MCT4-dependent lactate transport: a novel mechanism for cardiac energy metabolism injury and inflammation in type 2 diabetes mellitus.

Diabetic cardiomyopathy (DCM) is a major contributor to mortality in diabetic patients, characterized by a multifaceted pathogenesis and limited therapeutic options. While lactate, a byproduct of glycolysis, is known to be significantly elevated in type 2 diabetes, its specific role in DCM remains uncertain. This study reveals an abnormal upregulation of monocarboxylate transporter 4 (MCT4) on the plasma membrane of cardiomyocytes in type 2 diabetes, leading to excessive lactate efflux from these cells. The disruption in lactate transport homeostasis perturbs the intracellular lactate-pyruvate balance in cardiomyocytes, resulting in oxidative stress and inflammatory responses that exacerbate myocardial damage. Additionally, our findings suggest increased lactate efflux augments histone H4K12 lactylation in macrophages, facilitating inflammatory infiltration within the microenvironment. In vivo experiments have demonstrated that inhibiting MCT4 effectively alleviates myocardial oxidative stress and pathological damage, reduces inflammatory macrophage infiltration, and enhances cardiac function in type 2 diabetic mice. Furthermore, a clinical prediction model has been established, demonstrating a notable association between peripheral blood lactate levels and diastolic dysfunction in individuals with type 2 diabetes. This underscores the potential of lactate as a prognostic biomarker for DCM. Ultimately, our findings highlight the pivotal involvement of MCT4 in the dysregulation of cardiac energy metabolism and macrophage-mediated inflammation in type 2 diabetes. These insights offer novel perspectives on the pathogenesis of DCM and pave the way for the development of targeted therapeutic strategies against this debilitating condition.

Effect of proanthocyanidins on blood lipids: A systematic review and meta-analysis.

Proanthocyanidins (PCs) are natural antioxidant polyphenols and their effect on the regulation of blood lipids is still controversial. This study was conducted to evaluate the effect of PCs on lipid metabolism. We searched PubMed, Embase, Web of Science, Chinese biomedical literature service system, China National Knowledge Internet, and Wanfang Data with no time restriction until March 18, 2022, using various forms of "proanthocyanidins" and "blood lipid" search terms. Randomized controlled trials investigating the relationship between PCs and lipid metabolism were included. The standard system of Cochrane Collaboration was used to assess the quality of studies. We standardized mean differences (SMDs) with 95% confidence interval (CI) using the random-effects model, Cohen approach. Seventeen studies (17 trials, N = 1138) fulfilled the eligibility criteria. PCs significantly reduced triglyceride, and increased recombinant apolipoprotein A1. Subgroup analysis showed a significant reduction in triglycerides in older adults (≥60 years) and total cholesterol for participants who were not overweight or obese (body mass index <24). An intervention duration of greater than 8 weeks reduced triglyceride and low-density lipoprotein cholesterol levels but increased high-density lipoprotein cholesterol. Different doses of PCs could regulate triglycerides, high-density lipoprotein cholesterol and total cholesterol. PCs have beneficial effects on circulating lipids and may represent a new approach for treating or preventing lipid metabolism disorders. However, more high-quality studies are needed to confirm these results.

Hyperglycemia-induced STING signaling activation leads to aortic endothelial injury in diabetes.

Hyperglycaemia-induced endothelial dysfunction is a key factor in the pathogenesis of diabetic microangiopathy and macroangiopathy. STING, which is a newly discovered regulator of innate immunity, has also been reported to play an important role in various metabolic diseases. However, the role of STING in diabetes-induced endothelial cell dysfunction is unknown. In this study, we established a diabetic macroangiopathy mouse model by streptozotocin (STZ) injection combined with high-fat diet (HFD) feeding and a glucotoxicity cell model in high glucose (HG)-treated rat aortic endothelial cells (RAECs). We found that STING expression was specifically increased in the endothelial cells of diabetic arteries, as well as in HG-treated RAECs. Moreover, genetic deletion of STING significantly ameliorated diabetes-induced endothelial cell dysfunction and apoptosis in vivo. Likewise, STING inhibition by C-176 reversed HG-induced migration dysfunction and apoptosis in RAECs, whereas STING activation by DMXAA resulted in migration dysfunction and apoptosis. Mechanistically, hyperglycaemia-induced oxidative stress promoted endothelial mitochondrial dysfunction and mtDNA release, which subsequently activated the cGAS-STING system and the cGAS-STING-dependent IRF3/NF-kB pathway, ultimately resulting in inflammation and apoptosis. In conclusion, our study identified a novel role of STING in diabetes-induced aortic endothelial cell injury and suggested that STING inhibition was a potential new therapeutic strategy for the treatment of diabetic macroangiopathy. Video Abstract.

