Blue Nevus Hidden within the Nevus of Ota.

A 3-year-old boy presented with bluish patch and scattered blue spots on the left side of his face. After several sessions of laser treatment, the azury patch in the periorbital area became even darker. Histopathology showed many bipolar, pigment-laden dendritic cells scattered in the papillary and upper reticular dermis. Immunohistochemically, these cells were positive for S100, SOX-10, melan-A, P16, and HMB-45. The positive rate of Ki-67 was less than 5%. Finally, the lesion was diagnosed with nevus of Ota concurrent with common blue nevus. Therefore, for cases of the nevus of Ota with poor response to laser treatment, the possible coexisting diseases should be suspected.

Acute radiation dermatitis among patients with nasopharyngeal carcinoma treated with proton beam therapy: Prognostic factors and treatment outcomes.

A high incidence of severe acute radiation dermatitis (ARD) has been reported for cancer patients treated by proton beam therapy (PBT). This observational study investigated the prognostic factors and treatment outcomes of ARD among patients with nasopharyngeal carcinoma (NPC) treated with PBT. Fifty-seven patients with newly diagnosed NPC and treated with PBT were enrolled. ARD was recorded weekly based on the criteria of Common Terminology Criteria for Adverse Events version 4.0 at treatment visits (1st to 7th weeks) and 1 week (8th week) and 1 month (11th week) after the completion of PBT. The maximum ARD grade was 1, 2, and 3 in 26 (45.6%), 24 (42.1%), and 7 (12.3%) of the patients, respectively. The peak incidence of grade 2 and 3 ARD was observed during the period of the 6th to 8th weeks. Treatment of ARD included topical corticosteroid alone in 24 (42.1%) patients, topical corticosteroid plus silver sulfadiazine in 33 (57.9%) patients, and non-adhering silicone dressing to cover severe skin wound area in 25 (43.8%) patients. In the 11th week, most grade 2 and 3 ARD had disappeared and 93.0% of the patients had ARD of grade 1 or lower. In the binary logistic regression model, we identified habitual smoking (odds ratio [OR]: 5.2, 95% confidence interval [CI]: 1.3-18.8, P = .012) and N2 to N3 nodal status (OR: 4.9, 95% CI: 1.6-15.4, P = .006) as independent predictors of grade 2 and 3 ARD. The results show ARD is a major concern for patients with NPC treated with PBT, especially those with habitual smoking or advanced nodal status. Topical corticosteroid, silver sulfadiazine, and non-adhering silicone dressing are effective for treating ARD induced by PBT.

The bidirectional association of C-peptide with cardiovascular risk in nondiabetic adults and patients with newly diagnosed type 2 diabetes mellitus: a retrospective cohort study.

BACKGROUND: Recent literature reported the biological role of C-peptide, but this role is still controversial and unclear. The primary aim of this study was to investigate associations between C-peptide and cardiovascular biomarkers as well as events. METHODS: A total of 55636 participants who had a health examination from 2017 to 2021 were included. Of them, 6727 participants visited the hospital at least twice. Cardiovascular biomarkers like high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured and their relationships with fasting C-peptide were evaluated for all participants. Cardiovascular events were obtained during the last visit and their associations with C-peptide were evaluated for those participants who visited the hospital at least twice. RESULTS: Among the included participants, 11.1% had a previous type 2 diabetes mellitus (T2DM). In the participants without previous T2DM, the relationships between fasting C-peptide and hs-CRP and hs-cTnT were negative if the value of fasting C-peptide was < 1.4 ng/mL and positive if the value was ≥ 1.4 ng/mL. These relationships remained significant after adjusting for hemoglobin A1c, insulin resistance index, and its interaction with C-peptide, even if the participants were stratified by glucose metabolism status or levels of insulin resistance index. Hazard ratios of cardiovascular events were first decreased and then increased with the increasing of baseline C-peptide levels, though these associations became unsignificant using the multivariate Cox regression model. Unlike the participants without previous T2DM, the associations of C-peptide with cardiovascular biomarkers and events were not significant in the patients with previous T2DM. CONCLUSIONS: The associations of C-peptide with cardiovascular biomarkers and events were different between the participants without previous T2DM and those with previous T2DM. The effect of C-peptide on cardiovascular risk may be bidirectional, play a benefit role at a low level, and play a harmful role at a high level in the nondiabetic adults and the patients with newly diagnosed T2DM.

