Death from Pulmonary Embolism Caused by Vaginal Injection of Hyaluronic Acid: a Case Report and a Literature Review.

A 40-year-old woman underwent vaginoplasty with intramural injection of fillers from an illegal medical practitioner. Approximately 2 h after the injection, she developed lower abdominal pain. The patient was taken to the hospital approximately 5 h later due to worsening pain. When the patient was admitted for physical examination, she suddenly experienced cardiac and respiratory arrest. She was resuscitated but remained in a coma. Unfortunately, the patient died approximately 12 h after being admitted to the hospital. The forensic autopsy revealed extensive amorphous basophilic emboli in the small interstitial vascular lumen of both lungs, and a large amount of the same type of substances were also found in the vaginal wall. Hyaluronidase digestion and Alcian blue staining confirmed that most components of the injection were hyaluronic acid (HA). HA is widely used as a cosmetic filler in the field of plastic surgery and is generally considered to have few adverse effects. This paper reports the first anatomical case of fatal pulmonary embolism caused by vaginal injection of HA. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Loss of LKB1 Expression Decreases the Survival and Promotes Laryngeal Cancer Metastasis.

Background: Given recent results indicating that diminished LKB1 expression in laryngeal cancer correlates with shorter survival. We aim to perform an analysis estimate the role of decreased liver kinase B1(LKB1) and in the prognostication of human laryngeal squamous cell carcinoma (LSCC). Methods: We conducted a retrospective study and evaluate the expression of LKB1 and p16INK4a (p16) in 208 clinical advanced-stage LSCC tissue samples by using immunohistochemistry. The specimens were received at Sun Yat-sen University Cancer Center (Guangzhou, China). To evaluate the independent prognostic relevance of LKB1, univariate and multivariate Cox regression models were used, overall survival (OS) and distant metastasis-free survival (DMFS) were compared using the Kaplan-Meier method. Results: Immunohistochemical analyses revealed that 80/208 (38.5%) of the LSCC tissue samples expressed high LKB1. Low LKB1 expression was associated with a significantly shorter OS and DMFS than high LKB1 expression (P = 0.041 and 0.028, respectively; log-rank test), and there was a poorer OS in the p16-positive than p16-negative group. In the subgroup stratified by p16 status, the shorter OS were also seen with low LKB1 expression. Multivariate survival analysis indicated that high LKB1 expression was an independent prognostic factor for OS (hazard ratio [HR]: 1.628, 95% confidence interval [CI]: 1.060-2.500, P = 0.026) and DMFS (HR: 2.182, 95% CI: 1.069-4.456, P = 0.032). Conclusions: Our data indicated that low expression of LKB1 was significantly associated with poor prognosis and it may represent a marker of tumor metastasis in patients with LSCC. When combined with p16, LKB1 was also of prognostic value.

Association between the CYP2E1 polymorphisms and lung cancer risk: a meta-analysis.

The previous, published data on the association between CYP2E1 RsaI (rs2031920), DraI (rs6413432) polymorphisms and lung cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between lung cancer and CYP2E1 RsaI (5,074 cases and 6,828 controls from 34 studies), and CYP2E1 DraI (2,093 cases and 2,508 controls from 16 studies) in different inheritance models. Overall, significantly decreased lung cancer risk was observed (dominant model: odds ratio (OR) 0.80, 95 % confidence interval (95 % CI) 0.71-0.90; heterozygote model: OR 0.80, 95 % CI 0.70-0.90; additive model: OR 0.82, 95 % CI 0.72-0.94) when all the eligible studies were pooled into the meta-analysis of CYP2E1 RsaI polymorphism. In further stratified and sensitivity analyses, significantly decreased lung cancer risk was found among Asians (dominant model: OR 0.81, 95 % CI 0.71-0.93; heterozygous model: OR 0.81, 95 % CI 0.69-0.95), population-based studies (dominant model: OR 0.69, 95 % CI 0.54-0.88; recessive model: OR 0.39, 95 % CI 0.16-0.91; additive model: OR 0.67, 95 % CI 0.53-0.84; homozygous model: OR 0.34, 95 % CI 0.14-0.80; heterozygous model: OR 0.70, 95 % CI 0.54-0.91), hospital-based studies (dominant model: OR 0.80, 95 % CI 0.69-0.93; additive model: OR 0.84, 95 % CI 0.70-1.00; heterozygous model: OR 0.80, 95 % CI 0.68-0.95), lung AC (heterozygous model: OR 0.84, 95 % CI 0.71-1.00), smokers (dominant model: OR 0.72, 95 % CI 0.55-0.94), and non-smokers (dominant model: OR 0.74, 95 % CI 0.61-0.91). There was no significant association between CYP2E1 DraI polymorphism and the risk of lung cancer when all the eligible studies were pooled into the meta-analysis. However, in further stratified and sensitivity analyses, significant association was observed among smokers (dominant model: OR 0.49, 95 % CI 0.35-0.69). In summary, this meta-analysis indicates that CYP2E1 RsaI polymorphism is associated with lung cancer risk among Asians, CYP2E1 RsaI polymorphism may be associated with lung adenocarcinoma risk, and CYP2E1 RsaI and DraI polymorphisms may be associated with decreased lung cancer risk in smokers.