Phase II multicenter trial: first-line immunochemotherapy with or without radiotherapy in metastatic esophageal squamous cell cancer (SCR-ESCC-01).

This randomized phase II trial (NCT05978193) combines low-dose radiotherapy (LDRT) and conventionally fractionated radiotherapy (CFRT) with immunochemotherapy for metastatic esophageal squamous cell carcinoma, aiming to assess the potential enhanced effect of radiotherapy on immunotherapy. Patients are administered a PD-1 inhibitor along with paclitaxel and platinum-based chemotherapy (arm B), or combined with LDRT and CFRT (arm A). Immunotherapy is given every 3 weeks with chemotherapy for 4 cycles, followed by immunotherapy maintenance therapy for up to 24 months. In arm A, LDRT (2 Gy, 2 fractions; delivered to the primary and all metastatic tumors) precedes each immunochemotherapy cycle for 4 cycles, followed by CFRT (40-50 Gy, 20-25 fractions; delivered to the primary tumor) starting from the fifth immunotherapy cycle. The primary end point is median progression-free survival. Clinical Trial Registration: NCT05978193 (clinicaltrials.gov).

The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction.

Diabetes mellitus is a metabolic disease characterized by long-term hyperglycaemia, which leads to microangiopathy and macroangiopathy and ultimately increases the mortality of diabetic patients. Endothelial dysfunction, which has been recognized as a key factor in the pathogenesis of diabetic microangiopathy and macroangiopathy, is characterized by a reduction in NO bioavailability. Oxidative stress, which is the main pathogenic factor in diabetes, is one of the major triggers of endothelial dysfunction through the reduction in NO. In this review, we summarize the four sources of ROS in the diabetic vasculature and the underlying molecular mechanisms by which the pathogenic factors hyperglycaemia, hyperlipidaemia, adipokines and insulin resistance induce oxidative stress in endothelial cells in the context of diabetes. In addition, we discuss oxidative stress-targeted interventions, including hypoglycaemic drugs, antioxidants and lifestyle interventions, and their effects on diabetes-induced endothelial dysfunction. In summary, our review provides comprehensive insight into the roles of oxidative stress in diabetes-induced endothelial dysfunction.

Lipotoxicity-induced mtDNA release promotes diabetic cardiomyopathy by activating the cGAS-STING pathway in obesity-related diabetes.

Diabetic cardiomyopathy (DCM) is characterized by lipid accumulation, mitochondrial dysfunction, and aseptic inflammatory activation. Mitochondria-derived cytosolic DNA has been reported to induce inflammation by activating cyclic GMP-AMP synthase (cGAS)/the stimulator of interferon genes (STING) pathway in the adipose, liver, and kidney tissues. However, the role of cytosolic mtDNA in the progression of DCM is unclear. In this study, with an obesity-related DCM mouse model established by feeding db/db mice with a high-fat diet (HFD), we observed increased mtDNA in the cytosol and activated cGAS-STING signaling pathway during DCM, as well as the downstream targets, IRF3, NF-κB, IL-18, and IL-1ß. In a further study with a palmitic acid (PA)-induced lipotoxic cell model established in H9C2 cells, we revealed that the cytosolic mtDNA was the result of PA-induced overproduction of mitochondrial ROS, which also led to the activation of the cGAS/STING system and its downstream targets. Notably, treatment of extracted mtDNA alone was sufficient to activate the cGAS-STING signaling pathway in cultured H9C2 cells. Besides, both knockdown of STING in PA-induced H9C2 cells and inhibition of STING by C-176 injection in the DCM mouse model could remarkably block the inflammation and apoptosis of cardiomyocytes. In conclusion, our study elucidated the critical role of cytosolic mtDNA-induced cGAS-STING activation in the pathogenesis of obesity-related DCM and provided preclinical validation for using a STING inhibitor as a new potential therapeutic strategy for the treatment of DCM.

