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BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan. METHODS: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan-Meier method. Cox regression analysis was used to analyze the prognostic factors of survival. RESULTS: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01-14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39-10.89). CONCLUSIONS: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.
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Tumores del Estroma Gastrointestinal , Mutación , Recurrencia Local de Neoplasia , Inhibidores de Proteínas Quinasas , Proteínas Proto-Oncogénicas c-kit , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas , Sistema de Registros , Humanos , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Femenino , Masculino , Taiwán/epidemiología , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Anciano , Proteínas Proto-Oncogénicas c-kit/genética , Adulto , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Sunitinib/uso terapéutico , Mesilato de Imatinib/uso terapéutico , Pronóstico , Anciano de 80 o más Años , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/patología , Compuestos de Fenilurea/uso terapéutico , Piridinas/uso terapéutico , Tasa de Supervivencia , Supervivencia sin Progresión , Estimación de Kaplan-MeierRESUMEN
BACKGROUND/OBJECTIVES: Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study. METHODS: In total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups. RESULTS: The baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02). CONCLUSIONS: The efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC.
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Protocolos de Quimioterapia Combinada Antineoplásica , Combinación de Medicamentos , Fluorouracilo , Irinotecán , Leucovorina , Ácido Oxónico , Neoplasias Pancreáticas , Tegafur , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Leucovorina/uso terapéutico , Leucovorina/administración & dosificación , Persona de Mediana Edad , Masculino , Femenino , Fluorouracilo/uso terapéutico , Fluorouracilo/administración & dosificación , Anciano , Irinotecán/uso terapéutico , Irinotecán/administración & dosificación , Tegafur/administración & dosificación , Tegafur/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Ácido Oxónico/administración & dosificación , Ácido Oxónico/uso terapéutico , Liposomas , Resultado del Tratamiento , Metástasis de la Neoplasia , Adulto , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéuticoRESUMEN
BACKGROUND: Laparoscopic gastrectomy is an acceptable procedure for early-stage gastric cancer; however, most patients are diagnosed at an advanced stage and older age in Taiwan. The feasibility and safety of applying laparoscopic gastrectomy in daily practice remain unclear. This study aimed to examine the short- and long-term outcomes of laparoscopic gastrectomy versus open procedures. METHODS: From 2007 to 2015, 192 patients who underwent open gastrectomy and 189 patients who underwent laparoscopic gastrectomy for gastric cancer at a single center were included. Propensity score matching analysis was used to adjust selection biases associated with age, preoperative hemoglobin, the extent of resection, tumor size, and stage of the disease. The demographics, perioperative parameters, short-term postoperative results, and 5-year survival data were analyzed. RESULTS: Open gastrectomy was more frequently performed in the elderly, larger tumor size, advanced stage of the disease, and disease requiring total gastrectomy or combined organ resection. After propensity score matching, 108 patients with laparoscopic gastrectomy were compared to 108 patients with open gastrectomy. The morbidity rates were not different in both groups (25.9%), while hospital stay was shorter in the laparoscopic group (16.0 vs. 18.8 days, p = 0.04). The 5-year overall survival and disease-free survival were superior in the laparoscopic group (p = 0.03 and p = 0.01, respectively); however, the survival differences were not significant in the subgroup analysis by stage. Laparoscopic gastrectomy had fewer recurrences than open gastrectomy. The pattern of recurrence was not different between the groups. CONCLUSIONS: Laparoscopic gastrectomy can be safely applied in both early and locally advanced gastric cancer without compromising oncologic outcomes. TRIAL REGISTRATION: Retrospective registration.
