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1.
Cancer Sci ; 114(8): 3259-3269, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37208931

RESUMEN

Experimental techniques for patient-derived cancer stem-cell organoids/spheroids can be powerful diagnostic tools for personalized chemotherapy. However, establishing their cultures from gastric cancer remains challenging due to low culture efficiency and cumbersome methods. To propagate gastric cancer cells as highly proliferative stem-cell spheroids in vitro, we initially used a similar method to that for colorectal cancer stem cells, which, unfortunately, resulted in a low success rate (25%, 18 of 71 cases). We scrutinized the protocol and found that the unsuccessful cases were largely caused by the paucity of cancer stem cells in the sampled tissues as well as insufficient culture media. To overcome these obstacles, we extensively revised our sample collection protocol and culture conditions. We then investigated the following second cohort and, consequently, achieved a significantly higher success rate (88%, 29 of 33 cases). One of the key improvements included new sampling procedures for tumor tissues from wider and deeper areas of gastric cancer specimens, which allowed securing cancer stem cells more reproducibly. Additionally, we embedded tumor epithelial pieces separately in both Matrigel and collagen type-I as their preference to the extracellular matrix was different depending on the tumors. We also added a low concentration of Wnt ligands to the culture, which helped the growth of occasional Wnt-responsive gastric cancer stem-cell spheroids without allowing proliferation of the normal gastric epithelial stem cells. This newly improved spheroid culture method may facilitate further studies, including personalized drug-sensitivity tests prior to drug therapy.


Asunto(s)
Esferoides Celulares , Neoplasias Gástricas , Humanos , Esferoides Celulares/patología , Neoplasias Gástricas/patología , Células Madre Neoplásicas/patología
2.
J Antimicrob Chemother ; 78(5): 1231-1240, 2023 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-36918748

RESUMEN

OBJECTIVES: Limited evidence is available regarding alternative therapeutic agents to vancomycin in treating glycopeptide-susceptible Enterococcus faecium (GSEF) bacteraemia. This study assessed the effectiveness and safety of teicoplanin compared with vancomycin for treating GSEF bacteraemia. PATIENTS AND METHODS: This was a retrospective, non-inferiority cohort study. Patients aged ≥18 years who developed GSEF bacteraemia and received either teicoplanin or vancomycin were included. The primary effectiveness outcome was the clinical success at the end of treatment, with a generalized linear model using the propensity score for selecting the agent as a covariate. We used an absolute difference of 20% in clinical success as the non-inferiority margin. Using multivariable logistic regression, the primary safety outcome was the incidence of acute kidney injury (AKI). RESULTS: In total, 164 patients (74 and 90 in the teicoplanin and vancomycin groups, respectively) were included. Overall, 64.9% (48/74) and 48.9% (44/90) of patients in the teicoplanin and vancomycin groups, respectively, achieved the primary effectiveness outcome. A generalized linear analysis showed an adjusted effectiveness difference of 9.9% (95% CI, -0.9% to 20.0%; P = 0.07), indicating non-inferiority of teicoplanin versus vancomycin. The incidence of AKI was 8.1% (6/74) and 24.4% (22/90) in the teicoplanin and vancomycin groups, respectively, with an adjusted OR of 0.242 (95% CI, 0.068 to 0.864; P = 0.029), indicating significantly lower AKI risk in the teicoplanin than in the vancomycin group. CONCLUSIONS: Teicoplanin is a safe and useful alternative therapeutic agent for treating GSEF bacteraemia.


