RESUMEN
OBJECTIVES: Imaging appearances of immune checkpoint inhibitor-related nephritis have not yet been described. The primary objective of this study is to describe the appearances of immunotherapy-related nephritis on computerized tomography (CT) and positron emission tomography (PET). The secondary objectives are to investigate the association of radiologic features with clinical outcomes. METHODS: CT and PET-CT scans before the initiation of immunotherapy (baseline), at nephritis, and after resolution of pathology-proven nephritis cases were reviewed. Total kidney volume, renal parenchymal SUVmax, renal pelvis SUVmax, and blood pool SUVmean were obtained. RESULTS: Thirty-four patients were included. The total kidney volume was significantly higher at nephritis compared to baseline (464.7 ± 96.8 mL vs. 371.7 ± 187.7 mL; p < 0.001). Fifteen patients (44.1%) had > 30% increase in total kidney volume, which was associated with significantly higher renal toxicity grade (p = 0.007), higher peak creatinine level (p = 0.004), and more aggressive medical treatment (p = 0.011). New/increasing perinephric fat stranding was noted in 10 patients (29.4%) at nephritis. Among 8 patients with contrast-enhanced CT at nephritis, one (12.5%) developed bilateral wedge-shaped hypoenhancing cortical. On PET-CT, the renal parenchymal SUVmax-to-blood pool ratio was significantly higher at nephritis compared to baseline (2.13 vs. 1.68; p = 0.035). The renal pelvis SUVmax-to-blood pool SUVmean ratio was significantly lower at nephritis compared to baseline (3.47 vs. 8.22; p = 0.011). CONCLUSIONS: Bilateral increase in kidney size, new/increasing perinephric stranding, and bilateral wedge-shaped hypoenhancing cortical foci can occur in immunotherapy-related nephritis. On PET-CT, a diffuse increase in radiotracer uptake throughout the renal cortex and a decrease in radiotracer activity in the renal pelvis can be seen. KEY POINTS: ⢠CT features of immune checkpoint inhibitor-related nephritis include an increase in kidney volume, new/increasing perinephric stranding, and bilateral ill-defined wedge-shaped hypoenhancing cortical foci. ⢠FDG-PET features of immune checkpoint inhibitor-related nephritis include an increase in FDG uptake throughout the renal cortex and a decrease in FDG activity/excretion in the collecting system. ⢠> 30% increase in total kidney volume is associated with worse toxicity grade and more aggressive medical management.
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Nefritis , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Inhibidores de Puntos de Control Inmunológico , Radiofármacos , Estudios Retrospectivos , Nefritis/inducido químicamente , Nefritis/diagnóstico por imagenRESUMEN
BACKGROUND: There are few studies describing aminoglycoside pharmacokinetics during continuous renal replacement therapy (CRRT). OBJECTIVE: To characterize the effect of CRRT on aminoglycoside clearance and volume of distribution (Vd). METHODS: Retrospective observational pharmacokinetic study of adult critically ill oncologic patients who received a first dose of amikacin or tobramycin during CRRT between February 2012 and May 2017. Study outcomes included aminoglycoside clearance, Vd, and attainment of the target peak: MIC (minimum inhibitory concentration) ratio as a surrogate for dosing appropriateness. RESULTS: In total, 80 patients were included, sustained low-efficiency dialysis (SLED), n = 49; continuous venovenous hemodialysis (CVVHD), n = 19; continuous venovenous hemofiltration (CVVH), n = 12. Fifty-one patients received amikacin at a median dose of 14.5 mg/kg per actual body weight and achieved a median peak level of 26.7 mg/L. Twenty-nine patients received tobramycin at a median dose of 6.5 mg/kg actual body weight and achieved a median peak level of 10.3 mg/L. The median aminoglycoside clearance was 63.1 mL/min and was similar between CRRT modality groups (P = 0.97). The median Vd was 0.47 L/kg and was different between the SLED and CVVH groups (P = 0.007). Attainment of target peak: MIC occurred in 29% in the total study population and 44% in the subgroup of 23 patients with isolates tested for aminoglycoside susceptibility. CONCLUSION AND RELEVANCE: Critically ill oncology patients undergoing CRRT exhibited reduced clearance and expanded Vd that was not significantly different between CRRT modalities. Current dosing regimens led to low peak concentrations and poor attainment of pharmacokinetic targets.