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Laparoscopía , Neoplasias Gástricas , Anciano , Gastrectomía/efectos adversos , Humanos , Tiempo de Internación , Recurrencia Local de Neoplasia/cirugía , Complicaciones Posoperatorias/epidemiología , Pronóstico , Puntaje de Propensión , Neoplasias Gástricas/cirugía , Taiwán , Resultado del TratamientoRESUMEN
The trauma team leader is a professional who receives and treats trauma patients. We aimed to evaluate whether or not the seniority of a qualified trauma team leader was a prognostic factor for multiple-trauma patients managed by a trauma team. This was a retrospective cohort study conducted at a Level I Trauma Center in North Taiwan. From January 2009 to December 2013, 284 patients were randomly assigned to one of two trauma team leaders (junior and senior leaders) on duty, irrespective of the seniority of the qualified trauma team leader. All parameters were collected and compared between these two groups. In the subgroup of multiple-trauma patients with Glasgow Coma Scale (GCS) ≤ 8, there were significant differences in the injury severity score, revised trauma score, and seniority of the leader between the alive and dead groups. A multivariate logistic regression analysis showed that the seniority of the trauma team leader was an important mortality risk factor [odds ratio (OR): 14.529, 95% confidence interval (CI) 1.683-125.429, p = 0.015] in patients with GCS ≤ 8. However, in patients with GCS > 8, age was the only independent risk factor [OR: 1.055, 95% CI 1.023-1.087, p = 0.001]. The seniority of the qualified trauma leader is important for teamwork, organization, and efficiency, all of which play an important role in improving the survival outcome of patients with GCS ≤ 8.
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Traumatismos Craneocerebrales/mortalidad , Traumatismos Craneocerebrales/terapia , Liderazgo , Grupo de Atención al Paciente/estadística & datos numéricos , Centros Traumatológicos/estadística & datos numéricos , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Análisis Multivariante , Rol del Médico , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Taiwán/epidemiología , Índices de Gravedad del TraumaRESUMEN
PURPOSES: Researchers studying trauma have found that physicians are able to perform a focused assessment with sonography for trauma (FAST) with minimal training and achieve ideal accuracy. However, there are currently no consensus or standard guidelines regarding the performance of this assessment. The aim of our study was to clarify the value of FAST performed by well-qualified senior general surgery residents in cases of suspected blunt abdominal trauma, which presents an important diagnostic problem in emergency departments. METHODS: This was a retrospective study in the emergency department (ED) of our hospital performed from January 2011 to September 2013. Patients were included if they (1) had undergone a FAST examination performed by qualified residents and (2) had received subsequent formal radiographic or surgical evaluations. The results were compared against subsequent surgical findings or formal Department of Radiology reference standards. RESULTS: Among the 438 patients enrolled, false-negative results were obtained in 8 and false-positive results in 5. Only one patient was missed and required laparotomy to repair a small intestine perforation. The sensitivity and specificity were 87 and 99%, respectively; the accuracy was 97%. CONCLUSIONS: Senior general surgery residents can be trained to perform accurate FAST examinations on trauma patients.
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Traumatismos Abdominales/diagnóstico por imagen , Servicio de Urgencia en Hospital , Cirugía General/educación , Internado y Residencia , Cirujanos/educación , Ultrasonografía , Heridas no Penetrantes/diagnóstico por imagen , Adulto , Competencia Clínica , Errores Diagnósticos/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Type 1 diabetes mellitus (T1D) is caused by the destruction of insulin-producing ß cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective therapeutic strategy for T1D. However, the survival of islet grafts can be disrupted by recurrent autoimmunity. Dimethyl sulfoxide (DMSO) is a solvent for organic and inorganic substances and an organ-conserving agent used in solid organ transplantations. DMSO also exerts anti-inflammatory, reactive oxygen species scavenger and immunomodulatory effects and therefore exhibits therapeutic potential for the treatment of several human inflammatory diseases. In this study, we investigated the therapeutic potential of DMSO in the inhibition of autoimmunity. We treated an animal model of islet transplantation (NOD mice) with DMSO. The survival of the syngeneic islet grafts was significantly prolonged. The population numbers of CD8, DC and Th1 cells were decreased, and regulatory T (Treg) cell numbers were increased in recipients. The expression levels of IFN-γ and proliferation of T cells were also reduced following DMSO treatment. Furthermore, the differentiation of Treg cells from naive CD4 T cells was significantly increased in the in vitro study. Our results demonstrate for the first time that in vivo DMSO treatment suppresses spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Treg cells.
