Epidemiology and Prognostic Indicators of Survival in Tongue Lymphoma.

OBJECTIVES: Lymphoma, categorized as either non-Hodgkin's lymphoma or Hodgkin's lymphoma, is the second most common malignancy in the head and neck. Primary tongue lymphoma is exceedingly rare, with only case reports or small case series in the literature. This population-based analysis is the first to report the epidemiology and prognostic factors of survival in patients with primary tongue lymphoma. METHODS: The Surveillance, Epidemiology, and End Results 18 database from the National Cancer Institute was queried for patients diagnosed between the years 2000 and 2016 with tongue lymphoma. Outcomes of interest were overall and disease-specific survival. Independent variables included age at diagnosis, sex, race, marital status, primary subsite, histologic subtype, stage, and treatment type. RESULTS AND CONCLUSION: Seven hundred forty patients met criteria; the male-female ratio was 1.5:1 and the mean age at diagnosis was 67.8 years. The majority of lesions localized to the base of tongue (90.0%), were histologically diffuse large B-cell lymphoma (59.5%), and presented at stage I or II (77.9%). Most early-stage lymphomas were treated with chemotherapy only (40.5%) or a combination of both chemotherapy and radiation (31.3%), while late-stage cancers were primarily treated with chemotherapy alone (68.5%). In multivariate analysis, younger age at diagnosis, female sex, married/partnered marital status, mucosa-associated lymphoid tissue histologic subtype, and earlier cancer stage were found to be associated with improved survival. Chemotherapy treatment with or without radiation was also associated with better survival compared to no treatment or radiation alone, though data regarding immunotherapy was unavailable.

Gender differences in the laryngectomee experience.

BACKGROUND: Laryngectomy is a pivotal event in patients. lives, with pervasive and far-reaching effects. Understanding gender differences in these effects may improve care of laryngectomy patients. This paper describes gender differences in the experience after laryngectomy. AIM: To explore the similarities and differences in the laryngectomee experience based on gender. METHODS & PROCEDURES: Four gender-matched focus groups were conducted; dialogue was audio recorded, transcribed and studied using interpretative phenomenological analysis (IPA). OUTCOMES & RESULTS: A total of 17 laryngectomees, eight female and nine male, age range 41-80 years, participated in focus groups. Laryngectomy represented a turning point in the lives of both genders. Four themes emerged: perception of loss, adjusting to alaryngeal communication, finding a positive outlook and re-establishing the self. Themes applied to both genders, with subthemes demonstrating similarities and differences between men and women. CONCLUSIONS & IMPLICATIONS: Men and women experienced destabilization after laryngectomy related to perceived losses and shifts in identity. Men described navigating from physical disability toward recovery of function, while women described an emotional journey concerning loss and rediscovery of meaning in their lives. Understanding the laryngectomee experience in better detail, which includes recognizing gender differences and rejecting a one-size-fits-all approach, may facilitate more effective preoperative counselling and post-operative support from providers. WHAT THIS PAPER ADDS: What is already known on the subject Patients who undergo total laryngectomy often struggle with problems with physical, emotional, and social functioning and decreased quality of life. As the literature currently stands, the understanding of the experience of laryngectomees has primarily focused on the perspective of a singular gender. Thus, this is the first qualitative study specifically investigating differences in the laryngectomee experience between men and women. What this paper adds to existing knowledge This study finds that women and men both endorse significant mental and physical changes following laryngectomy; however, their perception of their experience differed by gender. Women endorsed alteration to meaningful life and men demonstrated distress related to loss of physical functioning; both genders described laryngectomy as a formative event that helped them rediscover joy and redefine themselves for the better. What are the potential or actual clinical implications of this work? Our findings suggest men and women have distinct mental and emotional struggles after laryngectomy despite similar physical changes. This suggests that tailoring care with consideration of these gender differences, including preoperative counselling, post-operative support and gender-matched visitors or support groups, may help beneficial in recovery after laryngectomy.

Temporal trends in oropharyngeal cancer incidence, survival, and cancer-directed surgery among elderly Americans.