Association between the TP53 polymorphisms and lung cancer risk: a meta-analysis.

The previous published data on the association between TP53 codon 72, intron 6, and intron 3 16 bp polymorphisms and lung cancer risk remained controversial. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. 38 publications with 51 studies were selected for this meta-analysis, including 17,337 cases and 16,127 controls for TP53 codon 72 (from 43 studies), 2,201 cases and 2,399 controls for TP53 intron 6 (from four studies), and 4,322 cases and 4,558 controls for TP53 intron 3 16 bp (from four studies). When all the eligible studies were pooled into the meta-analysis of codon 72 polymorphism, there was significant association between lung cancer risk and codon 72 polymorphism in any genetic model (dominant model: OR = 1.13, 95 % CI 1.05-1.21; recessive model: OR = 1.14, 95 % CI 1.02-1.27; additive model: OR = 1.19, 95 % CI 1.05-1.33). In the subgroup analysis by ethnicity, histological type, source of control, and smoking status, significantly increased risks were observed in subgroups such as Asians, Caucasians, lung squamous cell carcinoma patients for Asians, population-based study, hospital-based study, non-smokers, and smokers. When all the eligible studies were pooled into the meta-analysis of intron 6 polymorphism, there was significant association between lung cancer risk and intron 6 polymorphism in dominant model (OR = 1.27, 95 % CI 1.11-1.44). When all the eligible studies were pooled into the meta-analysis of intron 3 16 bp polymorphism, there was significant association between lung cancer risk and intron 3 16 bp polymorphism in dominant model (OR = 1.12, 95 % CI 1.02-1.23) and additive model (OR = 1.41, 95 % CI 1.04-1.90). Additionally, when one study was deleted in the sensitive analysis, the results of TP53 intron 3 16 bp duplication polymorphism were changed in the dominant model (OR = 1.11, 95 % CI 0.87-1.42) and additive model (OR = 1.01, 95 % CI 0.65-1.56). In summary, this meta-analysis indicates that codon 72 and intron 6 polymorphisms show an increased lung cancer risk. A study with the larger sample size is needed to further evaluated gene-environment interaction on TP53 codon 72, intron 6, and intron 3 16 bp polymorphisms and lung cancer risk.

Predictors for replanning in loco-regionally advanced nasopharyngeal carcinoma patients undergoing intensity-modulated radiation therapy: a prospective observational study.

