RESUMEN
Treatment with therapy targeting BRAF and MEK (BRAF/MEK) has revolutionized care in melanoma and other cancers; however, therapeutic resistance is common and innovative treatment strategies are needed1,2. Here we studied a group of patients with melanoma who were treated with neoadjuvant BRAF/MEK-targeted therapy ( NCT02231775 , n = 51) and observed significantly higher rates of major pathological response (MPR; ≤10% viable tumour at resection) and improved recurrence-free survival (RFS) in female versus male patients (MPR, 66% versus 14%, P = 0.001; RFS, 64% versus 32% at 2 years, P = 0.021). The findings were validated in several additional cohorts2-4 of patients with unresectable metastatic melanoma who were treated with BRAF- and/or MEK-targeted therapy (n = 664 patients in total), demonstrating improved progression-free survival and overall survival in female versus male patients in several of these studies. Studies in preclinical models demonstrated significantly impaired anti-tumour activity in male versus female mice after BRAF/MEK-targeted therapy (P = 0.006), with significantly higher expression of the androgen receptor in tumours of male and female BRAF/MEK-treated mice versus the control (P = 0.0006 and P = 0.0025). Pharmacological inhibition of androgen receptor signalling improved responses to BRAF/MEK-targeted therapy in male and female mice (P = 0.018 and P = 0.003), whereas induction of androgen receptor signalling (through testosterone administration) was associated with a significantly impaired response to BRAF/MEK-targeted therapy in male and female patients (P = 0.021 and P < 0.0001). Together, these results have important implications for therapy.
Asunto(s)
Antagonistas de Receptores Androgénicos , Melanoma , Quinasas de Proteína Quinasa Activadas por Mitógenos , Terapia Molecular Dirigida , Proteínas Proto-Oncogénicas B-raf , Receptores Androgénicos , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Humanos , Masculino , Melanoma/tratamiento farmacológico , Melanoma/patología , Ratones , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Receptores Androgénicos/metabolismo , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Análisis de SupervivenciaRESUMEN
Recent work by Kadosh et al. (2020) suggests that mutant p53 activity in gut epithelia is influenced by local production of microbial metabolites. The switch of p53 from tumor suppressor to oncogene is location-dependent and is impacted by microbially derived gallic acid.
Asunto(s)
Microbioma Gastrointestinal , Carcinogénesis , Humanos , Oncogenes , Proteína p53 Supresora de Tumor/genéticaRESUMEN
The unique optical properties of graphene, with broadband absorption and ultrafast response, make it a critical component of optoelectronic and spintronic devices. Using time-resolved momentum microscopy with high data rate and high dynamic range, we report momentum-space measurements of electrons promoted to the graphene conduction band with visible light and their subsequent relaxation. We observe a pronounced nonthermal distribution of nascent photoexcited electrons with lattice pseudospin polarization in remarkable agreement with results of simple tight-binding theory. By varying the excitation fluence, we vary the relative importance of electron-electron vs electron-phonon scattering in the relaxation of the initial distribution. Increasing the excitation fluence results in increased noncollinear electron-electron scattering and reduced pseudospin polarization, although up-scattered electrons retain a degree of polarization. These detailed momentum-resolved electron dynamics in graphene demonstrate the capabilities of high-performance time-resolved momentum microscopy in the study of 2D materials and can inform the design of graphene devices.