The Long Noncoding RNA RP11-728F11.4 Promotes Atherosclerosis.

OBJECTIVE: Noncoding RNAs are emerging as important players in gene regulation and cardiovascular diseases. Their roles in the pathogenesis of atherosclerosis are not fully understood. The purpose of this study was to determine the role played by a previously uncharacterized long noncoding RNA, RP11-728F11.4, in the development of atherosclerosis and the mechanisms by which it acts. Approach and Results: Expression microarray analysis revealed that atherosclerotic plaques had increased expression of RP11-728F11.4 as well as the cognate gene FXYD6 (FXYD domain containing ion transport regulator 6), which encodes a modulator of Na+/K+-ATPase. In vitro experiments showed that RP11-728F11.4 interacted with the RNA-binding protein EWSR1 (Ewings sarcoma RNA binding protein-1) and upregulated FXYD6 expression. Lentivirus-induced overexpression of RP11-728F11.4 in cultured monocytes-derived macrophages resulted in higher Na+/K+-ATPase activity, intracellular cholesterol accumulation, and increased proinflammatory cytokine production. The effects of RP11-728F11.4 were enhanced by siRNA-mediated knockdown of EWSR1 and reduced by downregulation of FXYD domain containing ion transport regulator 6. In vivo experiments in apoE knockout mice fed a Western diet demonstrated that RP11-728F11.4 increased proinflammatory cytokine production and augmented atherosclerotic lesions. CONCLUSIONS: RP11-728F11.4 promotes atherosclerosis, with an influence on cholesterol homeostasis and proinflammatory molecule production, thus representing a potential therapeutic target. Graphic Abstract: A graphic abstract is available for this article.

Stigma, depression, and anxiety among patients with head and neck cancer.

PURPOSE: Patients with head and neck cancer (HNC) are vulnerable to psychiatric comorbidities, particularly anxiety and depression, and also suffer from cancer stigma. This study aimed to comprehensively compare HNC patients' stigma, depression, and anxiety, and elucidate the underlying relationships among them. METHODS: This cross-sectional study recruited inpatients with HNC from a medical center. Measurements included a psychiatric diagnostic interview, the Shame and Stigma Scale (SSS), the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the Explanatory Model Interview Catalogue (EMIC), and stressors of HNC patients. Structural equation modeling was used to establish models of potential mechanisms. RESULTS: Those patients having stressors of worry about health (t = 5.21, p < 0.001), worry about job (t = 2.73, p = 0.007), worry about family (t = 2.25, p = 0.026), or worry about economic problems (t = 2.09, p = 0.038) showed significantly higher SSS score than those having no such stressor. The SSS total score was significantly correlated with HAM-A (r = 0.509, p < 0.001), HAM-D (r = 0.521, p < 0.001), and EMIC (r = 0.532, p < 0.001) scores. Structural equation modeling was used to propose the possible effect of stigma on anxiety (ß = 0.51, p < 0.001), and then the possible effect of anxiety on depression (ß = 0.90, p < 0.001). CONCLUSION: Stigma is significantly correlated with anxiety and depression and might in HNC patients. Proper identification of comorbidities and a reduction of stigma should be advised in mental health efforts among patients with HNC.

RSF1 requires CEBP/ß and hSNF2H to promote IL-1ß-mediated angiogenesis: the clinical and therapeutic relevance of RSF1 overexpression and amplification in myxofibrosarcomas.