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Enfermedades Autoinmunes/prevención & control , Diabetes Mellitus/prevención & control , Dimetilsulfóxido/farmacología , Linfocitos T Reguladores/efectos de los fármacos , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Insulina/metabolismo , Trasplante de Islotes Pancreáticos , Ratones , Ratones Endogámicos NOD , Ratones SCIDRESUMEN
BACKGROUND: Findings related to the influence of the -160C â A promoter polymorphism and haplotypes of the E-cadherin (CDH1) gene have not been consistent in previous studies regarding the risk for sporadic gastric cancer. Investigators in most previous studies detected those genotypes using restriction fragment length polymorphism analysis. Therefore, we conducted a case-control study to investigate the association of the CDH1 - 160C â A promoter polymorphism and haplotypes for cancer risk related to sporadic diffuse and intestinal gastric cancer by direct sequencing analysis. METHODS: We included 107 diffuse gastric cancer cases, 60 intestinal gastric cancer cases and 134 controls. The genotypic polymorphisms in the -160 promoter region, exons and intron-exon boundaries of CDH1 were detected by direct sequencing analysis. Genotype frequencies were compared. The CDH1 - 160C â A promoter polymorphism and four polymorphisms (48 + 6 T â C, 2076C â T, 2253C â T and 1937-13 T â C) were included in the haplotype analyses, which were estimated using the expectation-maximization algorithm. RESULTS: Compared to controls, the frequency of the -160A allele was significantly higher in diffuse gastric cancer cases (P = 0.005), but it was not significantly different in intestinal gastric cancer cases (P = 0.119). Two sets of three-marker haplotypes (-160C â A, 48 + 6 T â C, 2076C â T and -160C â A, 1937-13 T â C, 2253C â T) were associated with the risk of diffuse gastric cancer (P = 0.011 and P = 0.042, respectively). CONCLUSION: Based on direct sequencing analysis, our findings suggest that the CDH1 - 160C â A promoter polymorphism and haplotypes play significant roles in cancer risk for sporadic diffuse gastric cancer, but not for intestinal gastric cancer, in a Taiwanese population.
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Biomarcadores de Tumor/genética , Cadherinas/genética , Haplotipos/genética , Neoplasias Intestinales/genética , Polimorfismo de Nucleótido Simple/genética , Neoplasias Gástricas/genética , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD , Cadherinas/metabolismo , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Técnicas para Inmunoenzimas , Neoplasias Intestinales/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Regiones Promotoras Genéticas/genética , Análisis de Secuencia de ADN , Neoplasias Gástricas/patología , Adulto JovenRESUMEN
BACKGROUND/AIMS: Intra-peritoneal lavage is well known and used in intra-peritoneal malignancy However, the clinical role for patients with rupture of HCC has not yet been established. The aim of this study was to evaluate the clinical value of intraoperative peritoneal lavage for patients with rupture of HCC. METHODOLOGY: A retrospective study of operative findings, other factors, and outcome was performed in 66 patients with rupture of HCC who underwent distilled water peritoneal lavage (DWPL) during hepatectomy. RESULTS: There was a trend towards a higher intra-peritoneal, extra-hepatic recurrence rate in patients without DWPL. Patients who underwent DWPL had a significantly better 5-year disease-free survival rate than control group, 11.5±4.6 months and 30.2±8.4 months (p=0.018), respectively, and better overall survival rate, 21.7±6.2 months, than control group, 57.3±11.2 months (p=0.001). CONCLUSIONS: DWPL during liver resection retards tumor recurrence and improves the intraoperative survival rate in patients with spontaneously ruptured HCC.
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Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Lavado Peritoneal , Adulto , Anciano , Carcinoma Hepatocelular/mortalidad , Destilación , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rotura Espontánea , Tasa de Supervivencia , AguaRESUMEN
BACKGROUND: The nomogram derived from the pivotal phase III NAPOLI-1 study demonstrated a significant ability to predict median overall survival (OS) in gemcitabine-refractory metastatic pancreatic ductal adenocarcinoma (PDAC) treated with liposomal irinotecan plus fluorouracil and leucovorin (nal-IRI+5-FU/LV). However, the NAPOLI-1 nomogram has not been validated in a real-world setting and therefore the applicability of the NAPOLI-1 nomogram in daily practice remains unknown. This study aims to evaluate the NAPOLI-1 nomogram in a multicenter real-world cohort. METHODS: The NAPOLI-1 nomogram was applied to a previously established cohort of metastatic PDAC patients treated with nal-IRI+5-FU/LV in nine participating centers in Taiwan. Patients were divided into three risk groups according to the NAPOLI-1 nomogram. The survival impact of relative dose intensity at 6 weeks (RDI at 6 weeks) in different risk groups was also investigated. RESULTS: Of the 473 included patients, the median OSs of patients classified as low (n = 156), medium (n = 186), and high (n = 131) risk were 10.9, 6.3, and 4.3 months, respectively (p < 0.0001). The survival impact of RDI at 6 weeks remained significant after stratification by risk groups, adjustment with Cox regression, inverse probability weighting, or propensity score matching. CONCLUSIONS: Our results support the usefulness of the NAPOLI-1 nomogram for risk stratification in gemcitabine-refractory metastatic PDAC treated with nal-IRI+5-FU/LV in daily practice. We further showed that the RDI at 6 weeks is an independent prognostic factor beyond the NAPOLI-1 nomogram.