RESUMEN
INTRODUCTION: In colorectal cancer, the presence of para-aortic lymph nodes (PALN) indicates extraregional disease. Appropriately selecting patients for whom PALN dissection will provide oncologic benefit remains challenging. This study identified factors to predict survival among patients undergoing PALN dissection for colorectal cancer. METHODS: An institutional database was queried for patients who underwent curative-intent resection of clinically positive PALN for colorectal cancer between 2007 and 2020. Preoperative radiologic images were reviewed, and patients who did and did not have positive PALN on final pathology were compared. Survival analysis was performed to evaluate the impact of pathologically positive PALN on recurrence-free (RFS) and overall survival (OS). RESULTS: Of 74 patients who underwent PALN dissection, 51 had PALN metastasis at the time of primary tumor diagnosis, whereas 23 had metachronous PALN disease. Preoperative chemotherapy ± radiotherapy was given in 60 cases (81.1%), and 28 (37.8%) had pathologically positive PALN. Independent factors associated with positive PALN pathology included metachronous PALN disease and pretreatment and posttreatment radiographically abnormal PALN. On multivariable analysis, pathologically positive PALN was significantly associated with decreased RFS (hazard ratio 3.90) and OS (HR 4.49). Among patients with pathologically positive PALN, well/moderately differentiated histology was associated with better OS, and metachronous disease trended toward an association with better OS. CONCLUSIONS: Pathologically positive PALN are associated with poorer RFS and OS after PALN dissection for colorectal cancer. Clinicopathologic factors may predict pathologic PALN positivity. Curative-intent surgery may provide benefit, especially in patients with well-to-moderately differentiated primary tumors and possibly metachronous PALN disease.
Asunto(s)
Neoplasias Colorrectales , Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática , Humanos , Masculino , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/mortalidad , Femenino , Anciano , Persona de Mediana Edad , Tasa de Supervivencia , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Estudios Retrospectivos , Estudios de Seguimiento , Pronóstico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugíaRESUMEN
INTRODUCTION: Many patients with mucinous appendiceal adenocarcinoma experience peritoneal recurrence despite complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prior work has demonstrated that repeat CRS/HIPEC can prolong survival in select patients. We sought to validate these findings using outcomes from a high-volume center. PATIENTS AND METHODS: Patients with mucinous appendiceal adenocarcinoma who underwent CRS/HIPEC at MD Anderson Cancer Center between 2004 and 2021 were stratified by whether they underwent CRS/HIPEC for recurrent disease or as part of initial treatment. Only patients who underwent complete CRS/HIPEC were included. Initial and recurrent groups were compared. RESULTS: Of 437 CRS/HIPECs performed for mucinous appendiceal adenocarcinoma, 50 (11.4%) were for recurrent disease. Patients who underwent CRS/HIPEC for recurrent disease were more often treated with an oxaliplatin or cisplatin perfusion (35%/44% recurrent vs. 4%/1% initial, p < 0.001), had a longer operative time (median 629 min recurrent vs. 511 min initial, p = 0.002), and had a lower median length of stay (10 days repeat vs. 13 days initial, p < 0.001). Thirty-day complication and 90-day mortality rates did not differ between groups. Both cohorts enjoyed comparable recurrence free survival (p = 0.82). Compared with patients with recurrence treated with systemic chemotherapy alone, this select cohort of patients undergoing repeat CRS/HIPEC enjoyed better overall survival (p < 0.001). CONCLUSIONS: In appropriately selected patients with recurrent appendiceal mucinous adenocarcinoma, CRS/HIPEC can provide survival benefit equivalent to primary CRS/HIPEC and that may be superior to that conferred by systemic therapy alone in select patients. These patients should receive care at a high-volume center in the context of a multidisciplinary team.