The predictive value of peripheral blood cells and lymphocyte subsets in oesophageal squamous cell cancer patients with neoadjuvant chemoradiotherapy.

Purpose: Neoadjuvant chemoradiotherapy (nCRT) is a standard treatment option for patients with stage III oesophageal cancer. Approximately 30% of oesophageal cancer patients will have a pathological complete response (pCR) after nCRT. However, available clinical methods cannot accurately predict pCR for patients. We aimed to find more indicators that could be used to predict the pathological response to nCRT. Method: A total of 84 patients with stage III oesophageal squamous cell cancer were enrolled in this study. Ten patients failed to have surgery as a result of progressive disease (PD). Among the patients who underwent surgery, 32 patients had a pathologic complete response (pCR), whereas 42 patients showed no or partial response (npCR) after nCRT. Routine blood test results and lymphocyte subset assessments before and after nCRT were retrospectively analysed. Univariate and multivariate analyses were used to identify independent predictors of the clinical curative effect of nCRT. Eventually, nomograms were established for predicting the PD and pCR rates. Results: The numbers of lymphocytes, B lymphocytes, T lymphocytes, Th lymphocytes, Ts lymphocytes, and NK cells and the percentages of B lymphocytes and NK cells were decreased significantly after nCRT (P < 0.0001), whereas the percentages of T lymphocytes and Ts lymphocytes increased (P < 0.0001). Univariate analysis showed that age, the length of the lesion, the level of haemoglobin before nCRT, and the amount of change in haemoglobin were related to PD, and the percentage of NK cells after nCRT was related to pCR. Multivariate logistic analysis demonstrated that the length of the lesion, the neutrophil-to-lymphocyte ratio (NLR) before nCRT, and the amount of change in haemoglobin were independent predictors of PD, whereas the percentage of NK cells after nCRT was an independent predictor of pCR. Conclusion: Lymphocyte subsets changed dramatically during nCRT, and these changes together with baseline and posttreatment lymphocyte subsets have predictive value in determining the response to nCRT for oesophageal cancer.

Circular RNA hsa_circ_0003823 promotes the Tumor Progression, Metastasis and Apatinib Resistance of Esophageal Squamous Cell Carcinoma by miR-607/CRISP3 Axis.

Background: Circular RNAs (CircRNAs) have attracted a growing interest of research in cancer. The regulatory roles and mechanisms of circRNAs in progression, metastasis and drug resistance of esophageal squamous cell carcinoma (ESCC) needed to be clarified. Our previous study revealed the crucial role of Apatinib in ESCC therapy. However, the correlation between circRNAs and Apatinib resistance remained unclear. Methods: 3 pairs of tumor and paracancerous tissues of ESCC patients were used for RNA sequencing. Western blot analysis, RNA immunoprecipitation (RIP), dual-luciferase reporter assays, apoptosis and animal assays were conducted to confirm the roles and specific mechanisms of hsa_circ_0003823 as well as the effects of it on Apatinib sensitivity in ESCC. Results: Our results revealed that hsa_circ_0003823 was highly expressed in ESCC and associated with poor prognosis. Further results indicated that hsa_circ_0003823 promoted proliferation and metastasis ability of ESCC. In the section of mechanism experiments, hsa_circ_0003823 regulated CRISP3 by targeting microRNA-607 (miR-607) to promote progression of ESCC. Besides, we found that silencing hsa_circ_0003823 improved Apatinib sensitivity. hsa_circ_0003823 resulted in Apatinib resistance by miR-607/CRISP3 axis. Conclusions: In this study, we elucidated the function of hsa_circ_0003823 and its role in promoting tumor progression, metastasis and Apatinib resistance of ESCC through miR-607/CRISP3 axis.

