Imaging findings of granular cell tumours of the head and neck.

AIM: To review the imaging characteristics of granular cell tumours in the head and neck and assess their associations with pathological findings. MATERIALS AND METHODS: Eleven patients (10 [91%] women, mean age 43 years) with histopathologically confirmed granular cell tumours were included in this study. Preoperative imaging studies were performed, including computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound. The location of the tumours, their imaging features, and histopathological findings were analysed. RESULTS: Among the 11 granular cell tumours, four (36%), three (27%), and two (18%) tumours were found in the submucosal layer, subcutaneous layer, and intramuscular area, respectively. On CT, all tumours exhibited homogeneous iso-attenuating enhancement compared with adjacent muscle, and nine out of the 11 tumours (81%) demonstrated well-defined margins. On T2-weighted imaging (T2WI), four out of five tumours (80%) demonstrated iso-signal intensity compared with adjacent muscles, and four tumours (80%) exhibited homogeneous signal intensity. The apparent diffusion coefficient (ADC) values ranged from 0.68-0.81 × 10-3 mm2/s. Histopathological examination revealed densely packed tumour cells with variable amounts of fibrous stroma. CONCLUSION: Granular cell tumours were characterised by well-defined and iso-signals on T2WI and low mean ADC values, and were predominantly located in the submucosal, subcutaneous, or intramuscular areas in middle-aged women. The characteristic locations, demographic characteristics, and imaging findings can help to differentiate granular cell tumours from other soft-tissue tumours in the head and neck.

Nodal factors predictive of recurrence and survival in patients with oral cavity squamous cell carcinoma.

OBJECTIVES: Lymph node (LN) metastasis of oral cavity squamous cell carcinoma (OSCC) is associated with survival outcomes. However, the relationship between different metastatic nodal factors and treatment outcomes requires further elucidation. This study examined nodal factors predictive of recurrence and survival in patients with OSCC. METHODS: This prospective observational study included 157 patients with OSCC who underwent surgery between 2010 and 2015. Clinicopathological and follow-up information were recorded. Univariate and multivariate Cox proportional hazard models were performed to identify factors associated with recurrence-free survival, disease-specific survival and overall survival. RESULTS: Sixty-five of 157 patients (41.4%) had neck metastasis. During a median follow-up of 46 months, any recurrences and all deaths occurred in 43 (27.4%) and 43 (27.4%) of cases, respectively. All nodal factors (LN classification, size, number and ratio) and extra-nodal extension were significantly associated with all survival outcomes (P < .001). Multivariate analyses indicated that a tumour size >2 cm and LN ratio were independently associated with all survival (P < .05). Patients with LN ratio >0.05 had sixfold higher recurrence and mortality rates than other patients (P < .001). CONCLUSION: Lymph node ratio is an independent and predictive determinant of post-treatment recurrence and survival.

Surgical morbidity and mortality in patients after microvascular reconstruction for head and neck cancer.

OBJECTIVES: The aim was to evaluate the importance of clinical factors in the prediction of postoperative complications in patients with microvascular reconstruction for head and neck squamous cell cancer (HNSCC). DESIGN: A retrospective review of case notes was performed. SETTING: Patients treated at a single institute. PARTICIPANTS: This study included 259 patients with HNSCC treated with radical surgery and microvascular reconstruction between 1993 and 2014. MAIN OUTCOME MEASURES: We allocated the patients to three groups using a preoperative comorbidity score based on risk factors: group A (≥3 risk factors, n = 16), group B (2 risk factors, n = 49) and group C (0 or 1 risk factor, n = 194). RESULTS: Surgical mortality in this cohort was 1.9% (5 of 259 patients). The preoperative comorbidity score was associated with surgical mortality (P < .001). Pharyngocutaneous fistula (P = .001) and flap compromise (P = .023) were more frequent as preoperative comorbidity score increased. Preoperative comorbidity score (P < .001), advanced age (P = .007), advanced pathologic T stage (P = .028), advanced pathologic N stage (P = .005), preoperative (chemo) radiotherapy (P < .001), history of cardiovascular disease (P = .015) and pulmonary disease (P = .007), and diabetes (P < .001) had significant adverse effects on 5 year disease-specific survival (DSS) in a univariate analysis. The 5-DSS rates of groups A, B and C were 30%, 37% and 70%, respectively. Multivariate analysis showed that preoperative comorbidity score was significantly correlated with 5 year DSS (hazard ratio [HR], 3.56; 95% confidence interval [CI], 1.81-6.99; P < .001 for group A and HR, 1.91; 95% CI, 1.15-3.18; P = .013 for group B compared with group C). CONCLUSION: Patients with a high preoperative comorbidity score have an increased risk of surgical mortality and morbidity after microvascular reconstruction for HNSCC.

