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1.
Cancer Diagn Progn ; 4(4): 482-488, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962547

RESUMEN

Background/Aim: The Geriatric Nutritional Risk Index (GNRI) indicates nutritional status based on serum albumin concentration and ideal body weight. Pretreatment GNRI has been suggested as a prognostic factor for various malignancies. However, little is known about the clinical value of GNRI for small-cell lung cancer (SCLC), especially in elderly patients. Patients and Methods: We retrospectively analyzed 53 elderly (≥71) patients with extensive-disease (ED) SCLC treated with first-line platinum-doublet chemotherapy in relation to the pretreatment GNRI level in a real-world setting. Results: Thirty-six patients with a low GNRI (<92) had statistically poorer progression-free survival (PFS) and overall survival (OS) than 17 patients with a high GNRI (≥92) (median PFS=80 days vs. 133 days, respectively; p=0.002; median OS=123 days vs. 274 days, respectively; p=0.004). In a multivariate analysis, a low GNRI was also an independent poor prognostic factor for PFS [hazard ratio (HR)=0.396; 95% confidence interval (CI)=0.199-0.789; p=0.008] and OS (HR=0.295; 95%CI=0.143-0.608; p<0.001). Conclusion: The GNRI might be a predictive and prognostic marker in elderly patients with ED-SCLC treated with platinum-doublet chemotherapy.

2.
Cancer Sci ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38979893

RESUMEN

The global phase 3 DESTINY-Breast03 study (ClinicalTrials.gov; NCT03529110) showed statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) with trastuzumab deruxtecan (T-DXd) over trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. Here, we report a subgroup analysis of Asian patients enrolled in DESTINY-Breast03. In total, 309 patients (149 in the T-DXd arm and 160 in the T-DM1 arm) from Asian countries and regions were randomized. At data cutoff (July 25, 2022), the median duration of follow-up in the Asian subpopulation was 29.0 months with T-DXd and 26.0 months with T-DM1. The PFS (determined by blinded independent central review) hazard ratio was 0.30 (95% confidence interval 0.22-0.41) favoring T-DXd over T-DM1 (median PFS 25.1 vs. 5.4 months). Median OS was not reached in the T-DXd arm and was 37.7 months in the T-DM1 arm. The median treatment duration was 15.4 months with T-DXd and 5.5 months with T-DM1. The incidence of grade ≥3 drug-related treatment-emergent adverse events was similar between both treatment arms (49.0% vs. 46.5%) and was consistent with the overall DESTINY-Breast03 population. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 12.9% of patients treated with T-DXd and 2.5% treated with T-DM1, with a higher incidence in Japanese patients; none of these were grade ≥4 events. These efficacy and safety data reinforce the favorable benefit-risk profile of T-DXd in HER2-positive mBC, including in the Asian subgroup.

3.
Breast Cancer ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38884900

RESUMEN

BACKGROUND: In the global phase 3 DESTINY-Breast04 study (NCT03734029), the anti-human epidermal growth factor 2 (HER2) antibody-drug conjugate trastuzumab deruxtecan (T-DXd) demonstrated a statistically significant improvement in progression-free survival (PFS) and overall survival (OS), with manageable safety compared with treatment of physician's choice (TPC) in patients with HER2-low metastatic breast cancer (mBC) who had received 1-2 prior lines of chemotherapy. METHODS: This subgroup analysis examined the efficacy and safety of T-DXd versus TPC in 213 patients from Asian countries and regions who were enrolled in the DESTINY-Breast04 trial and randomized to T-DXd (n = 147) or TPC (n = 66). RESULTS: Median PFS with T-DXd and TPC was 10.9 and 5.3 months, respectively, in Asian patients with hormone receptor-positive mBC, and 10.9 and 4.6 months, respectively, in the overall Asian population. In both populations, median OS was not reached with T-DXd and was 19.9 months with TPC. The objective response rate was higher with T-DXd versus TPC in all Asian patients. Median treatment duration was 8.4 months with T-DXd and 3.5 months with TPC. The most common grade ≥ 3 drug-related treatment-emergent adverse events in Asian patients treated with T-DXd were neutropenia (16.3%), anemia (12.9%), and leukopenia (11.6%); the incidences of neutropenia and leukopenia were higher with TPC versus T-DXd. Adjudicated drug-related interstitial lung disease or pneumonitis with T-DXd was 14.3%; the majority of events were grade 1-2. CONCLUSIONS: T-DXd demonstrated clinically meaningful survival benefits versus TPC in Asian HER2-low mBC patients, regardless of hormone receptor status, with no new safety signals. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03734029.

