RESUMEN
Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy. We describe the largest cohort of IMT patients to date, aiming to further characterize this rare, poorly understood tumor. This is a multi-institutional review of IMT patients ≤39 years, from 2000 to 2018, at 18 hospitals in the Pediatric Surgical Oncology Research Collaborative. One hundred and eighty-two patients were identified with median age of 11 years. Thirty-three percent of tumors were thoracic in origin. Presenting signs/symptoms included pain (29%), respiratory symptoms (25%) and constitutional symptoms (20%). Median tumor size was 3.9 cm. Anaplastic lymphoma kinase (ALK) overexpression was identified in 53% of patients. Seven percent of patients had distant disease at diagnosis. Ninety-one percent of patients underwent resection: 14% received neoadjuvant treatment and 22% adjuvant treatment. Twelve percent of patients received an ALK inhibitor. Sixty-six percent of surgical patients had complete resection, with 20% positive microscopic margins and 14% gross residual disease. Approximately 40% had en bloc resection of involved organs. Median follow-up time was 36 months. Overall 5-year survival was 95% and 5-year event-free survival was 80%. Predictors of recurrence included respiratory symptoms, tumor size and distant disease. Gross or microscopic margins were not associated with recurrence, suggesting that aggressive attempts at resection may not be warranted.
Asunto(s)
Oncología Quirúrgica , Niño , Humanos , Recurrencia Local de Neoplasia , Inhibidores de Proteínas Quinasas , Proteínas Tirosina Quinasas ReceptorasRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis. METHODS: A multi-institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB-HCC). Univariate and multivariate analyses identified predictors of mortality and relapse. RESULTS: In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB-HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard ratio [HR], 1.63; P = .038), elevated α-fetoprotein (HR, 3.1; P = .014), multifocality (HR, 2.4; P < .001), and PRETEXT (pretreatment extent of disease) stage IV (HR, 5.76; P < .001). Multivariate analysis identified increased mortality in cHCC versus FLC (HR, 2.2; P = .004) and in unresectable tumors (HR, 3.4; P < .001). Disease-free status at any point predicted survival. CONCLUSIONS: This multi-institutional, detailed data set allowed a comprehensive analysis of outcomes for children with these rare hepatocellular neoplasms. The current data demonstrated that pediatric HCC subtypes are not equivalent entities because FLC and cHCC have distinct anatomic patterns and outcomes in concert with their known molecular differences. This data set will be further used to elucidate the impact of histology on specific treatment responses, with the goal of designing risk-stratified algorithms for children with HCC. LAY SUMMARY: This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Oncología Quirúrgica , Carcinoma Hepatocelular/patología , Niño , Humanos , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
BACKGROUND: Infants with congenital heart disease (CHD) often experience oral feeding intolerance requiring gastrostomy (GT). Complications related to GT use are common. The study aim was to identify factors associated with continued GT use at one-year. METHODS: A retrospective cohort study was performed at a tertiary children's hospital using the Society of Thoracic Surgeons database and patients' electronic medical record. Infants <1-year with CHD who underwent cardiac and GT surgery between January 2014-October 2019 were identified. Patient demographics, preoperative feeding, clinical variables, and GT use at one-year was evaluated. A separate cohort discharged with a nasogastric tube (NGT) was identified for longitudinal comparisons. RESULTS: Of 137 infants who received a GT, 115 (84%) continued using their GT at one-year. Factors associated with continued GT use included lower median percent of goal oral feeding before GT placement (0% IQR 0-6.5 versus 3.7% IQR 0-31), prolonged hospitalization after GT placement (36% versus 14%, P-value = 0.048), and failure to take oral feeds at discharge (69% versus 27%, P-value <0.001). There was no difference in demographics or clinical comorbidities between groups. Clinic/emergency room visits for GT complications were common (72%). Eight infants discharged with a NGT did not require GT placement. CONCLUSIONS: Patients with CHD tolerating minimal oral nutrition before GT placement, prolonged hospitalization after GT, and difficulty with oral feeds at discharge were more likely to use their GT at 1-year. Outpatient NGT feeding is feasible for select infants with CHD. Efforts to optimize care for this complex, device-dependent population are warranted to minimize risks and facilitate family engagement for long-term care.