Asunto(s)
Lesión Renal Aguda , Bacteriemia , Enterococcus faecium , Humanos , Adolescente , Adulto , Vancomicina/efectos adversos , Teicoplanina/efectos adversos , Glicopéptidos/efectos adversos , Antibacterianos/efectos adversos , Estudios Retrospectivos , Estudios de Cohortes , Puntaje de Propensión , Lesión Renal Aguda/tratamiento farmacológico , Bacteriemia/tratamiento farmacológico
3.
BMC Cancer ; 23(1): 979, 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37833660

RESUMEN

BACKGROUND: Weekly paclitaxel + ramucirumab (wPTX + RAM) therapy is recommended as the standard second-line chemotherapy regimen for unresectable advanced/recurrent gastric cancer (GC) or esophagogastric junction cancer. Recent subgroup analysis of the RAINBOW trial revealed a higher frequency of severe neutropenia due to wPTX + RAM in Japanese compared to Western patients. However, no risk factors for severe neutropenia have been identified. METHODS: This retrospective observational study included patients with advanced/unresectable gastric or esophagogastric junction cancer who received wPTX + RAM after failure to respond to platinum and fluoropyrimidine doublet chemotherapy between June 2015 and April 2020. We conducted multivariable logistic regression analyses to identify the risk factors associated with grade 4 neutropenia and febrile neutropenia (FN). In addition, we investigated the relationship between the number of risk factors and overall survival (OS) and progression-free survival (PFS). RESULTS: Among 66 patients who met the inclusion criteria, grade 4 neutropenia and FN occurred in 21 (31.8%) and 12 (18.2%) patients, respectively. Prior treatment with oxaliplatin-containing regimens was identified as an independent risk factor for developing grade 4 neutropenia (odds ratio (OR) 20.034, 95% confidence interval (95% CI) 3.216-124.807, P = 0.001). Total bilirubin of > 1.5 mg/dL (OR 31.316, 95% CI 2.052-477.843, P = 0.013) and prior treatment with oxaliplatin-containing regimen (OR 12.502, 95% CI 1.141-137.022, P = 0.039) were identified as independent risk factors for developing FN. Next, we classified patients with 0, 1, 2 risk factor(s) as RF-0, RF-1, and RF-2 subgroups, respectively, and compared the PFS and OS among the three subgroups. PFS was not significantly different among the three subgroups, whereas OS was significantly shorter in the RF-2 subgroup (median 1.4 month, 95% CI 0.0-5.3 month) than in the RF-0 subgroup (median 10.2 month, 95% CI 6.8-13.5 month, P < 0.01 vs RF-2) and RF-1 subgroup (median 13.3 month, 95% CI 10.9-15.7 month, P < 0.01 vs RF-2). CONCLUSIONS: Careful monitoring for grade 4 neutropenia and FN is needed for patients receiving wPTX + RAM therapy who have a history of treatment with oxaliplatin-containing regimens and higher total bilirubin levels.


Asunto(s)
Neutropenia Febril , Neoplasias Gástricas , Humanos , Paclitaxel , Oxaliplatino/efectos adversos , Estudios Retrospectivos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Unión Esofagogástrica , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bilirrubina , Neutropenia Febril/inducido químicamente , Neutropenia Febril/epidemiología , Ramucirumab
4.
Support Care Cancer ; 31(2): 150, 2023 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-36737558

RESUMEN

PURPOSE: Docetaxel + cisplatin + 5-fluorouracil (DCF) therapy, a frequently prescribed regimen for esophageal cancer, is associated with a high risk of febrile neutropenia (FN). This study investigated whether a low skeletal muscle mass index (SMI) is an independent risk factor for FN. METHODS: This retrospective, observational study investigated the SMI of patients with esophageal cancer who received DCF therapy between March 2018 and July 2020. Based on the Asian sarcopenia criteria, patients were divided into two groups: high and low SMI (SMI of < 7.0 and 5.7 kg/m2 for males and females, respectively). The incidence of FN was then compared between the two groups. RESULTS: Thirty-nine patients (20 and 19 in the high- and low-SMI groups, respectively) were included in this study. The incidence of FN was significantly higher in the low-SMI group (63.2% vs. 20.0%, P = 0.006). Univariable and multivariable logistic regression analyses revealed that a low SMI was an independent risk factor for FN (odds ratio, 7.178; 95% confidence interval, 1.272-40.507; P = 0.026). In addition, the frequency of dose reduction in DCF therapy was significantly higher in the low-SMI group (68.4% vs. 35.0%, P = 0.037). CONCLUSION: Low SMI is an independent risk factor for FN in patients with esophageal cancer receiving DCF therapy.