OBJECTIVE: This study assesses longitudinal epidemiologic trends in the oldest head and neck cancer (HNC) patients, comparing the oropharynx to other mucosal HNC sites. MATERIALS AND METHODS: Using data from the Surveillance, Epidemiology, and End Results database, trends in incidence, two-year cancer specific mortality, and percent of cases recommended for and which received surgery from 2000 to 2018 in patients ages ≥85 years were assessed using Joinpoint analysis by HNC site. Trends were quantified as annual percentage change (APC) with 95% confidence intervals (CI). RESULTS: Among older adults, oropharyngeal cancer (OPC) incidence increased (APC = 1.80% [95% CI: 0.94-2.67]), while mortality decreased (APC = -2.01% [95% CI: -3.26--0.74]) from 2000 to 2018. At other mucosal HNC sites, incidence and mortality remained stable. Percentage of patients who received surgery significantly changed for oropharyngeal (APC = -15.34% from 2000 to 2005 [95% CI: -24.37 to -4.79]) and laryngeal (APC = -4.61% from 2000 to 2008 [95% CI -8.28 to -0.80]) cancers. Trends in recommendation for surgery varied by site with significant decreases at the larynx, oral cavity, and oropharynx. CONCLUSION: OPC incidence is increasing among the oldest HNC patients. An increasing proportion of HPV-associated tumors could account for associated mortality improvement. There has been a shift towards non-surgical therapy possibly due to known favorable response of HPV-associated OPC to radiation therapy and/or poor surgical candidacy in this age group. The evolving treatment approach has not been detrimental to population-level survival outcomes, but optimal treatment has yet to be established. Future studies with pathologically confirmed HPV status are needed to better understand older adult OPC burden.

Radiation-Associated Sarcoma of the Head and Neck: Incidence, Latency, and Survival.

OBJECTIVES/HYPOTHESIS: Radiation-associated sarcomas of the head and neck (RASHN) are known but rare sequelae after radiation for squamous cell carcinoma. The purpose of this study was to characterize RASHN, estimate the risk of RASHN in head and neck squamous cell patients after therapeutic radiation, and compare their survival to that of patients with de novo sarcomas of the head and neck (dnSHN). STUDY DESIGN: Retrospective database analysis. METHODS: RASHN and dnSHN cases were collected from the Surveillance, Epidemiology, and End Results Database to identify risk factors and calculate incidence and latency. Survival was compared between RASHN and dnSHN. RESULTS: The risk of RASHN was 20.0 per 100,000 person-years. The average latency period was 124.2 months (range 38-329). The cumulative incidence of RASHN at 20 years was 0.13%. Oral cavity and oropharynx primaries demonstrate increased risk. Five-year overall survival of RASHN was 22.4% compared to 64.5% for dnSHN. CONCLUSIONS: RASHN are confirmed to be rare. RASHN have poor overall survival and worse survival compared to dnSHN. The impact of intensity-modulated radiation therapy protocols on this risk is unknown. Modifiable risk factors of smoking and alcohol consumption continue to dwarf radiation therapy as risk factors of second primary head and neck cancers. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1034-1041, 2022.

Does Subglottic Squamous Cell Carcinoma Warrant a Different Strategy Than Other Laryngeal Subsites?

OBJECTIVES/HYPOTHESIS: Subglottic squamous cell carcinoma (SSCC) is a rare cancer with limited evidence-based treatment guidelines. This study aimed to describe the treatment patterns for SSCC and to determine which treatments provide the best overall survival. STUDY DESIGN: Retrospective database review. METHODS: The National Cancer Database (NCDB) was queried for patients treated for SSCC from 2004 through 2014. Overall survival (OS) rates were determined by the Kaplan-Meier method. Clinicopathologic characteristics were assessed by univariable and multivariable Cox proportional hazards models, which corrected for age, sex, race, insurance status, income quartile, residence, Charlson-Deyo comorbidity score, facility type providing treatment, tumor grade, and clinical N and T category. RESULTS: In this cohort of 549 patients with SSCC, the 5-year OS was 48.2%. SSCC presented at an advanced stage (American Joint Committee on Cancer stage III or IV) in 60.1% of cases; 78.3% of cases had no nodal metastases. Among only stage IV cases, multivariable analysis showed that radiotherapy (RT) (hazard ratio [HR] = 5.944; 95% confidence interval [CI]: 2.76-12.8; P < .001) and chemoradiotherapy (CRT) (HR = 2.321; 95% CI: 1.36-3.97; P = .002) were both associated with decreased 5-year OS compared to a group consisting of all surgeries. When this analysis was repeated for only stage III cases, RT (HR = 1.134; 95% CI: 0.38-3.37; P = .821) and CRT (HR = 1.784; 95% CI: 0.78-4.08; P = .170) were equivalent to surgery. CONCLUSIONS: Using the NCDB to study the largest cohort of SSCC with known staging and treatment, primary surgery may provide a better 5-year OS in advanced-stage SSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1117-E1124, 2021.

Prognostic significance of surgical margins after transoral laser microsurgery for early-stage glottic squamous cell carcinoma.

