Src-type tyrosine kinase p56lck is critical for thymic stromal lymphopoietin-induced allergic rhinitis.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a regulator of mast cell-mediated allergic inflammatory reactions, but the manner in which TSLP contributes to allergic rhinitis (AR) remains unclear. OBJECTIVE: Here, we sought to determine that TSLP plays a crucial role in AR by interacting with Src-type tyrosine kinase p56lck and STAT6 and promoting mast cells degranulation. METHODS: The effects of TSLP on mast cell degranulation and AR were analysed in human mast cell line (HMC-1 cells), ovalbumin (OVA)-induced AR animal model, and human subjects. Small interfering RNA experiments were performed in HMC-1 cells and OVA-induced AR model. Immune responses were analysed by enzyme-linked immunosorbent assay, Western blotting, immunoprecipitation, and histological studies. RESULTS: Thymic stromal lymphopoietin levels and mast cell-derived p56lck activation were elevated in human subjects with AR, and in AR mice, exogenous TSLP accelerated TH2-allergic inflammatory reactions by up-regulating p56lck and STAT6. On the other hand, depletion of TSLP, p56lck, and STAT6 ameliorated clinical symptoms in AR mice. The selective inhibitor of p56lck, damnacanthal, inhibits AR reactions. CONCLUSION: Collectively, these observations suggest a role for TSLP/p56lck/STAT6 in AR and offer insight into potential therapeutic strategies.

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.

Capsaicin attenuates spermatogenic cell death induced by scrotal hyperthermia through its antioxidative and anti-apoptotic activities.

This study was performed to examine whether capsaicin, the main pungent ingredient of red peppers, exerts protective effects against testicular injuries induced by transient scrotal hyperthermia. Capsaicin (0.33 mg kg-1 ) was administered subcutaneously to mice one hour before heat stress (HS) in a 43°C water bath for 20 min. After 7 days, mice exposed to HS showed low testicular weight, severe vacuolisation of seminiferous tubules followed by loss of spermatogenic cells, and appearance of multinucleated giant cells and remarkable TUNEL-positive apoptotic cells, as well as weak immunoreactivity of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in spermatogenic cells. Levels of lipid peroxidation and heat shock 70-kDa protein 1 (Hsp72) and BCL2-associated X protein (Bax) mRNA were greatly increased, but PHGPx, manganese superoxide dismutase (MnSOD), and B-cell lymphoma-extra large (Bcl-xL) mRNAs were significantly diminished in the testes by HS. However, capsaicin pre-treatment significantly suppressed the spermatogenic cell death, oxidative stress (levels of MDA, PHGPx immunoreactivity, and Hsp72, PHGPx, and MnSOD mRNA) and apoptosis (levels of TUNEL-positive cells, and Bcl-xL and Bax mRNA) in testes by HS. These suggest that capsaicin has a protective effect against spermatogenic cell death induced by scrotal hyperthermia through its antioxidative and anti-apoptotic activities.

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.

Ectopic pregnancy occurring in the remnant tube of a previous adnexectomy: a case report.

Ectopic pregnancy occurring in the same region is a comparatively rare disease, but sometimes it is very serious to patients if it is delayed. The authors present a case of spontaneous ectopic pregnancy occurring in the ipsilateral salpingectomy stump of a previous adnexectomy that was successfully removed via laparoscopic surgery without complication. This case may support the idea of intrauterine transmigration of a fertilized egg as an etiology of spontaneous ectopic pregnancy. Thus, the potential for ectopic pregnancy in the tubal remnant in cases of previous salpingectomy or adnexectomy needs to be carefully considered.

Ethanol and/or radiofrequency ablation to treat venolymphatic malformations that manifest as a bulging mass in the head and neck.