Incidence and risk factors of late recurrence in patients with salivary gland cancer.

OBJECTIVES: Recurrence in the late post-treatment period is relatively common in salivary gland cancer (SGC), but risk factors and survival associated with late recurrence have been rarely studied. We investigated the incidence and risk factors of SGC recurrence >5 years after treatment and associated survival. DESIGN: A retrospective cohort study. SETTING: University hospital. PARTICIPANTS: A total of 240 patients with previously untreated SGC who underwent definitive treatment. MAIN OUTCOME MEASURES: Late recurrence was defined as recurrence at a time point >5 years after treatment. Univariate and multivariable analyses were used to identify the association of clinicopathologic factors with recurrence-free survival (RFS), cancer-specific survival (CSS) and late recurrence. RESULTS: Of the 240 patients, 124 (51.7%) patients developed recurrence during a median follow-up of 160.0 months (range 121.5-282.2 months). Sixteen (6.7%) patients developed late recurrence; the median time to late recurrence was 92.5 months (range 60.2-138.3 months) after treatment. Multivariable analysis showed that primary site, histologic grade and N classification were independent variables of both RFS and CSS (P < 0.05 each). Extraparenchymal extension was also an independent variable of CSS (P = 0.022). In addition, a non-parotid tumour location was a significant factor for late recurrence in multivariable analysis (P = 0.017). The median overall survival after the development of late recurrence was 79.7 months (range 0.2-163.4 months), significantly longer than that after early recurrence (19.7 months) (P = 0.043). CONCLUSION: Late recurrence occurs in some SGC patients. Long-term close surveillance may be required for patients with non-parotid SGC.

The effect of axial rotation of the anterior resection plane in patellofemoral arthroplasty.

BACKGROUND: Patellofemoral arthroplasty (PFA) has a small but definite place in replacement surgery of the knee, especially in young patients. The main surgical considerations in PFA are the patient's anatomy, the type of prosthesis and the surgical technique. The surgical technique and PFA success rely heavily on the anterior resection. In this study we investigate the effect of axial rotation of the anterior resection plane. METHODS: We tested the outcome of PFA fit based on resection footprint measurements, axial and coronal groove angles, and lateral trochlear inclination (LTI) angle in a virtual PFA model. The range of anterior resection plane axial rotations was from five degree internal to five degree external with an increment of one degree. RESULTS: Axial rotation of anterior resection plane changes the resection footprint dimension, which leads to coronal rotation of the femoral component. External rotation of the resection plane results in valgus rotation of the trochlear groove and decreased LTI after PFA and the opposite was observed for internal rotation. CONCLUSION: Our study showed that by changing the axial rotation of the anterior cut, the coronal groove of the prosthesis can be altered to lie more closely with the native groove line without compromising the prosthesis-cartilage transition.

Oligomycins as inhibitors of K-Ras plasma membrane localisation.

Frequently present in pancreatic, colorectal and non-small cell lung carcinomas, oncogenic mutant K-Ras must be localised to the plasma membrane (PM) to be functional. Inhibitors of K-Ras PM localisation are therefore putative cancer chemotherapeutics. By screening a microbial extract library in a high content cell-based assay we detected the rare oligomycin class of Streptomyces polyketides as inhibitors of K-Ras PM localisation. Cultivation and fractionation of three unique oligomycin producing Streptomyces strains yielded oligomycins A-E (1-5) and 21-hydroxy-oligomycin A (6), together with the new 21-hydroxy-oligomycin C (7) and 40-hydroxy-oligomycin B (8). Structures for 1-8 were assigned by detailed spectroscopic analysis. Cancer cell viability screening confirmed 1-8 were cytotoxic to human colorectal carcinoma cells (IC50 > 3 µM), and were inhibitors of the ABC transporter efflux pump P-glycoprotein (P-gp), with 5 being comparable in potency to the positive control verapamil. Significantly, oligomycins 1-8 proved to be exceptionally potent inhibitors of K-Ras PM localisation (Emax 0.67-0.75 with an IC50 ~ 1.5-14 nM).