OBJECTIVES: The impact of positive tumor margin status and other clinicopathological factors on prognosis in early stage glottic squamous cell carcinoma (SCC) treated with transoral laser microsurgery (TLM) remains unclear. This study examined overall survival (OS) rates of patients with positive tumor margin status compared to negative tumor margin status after TLM in clinical T1-2 glottic SCC. MATERIALS AND METHODS: The National Cancer Data Base (NCDB) was queried for patients who underwent resection of T1-2 glottic SCC by TLM. Patients were treated from 2004 to 2013. Overall survival was assessed with Kaplan-Meier curve analysis, and univariate and multivariate Cox proportional hazards analysis. Differences in clinicopathologic factors between positive and negative margin groups were compared using Pearson Chi-squared analysis. RESULTS: Of 747 patients meeting inclusion criteria, 598 (80.1%) had negative margins. Median follow-up time was 48.0 months. Unadjusted 5-year OS for positive margins (80.0%) was lower compared to that of negative tumor margins (82.9%), but this was not statistically significant (P = 0.265). This persisted after multivariate analysis (P = 0.960). When tumors were stratified by T stage (647 T1, 100 T2), unadjusted 5-year OS based on margin status remained statistically insignificant for both T1 (P = 0.933) and T2 tumors (P = 0.350). CONCLUSION: Positive margins did not negatively impact overall survival among patients with TLM-treated early-stage glottic cancer. This finding might be useful clinically in deciding treatment modality for early stage glottic SCC.

Comparison of the Financial Burden of Survivors of Head and Neck Cancer With Other Cancer Survivors.

IMPORTANCE: Head and neck cancer (HNC) is more common among socioeconomically disenfranchised individuals, making financial burden particularly relevant. OBJECTIVE: To assess the financial burdens of HNC compared with other cancers. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective review of nationally representative, publicly available survey, data from the Medical Expenditure Panel Survey were extracted from January 1, 1998, to December 31, 2015. A total of 444 867 adults were surveyed, which extrapolates to a population of 221 503 108 based on the weighted survey design. Data analysis was performed from April 18, 2018, to August 20, 2018. EXPOSURES: Of 16 771 patients with cancer surveyed (weighted count of 10 083 586 patients), 489 reported HNC (weighted count of 261 631). MAIN OUTCOMES AND MEASURES: Patients with HNC were compared with patients with other cancers on demographics, income, employment, and health. Within the HNC group, risk factors for total medical expenses and relative out-of-pocket expenses were assessed with regression modeling. Complex sampling methods were accounted for with weighting using balanced repeated replication. RESULTS: A total of 16 771 patients (mean [SD] age, 62.3 [18.9] years; 9006 [53.7%] female) with cancer were studied. Compared with patients with other cancers, patients with HNC were more often members of a minority race/ethnicity, male, poor, publicly insured, and less educated, with lower general and mental health status. Median annual medical expenses ($8384 vs $5978; difference, $2406; 95% CI, $795-$4017) and relative out-of-pocket expenses (3.93% vs 3.07%; difference, 0.86%; 95% CI, 0.06%-1.66%) were higher for patients with HNC than for patients with other cancers. Among patients with HNC, median expenses were lower for Asian individuals compared with white individuals ($5359 vs $10 078; difference, $4719; 95% CI, $1481-$7956]), Westerners ($8094) and Midwesterners ($5656) compared with Northwesterners ($10 549), and those with better health status ($16 990 for those with poor health vs $6714 for those with excellent health). Higher relative out-of-pocket expenses were associated with unemployment (5.13% for employed patients vs 2.35% for unemployed patients; difference, 2.78%; 95% CI, 0.6%-4.95%), public insurance (5.35% for those with public insurance vs 2.87% for those with private insurance; difference, 2.48%; 95% CI, -0.6% to 5.55%), poverty (13.07% for poor patients vs 2.06% for high-income patients), and lower health status (10.2% for those with poor health vs 1.58% for those with excellent health). CONCLUSIONS AND RELEVANCE: According to this study, HNC adds a substantial, additional burden to an already financially strained population in the form of higher total and relative expenses. The financial strain on individuals, assessed as relative out-of-pocket expenses, appears to be driven more by income than by health factors, and health insurance does not appear to be protective.

Basaloid Squamous Cell Carcinoma of the Larynx: A National Cancer Database Analysis.

