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ABSTRACT: BACKGROUND: While the receipt of a perioperative blood transfusion (PBT) has been associated with an increased risk of mortality for a number of malignancies, the relationship between PBT and survival following radical cystectomy (RC) for bladder cancer (BCa) has not been well established. OBJECTIVE: To evaluate the association of PBT with disease recurrence and mortality following RC. DESIGN, SETTING, AND PARTICIPANTS: We identified 2060 patients who underwent RC at the Mayo Clinic between 1980 and 2005. PBT was defined as transfusion of allogenic red blood cells during RC or postoperative hospitalization. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Survival was estimated using the Kaplan-Meier method and was compared with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of PBT with outcome, controlling for clinicopathologic variables. RESULTS AND LIMITATIONS: A total of 1279 patients (62%) received PBT. The median number of units transfused was 2 (interquartile range [IQR]: 2-4). Patients receiving PBT were significantly older (median: 69 yr vs 66 yr; p<0.0001), had a worse Eastern Cooperative Oncology Group performance status (p<0.0001), and were more likely to have muscle-invasive tumors (56% vs 49%; p=0.004). Median postoperative follow-up was 10.9 yr (IQR: 7.9-15.7). Receipt of PBT was associated with significantly worse 5-yr recurrence-free survival (58% vs 64%; p=0.01), cancer-specific survival (59% vs 72%; p<0.001), and overall survival (45% vs 63%; p<0.001). On multivariate analyses, PBT remained associated with significantly increased risks of postoperative tumor recurrence (hazard ratio [HR]: 1.20; p=0.04), death from BCa (HR: 1.31; p=0.003), and all-cause mortality (HR: 1.27; p=0.0002). Among patients who received PBT, an increasing number of units transfused was independently associated with increased cancer-specific mortality (HR: 1.07; p<0.0001) and all-cause mortality (HR: 1.05; p<0.0001). Limitations include selection bias and lack of standardized transfusion criteria. CONCLUSIONS: We found that PBT is associated with significantly increased risks of cancer recurrence and mortality following RC. While external validation is required, continued efforts to reduce the use of blood products in these patients are warranted.
European urology 01/2013; · 7.67 Impact Factor
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ABSTRACT: PURPOSE: Radical cystectomy (RC) continues to be associated with a non-negligible risk of perioperative death, while all-cause mortality (ACM) in the years after surgery remains relatively high as well. We investigated the comparative ability of various comorbidity indices to predict perioperative and 5-year ACM following RC. MATERIALS AND METHODS: We evaluated 891 patients who underwent RC between 1994-2005. The associations of American Society of Anesthesiologists (ASA) score, Charlson comorbidity index (CCI), Elixhauser index (EI), and Eastern Cooperative Oncology Group performance status (ECOG) with outcomes were assessed using Cox regression models. Model performance was compared with area under receiver operating curves (AUC). RESULTS: A total of 33 (3.7%) patients died within 90 days of RC. On multivariate analysis, locally-advanced pathologic tumor stage (HR 4.86;p=0.002), as well as EI (HR 1.48;p=0.002), ASA (HR 3.17;p=0.001), and ECOG (HR 2.40;p<0.0001) were significantly associated with 90-day perioperative mortality. Median follow-up after RC was 10.1 years, during which time 576 patients died. CCI (HR 1.23;p<0.0001), EI (HR 1.28;p<0.0001), ASA (HR1.44;p=0.007), and ECOG (HR 1.97;p<0.0001) were independent predictors of 5-year ACM. Moreover, CCI (AUC 0.798;p<0.0001), EI (AUC 0.770;p=0.03), and ECOG (AUC 0.769;p=0.03) significantly enhanced the performance of a base model which did not include comorbidity status (AUC 0.757) to predict 5-year ACM. CONCLUSIONS: Comorbidity status is predictive of perioperative death and 5-year ACM following RC, and should therefore be incorporated into patient counseling and risk stratification models. Further prospective studies are warranted to overcome the retrospective limitations in determining the relative prognostic value of various comorbidity indices.