Asunto(s)
Adenocarcinoma Mucinoso , Neoplasias del Apéndice , Hipertermia Inducida , Neoplasias Peritoneales , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Procedimientos Quirúrgicos de Citorreducción , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hipertermia Inducida/efectos adversos , Neoplasias Peritoneales/patología , Recurrencia Local de Neoplasia/patología , Neoplasias del Apéndice/patología , Adenocarcinoma Mucinoso/patología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To evaluate whether patients with advanced cancer prefer surgeons to use the best case/worst case (BC/WC) communication framework over the traditional risk/benefit (R/B) framework in the context of palliative surgical scenarios. BACKGROUND: Identifying the patient's preferred communication frameworks may improve satisfaction and outcome measures during difficult clinical decision-making. METHODS: In a video-vignette-based randomized, double-blinded study from November 2020 to May 2021, patients with advanced cancer viewed 2 videos depicting a physician-patient encounter in a palliative surgical scenario, in which the surgeon uses either the BC/WC or the R/B framework to discuss treatment options. The primary outcome was the patients' preferred video surgeon. RESULTS: One hundred fifty-five patients were approached to participate; 66 were randomized and 58 completed the study (mean age 55.8 ± 13.8 years, 60.3% males). 22 patients (37.9%, 95% CI: 25.4%-50.4%) preferred the surgeon using the BC/WC framework, 21 (36.2%, 95% CI: 23.8%-48.6%) preferred the surgeon using the R/B framework, and 15 (25.9%, 95% CI: 14.6%-37.2%) indicated no preference. High trust in the medical profession was inversely associated with a preference for the surgeon using BC/WC framework (odds ratio: 0.83, 95% CI: 0.70-0.98, P = 0.03). The BC/WC framework rated higher for perceived surgeon's listening (4.6 ± 0.7 vs 4.3±0.9, P = 0.03) and confidence in the surgeon's trustworthiness (4.3 ± 0.8 vs 4.0 ± 0.9, P = 0.04). CONCLUSIONS: Surgeon use of the BC/WC communication framework was not universally preferred but was as acceptable to patients as the traditional R/B framework and rated higher in certain aspects of communication. A preference for a surgeon using BC/WC was associated with lower trust in the medical profession. Surgeons should consider the BC/WC framework to individualize their approach to challenging clinical discussions.
Asunto(s)
Neoplasias , Cirujanos , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Femenino , Pacientes , Neoplasias/cirugía , Relaciones Médico-Paciente , ComunicaciónRESUMEN
OBJECTIVE: External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology. BACKGROUND: YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years. Its etiology is unknown. METHODS: YORC (<50 y old) or later-onset rectal cancer (LORC, ≥50 y old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal (TAN) tissue. After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors versus TANs and YORCs versus LORCs, controlling for multiple testing. Response to neoadjuvant therapy (NT) was categorized as major pathological response (MPR, ≤10% residual viable tumor) versus non-MPR. RESULTS: Our 107 tumors, 75 TANs from 37 (35%) YORCs, and 70 (65%) LORCs recapitulated bacterial species were previously associated with colorectal cancers (all P <0.0001). YORC and LORC tumoral microbiome signatures were distinct. After NT, 13 patients (12.4%) achieved complete pathologic response, whereas MPR occurred in 47 patients (44%). Among YORCs, MPR was associated with Fusobacterium nucleaum , Bacteroides dorei, and Ruminococcus bromii (all P <0.001), but MPR in LORC was associated with R. bromii ( P <0.001). Network analysis of non-MPR tumors demonstrated a preponderance of oral bacteria not observed in MPR tumors. CONCLUSIONS: Microbial signatures were distinct between YORC and LORC. Failure to achieve an MPR was associated with oral bacteria in tumors. These findings urge further studies to decipher correlative versus mechanistic associations but suggest a potential for microbial modulation to augment current treatments.
Asunto(s)
Microbiota , Neoplasias del Recto , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , BiopsiaRESUMEN
BACKGROUND: Heterogenous nomenclature describing appendiceal neoplasms has added to uncertainty around their appropriate treatment. Although a recent consensus has established the term low-grade appendiceal neoplasm (LAMN), we hypothesize that significant variation remains in the treatment of LAMNs. METHODS: We retrospectively reviewed our prospectively maintained appendiceal registry, identifying patients with LAMNs from 2009 to 2019. We assessed variability in treatment, including whether patients underwent colectomy, spread of disease at presentation, and long-term outcomes. RESULTS: Of 136 patients with LAMNs, 88 (35%) presented with localized disease and 48 (35%) with disseminated peritoneal disease. Median follow-up was 2.9 years (IQR 1.9-4.4), and 120 (88%) patients underwent pre-referral surgery. Among 26 pre-referral colectomy patients, 23 (88%) were performed for perceived oncologic need/nodal evaluation; no nodal metastases were identified. In patients with resected LAMNs without radiographic evidence of disseminated disease, 41 (47%) underwent second look diagnostic laparoscopy (DL) to evaluate for occult metastases. No peritoneal metastases were identified. Patients with disseminated disease were treated with cytoreductive surgery/heated intraperitoneal chemotherapy (CRS/HIPEC). For patients undergoing CRS/HIPEC, 5-year recurrence-free survival was 94% (95% CI 81-98%). For patients with localized disease, 5-year RFS was 98% (95% CI 85-99%). CONCLUSIONS: Significant variation exists in treatment patterns for LAMNs, particularly prior to referral to a high-volume center. Patients frequently underwent colectomy without apparent oncologic benefit. In the current era of high-quality cross sectional imaging, routine use of DL has low yield and is not recommended. Recurrence in this population is rare, and low-intensity surveillance can be offered. Overall prognosis is excellent, even with peritoneal disease.