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Terapia de Reemplazo Renal Continuo , Adulto , Humanos , Aminoglicósidos/uso terapéutico , Amicacina , Estudios Retrospectivos , Enfermedad Crítica/terapia , Antibacterianos , Tobramicina , Terapia de Reemplazo RenalRESUMEN
Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.
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Carcinoma de Células Escamosas , Trasplante de Riñón , Neoplasias Cutáneas , Carcinoma de Células Escamosas/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico , Trasplante de Riñón/efectos adversos , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
With the increasing use of immunotherapy, there has been an associated increased survival in many cancers but has also resulted in unregulated organ-specific toxicities. In this review, we will discuss the renal toxicities associated with a checkpoint inhibitor (CPI) from the typical acute tubulointerstitial nephritis to glomerulonephritis and their proposed mechanisms and treatments. We also discuss the use of CPI and reactivation of preexisting autoimmune disease with a focus on renal cell cancer in setting of chronic kidney disease (CKD). Transplant rejection in setting of CPI use has been further evaluated with single-center and multicenter retrospective studies, and available data will be presented in this chapter.
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Neoplasias , Nefritis Intersticial , Insuficiencia Renal Crónica , Humanos , Inmunoterapia , Estudios Multicéntricos como Asunto , Estudios RetrospectivosRESUMEN
BACKGROUND: Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse. METHODS: We conducted a multicenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI. RESULTS: Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. CONCLUSIONS: This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.
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Lesión Renal Aguda/inducido químicamente , Antígeno B7-H1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/terapia , Anciano , Femenino , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Nefritis Intersticial/inducido químicamente , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: BK polymavirus (BKPyV), a member of the family Polyomaviridae, is associated with increased morbidity and mortality in allogeneic stem cell transplant recipients. METHODS: In our previous retrospective study of 2477 stem cell transplant patients, BKPyV replication independently predicted chronic kidney disease and poor survival. In this study, using the same cohort, we derived and validated a risk grading system to identify patients at risk of BKPyV replication after transplantation in a user-friendly modality. We used 3 baseline variables (conditioning regimen, HLA match status, and underlying cancer diagnosis) that significantly predicted BKPyV replication in our initial study in a subdistribution hazard model with death as a competing risk. We also developed a nomogram of the hazard model as a visual aid. The AUC of the ROC of the risk-score-only model was 0.65. We further stratified the patients on the basis of risk score into low-, moderate-, and high-risk groups. RESULTS: The total risk score was significantly associated with BKPyV replication (P < .0001). At 30 days after transplantation, the low-risk (score ≤ 0) patients had a 9% chance of developing symptomatic BKPyV replication, while the high-risk (score ≥ 8) of the population had 56% of developing BKPyV replication. We validated the risk score using a separate cohort of 1478 patients. The AUC of the ROC of the risk-score-only model was 0.59. Both the total risk score and 3-level risk variable were significantly associated with BKPyV replication in this cohort (P < .0001). CONCLUSIONS: This grading system for the risk of symptomatic BKPyV replication may help in early monitoring and intervention to prevent BKPyV-associated morbidity, mortality, and kidney function decline.
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Virus BK , Trasplante de Células Madre Hematopoyéticas , Trasplante de Riñón , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Humanos , Estudios Retrospectivos , Medición de Riesgo , Trasplante de Células Madre , Receptores de TrasplantesRESUMEN
With the increasing use of immunotherapy, there has been an associated increased survival in many cancers but has also resulted in unregulated organ-specific toxicities. In this chapter, we discuss the renal toxicities associated with a checkpoint inhibitor (CPI) from the typical acute tubulointersitial nephritis to glomerulonephritis, their proposed mechanisms, and treatments. We also discuss the use of CPI and reactivation of preexisting auto-immune diseases and focus on renal cell cancer in setting of Chronic kidney disease (CKD). Transplant rejection in the setting of CPI use is yet to be further studied, and available data is presented in this chapter.