4.
Nat Med ; 30(7): 1933-1942, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38745009

RESUMEN

Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2+) gastric cancer in the DESTINY-Gastric01 trial. Exploratory results from DESTINY-Gastric01 suggested a potential benefit in patients with HER2-low gastric cancer. Spatial and temporal heterogeneity in HER2 expression or gene alteration, an inherent characteristic of gastric cancer tumors, presents a challenge in identifying patients who may respond to T-DXd. Specific biomarkers related to therapeutic response have not been explored extensively. Exploratory analyses were conducted to assess baseline HER2-associated biomarkers in circulating tumor DNA and tissue samples, and to investigate mechanisms of resistance to T-DXd. Baseline HER2-associated biomarkers were correlated with objective response rate (ORR) in the primary cohort of patients with HER2+ gastric cancer. The primary cohort had 64% concordance between HER2 positivity and HER2 (ERBB2) plasma gene amplification. Other key driver gene amplifications, specifically MET, EGFR and FGFR2, in circulating tumor DNA were associated with numerically lower ORR. Among 12 patients with HER2 gain-of-function mutations, ORR was 58.3% (7 of 12). ORR was consistent regardless of timing of immunohistochemistry sample collection. Further investigations are required in larger studies.


Asunto(s)
Biomarcadores de Tumor , Camptotecina , Receptor ErbB-2 , Neoplasias Gástricas , Trastuzumab , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapéutico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Femenino , Amplificación de Genes , Masculino , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Inmunoconjugados/uso terapéutico , Inmunoconjugados/farmacología , Persona de Mediana Edad , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Anciano , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo
5.
J Neurosurg Case Lessons ; 7(10)2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38437674

RESUMEN

BACKGROUND: The treatment of vertebrobasilar junction (VBJ) aneurysms is challenging. Although flow diverters (FDs) are a possible treatment option, geometrical conditions hinder intervention. VBJ aneurysms possess dual inflow vessels from the bilateral vertebral arteries (VAs), one of which is ideally occluded prior to FD treatment. However, it remains unclear which VA should be occluded. OBSERVATIONS: A 75-year-old male with a growing VBJ complex aneurysm exhibiting invagination toward the brainstem and causing perifocal edema required intervention. Preoperative computational fluid dynamics (CFD) analysis demonstrated that left VA occlusion would result in more stagnant flow and less impingement of flow than right VA occlusion. According to the simulated strategy, surgical clipping of the left VA just proximal to the aneurysm was performed, followed by FD placement from the basilar artery trunk to the right VA. The patient demonstrated tolerance of the VA occlusion, and follow-up computed tomography angiography at 18 months after FD treatment confirmed the disappearance of the aneurysm. LESSONS: Preoperative flow dynamics simulations using CFD analysis can reveal an optimal treatment strategy involving a hybrid surgery that combines FD placement and direct surgical occlusion for a VBJ complex aneurysm.

6.
Anticancer Res ; 44(2): 845-851, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38307561

RESUMEN

BACKGROUND/AIM: Pretreatment serum cytokeratin 19 fragment (CYFRA21-1) level predicts outcomes in patients with non-small cell lung cancer; however, little is known about the clinical value of serum CYFRA21-1 level in patients with small cell lung cancer (SCLC). The aim of this study was to evaluate the prognostic value of pretreatment serum CYFRA21-1 level in patients with extensive disease (ED)-SCLC treated using platinum-doublet chemotherapy. PATIENTS AND METHODS: We retrospectively analyzed the pretreatment serum CYFRA21-1 levels of patients with ED-SCLC who were treated using first-line platinum-doublet chemotherapy. RESULTS: A total of 98 patients were analyzed. The patients with a high CYFRA21-1 level (≥7.0 ng/ml) (n=29) had significantly shorter progression-free survival (PFS) and overall survival (OS) than the patients with low CYFRA21-1 levels (n=67) [median PFS=118 days vs. 125 days, respectively (p=0.018); median OS=213 days vs. 295 days, respectively (p=0.046)]. In addition, high CYFRA21-1 level was associated with a high refractory relapse rate. CONCLUSION: Serum CYFRA21-1 level may be a prognostic marker for patients with ED-SCLC treated with platinum-doublet chemotherapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Queratina-19 , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos , Platino (Metal)/uso terapéutico , Recurrencia Local de Neoplasia , Antígenos de Neoplasias , Biomarcadores de Tumor
7.
Jpn J Clin Oncol ; 54(4): 434-443, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38231777