AIM: To evaluate the efficacy of ultrasound (US)-guided ethanol ablation (EA) and radiofrequency ablation (RFA) for treating venolymphatic malformations (VLM) of the head and neck. MATERIALS AND METHODS: US-guided EA and/or RFA were performed on 17 patients with VLM of the head and neck. Computed tomography (CT) or magnetic resonance imaging (MRI) was used to locate the cranial nerves and salivary gland ducts that were close to targets, and these were avoided during the procedures. Treatment response was assessed using volume reduction and cosmetic grading scoring. RESULTS: Nine VLMs were located close to the functional structures: Stensen's duct (n=3), cranial nerve branch (n=3), or both (n=3). All patients demonstrated >50% volume reduction, except one patient with a microcystic lymphatic malformation that was abutting the facial nerve. Median cosmetic grading scores improved from 4 to 1 (p<0.001). CONCLUSION: US-guided EA and/or RFA are effective and safe treatment methods in patients with VLMs of the head and neck. Treatment selection of EA and/or RFA could be performed based on the composition of VLMs as assessed at CT and MRI.

Routine endoscopic screening for synchronous esophageal neoplasm in patients with head and neck squamous cell carcinoma: a prospective study.

Early detection of synchronous esophageal squamous cell neoplasm (ESCN) in head and neck squamous cell carcinoma (HNSCC) patients can significantly affect their prognosis. We investigated the prevalence of synchronous ESCN and the risk factors for developing ESCN in patients with HNSCC, and evaluated the effect of routine endoscopic screening in these patients. Subjects who were diagnosed as HNSCC from May 2010 to January 2014 were eligible. All patients underwent conventional white light endoscopic examinations with narrow band imaging and Lugol chromoendoscopy. Among 458 subjects screened, 28 synchronous ESCN were detected in 24 patients (5.2%). The prevalence of ESCN was greatest in patients with hypopharyngeal cancer (20.9%). In multivariate analysis, pyriform sinus involvement was independent risk factor for developing synchronous ESCN (odds ratio 171.2, P < 0.001). During the follow-up period (median, 24 months), the 3-year overall survival rates was significantly lower in patients with ESCN than in patients without ESCN (54.2% vs. 78.3%, P = 0.0013). Routine endoscopic screening for detecting synchronous ESCN should be recommended for patients with HNSCC, especially those with pyriform sinus involvement.

Postoperative hypoalbuminemia as a risk factor for surgical site infection after oral cancer surgery.

OBJECTIVES: Postoperative surgical site infection (SSI) is a frequent postoperative complication in patients with oral cancer and significantly affects patient recovery and medical expenses. The aim of this study was to examine the predictors of SSI in patients undergoing major surgery for oral or oropharyngeal squamous cell carcinoma (OSCC) and to determine the relationship between perioperative albumin and the development of SSI. SUBJECTS AND METHODS: In 337 consecutive patients who underwent clean-contaminated surgery for OSCC, serum albumin, glucose, and hemoglobin levels were perioperatively measured. Differences between the groups were examined using Fisher's exact test, Mann-Whitney U-test, and multiple logistic regression analysis. RESULTS: Surgical site infection was detected in 88 (26.1%) patients with median time to development of 10 (2-25) days. Multiple logistic regression analysis showed that only postoperative serum albumin < 2.5 g dl(-1) was an independent variable predictive of SSI (P = 0.003). The duration of hospital stay was negatively correlated with postoperative albumin (R(2) = -0.302, P < 0.001). CONCLUSION: Early postoperative hypoalbuminemia <2.5 g dl(-1) is an independent risk factor for the development of SSI in patients undergoing oral cancer surgery. Clinicians should be aware of the implications of postoperative hypoalbuminemia and consider more intensive postoperative care in these patients.

Noncancer health events as a leading cause of competing mortality in advanced head and neck cancer.