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BACKGROUND: Spontaneously ruptured hepatocellular carcinoma (HCC) with hemoperitoneum has a poor prognosis, especially in cases of cirrhosis. Patients usually present to emergency rooms (ERs) with acute abdomen. The aim of the present study was to determine the factors affecting mortality and to compare the prognosis of conservative treatment, transcatheter arterial embolization (TAE), or hepatectomy in these situations. METHODS: Fifty-four patients with spontaneously ruptured HCC diagnosed between January 2004 and August 2010 were enrolled in this retrospective review of clinical data. Grouping by survival or mortality, univariate and multivariate analyses of factors affecting 30-day mortality, and long-term survival were conducted. The outcomes of the various treatments were analyzed. RESULTS: After primary fluid resuscitation in the ER, 6 of 54 patients underwent conservative treatment. Emergency hepatectomy was performed on 19 patients; TAE was used for 29 patients, 18 of whom received staged hepatectomy thereafter. Poor liver function, prolonged international normalized ratio (INR), and conservative treatment were associated with increased 30-day mortality. Logistic regression analysis of cumulative survival revealed that INR ≥ 1.4, multiple intrahepatic HCC, and conservative treatment were related to poorer long-term survival. The patients who received hepatectomy, either immediate or staged after TAE, had higher survival rates of 85.2 % at 30 days and 62.2 % at 1 year. CONCLUSIONS: The treatment of ruptured HCC should be tailored to the individual case. Prolonged survival is possible in patients with preserved liver function through curative liver resection. Emergency physicians, radiologists, and surgeons play essential roles in managing these patients.
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Abdomen Agudo/etiología , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/terapia , Hemoperitoneo/complicaciones , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/terapia , Abdomen Agudo/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Urgencias Médicas , Femenino , Hemoperitoneo/mortalidad , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Rotura Espontánea , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Perivascular epithelioid cell tumors (PEComas) are very rare mesenchymal neoplasms, and have been found in various organs such as the liver, kidney, falciform ligament, uterus, uterine cervix, and both the small and large bowel. However, only 3 cases of mesenteric PEComa have been described in the literature so far. The treatment and prognosis of malignant mesenteric PEComas are discussed. CASE REPORT: We report the case of a 59-year-old man diagnosed with PEComa. He underwent segmental resection of the jejunum and tumor resection. Malignant mesenteric PEComa was confirmed on the basis of clinicopathological features. Tumor resection was followed by concurrent chemoradiotherapy. CONCLUSION: Besides surgery, no effective treatment for malignant PEComa has been established thus far because of the rarity of this tumor. Here, we report our experience of treating a malignant mesenteric PEComa using surgery and subsequent adjuvant therapy, which effectively controlled disease progression and prevented local recurrence.