OBJECTIVE: Basaloid squamous cell histology is a rare variant that accounts for about 2% of all head and neck squamous cell laryngeal carcinomas. The purpose of this study was to examine overall survival rates of patients according to treatment, stage, and laryngeal subsite. STUDY DESIGN: Retrospective analysis. SETTING: National Cancer Database (NCDB). SUBJECTS AND METHODS: The NCDB was queried for patients with basaloid squamous cell carcinoma (BSCC) who were treated from 2004 to 2014. Five-year overall survival rates were determined by the Kaplan-Meier method. Univariate and multivariate analysis was used to identify factors correlated with 5-year overall survival. RESULTS: The NCDB identified 440 patients meeting inclusion criteria. Median follow-up time was 31.2 months. On univariate analysis, the treatment modalities assessed (surgery alone, surgery with radiotherapy, surgery with chemoradiotherapy, radiotherapy, chemoradiotherapy) did not differ in their survival benefit. On multivariate analysis, only chemoradiotherapy (hazard ratio, 0.587; 95% CI, 0.37-0.93; P = .022) was associated with improved survival. All treatment modalities performed similarly between stage I and II tumors ( P = .340) and stage III and IV tumors ( P = .154). CONCLUSION: This study represents the largest laryngeal BSCC series to date. We found that chemoradiotherapy was associated with improved 5-year overall survival of laryngeal BSCC on multivariate analysis.

Demographic predictors of head and neck cancer survival differ in the elderly.

OBJECTIVES/HYPOTHESIS: Head and neck squamous cell carcinoma (HNSCC) prognosis strongly correlates with demographic factors. This study aimed to determine whether demographic predictors of HNSCC survival differ between age cohorts, with an emphasis on the growing elderly demographic. STUDY DESIGN: Outcomes research. METHODS: Adults with squamous cell carcinoma of the upper aerodigestive tract were identified from the Surveillance, Epidemiology and End Results 18 database. Demographic and oncologic factors were compared between three age groups: 18 to 49, 50 to 74, and >75 years. Factors associated with cancer-specific survival were assessed in each cohort using subdistribution hazard ratio (sHR) and 95% confidence interval (CI) produced by multivariate competing risk models. RESULTS: A cohort of 69,098 patients included 10,588 (15.3%) 75 years or older and 9,882 (14.3%) less than 50 years old. Older patients were more often female (35.4% vs. 25.1% aged 18-49 years and 20.4% aged 50-74 years), white (78.7% vs. 69.4% and 75.9%), insured (63.5% vs. 46.5% and 56.8%), and married (56.6% vs. 53% and 51.1%), but received adequate treatment less often (72.0% vs. 86.3% and 82.7%). In the older cohort, male sex was associated with lower mortality (sHR: 0.92, 95% CI: 0.85-1.00), and unlike the younger cohorts, black race was no longer associated with mortality (sHR: 1.07, 95% CI: 0.94-1.22). Marriage was associated with lower mortality in all age groups but with diminishing effects (single sHR: young 1.52, middle 1.31, older 1.14). CONCLUSIONS: Elderly HNSCC patients have distinct effects from demographic prognostic factors and should be considered a separate subgroup with unique epidemiology, risks, and preferences. LEVEL OF EVIDENCE: 2c Laryngoscope, , 129:146-153, 2018.

Does anatomic subsite influence oral cavity cancer mortality? A SEER database analysis.

OBJECTIVE: To determine if there are differences in mortality from oral cavity squamous cell carcinoma (OCSCC) based on oral cavity (OC) subsites. METHODS: Using the Surveillance, Epidemiology, and End Results Program (SEER) 9 database, patients with sequence number 0 or 1 squamous cell OCSCC were analyzed by OC subsite for 5-year cause-specific mortality (CSM) from OCSCC. Proportional hazards regression determined the association between 5-year CSM and OC subsites while controlling for treatment modality, stage, and demographic characteristics using hazard ratios. Significance was set at alpha = 0.05. RESULTS: 20,647 OC patients were included in the regression analysis. The most commonly diagnosed sites were floor of mouth (34.4%) and oral tongue (34.3%). Floor of mouth, upper gum, and retromolar trigone were associated with lower CSM compared to oral tongue. Not receiving surgery and receiving radiation were associated with increased CSM, and CSM increased with cancer staging when distant or regional disease was compared to localized disease. Also, patients diagnosed at 60 years or older and black patients had increased CSM. CONCLUSION: Among OCSCC patients, those with oral tongue cancer are more likely to experience CSM than patients with floor of mouth, upper gum, and retromolar trigone cancer. It is important to understand these mortality related differences in the management of OCSCC patients. Understanding subsite-specific mortality may benefit prognosis counseling of OCSCC patients and elicit subsite-directed research as a means to improve outcomes. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1400-1406, 2019.

