Statistical analysis of spatially resolved transcriptomic data by incorporating multiomics auxiliary information.

Effective control of false discovery rate is key for multiplicity problems. Here, we consider incorporating informative covariates from external datasets in the multiple testing procedure to boost statistical power while maintaining false discovery rate control. In particular, we focus on the statistical analysis of innovative high-dimensional spatial transcriptomic data while incorporating external multiomics data that provide distinct but complementary information to the detection of spatial expression patterns. We extend OrderShapeEM, an efficient covariate-assisted multiple testing procedure that incorporates one auxiliary study, to make it permissible to incorporate multiple external omics studies, to boost statistical power of spatial expression pattern detection. Specifically, we first use a recently proposed computationally efficient statistical analysis method, spatial pattern recognition via kernels, to produce the primary test statistics for spatial transcriptomic data. Afterwards, we construct the auxiliary covariate by combining information from multiple external omics studies, such as bulk and single-cell RNA-seq data using the Cauchy combination rule. Finally, we extend and implement the integrative analysis method OrderShapeEM on the primary P-values along with auxiliary data incorporating multiomics information for efficient covariate-assisted spatial expression analysis. We conduct a series of realistic simulations to evaluate the performance of our method with known ground truth. Four case studies in mouse olfactory bulb, mouse cerebellum, human breast cancer, and human heart tissues further demonstrate the substantial power gain of our method in detecting genes with spatial expression patterns compared to existing classic approaches that do not utilize any external information.

Intensive Surveillance with Biannual Dynamic Contrast-Enhanced Magnetic Resonance Imaging Downstages Breast Cancer in BRCA1 Mutation Carriers.

PURPOSE: To establish a cohort of high-risk women undergoing intensive surveillance for breast cancer.Experimental Design: We performed dynamic contrast-enhanced MRI every 6 months in conjunction with annual mammography (MG). Eligible participants had a cumulative lifetime breast cancer risk ≥20% and/or tested positive for a pathogenic mutation in a known breast cancer susceptibility gene. RESULTS: Between 2004 and 2016, we prospectively enrolled 295 women, including 157 mutation carriers (75 BRCA1, 61 BRCA2); participants' mean age at entry was 43.3 years. Seventeen cancers were later diagnosed: 4 ductal carcinoma in situ (DCIS) and 13 early-stage invasive breast cancers. Fifteen cancers occurred in mutation carriers (11 BRCA1, 3 BRCA2, 1 CDH1). Median size of the invasive cancers was 0.61 cm. No patients had lymph node metastasis at time of diagnosis, and no interval invasive cancers occurred. The sensitivity of biannual MRI alone was 88.2% and annual MG plus biannual MRI was 94.1%. The cancer detection rate of biannual MRI alone was 0.7% per 100 screening episodes, which is similar to the cancer detection rate of 0.7% per 100 screening episodes for annual MG plus biannual MRI. The number of recalls and biopsies needed to detect one cancer by biannual MRI were 2.8 and 1.7 in BRCA1 carriers, 12.0 and 8.0 in BRCA2 carriers, and 11.7 and 5.0 in non-BRCA1/2 carriers, respectively. CONCLUSIONS: Biannual MRI performed well for early detection of invasive breast cancer in genomically stratified high-risk women. No benefit was associated with annual MG screening plus biannual MRI screening.See related commentary by Kuhl and Schrading, p. 1693.

Efficacy of Anti-HER2 Agents in Combination With Adjuvant or Neoadjuvant Chemotherapy for Early and Locally Advanced HER2-Positive Breast Cancer Patients: A Network Meta-Analysis.