Asunto(s)
Gastrostomía , Cardiopatías Congénitas , Niño , Gastrostomía/efectos adversos , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/terapia , Humanos , Lactante , Recién Nacido , Intubación Gastrointestinal/efectos adversos , Alta del Paciente , Estudios RetrospectivosRESUMEN
INTRODUCTION: Children with congenital heart disease (CHD) often experience feeding intolerance due to aspiration, inability to tolerate feed volume, or reflux within the first few months of life, requiring a surgically placed gastrostomy tube (GT) for durable enteral access. However, complications such as GT dislodgement, cellulitis, and leakage related to GT use are common. GT-related complications can lead to unscheduled pediatric surgery clinic or emergency room (ER) visits, which can be time consuming for the family and increase overall healthcare costs. We sought to identify factors associated with GT complications within 2 wk after GT surgery and 1-y after discharge home following GT placement in infants with CHD. METHODS: We performed a retrospective cohort study using the Society of Thoracic Surgeons database and electronic medical records from a tertiary children's hospital. We identified infants <1 y old underwent CHD surgery followed by GT surgery between September 2013-August 2018. Demographics, pre-operative feeding regimen, comorbidities, and GT-related utilization were measured. Postoperative GT complications (e.g., GT cellulitis, leakage, dislodgement, obstruction, and granulation tissue) within 2 wk after the GT surgery and an unplanned pediatric surgery clinic or ER visit within 1-y after discharge home were captured. Bivariate comparisons and multivariable logistic regression evaluated factors associated with GT complications and unplanned clinic or ER visits. A Kaplan-Meier failure curve examined the timing of ER/clinic visits. RESULTS: Of 152 infants who underwent CHD then GT surgeries, 66% (N = 101) had postoperative GT complications. Overall, 83 unscheduled clinic visits were identified after discharge, with 37% (N = 31) due to concerns about granulation tissue. Of 137 ER visits, 48% (N = 66) were due to accidental GT dislodgement. Infants who were hospitalized for ≥2 wk after GT surgery had more complications than those discharged home within 2 wk of the GT surgery (40.6% versus 15.7%, P = 0.002). Infants receiving oral nutrition before CHD surgery (38.6% versus 60%, P=<0.001) or with single ventricle defects (19.8% versus 37.3%, P = 0.02) had fewer GT complications. After adjusting for type of cardiac anomaly, infants receiving oral nutrition prior to CHD surgery had a decreased likelihood of GT complications (odds ratio OR 0.46; 95% confidence intervals CI:0.23-0.93). A Kaplan-Meier failure curve demonstrated that 50% of the cohort experienced a complication leading to an unscheduled ER/clinic visit within 6 mo after discharge. CONCLUSIONS: Unplanned visits to the ER or pediatric surgery clinic occur frequently for infants with CHD requiring a surgically placed GT. Oral feedings before cardiac surgery associated with fewer GT complications. Prolonged hospitalization associated with more GT complications. Optimizing outpatient care and family education regarding GT maintenance may reduce unscheduled visits for this high-risk, device-dependent infant population.
Asunto(s)
Gastrostomía , Cardiopatías Congénitas , Humanos , Lactante , Recién Nacido , Niño , Gastrostomía/efectos adversos , Estudios Retrospectivos , Celulitis (Flemón) , Intubación Gastrointestinal/efectos adversos , Cardiopatías Congénitas/cirugía , Cardiopatías Congénitas/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
BACKGROUND: Central hepatectomy (CH) is an uncommon surgical technique that is an option for resection of centrally located tumors, with the advantage of sparing normal hepatic parenchyma. Few studies have described outcomes in children undergoing CH. MATERIALS AND METHODS: An IRB-approved, retrospective chart review of patients who underwent CH at Children's Hospital Los Angeles between 2005 and 2016 was performed. Data included patient demographics, peri-operative factors, and post-operative outcomes. The IRB approved waiver of consent. RESULTS: Eight patients (4F:4M) with median age of 1.9 Y underwent CH: 7 patients for HB and 1 patient for focal nodular hyperplasia. Two of the seven HB patients had metastatic disease at diagnosis. Six of the seven HB patients received a median of 4 rounds (3-7 rounds) of pre-operative chemotherapy. The median operative time was 197.5 Min (143-394 Min) with median blood loss of 175 mL (100-1200 mL). Complications included a bile fluid collection requiring aspiration. Seven patients had negative margins on pathology. One patient with a positive margin successfully completed therapy, without recurrent disease. All patients survived to follow-up, with a median follow-up duration of 1.1 Y (0.1-12.1 Y). Two patients developed recurrent disease requiring formal hepatic lobectomy and orthotopic liver transplantation. These patients had negative pathologic margins, with tumor within 1 mm of resection margins. CONCLUSION: CH is an effective alternative to extended hepatectomy for patients with centrally located liver tumors and is associated with good clinical and pathologic outcomes.