Myxofibrosarcoma is genetically complex and lacks effective nonsurgical treatment strategies; thus, elucidation of novel molecular drivers is urgently needed. Reanalyzing public myxofibrosarcoma datasets, we identified mRNA upregulation and recurrent gain of RSF1 and characterized this chromatin remodeling gene. Myxofibrosarcoma cell lines were employed to elucidate the oncogenic mechanisms of RSF1 by genetic manipulation and two IL-1ß-neutralizing antibodies (RD24, P2D7KK), highlighting the regulatory basis and targetability of downstream IL-1ß-mediated angiogenesis. Tumor samples were assessed for RSF1, IL-1ß, and microvascular density (MVD) by immunohistochemistry and for RSF1 gene status by FISH. In vivo, RSF1-silenced and P2D7KK-treated xenografts were analyzed for tumor-promoting effects and the IL-1ß-linked therapeutic relevance of RSF1, respectively. In vitro, RSF1 overexpression promoted invasive and angiogenic phenotypes with a stronger proangiogenic effect. RT-PCR profiling identified IL1B as a top-ranking candidate upregulated by RSF1. RSF1 required hSNF2H and CEBP/ß to cotransactivate the IL1B promoter, which increased the IL1B mRNA level, IL-1ß secretion and angiogenic capacity. Angiogenesis induced by RSF1-upregulated IL-1ß was counteracted by IL1B knockdown and both IL-1ß-neutralizing antibodies. Clinically, RSF1 overexpression was highly associated with RSF1 amplification, IL-1ß overexpression, increased MVD and higher grades (all P ≤ 0.01) and independently predicted shorter disease-specific survival (P = 0.019, hazard ratio: 4.556). In vivo, both RSF1 knockdown and anti-IL-1ß P2D7KK (200 µg twice weekly) enabled significant growth inhibition and devascularization in xenografts. In conclusion, RSF1 overexpression, partly attributable to RSF1 amplification, contributes a novel proangiogenic function by partnering with CEBP/ß to cotransactivate IL1B, highlighting its prognostic, pathogenetic, and therapeutic relevance in myxofibrosarcomas.

Evaluation of the Z-score accuracy of noninvasive prenatal testing for fetal trisomies 13, 18 and 21 at a single center.

OBJECTIVE: To assess the correlation between Z-scores of positive noninvasive prenatal testing (NIPT) results and the positive predictive value (PPV) of NIPT. METHODS: Pregnancies with positive NIPT results at Guangzhou Women and Children's Medical Centre between July 2017 and May 2020 were included in this study. Fetal karyotyping or microarray analysis was provided to patients with abnormal NIPT results for confirmatory testing. Logistic regression analyses was applied to study the relationship between the Z scores and the PPV performance. The optimal cutoff values for indicating fetal common trisomies were obtained based on receiver operating characteristic (ROC) curve analysis, and then the PPV were calculated in pregnancies with positive NIPT results at Z-score greater than or equal to cutoff value and in patients with a Z-score between 3 and cutoff value respectively. RESULTS: A total of 214 pregnancies with positive NIPT results for fetal common trisomies were validated by invasive prenatal diagnosis and follow up in this study. Of these, NIPT indicated trisomy 13 in 25 cases, trisomy 18 in 54 cases and trisomy 21 in 135 patients. Logistic regression analyses showed a significant association (p < 0.05) between the Z-scores and true positive results for T21 and T18. For T13, the significant association was not observed (p > 0.05). The ROC curve analysis showed that the optimal cutoff Z-score for indicating fetal trisomies 13, 18, and 21 were 6.889, 7.574 and 6.612 respectively, and the corresponding area under curve were 0.706, 0.916, and 0.954. In this cohort with abnormal NIPT results, the cutoff values revealed a sensitivity of 96.8% and a specificity of 90% for indicating trisomies 21, and a sensitivity of 88.9% and a specificity of 92.6% for trisomies 18. However, probably due to the sample size, the sensitivity and specificity for indicating trisomy 13 were lower (85.7% and 61.1%) than that for trisomies 21 and 18. The PPVs in pregnancies with positive NIPT results at Z-score greater than or equal to cutoff value were 99.18% (121/122) for trisomy 21, 92.31% (24/26) for trisomy 18 and 46.15% (6/13) for trisomy 13. In patients with a Z-score between 3 and cutoff Z-score, the PPV of NIPT for trisomies 21, 18, and 13 were 30.77% (4/13), 10.71% (3/28), and 8.33% (1/12) respectively. Moreover, by classifying Z scores as 3 ≤ Z < 5, 5 ≤ Z < 10, and Z ≥ 10, the majority of Z scores were above 10 with a PPV of 99% for T21 and just 5.2% were between 3 and 5 with a PPV of 14.3%. In contrast for T18, over a third of tests had Z scores between 3 and 5. The PPV in this group is just over 5%. CONCLUSIONS: The present results show that the PPV performance of NIPT for fetal trisomies 13, 18, and 21 are closely associated with Z-score. The higher the Z-score, the greater the likelihood that the aneuploidy result is correct. Our experience in evaluating the Z-score accuracy of NIPT in this study could be of use in similar work.