RESUMEN

BACKGROUND: HER2-expressing salivary gland carcinoma (SGC) is associated with poor prognosis. Trastuzumab deruxtecan (T-DXd, DS-8201) has shown evidence of antitumor activity for several HER2-expressing solid tumors in multiple studies. This study aimed to present the efficacy and safety of T-DXd in patients with HER2-expressing SGC from a pooled analysis. METHODS: Patients with HER2-expressing SGC were pooled from two phase I, open-label studies of T-DXd: a two-phase, multiple-dose, first-in-human study (NCT02564900) and a single-sequence crossover drug-drug interaction study (NCT03383692). Endpoints included efficacy (objective response rate [ORR], duration of response [DoR] and progression-free survival [PFS]) and safety. RESULTS: This pooled analysis included 17 patients with SGC (median age: 57 years; male: 88.2%); median (range) follow-up duration was 12.0 (2.3-|34.8) months. Among these patients, 14 had received prior HER2-targeted agents and 13 had undergone prior radiotherapy. The investigator-assessed confirmed ORR was 58.8% (95% confidence interval [CI], 32.9-|81.6). The median (95% CI) DoR and PFS were 17.6 months (4.0 to not evaluable [NE]) and 20.5 months (11.1-NE), respectively. All 17 patients reported treatment-emergent adverse events (TEAEs); 76.5% reported TEAEs of grade ≥3. The most common TEAEs were decreased appetite (94.1%), nausea (88.2%) and neutrophil count decreased (76.5%). Of the 17 patients, five (29.4%) reported adjudicated drug-related interstitial lung disease (grade 1, n = 3; grade 2, n =1; grade 3, n = 1). CONCLUSION: The results of this pooled analysis provide evidence that clinical benefit is achievable with T-DXd in patients with HER2-expressing SGC. CLINICAL TRIAL INFORMATION: FIH study, NCT02564900; DDI study, NCT03383692.


Asunto(s)
Camptotecina , Carcinoma , Inmunoconjugados , Trastuzumab , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Camptotecina/uso terapéutico , Camptotecina/análogos & derivados , Carcinoma/tratamiento farmacológico , Inmunoconjugados/efectos adversos , Inmunoconjugados/uso terapéutico , Receptor ErbB-2/metabolismo , Glándulas Salivales/metabolismo , Trastuzumab/efectos adversos , Trastuzumab/uso terapéutico , Femenino
8.
Radiol Case Rep ; 19(3): 895-900, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38188958

RESUMEN

A 69-year-old woman was diagnosed with an asymptomatic intracranial tumor nine years ago and has been followed with annual MR imaging studies. Two years ago, the tumor had grown in size, requiring treatment. She experienced ophthalmopathy due to hyperthyroidism 27 years ago and was treated with 20 Gy in 10 fractions using parallel opposed beams to her bilateral posterior eyeballs, supplemented with steroid pulse therapy. The tumor originated in the medial aspect of the right sphenoid border and compressed the temporal lobe, while bone infiltration was observed, partially extending to the soft tissue outside the maxillary sinus. The tumor was removed by craniotomy. The pathological diagnosis was atypical meningioma (WHO grade II). Four months postsurgery, the resection cavity's tumor exhibited growth inclination, necessitating Gamma Knife radiosurgery. Radiation planning was executed at a marginal tumor dose of 30 Gy in 5 fractions. Since the optic nerve had been previously exposed to radiation, a plan was devised to minimize radiation exposure. The dose on the optic nerve was limited to 6.9 Gy in 5 fractions. She did not experience any visual or visual field disruptions postradiation. This is a case of radiation-induced meningioma resulting from radiation therapy for Graves' ophthalmopathy and is the first reported case of a grade II meningioma. The patient's condition calls for adjuvant radiation therapy following surgical removal. Accordingly, a radiation treatment plan that safeguards the optic nerve, which was previously exposed to radiation, was deemed indispensable.