Asunto(s)
Neoplasias Hepáticas , Trasplante de Hígado , Niño , Hepatectomía/efectos adversos , Hepatectomía/métodos , Humanos , Neoplasias Hepáticas/secundario , Tempo Operativo , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: We aimed to determine incidence, pathologic findings, prognostic factors and clinical outcomes for patients with clinically localized papillary RCC. METHODS: Demographic, clinical and pathologic findings were collected on all patients with PRCC undergoing surgery at four academic medical centers. The primary endpoint was cancer-specific survival (CSS). Relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Kaplan-Meier estimates were obtained, and Cox proportional hazard regression models were used to assess predictors of mortality and relapse. RESULTS: We identified 626 PRCC, of which 373 (60 %) were type 1 and 253 (40 %) were type 2, with three-quarters of all tumors being pT1. Compared to patients with type 1, those with type 2 were older (mean age: 63 vs 61; p = 0.02), presented more commonly with symptoms (13 vs 7 %; p = 0.02) and had larger mean tumor size (5.2 vs 4.3 cm; p = 0.001). With a median follow-up of 41 months (IQR: 16-68), 92 patients had died of PRCC (15 %), 48 (8 %) experienced relapse, and 101 died from all causes (16 %). The estimated 5-year CSS, RFS and OS were 83, 91 and 82 %, respectively. In multivariable analysis, older age, T stage and nodal status were predictors of CSS and OS. However, PRCC subtype was not a predictor of CSS, RFS or OS. CONCLUSION: While patients with type 2 PRCC appear to present with more advanced disease than patients with type 1, PRCC subtype does not appear to be an independent predictor of CSS, RFS or OS for treated localized disease.
Asunto(s)
Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Carcinoma de Células Renales/clasificación , Carcinoma de Células Renales/patología , Femenino , Humanos , Neoplasias Renales/clasificación , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To determine whether heterogeneity of tumor grade affects the response to Bacillus Calmette-Guérin (BCG) treatment for patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: Patients with Ta or T1 NMBIC receiving a 6-week induction course of intravesical BCG therapy after transurethral resection were divided according to the tumor grade. Clinical and pathological variables were compared. Advanced intervention-free survival (AIFS), defined as duration of freedom from advanced intervention (including non-BCG intravesical agents or cystectomy) or metastasis, was plotted using Kaplan-Meier methods. The effect of grade on survival duration was assessed by multivariate Cox proportional hazards modeling. RESULTS: One hundred and fifty-three patients were identified: 17 with mixed low- and high-grade (MG) and 136 with pure high-grade (PHG) NMIBC. Demographic and additional pathologic variables were comparable between groups (p > 0.05). Five-year AIFS was 88.2% for MG patients, compared to 48.5% for PHG patients (p = 0.030 by log-rank test). On multivariate analysis, PHG was an independent risk factor for worse AIFS (HR 4.4, 95% CI 1.1-18.4, p = 0.040). Among patients failing to respond to primary BCG induction, who underwent a secondary induction of BCG with interferon, MG patients had better response than PHG patients (100 vs. 26.3%, p = 0.035). CONCLUSIONS: Mixed low- and high-grade NMIBC exhibits a significantly better response profile to intravesical BCG therapy compared to PHG NMIBC. The implications of these results are that less aggressive treatment strategies for this unique cancer entity may be needed and that there is a benefit to the reporting of tumor heterogeneity in transurethral resection of bladder tumor specimens.