Effects of Camellia tea and herbal tea on cardiometabolic risk in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

Evidence for the anti-diabetic actions of camellia and herbal tea in diabetic patients has not been summarized. Several data sources were searched for randomized trials assessing the effect of different teas on cardiometabolic risk factors in T2D subjects. Two independent reviewers extracted relevant data and assessed the risk of bias. Results were summarized using mean differences (MDs) based on a random model. Sixteen studies (19 trials, N = 832) fulfilled the eligibility criteria. Mean differences were measured for body weight, body mass index, fasting blood glucose, glycosylated hemoglobin, a homeostatic model for insulin resistance, high and low-density lipoproteins, triglycerides, and systolic and diastolic blood pressure. No effects on total cholesterol and waist circumference were observed when either camellia or herbal tea was consumed. Tea produced moderate regulatory effects on adipose, glycemic control, lipid profiles, and blood pressure. In terms of efficacy, camellia and herbal teas yield different benefits in regulating metabolism. This discovery has some implications for clinical research and drug development. However, more high-quality trials are needed to improve the certainty of our estimates.

Apatinib induces endoplasmic reticulum stress-mediated apoptosis and autophagy and potentiates cell sensitivity to paclitaxel via the IRE-1α-AKT-mTOR pathway in esophageal squamous cell carcinoma.

BACKGROUND: Apatinib, a novel vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, has been approved for the treatment of metastatic gastric cancer and other tumors. Apatinib exerts antiproliferative and proapoptotic effects in different kinds of cancer cells. However, the molecular mechanisms by which apatinib effective against esophageal squamous cell carcinoma (ESCC) have only been partially researched and whether it has a sensitizing effect on paclitaxel remains unclear. MATERIALS AND METHODS: The effects of apatinib or paclitaxel on endoplasmic reticulum (ER) stress, autophagy, apoptosis and proliferation of ESCC cell lines were evaluated. Western blot and immunohistochemistry analyses were performed to detect the expression of related genes. The weight and volume of xenograft tumors in mice were measured. RESULTS: In the current study, we elucidated the antiproliferative and ER-stress-mediated autophagy-inducing effects of apatinib on ECA-109 and KYSE-150 esophageal squamous cancer cells and identified the underlying mechanisms of its action. We demonstrated that apatinib not only inhibited the proliferation and induced the apoptosis of ESCC cells, but also activated ER stress and triggered protective autophagy. Moreover, inhibiting autophagy by chloroquine (CQ) enhanced the apatinib-induced apoptosis of ESCC cells through the IRE-1α-AKT-mTOR pathway. In addition, we showed, for the first time, the paclitaxel combined with apatinib and CQ exhibited the best antitumor effect on ESCC both in vivo and in vitro via the IRE-1α-AKT-mTOR pathway. CONCLUSIONS: Our data showed that apatinib induced ER stress, autophagy and apoptosis in ESCC. Inhibiting autophagy by CQ enhanced apatinib-induced apoptosis. The combination of apatinib and CQ sensitized ESCC cells to paclitaxel to induce apoptosis through the IRE-1α-AKT-mTOR signaling pathway, thus providing the basis for its use in innovative anticancer therapeutic strategies.