Comparison of fine-needle aspiration and core needle biopsy under ultrasonographic guidance for detecting malignancy and for the tissue-specific diagnosis of salivary gland tumors.

BACKGROUND AND PURPOSE: Diagnostic test accuracy studies for ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy have shown inconclusive results due to their heterogenous study designs. Our aim was to compare the diagnostic accuracy of ultrasonography-guided fine-needle aspiration versus ultrasonography-guided core needle biopsy for detecting malignant tumors of the salivary gland and for the tissue-specific diagnosis of salivary gland tumors in a single tertiary hospital. MATERIALS AND METHODS: This retrospective study was approved by our institutional review board and informed consent was waived. Four hundred twelve patients who underwent ultrasonography-guided fine-needle aspiration (n = 155) or ultrasonography-guided core needle biopsy (n = 257) with subsequent surgical confirmation or clinical follow-up were enrolled. We compared the diagnostic accuracy of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy regarding malignant salivary gland tumors and the correct tissue-specific diagnosis of benign and malignant tumors. We also tested the difference between these procedures according to the operator's experience and lesion characteristics. RESULTS: The inconclusive rates of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy were 19% and 4%, respectively (P < .001). The overall accuracy of ultrasonography-guided core needle biopsy for diagnosing malignant tumors was significantly higher than that of ultrasonography-guided fine-needle aspiration (P = .024). The correct tissue-specific diagnosis rates of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy were 95% versus 97% for benign tumors (P = .648) and 67% versus 80% for malignant tumors (P = .310). Trainees showed significantly lower accuracy with ultrasonography-guided fine-needle aspiration than with ultrasonography-guided core needle biopsy for diagnosing malignant tumors (P = .021). There was no difference between the diagnostic accuracy of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy according to the internal composition of the lesions. There were no complications requiring intervention or hospitalization in our patients. CONCLUSIONS: Ultrasonography-guided core needle biopsy is superior to ultrasonography-guided fine-needle aspiration in detecting and characterizing malignant tumors of the salivary gland and could emerge as the diagnostic method of choice for patients presenting with a salivary gland mass.

The value of preoperative 18F-FDG PET/CT for the assessing contralateral neck in head and neck cancer patients with unilateral node metastasis (N1-3).

OBJECTIVES: The purpose of this study was to determine whether preoperative (18) F-FDG PET/CT is useful in assessing contralateral lymph node metastasis in the neck. DESIGN: A retrospective review of medical records was performed. SETTING: Patients treated at a single institute. PARTICIPANTS: One hundred and fifty-seven patients whose pathology results were positive for unilateral node metastasis (N1-3) involvement and underwent preoperative (18) F-FDG PET/CT for head and neck squamous cell carcinoma (HNSCC) were reviewed. MAIN OUTCOME MEASURES: Prognostic factors and nodal SUVmax were studied to identify the risk of contralateral disease. RESULTS: Thirty-six (22.9%) patients had contralateral cervical lymph node metastases. The (18) F-FDG PET/CT had a sensitivity of 80% and a specificity of 96% in identifying the contralateral cervical lymph node metastases on a level-by-level basis. The median SUVmax values of the ipsilateral and contralateral lymph nodes were 3.99 ± 3.36 (range, 0-20.4) and 2.94 ± 2.04 (range, 0-8.7), respectively (P = 0.001). There was a significant difference in the median SUVmax of contralateral nodes between the benign and malignant cervical lymph nodes (2.31 ± 0.62 versus 3.28 ± 2.43, P = 0.014). The cut-off value of contralateral median SUVmax in the context of contralateral cervical metastasis was 2.5 with the sensitivity of 75% and the specificity of 94%. A median contralateral lymph node SUVmax  ≥ 2.5 was associated with 5-year disease-specific survival (P = 0.038). CONCLUSION: (18) F-FDG PET/CT median SUVmax cut-off values of contralateral lymph nodes ≥2.5 were associated with contralateral cervical lymph node metastases and 5-year disease-specific survival in HNSCC patients with unilateral metastases.