BACKGROUND: Several (neo)adjuvant treatments for patients with HER2-positive breast cancer have been compared in different randomized clinical trials. Since it is not feasible to conduct adequate pairwise comparative trials of all these therapeutic options, network meta-analysis offers an opportunity for more detailed inference for evidence-based therapy. METHODS: Phase II/III randomized clinical trials comparing two or more different (neo)adjuvant treatments for HER2-positive breast cancer patients were included. Relative treatment effects were pooled in two separate network meta-analyses for overall survival (OS) and disease-free survival (DFS). RESULTS: 17 clinical trials met our eligibility criteria. Two different networks of trials were created based on the availability of the outcomes: OS network (15 trials: 37,837 patients); and DFS network (17 trials: 40,992 patients). Two studies-the ExteNET and the NeoSphere trials-were included only in this DFS network because OS data have not yet been reported. The concept of the dual anti-HER2 blockade proved to be the best option in terms of OS and DFS. Chemotherapy (CT) plus trastuzumab (T) and lapatinib (L) and CT + T + Pertuzumab (P) are probably the best treatment options in terms of OS, with 62.47% and 22.06%, respectively. In the DFS network, CT + T + Neratinib (N) was the best treatment option with 50.55%, followed by CT + T + P (26.59%) and CT + T + L (20.62%). CONCLUSION: This network meta-analysis suggests that dual anti-HER2 blockade with trastuzumab plus either lapatinib or pertuzumab are probably the best treatment options in the (neo)adjuvant setting for HER2-positive breast cancer patients in terms of OS gain. Mature OS results are still expected for the Aphinity trial and for the sequential use of trastuzumab followed by neratinib, the treatment that showed the best performance in terms of DFS in our analysis.

Clinical Evaluation of Cisplatin Sensitivity of Germline Polymorphisms in Neoadjuvant Chemotherapy for Urothelial Cancer.

BACKGROUND: Level 1 evidence has demonstrated increased overall survival with cisplatin-based neoadjuvant chemotherapy for patients with muscle-invasive urothelial cancer. Usage remains low, however, in part because neoadjuvant chemotherapy will not be effective for every patient. To identify the patients most likely to benefit, we evaluated germline pharmacogenomic markers for association with neoadjuvant chemotherapy sensitivity in 2 large cohorts of patients with urothelial cancer. PATIENTS AND METHODS: Patients receiving neoadjuvant cisplatin-based chemotherapy for muscle-invasive urothelial cancer were eligible. Nine germline single nucleotide polymorphisms (SNPs) potentially conferring platinum sensitivity were tested for an association with a complete pathologic response to neoadjuvant chemotherapy (pT0) or elimination of muscle-invasive cancer (

The association between infectious burden and Parkinson's disease: A case-control study.

INTRODUCTION: The etiology of Parkinson's disease (PD) remains unclear. The aim of this study was to examine the association between common pathogenic infections and PD. METHODS: Antibody titers to common infectious pathogens including cytomegalovirus (CMV), Epstein Barr virus (EBV)，herpes simplex virus type-1 (HSV-1), Borrelia burgdorferi (B. burgdorferi), Chlamydophila pneumoniae (C. pneumoniae) and Helicobacter pylori (H. pylori) were measured by ELISA in serum of 131 PD patients and 141 normal controls. Infectious burden (IB) was defined as a composite serologic measure of exposure to these common pathogens. RESULTS: Seropositivities toward zero-two, three-four and five-six of these pathogens were found in 11%, 74% and 15% of normal controls while in 4%, 61% and 35% of PD patients, respectively. IB, bacterial burden and viral burden were independently associated with PD. Schwab and England (S&E) scores were negatively correlated with IB in patients with PD. Serum α-synuclein protein levels and inflammatory cytokines (interleukin-1ß and interleukin-6) in individuals with higher IB were also significantly higher. CONCLUSIONS: IB consisting of CMV, EBV, HSV-1, B. burgdorferi, C. pneumoniae and H. pylori is associated with PD. This study supports the role of infection in the etiology of PD.

Angiotensin-converting enzyme inhibitors predict acute kidney injury during chemoradiation for head and neck cancer.

Head and neck cancer patients undergoing chemoradiation experience considerable toxicities including acute kidney injury (AKI). However, it remains unclear what factors predispose patients to renal toxicity during treatment. Here, we assessed the predictors and outcomes of patients experiencing AKI during chemoradiation. We carried out a retrospective cohort study to assess the maximum changes in serum creatinine (Cr) in 173 patients with stage III-IV head and neck cancer treated with chemoradiation between 1999 and 2012. We defined AKI as Cr increases 26.5 µmol/l or more over the pretreatment baseline. AKI was associated with angiotensin-converting enzyme inhibitor (ACEI) use (33.0 vs. 11.0%; P=0.0004), but no other medications or comorbidities. On multivariate analysis, ACEI use, weight loss 10% or more of body weight, and performance status 70 or more predicted for Cr increments 26.5 µmol/l or more, whereas only ACEI use predicted for Cr increments of 44.2 µmol/l or greater. Furthermore, on multivariate analysis, AKI predicted for more interventions during radiotherapy including intravenous fluid use (P=0.0005) and hospitalizations (P=0.007), as well as long-term renal dysfunction (P<0.0001). Renal toxicity was not associated with worse locoregional control, progression-free survival, or overall survival. Renal toxicity during chemoradiation was associated with ACEI use alone or coupled with weight loss 10% or more of body weight during therapy. Our results suggest that actively managing ACEI use and intravascular volume status during chemoradiation may avoid AKI, minimize subsequent interventions, and reduce the risk for long-term renal dysfunction.