Asunto(s)
Neoplasias Esofágicas , Neutropenia Febril , Masculino , Femenino , Humanos , Cisplatino , Docetaxel , Estudios Retrospectivos , Fluorouracilo , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Esofágicas/tratamiento farmacológico , Neutropenia Febril/tratamiento farmacológico
5.
Support Care Cancer ; 31(5): 283, 2023 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-37074471

RESUMEN

PURPOSE: Pegylated liposomal doxorubicin (PLD)-induced hand-foot syndrome (HFS) frequently lowers the quality of life of ovarian cancer patients. Wrist and ankle cooling, having a limited preventive effect, has been the commonest supportive HFS care. In this study, we retrospectively assessed the primary preventive effect of a combination of regional cooling and oral dexamethasone therapy (cooling + oral Dex) on HFS. METHODS: This study is a single-arm retrospective, observational study. Recurrent ovarian cancer patients were administered PLD ± bevacizumab. We retrospectively examined the efficacy of hands and feet cooling (from the start of PLD to the end) + oral Dex (day 1-5: 8 mg/day, day 6, 7: 4 mg/day) for primary HFS prevention. RESULTS: This study included 74 patients. The initial dose of PLD was 50 mg/m2 and 40 mg/m2 for 32 (43.2%) and 42 (56.8%) patients, respectively. HFS of Grade ≥ 2 and Grade ≥ 3 developed in five (6.8%) and one (1.4%) patient(s), respectively. The incidence of ≥ Grade 2 and ≥ Grade 3 HFS was much lower than those reported in previous studies. Dose reduction was required in 13 patients (17.6%) mainly because of neutropenia or mucositis; there was no HFS-induced dose reduction. Meanwhile, PLD therapy was discontinued mainly because of interstitial pneumonia (4 patients) and HFS (one patient). CONCLUSIONS: We demonstrated the efficacy of regional cooling and oral Dex for primary prevention of PLD-induced HFS. Although future prospective studies are needed to confirm its efficacy, this combination therapy can be considered for primary prevention of HFS in ovarian cancer patients on PLD.


Asunto(s)
Síndrome Mano-Pie , Neoplasias Ováricas , Femenino , Humanos , Síndrome Mano-Pie/etiología , Síndrome Mano-Pie/prevención & control , Síndrome Mano-Pie/tratamiento farmacológico , Antibióticos Antineoplásicos/uso terapéutico , Estudios Retrospectivos , Calidad de Vida , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Doxorrubicina/uso terapéutico , Polietilenglicoles/uso terapéutico , Dexametasona/uso terapéutico , Prevención Primaria , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
6.
Int J Clin Oncol ; 28(10): 1298-1314, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37572198

RESUMEN

This comprehensive review discusses the dosing strategies of cancer treatment drugs for patients with impaired kidney function, specifically those with chronic kidney disease (CKD), undergoing hemodialysis, and kidney transplant recipients. CKD patients often necessitate dose adjustments of chemotherapeutic agents, e.g., platinum preparations, pyrimidine fluoride antimetabolites, antifolate agents, molecularly targeted agents, and bone-modifying agents, to prevent drug accumulation and toxicity due to diminished renal clearance of the administered drugs and their metabolites. In hemodialysis patients, factors such as drug removal from hemodialysis and altered pharmacokinetics demand careful optimization of anticancer drug therapy, including dose adjustment and timing of administration. While free cisplatin is removed by hemodialysis, most of the tissue- and protein-bound cisplatin remains in the body and rebound cisplatin elevations are observed after hemodialysis. It is not recommended hemodialysis for drug removal, regardless of timing. Kidney transplant patients encounter unique challenges in cancer treatment, as maintaining the balance between reduction of immunosuppression, switching to mTOR inhibitors, and considering potential drug interactions with chemotherapeutic agents and immunosuppressants are crucial for preventing graft rejection and achieving optimal oncologic outcomes. The review underscores the importance of personalized, patient-centric approaches to anticancer drug therapy in patients with impaired kidney function.