Asunto(s)
Neoplasias del Apéndice , Hipertermia Inducida , Neoplasias Peritoneales , Humanos , Neoplasias del Apéndice/patología , Estudios Retrospectivos , Neoplasias Peritoneales/terapia , Hipertermia Inducida/efectos adversos , Pronóstico , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Tasa de Supervivencia , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMEN
Using time- and angle-resolved photoemission, we present momentum- and energy-resolved measurements of exciton coupling in monolayer WS_{2}. We observe strong intravalley coupling between the B_{1s} exciton and A_{n>1} states. Our measurements indicate that the dominant valley depolarization mechanism conserves the exciton binding energy and momentum. While this conservation is consistent with Coulomb exchange-driven valley depolarization, we do not observe a momentum or energy dependence to the depolarization rate as would be expected for the exchange-based mechanism.
RESUMEN
Kinetic Monte Carlo (kMC) simulations along with density functional theory (DFT) calculations were used to investigate the aggregation of size-selected Nb3Oy (y = 5, 6, 7) clusters deposited onto the Au(111) surface. Recent STM experiments showed that the cluster binding sites and sizes of the cluster assemblies on the Nb3Oy/Au(111) surfaces strongly depend on the stoichiometry of the clusters, i.e., the oxygen-to-niobium ratio. To better understand the origins of these differences, kMC simulations of the nucleation and growth of cluster assemblies were performed using energy barriers for diffusion and intercluster interactions estimated from DFT calculations of cluster binding and dimerization energies, respectively. Comparisons of the kMC simulations with STM images of the as-deposited Nb3Oy/Au(111) surfaces at RT and after high temperature annealing were used to further optimize the energetics and gauge the importance of nearest neighbor interactions. The kMC simulations demonstrate that the assembly of Nb3Oy clusters on Au(111) are largely controlled by the magnitude of the barriers for diffusion and interparticle-bond formation, while changes at higher temperatures are sensitive to the binding energies between nearest neighbors. Simulations for the Nb3O5 and Nb3O6 clusters, which exhibit smaller cluster assembly sizes in STM, required larger diffusion barriers as well as different barriers for interparticle binding, which reflected differences in DFT calculated dimerization energies. The results demonstrate the effectiveness of combined DFT and kMC calculations for understanding how the stoichiometry affects the aggregation of small oxide clusters on a metal surface.
RESUMEN
The microbiome (bacteria, viruses, and fungi) that exist within a patient's gastrointestinal tract and throughout their body have been increasingly understood to play a critical role in a variety of disease, including a number of cancer histologies. These microbial colonies are reflective of a patient's overall health state, their exposome, and germline genetics. In the case of colorectal adenocarcinoma, significant progress has been made in understanding the mechanism the microbiome plays beyond mere associations in both disease initiation and progression. Importantly, this improved understanding holds the potential to further identify the role these microbes play in colorectal cancer. We hope this improved understanding will be able to be leveraged in the future through either biomarkers or next-generation therapeutics to augment contemporary treatment algorithms through the manipulation of a patient's microbiome-whether through diet, antibiotics, prebiotics, or novel therapeutics. Here we review the role of the microbiome in the setting of patients with stage IV colorectal adenocarcinoma in both the development and progression or disease as well as response to therapeutics.