[Prognostic factors affecting results of comprehensive treatment of hypopharyngeal carcinoma].

OBJECTIVE: To investigate the efficacy of surgery followed by adjuvant radiotherapy and the prognostic factors affecting the results of treatment in hypopharyngeal carcinoma. METHODS: A retrospective review of 149 patients with hypopharyngeal carcinoma that received surgical treatment from Jun 2003 to Jun 2010 was accomplished. In the 149 patients, the site of origin were pyriform sinus (n = 121), posterior pharyngeal wall (n = 21) and postcricoid (n = 7). According to UICC 2002 criteria, there were 3 in stage I, 15 in stage II, 29 in stage III and 102 in stage IV. Surgical methods for primary tumor were: pyriform sinus resection or posterior pharyngeal wall resection in 22 cases, partial pharyngectomy and partial laryngectomy in 29 cases, partial pharyngectomy and total laryngectomy in 67 cases, total pharyngectomy and total laryngectomy in 16 cases, total pharyngolaryngectomy and partial esophagus resection in 12 cases, and total esophagus resection in 3 cases. All the patients received elective and/or radical neck dissection. Unilateral or bilateral thyroid lobectomy was performed in 98 cases. Eighty-seven patients received intensity modulation radiated therapy (IMRT) postoperatively in the cancer center of Provincial Hospital Affiliated to Shandong University. Individualized adjustment of the radiation field was made according to the surgical condition. Forty-nine cases received radiotherapy in other hospitals (dose 50-70 Gy). Laryngeal function was restored in 51 patients (34.2%). The risk clinicopathological factors of survival and the causes of death were analyzed. RESULTS: The survival rate was calculated with Kaplan-Meier method. The overall 3- and 5- year survival rates were 47.7% and 38.7%, respectively. There were no significant differences in 3-year survival between T1-2 and T3-4 groups, N0 and N+ groups, stage I-II and III-IV groups, laryngeal function preserved and unpreserved groups. The overall 3 years survival rate of patients received surgery and adjuvant radiotherapy was higher than those just received surgery alone (χ² = 6.851, P < 0.05). The 3-year survival rate in patients treated in comprehensive treatment group has showed a good trend, although still no statistical significance (χ² = 0.176, P > 0.05). The cause of death in 86 patients, including regional lymph nodes recurrence in 25 cases (29.1%). Of them, one was stoma recurrence and 9 were retropharyngeal lymph nodes metastasis; distant metastasis in 19 cases (22.1%); local recurrence in 13 cases, local or regional recurrence with distant metastasis in 8 cases (9.3%), and second primary cancer in 6 cases (7.0%). CONCLUSIONS: The overall prognosis of hypopharyngeal carcinoma was poor and dismal. In accordance with specific conditions of surgery, active adjustment of the personalized protocol of IMRT was the key of improving the efficacy of hypopharyngeal carcinoma.

[Efficacy of retropharyngeal nodes dissection in hypopharyngeal cancer].