Asunto(s)
Antineoplásicos , Insuficiencia Renal Crónica , Humanos , Cisplatino , Inmunosupresores/metabolismo , Riñón/metabolismo , Diálisis Renal , Insuficiencia Renal Crónica/tratamiento farmacológico , Guías de Práctica Clínica como Asunto
7.
Int J Clin Oncol ; 28(9): 1207-1217, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37347381

RESUMEN

BACKGROUND: Single-agent chemotherapy with or without bevacizumab (Bev) is a standard therapy for platinum-resistant ovarian cancer (PR-OC). However, there is a lack of literature on chemotherapy agent selection in heterogenous PR-OC. Therefore, we aimed to clarify the heterogeneous treatment effects of each chemotherapy agent. METHODS: Patients who underwent single-drug chemotherapy agents or Bev combination therapy for PR-OC between January 2009 and June 2022 were included in this study. We assessed the impact of each chemotherapy agent on the time to treatment failure (TTF) according to histological type, platinum-free interval (PFI), and Bev usage. RESULTS: A total of 158 patients received 343 different chemotherapy regimens. In patients with clear cell carcinoma/mucinous carcinoma (CC/MC), gemcitabine (GEM) had the strongest effect with a median TTF of 5.3 months, whilst nedaplatin (NDP) had the lowest effect with a median TTF of 1.4 months. In contrast, in the non-CC/MC group, irinotecan (CPT-11) and NDP had a better TTF than GEM and pegylated liposomal doxorubicin (PLD). There were notable differences in the treatment efficacy of NDP according to PFI. Specifically, NDP prolonged the TTF in patients with a PFI ≥ 3 months. Compared with GEM alone, GEM + Bev tended to prolong the TTF more effectively; however, an additive effect was not observed with PLD + Bev. CONCLUSIONS: This study demonstrated that the effect of chemotherapy agents differed according to the tumor and background characteristics of the patient. Our findings will improve selection of effective therapies for patients with PR-OC by considering their background characteristics.


Asunto(s)
Antineoplásicos , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/patología , Antineoplásicos/uso terapéutico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Bevacizumab/uso terapéutico , Doxorrubicina/uso terapéutico , Gemcitabina , Irinotecán/uso terapéutico , Polietilenglicoles , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
8.
Cancer Sci ; 113(11): 4005-4010, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35950366

RESUMEN

Fibroblast growth factor receptor inhibitors (FGFRi) were introduced into clinical trials on several cancer types and found to be particularly efficacious on urothelial cancer and cholangiocarcinoma. Although many enrolled patients responded well in clinical trials, there were some patients who did not respond to FGFRi even though their tumors carried the genomic changes that met the enrollment criteria. As already established, fibroblast growth factor receptor (FGFR) and epidermal growth factor receptor (EGFR) share the downstream signaling pathway of MAPK activation. Accordingly, it is conceivable that targeted inhibition of FGFR alone could leave the MAPK signaling unaffected when the signaling through EGFR is relatively strong. To test this hypothesis, we calculated here the FGFR to EGFR mRNA ratio (F/E for short) of biliary tract and urothelial cancer cell lines utilized in preclinical studies. In six biliary tract cancer cell lines, two responsive lines had an F/E of 9.5 and 9.0, whereas the F/E of four nonresponsive lines was 0.1-1.8. In 22 urothelial cancer cell lines, four of the five responsive lines showed an F/E of 2.8-4.9 (median, 3.6), whereas the F/E range of 17 nonresponsive lines was 0.01-2.7 (median, 0.6) (p = 0.004). We further investigated our 47 patient-derived colorectal cancer-stem cell spheroid lines. The 18 responsive lines showed relatively high F/E (median, 16.4), whereas 29 nonresponsive lines had low F/E (median, 9.2) (p = 0.0006). These results suggest that F/E is another strong predictor of responses to FGFRi that is as useful as the current genomic criteria based solely on the FGFR genomic changes.