9.
Int J Clin Oncol ; 29(1): 27-35, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37964066

RESUMEN

BACKGROUND: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate that consists of an anti-human epidermal growth factor receptor 2 (HER2) antibody bound by a cleavable tetrapeptide-based linker to a cytotoxic topoisomerase I inhibitor. Prior to marketing approval in Japan in September 2020, this expanded-access study was conducted to provide T-DXd to previously treated patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinomas. METHODS: This multicenter, open-label, expanded-access study was conducted between March 25 and September 25, 2020 at 17 Japanese sites. Previously treated patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinomas received T-DXd 6.4 mg/kg via intravenous infusions at 3-week intervals. Serious adverse events (SAEs), all potential cases of interstitial lung disease (ILD)/pneumonitis, all liver-related events potentially meeting Hy's Law criteria, and all cases of overdose were reported on the case report forms. RESULTS: A total of 64 patients were treated with T-DXd. Among the 17 (26.6%) patients with reported SAEs, 10 (15.6%) had SAEs related to T-DXd treatment. Febrile neutropenia was the most common SAE (n = 6). SAEs led to death in six patients; drug-related SAEs (sepsis and febrile neutropenia) led to death in one patient. Drug-related ILD, as determined by the external Adjudication Committee, occurred in three patients (Grade 1, Grade 2, and Grade 3: all n = 1). CONCLUSION: This expanded-access study provided T-DXd to a broader population of Japanese patients prior to marketing approval in Japan, bridging the gap between clinical trials and drug approval. No new safety concerns were identified.


Asunto(s)
Adenocarcinoma , Neutropenia Febril , Inmunoconjugados , Enfermedades Pulmonares Intersticiales , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Trastuzumab/efectos adversos , Camptotecina/efectos adversos , Receptor ErbB-2 , Inmunoconjugados/efectos adversos , Adenocarcinoma/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inducido químicamente , Neutropenia Febril/inducido químicamente
10.
Oncol Lett ; 26(6): 515, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37927416

RESUMEN

The benefits of crizotinib therapy in patients with tyrosine receptor kinase ROS proto-oncogene 1 (ROS1)-rearranged non-small cell lung cancer (NSCLC) have been demonstrated. The present study reports a 47-year-old woman with lung adenocarcinoma harboring a rare HLA_A-ROS1 rearrangement with clinical response to crizotinib. To the best of our knowledge there have been no reports of HLA_A-ROS1-rearranged lung cancer regarding clinical course and the efficacy of treatment with crizotinib. A good response to crizotinib therapy in the present case could be a reference for the treatment and prognosis of ROS1-rearranged NSCLC with the same fusion partner. The current report will remind oncologists and pulmonologists to consider the importance of accurate multigene panel assays for detecting driver oncogenes in treating patients with NSCLC.

11.
Surg Neurol Int ; 14: 277, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37680916

RESUMEN

Background: Excessive glue injection into the drainage vein in patients with dural arteriovenous fistula (dAVF) can result in venous obstruction. We performed transarterial embolization (TAE) combined with transvenous embolization (TVE) with coils to prevent the glue from migrating into the normal cortical veins. Case Description: A 57-year-old man was pointed out to have a Borden Type III anterior cranial fossa dAVF during a check-up for putaminal hemorrhage. Because a left frontal normal cortical vein drained into the pathological drainage vein, excessive glue injection into the drainage vein may have caused venous obstruction. We performed TVE with coils at the foot of the draining vein to prevent excessive migration of glue into the drainer, followed by TAE with glue. With this technique, complete obliteration of the shunt without venous ischemia was obtained. Conclusion: The combined treatment of TAE and TVE is effective in preventing venous ischemia caused by unintended migration of glue cast into the drainage vein.

12.
Intern Med ; 62(7): 1049-1054, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36070940

RESUMEN

A 77-year-old man presented with a 1-month history of cough, pharyngeal discomfort, and weight loss. Chest radiography revealed a mass shadow in the right upper lung field. Bronchoscopy showed multiple white nodules along the tracheal cartilage ring. Although adenocarcinoma cells were detected in the mass, several biopsy specimens of the tracheal lesions exhibited no malignancy. 18F-fluorodeoxyglucose positron emission tomography revealed an intense accumulation in the mass, nasal septum, and tracheal cartilage. Furthermore, anti-type II collagen antibody levels were elevated. We finally diagnosed him with lung cancer complicated by relapsing polychondritis. Treatment with oral prednisolone was initiated, followed by sequential chemoradiotherapy for lung cancer.