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Células Epitelioides/patología , Neoplasias del Yeyuno/diagnóstico , Mesenterio/patología , Neoplasias Peritoneales/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Terapia Combinada , Diagnóstico Diferencial , Estudios de Seguimiento , Humanos , Neoplasias del Yeyuno/tratamiento farmacológico , Neoplasias del Yeyuno/radioterapia , Neoplasias del Yeyuno/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/radioterapia , Neoplasias Peritoneales/cirugía , Neoplasias de Células Epitelioides Perivasculares/tratamiento farmacológico , Neoplasias de Células Epitelioides Perivasculares/radioterapia , Neoplasias de Células Epitelioides Perivasculares/cirugía , Terapia Recuperativa , Tomografía Computarizada por Rayos XRESUMEN
Lung cancer is one of the leading causes of cancer death in worldwide and required for novel therapeutic strategy. Our previous research demonstrated that the crude acetone extract of Bupleurum scorzonerifolium (BS-AE) and its component isochaihulactone induce antiproliferative and apoptotic effects on the lung adenocarcinoma cell line. Structural analysis has identified isochaihulactone as a lignan, with a chiral center and two racemic forms (Z-isochaihulactone and E-isochaihulactone). In this study, Z-isochaihulactone displayed significantly higher tumor cytotoxicity than E-isochaihulactone in A549 cells. The notch signaling pathway plays a pivotal role in determination of cell fate during development, while in lung cancer, it might have oncogenic or tumor-suppressive controversial functions. We showed that Z-isochaihulactone induced morphological changes in the A549 cells, inhibited cell growth, and arrested the cell cycle at the G2/M phase. It also induced upregulation of the active form of Notch1 (notch intracellular domain, NICD), which further induced p21 and c-Myc expression in time- and dose-dependent manners. Administrations of Z-isochaihulactone in nude mice can significantly inhibit tumor growth due to enhancement of NICD expression confirmed by immunohistochemical analysis. Taken together, our results supported that Z-isochaihulactone can efficiently inhibit tumorigenicity and be a potential compound for therapy.
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Osteopontin (OPN) and epidermal growth factor receptor (EGFR) are important factors associated with tumor progression, invasion and metastasis in humans. The aim of this study was to assess the correlation of OPN and EGFR expression with hepatocellular carcinoma (HCC) progression. Expression of OPN and EGFR was assessed by immunohistochemistry in 100 HCC specimens. Immunostaining scores (0 to 400) were calculated from the percentage of cells (0 to 100) at each immunostaining intensity and the immunostaining intensity (0 to 4). The average immunostaining score for OPN was correlated with tumor grade (56.1 for grade I, 104.6 for grade II, and 141.2 for grade III; P = 0.023) and T stage (58.6 for stage T1, 85.9 for stage T2, 126.8 for stage T3, and 189.1 for stage T4; P = 0.029). Similarly, the average immunostaining score for EGFR was correlated with tumor grade (80.5 for grade I, 142.1 for grade II, 230.6 for grade III; P = 0.011) and T stage (96.4 for stage T1, 135.5 for stage T2, 221.3 for stage T3, and 261.4 for stage T4; P = 0.026). In addition, OPN and EGFR immunostaining scores were also correlated with M, N, and AJCC stages. In conclusion, higher expression of OPN and EGFR is significantly associated with advanced histological grades, advanced pathological stages and poorer survival rates in HCC. OPN and EGFR may be used as novel biomarkers for diagnosis or monitoring of progression of hepatocellular carcinoma.
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Carcinoma Hepatocelular , Osteopontina , Progresión de la Enfermedad , Humanos , Inmunohistoquímica , Neoplasias HepáticasRESUMEN
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INTRODUCTION: Patients with clinical T4 gastric cancers have high recurrence rates and low 5-year overall survival (OS) despite radical gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy. The invisible peritoneal metastasis may result in local recurrence due to the tumor invading the serosa and nearby organs. Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested as an adjuvant treatment strategy in these patients. We evaluated the efficacy of prophylactic HIPEC post-gastrectomy for patients with clinical T4 gastric cancer. MATERIALS AND METHODS: We retrospectively reviewed data from 132 patients with clinical T4 gastric cancer who underwent gastrectomy + D2 lymphadenectomy between 2014 and 2020. Thirty-five of these patients also underwent prophylactic HIPEC perioperatively. We used propensity score matching (PSM) to reduce selection bias. We evaluated the risk factors for recurrence and compared the OS and disease-free survival (DFS) between the gastrectomy and prophylactic HIPEC groups. RESULTS: A total of 132 eligible patients were included in the study. Seventy preoperative patient characteristics were homogeneous post-PSM. Prophylactic HIPEC seemed to reduce the risk of postoperative peritoneal recurrence but did not influence the risk of distant metastasis. The risk factors for recurrence included advanced N stage, ascites, and lymphovascular invasion. OS (adjusted hazard ratio, 0.37; 95% CI, 0.17 to 0.81; p = 0.035) and DFS (adjusted hazard ratio, 0.33; 95% CI, 0.15 to 0.72; p = 0.017) were better in the prophylactic HIPEC group than in the gastrectomy alone group. CONCLUSIONS: Prophylactic HIPEC plus radical gastrectomy can reduce peritoneal recurrence and improve OS and DFS in patients with clinical T4 gastric cancer.