Asunto(s)
Neoplasias , Inhibidores de Proteínas Quinasas , Humanos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Receptores de Factores de Crecimiento de Fibroblastos/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Transducción de Señal , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética
9.
Int J Colorectal Dis ; 37(10): 2207-2218, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36156129

RESUMEN

PURPOSE: For rectal cancer, a multimodality approach is mandatory including neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy, and lateral pelvic lymph node (LPLN) dissection, in addition to the total mesorectal excision (TME). However, these treatments are associated with adverse events. It is important to select patients who do or do not need these treatments. METHODS: We retrospectively analyzed patients with cStage II and III rectal cancer who underwent curative resection at three hospitals. Recurrence patterns were classified into three types; pelvic cavity, LPLN, and distant recurrences, and the risk factors for each pattern of recurrence were compared. We then analyzed the risk of recurrence in the patients who underwent TME alone. RESULTS: In total, 506 patients were enrolled in this study. Pelvic cavity recurrence was significantly associated with clinical assumption of circumferential resection margin involvement (cCRM) (p < 0.001), distant recurrence was associated with cN positivity (p < 0.001), and LPLN recurrence was associated with pretreatment LPLN swelling ≥ 5 mm (p < 0.001), lower tumor location (p = 0.016), and serum CEA level > 5 ng/mL (p = 0.008). In patients without cCRM and swollen LPLN, the local recurrence rate was extremely low even if they underwent TME alone; the 5-year recurrence rates of pelvic cavity and LPLN were 2.2% and 1.9%, respectively. CONCLUSION: Additional treatments to TME for rectal cancer need to be performed based on the risk factors for each recurrence pattern.


Asunto(s)
Antígeno Carcinoembrionario , Neoplasias del Recto , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias del Recto/patología , Estudios Retrospectivos , Factores de Riesgo
10.
J Infect Chemother ; 27(1): 26-31, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32828677

RESUMEN

INTRODUCTION: Arbekacin is the first aminoglycoside antibacterial agent approved for treating methicillin-resistant Staphylococcus aureus infection in Japan. Although therapeutic drug monitoring (TDM) is recommended during arbekacin treatment, little evidence for the target exposure and once-daily dosing has been reported. This study aimed to clarify the target peak/trough concentrations and the effectiveness of once-daily dosing of arbekacin against nephrotoxicity or treatment failure via meta-analysis. METHODS: A literature search was performed using MEDLINE, Cochrane Library, and Ichushi-Web. RESULTS: Nine observational cohort studies met the inclusion criteria. A peak arbekacin concentration of ≥15-16 µg/mL did not exhibit a statistically significant lower risk of treatment failure (risk ratio [RR] = 0.61, 95% confidence interval [CI] = 0.30-1.24). A trough arbekacin concentration of <2 µg/mL resulted in a significantly lower risk of nephrotoxicity (RR = 0.30, 95% CI = 0.15-0.61). Once-daily dosing significantly reduced the risk of treatment failure (RR = 0.61, 95% CI = 0.39-0.97) but not nephrotoxicity (RR = 0.54, 95% CI = 0.16-1.75). CONCLUSIONS: Once-daily dosing can improve the therapeutic efficacy of arbekacin, and a trough arbekacin concentration of <2 µg/mL can reduce the risk of nephrotoxicity. A peak arbekacin concentration of ≥15-16 µg/mL did not exhibit the significant lower risk of treatment failure. Additional clinical trials are required to confirm these findings.