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Rechazo de Injerto/inducido químicamente , Inmunoterapia/efectos adversos , Neoplasias/terapia , Nefritis/inducido químicamente , Rechazo de Injerto/inmunología , Humanos , Neoplasias/complicaciones , Neoplasias/inmunología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/cirugíaRESUMEN
Recent evidence suggests that renal dysfunction may be a direct consequence of primary myelofibrosis (PMF). We performed a retrospective analysis of 100 patients with previously untreated PMF, receiving frontline treatment with single agent ruxolitinib, and compared them to 105 patients, receiving frontline treatment with a non-ruxolitinib-based therapy, matched by age, sex, DIPSS plus, and estimated glomerular filtration rate (eGFR). Use of ruxolitinib associated with a significantly higher rate of renal improvement (RI) > 10% (73% vs 50%, p = 0.01) confirmed on multivariate analysis (MVA) [odds ratio 3, 95% confidence interval (CI) 1.6-5.5, p < 0.001]. After a median follow-up of 41 months (range, 1-159 months), median failure-free survival (FFS) was 14 months (range, 1-117 months). Achievement of a RI > 10% maintained its independent association with prolonged FFS on MVA (hazard ratio 1.4, 95% CI 1.1-2, p = 0.02). Ruxolitinib can significantly improve renal function in patients with PMF, significantly impacting failure-free survival.
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Bases de Datos Factuales , Tasa de Filtración Glomerular/efectos de los fármacos , Riñón , Mielofibrosis Primaria , Pirazoles/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Riñón/metabolismo , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Nitrilos , Mielofibrosis Primaria/tratamiento farmacológico , Mielofibrosis Primaria/metabolismo , Mielofibrosis Primaria/mortalidad , Mielofibrosis Primaria/fisiopatología , Pirimidinas , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Intervention strategies in familial adenomatous polyposis (FAP) patients and other high-risk colorectal cancer (CRC) populations have highlighted a critical need for endoscopy combined with safe and effective preventive agents. We performed transcriptome profiling of colorectal adenomas from FAP patients and the polyposis in rat colon (Pirc) preclinical model, and prioritized molecular targets for prevention studies in vivo. At clinically relevant doses in the Pirc model, the drug Clotam (tolfenamic acid, TA) was highly effective at suppressing tumorigenesis both in the colon and in the small intestine, when administered alone or in combination with Sulindac. Cell proliferation in the colonic crypts was reduced significantly by TA, coincident with increased cleaved caspase-3 and decreased Survivin, ß-catenin, cyclin D1 and matrix metalloproteinase 7. From the list of differentially expressed genes prioritized by transcriptome profiling, Mmp7, S100a9, Nppb and Aldh1a3 were defined as key oncogene candidates downregulated in colon tumors after TA treatment. Monthly colonoscopies revealed the rapid onset of tumor suppression by TA in the Pirc model, and the temporal changes in Mmp7, S100a9, Nppb and Aldh1a3, highlighting their value as potential early biomarkers for prevention in the clinical setting. We conclude that TA, an "old drug" repurposed from migraine, offers an exciting new therapeutic avenue in FAP and other high-risk CRC patient populations.