OBJECTIVE: To investigate the necessity and feasibility of planned dissection of the retropharyngeal lymph nodes (RPLN) in advanced hypopharyngeal cancer. METHODS: Between February 2011 and December 2012, 54 patients with advanced hypopharyngeal cancer accepted planned dissection of the RPLN during primary surgery. There were 45 cases of pyriform sinus carcinoma, 5 cases of posterior pharyngeal wall carcinoma, and 4 cases of postcricoid carcinoma. All patients underwent surgery and postoperative adjuvant radiotherapy, meanwhile bilateral neck dissection and RPLN dissection were performed. All patients received preoperative CT scanning (with contrast). The results of the radiographic assessment were compared with the postoperative pathologic findings respectively. RESULTS: RPLN were confirmed positive by pathology in 13 cases, and negative in another 43 cases. For the entire treatment group, metastasis to the RPLN was confirmed hispathologically in 12 patients (22.2%). Eight patients were pyriform sinus carcinoma, 4 were posterior pharyngeal wall carcinoma. Among them, seven patients were diagnosed as RPLN metastasis by CT imaging and another 5 patients were not confirmed. The overall accuracy for the radiologist's interpretation was 79.6%, the sensitivity was 58.3%, and the specificity was found to be 85.7%. Eleven patients were N2-3 and 6 patients were N2c. No RPLN metastasis or recurrence was found during more than one year follow-up period. CONCLUSIONS: It is not rare for the RPLN metastasis in patients with advanced hypopharyngeal carcinoma. CT imaging is not effective in determining the early presence of RPLN metastasis. The planned dissection of the RPLN is highly recommended during the initial surgery of hypopharyngeal cancer, especially in posterior pharyngeal wall carcinoma, T3-4 pyriform sinus carcinoma and staged N2-3 cases.

Clofarabine-associated acute kidney injury in patients undergoing hematopoietic stem cell transplant.

Abstract We examined clofarabine pharmacokinetics and association with renal toxicity in 62 patients participating in a phase I-II study of clofarabine-melphalan-alemtuzumab conditioning for hematopoietic stem cell transplant (HSCT). Pharmacokinetic parameters, including clofarabine area under the concentration-time curve (AUC), maximum concentration and clearance, were measured, and patients were monitored for renal injury. All patients had normal pretreatment creatinine values, but over half (55%) experienced acute kidney injury (AKI) after clofarabine administration. Age was the strongest predictor of AKI, with older patients at greater risk (p = 0.002). Clofarabine AUC was higher in patients who developed AKI, and patients with the highest dose-normalized AUCs experienced the most severe grades of AKI (p = 0.01). Lower baseline renal function, even when normal, was associated with lower clofarabine clearance (p = 0.008). These data suggest that renal-adjustment of clofarabine dosing should be considered for older and at-risk patients even when renal function is ostensibly normal.

Racial parities in outcomes after radiotherapy for head and neck cancer.

BACKGROUND: Although black patients experience worse outcomes after treatment for squamous cell carcinoma of the head and neck (HNSCC), these conclusions were based on populations in which blacks comprised a minority of patients. The objective of the current study was to determine the impact of race on outcomes in patients with HNSCC who received radiotherapy at an institution in which blacks comprised the majority of patients. METHODS: In this retrospective cohort study, the authors reviewed 366 black patients and 236 white patients who had nonmetastatic HNSCC for which they received radiotherapy between 1990 and 2012. The primary study outcome measures were locoregional control, freedom from distant metastasis, progression-free survival, and overall survival. RESULTS: The median follow-up was 18.3 months for all patients. The 2-year locoregional control rate was 71.9% for black patients compared with 64.2% for white patients (hazard ratio, 0.72; P=.03). There was no difference between blacks and whites regarding 2-year freedom from distant metastasis, progression-free survival, or overall survival. Among the patients who had stage III through IVB disease, blacks and whites had similar outcomes. On multivariate analysis, race was not statistically significant for locoregional control, freedom from distant metastasis, progression-free survival, or overall survival. Despite these similar outcomes, black patients had worse socioeconomic factors and increased comorbidities but had similar treatment compliance compared with white patients. CONCLUSIONS: With more adverse prognostic factors, black patients experienced oncologic outcomes similar to the outcomes of white patients after receiving radiotherapy for HNSCC. The current data suggest that centers that treat large percentages of minority patients who receive radiotherapy for HNSCCs may overcome existing health care disparities through improved treatment compliance.

[Recurrent laryngeal nerve decompression for bilateral recurrent laryngeal nerve paralyses after thyroid surgery].