Protective effect of sevoflurane on vascular endothelial glycocalyx in patients undergoing heart valve surgery: A randomised controlled trial.

BACKGROUND: The glycocalyx plays an important physiological role and may be damaged during cardiopulmonary bypass. Sevoflurane can protect the glycocalyx; however, its relevance in a clinical setting is unknown. OBJECTIVE: Glycocalyx degradation during cardiopulmonary bypass in patients was investigated. On the basis of the available experimental data, we hypothesised that sevoflurane-based anaesthesia would confer additional protection against cardiopulmonary bypass-induced glycocalyx damage. DESIGN: Randomised controlled study. SETTING: Clinical study at The First Affiliated Hospital of Wenzhou Medical University between June 2018 and March 2019. PATIENTS: Fifty-one patients. INTERVENTIONS: After intubation and mechanical ventilation, patients undergoing elective heart valve surgery were maintained under general anaesthesia with either propofol or sevoflurane during surgery. MAIN OUTCOME MEASURES: Glycocalyx markers (such as syndecan-1, heparan sulphate and hyaluronan), sheddases responsible for the degradation of the endothelial glycocalyx (such as matrix metalloproteinase-9 and cathepsin-B), urine albumin-to-creatinine ratio and levels of lactic acid and myocardial enzymes were all measured. Postoperative mechanical ventilation time and length of stay in the cardiac care unit and hospital were also measured. Morbidity and mortality after 30 days and 1 year were evaluated. RESULTS: The vascular endothelial glycocalyx was damaged during cardiopulmonary bypass. The glycocalyx damage in the sevoflurane group was less extensive than that in the propofol group. The urine albumin-to-creatinine ratio increased in both groups but was lower in the sevoflurane group. Enzymes including matrix metalloproteinase-9 and cathepsin-B were positively correlated with glycocalyx marker concentrations. After operation, the sevoflurane group showed lower levels of lactic acid and myocardial enzyme, as well as shorter duration of postoperative mechanical ventilation than the propofol group. CONCLUSION: Sevoflurane can decrease glycocalyx degradation in patients undergoing heart valve surgery under cardiopulmonary bypass. TRIAL REGISTRATION: Chinese Clinical Trial Registry, chictr.org.cn, identifier: ChiCTR1800016367.

Cerebral infarction After Laparoscopic Right Lung Wedge or Segment Resection: A Report of Four Cases.

Several cases have been reported of patients who experienced cerebral infarction following thoracoscope left lobectomy. Compared with right lung surgery, the pulmonary veins stump after left lobe surgery were longer and thrombosis was more likely. Besides, cases of cerebral infarction after right lung surgery are rarely reported. Left lobectomy is therefore considered as the main risk factor for postoperative cerebral infarction. However, here we report four cases of cerebral infarction after thoracoscopic wedge or segment resection of right lobe, which cause less damage to the pulmonary vein compared with lobectomy. Magnetic resonance imaging and computed tomography scan reveal intracranial vascular obstruction and cerebral infarction. The case 1 had a poor prognosis because doctors lacked experience treating such complications. In the case 2, the sequela of cerebral infarction was obvious due to the large cerebral infarction area. Benefiting from timely treatment, the rest recovered better.

Targeting mTOR-CCL20 Signaling May Improve Response to Docetaxel in Head and Neck Squamous Cell Carcinoma.

