Endoscopic closure techniques of bariatric surgery complications: a meta-analysis.

BACKGROUND: Leaks following bariatric surgery, while rare, are potentially fatal due to risk of peritonitis and sepsis. Anastomotic leaks and gastro-gastric fistulae following Roux-En-Y gastric bypass (RYGB) as well as staple line leaks after sleeve gastrectomy have historically been treated multimodally with surgical drainage, aggressive antibiotic therapy, and more recently, endoscopically. Endoscopic clipping using over-the-scope clips and endoscopic suturing are two of the most common approaches used to achieve full thickness closure. METHODS: A systematic literature search was performed in PubMed to identify articles on the use of endoscopic clipping or suturing for the treatment of leaks and fistulae following bariatric surgery. Studies focusing on stents, and those that incorporated multiple closure techniques simultaneously, were excluded. Literature review and meta-analysis were performed with the PRISMA guidelines. RESULTS: Five studies with 61 patients that underwent over-the-scope clip (OTSC) closure were included. The pooled proportion of successful closure across the studies was 81.1% (95% CI 67.3 to 91.7). The successful closure rates were homogeneous (I2 = 39%, p = 0.15). Three studies with 92 patients that underwent endoscopic suturing were included. The weighted pooled proportion of successful closure across the studies was shown to be 22.4% (95% CI 14.6 to 31.3). The successful closure rates were homogeneous (I2 = 0%, p = 0.44). Three of the studies, totaling 34 patients, examining OTSC deployment reported data for reintervention rate. The weighted pooled proportion of reintervention across the studies was 35.0% (95% CI 11.7 to 64.7). We noticed statistically significant heterogeneity (I2 = 68%, p = 0.04). One study, with 20 patients examining endoscopic suturing, reported rate of repeat intervention 60%. CONCLUSION: Observational reports show that patients managed with OTSC were more likely to experience healing of their defect than those managed with endoscopic suturing. Larger controlled studies comparing different closure devices for bariatric leaks should be carried out to better understand the ideal endoscopic approach to these complications.

Splicing modulators impair DNA damage response and induce killing of cohesin-mutant MDS and AML.

Splicing modulation is a promising treatment strategy pursued to date only in splicing factor-mutant cancers; however, its therapeutic potential is poorly understood outside of this context. Like splicing factors, genes encoding components of the cohesin complex are frequently mutated in cancer, including myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (AML), where they are associated with poor outcomes. Here, we showed that cohesin mutations are biomarkers of sensitivity to drugs targeting the splicing factor 3B subunit 1 (SF3B1) H3B-8800 and E-7107. We identified drug-induced alterations in splicing, and corresponding reduced gene expression, of a number of DNA repair genes, including BRCA1 and BRCA2, as the mechanism underlying this sensitivity in cell line models, primary patient samples and patient-derived xenograft (PDX) models of AML. We found that DNA damage repair genes are particularly sensitive to exon skipping induced by SF3B1 modulators due to their long length and large number of exons per transcript. Furthermore, we demonstrated that treatment of cohesin-mutant cells with SF3B1 modulators not only resulted in impaired DNA damage response and accumulation of DNA damage, but it sensitized cells to subsequent killing by poly(ADP-ribose) polymerase (PARP) inhibitors and chemotherapy and led to improved overall survival of PDX models of cohesin-mutant AML in vivo. Our findings expand the potential therapeutic benefits of SF3B1 splicing modulators to include cohesin-mutant MDS and AML.

Effects of Spinal Deformities on Hiatal Hernia Occurrence and Recurrence.