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Hipertermia Inducida , Neoplasias Peritoneales , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales/secundario , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Tasa de SupervivenciaRESUMEN
Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) improves survival in patients with pancreatic ductal adenocarcinoma (PDAC) after progression to gemcitabine-based therapy. Few studies have examined whether the starting dose and dose escalation of nal-IRI in subsequent treatment cycles may influence patient outcomes and toxicity profiles. A total of 667 patients who received nal-IRI + 5-FU/LV for PDAC treatment between August 2018 and November 2020 at nine medical centers in Taiwan were included and retrospectively analyzed. Patients were allocated to the standard starting dose (SD), reduced starting dose (RD) without escalation, and RD with escalation of nal-IRI groups for comparison of survival outcome and safety. Propensity score matching (PSM) was performed to adjust for possible confounding variables. Nal-IRI was prescribed at SD, RD without escalation, and RD with escalation in 465 (69.7%), 147 (22.0), and 55 (8.2%), respectively. RD with escalation patients had significantly longer treatment cycles (6, range 2-25) than SD (5, range 1-42, P<0.001) and RD without escalation patients (4, range 1-26, P<0.001). The median overall survival (OS) of the patients were as follows: SD, 6.2 months (95% confidence interval [CI], 5.7-6.7); RD with escalation, 7.6 months (95% CI, 6.1-9.2); and RD without escalation, 3.6 months (95% CI, 2.6-4.5). After PSM to adjust for potential confounders, RD without escalation patients still had the poorest OS compared to the other two groups (P<0.001), while the OS difference between SD and RD with escalation patients was insignificant (P=0.10). SD patients had higher incidences of ≥ grade 3 neutropenia and febrile neutropenia than the other two groups. Administering nal-IRI at RD followed by dose escalation in subsequent treatment cycles is safe and does not compromise survival outcomes in selected patients with PDAC receiving nal-IRI plus 5-FU/LV.
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Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) treatment has demonstrated survival benefits but noticeable side effects in patients with pancreatic ductal adenocarcinoma (PDAC) that is refractory to gemcitabine-based therapy. This study aimed to explore whether combining albumin with the neutrophil-to-lymphocyte ratio (NLR), herein known as the albumin and neutrophil-to-lymphocyte ratio score (ANS), could be utilized as a simple tool to predict survival and safety profiles in such patient groups. We retrospectively enrolled 434 consecutive PDAC patients treated with nal-IRI + 5-FU/LV between 2018 and 2020 at nine medical centers in Taiwan. Patients were divided into three groups: ANS 0 (high albumin and low NLR), ANS 1 (low albumin or high NLR), and ANS 2 (low albumin and high NLR), for comparison. The median overall survival times for the ANS 0, 1, and 2 groups were 8.7 months (95% confidence interval (CI), 7.0-10.3 months), 5.2 months (95% CI, 4.3-6.0 months), and 2.6 months (95% CI, 1.9-3.3 months), respectively. The ANS was found to be an independent variable for overall survival and time-to-treatment failure in multivariate analyses. Patients in the ANS 2 group had significantly higher incidences of grade 3 or higher treatment-related adverse events than those in the other two groups. The present study showed that the ANS was an independent prognosticator in PDAC patients receiving nal-IRI + 5-FU/LV therapy. The ANS can be a simple predictor of survival outcome and safety profiles in PDAC patients treated with nal-IRI + 5-FU/LV.
