatment after childbirth, her skin symptoms and eosinophilia persisted. Reslizumab treatment was also attempted, but only the eosinophilia resolved. These clinical findings were much improved after Janus kinase (JAK) inhibitor (upadacitinib 15 mg/day) treatment; consequently, OCS was stopped. Here, we report a case of relapsing DRESS triggered by exogenous progesterone, which has been controlled by JAK inhibitor treatment.

Cat-pork syndrome is an uncommon food allergy induced by red meat (pork/beef) that cross-reacts with cat/dog allergens, which is mediated by immunoglobulin E (IgE) response to the cat/dog albumin component. We report 2 cases of cat-pork syndrome occurred in adult pet breeders. They had suffered from allergic rhinitis/atopic dermatitis sensitive to cat/dog dander as well as house dust mites for several years, during which an immediate type of food allergy due to red meats developed whenever taking pork or beef. ImmunoCAP results showed the increased levels of serum-specific IgE to pork and beef allergens (f26, f27) as well as cat and dog dander (e1, e5); moreover, increased level of serum-specific IgE to the cat albumin component (e224) was noted. In conclusion, cat-food allergy can be found in allergic patients among whom are sensitive to cats and dogs and develop food allergy due to red meat.

Progesterone hypersensitivity is mediated by type I, III, and IV hypersensitivity reactions to endogenous or exogenous progesterone, involving autoimmune mechanisms in females of reproductive age. It presents with a range of dermatologic manifestations, most commonly urticaria, angioedema, eczema, and maculopapular rashes. Systemic and severe symptoms, such as generalized erythema multiforme or lesions resembling severe cutaneous adverse reactions, have rarely been reported. We describe a case of a 42-year-old woman who developed drug reaction with eosinophilia and systemic symptoms (DRESS) following exogenous progesterone therapy administered for assisted reproduction. She received high-dose subcutaneous progesterone and vaginal tablets. Despite this being her first procedure, she achieved pregnancy. However, at 8 weeks of gestation and during the third month of progesterone treatment, she developed generalized erythema multiforme, pruritus, and high-grade fever. Her laboratory findings showed increased blood eosinophil counts and inflammatory markers. After oral corticosteroid (OCS) treatment for several weeks, her skin lesions were partially improved. However, after tapering of OCS, her skin lesions were aggravated with increased blood eosinophil counts. Despite daily OCS (prednisolone, 12.5–60 mg/day) treatment after childbirth, her skin symptoms and eosinophilia persisted. Reslizumab treatment was also attempted, but only the eosinophilia resolved. These clinical findings were much improved after Janus kinase (JAK) inhibitor (upadacitinib 15 mg/day) treatment; consequently, OCS was stopped. Here, we report a case of relapsing DRESS triggered by exogenous progesterone, which has been controlled by JAK inhibitor treatment.

Cat-pork syndrome is an uncommon food allergy induced by red meat (pork/beef) that cross-reacts with cat/dog allergens, which is mediated by immunoglobulin E (IgE) response to the cat/dog albumin component. We report 2 cases of cat-pork syndrome occurred in adult pet breeders. They had suffered from allergic rhinitis/atopic dermatitis sensitive to cat/dog dander as well as house dust mites for several years, during which an immediate type of food allergy due to red meats developed whenever taking pork or beef. ImmunoCAP results showed the increased levels of serum-specific IgE to pork and beef allergens (f26, f27) as well as cat and dog dander (e1, e5); moreover, increased level of serum-specific IgE to the cat albumin component (e224) was noted. In conclusion, cat-food allergy can be found in allergic patients among whom are sensitive to cats and dogs and develop food allergy due to red meat.

Progesterone hypersensitivity is mediated by type I, III, and IV hypersensitivity reactions to endogenous or exogenous progesterone, involving autoimmune mechanisms in females of reproductive age. It presents with a range of dermatologic manifestations, most commonly urticaria, angioedema, eczema, and maculopapular rashes. Systemic and severe symptoms, such as generalized erythema multiforme or lesions resembling severe cutaneous adverse reactions, have rarely been reported. We describe a case of a 42-year-old woman who developed drug reaction with eosinophilia and systemic symptoms (DRESS) following exogenous progesterone therapy administered for assisted reproduction. She received high-dose subcutaneous progesterone and vaginal tablets. Despite this being her first procedure, she achieved pregnancy. However, at 8 weeks of gestation and during the third month of progesterone treatment, she developed generalized erythema multiforme, pruritus, and high-grade fever. Her laboratory findings showed increased blood eosinophil counts and inflammatory markers. After oral corticosteroid (OCS) treatment for several weeks, her skin lesions were partially improved. However, after tapering of OCS, her skin lesions were aggravated with increased blood eosinophil counts. Despite daily OCS (prednisolone, 12.5–60 mg/day) treatment after childbirth, her skin symptoms and eosinophilia persisted. Reslizumab treatment was also attempted, but only the eosinophilia resolved. These clinical findings were much improved after Janus kinase (JAK) inhibitor (upadacitinib 15 mg/day) treatment; consequently, OCS was stopped. Here, we report a case of relapsing DRESS triggered by exogenous progesterone, which has been controlled by JAK inhibitor treatment.