BACKGROUND: Replanning in intensity-modulated radiotherapy (IMRT) has been reported to improve quality of life and loco-regional control in patients with nasopharyngeal cancer (NPC). Determination of the criteria for replanning is, however, urgently needed. We conducted a prospective study to determine when and for what type of patients is replanning preferred through weekly repeat computed tomography (CT) imaging during the course of IMRT. METHODS: We recruited 20 patients who were diagnosed as having loco-regionally advanced, non-metastatic stage III or IVa NPC and treated with concurrent platinum-based chemoradiotherapy (CRT) using IMRT. Patients received CT simulation (sim-CT) and plain magnetic resonance imaging (MRI) plus diffusion-weighted imaging (DWI) weekly for five consecutive weeks. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated and recorded weekly based on the CT-CT fusion. The relationship between GTV/CTV reduction and clinical characteristics of the patients were assessed using Pearson correlation test. RESULTS: GTV and CTV decreased during the treatment by 36.03 mL (range, 10.91-98.82 mL) and 76.79 mL (range, 33.94-125.14 mL), respectively, after 25 fractions of treatment. The percentage reductions from their initial volume were 38.4% (range, 25.3-50.7%) and 11.8% (range, 6.7-18.3%), respectively. The greatest reductions in GTV and CTV were observed at the fourth week (i.e., upon completion of 20 fractions), compared to pre-treatment sim-CT. Weight loss and CTV reduction were significantly correlated with pre-treatment body mass index (BMI ) (r =0.58, P =0.012, and r =0.48, P =0.046, respectively). However, no significant correlation was observed between CTV reduction and initial tumor volume. In addition, GTV reduction was not significantly correlated with pre-treatment tumor volume (P =0.65), but negatively correlated with pre-treatment tumor apparent diffusion coefficient (ADC) values (r = -0.46, P =0.042). CONCLUSIONS: Our results indicate that the most appropriate replanning time is after 20 fractions of treatment, and pre-treatment BMI and ADC are potential predictive factors for the determination of replanning during IMRT.

Effect of antisense oligodeoxynucleotides glucose transporter-1 on enhancement of radiosensitivity of laryngeal carcinoma.

PURPOSE: Laryngeal carcinomas always resist to radiotherapy. Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngeal carcinoma. METHODS: We assessed the effect of GLUT-1 expression on radioresistance of laryngeal carcinoma and the effect of GLUT-1 expressions by antisense oligodeoxynucleotides (AS-ODNs) on the radiosensitivity of laryngeal carcinoma in vitro and in vivo. RESULTS: After transfection of GLUT-1 AS-ODNs: MTS assay showed the survival rates of radiation groups were reduced with the prolongation of culture time (p<0.05); Cell survival rates were significantly reduced along with the increasing of radiation dose (p<0.05). There was significant difference in the expression of GLUT-1mRNA and protein in the same X-ray dose between before and after X-ray radiation (p<0.05). In vivo, the expressions of GLUT-1 mRNA and protein after 8Gy radiation plus transfection of GLUT-1 AS-ODNs were significant decreased compared to 8Gy radiation alone (p<0.001). CONCLUSION: Radioresistance of laryngeal carcinoma may be associated with increased expression of GLUT-1 mRNA and protein. GLUT-1 AS-ODNs may enhance the radiosensitivity of laryngeal carcinoma mainly by inhibiting the expression of GLUT-1.

Hemorrhage of brain metastasis from non-small cell lung cancer post gefitinib therapy: two case reports and review of the literature.

BACKGROUND: Gefitinib is one of the small molecule inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR TKIs). Clinical trials have demonstrated it is effective for treatment of a subset of patients with advanced non-small cell lung cancer (NSCLC). Gefitinib has been generally considered to be a relatively safe agent. Besides a small proportion of fatal interstitial pneumonia, the common adverse drug reactions of gefitinib include diarrhea and skin rash, which are generally mild and reversible. Herein, we report the first two cases of brain metastasis hemorrhage that might be involved with the use of gefitinib. CASE PRESENTATION: Two patients with brain metastasis from NSCLC developed brain hemorrhage after gefitinib therapy. The hemorrhage in one case occurred one month after gefitinib combined with whole brain radiation therapy (WBRT), and in the another case hemorrhage developed slowly within brain metastases eight months post gefitinib monotherapy for diffuse pulmonary metastasis from a lung cancer undergone surgical removal previously. CONCLUSION: We speculate brain hemorrhage could be one of the adverse drug reactions of gefitinib treatment for NSCLC and suggest clinicians be aware of this possible rare entity. More data are needed to confirm our findings, especially when gefitinib is used in the settings of brain metastases from NSCLC or other origins.

Prognostic impact of magnetic resonance imaging-detected cranial nerve involvement in nasopharyngeal carcinoma.