The Journal of urology 01/2013; · 4.02 Impact Factor
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ABSTRACT: PURPOSE: Micropapillary (MP) bladder cancer is a rare variant of urothelial carcinoma (UC) which has been associated with an aggressive natural history. We sought to report the outcomes of patients with MP bladder cancer treated with radical cystectomy (RC) and compare survival to patients with pure UC of the bladder. METHODS: We identified 73 patients with MP bladder cancer and 748 patients with pure UC who underwent RC at our institution with median postoperative follow-up of 9.6 years. MP patients were stage-matched 1:2 to patients with pure UC. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: MP cancers were associated with a high rate of adverse pathologic features, as 48/73 patients (66 %) had pT3/4 tumors and 37 (50 %) had pN+ disease. Ten-year cancer-specific survival in MP patients was 31 %, compared with 53 % in the overall cohort with pure UC (p = 0.001). When patients with MP bladder cancer were then stage-matched to those with pure UC, no significant differences between the groups were noted with regard to 10-year local recurrence-free survival (62 vs. 69 %; p = 0.87), distant metastasis-free survival (44 vs. 56 %; p = 0.54), or cancer-specific survival (31 vs. 40 %; p = 0.41). CONCLUSION: MP cancers are associated with a higher rate of locally advanced disease. However, when matched to patients with pure UC, patients with MP tumors did not have increased local/distant recurrence or adverse cancer-specific survival following RC.
World Journal of Urology 11/2012; · 2.41 Impact Factor
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ABSTRACT: PURPOSE: To evaluate the oncologic outcomes following radical cystectomy for patients with nested variant (NV) of urothelial carcinoma (UC), and compare survival to patients with pure UC of the bladder. METHODS: We identified 52 patients with NV treated with radical cystectomy between 1980-2004. Pathologic specimens were re-reviewed by a single genitourinary pathologist. These patients were matched in a 1:2 fashion by age, gender, ECOG performance status, pathologic tumor stage, and nodal status to patients with pure UC. Survival was estimated using the Kaplan Meier method and compared with the log-rank test. RESULTS: Patients with NV had a median age of 69.5 years (IQR 62, 74) and a median post-operative follow-up of 10.8 years (IQR 9.3, 11.2). NV cancers were associated with a high rate of adverse pathologic features as 36 (69%) had pT3-T4 disease, and 10 (19%) had nodal invasion. A total of 8 (15%) patients with NV cancer received peri-operative chemotherapy. When patients with NV were then matched to a cohort of patients with pure UC, no significant differences were noted with regard to 10-year local recurrence-free survival (83% versus 80%; p= 0.46) or 10-year cancer-specific survival (41% versus 46%; p=0.75). CONCLUSIONS: NV of UC is associated with a high rate of locally-advanced disease at RC. However, when stage-matched to patients with pure UC, patients with NV did not have increased rates of recurrence or adverse survival. Further studies will be required to validate these findings and guide the optimal multimodal management approach to these patients.
The Journal of urology 11/2012; · 4.02 Impact Factor
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ABSTRACT: To our knowledge long-term oncologic outcomes following partial cystectomy for urothelial carcinoma remain to be defined. We evaluated patterns of recurrence and survival among matched patients treated with partial vs radical cystectomy for bladder cancer.
We identified 86 patients who underwent partial cystectomy for pT1-4N0-1Mx urothelial carcinoma between 1980 and 2006 at our institution. They were matched 1:2 to patients undergoing radical cystectomy based on age, gender, pathological T stage and receipt of neoadjuvant chemotherapy. Survival was estimated using Kaplan-Meier analysis and compared with the log rank test.