RESUMEN
OPINION STATEMENT: In recent years, we have seen an increase in the study and interest of the role of the microbiome in the development of malignancies, their progression, and evasion of therapies. This has been particularly fruitful in the case of colorectal cancer; multiple investigators have described correlative observations as well as hypotheses strengthened in preclinical studies that have begun to elucidate the critical role the gut and tumoral microbiome plays in carcinogenesis. Furthermore, these landmark studies lay the groundwork in describing the microbiome's role in carcinogenesis and provide a rich field of future study. Here, we review contemporary understandings of these observations and proposed mechanisms behind them.
Asunto(s)
Neoplasias Colorrectales , Microbioma Gastrointestinal , Microbiota , Carcinogénesis , Neoplasias Colorrectales/etiología , HumanosRESUMEN
Programmed death-ligand 1 (PD-L1) expression has been described in patients with malignant peritoneal mesothelioma (MPM), but treatment strategies utilising immune checkpoint inhibition are yet to be defined. Here, we examine levels of PD-L1 expression in MPM patients treated with systemic and/or intraperitoneal chemotherapy using tissue from patient tumour biopsies or resections at multiple time points. We found the mean PD-L1 expression was higher in those with a germline mutation and/or those with a higher somatic mutation burden. Moreover, PD-L1 expression was lower in patients who had received prior chemotherapy as compared to the treatment-naive cohort. Twenty patients who received chemotherapy, either systemic and/or peritoneal, between PD-L1 measurements showed marked heterogeneity. Six (30%) patients demonstrated upregulation of PD-L1, while eight (40%) demonstrated downregulation. Heterogeneity in PD-L1 expression in MPM before and after cytotoxic therapies may present an additional consideration when initiating immune checkpoint inhibition in this rare and challenging disease.
Asunto(s)
Antígeno B7-H1/metabolismo , Mesotelioma Maligno/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Peritoneales/metabolismo , Antineoplásicos/uso terapéutico , Regulación hacia Abajo , Femenino , Humanos , Masculino , Mesotelioma Maligno/tratamiento farmacológico , Mesotelioma Maligno/genética , Mesotelioma Maligno/patología , Persona de Mediana Edad , Mutación , Pemetrexed/uso terapéutico , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/patología , Compuestos de Platino/uso terapéutico , Estudios Retrospectivos , Regulación hacia ArribaRESUMEN
The application of minimally invasive surgery (MIS) techniques in the treatment of hepatobiliary malignancies offers advantages of shorter length of stay, quicker functional recovery, and decreased need for postoperative opioids. However, MIS completion radical cholecystectomy for incidentally diagnosed gallbladder cancer can be challenging due to a reoperative field and lack of tactile feedback. This video demonstrates the utility of the robotic platform and highlights the ways in which it assists surgeons in overcoming these limitations. These include (1) versatile wristed instruments and excellent visualization that facilitate a thorough regional lymphadenectomy; and (2) built-in fluorescence imaging technology that can be used with intravenous indocyanine green (ICG) to confirm porta hepatis anatomy in a reoperative field. ICG pharmacokinetics enable fluorescence angiography 15-20 s after ICG injection and fluorescence cholangiography 15-20 min after ICG injection as the dye accumulates in the biliary system. Systematic and intentional application of these techniques allows for the safe performance of robotic completion radical cholecystectomy following sound oncologic principles, with excellent perioperative outcomes.