BACKGROUND: Spinal deformities such as kyphosis, lordosis, and scoliosis have demonstrated a possible association between these deformities. Our hypothesis is that the presence of spinal deformities will increase the risk of hiatal hernia recurrence after repair. METHODS: The following data was retrospectively gleaned for patients undergoing hiatal hernia repair (1997-2022): age, sex, date of hiatal hernia repair, presence and type of spinal deformity, Cobb angle, type of hiatal hernia and size, type of hiatal hernia repair, recurrence and size, time to recurrence, reoperation, type of reoperation, and time to reoperation. RESULTS: Spinal deformities were present in 15.8% of 546 patients undergoing hiatal hernia repair, with a distribution of 21.8% kyphosis, 2.3% lordosis, 58.6% scoliosis, and 17.2% multiple. There was no difference in sex or age between groups. Spinal deformity patients were more likely to have types III and IV hiatal hernias (52.3% vs. 38.9%, p = 0.02) and larger hernias (median 5 [3-8] vs. 4 [2-6], p = 0.01). There was no difference in access, fundoplication use, or mesh use between groups. However, these patients had a higher recurrence rate (47.7% vs 30.0%, p = 0.001) and a shorter time to recurrence (months) (10.3 [5.6-25.1] vs 19.2 [9.8-51.0], p = 0.02). Cobb angle did not affect recurrence. CONCLUSIONS: Spinal deformity patients were more likely to have more complex and larger hiatal hernias. They were at higher risk of hiatal hernia recurrence after repair with shorter times to recurrence. This is a group that requires special attention with additional preoperative counseling and possibly use of surgical adjuncts in repair.

A Case of Brodifacoum-Induced Epiglottitis.

This case report presents a 33-year-old woman who presented to the emergency department with abdominal pain and gingival and vaginal bleeding. She admitted to using synthetic cannabinoids, and contamination with brodifacoum was suspected, for which qualitative testing was positive. The patient was discharged with an improved international normalized ratio (INR) seven days later with oral vitamin K. Fourteen days after discharge, she re-presented with widespread ecchymosis, leg swelling, and intermittent gingival and vaginal bleeding. Her INR was again elevated. She was controlled with oral vitamin K therapy, stabilized, and discharged three days later. Twenty-eight days following the second discharge, the patient re-presented with oral swelling, right eye ecchymosis, and vaginal bleeding after abstaining from vitamin K therapy for two weeks. A bedside nasopharyngolaryngoscopy showed the base of the tongue, epiglottis, aryepiglottic (AE) folds, arytenoids, and false vocal folds were all edematous with ecchymosis. Due to the diffuse epiglottic and supraglottic edema, the patient was intubated to avoid further decompensation. After receiving IV and oral vitamin K, she was extubated two days later. Her INR fully normalized, and she was then discharged on day 4. Our case of epiglottitis could demonstrate thermal injury associated with smoking synthetic cannabinoids, but given diffuse ecchymosis and severe coagulopathy, hematoma associated with brodifacoum poisoning was considered the most likely etiology. The patient's coagulopathy was rapidly reversed, empiric antibiotic coverage was provided, and she rapidly improved. Brodifacoum exposure has been known to cause increased bleeding, as seen in this case. However, it should also be considered that exposure can lead to epiglottitis. If a similar patient is presented in the future, it is important to consider that coagulopathy may be caused by the adulteration of drugs of abuse, specifically brodifacoum with synthetic cannabinoids.

Laparoscopic vs. robotic colectomy for left-sided diverticulitis.

Diverticulitis is a prevalent gastrointestinal disease that often warrants surgical intervention. However, the optimal approach between traditional laparoscopy (LC) and robotic-assisted laparoscopy (RAC) for diverticulitis remains unclear. Our research compares these techniques in patients diagnosed with left-sided diverticulitis treated at a single, tertiary referral center from 2019 to 2022. Among the 134 patients, 86 underwent laparoscopic and 48 robotic-assisted surgeries. The surgeries included in this analysis are left colectomy, sigmoid colectomy, low anterior resection, and Hartmann's procedure. Primary outcomes were major morbidity and 30-day mortality. Secondary outcomes were operative time, conversion to open, length of stay, unplanned return to the operating room, 30-day readmission rate, and overall morbidity. While demographics and comorbidities were similar for both groups, the robotic-assisted group displayed a statistically significant longer operative time (198.0 ± 84.4 LC vs. 264.8 ± 78.5 min RAC, p < 0.001). When investigated further, there was a significant difference in operative time for uncomplicated diverticulitis cases favoring the LC approach (169.17 ± 58.1 LC vs. 244.82 ± 58.79 min RAC, p < 0.001). This significant difference, however, was not present in complicated diverticulitis cases. Other factors, such as overall and major morbidity, rate of conversion to open approach, ostomy creation, estimated blood loss, time to return of bowel function, length of stay, and 30-day readmission rate, did not significantly differ between the groups. There was no 30-day mortality in either group. Favorable patient outcomes, lack of significant difference in operative time compared with traditional laparoscopy, and absence of differences in morbidities or efficacy, raises an interesting question in the world of minimally invasive surgery: is the robotic-assisted approach emerging as the advantageous approach for complicated diverticulitis cases? We encourage additional, multi-center analysis of specifically complicated diverticulitis managed with both surgical approaches to investigate if these findings are replicated outside of our institution.