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Vacuna BCG/uso terapéutico , Carcinoma de Células Transicionales/terapia , Cistectomía , Músculo Liso/patología , Neoplasias de la Vejiga Urinaria/terapia , Vejiga Urinaria/patología , Administración Intravesical , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/patología , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Small-molecule CCR5 inhibitors such as vicriviroc (VVC) and maraviroc (MVC) are allosteric modulators that impair HIV-1 entry by stabilizing a CCR5 conformation that the virus recognizes inefficiently. Viruses resistant to these compounds are able to bind the inhibitor-CCR5 complex while also interacting with the free coreceptor. CCR5 also interacts intracellularly with G proteins, as part of its signal transduction functions, and this process alters its conformation. Here we investigated whether the action of VVC against inhibitor-sensitive and -resistant viruses is affected by whether or not CCR5 is coupled to G proteins such as Gαi. Treating CD4(+) T cells with pertussis toxin to uncouple the Gαi subunit from CCR5 increased the potency of VVC against the sensitive viruses and revealed that VVC-resistant viruses use the inhibitor-bound form of Gαi-coupled CCR5 more efficiently than they use uncoupled CCR5. Supportive evidence was obtained by expressing a signaling-deficient CCR5 mutant with an impaired ability to bind to G proteins, as well as two constitutively active mutants that activate G proteins in the absence of external stimuli. The implication of these various studies is that the association of intracellular domains of CCR5 with the signaling machinery affects the conformation of the external and transmembrane domains and how they interact with small-molecule inhibitors of HIV-1 entry.
Asunto(s)
Farmacorresistencia Viral , Proteínas de Unión al GTP/metabolismo , Inhibidores de Fusión de VIH/farmacología , VIH-1/efectos de los fármacos , Receptores CCR5/metabolismo , Fármacos Anti-VIH/farmacología , Antagonistas de los Receptores CCR5 , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/virología , Línea Celular , Ciclohexanos/farmacología , Células HEK293/virología , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , VIH-1/metabolismo , Humanos , Maraviroc , Toxina del Pertussis/farmacología , Piperazinas/farmacología , Pirimidinas/farmacología , Receptores CCR5/genética , Transfección , Triazoles/farmacología , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
BACKGROUND: Surgical resection is a mainstay of treatment in high-risk neuroblastoma (HR-NB), but there exists wide variability in perioperative management practices. The aim of this study was to evaluate two standardized adult perioperative enhanced recovery practices (ERPs) in pediatric patients undergoing open resection of abdominal HR-NB. METHODS: All patients with abdominal HR-NB surgically resected at a free-standing children's hospital between 12/2010 and 7/2020 were retrospectively reviewed. Perioperative ERPs of interest included avoidance of routine nasogastric tube (NGT) use and the use of neuraxial anesthesia. Primary outcomes included time to enteral intake, urinary catheter use, opioid utilization, and length of stay (LOS). RESULTS: Overall, 37 children, median age 33 months (IQR: 20-48 months), were identified. Avoidance of an NGT allowed for earlier feeding after surgery (P = .03). Neuraxial anesthesia use more frequently required an indwelling urinary catheter (P < .01) for a longer duration (P = .02), with no difference in total opioid utilization (P = .77) compared to patients without neuraxial anesthesia. Postoperative LOS was unaffected by avoidance of routine NGT use (P = .68) or use of neuraxial anesthesia (P = .89). CONCLUSION: Children undergoing open resection of abdominal HR-NB initiated diet sooner when an NGT was not left postoperatively, and the need for a urinary catheter was significantly higher in patients who received neuraxial anesthesia. However, these two ERP components did not decrease postoperative LOS. To optimize the postoperative management of NB patients, postoperative NGTs should be avoided, while the benefit of neuraxial anesthesia is less clear as it necessitates the placement of a urinary catheter without decreasing opioid utilization.