Asunto(s)
Colecistectomía Laparoscópica , Procedimientos Quirúrgicos Robotizados , Colangiografía , Colecistectomía , Colorantes , Fluorescencia , Humanos , Verde de IndocianinaRESUMEN
BACKGROUND: This study investigated the safety and feasibility of intraoperative portal vein blood (PVB) collection at the time of pancreatic ductal adenocarcinoma (PDAC) resection. Relationships of circulating tumor cells (CTCs) in PVB and peripheral blood (PB) with overall survival (OS) and recurrence-free survival were studied. METHODS: Patients undergoing PDAC resection were offered enrollment in a prospective liquid biopsy protocol. The patients had PB drawn before incision and PVB drawn before tumor mobilization, then again immediately after resection. Using standard CellSearch protocols, CTCs were identified and compared with OS. RESULTS: Of the 34 patients enrolled in this study, 23 (68%) underwent pancreaticoduodenectomy, 8 (23%) underwent distal pancreatectomy, and 3 (9%) underwent total pancreatectomy. Peripheral blood was available for 22 (65%) and PVB for 31 (91%) of the patients. No bleeding or thrombotic complications occurred with the PVB draws. The CTC counts per 7.5 mL of PVB collected before and after resection were highly correlated (R2 = 0.89). The study found CTCs in 11 (50%) of 22 PB samples and 22 (71%) of 31 PVB samples. The OS rate at 18 months was 92% for the patients with < 3 CTCs, 71% for the patients with ≥ 3 CTCs per 7.5 mL of PB (p = 0.30), 100% for the patients without PVB CTCs, and 70% for the patients with PVB CTCs (p < 0.01). CONCLUSIONS: Collection of PVB during PDAC resection is safe. In this pilot study, PVB CTC counts but not PB CTC counts were significantly correlated with OS. This opens the door for future studies on selective omission of adjuvant chemotherapy for patients treated preoperatively and tailored surveillance intensity for patients without PVB CTCs at PDAC resection.
Asunto(s)
Carcinoma Ductal Pancreático , Células Neoplásicas Circulantes , Neoplasias Pancreáticas , Biomarcadores de Tumor , Carcinoma Ductal Pancreático/cirugía , Humanos , Neoplasias Pancreáticas/cirugía , Proyectos Piloto , Vena Porta/cirugía , Estudios ProspectivosRESUMEN
BACKGROUND AND OBJECTIVES: Recent studies suggest that bacteria influence the pathogenesis of primary colorectal cancer (CRC), yet their role in recurrence after resection is largely unknown. We have discovered that collagenase-producing bacteria promote cancer recurrence in mice, and that antibiotic bowel decontamination decreases colonization of these same organisms in humans. We hypothesized that preoperative combined mechanical and oral antibiotic bowel preparation would improve disease-free survival (DFS) in patients undergoing surgery for CRC. METHODS: We reviewed a cancer registry of patients treated for CRC at a tertiary center. Patients who received bowel preparation were compared to those that did not via a 1:1-propensity score matched for follow-up, age, sex, BMI, stage, location, chemoradiation, infection, anastomotic leak, and blood transfusion. RESULTS: One thousand two hundred and seventy-nine patients met inclusion criteria. Following propensity score matching, 264 patients receiving bowel prep were matched to 264 patients who did not. Kaplan-Meier estimates showed that patients who received bowel prep had a significantly improved 5-year DFS compared to those that did not (76.3% vs. 64.2%; p < .01). Cox regression demonstrated that bowel prep was associated with improved DFS (HR, 0.57; 95% CI, 0.37-0.89; p < .01). CONCLUSION: Combined mechanical and oral antibiotic bowel preparation is independently associated with improved recurrence-free survival in patients undergoing surgery for CRC.
Asunto(s)
Profilaxis Antibiótica , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Supervivencia sin Enfermedad , Laxativos/administración & dosificación , Adenocarcinoma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Cuidados Preoperatorios , Sistema de Registros , Estudios Retrospectivos , Adulto JovenRESUMEN
The structures formed by the deposition of mass-selected niobium oxide clusters, Nb3Oy(y = 5, 6, 7), onto Au(111) were studied by scanning tunneling microscopy. The as-deposited Nb3O7clusters assemble into large dendritic structures that grow on the terraces as well as extend from the top and bottom of step edges. The Nb3O6cluster also forms dendritic assemblies but they are generally much smaller in size. The assemblies are composed of smaller discrete structures (<1 nm) which are likely to be single clusters. The dendritic assemblies for both the Nb3O7and Nb3O6clusters have fractal dimensions of about 1.7 which is very close to that expected for simple diffusion limited aggregation. Annealing the Nb3O7,6/Au(111) surfaces up to 550 K results in changes in assembly sizes and increases in heights, while heating to 700 results in the disruption of the assemblies into smaller structures. By contrast, the as-deposited Nb3O5/Au(111) surface at RT exhibits compact cluster structures which become 3D nanoparticles when annealed above 550 K. Differences in the observed surface structures and thermal stability are attributed to differences in metal-oxygen stoichiometry which can influence cluster binding energies, mobility and inter-cluster interactions.