Asunto(s)
Dibekacina , Staphylococcus aureus Resistente a Meticilina , Antibacterianos/efectos adversos , Dibekacina/análogos & derivados , Monitoreo de Drogas , Humanos , Japón
11.
Int J Clin Oncol ; 26(9): 1759-1766, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34086110

RESUMEN

BACKGROUND: Radiation-based therapy is widely used for advanced cervical cancer. Prior radiation-based therapy is a potential risk factor for febrile neutropenia (FN). However, the effect of irradiation field size on the incidence of FN during recurrent cervical cancer treatment is unclear. This study aimed to investigate the relationship between prior irradiation field size and FN development during recurrent chemotherapy. METHODS: This retrospective, observational study included cervical cancer patients who received recurrent chemotherapy between November 2006 and June 2020. The patients were classified into two groups based on the area of irradiation fields. The first group included patients with a history of whole pelvis (WP) irradiation (WP group). The second group had patients who underwent WP plus para-aortic lymph node (PAN) irradiation (WP + PAN group). The incidences of hematological toxicities and FN during the recurrent chemoradiotherapy were compared between the two groups. RESULTS: The FN incidence was significantly higher in the WP + PAN group than in the WP group (32.1% vs. 0%, P < 0.001). The incidence of Grade 4 neutropenia was not significantly different between the WP + PAN and WP groups. The nadir absolute neutrophil counts were significantly lower and the dose reduction or discontinuation rate of chemotherapy was significantly higher in the WP + PAN group than in the WP group. CONCLUSION: History of WP plus PAN radiation is a risk factor for developing FN during recurrent cervical cancer chemotherapy.

12.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-34360768

RESUMEN

Colorectal cancer (CRC) is the leading cause of cancer deaths around the world. It is necessary to identify patients with poor prognosis or with high risk for recurrence so that we can selectively perform intensive treatments such as preoperative and/or postoperative chemotherapy and extended surgery. The clinical usefulness of inflammation-related prognostic biomarkers available from routine blood examination has been reported in many types of cancer, e.g., neutrophil-lymphocyte ratio (NLR), lymphocyte-C-reactive protein ratio (LCR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and so on. Moreover, some scoring systems based on circulating blood cell counts and albumin concentration have been also reported to predict cancer patients' prognosis, such as the Glasgow prognostic score (GPS), systemic inflammation score (SIS), and prognostic nutritional index (PNI). The optimal biomarker and optimal cutoff value of the markers can be different depending on the cancer type. In this review, we summarize the prognostic impact of each inflammation-related marker in CRC.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/mortalidad , Humanos , Inflamación/sangre , Inflamación/diagnóstico , Recuento de Leucocitos , Evaluación Nutricional , Valor Predictivo de las Pruebas , Pronóstico
13.
J Infect Chemother ; 26(2): 312-315, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31481306

RESUMEN

OBJECTIVES: Studies on the penetration of orally administered cephalosporins to the aqueous humor are scarce. Therefore, in this study, we determined the concentration of cefcapene, a third-generation cephalosporin administrated orally as pivalate ester (cefcapene pivoxil), in the aqueous humor of patients undergoing cataract surgery to assess its potential for preventing postoperative endophthalmitis. METHODS: Forty-four patients were administered a single dose of 100 mg cefcapene pivoxil preoperatively. Blood and aqueous humor samples were obtained at the time of surgery, and cefcapene concentrations were measured using ultra-performance liquid chromatography with tandem mass spectrometric detection. RESULTS: The samples were obtained from 41 eyes of 39 patients (two patients underwent surgery in both eyes). The median cefcapene concentrations in the aqueous humor after 1-2 h, 2-3 h, and later than 3 h were 8.3, 18.4, and 23.7 ng/mL, respectively. The median cefcapene concentrations in serum after 1-2 h, 2-3 h, and later than 3 h were 198.5, 287.2, and 170.3 ng/mL, respectively. Aqueous humor penetration of cefcapene after 1-2 h, 2-3 h, and later than 3 h was 4.1, 7.9, and 13.5% respectively. CONCLUSIONS: Aqueous humor penetration of orally-administered cefcapene pivoxil in patients undergoing cataract surgery was poor. Therefore, cefcapene pivoxil was unlikely to be effective for preventing endophthalmitis after cataract surgery.