Asunto(s)
Tiempo de Internación , Neuroblastoma , Humanos , Neuroblastoma/cirugía , Masculino , Femenino , Estudios Retrospectivos , Preescolar , Lactante , Tiempo de Internación/estadística & datos numéricos , Cuidados Posoperatorios/métodos , Neoplasias Abdominales/cirugía , Recuperación Mejorada Después de la Cirugía , Analgésicos Opioides/uso terapéutico , Intubación Gastrointestinal , Cateterismo UrinarioRESUMEN
BACKGROUND: Gabapentin is increasingly used as an off-label, opioid-sparing pain medication in children. We investigated perioperative gabapentin administration and postoperative opioid use in children who underwent appendectomy for perforated appendicitis. METHODS: A retrospective cohort study of healthy children ages 2-18 years undergoing appendectomy for perforated appendicitis from 2014 to 2019 was performed using the Pediatric Health Information System®. Propensity score matched (PSM) analysis was conducted with 1:1 matching based on patient and hospital characteristics. Multivariable linear regression analysis was used to evaluate an association between gabapentin, postoperative opioid use, and postoperative length of stay. RESULTS: Of 29,467 children with perforated appendicitis who underwent appendectomy, 236 (0.8%) received gabapentin. In 2014, <10 children received gabapentin, but by 2019, 110 children received gabapentin. On univariate analysis of the PSM cohort, children receiving gabapentin had decreased total postoperative opiate use (2.3 SD ± 2.3 versus 3.0 SD ± 2.5 days, p < 0.001). On adjusted analysis, children receiving gabapentin had 0.65 fewer days of postoperative total opioid use (95% CI: -1.09, -0.21) and spent 0.69 fewer days in the hospital after surgery (95% CI: -1.30, -0.08). CONCLUSION: While overall use is infrequent, gabapentin is increasingly administered to children with perforated appendicitis who undergo an appendectomy and is associated with decreased postoperative opioid use and reduced postoperative length of stay. Multimodal pain management strategies incorporating gabapentin may reduce postoperative opioid consumption, but further studies of drug safety are needed for this off-label use in children undergoing surgery. LEVEL OF EVIDENCE: III.
Asunto(s)
Analgésicos Opioides , Apendicitis , Humanos , Niño , Gabapentina/uso terapéutico , Analgésicos Opioides/uso terapéutico , Apendicectomía , Apendicitis/complicaciones , Apendicitis/tratamiento farmacológico , Apendicitis/cirugía , Puntaje de Propensión , Estudios Retrospectivos , Tiempo de InternaciónRESUMEN
C-C motif chemokine ligand 2 (CCL2) is a monocyte chemoattractant that promotes metastatic disease and portends a poor prognosis in many cancers. To determine the potential of anti-CCL2 inhibition as a therapy for recurrent metastatic disease in neuroblastoma, a mouse model of minimal residual disease was utilized in which residual disease was treated with anti-CCL2 monoclonal antibody with etoposide. The effect of anti-CCL2 antibody on neuroblastoma cells was determined in vitro with cell proliferation, transwell migration, and 2-dimensional chemotaxis migration assays. The in vivo efficacy of anti-CCL2 antibody and etoposide against neuroblastoma was assessed following resection of primary tumors formed by two cell lines or a patient-derived xenograft (PDX) in immunodeficient NOD-scid gamma mice. In vitro, anti-CCL2 antibody did not affect cell proliferation but significantly inhibited neuroblastoma cell and monocyte migration towards an increasing CCL2 concentration gradient. Treatment of mice with anti-CCL2 antibody combined with etoposide significantly increased survival of mice after resection of primary tumors, compared to untreated mice.