Dysequilibrium of the PTH-FGF23-vitamin D axis in relapsing remitting multiple sclerosis; a longitudinal study.

BACKGROUND: Parathyroid glands of people with relapsing remitting multiple sclerosis (RRMS) fail to respond to low serum 25-hydroxyvitamin D (25OHD) and low serum calcium, which are stimuli for parathyroid hormone (PTH) secretion. This led us to hypothesise: that there is suppression of PTH in RRMS due to higher than normal serum concentrations of fibroblast growth factor 23 (FGF23). We therefore sought evidence for dysregulation of the PTH-FGF23-vitamin D axis in RRMS. METHODS: Longitudinal study (winter to summer) with fasting venepunctures. For RRMS subjects who recruited a healthy control (HC) friend, pairs analyses were performed. For each pair, the within-pair difference of the variable of interest was calculated (RRMS minus HC). Then, the median of the differences from all pairs was compared against a median of zero (Wilcoxon) and the 95% confidence interval of that median difference (CI) was calculated (Sign Test). RESULTS: RRMS had lower winter PTH than HC, P = 0.005, (CI -2.4 to 0.5 pmol/L, n = 28 pairs), and lower summer PTH, P = 0.04, (CI -1.8 to 0.5, n = 21 pairs). Lower PTH associates physiologically with lower intact FGF23 (iFGF23), yet RRMS had higher iFGF23 than HC in winter, P = 0.04, (CI -3 to 15 pg/mL, n = 28 pairs) and iFGF23 levels comparable to HC in summer, P = 0.14, (CI -5 to 13, n = 21 pairs). As PTH stimulates and FGF23 reduces, renal 1-alpha hydroxylase enzyme activity, which synthesises serum 1,25-dihyroxyvitamin D (1,25(OH)2D) from serum 25OHD, we examined the ratio of serum 1,25(OH)2D to serum 25OHD. In winter, this ratio was lower in RRMS versus HC, P = 0.013, (CI -1.2 to - 0.3, n = 28 pairs). CONCLUSIONS: This study revealed a dysequilibrium of the PTH-FGF23-vitamin D axis in RRMS, with lower plasma PTH, higher plasma iFGF23 and a lower serum 1,25(OH)2D to 25OHD ratio in RRMS compared with HC subjects. This dysequilibrium is consistent with the study hypothesis that in RRMS there is suppression of the parathyroid glands by inappropriately high plasma concentrations of iFGF23. Studying the basis of this dysequilibrium may provide insight into the pathogenesis of RRMS.

An assessment of patient burdens from head and neck cancer survivorship care.

OBJECTIVES: To assess head and neck cancer (HNC) patients' perspectives on the value and burdens of routine cancer follow-up care. MATERIALS AND METHODS: Data was obtained from HNC patients (n = 100) at an urban, tertiary head and neck cancer clinic. A novel 15-question survey tool evaluated the logistic, financial, and psychosocial burdens associated with clinic visits. The clinical characteristics and survey responses of demographic groups were analyzed with comparative statistics. Linear regression modeling was utilized to identify predictors of overall stress. RESULTS: A majority of study participants were male (74%), white (83%), and had histories of tobacco (77%) and alcohol (77%) use. Most participants were satisfied with the frequency of their office visits (75%). Patients with laryngeal cancer, advanced stage disease, or who underwent multimodality therapy more often desired increased appointment frequency. These patients also rated the burdens of travel cost and overall stress higher, compared to patients desiring visits less often (41.5% vs 28.4%, p = 0.047 and 46.6% vs 38.3%, p = 0.003, respectively). Travel stress was associated with highest overall stress (beta 0.6, CI: 0.4, 0.7). CONCLUSION: The HNC survivor population is uniquely disenfranchised in several social and economic ways. While most patients are satisfied with their follow-up care, a significant subset of patients - those with limited social support, high financial stress, functional deficits, and those with transportation burdens - desire more frequent care. Survivorship care plans should incorporate the perspectives of current survivors.

Survival after refusal of surgical treatment for locally advanced laryngeal cancer.