Prognostic value of metastatic nodal volume and lymph node ratio in patients with cervical lymph node metastases from an unknown primary tumor.

OBJECTIVE: The presence of metastatic cervical lymph nodes (MCNs) is an unfavorable prognostic factor in head and neck cancer. The total volume of MCNs (MNV) and the lymph node ratio (LNR) may be superior to conventional nodal staging in cervical metastasis from an unknown primary tumor (CUP). We evaluated the prognostic value of MNV and LNR in CUP patients. METHODS: Thirty-nine patients with CUP who underwent surgery plus postoperative radiotherapy were reviewed. MNV was measured by preoperative computed tomography and LNR was determined using neck dissection samples. The association of clinicopathologic factors, MNV, and LNR with disease-free survival (DFS) and overall survival (OS) was analyzed. RESULTS: Five-year DFS and OS were 68.4 and 70.8%, respectively, for a median follow-up of 49 months. In multivariate analysis, MNV (>30 ml) was an independent prognostic factor for both DFS and OS (p = 0.004 and p < 0.001, respectively). LNR (>0.14) was identified as an independent predictive factor for DFS (p = 0.041). CONCLUSION: MNV and LNR are independent prognostic factors in patients with CUP and could facilitate the identification of high-risk patients requiring intensive treatment and surveillance.

Twelve-month medication persistence in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

AIMS: This study aimed to assess patients' baseline characteristics and provider factors influencing the continuation of medication for 12 months in patients who were newly diagnosed with benign prostatic hyperplasia (BPH). METHODS: This study was conducted in patients with newly diagnosed lower urinary tract symptoms (LUTS)/BPH (age ≥ 40) who received either one or a combination of the two pharmacological classes of drugs (alpha-blockers or 5-alpha-reductase inhibitors) from January 2008 to January 2010. Patient demographics and clinical data were assessed from the electronic patient records and telephone surveys. Persistence was defined as continuation of all BPH medications prescribed at the start of the first treatment. Logistic regression analysis was used to evaluate the association between 12-month persistence and patient or provider factors. RESULTS: Of the 789 newly diagnosed LUTS/BPH patients, 670 (84.9%) were included in the study. Twelve-month persistence for LUTS/BPH medication was 36.6%. Independent predictors of 12-month medication persistence included larger prostate volume, higher prostate specific antigen, having an adequate income and a good patient-doctor relationship. Important reasons for discontinuation were resolved symptoms (31.1%), no improvement in symptoms (23.7%) and adverse events (20.0%). CONCLUSIONS: About two-thirds of newly diagnosed LUTS/BPH patients discontinued medications within 1 year of starting treatment. We found several potential patient and provider factors associated with persistence, which could be exploited to increase continuation of treatment in future clinical settings.

(18)F-FDG PET/CT surveillance at 3-6 and 12 months for detection of recurrence and second primary cancer in patients with head and neck squamous cell carcinoma.

BACKGROUND: Early detection of recurrence of head and neck squamous cell carcinoma (HNSCC), which is often obscured by surgical or radiotherapy-induced tissue distortion, is essential for proper patient management. METHODS: A total of 143 consecutive patients with previously untreated HNSCC were evaluated by whole-body fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and regular clinical follow-up after curative treatment. The (18)F-FDG PET/CT was performed ∼3-6 and 12 months after treatment and findings suspicious for recurrence or SPC were confirmed using histopathology. RESULTS: The sensitivities of 3-6- and 12-month PET/CT scans at patient level were 96% and 93%, respectively, and those of regular clinical follow-up were 11% and 19%, respectively (McNemar test, P<0.001). In patients with no clinical suspicion, PET/CT detected 95% and 91% of recurrent patients at 3-6 and 12 months, respectively. The sensitivity of PET/CT for the identification of SPC was 29% and 80% at 3-6 and 12 months, respectively. A positive interpretation of PET/CT was significantly associated with poor overall survival (log-rank test, P<0.001). CONCLUSION: The (18)F-FDG PET/CT surveillance is beneficial for the detection of recurrence that may be missed by regular follow-up physical and endoscopic examinations of the head and neck area after curative treatment for HNSCC.