BACKGROUND: : The purpose of this study was to evaluate the prognostic value of magnetic resonance imaging (MRI)-detected cranial nerve (CN) involvement in nasopharyngeal carcinoma (NPC). METHODS: : Retrospective analysis was made of the magnetic resonance images and medical records of 924 consecutive patients with newly diagnosed NPC. RESULTS: : Of 924 patients, 82 (8.9%) initially presented with CN palsy. CN involvement was seen on MRI in 333 (36%) patients. In T3-4 disease, MRI-evidenced CN involvement was associated with poor 3-year overall survival (OS) (35.7% vs 89.2%, P = .001) and distant metastasis-free survival (DMFS) (77.1% vs 87.8%, P = .002) rates. The survival curves of OS and DMFS for T3 disease with MRI-detected CN involvement approximated those of T4 disease (P = .322 and P = .809, respectively). In patients with MRI-detected CN involvement, no significant differences were observed in 3-year OS (78.3% vs 72.9%, P = .120), local relapse-free survival (LRFS) (89.7% vs 84.1%, P = .154), or DMFS (79.6% vs 74.8%, P = .466) rates between those with and without intracranial or orbital CN involvement. Furthermore, in patients with clinical and/or MRI-detected CN involvement, there were no significant differences in the 3-year OS (74.2% vs 80.1%, P = .067), LRFS (86.7% vs 87.9%, P = .899), or DMFS (74.6% vs 84.6%, P = .094) rates between symptomatic and asymptomatic patients. CONCLUSIONS: : The incidence of MRI-detected CN involvement was higher than CN palsy. MRI-detected CN involvement has a negative impact on the prognosis independent of lesion localization and symptoms. Cancer 2009. (c) 2009 American Cancer Society.

The volume to be irradiated during selective neck irradiation in nasopharyngeal carcinoma: analysis of the spread patterns in lymph nodes by magnetic resonance imaging.

BACKGROUND: For this report, the authors analyzed the spread pattern of lymph node (LN) metastases in patients with nasopharyngeal carcinoma (NPC) by using magnetic resonance imaging (MRI). In addition, the efficacy of selective neck irradiation was assessed based on the volume irradiated. METHODS: This was a retrospective review of data from 924 patients with newly diagnosed and nondisseminated NPC who underwent MRI and treatment between January 2003 and December 2004. RESULTS: According to the criteria for involved LNs detected by MRI, the incidence of LN metastases was 85.1% (786 of 924 patients). An analysis of the distribution of LN metastases in these 786 patients demonstrated that the retropharyngeal LNs (RLN) and Level II LNs were the most frequently involved regions, followed in order by Level III and Level V LNs, Level IV LNs, and supraclavicular fossa (SCF) LNs. In only 4 of 786 patients (0.5%) did metastasis skip LNs in their progression. In addition, 5 of 354 patients (1.4%) who had unilateral, higher level LN metastases (including RLNs and Level II LNs) had contralateral or bilateral, lower level LN involvement (including Level III, Level IV, Level V, and SCF LNs). In patients who had LN-negative (N0) disease, the risks of regional recurrence and distant metastasis did not differ statistically between patients with inferior border of the neck irradiation field either at the cricoid cartilage or below the cricoid cartilage. CONCLUSIONS: By using MRI, LN metastases spread in an orderly fashion from higher level LNs to lower level LNs. The current results did not support prophylactic irradiation of Level IV and SCF LNs in patients who were negative for LN metastases, and these concepts need to be tested clinically before they may be recommended generally.

Re-evaluation of 6th edition of AJCC staging system for nasopharyngeal carcinoma and proposed improvement based on magnetic resonance imaging.

PURPOSE: To use magnetic resonance imaging to re-evaluate and improve the 6th edition of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma. METHODS AND MATERIALS: We performed a retrospective review of the data from 924 biopsy-proven nonmetastatic nasopharyngeal carcinoma cases. All patients had undergone magnetic resonance imaging examinations and received radiotherapy as their primary treatment. RESULTS: The T classification, N classification, and stage group were independent predictors. No significant differences in the local failure hazards between adjacent T categories were observed between Stage T2b and T1, Stage T2b and T2a, and Stage T2b and T3. Although the disease failure hazards for Stage T1 were similar to those for Stage T2a, those for Stage T2b were similar to those for Stage T3. Survival curves of the different T/N subsets showed a better segregation when Stage T2a was downstaged to T1, T2b and T3 were incorporated into T2, and the nodal greatest dimension was rejected. The disease failure hazard for T3N0-N1 subsets were similar to those of the T1-T2N1 subsets belonging to Stage II; the same result was found for the T4N0-N2 subsets in the sixth American Joint Committee on Cancer staging system. However, the staging system we propose shows more consistent hazards within the same stage group and better survival discrimination among T categories, N categories, and overall stages. CONCLUSION: Using the 6th American Joint Committee on Cancer staging system produces an acceptable distribution of patient numbers and segregation of survival curves among the different stage groups. The prognostic accuracy of the staging system could be improved by recategorizing the T, N, and group stage criteria.

