Project description:Lung cancer is the leading cause of cancer deaths worldwide. Unfortunately, high recurrence rates and poor survival remain despite surgical resection and conventional chemotherapy. Local drug delivery systems are a promising intervention for lung cancer treatment with the potential for improved efficacy with reduced systemic toxicity. Here, we describe the development of a chemotherapy-loaded polymer buttress, to be implanted along the surgical margin at the time of tumor resection, for achieving local and prolonged release of a new anticancer agent, eupenifeldin. We prepared five different formulations of buttresses with varying amounts of eupenifeldin, and additional external empty polymer coating layers (or thicknesses) to modulate drug release. The in vitro eupenifeldin release profile depends on the number of external coating layers with the formulation of the greatest thickness demonstrating a prolonged release approaching 90 days. Similarly, the long-term cytotoxicity of eupenifeldin-loaded buttress formulations against murine Lewis lung carcinoma (LLC) and human lung carcinoma (A549) cell lines mirrors the eupenifeldin release profiles and shows a prolonged cytotoxic effect. Eupenifeldin-loaded buttresses significantly decrease local tumor recurrence in vivo and increase disease-free survival in a lung cancer resection model.
Project description:The fungal metabolite verticillin A is a potent and selective histone methyltransferase inhibitor. It regulates apoptosis, the cell cycle, and stress response, and displays potent activity in the suppression of tumor cell growth in several different in vivo models. Verticillin A sensitizes pancreatic cancer cells to anti-PD-1 immunotherapy by regulating PD-L1 expression. However, as with many natural products, delivery and systemic toxicity are challenges that must be overcome to advance their use as a chemotherapeutic. To both reduce systemic toxicity and improve delivery, we report a verticillin A-loaded surgical buttress, which is well-tolerated at a dose as high as 40 mg/kg. In contrast, free verticillin A administered systemically results in toxicity at a dose of 3 mg/kg. The verticillin A-loaded buttress suppresses tumor recurrence in vivo in a safe and dose-dependent manner against a highly aggressive and metastatic model of pancreatic cancer.
Project description:Image-guided thermal ablations are increasingly applied in the treatment of renal cancers, under the guidance of ultrasound (US) or computed tomography (CT). Fusion imaging allows exploitation of the strengths of all imaging modalities simultaneously, eliminating or minimising the weaknesses of every single modality. We present a case of a 68-year-old patient treated using US/CT fusion imaging to guide radiofrequency ablation for local recurrence of renal cell carcinoma undetectable by ultrasound.
Project description:The present study aims to evaluate the impact of tumor microRNA-125b (miR-125b) on recurrence and survival of patients with clear-cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 276 patients (200 in the training cohort and 76 in the validation cohort) with ccRCC undergoing nephrectomy at a single institution. Clinicopathologic features, cancer-specific survival (CSS) and recurrence-free survival (RFS) were recorded. Tumor miR-125b levels were assessed by in situ hybridization (ISH) in specimens of patients. The Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on CSS and RFS. A concordance index (C-index) was calculated to assess predictive accuracy. In both cohorts, tumor miR-125b positively correlated with Fuhrman grade. High tumor miR-125b indicated poor survival and early recurrence for patients with ccRCC, especially with advanced stage disease. After multivariable adjustment, tumor miR-125b was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of traditional TNM and UCLA Integrated Staging System prognostic models was improved when tumor miR-125b was added. The results showed that tumor miR-125b is a potential independent adverse prognostic biomarker for recurrence and survival of patients with ccRCC after nephrectomy.
Project description:ObjectiveTo evaluate the survival outcomes of patients with local recurrence after radical nephrectomy (RN) and to test the effect of surgery, as monotherapy or in combination with systemic treatment, on cancer-specific mortality (CSM).MethodsPatients with local recurrence after RN were abstracted from an international dataset. The primary outcome was CSM. Cox's proportional hazard models tested the main predictors of CSM. Kaplan-Meier method estimates the 3-year survival rates.ResultsOverall, 96 patients were included. Of these, 44 (45.8%) were metastatic at the time of recurrence. The median time to recurrence after RN was 14.5 months. The 3-year cancer-specific survival rates after local recurrence were 92.3% (± 7.4%) for those who were treated with surgery and systemic therapy, 63.2% (± 13.2%) for those who only underwent surgery, 22.7% (± 0.9%) for those who only received systemic therapy and 20.5% (± 10.4%) for those who received no treatment (p < 0.001). Receiving only medical treatment (HR: 5.40, 95% CI 2.06-14.15, p = 0.001) or no treatment (HR: 5.63, 95% CI 2.21-14.92, p = 0.001) were both independently associated with higher CSM rates, even after multivariable adjustment. Following surgical treatment of local recurrence 8 (16.0%) patients reported complications, and 2/8 were graded as Clavien-Dindo ≥ 3.ConclusionsSurgical treatment of local recurrence after RN, when feasible, should be offered to patients. Moreover, its association with a systemic treatment seems to warrantee adjunctive advantages in terms of survival, even in the presence of metastases.