OBJECTIVE: Survival of advanced laryngeal cancer is declining while the popularity of organ preservation protocols grows. This study assesses the survival impact of refusing surgical treatment for locally advanced, resectable laryngeal cancer. METHODS: Adult patients with T3 and T4a non-metastatic laryngeal squamous cell carcinoma were identified from the Surveillance, Epidemiology and End Results 18 database from 2004 to 2013. Patients were stratified based on a recommendation for extirpative surgery and the refusal of surgery. Multivariate logistic regression modeling identified variables associated with refusal. A multivariate cox proportional hazard model produced adjusted Kaplan-Meier survival curves. Survival was compared using adjusted hazard ratios (aHR) with 95% confidence intervals (CI). RESULTS: Of 5786 patients in the study, 2877 were recommended for surgical treatment and 138 (4.8%) refused. Refusal of surgery was associated with unmarried status (Single, odds ratio (OR) 1.79, CI 1.10-2.92), black race (OR 1.50, CI 1.00-2.22), T3 tumors (OR 1.80, CI 1.26-2.61) and N3 nodal disease (OR 3.50, CI 1.24-8.48). Compared to patients undergoing surgery, those who refused had lower 5-year cancer specific survival and increased hazard of cancer-specific mortality (aHR 1.60, CI 1.24-2.07) which resulted in decreased 5-year survival (50.0vs 60.1%), after controlling for other factors. CONCLUSION: Refusal of surgery for locally advanced laryngeal cancer is more common in patients without marital support and with T3 tumors. This decision results in a 10% survival decrease at 5-year. Future study is needed to understand patients' reasoning behind this decision and to investigate additional factors not available in this dataset.

Effect of Combined Hormonal Replacement Therapy on the Aldosterone/Renin Ratio in Postmenopausal Women.

Background: Plasma aldosterone/renin ratio (ARR) is the most popular screening test for primary aldosteronism (PA). Because both estrogen and progesterone (including in oral contraceptive agents) affect aldosterone and renin levels, we studied the effects of combined hormonal replacement therapy (HRT) on ARR; renin was measured as both direct renin concentration (DRC) and plasma renin activity (PRA). Methods: Fifteen normotensive, healthy postmenopausal women underwent measurement (seated, midmorning) of plasma aldosterone, DRC, PRA, electrolytes, and creatinine and urinary aldosterone, cortisol, electrolytes, and creatinine at baseline and after 2 weeks and 6 weeks of treatment with combined HRT (conjugated estrogens 0.625 mg and medroxyprogesterone 2.5 mg daily). Results: Combined HRT was associated with statistically significant increases in aldosterone [median (range): baseline, 150 (85 to 600); 2 weeks, 230 (129 to 790); 6 weeks, 434 (200 to 1200) pmol/L; P < 0.001 (Friedman test)] and PRA [2.3 (1.2 to 4.3), 3.8 (1.4 to 7.0), 5.1 (1.4 to 10.8) ng/mL/h, respectively; P < 0.001] but decreases in DRC [21 (10 to 31), 21 (10 to 39), and 14 (8.0 to 30) mU/L, respectively; P < 0.01], leading to increases in ARR calculated by DRC [7.8 (3.6 to 34.8), 11.4 (5.4 to 48.5), and 30.4 (10.5 to 90.2), respectively; P < 0.001]. The ARR calculated by DRC exceeded the cutoff value (70) in three patients after 6 weeks. There were no significant changes in ARR calculated by PRA [79 (26 to 184), 91 (23 to 166), and 88 (50 to 230), respectively; P = 0.282], plasma electrolytes and creatinine, or any urinary measurements. Conclusion: The combined oral HRT used in this study is capable of significantly increasing ARR with a risk of false-positive results during screening for PA but only if DRC (and not PRA) is used to calculate the ratio.

Effect of Moxonidine on the Aldosterone/Renin Ratio in Healthy Male Volunteers.

Background: The most popular screening test for primary aldosteronism is the plasma aldosterone/renin ratio (ARR). Medications, dietary sodium, posture, and time of day all affect renin and aldosterone levels and can result in false-negative or false-positive ARRs if not controlled. Most antihypertensive medications affect the ARR and can interfere with interpretation of results. To our knowledge, no study has been undertaken to evaluate the effects of moxonidine on the ARR. Methods: Normotensive, nonmedicated male volunteers (n = 20) underwent measurement (seated, midmorning) of plasma aldosterone (by high-performance liquid chromatography-tandem mass spectrometry), direct renin concentration (DRC), plasma renin activity (PRA), cortisol, electrolytes and creatinine; and urinary aldosterone, cortisol, electrolytes and creatinine at baseline and after 1 week of moxonidine at 0.2 mg/d and a further 5 weeks at 0.4 mg/d. Results: Compared with baseline, despite the expected significant falls in both systolic and diastolic blood pressure, levels of plasma aldosterone [median, 134 (range, 90 to 535) pmol/L], DRC [20 (10 to 37) mU/L], PRA [2.2 (1.0-3.8) ng/mL/h], and ARR using either DRC [8.0 (4.4 to 14.4)] or PRA [73 (36 to 218)] were not significantly changed after either 1 [135 (98-550) pmol/L, 20 (11-35) mU/L, 2.0 (1.2-4.1) ng/mL/h, 8.8 (4.2 to 15.9), and 73 (32-194), respectively] or 6 weeks [130 (90-500) pmol/L, 22 (8 to 40) mU/L, 2.1 (1.0 to 3.2) ng/mL/h, 7.7 (4.3 to 22.4), and 84 (32 to 192), respectively] of moxonidine. There were no changes in any urinary measurements. Conclusion: Moxonidine was associated with no significant change in the ARR and may therefore be a good option for maintaining control of hypertension when screening for primary aldosteronism.