Patients with advanced head and neck squamous cell carcinoma (HNSCC) usually show a dismal prognosis. It is this worthwhile to develop new, effective therapeutic regimens for these patients, such as molecular targeted therapy, which is promising as an alternative or combination treatment for HNSCC. The mammalian target of rapamycin (mTOR) pathway, which plays an important role in the carcinogenesis of HNSCC, is the most frequently activated, and is thus worthy of further investigation. In this study, two human HNSCC cell lines, FaDu and SAS, were evaluated for cell growth with trypan blue staining and tumor growth using an orthotopic xenograft model. The immunohistochemical expression of mTOR in the subcutaneous xenograft model and the inhibitory effects of docetaxel on the growth and state of activation of the PI3K/mTOR pathway were also evaluated and examined by colony formation and Western blot, respectively. Cell proliferation and migration were measured by water-soluble tetrazolium salt (WST-1) and OrisTM cell migration assay, respectively. Furthermore, the effects of rapamycin and BEZ235, a phosphatidylinositol 3-kinases (PI3K) and mTOR inhibitor in combination with docetaxel or CCL20 were evaluated in the FaDu and SAS cells. The results showed that the expression of mTOR was significantly higher in the SAS and FaDu xenograft models than in the control. Docetaxel treatment significantly suppressed HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. Additionally, when administered in a dose-dependent fashion, mTOR inhibitors inhibited the growth and migration of the HNSCC cells. This combination was synergistic with docetaxel, resulting in almost complete cell growth and migration arrest. In conclusion, docetaxel significantly inhibited HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. The synergistic and additive activity of mTOR inhibitors combined with docetaxel shows potential as a new treatment strategy for HNSCC.

Risk factors associated with fetal pleural effusion in prenatal diagnosis: a retrospective study in a single institute in Southern China.

The aim of this study was to analyse the factors associated with fetal pleural effusion over the past five years in a single institute in the South of China. Between January 2011 and May 2016, 129 foetuses with pleural effusion were referred to the Fetal Medicine Unit in Guangzhou's Women and Children's Medical Center. Seventy-nine women accepted an invasive procedure to rule out chromosomal abnormalities, fetal anaemia, intrauterine infections or some of the submicroscopic chromosomal abnormalities. Our results showed that chromosomal anomalies occurred in 15.2% (12/79) of cases including 8 Turner syndrome (45, X) (10.1%), 3 trisomy 21 (3.8%) and 1 trisomy 13 (1.3%). Pathological microdeletion or microduplication syndrome occurred in 3 out of 36 (8.3%) prenatal samples with normal karyotype and structural defects. Eight foetuses (10.1%) affected with haemoglobin Bart's disease showed pleural effusion at second or third trimester. Two cases (2.5%) were found to have an intrauterine infection. In conclusion, fetal pleural effusion has a close correlation with chromosomal abnormality. CMA may increase the detection rate of chromosomal aberrations, especially for micro-deletion or micro-duplication syndromes. In the South of China, Thalassemia must be considered when a fetal pleural effusion is detected.Impact statementWhat is already known on this subject? The aetiology of fetal pleural effusion includes a chromosomal abnormality, a congenital heart disease, congenital infections and a number of genetic syndromes.What do the results of this study add? This is the first retrospective study to analyse the aetiology of fetal pleural effusion in one institute in the South of China.What are the implications of these findings for clinical practice and/or further research? Besides the chromosomal abnormality, micro-deletion and micro-duplication syndromes were also detected in our study. We feel that thalassemia must be considered when fetal pleural effusion is detected in South China.

The proposed physiology-based FDG PET/CT criteria in reducing false-positive results in advanced head and neck cancer after chemoradiotherapy.

BACKGROUND: Distinguishing benign complications after concurrent chemoradiotherapy (CCRT) from a local residual tumor in advanced head and neck squamous cell carcinoma (HNSCC) remains a clinical challenge. In this study, we propose criteria when considering physiological uptake patterns on F-18-fluorodeoxyglucose (FDG) PET/CT in patients with advanced HNSCC after CCRT. METHODS: We retrospectively reviewed FDG PET/CT images of 62 patients with advanced HNSCC, which were taken within 16 weeks following CCRT. Visual interpretation criteria were rated by three nuclear medicine physicians, independently, according to the uptake patterns of the primary site. The Cohen k coefficient was calculated to assess inter-reader agreement. The histology of the primary site within a 1 month of the PET/CT study was used as the gold standard for sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: PET/CT was arranged at a median interval of 10.5 weeks (range 4-16 weeks) after CCRT, and the pathologic residual rate was 55.7% at the primary site. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of identifying residual disease were 91.1%, 50.0%, 68.9%, 82.3%, and 72.6%, respectively, by the previously established criteria, and 88.2%, 92.9%, 93.8%, 86.7%, and 90.3%, respectively, by our physiology-based criteria. Our visual rating criteria corrected 12 of 14 (84.6%) false-positive results from the established criteria, while two more false-negative cases identified with our criteria were proven to be small residual tumors. CONCLUSIONS: By incorporating physiological changes following CCRT, our visual rating criteria improved the accuracy of the currently used FDG PET/CT visual rating system, especially the number of false-positive cases with advanced HNSCC after CCRT.