Project description:Oral leukoplakia (OL) is a potentially malignant oral disorder. The Gold Standard treatment is to remove surgically the OL. Despite optimal surgery, the recurrence rates are estimated to be 30%. The reason for this is unknown. The aim of this study was to investigate the clinical factors that correlate with recurrence after surgical removal of OL. In a prospective study data were collected from 226 patients with OL. Forty-six patients were excluded due to incomplete records or concomitant presence of other oral mucosal diseases. Overall, 180 patients proceeded to analysis (94 women and 86 men; mean age, 62 years; age range, 28-92 years). Clinical data, such as gender, diagnosis (homogeneous/non-homogeneous leukoplakia), location, size, tobacco and alcohol use, verified histopathological diagnosis, and clinical photograph, were obtained. In patients who were eligible for surgery, the OL was surgically removed with a margin. To establish recurrence, a healthy mucosa between the surgery and recurrence had to be confirmed in the records or clinical photographs. Statistical analysis was performed with the level of significance set at P<0.05. Of the 180 patients diagnosed with OL, 57% (N = 103) underwent surgical removal in toto. Recurrence was observed in 43 OL. The cumulative incidence of recurrence of OL was 45% after 4 years and 49% after 5 years. Fifty-six percent (N = 23) of the non-homogeneous type recurred. Among snuff-users 73% (N = 8) cases of OL recurred. A non-homogeneous type of OL and the use of snuff were significantly associated with recurrence after surgical excision (P = 0.021 and P = 0.003, respectively). Recurrence was also significantly associated with cancer transformation (P<0.001). No significant differences were found between recurrence and any of the following: dysplasia, site of lesion, size, multiple vs. solitary OL, gender, age, use of alcohol or smoking. In conclusion, clinical factors that predict recurrence of OL are non-homogeneous type and use of snuff.
Project description:Local recurrence of rectal cancer is difficult to treat, may cause severe and disabling symptoms, and usually has a fatal outcome. The aim of this study was to document the clinical nature of locally recurrent rectal cancer and to determine the effect of surgical resection on long-term survival.A retrospective review was conducted of the prospectively collected medical records of 2485 patients with primary rectal adenocarcinoma who underwent radical resection between September 1994 and December 2008.In total, 147 (5.9%) patients exhibited local recurrence. The most common type of local recurrence was lateral recurrence, whereas anastomotic recurrence was the most common type in patients without preoperative concurrent chemoradiotherapy (CCRT). Tumor location with respect to the anal verge significantly affected the local recurrence rate (P < 0.001), whereas preoperative CCRT did not affect the local recurrence rate (P = 0.433). Predictive factors for surgical resection of recurrent rectal cancer included less advanced tumor stage (P = 0.017, RR = 3.840, 95% CI = 1.271-11.597), axial recurrence (P < 0.001, RR = 5.772, 95% CI = 2.281-14.609), and isolated local recurrence (P = 0.006, RR = 8.679, 95% CI = 1.846-40.815). Overall survival after diagnosis of local recurrence was negatively influenced by advanced pathologic tumor stage (P = 0.040, RR = 1.867, 95% CI = 1.028-3.389), positive CRM (P = 0.001, RR = 12.939, 95% CI = 2.906-57.604), combined distant metastases (P = 0.001, RR = 2.086, 95% CI = 1.352-3.218), and nonsurgical resection of recurrent tumor (P < 0.001, RR = 4.865, 95% CI = 2.586-9.153).In conclusion, the clinical outcomes of local recurrence after curative resection of rectal cancer are diverse. Surgical resection of locally recurrent rectal cancer should be considered as an initial treatment, especially in patients with less advanced tumors and axial recurrence.