Median postoperative followup was 6.2 years (range 0 to 27). No difference was noted for 10-year distant recurrence-free survival (61% vs 66%, p = 0.63) or cancer specific survival (58% vs 63%, p = 0.67) between patients treated with partial and radical cystectomy, respectively. Interestingly, 4 of 86 patients (5%) who underwent partial cystectomy showed extravesical pelvic tumor recurrence postoperatively vs 29 of 167 (17%) who underwent radical cystectomy (p = 0.004). In addition, 33 of 86 patients (38%) were diagnosed with intravesical recurrence of tumor after partial cystectomy and 16 of 86 (19%) initially treated with partial cystectomy ultimately underwent radical cystectomy.
Our matched analysis demonstrated no difference in metastasis-free or cancer specific survival between select patients undergoing partial cystectomy and those undergoing radical cystectomy. Nevertheless, patients treated with partial cystectomy remain at risk for intravesical recurrence and, thus, they should be counseled and surveilled accordingly.
The Journal of urology 08/2012; 188(4):1115-9. · 4.02 Impact Factor
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ABSTRACT: We investigated the clinicopathological outcomes of patients treated with cystectomy for pure urothelial carcinoma vs urothelial carcinoma, and squamous and/or glandular differentiation.
We reviewed the records of 1,013 patients who underwent radical cystectomy, including 827 (72%) with pure urothelial carcinoma and 186 (18%) with urothelial carcinoma, and squamous and/or glandular differentiation. Of patients with variant histology 132 had squamous differentiation, 41 had glandular features and 13 had each type. Cancer specific survival was estimated using the Kaplan-Meier method. The association of histological differentiation with death from bladder cancer was evaluated using multivariate Cox proportional hazard regression analysis.
Patients with urothelial carcinoma, and squamous and/or glandular differentiation were more likely to have pT3-T4 tumors (70% vs 38%, p <0.0001) and pN+ disease (20% vs 15%, p = 0.05) than those with pure urothelial carcinoma. Median followup was 11.4 years. A total of 432 patients died of bladder cancer, including 77 with histological differentiation and 355 with pure urothelial carcinoma. Ten-year cancer specific survival did not significantly differ between patients with urothelial carcinoma and histological differentiation, and those with pure urothelial carcinoma (52% vs 51%, p = 0.71). After adjusting for clinicopathological features squamous and/or glandular differentiation was not significantly associated with the risk of death from bladder cancer (HR 0.79, p = 0.10).
Patients with urothelial carcinoma, and squamous and/or glandular differentiation were more likely to have extravesical tumors and node positive disease. Nevertheless, they did not have adverse survival compared to patients with pure urothelial carcinoma. Additional studies are needed to further define prognostic factors in such patients.
The Journal of urology 06/2012; 188(2):405-9. · 4.02 Impact Factor
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ABSTRACT: Whether routine surveillance to detect tumor recurrence after radical cystectomy improves patient survival remains in debate. We determined the impact on all cause mortality of symptoms at recurrence after cystectomy.
We identified 1,599 patients who underwent radical cystectomy for urothelial carcinoma at our institution between 1980 and 2000. Median postoperative followup was 9.8 years (range 0 to 30.3). Overall survival in patients with recurrence stratified by the mode of diagnosis (asymptomatic vs symptomatic) was estimated using the Kaplan-Meier method and compared with the log rank test. Cox proportional hazard regression models were used to evaluate the impact of the mode of diagnosing recurrence on survival.
A total of 606 patients (38%) experienced recurrence after surgery, of whom 137 (23%) were asymptomatic and 469 (77%) were symptomatic. Recurrence sites included abdomen/pelvis in 450 patients, bone in 185, thorax in 176, urothelium in 154 and brain in 39. The most common symptoms at recurrence were pain in 75.3% of patients, constitutional symptoms in 57.4% and hematuria in 12.4%. Five and 10-year overall survival in patients with symptomatic vs asymptomatic recurrence was 22% and 10% vs 46% and 26%, respectively (p <0.0001). On multivariate analysis patients who were symptomatic at recurrence were at almost 60% increased risk for death than those who were asymptomatic (HR 1.59, p = 0.0001).