Phospho-Rb (Ser780) as a biomarker in patients with cervical lymph node metastases from an unknown primary tumour: a retrospective cohort study.

OBJECTIVES: Cervical lymph node metastases from an unknown primary tumour are a heterogeneous disease entity with various clinical features. There are many controversies regarding treatment methods and treatment response predictions. Therefore, we examined the prognostic significance of biomarkers in patients with cervical metastasis of unknown primary tumour. DESIGN: A molecular study of retrospective cohorts. SETTING: University teaching hospital. MAIN OUTCOME MEASURES: Metastatic cervical lymph nodes of 36 patients with cervical unknown primary metastasis of squamous cell carcinoma were assessed by in situ hybridisation for human papillomavirus and immunohistochemistry for p16, retinoblastoma protein (phospho-Ser780), hypoxia-inducible factor-1α, glucose transporter 1 and carbonic anhydrase 9 expression. Clinicopathological factors and biomarkers were analysed for their associations with disease-free survival and overall survival. RESULTS: Univariate analysis showed that nodal extracapsular spread was associated with poor overall survival (P = 0.049), nodal-positive retinoblastoma protein staining were significantly associated with poor outcomes of both disease-free survival (P = 0.035) and overall survival (P = 0.019), Multivariate analysis revealed that nodal positivity of retinoblastoma protein and nodal extracapsular spread were the significant predictors of overall survival (P = 0.049, hazard ratio = 6.21, 95% confidence interval = 1.01-38.35 and P = 0.037, hazard ratio = 4.34, 95% confidence interval = 1.09-17.21, respectively). CONCLUSION: The retinoblastoma protein expression of metastatic lymph nodes represents an independent prognostic indicator in patients with cervical metastasis of unknown primary tumour.

Utility of quantitative 18 F-fluorodeoxyglucose uptake measurement to identify occult tonsillar carcinoma in patients with cervical metastasis of unknown primary tumours: a retrospective case-control study.

OBJECTIVES: Due to relatively high (18) F-fluorodeoxyglucose accumulation in the tonsillar region, the detection of occult tonsillar cancers by (18) F-fluorodeoxyglucose positron emission tomography/computerised tomography remains controversial. Therefore, we assessed the usefulness of quantitative tonsil (18) F-fluorodeoxyglucose uptake in identifying occult tonsillar squamous cell carcinoma. DESIGN: A case-control study of retrospective cohorts. SETTING: University Teaching Hospital. MAIN OUTCOME MEASURES: We assessed all patients diagnosed with tonsillar cancers or cervical lymph node metastasis of unknown primary tumours between 2005 and 2010 who underwent (18) F-fluorodeoxyglucose positron emission tomography/computerised tomography. The subjects were grouped into A (apparent early pT-stage tonsillar squamous cell carcinoma; n = 27), B (occult tonsillar squamous cell carcinoma, primary tumours were found by surgery; n = 21), C (cervical metastasis of unknown primary tumour, primary tumours were not found by surgery and for follow-up; n = 16) and D (33 healthy controls). Tonsillar maximum standardised uptake values were bilaterally measured and compared between groups. RESULTS: The sensitivity and specificity of qualitative assessment of (18) F-fluorodeoxyglucose positron emission tomography/computerised tomography for detection of occult tonsillar cancers were 67% and 69%, respectively. Mean maximum standardised uptake values of tonsils with cancer were 11.19 ± 5.46 in group A and 8.12 ± 4.52 in group B, which were significantly higher than that of group C (4.62 ± 1.76) or group D (4.57 ± 1.62) (P < 0.01). The mean maximum standardised uptake value differences of groups A (6.35) and B (3.11) were significantly greater than those of groups C (0.32) and D (0.59) (P < 0.01). Similarly, the mean maximum standardised uptake value ratios of groups A (2.47) and B (1.73) were significantly greater than those of groups C (1.06) and D (1.16) (P < 0.01). CONCLUSION: (18) F-fluorodeoxyglucose positron emission tomography/computerised tomography with tonsil SUVmax measurement is useful to identify occult tonsillar squamous cell carcinoma.

Extracapsular spread and FDG PET/CT correlations in oral squamous cell carcinoma.