Asunto(s)
Antibacterianos/farmacocinética , Humor Acuoso/metabolismo , Extracción de Catarata/métodos , Cefalosporinas/farmacocinética , Endoftalmitis/prevención & control , Administración Oral , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Cefalosporinas/administración & dosificación , Endoftalmitis/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/prevención & control
16.
Int J Clin Oncol ; 24(6): 677-685, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30721379

RESUMEN

BACKGROUND: For rectal cancer, multimodality therapeutic approach is necessary to prevent local recurrence and distant metastasis. However, the efficacy of additional treatments, such as neoadjuvant chemoradiotherapy (nCRT), neoadjuvant chemotherapy (NAC), and lateral pelvic lymph node dissection (LPLND), has not been scrutinized. METHODS: Recurrence patterns were categorized into local recurrence and distant metastasis. Local recurrence was classified into two types: (1) pelvic cavity recurrence and (2) LPLN recurrence. First, we analyzed the risk factors for each recurrence pattern. Second, based on the status of clinically suspected involvement of circumferential resection margin (cCRM), the efficacy of additional treatments was investigated. RESULTS: A total of 240 patients was enrolled. nCRT was performed for 25 (10%), NAC was for 46 (19%), and LPLND was for 35 patients (15%). As the recurrence patterns, pelvic cavity recurrence occurred in 15 (6%), LPLN recurrence in 8 (3%), and distant metastasis in 42 patients (18%). Five-year overall survival and relapse-free survival were 87% and 70%, respectively. Multivariate analysis indicated that pelvic cavity recurrence was associated with cCRM status and tumor histology, that LPLN recurrence was with serum carcinoembryonic antigen level and LPLN swelling, and that distant metastasis was with clinical N category. In the cCRM-positive subgroup (n = 66), cumulative rate of pelvic cavity recurrence was lower in the nCRT group than in the NAC or non-NAC/nCRT group (P = 0.02 and 0.09, respectively). CONCLUSION: cCRM status was associated with pelvic cavity recurrence, and LPLN swelling was with LPLN recurrence. nCRT could reduce pelvic cavity recurrence in cCRM-positive subgroup.


Asunto(s)
Quimioradioterapia/mortalidad , Escisión del Ganglio Linfático/mortalidad , Ganglios Linfáticos/patología , Terapia Neoadyuvante/mortalidad , Recurrencia Local de Neoplasia/terapia , Neoplasias Pélvicas/terapia , Neoplasias del Recto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Humanos , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Neoplasias Pélvicas/patología , Pronóstico , Neoplasias del Recto/patología , Factores de Riesgo , Tasa de Supervivencia , Adulto Joven
18.
Ann Clin Microbiol Antimicrob ; 16(1): 27, 2017 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-28399872

RESUMEN

BACKGROUND: Daptomycin has been reported to cause artificial prolongation of prothrombin time (PT) by interacting with some test reagents of PT. This prolongation was particularly prominent with high concentrations of daptomycin in vitro. However, whether this prolongation is important in clinical settings and the optimal timing to assess PT remain unclear. METHODS: A prospective clinical study was conducted with patients who received daptomycin for confirmed or suspected drug-resistant, gram-positive bacterial infection at a university hospital in Japan. PT at the peak and trough of daptomycin was tested using nine PT reagents. Linear regression analyses were used to examine the difference in daptomycin concentration and the relative change of PT-international normalized ratios (PT-INR). RESULTS: Thirty-five patients received daptomycin (6 mg/kg). The mean ± standard deviation of the trough and peak concentrations of daptomycin were 13.5 ± 6.3 and 55.1 ± 16.9 µg/mL, respectively. Twelve patients (34%) received warfarin. With five PT reagents, a significant proportion of participants experienced prolongation of PT-INR at the daptomycin peak concentration compared to the PT-INR at the trough, although the mean relative change was less than 10%. None of the participants clinically showed any signs of bleeding. A linear, dose-dependent prolongation of PT was observed for one reagent [unadjusted coefficient ß 3.1 × 10-3/µg/mL; 95% confidence interval (CI) 2.3 × 10-5-6.3 × 10-3; p = 0.048]. When patients were stratified based on warfarin use, this significant linear relationship was observed in warfarin users for two PT reagents (adjusted coefficient ß, 6.4 × 10-3/µg/mL; 95% CI 3.5 × 10-3-9.3 × 10-3; p < 0.001; and adjusted coefficient ß, 8.3 × 10-3/µg/mL; 95% CI 4.4 × 10-3-1.2 × 10-2; p < 0.001). In non-warfarin users, this linear relationship was not observed for any PT reagents. CONCLUSIONS: We found that a higher concentration of daptomycin could lead to artificial prolongation of PT-INR by interacting with some PT reagents. This change may not be clinically negligible, especially in warfarin users receiving a high dose of daptomycin. It may be better to measure PT at the trough rather than at the peak daptomycin concentration.