Asunto(s)
Neoplasias Pulmonares , Policondritis Recurrente , Masculino , Humanos , Anciano , Policondritis Recurrente/complicaciones , Policondritis Recurrente/diagnóstico , Neoplasias Pulmonares/complicaciones , Tráquea , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X
13.
J Clin Oncol ; 41(4): 816-825, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36379002

RESUMEN

PURPOSE: To investigate efficacy and safety of trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2 (HER2)-low gastric or gastroesophageal junction (GEJ) adenocarcinoma. METHODS: Patients with locally advanced or metastatic HER2-low (cohort 1, immunohistochemistry 2+/in situ hybridization-negative; cohort 2, immunohistochemistry 1+) gastric/GEJ adenocarcinoma treated with at least two prior regimens, including fluoropyrimidine and platinum, but anti-HER2 therapy naive, received T-DXd 6.4 mg/kg intravenously once every 3 weeks. The primary end point was confirmed objective response rate by independent central review. RESULTS: Among 21 patients enrolled in cohort 1 and 24 enrolled in cohort 2, 19 and 21 patients, respectively, had central HER2 confirmation, received T-DXd, and had measurable tumors at baseline. The confirmed objective response rate was 26.3% (95% CI, 9.1 to 51.2) from five partial responses in cohort 1 and 9.5% (95% CI, 1.2 to 30.4) from two partial responses in cohort 2. Thirteen patients (68.4%) in cohort 1 and 12 (60.0%) in cohort 2 experienced reduced tumor size. The median overall survival was 7.8 months (95% CI, 4.7 to nonevaluable) in cohort 1 and 8.5 months (95% CI, 4.3 to 10.9) in cohort 2; the median progression-free survival was 4.4 months (95% CI, 2.7 to 7.1) and 2.8 months (95% CI, 1.5 to 4.3), respectively. The most common grade ≥ 3 treatment-emergent adverse events in cohorts 1 and 2 were anemia (30.0% and 29.2%), decreased neutrophil count (25.0% and 29.2%), and decreased appetite (20.0% and 20.8%). Drug-related interstitial lung disease/pneumonitis occurred in one patient in each cohort (grade 1 or 2). No drug-related deaths occurred. CONCLUSION: This study provides preliminary evidence that T-DXd has clinical activity in patients with heavily pretreated HER2-low gastric/GEJ adenocarcinoma.


Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Trastuzumab , Receptor ErbB-2 , Adenocarcinoma/patología , Unión Esofagogástrica/patología , Neoplasias Gástricas/patología
14.
Gan To Kagaku Ryoho ; 49(12): 1361-1364, 2022 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-36539250

RESUMEN

We report the case of a 72-year-old woman who underwent partial mastectomy due to left breast cancer(invasive ductal carcinoma)in March 20XX-4. This was followed by radiotherapy(50 Gy/25 Fr)and hormone therapy. In July 20XX, she was referred to our department because a chest computed tomography(CT)scan performed at the postoperative follow-up revealed a band-like consolidation adjacent to the pleura in the lingular segment, with enlarged ipsilateral hilar and mediastinal lymph nodes. CT-guided lung tumor biopsy was performed, and she was diagnosed with limited-stage small cell lung cancer. Chemotherapy with carboplatin, etoposide, and atezolizumab was initiated. Radiotherapy was not performed due to the overlap between the distribution of the lung tumor and the postoperative irradiation field of breast cancer. Due to the difference in the histopathological findings of the first and second primary tumors, and the location of the tumor in the postoperative irradiation field, the second cancer was considered to be radiation-induced cancer despite the short latency period.