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Adenoma/tratamiento farmacológico , Poliposis Adenomatosa del Colon/tratamiento farmacológico , Aldehído Oxidorreductasas/genética , Calgranulina B/genética , Neoplasias Colorrectales/tratamiento farmacológico , Metaloproteinasa 7 de la Matriz/genética , ortoaminobenzoatos/farmacología , Adenoma/genética , Poliposis Adenomatosa del Colon/genética , Animales , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Caspasa 3/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Neoplasias Colorrectales/genética , Ciclina D1/genética , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Perfilación de la Expresión Génica/métodos , Humanos , Masculino , Oncogenes/genética , Ratas , beta Catenina/genéticaRESUMEN
BACKGROUND: BK polyomavirus (BKPyV) infections are known indicators of immune suppression in hematopoietic stem cell transplant (HSCT) recipients; they can lead to hemorrhagic cystitis, ureteral stenosis, renal dysfunction, and prolonged hospital stays. In this study, we determined transplant-associated variables and immune parameters that can predict for the risk of BKPyV viruria. We hypothesized that BKPyV infection is a marker of poor immune recovery. METHODS: We analyzed all engrafted patients undergoing first allogeneic HSCT at MD Anderson Cancer Center in Houston between January 2004 and December 2012. We evaluated their immune parameters and their transplant-associated factors. BKPyV positivity was defined as BKPyV detection in urine by polymerase chain reaction testing. Cox proportional hazards model, as well as competing risk analysis method using subdistribution hazard models with death as competing risk, were applied to assess risk of BKPyV viruria. RESULTS: We identified a total of 2477 patients with a median age of 52 years. BKPyV viruria was manifest in 25% (n=629) of the patients. The median time from transplantation to BKPyV viruria development was 42 days among the patients who had BKPyV viruria. On multivariate analysis, tumor type, acute GVHD, chronic GVHD, myeloablative conditioning regimen, cord blood as the graft source, CD3+ , CD4+ , CD8+ , CD56+ , NK counts, and low platelet count were shown to be significantly associated with BKPyV infection. These finding were further confirmed when models incorporating the competing risk of death yielded similar findings. CONCLUSION: In this study, we report significant associations between BKPyV reactivation following allogeneic HSCT and suppressed immune variables. In addition, this study provides valuable information on the immune status of HSCT recipients as a predictor of BKPyV infections that may in turn help us formulate plans for more effective prevention and treatment of this infection.
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Virus BK/fisiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones por Polyomavirus/inmunología , Acondicionamiento Pretrasplante/efectos adversos , Infecciones Tumorales por Virus/inmunología , Enfermedades Urológicas/inmunología , Activación Viral/inmunología , Virus BK/aislamiento & purificación , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/efectos adversos , Agonistas Mieloablativos/uso terapéutico , Infecciones por Polyomavirus/orina , Infecciones por Polyomavirus/virología , Estudios Retrospectivos , Medición de Riesgo , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/efectos adversos , Infecciones Tumorales por Virus/orina , Infecciones Tumorales por Virus/virología , Enfermedades Urológicas/orina , Enfermedades Urológicas/virologíaRESUMEN
BACKGROUND: Hypermagnesemia is rare and usually iatrogenic. Due to decreased renal function, older patients are generally more susceptible to hypermagnesemia than are younger patients. Because it is not one of the commonly assessed electrolytes in the blood work panel of patients, high levels are usually missed. CASE REPORT: An elderly gentleman with history of leukemia presented with complaints of shortness of breath and extreme weakness while walking. He was diagnosed with severe hypermagnesemia, but unfortunately succumbed to cardiorespiratory arrest. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Thorough history taking is crucial in evaluating weakness in elderly patients because the differential diagnosis is vast. Prompt consultation for emergent dialysis is critical to avoiding unfavorable outcomes due to electrolyte abnormalities.
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Magnesio/sangre , Resultado del Tratamiento , Anciano de 80 o más Años , Bradicardia/etiología , Humanos , Hipotensión/etiología , Magnesio/análisis , Masculino , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Insuficiencia Renal Crónica/complicaciones , Resucitación/métodosRESUMEN
The antidiabetic drug metformin exhibits both chemopreventive and chemotherapeutic activity for multiple cancers including pancreatic cancer; however, the underlying mechanism of action of metformin is unclear. A recent study showed that metformin down-regulated specificity protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 in pancreatic cancer cells and tumors, and this was accompanied by down-regulation of several pro-oncogenic Sp-regulated genes. Treatment with metformin or down-regulation of Sp TFs by RNAi also inhibits two major pro-oncogenic pathways in pancreatic cancer cells, namely mammalian target of rapamycin (mTOR) signaling and epidermal growth factor (EGFR)-dependent activation of Ras. Metformin and Sp knockdown by RNAi decreased expression of the insulin-like growth factor-1 receptor (IGF-1R), resulting in inhibition of mTOR signaling. Ras activity was also decreased by metformin and Sp knockdown of EGFR, another Sp-regulated gene. Thus, the antineoplastic activities of metformin in pancreatic cancer are due, in part, to down-regulation of Sp TFs and Sp-regulated IGF-1R and EGFR, which in turn results in inhibition of mTOR and Ras signaling, respectively.