The purpose of this study was to evaluate the use of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) to identify extracapsular spread (ECS) with histologic correlations in oral squamous cell carcinoma (OSCC). The medical records of 80 patients who underwent of FDG PET/CT for OSCC before surgery were reviewed. ECS was present in 60% (24/40) dissected necks and in 55% (39/71) of dissected cervical levels. A significant difference was found between the maximum standardized uptake (SUVmax) values of cervical lymph nodes with ECS and without ECS (3.33±1.91 vs. 1.12±1.24, p<0.001). When receiver operating characteristic (ROC) curve analysis and SUVmax values were used to detect ECS, the area under the ROC curve was 0.864±0.045 (p<0.001). At an optimal SUVmax cut-off value of 2.25 the sensitivity and specificity were 85% and 88%, respectively. The presence of ECS and a SUVmax>2.25 had a significant adverse effect on 5-year disease specific survival. A SUV(max)>2.25 was found to be associated with a greater risk of cervical lymph node metastasis in OSCC.

Treatment results of post-operative radiotherapy in patients with salivary duct carcinoma of the major salivary glands.

OBJECTIVE: Salivary duct carcinoma (SDC) is a rare malignancy of high-grade pathological type. We evaluated clinical outcomes and prognostic factors in 35 patients with SDC treated post-operatively with adjuvant radiation. METHODS: We retrospectively assessed overall survival, locoregional control and disease-free survival in 35 patients with SDC of the major salivary glands who underwent surgery and were subsequently treated with radiotherapy. The evaluated prognostic factors included gender, age, symptom duration, tumour site, tumour size, TNM classification, and the following pathological features: perineural invasion, lymphovascular invasion, extraparenchymal invasion and resection-margin status. RESULTS: Of the 35 patients, 30 (85.7%) were male. Median age at initial diagnosis was 62 years (range 38-75 years). The parotid gland was the main site affected in 22 patients (62.9%). 18 patients (51.5%) had pathological T3/T4 tumours, and 26 (74.3%) showed pathological nodal involvement. Actuarial 5-year locoregional control, disease-free survival and overall survival rates were 63.3%, 47.4% and 55.1%, respectively. The cause-specific death rate was 31.4% (n=11). Pathological nodal involvement was correlated with distant metastasis (p=0.011). Lymphovascular invasion was significantly prognostic for distant metastasis-free survival (p=0.049), locoregional control (p=0.012) and overall survival (p=0.003) in a Cox proportional hazard model, whereas perineural invasion was only significantly prognostic for overall survival (p=0.005). CONCLUSIONS: Surgery and post-operative radiotherapy were effective for locoregional control. Lymphovascular invasion and perineural invasion were significant prognostic factors in patients with SDC.

[Factors of failure of prosthetic restoration of the acquired losses of substance of the jawbone and the mandible in sub-Saharan Africa]. / Facteurs d'échec de la restauration prothétique des pertes de substances maxillaires et mandibulaires acquises en Afrique subsaharienne.

The obturating prostheses of the jawbone and the prostheses of rebuilding of the mandible make it possible to restore the losses of substance of the jawbone and of the mandible and to cure the functional and Aesthetic disorders which result from these losses of substance. The success of these prosthetic restorations can be compromised by technical, economic and cultural factors. The principal factors are the importance of the losses of substance, the reduced number of teeth, the poverty of the technical plate, the persistence of certain traditional concepts. The fight against these factors requires the promotion of therapeutic associations in maxillo-facial cancerology, the sensitizing of the populations to the early hospital consultations, the improvement of the technical plate of the prosthesis of the jawbone and the face, the facilitation of the access of the most underprivileged groups to the prosthetic restorations, the promotion of multi-field collaboration, the whole co-operation of the patient throughout the treatment and the follow-up postprothetic.

Ras-induced invasion and metastasis are regulated by a leukotriene B4 receptor BLT2-linked pathway.