Asunto(s)
Neoplasias de la Mama , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Femenino , Humanos , Anciano , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Mastectomía , Neoplasias Pulmonares/cirugía , Pulmón/patología
15.
Int J Colorectal Dis ; 37(6): 1393-1402, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35585358

RESUMEN

PURPOSE: Fibroblast growth factor receptor 2 (FGFR2) and human epidermal growth factor receptor 2 (HER2) proteins are both molecular targets for cancer therapy. The objective of this study was to evaluate the expression status of FGFR2 and HER2 in patients with gastric cancer (GC) or colorectal cancer (CRC). METHODS: Archived tumor tissue samples from patients with histologically-confirmed GC or CRC suitable for chemotherapy were analyzed for FGFR2 and HER2 expression using immunohistochemistry and fluorescence in situ hybridization (HER2 in CRC only). RESULTS: A total of 176 GC patients and 389 CRC patients were enrolled. Among patients with GC, 25.6% were FGFR2-positive and 26.1% were HER2-positive. Among patients with CRC, 2.9% were FGFR2-positive and 16.2% were HER2-positive. No clear relationship was found between FGFR2 and HER2 status in either GC or CRC. In GC, FGFR2 and HER2 statuses did not differ between different primary cancer locations, whereas there were some differences between histological types. Based on FGFR2- and/or HER2-positive status, 117 patients were identified as potentially suitable for inclusion in clinical trials of therapeutic agents targeting the relevant protein (GC = 45, CRC = 72; FGFR = 56, HER2 = 62), of whom 7 were eventually enrolled into such clinical trials. CONCLUSIONS: This study indicated the prevalence of FGFR2 and HER2 in GC and CRC in the Japanese population. The screening performed in this study could be useful for identifying eligible patients for future clinical trials of agents targeting these proteins. TRIAL REGISTRATION: Clinical trial registration Japic CTI No.: JapicCTI-163380.  https://www. CLINICALTRIALS: jp/cti-user/trial/ShowDirect.jsp?directLink=RNlzx1PPCuT.PrVNPxPRwA .


Asunto(s)
Neoplasias Colorrectales , Neoplasias Gástricas , Neoplasias Colorrectales/genética , Humanos , Hibridación Fluorescente in Situ , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/uso terapéutico , Neoplasias Gástricas/genética
16.
Case Rep Urol ; 2021: 7577632, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34422431

RESUMEN

Persistent Müllerian duct syndrome can cause an inguinal hernia, although this is a rare occurrence; recurrent inguinal hernias can, in turn, cause ongoing groin pain. Management of groin pain plays an important role in patients' quality of life. We present our experience with a 43-year-old man who had a 2-week history of left-sided groin pain. The patient underwent laparoscopic surgery for a left inguinal hernia via the transabdominal preperitoneal approach. Right-sided cryptorchidism was noted during surgery, with a solid structure-thought to be a uterus-extending into the left inguinal canal. The diagnosis was persistent Müllerian duct syndrome, and the groin pain was relieved after a laparoscopic right orchiectomy with a bilateral preperitoneal hernia repair using a mesh. Four years later, magnetic resonance imaging performed for new-onset left groin pain showed a left inguinal hernia caused by the uterine structure. We diagnosed the recurrent hernia as the cause of his pain. Prior to performing any invasive surgical procedures, an iliohypogastric nerve block was performed using 1% lidocaine. Short-term analgesia was provided by the block, improving his quality of life. He has been followed since then and has declined surgical neurectomy. An iliohypogastric nerve block can be an effective method of controlling groin pain caused by an inguinal hernia resulting from persistent Müllerian duct syndrome; the effectiveness of the nerve block will help determine whether surgical neurectomy is indicated for permanent pain control.

17.
Nihon Yakurigaku Zasshi ; 156(1): 47-51, 2021.
Artículo en Japonés | MEDLINE | ID: mdl-33390481

RESUMEN

Antibody-drug conjugates (ADCs) combine the specific antibody and cytotoxic agent by a linker and represent a promising drug class with a wider therapeutic window than conventional chemotherapeutic agents by substantiating efficient and specific drug delivery to antigen-expressing tumor cells. However, there are rooms for improvement in terms of efficacy, safety, physicochemical property; therefore, the development of promising ADC drugs across multiple indications are eagerly awaited. In 2015, Daiichi Sankyo initiated the first-in-human study of HER2 ADC, trastuzumab deruxtecan (T-DXd, ENHERTU®) which possesses DNA topoisomerase I inhibitor, exatecan derivative and proprietary linker, in Japan. Based on the provocative results in phase 1 study, the global development program has been accelerated to show the high and durable efficacy in patients with HER2 positive breast cancer pretreated with trastuzumab emtansine. As a result, T-DXd was approved based on single arm phase 2 study in the US (Dec 2019) and Japan (March 2020) by leveraging the breakthrough designation and conditional early approval system, respectively, at the first time for the HER2 positive breast cancer. In addition, T-DXd was recently approved in gastric cancer through Sakigake designation in Japan based on a randomized phase 2 study. T-DXd is also being developed in the earlier lines or other indications where no anti-HER2 therapies were approved to date. Combination studies with other agents, such as immune checkpoint inhibitors are underway. In the near future, we hope that more patients worldwide can enjoy the therapeutic benefits of T-DXd through our continuous efforts to expand its indications.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Camptotecina/análogos & derivados , Humanos , Inmunoconjugados , Japón , Receptor ErbB-2/uso terapéutico , Trastuzumab/uso terapéutico
18.
World Neurosurg ; 143: 353-359, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32791218