Asunto(s)
Neuroblastoma , Humanos , Animales , Ratones , Etopósido/farmacología , Etopósido/uso terapéutico , Ligandos , Neoplasia Residual/tratamiento farmacológico , Ratones Endogámicos NOD , Neuroblastoma/patología , Quimiocinas , Quimiocina CCL2 , Línea Celular TumoralRESUMEN
Resistance to small-molecule CCR5 inhibitors arises when HIV-1 variants acquire the ability to use inhibitor-bound CCR5 while still recognizing free CCR5. Two isolates, CC101.19 and D1/85.16, became resistant via four substitutions in the gp120 V3 region and three in the gp41 fusion peptide (FP), respectively. The binding characteristics of a panel of monoclonal antibodies (MAbs) imply that several antigenic forms of CCR5 are expressed at different levels on the surfaces of U87-CD4-CCR5 cells and primary CD4(+) T cells, in a cell-type-dependent manner. CCR5 binding and HIV-1 infection inhibition experiments suggest that the two CCR5 inhibitor-resistant viruses altered their interactions with CCR5 in different ways. As a result, both mutants became generally more sensitive to inhibition by CCR5 MAbs, and the FP mutant is specifically sensitive to a MAb that stains discrete cell surface clusters of CCR5 that may correspond to lipid rafts. We conclude that some MAbs detect different antigenic forms of CCR5 and that inhibitor-sensitive and -resistant viruses can use these CCR5 forms differently for entry in the presence or absence of CCR5 inhibitors.
Asunto(s)
Fármacos Anti-VIH/farmacología , Antagonistas de los Receptores CCR5 , Proteína gp120 de Envoltorio del VIH/metabolismo , Proteína gp41 de Envoltorio del VIH/metabolismo , VIH-1/efectos de los fármacos , Piperazinas/farmacología , Pirimidinas/farmacología , Receptores CCR5/metabolismo , Proteínas Virales de Fusión/metabolismo , Anticuerpos Monoclonales/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/virología , Línea Celular , Membrana Celular , Ciclohexanos/farmacología , Farmacorresistencia Viral , Epítopos , Citometría de Flujo , Células HEK293 , Proteína gp120 de Envoltorio del VIH/genética , Proteína gp41 de Envoltorio del VIH/genética , VIH-1/genética , VIH-1/metabolismo , Humanos , Maraviroc , Microdominios de Membrana , Microscopía Fluorescente , Receptores CCR5/inmunología , Triazoles/farmacología , Proteínas Virales de Fusión/genética , Internalización del Virus/efectos de los fármacosRESUMEN
BACKGROUND: Ketorolac is an opioid sparing agent commonly used in children. However, ketorolac may be avoided in children with peritonitis owing to a possible increased risk of bleeding. METHODS: A retrospective cohort study of healthy children 2-18 years who underwent appendectomy for perforated appendicitis was performed using the Pediatric Health Information System (2009-2019). Multivariable logistic regression was used to evaluate the association between perioperative ketorolac use and postoperative blood transfusions within 30 days of surgery, adjusting for patient and hospital level factors. An interaction between ketorolac and ibuprofen was evaluated to identify synergistic effects. RESULTS: Overall, 55,603 children with perforated appendicitis underwent appendectomy and 82.3% (N = 45,769) received ketorolac. Of those, 32% (N = 14,864) also received ibuprofen. Receipt of a blood transfusion was infrequent (N = 189, 0.3%). On multivariable logistic regression analysis, perioperative ketorolac administration was associated with decreased odds of a blood transfusion (OR 0.53, 95% CI: 0.35-0.79). However, children receiving ketorolac and ibuprofen were more likely to require a blood transfusion (OR 1.99, 95% CI: 1.42-2.79). In a subset of children receiving ketorolac, each additional day of ketorolac was associated with an increase odds of blood transfusion (OR 1.39, 95% CI: 1.30-1.49). CONCLUSION: Perioperative ketorolac alone is not associated with an increased risk of significant bleeding in children undergoing appendectomy for perforated appendicitis. However, use of both ketorolac and ibuprofen during hospitalization was associated with increased risk of bleeding, although precise timing of administration of these medications was unable to be determined. Extended ketorolac use was also associated with increased risk of bleeding requiring blood transfusion. LEVEL OF EVIDENCE: Level III.
Asunto(s)
Apendicectomía , Apendicitis , Apendicectomía/efectos adversos , Apendicitis/cirugía , Niño , Hemorragia/etiología , Humanos , Ibuprofeno/efectos adversos , Ketorolaco/efectos adversos , Estudios RetrospectivosRESUMEN
Introduction: Isolated seminal vesicle cysts not associated with Zinner syndrome is a rare disorder that can present initially with urinary obstructive symptoms or nonspecific groin pain. Case description: We present the uncommon case of a dermoid cyst mimicking a seminal vesicle cyst treated with robotic-assisted laparoscopic seminal vesiculectomy. Conclusion: For dermoid cysts, surgical excision is the gold standard of treatment with a high cure rate and little risk of regrowth if spillage is avoided and full resection is completed. Robotic-assisted laparoscopic surgery is a viable management option with good visualization of the anatomy.