Should aldosterone suppression tests be conducted during a particular phase of the menstrual cycle, and, if so, which phase? Results of a preliminary study.

BACKGROUND: As renin and aldosterone levels vary during the menstrual cycle, and are critical criteria for interpretation of aldosterone suppression tests to confirm or exclude primary aldosteronism, outcome of testing may vary depending on the menstrual cycle phase. We assessed the effect of timing within the menstrual cycle on levels of renin, aldosterone and female sex steroids during fludrocortisone suppression testing (FST). METHODS: In 22 women undergoing FST who experienced regular menstrual cycles, renin (measured as both plasma renin activity and direct renin concentration), aldosterone (mass spectrometry) and cortisol, progesterone, oestradiol, LH and FSH (immunoassay) levels were compared, relative to phase of cycle. Aldosterone levels were compared to those in age-matched males undergoing FST. RESULTS: Progesterone (P < 0·0001) and aldosterone (P = 0·006) levels were higher in nine women (after one of 10 was excluded with anovulatory cycle) studied during the luteal phase than in the 12 studied during the follicular phase. All studied during the luteal phase had positive FST, and all three with negative FST were studied during the follicular phase. There were no significant differences in other parameters measured except FSH, which was higher (P = 0·02) during the follicular phase. Aldosterone was higher (P = 0·01) in women studied in the luteal (but not follicular) phase compared to men. CONCLUSION: The menstrual cycle may affect the outcome of FST and other suppression testing used to diagnose primary aldosteronism. Larger patient numbers and preferably restudy of the same patient in both phases should clarify this and determine the optimum time in the cycle for testing.

Impact of water exchange colonoscopy on serum sodium and potassium levels: an observational study.

BACKGROUND: Concerns over the hypothetical adverse effects of water absorption and the disturbance of serum sodium and potassium levels prompted a quality assurance evaluation of water exchange (WE) colonoscopy. AIM: The purpose of this study was to evaluate the balance of water infused and suctioned in WE colonoscopy, and to quantify the acute impact on serum levels of sodium and potassium. METHODS: Prospectively collected quality monitoring data of patients undergoing screening and surveillance colonoscopy at the Sacramento Veterans Affairs Medical Center were analyzed. Measurements were made of volume infused and suctioned during, and blood samples drawn 10 min before the start of and 10 min after completion of WE colonoscopy. Outcome measures included volume of water infused and suctioned, and serum levels of sodium and potassium. RESULTS: A total of 140 patients (134M:6F), mean age of 59, underwent WE colonoscopy. Mean total volume of water infused was 1,839 mL. A negative balance of an average of 22 mL was documented. The mean (standard deviation) values (in meq/L) of serum levels of sodium 139.33 (2.27) and 139.28 (2.32), and potassium 3.86 (0.36) and 3.91 (0.39), before and after colonoscopy, respectively, showed no significant change. CONCLUSION: The WE method allowed most of the water infused during colonoscopy to be recovered by suction at the completion of colonoscopy. Serum sodium and potassium levels did not change significantly within 10 min after completion. The WE method appears to be safe with minimal water retention and is devoid of acute fluctuations in serum levels of sodium and potassium.

Mortality of intra-abdominal desmoid tumors in patients with familial adenomatous polyposis: a single center review of 154 patients.