Diffusion-weighted MRI and 18F-FDG PET/CT in assessing the response to neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is a currently widely used strategy for locally advanced esophageal cancer (EC). However, the conventional imaging methods have certain deficiencies in the evaluation and prediction of the efficacy of nCRT. This study aimed to explore the value of functional imaging in predicting the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Fifty-four patients diagnosed with locally advanced ESCC from August 2017 to September 2019 and treated with nCRT were retrospectively analyzed. DW-MRI scanning was performed before nCRT, at 10-15 fractions of radiotherapy, and 4-6 weeks after the completion of nCRT. 18F-FDG PET/CT scans were performed before nCRT and 4-6 weeks after the completion of nCRT. These 18F-FDG PET/CT and DW-MRI parameters and relative changes were compared between patients with pathological complete response (pCR) and non-pCR. RESULTS: A total of 8 of 54 patients (14.8%) were evaluated as disease progression in the preoperative assessment. The remaining forty-six patients underwent operations, and the pathological assessments of the surgical resection specimens demonstrated pathological complete response (pCR) in 10 patients (21.7%) and complete response of primary tumor (pCR-T) in 16 patients (34.8%). The change of metabolic tumor volume (∆MTV) and change of total lesion glycolysis (∆TLG) were significantly different between patients with pCR and non-pCR. The SUVmax-Tpost, MTV-Tpost, and TLG-Tpost of esophageal tumors in 18F-FDG PET/CT scans after neoadjuvant chemoradiotherapy and the ∆ SUVmax-T and ∆MTV-T were significantly different between pCR-T versus non-pCR-T patients. The esophageal tumor apparent diffusion coefficient (ADC) increased after nCRT; the ADCduring, ADCpost and ∆ADCduring were significantly different between pCR-T and non-pCR-T groups. ROC analyses showed that the model that combined ADCduring with TLG-Tpost had the highest AUC (0.914) for pCR-T prediction, with 90.0% and 86.4% sensitivity and specificity, respectively. CONCLUSION: 18F-FDG PET/CT is useful for re-staging after nCRT and for surgical decision. Integrating parameters of 18F-FDG PET/CT and DW-MRI can identify pathological response of primary tumor to nCRT more accurately in ESCC.

Research of Biological Dose Conversion Platform Based on a Modified Linear Quadratic Model.

The study aimed to develop a novel dose conversion platform by improving linear-quadratic (LQ) model to more accurately describe radiation response for high fraction/acute doses. This article modified the LQ model via piecewise fitting the biological dose curve using different fractionated dose and optimizing the consistency between mathematical model and experimental data to gain a more reasonable transform. That mathematical development of the LQ model further amended certain deviations of various cell curves with high doses and implied the rationality of the present model at low dose range. The modified biologically effective dose model that solved the dilemma of inaccurate LQ model had been used in comparing between hypofractionated and conventional fractioned dose. It has been verified that the calculated values are similar in the treatment of same efficacy, no matter what α/ß is, and provided a more rational explanation for significant differences among various hypofractionations. The equivalent uniform dose based on the subsection function could represent arbitrary inhomogeneous dose distributions including high-dose fractions, providing a foundation for the implementation of detailed evaluation of different cell dose effects.

Heparanase promotes human gastric cancer cells migration and invasion by increasing Src and p38 phosphorylation expression.

Gastric cancer is one of the most common cancers and it remains difficult to cure, primarily because most cancer stem like cells possess higher capability of invasion and metastasis. Heparanase acts as a master regulator of the aggressive tumor phenotype in part by enhancing expression of proteins and activating signaling molecules. There were less associated with heparanase of molecular biology mechanism in human gastric cancer. We first evaluated the endogenous expression of heparanase in human gastric cancer cell lines and found Heparanase expression higher in SGC-7901 than MGC-803. Using the technology of RNAi in SGC-7901 cells down regulated heparanase gene, and reduced SGC-7901 cells migration and invasion. On the other hand, recombinant heparanase protein added in MGC-803 cells enhanced MGC-803 cell migration and invasion. The elevated cell migration and invasion were impaired by treatment of Src inhibitor pp2 or p38 inhibitor SB 203580. We further found that Stable knockdown of heparanase in SGC-7901 cells decreased phosphorylation of Src and p38. The phosphorylation of p38 was inhibited in response to pp2 treatment while the addition of SB 203580 to SGC-7901 cells did not change phosphorylation of Src. These data suggest that heparanase facilitates invasion and migration of human gastric cancer cells probably through elevating phosphorylation of Src and p38.

Esophageal perforation during or after conformal radiotherapy for esophageal carcinoma.