BACKGROUND: The survival of patients with head and neck squamous cell carcinoma (HNSCC) can be affected by noncancer health events (NCHE) as well as by index cancer progression and second primary cancer (SPC). This study aimed to investigate the risk factors for NCHE and noncancer mortality (NCM) in patients with advanced-stage HNSCC. PATIENTS AND METHODS: This cohort study involved 600 consecutive patients with overall stage III to IV HNSCC who were treated between 2001 and 2010 at our tertiary referral hospital. NCHE was defined as re-admission (i.e. after the primary treatments for the index tumors) due to noncancer-related causes. The incidences of NCHE and NCM and their risk factors were analyzed by using cumulative incidence and cause-specific hazard functions. RESULTS: During a median follow-up period of 54 months, 224 (37.3%) and 55 (9.2%) of the 600 patients had NCHE and NCM, respectively. The 5-year index cancer mortality, SPC mortality, and NCM rates were 23.8%, 4.2%, and 8.9%, respectively. Multivariate analyses revealed that body mass index <20 kg/m(2) (P = 0.018), Charlson comorbidity index (CCI) ≥1 (P < 0.001), tumor recurrence (P < 0.001), SPC occurrence (P < 0.001), and initial chemotherapy (P = 0.049) were independent NCHE predictors. Older age (P < 0.001), CCI ≥1 (P = 0.008), tumor recurrence (P < 0.001), and SPC occurrence (P = 0.047) were independent NCM predictors. Patients with respiratory NCHE were at a higher risk of NCM than patients with other NCHE types (P < 0.001). CONCLUSIONS: One or more comorbidities, tumor recurrence, and SPC occurrence were independent predictors of both NCHE and NCM. Patients with respiratory NCHE had a particularly high risk of NCM.

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.

(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.

Prognostic value of metabolic tumor volume measured by 18F-FDG PET/CT in advanced-stage squamous cell carcinoma of the larynx and hypopharynx.

BACKGROUND: Metabolic tumor volume (MTV) of (18)F-FDG PET/CT is a volumetric measurement of tumor cells with increased 18F-FDG uptake. We evaluated the prognostic value of MTV in patients with locoregionally advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: We evaluated 81 patients with advanced-stage squamous cell carcinoma of the laryngohypopharynx who underwent 18F-FDG PET/CT between January 2004 and September 2009. Clinicopathologic factors and MTV were analyzed for their association with locoregional control (LRC) and overall survival (OS). RESULTS: The 3-year LRC and OS for all patients were 70.9 and 78.7%, respectively, with a median follow-up of 40.4 months (range 24.5-90.1). In univariate analyses, MTV, primary site, and primary treatment strategy were associated with both LRC and OS (P<0.05). On multivariate analysis, MTV was an independent prognostic factor for both LRC [P=0.018; HR=3.141, 95% confidence interval (CI)=1.175-8.399] and OS (P=0.008; HR=3.758, 95% CI=1.415-9.982). Primary site was also a significant prognostic factor for LRC (P=0.047). CONCLUSION: Pretreatment MTV is an independent prognostic factor in patients with locoregionally advanced squamous cell carcinoma of the larynx and hypopharynx.

Risk factors for non-cancer health events in patients with head and neck squamous cell carcinoma.

BACKGROUND: Cancer progression and non-cancer-related morbidities can affect the quality of life and survival of patients with head and neck squamous cell carcinomas (HNSCC). The aim of this study was to investigate the risk factors for the development of non-cancer health events (NCHEs) in HNSCC. PATIENTS AND METHODS: The study involved 465 previously-untreated patients with HNSCC diagnosed between 2005 and 2009 at the Asan Medical Center. Non-cancer-associated morbidity was defined as readmission after treatment of HNSCC due to non-cancer-related causes. NCHEs were defined as the occurrence of non-cancer-associated morbidity or mortality. The incidence and risk factors for NCHEs were analyzed. RESULTS: During the median follow-up of 47.6 months, non-cancer morbidity and mortality occurred in 83 (17.8%) and 25 patients (5.4%), respectively. Thirteen patients (52%) died from non-cancer-related causes with no previous admission for non-cancer causes. Multivariate analysis showed that the incidence of NCHEs was significantly associated with a Charlson comorbidity index ≥1 and stage III/IV disease (P < 0.001). CONCLUSIONS: Patients with comorbidities and advanced diseases may be at higher risk of NCHEs. Because NCHEs are sometimes life-threatening, every effort should be made to avoid unexpected non-cancer-associated mortality in the HNSCC patients.