Asunto(s)
Antibacterianos/uso terapéutico , Anticoagulantes/uso terapéutico , Daptomicina/uso terapéutico , Reacciones Falso Positivas , Indicadores y Reactivos/metabolismo , Tiempo de Protrombina , Warfarina/uso terapéutico , Anciano , Antibacterianos/metabolismo , Infecciones Bacterianas/tratamiento farmacológico , Daptomicina/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Hospitales Universitarios , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Prospectivos
19.
Surg Today ; 47(2): 193-201, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27502598

RESUMEN

PURPOSE: For hepatocellular carcinoma (HCC), the superiority of anatomical resection (AR) over non-anatomical resection (NR) is still controversial. In this study, we assessed the potential benefits of AR for HCC. METHODS: We enrolled 173 consecutive patients with HCC who underwent hepatectomy in our hospital from August 2003 to May 2013 and compared the outcomes for the AR group (n = 125) with those for the NR group (n = 48). RESULTS: The median observational period was 790 days. The 1- and 2-year overall survival (OS) rates were 92.1 and 85.8 %, respectively; the 1- and 2-year disease-free survival (DFS) rates were 78.2 and 63.0 %, respectively. The AR and NR groups did not significantly differ in the OS or DFS. However, the 2-year DFS was significantly better for the AR group than the NR group among HCV patients (68.2 vs. 32.2 %; P = 0.004) and patients with alpha-fetoprotein (AFP) within the normal range (<20 ng/ml; 76.7 vs. 60.9 %; P = 0.031), total bilirubin <0.8 mg/dl (70.8 vs. 47.0 %; P = 0.034), and tumors 2-5 cm in diameter (82.0 vs. 62.5 %; P = 0.025). CONCLUSIONS: If a patient is HCV-negative, has low AFP, low total bilirubin, or a tumor diameter of 2-5 cm, AR is recommended.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Anciano , Bilirrubina/sangre , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Femenino , Hepacivirus , Hepatectomía/mortalidad , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Selección de Paciente , Resultado del Tratamiento , alfa-Fetoproteínas/análisis
20.
Hepatogastroenterology ; 62(138): 363-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25916064

RESUMEN

BACKGROUND/AIMS: For hepatocellular carcinoma (HCC) within a single subsegment, the superiority of anatomical subsegmentectomy over non-anatomical partial resection is still controversial. In this study, we assessed the potential benefit of subsegmentectomy. METHODOLOGY: We selected 44 patients with a single HCC lesion within one subsegment who had undergone anatomical subsegmentectomy or non-anatomical partial resection from among 173 patients who underwent hepatectomy in our hospital from August 2003 to May 2013. We compared the results following anatomical subsegmentectomy (Group A; n = 16) and non-anatomical partial resection (Group N; n = 28). RESULTS: One- and two-year survival rates were 92.5% and 89.3%, respectively; 1- and 2-year recurrence-free survival (RFS) rates were 88.9% and 69.1%, respectively. There was no significant difference in overall survival or RFS between the groups. However, among HBV-positive patients, RFS was significantly better for Group A than Group N (p = 0.008). CONCLUSIONS: For HBV-positive HCC within a single subsegment, we recommend subsegmentectomy.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Anciano , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Supervivencia sin Enfermedad , Femenino , Hepatectomía/efectos adversos , Hepatectomía/mortalidad , Hepatitis B/complicaciones , Humanos , Japón , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Selección de Paciente , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
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