Cat-pork syndrome is an uncommon food allergy induced by red meat (pork/beef) that cross-reacts with cat/dog allergens, which is mediated by immunoglobulin E (IgE) response to the cat/dog albumin component. We report 2 cases of cat-pork syndrome occurred in adult pet breeders. They had suffered from allergic rhinitis/atopic dermatitis sensitive to cat/dog dander as well as house dust mites for several years, during which an immediate type of food allergy due to red meats developed whenever taking pork or beef. ImmunoCAP results showed the increased levels of serum-specific IgE to pork and beef allergens (f26, f27) as well as cat and dog dander (e1, e5); moreover, increased level of serum-specific IgE to the cat albumin component (e224) was noted. In conclusion, cat-food allergy can be found in allergic patients among whom are sensitive to cats and dogs and develop food allergy due to red meat.

Progesterone hypersensitivity is mediated by type I, III, and IV hypersensitivity reactions to endogenous or exogenous progesterone, involving autoimmune mechanisms in females of reproductive age. It presents with a range of dermatologic manifestations, most commonly urticaria, angioedema, eczema, and maculopapular rashes. Systemic and severe symptoms, such as generalized erythema multiforme or lesions resembling severe cutaneous adverse reactions, have rarely been reported. We describe a case of a 42-year-old woman who developed drug reaction with eosinophilia and systemic symptoms (DRESS) following exogenous progesterone therapy administered for assisted reproduction. She received high-dose subcutaneous progesterone and vaginal tablets. Despite this being her first procedure, she achieved pregnancy. However, at 8 weeks of gestation and during the third month of progesterone treatment, she developed generalized erythema multiforme, pruritus, and high-grade fever. Her laboratory findings showed increased blood eosinophil counts and inflammatory markers. After oral corticosteroid (OCS) treatment for several weeks, her skin lesions were partially improved. However, after tapering of OCS, her skin lesions were aggravated with increased blood eosinophil counts. Despite daily OCS (prednisolone, 12.5–60 mg/day) treatment after childbirth, her skin symptoms and eosinophilia persisted. Reslizumab treatment was also attempted, but only the eosinophilia resolved. These clinical findings were much improved after Janus kinase (JAK) inhibitor (upadacitinib 15 mg/day) treatment; consequently, OCS was stopped. Here, we report a case of relapsing DRESS triggered by exogenous progesterone, which has been controlled by JAK inhibitor treatment.

Cat-pork syndrome is an uncommon food allergy induced by red meat (pork/beef) that cross-reacts with cat/dog allergens, which is mediated by immunoglobulin E (IgE) response to the cat/dog albumin component. We report 2 cases of cat-pork syndrome occurred in adult pet breeders. They had suffered from allergic rhinitis/atopic dermatitis sensitive to cat/dog dander as well as house dust mites for several years, during which an immediate type of food allergy due to red meats developed whenever taking pork or beef. ImmunoCAP results showed the increased levels of serum-specific IgE to pork and beef allergens (f26, f27) as well as cat and dog dander (e1, e5); moreover, increased level of serum-specific IgE to the cat albumin component (e224) was noted. In conclusion, cat-food allergy can be found in allergic patients among whom are sensitive to cats and dogs and develop food allergy due to red meat.

Progesterone hypersensitivity is mediated by type I, III, and IV hypersensitivity reactions to endogenous or exogenous progesterone, involving autoimmune mechanisms in females of reproductive age. It presents with a range of dermatologic manifestations, most commonly urticaria, angioedema, eczema, and maculopapular rashes. Systemic and severe symptoms, such as generalized erythema multiforme or lesions resembling severe cutaneous adverse reactions, have rarely been reported. We describe a case of a 42-year-old woman who developed drug reaction with eosinophilia and systemic symptoms (DRESS) following exogenous progesterone therapy administered for assisted reproduction. She received high-dose subcutaneous progesterone and vaginal tablets. Despite this being her first procedure, she achieved pregnancy. However, at 8 weeks of gestation and during the third month of progesterone treatment, she developed generalized erythema multiforme, pruritus, and high-grade fever. Her laboratory findings showed increased blood eosinophil counts and inflammatory markers. After oral corticosteroid (OCS) treatment for several weeks, her skin lesions were partially improved. However, after tapering of OCS, her skin lesions were aggravated with increased blood eosinophil counts. Despite daily OCS (prednisolone, 12.5–60 mg/day) treatment after childbirth, her skin symptoms and eosinophilia persisted. Reslizumab treatment was also attempted, but only the eosinophilia resolved. These clinical findings were much improved after Janus kinase (JAK) inhibitor (upadacitinib 15 mg/day) treatment; consequently, OCS was stopped. Here, we report a case of relapsing DRESS triggered by exogenous progesterone, which has been controlled by JAK inhibitor treatment.