Pif1 is a force-regulated helicase.

Pif1 is a prototypical member of the 5' to 3' DNA helicase family conserved from bacteria to human. It has a high binding affinity for DNA, but unwinds double-stranded DNA (dsDNA) with a low processivity. Efficient DNA unwinding has been observed only at high protein concentrations that favor dimerization of Pif1. In this research, we used single-molecule fluorescence resonance energy transfer (smFRET) and magnetic tweezers (MT) to study the DNA unwinding activity of Saccharomyces cerevisiae Pif1 (Pif1) under different forces exerted on the tails of a forked dsDNA. We found that Pif1 can unwind the forked DNA repetitively for many unwinding-rezipping cycles at zero force. However, Pif1 was found to have a very limited processivity in each cycle because it loosened its strong association with the tracking strand readily, which explains why Pif1 cannot be observed to unwind DNA efficiently in bulk assays at low protein concentrations. The force enhanced the unwinding rate and the total unwinding length of Pif1 significantly. With a force of 9 pN, the rate and length were enhanced by more than 3- and 20-fold, respectively. Our results imply that the DNA unwinding activity of Pif1 can be regulated by force. The relevance of this characteristic of Pif1 to its cellular functions is discussed.

Differences in the outcomes and complications between elderly and younger uterine cervical cancer patients treated by definitive radiotherapy - A propensity score-matched study.

PURPOSE: To evaluate the differences in the treatment outcomes and complications between elderly patients and younger patients with uterine cervical cancer (CxCa). METHODS AND MATERIALS: From April 1993 to December 2007, 138 CxCa patients aged ≥75years (Elderly group) and 334 CxCa patients aged <60years (Young group) who underwent definitive radiotherapy/chemoradiotherapy at our institution were reviewed. Two propensity score-matched cohorts of patients were selected from both age groups to evaluate the differences in the outcomes and complications. The overall survival (OS), cancer-specific survival (CSS), local failure (LF), distant failure (DF), late proctitis, and cystitis were compared between the age groups. RESULTS: The median follow-up time for survivors was 60.6months. A cohort of 99 pairs of patients was selected for the outcome comparison; there was a significant difference in the 5-year OS between the Elderly and Young groups (49.2% and 71.5%, respectively; p<0.001) but no differences in CSS, LF, and DF. Another cohort of 79 pairs of patients was selected for complication analysis. Significant differences between the Elderly and Young groups were observed in the 5-year cumulative grade 2 proctitis (39.7% and 17.2%, respectively; p=0.015) and grade 3 proctitis (18.1% and 6.2%, respectively; p=0.040). CONCLUSIONS: Although OS was worse in the elderly patients, no differences were observed in CSS, LF, and DF. Meanwhile, elderly patients tended to have higher radiation-related proctitis than younger patients. A more conservative treatment strategy for elderly CxCa patients is reasonable in our future practice.

The Therapeutic Benefit of Radical Resection for T4b Oral Cavity Squamous Cell Carcinoma with Partial or Complete Response After Radical Chemo-Intensity-Modulated Radiotherapy (IMRT).

