RESUMEN
BACKGROUND/AIM: Alectinib is recommended for anaplastic lymphoma kinase fusion gene-positive non-small cell lung cancer. We have experienced early alectinib discontinuation due to disease progression and adverse effects in real world. Because alectinib has a high protein-binding rate of >99%, low serum albumin may increase the concentration of free drug and affect efficacy and adverse events. However, no association between serum albumin and the clinical impact of alectinib has been reported. The purpose of this study was to determine the effect of serum albumin on time-to-treatment failure (TTF) in alectinib. PATIENTS AND METHODS: Fifty-six patients who were admitted to four hospitals (National Hospital Organization Hokkaido Cancer Center, Sapporo Minami-Sanjo Hospital, KKR Sapporo Medical Center, Otaru General Hospital) between October 2014 and September 2020 were retrospectively evaluated to identify those treated with alectinib. RESULTS: The multivariate analysis showed that the risk of discontinuation was significantly higher with serum albumin <3.6 g/dl compared to ≥3.6 g/dl at the start of alectinib administration (hazard ratio=3.00; 95% confidence interval=1.36-6.66; p<0.01). On Kaplan-Meier curves, TTF for serum albumin <3.6 was significantly shorter than that for ≥3.6. (median TTF: 12.1 months vs. not reach, p<0.01). CONCLUSION: To the best of our knowledge, this study is the first to report that serum albumin <3.6 g/dl at alectinib induction is associated with poor TTF. Low serum albumin is a poor prognostic factor in cancer patients. Thus, serum albumin levels must be measured before treatment.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios Retrospectivos , Crizotinib/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Albúmina Sérica , Tiempo de Tratamiento , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinasa de Linfoma AnaplásicoRESUMEN
BACKGROUND: Oral-sustained release gel formulations with suitable rheological properties have been proposed as a means of improving the compliance of dysphagic and geriatric patients who have difficulties with handling and swallowing oral dosage forms. AIM: We have modified the rheological and release properties of thermally reversible methylcellulose solutions by admixture with pectin, the gelation of which is ion-responsive, with the aim of formulating an in situ gelling vehicle suitable for oral-sustained drug delivery. METHOD: Gels formed by solutions containing methylcellulose (1.0-2.0%) and pectin (0.5-2.0%) were assessed for suitable gel strength, and in vitro and in vivo release of paracetamol. RESULTS: Addition of 1.5% pectin to a 2.0% methylcellulose formulation containing 20% d-sorbitol and calcium ions in complexed form increased the gel strength and provided a formulation with a suitable viscosity for ease of swallowing by dysphagic patients. Gels formed in situ after oral administration of this formulation retained their integrity in the rat stomach for sufficient time for sustained release to be achieved. In vitro release of paracetamol from methylcellulose, pectin, and methylcellulose/pectin gels was diffusion-controlled. Plasma levels of paracetamol after oral administration to rats (gastric pH 2.6 and 5.5) of a solution including 2.0% methylcellulose/1.5% pectin showed improved sustained release compared with that from both 2.0% methylcellulose and 1.5% pectin solutions. CONCLUSIONS: The addition of suitable concentrations of pectin to methylcellulose solutions produces in situ gelling formulations with suitable viscosity for administration to dysphagic patients and improved sustained release characteristics.
Asunto(s)
Trastornos de Deglución/tratamiento farmacológico , Preparaciones de Acción Retardada/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Acetaminofén/administración & dosificación , Acetaminofén/farmacocinética , Administración Oral , Animales , Preparaciones de Acción Retardada/farmacocinética , Composición de Medicamentos/métodos , Mucosa Gástrica/metabolismo , Geles , Humanos , Masculino , Metilcelulosa , Pectinas , Ratas , Ratas Wistar , Reología , ViscosidadRESUMEN
The aim of this study was to examine the effect of D-sorbitol on the gelation characteristics of methylcellulose in aqueous solution. The addition of D-sorbitol at concentrations of between 25 and 30% (w/v) to 1.0-2.0% (w/v) methylcellulose solutions reduced the gelation temperature from approximately 53 degrees Celsius to values between ambient and 37 degrees Celsius and increased the strength of the gel. The in vitro release of acetaminophen (paracetamol) from 2.0% (w/v) methylcellulose gels containing 20-30% (w/v) D-sorbitol gel was diffusion-controlled.