RESUMEN
This review discusses complications unique to pediatric surgical populations. Here the authors focus primarily on five of the most common procedures performed in children: appendectomy, central venous catheterization, pyloromyotomy, gastrostomy, and inguinal/umbilical hernia repair.
Asunto(s)
Procedimientos Quirúrgicos Operativos/efectos adversos , Apendicectomía/efectos adversos , Apendicectomía/métodos , Apendicitis/terapia , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/métodos , Niño , Gastrostomía/efectos adversos , Gastrostomía/instrumentación , Hernia Inguinal/cirugía , Herniorrafia/efectos adversos , Humanos , Venas Yugulares/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Estenosis Hipertrófica del Piloro/complicaciones , Estenosis Hipertrófica del Piloro/cirugía , Estenosis Hipertrófica del Piloro/terapia , Piloromiotomia/efectos adversosRESUMEN
BACKGROUND AND OBJECTIVES: Prior research shows an association between increased length of stay (LOS) and weekend surgical admissions, but none have looked at this relationship in children undergoing nonelective cholecystectomy for benign noncongenital biliary disease. We investigated whether weekend admissions lead to a longer LOS in this patient population. METHODS: The Statewide Planning and Research Cooperative System database was queried for children ≤ 17 years undergoing cholecystectomy in New York State between January 1, 2009 and December 31, 2012. Parametric and nonparametric statistical testing was used for univariate analysis; multivariable binary logistic regression and linear regression models were used for multivariable analysis. Statistical significance was < 0.05. RESULTS: A total of 1066 pediatric patients underwent nonelective cholecystectomy for gallstone pancreatitis (9.7%) and other benign biliary noncongenital diseases (90.3%), of which 22.1% of all patients were admitted over the weekend. Most cases (97.2%) were treated laparoscopically with an overall 3-day median LOS. Weekend admission was associated with an increased LOS of 4 days as opposed to 3 days during the weekday (p < 0.001). On a multivariable binary logistic regression model controlling for hospital factors, indication for surgery, and comorbidities, weekend admission was associated with 1.92 odds of increased length of stay (adjusted odds ratio of 1.924, 95% confidence interval: 1.386-2.673). CONCLUSION: Weekend admissions were associated with increased LOS and charges for children requiring nonelective cholecystectomy, despite the wide use of laparoscopic surgery.
Asunto(s)
Colecistectomía , Hospitalización , Niño , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Immunotherapy with anti-disialoganglioside dinutuximab has improved survival for children with high-risk neuroblastoma (NB) when given after induction chemotherapy and surgery. However, disease recurrence and resistance persist. Dinutuximab efficacy has not been evaluated when initiated before primary tumor removal. Using a surgical mouse model of human NB, we examined if initiating dinutuximab plus ex vivo-activated natural killer (aNK) cells before resection of the primary tumor improves survival. METHODS: In vitro, human NB cells (SMS-KCNR-Fluc, CHLA-255-Fluc) were treated with dinutuximab and/or aNK cells and cytotoxicity was measured. In vivo, NB cells (SMS-KCNR-Fluc, CHLA-255-Fluc, or COG-N-415x PDX) were injected into the kidney of NOD-scid gamma mice. Mice received eight intravenous infusions of aNK cells plus dinutuximab beginning either 12 days before or 2 days after resection of primary tumors. Tumors in control mice were treated by resection alone or with immunotherapy alone. Disease was quantified by bioluminescent imaging and survival was monitored. aNK cell infiltration into primary tumors was quantified by flow cytometry and immunohistochemistry at varying timepoints. RESULTS: In vitro, aNK cells and dinutuximab were more cytotoxic than either treatment alone. In vivo, treatment with aNK cells plus dinutuximab prior to resection of the primary tumor was most effective in limiting metastatic disease and prolonging survival. aNK cell infiltration into xenograft tumors was observed after 1 day and peaked at 5 days following injection. CONCLUSION: Dinutuximab plus aNK cell immunotherapy initiated before resection of primary tumors decreases disease burden and prolongs survival in an experimental mouse model of NB. These findings support the clinical investigation of this treatment strategy during induction therapy in patients with high-risk NB.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Inmunoterapia/métodos , Células Asesinas Naturales/inmunología , Neuroblastoma/tratamiento farmacológico , Animales , Anticuerpos Monoclonales/farmacología , Humanos , Ratones , Neuroblastoma/mortalidad , Análisis de SupervivenciaRESUMEN