BACKGROUND: This study investigated the therapeutic benefit of radical resection (SRR) for clinical T4b oral cavity squamous cell carcinoma (OSCC) with partial or complete response after radical chemoradiotherapy (CRT). METHODS: At the authors' institution, 79 patients with newly diagnosed non-metastatic T4b OSCC were treated with CRT from January 2009 to December 2014. All of them were irradiated using intensity-modulated radiotherapy (IMRT), with a radical dose (median 70 Gy; range 66-76 Gy) in the gross tumor area. Of the 65 cases achieving partial or complete response after CRT, 33 were treated further with SRR and 32 with adjuvant chemotherapy or observation. The locoregional control (LRC), overall survival (OS), and cancer-free survival (CFS) rates were compared between the two groups. RESULTS: The 3-year LRC, OS, and CFS rates were respectively 72.3, 75.1, and 72.6 % in the SRR group compared with 32.8, 47.7, and 44.3 % in the non-SRR group (p < 0.05). Multivariate analysis showed that SRR was the only statistically significant prognostic factor related to LRC, OS, and CFS. For those with SRR, pathologic downstaging was observed in 27 cases (81.8 %). Perioperative flap failure was observed in three cases (9.2 %) and neck wound necrosis in four cases (12.1 %). CONCLUSIONS: For T4b OSCC, incorporating SRR in the therapy is technically safe and has survival benefit, with a significant response after CRT applied by IMRT, with a radical dose in the gross tumor area.

Circulating CD105 shows significant impact in patients of oral cancer and promotes malignancy of cancer cells via CCL20.

CD105 is rich in endothelium cells and is involved in angiogenesis. Higher microvascular density of tumor is also related to the prognosis in a variety of cancers. In this present study, patients with positive N classification, advanced T classification, advanced TNM stage, extracapsular spread of lymph nodes (ECS), and perineural invasion had significantly higher levels of peripheral vein (pCD105) and venous return from tumor (tCD105) in 71 patients with OSCC compared to 13 healthy volunteers. Those with higher pCD105 or tCD105 levels had significantly poorer 5-year disease-specific survival rate (DDS) and overall survival rate (OS). The tCD105 and pCD105 levels and ECS were the independent prognostic factors by the multivariate analysis according to the Cox regression model in 5-year DDS and OS rate. SAS and SCC4 cells treated with CD105 showed the increase in migration, invasion, and proliferation in vitro and in vivo. Furthermore, CCL20 expression participated in CD105-elicited cell motility in oral cancer cells. In conclusion, higher level of circulating CD105 is related to adverse pathological features among patients with OSCC. It is also a useful marker for evaluating the prognosis and targeting therapeutics of OSCC.

Betel nut chewing history is an independent prognosticator for smoking patients with locally advanced stage IV head and neck squamous cell carcinoma receiving induction chemotherapy with docetaxel, cisplatin, and fluorouracil.

BACKGROUND: Smoking and betel nut chewing are well-known risk factors for head and neck squamous cell carcinoma (HNSCC). Smoking is also a strong prognosticator for patients with locally advanced HNSCC receiving induction chemotherapy. Smoking with or without betel nut chewing is a common practice in Asia. However, little is known regarding whether betel nut chewing can serve as a prognostic factor for smoking patients with locally advanced HNSCC receiving induction chemotherapy. The aim of this study was to evaluate the prognostic impact of betel nut chewing in such patients receiving induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF). METHODS: From January 2010 to December 2012, we retrospectively analyzed 162 smoking patients with locally advanced HNSCC who received induction chemotherapy with TPF at our institution. Background characteristics, including a history of betel nut chewing, were analyzed as potential prognostic factors. RESULTS: Among the 162 smoking patients, 131 patients (81%) were betel nut chewers, while 31 (19%) were non-betel nut chewers. One hundred fifty-six (96%) were men, and 6 (4%) were women. The median age was 53 years. The overall response rates to induction chemotherapy were 57 and 77% in patients with and without betel nut chewing history, respectively (P = 0.038). The 2-year progression survival rates were 37 and 67% in patients with and without betel nut chewing history, respectively (P = 0.004). The 2-year overall survival rates were 47 and 71% in patients with and without betel nut chewing history, respectively (P = 0.017). Betel nut chewing history was independently associated with a poor response to induction chemotherapy, an inferior progression-free survival rate, and a poor overall survival rate. CONCLUSIONS: Our results indicate that betel nut chewing history is independently associated with poor prognosis in smoking patients with locally advanced HNSCC receiving induction chemotherapy with TPF. Further investigation is warranted to explain this effect of betel nut chewing history on these patients' prognosis.

NAB2-STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors.