Detecting asymptomatic recurrence after cystectomy was associated with significantly improved patient survival. Continued investigation to establish the optimal followup regimen remains necessary, balancing the benefit of early detection with the increased cost of routine surveillance.
The Journal of urology 09/2011; 186(5):1796-802. · 4.02 Impact Factor
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ABSTRACT: Conflicting data exist regarding predictors of urethral recurrence (UR) following radical cystectomy (RC) as well as variables associated with survival in patients who experience UR.
To evaluate the incidence, risk factors, and outcomes of patients with UR.
We reviewed 1506 patients who underwent RC to identify patients with UR. Median follow-up after RC was 13.5 yr (interquartile range [IQR]: 10.5-18.4).
Urethrectomy.
Cox proportional hazard regression models were used to analyze predictors of UR and evaluate factors associated with death from urothelial carcinoma (UC) in patients who experienced UR. Cancer-specific survival (CSS) for patients with UR, stratified according to the mode of diagnosis (abnormal urethral cytology vs symptoms), was estimated using the Kaplan-Meier method and compared with the log-rank test.
UR was identified in 85 patients (5.6%) at a median of 13.3 mo (IQR: 6.1-23.2) after RC, including 80 of 1243 (6.4%) who underwent cutaneous urinary diversion and 5 of 242 (2.1%) who received an orthotopic neobladder (p=0.002). On multivariate analysis, prostate involvement with UC (hazard ratio [HR]: 4.89; p<0.0001), bladder tumor multifocality (HR: 2.34; p=0.001), and orthotopic diversion (HR: 0.34; p=0.02) were significantly associated with the risk of UR. The 5-yr CSS after UR diagnosed by cytology was 80% versus 41% for patients who presented with symptoms (p<0.0001). Patients with symptomatic UR were noted to have significantly higher stage disease at urethrectomy (p=0.04) and tended toward an increased risk of death from UC (HR: 1.94; p=0.08). Limitations included retrospective study design.
Prostate involvement with UC, tumor multifocality, and type of urinary diversion are significantly associated with UR following RC. Although UR is relatively uncommon, the detection of asymptomatic UR was associated with significantly lower stage disease and improved patient survival, suggesting the importance of continued postoperative evaluation of the urethra.
European urology 08/2011; 60(6):1266-72. · 7.67 Impact Factor
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Sombat Treeprasertsuk,
Kris V Kowdley,
Velimir A C Luketic,
M Edwyn Harrison,
Timothy McCashland,
Alex S Befeler,
Denise Harnois,
Roberta Jorgensen,
Jan Petz,
Jill Keach,
Jeff Schmoll,
Tanya Hoskin, Prabin Thapa,
Felicity Enders,
Keith D Lindor
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ABSTRACT: The predictors for developing varices in patients with primary sclerosing cholangitis (PSC) have not been well studied prospectively. We sought to define the predictors for the presence of varices at baseline and for newly developing varices in patients with PSC. We used prospectively collected data from a multicenter randomized trial of high dose ursodeoxycholic acid for PSC. All 150 patients enrolled were reviewed for predictors of varices and we excluded 26 patients who had esophageal varices at baseline so that predictors of newly developing varices could be determined. Clinical examination, blood tests, and upper endoscopy were done before randomization, at 2 years and after 5 years. Liver biopsy was performed at entry and at 5 years. The median age (interquartile range) of patients was 45.9 years (35.8, 54.9). In a multivariable logistic regression, a higher Mayo risk score (> or =0.87) or a higher aspartate/alanine aminotransferase (AST/ALT) ratio (> or =1.12) were significantly associated with the presence of varices at initial endoscopy (odds ratio = 1.9 and 3.9). By the end of the study, 25 patients had new varices (20.2%). In a Cox model, after adjustment for baseline variables lower platelet count and higher total bilirubin at 2 years were significantly associated with the presence of new varices. The platelet count of 205 (x 10(9)/L) and the total bilirubin level of 1.7 mg/dL were the best cutoff values for the detection of new varices. Conclusion: A higher Mayo risk score and higher AST/ALT ratio were significantly associated with the presence of varices at initial endoscopy. Lower platelet count and higher total bilirubin at 2 years were significantly associated with an increased risk of developing new varices in patients with PSC.