BACKGROUND: To compare oncologic outcomes of different definitive treatment (DT) modalities in a cohort of patients with prostate cancer (PCa) after active surveillance (AS). METHODS: We identified 237 patients with National Comprehensive Cancer Network (NCCN) low- and intermediate-risk prostate cancer diagnosed from 1990 to 2012 who did not undergo immediate DT within 12 months of diagnosis (ie, AS patients as well as watchful waiting and those refusing DT). Charts were examined for clinical/pathologic data and type of DT: surgery (RP), radiation including brachytherapy (XRT), cryotherapy, and androgen deprivation therapy monotherapy (ADT). The impact of DT on oncologic outcomes of biochemical recurrence (BCR), metastasis, disease-specific (DSS), and overall survival (OS) was examined with the Cox proportional hazards model, along with the Kaplan-Meier method and log-rank test. RESULTS: After median time on AS of 63.4 months, 40% of patients underwent DT: 47% XRT, 28% RP, 14% ADT, and 11% cryotherapy. On multivariable analysis, the use of XRT predicted higher BCR (hazard ratio [HR] 6.1, P = .001) and worse overall mortality (HR 2.1, P = .03) compared with other treatments, controlling for age, Charlson Comorbidity Index (CCI), stage, Gleason score, and NCCN risk category. Median follow-up was 71.7 months. On Kaplan-Meier analysis, 10-year OS was superior for RP versus XRT among patients with prostatic specific antigen (PSA) velocity >2.0 ng/mL/y. CONCLUSIONS: Low- and intermediate-risk patients with PCa who progress to DT after AS may be inadequately treated with radiation therapy compared with other DT modalities, especially when pretreatment PSA velocity is > 2 ng/mL/y.
Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Braquiterapia/métodos , Crioterapia/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/terapia , Anciano , Supervivencia sin Enfermedad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Factores de Riesgo , Espera VigilanteRESUMEN
INTRODUCTION: Partial cystectomy use has historically been limited by stringent selection criteria. We compared outcomes following partial cystectomy at our institution with those in other contemporary series. Also, we specifically characterized outcomes in patients with tumors in bladder locations traditionally considered unamenable to partial cystectomy. METHODS: Patients who underwent partial cystectomy for primary bladder cancer from 1990 to 2012 were identified from our database. Clinical and pathological data were reviewed. Survival analyses were performed using Kaplan-Meier methods. Cox regression was done to identify factors associated with survival and recurrence. RESULTS: A total of 55 patients were included in analysis. Five-year overall, disease specific and recurrence-free survival was 70.3%, 77.0% and 39.4%, respectively. When controlling for clinical and pathological covariates, lymphovascular invasion predicted decreased recurrence-free survival (HR 10.6, p = 0.025). Perioperative morbidity and mortality rates were 4% and 5%, respectively. In 8 patients (15%) trigone tumors required ureteral reimplantation. Two of the 8 patients (25%) experienced complications, including hydronephrosis and bladder neck contracture, which were treated conservatively. Cancer recurred in 2 of the 8 patients (25%) and both were treated successfully. None of the 8 patients died of bladder cancer. CONCLUSIONS: Patients treated with partial cystectomy for primary bladder cancer had satisfactory cancer control and favorable perioperative morbidity consistent with other contemporary reports. Patients with tumors in the bladder trigone, historically considered poor candidates for partial cystectomy, also had good oncologic outcomes without significant complications related to reimplantation. Our data further support partial cystectomy in select patients with bladder cancer.