Asunto(s)
Acetaminofén/administración & dosificación , Analgésicos no Narcóticos/administración & dosificación , Preparaciones de Acción Retardada/química , Geles/química , Metilcelulosa/química , Sorbitol/química , Difusión , TemperaturaRESUMEN
PURPOSE: This study compared the clinical and physiological results of non-sphincter splitting fistulectomy (N-SSF) with those of sphincter splitting fistulotomy (SSF) for treatment of high trans-sphincteric fistula-in-ano. MATERIALS AND METHODS: A prospective, observational study was undertaken in 70 consecutive patients with high trans-sphincteric fistula treated by SSF (n = 35) or N-SSF (n = 35). Anal manometry was performed before and 3 months after surgery. Anal continence was assessed using the Cleveland Clinic Florida Incontinence Score. RESULTS: There was no difference between the two groups in age, gender, presence of horseshoe extension, preoperative incontinence score and manometric values. The incidence of recurrence was similar between the two groups. The postoperative incontinence score of the SSF group was significantly higher than that of the N-SSF group (1.9 +/- 2.9 vs 1.1 +/- 2.9, P = 0.0347). Maximum resting pressure showed significant decrease after surgery in both groups (83.2 to 56.1 mmHg, P = 0.0001 and 85.1 to 58.4 mmHg, P = 0.0001). Voluntary contraction pressure and functional anal canal length did not change after N-SSF (137.6 to 138.2 mmHg, P = 0.9524 and 4.06 to 4.07 cm, P = 0.9524), but significantly decreased after SSF (120.2 to 96.7 mmHg, P = 0.0085 and 4.12 to 3.74 cm, P = 0.0183). CONCLUSION: Non-sphincter splitting fistulectomy for high trans-sphincteric fistula provided better functional results than fistulotomy. Less impairment of anal continence was achieved possibly not only by maintenance of the external anal sphincter function but also by preservation of the length of the high-pressure zone.
Asunto(s)
Canal Anal/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Manometría/métodos , Fístula Rectal/cirugía , Adulto , Anciano , Incontinencia Fecal/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Fístula Rectal/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: This study was undertaken to determine the incidence of and risk factors for anal incontinence after fistulotomy for intersphincteric fistula-in-ano. We also evaluated the role of anal manometry in preoperative assessment of intersphincteric fistula. MATERIALS AND METHODS: A prospective, observational study was undertaken in 148 patients who underwent fistulotomy for intersphincteric fistula between January and December 2004. Functional results were assessed by standard questionnaire and anal manometry. Possible factors predicting postoperative incontinence were examined by univariate and multivariate regression analyses. RESULTS: The mean follow-up period was 12 months. Postoperative anal incontinence occurred in 30 patients (20.3%), i.e., soiling in 6, incontinence for flatus in 27, and incontinence for liquid stool in 4. Fistulotomy significantly decreased maximum resting pressure (85.9 +/- 20.4 to 60.2 +/- 18.4 mmHg, P < 0.0001) and length of the high pressure zone (3.92 +/- 0.69 to 3.82 +/- 0.77 cm, P = 0.035), but it did not affect voluntary contraction pressure (164.7 +/- 85.2 to 160.3 +/- 84.8 mmHg, P = 0.2792). Multivariate analysis showed low voluntary contraction pressure and multiple previous drainage surgeries to be independent risk factors for postoperative incontinence. CONCLUSION: Fistulotomy produces a satisfactory outcome in terms of eradicating sepsis and preserving function in the vast majority of patients with intersphincteric fistula with intact sphincters. However, sphincter-preserving treatment may be advocated for patients with low preoperative voluntary contraction pressure or those who have undergone multiple drainage surgeries. Preoperative anal manometry is useful in determining the proper surgical procedure.
Asunto(s)
Canal Anal/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Manometría/métodos , Complicaciones Posoperatorias , Fístula Rectal/cirugía , Adolescente , Adulto , Anciano , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Incontinencia Fecal/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Fístula Rectal/fisiopatología , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: Treatment of anorectal sepsis requires prompt surgical drainage, but it is important to identify any associated anal fistula for preventing recurrence. We evaluated whether microbiological analysis and/or endoanal ultrasonography could be used to predict anal fistula in patients with acute anorectal sepsis. METHODS: Five hundred fourteen consecutive patients with acute anorectal sepsis were studied. Clinical data, digital examination findings, endosonographic findings, and results of microbiological analysis were compared with definitive surgical findings of the presence or absence of anal fistula. RESULTS: Anorectal abscess with anal fistula was found in 418 patients, and anorectal abscess without anal fistula was found in 96 patients. Microbiological examination showed that Escherichia coli, Bacteroides, Bacillus, and Klebsiella species were significantly more prevalent in patients with fistula (P<0.01), and coagulase-negative Staphylococci and Peptostreptococcus species were significantly more prevalent in patients without fistula (P<0.01). Results of endoanal ultrasonography were concordant with the definitive surgical diagnosis in 421 (94%) of 448 patients studied. CONCLUSION: Acute anorectal sepsis due to colonization of "gut-derived" microorganisms rather than "skin-derived" organisms is more likely to be associated with anal fistula. When the microbiological analysis yields gut-derived bacteria, but no fistula has been found in the initial drainage operation, repeat examinations during a period of quiescence, including careful digital assessment and meticulous endosonography, are warranted to identify a potentially missed anal fistula.