Seamguard Buttressing of the Staple Line During Laparoscopic Sleeve Gastrectomy Appears to Decrease the Incidence of Postoperative Bleeding, Leaks, and Reoperations. A Systematic Review and Meta-Analysis of Non-Randomized Comparative Studies.

Leaks and bleeding are major acute postoperative complications following laparoscopic sleeve gastrectomy (LSG). Various staple line reinforcement (SLR) methods have been invented such as oversewing/suturing (OS/S), omentopexy/gastropexy (OP/GP), gluing, and buttressing. However, many surgeons do not use any type of reinforcement. On the other hand, surgeons who use a reinforcement method are often confused of what kind of reinforcement they should use. No robust and high-quality data supports the use of one reinforcement over the other or even supports the use of reinforcement over no-reinforcement. Therefore, SLR is a controversial topic that is worth our focus. The aim of this study is to compare the outcomes of LSG with versus without Seamguard buttressing of the staple line during LSG.

Changes in Perioperative Outcomes after Robotic-Assisted Pulmonary Lobectomy during the COVID-19 Era.

Background: The COVID-19 pandemic presented patients with barriers to receiving healthcare. We sought to determine whether changes in healthcare access and practice during the pandemic affected perioperative outcomes after robotic-assisted pulmonary lobectomy (RAPL). Methods: We retrospectively analyzed 721 consecutive patients who underwent RAPL. With March 1st, 2020, defining the start of the COVID-19 pandemic, we grouped 638 patients as "PreCOVID-19" and 83 patients as "COVID-19-Era" based on surgical date. Demographics, comorbidities, tumor characteristics, intraoperative complications, morbidity, and mortality were analyzed. Variables were compared utilizing Student's t-test, Wilcoxon rank-sum test, and Chi-square (or Fisher's exact) test, with significance at p ≤ 0.05 . Multivariable generalized linear regression was used to investigate predictors of postoperative complication. Results: COVID-19-Era patients had significantly higher preoperative FEV1%, lower cumulative smoking history and higher incidences of preoperative atrial fibrillation, peripheral vascular disease (PVD), and bleeding disorders compared to PreCOVID-19 patients. COVID-19-Era patients had lower intraoperative estimated blood loss (EBL), reduced incidence of new-onset postoperative atrial fibrillation (POAF), but higher incidence of effusion or empyema postoperatively. Overall postoperative complication rates between the groups were similar. Older age, increased EBL, lower preoperative FEV1%, and preoperative COPD are all predictive of an increased risk for postoperative complication. Conclusions: COVID-19-Era patients having lower EBL and less new-onset POAF, despite greater incidences of multiple preoperative comorbidities, demonstrates that RAPL is safe during the COVID-19 era. Risk factors for development of postoperative effusion should be determined to minimize risk of empyema in COVID-19-Era patients. Age, preoperative FEV1%, COPD, and EBL should all be considered when planning for complication risk.

A High Preoperative Blood Urea Nitrogen to Serum Albumin Ratio Does Not Predict Worse Outcomes Following the Robotic-Assisted Pulmonary Lobectomy for Lung Cancer.

BACKGROUND:  The blood urea nitrogen to serum albumin ratio (BAR) is an emerging prognostic parameter of interest. The utility of BAR as a prognostic factor has not been analyzed in lung cancer patients undergoing pulmonary lobectomy. We evaluated the ability of High BAR to predict worse outcomes after robotic-assisted pulmonary lobectomy (RAPL) for lung cancer. METHODS:  We retrospectively analyzed 400 patients who underwent RAPL from September 2010 to March 2022 by one surgeon. Patients were stratified by Low BAR (<6.25 mg/g) and High BAR (≥6.25 mg/g). Patients' demographics, tumor characteristics, comorbidities, surgical complications, outcomes, and survival were collected and compared by High and Low BAR groups. The primary outcome of interest was 30-day mortality. RESULTS:  Receiver operator curves (ROC) confirmed that 6.25 was an optimal threshold for estimating mortality based on Low and High BAR. There were no differences in surgical complications or outcomes between the Low and High BAR groups. The ability of BAR to predict 30-day mortality was evaluated with the area under the curve (AUC) analysis, which showed that higher BAR could not predict mortality (AUC=0.655; 95% CI, 0.435-0.875; p=0.166). Similarly, survival analysis revealed no difference in five-year overall survival between the Low and High BAR groups (p=0.079). CONCLUSION:  High BAR did not predict worse outcomes after RAPL for lung cancer in our study. Further studies are needed to better determine the prognostic ability of BAR in lower-risk populations.