RESUMEN

BACKGROUND: Aneurysms at the origin of a duplicated middle cerebral artery (DMCA) are quite rare. Here, we report a patient with such an aneurysm successfully treated endovascularly using our novel "wrapped-candy" low-profile visualized intraluminal support (LVIS) technique. CASE DESCRIPTION: A 44-year-old woman underwent endovascular treatment for an unruptured wide-necked aneurysm at the origin of a DMCA that incorporated the origin of the DMCA into its neck. Stent-assisted coiling was performed using our newly developed "wrapped-candy" LVIS technique. To protect the origin of the DMCA and increase the stent metal density at the neck, an LVIS blue 3.5-mm × 22-mm stent was deployed by pushing the delivery wire aggressively to transform the visible wire components of the LVIS into a shape like "wrapped candy," maximizing the strut compaction at the neck of the aneurysm. Subsequently, the aneurysm component was coiled using a jailed microcatheter. The final procedural angiography demonstrated almost complete aneurysm occlusion with DMCA preservation. CONCLUSIONS: Stent-assisted coiling can be a feasible treatment for an unruptured, usually wide-necked, aneurysm at the origin of a DMCA. The wrapped-candy LVIS technique may be useful in more challenging morphologies such as wide-necked aneurysms that incorporate the branch origin into the aneurysm neck.


Asunto(s)
Procedimientos Endovasculares/métodos , Aneurisma Intracraneal/cirugía , Arteria Cerebral Media/anomalías , Arteria Cerebral Media/cirugía , Procedimientos Neuroquirúrgicos/métodos , Stents , Adulto , Anciano , Catéteres , Angiografía Cerebral , Femenino , Humanos , Aneurisma Intracraneal/etiología , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
20.
World Neurosurg ; 141: 175-183, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32522654

RESUMEN

BACKGROUND: Mechanical thrombectomy has become the standard treatment for acute ischemic stroke caused by large vessel occlusion; however, refractory occlusions still occur despite various thrombectomy procedures. The double stent retriever (SR) technique, which employs 2 SRs simultaneously at the occlusion, can be useful for such refractory occlusions. METHODS: We described 2 cases of refractory acute cerebral occlusion despite the use of conventional thrombectomy procedures that were both treated with the double SR technique. To discuss the technical aspects of how this easy-to-perform technique facilitates the device-clot interaction, we also evaluated radiographic findings of the SR strut during the procedure. RESULTS: In both cases, conventional thrombectomy procedures, including an SR alone, an aspiration catheter alone, and combined use of the SR and aspiration catheter, failed to recanalize the occlusion. The double SR technique was then performed with the stent-in-stent method in 1 patient and the parallel stent method in 1 patient. One pass of this technique retrieved hard clots and successfully recanalized the refractory occlusion in both cases. Intraprocedural radiographic images of these cases showed that the degree of stent expansion improved after deployment of the second SR compared with the first SR. CONCLUSIONS: Our radiographic findings suggested that adding a second SR facilitates the device-clot interaction at the occlusion site. The double SR technique may be an easy-to-perform thrombectomy technique to improve clot-capturing ability for the management of refractory acute cerebral artery occlusions.


Asunto(s)
Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/métodos , Accidente Cerebrovascular Isquémico/cirugía , Stents , Trombectomía/instrumentación , Trombectomía/métodos , Anciano , Arteriopatías Oclusivas/complicaciones , Arteriopatías Oclusivas/cirugía , Femenino , Humanos , Accidente Cerebrovascular Isquémico/etiología , Masculino
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