Solitary fibrous tumor (SFT) is characterized by the inv12(q13q13)-derived NAB2-STAT6 fusion, which exhibits variable breakpoints and drives STAT6 nuclear expression. The implications of NAB2-STAT6 fusion variants in pathological features and clinical behavior remain to be characterized in a large cohort of SFTs. We investigated the clinicopathological correlates of this genetic hallmark and analyzed STAT6 immunoexpression in 28 intrathoracic, 37 extrathoracic, and 23 meningeal SFTs. These 88 tumors were designated as histologically nonmalignant in 75 cases and malignant in 13, including 1 dedifferentiated SFT. Eighty cases had formalin-fixed and/or fresh samples to extract assessable RNAs for RT-PCR assay, which revealed NAB2-STAT6 fusion variants comprising 12 types of junction breakpoints in 73 fusion-positive cases, with 65 (89%) falling into 3 major types. The predominant NAB2ex4-STAT6ex2 (n=33) showed constant breakpoints at the ends of involved exons, whereas the NAB2ex6-STAT6ex16 (n=16) and NAB2ex6-STAT6ex17 (n=16) might exhibit variable breakpoints and incorporate NAB2 or STAT6 intronic sequence. Including 73 fusion-positive and 7 CD34-negative SFTs, STAT6 distinctively labeled 87 (99%) SFTs in nuclei, exhibited diffuse reactivity in 73, but did not decorate 98 mimics tested. In seven fusion-negative cases, 6 were STAT6-positive, suggesting rare fusion variants not covered by RT-PCR assay. Regardless of histological subtypes, intrathoracic SFTs affected older patients (P=0.035) and tended to be larger in size (P=0.073). Compared with other variants, NAB2ex4-STAT6ex2/4 fusions were significantly predominant in the SFTs characterised by intrathoracic location (P<0.001), older age (P=0.005), decreased mitoses (P=0.0028), and multifocal or diffuse STAT6 staining (P=0.013), but not found to correlate with disease-free survival. Conclusively, STAT6 nuclear expression was distinctive in the vast majority of SFTs, including all fusion-positive tumors, and exploitable as a robust diagnostics of CD34-negative cases. Despite the associations of NAB2-STAT6 fusion variants with several clincopathological factors, their prognostic relevance should be further validated in large-scale prospective studies of SFTs.

Prevalence and risk factors of depressive disorder in caregivers of patients with head and neck cancer.

OBJECTIVE: The purpose of this study is to examine the prevalence and risk factors of depressive disorder in caregivers of patients with head and neck cancer. METHODS: Study subjects were recruited from a multidisciplinary outpatient clinic for head and neck cancer in a medical center from February to July 2012. Caregivers of patients with head and neck cancer were enrolled and assessed using the Structured Clinical Interview for the DSM-IV, Clinician Version, the Short Form 36 Health Survey, and the Family APGAR index. The main aim of the study was to examine the difference in demographic data and clinical characteristics between the caregivers with and without depressive disorders. In addition, a stepwise forward model of logistic regression was used to test the possible risk factors. RESULTS: One hundred and forty-three caregivers were included in the study. The most prevalent psychiatric disorder was depressive disorder (14.7%), followed by adjustment disorder (13.3%). Nearly one-third of the caregivers had a psychiatric diagnosis. By using logistic regression analysis, it was found that unemployment (odds ratio (OR) = 3.16; 95% CI, 1.04-9.68), lower social functioning (OR = 1.43; 95% CI, 1.18-1.72), and lower educational level (OR = 1.16; 95% CI, 1.01-1.34) were significant risk factors for the depressive disorder. CONCLUSIONS: The clinical implication of our results is the value of using the standardized structured interview for early diagnosis of depressive disorder in caregivers of head and neck cancer patients. Early screening and management of depression in these caregivers will raise their quality of life and capability to care patients.

Terpenoids from Euphorbia pekinensis.

Euphorpekone A (1) and euphorpekone B (2), two new diterpenoids, 3ß-hydroxy-25-methyloxylanosta-8,23-diene, a new triterpenoid (3), together with a known triterpenoid, 3ß,25-dihydroxylanosta-8,23-diene (4), were isolated from Euphorbia pekinensis Rupr. Their structures were elucidated on the basis of UV, IR, 1D ((1)H, (13)C, NOE) and 2D ((1)H-(1)H COSY, HSQC, HMBC) NMR, HR-ESI-MS, X-ray diffraction analysis, and CD method.