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Antineoplásicos/farmacología , Metformina/farmacología , Neoplasias Pancreáticas/genética , Factores de Transcripción Sp/genética , Serina-Treonina Quinasas TOR/genética , Proteínas ras/genética , Animales , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Desnudos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Transducción de Señal , Factores de Transcripción Sp/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Proteínas ras/antagonistas & inhibidores , Proteínas ras/metabolismo , Neoplasias PancreáticasRESUMEN
BACKGROUND: Primary myelofibrosis (PMF) is a type of myeloproliferative neoplasm (MPN) characterized by the predominant proliferation of megakaryocytes and granulocytes in the bone marrow, leading to the deposition of fibrous tissue, and by a propensity toward extramedullary hematopoiesis. Renal involvement in PMF is rare, but kidney tissue samples from these patients reveal MPN-related glomerulopathy, a recently discovered condition, in the late stages of the disease. CASE PRESENTATION: We present the first case described in the medical literature of a patient with early renal glomerular involvement in PMF/MPN. A 60-year-old man with stage 4 chronic kidney disease and a recent diagnosis of PMF (within 4 weeks of presentation at our renal division) presented with generalized body swelling, acute kidney injury, and massive nephrotic-range proteinuria. Kidney biopsy was performed to determine the etiology of the patient's renal dysfunction and revealed early renal glomerular involvement that was histologically characteristic of MPN-related glomerulopathy. Early diagnosis and prompt medical management returned the patient's kidney functionality to the levels seen on initial presentation at our hospital. CONCLUSION: Large studies with long follow-up durations are necessary to identify and categorize the risk factors for the development of MPN-related glomerulopathy, to standardize therapeutic regimens, and to determine whether aggressive management of the myelofibrosis slows the progression of kidney disease.
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Lesión Renal Aguda/tratamiento farmacológico , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Mielofibrosis Primaria/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteinuria/tratamiento farmacológico , Pirazoles/uso terapéutico , Insuficiencia Renal Crónica/tratamiento farmacológico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Glomerulonefritis Membranoproliferativa/etiología , Glomerulonefritis Membranoproliferativa/patología , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Nitrilos , Mielofibrosis Primaria/complicaciones , Mielofibrosis Primaria/patología , Proteinuria/etiología , Pirimidinas , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/patología , Resultado del TratamientoRESUMEN
Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor resection is only 25%, given that tumor recurrence is the leading cause of death in 53-79% of patients. Pre-operative assessments for iCCA focus on pinpointing tumor location, biliary tract involvement, vascular encasements, and metastasis detection. Numerous studies have revealed that portal vein embolization (PVE) is linked to enhanced survival rates, improved liver synthetic functions, and decreased overall mortality. The challenge in achieving clear resection margins contributes to the notable recurrence rate of iCCA, affecting approximately two-thirds of cases within one year, and results in a median survival of less than 12 months for recurrent cases. Nearly 50% of patients initially considered eligible for surgical resection in iCCA cases are ultimately deemed ineligible during surgical exploration. Therefore, staging laparoscopy has been proposed to reduce unnecessary laparotomy. Eligibility for orthotopic liver transplantation (OLT) requires certain criteria to be granted. OLT offers survival advantages for early-detected unresectable iCCA; it can be combined with other treatments, such as radiofrequency ablation and transarterial chemoembolization, in specific cases. We aim to comprehensively describe the surgical strategies available for treating CCA, including the preoperative measures and interventions, alongside the current options regarding liver resection and OLT.