Hepatology 04/2010; 51(4):1302-10. · 11.66 Impact Factor
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Thomas P Moyer,
Dennis J O'Kane,
Linnea M Baudhuin,
Carmen L Wiley,
Alexandre Fortini,
Pamela K Fisher,
Denise M Dupras,
Rajeev Chaudhry, Prabin Thapa,
Alan R Zinsmeister,
John A Heit
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ABSTRACT: The antithrombotic benefits of warfarin are countered by a narrow therapeutic index that contributes to excessive bleeding or cerebrovascular clotting and stroke in some patients. This article reviews the current literature describing warfarin sensitivity genotyping and compares the results of that review to the findings of our study in 189 patients at Mayo Clinic conducted between June 2001 and April 2003. For the review of the literature, we identified relevant peer-reviewed articles by searching the Web of Knowledge using key word warfarin-related adverse event. For the 189 Mayo Clinic patients initiating warfarin therapy to achieve a target international normalized ratio (INR) in the range of 2.0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among the initial warfarin dose, steady-state dose, time to achieve steady-state dose, variations in INR, and allelic variance. Results were compared with those previously reported in the literature for 637 patients. The relationships between allelic variants and warfarin sensitivity found in our study of Mayo Clinic patients are fundamentally the same as in those reported by others. The Mayo Clinic population is predominantly white and shows considerable allelic variability in CYP2C9 and VKORC1. Certain of these alleles are associated with increased sensitivity to warfarin. Polymorphisms in CYP2C9 and VKORC1 have a considerable effect on warfarin dose in white people. A correlation between steady-state warfarin dose and allelic variants of CYP2C9 and VKORC1 has been demonstrated by many previous reports and is reconfirmed in this report. The allelic variants found to most affect warfarin sensitivity are CYP2C9*1*1-VKORC1BB (less warfarin sensitivity than typical); CYP2C9*1*1-VKORC1AA (considerable variance in INR throughout initiation); CYP2C9*1*2-VKORC1AB (more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*2-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AA (much more sensitivity to warfarin than typical); and CYP2C9*2*2-VKORC1AB (much more sensitivity to warfarin than typical). Although we were unable to show an association between allelic variants and initial warfarin dose or dose escalation, an association was seen between allelic variant and steady-state warfarin dose. White people show considerable variance in CYP2C9 allele types, whereas people of Asian or African descent infrequently carry CYP2C9 allelic variants. The VKORC1AA allele associated with high warfarin sensitivity predominates in those of Asian descent, whereas white people and those of African descent show diversity, carrying either the VKORC1BB, an allele associated with low warfarin sensitivity, or VKORC1AB or VKORC1AA, alleles associated with moderate and high warfarin sensitivity, respectively.
Mayo Clinic Proceedings 12/2009; 84(12):1079-94. · 5.70 Impact Factor
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Dana Erickson,
Bradley Erickson,
Robert Watson,
Alice Patton,
John Atkinson,
Fredric Meyer,
Todd Nippoldt,
Paul Carpenter,
Neena Natt,
Adrian Vella, Prabin Thapa
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ABSTRACT: We sought to determine if higher resolution 3 Tesla (T) magnetic resonance imaging (MRI) with or without ovine corticotropin releasing hormone (o-CRH) stimulation would increase the sensitivity for detection of pituitary microadenomas in ACTH-dependent Cushing's syndrome (CS).