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Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (NalFL) comprises the current standard for gemcitabine-failed metastatic pancreatic ductal adenocarcinoma (PDAC). As liposomes generally accumulate in the spleen, we evaluated the impact of spleen volume on prognosis. We enrolled patients with metastatic PDAC who failed gemcitabine-based therapy and were initiated on NalFL between August 2018 and November 2020. The spleen volume before NalFL administration was evaluated. They were stratified into dose subgroups (i.e. low, < 48 mg/m2; intermediate, 48 - < 64 mg/m2; high, ≥ 64 mg/m2) by the average nal-IRI dose during the entire treatment, and multivariate analysis of overall survival (OS) was performed. We included 547 patients with a median age of 63 years (range, 27-89 years) and a median of 1 (range, 0-7) palliative chemotherapy regimen. The median spleen volume was 245 mL (range, 82-817 mL). Among patients with splenomegaly (≥ 245 mL), the low-dose subgroup had the worst median time to treatment failure (TTF, 1.8 months vs. 2.5 months vs. 2.5 months, P = 0.020) and OS (3.3 months vs. 5.9 months vs. 6.6 months, P = 0.018) as against no prognostic impact in patients without splenomegaly. In the multivariate analysis of patients with splenomegaly, performance status (PS) ≥ 2, body surface area (BSA) < 1.6 m2, prior fluoropyrimidine use, liver metastasis, and low-dose subgroup were independent poor prognostic factors. A low average nal-IRI dose was significantly associated with poor prognosis, especially among patients with splenomegaly. Further pharmacological studies should validate the relevance of spleen volume on the treatment outcomes of nal-IRI.
RESUMEN
Introduction: This multicenter, real-world cohort study aimed to evaluate the effectiveness of early cumulative dose administration and dosing pattern of liposomal irinotecan plus fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with gemcitabine-refractory metastatic pancreatic ductal adenocarcinoma (mPDAC). Material and Methods: The electronic medical records of mPDAC patients treated with nal-IRI+5-FU/LV in nine participating centers were manually reviewed. To accommodate to the NAPOLI-1 study population, only patients with an Eastern Cooperative Oncology Group Performance Score of 0-1 were included. The survival impact of the relative 6-week cumulative dose and dosing pattern (standard vs. reduced starting dose, with and without further dose modification) were investigated. Results: Of the 473 included patients, their median overall survival (mOS) was 6.8 [95% CI, 6.2-7.7] months. The mOS of patients who received a relative 6-week cumulative dose of >80%, 60%-80%, and <60% were 7.9, 8.2, and 4.3 months, respectively (p<0.0001). Their survival impact remained significant after covariate adjustment using Cox regression. The mOS was 8.0-8.2 months in patients with a standard starting dose with and without early dose modification, and 9.3 and 6.7 months in those who had a reduced starting dose with and without escalation in the subsequent treatment, respectively. The incidence of grade 3-4 neutropenia and diarrhea was 23.3% and 2.7%, respectively. Conclusion: Our results support the use of nal-IRI+5-FU/LV in gemcitabine-refractory mPDAC and suggest that a lower starting dose followed by a re-escalation strategy could achieve clinical outcomes comparable to those with standard starting doses in real-world practice.
RESUMEN
BACKGROUND: Recent studies have suggested the suboptimal efficacy of liposomal irinotecan plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in metastatic pancreatic ductal adenocarcinoma (mPDAC) patients previously treated with conventional irinotecan. This study investigated the effect of conventional irinotecan treatment in mPDAC patients receiving nal-IRI+5-FU/LV by analyzing a population-based dataset. METHODS: We reviewed 667 consecutive mPDAC patients treated with nal-IRI+5-FU/LV between August 2018 and November 2020 at Taiwanese medical centers. Eighty-six patients previously treated with conventional irinotecan were matched to 86 patients not treated with conventional irinotecan, following propensity matching for age, sex, performance status, metastatic organ site, pre-treatment carbohydrate antigen 19-9 level, lines of prior chemotherapy treatment, and time from first-line treatment to nal-IRI+5-FU/LV therapy. RESULTS: The median overall survival and time-to-treatment failure were 4.8 and 2.6 vs 4.1 and 2.1 months, respectively, for patients who were and were not previously treated with conventional irinotecan. The tumor response and disease control rates were 5.8% and 32.6% vs 5.8% and 37.2%, respectively, for patients previously treated and not treated with conventional irinotecan. No significant differences were observed in survival times and tumor response rates between the two groups. CONCLUSIONS: Previous conventional irinotecan treatment does not compromise the efficacy of subsequent nal-IRI+5-FU/LV treatment in mPDAC patients.