Preoperative detection and predictors of level V lymph node metastasis in patients with papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) frequently metastasizes to regional lymph nodes. Metastasis to the posterior neck, level V, is uncommon, and level V lymphadenectomy may lead to spinal accessory nerve injury and associated postoperative morbidities. The aim of this study was to assess the diagnostic efficiency of preoperative ultrasonography and to identify predictors of level V metastasis in patients with PTC. METHODS: This study involved patients with previously untreated PTC that had metastasized to the lateral neck, and who underwent total thyroidectomy with central and lateral neck dissection. Histopathological findings were compared with ultrasound results for various neck levels. Clinical and histopathological factors that predicted level V metastasis were identified. RESULTS: Of 143 patients, 26 (18·2 per cent) had lymph node metastasis at level V. The sensitivity and positive predictive value of ultrasonography for level V metastasis were 46·2 and 30·0 per cent respectively. Univariable analysis showed that male sex, extranodal disease extension, a metastatic lymph node ratio in the ipsilateral lateral neck of more than 0·2, and simultaneous involvement of ipsilateral levels II-IV or level III were associated with ipsilateral level V metastasis. Multivariable analysis revealed an independent association between macroscopic extranodal disease extension and level V metastasis (odds ratio 26·05, 95 per cent confidence interval 5·63 to 120·56; P < 0·001). CONCLUSION: Preoperative ultrasonography frequently failed to detect level V metastasis in patients with metastatic PTC. Level V lymphadenectomy may be considered in patients with lymph node metastasis in the ipsilateral lateral neck with macroscopic extranodal extension.

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.

A hypoxia-dependent upregulation of hypoxia-inducible factor-1 by nuclear factor-κB promotes gastric tumour growth and angiogenesis.

BACKGROUND: The underlying mechanisms involved in the activation of hypoxia-inducible factor-1 (HIF-1) in gastric cancer remain unclear. As nuclear factor-κB (NF-κB) as well as HIF-1 have been implicated in angiogenesis of various cancers, we investigated their relationship in gastric cancer. METHODS: Nuclear expressions of HIF-1α and NF-κB/RelA were assessed in 251 human gastric carcinoma specimens by immunohistochemical tissue array analysis. Stable human gastric cancer cells, infected with a retroviral vector containing super-suppressive mutant form of IκBα (IκBαM), were used for animal studies as well as cell culture experiments. Xenografted tumours were measured and IκBαM effects on angiogenesis and HIF-1α activation were assessed by immunohistochemistry, western blotting, luciferase reporter assay, and semiquantitative reverse transcription-polymerase chain reaction. In addition, NF-κB effects on the HIF-1α degradation and synthesis were examined. RESULTS: Hypoxia-inducible factor-1α activation positively correlated with RelA activation in clinical gastric cancer samples (P<0.001). The IκBαM overexpression suppressed tumour growth, microvessel density, and HIF-1α activation in xenografted tumours. Cell culture experiments showed that hypoxia-induced HIF-1α expression was reduced by NF-κB inhibition under hypoxic conditions at the translational level. CONCLUSION: The hypoxia-dependent activation of the NF-κB/HIF-1α/VEGF pathway contributes, at least in part, to gastric cancer promotion via enhancement of angiogenesis.

Risk of hemorrhagic gastropathy associated with colonoscopy bowel preparation using oral sodium phosphate solution.