We prospectively identified 23 patients over a 2-year period with clinical and biochemical evidence of ACTH-dependent CS with no lesion (n = 11) or equivocal lesion (n = 10) on 1.5T MRI. Subsequently, two additional MRIs were performed in random order: 3T nonstimulated MRI or 3T MRI with o-CRH in all patients. Three neuroradiologists reviewed all examinations in a randomized blinded fashion. Patients were divided into four groups, depending on the outcome of their evaluation and treatment for CS. Two patients had to be excluded, and so we report on 21 subjects.
Both 3T MRI without (P < 0.016) and with o-CRH stimulation (P < 0.013) was significantly more sensitive for detection of pituitary microadenomas than 1.5T MRI for Group 1 (definitive proof of Cushing's disease, n = 10). Group 2 (those in group 1, plus three patients where dynamic/invasive testing suggested pituitary source) also showed a significant (P < 0.012) advantage for 3T. There was no difference between the 3T and the 3T o-CRH examinations for any of the pulse sequences. We did not observe a statistically significant difference in other patient groups [patients with recurrent CD (n = 6) and patients with ectopic CS (n = 2)].
The results of our prospective blinded studies suggest that 3T MRI of pituitary gland should be considered in evaluation of patients with ACTH-dependent CD when 1.5T imaging is negative or equivocal.
Clinical Endocrinology 10/2009; 72(6):793-9. · 3.17 Impact Factor
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Keith D Lindor,
Kris V Kowdley,
Velimir A C Luketic,
M Edwyn Harrison,
Timothy McCashland,
Alex S Befeler,
Denise Harnois,
Roberta Jorgensen,
Jan Petz,
Jill Keach,
Jody Mooney,
Carol Sargeant,
Julie Braaten,
Tamara Bernard,
Debra King,
Ellen Miceli,
Jeff Schmoll,
Tanya Hoskin, Prabin Thapa,
Felicity Enders
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ABSTRACT: Previous controlled trials are inconclusive regarding the efficacy of ursodeoxycholic acid (UDCA) for treating primary sclerosing cholangitis (PSC). One hundred fifty adult patients with PSC were enrolled in a long-term, randomized, double-blind controlled trial of high-dose UDCA (28-30 mg/kg/day) versus placebo. Liver biopsy and cholangiography were performed before randomization and after 5 years. The primary outcome measures were development of cirrhosis, varices, cholangiocarcinoma, liver transplantation, or death. The study was terminated after 6 years due to futility. At enrollment, the UDCA (n = 76) and placebo (n = 74) groups were similar with respect to sex, age, duration of disease, serum aspartate aminotransferase and alkaline phosphatase levels, liver histology, and Mayo risk score. During therapy, aspartate aminotransferase and alkaline phosphatase levels decreased more in the UDCA group than the placebo group (P < 0.01), but improvements in liver tests were not associated with decreased endpoints. By the end of the study, 30 patients in the UDCA group (39%) versus 19 patients in the placebo group (26%) had reached one of the pre-established clinical endpoints. After adjustment for baseline stratification characteristics, the risk of a primary endpoint was 2.3 times greater for patients on UDCA than for those on placebo (P < 0.01) and 2.1 times greater for death, transplantation, or minimal listing criteria (P = 0.038). Serious adverse events were more common in the UDCA group than the placebo group (63% versus 37% [P < 0.01]). Conclusion: Long-term, high-dose UDCA therapy is associated with improvement in serum liver tests in PSC but does not improve survival and was associated with higher rates of serious adverse events.
Hepatology 06/2009; 50(3):808-14. · 11.66 Impact Factor
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ABSTRACT: To determine whether dehydroepiandrosterone (DHEA) replacement therapy in hypoadrenal women improves performance, muscle protein accretion, and mitochondrial functions.
Thirty-three hypoadrenal women were enrolled in the study from May 1, 2002, through May 31, 2003. Twenty-eight completed a 12-week, prospective, randomized, placebo-controlled, crossover study with either daily placebo or 50 mg of DHEA with a 2-week washout period and then crossed over to the other treatment. Body composition, physical performance, whole-body and muscle protein metabolism, and mitochondrial functions were determined.