Project description:BackgroundFor recurrent laryngeal cancer, the feasibility of salvage transoral laser microsurgery (TLM) remains controversial. This study compared the efficacy of TLM and open partial laryngectomy (OPL) for treatment of early local recurrence of glottic squamous cell cancer (GSCC) and confirm the effectiveness of salvage TLM as a treatment option.MethodsThis retrospective study involved 55 patients with early local recurrent GSCC treated with TLM, and the oncologic outcomes, functional outcomes, hospitalization time and complications were compared with a group of 40 recurrent GSCC patients matched for clinical variables of TLM group, treated by OPL by the same team of surgeons.ResultsThe 5-year overall survival and disease-specific survival rates were 65.8% and 91.5%, respectively, for 55 patients with rTis-rT2 stage treated by TLM and 77.1% and 94.7%, respectively, for 40 patients with rTis-rT2 stage treated by OPL (OPL group). In the TLM and OPL groups, the local control rates after 5 years were 77.5% and 79.3%, respectively, and the laryngeal preservation rates were 94.4% and 83.6%, respectively (p > 0.05). Compared with the OPL group, the complication rate (1.82%) and hospitalization duration (5.42 ± 2.26 days) were significantly lower in the TLM group (p < 0.05). Compared with the OPL group, postsurgical health-related quality of life and quality of voice were significantly better in the TLM group (p < 0.001).ConclusionSalvage TLM can be used as an effective treatment option for suitable patients after a full, comprehensive, and careful assessment of the characteristics of early locally recurrent glottic carcinoma.
Project description:BackgroundRenal papillary cell carcinoma (KIRP) is a relatively rare renal malignancy. Although KIRP subtyping about clinical relevance has been defined, there have been scarce number of studies on the molecular characteristics of KIRP subtypes.MethodIn this study, a independent samples t-test was used to identify differentially expressed (DE) miRNAs between tumor and normal samples of KIRP. Meanwhile, we performed unsupervised clustering using DE miRNA expression data to analyze molecular characteristics of KIRP. The Partitioning Around Medoids clustering approach was used to identify molecular subtypes. The cumulative distribution function (CDF), proportion of ambiguously clustered pairs (PAC), principal component analysis (PCA) and consensus heatmaps were used to assess the optimal subtypes. In the differential molecular subtypes, we performed an integrated analysis of survival, DE genes, biological function and somatic mutations on the cohort of KIRP patients from The Cancer Genome Atlas.ResultsFrom solutions with 2, 3, 4, 5, 6 and 7 clusters we selected three KIRP molecular subtypes after assessing PCA, PAC, CDF and consensus heatmaps. We found that the three subtypes are associated with different overall survival and molecular characteristics. Compared with subtype1 and subtype3, subtype2 had a better prognosis in KIRP patients. After exploring their signaling pathways and biological characteristics, we identified the significantly enriched KEGG pathways and Gene Ontology terms for the three subtypes. The distribution of PARD6B, SETD2, STAG2, CUL3, TNRC18, LRBA, IGSF9B and DUNC1H1 mutations differed between the subtypes.ConclusionWe performed unsupervised clustering using differentially expressed miRNA expression data and described the three KIRP molecular subtypes. The three subtypes differed in overall survival, molecular characteristics and gene mutation frequency.
Project description:BackgroundPerioperative C-reactive protein (CRP) levels have effects on the prognosis of cancer patients. We intended to determine the prognostic value of combining the two for gastric cancer (GC).MethodsData were extracted from a clinical trial. By calculating the area under the curve (AUC) and the C-index, the predictive value of CRPs among different time points, including preoperative (pre-CRP), postoperative days 1, 3, and 5 (post-CRPs), and postoperative maximum CRP (post-CRPmax ), was derived. Multivariate analysis was performed to further explore the independent variates for recurrence-free survival (RFS).ResultsFinally, 401 patients were available in the present study. For RFS, higher AUC (0.692) and concordance index (0.678) of pre-CRP were observed when compared with those of post-CRPs. Further, among post-CRPs, post-CRPmax had the highest predictive values (AUC: 0.591; concordance index: 0.585) among the other post-CRPs. The threshold values in predicting RFS for pre-CRP and post-CRPmax were 3.1 mg/L and 77.1 mg/L. Multivariate analysis showed both pre-CRP≥3.1 mg/L (high-pre-CRP) and post-CRPmax ≥77.1 mg/L (high-post-CRPmax ) were risk factors for RFS. Postoperative chemotherapy benefit was further analyzed for patients with stage II/III GC and indicated that patients with pre-CRP<3.1 mg/L had better prognosis without benefit from postoperative adjuvant chemotherapy (ACT), p = 0.557. In high-pre-CRP patients, only patients with post-CRPmax ≥77.1 mg/L but not post-CRPmax <77.1 mg/L benefited from postoperative ACT (RFS: 33.2% vs 49.9% for non-chemotherapy group and chemotherapy group, respectively, p = 0.037). Analyses for overall survival obtained the similar outcomes.ConclusionsBoth high-pre-CRP and high-post-CRPmax are associated with worse prognosis in GC. ACT seems to only improve the prognosis for stage II/III GC with pre-CRP≥3.1 mg/L and post-CRPmax ≥77.1 mg/L after radical gastrectomy. Further studies are needed to confirm these findings and explore the potential mechanism.