BACKGROUND AND STUDY AIMS: Oral sodium phosphate (NaP) solution is widely used for colonoscopy bowel preparation and it may cause aphthous ulcers in the colon. Our aim was to evaluate whether oral NaP solution is associated with gastric mucosal lesions. METHODS: A total of 20 070 individuals underwent esophagogastroduodenoscopy (EGD) with colonoscopy, and 4271 individuals underwent EGD without colonoscopy, for cancer screening. Oral NaP solutions were used for bowel preparation prior to colonoscopy. Hemorrhagic gastropathy was graded using a five-point scale for erosive mucosal injury. The effect of NaP bowel preparation on hemorrhagic gastropathy was estimated using multiple logistic regression analysis with odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS: The incidence of hemorrhagic gastropathy was 1.6 % (70/4271) in the EGD only group and 4.0 % (809/20 070) in the EGD with colonoscopy group ( P < 0.001, unadjusted OR 2.55, 95 %CI 1.99 - 3.27). The ORs for mild (grade 1 - 2), moderate (grade 3), and severe (grade 4) hemorrhagic gastropathy according to NaP use were 1.92 (95 %CI 1.45 - 2.54), 4.72 (95 %CI 2.65 - 8.47), and 5.99 (95 %CI 1.46 - 24.63), respectively. After adjustment for confounding factors, NaP solution was a significant risk factor for acute hemorrhagic gastropathy in the multivariate analysis (OR 1.92, 95 %CI 1.34-2.74). In addition, male sex, a body mass index (kg/m (2)) of less than 20, concurrent use of antihypertensive or nonsteroidal anti-inflammatory drugs, and duodenal ulcers were independently associated with the development of hemorrhagic gastropathy. HELICOBACTER PYLORI infection and atrophic gastritis were negatively associated with hemorrhagic gastropathy. CONCLUSION: Oral NaP bowel preparation for colonoscopy was associated with hemorrhagic gastropathy.

Defective MHC class I antigen surface expression promotes cellular survival through elevated ER stress and modulation of p53 function.

Defects in Major Histocompatibility class I cell surface expression is thought to allow escape of tumor cells from immune surveillance. Hitherto, it is unclear whether this deficiency confers immune-independent survival advantage. We show here that class I cell surface expression deficiency due to defects in beta2 microglobulin or the transporter-associated with antigen processing (TAP) results in resistance to apoptosis in response to various cytotoxic signals. Reduced apoptosis correlated with altered p53 activation, which was due to compromised nuclear translocation of p53. Binding of p53 to glycogen synthase kinase-3beta (GSK3beta), which is known to phosphorylate and lead to cytoplasmic sequestration of p53, was enhanced in these cells. Consistently, endoplasmic reticulum (ER) stress, which promotes binding of p53 to GSK3beta was constitutively elevated in the absence of class I cell surface expression. Taken together, the results suggest a non-immunological causal role for defective class I cell surface expression in regulating cellular survival in a p53-dependent manner, through the upregulation of ER stress, which could be another mechanism leading to carcinogenesis.

Combined 18F-fluorodeoxyglucose-positron emission tomography and computed tomography as a primary screening method for detecting second primary cancers and distant metastases in patients with head and neck cancer.

BACKGROUND: The aim of this study was to evaluate the ability of (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) to detect second primary cancers and distant metastases in patients with head and neck cancer (HNC). PATIENTS AND METHODS: Patients with previous untreated HNC, between 2004 and 2005, underwent head and neck CT and whole-body FDG-PET/CT, before and at fixed intervals after therapy, for staging and detection of second primary cancers and distant metastases. Patients with malignant or equivocal findings on FDG-PET/CT underwent further imaging, endoscopy and/or biopsy. RESULTS: Of the 349 eligible patients (267 men and 82 women), 14 (4.0%) had second primary cancers and 26 (7.4%) had distant metastases at initial staging or during mean follow-up of 15 months after treatment. FDG-PET/CT correctly identified second cancers or distant metastases in 39 of these 40 patients; there was one false negative and 23 false positive FDG-PET/CT results. Therefore, FDG-PET/CT had a sensitivity of 97.5%, a specificity of 92.6%, a positive predictive value of 62.9% and a negative predictive value of 99.7% in detecting second primary cancers and distant metastases. CONCLUSION: Combined FDG-PET/CT is useful as a primary method for detecting second cancers and distant metastases in patients with HNC.