Administration of DHEA significantly increased plasma levels of DHEA sulfate, testosterone, and androstenedione but did not change body composition, muscle strength, peak aerobic capacity, and whole-body protein turnover or synthesis rates of mitochondrial, sarcoplasmic, or mixed muscle proteins. Muscle mitochondrial oxidative enzymes and messenger RNA (mRNA) levels of genes encoding mitochondrial proteins and nuclear transcription factors did not change after DHEA administration. However, mRNA levels of muscle myosin heavy chain 1 (P=.004), which determines muscle fiber type, and those of insulinlike growth factor binding proteins 4 and 5 significantly decreased (P=.02 and P=.03, respectively).
Three months of DHEA administration increased DHEA sulfate and androgen levels but had no effect on physical performance, body composition, protein metabolism, or muscle mitochondrial biogenesis in hypoadrenal women. However, lowering of mRNA levels of binding proteins of insulinlike growth factor 1 and myosin heavy chain 1 suggests potential effects of longterm treatment with DHEA on muscle fiber type.
Mayo Clinic Proceedings 12/2008; 83(11):1218-25. · 5.70 Impact Factor
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ABSTRACT: Recently, two ion channels associated with congenital long QT syndrome, the SCN5A-encoded Nav1.5 sodium channel and the KCNH2-encoded HERG potassium channel (IKr), have been found on gastrointestinal smooth muscle and interstitial cells of Cajal. The aim of this study was to determine if the cardiac channelopathy-associated mutations in SCN5A or KCNH2 are associated with GI symptom complexes.
Mayo Clinic's Sudden Death Genomics Laboratory performed comprehensive mutational analysis on index patients referred for long QT syndrome genetic testing and their family members thus establishing a cohort of families for which the genotype status for SCN5A or KCNH2 is known. A valid GI symptom questionnaire was mailed to all family members (both genotype positive and genotype negative) in this cohort. The association between cardiac channel genotype and GI symptoms was assessed by logistic regression adjusted for age and sex.
Two hundred and nineteen (43% of 529) subjects returned the questionnaire. Fifty percent of the subjects with an SCN5A mutation reported abdominal pain compared to only 13% of controls (OR 5.7; 95% CI 1.3-24.4). Over 65% of subjects with an SCN5A mutation reported a GI symptom complex compared to 28% of controls (OR 5.2; 95% CI 1.5-18.3). No associations with KCNH2 genotype status were detected.
This study is the first to suggest an association between a well-defined cardiac channelopathy and GI symptoms. The role of sodium channelopathies in the pathogenesis of digestive diseases merits exploration.
The American Journal of Gastroenterology 07/2006; 101(6):1299-304. · 7.28 Impact Factor
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ABSTRACT: Antidepressants are widely used to treat functional gastrointestinal disorders but their effect on postprandial symptoms remains unstudied. We hypothesized that desipramine and escitalopram would enhance the maximum tolerated volume of nutrient ingested and decrease postprandial symptoms.
Healthy participants (n=45) all underwent an assessment of symptoms, anxiety and depression, and a standard nutrient drink test (Ensure). Participants were randomized to 11 days of desipramine (50 mg once daily), escitalopram (10 mg once daily) or identical placebo.
The maximum tolerated gastric volumes were not significantly different on day 11 for desipramine (1,136+/-478 ml, mean+/-SD), escitalopram (1,198+/-422 ml) and placebo (1,231+/-318 ml). A univariate analysis indicated significant treatment group effects on total symptom scores (p=0.049), but after adjusting for age, gender, BMI and baseline scores, treatment effects were no longer significant (p=0.15).
While this study does not rule out a beneficial effect of tricyclics or selective serotonin reuptake inhibitors in functional dyspepsia, neither desipramine nor escitalopram significantly altered the nutrient volume ingested or symptoms induced by the nutrient drink test in healthy volunteers.
Digestion 02/2005; 72(2-3):97-103. · 2.05 Impact Factor