OBJECTIVE: To study the feasibility and therapeutic effect of recurrent laryngeal nerve (RLN) decompression in the treatment of bilateral paralyzed RLN after thyroid surgery. METHODS: From March 2005 to June 2013, 15 cases of bilateral RLN paralyses occurring within 3 months after thyroid surgery were treated with RLN decompression. Bilateral RLN paralyses were caused by revised thyroid surgery in 8 cases and by primary thyroid surgery in 7 cases. RESULTS: RLN injuries were found in 15 cases/22 side, including RLN-cut in 9 sides and RLN-ligated in 13 sides. RLN decompression was performed in the 10 cases/13 sides of ligated RLN. Vocal cord mobility was detected through electrolaryngoscope for evaluating the postoperative functional recovery of decompressed RLN.Of 8 patients with bilateral RLN paralyses due to the ligation of RLN after previous revised thyroid surgeries, functional adduction and abduction of the vocal cord was recovered completely in 4 patients and recovered basically with a slight weak abduction in one patient after RLN decompression, and the 5 patients were decannulated in 1-4 months postoperatively. For 7 patients with bilateral RLN paralyses resulted from previous primary surgeries, unilateral or bilateral RLN decompress was performed in 2 cases and in 3 cases respectively. The mobility of the paralyzed vocal cord restored in 1-6 months after RLN decompression, besides one case with relative deficient abduction and one case with slight limited abduction and adduction, and the 5 patients were decannulated successfully. CONCLUSION: Exploration surgery could be performed as soon as possible in patients with bilateral RLN paralyses and RLN decompress is effective for the restoration of the function of the nerve.

A study of recurrence and death from papillary thyroid cancer with 27 years of median follow-up.

BACKGROUND: Although recurrence and death can occur in patients with papillary thyroid cancer (PTC) several years after being diagnosed, the necessary duration of follow-up for these patients remains unclear. METHODS: This was a single-institution, retrospective review of 269 patients with PTC. Cox proportional hazards model and Kaplan-Meier curves were used to identify risk factors for recurrence and death. Risk predictors included age, sex, radiation exposure history, extent of operation, radioactive iodine treatment, follicular variant of PTC (FVPTC), extrathyroidal invasion, multifocality, TNM status, and stage. RESULTS: Median follow-up was 27 years. Of 269 patients, 180 (66%) were female, and 196 (73%) were ≤45 years of age. Recurrence and cancer-specific death rates were 28% and 9%, respectively. Time to recurrence (±SD) was 8.1 (± 8.3) years and to cancer-specific death was 9.0 (± 11.0) years; however, 11% of recurrences and 17% of deaths occurred after 20 years. Risk factors for recurrence were older age, FVPTC, T4 tumors, cervical lymph node involvement, metastases, and stage ≥ 4a. Predictors of death from PTC were older age, metastases, and stage ≥ 3. CONCLUSION: Both recurrences and death from PTC can occur more than 30 years after being treated, thus lifelong follow-up of patients with PTC is necessary.

[Association between lymphangiogenesis and clinicopathological features and prognosis in laryngeal carcinoma].

OBJECTIVE: To detect lymphangiogenesis by labeling the lymphatic endothelial marker, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), and study the prognostic relevance of lymphangiogenesis in laryngeal squamous carcinoma. METHODS: Clinical files and specimens of 78 patients with histologically diagnosed laryngeal carcinoma were stained with LYVE-1 as a specific lymphatic endothelial marker. The lymphatic vessel density (LVD) was measured, and the correlation between LVD and clinicopathological features of the tumor cases was analyzed. RESULTS: The mean LVD in laryngeal carcinoma (13.24 ± 5.09) was significantly higher than that in adult laryngeal papilloma (5.54 ± 3.15) and squamous dysplasia (6.76 ± 4.45, P < 0.05). The LVD of poorly differentiated tumors (15.74 ± 5.24) was significantly higher than that in the moderately differentiated tumors (13.84 ± 6.20), and the LVD in the moderately differentiated tumors was significantly higher than that in the well-differentiated tumors (11.68 ± 6.34). The LVD in stage 0 to stage II group (10.66 ± 5.70) was significantly lower than that in the stage III to IV group (17.01 ± 6.35). The lymph node metastasis group (17.25 ± 7.37) was significantly higher than non-lymph node metastasis group (8.60 ± 5.23, P < 0.05). There was no significant association between LVD and age, sex, primary site and distant metastasis. The overall survival in the patients with a LVD higher than the mean value was 33.5 month, and that of cases with a LVD lower than the mean value was 81.6 month (P < 0.05). The multivariate survival analysis showed that the clinical stage and LVD were independent prognostic factors of laryngeal cancer. CONCLUSIONS: The LYVE-1 staining histochemistry demonstrates that the lymphangiogenesis occurrs mainly at the edge of the tumors, and lymphangiogenesis plays an important role in the carcinogenesis, cancer progression and lymph node metastasis in laryngeal cancer. LVD may be an independent indicator of poor prognosis of laryngeal cancer.