INTRODUCTION: Intra-abdominal desmoid tumors are one of the leading causes of death in patients with familial adenomatous polyposis. Their behavior is unpredictable and their biology is poorly understood, accounting for the lack of a standardized medical and surgical approach. The aim of this study was to evaluate the mortality rate of patients with intra-abdominal desmoid tumors and to identify prognostic factors for the evolution of the disease. MATERIALS AND METHODS: A total of 154 patients with intra-abdominal desmoid tumors were included in the study. Each tumor was staged and each patient was categorized according to the stage of their most advanced tumor. Mortality was analyzed and the univariate risk factors associated with survival were included in a multivariable Cox regression model. A scoring system was derived from the multivariate analysis to refine outcomes within stages. RESULTS: Five-year survival of patients with stage I, II, III, and IV intra-abdominal desmoid tumor were 95%, 100%, 89%, and 76% respectively (P < 0.001). Severe pain/narcotic dependency, tumor size larger than 10 cm, and need for total parenteral nutrition were shown to further define survival within stages. Five-year survival rate of stage IV patient with all of the above-mentioned risk factors was only 53%. CONCLUSIONS: Our study confirmed the validity of the staging system to predict mortality in patients with intra-abdominal desmoid tumors and identified additional risk factors able to better define the risk of death within each stage. Risk stratification is crucial in directing patients with advanced disease and poor prognosis to the most appropriate medical and surgical options.

Magnetic endoscope imaging (ScopeGuide) elucidates the mechanism of action of the pain-alleviating impact of water exchange colonoscopy - attenuation of loop formation.

BACKGROUND: The explanation why water exchange colonoscopy produces a significant reduction of pain during colonoscopy is unknown. A recent editorial recommended use of magnetic endoscope imaging (MEI) to elucidate the explanation. OBJECTIVE: In unselected patients to show that MEI documents less frequent loop formation when water exchange is used. DESIGN: Observational, performance improvement. SETTING: Veterans Affairs outpatient endoscopy. PATIENTS: Routine colonoscopy cases. INTERVENTIONS: Colonoscopy using air or water exchange method was performed as previously described. The MEI equipment (ScopeGuide, Olympus) with built-in magnetic sensors displays the configuration of the colonoscope inside the patient. During sedated colonoscopy the endoscopist was blinded to the ScopeGuide images which were recorded and subsequently reviewed. MAIN OUTCOME MEASURES: Loop formation based on a visual guide provided by Olympus. RESULTS: There were 41 and 32 cases in the water exchange and air group, respectively. The sigmoid N loop was most common, followed by the sigmoid alpha loop, and exaggeration of scope curvature at the splenic flexure/transverse colon. Of these, 20/32 vs. 9/41 patients (p=0.0007) had sigmoid looping, and 17/32 vs. 9/41 patients (p=0.0007) had sigmoid/splenic looping when the scope tip was in the transverse colon, in the air and water exchange group, respectively. LIMITATIONS: Colonoscopy method was not blinded and non randomized. CONCLUSION: MEI data objectively demonstrated significantly fewer loops during water exchange colonoscopy, elucidating its mechanism of pain alleviation - attenuation of loop formation. Since MEI feedback enhances cecal intubation by trainees, the role of MEI combined water exchange in speeding up trainee learning curves deserves further evaluations.

ß-blockers protect against dispersion of repolarization during exercise in congenital long-QT syndrome type 1.

INTRODUCTION: ß-Blocker therapy reduces syncope and sudden death in long-QT syndrome type 1 (LQT1), but the mechanism of protection is incompletely understood. This study tested the hypothesis that ß-blockade reduces QT prolongation and dispersion of repolarization, measured as the T peak-to-end interval (T(pe) ), during exercise and recovery in LQT1 patients. METHODS AND RESULTS: QT and T(pe) were measured in 10 LQT1 patients (33 ± 13 years) and 35 normal subjects (32 ± 12 years) during exercise tests on and off ß-blockade. In LQT1 patients, ß-blockade reduced QT (391 ± 25 milliseconds vs 375 ± 26 milliseconds, P = 0.04 during exercise; 419 ± 41 milliseconds vs 391 ± 39 milliseconds, P = 0.02 during recovery) and markedly reduced T(pe) (91 ± 26 milliseconds vs 67 ± 19 milliseconds, P = 0.03 during exercise; 103 ± 26 milliseconds vs 78 ± 11 milliseconds, P = 0.02 during recovery). In contrast, in normal subjects, ß-blockade had no effect on QT (320 ± 17 milliseconds vs 317 ± 16 milliseconds, P = 0.29 during exercise; 317 ± 13 milliseconds vs 315 ± 14 milliseconds, P = 0.15 during recovery) and mildly reduced T(pe) (69 ± 13 milliseconds vs 61 ± 11 milliseconds, P = 0.01 during exercise; 77 ± 19 milliseconds vs. 68 ± 14 milliseconds, P < 0.001 during recovery). CONCLUSION: In LQT1 patients, ß-blockers reduced QT and T(pe) during exercise and recovery, supporting the theory that ß-blocker therapy protects LQT1 patients by reducing dispersion of repolarization during exercise and recovery.