Anti-obesity Medication Use for Adolescent Metabolic and Bariatric Surgery Patients: A Systematic Literature Review.

Bariatric surgery, in combination with pharmacotherapy, has been proven to be successful in combatting weight regain in adults; however, the use of anti-obesity medications to augment weight loss in adolescents before and after bariatric surgery is not well studied. In adolescent obese patients, the efficacy of anti-obesity pharmacotherapy before and after bariatric surgery on weight loss compared to no interventions in various studies was investigated. A PubMed literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed to identify studies related to the pharmacologic treatment of obesity in adolescents with a history of bariatric surgery. Inclusion criteria consisted of clinical trials, case reports, case series, chart reviews, systematic reviews, and meta-analyses written in English and published between 2005 and 2022 using our search criteria. Exclusion criteria were studies that investigated adults, did not include pharmacotherapy, and were not relevant to the outcome of interest. The initial search yielded 1275 results, which was reduced to 879 after removal of duplicates. After applying exclusion criteria, the number of articles was reduced to 63. Full articles were examined and 44 were excluded due to relevance. Nineteen articles were included in the qualitative analysis. A total of 2471 adolescents were treated with various types of pharmacotherapy, 65 of whom had a history of bariatric surgery. The results showed varied effects of pharmacotherapy with the different medications studied. However, the 65 patients were included in cohorts of patients with no history of bariatric surgery. These studies did not include data specific to adolescent bariatric surgery patients.  There is a wealth of evidence highlighting the efficacy of pharmacotherapy in assisting with weight loss in adolescents with obesity; however, our literature search showed a lack of studies focusing on the use of pharmacotherapy in the adolescent bariatric surgery population. Potential limitations include missing studies in our literature search, the variability in methods between studies, and the lack of standardized quality assessment. Additionally, studies involving our objective of choice regarding bariatric surgery with anti-obesity medication were limited. Clinical trials to determine the efficacy of medications as an adjunct to bariatric surgery in preventing weight regain and leading to optimal weight loss in this population are of utmost importance.

Vitamin D intake is associated with decreased risk of immune checkpoint inhibitor-induced colitis.

BACKGROUND: There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis. METHODS: We performed a retrospective analysis of melanoma patients at Dana-Farber Cancer Institute who received PD-1, CTLA-4, or combination ICIs between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariable logistic regression analyses. External confirmation was performed on an independent cohort from Massachusetts General Hospital. RESULTS: The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). Vitamin D use was recorded in 66/213 patients (31%) before starting ICIs. In multivariable regression analysis, vitamin D use conferred significantly reduced odds of developing ICI colitis (OR 0.35, 95% CI 0.1-0.9). These results were also demonstrated in the confirmatory cohort (OR 0.46, 95% CI 0.2-0.9) of 169 patients of whom 49 developed ICI colitis (29%). Pre-treatment neutrophil-to-lymphocyte ratio (NLR) ≥5 predicted reduced odds of colitis (OR 0.34, 95% CI 0.1-0.9) only in the discovery cohort. CONCLUSIONS: This is the first study to report that among patients treated with ICIs, vitamin D intake is associated with reduced risk for ICI colitis. This finding is consistent with prior reports of prophylactic use of vitamin D in ulcerative colitis and graft-versus-host-disease. This observation should be validated prospectively in future studies.

Positron emission tomography-computed tomography predictors of progression after DA-R-EPOCH for PMBCL.

Dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) has produced good outcomes in primary mediastinal B-cell lymphoma (PMBCL), but predictors of resistance to this treatment are unclear. We investigated whether [18F]fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) findings could identify patients with PMBCL who would not respond completely to DA-R-EPOCH. We performed a retrospective analysis of 65 patients with newly diagnosed stage I to IV PMBCL treated at 2 tertiary cancer centers who had PET-CT scans available before and after frontline therapy with DA-R-EPOCH. Pretreatment variables assessed included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Optimal cutoff points for progression-free survival (PFS) were determined by a machine learning approach. Univariate and multivariable models were constructed to assess associations between radiographic variables and PFS. At a median follow-up of 36.6 months (95% confidence interval, 28.1-45.1), 2-year PFS and overall survival rates for the 65 patients were 81.4% and 98.4%, respectively. Machine learning-derived thresholds for baseline MTV and TLG were associated with inferior PFS (elevated MTV: hazard ratio [HR], 11.5; P = .019; elevated TLG: HR, 8.99; P = .005); other pretreatment clinical factors, including International Prognostic Index and bulky (>10 cm) disease, were not. On multivariable analysis, only TLG retained statistical significance (P = .049). Univariate analysis of posttreatment variables revealed that residual CT tumor volume, maximum standardized uptake value, and Deauville score were associated with PFS; a Deauville score of 5 remained significant on multivariable analysis (P = .006). A model combining baseline TLG and end-of-therapy Deauville score identified patients at increased risk of progression.

Outcomes of adults and children with primary mediastinal B-cell lymphoma treated with dose-adjusted EPOCH-R.

Treatment with dose-adjusted EPOCH (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone) chemotherapy and rituximab (DA-EPOCH-R) has become the standard of care for primary mediastinal B-cell lymphoma (PMBCL) at many institutions despite limited data in the multi-centre setting. We report a large, multi-centre retrospective analysis of children and adults with PMBCL treated with DA-EPOCH-R to characterize outcomes and evaluate prognostic factors. We assessed 156 patients with PMBCL treated with DA-EPOCH-R across 24 academic centres, including 38 children and 118 adults. All patients received at least one cycle of DA-EPOCH-R. Radiation therapy was administered in 14·9% of patients. With median follow-up of 22·6 months, the estimated 3-year event-free survival (EFS) was 85·9% [95% confidence interval (CI) 80·3-91·5] and overall survival was 95·4% (95% CI 91·8-99·0). Outcomes were not statistically different between paediatric and adult patients. Thrombotic complications were reported in 28·2% of patients and were more common in paediatric patients (45·9% vs. 22·9%, P = 0·011). Seventy-five per cent of patients had a negative fluorodeoxyglucose positron emission tomography (FDG-PET) scan at the completion of DA-EPOCH-R, defined as Deauville score 1-3. Negative FDG-PET at end-of-therapy was associated with improved EFS (95·4% vs. 54·9%, P < 0·001). Our data support the use of DA-EPOCH-R for the treatment of PMBCL in children and adults. Patients with a positive end-of-therapy FDG-PET scan have an inferior outcome.

Eustachian Tube Function in 6-Year-Old Children with and without a History of Middle Ear Disease.

OBJECTIVE: To test the hypothesis that eustachian tube opening efficiency, measured as the fractional gradient equilibrated (FGE), is lower in 6-year-old children with no middle ear disease but a well-documented history of recurrent acute otitis media, as compared with children with a negative disease history (control). STUDY DESIGN: Cross-sectional study. SETTING: Tertiary care pediatric hospital. SUBJECTS AND METHODS: Bilateral eustachian tube function was evaluated in 44 healthy 6-year-old children (19 boys, 29 white). None had middle ear disease at the time of testing, but 23 had a history of recurrent acute otitis media. Twenty-one had no significant past otitis media. Eustachian tube function was measured with a pressure chamber protocol that established negative middle ear gauge pressures (referenced to the chamber pressure) and recorded that pressure before and after a swallow. FGE was calculated as the change in middle ear gauge pressure with swallowing divided by the preswallow pressure. Between-group comparisons of the preswallow pressures and FGEs were made with a 2-tailed Student's t test. RESULTS: FGE was independent of the preswallow middle ear gauge pressure. For the 39 and 44 evaluable ears in the control and recurrent acute otitis media groups, the mean preswallow pressures were -194 daPa (95% confidence interval [95% CI] = -211 to -177) versus -203 (95% CI = -216 to -190; P > .40), and FGEs were 0.32 (95% CI = 0.21-0.43) vs 0.16 (95% CI = 0.08-0.24; P = .016), respectively. CONCLUSION: In children with past recurrent acute otitis media, residual eustachian tube opening inefficiency is maintained after they have "outgrown" their middle ear disease.