[Vocal fold augmentation by injection of autologous fascia and fat].

OBJECTIVE: To evaluate the effect of combination of autologous fascia and fat injection into vocal fold for the treatment of patients with unilateral vocal fold paralysis and to observe the long-term effectiveness of this procedure. METHODS: A total of 26 unilateral vocal fold paralysis patients underwent vocal fold injection under general anesthesia, meanwhile, the mucosa of the injected point was sutured through laryngoscope under direct vision. There were 6 patients underwent autologous fat injection into vocal fold (group A), and 20 patients underwent autologous anterior rectus sheath fascia and fat injection (group B). Therapeutic efficacy were evaluated by videostroboscopy, voice-related parameters analysis and voice evaluation before and after treatment. Clinical analysis of this procedure was retrospectively performed in this serial of patients. RESULTS: All patients were followed up for 24 months. On the third day after operation, there was an acute inflammatory reaction induced by the graft. This reaction disappeared three months later. In all 20 cases, videolaryngostroboscopy showed significant improvement of the glottic closure, the improvement in acoustical parameters was statistically significant (P < 0.01). Perceptual evaluation of GRBAS scale showed significant improvement of phonatory function on G, B, A scale. The results remained stable 6 - 24 months after operation and were not changed by the length of follow-up. And in the 6 cases, videolaryngostroboscopy showed significant improvement of the glottic closure at 3 months compared with preoperative observation, a little spindle-shaped disclosure. The improvement in acoustical parameters was significant statistically at 3, 6 and 24 months (P < 0.05 or < 0.01), the voice quality decreased significantly at 6 and 24 months compared with 3 months (P < 0.05 or < 0.01). The significant differences were not observed between 6 and 24 months (P > 0.05). No complications were observed in all patients perioperatively or during the follow-up period. Voice-related parameters jitter, normalized noise energy and maximum phonation time showed significant differences between Group A and Group B on 24 months (P < 0.05 or < 0.01). CONCLUSION: The combination of autologous fascia and fat vocal fold injection is an effective procedure for the treatment of unilateral vocal fold paralysis, and the stable results can be achieved during the follow-up period for 24 months.

Simultaneous Critical Values For T-Tests In Very High Dimensions.

This article considers the problem of multiple hypothesis testing using t-tests. The observed data are assumed to be independently generated conditional on an underlying and unknown two-state hidden model. We propose an asymptotically valid data-driven procedure to find critical values for rejection regions controlling k-family wise error rate (k-FWER), false discovery rate (FDR) and the tail probability of false discovery proportion (FDTP) by using one-sample and two-sample t-statistics. We only require finite fourth moment plus some very general conditions on the mean and variance of the population by virtue of the moderate deviations properties of t-statistics. A new consistent estimator for the proportion of alternative hypotheses is developed. Simulation studies support our theoretical results and demonstrate that the power of a multiple testing procedure can be substantially improved by using critical values directly as opposed to the conventional p-value approach. Our method is applied in an analysis of the microarray data from a leukemia cancer study that involves testing a large number of hypotheses simultaneously.

Variable reliability of endoscopic findings with white-light and narrow-band imaging for patients with suspected eosinophilic esophagitis.

BACKGROUND & AIMS: Endoscopic findings have been used to support a diagnosis of eosinophilic esophagitis (EoE) and to assess response to therapy, but their reliability is unknown. The aim of the study was to assess inter- and intraobserver reliability of endoscopic findings with white-light endoscopy and to assess changes in interobserver reliability when narrow band imaging (NBI) was added to white light. METHODS: We collected data from 35 academic and 42 community adult gastroenterologists using 2 self-administered, online assessments of endoscopic images in patients with suspected EoE. First, gastroenterologists evaluated 35 single white light images. Next, they examined 35 paired images of the initial white light image and its NBI counterpart. To assess intraobserver reliability, a second survey to re-examine the single white light images was performed ≥2 weeks later. Agreement was determined by calculating κ values for multiple observers. RESULTS: Among all gastroenterologists, interobserver agreement was fair to good when white light was used to identify rings (κ = 0.56) and furrows (κ = 0.48). Interobserver agreement was poor for identification of plaques (κ = 0.29) and for images with no findings (κ = 0.34). Levels of agreement did not change in an analysis stratified by practice setting or patient volume. Agreement did not improve when NBI images were added to white light images. Levels of intraobserver agreement varied greatly and in some cases were not greater than those expected by chance. CONCLUSIONS: Using white light endoscopy and NBI to analyze EoE, gastroenterologists identified rings and furrows with fair to good reliability, but did not reliably identify plaques or normal images. Intraobserver agreement varied. Endoscopic findings might not be reliable for supporting a diagnosis of EoE or for making treatment decisions.