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Cholangiocarcinoma (CCA) is a hepatic malignancy that has a rapidly increasing incidence. CCA is anatomically classified into intrahepatic (iCCA) and extrahepatic (eCCA), which is further divided into perihilar (pCCA) and distal (dCCA) subtypes, with higher incidence rates in Asia. Despite its rarity, CCA has a low 5-year survival rate and remains the leading cause of primary liver tumor-related death over the past 10-20 years. The systemic therapy section discusses gemcitabine-based regimens as primary treatments, along with oxaliplatin-based options. Second-line therapy is limited but may include short-term infusional fluorouracil (FU) plus leucovorin (LV) and oxaliplatin. The adjuvant therapy section discusses approaches to improve overall survival (OS) post-surgery. However, only a minority of CCA patients qualify for surgical resection. In comparison to adjuvant therapies, neoadjuvant therapy for unresectable cases shows promise. Gemcitabine and cisplatin indicate potential benefits for patients awaiting liver transplantation. The addition of immunotherapies to chemotherapy in combination is discussed. Nivolumab and innovative approaches like CAR-T cells, TRBAs, and oncolytic viruses are explored. We aim in this review to provide a comprehensive report on the systemic and locoregional therapies for CCA.
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Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of death in the United States and is expected to be ranked second in the next 10 years due to poor prognosis and a rising incidence. Distant metastatic PDAC is associated with the worst prognosis among the different phases of PDAC. The diagnostic options for PDAC are convenient and available for staging, tumor response evaluation, and management of resectable or borderline resectable PDAC. However, imaging is crucial in PDAC diagnosis, monitoring, resectability appraisal, and response evaluation. The advancement of medical technologies is evolving, hence the use of imaging in PDAC treatment options has grown as well as the utilization of ctDNA as a tumor marker. Treatment options for metastatic PDAC are minimal with the primary goal of therapy limited to symptom relief or palliation, especially in patients with low functional capacity at the point of diagnosis. Molecular profiling has shown promising potential solutions that would push the treatment boundaries for patients with PDAC. In this review, we will discuss the latest updates from evidence-based guidelines regarding diagnosis, therapy response evaluation, prognosis, and surveillance, as well as illustrating novel therapies that have been recently investigated for PDAC, in addition to discussing the molecular profiling advances in PDAC.
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Understanding of immune-related adverse events (irAEs) has evolved rapidly, and management guidelines are continually updated. We explored temporal changes in checkpoint inhibitor-induced irAE management at a tertiary cancer care center to identify areas for improvement. We conducted a single-center retrospective study of patients who developed a gastrointestinal, pulmonary, renal, or cardiac irAE between July and 1 October in 2019 or 2021. We collected patient demographic and clinical information up to 1 year after toxicity. Endoscopic evaluation and specialty follow-up after discharge for patients with gastrointestinal irAEs declined between the 2019 and 2021 periods. Symptom duration and steroid taper attempts also declined. For pulmonary irAEs, rates of specialty consultation, hospital admission and readmission, and mortality improved in 2021 compared with 2019. Follow-up rates after hospital discharge were consistently low (<50%) in both periods. For cardiac irAEs, consultation with a cardiologist was frequent and prompt in both periods. Outpatient treatment and earlier specialty consultation improved outcomes with gastrointestinal irAEs. Our study exploring irAE practice changes over time identified areas to improve management; specifically, timely specialty consultation was associated with better outcomes for gastrointestinal irAEs. These findings can help improve the quality of management algorithms at our institution and may inform policies in other institutions.