Addition of B-Type Natriuretic Peptide to Existing Clinical Risk Scores Enhances Identification of Patients at Risk for Atrial Fibrillation Recurrence After Pulmonary Vein Isolation.

INTRODUCTION: Predicting which patients will be free from atrial fibrillation (AF) after pulmonary vein isolation (PVI) remains challenging. Clinical risk prediction scores show modest ability to identify patients at risk for AF recurrence after PVI. B-type natriuretic peptide (BNP) is associated with risk for incident and recurrent AF but is not currently included in existing AF risk scores. We sought to evaluate the incremental benefit of adding preoperative BNP to existing risk scores for predicting AF recurrence during the 6 months after PVI. METHODS: One hundred sixty-one patients with paroxysmal or persistent AF underwent an index PVI procedure between 2010 and 2013; 77 patients (48%) had late AF recurrence after PVI (>3 months post-PVI) over the 6-month follow-up period. RESULTS: A BNP greater than or equal to 100 pg/dL (P=0.01) and AF recurrence within 3 months after PVI (P<0.001) were associated with late AF recurrence in multivariate analyses. Addition of BNP to existing clinical risk scores significantly improved the areas under the curve for each score, with an integrated discrimination improvement of 0.08 (P=0.001) and a net reclassification improvement of 60% (P=0.001) for all risk scores. CONCLUSIONS: Circulating BNP levels are independently associated with late AF recurrence after PVI. Inclusion of BNP significantly improves the discriminative ability of CHADS2, CHA2DS2-VASc, R2CHADS2, and the HATCH score in predicting clinically significant, late AF recurrence after PVI and should be incorporated in decision-making algorithms for management of AF. B-R2CHADS2 is the best score model for prediction of late AF recurrence.

Molecular biology of bladder cancer.

Classic as well as more recent large-scale genomic analyses have uncovered multiple genes and pathways important for bladder cancer development. Genes involved in cell-cycle control, chromatin regulation, and receptor tyrosine and PI3 kinase-mammalian target of rapamycin signaling pathways are commonly mutated in muscle-invasive bladder cancer. Expression-based analyses have identified distinct types of bladder cancer that are similar to subsets of breast cancer, and have prognostic and therapeutic significance. These observations are leading to novel therapeutic approaches in bladder cancer, providing optimism for therapeutic progress.

Improving selection criteria for early cystectomy in high-grade t1 bladder cancer: a meta-analysis of 15,215 patients.

PURPOSE: High-grade T1 (HGT1) bladder cancer is the highest risk subtype of non-muscle-invasive bladder cancer, with highly variable prognosis, poorly understood risk factors, and considerable debate about the role of early cystectomy. We aimed to address these questions through a meta-analysis of outcomes and prognostic factors. METHODS: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and American Society of Clinical Oncology abstracts were searched for cohort studies in HGT1. We pooled data on recurrence, progression, and cancer-specific survival from 73 studies. RESULTS: Five-year rates of recurrence, progression, and cancer-specific survival were 42% (95% CI, 39% to 45%), 21% (95% CI, 18% to 23%), and 87% (95% CI, 85% to 89%), respectively (56 studies, n = 15,215). In the prognostic factor meta-analysis (33 studies, n = 8,880), the highest impact risk factor was depth of invasion (T1b/c) into lamina propria (progression: hazard ratio [HR], 3.34; P < .001; cancer-specific survival: HR, 2.02; P = .001). Several other previously proposed factors also predicted progression and cancer-specific survival (lymphovascular invasion, associated carcinoma in situ, nonuse of bacillus Calmette-Guérin, tumor size > 3 cm, and older age; HRs for progression between 1.32 and 2.88, P ≤ .002; HRs for cancer-specific survival between 1.28 and 2.08, P ≤ .02). CONCLUSION: In this large analysis of outcomes and prognostic factors in HGT1 bladder cancer, deep lamina propria invasion had the largest negative impact, and other previously proposed prognostic factors were also confirmed. These factors should be used for prognostication and patient stratification in future clinical trials, and depth of invasion should be considered for inclusion in TNM staging criteria. This meta-analysis can also help define selection criteria for early cystectomy in HGT1 bladder cancer, particularly for patients with deep lamina propria invasion combined with other risk factors.