[Tubed pectoralis major myocutaneous flap for reconstruction of circumference pharyngoesophageal defects].

OBJECTIVE: To investigate the feasibility and efficacy of tubed pectoralis major myocutaneous flap in the reconstruction of circumferential defects following resection for locally advanced hypopharyngeal and cervical esophageal carcinoma. METHODS: From Dec. 2004 to Oct. 2008, 30 patients underwent immediate reconstruction by tubed pectoralis major myocutaneous flap for circumferential defects following resection of primary tumours. Among them, 22 were hypopharyngeal carcinoma, 7 were cervical esophageal carcinoma and one was recurrent laryngeal carcinoma involved the hypopharyngeal lumen. Five of 30 patients had received previous radiotherapy and three had failed in the previous surgical procedure. In this series, 12 patients had total pharyngolaryngectomy and 18 had total pharyngolaryngectomy and partial cervical esophagectomy. RESULTS: Postoperative pharyngocutaneous fistula formation occurred in 4 patients, 2 of them with previous radiotherapy and 2 with diabetes, and the fistulae healed later. Two patients developed anastomotic strictures at the upper junction, but they had good responses to dilatation treatment and had satisfactory oral intake. The postoperative follow-up time ranged from 8 to 56 months. Median follow-up was 18 months. One-year survival rate was 71.4% and three-year survival rate was 42.5%. CONCLUSIONS: The tubed pectoralis major myocutaneous flap is a reliable procedure to reconstruct hypopharyngeal circumferential defects following resection of advanced hypopharyngeal and cervical esophageal carcinoma. This method may be the optimal choice for the reconstruction of hypopharyngeal circumferential defects following resection of recurrent carcinoma. The incidence of fistula and stenosis could be kept at an acceptable level.

Universal screening for postpartum depression: an inquiry into provider attitudes and practice.

OBJECTIVE: This study evaluated the use of the Edinburgh Postnatal Depression Scale (EPDS) for detection of postpartum depression (PPD) in an academic medical center outpatient population and assessed knowledge and attitudes of obstetric providers regarding detection and treatment of PPD. STUDY DESIGN: A total of 512 charts were reviewed for demographic, medical, and psychiatric information. Also, a validated e-mail survey was sent to University of North Carolina obstetrical providers (n = 47). RESULTS: Our chart review revealed that providers documented the EPDS score in 39% of visits and counseled patients on their score and/or depression in 35% of visits. The survey results show that all respondents agree that they are responsible for screening for PPD, and 94% are confident in diagnosing PPD. CONCLUSION: The majority of obstetric providers are not documenting the EPDS in their postpartum assessment, yet they feel responsible for and confident in screening for postpartum depression.

Methylenetetrahydrofolate reductase polymorphisms and susceptibility to gastric cancer in Chinese populations: a meta-analysis.

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene are thought to have significant effects on folate metabolism and, thus, on cancer risk, but the reported results are not always consistent. In this meta-analysis including 2165 patients and 3279 controls, we assessed reported studies of associations between polymorphisms of MTHFR and susceptibility to gastric cancer in Chinese populations. An increased risk was found for MTHFR C677T in the meta-analysis [odds ratio (OR): 1.42; 95% confidence interval (CI): 1.24-1.62]. No association resulted for MTHFR A1298C (OR: 0.95; 95% CI: 0.78-1.17). Results from the subgroup analyses showed an increased risk for individuals with low (OR: 1.50; 95% CI: 1.18-1.91) versus high (OR: 1.21; 95% CI: 0.98-1.51) folate levels. The sensitivity analysis and publication bias diagnostics confirmed the reliability and stability of this meta-analysis. Overall, these findings support the hypothesis that folate plays a role in gastric carcinogenesis. Regarding cardia or noncardia gastric cancer, more studies are required for definite conclusions, as the number of studies is relatively small.