RESUMEN
PURPOSE: Although laparoscopic hyperthermic intraperitoneal chemotherapy (LS-HIPEC) has been proven safe in patients with gastric adenocarcinoma and carcinomatosis or positive cytology, patient selection criteria remain unclear. Thus, we perform a retrospective analysis to identify factors associated with improved survival and resection rates. PATIENTS AND METHODS: Data for all patients undergoing LS-HIPEC for stage IV gastric adenocarcinoma between June 2014 and November 2018 were collected prospectively and analyzed for associations with survival and resection using uni- and multivariate logistic regression, Cox proportional hazards models, and Kaplan-Meier survival functions. RESULTS: Of 70 patients who underwent LS-HIPEC, 43 (61%) received two drugs (mitomycin C and cisplatin), and 27 (39%) received three drugs (mitomycin C, cisplatin, and paclitaxel). The two groups' demographic and oncologic differences were not significant, although the three-drug group had a significantly lower rate of radiation therapy use (58% vs. 15%; p < 0.01). Univariate analysis revealed that poor differentiation [Cox hazard ratio (HR) 2.75; 95% confidence interval (CI) 1.34-5.63; p < 0.01], gross carcinomatosis (HR 3.10; 95% CI 1.52-6.30; p = 0.03), and ascites (HR 3.43; 95% CI 1.88-6.26; p < 0.01) were associated with shorter median survival. Gastrectomy was associated with improved overall survival (HR 0.32; 95% CI 0.15-0.70; p < 0.01). The resection rate of the 45 patients without ascites (38%) was significantly higher than that of the 25 patients with ascites (0%; p < 0.01). CONCLUSIONS: Our findings identify ascites as a significant prognostic factor for gastric cancer patients with peritoneal metastases undergoing LS-HIPEC. Our findings can be used to help identify patients who are unlikely to proceed to resection after LS-HIPEC and are good candidates for novel therapeutic approaches or clinical trials.
Asunto(s)
Quimioterapia Intraperitoneal Hipertérmica , Laparoscopía , Neoplasias Peritoneales , Neoplasias Gástricas , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Humanos , Neoplasias Peritoneales/cirugía , Neoplasias Peritoneales/terapia , Estudios Retrospectivos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/terapia , Tasa de SupervivenciaRESUMEN
The morphology and reactivity of mass-selected titania clusters, Ti3O6 and Ti3O5, deposited onto Au(111) were studied by scanning tunneling microscopy and temperature programmed desorption. Despite differing by only one oxygen atom, the stoichiometric Ti3O6 and the sub-stoichiometric ("reduced") Ti3O5 clusters exhibit very different structures and preferred binding sites. The Ti3O6 clusters bind at step edges and form small assemblies (2-4 clusters) on Au terraces, while the "reduced" Ti3O5 clusters form much larger fractal-like assemblies that can extend across step boundaries. Annealing the Ti3O5,6/Au(111) systems to higher temperatures causes changes in the size-distributions of cluster assemblies, but does not lead to the formation of TiOx nanoislands for temperatures ≤700 K. Reactivity studies show that the reduced Ti3O5 cluster has higher activity than Ti3O6 for 2-propanol dehydration, although both clusters exhibit substantial activity for dehydrogenation to acetone. Calculations using DFT+U suggest that the differences in aggregate morphology and reactivity are associated with the number of undercoordinated Ti3c sites in the supported clusters.