The aim of this study was to analyze the risk factors and prognosis for patients with esophageal perforation occurring during or after radiotherapy for esophageal carcinoma. We retrospectively analyzed 322 patients with esophageal carcinoma. These patients received radiotherapy for unresectable esophageal tumors, residual tumors after operation, or local recurrence. Of these, 12 had radiotherapy to the esophagus before being admitted, 68 patients had concurrent chemoradiotherapy (CRT), and 18 patients had esophageal perforation after RT (5.8%). Covered self-expandable metallic stents were placed in 11 patients. Two patients continued RT after stenting and control of infection; one of these suffered a new perforation, and the other had a massive hemorrhage. The median overall survival was 2 months (0-3 months) compared with 17 months in the non-perforation group. In univariate analysis, the Karnofsky performance status (KPS) being ≤ 70, age younger than 60, T4 stage, a second course of radiotherapy to the esophagus, extracapsular lymph nodes (LN) involving the esophagus, a total dose >100 Gy (biologically effective dose-10), and CRT were risk factors for perforation. In multivariate analysis, age younger than 60, extracapsular LN involving the esophagus, T4 stage, and a second course of radiotherapy to the esophagus were risk factors. In conclusion, patients with T4 stage, extracapsular LN involving the esophagus, and those receiving a second course of RT should be given particular care to avoid perforation. The prognosis after perforation was poor.

Analysis of simultaneous modulated accelerated radiotherapy (SMART) for nasopharyngeal carcinomas.

The purpose of this study was to analyze the clinical outcomes of simultaneous modulated accelerated radiotherapy (SMART) in patients with nasopharyngeal carcinoma (NPC). A total of 97 patients who underwent SMART for NPC between August 2005 and November 2011 were evaluated. The prescribed dose was 69.9 Gy/30 fractions at 2.33 Gy/fraction to the primary gross tumor volume (PGTV) including the nasopharynx gross target volume and the positive neck lymph nodes, and 60 Gy/30 fraction at 2.0 Gy/fraction to the PCTV1; 54 Gy/30 fractions at 1.8 Gy/fraction was given to the PCTV2. Among 59 patients with local advanced disease, 31 patients received concurrent chemoradiotherapy (chemo-RT) with a regimen consisting of 135 mg/m(2) paclitaxel on Day 1 and 25 mg/m(2) cisplatin on Days 1-3. The median follow-up period was 42 months. The local control rate (LCR), distant metastases-free survival (DMFS) and overall survival (OS) rates were 93.3%, 90.3% and 91.6% at 3 years, and 87.6%, 87.9% and 85.7% at 5 years, respectively. There was no significant difference in outcome with respect to these three indicators for Stage III and IV disease treated with/without concurrent chemoradiotherapy (P > 0.05). Acute toxicities included Grade 3 mucositis, skin desquamation, and leucopenia, which occurred in 78 (80.4%), 8 (8.2%), and 45 (46.4%) patients, respectively. No patient had a Grade 3-4 late toxicity. SMART was associated with a favorable outcome for NPC with acceptable toxicity. The local-regional control was excellent but distant metastasis remains the main risk. The combination of SMART and chemotherapy needs to be optimized through further studies to enhance outcomes for locally advanced diseases.

Photoelectrical properties of insulating LaAlO3-SrTiO3 interfaces.

We report photoconductivity of an insulating LaAlO3-SrTiO3 (LAO-STO) heterointerface. Persistent photocurrent induced by a 514 nm laser at room temperature is significant, which is attributed to carriers trapped by a built-in potential well at the interface. Further studies of photoconductivity of the insulating LAO-STO interface performed with a monochrometer demonstrate the photoelectrical response not only in the ultraviolet region but also in the visible and infrared regions. The extrinsic photoconductivity indicates several midgap states located in the insulating LAO-STO interface. Our results provide a deep understanding of the band structure of the insulating LAO-STO heterointerface and promising applications as optoelectronic devices.

Reversible insulator-metal transition of LaAlO3/SrTiO3 interface for nonvolatile memory.