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Accurate assessment of GFR is crucial to guiding drug eligibility, dosing of systemic therapy, and minimizing the risks of both undertreatment and toxicity in patients with cancer. Up to 32% of patients with cancer have baseline CKD, and both malignancy and treatment may cause kidney injury and subsequent CKD. To date, there has been lack of guidance to standardize approaches to GFR estimation in the cancer population. In this two-part statement from the American Society of Onco-Nephrology, we present key messages for estimation of GFR in patients with cancer, including the choice of GFR estimating equation, use of race and body surface area adjustment, and anticancer drug dose-adjustment in the setting of CKD. These key messages are based on a systematic review of studies assessing GFR estimating equations using serum creatinine and cystatin C in patients with cancer, against a measured GFR comparator. The preponderance of current data involving validated GFR estimating equations involves the CKD Epidemiology Collaboration (CKD-EPI) equations, with 2508 patients in whom CKD-EPI using serum creatinine and cystatin C was assessed (eight studies) and 15,349 in whom CKD-EPI with serum creatinine was assessed (22 studies). The former may have improved performance metrics and be less susceptible to shortfalls of eGFR using serum creatinine alone. Since included studies were moderate quality or lower, the American Society of Onco-Nephrology Position Committee rated the certainty of evidence as low. Additional studies are needed to assess the accuracy of other validated eGFR equations in patients with cancer. Given the importance of accurate and timely eGFR assessment, we advocate for the use of validated GFR estimating equations incorporating both serum creatinine and cystatin C in patients with cancer. Measurement of GFR via exogenous filtration markers should be considered in patients with cancer for whom eGFR results in borderline eligibility for therapies or clinical trials.
Asunto(s)
Antineoplásicos , Creatinina , Cistatina C , Tasa de Filtración Glomerular , Neoplasias , Insuficiencia Renal Crónica , Humanos , Neoplasias/complicaciones , Neoplasias/fisiopatología , Cistatina C/sangre , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/sangre , Creatinina/sangre , Antineoplásicos/efectos adversos , Biomarcadores/sangreRESUMEN
OBJECTIVE: To develop and externally validate a prediction model for severe cisplatin associated acute kidney injury (CP-AKI). DESIGN: Multicenter cohort study. SETTING: Six geographically diverse major academic cancer centers across the US. PARTICIPANTS: Adults (≥18 years) receiving their first dose of intravenous cisplatin, 2006-22. MAIN OUTCOME MEASURES: The primary outcome was CP-AKI, defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of intravenous cisplatin. Independent predictors of CP-AKI were identified using a multivariable logistic regression model, which was developed in a derivation cohort and tested in an external validation cohort. For the primary model, continuous variables were examined using restricted cubic splines. A simple risk model was also generated by converting the odds ratios from the primary model into risk points. Finally, a multivariable Cox model was used to examine the association between severity of CP-AKI and 90 day survival. RESULTS: A total of 24 717 adults were included, with 11 766 in the derivation cohort (median age 59 (interquartile range (IQR) 50-67)) and 12 951 in the validation cohort (median age 60 (IQR 50-67)). The incidence of CP-AKI was 5.2% (608/11 766) in the derivation cohort and 3.3% (421/12 951) in the validation cohort. Each of the following factors were independently associated with CP-AKI in the derivation cohort: age, hypertension, diabetes mellitus, serum creatinine level, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose. A simple risk score consisting of nine covariates was shown to predict a higher risk of CP-AKI in a monotonic fashion in both the derivation cohort and the validation cohort. Compared with patients in the lowest risk category, those in the highest risk category showed a 24.00-fold (95% confidence interval (CI) 13.49-fold to 42.78-fold) higher odds of CP-AKI in the derivation cohort and a 17.87-fold (10.56-fold to 29.60-fold) higher odds in the validation cohort. The primary model had a C statistic of 0.75 and showed better discrimination for CP-AKI than previously published models, the C statistics for which ranged from 0.60 to 0.68 (DeLong P<0.001 for each comparison). Greater severity of CP-AKI was monotonically associated with shorter 90 day survival (adjusted hazard ratio 4.63 (95% CI 3.56 to 6.02) for stage 3 CP-AKI versus no CP-AKI). CONCLUSION: This study found that a simple risk score based on readily available variables from patients receiving intravenous cisplatin could predict the risk of severe CP-AKI, the occurrence of which is strongly associated with death.