Ras signaling pathways are well-recognized for their involvement in cancer cell proliferation; however, considerably less is known regarding their contribution to invasion and metastasis. Here, we demonstrate that a novel BLT2, a low-affinity leukotriene B(4) receptor-linked signaling cascade involving the generation of reactive oxygen species (ROS) via Nox1, NF-kappaB stimulation and subsequent upregulation of matrix metalloproteinase-9 (MMP-9) is a potential mechanism by which Ras promotes invasion and metastasis. We found that inhibition of BLT2 signaling markedly suppressed Ras-evoked metastasis and reduced the associated mortality in mice. Consistent with the proposed role of BLT2 as a key downstream mediator of Ras signaling to metastasis, BLT2 expression alone resulted in the formation of numerous metastatic lung nodules and the nodules formation was significantly attenuated by the inhibition of MMP-9, a downstream component of BLT2. Together, our results reveal the previously unsuspected function of BLT2-linked cascade in driving oncogenic Ras-induced metastasis and would provide a valuable insight into invasion and metastasis.

Pathological validation of supracricoid partial laryngectomy in laryngeal cancer.

OBJECTIVES: To validate pathologically whether supracricoid partial laryngectomy is an oncologically sound procedure in cases with invasion of the thyroid cartilage, paraglottic space, pre-epiglottic space, anterior commissure, or subglottis. DESIGN: A retrospective review of case notes was performed. SETTING: Patients treated at a single institute in the Republic of Korea. PARTICIPANTS: Sixty-three patients who underwent supracricoid partial laryngectomy for laryngeal squamous cell carcinoma between June 1994 and May 2005 who were followed for at least 2 years. MAIN OUTCOME MEASURES: Local control and overall survival rates. Pathological invasion of the thyroid cartilage, anterior commissure, pre-epiglottic space, paraglottic space, or subglottis was also investigated as a cause of recurrence. Prognostic factors for local control and survival were evaluated with univariate and multivariate models. RESULTS: Invasion of the anterior commissure, paraglottic space, thyroid cartilage, pre-epiglottic space, or subglottis had no significant impact on the recurrence or overall survival rates. The presence of a positive resection margin was significantly associated with recurrence in the univariate and multivariate analyses (P = 0.026, 0.028, respectively). When considering the prognostic factors influencing survival, the univariate analysis showed that N stage, a positive resection margin and recurrence had significant influences on the overall survival rate (P = 0.010, 0.0004 and 0.000 respectively). In the multivariate analysis, only recurrence affected the survival rate (P = 0.002). CONCLUSION: Supracricoid partial laryngectomy can be used with oncological safety in selected cases of laryngeal cancer with invasion of the anterior commissure, thyroid cartilage, pre-epiglottic space, paraglottic space, or subglottis.

Carbon dioxide wedged arterial splenoportography: a new technique--a case report and an experimental study.

BACKGROUND: Patients with splenic vein occlusion may present a diagnostic problem when the location, morphology, and cause of the obstructive lesion and the associated collateral veins cannot be clearly defined by standard diagnostic imaging modalities such as computed tomography, magnetic resonance venography, or indirect splenoportography (arterial portography). PURPOSE: To evaluate the safety and effectiveness of carbon dioxide (CO(2)) wedged arterial splenoportography for definitive investigation of splenic vein occlusion. MATERIAL AND METHODS: Following unsuccessful diagnosis with computed tomography and standard contrast arterial portography in a patient with recurrent gastric variceal bleeding, CO(2) was injected into a wedged splenic arterial catheter and successfully outlined splenic vein occlusion and gastric varices. Our experience with this patient prompted us to perform an experimental study in swine to evaluate the safety and effectiveness of CO(2) wedged arterial splenoportography for visualization of the splenic and portal veins. A microcatheter was advanced coaxially and wedged into the splenic arteries of three pigs. After checking the wedged positioning with contrast medium injection, CO(2) was injected manually and the splenic region imaged. The spleens were then removed for gross and microscopic examinations. RESULTS: In the patient, CO(2) wedged arterial splenoportography demonstrated gastric varices associated with splenic vein occlusion. In all animals, CO(2) wedged arterial splenoportography visualized the splenic and portal veins. No CO(2) extravasations occurred in the spleen. Gross and microscopic examinations revealed no evidence of splenic rupture or intrasplenic hematoma. CONCLUSION: CO(2) wedged arterial splenoportography may be a useful method for visualizing gastric varices associated with splenic vein occlusion. This new technique has the potential to replace the standard splenic arterial portography for visualization of splenic and portal veins, thus eliminating the need for injection of a large volume of iodinated contrast material. Further clinical studies are justified to evaluate this technique.