How does magnetic resonance imaging influence staging according to AJCC staging system for nasopharyngeal carcinoma compared with computed tomography?

PURPOSE: To analyze the degree and pattern of influence of magnetic resonance imaging (MRI) on staging according to the 6th edition of the American Joint Committee on Cancer staging system compared with computed tomography (CT). METHODS AND MATERIALS: The MRI and CT scans and medical records of 420 consecutive patients with newly diagnosed nasopharyngeal carcinoma (NPC) were analyzed retrospectively. The tumors of all patients were staged according to the 6th edition of the American Joint Committee on Cancer staging system. RESULTS: A significant difference (p <0.05) was found between CT and MRI in demonstrating involvement in the oropharynx (CT, 25.0% vs. MRI, 14.5%), prevertebral muscle (CT, 18.4% vs. MRI, 36.0%), parapharyngeal space (CT, 82.6% vs. MRI, 68.8%), skull base (CT, 31.0% vs. MRI, 52.6%), sphenoid sinus (CT, 13.6% vs. MRI, 16.7%), ethmoid sinus (CT, 7.1% vs. MRI, 3.3%), intracranial area (CT, 4.8% vs. MRI, 16.0%), and retropharyngeal lymph nodes (CT, 52.1% vs. MRI, 69.0%). The incidence of cervical lymph node metastasis and lymph node metastasis at each level was similar according to CT and MRI. MRI resulted in changes in 49.8% of T stage cases, 10.7% of N stage cases, and 38.6% of clinical stage cases. CONCLUSION: MRI demonstrated early primary tumor involvement more precisely and deep primary tumor infiltration more easily. The use of MRI caused dramatic changes in the results of the T stage and clinical staging and should be preferred to CT in staging NPC. Patients would benefit from changes in treatment strategies resulting from the use of MRI.

Retropharyngeal lymph node metastasis in nasopharyngeal carcinoma detected by magnetic resonance imaging : prognostic value and staging categories.

BACKGROUND: Retropharyngeal lymph node (RLN) metastasis was not included in the current American Joint Committee on Cancer (AJCC) staging system (6th edition) for nasopharyngeal carcinoma (NPC). The object of the current study was to investigate the prognostic value and staging categories of RLN metastasis in NPC detected by magnetic resonance imaging (MRI). METHODS: All 924 consecutive patients with newly diagnosed NPC were examined with MRI before treatment with definitive intent radiotherapy. RESULTS: The incidence of RLN metastasis was 73.5%. On multivariate analysis, RLN metastasis was found to be an independent prognostic factor for distant metastasis-free survival (DMFS) in all patients (P = .040). In patients with N0 disease, significant differences were observed between patients with and those without RLN metastasis after adjusting for T classification (P = .046). With regard to laterality, no significant differences were observed in DMFS between patients with unilateral and bilateral RLN metastasis in N0 disease (P = .734). No significant difference in the hazards ratios for either DMFS or disease-free survival (DFS) was found between patients with N0 disease with RLN metastasis and patients with N1 disease (P = .092 and P = .149, respectively). When RLN was classified as N1 disease, there was a better segregation of different N classifications in terms of DFS and DMFS curves, whereas the difference in hazards ratios for N0 and N1 disease was more obvious in DMFS (from 0.461 vs 0.785 to 0.317 vs 0.690). CONCLUSIONS: The results of the current MRI-based study demonstrate that RLN metastasis affects the DMFS rates of NPC. The authors propose that RLN metastasis be classified as N1 disease, regardless of its laterality.