Quantitative description of eustachian tube movements during swallowing as visualized by transnasal videoendoscopy.

IMPORTANCE: Eustachian tube (ET) dysfunction predisposes ears to otitis media, tympanic membrane retraction, retraction pocket and perforation, or cholesteatoma. OBJECTIVE: To develop a method to quantitatively measure the eustachian tube (ET) component movements and their interactions captured by transnasal videoendoscopy of the ET during swallowing. DESIGN, SETTING, AND PARTICIPANTS: A blinded analysis of ET mechanics in 33 adults, aged 18 to 54 years, with no middle ear disease at present but without (group 1 [n = 16]) or with (group 2 [n = 17]) history of disease, conducted at a clinical research laboratory. INTERVENTIONS: Videoendoscopy of the ET orifice at the nasopharynx. MAIN OUTCOMES AND MEASURES: Eustachian tube component translations and structural interactions during a swallow and the between-group differences in those variables. After topical anesthesia of the nose, a 45° telescope was introduced unilaterally and focused on the ipsilateral ET orifice. A video recording of ET component movements was made during 3 swallows. Swallow and ET opening durations and times to selected events were calculated. Images at 3 time points were analyzed by measuring the apex angle, the medial-lateral luminal width, and the medial angles between a frame-normal horizontal line through the apex and fixed points on the torus and medial and lateral luminal walls. Linear and angular variables during a swallow were expressed as change from baseline. RESULTS: Luminal opening was driven by soft palate elevation-related medial rotation of the torus and medial wall, coupled with lateral wall fixedness. The magnitude of the change from baseline for most variables was statistically greater than 0. Swallow time, palatal elevation time, time interval between maximum palatal elevation, and maximum eustachian tube opening time were not different between groups 1 and 2. Opening time was longer (mean [SD], 0.49 [0.28] vs 0.67 [0.51] seconds; P = .03) in group 2. Higher magnitude of torus rotation (mean [SD], 36.05° [12.96°] vs 27.72° [9.45°]; P = .002) with maximum soft palate elevation in group 1 resulted in greater degree of eustachian tube orifice widening (mean [SD], 0.34% [0.47%] vs -0.02% [0.49%]; P = .001) compared with the resting position in that group. CONCLUSIONS AND RELEVANCE: This methodology has application in developing quantitative descriptions of ET mechanics in groups of persons without and with history or suspected ET dysfunction. A lesser degree of soft palate elevation during swallow that derives the ET medial lamina rotation and widening of the ET orifice may be associated with poor ET function and higher risk for otitis media. Videoendoscopic evaluation of the ET orifice may assist in diagnosing presence and mechanism of ET dysfunction.

A method to assess the accuracy of sonotubometry for detecting Eustachian tube openings.

Sonotubometry is a simple test for Eustachian tube (ET) opening during a maneuver. Different sonotubometry configurations were suggested to maximize test accuracy, but no method has been described for comparing sonotubometry test results with those for a definitive measure of ET opening. Here, we present such a method and exemplify is use by an accuracy assessment of a simple sonotubometry configuration. A total of 502 data-sequences from 168 test sessions in 103 adult subjects were analyzed. For each session, subjects were seated in a pressure chamber and relative middle ear over- and under-pressures created by changing chamber pressure. At each pressure, the test sequence of bilateral tympanometry, bilateral sonotubometry while the subject swallowed twice, and bilateral tympanometry was done. Tympanometric data were expressed as the fractional gradient equilibrated (FGE) by swallowing and sonotubometric signals were analyzed to record the shape of detected sound signals. Tympanometric and sonotubometric tubal opening assignments were analyzed by cross-correlation. For the data sequences with FGE = 0 (n = 32) evidencing no tubal opening and one (n = 249) evidencing definitive tubal opening, detection of a sonotubometry sound signal during a swallow had a sensitivity and specificity of 74.2 and 65.6 % for identifying ET openings and an accuracy of 73.3 % for assigning ET opening/non-opening by swallowing. Measures of sound signal shape were significantly different between those groups. This protocol allows a sonotubometry accuracy assessment for detecting ET openings. For the test configuration used, accuracy was moderate, but this should improve as more sophisticated sonotubometry test configurations are evaluated.