We report a new type of memory device based on insulating LaAlO3/SrTiO3 (LAO/STO) hetero-interface. The microstructures of the LAO/STO interface are characterized by Cs-corrected scanning transmission electron microscopy, which reveals the element intermixing at the interface. The inhomogeneous element distribution may result in carrier localization, which is responsible for the insulating state. The insulating state of such interface can be converted to metallic state by light illumination and the metallic state maintains after light off due to giant persistent photoconductivity (PPC) effect. The on/off ratio between the PPC and the initial dark conductance is as large as 105. The metallic state also can be converted back to insulating state by applying gate voltage. Reversible and reproducible resistive switching makes LAO/STO interface promising as a nonvolatile memory. Our results deepen the understanding of PPC phenomenon in LAO/STO, and pave the way for the development of all-oxide electronics integrating information storage devices.

Effectiveness and toxicities of intensity-modulated radiotherapy for patients with locally recurrent nasopharyngeal carcinoma.

PURPOSE: To analyze the effectiveness and toxicities in the re-irradiation of locally recurrent nasopharyngeal carcinoma (NPC) using intensity-modulated radiotherapy (IMRT). METHODS: This is a retrospective analysis of 54 NPC patients with local recurrence re-irradiated with IMRT. The re-staging for rT1, rT2, rT3, rT4 were 3 (5.6%), 8 (14.8%), 9 (16.7%), 34 (63%) respectively. The average dose to GTV was 69.95 Gy (49.8-76.58 Gy), the average BED(3Gy) was 116.8 Gy (83.5-127.9 Gy). V95 was 96%, and D95 was 65.75 Gy. 33.3% of them received concurrent chemoradiotherapy. RESULTS: Median overall survival (OS) was 21 months (1-93 mon). The 1-, 2-year local progression free survival (LPFS) rate was 84.5%, 64% and OS rate was 71.7%, 44.3%. Severe late adverse events (SLAE) occurred in 48.1% of patients, including 31.5% with ulcer or necrosis of the nasopharyngeal mucosa, 20.4% with difficulty in feeding, 18.5% with temporal lobe necrosis, 11.1% with massive hemorrhage. 15.4% died of local regional progression, 5.8% died of distant metastasis, 25% died of SLAE, 9.6% died of both local regional progression and SLAE that could not be differentiated, 5.8% died of other medical complications. Concurrent chemoradiotherapy was the independent negative prognostic factors for LPFS; PTV>100 ml was a predictive factor of poor OS; patients with invasion of post-styloid space were at higher risk of SLAE. CONCLUSIONS: The present study demonstrated that IMRT with 70Gy was efficient for local tumor control. However, we observed a high frequency of serious late complications. More optimized combination treatment and patient selection are required to achieve excellent local control without significant late morbidities in locally recurrent NPC.

CT-pathologic correlation in primary hepatocellular carcinoma: an implication for target delineation.

The purpose of this investigation was to analyze the correlation between CT size and gross pathologic size for subjects with primary hepatocellular carcinoma (HCC). This analysis included 174 patients with HCC who underwent surgery. Enhanced computed tomography (CT) was performed up to 30 days before surgery. After resection, the size of the tumor on gross pathologic examination was recorded. The maximal measurement in one dimension on axial imaging and pathologic examination was extracted for statistical analysis. The clinical and pathologic sizes were compared using a percent size difference (%Δsize) as an end point. A regression analysis was applied to study the association between pathologic and radiographic size. The median radiographic and pathologic size were 70.58 ± 38.9 mm and 68.59 ± 40.56 mm, respectively. The radiographic size was larger than or equal to the pathologic size in 110/174 tumors (63.2%), and smaller in 64/174 (36.8%) tumors. Overall, the radiographic and pathologic sizes were positively correlated (r = 0.983, P = 0.000). CT seemed to overestimate the tumor size by 2.16 mm compared to final pathology (P = 0.024). The median %Δsize was 3.3%. Pathologic tumor size was significantly underestimated in patients with a tumor size 3-5 cm (P = 0.011), Grade I HCC (P = 0.023), with clear boundary (P = 0.013). We concluded that CT size and pathologic size were positively correlated, but differences did exist. Utilizing the radiographic tumor when planning radiation would have covered 63.2% of gross tumors. For a radiographic tumor size < 50 mm, utilizing a 3-mm margin around the radiographic tumor would have covered 90% of gross lesions, while a margin of 5 mm would have covered 95%, and a margin of 15 mm would have covered 100%.